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Corneal incision architecture after IOL implantation with three different injectors: an environmental scanning electron microscopy study. To evaluate by Environmental Scanning Electron Microscopy (ESEM) the corneal incision architecture after intraocular lens (IOL) implantation in pig eyes, using manual, automated injectors or preloaded delivery systems. Twenty-four pig eyes underwent IOL implantation in the anterior chamber using three different injectors: manual (Monarch III) (n = 8), automated (AutoSert) (n = 8), or a preloaded system (UltraSert) (n = 8). Acrysof IQ IOLs, 21 Dioptres (D) (n = 12) and 27D (n = 12), were implanted through 2.2 mm clear corneal incisions. Incision width was measured using corneal calipers. The endothelial side of the incision was analyzed with ESEM. In each group, the final size of the corneal wound after IOL implantation, measured by calipers, was 2.3-2.4 mm. The incision architecture resulted more irregular in the Monarch group compared with the other injectors. In every group the 27D IOL-implanted specimens showed more alterations than in 21D IOL-implanted samples, and this was less evident in the UltraSert group. The Descemet tear length was higher in the Monarch group than AutoSert and UltraSert group. The automated and preloaded delivery systems provided a good corneal incision architecture; after high-power IOL implantation the incisions were more regular and less damaged with the preloaded system than with the other devices.

Breakthrough varicella infection in a healthcare worker despite immunity after varicella vaccination. Although varicella vaccination is recommended for varicella-susceptible healthcare workers (HCWs), breakthrough infection after vaccination is not unusual, especially following household exposures. We report breakthrough varicella in a vaccinated HCW and review the data on breakthrough infection and concerns for the healthcare setting.

Firm myocardium in cardiopulmonary resuscitation. Firm myocardium in cardiopulmonary resuscitation (CPR) is a rarely described yet potentially important condition. To investigate the clinical nature and implications of firm myocardium in CPR, we retrospectively analyzed 59 adult patients with nontraumatic out-of-hospital cardiac arrest who underwent open-chest CPR in the emergency department and had heart consistency recorded. Consistency of the myocardium varied considerably between patients. Firm myocardium was noticed in 36 cases, mainly in the left ventricle (firm myocardium group). The remaining 23 hearts were not firm (soft myocardium group). Some hearts had an increase in their consistency during CPR. Patient characteristics were similar in the two groups. The firm myocardium group showed greater base deficit on arterial blood gas analysis, suggesting more severe ischemic injury. Very firm heart had a close association with an extremely low end-tidal CO2 tension. Histopathological examination revealed hypertrophy and fibrosis common to the two groups. Both groups received similar treatment except for a shorter duration of direct cardiac massage in the firm myocardium group, although a reasonably prolonged effort was made in most cases. The firm myocardium group responded poorly to treatment. Very firm myocardium never contracted, whereas less firm myocardium usually showed some, albeit insufficient, activity. Most cases in the soft myocardium group regained a pulse. Our results suggest that firm myocardium: (1) is common in patients who receive CPR in the emergency department, (2) indicates ischemic contracture, (3) is not uniform in firmness, reflecting the degree of ischemia and (4) is a grave prognostic factor in cardiac resuscitation.

Escape behavior under tonic inhibitory control of histamine H(2)-receptor mediated mechanisms in the midbrain tectum. The dorsal periaqueductal gray matter (DPAG), superior and inferior colliculus have been implicated in the control of defense reactions in the midbrain. Electrical and chemical stimulation of these structures induces escape behavior, usually accompanied by autonomic responses and antinociception. GABA, 5-HT, opioids, excitatory amino acids and neuropeptides have been postulated to participate in the organization of such defensive reactions in the midbrain tectum. However, little attention has been given to a possible involvement of histamine in the generation of such behavior. To examine this issue in the present study, we assessed the effects of injections into the midbrain tectum of histamine and the H(1) and H(2) receptor antagonists, chlorpheniramine and ranitidine on the behavioral manifestations of the defense reaction. The effects of these drugs were also examined on antinociception, which has been considered to be an inherent component of the defense reaction. Thus, the animals were submitted to an open field test and after 30 min, antinociceptive behavior was measured with the aid of the tail-flick test. The results show that histamine reduced exploratory activity without causing motor deficit, as evaluated by the rotarod test. Ranitidine led to a dose-dependent behavioral activation, with clear signs of fear, whereas no apparent effect was observed following injections of chlorpheniramine. Antinociception always followed the escape reaction induced by the H(2) receptor blocker ranitidine. The present results suggest that H(2) receptors may be involved in the control of escape behavior and antinociception following activation of the neural substrates of fear in the midbrain tectum.

[Neonatal renal vein thrombosis in a heterozygous carrier of both factor V Leiden and the MTHFR gene mutation]. Renal vein thrombosis (RVT) is a rare but potentially serious neonatal disease. Its epidemiology and its clinical and biological expression are currently well known, but its etiological exploration, like that of venous thromboembolism, is increasingly complex. Perinatal risk factors such as prematurity, dehydration, and birth asphyxia have lost their direct accountability at the expense of their interaction with constitutional disorders of hemostasis. We report a case of RVT in a newborn who was a heterozygous carrier of both factor V Leiden and the methylene tetrahydrofolate reductase (MTHFR) gene mutation. We recall the clinical and epidemiological characteristics. A search for inborn blood coagulation disorders should be systematic in the newborn infant with venous thrombosis because of the risk of recurrence, taking into account perinatal factors and maternal thrombophilia (especially if RVT is established during the prenatal period).

Increased locomotor activity in estrogen-treated ovariectomized rats is associated with nucleus accumbens dopamine and is not reduced by dietary sodium deprivation. Estrogens are well known to increase locomotor activity in laboratory rodents; however, the underlying mechanism remains unclear. We used voluntary wheel running by female rats as an index of locomotor behavior to investigate this issue. We first determined whether the estrogen-induced increase in locomotion was susceptible to inhibition by a physiological challenge, and next whether it was associated with dopaminergic activation in the central reward area, nucleus accumbens. Ovariectomized rats were given estradiol or the oil vehicle and housed in cages with or without running wheels. All rats were given regular rodent chow for 1 week, a sodium-deficient diet for the next week, and then were returned to a regular diet for another week. At the end of the last week, all rats were killed, brains were extracted and dopamine levels in the nucleus accumbens were measured. As expected, estradiol treatment increased distance run. Surprisingly, dietary sodium deprivation further increased running, but this appeared to be related to experience with wheel running, rather than to sodium deprivation, per se. Dopamine was greater in the nucleus accumbens of estradiol-treated rats that ran compared to all other groups. Thus, the estrogen-induced increase in locomotion is a robust phenomenon that is not inhibited by a body sodium challenge and is associated with elevated levels of dopamine in reward pathways. These findings raise the possibility that the estrogen-induced increase in locomotor activity, which occurs during a hormonal milieu conducive to reproduction, may reflect mate-seeking behavior and, thereby, maximize reproductive success.

Distinguishing globally-driven changes from regional- and local-scale impacts: The case for long-term and broad-scale studies of recovery from pollution. Marine ecosystems are subject to anthropogenic change at global, regional and local scales. Global drivers interact with regional- and local-scale impacts of both a chronic and acute nature. Natural fluctuations and those driven by climate change need to be understood to diagnose local- and regional-scale impacts, and to inform assessments of recovery. Three case studies are used to illustrate the need for long-term studies: (i) separation of the influence of fishing pressure from climate change on bottom fish in the English Channel; (ii) recovery of rocky shore assemblages from the Torrey Canyon oil spill in the southwest of England; (iii) interaction of climate change and chronic Tributyltin pollution affecting recovery of rocky shore populations following the Torrey Canyon oil spill. We emphasize that "baselines" or "reference states" are better viewed as envelopes that are dependent on the time window of observation. Recommendations are made for adaptive management in a rapidly changing world.

HMGB1 Is Increased by CFTR Loss of Function, Is Lowered by Insulin, and Increases In Vivo at Onset of CFRD. Cystic fibrosis-related diabetes (CFRD) is associated with worsening of inflammation and infections, and the beginning of insulin treatment is debated. To verify high-mobility group box 1 protein (HMGB1) levels in CF patients according to glucose tolerance state, and analyze relationships with insulin secretion and resistance. To verify, in an in vitro model, whether HMGB1 gene expression and protein content were affected by insulin administration and whether these changes were dependent on CF transmembrane conductance regulator (CFTR) loss of function. Forty-three patients in stable clinical conditions and 35 age- and sex-matched controls were enrolled. Glucose tolerance was established in patients based on a 5 point oral glucose tolerance test (OGTT). Fasting glucose to insulin ratio (FGIR), HOMA-IR index, whole-body insulin sensitivity index (WIBISI), and the areas under the curve for glucose (AUCG) and insulin (AUCI) were calculated. HMGB1 was assayed in serum, in cell lysates and conditioned media using a specific ELISA kit. For the in vitro study we used CFBE41o- cells, homozygous for the F508del mutation, and 16HBE14o- as non-CF control. HMGB1 gene expression was studied by real-time RT-PCR. Cells were stimulated with insulin at 2.5 and 5 ng/mL. The CFTR inhibitor 172 and CFTR gene silencing were used to induce CFTR loss of function in 16HBE14o- cells. HMGB1 levels were increased at onset of CFRD (5.04 ± 1.2 vs 2.7 ± 0.3 ng/mL in controls; P < .05) and correlated with FGIR (R = +0.43; P = .038), and AUCI (R = +0.43; P = .013). CFTR loss of function in the 16HBE14o- cells increased HMGB1 and was lowered by insulin. HMGB1 was increased in CF patients with deranging glucose metabolism and showed relationships with indexes of glucose metabolism. The increase in HMGB1 was related to CFTR loss of function, and insulin lowered HMGB1. Further research is required to verify whether HMGB1 could potentially be a candidate marker of onset of CFRD and to establish when to start insulin treatment.

Carcinogenicity of dimethylnitramine in NZR rats in NZO mice. Lifetime tests were done in NZR inbred rats of dimethylnitramine (DMNO) by addition to the drinking water (average dose 1.83 g/kg body weight) and in NZO mice by repeated subcutaneous injection from birth to 7 months of age followed by administration in drinking water (total average dose 4.72 g/kg body weight). Rats developed hepatocellular carcinomas (85%), some of which metastasized. Mice developed hepatocellular carcinomas (81%) and renal adenocarcinomas (48%). Statistically significant increases of other tumor types also occurred in mice. The main targets for DMNO carcinogenesis appeared to be the liver cell epithelium and, at higher dose rates, renal tubular epithelium.

Endothelium-dependent vascular relaxation in patients with type I diabetes. The endothelium plays an important role in the regulation of vascular tone. Although animal data show evidence for an impaired endothelium-dependent vasodilation in diabetes, human in vivo data are scarce. We investigated 11 type I diabetic patients and 11 matched healthy control subjects. The diabetic patients were selected on their relatively poor metabolic regulation (HbA1c > 8.5%), but none showed signs of microvascular complications. In all subjects, we recorded the forearm vasodilator responses to three different stimuli: 1) 5 min of forearm ischemia to obtain a maximal vasodilator response; 2) infusion of MCh into the brachial artery (dosages: 0.03-0.3-1.0 micrograms.min-1.100 ml-1 forearm volume) to evaluate endothelium-dependent vasodilation; and 3) intra-arterial infusion of SNP (dosages: 0.06-0.2-0.6 micrograms.min-1.100 ml-1) to evaluate endothelium-independent vasodilation. The diabetic patients had their usual subcutaneous insulin dose and breakfast 90 min before the start of the test. Baseline levels of BP and FBF were similar in both groups. The PORH response was similar in both groups, with a percentage fall in FVR of 92 +/- 1% in diabetic patients and 94 +/- 1% in control subjects. In the control subjects, MCh infusions exerted a dose-dependent vasodilator response with a maximal fall in the FVR of 90 +/- 2%. The highest dose of SNP induced a fall in FVR of 81 +/- 6% in this group. In diabetic patients, the percentage decrements in FVR during the several dosages of MCh and SNP were similar when compared with the control group. We conclude that chronic hyperglycemia, as occurred in our patients with uncomplicated diabetes mellitus, does not impair endothelium-dependent vasodilation in vivo.

Cell-penetration by Co(III)cyclen-based peptide-cleaving catalysts selective for pathogenic proteins of amyloidoses. Derivatives of the Co(III) complex of 1,4,7,10-tetraazacyclododecane (cyclen) with various organic pendants have been reported as target-selective peptide-cleaving catalysts, which can be exploited as catalytic drugs. In order to provide a firm basis for the catalytic drugs based on Co(III)cyclen, the ability of the Co(III)cyclen-containing peptide-cleaving catalysts to penetrate animal cells such as mouse fibroblast NIH-3T 3 or human embryonic kidney (HEK) 293 cells is demonstrated in the present study. Since the catalysts destroy pathogenic proteins for amyloidoses, results of the present study are expected to initiate extensive efforts to obtain therapeutically safe catalytic drugs for amyloidoses such as Alzheimer's disease, type 2 diabetes mellitus, Parkinson's disease, Huntington's disease, mad cow disease, and so on.

Accumulation and risk assessment of heavy metals in water, sediments, and aquatic organisms in rural rivers in the Taihu Lake region, China. Concentrations of heavy metals (Cd, Cr, Cu, Ni, Pb, and Zn) were measured in water, sediments, Ceratophyllum (hornwort), and Bellamya sp. (edible snail) from residential, mixed (industrial and commercial), and agricultural areas with rural rivers in the Taihu Lake region, China. Zn concentrations were the highest, whereas Cd concentrations were the lowest among the six metals in water, sediments, and aquatic organisms. Cd was mainly present in the acid-soluble fraction, Cr in the residual fraction, and Pb in the reducible fraction of sediments. Heavy metal concentrations in water, sediments, and aquatic organisms in the three areas followed the order of the mixed area > residential area > agricultural area. Heavy metal concentrations in aquatic organisms were not only related to total metal concentrations in water and sediments but also to metal speciation concentrations in sediments. In addition, the bio-concentration factor (BCF) values of Cr, Cu, Pb, and Zn for Bellamya sp. were higher than those for Ceratophyllum, whereas the BCF values of Cd and Ni for Bellamya sp. were lower than those for Ceratophyllum. An ecological risk assessment of heavy metals in sediments showed that Cd posed the highest ecological risk to the environment. A health risk assessment showed that consuming Bellamya sp. from the mixed area could cause a potential health risk.

Functional torque-velocity and power-velocity characteristics of elite athletes. Technical limitations of some isokinetic dynamometers have called into question the validity of some data on human muscle mechanics. The Biodex dynamometer has been shown to minimize the impact artefact while permitting automatic gravity correction. This dynamometer was used to study quadriceps muscle torque and power generation in elite power (n = 6) and elite endurance (n = 7) athletes over 12 randomly assigned isokinetic velocities from 30 degrees.s-1 to 300 degrees.s-1. The angle at peak torque varied as a negative, linear function of angular velocity, with the average angle across test velocities being 59.5 degrees (SD 10.2 degrees). Power athletes developed greater peak torque at each angular velocity (P less than 0.05) and experienced a 39.7% decrement in torque over the velocity range tested. Endurance athletes encountered a 38.8% decline in peak torque. Torques measured at 60 degrees of knee flexion followed a similar trend in both groups; however the greatest torques were recorded at 60 degrees.s-1 rather than at 30 degrees.s-1. Leg extensor muscle power increased monotonically with angular velocity in both power (r2 = 0.728) and endurance athletes (r2 = 0.839); however these curves diverged significantly so that the power athletes produced progressively more power with each velocity increment. These inter group differences probably reflected a combination of natural selection and training adaptation.

[Mechanism of action of biogenic chloramines and hypochlorite on initial aggregation of blood platelets]. The antiaggregant action of two reactive oxidants N,N-dichlorotaurine (chloramine of biogenic type) and sodium hypochlorite on the initial ADP-induced aggregation of rabbit blood platelets has been studied. Platelet aggregation in the reconstructed platelet-rich plasma (PRP) was measured by the nephelometric method, and the aggregation index was an increase in the intensity of small-angle light scattering. The introduction of chloramine at comparatively small concentrations (no greater than 1 mM active chlorine) directly into the reconstructed platelet-rich plasma induces the suppression of the initial aggregation (formation of small aggregates) several times stronger than in the case of its preliminary incubation with plasma alone. This suggests that N,N-dichlorotaurine exerts its antiaggeregant action on the platelet-rich plasma by direct interaction with cells. The effects of the inhibition of platelet aggregation in two variants of introduction of high concentrations of N,N-dichlorotaurine do not significantly differ. In this case a great amount of residual chloramine remains in the plasma, which just induces the suppression of platelet aggregation during subsequent reconstruction of the platelet-rich plasma. Similar data have been obtained in the study of the antiaggregant action of hypochlorite. N,N-Dichlorotaurine and hypochlorite at final concentrations of 0.2-0.3 and 0.15 mM, respectively, inhibit strongly the initial aggregation of isolated platelets (approximately 2 x 10(8) cells in 1 ml) preliminarily activated for 1.5 min by the addition of 100-500 nM ADP. However, the antiaggregants show a more profound suppression of aggregation of unstimulated platelets. The antiaggregant effects of N,N-dichlorotaurine and hypochlorite are probably due to the oxidative modification of sulfur-containing groups in platelet plasmatic membrane.

Simple practice changes lead to better patient experiences. ABOUT 250 patients a month used to have falls at York Teaching Hospital NHS Foundation Trust. But when, in August, nurse managers introduced a new system to assess, monitor and check patients at risk of falling, the figure almost halved, to 140.

Generalized eczéma craquelé as a presenting feature of lymphoma. Two cases of lymphoma are reported--in both, extensive eczéma craquelé resistant to treatment was a presenting feature.

Primary health care. Development of primary care in Japan in still relatively unorganized and unstructured. As mentioned above, the author describes some strengths and weaknesses of the Japanese primary care system. In addressing the weaknesses the following suggestions are offered for the Japanese primary care delivery system: Increase the number of emergency rooms for all day, especially on holidays and at night. Introduce an appointment system. Introduce an open system of hospitals. Coordinate with public hospitals and primary care clinics. Organize the referral system between private practitioners and community hospitals. Increase the number of paramedical staff. Strengthen group practice among primary care physicians. Increase the establishment of departments of primary care practice with government financial incentives to medical schools and teaching hospitals. Develop a more active and direct teaching role for primary care practice or family practice at undergraduate, graduate, and postgraduate levels. Improve and maintain present health insurance payment method, shifting from quantity of care to quality and continuity of care. Introduce formal continuing education. Introduce formal training programs of primary care and strengthen ambulatory care teaching programs.

[Health care in agricultural work in the Sicilian Services of Prevention and Healthcare]. Agriculture is a work sector at high risk for the health of those who work there. The services of prevention and safety in the work area of the AA.SS.PP. (Provincial Health Agencies) of the Sicilian Region began a program of prevention, in the three year term 2010/2013, in this sector. A plan that has been laid out in the "Regional Plan for Prevention and Safety in Agriculture and Fowl Farming" outlined in DA (Administrative Decree number 1174/10. To be able to activate such a plan, the SPreSAL (Prevention and Health Service for the Work Area), have received extra resources that have permitted us to reach pre-planned objectives. The activity carried out brought to light serious defects, in respect to the maintenance of health and safety at work. These tend to derive mainly from the individual and family typologies of companies in the sector. For a more efficient activity of prevention we have shown the opportunity to underline and empower the preventative activity of a support type, rather than surveillance, and to reinforce the Services in such a way that, with their multi-disciplinary competences, they will be able to recover their capacity to carry out a direct control over the risk factors present in the work area.

Chemocoagulation of metastatic lymph nodes using a suspension of mitomycin C-adsorbing activated carbon particles in 80% ethanol. Chemocoagulation therapy was evaluated in an experimental model of metastasis of murine lymph nodes following injection of a suspension of mitomycin C--containing activated carbon particles in 80% ethanol (MMC-CH-ET) into the popliteal lymph node. Lymph node metastasis was induced in the left popliteal and the lumbar lymph nodes 8 days after injection of mouse leukemia P388 cells into the footpad of the left hindleg of BDF1 mice. When MMC-CH-ET was injected into the left popliteal lymph node, it immediately left this site and entered the lumbar lymph node via lymphatic vessels. When compared with tissue concentrations of mitomycin C following injection of an aqueous solution of this drug, the mitomycin C concentration of MMC-CH-ET was maintained at significantly higher levels for 2 hr following injection both at the site of injection and at secondary lymph nodes. Furthermore, coagulative necrosis was identified histologically throughout the injected lymph node and the secondary lymph node, including the metastatic site. The mortality of mice treated with MMC-CH-ET injection was significantly reduced and lymph node metastasis was controlled with MMC-CH-ET when compared with the results for mice treated with an aqueous solution of mitomycin C or treated by surgical lymph node dissection. In this report, we suggest that the use of MMC-CH-ET as a therapeutic agent may be useful in targeting lymph node metastasis.

Drug-related admissions to a family medicine inpatient service. Admissions to a family medicine inpatient service were monitored retrospectively over a one-year period to determine the incidence of drug-related hospitalizations. Of the 293 admissions, 45 (15.4%) were identified as drug related; in 29 admissions (9.9%), a drug-related problem was identified as the primary cause of hospitalization. The two patient characteristics associated with a drug-related admission (DRA) were marital status (divorced) and age (older patients). The two most common types of DRAs were adverse drug reactions (17/45, 37.8%) and drug abuse (14/45, 31.1%), with alcohol being the most commonly abused agent. Adverse drug reactions were most commonly implicated in DRAs for patients over 70 years old, with drug abuse more evenly distributed among age groups. Educational programs that incorporate pharmacoepidemiologic strategies into all health care disciplines are necessary to address this public health issue.

A critical analysis of new molecular targets and strategies for drug developments in Alzheimer's disease. Alzheimer's disease (AD), a progressive, degenerative disorder of the brain, is believed to be the most common cause of dementia amongst the elderly. AD is characterized by the presence of amyloid deposits and neurofibrillary tangles in the brain of afflicted individuals. AD is associated with a loss of the presynaptic markers of the cholinergic system in the brain areas related to memory and learning. AD appears to have a heterogeneous etiology with a large percentage termed sporadic AD arising from unknown causes and a smaller fraction of early onset familial AD (FAD) caused by mutations in one of several genes, such as the beta-amyloid precursor protein (APP) and presenilins (PS1, PS2). These proteins along with tau, secretases, such as beta-amyloid cleaving enzyme (BACE), and apolipoprotein E play important roles in the pathology of AD. On therapeutic fronts, there is significant research underway in the development of new inhibitors for BACE, PS-1 and gamma-secretase as targets for treatment of AD. There is also a remarkable advancement in understanding the function of cholinesterase (ChE) in the brain and the use of ChE-inhibitors in AD. A new generation of acetyl- and butyryl cholinesterase inhibitors is being studied and tested in human clinical trials for AD. The development of vaccination strategies, anti-inflammatory agents, cholesterol-lowering agents, anti-oxidants and hormone therapy are examples of new approaches for treating or slowing the progression of AD. In addition, nutritional, genetic and environmental factors highlight more effective preventive strategies for AD. Developments of early diagnostic tools and of quantitative markers are critical to better follow the course of the disease and to evaluate different therapeutic strategies. In this review, we attempt to critically examine recent trends in AD research from molecular, genetic to clinical areas. We discuss various neurobiological mechanisms that provide the basis of new targets for AD drug development. All these current research efforts should lead to a deeper understanding of the pathobiochemical processes that occur in the AD brain in order to effectively diagnose and prevent their occurrence.

[Identification of NMDA receptor in normal bovine ovary and ovum]. To clarify the pathogenesis of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in patients without ovarian teratoma, we investigate normal human ovary, normal bovine ovary and bovine ova. On the basis of immunohistochemical studies, normal human ovary expressed NR2B epitope in primordial oocytes. The results of SDS-PAGE and immunoblotting using bovine ovarian tissues and ova, we identified two bands of NR1 and NR2B. Moreover, reverse phase liquid chromatography coupled to tandem mass spectrometry showed peptides fractions of NR1, NR2A, NR2B and NR2C. Immunocytochemical study disclosed that normal bovine oocyte has a strong affinity for a patient's disease-specific IgG. Anti-NMDAR encephalitis involves mainly young women who are in their reproductive age. Ovarian teratoma is important as simultaneous tumor, the percentage of patients with ovarian teratoma is less than 40%. It is obvious that the origin of ovarian teratoma is oocyte. So the existence of NMDAR in normal oocytes is very important to assert that ovary itself is the antigen presenting tissue. And also it is helpful to explain why young women are mainly affected from this disease. It seems to conclude that anti-NMDAR encephalitis is one form of autoimmune synaptic encephalitis and that the antigen presenting tissue is ovary itself.

Structure elucidation of a purple peptide found during the purification of a recombinant protein from Escherichia coli. A purple substance (4) partially co-purified with a recombinant human B-type natriuretic peptide (hBNP), following an E. coli fermentation. The structure of the compound was elucidated by NMR, electrospray and FAB mass spectrometry. The chromophore is a 1,4-naphthoquinone condensed with the N-terminal cysteine of a heptapeptide by its NH2- and SH-groups to form a dihydro-thiazine ring. The peptide sequence was determined as Cys-Lys-Val-Leu-Arg-Arg-His by mass spectrometric techniques. CID and data base matching identified it as the C-terminus of the 32-amino-acid recombinant peptide hBNP. This modification of an N-terminal Cys may be a more general phenomenon with implications for the production of heterologous proteins by microorganisms.

Development of a regionally sensitive water-productivity indicator to identify sustainable practices for sugarcane growers. Standards that credibly and effectively certify sustainable commodity production are important to both producers and consumers. Agriculture is the dominant user of water worldwide, so water sustainability in agriculture is an area of particular interest. In conjunction with Bonsucro, a sustainability standard setting body for the sugarcane sector, an indicator was developed to ensure that water consumed in sugarcane cultivation is used productively (i.e., that producers achieve high "crop per drop"). To be easily measurable, sugarcane water productivity was adapted so that yield could be compared within a climate zone in which water demand is assumed to be uniform. The indicator identifies efficient performers, defined as those exceeding median historical yield in each climate zone, with rainfed and irrigated systems evaluated separately. Both the expert-driven and stakeholder-driven aspects of standard development are discussed. We address the advantages and the limitations of this new indicator, its potential application to other crops, and the possibility of improvement to include further criteria. Integr Environ Assess Manag 2016;12:811-820. © 2015 SETAC.

[Mitochondrial diseases--a new branch of the modern medicine]. The review highlights current aspects of a large group of diseases the main pathogenetic element of which is an inherited or acquired disturbance of gene expression of nuclear or mitochondrial genome encoding mitochondrial proteins. The recent data on mutant genetic loci specific to the most wide spread mitochondrial diseases are considered. The steps of pathogenesis, include the mutations of nuclear or mitochondrial genes, disturbances of mitochondrial protein synthesis, dissipation of proton membrane potential, opening of a permeability transition pore, releasing of procaspases, cytochrome c, and other proapoptotic molecules, and finally chromatin fragmentation and apoptotic cell death. We discuss the possible reasons of polysymptomatic character and different variants of mitochondrial disease manifestations on the basis of the phenomenon of mitochondrial DNA heteroplasmy and metabolic compensation of the genetic defects. Modern biochemical methods of a mitochondrial disease diagnostics: (PCR-amplification, polarographic research of mitochondrial respiration and oxidative phosphorylation, analysis and monitoring of metabolites in biological liquids) are characterized. The basic principles and perspectives of the treatment of mitochondrial diseases, (gene therapy, correction of metabolic disorders, application of antioxidants and neuropeptides) are described.

Amelioration of oxygen-induced osteoporosis in the in vitro fetal rat tibia with a capacitively coupled electrical field. Near-term fetal rat tibiae were grown in M.E.M. Eagle/NCTC 135/15% newborn calf serum in 5% carbon dioxide and 5, 10, 21, 35, 60, and 90% oxygen for 3, 7, 10, and 14 days. Linear growth of the explants, as measured from macrophotographs of the explants at day zero and each of the days above, was greatest in the lower oxygen concentrations and least in the higher oxygen concentrations. Breaking strengths of the tibial diaphyses were significantly reduced in those explants grown in 60 and 90% oxygen. When the fetal rat tibiae were grown in 60% oxygen for 7 days and were subjected to a capacitively coupled electrical signal (sine wave, 60 kHz, 10 V peak-to-peak output signal; current density and field in the culture dish calculated to be 5.2 microA/cm2 and 0.32 mV/cm, respectively), the breaking strengths and middiaphyseal widths were statistically significantly greater than control tibiae grown in 60% oxygen alone. It is concluded that an appropriate capacitively coupled electrical field can inhibit an oxygen-induced osteoporosis in an in vitro mammalian long bone model.

[A case of acute respiratory distress syndrome (ARDS) caused by splenic infarction]. Acute respiratory distress syndrome (ARDS) is the most severe lung injury caused by many pathologic states. We treated a patient who suffered from ARDS caused by splenic infarction. A 75-year-old patient had a gastric cancer with multiple lung and liver metastasis. During anti-cancer therapy, she developed a high fever (above 39 degrees C) and a chest and an abdominal CT scan revealed splenic infarction. Hypoxia progressed gradually and she was transferred to ICU with tracheal intubation. Mechanical ventilation was performed according to open lung strategy, but she did not recover. On ICU day 3, the bilateral infiltration shadow on her chest X-ray was pointed out, and she had a low central venous pressure. We diagnosed her ARDS. The administration of methylprednisolone was started according to Meduri's report. Hypoxia was improved gradually and on ICU day 7, she was weaned from mechanical ventilation, and extubated. On ICU day 8, she was returned to her ward without ventilatory support.

Psychosocial factors and medication adherence in HIV-positive youth. The purpose of this study was to test variables consistently identified in the adult HIV literature as predictors of adherence (self-efficacy, social support, and psychological distress) in a sample of 24 HIV-positive youth (ages 16-24). Self-efficacy and psychological distress were significantly correlated with adherence but social support was not. Social support specific to taking medications was correlated with self-efficacy. In regression analysis, both self-efficacy and psychological distress were independently related to adherence and together accounted for 47% of the variance. Results suggest the potential of mental health interventions that boost self-efficacy and reduce psychological distress but require replication with larger samples.

Ultrasound backscatter microscopy image-guided intraventricular gene delivery at murine embryonic age 9.5 and 10.5 produces distinct transgene expression patterns at the adult stage. In utero injection of a retroviral vector into the embryonic telencephalon aided by ultrasound backscatter microscopy permits introduction of a gene of interest at an early stage of development. In this study, we compared the tissue distribution of gene expression in adult mice injected with retroviral vectors at different embryonic ages in utero. Following ultrasound image-guided gene delivery (UIGD) into the embryonic telencephalon, adult mice were subjected to whole-body luciferase imaging and immunohistochemical analysis at 6 weeks and 1 year postinjection. Luciferase activity was observed in a wide range of tissues in animals injected at embryonic age 9.5 (E9.5), whereas animals injected at E10.5 showed brain-localized reporter gene expression. These results suggest that mouse embryonic brain creates a closed and impermeable structure around E10. Therefore, by injecting a transgene before or after E10, transgene expression can be manipulated to be local or systemic. Our results also provide information that widens the applicability of UIGD beyond neuroscience studies.

[Morphological substrate of antalgia and analgesia in the odontostomatological and facial area]. Prior personal work is further extended by a description of the way in which odontostomatological and facial pain is sedated by acupuncture: via peripheral receptors, whose stimulations are intercepted and modulated by various filters lying between the periphery and the cortex: cord (gelatinous substance of Rolando, gate control system), reticular formation and thalamocortical pathways.

Functional outcome following spinal cord injury. A comparison of specialized spinal cord injury center vs general hospital short-term care. The functional outcomes of 185 patients with spinal cord injuries undergoing rehabilitation who were initially treated in a specialized short-term care unit (center patients) were compared with those of 153 patients initially treated in general hospitals (noncenter patients). After stabilization, all patients were admitted to the Rehabilitation Institute of Chicago (Ill) and received the same rehabilitation program. The groups were comparable in terms of demographic, injury, and medical characteristics at the time of rehabilitation center admission, but the duration from injury to rehabilitation was more than twice as long for noncenter patients. While center patients were discharged from the rehabilitation center at equivalent functional skill levels, their daily rate of functional gains during the rehabilitation center stay was significantly greater than that of noncenter patients although the length of stay at the rehabilitation center was comparable for the two groups. These results support the practice of specialized short-term spinal cord injury care as a means of enhancing rehabilitation outcome.

The effect of iron therapy on the exercise capacity of nonanemic iron-deficient adolescent runners. Iron-deficiency anemia impairs exercise capacity, but whether nonanemic iron depletion decreases endurance performance is unclear. In 14 iron-deficient (serum ferritin level, less than 20 micrograms/L [less than 20 ng/L])nonanemic runners, hematologic and treadmill running values were followed up during a competitive season. Following a four-week control period, runners were treated for one month in a double-blind protocol with ferrous sulfate (975 mg/d) or placebo. During treatment, the mean ferritin level rose from 8.7 to 26.6 micrograms/L (8.7 to 26.6 ng/mL) in those patients taking iron and fell from 10.6 to 8.6 micrograms/L (10.7 to 8.6 ng/mL) in the placebo group. Treadmill endurance times improved significantly in the iron-treated runners compared with controls. Endurance time declined in all seven controls (range, 0.07 to 1.30 minutes), while six of seven iron-treated subjects improved their performance (range, 0.03 to 1.92 minutes). No significant differences in maximal or submaximal oxygen consumption, ventilation, or heart rate were observed between the groups except for a 4% increase in maximum oxygen consumption during placebo treatment. These data indicate that nonanemic iron deficiency impairs exercise performance but does not influence gas exchange or cardiac measures.

Heat shock proteins and cardiac protection. The heat shock proteins (hsps) are expressed in normal cells but their expression is enhanced by a number of different stresses including heat and ischaemia. They play important roles in chaperoning the folding of other proteins and in protein degradation. In the heart a number of studies have shown that prior induction of the hsps by a mild stress has a protective effect against a more severe stress. Moreover, over-expression of an individual hsp in cardiac cells in culture or in the intact heart of either transgenic animals or using virus vectors, also produces a protective effect, directly demonstrating the ability of the hsps to produce protection. These findings indicate the potential importance of developing procedures for elevating hsp expression in a safe and efficient manner in human individuals using either pharmacological or gene therapy procedures.

Connection of the Posterior Occipital Muscle and Dura Mater of the Siamese Crocodile. The myodural bridge was proposed initially in 1995. The myodural bridge is a connective tissue bridge that connects a pair of deep muscles at the suboccipital region to the dura mater. There have been numerous studies concerning the morphology and function of the myodural bridge. To determine whether a myodural bridge exists in reptiles, six Siamese crocodiles were investigated using gross anatomy dissection and P45 sheet plastination technologies. As a result, we demonstrated that the posterior occipital muscles of the Siamese crocodile are directly or indirectly connected to the proatlas, atlas, and intermembrane between them. Multiple trabeculae existing in the posterior epidural space extended from the ventral surface of the proatlas, atlas, and intermembrane between them to the dorsal surface of the spinal dura mater. This study showed that the posterior occipital muscle in the suboccipital region of the Siamese crocodile is connected to the spinal dura mater through the proatlas, atlas, and the trabeculae. In conclusion, a myodural bridge-like structure exists in reptiles. This connection may act as a pump to provide cerebrospinal fluid (CSF) circulation at the occipitocervical junction. We hypothesize that a physiologic role of the Siamese crocodile's myodural bridge may be analogous to the human myodural bridge. Anat Rec, 299:1402-1408, 2016. © 2016 Wiley Periodicals, Inc.

Two-year urinary outcomes of sacrocolpopexy with or without transobturator tape: results of a prolapse-reduction stress test-based approach. Women undergoing sacrocolpopexy (SCP) are at risk for postoperative stress urinary incontinence (SUI). However, the optimal management for this condition remains debatable. The aim of this study was to evaluate urinary outcomes 2 years after SCP with or without transobturator tape (TOT) based on the results of a prolapse-reduction stress test. A prospective, observational study was conducted assessing a cohort of women undergoing SCP. Patients were assigned to the TOT or non-TOT group based on results of a prolapse-reduction stress test. The primary outcome was SUI (defined as a positive cough stress test or bothersome symptoms) or additional surgery for this condition. Among the 247 women enrolled, 223 (90 %) received surgery per assignment and completed the follow-up. Two years after surgery, 5.4 % of women in the TOT group and 28.6 % in the non-TOT group had SUI or received additional anti-incontinence surgery (p < 0.01). In the non-TOT group, more women with symptoms of SUI prior to surgery had postoperative SUI or received additional anti-incontinence surgery than those without symptoms (42.9 % vs. 20.0 %, p = 0.01). A preoperative prolapse-reduction stress test alone is not sufficient to determine the need for anti-incontinence surgery at the time of SCP. In particular, women with symptoms of SUI despite a negative prolapse-reduction stress test are more likely to experience postoperative SUI or additional anti-incontinence surgery.

Repeated allergen inhalation induces phenotypic modulation of smooth muscle in bronchioles of sensitized rats. Repeated ovalbumin (OA) or saline exposure of sensitized Brown Norway rats was examined on agonist reactivity, airway smooth muscle (ASM) content, and contractile protein expression in small bronchioles at 24 h, 7 days, and 35 days after challenge. OA increased ASM content (P < 0.05 vs. saline) at 24 h, which resolved by 7 days. Maximum developed tension (T(max)) to carbachol, KCl, and 4-beta-phorbol 12,13-dibutyrate was increased (P < 0.05) by OA in bronchioles at 24 h but was abrogated after correction for ASM. Differences in T(max) were not present at 7 days. In contrast, at 35 days, T(max) was increased (P < 0.05) after correction for ASM. Smooth muscle (sm)-alpha-actin, sm-myosin heavy chain (MHC) isoform 1, calponin, smoothelin-A, and sm-myosin light chain kinase expression were reduced (P < 0.05) by OA at 24 h in bronchioles but not in trachealis. Consistent with contraction findings, no difference in expression of these proteins was detected at 7 days. At 35 days, however, with the exception of sm-alpha-actin, their abundance was again reduced (P < 0.05) by OA. Nonmuscle MHC and beta-actin were unchanged throughout by OA. These findings indicate persistent changes in contractile protein content, consistent with ASM phenotypic modulation in vivo, which occur in response to repeated OA inhalation. Thus, OA exposure induces structural changes in bronchiole ASM content and in agonist responsiveness ex vivo that resemble remodeling in asthma.

[Case report of introducing MMF and steroids as an immunosuppressive therapy after living-donor liver transplantation for a patient with the diabetic nephropathy]. Calcineurin inhibitor (CNI) combined with mycophenolate mofetil (MMF) and steroid is mainly used as immunosuppressive therapy after the living-donor liver transplantation (LDLT). However, the nephrotoxicity caused by CNI remains a critical problem for patients with chronic renal failure, especially on early postoperative period. A 62-year-old woman with decompensated liver cirrhosis secondary to hepatitis B (Child-Pugh C, MELD score 11 points) and chronic renal failure due to diabetic nephropathy (Cr 1.56 mg/dl, GFR 27 ml/min/1.73 m2) experienced LDLT. During the reconstruction of hepatic vein, the supra-and infra-hepatic vena cava was totally clamped. The estimated right lobe liver graft volume was 540 g, representing 51.3% of the standard liver volume of the recipient. Because of the perioperative renal dysfunction due to diabetic nephropathy and the total clamping the vena cava which induced the congestion kidney, MMF (1500 mg/day) and steroid (250 mg/day converted into predonisolone) were mainly introduced as an immunosuppressive therapy after LDLT. The low-dose CNI, tacrolimus also induced the nephrotoxicity and was given for only a short time. Finally, according to the postoperative renal function, the low-dose CNI, cyclosporin (50 mg/day) was able to be added to the introduced immunosuppressive therapy. After having left the hospital, MMF (1500 mg/day), steroid (20 mg/day converted into predonisolone) and cyclosporin (75 mg/day) continued to be given as the immunosuppressive therapy and neither acute graft rejection nor drug-induced renal dysfunction was occurred. This is a case report of introducing with mainly MMF and steroid as an immunosuppressive therapy after LDLT for a patient with perioperative renal dysfunction.

Rab24 is required for normal cell division. Rab24 is an atypical member of the Rab GTPase family whose distribution in interphase cells has been characterized; however, its function remains largely unknown. In this study, we have analyzed the distribution of Rab24 throughout cell division. We have observed that Rab24 was located at the mitotic spindle in metaphase, at the midbody during telophase and in the furrow during cytokinesis. We have also observed partial co-localization of Rab24 and tubulin and demonstrated its association to microtubules. Interestingly, more than 90% of transiently transfected HeLa cells with Rab24 presented abnormal nuclear connections (i.e., chromatin bridges). Furthermore, in CHO cells stably transfected with GFP-Rab24wt, we observed a large percentage of binucleated and multinucleated cells. In addition, these cells presented an extremely large size and multiple failures in mitosis, as aberrant spindle formation (metaphase), delayed chromosomes (telophase) and multiple cytokinesis. A marked increase in binucleated, multinucleated and multilobulated nucleus formation was observed in HeLa cells depleted of Rab24. We also present evidence that a fraction of Rab24 associates with microtubules. In addition, Rab24 knock down resulted in misalignment of chromosomes and abnormal spindle formation in metaphase leading to the appearance of delayed chromosomes during late telophase and failures in cytokinesis. Our findings suggest that an adequate level of Rab24 is necessary for normal cell division. In summary, Rab24 modulates several mitotic events, including chromosome segregation and cytokinesis, perhaps through the interaction with microtubules.

Intracellular labile iron determines H2O2-induced apoptotic signaling via sustained activation of ASK1/JNK-p38 axis. Hydrogen peroxide (H2O2) acts as a second messenger in signal transduction participating in several redox regulated pathways, including cytokine and growth factor stimulated signals. However, the exact molecular mechanisms underlying these processes remain poorly understood and require further investigation. In this work, using Jurkat T lymphoma cells and primary human umbilical vein endothelial cells, it was observed that changes in intracellular "labile iron" were able to modulate signal transduction in H2O2-induced apoptosis. Chelation of intracellular labile iron by desferrioxamine rendered cells resistant to H2O2-induced apoptosis. In order to identify the exact points of iron action, we investigated selected steps in H2O2-mediated apoptotic pathway, focusing on mitogen activated protein kinases (MAPKs) JNK, p38 and ERK. It was observed that spatiotemporal changes in intracellular labile iron, induced by H2O2, influenced the oxidation pattern of the upstream MAP3K ASK1 and promoted the sustained activation of JNK-p38 axis in a defined time-dependent context. Moreover, we indicate that H2O2 induced spatiotemporal changes in intracellular labile iron, at least in part, by triggering the destabilization of lysosomal compartments, promoting a concomitant early response in proteins of iron homeostasis. These results raise the possibility that iron-mediated oxidation of distinct proteins may be implicated in redox signaling processes. Since labile iron can be pharmacologically modified in vivo, it may represent a promising target for therapeutic interventions in related pathological conditions.

Monitoring ambient air pollutants and apply Woods' model in the prediction seasonal dry deposition at Chang-Hua (urban) and Kao-Mei (wetland) county, Taiwan. The main purpose for this study was to monitor ambient air particles and metallic elements (Mn, Fe, Zn, Cr, Cu and Pb) in total suspended particulate (TSP) concentration and dry deposition. In addition, the calculated/measured dry deposition flux ratios of ambient air particles and metallic elements (Mn, Fe, Zn, Cr, Cu and Pb) were evaluated using Woods' model at urban and wetland areas for the 2009-2010 period. The results indicated that the mean highest concentrations of metallic elements Mn, Fe, Zn, Cr, Cu and Pb in TSP were found in Chang-Hua (urban) sampling site. And as for the two characteristic sampling sites, the Woods' model exhibits better dry deposition of particulates of 18 µm particle size than the rest of the other particle sizes at any sampling site in this study. The average calculated/measured flux ratios for two seasons (summer and fall) by using Woods model at 2.5, 10 and 18 µm particles sizes were also studied. The results indicated that the average calculated/measured flux ratios orders for two seasons of various particles sizes were all displayed as Fe > Mn > Zn > Cu > Cr > Pb > particle. And these calculated/measured flux ratios orders were Fe > Mn > Cu > Zn > Cr > Pb > particle and were Fe > Mn > Zn > Cu > Cr > particle > Pb, during spring and winter seasons, respectively. Finally, in the spring and summer seasons of Gao-Mei (wetland) sampling site, the average calculated/measured flux ratios using Woods' model was found to be 2.5, 10 and 18 µm, showing the order of the calculated/measured flux ratios to be Fe > Cu > Zn > Mn > Cr > Pb > particle. And the calculated/measured flux ratio orders were Fe > Zn > Mn > Cu > Cr > particle > Pb and were Fe > Cu > Zn > Mn > Cr > particle > Pb for fall and winter season, respectively.

Fabrication of poly(lactic acid)-poly(ethylene oxide) electrospun membranes with controlled micro to nanofiber sizes. Biodegradable poly(L-lactide acid) (PLLA) nanofiber membranes were prepared by electrospinning of PLLA and poly(ethylene oxide) (PEO). The selective removal of PEO by water allows to obtain smaller fiber diameters and to increase the porosity of the membranes in comparison to PLLA membranes obtained under the same electrospinning conditions. After removal of PEO membranes with fiber sizes of 260 nm and average porosity close to 80% are obtained. Thermal and infrared results confirm the poor miscibility of PLLA and PEO, with the PEO randomly distributed along the PLLA fibers. On the other, PLLA and PEO mixing strongly affect their respective degradation temperatures. The influence of the PEO in the electrospinning process is discussed and the results are correlated to the evolution of the PLLA fiber diameter.

Immunohistochemical study of epithelial cell proliferation in hyperplastic polyps, adenomas, and adenocarcinomas of the large bowel. A monoclonal antibody to bromodeoxyuridine was used in tissue specimens previously incubated with bromodeoxyuridine to show S-phase cells by immunohistochemical technique. Biopsy specimens of normal mucosa (n = 10), hyperplastic polyps (n = 10), adenomas with low-grade dysplasia (n = 20), adenomas with high-grade dysplasia (n = 10), and invasive adenocarcinomas (n = 10) of the large bowel were studied. Labeling index and cell proliferative patterns were analyzed. No statistically significant difference was found in labeling index between normal mucosa and hyperplastic polyps or between adenomas with high-grade dysplasia and adenocarcinomas. The labeling index was significantly lower in normal mucosa and in hyperplastic polyps than in adenomas and adenocarcinomas (p less than 0.001). The difference in labeling index between adenomas with high-grade dysplasia and low-grade dysplasia was also statistically significant (0.01 less than p less than 0.05). In normal mucosa and in hyperplastic polyps the proliferative zone was confined to the lower two-thirds of the crypt; no kinetic activity was found in the upper portions of the crypt or in surface epithelium. In adenomas the labeled cells were either present in the upper third or scattered along the whole axis of the crypt and in the surface epithelium. Labeling patterns in invasive carcinomas were similar to those observed in adenomas with high-grade dysplasia. The difference in proliferative patterns between hyperplastic polyps and adenomas supports a different significance of the two polypoid lesions in the histogenesis of large bowel cancer; our results confirm the subsequent steps of the adenoma-carcinoma sequence. Immunohistochemical labeling patterns observed with monoclonal antibody to bromodeoxyuridine in polypoid and cancer lesions of the large bowel are similar to those described by autoradiographic studies.

Fluorophotometric studies on postmortem changes in porcine corneal endothelial barrier functions. Using an in vitro fluorophotometric technique, we studied the effect of postmortem storage duration on the endothelial barrier function of porcine corneas. A marked decay in endothelial barrier function was demonstrated that correlated with duration of storage. This decay appears to be nearly complete after 2 weeks of storage. This loss of barrier function correlated grossly with ultrastructural changes demonstrated on scanning electron microscopy.

Inhibition of mitochondrial function reduces DNA repair in human mononuclear cells. Mitochondria provide ATP and Ca(2+) needed for DNA repair, but also produce reactive oxygen species (ROS), which may damage DNA. To investigate the effect of mitochondrial function inhibition on DNA repair. Five mitochondrial inhibitors acting at various sites of electron transport were studied. Human peripheral blood mononuclear cells, spontaneous and H(2)O(2)-induced DNA repair, as well as %-double-stranded-DNA, were measured. All mitochondrial inhibitors suppressed spontaneous and H(2)O(2)-induced DNA repair. However, their effect on %-double-stranded-DNA differed, which is partly related to ROS suppression. Mitochondrial inhibition may enhance efficacy and reduce toxicity of radiation and cytotoxic drugs therapy.

[The serological characteristics of the O antigens of Pseudomonas aeruginosa isolated from patients with a Pseudomonas infection during immunotherapy]. Serologic characteristics of P. aeruginosa O-antigens isolated from patients with P. aeruginosa infection were studied over the course of treatment with anti-P. aeruginosa sheep immunoglobulin. The preparation was used in 54 patients with nongeneralized forms of P. aeruginosa infection (infected wounds, pleural empyema) externally or intraperitoneally. From the clinical material collected from the patients a total of 54 P. aeruginosa strains were isolated. Serologic typing of the isolated strains with factor or group diagnostic agglutinating sera has revealed the O-group composition of the isolated strains; 66% of them were classified with O-groups 2,3, and 6. Serologic variants of the strains isolated from patients proved to be stable over the course of the disease immunotherapy. Analysis of the results of bacteriologic control of immunotherapy. efficacy and the clinical data has demonstrated the efficacy of immunotherapy in 61.1% of cases and its partial effect in 20.4% of cases of P. aeruginosa infection.

Mechanisms in the pathogenesis of amiodarone-induced pulmonary toxicity. Although amiodarone is a highly efficacious antidysrhythmic agent, the drug produces numerous adverse effects. The most critical of these is pulmonary toxicity because of the potential for mortality. This review examines the experimental model systems used to study amiodarone toxicity, summarizes the current state of knowledge regarding the processes involved in amiodarone-induced pulmonary toxicity (AIPT), and includes a discussion of potential future directions. Possible contributing processes to initiation of AIPT include phospholipidosis, altered calcium ion regulation, generation of reactive oxygen species, formation of an amiodarone aryl radical, and perturbation of cellular energy production. In addition, an immune response to the parent compound or to a metabolite could play a role. It is expected that elucidation of the mechanism(s) of AIPT will lead to safer antidysrhythmic agents and (or) to effective treatments for the prevention or amelioration of AIPT.

In vitro effect of hormones and growth factors on the incorporation of [3H]leucine, [35S]sulfate and [3H]proline by chondrocytes of aging mice. The ability of parathyroid hormone (PTH 1-84), dexamethasone, prostaglandin E1 (PGE1), prostaglandin E2 (PGE2) and human transforming growth factor beta (hTGF-beta) to stimulate the synthesis of matrical components in articular cartilage of aging mice, was studied in an organ culture system. A marked age-dependent decrease was observed in the synthesis of sulfated glycosaminoglycans (GAGs), protein, collagen digestible protein (CDP) and non-collagen protein (NCP) between 1 and 18 months of age. The addition of hTGF-beta (1 ng/ml) into the culture medium resulted in a significant (P < 0.01) increase of both protein and sulfated GAGs in condylar cartilage from animals aged 1, 3, 6 and 12 months. PGE2 (10 micrograms/ml) induced [3H]leucine and [35S]SO4 incorporation into condylar cartilage from 1, 3 and 6 months old animals. A stimulatory effect of PGE1 (10 micrograms/ml) on [3H]leucine incorporation was noted at 1 and 3 months of age. The effect of PTH appeared to be stimulatory only for protein synthesis in young (1 and 3 months old) animals, whereas it had no effect at 6, 12 and 18 months of age. In contrast, dexamethasone exerted a stimulatory effect on young adults (6 months old) and in matured (12 months old) animals, respectively and a slight inhibitory effect on young (1 and 3 months old) animals. [3H]Proline incorporation was enhanced by all the factors tested in 1-month-old animals. In cultures from 6- and 18-month-old animals only PGE1 and PGE2 appeared to be stimulatory. It is concluded that synthesis of protein, sulfated GAGs and collagen by chondrocytes from maturing and osteoarthritic senescent animals can be stimulated by hormones and growth factors. The efficiency of this response, however, varied according to the animal's age and the factor studied.

Cdh1-APC/C, cyclin B-Cdc2, and Alzheimer's disease pathology. The anaphase-promoting complex/cyclosome (APC/C) is a key E3 ubiquitin ligase complex that functions in regulating cell cycle transitions in proliferating cells and has, as revealed recently, novel roles in postmitotic neurons. Regulated by its activator Cdh1 (or Hct1), whose level is high in postmitotic neurons, APC/C seems to have multiple functions at different cellular locations, modulating diverse processes such as synaptic development and axonal growth. These processes do not, however, appear to be directly connected to cell cycle regulation. It is now shown that Cdh1-APC/C activity may also have a basic role in suppressing cyclin B levels, thus preventing terminally differentiated neurons from aberrantly re-entering the cell cycle. The result of an aberrant cyclin B-induced S-phase entry, at least for some of these neurons, would be death via apoptosis. Cdh1 thus play an active role in maintaining the terminally differentiated, non-cycling state of postmitotic neurons--a function that could become impaired in Alzheimer's and other neurodegenerative diseases.

HMGB1 and RAGE levels in induced sputum correlate with asthma severity and neutrophil percentage. Previous work indicated that high mobility group box-1 (HMGB1) protein may be involved in neutrophilic asthma. Here, we sought to investigate the correlation between HMGB1 and one of its receptors, receptor for advanced glycosylation end products (RAGE), with the severity of bronchial asthma. Compared to the control group (30 healthy individuals), patients in the asthma group (n=72) exhibited a higher percentage of neutrophils and higher HMGB1 and RAGE levels in induced sputum samples (P<0.05). Concurrently, FEV(1)% was significantly lower in the asthma group (P<0.05). Further, compared to mild and moderate asthma, in patients with severe asthma ACQ scores, the percentage of neutrophils, and HMGB1 levels were significantly higher, while FEV(1)% was significantly lower (P<0.05). The percentage of neutrophils and HMGB1 and RAGE levels were lower after treatment than before treatment (P<0.05). Finally, negative correlations were observed between HMGB1 or RAGE levels and FEV(1)% (r=-0.777 and r=-0.291, P<0.05), and positive correlations were detected between HMGB1 or RAGE levels and percentage of neutrophils (r=0.803 and r=0.326, P<0.05). Additionally, positive correlations were observed between HMGB1 and RAGE levels within the asthma group (r=0.306, P<0.05). Therefore, HMGB1 protein levels correlate with the severity of asthma, and HMGB1 may contribute to the inflammatory process of asthma.

An update on the detoxification processes for silica particles and asbestos fibers: successess and limitations. Inhalation of asbestos fibers and crystalline silica produces a number of diseases including fibrosis and cancer. Investigations into the mechanisms involved in mineral particle-induced toxicity indicated the importance of their surfaces in the pathological consequences. Masking of the surface sites has therefore featured prominently in a number of detoxification processes that have been investigated. The majority of the detoxification processes were, however, conducted to elucidate the involvement of a particular surface site in the toxicity of a specific mineral. Others were investigated with the aim of large industrial applications to be applied during mining, handling, processing, transporting, and disposing of minerals. It can be concluded that, to date, there is no single detoxification process that could be applied universally to all different types of mineral particles. Those that have shown some success could not completely abolish all adverse effects. Further elucidation of mechanisms of particle-induced toxicity may open new possibilities for detoxification processes.

p53 accumulation in polynuclear-giant-cells. Accumulation of p53 has been reported in nearly all malignant human tumours. Macrophage derived giant cells of sarcoid granulomas in human lung tissue also show intense staining for p53 while normal alveolar macrophages remain unstained. Since sarcoid giant cells are not considered to be either pre-neoplastic nor to exhibit p53 gene mutations, two different physiological functions of p53 may be illustrated. Alveolar macrophages were isolated from rat lungs and cultured in vitro. Accumulation of p53 was observed by indirect immunohistochemistry after application of polyclonal rabbit serum directed against murine p53 (CM5). Antiproliferating cell nuclear antigen (PCNA) antibodies were used to study DNA synthesis. Most of the multinucleated giant cells derived from macrophages accumulated p53 in the cytoplasm, while only few nuclei were stained. PCNA was found in most giant cells nuclei. However, PCNA positivity was visible in few mononucleated macrophages. Isolated alveolar macrophages in vitro clearly divide and since nuclear division is a late event in the cell cycle, p53 may be involved in G1/S-control and in other cell-cycle-checkpoints between mitosis and cytokinesis.

Diagnosis of cardiac sarcoidosis despite negative findings on serial late gadolinium enhancement with cardiac magnetic resonance imaging/18F-fluorodeoxyglucose positron emission tomography examinations. We present a case of a 42-year-old Japanese man with ocular and pulmonary sarcoidosis who eventually led to a diagnosis with cardiac sarcoidosis (CS) through endomyocardial biopsy (EMB), despite negative findings on both late gadolinium enhancement with cardiac magnetic resonance (LGE-CMR) imaging and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). Cardiac sarcoidosis (CS) develops in only 5% of patients with systemic sarcoidosis. Previous studies have reported that CS was found in up to 50% of autopsy series with fatal sarcoidosis, implying that CS is frequently underdiagnosed with potentially life-threatening consequences. Therefore, the diagnostic accuracy and prognostic value of CS are important. Currently, LGE-CMR and FDG-PET play an important role in establishing a diagnosis of CS with high sensitivity. In the presented case, regardless of serial examinations with LGE-CMR and FDG-PET, confirmed diagnosis of CS could not be achieved; ultimately, a definitive diagnosis of CS was obtained through EMB. To the best of our knowledge, this is the first reported case showing the diagnosis of CS despite negative findings on serial LGE-CMR and FDG-PET examinations.

Microcalorimetric study for the binding of ionic drugs to human erythrocytes and the ghost membranes. The binding of phenothiazine derivatives (as cationic drugs) and non-steroidal anti-inflammatory drugs (as anionic drugs) to human erythrocytes and ghost membranes has been compared with respect to their thermodynamic characteristics, by flow microcalorimetry at pH 7.4 and 37 C. From enthalpyentropy correlation, it was shown that anionic and cationic drugs are bound to different binding sites on the membranes. Phenothiazines bind to a single common site of the erythrocyte membranes with relatively high binding affinities (K = 10(4)-10(5) M-1). The binding is entropy-driven and characterized by a small negative enthalpy (delta H) and a positive entropy change (delta S), reflecting hydrophobic interactions. However, the binding reaction for the intact erythrocytes shows large negative values for both delta H and delta S. The values of K for the membranes and delta H for the intact erythrocytes increased with the increase of the hydrophobic character of the substituent group at the C-2 position of the phenothiazine nucleus (H less than Cl less than CF3). The results indicate that phenothiazines bind and or penetrate to the inner membranes of the erythrocytes and react with intracellular components such as haemoglobin, while anti-inflammatory drugs bind to the surface protein on the membranes with a lower affinity (K = 10(3) M-1) than phenothiazines, reflecting the small negative delta H and positive delta S for the interaction with intact erythrocytes.

Wavefront sensing using a liquid-filled photonic crystal fiber. A novel wavefront sensor based on a microstructural array of waveguides is proposed. The method is based on the sensitivity in light-coupling efficiency to the wavefront gradient present at the entrance aperture of each waveguide in an array, and hence the amount of incident light that couples is influenced by wavefront aberrations. The concept is illustrated with wavefront measurements that have been performed using a liquid-filled photonic crystal fiber (LF-PCF) working as a coherent fiber bundle. The pros and cons of the LF-PCF based sensor are discussed.

Methotrexate and misoprostol for early abortion in adolescent women. Investigate the potential effectiveness, side effects, and acceptability of medical abortion in female adolescents. Multicenter cohort study. Magee-Womens Hospital (Pittsburgh, PA) and University of British Columbia (Vancouver, BC, Canada). Twenty-five pregnant adolescents less than 18 years old up to 49 days' gestation. Methotrexate, 50 mg/m2 intramuscularly, followed 5 to 6 days later by misoprostol, 800 micrograms vaginally, self-administered at home. Misoprostol administration was repeated by a doctor if abortion did not occur within 1 or 2 days. Acceptability was assessed before methotrexate injection and at follow-up 5 weeks later. Successful abortion (complete abortion without requiring a surgical procedure), immediate success (abortion within 24 hours of initial or repeat misoprostol administration), and acceptability. Complete abortion occurred in 24 of 25 (96%; 95% confidence interval [CI], 88%-100%) subjects. Immediate success abortion occurred in 23 (92%; 95% CI, 81%-100%) of these young women; the remaining subject who aborted did so on study day 10. The single failure was an incomplete abortion. Of the 23 participants who completed the follow-up acceptability evaluation, 4 (17%) believed that the process was a negative experience; 83% of participants would choose this same method again for a future abortion if needed and would recommend this method to a friend. Those who would not try this method again were without support of another individual at the time of the abortion. This medical abortion regimen is effective in adolescents. The overall acceptability in adolescents is similar to that reported for women 18 years of age or older. To minimize the likelihood of a negative experience with this abortion method in adolescents, home support for these patients should be evaluated during pretreatment counseling.

Syncarcinogenic effects of methyl methanesulfonate with methylazoxymethanol acetate in rat small intestine and liver. The carcinogenic potency of methyl methanesulfonate (MMS) and its combination effect with methylazoxymethanol (MAM) acetate were evaluated in rats. MMS was suggested to be weakly carcinogenic for the small intestine. Syncarcinogenic effects of MMS and MAM acetate which could be due to summation of their genotoxic influences were obtained in the small intestine and liver.

Influence of age on chromatic aberration of the human eye. We examined the difference in refraction when using portions of the visible spectrum from 437 to 671 nm, and report on the influence of age on the chromatic aberration in one subject 20 years after previous measurements. Changes in refraction were measured with a Rodenstock refractometer which has an exit pupil of 3 mm, and nine narrow band interference filters. Eight subjects were examined under cycloplegia and with dilated pupils. Results confirm previous reports that the magnitude of chromatic aberration decreases with age.

[Investigation on individualized adjustment of target range of high-dose methotrexate]. To explore the way of individualized adjustment of target range of each high-dose methotrexate (MTX) 24 hours infusion to treat acute lymphoblastic leukemia in children. Twenty-four children and 105 infusions were included in the study. According to 1 h and 6 h plasma MTX concentrations after infusion, based on established high-dose MTX population pharmacokinetics model, the course predicted value of drug concentration at steady state (C(SS)) was calculated. MTX infusion rate and dosage was adjusted 8 h after the start according to the predicted value of C(SS). Then MTX concentration at 23 h (actual value of C(SS)) was measured. To achieve the target range of C(SS), adjustments of MTX dosage were required in 17 (71%) patients. Adjustments of MTX dosage were required in 45 (43%) infusions, the dose was increased in 42 infusions and decreased in 3 infusions. There were 29 infusions of high-dose MTX during consolidation therapy (after remission induction therapy). Among them, 16 infusions had increased dosage, and 1 infusion had decreased dosage. There were 76 infusions during maintenance therapy. Among them, 26 infusions increased dosage, and 2 infusions decreased dosage. Overall 95 (90%) infusions achieved the target range of C(SS), while in 8 infusions the doses were lower than the target range in 2 infusions the doses were higher than the target range. If there had been no adjustments, only 74 (70%) infusions could have achieved the target range. Adjustments of MTX dosage, compared with no adjustments, could remarkably enhance the rate of achieving the target range of C(SS) (chi(2) = 13.366, P = 0.000). Among 60 infusions of no adjustments, the actual values of C(SS) were well correlated with the predicted values of C(SS) (r = 0.487, P = 0.000), and the actual values of C(SS) were also correlated with the 6 h plasma MTX concentrations after infusions (r = 0.389, P = 0.002). The actual values of total clearance (CL) of MTX of 105 infusions were 7.01 +/- 2.06 L/(m(2).h). Inter-courses variability in CL was up to 4.4-fold. Intra-patient variability in CL was up to 2.9-fold. Predisposing factors that correlated with decreased CL of MTX were old age, heavy body weight, low blood phosphate, high blood bilirubin and infusions during maintenance therapy (P < 0.05). High-dose methotrexate chemotherapy needed individualized adjustment, as inter-courses variability of CL was up to 4.4-fold among 105 infusions. According to 1 h and 6 h plasma MTX concentrations after infusion, adjusting MTX infusion rate and dosage, overall 90% infusions achieved the target range of C(SS). High-dose MTX infusions during consolidation therapy needed individualized adjustment of target range more.

Transient ischemic attack in the vertebro-basilar circulation due to a hemodynamically significant variation - kinking of the extracranial section of the left vertebral artery. We present a case report of a 74-year old female patient with the clinical diagnosis of transient ischemic attack (TIA) in the vertebro-basilar (VB) circulation, in whom we found bilateral variation of the extracranial section of vertebral arteries on ultrasound, on the left side to the extent of kinking. This finding was later confirmed by magnetic resonance angiography (MRA). We discuss the presumed hemodynamic significance of this variation and its etiological relation to the patient's clinical picture. Ultrasound examination of the carotid and vertebro-basilar circulations is an important examination technique contributing to an early detection of possible aetiology of the cerebral circulation disorders (Fig. 7, Ref. 18).

Significance of overexpression of metallothionein in mouse urinary bladder focal lesions induced by treatment with N-butyl-N-(4-hydroxybutyl)-nitrosamine. Metallothionein (MT) is expressed in various types of human tumors, including transitional cell carcinomas of the urinary bladder, but its biological significance remains unclear. In the present study, the role of MT in urinary bladder carcinogenesis induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) treatment was investigated using C57BL/6 mice. One hundred 5-week-old male C57BL/6 mice were divided into two groups, which were given drinking water with or without 0.05% BBN throughout the experimental period. Subgroups of ten animals from each group were sacrificed at weeks 5, 10, 15, 20 and 25, and urinary bladder samples were examined immunohistochemically for MT, proliferating cell nuclear antigen (PCNA) and apoptosis. MT was found to be abundant in normal-looking mucosa, but decreased with progression from precancerous lesions to invasive carcinoma in the urinary bladder obtained from BBN-treated mice. Lesions could be divided into MT-positive and negative. There was a tendency for greater MT expression in PCNA-positive lesions, while apoptosis was rather associated with MT-negativity. These data suggest that the overexpression of MT may play a role in mouse urinary bladder carcinogenesis.

Effect of manganese (II) bis(glycinate)dichloride on Ca2+ channel function in cultured chick atrial cells. Manganese (II) bis(glycinate)dichloride (Mn(glycinate)2) is a coordination complex of manganese with application as a contrast enhancement agent for magnetic resonance imaging in the heart. To determine the cardioactivity of the manganese ion in this chelation cage, the effects of Mn(glycinate)2 on Ca channel function in the cultured chick atrial cell was studied. Mn(glycinate)2 decreased amplitude of contraction in chick atrial cells from embryos 14 days in ovo with complete inhibition of beating at 1 mM and half-maximal effect at 0.1 mM. Under control conditions, Bay K 8644, a Ca channel activator increased amplitude of contraction by 86% with a half maximal effect at 3.2 x 10(-7) M. In the presence of 0.025 mM Mn(glycinate)2, a concentration which had no effect on the amplitude of contraction, the maximum response to Bay K 8644 was decreased to 31%. Mn(glycinate)2 had no effect on the EC50 for the response to Bay K 8644, 1.7 +/- 0.1 x 10(-9) M (S.E.M., n = 4) in control cells compared to 2.2 +/- 0.4 x 10(-9) M (S.E.M., n = 4) in cells incubated with Mn(glycinate)2. 45Ca2+ uptake over 5 min in cultured chick atrial cells decreased from 2.0 nmol/mg protein in control cells to 1.5 nmol/mg protein in the presence of 10(-5) M PN200-110, a Ca2+ channel blocker, a decrease of 28%. 45Ca2+ uptake decreased to 0.94 nmol/mg protein (53%) in the presence of 1 nmol Mn(glycinate)2. Effects of Mn(glycinate)2 and PN200 were not additive. These data demonstrate that Mn(glycinate)2 exerts its negative inotropic effect, at least partially, by interfering with the function of the L-type Ca channels at high concentrations.

Pancreatic lipase-catalyzed hydrolysis of esters of hydroxymethyl phenytoin dissolved in various metabolizable vehicles, dispersed in micellar systems, and in aqueous suspensions. Lipase-catalyzed hydrolysis of fatty acid esters of 3-hydroxymethyl phenytoin was studied in various triglyceride and ethyl oleate emulsions, dispersed in micellar solutions, and suspended in an aqueous buffered solution. Phenytoin release from ethyl oleate emulsions of the prodrugs show apparent first-order kinetics with the pentanoate to nonanoate derivatives and sigmoidal kinetics with the long-chain fatty acid derivatives (stearate and oleate). A transition in the kinetic behavior, between the short- and the long-chain acyl prodrugs, was observed with the decanoate derivative. These observations are accounted for by a proposed kinetic model. Phenytoin release from the solid prodrugs follows zero-order kinetics and is independent of the total amounts of suspended material but directly proportional to the lipase concentration. Lipolysis of the solid suspended prodrugs was dependent on the length of the acyl side chain of the prodrug, with maxima for the pentanoate and the octanoate derivatives. The short-chain derivatives, acetate and propionate, as well as the long-chain prodrug, stearate, showed the slowest lipolysis rate when present as solid dispersions. The zero-order rate is qualitatively correlated with the melting point of the prodrugs. This result might be expected if the melting point is taken as a measure of the cohesivity or packing of the molecules at the surface of a crystal.

Optimisation of a sample preparation procedure for the screening of fungal infection and assessment of deoxynivalenol content in maize using mid-infrared attenuated total reflection spectroscopy. A sample preparation procedure for the determination of deoxynivalenol (DON) using attenuated total reflection mid-infrared spectroscopy is presented. Repeatable spectra were obtained from samples featuring a narrow particle size distribution. Samples were ground with a centrifugal mill and analysed with an analytical sieve shaker. Particle sizes of <100, 100-250, 250-500, 500-710 and 710-1000 microm were obtained. Repeatability, classification and quantification abilities for DON were compared with non-sieved samples. The 100-250 microm fraction showed the best repeatability. The relative standard deviation of spectral measurements improved from 20 to 4.4% and 100% of sieved samples were correctly classified compared with 79% of non-sieved samples. The DON level in analysed fractions was a good estimate of overall toxin content.

Artificial aggregate made from waste stone sludge and waste silt. In this research, waste stone sludge obtained from slab stone processing and waste silt from aggregate washing plants were recycled to manufacture artificial aggregate. Fine-powdered stone sludge was mixed with waste silt of larger particle size; vibratory compaction was applied for good water permeability, resulting in a smaller amount of solidifying agent being used. For the densified packing used in this study, the mix proportion of waste stone sludge to waste silt was 35:50, which produced artificial aggregate of more compact structure with water absorption rate below 0.1%. In addition, applying vibratory compaction of 33.3 Hz to the artificial aggregate and curing for 28 days doubled the compressive strength to above 29.4 MPa. Hence, recycling of waste stone sludge and waste silt for the production of artificial aggregate not only offers a feasible substitute for sand and stone, but also an ecological alternative to waste management of sludge and silt.

Imaging fingerprinting of excitation emission matrices. The spectral fingerprinting of the excitation emission matrix (EEM) of fluorescent substances is demonstrated using polychromatic light sources and tri-chromatic image detectors. A model of the measured fingerprints explaining their features and classification performance, based on the polychromatic excitation of the indicators is proposed. Substantial amount of spectral information is retained in the fingerprints as corroborated by multivariate analysis and experimental conditions that favor such situation are identified. In average, for five different substances, the model shows a fitting goodness measured by the Pearson's r coefficient and the root mean square deviation of 0.8541 and 0.0247 respectively, while principal component classification patterns satisfactorily compare with the EEM spectroscopy classification and respectively explain 96% and 93% of the information in the fist two principal components. The measurements can be performed using regular computer screens as illumination and web cameras as detectors, which constitute ubiquitous and affordable platforms compatible with distributed evaluations, in contrast to regular instrumentation for EEM measurements.

Patterned multiplex pathogen DNA detection by Au particle-on-wire SERS sensor. A Au particle-on-wire system that can be used as a specific, sensitive, and multiplex DNA sensor is developed. A pattern formed by multiple Au nanowire sensors provides positional address and identification for each sensor. By using this system, multiplex sensing of target DNAs was possible in a quantitative manner with a detection limit of 10 pM. Target DNAs from reference bacteria and clinical isolates were successfully identified by this sensor system, enabling diagnostics for infectious diseases.

Posterior epidural migration of herniated lumbar disc fragment. Posterior epidural migration of a free disc fragment in the lumbar region is a very rare condition that has only been reported in isolated cases to date. Patients with this condition present with radiculopathy or major neurological deficits. Difficulties in diagnosis and the choice and timing of surgical treatment are important in these cases. In this clinical case series, features of cases with posterior epidural migration of free lumbar disc fragments accompanied by cauda equina syndrome are discussed. Eight cases (0.27%) of posterior epidural migration of disc fragments were detected among 2880 patients surgically treated for lumbar disc herniation between 1995 and 2008. Seven of these patients had cauda equina syndrome. The mean duration of symptoms in the 8 cases was 4.2 days (range 1-10 days). The group included 6 men and 2 women, with a mean age of 48 years (range 34-72 years). The sequestered disc fragments were at the L3-4 level in 6 patients (75%) and the L4-5 level in 2 (25%). Magnetic resonance imaging showed tumor-like ring contrast enhancement around sequestered fragments in 5 patients. The patients' motor, sensory, sexual, and urological functions were evaluated postoperatively, and modified Odom criteria and a visual analog scale were used in the assessment of postoperative outcomes. A microsurgical approach was used in all cases. Sequestrectomy with minimal hemilaminotomy and removal of the free segments were performed. The patients were followed up for a mean period of 28.5 months. Three patients (37.5%) had excellent results, 3 (37.5%) had good results, 1 patient (12.5%) had fair results, and only 1 patient had poor results according to the Odom criteria. The main factors affecting the long-term outcomes were the presence of cauda equina syndrome and the time period between onset of symptoms and surgery. Patients with posterior migration of a disc fragment present with severe neurological deficits such as cauda equina syndrome. Because the radiological images of disc fragments may mimic those of other more common posterior epidural space-occupying lesions, definite diagnosis of posteriorly located disc fragments is difficult. All of these lesions can be completely removed with hemilaminotomy and sequestrectomy, and early surgical treatment is important as a first choice to prevent severe neurological deficits.

Australian surgeons and society. Surgery and society are living entities, forever changing and evolving. The quality of the men who served them will never change. In this brief sketch I have traced a lineage of men - men of good heart - men who have mastered their craft - men who have applied it in accordance with the ancient tradition of helping those in need - men who matched their times and the leaders of Australian society.

Surface display of acid protease on the cells of Yarrowia lipolytica for milk clotting. The acid protease structural gene was amplified from the genomic DNA of Saccharomycopsis fibuligera A11. When the gene was cloned into the multiple cloning site of the surface display vector pINA1317-YlCWP110 and expressed in the cells of Yarrowia lipolytica, the cells displaying the acid protease could form clear zone on the plate-containing milk indicating that they had extracellular acid protease activity. The cells displaying the acid protease can be used to effectively clot skimmed milk. The highest clotting milk activity (1,142.9 U/ml) was observed under the conditions of pH 3.0, 40 degrees C, 20 mM of CaCl(2), and 10% skimmed milk powder. We found that the acid protease displayed on the cells of Y. lipolytica which has generally regarded as safe status could be easily isolated and concentrated compared to the free acid protease. Therefore, the displayed acid protease may have many potential applications in food and cheese industries. This is the first report that the yeast cells displaying the acid protease were used to clot milk.

Risk of malignancy after gamma knife stereotactic radiosurgery. To assess the risk of radiosurgery to cause malignant transformation in benign tumors or to induce new malignancies. A retrospective cohort study comparing the Sheffield, England, radiosurgery patient database with national mortality and cancer registries. This data set comprises approximately 5000 patients and 30,000 patient-years of follow-up, with more than 1200 patients having a follow-up period longer than 10 years. In this material, a single new astrocytoma was diagnosed, whereas, based on national incidence figures, 2.47 cases would have been predicted. No increased risk of malignancy was detected in this series, supporting the safety of radiosurgery. Pragmatically, in advising patients, the risks of malignancy would seem small, particularly if such risks are considered in the context of the other risks faced by patients with intracranial pathologies requiring radiosurgical treatments.

Metformin protects against carbon tetrachloride hepatotoxicity in mice. In the present study, the hepatoprotective effect of metformin (Met), a dimethylbiguanide anti-hyperglycemic, was examined in a mouse model of liver damage induced by chronic repeated administration of carbon tetrachloride (CCl(4)) (5 microl/kg, twice a week for 12 weeks). Met, when given orally in drinking water at an estimated daily dose of 25 or 50 mg/kg for 10 weeks starting 2 weeks after CCl(4) challenge, protected against CCl(4) hepatotoxicity. The results indicate that the hepatoprotection afforded by Met treatment at a dose of 25 mg/kg against CCl(4) toxicity may at least in part be mediated by the enhancement of mitochondrial glutathione redox status.

Does a 'reverse' atopic march exist? The classical description of the atopic march usually refers to the progression from atopic dermatitis towards asthma, but this pathway has been questioned. We assessed in a prospective observation the possible onset of atopic dermatitis in children with asthma alone at baseline, and evaluated retrospectively their characteristics. Seven hundred and forty-five children (360 male, 6-9 years of age) with asthma alone, without food allergy or atopic dermatitis, were followed-up with regular visits for 9 years. 692 children completed the 9-year observation, and 20% of them were found to have developed atopic dermatitis at 9 years. Comparing retrospectively the children who developed AD with the remaining, no significant difference existed at baseline concerning the demographic characteristics and family history. There was a significantly higher proportion ( chi2 = 0.01) of subjects with single sensitization to mites and a significantly lower proportion of polysensitized subjects ( chi2 = 0.01) within the children who developed AD. Sensitization to foods appeared in 9% of children who developed AD and in 3.8% in the other children (NS). According to these observations, the development of a particular allergic disease does not necessarily follow the classical paradigm of the atopic march.

Distribution of 3-hydroxy-3-methylglutaryl-CoA reductase in isolated villus and crypt cells of chick duodenum, jejunum and ileum. 3-Hydroxy-3-methylglutaryl-CoA reductase (EC 1.1.1.34), the major rate-limiting enzyme of cholesterogenesis, was studied in epithelial cells isolated in a villus to crypt gradient from chick duodenum, jejunum and ileum, in order to resolve the apparent controversy that exists on the anatomical localization of sterol synthesis in the intestine. Consistent separation was demonstrated by using the marker enzymes alkaline phosphatase, specific to the villus cells, and thymidine kinase, specific to the crypt cells. No relative difference in stability was observed, as shown by the equal distribution of acid phosphatase. Cells were 90-95 per cent viable. The highest specific activity of reductase was located in the microsomal fraction (41 per cent of the total). The mitochondria had lower specific activity (8 per cent of the total). The distribution of reductase activity in epithelial cells of the villus-crypt axis was also studied. The specific activity in each cell fraction from chick duodenum was clearly lower than that in jejunum and ileum. The jejunal and ileal crypt regions showed lower specific activity than the villus cells. About 70 per cent of total reductase activity was found in cells from the upper and the mid villus fraction in each intestinal segment.

N-3 fatty acids and pregnancy outcomes. To discuss new data from the literature on the relationship between the supply of n-3 polyunsaturated fatty acids during pregnancy and pregnancy outcomes, evaluated as the fatty acid composition of blood and breast milk, fetal and infantile development and maternal health. Supplementation of alpha-linolenic acid in high doses or docosahexaenoic acid in low doses did not result in a significant enhancement of the blood docosahexaenoic acid status of the offspring. In contrast, supplementation of docosahexaenoic acid in relatively high doses led to significant increases in infantile docosahexaenoic acid values and to a significant enhancement of breast milk docosahexaenoic acid content. Electroretinogram data obtained during the first week of life and pattern-reversal visual evoked potentials investigated at 50 and 66 weeks postconception were significantly associated with the docosahexaenoic acid status of the infant at birth. Children whose mothers received docosahexaenoic acid supplementation during pregnancy and lactation scored better in mental processing tests carried out at 4 years than children whose mothers received placebo. Beneficial health outcomes are more likely to result from supplementation with docosahexaenoic acid itself, rather than its precursor alpha-linolenic acid. Trials have shown that a higher maternal docosahexaenoic acid intake during pregnancy may be favourable for the visual and cognitive development of the offspring. The significant positive association between maternal docosahexaenoic acid intake during pregnancy and the children's mental processing scores at 4 years suggest that optimization of the docosahexaenoic acid status of expectant women may offer long-term developmental benefits to their children.

Parkinson's disease with and without REM sleep behaviour disorder: are there any clinical differences? Rapid eye movement sleep behaviour disorder (RBD) may serve as a useful indicator to approach Parkinson's disease (PD); however, PD patients do not always exhibit RBD. We wondered whether the presence of RBD would be reflected in the expansion of PD lesions and represent the same PD entity. We examined the clinical differences between PD with and without RBD and studied the frequency of RBD-like symptoms (RBD-s) and clinical differences in 150 PD patients, including 81 patients (54.0%) who satisfied the International Classification of Sleep Disorders, Revised, minimum clinical criteria for RBD. RBD-s preceding the appearance of parkinsonism were found in 44.4% of patients. Statistically, the presence of RBD-s was associated with ages above 65 years, male gender, constipation, dopa-induced dyskinesia and 'sleep attack', with odds ratios of 3.709, 2.469, 2.184, 5.046 and 6.562, respectively. No differences were found between the 2 groups with regard to symptoms at PD onset, disease duration, Hoehn-Yahr stage, hallucination, dementia, wearing-off, orthostatic hypotension, cerebral blood flow and antiparkinsonism drugs. In the early stage, RBD and autonomic system dysfunction are important factors in the progression of PD.

Acute and Recurrent Pericarditis. Acute and recurrent pericarditis is the most common pericardial syndrome encountered in clinical practice either as an isolated process or as part of a systemic disease. The diagnosis is based on clinical evaluation, electrocardiogram, and echocardiography. The empiric therapy is based on nonsteroidal anti-inflammatory drugs plus colchicine as first choice, resorting to corticosteroids for specific indications (eg, systemic inflammatory disease on corticosteroids, pregnancy, renal failure, concomitant oral anticoagulants), for contraindications or failure of the first-line therapy. The most common complication is recurrence, occurring in up to 30% of cases after a first episode of pericarditis.

[On the problem of industrial accidents under drug influence (author's transl)]. Industrial accidents resulting from technical defects have decreased in the last eights because of improved safety precautions. In contrast, accidents resulting from "human error" are increasing steadily. Toxicological urine analysis for drugs--directed mainly at soporifics, sedatives, tranquilizers, and pain-relievers--on 84 patients involved in industrial accidents yielded the following results. 1. Drugs were identified in 44 patients (= 52%). 2. In 13.4 patients, more than one drug was identified (= 16%). 3. Only five of the 44 patients admitted on being questioned that they had taken drugs (= 10%). On the other hand, in a control group of 47 persons who and not suffered any accident, drugs were detected in 19 cases (= 40%). The results show that the physician will have to take into account that healthy and efficient persons, too, are very often likely to practise drug abuse. It must be considered probable that this helps to promote accidents. Medical prescription, especially of neuroleptics and psychotropics, as well as of sedatives, should be practiced more.

[Histochemical study of the subcommissural organ in chickens during development]. Some histochemical and particularly histoenzymological tests are performed on the subcommissural organ of chick embryos. A secretory activity appears about the 7th day. In 10 days old embryos and new hatched chicken the enzyme activities are of rather low intensity. Compared with the 10 days embryos, the newborn show some increase, but compared with the adult birds the activities remain weak. However the acid phosphatase activity is higher in the subcommissural organ than in the ependyma even in 10 days embryos.

Synopsis of the genus Pseudosparna Mermudes & Monné (Coleoptera, Cerambycidae, Lamiinae), with description of two new species . Two new species of Pseudosparna Mermudes & Monné, 2009 are described: P. tucurui sp. nov. from Brazil (Pará) and P. pichincha sp. nov. from Ecuador (Pichincha). A key to the species of Pseudosparna is also included.

[SOCIAL SERVICES ORGANIZATION FOR ELDERLY CITIZENS AND DISABLED PERSONS IN SOUTH FEDERAL DISTRICT OF RUSSIA]. The article presents a comparative analysis of the effectiveness of the individual rehabilitation programs among elderly citizens and disabled persons of the Astrakhan region, the part of the South Federal District of Russia. We analyzed the data of the statistical survey of the social services provided rehabilitation facilities for the elderly and disabled people in the Astrakhan region. Analytical results thus obtained shown that the network of agencies and centers of social rehabilitation in the Astrakhan region did not correspond to the needs of elderly people and disabled persons. The negative dynamics in the number of social care centers as well as in the number of people who were provided with their services revealed the need for optimization of the institutional structure and its management. These specific characteristics of the social rehabilitation services in the Astrakhan region thus identified should be taken into consideration in order to improve the rehabilitation programs among elderly citizens and disabled persons in the South Region of the Russian Federation.

Preparation of human chromosomes for high resolution scanning electron microscopy. The addition of ethidium bromide during the last 2.5-3 h of lymphocyte culturing restricted chromosome contraction and preserved the banding structure in scanning electron microscopy. Treatment of the chromosomes with trypsin and use of impregnation with osmium tetroxide and thiocarbohydrazide resulted in a structural preservation of high resolution quality.

Observation of anomalous diffusion in excised tissue by characterizing the diffusion-time dependence of the MR signal. This report introduces a novel method to characterize the diffusion-time dependence of the diffusion-weighted magnetic resonance (MR) signal in biological tissues. The approach utilizes the theory of diffusion in disordered media where two parameters, the random walk dimension and the spectral dimension, describe the evolution of the average propagators obtained from q-space MR experiments. These parameters were estimated, using several schemes, on diffusion MR spectroscopy data obtained from human red blood cell ghosts and nervous tissue autopsy samples. The experiments demonstrated that water diffusion in human tissue is anomalous, where the mean-square displacements vary slower than linearly with diffusion time. These observations are consistent with a fractal microstructure for human tissues. Differences observed between healthy human nervous tissue and glioblastoma samples suggest that the proposed methodology may provide a novel, clinically useful form of diffusion MR contrast.

A generalized item response tree model for psychological assessments. A new item response theory (IRT) model with a tree structure has been introduced for modeling item response processes with a tree structure. In this paper, we present a generalized item response tree model with a flexible parametric form, dimensionality, and choice of covariates. The utilities of the model are demonstrated with two applications in psychological assessments for investigating Likert scale item responses and for modeling omitted item responses. The proposed model is estimated with the freely available R package flirt (Jeon et al., 2014b).

Sensory representations in cerebellar granule cells. Cerebellar granule cells are an attractive model system for examining synaptic transmission and temporal integration, because of their small number of excitatory synaptic inputs and electrotonic compactness. Recent in vivo whole-cell recordings have revealed how sensory stimuli are represented by synaptic activity across multiple modalities and cerebellar regions. By monitoring the activity of individual synapses, the reliability of these unitary signals has been quantified, and the complexity of a granule cell's receptive field has been explored at the highest resolution. Here we describe the emerging principles of synaptic sensory representation and their consequences for information processing in the granule cell layer.

Influence of blood volume on cerebrospinal fluid levels of arachidonic acid metabolites after subarachnoid hemorrhage: experimental study on the pathogenesis of cerebral vasospasm. Based on accumulating data indicating the important role of arachidonic acid metabolites in the pathogenesis of cerebral vasospasm, we examined the influence of alterations in blood volume on the cerebrospinal fluid (CSF) level of the subarachnoid hemorrhage (SAH). Three separate injections of autologous blood into the cisterna magna of dogs within subarachnoid hemorrhage (SAH). Three separate injections of autologous blood into the cisterna magna of dogs within 72 hours were performed. Three experimental groups were formed, with an overall injected blood volume of 6, 9, and 12 ml. Arterial spasm was verified by comparison of the angiographic diameter of the basilar artery on Day 8 vs. Day 1. Additionally, light microscopic, scanning and transmission electron microscopic, and freeze cracking technique examinations of the basilar artery demonstrated the typical morphological features of proliferative vasculopathy. Increasing the volume of experimental SAH led to a linear decrease of the mean vessel diameter from 45% to 53% and finally to 75% of normal. Parallel to the reduction of angiographic vessel lumen, a volume-dependent significant increase of all three eicosanoids was demonstrated. A deficiency of prostacyclin concentration during the course of the experiment was not observed. Despite highly elevated CSF levels of vasodilating prostacyclin, however, severe angiographic constriction of the basilar artery occurred in the presence of high concentrations of TXA2 and PGE2. It is concluded that increasing volumes of SAH led to a concomitant release of arachidonic acid metabolites during posthemorrhagic clot lysis. From our data, it seems questionable whether a prostacyclin deficiency is an important underlying factor for the development of cerebral spasm.(ABSTRACT TRUNCATED AT 250 WORDS)

Characterisation of ATP binding inhibition to the sarcoplasmic reticulum Ca(2+)-ATPase by thapsigargin. The inhibition of Ca(2+)-ATPase of sarcoplasmic reticulum by thapsigargin has been reported to be associated with a suppression of calcium binding to the high affinity transport sites. We report here that thapsigargin also acts as an inhibitor of ATP binding by reducing its apparent affinity by about two orders of magnitude. This inhibition is non-competitive indicating that thapsigargin does not bind to the ATP binding site. This is confirmed by the fact that thapsigargin binding to the Ca(2+)-ATPase does not affect the binding of 2',3'-O-(2,4,6-trinitrocyclohexadienylidene)-ATP (TNP-ATP).

Effect of L-dopa methylester and glutathione depletion on murine B16BL6 melanoma growth in vitro. The cytotoxic and growth-inhibitory effect of levodopa methylester (LDME) in murine B16BL6 (BL6) melanoma cells after glutathione (GSH) depletion was studied in vitro. Pretreatment of BL6 cells with 50 microM buthionine sulfoximine (BSO) depleted GSH content by nearly 90% and enhanced the growth-inhibitory effect of even a minimally cytotoxic concentration of LDME. Radiothymidine incorporation into BL6 cells significantly increased compared to untreated controls during the first 4 h of exposure to 0.2 mM LDME. However, pretreatment with BSO prevented this LDME-induced increase in radiothymidine incorporation. Because the percentage of cells in S-phase of the cell cycle was not altered, these results suggest that BSO exposure may be inhibiting unscheduled DNA synthesis, which could contribute to the cytotoxic effects of LDME. In addition, spectrophotometric studies indicated that in a cell-free system, GSH scavenged dopaquinone produced by the tyrosinase-mediated oxidation of LDME, presumably by formation of glutathionyldopa. Thus, enhancement of LDME cytotoxicity by BSO may also involve depleting the amount of GSH available for the nucleophilic addition to the quinone.

Cell motility during wound healing in giant algal cells: contraction in detergent-permeabilized cell models of Ernodesmis. Triton-treated cells of the coenocytic green alga, Ernodesmis verticillata, manifest longitudinal contraction and centripetal closure of the cytoplasm in the presence of exogenous free calcium ions. Complete closure of the cytoplasm around the vacuolar remnants is obtained with 1 mM ATP present in the activation medium. The cytoplasmic contractions in these cell models closely resemble normal wound healing motility phenomena previously reported for this organism, thereby providing a system for studying the contractions associated with cellular wound healing. Dye-exclusion experiments with eosin B reveal that the tritonized models are freely permeable, whereas untreated cells do not take up the stain. Ultrastructurally, activated (contracting) models possess a network of microfilaments beneath the plasma membrane remnants in regions of active contraction. Microtubules are associated with the microfilaments, but they also occur throughout the periphery of the entire cells, even in unactivated models. This suggests that microfilaments may be involved in localized contractions leading to wound healing, whereas microtubules are probably providing a cytoskeletal framework upon which the microfilaments act. Colchicine (5 mM) has no effect on contraction in the models; extensive experiments with cytochalasins B and D (up to 100 micrograms/ml) have failed to show regular, reproducible inhibition of contraction also. Trifluoperazine (10 microM) or La3+ (1 mM) decreases the rate and magnitude of contraction to some extent, perhaps by preventing Ca2+ interaction with the contractile apparatus. The threshold concentration of free Ca2+ necessary to activate contraction in the models appears to be 10(-6) M, an order of magnitude higher than the preliminary value reported for non-permeabilized, wounded cells. Free Mg2+ also must be present for activation of models, with a minimum concentration of ca. 5 mM. The requirement of ATP for contraction can be demonstrated by the fact that either excessive washing of cell models prior to activation or inclusion of uncoupling agents in the solutions largely prevents activation of the models unless ATP is added to the Ca2+ -containing activation medium. These results provide further evidence that cellular wound healing in Ernodesmis is similar to the majority of other non-muscle cell motility phenomena in requiring ATP and micromolar amounts of free Ca2+ and that microfilaments are implicated in the contractile process. Moreover, the Ernodesmis cell models should be excellent systems for the further probing of cytoplasmic contractions associated with wound healing at the cellular level of organization.

The baculovirus transcriptional transactivator ie0 produces multiple products by internal initiation of translation. Ie0 is the only gene of the baculovirus Orgyia pseudotsugata multiple nucleopolyhedrovirus (OpMNPV) that is known to be spliced. In this study, cDNAs of ie0 were isolated, cloned, and sequenced. It was observed that IE0 contains 35 amino acids (aa) added to the N-terminus of IE1. In addition, it was found that the leader sequence of ie0 contains a 4-aa minicistron. To functionally characterize IE0, ie0 cDNAs were expressed under control of either the ie1 or the ie0 promoter. Unexpectedly, examination of ie0 translation products revealed that the predominant product from ie0 mRNAs was not IE0, but IE1. Mutation analysis showed that IE1 translation was preferentially initiated from either of two AUGs found in the first 15 nucleotides (nt) of the ie1 ORF that are internal to the ie0 ORF. It is unknown whether the internal translation initiation occurs via a leaky scanning mechanism or by an internal ribosomal entry site. Transactivation analysis with constructs that had point mutations in the ie1 AUGs and were translated only as IE0 revealed that OpMNPV IE0 is a 14- to 15-fold stronger transactivator than IE1. IE0 was also shown to be autoregulatory and to transactivate early genes in an enhancer-independent or -dependent manner. These results suggest that differential expression of baculovirus early genes can be obtained by coexpression of IE0 and IE1 in infected cells, which may permit subtle regulation of specific sets of viral genes.

Genetic counseling in limb reduction defects. During several years experience in a multidisciplinary out-patient clinic for children with congenital hand malformations a systematic approach was devised to arrive at an accurate diagnosis and recurrence risk in patients with congenital limb reduction defects. Classification and diagnostic work-up was done according to a protocol, derived from data in the literature and from our own experience. This protocol is described for the different types of congenital upper limb reduction defects.

Extension of a shortened ureter using the in situ appendix during Indiana pouch urinary diversion. A short ureteral length can preclude the use of a continent urinary diversion during urinary tract reconstruction after bladder removal. We present a surgical technique using the in situ appendix to provide length to a shortened left ureter, thus allowing formation of a continent ileocecal urinary diversion.

[Multiparametric magnetic resonance imaging of the prostate - technique and clinical applications]. Multiparametric magnetic resonance imaging (MRI) includes 1 H magnetic resonance spectroscopy, diffusion-weighted imaging, and dynamic contrast-enhanced MRI. These new MRI techniques are increasingly being used to supplement conventional T 2 and T 1-weighted MR sequences in prostate imaging. The first part of this review outlines each of these techniques, the most important diagnostic parameters, and the pathophysiological background. The characteristic features of prostate cancer and noncancerous prostate tissue as depicted with each of the three techniques are presented. The second, clinical part outlines the diagnostic applications of the three MRI techniques for the early detection and localization of prostate cancer, staging, and the identification of recurrent cancer and discusses the most recent publications in this field. The review concludes with a look at emerging clinical applications such as the evaluation of biological aggressiveness and tumor volume.

Retinoic acid 4-hydroxylase-mediated catabolism of all-trans retinoic acid and the cell proliferation in head and neck squamous cell carcinoma. All-trans retinoic acid (RA) can be catabolized to polar metabolites by microsomal P450s (P450). The aim of this study was to confirm if retinoic acid 4-hydroxylase (CYP26) is a P450 induced by RA and to investigate the role of cellular RA binding proteins (CRABPs), using a slow catabolizer, AMC-HN-4, and a rapid catabolizer, AMC-HN-6. Also, we analyzed the effect of RA catabolism on cell proliferation of head and neck squamous cell carcinoma (HNSCC) in vitro and in vivo. Both cell lines weakly expressed CYP26 and CRABPs, but RA induced CYP26 only in AMC-HN-6. The sensitivity to RA was variable by the amount of CYP26, and the rapid catabolism by CYP26 made AMC-HN-6 resistant to RA in vitro. In addition, The RA had a stronger effect on the inhibition of tumor growth of AMC-HN-4 than that of AMC-HN-6 in vivo. Conclusively, the CYP26 activity might be one essential factor for the RA sensitivity, but in cells showing induction of CYP26, the RA sensitivity is inversely related to the rate of RA catabolism.

Why some fruits are green when they are ripe: carbon balance in fleshy fruits. Fruits that are green upon ripening ("green-ripe") tend to be dispersed by a limited range of frugivores, whereas those that are brightly colored ("bright-ripe") are dispersed by a wide range of birds and mammals. Because green fruits are probably less conspicuous than other colors of fruits, their pigmentation cannot be attributed to the attraction of seed dispersers. Instead, we hypothesize that a major benefit of green pigmentation is the ability to photosynthesize when ripe. Photosynthesis by fruits may lower their costs of production, and could result in fruits with greater nutrient reward. We present data on physical, chemical, and photosynthetic characteristics of ripe fleshy fruit of variable colors for 28 plant species at the La Selva Biological Station, Costa Rica. In addition to color and morphological characteristics of pulp and seeds, we report soluble solids content (refractive index), and photosynthetic/respiratory carbon-dioxide balance of ripe fruits. Carbon balance was much more dependent upon ambient light levels in green-ripe fruits than in bright-ripe fruit. In particular, data from light response curves indicated that green-ripe fruits may go into positive carbon balance at high light levels (above 300 μmol/m2/s). Rather than finding a positive relationship between soluble solids content and green fruit, as we predicted based on photosynthetic capacity, our data indicate that greater respiration rates of green-ripe fruits may result in carbon losses at low light levels. Our results were consistent with previously described morphological differences between the two color classes, with green-ripe fruits displaying significantly greater wet pulp mass, wet seed mass, and total fruit mass. Our data suggest that photosynthesis due to the retention of chlorophyll in ripe fleshy fruit may offset respiratory costs for plants with large or otherwise costly fruit, but this advantage should be evident only under high-light conditions.

The study of the full spectrum of variants leading to hyperphenylalaninemia have revealed 10 new variants in the PAH gene. This study presents further research into the spectrum of variants in genes responsible for the development of phenylketonuria (PKU) and hyperphenylalaninemia (HPA) in patients in Russia. After a study of 25 frequent variants, 293 patients (327 chromosomes without detected variants) from among 1265 probands still had no confirmed diagnosis. A study involving methods of next generation sequencing (NGS) of PAH, PTS, GCH1, PCBD1, QDPR, SPR and DNAJC12 genes to search for point mutations and multiplex ligation-dependent probe amplification (MLPA) methods to search for gross deletions were conducted for these patients. Among 327 chromosomes without identified variants, variants in the PAH gene were found on 260 chromosomes, and variants in the PTS gene were found on 10 chromosomes. On 10 chromosomes gross deletions by the MLPA method were detected. 104 rare variants of the РАН gene, including 10 variants not previously described, and 6 variants of the PTS gene were revealed. The NGS method revealed additional РАН gene variants on 10.3% of chromosomes and PTS gene variants on 0.4%. Gross deletions of the РАН gene were revealed in 0.5% of chromosomes. Thus, the most complete understanding of the spectrum of variants leading to the development of the PKU and HPA in Russia with the use of all methods available today has been obtained. Such a detailed study of the spectrum of rare variants on the genetic material from Russia was undertaken for the first time.

Heterogeneity of methotrexate binding in human colon tumor cells. [3H]-methotrexate binding at pH 5.0 and pH 7.2 by the cytosol of tumor tissues and the surrounding normal areas of the gastrointestinal tract of patients suffering from colon or gastric cancer has been used to identify in these cells the presence of a binder of methotrexate having low-affinity for this drug in addition to the enzyme dihydrofolate reductase. Scatchard analysis of the [3H]-methotrexate binding data by a colon tumor sample also reveals that there are two binders of this drug present in the cytosol of these cells. The association constant (Kass) for one binder of methotrexate is = 5.6 x 10(7) M-1 while the Kass for the second binder is = 1.0 x 10(6) M-1. The two binders do not differ very much in their apparent molecular weight. Upon isoelectric focusing, the tumor cell cytosol resolves into 4 major isoproteins each having the ability not only to bind [3H]-methotrexate but also reduce [3H]-pteroylglutamic acid to [3H]-tetrahydropteroylglutamic acid. This suggests that the two binders of methotrexate may be the two forms of dihydrofolate reductase having different affinities for this anticancer drug.

Nigral degeneration in a case of amyotrophic lateral sclerosis: evidence of Lewy body-like and skein-like inclusions in the pigmented neurons. This report describes a 58-year-old man who exhibited the clinical features of amyotrophic lateral sclerosis (ALS) at autopsy, 1 year after clinical onset of the disease. Neuropathologically, in addition to degeneration of the upper and lower motor neurons, marked degeneration of the substantia nigra with the appearance of Lewy body-like inclusions (LBI) and skein-like inclusions (SLI) were observed in the remaining pigmented neurons. An immunohistochemical study revealed that both LBI and SLI were immunopositive for ubiquitin. Ultrastructurally, LBI in the substantia nigra were composed of randomly arranged 15 nm thick tubular structures associated with ribosome-like granules, similar to those of LBI in the lower motor neurons. SLI in the substantia nigra were composed of curved bundles of 5 nm thick filaments (thinner than those comprising the SLI in the lower motor neurons). We believe that degeneration of the substantia nigra could be one of the degenerative processes involved in ALS.

Studies on the formulation and in vitro release of ophthalmic liposomes containing dexamethasone sodium phosphate. Several liposome formulations containing Dexamethasone Sodium Phosphate (DSP) were characterised in this study. For this purpose, phospholipids (gel and liquid types) and charge inducers, with or without cholesterol, were employed as bilayer components. Liquid state (PL 100:SA and PL 100:SA:CHOL) and gel state (PL 90H:SA and PL 90H:SA:CHOL) liposomes were prepared in molar ratios of (7:1:2), (10:1:4), (7:1) and (10:1). The film technique followed by sonication and membrane extrusion were used for the preparation of DSP liposomes. Particle size and particle-size distribution of MLVs, entrapment efficiency, free DSP (in supernatant) and, phospholipid content were determined for the characterization of the liposomes. The characterized liposomes were investigated for in-vitro release and different profiles were observed. The in-vitro release rates were evaluated kinetically and the best fitting equation was found to be the Higuchi equation.

Lesion mimic mutants: keys for deciphering cell death and defense pathways in plants? The identification of several lesion mimic mutants (LMM) that misregulate cell death constitutes a powerful tool to unravel programmed cell death (PCD) pathways in plants, particularly the hypersensitive response (HR), a form of PCD associated with resistance to pathogens. Recently, the characterization of novel LMM has enabled genes that might regulate cell death programmes to be identified as well as the dissection of defense signaling pathways and of crosstalk between multiple pathways in ways that might not be possible by studying the responses of wild-type plants to pathogens.

The value of the 14C breath test in the assessment of fat absorption. The absorption of oral 14C-glyceryl tripalmitate was tested in 77 subjects by hourly interval sampling of breath 14CO2 for up to 6 h. A highly significant correlation was obtained between maximum breath 14CO2 activity and faecal fat excretion. The test was very effective in differentiating between patients with and without steatorrhoea. Repetition of this examination with oral 14C-palmitic acid demonstrated normal absorption in pancreatic steatorrhoea but impaired absorption in intestinal steatorrhoea, thus enabling these conditions to be distinguished. The 14C breath tests are most useful as simple and inexpensive outpatient screening tests for steatorrhoea.