Biomedical subjects
Publications and source records attributed to N Brown.
A method for the storage of non-diapausing eggs of Simulium ornatum Meigen has been developed. High survival rates for 5-6 months depend on the age of eggs when placed at reduced temperature. A period of precooling or conditioning is required for 28 days before storage of the eggs at 1 degree C with lowering of oxygen partial pressure. Induced quiescence does not appear to affect development from egg to adult.
In a histological survey of 19 mammalian species, Call-Exner bodies of conventional size and appearance were found in only 5, namely, human, rhesus monkey, rabbit, guinea-pig and sheep. Rabbit ovaries were used for characterizing these bodies using quantitative histochemistry, lectin binding and electron microscopy. Call-Exner bodies were topographically distinct lacunae of the extracellular space probably containing hyaluronic acid with proteoglycan complexes. The staining characteristics of the antrum and Call-Exner bodies were generally similar. However, in contrast to the antrum, the smaller lacunae contained suspended filaments with a distinctive peripheral membrane upon which a rosette of granulosa cells was resting. The membrane and narrow intercellular clefts probably prevent much exchange of large glycosaminoglycan complexes with the antrum. The origin and significance of Call-Exner bodies require further study, but it is clear that they are associated with secretion rather than with necrosis as sometimes suggested.
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Data on the temporal and spatial distribution of Biomphalaria alexandrina were collected throughout one year in two village irrigation systems near Alexandria, Egypt. Snails bearing Schistosoma mansoni cercariae were found from May to December but about 80% of annual transmission potential was confined from June to August. Although snail infection rates were generally 0-2%, higher rates were recorded and tended to be associated with smaller number snail collections. Infected snails were found in most canal and drain types and were judged to be present across most of the irrigated area of each village. In view of the dispersed nature of both infected snails and human-water contact in the area, it is suggested that schistosomiasis transmission is more widespread than focal. Effective transmission control using molluscicides should therefore require application to all village irrigation water-courses. The difficulties these various findings might impose on the use of commercial molluscicides are discussed and some possible advantages of the alternative plant molluscicide, Ambrosia maritima are noted.
We have examined the capacity of a series of 6-substituted pyrimidine and 2-substituted purine derivatives to inhibit mammalian thymidine kinase and the thymidine kinases encoded by type 1 and type 2 herpes simplex viruses. Several N2-substituted guanine and deoxy guanosine derivatives displayed selective inhibitory activity against the HSV-1 and HSV-2 thymidine kinases by competing with the phosphorylation of thymidine, suggesting a possible novel pharmacological approach to herpes viruses infections.
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17-Acetylaphidicolin was 10-fold weaker and two derivatives lacking hydroxyl groups at the 16 and 17 positions were 100-fold weaker than aphidicolin as inhibitors of DNA polymerase alpha from HeLa and Chinese hamster ovary cells. 17,18-Diacetyl, 3,17,18-triacetyl and 3-epi derivatives of aphidicolin were inactive. Active compounds were, like aphidicolin, competitive with dCTP and did not inhibit aphidicolin-resistant DNA polymerases.
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We have isolated cDNA clones encoding human IL-3 from libraries constructed in a modified pcD mammalian expression vector by using mRNA prepared from activated human T cell clones. Amino acid sequence of human IL-3 deduced from DNA sequence of these cDNA clones agrees with that predicted from genomic sequence except at amino acid position 27. Northern blotting analysis and S1 nuclease analysis show that almost all activated T cell clones express IL-3 mRNA with kinetics similar to that observed in mouse T cell clones. However, striking difference was found in the level of granulocyte-macrophage-CSF and IL-3 mRNA expressed in activated human T cells. In contrast to mouse T cell clones, granulocyte-macrophage-CSF mRNA is expressed at least two orders of magnitude more abundant than IL-3 mRNA. Yeast Saccharomyces cerevisiae carrying human IL-3 cDNA fused downstream to alpha-factor leader sequence expressed and secreted biologically active IL-3. Several different rat anti-peptide antisera have been used to confirm the presence of human rIL-3 immunochemically. The immunoreactive human IL-3 expressed in transiently transfected COS7 cells or in yeast was observed to be heterogeneous. Human rIL-3 expressed in COS7 cells has multipotential CSF activity in semisolid cultures of bone marrow cells, and selectively induced the proliferation of My-10+ marrow or cord blood cells in liquid cultures.
Emphysematous pyelonephritis is a rare, life-threatening suppurative infection of the renal parenchyma and perinephric tissues. The disease is encountered primarily in patients with diabetes mellitus or ureteral obstruction associated with perinephric and intrarenal gas. Causative organisms are those normally found in the urinary and gastrointestinal tracts; however, anaerobic bacteria have been demonstrated in only 1% of cases. We describe a case of emphysematous pyelonephritis, which presented as an acute abdomen with pneumoperitoneum in a nondiabetic patient. No visceral injury was found at laparotomy. Multiple gas-producing organisms, including Clostridium ramosum (not previously reported, to our knowledge), were the cause of the free intraperitoneal and perinephric air. Subsequent radical nephrectomy revealed a xanthogranulomatous kidney. An aggressive surgical approach combined with intensive antibiotic therapy, after aerobic and anaerobic culture of excised tissue, is lifesaving.
A single dose in the range 0.25-1.0 mg metallothionein-bound cadmium (MT-Cd)/kg body weight, when administered parenterally to the rat between day 8 and day 14 of gestation (gd 8-gd 14), is teratogenic. In vitro, the development of the isolated rat conceptus, explanted at 8.5 days of gestation, is unaffected by the addition of 1.5 microM MT-Cd to the culture medium, whereas the same concentration of ionic Cd (as CdCl2) is lethal. The incorporation of appreciable amounts of Cd into the embryo (860 pg), placenta (970 pg) and yolk sac (65.4 ng) without toxic manifestations under the former conditions suggests that the metalloprotein is incorporated pinocytotically, but without degradation, by the conceptus in vitro. It does not follow, therefore, that MT-Cd is without embryo/foetotoxicity in the pregnant rat since, in-vivo, liberation of some of the protein-bound Cd is known to occur in the blood. At short times after injection of 0.25 mg MT-Cd/kg body weight on gd 12, however, the maximal foetal and placental contents of Cd (less than 25 pg and 2 ng, respectively) are low in comparison with those after a teratogenic dose of CdCl2 and are of the same order as those in the embryo (46 pg) and placenta (100 pg) + yolk sac (3.8 ng) of the rat conceptus, cultured in the presence of the highest no-effect concentration of CdCl2 (0.065 microM). From this evidence, therefore, it is concluded that the uptake by the conceptus in vivo of either CdMT, or of Cd liberated therefrom, is unlikely to contribute to the teratogenic response. In the pregnant, as in the non-pregnant rat, the kidney appears to be the only organ that is affected directly by the metalloprotein. All doses in the range 0.25-1.0 mg MT-Cd/kg body weight are nephrotoxic and, because of this, result in prolonged anorexia in the pregnant animal. While some of the foetal deformities that occur in the CdMT-dosed animal seem to be direct consequences of the renal dysfunction, others apparently are secondary to the maternal anorexia, since they are induced in pregnant, normal rats by appropriate reductions in food intake. In rats that are injected i.p. on gd 12 with 0.25 mg MT-Cd/kg body weight, renal uptake of Cd is slower, but the final concentration is higher than in animals that are given the same dose i.v.(ABSTRACT TRUNCATED AT 400 WORDS)
A series of N2-substituted guanine derivatives was screened against mammalian thymidine kinase and the thymidine kinase encoded by type I herpes simplex virus to examine their capacity to selectivity inhibit the viral enzyme. Several bases, nucleosides, and nucleotides displayed selective activity. The mechanism of action of the most potent derivative, N2-phenyl-2'-deoxyguanosine (PhdG) was studied in detail. PhdG (a) inhibited the viral enzyme competitively with respect to the substrates thymidine and deoxycytidine, (b) was completely resistant to phosphorylation, (c) displayed limited toxicity for the HeLa cell lines employed as hosts for viral infection, and (d) selectively inhibited viral thymidine kinase function in intact cultured cells. The results indicate that the PhdG drug prototype has potential as a selective anti-herpes agent and as a novel molecular probe of the structure and function of herpes simplex thymidine kinase.
The case is described of anorexia nervosa arising in a 62 year old woman with symptoms persisting over the following 5 years.
We measured intact hCG, free alpha hCG, and free beta hCG levels in amniotic fluid and maternal serum using specific monoclonal antibody-based immunoradiometric assays. Compared to maternal serum, amniotic fluid had low levels of intact hormone along with high levels of its free subunits. The mean amniotic fluid hCG level was 1 mg/L at 13 weeks, and it progressively decreased to 0.100 mg/L by the 23rd week. Amniotic fluid alpha hCG levels were highest at 15 and 16 weeks (0.340 mg/L) and rapidly declined to concentrations less than 0.050 mg/L at 21 weeks. Amniotic fluid beta hCG concentrations were about 0.200 mg/L between 13 and 16 weeks and progressively decreased until the 23rd week. In vitro stability studies of hCG and its subunits demonstrated that dissociation of hCG into its subunits was not responsible for these results. Both hCG and free subunits detected in amniotic fluid were indistinguishable from standard hCG and free subunit preparations, as analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Our findings are consistent with the hypothesis that the presence of hCG and free subunits in the amniotic fluid represents secretion from the trophoblastic tissue into the amniotic fluid compartment. Furthermore, high serum hCG levels in association with low levels of its free subunits are probably the result of polarized secretion of the intact hormone from the syncytiotrophoblasts into the maternal circulation.
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Molluscicide resistance literature is reviewed. Alterations in tolerance have been recorded in some laboratory experiments and field surveys but not others. Resistance, as the failure to control a natural snail population, has not been reported. A kit is described for measuring molluscicide susceptibility of snails. A microlitre delivery device is used to prepare molluscicide solutions. Trials have shown that the kit can be used successfully in the field.
We establish that the position-specific antigen 2 (PS2), a Drosophila cell surface glycoprotein complex, is an invertebrate member of the vertebrate fibronectin receptor (integrin) family. New monoclonal antibodies show that in Drosophila embryos and larvae PS2 alpha subunits have a size of ca. 140 kd. Analysis of cDNA and genomic clones revealed that the canonical PS2 alpha subunit contains 1394 amino acids and has extensive homology to the heavy and light chains of integrin alpha subunits. The distribution of the PS2 antigen is regulated at the level of PS2 alpha subunit mRNA. In early Drosophila development the protein is restricted to mesoderm and appears to be involved in muscle attachment. We suggest that PS2, like vertebrate fibronectin receptors, mediates changes in cell shape and cell-extracellular matrix adhesion by binding to a basement membrane protein.