GM-CSF induces expression of soluble VEGF receptor-1 from human monocytes and inhibits angiogenesis in mice

GM-CSF promotes homeostasis of myeloid cells. We report that GM-CSF upregulates mRNA and protein production of the soluble form of membrane bound VEGF receptor-1 (sVEGFR-1) in human monocytes. This sVEGFR-1 was biologically active, as cell-free supernatants from GM-CSF-stimulated monocytes blocked detection of endogenously expressed VEGF and inhibited endothelial cell migration and tube formation, even in the presence of exogenous rhVEGF. VEGF activity was recovered by neutralizing sVEGFR-1. To determine whether these events were important in vivo, Matrigel plugs were incubated with rhVEGF, rhGM-CSF, or rhGM-CSF/rhVEGF and injected into mice. Plugs containing GM-CSF or GM-CSF/VEGF had less endothelial cell invasion than plugs containing rhVEGF and were similar to plugs incubated with PBS alone. Neutralizing antibodies specific for sVEGFR-1 injected in these plugs reversed the effects of GM-CSF or GM-CSF/VEGF, while an isogenic antibody did not. Thus, GM-CSF and monocytes play a vital role in angiogenesis through the regulation of VEGF and sVEGFR-1.     

Autogeny in Ochlerotatus vigilax (Diptera: Culicidae) from southeast Queensland, Australia

Field and laboratory investigations were undertaken to determine the level of expression of autogeny in the mosquito Ochlerotatus vigilax (Skuse) from southeast Queensland, Australia, and whether there was evidence of seasonal variation. At two field sites in southeast Queensland, Wellington Point and Donnybrook, autogeny rates were determined on six occasions between January 2001 and January 2002. The autogeny rate varied between 71 and 100% at Wellington Point and between 63 and 100% at Donnybrook. Autogenous fecundity ranged from 17 to 63 eggs per female at Wellington Point and from 13 to 88 eggs per female at Donnybrook. Positive relationships were found between adult body size (indicated by wing length), autogeny rate, and fecundity. A laboratory study was conducted to investigate the influence of larval nutrition and adult diet (water versus sucrose) on the expression of autogeny. The autogeny rate at a low-diet treatment was between 73 and 90% when sucrose was withheld from females and 100% when sucrose was provided. All high-diet females were autogenous. Autogenous egg development required 80 +/- 6 h from emergence at 27 degrees C. We conclude that autogeny rates are consistently high in Oc. vigilax from the southeast Queensland region.     

Experimental staphylococcal endocarditis and aortitis

Summary The initial colonization, byStaphylococcus aureus, of the catheter damaged aortic valve and aorta of the rabbit, was examined by light and electron microscopy at 15 min, 3 h and 24 h post inoculation (PI). At 15 min PI, the majority of bacteria (80%) were located on the lateral surfaces of the thrombic vegetations while 20% were attached directly to the connective tissue of the aortic valve and aorta in areas where the endothelial lining was disrupted. By 3 h the bacteria on the thrombic vegetations were covered by fibrin. At this time, the bacteria both within the vegetations and on the surface of the vasculature were undergoing multiplication to form small groups. The precipitation of thrombus around the bacteria attached to the surface of the aorta to form microscopic infected vegetations had occurred by 24 h PI. The colonizing bacteria did not elicit any phagocytic response. The colonization of the cardiovasculature byStaph. aureus did not necessarily require pre-existing vegetations.     

Cytogenetic analysis of the Asian Plethodontid salamander, Karsenia koreana: Evidence for karyotypic conservation, chromosome repatterning, and genome size evolution

A cytogenetic analysis, including the karyotype, C-bands, silver-stained nucleolus organizer regions and genome size, was performed on the recently discovered species, Karsenia koreana, the first plethodontid salamander from Asia. The karyotype consists of 14 pairs of bi-armed chromosomes, with no evidence of heteromorphic sex chromosomes. C-banding reveals a concentration of heterochromatin at the centromeres as well as at interstitial locations. The smallest chromosome (pair number 14) has symmetrical interstitial C-bands in each arm, resembling chromosome no. 14 of North American species of its sister group taxon, supergenus Hydromantes. Acomparative analysis of C-band heterochromatin and silver-stained nucleolus organizer regions of Karsenia and other plethodontid genera reveals that chromosomal evolution may have featured chromosome 'repatterning' within the context of conserved chromosome number and shape in this clade. Genome size is correlated with geographic distribution in plethodontids and appears to have important phenotypic correlates as well. The genome size of Karsenia is relatively large, and resembles that of the geographically closest plethodontids from western North America, especially species of the genus Hydromantes. The biological significance of these cytogenetic characteristics of plethodontid salamanders is discussed within an evolutionary context.     

Preferences for self-care or professional advice for minor illness: a discrete choice experiment

AIM: To determine the relative importance of factors that influence decision making in the management of minor illness, and how people trade between these factors. DESIGN OF STUDY: Discrete choice experiment.Setting:Scottish electoral roll. METHOD: Six hundred and fifty-two responders of a previous national survey were invited to complete a discrete choice experiment questionnaire. This was used to measure relative preferences for managing symptoms of minor illness often associated with analgesic use. Three attributes were identified as important to participants: type of management, availability, and cost of managing symptoms. Trade-offs between these attributes were examined. RESULTS: A 57% response rate was achieved (51% valid response rate). People preferred to manage symptoms by self-care and were willing to pay almost pounds 23 to do so. Community pharmacy was the preferred source of advice. Responders preferred less waiting time and paying less money when managing symptoms, and were willing to trade between factors. A less preferred type of management became more attractive when waiting times and cost were reduced. CONCLUSION: Findings suggest that self-care is the preferred method of managing symptoms of minor illness. When developing services to support self-care, policy makers should invest in services that reduce waiting times and incur least cost to users.     

Changes in the nuclei of astrocytes following portacaval shunting and portacaval transposition in the rat.

Structural abnormalities are found in the astrocytes of the dentate nuclei of animals after portacaval shunting (PCS). These changes are also found in man in association with portal-systemic encephalopathy. To investigate the relationship between portal-systemic shunting and hepatocellular dysfunction in the pathogenesis of these changes, PCS and protacaval transposition (PCT) were performed in rats. PCT diverts portal blood into the systemic circulation, but retains normal total hepatic blood flow by perfusion with systemic venous blood. Liver function and mass are better preserved than after PCS. Abnormal glial cells were found in 4.03% of animals following sham operation, 13.45% following PCT, and 19.09% following PCS. Both experimental groups differed significantly from control animals, and the number of abnormal cells was significantly higher after PCS than after PCT. These findings are in keeping with the hypothesis that hepatocellular dysfunction plays an important role in addition to portal-systemic shunting in the aetiology of the structural changes in the brain associated with hepatic encephalopathy.     

Protection against infection with Neisseria meningitidis group B serotype 2b by passive immunization with serotype-specific monoclonal antibody

Hybridomas derived from mice immunized with Neisseria meningitidis serogroup B serotype 2b (B,2b) outer membrane preparations produced monoclonal antibodies (MAbs) specific for major outer membrane proteins of classes 1, 2, and 5. The MAbs were examined by enzyme-linked immunosorbent assay against a selected panel of seven strains of N. meningitidis (B,2b) of different sodium dodecyl sulfate-polyacrylamide gel electrophoresis patterns, a serotype 2a, and a nontypable strain. The five MAbs selected were all bactericidal and of different immunoglobulin subclasses. None of the MAbs reacted with other bacterial strains in a dot-enzyme immunoassay. The corresponding antigenic determinant for each MAb was localized on a specific outer membrane protein by immunoblotting of sodium dodecyl sulfate-polyacrylamide gel electrophoresis patterns of major outer membrane proteins. MAbs M5-11 and M5-30 bound to the class 2 protein and were serotype 2b specific. MAb M2-20 bound to the class 1 protein, and MAbs M5-16 and M5-19 bound to the class 5 protein. A mouse model of infection was established whereby a local infection progressed to lethal bacteremia over 3 days, and 50% of the animals were killed with an intraperitoneal injection of 10 meningococci plus 4% mucin and 1.6% hemoglobin. The ability of the MAbs to provide passive protection against experimental infection with N. meningitidis (B,2b) was examined. Both serotype-specific MAbs M5-11 and M5-30 were highly protective even though they were of different immunoglobulin subclasses. The class 5-specific MAb offered no protection, while the class 1-specific MAb gave limited protection. It may therefore be possible to provide protection against serotype 2b infection by using as vaccine the class 2 serotype-specific surface-exposed outer membrane protein epitopes defined by MAb M5-11 or M5-30.     

Glomerular epithelial abnormalities associated with the onset of proteinuria in aminonucleoside nephrosis.

A sequential ultrastructural study has been made of glomerular podocytic epithelium before and after the onset of proteinuria induced by daily subcutaneous injections of low doses of puromycin aminonucleoside (PAN). At 4 days, before the onset of proteinuria, the principal change was extensive replacement of podocytic foot processes by broad expanses of epithelial cytoplasm. At 5 days, when proteinuria had developed, the epithelial cells showed in addition multiple cytoplasmic droplets, many large balloon like vacuoles, some of which were ruptured, and many foci of epithelial detachment from the glomerular basement membrane (GBM). Of particular significance, the onset of proteinuria coincided precisely with the development of areas of epithelial detachment that led to direct continuity between externally denuded GBM and the urinary space. It seems likely that these areas are the primary sites of protein leakage across the GBM in this experimental model.     

Psychiatric complications of anabolic steroid abuse

The authors review the literature from human and animal studies on the neurochemical and pathological psychiatric effects of supraphysiological doses of anabolic-androgenic steroids (AAS) and discuss the AAS use and abuse patterns, additional drug use patterns, and personality and behavioral characteristics of AAS abusers.