FISHing in the microwave: the easy way to preserve proteins. I. Colocalization of DNA probes and surface antigens in human leukocytes.
Most of the techniques for simultaneous visualization of proteic cell components and DNA probes are difficult to carry out. We have developed an alternative protocol for simultaneous visualization of DNA probes and cell surface antigens in human cells. The method exploits microwave energy to denature DNA and to anneal the probe after antigen fluorescent detection of unfixed cells previously embedded in a microgel. CD3 antigens and whole genome DNA probes or specific repetitive DNA sequences were colocalized in peripheral blood samples. The results show a strong, specific and consistent hybridization pattern in each cell that allowed correlation between cell subtype (PROTEINS) and nuclear phenotype (DNA).


The detection and estimation of linkage using doubled haploid or single seed descent populations.
In many plant species, particularly those of agricultural importance, there is now much effort being devoted to developing comprehensive genetic maps using biochemical and molecular markers. Because these techniques often involve destructive sampling of individual plants the use is increasingly made of homozygous or near-homozygous recombinant lines for linkage studies in preference to F2 or backcross generations. The present paper describes methods for the detection and estimation of linkage using such generations for commonly encountered genetic situations.


Effect of renal dysfunction on the individual components of the acyl-glucuronide futile cycle.
Drugs which are cleared predominantly by forming acyl-glucuronides undergo a futile cycle in which plasma drug clearance is a function of the formation, hydrolysis and renal clearance of the glucuronide conjugate. The effect of impaired renal function, induced by uranyl nitrate administration, on each component of this process was studied in rabbits using diphenylacetic acid. Uranyl nitrate administration produced a decrease in creatinine clearance of approximately 70% and diphenylacetic acid plasma clearance of approximately 35%. In healthy rabbits the primary determinant of diphenylacetic acid net clearance was the very large component of glucuronide renal clearance (14.10 ml/min/kg) compared with glucuronide formation (4.79 ml/min/kg) or glucuronide hydrolysis (2.56 ml/min/kg). Uranyl nitrate treatment reduced both creatinine clearance and the glucuronide renal clearance by approximately 70%. Renal dysfunction had little effect on the hydrolysis clearance of the glucuronide, but reduced its formation clearance by 22.8%. The reduction in plasma clearance of diphenylacetic acid was a function of both the decrease in glucuronidation (60% contribution) and the decrease in renal clearance of the glucuronide (40% contribution). This study supports the futile cycle mechanism of reversible glucuronide conjugation for acyl-glucuronides in general, and provides a mechanism for the impairment of the plasma clearance in renal failure of drugs forming acyl-glucuronides.


Achieving a narrow size distribution of Au particles at a precise depth in SiO2 by segregation of Au precipitates.
We propose a new method of confining Au nanoparticles of a narrow size distribution at a precise depth in an SiO2 matrix. The process involves the formation of nanocavities in silicon by hydrogen implantation and annealing (at 850 degrees C), followed by Au gettering to and precipitation in such cavities and a wet oxidation at 900 degrees C. Starting with a silicon-on-insulator wafer, Au precipitates can be segregated behind a growing Si/SiO2 interface during wet oxidation and ultimately trapped in SiO2 at the front interface of a buried oxide layer. The shape of the precipitates has been examined by transmission electron microscopy and found to be spherical. The average diameters of these precipitates before and after oxidation have been determined as around 15 nm and 30 nm, respectively.


Haptoglobin: old protein with new functions.
When released from red blood cells (RBCs), hemoglobin (Hb) is extremely toxic due in large part to the redox activity of its heme center. Nature however, has provided a multitude of protective mechanisms that can detoxify free Hb effectively under physiological conditions. Chief amongst them is haptoglobin (Hp) which chaperones Hb subunits to the macrophages for safe degradation. Recent research on the interactions between Hb and Hp under oxidative conditions revealed that Hp specifically shields key amino acids on the Hb molecule, allowing the heme to consume oxidants and short-circuits the emerging and damaging radicals. Moreover, animal studies showed that the infusion of Hb complexed with Hp prevents Hb-induced systemic hypertension and tissue injury. It may prove necessary to explore these protective clearing mechanisms to counter the toxicity associated with free Hb when used as oxygen therapeutics in hemolytic anemias and in RBC storage lesions.


Drive for muscularity and disordered eating among French adolescent boys: a sociocultural model.
The pursuit of muscularity is an important body image concern among boys which has been described within sociocultural models of risk for eating disorders. This study explored a sociocultural model of disordered eating in which drive for thinness and pursuit of muscularity were both pathways to disordered eating among French adolescent boys. A sample of 146 adolescents completed a questionnaire assessing drive for thinness, drive for muscularity, media-ideal internalization, appearance comparison, and sociocultural pressure. The model was a good fit to the data and both drive for thinness and the pursuit of muscularity were related to disordered eating. Furthermore, internalization and appearance comparison mediated the relationships between pressure to increase muscle and both drive for muscularity and drive for thinness. Longitudinal research could help clarify the role of the pursuit of muscularity in the development of disordered eating and extreme body shape changing behaviors.


DARK Classics in Chemical Neuroscience: Gamma-Hydroxybutyrate (GHB).
Gamma-hydroxybutyrate (GHB) is a naturally occurring short-chain fatty acid that rose to prominence as a popular club drug in the 1990s. Originally developed as an anesthetic in the early 1960s, it was later sold as an over-the-counter dietary supplement before becoming a rising substance of abuse in the following decades as one of the "date rape" drugs. Despite its abuse potential, there has been a recent surge in therapeutic interest in the drug due to its clinical viability in the treatment of narcolepsy and alcohol abuse/withdrawal. Its interactions with the GABAergic framework of higher mammals has made it the prototypical example for the study of the chief inhibitory mechanism in the human central nervous system. Though relatively obscure in terms of popular culture, it has a storied history with widespread usage in therapeutic, recreational ("Chemsex"), and some disturbingly nefarious contexts. This Review aims to capture its legacy through review of the history, synthesis, pharmacology, drug metabolism, and societal impact of this DARK classic in chemical neuroscience.


Immunization with cholesterol-rich liposomes induces anti-cholesterol antibodies and reduces diet-induced hypercholesterolemia and plaque formation.
Immunization of rabbits with a protein-free formulation consisting of liposomes containing 71% cholesterol and lipid A as an adjuvant induced anticholesterol antibodies that caused complement-dependent lysis of liposomes lacking lipid A. The antibodies, immunoglobulin G (IgG) and immunoglobulin M (IgM), also recognized nonoxidized crystalline cholesterol as an antigen by enzyme-linked immunosorbent assay (ELISA). The effects of immunization against cholesterol on elevations in serum cholesterol and development of atherosclerosis were examined in rabbits fed a diet containing 0.5% to 1.0% cholesterol. Although the mean serum cholesterol level, mainly in the form of very-low-density lipoprotein cholesterol, rose as much as 60-fold in the nonimmunized rabbits, the elevation was significantly less--as much as 35% lower--in the immunized rabbits. Elevation of serum cholesterol was accompanied by an apparent drop in the level of antibodies on initiating the diet, followed by a rebound on stopping the diet, thus suggesting that the antibodies were adsorbed to cholesterol that was present in circulating lipoproteins. When lipoprotein fractions--composed of either very-low-density and intermediate-density lipoproteins derived from cholesterol-fed nonimmunized rabbits or human low-density lipoproteins--were tested as capture antigens by solid-phase ELISA, reactivity was observed with IgG and IgM antibodies present in the serum of immunized rabbits. Immunization also resulted in a marked decrease in the risk of developing atherosclerosis. Analysis of aortic atherosclerosis by quantitative histologic examination and fatty streaks by automated morphometric probability-of-occurrence mapping showed diminished atherosclerosis in most areas of the aorta in vaccine recipients. It is proposed that immunization with liposomes containing 71% cholesterol and lipid A can reduce diet-induced hypercholesterolemia and atherosclerosis.


Encapsulation of xenon by a self-assembled Fe4L6 metallosupramolecular cage.
We report (129)Xe NMR experiments showing that a Fe4L6 metallosupramolecular cage can encapsulate xenon in water with a binding constant of 16 M(-1). The observations pave the way for exploiting metallosupramolecular cages as economical means to extract rare gases as well as (129)Xe NMR-based bio-, pH, and temperature sensors. Xe in the Fe4L6 cage has an unusual chemical shift downfield from free Xe in water. The exchange rate between the encapsulated and free Xe was determined to be about 10 Hz, potentially allowing signal amplification via chemical exchange saturation transfer. Computational treatment showed that dynamical effects of Xe motion as well as relativistic effects have significant contributions to the chemical shift of Xe in the cage and enabled the replication of the observed linear temperature dependence of the shift.


The use of near-infrared spectroscopy in understanding skeletal muscle physiology: recent developments.
This article provides a snapshot of muscle near-infrared spectroscopy (NIRS) at the end of 2010 summarizing the recent literature, offering the present status and perspectives of the NIRS instrumentation and methods, describing the main NIRS studies on skeletal muscle physiology, posing open questions and outlining future directions. So far, different NIRS techniques (e.g. continuous-wave (CW) and spatially, time- and frequency-resolved spectroscopy) have been used for measuring muscle oxygenation during exercise. In the last four years, approximately 160 muscle NIRS articles have been published on different physiological aspects (primarily muscle oxygenation and haemodynamics) of several upper- and lower-limb muscle groups investigated by using mainly two-channel CW and spatially resolved spectroscopy commercial instruments. Unfortunately, in only 15 of these studies were the advantages of using multi-channel instruments exploited. There are still several open questions in the application of NIRS in muscle studies: (i) whether NIRS can be used in subjects with a large fat layer; (ii) the contribution of myoglobin desaturation to the NIRS signal during exercise; (iii) the effect of scattering changes during exercise; and (iv) the effect of changes in skin perfusion, particularly during prolonged exercise. Recommendations for instrumentation advancements and future muscle NIRS studies are provided.


Biochemical, Hormonal and Histological Changes in Prostate of Wistar Rats Following Long Term Streptozotocin-induced Diabetes Mellitus.
Diabetes mellitus (DM) is characterized by hyperglycemia and endocrine disorder. Diabetes mellitus is knownto promote male infertility by affecting sperm quality through altered steroidogenesis. The role of prostatic fluid in maintenance of sperm quality have been established. However, the effect of DM on prostate health is poorly understood.This study was designed to investigate the biochemical, hormonal and histological changes in prostate of male Wistar ratsafter 3- and 5-months DM. Twenty-six adult male Wistar rats were assigned into three groups. Group I (non-diabetic rats)served as control (n=10), out of which five rats (n=5) were sacrificed as control for 3-month study and the remaining animals(n=5) as control for 5-month study. Group II served as 3-month DM (n=8) and group III served as 5-month DM (n=8).Diabetes mellitus was induced by administration of a single dose of streptozotocin (STZ) (35 mg/kg i.p.). Rats were sacrificedat 3- and 5- months after DM. Biochemical indices in serum and prostate, histological and immunohistochemical studies ofthe prostate were evaluated. Results indicated that the weight of prostate of 3- and 5-months DM rats significantly (p<0.05)decreased by 33% and 59%, respectively. Fasting blood glucose, plasma glycated haemoglobin and number ofmicronucleated polychromatic erythrocytes in the bone marrow significantly (p<0.05) increased in 3- and 5-months DM.Activities of serum alanine and aspartate aminotransferases significantly (p<0.05) increased in 3 months DM withconcomitant increase in serum total bilirubin and urea in both models. The activities of total acid phosphatase in 3- and 5-months DM decreased by 34% and 76%, respectively while prostatic acid phosphatase decreased by 48% in 5-months DM.Prostatic zinc and bicarbonate increased in 3-months DM by 1.7 and 1.9 folds, and in 5-months DM by 5.8 and 1.7 folds,respectively. The levels of serum luteinizing and follicle stimulating hormones and testosterone decreased in both models.Prostatic lipid peroxidation increased while activities of antioxidative enzymes decreased in both models. Histology revealedhyperplasia, intra-luminal budding of epithelia, mild expressions of Bcl2 and Ki67 in 3- and 5-months DM. Overall, prostate health was compromised and may increase infertility in diabetic animals.


Size-controlled synthesis of mesoporous palladium nanoparticles as highly active and stable electrocatalysts.
We report a solution phase synthesis of monodispersed mesoporous Pd nanoparticles (MPNs) with narrow particle size distributions. The average particle sizes can be controlled to a range of 25 nm to 42 nm, by utilizing cationic surfactants (as structure-directing agents) and triblock copolymers (as protective agents for controlled Pd deposition). The obtained MPNs exhibit very high electrocatalytic activity in formic acid oxidation.


BRAF gene is somatically mutated but does not make a major contribution to malignant melanoma susceptibility: the Italian Melanoma Intergroup Study.
Ocogenic activation of the BRAF gene has been demonstrated to be involved in the pathogenesis of malignant melanoma (MM). In this study, we investigated the contribution of BRAF to melanoma susceptibility, also making a comparison with frequency of CDKN2A germline mutations in MM patients from different areas in Italy. sing a combination of denaturing high-performance liquid chromatography analysis and automated sequencing on genomic DNA from peripheral blood or tumor tissue samples, 569 MM patients (211 from northern Italy and 358 from southern Italy) were screened for BRAF mutations. Three BRAF germline sequence variants (M116R, V599E, and G608H) were identified in four (0.7%) of 569 MM patients. The most common BRAF mutation, V599E, was detected in one germline DNA sample only; M116R and G608H were newly described mutations. A high frequency (59%) of BRAF mutations was instead observed in tumor samples from patients also undergoing germline DNA analysis; at the somatic level, substitution of valine 599 was found to account for the majority (88%) of BRAF mutations. We then estimated the germline mutation rates in BRAF and CDKN2A among 358 consecutively collected patient samples originating in southern Italy; a low (2.5%) or very low (0.29%) prevalence of CDKN2A and BRAF mutations, respectively, was detected. utation analysis of either blood DNA from a large collection of MM patients or matched MM tissues from a subset of such patients revealed that BRAF is somatically mutated and does not play a major role in melanoma susceptibility. The present study further suggests that patient origin may account for different mutation rates in candidate genes.


Novel GC-MS/MS Technique Reveals a Complex Steroid Fingerprint of Subclinical Hypercortisolism in Adrenal Incidentalomas.
Improvement of imaging methods has led to more incidental adrenal tumor findings, especially adenomas. Routine hormonal evaluation uses only a few steroids to evaluate possible hormonal hypersecretion of these adenomas, but a wide spectrum of serum steroid hormone changes has not been published. To measure the serum levels of 83 steroids from patients with unilateral and bilateral adrenal incidentalomas to uncover full steroid profile changes in patients with subclinical hypercortisolism (SH). Cross-sectional study. The study was conducted at a tertiary inpatient clinic. Fifty-two patients with adrenal incidentalomas (unilateral, n = 29; bilateral, n = 23), including nonfunctioning (n = 11) vs SH (n = 41), and 26 age- and sex-matched controls from the general population were included. Eighty-three serum steroids were measured by gas chromatography-tandem mass spectrometry (GC-MS/MS) before and after 1 mg dexamethasone, ACTH, midnight serum cortisol, and urinary free cortisol/24 hour. Of 83 measured steroids, 10 were significantly decreased in patients with SH, including dehydroepiandrosterone sulfate (DHEAS), androsterone sulfate, epiandrosterone sulfate, androstenediol sulfate, conjugated 5α-androstane-3β,17β-diol, and conjugated 5α-androstane-3α,17β-diol. This finding was observed even when unilateral, bilateral, male, and female subgroups were analyzed separately. When we compared routine clinical methods and GC-MS/MS‒measured steroids, the most discriminatory was DHEAS followed by midnight serum cortisol, epiandrosterone sulfate, androsterone sulfate, ACTH, and 16α-hydroxypregnenolone. SH was associated with decreased levels of adrenal androgens, their metabolites, and pregnenolone metabolite. GC-MS/MS is a powerful tool for measuring serum levels of these undescribed changes in steroid metabolism, which are characteristic of SH in adrenal incidentalomas.


[Aggressive vertebral hemangiomas: optimization of management tactics].
Today vertebral hemangioma is not completely understood entity, neither its pathogenesis nor optimal treatment is determined. Nowadays in majority of clinics in this country ineffective radiotherapy remains the first-line treatment. We analyzed results of treatment of 205 patients (286 lesions) with aggressive hemangiomas operated in Department of Neurosurgery of Military Medical Academy and Department of Nuclear Medicine of of Russian Scientific Center of Radiological and Surgical Technologies (Saint-Petersburg, Russia) since 1999 till 2009. Percutaneus vertebroplasty was performed in 167 lesions, radiotherapy was applied in 119 aggressive hemangiomas. Vertebroplasty is more effective for treatment of aggressive hemangiomas in comparison with radiotherapy. Signs of hemangiomas aggression, indications for surgery, and tactics of management were determined. Use of percutaneous vertebroplasty for treatment of aggressive hemangiomas resulted in fast recovery of the patients. This procedure is minimally invasive, it reduces hospital stay and duration of recovery.


Gene silencing with STAT6 specific siRNAs blocks eotaxin release in IL-4/TNFalpha stimulated human epithelial cells.
Small interfering RNAs have evolved as effective tools for the study of gene functions. Here, we demonstrate the use of different siRNAs for the specific knock down of the STAT6 transcription regulator and the complete silencing of the downstream signaling pathway. The knock down of STAT6 resulted in a complete loss of STAT6 specific DNA binding activity and blocked the release of eotaxin-3 in human epithelial cells (BEAS-2B) stimulated with IL-4 and TNFalpha with no signs of unspecific gene silencing. Other signaling pathways like the EGF stimulated release of IL-8 were still active in BEAS-2B cells treated with STAT6 specific siRNAs, demonstrating the specificity of these molecules.


[Changes in lipid metabolism during oxidative stress caused by cobalt chloride injection].
The cobalt chloride influence on rat liver and serum blood lipids and lipoproteins content and composition was investigated. The data obtained show that the cobalt chloride injection leads to the oxidative stress development and to activation of lipid transport and metabolism. It has been shown that there is system of lipids homeostasis in the organism and it is activated under conditions of oxidative stress. The system blood lipoproteins and liver lipoproteins was found to participate in metabolism adaptation on oxidative stress and in maintenance of biological membranes structure and functioning.


From antibodies to sperm to antibodies in transplantation.
a) To assess the use of "panning" procedures for the detection of antibodies to sperm. b) To develop and use human monoclonal antibodies for the analysis of human transplantation antigens. "Panning" assays were developed. The procedures and their use in the analysis of mouse monoclonal antibodies to human sperm are described. B-lymphocytes from individuals sensitized by pregnancy, graft rejection, or blood transfusion were immortalized with Epstein-Barr virus (EBV). Selected sublines producing antibodies to human leukocyte series A (HLA) antigens were fused with mouse myeloma cells and selected clones of hybrid cells secreting monoclonal antibodies were selected. The results of panning assays correlated with those of agglutination assays, but not immunofluorescence or enzyme-linked immunosorbent assays (ELISA). Monospecific and cross-reactive human monoclonal antibodies to HLA antigens were produced. Panning assays can be used for the detection of antibodies to sperm and can be useful where target sperm are of poor motility. The assays may be more sensitive for antibodies to superficial antigens. Human monoclonal antibodies may be used for investigating the identity of, and responses to, transplantation antigens.


Acuticoccus sediminis sp. nov., isolated from deep-sea sediment of the Indian Ocean and proposal of Acuticoccaceae fam. nov.
A Gram-staining negative, aerobic, oval-shaped bacterium, designated strain PTG4-2T, was isolated from deep-sea sediment of the Indian Ocean. Growth was observed with 1-9 % (w/v) NaCl with optimal growth with 3 %, at pH 6.0-10.0 with an optimum of pH 7.0, and at 4-40 °C with an optimum of 30 °C. Positive for catalase and oxidase. The results of a 16S rRNA gene sequence comparison indicated that PTG4-2T was most closely related to Acuticoccus yangtzensis JL1095T (97.3 %), followed by Acuticoccus kandeliae J103T (96.5 %), all other species shared <93 % sequence similarity. The results of phylogenetic analysis based on 16S rRNA gene sequences indicated that PTG4-2T forms a distinct lineage within the genus Acuticoccus, and revealed that the genus Acuticoccus forms a novel family-level clade in the order Rhizobiales. The ANI and the DNA-DNA hybridization estimate values between PTG4-2T and two type strains (A. yangtzensis JL1095T and A. kandeliae J103T) were 79.9-76.2 % and 23.1-20.8 %, respectively. PTG4-2T contained Q-10 as the predominant ubiquinone. The principal fatty acids (>5 %) were summed feature 8 [C18 : 1ω7c/ω6c (72.2 %)], C18 : 0 (8.4 %), C20 : 1ω7c (6.4 %) and C16 : 0 (6.3 %). The polar lipids consisted of phosphatidylglycerol, three unidentified phospholipids, two unidentified glycolipids, one unidentified aminolipid and one unknown lipid. The DNA G+C content of PTG4-2T is 69.2 mol%. On the basis of the polyphasic taxonomic evidence presented in this study, PTG4-2T should be classified as representing a novel species of the genus Acuticoccus, for which the name Acuticoccus sediminis sp. nov. is proposed, with the type strain PTG4-2T (=MCCC 1A01274T=KCTC 52323T). In addition, a novel family, Acuticoccaceae fam. nov., is proposed to accommodate the genus Acuticoccus.


[Surgical treatment of superficial femoral vein thrombosis--a new technique].
In 4 patients who suffered from superficial vein thrombosis new technique was applied. The main issue of this technique are: ligation of superficial vein in the point inferior to vein profunda femoris and sapheno-popliteal vein anastomoses. In two patients sapheno-popliteal anastomoses was competent after 30,18 months. In one patient sapheno-poplietal anastomoses was incompetence after 3 months. And one patient was lost for follow-up.


Neuropeptide Y (NPY) cleaving enzymes: structural and functional homologues of dipeptidyl peptidase 4.
N-terminal truncation of NPY has important physiological consequences, because the truncated peptides lose their capability to activate the Y1-receptor. The sources of N-terminally truncated NPY and related peptides are unknown and several proline specific peptidases may be involved. First, we therefore provide an overview on the peptidases, belonging to structural and functional homologues of dipeptidyl peptidase 4 (DP4) as well as aminopeptidase P (APP) and thus, represent potential candidates of NPY cleavage in vivo. Second, applying selective inhibitors against DP4, DP8/9 and DP2, respectively, the enzymatic distribution was analyzed in brain extracts from wild type and DP4 deficient F344 rat substrains and human plasma samples in activity studies as well as by matrix assisted laser desorption/ionisation-time of flight (MALDI-TOF)-mass spectrometry. Third, co-transfection of Cos-1 cells with Dpp4 and Npy followed by confocal lasermicroscopy illustrated that hNPY-dsRed1-N1 was transported in large dense core vesicles towards the membrane while rDP4-GFP-C1 was transported primarily in different vesicles thereby providing no clear evidence for co-localization of NPY and DP4. Nevertheless, the review and experimental results of activity and mass spectrometry studies support the notion that at least five peptidases (DP4, DP8, DP9, XPNPEP1, XPNPEP2) are potentially involved in NPY cleavage while the serine protease DP4 (CD26) could be the principal peptidase involved in the N-terminal truncation of NPY. However, DP8 and DP9 are also capable of cleaving NPY, whereas no cleavage could be demonstrated for DP2.


Conformational stability of neuroglobin helix F--possible effects on the folding pathway within the globin family.
Neuroglobin is a recently discovered member of the globin family, mainly observed in neurons and retina. Despite the low sequence identity (less than 20% over the whole sequence for the human proteins), the general fold of neuroglobin closely resembles that of myoglobin. The latter is a paradigmatic protein for folding studies, whereas much less is known about the neuroglobin folding pathway. In this work, we show how the structural features of helix F in neuroglobin and myoglobin could represent a pivotal difference in their folding pathways. Former studies widely documented that myoglobin lacks helix F in the apo form. In this study, limited proteolysis experiments on aponeuroglobin showed that helix F does not undergo proteolytic cleavage, suggesting that, also in the apo form, this helix maintains a rigid and structured conformation. To understand better the structural properties of helices F in the two proteins, we analyzed peptides encompassing helix F of neuroglobin and myoglobin in the wild-type and mutant forms. NMR and CD experiments revealed a helical conformation for neuroglobin helix F peptide, at both pH 7 and pH 2, absent in the myoglobin peptide. In particular, NMR data suggest a secondary structure stabilization effect caused by hydrophobic interactions involving Tyr88, Leu89 and Leu92. Molecular dynamics simulations performed on the apo and holo forms of the two proteins reveal the persistence of helix F in neuroglobin even in the absence of heme. Conversely myoglobin shows a higher mobility of the N-terminus of helix F on heme removal, which leads to the loss of secondary structure.


Improvement of hyperlipidaemia by bezafibrate treatment in RDT patients.
The pharmacokinetics and therapeutic effects of bezafibrate were studied in 15 RDT patients in a placebo controlled trial. Serum half life of bezafibrate was prolonged to 17--21.5 hours compared to 1.6--2.1 hours in normals. Adequate dosage in RDT patients was found to be 200mg every 3rd day. Bezafibrate treatment resulted in significant decrease in the serum concentrations of triglycerides, total cholesterol and LDL-cholesterol, whereas HDL-cholesterol serum levels increased. Under this dosage regimen no adverse side effects were observed. Bezafibrate offers the possibility of correcting disturbances of lipid metabolism of RDT patients, possibly involved in the pathogenesis of atherosclerosis of these patients.


Control of circulation in insects.
1. Studies on the physiology of insect circulation have revealed that the insect central nervous system can exert a strong nervous control over certain dorsal vessels and diaphragms. 2. The function of neurohormonal control over the heartbeat of insects, though demonstrated, is less clear. In contrast with studies on the central nervous and skeletal neuromuscular systems, not one neurotransmitter substance has been identified in any of the vessels, pumps or diaphragms responsible for circulation in insects. 3. A coelopulse system was identified and described that suggested a very sophisticated coordination between circulation and respiration in insects. The circulatory systems of cockroach, locust, fly, moth and bee all involve unique specializations. 4. It is suggested that an autonomic nervous system is present in insects and is responsible for coordination and control of both circulation and respiration.


Affinity of labetalol for ocular melanin.
1 The toxicity of labetalol has been studied in mice, rats, rabbits, and dogs, and reproductive studies have been carried out in rats and rabbits. Nothing was observed in any of these species to suggest that patients taking labetalol might be exposed to any toxic hazard. 2 During the reproductive studies 14C-labetalol was used to study placental transfer. Radioactivity was present in the uveal tract of the foetal eye. 3 Radioactive labetalol but not its metabolites was bound to the melanin pigment of the eye. This binding was reversible. It was not possible to saturate the melanin of the cat and dog eye even with prolonged dosing with labetalol. 4 Chloroquine, given orally at doses of 1.5-6 mg/kg/d for 4-7 weeks, produced changes in the cat retina. When oral doses of 20 mg labetalol/d were given to cats for 7 months, no oculotoxic effects were observed. 5 Detailed ophthalmological and histological examinations were carried out on the rats, rabbits, cats and dogs used in these studies. No changes indicative of oculotoxicity were observed. In the reproductive studies no effects were observed in the developing rat or rabbit eye, which could be consequent on the placental transfer of labetalol or its metabolites.


Informed consent, vulnerability and the risks of group-specific attribution.
People in extraordinary situations are vulnerable. As research participants, they are additionally threatened by abuse or exploitation and the possibility of harm through research. To protect people against these threats, informed consent as an instrument of self-determination has been introduced. Self-determination requires autonomous persons, who voluntarily make decisions based on their values and morals. However, in nursing research, this requirement cannot always be met. Advanced age, chronic illness, co-morbidity and frailty are reasons for dependencies. These in turn lead to limited abilities or opportunities for decision-making and self-determination. Exclusion of vulnerable people from research projects would disadvantage them by not covering their needs, which would violate the ethical principles of justice and beneficence. Commonly, vulnerability is attributed to social groups. The consequence for individuals, attributed as belonging to such a vulnerable group, is that the principles of respect for autonomy, justice and beneficence are subordinated to the principle of non-maleficence, understood as avoiding the risk to cause more harm than good. In addition, group-specific attribution could lead to stigmatizing because labelling a person as deviation from a norm violates integrity. For clinical nursing research, the question arises how the protection of vulnerable people could be granted without compromising ethical principles. The concept of relational ethics provides a possible approach. It defines vulnerability as the relation between a person's health status and the extent to which this person is dependent on the researcher and the research context. Vulnerability is not attributed solely to a person but to a situation, meaning the person is viewed in context. By combining vulnerability as a context-related and situational concept with existing approaches of informed consent, the different ethical principles can be balanced and preserved at every step of the research process.


P53 point mutations in initial superficial bladder cancer occur only in tumors from current or recent cigarette smokers.
Sequencing of p53 exons 5-8 was carried out on 51 initial superficial bladder tumors selected on the basis of high grade and/or p53 overexpression (immunohistochemistry without antigen retrieval). Fourteen point mutations in 13 tumors and one 21 bp deletion in another tumor were identified. In addition, a germ-line mutation corresponding to a previously described polymorphism was detected in exon 6, in two tumors. Mostly G-->A transitions (10) were found. Only three occurred at CpG sites, suggesting a major role for exogenous carcinogens in bladder tumorigenesis. Immunostaining for p53 and MDM2, using antigen retrieval, was carried out on the same tumors. A correlation was found between the percentage of p53-positive cells and the presence of p53 mutations (P = 0.005). No correlation was found between overexpression of p53 and MDM2 in this selected cohort of mostly high grade tumors. The presence of p53 mutations was also analyzed as a function of the smoking habits of the patients. A significant association was found between the presence of p53 point mutations and the number of years of smoking (P = 0.043). All patients with tumors carrying missense or nonsense p53 mutations had smoked for >/=30 years and if former smokers, had stopped for </=5 years. However, no correlation was found between the presence of p53 point mutations and the number of cigarettes smoked. The deletion mutation was the only one present in a tumor from a non-smoker. The data suggest that duration of exposure to carcinogens is the most critical factor in p53 mutagenesis in bladder cancer.


The calcium deficiency hypothesis of hypertension: a critique.
Primary (essential) hypertension has recently been related to calcium deficiency, rather than excess. The evidence used to support this hypothesis includes surveys showing lesser dietary intake of calcium, lower levels of ionized calcium in the blood, and reduction of blood pressure with calcium supplements. This critique examines each of these points and the theoretical construct used to explain the hypothesis. We conclude that the theoretical construct is based on the use of only a portion of available experimental data and the clinical evidence remains inconclusive. Until the hypothesis is supported further, calcium deficiency should not be accepted as a mechanism responsible for hypertension and calcium supplements should be used with caution.


Hepatic overexpression of caveolins increases bile salt secretion in mice.
Caveolins are cholesterol-binding proteins involved in the regulation of several intracellular processes, including cholesterol transport. Because hepatocytes express caveolin-1 and caveolin-2, these proteins might modulate hepatic lipid metabolism and biliary lipid secretion. Our aim was to investigate the potential physiologic role of caveolins in hepatic cholesterol and bile salt (BS) metabolism and transport using adenoviral gene transfer. C57BL/6 mice were infected with recombinant human caveolin-1 and caveolin-2 adenoviruses. Mice infected with adenovirus lacking the transgene were used as controls. Hepatic caveolin expression was evaluated by immunochemical methods. Reverse-transcription polymerase chain reaction (RT-PCR) and immunoblotting were used to assess messenger RNA (mRNA) levels and protein mass of BS transporters (sodium taurocholate cotransporting polypeptide [Ntcp] and bile salt export pump [Bsep]). Serum, liver, biliary, and fecal biochemical determinations and BS maximal secretory rate (SRm) were performed by standard methods. Ad.Cav-1- and Ad.Cav-2-infected mice exhibited a 10- and 7-fold increase in hepatic caveolin-1 and caveolin-2 protein expression, respectively. Caveolin-1-overexpressing mice had a significant increase in plasma high-density lipoprotein (HDL) cholesterol and hepatic free cholesterol content, whereas total plasma cholesterol and triglyceride levels remained unchanged. Hepatic caveolin-1 and/or caveolin-2 overexpression significantly increased bile flow and secretion of all biliary lipids. Caveolin-1-overexpressing mice showed a 2.5-fold increase in taurocholate (TC) SRm, indicating increased canalicular BS transport capacity. BS pool size and fecal BS excretion remained within the normal range in mice with Cav-1 overexpression. No changes were seen in the protein mass of BS transporters Ntcp and Bsep. In conclusion, our findings indicate that caveolins may play an important role in regulating hepatic BS and cholesterol metabolism.


Simultaneous determination of ethyl carbamate and 4-(5-)methylimidazole in yellow rice wine and soy sauce by gas chromatography with mass spectrometry.
We developed a new method, based on alkaline diatomite solid-phase extraction followed by gas chromatography with mass spectrometry, for the simultaneous determination of the toxic contaminants ethyl carbamate (EC) and 4-(5-)methylimidazole (4-MEI) in yellow rice wine and soy sauce. The optimal extraction conditions were defined. With the application of alkaline diatomite solid-phase extraction, damage to the capillary column by organic acids was greatly reduced. With deuterated EC used as the internal standard, the linearity of the calibration curves for EC and 4-MEI was good with correlation coefficient above 0.99. In a spiked experiment with EC and 4-MEI in yellow rice wine and soy sauce, recovery of the added EC was 80.5-102.5% and that of 4-MEI was 78.3-92.8%. The limit of quantification and limit of detection for EC were 6.0 and 2.0 μg/kg, respectively, and for 4-MEI were 15.0 and 5.0 μg/kg, respectively. The validation results demonstrate that the method is fast, simple, and selective, and therefore is suitable for simultaneously determining the presence of EC and 4-MEI in fermented food.


Family attitudes to caring for the elderly mentally infirm at home.
Attitudes towards care-giving were examined in a sample of 129 supporters of elderly mentally infirm patients referred for psychogeriatric day care. As in previous studies, spouses felt more commitment to care-giving than other relatives. Commitment to care-giving was influenced by different factors in adult children and spouses, but consistently predicted subsequent decisions to institutionalize the dependant. Following institutionalization, most supporters felt relieved. They tended to perceive the decision to have been made by others, and to have resulted from a deterioration in their dependents' mental condition, rather than a failure of the care-giving relationship.


Improving the Gene Transfection in Human Embryonic Stem Cells: Balancing with Cytotoxicity and Pluripotent Maintenance.
Manipulation of genes in human embryonic stem cells (hESCs) is imperative for their highly potential applications; however, the transduction efficiency remains very low. Although existing evidence revealed the type, size, and zeta potential of vector affect gene transfection efficiency in cells, the systematic study in hESCs is scarce. In this study, using poly(amidoamine) (PAMAM) dendrimers ended with amine, hydroxyl, or carboxyl as model, we tested the influences of size and surface group as well as cytotoxicity and endocytosis on hESC gene transfection. We found that in culture medium of mTeSR the particle sizes of G5, G7, G4.5COOH, and G5OH were around 5 nm and G1 had a smaller size of 3.14 nm. G5 and G7 had a slight and significant positive zeta potential, respectively, whereas G1 was slightly negative, and G4.5COOH and G5OH were significantly negative. We demonstrated that only amine-terminated dendrimers accomplished gene transfection in hESCs, which is greater than that from Lipofectamine 2000 transfection. Ten micromolar G5 had the greatest efficiency and was better than 1000 μM G1. Only a low concentration (0.5 and 1 μM) of G7 realized gene delivery. Amine-ended dendrimers, especially with higher generations, were detrimental to the growth and pluripotent maintenance of hESCs. In contrast, similarly sized hydroxyl- and carboxyl-terminated dendrimers exerted much lower cytotoxicity, in which carboxyl-terminated dendrimer maintained pluripotency of hESCs. We also confirmed the endocytosis into and significant exocytosis from hESCs using FITC-labeled G5 dendrimer. These results suggested that careful considerations of size, concentration, and zeta potential, particularly the identity and position of groups, as well as minimized exocytosis in the design of a vector for hESC gene delivery are necessary, which helps to better design an effective vector in hESC gene transduction.


Ureases: quantum chemical calculations on cluster models.
Herein, we present results from a computational study of dinickel complexes that are relevant to the catalytic hydrolysis of urea exerted by the urease enzymes. The B3LYP density functional is used to characterize the equilibrium geometry, electronic and magnetic properties, and energies for a series of realistic complexes modeling the active site of ureases. The analysis of the theoretical results gives new insight into the structure, substrate binding, and catalytic mechanism. The water bridge between the two Ni(II) ions observed in the crystallographic structures of the ureases was assigned to a hydroxide bridge in agreement with the observed small antiferromagnetic coupling. Both monodentate and bidentate urea-bound complexes, in which urea had favorable orientations for catalysis, were characterized. Finally, two reaction mechanisms were investigated starting from the monodentate and bidentate urea-bound complexes, respectively. Both a Ni1...Ni2 bridging hydroxide and a Ni2-bound water molecule play crucial roles in the two mechanisms.


[Sanitary and antiepidemic regulations of medical services of the state administration in Lodz at the turn of the XIXth and XXth c. (till 1914)].
At the turn of XIX and XX c., because of the spreading of acute infectious diseases in Lodz, the medical services of the state administration, responsible for the public health care, were obliged to publish and to enforce different sanitary and anti-epidemic regulations. They contained basic instructions e.g. the care of sanitary state of dwellings, hospitalization of infectious patients and isolation of persons suspected of contact with diseased, disinfection and anti-smallpox vaccination. Such prophylactic and therapeutic activity was neither systematic nor complementary due to the bureaucratic and incompetent administration of Lodz affairs by municipal authorities and had no essential influence on the melioration of the sanitary situation of the city and of the health of its inhabitants.


Proteomic analysis of hyphae-specific proteins that are expressed differentially in cakem1/cakem1 mutant strains of Candida albicans.
The yeast-to-hyphal transition is a major virulence factor in the fungal pathogen Candida albicans. Mutations in the CaKEM1 gene, which encodes a 5'-3' exoribonuclease responsible for mRNA degradation, show a defect in hyphal growth. We applied two-dimensional gel electrophoresis to identify hyphae-specific proteins that have altered expressions in the presence of the cakem1 mutation. Eight proteins, Eno1, Eps1, Fba1, Imh3, Lpd1, Met6, Pdc11, and Tsa1 were upregulated during hyphal transition in wild-type but not in cakem1/cakem1 mutant cells. A second group of proteins, Idh1, Idh2, and Ssb1, showed increased levels of expression in cakem1/cakem1 mutant cells when compared to wild-type cells. Overexpression of Lpd1, a component of the pyruvate dehydrogenase complex, caused slight hyperfilamentation in a wild-type strain and suppressed the filamentation defect of the cakem1 mutation. The Ssb1 protein, which is a potential heat shock protein, and the Imh3 protein, which is a putative enzyme in GMP biosynthesis also showed the filamentation-associated phenotypes.


Alterations in systemic levels of Th1, Th2, and Th17 cytokines in overweight adolescents and obese mice.
Obesity represents a major problem for patients and health care systems in most industrialized countries. A chronic inflammatory state in obese individuals leads to disease conditions associated with activation of cellular immune mechanisms. Here, we sought to investigate the role of Th1-, Th2-, and Th17-related cytokines in overweight adolescents and mice on a high-fat diet. Plasma samples were obtained from 79 male adolescents aged 13-17 years. Thirty-seven of them had a body mass index (BMI) above the 90th age-specific percentile. Th1, Th2, and Th17 cytokines were measured using Bio-Plex multiplex technology (Bio-Rad, Hercules, USA). In an experimental approach, mice were fed with high-fat (HFD) or normal chow for 15 weeks. Interleukin (IL)-17 concentrations were significantly decreased in overweight adolescents compared to lean controls [99.8 ± 7.3 pg/mL standard error of the mean (SEM) vs 146.6 ± 11.5 pg/mL SEM P = .001]. Levels of IL-17 correlated significantly with anthropometrical parameters of obesity. A concordant response was found in mice consuming a HFD for 15 weeks compared to controls (861 ± 165 pg/mL SEM vs 1575 ± 187 pg/ml SEM, P = .0183). However, a biphasic response was evident for most Th1, Th2, and Th17 cytokines as levels initially increased within the first 5 weeks on HFD and showed a decline afterwards. In contrast to previous studies showing elevated levels of IL-17 in obese adults, we found a decreasing trend in overweight adolescents. This difference could possibly be related to the fact that disease conditions associated with obesity such as hypertension, vascular pathologies, diabetes, and a triggering of the Th1/Th17 axis were not yet present in overweight teenagers.


A Case of a Cardiac Resynchronization Therapy-Defibrillator Exhibiting a Lower and Alternately Variable Basic Rate.
A cardiac resynchronization therapy defibrillator (CRT-D) (Medtronic Inc. Protecta XT) was implanted in a 67-year-old man who had cardiac sarcoidosis with extremely low cardiac function. He had ventricular tachycardia which was controlled by catheter ablation, medication and pacing. The programmed mode was DDI, lower rate was 90 beats/minute, paced AV delay was 150 ms, and the noncompetitive atrial pacing (NCAP) function was programmed as 300 ms.After his admission for pneumonia and heart failure, we changed his DDI mode to a DDD mode because he had atrial tachycardia, which led to inadequate bi-ventricular pacing. After a while, there were cycle lengths which were longer than his device setting and alternately varied. We were able to avoid this phenomenon with AV delay of 120 ms and NCAP of 200 ms.NCAP is an algorithm which creates a gap above a certain period after the detection of an atrial signal during the postventricular atrial refractory period of the pacemaker. This is to prevent atrial tachycardia and repetitive non-reentrant ventriculoatrial (VA) synchrony in the presence of retrograde VA conduction. But in this case, NCAP algorithm induced much lower rate than the programmed basic lower rate. This situation produced some arrhythmias and exacerbated symptoms of heart failure. This had to be paid attention to, especially when the device was programmed at high basic heart rate.


Towards automatic measurement of anteversion and neck-shaft angles in human femurs using CT images.
Automatic assessment of human femur morphology may provide useful clinical information with regard to hip and knee surgery, prosthesis design and management of hip instability. To this end, neck-shaft and anteversion angles are usually used. We propose a full automatic method to estimate these angles in human femurs. Multislice CT images from 18 dried bones were analysed. The algorithm fits 3D cylinders to different regions of the bone to estimate the angles. A manual segmentation and a conventional angle assessment were used for validation. We found anteversion angle as 20 ± 7° and neck-shaft angle as 130 ± 9°. Mean distances from femur surface to cylinders were 5.5 ± 0.6, 3.5 ± 0.6 and 2.4 ± 0.4 mm for condyles, diaphysis and neck regions, respectively. Automatic and conventional angles were positively correlated (r(2)>0.85). Manual and automatic segmentations did not differ. The method was fast and 100% reproducible. A robust in vivo segmentation algorithm should be integrated to advance towards a clinically compliant methodology.


Psychiatric symptom changes after corticoamygdalohippocampectomy in patients with medial temporal lobe epilepsy through Symptom Checklist 90 Revised.
Corticoamygdalohippocampectomy (anterior temporal lobe resection plus amygdalohippocampectomy) is common in epilepsy surgery. Pre- and postoperative psychiatric disorders occurred sometimes in patients with refractory medial TLE. We want to know if CAH has an affirmative effect on the psychiatric symptom of patients with medial TLE through a quantitative method. Sixty-two patients with medial TLE who had CAH accomplished SCL-90-R questionnaires thrice (presurgical and postsurgical 1 and 2 years). Average GSI scores in SCL-90-R were calculated and statistically analyzed. There was no statistical difference in the presurgical average GSI scores between Engel I and Engel II to IV subgroup. Postoperative 1 and 2 years' average GSI scores of Engel II to IV subgroup were both statistically higher than those of Engel I subgroup. There were no statistical differences between other subgroups in different time. Postsurgical 1 and 2 years' average GSI scores of the whole group and Engel I subgroup were statistically lower than those of presurgery. Postoperative 2 years' average GSI scores of the whole group and Engel I subgroup were statistically lower than those of postsurgical 1 year. For Engel II to IV subgroup, there were no statistical differences among the average GSI scores in different time. Corticoamygdalohippocampectomy could improve the psychiatric symptoms of patients with TLE as assessed by the SCL-90-R. This improvement was related to the therapeutic effect and was not related to sex, lateralization, and MRI abnormality.


Impact of thermooxidation of phytosteryl and phytostanyl fatty acid esters on cholesterol micellarization in vitro.
The effects of thermooxidation of a phytosteryl/-stanyl and a phytostanyl fatty acid ester mixture on cholesterol micellarization were investigated using an in vitro digestion model simulating enzymatic hydrolysis by cholesterol esterase and subsequent competition of the liberated phytosterols/-stanols with cholesterol for incorporation into mixed micelles. As a first step, relationships between different doses of the ester mixtures and the resulting micellarized cholesterol were established. Subsequent subjection of the thermooxidized ester mixtures to the in vitro digestion model resulted in three principal observations: (i) thermal treatment of the ester mixtures led to substantial decreases of the intact esters, (ii) in vitro digestion of cholesterol in the presence of the thermooxidized ester mixtures resulted in significant increases of cholesterol micellarization, and (iii) the extents of the observed effects on cholesterol micellarization were strongly associated to the remaining contents of intact esters. The loss of efficacy to inhibit cholesterol micellarization due to thermally induced losses of intact esters corresponded to a loss of efficacy that would have been induced by an actual removal of these amounts of esters prior to the in vitro digestion. The obtained results suggest that in particular oxidative modifications of the fatty acid moieties might be responsible for the observed increases of cholesterol micellarization.


[Modern general metaphylaxis of stone disease. New risks, new evidence, new recommendations].
The prevalence and incidence of urolithiasis have markedly increased over the past several decades. Inappropriate dietary habits, overweight, and lifestyle are considered to be important risk factors for stone formation. The primary goal of metaphylaxis of stone disease is to correct the individual biochemical risk profile. A reduction in the risk of stone formation and recurrence rate can already be achieved by appropriate dietary treatment. One of the most effective dietary measures is a sufficient circadian fluid intake of suitable beverages. The reduction of overweight is suggested to additionally contribute to a decrease in the risk of recurrent stone formation.


Cannabis use and traffic accidents in a birth cohort of young adults.
to examine linkages between cannabis use and traffic accident risks in a birth cohort of 907 young New Zealanders studied from 18 to 21 years. during the course of a 21-year longitudinal study of a birth cohort of 907 New Zealand born children information was gathered on (a) annual frequency of cannabis use over the period from 18 to 21 years; (b) annual rates of traffic accidents during the period 18-21 years; (c) measures of driver behaviours and characteristics. The association between cannabis use and traffic accident risk was examined among the 907 sample members who reported driving a motor vehicle between the ages of 18 and 21 years. there were statistically significant relationships between reported annual cannabis use and annual accident rates. This association was present only for 'active' accidents in which driver behaviours contributed to the accident; those using cannabis more than 50 times per year had estimated rates of active accidents that were 1.6 (95% CI 1.2-2.0) times higher than the rate for non-users. However, statistical control for driver behaviours and characteristics related to cannabis use (drink driving behaviour; risky/illegal driving behaviours; driver attitudes; gender) eliminated the association between cannabis use and traffic accident risks. although cannabis use was associated with increased risks of traffic accidents among members of this birth cohort, these increased risks appear to reflect the characteristics of the young people who used cannabis rather than the effects of cannabis use on driver performance.


Differentiation of embryonic stem cells to cardiomyocytes on electrospun nanofibrous substrates.
The potential of pluripotent embryonic stem cells (ESCs) isolated from the inner mass of blastocysts are investigated for its ability to differentiate on biocompatible electrospun nanofibers, for regeneration of the myocardially infracted heart. Nanostructured poly(d,l-lactide-co-glycolide)/collagen (PLGA/Col) scaffolds with fiber diameters in the range of 300 ± 65 nm, was fabricated by electrospinning to mimic the extracellular matrix of the native tissue. During the culture of embryoid bodies outgrowth on the scaffolds, and further differentiation of ESCs to cardiomyocytes, the PLGA/Col nanofibers was found better than that of the electrospun PLGA nanofibers, where a better interaction and growth of ESC differentiated cardiomyocytes was observed on the composite scaffolds. The phenotypical characteristics of ESC-derived cardiomyocytes and molecular protein expression were carried out by scanning electron microscopy and immunocytochemistry, respectively. Our studies highlight the significance of a suitable material, its architecture, and cell-biomaterial interactions that is essential at a nanoscale level signifying the application of a bioengineered cardiac graft for stem cell differentiation and transplantation, which could be an intriguing strategy for cardiac regeneration.


Synthesis of hollow NiCo2O4 nanospheres with large specific surface area for asymmetric supercapacitors.
Hollow micro-/nanostructured electrode materials with high active surface area are highly desirable for achieving outstanding electrochemical properties. Herein, we report the successful synthesis of hierarchical hollow NiCo2O4 nanospheres with high surface area as electrode materials for supercapacitors. Electrochemical measurements prove that such electrode materials exhibit excellent electrochemical behavior with a specific capacitance reaching 1229 F/g at 1 A/g, remarkable rate performance (∼83.6% retention from 1 to 25 A/g) and good cycling performance (86.3% after 3000 cycles). Furthermore, the asymmetric supercapacitor is fabricated with hollow NiCo2O4 nanospheres electrode and activated carbon (AC) electrode as the positive and negative, respectively. This device exhibits a maximum energy density of 21.5 W h/kg, excellent cycling performance and coulombic efficiency. The results show that hollow NiCo2O4 nanosphere electrode is a promising electrode material for the future application in high performance supercapacitors.


[Sandostatin treatment of destructive pancreatitis].
Sandostatin has been used in combined treatment of 30 patients with destructive pancreatitis in a dose 200-600 micrograms/day subcutaneously. The drug significantly depressed production of enzyme toxins in the pancreas but failed to prevent widening of necrotic zones and progression of the process in the retroperitoneal fat. The duration of sandostatin treatment should not be longer than 5-7 days. If no response is achieved for this time, surgical treatment is indicated. It is not reasonable to reject conventional drugs used in acute destructive pancreatitis for sandostatin monotherapy.


Inhibition of translational initiation in eukaryotic cells by calcium ionophore.
Ca2+ has been recently reported to be required for high rates of translational initiation in GH3 pituitary cells (Chin, K.-V., Cade, C., Brostrom, C.O., Galuska, E.M., and Brostrom, M.A. (1987) J. Biol. Chem. 262, 16509-16514). In the present investigation low concentrations of the Ca2+ ionophores, A23187 and ionomycin, were found to rapidly suppress the Ca2+-dependent component of protein synthesis in GH3 cells. More ionophore was required to inhibit amino acid incorporation into protein as extracellular Ca2+ was increased. Pre-existing inhibitions of protein synthesis produced by low concentrations of ionophore at low extracellular Ca2+ concentrations were reversed by adjustment to high extracellular Ca2+. Treatment with ionophore reduced the cellular contents of polysomes and 43 S preinitiation complex to values equivalent to those found for Ca2+-depleted cells. Average ribosomal transit times were unaffected by ionophore, and treated cells retained the ability to accumulate polysomes when incubated with cycloheximide. Cell types, such as HeLa and Chinese hamster ovary, that normally display only a modest Ca2+-dependent component of protein synthesis, manifested a strong underlying Ca2+ dependence in amino acid incorporation and polysome formation following treatment with low concentrations of ionophore. Protein synthesis in GH3 or HeLa cells during recovery from heat shock and arsenite treatment was not affected by cellular Ca2+ depletion or ionophore treatment. On the basis of these results, Ca2+ ionophore is proposed to inhibit Ca2+-dependent translational initiation through facilitating the mobilization of sequestered intracellular Ca2+.


Decoration of TiO2 nanotubes with metal nanoparticles using polyoxometalate as a UV-switchable reducing agent for enhanced visible and solar light photocatalysis.
We present the employment of the Keggin ion 12-phosphotungstic acid as a UV-switchable reducing agent for the decoration of Au, Ag, Pt, and Cu nanoparticles onto the surface of TiO(2) nanotubes synthesized by electrochemical anodization. The synthesized composites were studied using SEM, GADDS XRD, and EDX, and the photocatalytic activity of the composites was examined by measuring the photodegradation of the organic dye "Congo red" under simulated solar light. Decoration with metal nanoparticles was observed to enhance the activity of the photocatalytic process by upward of 100% with respect to unmodified TiO(2) nanotubes.


The tale of Phineas Gage, digitally remastered.
The injury of Phineas Gage has fueled research on and fascination with the localization of cerebral functions in the past century and a half. Most physicians and anatomists believed that Gage sustained a largely bilateral injury to the frontal lobes. However, previous studies seem to have overlooked a few less obvious, but essential details. This has led us to reanalyze the injury using three-dimensional reconstruction and quantitative computer-aided techniques and to propose a new biomechanical model, in order to determine the location and extent of the injury and explain Gage's improbable survival. Unlike previous studies on this subject, our findings are based on computer-generated three-dimensional reconstructions of a thin-slice computed tomography scan (CAT) of Phineas Gage's skull. The results of our image analysis were corroborated with the clinical findings, thoroughly recorded by Dr. Harlow in 1848, as well as with a systematic examination of the original skull specimen. Our results show that the cerebral injury was limited to the left frontal lobe, did not extend to the contralateral side, did not affect the ventricular system, and did not involve vital intracranial vascular structures. Although modern neuroscience has perhaps outgrown the speculations prompted by this famous case, it is still a living part of the medical folklore and education. Setting the record straight based on clinical reasoning, observation of the physical evidence, and sound quantitative computational methods is more than mere minutia and of interest for the broad medical community.


[Cholinergic mechanisms in the development of hydrolysis-transport function of the small intestine during ontogeny of intact and stress-exposed rats].
The blockade of peripheric m-cholinoreceptors by atropine in early periods after rat birth is shown to delay the further development of intestinal transport and also hydrolysis-transport mechanisms for carbohydrates.


Endothelium-dependent and endothelium-independent skin vasoreactivity in the elderly.
It was demonstrated that endothelium-dependent vasoreactivity, an aspect of endothelial functioning, is impaired in coronary and brachial arteries, and in skeletal muscle resistance vessels of elderly people. However, little data is available about the influence of aging per se on the endothelial function of the skin microcirculation. The aim of the present study was to evaluate the endothelial function and intrinsic vasodilatory capacity of the skin microcirculation in elderly people with a low atherosclerosis risk profile. Using laser Doppler flowmetry, we measured the cutaneous hyperemic responses following local iontophoresis delivery of an endothelium-dependent vasodilator, acetylcholine (ACh), and an endothelium-independent vasodilator, sodium nitroprusside (SNP), in 15 subjects older than 65 years and in 15 subjects younger than 50 years. Exclusion criteria were diabetes, hyperlipidemia, smoking, arterial hypertension and cardiovascular diseases. Skin maximal hyperemic responses induced both by ACh and by SNP delivery did not differ between the younger and the older groups. Cutaneous blood flow progressively increased in response to the 8 ACh delivery steps, both in the older and younger groups; however, the dose-response curve following ACh delivery was significantly lower in the former (p < 0.001). While these results should be viewed as preliminary due to the small sample size, they suggest that aging in itself is associated with a mild endothelium dysfunction in the skin microcirculation, whereas its overall vasodilatory capacity is preserved.


Prolonged bone marrow T1-relaxation in patients with polycythemia vera.
In vitro as well as in vivo studies have shown prolonged T1 relaxation times in patients with acute leukemia. The mechanism behind this finding is not known. In order to evaluate if this was specific for leukemia we examined eight patients with polycythemia vera, representing a condition with a rather benign bone marrow neoplasia. In this group of patients we found prolonged T1 relaxation times but normal T2 relaxation times. This may indicate that the prolonged T1 relaxation time seen in leukemic bone marrow is not due to the malignant cell per se.


High-yield purification of fetal tau preserving its structure and phosphorylation pattern.
The fetal type of tau phosphorylation always re-appears during pathogenesis of Alzheimer's disease and related tauopathies. The major obstacle in the study of the fetal tau phosphorylation has been the lack of a simple and reproducible purification method yielding fetal tau with high purity and unmodified phosphorylation pattern. We have developed a two-step, highly efficient purification procedure of perchloric acid-extracted fetal tau by immunoaffinity chromatography and trichloroacetic acid (TCA) precipitation. The method yielded tau with more than 90% purity. Most importantly, purified fetal tau exhibited unmodified phosphorylation pattern as confirmed by phosphorylation-dependent antibodies. In summary, this purification process preserves and protects unstable phosphoresidues from dephosphorylation and allows their detailed molecular analysis especially in the pathogenesis of Alzheimer's disease and related tauopathies.


Precise quantification of dialysis using continuous sampling of spent dialysate and total dialysate volume measurement.
The "gold standard" method to evaluate the mass balances achieved during dialysis for a given solute remains total dialysate collection (TDC). However, since handling over 100 liter volumes is unfeasible in our current dialysis units, alternative methods have been proposed, including urea kinetic modeling, partial dialysate collection (PDC) and more recently, monitoring of dialysate urea by on-line devices. Concerned by the complexity and costs generated by these devices, we aimed to adapt the simple "gold standard" TDC method to clinical practice by diminishing the total volumes to be handled. We describe a new system based on partial dialysate collection, the continuous spent sampling of dialysate (CSSD), and present its technical validation. Further, and for the first time, we report a long-term assessment of dialysis dosage in a dialysis clinic using both the classical PDC and the new CSSD system in a group of six stable dialysis patients who were followed for a period of three years. For the CSSD technique, spent dialysate was continuously sampled by a reversed automatic infusion pump at a rate of 10 ml/hr. The piston was automatically driven by the dialysis machine: switched on when dialysis started, off when dialysis terminated and held during the by pass periods. At the same time the number of production cycles of dialysate was monitored and the total volume of dialysate was calculated by multiplying the volume of the production chamber by the number of cycles. Urea and creatinine concentrations were measured in the syringe and the masses were obtained by multiplying this concentration by the total volume. CSSD and TDC were simultaneously performed in 20 dialysis sessions. The total mass of urea removed was calculated as 58038 and 60442 mmol/session (CSSD and TDC respectively; 3.1 +/- 1.2% variation; r = 0.99; y = 0.92x -28.9; P < 0.001). The total mass of creatinine removed was 146,941,143 and 150,071,195 mumol/session (2.2 +/- 0.9% variation; r = 0.99; y = 0.99x + 263; P < 0.001). To determine the long-term clinical use of PDC and CSSD, all the dialysis sessions monitored during three consecutive summers with PDC (during 1993 and 1994) and with CSSD (1995) in six stable dialysis patients were included. The clinical study comparing PDC and CSSD showed similar urea removal: 510 +/- 59 during the first year with PDC and 516 +/- 46 mmol/dialysis session during the third year, using CSSD. Protein catabolic rate (PCR) could be calculated from total urea removal and was 1.05 +/- 0.11 and 1.05 +/- 0.09 g/kg/day with PDC and CSSD for the same periods. PCR values were clearly more stable when calculated from the daily dialysate collections than when obtained with urea kinetic modeling performed once monthly. We found that CSSD is a simple and accurate method to monitor mass balances of urea or any other solute of clinical interest. With CSSD, dialysis efficacy can be monitored at every dialysis session without the need for bleeding a patient. As it is external to the dialysis machine, it can be attached to any type of machine with a very low cost. The sample of dialysate is easy to handle, since it is already taken in a syringe that is sent directly to the laboratory. The CSSD system is currently in routine use in our unit and has demonstrated its feasibility, low cost and high clinical interest in monitoring dialysis patients.


Novel isoforms of tau that lack the microtubule-binding domain.
Tau is a microtubule-associated protein (MAP) whose transcript undergoes complex regulated splicing in the mammalian nervous system. Our previous work with exon 6 established that tau shows a unique expression pattern and splicing regulation profile, and that it utilizes alternative splice sites in several human tissues. The mRNAs from these splicing events, if translated, would result in truncated tau variants that lack the microtubule-binding domain. In this study, we demonstrate that at least one of these tau variants is present as a stable protein in several tissues. The novel isoform shows a localization distinct from that of canonical tau in SH-SY5Y neuroblastoma cells which stably overexpress it. In both normal and Alzheimer's hippocampus, the novel isoform is found in dentate gyrus granular cells and CA1/CA3 pyramidal cells. However, it does not co-localize with canonical tau but, rather, partly co-localizes with MAP2.


Conservation and evolution of (CT)n/(GA)n microsatellite sequences at orthologous positions in diverse mammalian genomes.
The distribution and evolution of (CT)n microsatellites were examined in GenBank mammalian DNA sequences because these microsatellites are known to play important roles in the regulation of some genes in Drosophila melanogaster. A total of 236 (CT)n microsatellite loci were found in GenBank mammalian gene sequences. To determine whether (CT)n microsatellite arrays were conserved at orthologous positions in distantly related mammalian sequences, we determined whether orthologous sequences existed in GenBank for each of the 236 loci. A total of 47 sequence alignments could be made. For rodent x rodent comparisons, 7 of 8 (CT)n arrays were conserved at identical positions in each pair of orthologous sequences. Comparisons of orthologous sequences between different orders of mammals indicated that 11 of 39 (CT)n arrays occurred at orthologous positions or within 1 kb of orthologous positions in each pair of sequences. It appears that there is some level of conservation of (CT)n repeats in distantly related mammals. However, this level of conservation may not be greater than what might be expected to occur by chance. In 13 cases where (CT)n arrays were not conserved at orthologous positions, the lack of a (CT)n array in one sequence resulted from either nucleotide substitution within an array or nonexpansion of a shorter (CT)n element. In these cases, significant sequence identity could be detected throughout the entire region even though the repeat array was not detected in one of the sequences. In contrast, there was a disruption of sequence identity in the (CT)n microsatellite region that ranged from 24 to 1600 bp in 21 cases.(ABSTRACT TRUNCATED AT 250 WORDS)


Agreement between DSM-IV and DSM-5 criteria for alcohol use disorder among outpatients suffering from depressive and anxiety disorders.
Since significant differences have been reported, we estimated agreement between DSM-5 and DSM-IV criteria for alcohol use disorder (AUD). We assessed 327 outpatients (mean age: 45.2 ± 13.4) with depressive or anxiety disorders. Absolute differences in prevalence rates between DSM-5 and DSM-IV AUD ranged from -1.1% (subjects with anxiety disorders) to +1.8% (tobacco smokers). The agreement was excellent (k = 0.88), also accounting for specific subgroups (relevant k coefficients >0.80). DSM-5 criteria did not inflate AUD rates. Our results have epidemiological significance since, unlike previous reports, we found diagnostic stability between new and old AUD criteria in this clinical population. (Am J Addict 2017;26:53-56).


Analysis of possible influence of conjugated linoleic acid on growth performance and losses of piglets.
The aim of this work was to evaluate the effect of supplementing the feed ration for lactating sows with the conjugated linoleic acid (CLA) on the growth performance and losses of piglets from birth to weaning. The monitoring comprised 20 litters in control and 20 litters in experimental group of Czech Large White × Czech Landrace hybrid combination sows. The control group was given a standard feed mixture for lactating sows, and experimental group was fed with the feed mixture supplemented with 2% of CLA, from the day of farrowing to the weaning of piglets, that is for the time of 28 days. The results of the experiment indicate the significantly better parameters of the numbers of reared piglets in the experimental group and the related lower level of losses of piglets from birth to weaning (p < 0.01). However, the feed mixture for lactating sows enriched in conjugated linoleic acid had no significant effect on the growth performance of piglets from birth to weaning (p > 0.05). Sows in the experimental group showed earlier onset of post-partal oestrus after weaning of piglets (p < 0.05). These findings demonstrate that the supplementation of diet for lactating sows with CLA can improve survival of piglets from birth to weaning and shortening of weaning-to-oestrous interval in sows.


Pigmentary complication of the peristomal skin in colorectal cancer patients under systemic chemotherapy using S-1: report of cases.
This study describes hyperpigmentation at the epidermis around a colostomy during and after systemic chemotherapy with S-1 (a compound of tegaful, gimestat, and potassium oxonate). Thirty-one colorectal cancer patients (male 17, female 14) visited the stoma-care clinic, akita university hospital between april 2003 and march 2006. fourteen patients (male 8, female 6) had been observed continuously for more than 3 months. Results of 5 male patients who received systemic chemotherapy using S-1 were compared to those of 9 male and female patients who did not receive S-1. the shades of epidermal pigmentation at the peristomal area were graded on a 3-point likert scale, where grade 2 indicated very dark pigmentation, grade 1 indicated moderately dark pigmentation, and grade 0 indicated no pigmentation of the peristomal skin. Pigmentation scores in patients receiving S-1 were significantly higher than scores in patients who did not receive S-1 systemic chemotherapy. Rapid and excessive pigmentation of the peristomal skin may occur in patients receiving S-1 systemic chemotherapy because it indicates an adverse event related with systemic chemotherapy and leads to peristomal skin problems.


Relationship of electric power quality to milk production of dairy herds - field study with literature review.
Public Utility Commissions (PUC) in several states adopted 0.5 volt rms (root mean squared) or 1.0 milliampere as the actionable limit for utilities to respond to complaints of uncontrolled voltage. This study clearly shows that the actionable level should be reduced to 10 mV p-p (peak-to-peak), which is 140 times less than the current standard. Dairy farmer complaints that animal behavior and milk production were affected by electrical shocks below adopted standards were investigated on 12 farms in Wisconsin, Michigan, and Minnesota. Milk production per cow was determined from daily tank-weight pickup and number of cows milked. Number of transient events, transients, voltage p-p, waveform phase angle degree, sags, and sag-Vrms were measured from event recorders plugged into milk house wall outlets. Data from 1705 cows and 939 data points were analyzed by multiherd least-squares multiple regression and SAS-ANOVA statistical programs. In five herds for 517 days, milk/cow/day decreased -0.0281 kg/transient event as transient events increased from 0 to 122/day (P<0.02). Negative effects on milk/cow/day from event recorder measurements were significant for eight independent electrical variables. Step-potential voltage and frequency of earth currents were measured by oscilloscope from metal plates grouted into the floor of milking stalls. Milk decreased as number of 3rd, 5th, 7th, 21st, 28th, and 42nd harmonics and the sum of triplen harmonics (3rd, 9th, 15th, 21st, 27th, 33rd, and 39th) increased/day (P<0.003). Event recorder transient events were positively correlated with oscilloscope average V p-p event readings. Steps/min counted from videotapes of a dancing cow with no contact to metal in the barnyard were correlated with non-sinusoidal 8.1 to 14.6 mV p-p impulses recorded by oscilloscope for 5 min from EKG patches on legs. PUC standards and use of 500-Ohm resistors in test circuits underestimate effects of non-sinusoidal, higher frequency voltage/current common on rural power lines.


Embolic microspheres within ovarian arterial vasculature after uterine artery embolization.
Adverse events after uterine artery embolization, including hysterectomy and premature ovarian failure, are concerning for women who desire future fertility. A 39-year-old woman underwent emergency hysterectomy after uterine artery embolization embolic microspheres found within the ovarian arterial vasculature. Uterine artery embolization for the treatment of uterine fibroids has been associated with loss of ovarian function in up to 14% of patients. This case report demonstrates that embolic microspheres injected into the uterine artery can unintentionally migrate through anastomotic channels into the ovarian arterial vasculature and potentially compromise ovarian blood flow. Hypoxic tissue injury may be the mechanism of premature ovarian failure observed after uterine artery embolization. Understanding the etiology of premature ovarian failure after uterine artery embolization might allow better patient selection.


Predictors of Severity in Pediatric Scrub Typhus.
To identify the factors that can predict the severity of scrub typhus in children. This prospective study was conducted at a tertiary care teaching hospital between November 2014 to October 2016. All children <12y of age admitted with fever for more than 7d and positive IgM ELISA for scrub typhus were included in the study. These children were followed during the hospital course and their laboratory results, response to treatment and complications were documented. Cases of 'severe scrub typhus' were identified based on criteria from published adult and pediatric studies. Out of 930 children with fever for more than 7d, IgM ELISA for scrub typhus was positive in 230 children. Ninety one (40.6%) cases fulfilled the criteria of 'severe scrub typhus' in children. Out of 45 factors, 27 potential factors were studied. The multivariate analysis identified 5 factors, breathlessness (OR: 6.85, 95%CI: 2.69 to 9.87), altered sensorium (OR: 11.48, 95% CI 3.43 to 10.19), leucocytosis (OR: 3.38, 95% CI 1.12 to 10.16), hypoalbuminemia (OR: 10.78, 95% CI 2.66 to 48.76), and hyponatremia (OR: 10.08, 95% CI 2.11 to 23.42) to be significantly associated with the 'severe scrub typhus' cases. Breathlessness, altered sensorium, leucocytosis, hypoalbuminemia, and hyponatremia predict severity in childhood scrub typhus. Presence of these factors should alert the treating physician regarding the need for intensive monitoring, treatment or referral.


Role of total mesorectal excision and of circumferential resection margin in local recurrence and survival of patients with rectal carcinoma.
Rectal cancer is a common disease with poor prognosis because of local recurrence and metastases. Local recurrence arises mainly as a result of incomplete surgical resection. Evaluation of completeness of the mesorectum provides significant information about prognosis. Total mesorectal excision (TME) has become the surgical treatment of choice for rectal cancer because adopting the principles of TME achieves very low local recurrence rates. The adoption of the TME principles along with the estimation of the circumferential resection margin on the non-peritonealized surface of the resected rectal specimen are the most important predictors of local recurrence.


Conformation of a peptide corresponding to T4 lysozyme residues 59-81 by NMR and CD spectroscopy.
The conformation, in solution, of a peptide corresponding to residues 59-81 from T4 lysozyme [LYS(59-81)] has been determined by 1H NMR and CD spectroscopy. This peptide spans the region corresponding to helix C in the crystal structure of T4 lysozyme. Secondary structure predictions indicated that the peptide would possibly be helical in an aqueous environment, but in a more hydrophobic environment the peptide would certainly adopt a helical conformation. This prediction was confirmed by the far-UV CD and NMR studies, which showed the peptide to be relatively unstructured in aqueous solution and significantly helical in the presence of either TFE or SDS micelles, although the 1H NMR results did give some indication of the presence of nascent helix in aqueous solution. For LYS(59-81), in TFE, the three-dimensional structure derived from the NMR data showed that the helix had a more pronounced curvature than the gradual bend observed in the crystal structure.


High Prevalence of BRAF V600E Mutations in Langerhans Cell Histiocytosis of Head and Neck in Chinese Patients.
Langerhans cell histiocytosis (LCH) is characterized by clonal proliferation of Langerhans cells and has been classified as a hematolymphoid tumor. BRAF V600E mutation was found to be frequent in LCH; however, it has also been reported that Asia patients with LCH tend to show a lower rate of BRAF V600E mutation. In this study, we found LCH from the head and neck region often involved bone especially the posterior of the mandible and presented a high prevalence of BRAF V600E mutation in Chinese patients. Our findings also showed immunohistochemical detection correlated very well to DNA sequencing of BRAF alterations, which may be useful in the diagnosis of LCH, especially in cases with a low proportion of Langerhans cells, and BRAF inhibitors might be a treatment option for patients with LCH harboring BRAF V600E mutation.


Radiographic findings of Wistar rats fed with T-2 toxin and Kashin-Beck disease-affected diet.
To characterize the features of radiographic abnormalities of the tibial bone in Wistar rats which have been fed T-2 toxin and Kashin-Beck disease (KBD) epidemic district food. Ninety Wistar rats were divided into five groups. Group A was fed with a normal diet as control; group B was fed with a normal diet and T-2 toxin; group C was fed with a low-nutrition diet and T-2 toxin; group D was fed with a low-nutrition diet; and group E was fed with a KBD-affected diet. At 4, 8 and 12 weeks, six rats from each group were radiographed. After radiographic examination, samples of left knees were harvested and stained with hematoxylin and eosin. At 8 and 12 weeks, there were radiological changes in the epiphyseal plate. Abnormal radiological signs of blurring, thinning and irregularity were seen in groups C and E rats, and the length of tibial bones showed significant difference in the KBD-fed rats and low-nutrition diet combined T-2 toxin rats, compared to the control group rats (P < 0.05). The epiphyseal plates showed more obvious necrosis of chondrocytes in groups C and E. A rat model of KBD can be established by a KBD-affected diet; proximal epiphyseal plate and metaphyseal bone of the tibia abnormalities on radiographs and histopathology were present in KBD model rats. A low nutrition diet may be involved the aetiology of KBD, and determination of this should be studied in the future.


Measurement of outcomes, mediators, and moderators in behavioral obesity prevention research.
Measurement enables intervention scientists to determine whether their interventions had the intended outcome effects and the expected pathways of effects across mediating variables. Low reliability of measurement (i.e., substantial random error) attenuates the relationships of these measures to other variables, including treatment effects. This attenuation may indicate that interventions were not effective, when in truth they were. There has been little assessment of the quality of measurement in obesity prevention trials. A brief review is provided of measurement issues within classical test theory. Seventeen obesity prevention trials were then identified in the literature. The extent to which the reliability and validity of the measures were reported in the articles was assessed. With few exceptions reliability coefficients of measures were not reported in the obesity prevention literature. When they were reported, there was evidence that low reliability attenuated reported intervention outcome relationships. The quality of measurement is important in intervention science and consequently should be clearly presented in scientific reports of outcomes. Better measures are needed in obesity prevention to provide appropriate tests of state of the art interventions. A brief overview is provided of each of the articles in this special issue on measurement in the Girls health Enrichment Multisite Studies (GEMS).


Competition of motile and immotile bacterial strains in a petri dish.
Bacterial competition is an important component in many practical applications such as plant roots colonization and medicine (especially in dental plaque). Bacterial motility has two types of mechanisms -- directed movement (chemotaxis) and undirected movement. We study undirected bacterial movement mathematically and numerically which is rarely considered in literature. To study bacterial competition in a petri dish, we modify and extend the model used in Wei et al. (2011) to obtain a group of more general and realistic PDE models. We explicitly consider the nutrients and incorporate two bacterial strains characterized by motility. We use different nutrient media such as agar and liquid in the theoretical framework to discuss the results of competition. The consistency of our numerical simulations and experimental data suggest the importance of modeling undirected motility in bacteria. In agar the motile strain has a higher total density than the immotile strain, while in liquid both strains have similar total densities. Furthermore, we nd that in agar as bacterial motility increases, the extinction time of the motile bacteria decreases without competition but increases in competition. In addition, we show the existence of traveling-wave solutions mathematically and numerically.


Correlation of reaction-center chlorophyll (P-700) oxidation and bound iron-sulfur protein photoreduction in chloroplast photosystem I at low temperatures.
The extent of P-700 photooxidation at 18 degrees K has been followed in three different chloroplast preparations (unfractionated chloroplasts and two preparations enriched in Photosystem I). More than 90% of P-700+ formation in all preparations was eliminated by the addition of sodium dithionite at pH 10. Photoreduction of a bound chloroplast iron-sulfur protein was also decreased by at least 90% under similar conditions. Electron paramagnetic resonance spectra of the chloroplast preparations in the presence of dithionite showed chemical reduction of bound iron-sulfur protein under conditions where primary photochemistry is eliminated. These results indicate that P-700 photooxidation is concomitant with photoreduction of a bound iron-sulfur protein and that this iron-sulfur protein functions as the primary electron acceptor of Photosystem I.


Ring-shaped vortex domain in type-II superconductors.
We present results of experiments in superconducting niobium and numerical simulations showing the creation of a metastable ring-shaped vortex domain by heating. Such vortex rings, if pinned by structural defects, can exist forever.


Sickle cell trait and hematuria associated with von Willebrand syndromes.
A von Willebrand syndrome was present in four patients with sickle cell trait and hematuria. The first two patients had severe anemia and active bleeding and received cryoprecipitate, with prompt cessation of hemorrhage. All of the patients had repetitive laboratory and clinical features; that is, reduced, but detectable, factor VIII-related antigen, heterogeneity of, and incongruities within, the coagulation studies performed by consistently defective platelet aggregation to ristocetin correctable only with normal plasma. Bleeding outside the genitourinary tract never was observed. Because of the focal nature of the hemorrhage, the hematuria may not have been perceived as part of a general hemorrhagic disorder and the diagnosis not pursued. These observations suggest that when sickle cell trait and hematuria occur together, a von Willebrand syndrome should be a major diagnostic consideration that ultimately may point toward a rational, effective, easily administered, and clinicially acceptable form of treatment with cryoprecipitate.


Generation and application of a fluorescein-specific single chain antibody.
A recombinant single chain antibody fragment (designated scDE1) of the murine monoclonal anti-fluorescein antibody B13-DE1 was generated using the original hybridoma cells as source for the variable antibody heavy and light chain (VH and VL) genes. After cloning the variable genes into a phage vector a functional antibody fragment was selected by phage display panning. Recombinant antibody could be expressed as phage antibody and as soluble single chain antibody in Escherichia coli. High yield of scDE1 could also be detected in bacterial culture supernatant. The scDE1 showed the same binding specificity as the parental monoclonal antibody, i.e. it bound fluorescein, fluorescein derivatives and a fluorescein peptide mimotope. Surface plasmon resonance revealed a K(D) of 19 nM for the scDE1 compared to 0.7 nM for the monoclonal antibody. The isolated soluble scDE1 could easily be conjugated to horseradish peroxidase which allowed the use of the conjugate as universal indicator for the detection of fluorescein-labelled proteins in different immunoassays. Detection of hCG in urine was performed as a model system using scDE1. In addition to E. coli the scFv genes could also be transferred and expressed in eukaryotic cells. Finally, we generated HEK293 cells expressing the scDE1 at the cell surface.


[Almas delirantes (1925) by Luís Cebola: the poetics of the human psyche and the physician as mediator between the universe of mental illness and society].
Lúis Cebola's 1925 work Almas delirantes [Delusional Souls] presented various psychopathologies through metaphorical and lyrical portraits rather than from a medical/ scientific point of view, showing that he perceived his patients as more than objects of scientific study in a process of identification, empathy, and compassion. Cebola defined psychopathological states according to contrast with normality, but stressed that these diseases could arise in any individual, and the book simultaneously acted as a warning to readers. The text also publicized the Museum of Madness [Museu da Loucura], which he created at the Casa de Saúde do Telhal, and the art produced by his patients, positioning himself as a messenger between the closed universe of the psychiatric hospital and Portuguese society.


Species-specific aggregation factor in sponges : VIII. Nature and alteration of cell surface charge.
Isolated cells from the siliceous spongeGeodia cydonium have been studied with respect to their partition behaviour in a two-phase aqueous polymer system. With this method it is possible to determine subtle changes in the cell surface charge. Addition of a homologous aggregation factor to the isolated cells lowers the partition rate, a finding which indicates that after binding of the aggregation factor to the cells their surface charge is reduced. The partition rate of the cells is strongly correlated with their content of membranebound sialic acid.Sixty-nine percent of the total, membrane-bound hexuronic acid is associated with the aggregation receptor; 1.8×107 aggregation receptor molecules are present on the surface of one cell which means that the average surface density amounts to 2.8×105 molecules per μm2.Removal of the aggregation receptor molecules from the cell surface results in a decrease of the partition rate in the two-phase system. After charging the receptor-depleted cells with soluble aggregation receptor, the partition behaviour of these cells can be reconstituted.


Lidocaine reduces endotracheal tube associated side effects when instilled over the glottis but not when used to inflate the cuff: A double blind, placebo-controlled, randomized trial.
Tracheal intubation results in an alteration of the laryngeal mucosa which can lead to undesirable effects at emergence from anaesthesia. Local anesthetics, when administered topically, may represent an interesting alternative to reduce these side effects. In this trial, we aimed to evaluate the effect of lidocaine in preventing tracheal intubation related side effects at emergence from anaesthesia, when instilled onto the glottis before intubation or used to inflate the endotracheal tube cuff. Eighty patients scheduled to elective surgery of less than 120 minutes under general anaesthesia were enrolled in this prospective, randomized, controlled, double blind study. As they receive instillation of 2% lidocaine or saline onto the glottis before intubation, and as they have their endotracheal tube cuff filled with 2% lidocaine or saline, the patients were randomized in four groups. S-S (Saline instillation and saline in the cuff); S-Lido (saline instillation and lidocaine in the cuff); Lido-S (lidocaine instillation and saline in the cuff); Lido-Lido (lidocaine instillation and lidocaine in the cuff). The primary outcome was the incidence of coughing before extubation. The secondary outcomes were sore throat scores at H1 and H24 postoperatively and incidence of dysphagia, dysphonia and laryngeal dyspnea during the first 24 hours. Coughing occurred in 80%, 70%, 30% and 20% of patients in S-S, S-Lido, Lido-S and Lido-Lido groups respectively. When compared to S-S group, the incidence of coughing was significantly reduced in Lido-S and Lido-Lido groups but not in S-Lido group (p1=0.003; p2=0.0003; p3=0.7 respectively). Sore throat scores at H1 and H24 were significantly lower in Lido-S and Lido-Lido groups (p1=0.00002 and p2=0.01). There was no significant difference between groups regarding the incidence of dysphagia, dysphonia and laryngeal dyspnea. When instilled onto the glottis before intubation, lidocaine reduced both the incidence of coughing and the severity of postoperative sore throat in surgery of less than 120 minutes. Intracuff lidocaine was not effective to reduce neither coughing nor sore throat severity.


Effects of TNF-alpha on the production of vasoactive substances by cerebral endothelial and smooth muscle cells in culture.
The effects of tumor necrosis factor-alpha (TNF-alpha) on the production of the vasoactive substances nitric oxide (NO) and endothelin-1 (ET-1) were investigated in cerebrovascular cells in culture. Bovine cerebral endothelial cells (BCEC) stained positively for NADPH-diaphorase/NO synthase activity and spontaneously produced nitrite, a stable NO oxidation product, which accumulated in the culture medium in a linear way for 48 h. Low concentrations of TNF-alpha (0.5-2 ng/ml) significantly enhanced nitrite production after a 24-h incubation. Higher concentrations or longer exposure times resulted in a cytotoxic effect that altered cell morphology, released lactate dehydrogenase (LDH) to the culture medium, and reduced the protein content. Dexamethasone, but not the NO synthase inhibitor N-iminoethyl-L-ornithine (L-NIO), prevented the cytotoxic effect of TNF-alpha in BCEC. TNF-alpha also significantly enhanced nitrite production in bovine cerebral smooth muscle cells (BCSMC). The enhancement was detected at all times between 8 and 72 h and at all concentrations tested (2-100 ng/ml). Signs of cytotoxicity were not observed in BCSMC after incubation with TNF-alpha. ET-1 was constitutively secreted by BCEC. The production of ET-1 was stimulated by thrombin. TNF-alpha enhanced the release of ET-1 in BCEC, and this enhancement was not modified by the simultaneous addition of interferon-gamma (IFN-gamma). BCSMC did not produce ET-1, either spontaneously or in the presence of TNF-alpha, IFN-gamma, or of both together.(ABSTRACT TRUNCATED AT 250 WORDS)


The pre-school child: diet, growth and obesity.
In this review the question of obesity in the pre-school child has been examined in three areas of interest: first, the extent of our knowledge of food intake and its relationship to growth in the young child; secondly, the difficulties in defining obesity on a practical level in this group, and thirdly the constraints in the examination of energy balance because of the limitations of techniques available for this type of work. The conclusion is that studies are needed to analyse factors regulating energy balance, and thereby explain why, in the very young child, there is an individual difference in the utilization of energy for growth, activity and basal processes.