IL-10 regulates thrombus-induced vein wall inflammation and thrombosis

Vein wall inflammation associated with venous thrombosis is mediated by an imbalance in proinflammatory as compared with antiinflammatory molecules. We hypothesize that IL-10 is an important antiinflammatory cytokine that influences vein wall inflammation and thrombus propagation during venous thrombosis. To test this hypothesis a model of inferior vena caval thrombosis was used. Studies were performed at sacrifice 2 days after thrombus induction and included leukocyte morphometrics, myeloperoxidase activity, vein wall permeability, thrombus weight, and IL-10 ELISA analysis from the vein wall. IL-10 was elevated in the vein wall during venous thrombosis. Neutralization of IL-10 increased inflammation, while supplementation with rIL-10 demonstrated a dose- and time-dependent decrease in inflammation. Interestingly, a low 2.5-microg rIL-10 dose given at time of initiation of thrombosis most significantly decreased inflammation. Thrombus weight was importantly diminished by reconstitution of IL-10. These studies support an important role for IL-10 in the regulation of thrombus-associated inflammation and thrombosis and suggest that IL-10 could be used as a therapeutic agent in the treatment of venous thrombosis.     

Pathways of risk for accelerated heavy alcohol use among adolescent children of alcoholic parents

The current study examined two questions. First, do internalizing symptoms and externalizing behavior each mediate the relations between parent psychopathology (alcoholism, antisocial personality disorder, and affective disorder) and growth in adolescent heavy alcohol use? Second, are there gender differences in these mediated pathways? Using latent curve analyses, we examined these questions in a high-risk sample of 439 families (53% children of alcoholic parents; 47% female). Collapsing across gender, adolescent-reported externalizing behavior mediated both the relation between parent alcoholism and growth in heavy alcohol use and the relation between parent antisociality and growth in heavy alcohol use. Parent-reported externalizing behavior only mediated the relation between parent antisociality and growth in heavy alcohol use in males. No support was found for internalizing symptoms as a mediator of these relations. Avenues are suggested for further exploring and integrating information about different mediating processes accounting for children of alcoholics' risk for heavy alcohol use.     

Use of the recombinant 38-kDa antigen of Mycobacterium tuberculosis as an immunogen for specific antisera production

The Mycobacterium tuberculosis 38-kDa protein antigen is one of the secreted immunodominant antigens showing high immunogenicity at B-cell and T-cell levels. Although monoclonal antibodies to this antigen have been produced, specific polyclonal antisera is required for standardization of specific immunodiagnostic assays. This protein has been overexpressed and purified from recombinant Escherichia coli using an inducible vector system. During each stage of expression and purification, the recombinant protein was used to immunize mice and rabbits by several methods: 1) as overexpressed protein present as inclusion bodies in recombinant E. coli; 2) embedded in a polyacrylamide gel; 3) fixed to a solid-phase nitrocellulose membrane and 4) emulsified with an adjuvant. All strategies yielded specific antisera as determined by enzyme-linked immunosorbent assay (ELISA) and immunoblot analyses. The results obtained, both quantitative (ELISA) and qualitative (immunoblot) demonstrate that the purified recombinant antigen retains its antigenicity and immunogenicity throughout the various steps in the process of expression and purification and serves as a potent antigen for production of specific antisera to be used in immunoassays.     

Monoclonal antibodies directed against lipopolysaccharide of Legionella pneumophila serogroup 1

The monoclonal antibodies (MAbs) against lipopolysaccharide of virulent strain of Legionella pneumophila serogroup 1 were produced. Three most productive hybrid clones (5F4, 5F10 and 2C9) were selected from fusions of mouse myeloma cells with spleen cells from BALB/c mice, immunized with bacterial outer membrane antigens. All generated clones were IgG-secreting. The MAbs had narrow strain specificity and showed no cross-reactions with other unrelated bacterial species. These antibodies were tested in sandwich ELISA. The results suggest that the MAbs could be used for diagnostic purposes.     

Human and clinical perspectives on leptin

The neurochemical coding of neurones located in ganglia of the nerve trunk accompanying the chicken ureter was analysed and quantified using NADPH-diaphorase reactivity and immunohistochemistry against tyrosine hydroxylase (TH), nitric oxide synthase (NOS), calbindin (CAL), vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), somatostatin (SOM), substance P (SP) and calcitonin gene-related peptide (CGRP) in untreated or colchicine-treated preparation. Almost all neurones were either positive for TH (38%) or for SOM (60%). Only 4% of the neurones were both TH- and SOM-positive and 3% of the neurones exhibited neither TH nor SOM immunoreactivity. The relative numbers of NPY-, NOS-, CAL- and VIP-positive neurones were 57%, 28%, 14% and 7%, respectively. No SP- or CGRP-positive neurones were observed. All NADPH-diaphorase-positive neurones expressed NOS immunoreactivity. Only in some TH-positive neurones was NPY and/or NOS found. Four major subpopulations were found in the ureteric ganglia. The SOM-positive neurones were subdivided into SOM/NPY/NOS- (28% of all neurones), SOM/NPY- (18%) and SOM/CAL/NPY-positive neurones (14%). A subpopulation of these peptid- ergic neurones also contained VIP. About 35% of the neurones contained TH only. Neurones of all subpopulations (72% of the neurones), except most of the CAL-positive neurones, were encircled by dense plexus of varicose SP/CGRP-positive, presumably sensory nerve fibres. Dense plexus of VIP-positive fibres were observed around 89% of the neurones. The chemical coding of the neuronal subpopulations identified in the ganglia accompanying the chicken ureter resembled that observed in the ganglia of Remak's nerve but was remarkably different from that of the autonomic neurones described in mammalian species.     

Cell-specific transcription of the smooth muscle gamma-actin gene requires both positive- and negative-acting cis elements

We recently labeled with carbon-11, a high affinity, selective, 5-HT3 receptor (5-HT3R) ligand, S21007, for potential positron emission tomography (PET) applications. To evaluate the in vivo binding properties of [11C]S21007, its brain regional distribution, tissue and plasma pharmacokinetics and plasma metabolisation were characterized. To circumvent the problem of highly discrete brain localization of the 5-HT3R (area postrema, hippocampus), we designed an original approach combining high-resolution imaging techniques (ex vivo phosphor plate autoradiography and MRI-guided coronal PET in the rat and baboon, respectively). After i.v. injection of trace amounts of [11C]S21007 to rats, phosphorimager autoradiography failed to reveal in vivo specific binding to, nor selectivity for 5-HT3R-rich areas. PET studies in the baboon showed consistent results, i.e., there was no selective accumulation of [11C]S21007 in the area postrema or hippocampus, and neither displacement nor presaturation with cold S21007 resulted in significant changes in tissue distribution or kinetics of [11C]S21007.     

Artemisinin-derived sesquiterpene lactones as potential antitumour compounds: cytotoxic action against bone marrow and tumour cells

Epidemiologic and public health researchers frequently include several dependent variables, repeated assessments, or subgroup analyses in their investigations. These factors result in multiple tests of statistical significance and may produce type 1 experimental errors. This study examined the type 1 error rate in a sample of public health and epidemiologic research. A total of 173 articles chosen at random from 1996 issues of the American Journal of Public Health and the American Journal of Epidemiology were examined to determine the incidence of type 1 errors. Three different methods of computing type 1 error rates were used: experiment-wise error rate, error rate per experiment, and percent error rate. The results indicate a type 1 error rate substantially higher than the traditionally assumed level of 5% (p < 0.05). No practical or statistically significant difference was found between type 1 error rates across the two journals. Methods to determine and correct type 1 errors should be reported in epidemiologic and public health research investigations that include multiple statistical tests.     

An outbreak of needlestick injuries in hospital employees due to needles piercing infectious waste containers

OBJECTIVES: To investigate the cause of an outbreak of needlestick injuries (NSIs) in hospital employees. SETTING: A 700-bed university hospital. DESIGN: Outbreak investigation, laboratory evaluation of a medical waste disposal device, cost analysis. METHODS: Employee health department records were reviewed of workers suffering sticks from needles piercing fiberboard-contaminated material containers (CMCs). A laboratory evaluation of needle-puncture resistance properties of the CMCs was performed using a testing apparatus. The cost of a hospital waste disposal program using fiberboard CMCs was compared with the cost of a program using rigid plastic (polypropylene) boxes. RESULTS: During 40 months of surveillance in 1986 and from 1989 to 1991, only one NSI had occurred from a needle piercing a CMC. During 9 months in 1993, 13 NSIs occurred due to needles piercing CMCs (P < .001). No clinical illness resulted from the NSIs. The outbreak was halted by a temporary change to plastic (polypropylene) boxes for sharps disposal ($4.92 to $23.33/cu ft) until receipt of a box with a newly designed solid fiberboard liner ($1.25/cu ft). CMC liners used during the epidemic had a mean needle puncture resistance of 527 g, as compared with 660 g for liners used before the outbreak (P < .001). The new solid fiberboard liner has a mean puncture resistance of 1,765 g. A program of waste disposal using fiberboard CMCs was found to cost approximately one-seventh the cost of a program using plastic boxes for disposal of infectious waste. CONCLUSION: A program for infectious waste disposal using fiberboard CMCs can be safe and cost-effective if appropriate standards for puncture resistance are met.     

Cross-form priming in normal aging and in mild dementia of the Alzheimer type

Twenty patients at early stages of Alzheimer's disease (AD), 20 elderly control subjects and 20 young subjects completed a cross-form priming task, followed by a free recall task. Results show that patients with mild AD display priming effects, and that these priming effects are strictly comparable to those obtained by elderly and young control subjects. Moreover, while the patients' performances are normal in the implicit part of the task, they are massively impaired in the explicit free recall task. These results don't support the hypothesis of a dissociation of performances between identification tasks and generation tasks in Alzheimer's disease, and show that conceptual priming can be observed at early stages of the disease, despite semantic memory impairments.