Endotoxin impairs the engraftment of rat islets transplanted beneath the kidney capsule of C57BL/6-mice

The primary objective of this investigation was to determine the effect of endotoxin on islet xenograft survival within the first three days after transplantation. Pancreatic islets from Lewis rats were prepared under endotoxin-free conditions with Liberase (Boehringer) and purified by centrifugation on endotoxin-free Ficoll/Histopaque. After overnight incubation, with or without 10 microg/ml endotoxin, the islets were transplanted beneath the kidney capsule of normoglycemic C57Bl/6-mice. Three days later, kidneys were removed and their insulin content were measured. We could demonstrate significant differences (P<0.01) in insulin recovery between lipopolysaccharide-free and lipopolysaccharide-containing grafts. In case of endotoxin contaminated islets, we found only 13+/-2% (n=9) of the original insulin content, in contrast to 53+/-7% (n=9) when endotoxin-free islets where grafted. In experiments with islets isolated by use of conventional (lipopolysaccharide-containing) collagenase, and then cultured in endotoxin-free medium, insulin recovery three days after transplantation was 36+/-1% (n=13).     

Differences in prostate size between patients from University and Veterans Affairs Medical Center populations

We have previously determined that Nippostrongylus brasiliensis secretes three monomeric nonamphiphilic (G1na) variants of acetylcholinesterase (AChE) with broadly similar properties. In this study we have examined AChE expression in somatic extracts of N. brasiliensis and report the identification of an additional enzyme which is not secreted. The enzyme was resolved by sucrose density gradient centrifugation with a sedimentation coefficient of 10.2 S which was shifted to 9.4 S in the presence of Triton X-100, identifying the enzyme as a tetrameric amphiphilic (G4a) form. The amphiphilic properties of this enzyme were confirmed by charge-shift electrophoresis, in which migration was accelerated by interaction with sodium deoxycholate. The enzyme showed low activity with butyrylthiocholine, and a Michaelis constant of 91 +/- 13 microM for acetylthiocholine was determined. It was highly sensitive to the AChE-specific inhibitor bis (4-allyldimethylammoniumphenyl)pentan-3-one dibromide, with an IC50 of 6.5 +/- 0.4 microM, but was also inhibited by the butyrylcholinesterase-specific inhibitor tetramonoisopropylpyrophosphortetramide, albeit with a higher IC50 of 46.5 +/- 6.1 microM. This enzyme can therefore be distinguished from the secreted AChEs by its amphiphilic properties, sedimentation in sucrose gradients, and sensitivity to cholinesterase inhibitors.     

Characterization of Y3 receptor-mediated synaptic inhibition by chimeric neuropeptide Y-peptide YY peptides in the rat brainstem

Archival material from primary and metastatic renal clear cell carcinomas of 25 patients was studied by comparative genomic hybridization. Copy number changes of entire chromosomes or chromosomal subregions were detected in 22 primary and 21 metastatic tumors. Copy number changes affected the following chromosomes in at least 20% of the 25 primary tumors (minimal common region given in parentheses): gains were noted for chromosomes 1 (1q21-->q23), 5 (5q31-->q34), 7 (7p), 8 (8q), 16 (16p), 17 (17q12-->qter), 19, and 22 (22q12-->qter); losses were revealed for chromosomes 3 (3p21-->pter), 8 (8p23-->pter), 14(14q21-->qter), and Y. The same chromosomal regions that were involved in primary renal clear cell carcinomas were also found in the respective metastatic tumors but with strikingly different frequencies for a few regions. Metastatic tumors showed a significantly higher frequency of complete or partial gains of the long arm of chromosome 1, in particular at 1q21-->q23 than primary tumors (16 cases versus 6 cases; P < 0.005). These data suggest a correlation of metastatic events in renal clear cell carcinomas with an increase in the copy number of genes located at 1q, in particular at 1q21-->q23. In contrast, the entire or partial loss of the short arm of chromosome 3 was significantly less frequent in metastatic tumors (8 cases versus 15 cases; P < 0.025). The validity of 1q and 3p copy number changes detected by comparative genomic hybridization was confirmed by interphase cytogenetics with region-specific yeast artificial chromosomes to paraffin-embedded tumor tissue sections.     

Monitoring of impurities using high-performance liquid chromatography with diode-array detection: eigenvalue plots of partially overlapping tailing peaks

The chromatogram of ropinirole in the presence of about 5% of a closely eluting impurity, obtained by HPLC with diode-array detection, was analysed by chemometric procedures. Log eigenvalue plots were used to determine the relative composition of regions of the chromatogram. It is shown that since the peaks exhibit tailing, unusual behaviour is found in the plots. This is verified by performing simulations, in which it is demonstrated that peak asymmetry has a pronounced influence on this chemometric approach. In many cases of liquid chromatographic analysis, asymmetric peak shapes are encountered and methods for peak purity assessment should be re-evaluated in the light of these asymmetries.     

Sexually transmitted diseases: risk behaviors of female active duty U.S. Army recruits

This study examined the sexually related behaviors of 594 unmarried female Army recruits at the beginning of their basic training. The response rate for the entire sample of 818 recruits was 99.4%, with data from the 224 married recruits being eliminated from the analysis. The recruits completed an anonymous survey examining several independent variables: frequency of condom use, number of sexual partners, screening behaviors, and pregnancy and sexually transmitted disease prevention methods. The findings are discussed with regard to suggested appropriate and cost-effective educational interventions.     

Of sick turkeys, kwashiorkor, malaria, perinatal mortality, heroin addicts and food poisoning: research on the influence of aflatoxins on child health in the tropics

Similarities between the geographical and climatic prevalences of kwashiorkor and of exposure to dietary aflatoxins, and between the biochemical, metabolic and immunological derangements in kwashiorkor and those in animals exposed to aflatoxins, prompted investigation of the associations between kwashiorkor and aflatoxins. Studies in Africa in the 1980s indicated a role for these toxins in the pathogenesis of the disease. Paediatric cases of kwashiorkor are less prone to severe Plasmodium falciparum malaria than normal children. In mice infected with P. berghei, aflatoxin exposure inhibits parasite growth and ameliorates morbidity. Aflatoxins occur in < or = 40% of samples of breast milk from tropical Africa, usually as low concentrations of the relatively non-toxic derivatives of aflatoxin B1 (AFB1) but sometimes as high concentrations of the very toxic AFB1. This could explain kwashiorkor in breast-fed babies. Aflatoxin exposure occurs in > or = 30% of pregnancies in tropical Africa and the toxins are often in cord blood, sometimes at extremely high concentrations. Aflatoxins are now incriminated in neonatal jaundice and there is circumstantial evidence that they cause perinatal death and reduced birthweight. Aflatoxin-induced immunosuppresion may explain the aggressive behaviour of HIV infection in Africa. There are similarities between observations on HIV cases in Africa and those on heroin addicts in Europe, where 'street' heroin is frequently contaminated with aflatoxin. Aflatoxins were found in 20% of random urine samples from heroin addicts in the U.K. and the Netherlands. Aflatoxins have also been incriminated in episodes of food poisoning which have been associated with serious morbidity and mortality, particularly among young children.     

Initial feasibility of a researcher configurable computerized self-monitoring system

This study sought to evaluate the feasibility of a researcher configurable self-monitoring program. An initial prototype of the program was developed as a Windows-based drag and drop flow chart interface for the researcher to construct the self-monitoring or diary protocol to be scheduled and displayed to the subject on a Pocket PC. The usability of the desktop researcher interface was evaluated in a small sample of medication trial researchers whose ratings of the prototype were generally positive and provided directions for improvement. The subject interface was then evaluated in an “analog” drug trial of 49 smokers using nicotine gum. These subjects were randomly assigned to either paper-based log or Pocket PC self-monitoring for 3 weeks. Pocket PC subjects were significantly more compliant than the log subjects on recording in the second (65% vs. 39%) and third (69% vs. 39%) weeks of the trial but did not differ from the log condition on total recording entries, likely due to the restrictions on retrospective recording in the Pocket PC program. This study provides support for the feasibility of a researcher configurable electronic diary system which should substantially reduce the programming barriers to electronic self-monitoring and increase the use of real-time monitoring in clinical and research venues.     

Danger ideation reduction therapy (DIRT): preliminary findings with three obsessive-compulsive washers

Three obsessive-compulsive patients received Danger Ideation Reduction Therapy (DIRT) in an initial treatment trial. All three subjects presented with contamination/washing concerns but refused to participate in exposure and response prevention. DIRT is solely directed at decreasing danger-related expectancies concerning contamination. DIRT procedures do not attempt to address inflated personal responsibility. In addition, DIRT does not involve direct or filmed exposure to contamination-related stimuli, or behavioural experiments. Components of DIRT include corrective information cognitive restructuring, filmed interviews, microbiological experiments, attentional focusing and Hoekstra's (1989) probability of catastrophe estimation task. Treatment consisted of between six and ten 1-hr weekly sessions. At post-treatment, substantial reductions in scores on the Padua Inventory, Maudsley Obsessional-Compulsive Inventory and two global rating scales were apparent for all subjects. These improvements were maintained at a 3-month follow-up. The theoretical and clinical implications of these preliminary findings are discussed.