Mothers of the earth.
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Conservation of Natural Resources↗
Biomedical subjects
M Black
Publications and source records attributed to M Black.
Simple audit of trainee/trainer consultation profiles as a method of assessing whether non structured surgeries give adequate training.
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Education, Medical, Graduate↗
Hepatotoxic and hepatoprotective potential of histamine (H2)-receptor antagonists.
It has been increasingly recognized that the histamine (H2)-receptor antagonists are associated in rare instances with idiosyncratic hepatotoxic reactions and with drug interactions related to their inhibition of the hepatic cytochrome P-450 enzymes. What have not been appreciated until recently are the potential therapeutic benefits that may be derived from cytochrome P-450 inhibition. Evidence is presented here that cytochrome P-450 inhibition may protect against hepatic damage induced by acetaminophen and other drugs metabolized via this system. Acetaminophen hepatotoxicity is an especially important problem because of the widespread use of this agent and the evidence that the potential for such injury may be increased in alcoholic persons. Cimetidine has been used in selected cases, one of which is described here, to treat acetaminophen hepatotoxicity. All H2-receptor antagonists may not be alike in this regard. Experimental studies in animal models indicate that although cimetidine protects against the hepatotoxic effects of acetaminophen, ranitidine may actually potentiate hepatic damage. It is thought that the difference between these two H2-receptor antagonists may lie in their affinities for binding to the cytochrome P-450 enzymes. Cimetidine, which binds more strongly, inhibits this system more efficiently, whereas the inhibition produced by ranitidine is not sufficient to confer a protective effect against drug-induced hepatotoxicity.
Acetaminophen↗
Purification and characterization of human liver cytochrome P-450-ALC.
Cytochrome P-450-ALC, an ethanol-oxidizing form of microsomal cytochrome P-450 (P-450), has been purified from human liver. P-450-ALC (Mr = 54,000 daltons) is a low-spin ferric hemeprotein with a CO-reduced Soret maximum at 452 nm, and has an NH2-terminal amino acid sequence nearly identical to that deduced from a human P-450-ALC cDNA clone. In a reconstituted system, P-450-ALC oxidizes ethanol and aniline at turnover rates (12.2 and 7.3 nmol min-1, respectively) 10-fold greater than two other human P-450 isozymes (termed P-450-B and P-450-C) purified from the same liver. Both P-450-ALC and P-450-C effectively demethylate N-nitrosodimethylamine (NDMA) at low substrate concentrations (0.5 mM), especially in the presence of cytochrome b5. Our results provide direct evidence for a liver P-450 isozyme in humans with catalytic properties similar to the related alcohol-inducible rodent P-450s and also reveal a new human NDMA demethylase.
Amino Acid Sequence↗
Identification of a human liver cytochrome P-450 exhibiting catalytic and immunochemical similarities to cytochrome P-450 3a of rabbit liver.
Immunoblot analysis of liver microsomes from nine patients demonstrated that each contained a cytochrome P-450 that reacted with an antibody directed against the ethanol-inducible rabbit liver cytochrome, P-450 3a. Two of the liver specimens exhibited high concentrations of the immunoreactive protein, high rates of aniline hydroxylation and N-nitrosodimethylamine demethylation, and extensive inhibition of activity in the presence of antibody to P-450 3a. One other liver specimen exhibited a very low rate of aniline hydroxylation with significantly less antibody inhibition. The variability witnessed was independent of the alcohol history of the individual patients, suggesting that the human cytochrome may be under some other environmental, dietary or genetic regulation. Its inducibility by ethanol was not directly studied in this investigation. However, we conclude that there is a cytochrome P-450 present in human liver which is immunochemically and catalytically similar to the ethanol-inducible P-450 of rabbit liver.
Aniline Hydroxylase↗
Hepatic cytochrome P-450 system in experimental hepatosplenic schistosomiasis. Presence of an artifact in spectrophotometric analysis.
Several recent reports suggesting that the liver microsomal cytochrome P-450 system is impaired in Schistosoma mansoni infections in mice prompted a detailed investigation of the hepatic cytochrome P-450 system in murine schistosomiasis. Mice were prepared with three levels of Schistosoma mansoni infection and studied 8, 12 and 14 weeks post-exposure. Histological sections of the liver confirmed prominent granuloma formation and portal fibrosis which was dose and time dependent. Cytochrome P-450 levels appeared reduced grossly in microsomes from homogenates of infected livers, but accurate quantitation was complicated by the presence of a prominent peak at 422 nm. Ethylmorphine N-demethylase activity also appeared to be reduced in all infected animals, reaching a maximum decrease at 14 weeks of 44% of control values in the most heavily infected mice. NADPH-cytochrome c reductase activity and cytochrome b5 levels were similarly reduced. Utilization of techniques to separate hepatocytes from granulomatous material in infected livers eliminated the 422 nm peak and reversed several of the findings made with whole-liver derived microsomes. Cytochrome P-450 levels were reduced modestly (30%) at 8 weeks in the most heavily infected mice but returned to normal values by 14 weeks. Specific ethylmorphine N-demethylase activity of isolated hepatocytes was increased at 8 weeks with a return to normal by 14 weeks. Isolated granulomata were incriminated as one possible source of the 422 nm pigment in whole-liver derived microsomes but appeared unlikely to account fully for this finding. Thus, this investigation concluded that the cytochrome P-450 system is altered by experimental murine hepatosplenic schistosomiasis, but such alterations are subtle in nature and unlikely to contribute in major fashion to the observed changes in drug disposition.
Animals↗
Passive Heymann nephritis induced by rabbit antiserum to membrane antigens isolated from rat visceral yolk-sac microvilli.
Passive Heymann nephritis (PHN) is an animal model of immune-complex-induced renal disease resembling human membranous glomerulonephritis. It was induced in rats by injecting rabbit antiserum directed against glycoprotein antigens isolated from rat embryonic visceral yolk-sac microvilli (VYS-MV). The glycoprotein antigens were isolated by extracting the VYS-MV with detergent Nonidet P-40 followed by gel filtration in Sephacryl S-300 and finally by lectin affinity chromatography with Ricinus communis agglutinin I. In vitro immunofluorescent localization studies demonstrated that the nephritogenic antibodies were localized along the apical region of the visceral yolk-sac endodermal cells and the brush border of the proximal tubular cells of the kidney. Rats injected with a single dose of the antiserum manifested proteinuria. Indirect immunofluorescent studies showed that the injected rabbit IgG was localized in vivo along the capillary walls of the glomerulus in a granular fashion. Electron microscopic examination of the same kidney glomeruli revealed numerous electron-dense deposits along the lamina rara externa of the glomerular basement membrane. Fusion of the epithelial foot processes was also present. These findings represent the typical immunopathological characteristics of Heymann nephritis. Furthermore, with the aid of Ouchterlony analysis, the antiserum against the isolated VYS antigens exhibited an immunoprecipitin band which was in common with that formed by the antiserum against the homogeneous nephritogenic antigen (gp330) of renal brush border origin. Thus, the nephritogenic antigens which have been found to be associated with the brush border of the renal proximal tubules may also be present or cross-reacted in the microvilli of the rat embryonic visceral yolk-sac.
Animals↗
The children and the nations in the post-war world.
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Child↗
Detection of Chlamydia trachomatis infection by direct immunofluorescence staining of genital secretion.
A monoclonal antibody specific for Chlamydia trachomatis (Syva Microtrak) was used to stain directly 249, 127, and 67 specimens obtained from the cervix, and the female and the male urethra, respectively. The Microtrak system identified 100% or 23 culture-positive cases from the cervix (prevalence 9.2), 100% or seven culture-positive cases from the female urethra (prevalence 5.5%), and 93% or 14 culture-positive cases from the male urethra (prevalence 22.4%). Because the Microtrak system is readily available, relatively inexpensive, and easy to read with a fluorescent microscope, it should become a valuable tool to assess objectively both men and women suspect for this common sexually transmitted disease.
Chlamydia Infections↗
A novel chlorophyll a/b binding (Cab) protein gene from petunia which encodes the lower molecular weight Cab precursor protein.
The 16 petunia Cab genes which have been characterized are all closely related at the nucleotide sequence level and they encode Cab precursor polypeptides which are similar in sequence and length. Here we describe a novel petunia Cab gene which encodes a unique Cab precursor protein. This protein is a member of the smallest class of Cab precursor proteins for which no gene has previously been assigned in petunia or any other species. The features of this Cab precursor protein are that it is shorter by 2-3 amino acids than the formerly characterized Cab precursors, its transit peptide sequence is unrelated, and the mature polypeptide is significantly diverged at the functionally important N terminus from other petunia Cab proteins. Gene structure also discriminates this gene which is the only intron containing Cab gene in petunia genomic DNA.
Amino Acid Sequence↗
Abnormal regulation of insulin secretion in the genetically obese (ob/ob) mouse.
To determine whether the abnormal insulin-secretory activity encountered in obese mice is due to an anomaly in the production of cyclic AMP, islets of lean and obese mice were incubated with forskolin under various conditions. Our data show that, in addition to the well-known quantitative differences in insulin-secretory activity between islets of lean and obese mice, there are important qualitative differences. The islets of obese mice accumulated less cyclic AMP than did those of lean mice in response to given doses of forskolin, yet their insulin secretion was enhanced to much higher values. In the islets of obese mice, but not in those of lean mice, the stimulatory effect of forskolin on insulin secretion was evident even at non-stimulatory concentrations of glucose or in Ca2+-deprived incubation media, showing that the islet of the obese mouse is less dependent on a primary stimulus (glucose) and on the provision of normal concentrations of Ca2+ in the bathing medium than is the islet of the lean mouse.
Animals↗
Magnetic resonance imaging diagnosis of Budd-Chiari syndrome.
Noninvasive imaging modalities may suggest the diagnosis of Budd-Chiari syndrome but they are rarely diagnostic. Inferior vena cavography, hepatic venography, and liver biopsy, alone or in combination, are usually necessary for definitive diagnosis. Because of its excellent depiction of blood vessels as regions of absent signal, magnetic resonance imaging has the potential to make a noninvasive diagnosis of hepatic vein thrombosis. A case illustrating the usefulness of magnetic resonance imaging in the diagnosis of Budd-Chiari syndrome is presented.
Adult↗
Frozen recovered red cell boosting of female donors for anti-D-production.
A selected group of women previously immunized in pregnancy by the Rh(D) antigen were boosted with 0.5 ml of Rh(D)-positive frozen recovered red cells from an accredited donor panel. The response was prompt and sustained and increased the anti-D content by almost 10-fold. In spite of the reduced rate of clinical immunisation to the Rh(D) antigen, it was possible to recruit females with anti-D, acquired in pregnancy, for secondary boosting and a programme is recommended which maximizes efficiency and safety.
Adult↗
Acetaminophen, alcohol, and cytochrome P-450.
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Acetaminophen↗
A case-control study of caffeine and methylxanthines in benign breast disease.
A dietary case-control study of 854 histologically diagnosed cases of benign breast disease (BBD), 755 matched surgical controls, and 723 matched neighborhood controls was conducted in Israel between 1977 and 1980. No association between coffee consumption and BBD was found. Analyses by histological type, degree of ductal atypia, age, sex, and ethnic origin, controlling for several confounding factors, confirmed the lack of association. The estimated mean intake of methylxanthines was also similar for cases and controls (302, 312, and 313 mg for cases, surgical controls, and neighborhood controls, respectively). No evidence of a dose-response was noted. Our results suggest that there is no association between coffee or methylxanthine consumption and BBD, although we had a 70% chance of finding a risk ratio of 1.5 with an error of 5%.
Adult↗
Photocontrol of Hypocotyl Elongation in Light-Grown Cucumis sativus L. : Responses to Phytochrome Photostationary State and Fluence Rate.
The effects of the calculated photostationary state of phytochrome (phi(c)) and the photon fluence rate on the elongation growth of the hypocotyl of light-grown seedlings of Cucumis sativus L. are examined. Two threshold responses to phi(c) are found at values of 0.06 and 0.43. At phi(c) = 0.06, there is no response at any fluence rate. In the phi(c) range 0.1 to 0.43, elongation growth does not respond to changes in phi(c). Above the second threshold (phi(c) = 0.43), there is a strong response to changes in phi(c). At all values of phi(c) at and above 0.1, there is a response to fluence rate. A linear relationship can be demonstrated between a factor comprised of the logarithm of phytochrome cycling rate (a fluence-rate-dependent process) and phi(c), and the growth response.
Journal Article↗
Colloid milium: a final degeneration product of actinic elastoid.
Serum amyloid P component (SAP) is present not only in all types of cutaneous amyloidosis, but also in the normal dermal elastic fibers as well as abnormal elastic fibers, such as elastotic degeneration of elastic fibers in actinic keratosis. It was previously postulated that the colloid substance in colloid milium is a final degeneration stage of actinic elastosis. In a lesion of colloid milium SAP was intensely positive with an indirect immunofluorescence method using rabbit antiserum to human SAP. Electron microscopy of the colloid lesion revealed components of normal elastic fibers as well as those of actinic elastoid as seen in actinic elastosis. It is concluded that the colloid substance derives, at least in major part, from elastic fibers through actinic degeneration.
Aged↗
Measurement of antigen-specific IgE in nasal secretions of patients with perennial rhinitis.
Sixteen of 53 patients with rhinitis had positive skin tests corresponding with serum-specific IgE (RAST). Concomitant positive nasal secretion (NS) RAST was found in 10/16. Four patients with both negative skin tests and serum RAST had positive NS RAST. In a subset of patients with perennial rhinitis, specific IgE may be detected only in NS. Further studies are necessary to document the clinical relevance of such NS IgE antibodies.
Absorption↗