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Biomedical subjects

J L Clarke

Publications and source records attributed to J L Clarke.

27 records · Page 2Linked to original sources

Identification of an autoantibody to vascular endothelial cell-specific antigens in patients with systemic vasculitis.

PURPOSE: Although immunologic mechanisms have been postulated in the pathogenesis of vasculitis, an autoimmune process directed against specific autologous vascular wall antigens has not been previously documented. We examined the role of an immunologic response to vascular endothelial cell (VEC) antigens in patients with vasculitis, because of the observed immunogenicity of VECs in renal and cardiac allograft recipients. PATIENTS AND METHODS: The study patients included 21 with systemic vasculitis and four with hypersensitivity vasculitis. A healthy, normal control group consisted of 51 young subjects and 61 older subjects. Thirty-two patients with connective tissue diseases were also evaluated. The presence of autoantibody to autologous monocytes and other cell types was determined with previously described standard crossmatch techniques. Patient sera exhibiting autoantibody to autologous monocytes were screened against a panel of allogeneic cells. The cell panel consisted of concordant T and B lymphocytes, monocytes, and VECs from 16 umbilical cord donors. Sera from four patients were analyzed for specificity to the vascular endothelium of frozen sections of vessels. RESULTS: An autoantibody to VEC antigens was detected in 18 of the 21 patients (86%) with confirmed systemic vasculitis, not of the hypersensitivity type. This autoantibody was highly cytotoxic, complement-fixing, and specific for antigens on the surface of the VEC. Findings on allogeneic VEC panel analysis support the existence of multiple allotypes in the VEC antigen system. In three patients, fluctuations in the titer of the autoantibody generally correlated with clinical symptoms. In the four patients screened for the specificity of the autoantibody to anatomically different cadaveric blood vessels, specific anatomic patterns of reactivity were observed. Autoantibody to VEC antigens was not found in young controls and was documented in low frequency in older controls and in patients with connective tissue diseases. The autoantibody was seen in one of four patients (25%) with hypersensitivity vasculitis. CONCLUSION: Our results indicate that an autoantibody to VEC antigens may be involved in the pathogenesis of systemic vasculitis or may be a diagnostic marker for the disease process.

Adolescent↗

Distribution and ovarian control of progestin-metabolizing enzymes in various rat hypothalamic regions.

The three principal hypothalamic progesterone metabolizing enzyme activities, namely the progesterone 5 alpha-reductase and 5 alpha-dihydroprogesterone NADH- and NADPH-linked 3 alpha-hydroxysteroid oxidoreductase (3 alpha-HSOR) activities, were examined in discrete rat hypothalamic subsections throughout the estrous cycle and from ovariectomized rats treated with estradiol benzoate or vehicle. The regions studied included the median eminence, the medial preoptic area and the ventromedial and arcuate nuclei. The enzyme assays were performed using radiolabeled steroid substrates and reverse isotopic dilution analysis. While all four hypothalamic regions obtained from intact cycling animals possessed substantial amounts of these three enzyme activities, the median eminence generally had the highest activity levels (2- to 4-fold greater) except during estrus. The other three regions usually had comparable levels. No significant fluctuations were observed in any enzyme activity over the estrous cycle. After ovariectomy, there was a significant decrease (approximately 35%) in the level of the NADPH-linked 3 alpha-HSOR activity in the median eminence compared to the level observed in intact cycling animals, suggesting ovarian control. Estrogen treatment for 3 days did not restore this enzyme level to that observed in intact animals. The NADPH-linked 3 alpha-HSOR activity from the other three hypothalamic regions, as well as the NADH-linked 3 alpha-HSOR and the 5 alpha-reductase activities from all four brain regions, did not change significantly after ovariectomy. These results indicate that the median eminence possesses an increased capacity for progesterone metabolism relative to the other hypothalamic regions tested, and that the NADPH-linked 3 alpha-HSOR activity in this region may be under ovarian control.

20-alpha-Dihydroprogesterone↗

Assessment of insecticidal impact on the malaria mosquito's vectorial capacity, from data on the man-biting rate and age-composition.

The reduction in average age of a vector population after application of a residual insecticide is commonly interpreted under the implicit assumption that the vector population is uniformly exposed to the insecticide. This assumption maximizes the calculated impact of the insecticide on the vectorial capacity. An alternative assumption, namely that the vector population is composed of two subpopulations, one endophilic and exposed, the other exophilic and not exposed, leads to a much smaller calculated impact of insecticide on the vectorial capacity. This is illustrated with data collected before and after application of propoxur in the Garki District, Kano State, Nigeria. These data were also used to estimate, on the one hand, before spraying, the proportion of blood meals taken by Anopheles gambiae s.l. on man that are followed by rest indoors, and on the other hand, after spraying, the proportion exposed after the first blood meal, according to the model of non-uniform exposure; the two estimates agree fairly well. The discussion compares the models of uniform and non-uniform exposure in terms of plausibility and concludes that the latter is more realistic. It is therefore prudent to take it into account when evaluating the impact of insecticides on the transmission of malaria.

Anopheles↗

The impact of propoxur on Anopheles gambiae s.1. and some other anopheline populations, and its relationship with some pre-spraying variables.

A significant and stable difference in the residual night-biting collection (NBC, observed/expected) of A. gambiae s.l. was observed among different villages of the West African savannah when sprayed for 2 years with propoxur. The residual mosquito density of a given village was positively associated with some of its pre-spraying characteristics: the NBC/PSC (pyrethrum spray collections) ratio, the median biting hour, and possibly the proportion of species B. It was not significantly associated with several other pre-spraying characteristics (absolute mosquito density, the ratios between NBC indoors and NBC outdoors, between ETC (exit-trap collections) and PSC, between fed and gravid in the PSC or ETC, between males and females in the PSC), and was not associated with variations in recorded coverage, with latitude, or with distance from unsprayed villages.In a comparison between A. gambiae s.l., A. funestus, and A. pharoensis, the residual NBC (observed/expected) was positively associated with the pre-spraying NBC/PSC ratio, and was negatively associated with the median biting hour.The pre-spraying NBC/PSC ratio thus appears to be a predictor of the variation, between villages or species, in the reduction of the NBC by residual spraying, and may assist in forecasting the effect of a residual insecticide. The limitations of any absolute prediction must, however, be kept in mind.

Animals↗

Use of larvivorous fish for vector control in the Malvides Republic.

The paper reports on the use of three larvivorous fishes in the Maldives Republic: Poecilia reticulata (Poeciliidae), Mollienesia sphenops (Cyprinodontidae) and for the first time Kuhlia taeniurus (Kuhliidae), a sea fish adapted to life in wells, which are the only sources of water supply (with the exception of a few rain-water cisterns). The approximately 20 000 wells are the main and all-year-round breeding places for both Anophelines and Culicines. Due to this type of breeding places, Maldives are in a unique situation, that the fish can theoretically be used as the main control measure for filariasis. This requires an absolute minimum of work and no cost at all. There has been a reduction of the filariasis overall endemicity rates over the last 10 years although no specific measures have been carried out (except in the capital city of Male) nor have any ecological changes taken place, which could explain this decrease. With this decrease however there has been lately a marked reduction in the percentage of wells with fish in some atolls.

Animals↗