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Biomedical subjects

L May

Publications and source records attributed to L May.

At least 19 recordsLinked to original sources
PubMed1995

Induction of interleukin 6 (IL-6) by hypoxia in vascular cells. Central role of the binding site for nuclear factor-IL-6.

The pathologic picture in ischemic tissue injury shares features with the inflammatory response, including production of proinflammatory cytokines. Hypoxia-mediated induction of interleukin-6 (IL-6), a cytokine with anti-inflammatory properties, could set in motion mechanisms limiting inflammation in ischemia. Exposure of cultured endothelial cells (ECs) to H (pO2 approximately 12-16 torr) increased transcription of IL-6, elevated levels of IL-6 mRNA, and induced elaboration of IL-6 antigen in a time-dependent manner. Exposure of mice to hypoxia increased IL-6 transcripts in the lung, and immunostaining revealed a striking increase in IL-6 antigen in pulmonary vasculature. Transfection of ECs with deletion chimeric IL-6 promoter-chloramphenicol acetyl-transferase (CAT) constructs showed hypoxia-mediated 9-11-fold induction with -1200/+13, -596/+13, and -225/+13 but no induction with -111/+13. Electrophoretic mobility shift assays (EMSAs) using -225/-111 as the labeled probe demonstrated enhanced binding activity in nuclear extracts of hypoxic ECs and lung; the appearance of the gel shift band was prevented by excess unlabeled probe (-225/-111), and hypoxia-mediated enhancement of the band was blocked by a probe corresponding to the nuclear factor (NF)-IL-6 site (-158/-145). The hypoxia-enhanced band on EMSA displayed a supershift with antibody to CCAAT-enhancer-binding protein beta (C/EBP-beta), but antibody to C/EBP-alpha or -delta was without effect. Transfection of ECs with a construct comprising thymidine kinase promoter, -225/-111 in either the 5' to 3' to 5' orientation, and the reporter CAT showed this region to be an enhancer (approximately 8-fold) under hypoxia. EMSA with the NF-IL-6 probe revealed a prominent induction of binding activity with nuclear extracts from hypoxic ECs and whole lung. Constructs with -158/-145 and the CAT reporter gene showed induction when transfected into hypoxic ECs, whereas a similar construct with the NF-IL-6 motif mutationally inactivated failed to display hypoxia-induced expression. Furthermore, the tumor necrosis factor (TNF) gene, whose product contributes to ischemic pathology and contains a putative regulatory NF-IL-6 site, demonstrated enhanced binding activity for its NF-IL-6 motif and induction of TNF mRNA based on analysis of hypoxic lung. These data indicate that hypoxia induces expression of IL-6, most likely a result of hypoxic activation at the NF-IL-6 site, and suggest that other genes with regulatory NF-IL-6 sites may also be induced by a similar mechanism.

Animals↗
PubMed1992

Laser card.

Explore the source record for details and available documents.

Diabetic Retinopathy↗
PubMed1992

Craniosynostosis--corrective surgery for a cosmetic defect.

Premature fusion of the sutures of the skull is known as craniosynostosis, and is characterised by an abnormal skull shape. Early surgery allows the brain to resume its normal shape, encouraging a more natural pattern of development. Nursing care in a craniofacial unit aims to promote maximum physical recovery and improvement, while offering psychological support and understanding to the child and family.

Aftercare↗
PubMed1991

Characterization of bromhexine and ambroxol in equine urine: effect of furosemide on identification and confirmation.

The purpose of this study was two-fold: (1) to develop a simple and sensitive screening procedure for identifying and confirming bromhexine and ambroxol and, (2) to determine the effect of furosemide on the detection of bromhexine, ambroxol, or their metabolites in urine. Female horses (450-550 kg) treated with bromhexine or ambroxol (1 g, p.o.) were used. Urine samples were collected up to 48 h post-drug administration and analysed. Blind samples were used in evaluating the sensitivity of these methods and reproducibility of the results. Bromhexine and ambroxol were extensively metabolized in the horse. These agents and their respective metabolites were identified and confirmed using thin-layer chromatography (TLC) and gas chromatography-mass spectrometry (GC-MS), respectively. Hydroxy-bromhexine and desmethyl-bromhexine were major metabolites found to be unique to bromhexine-treated horses. These metabolites selectively absent from ambroxol-treated horse urine provide a chemical means to distinguish bromhexine from ambroxol administration in horses. These specific metabolites were similarly identified and confirmed in "blind" horse urine samples. The concomitant presence of furosemide (300 mg, i.v.) with bromhexine or ambroxol did not mask the presence of these agents or alter their metabolite profile. By application of the methods described in this study, bromhexine and ambroxol metabolites in horse urine can be easily identified and confirmed.

Ambroxol↗
PubMed1991

Glutathione S-transferases in human liver cancer.

An immunohistochemical study of glutathione S-transferase (GST) expression in hepatocellular carcinoma and cholangiocarcinoma is described. Unlike most animal models of hepatic malignancy pi class GST was not consistently overexpressed in hepatocellular carcinoma. This tumour type either predominantly expressed alpha class GST or failed to express GST. By contrast, cholangiocarcinoma always expressed pi class GST, presumably reflecting the tissue of origin, since in human biliary epithelium pi class GST is the predominant GST. The variable expression of pi class GST which was observed in hepatocellular carcinoma may reflect transformation of hepatocytes damaged by toxins, since this GST can be induced after a chemical insult such as alcohol. As well as indicating the biochemical heterogeneity of hepatocellular carcinoma with respect to GST, this study indicates the need for further study of the nature of inherent drug resistance in these tumour types.

Adenoma, Bile Duct↗
PubMed1991

The effect of postnatal age on the adherence of enterohemorrhagic Escherichia coli to rabbit intestinal cells.

Enterohemorrhagic Escherichia coli (EHEC) are associated with hemorrhagic colitis and hemolytic uremic syndrome. These illnesses are typically seen in young children, but are rare before 6 mo of age. The cause of this age restriction is unclear. Because bacterial adherence to intestinal mucosa is considered a critical initial event in pathogenesis, we studied the ontogeny of the adherence of EHEC (O157:H7 and other serotypes) isolated from children with diarrhea, hemorrhagic colitis, or hemolytic uremic syndrome. Adherence was quantitatively determined by incubating radiolabeled bacteria with viable rabbit intestinal cells, which were prepared by treating loops of distal ileum and proximal colon with EDTA, DTT, and citrate. Cells obtained from animals of different ages were studied simultaneously. The adherence of the various EHEC strains varied significantly. A non-O157:H7 E. coli strain 43-12 bound best (35 and 32 bacteria/cell to ileal and colonic cells, respectively) with 48-60% inhibition by D-mannose and alpha-methyl mannoside (p less than 0.01) and 20-28% inhibition by L-fucose (p less than 0.05), but no significant inhibition by other carbohydrates. Analysis of variance and polynomial regression showed that postnatal age significantly affected the adherence to ileal and colonic cells. Adherence during the 1st wk of life was 13-19% of that in the adult animal; it increased gradually, reaching the adult level at about 4 wk of age. Our study shows that postnatal age affects the adherence of EHEC to intestinal cells. These findings are compatible with postnatal development of gut receptors and may be relevant to the age-related risk of EHEC disease in children.

Age Factors↗
PubMed1990

Glutathione S-transferase localization in aflatoxin B1-treated rat livers.

Overexpression of detoxication enzymes is associated with the development of drug-resistant, preneoplastic nodules in the carcinogen-treated rat liver. The most consistent marker of preneoplasia in many experimental models is increased expression of the pi-class glutathione S-transferase (GST) YfYf. We have confirmed by immunostaining that the pi-class GST is overexpressed in aflatoxin B1-induced preneoplastic nodules and liver tumours in rats. However, pi-class GST YfYf has low activity against aflatoxin B1-8,9-epoxide, and most activity against this cytotoxic and genotoxic metabolite is associated with the alpha-class GSTs YaYa, YaYc and YcYc. We have demonstrated that there is also a consistent increase in the alpha-class GSTs in this model. It seems likely that the overexpression of the Ya and Yc subunits, rather than increased levels of the pi-class GST YfYf, is responsible for the acquisition of a drug-resistant phenotype in rat liver preneoplastic nodules and tumours induced by aflatoxin B1.

Aflatoxin B1↗
PubMed1990

Glutathione S-transferases in alcoholic liver disease.

There is already evidence in alcoholic liver disease, mostly from studies of morphology and cytokeratin distribution, that hepatocytes can undergo a variety of phenotypic changes. This study reports findings of immunohistochemistry using antibodies against members of the glutathione S-transferase supergene family of detoxification enzymes. Hepatocytes in severe alcoholic liver disease coexpressed both alpha and pi class glutathione S-transferase. This coexpression has been previously described only in human fetal liver and in chemically-induced preneoplastic foci in rat liver. The use of function associated markers should provide additional information in the investigation of liver disease.

Adult↗
PubMed1990

Effect of gamma radiation on membrane fluidity of MOLT-4 nuclei.

These experiments measured the effect of gamma radiation on the nuclear envelope using doxyl-fatty acid spin-label probes. Nuclei were isolated from cultured MOLT-4 cells, a radiation-sensitive human T-cell lymphocyte. Membrane fluidity was measured from the electron paramagnetic resonance spectra of the probes. MOLT-4 cells were grown under standard conditions, and suspensions were exposed to 60Co gamma radiation at room temperature. The spectra of 5-doxylstearic acid in the nuclei were those of a strongly immobilized label. A difference in the membrane fluidity was detected in a series of experiments comparing labeled irradiated and nonirradiated nuclei. The change in fluidity was measured by comparing the changes in the order parameter, S, of the spin label in irradiated nuclei with those in control nuclei. The change in the S ratio is dependent on radiation dose, increasing with doses up to 15 Gy. The maximum change of the order parameter with time after irradiation occurs 16-20 h after radiation exposure. These observations are correlated with changes in cell viabilities.

Cell Line↗
PubMed1983

Gamma interferon production by different populations of human splenic lymphocytes.

The treatment of cultures of human splenic lymphocytes with Staphylococcal enterotoxin A (SEA) resulted in the production of human gamma interferon (HuIFN-gamma). Separation of lymphocyte populations to give preparations enriched in T or B lymphocytes after removal of macrophages demonstrated that maximum IFN titers were detected when T lymphocytes were incubated with macrophages for a period of three days. The levels of IFN-gamma varied from donor to donor but the kinetics of induction were quite similar in all cases. Concentrations of 0.5-1.0 microgram/ml SEA gave optimal induction of IFN and the addition of thymosin alpha-1 at 10 micrograms/ml to the culture medium enhanced IFN-gamma production.

Cell Separation↗
PubMed1982

Induction and augmentation of mitogen-induced immune interferon production in human peripheral blood lymphocytes by N alpha-desacetylthymosin alpha 1.

Treatment of human peripheral blood lymphocytes with cloned N alpha-desacetylthymosin alpha 1 induced interferon production. The kinetics is similar to that of mitogen-induced interferon induction. N alpha-desacetylthymosin alpha 1, in combination with mitogen, augments the amount of interferon produced. This interferon is immune interferon (IFN-gamma) as determined by sensitivity to pH 2, lack of neutralization by antibodies to IFN-alpha or IFN-beta and absence of activity of MDBK cells. Although the mechanism of induction of IFN-gamma by N alpha-desacetylthymosin alpha 1 is unclear, this compound is not mitogenic at concentrations causing IFN-gamma production. These results indicate that thymic factors may also participate in the regulation of IFN-gamma-production.

Cells, Cultured↗
PubMed1982

Comparisons of dose-response data for various standard and recombinant DNA-derived human interferons.

Dose responses of the NIH standard IFN-alpha and IFN-beta preparations were compared with recombinant DNA-derived IFN-beta (IFN-beta 1) and various IFN-alpha subtypes, molecular hybrids and mixtures. Cytopathic effect assays were employed using vesicular stomatitis virus on human HeLa and bovine MDBK cells. A natural peripheral blood lymphocyte and recombinant DNA-derived IFN-gamma were also included in the comparisons. Two-tailed t-tests between slopes showed no significant differences in any pair-wise comparison using crude or highly purified preparations.

Animals↗
PubMed1981

Comparison of the antiviral activities of various cloned human interferon-alpha subtypes in mammalian cell cultures.

Five human interferon-alpha (leukocyte) subtypes derived from genes cloned in Escherichia coli have been compared for their ability to induce antiviral activity against vesicular stomatitis virus infection of various mammalian cell cultures. These interferons, designated LeIF-A (IFN-alpha 2), -B, -C, -D (IFN-alpha 1) and LeIF-F, show different relative activities when assayed on human, bovine, hamster, mouse, rabbit and monkey cell lines. As with a natural human buffy-coat interferon-alpha preparation, three subtypes (LeIF-B, -C and -D) showed considerable activity on RK-13 rabbit cells, but two (LeIF-D and -F) also showed some activity on mouse L-929 cells. Of the five interferon subtypes examined, LeIF-F demonstrated the highest degree of species specificity.

Animals↗