The continuing significance of race: a study of race, class, and quality of life in America, 1972-1985.
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History, Modern 1601-↗
Biomedical subjects
M Hughes
Publications and source records attributed to M Hughes.
A transition-state analogue inhibitor of human renin (H.261): test in vitro and a comparison with captopril in the anaesthetized baboon.
H.261, a new transition state inhibitor of human renin with an IC50 of 6.9 X 10(-10) M, was given by intravenous infusion to six anaesthetized baboons. The inhibitor was infused first at 0.1 mumol/kg/h for 15 min, then at 1.0 mumol/kg/h for a further 15 min. After a recovery period of 2 h in which the animals received 5% dextrose, they were infused with captopril, 25 mumol/kg/h for 15 min. At both rates of infusion H.261 markedly and significantly reduced the enzymatic action of renin in plasma, the blood concentration of angiotensin I, the plasma concentration of angiotensin II and mean arterial pressure. All changes reverted towards or to control values in the subsequent control period. Captopril also lowered plasma angiotensin II concentration and mean arterial pressure markedly and significantly but, as expected for an inhibitor of the angiotensin I-converting enzyme, plasma active renin concentration and blood angiotensin I concentration increased. The changes of angiotensin II and arterial pressure were similar with captopril and H.261.
Angiotensin I↗
The morphology of redox-dye-treated HbH-containing red cells: differences between cells treated with brilliant cresyl blue, methylene blue and new methylene blue.
The ultrastructure of redox-dye-treated HbH-containing red cells has been shown to be dependent on the nature of the redox dye used. Brilliant cresyl blue causes the formation of a large number of small inclusions which are invariably attached to the inner surface of the red cell membrane. Methylene blue and new methylene blue cause the formation of a much smaller number of larger inclusions only some of which appear to be membrane-bound. These ultrastructural differences are reflected in marked differences in the light microscope appearances of the supravitally-stained cells.
Adult↗
Increased co-activation of the upper limb muscles in writer's cramp.
Eleven patients with writer's cramp were studied during the performance of a series of writing and non-writing tasks. Their performance in the tasks and the intensity of contraction in the flexor and extensor muscles of the fingers and elbow (recorded electromyographically) were compared with the results from a group of matched normal controls. The patients showed highly significant increases in muscle activation especially in the triceps muscle which was overactive in all but one of the tasks undertaken. Psychometric testing showed no difference between patients and controls. The results support the view that writer's cramp is a form of focal dystonia in which the disorder of motor control is not confined to writing activities.
Adult↗
Is intestinal transport of sugars and amino acids subject to critical-period programming?
Physiological responses include three sorts: reversible within an individual's lifetime, fixed irreversibly at some critical period in life, and genetic. Examples of the first and third but not the second sort have been demonstrated for intestinal nutrient transport. Hence, we searched for critical-period programming of sugar and amino acid transport by mouse small intestine. Mice were maintained on either of two rations from gestation through birth, lactation, and weaning until adulthood: a high-carbohydrate, maintenance-protein ration and a carbohydrate-free, high-protein ration. The two groups of mice were then compared in adulthood while both groups were on the former or the latter ration. Early diet has irreversible effects on gut and body size; because of higher growth rates until weaning mice receiving high-carbohydrate diets achieved and maintained higher weights, longer guts, and heavier proximal guts than the mice receiving carbohydrate free diets. This difference increased with litter size and may have arisen from limitations on nursing mothers' ability to convert dietary protein into milk carbohydrate or fat. Early diet appears to exert some general effects on adult intestinal transport as a result of these differences in body and gut size but does not appear to exert specific irreversible effects on transport of D-glucose, L-proline, L-leucine, L-lysine, or L-aspartate or on passive glucose permeability. Active and passive glucose transport increases reversibly on a high-carbohydrate diet, whereas amino acid transport increases reversibly on a high-protein diet.
Amino Acids↗
The apamin-sensitive Ca2+-dependent K+ channel molecular properties, differentiation and endogenous ligands in mammalian brain.
Apamin is a bee venom neurotoxin of 10 amino acids containing two disulphide bridges. Current-clamp and voltage-clamp experiments have shown that apamin externally applied blocks specifically at low concentration (0.1 microM) the Ca2+-dependent slow K+ conductance which mediates the long-lasting after-hyperpolarization in neuroblastoma cells and rat muscle cells in culture. The apamin-sensitive Ca2+-dependent slow K+ conductance is voltage-dependent and tetraethylamonium-insensitive. It is distinct from the high conductance Ca+-dependent K+ channel revealed by patch-clamp experiments. Biochemical characterization of the apamin receptor in rat striated muscle, neuroblastoma cells, rat synaptosomes, smooth muscles and hepatocytes was carried out with the use of a radiolabelled monoiodo-apamin derivative (125I-apamin) of high specific radioactivity (2000 Ci/mmol). The dissociation constant of the apamin-receptor complex is between 15 and 60 pM for all tissue preparations. The density of binding sites is very low: between 1 and 40 fmol/mg of protein. Radiation-inactivation analysis indicates a molecular mass for the apamin receptor of 250 000 Da whereas affinity labelling with 125I-apamin results in covalent labelling of a single polypeptide chain with a molecular mass of about 30 000 Da. Autoradiography of 125I-apamin binding sites reveals the presence of Ca2+-activated K+ channels in many regions of the brain. There is an all-or-none control of the expression of the apamin-sensitive Ca2+-dependent K+ channel by innervation in mammalian skeletal muscle. There exists an endogenous equivalent of apamin in rat brain.
Action Potentials↗
American Academy of Pediatrics. Committee on School Health. Health Education and schools.
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Health Education↗
Unwinding of the DNA helix in simian virus 40 chromosome templates by RNA polymerase.
We measured the distortion of the DNA helix by RNA polymerase transcribing simian virus 40 (SV40) chromosome templates and compared it with the distortion caused by the enzymes as it transcribes naked SV40 DNA, using RNA polymerase from Escherichia coli. Purified DNA topoisomerase I was added to the transcription reactions and the number of supercoil turns in DNA, after deproteinising and removal of RNA, was determined by gel electrophoresis and band-counting. The number of polymerase molecules bound per naked DNA molecule was determined by electron microscopy. Each bound RNA polymerase distorted the template in such a way as to lead to on apparent average of 0.6-0.7 negative superhelical turn in the extracted DNA. Thus only few base-pairs are melted per RNA polymerase molecule. When SV40 chromosomes were transcribed the extracted DNA had a higher number of supercoil turns than DNA extracted from the initial chromosomes. We conclude that the polymerase deforms the DNA in chromatin in the same way as it deforms pure DNA. From control experiments with inhibitors of initiation we estimated that on average 9-10 RNA polymerase molecules were bound per SV40 chromosome. This suggests that transcription can proceed while the majority or all the nucleosomal structures are intact on an SV40 DNA molecule. We discuss the implications of these findings for the mechanism of transcription of chromatin.
DNA Topoisomerases, Type I↗
The Chepstow feeding aid.
A specially designed spoon or scoop has been developed to enable controlled amounts of semi-solid food to be accurately and easily inserted into the mouth. This device simplifies feeding following major surgery for intra-oral cancer. Its use and other possible applications are described.
Female↗
Toxicity of 4-nitroquinoline 1-oxide in Chinese hamster ovary cells: influence of cell density and of position in the cell cycle.
Various factors influencing toxicity of 4-nitroquinoline 1-oxide (4-NQO) in Chinese hamster ovary cells were determined. Cell density during 4-NQO treatment and volume of treatment medium had a great effect on cell survival indicating that not the 4-NQO concentration per se, but the amount of 4-NQO per cell determines the toxic effect. When the cell-cycle response for 4-NQO-induced cell killing was measured in synchronous cells, a characteristic age response was seen in wild-type cells with greatly increased sensitivity in late G1 to early S and resistance increasing through the S-phase. In contrast, a UV-hypersensitive mutant, which is also more sensitive to 4-NQO showed only minor cell-cycle variations in its response to 4-NQO. Therefore, it appears that the cell-cycle pattern observed in the wild-type cells is associated with DNA repair.
4-Nitroquinoline-1-oxide↗
Factors affecting the choice of anesthesiology by medical students for specialty training.
To learn some of the reasons why anesthesiology as a specialty is not preferred by more graduating medical students and to determine the effects of various factors on their specialty choice, the authors studied the number of medical students who chose anesthesiology as a specialty after graduation and the quality of clerkships available in various departments. The study established that medical students do not find anesthesiology as attractive as other specialties and that several factors are related to the students' choice of anesthesiology. Most surprising was the negative effect of the presence of certified registered nurse anesthetists on the operating room floor. These results suggest the need for a thorough study of the use of nurse practitioners, physician's assistants, and nurse-clinicians, at least where teaching of medical students is taking place.
Anesthesiology↗
Ultrastructure and cell cycle distribution of erythropoietic cells in heterozygotes and homozygotes for haemoglobin E.
Marrow aspirates from heterozygotes and homozygotes for haemoglobin E (HbE) have been studied by electron microscopy and by the technique of combined Feulgen microspectrophotometry and 3H-thymidine autoradiography. The erythropoietic cells of heterozygotes did not contain any precipitated globin chains and the proliferating erythroblasts of such individuals showed no abnormality in their distribution in the different stages of interphase. By contrast, 0-1.5% of late erythroblast profiles and 3.1-12.8% of marrow reticulocyte profiles of homozygotes contained intracellular inclusions resembling precipitated alpha-chains. Although precipitated globin chains were not seen in the early polychromatic erythroblasts of homozygotes, the number of these cells in the G2 phase relative to that in the S phase was increased. These data indicate that there is probably little or no imbalance of globin chain synthesis in heterozygotes, a substantial degree of imbalance in homozygotes, and a disturbance of erythroblast proliferation in homozygotes which cannot be attributed to the deleterious effects of detectable intracellular alpha-chain precipitates. The electron microscope and cell cycle distribution data in the homozygotes for HbE were similar to those in two heterozygotes for beta thalassaemia.
Bone Marrow↗
The fate of excess beta-globin chains within erythropoietic cells in alpha-thalassaemia 2 trait, alpha-thalassaemia 1 trait, haemoglobin H disease and haemoglobin Q-H disease: an electron microscope study.
Electron microscope studies have been performed on bone marrow cells from individuals with various alpha-thalassaemia syndromes. Globin chain precipitates were rarely found in the erythropoietic cells of a subject with alpha-thalassaemia 2 trait. By contrast, such precipitates were found in 0.6 - 1.3% of the erythroblast and marrow reticulocyte profiles in two cases of alpha-thalassaemia 1 trait, 2.1 - 13.7% of profiles in five patients with haemoglobin H (HbH) disease and 6.2% of profiles in one patient with haemoglobin Q-H (HbQ-H) disease. In the patient with HbQ-H disease, but not in the others, the nuclei of some erythroblasts displayed the 'Swiss cheese' appearance which has been reported in some forms of congenital dyserythropoietic anaemia. It is proposed that in alpha-thalassaemia 2 trait, where the degree of excess of beta-chains is slight, most of the excess chains are degraded by proteolysis. In alpha-thalassaemia 1 trait, where there is a greater excess of beta-chains, the excess chains can undergo either proteolysis or precipitation, but there is little or no tetramerization to form soluble HbH. Finally, in HbH disease, where the degree of excess is considerable, the excess beta-chains may be subject to proteolysis, precipitation and tetramerization.
Adult↗
Respiratory syncytial virus infection in mice.
The A2 strain of human respiratory syncytial virus replicated in the nose and lung of BALB/c mice, with virus growing to higher titers in older animals than in younger animals. Virus was recovered from the nose between days 2 and 7 with peak titers on days 3 and 4, and from the lungs between days 2 and 9, with peak titers on days 4 through 6. Serum antibody developed 2 weeks after infection. Viral antigen was demonstrated in the alveolar cells of the lung by immunofluorescence. Histopathological changes included infiltration by mononuclear cells of the peribronchiolar and perivascular tissue, some interstitial thickening, and formation of multinucleated giant cells. Virus could not be recovered from the respiratory tract of mice inoculated with bovine strains of respiratory syncytial virus. Growth of the A2 strain of human respiratory syncytial virus in different cell lines affected its infectivity for mice. Infection of BALB/c mice with respiratory syncytial virus provides a highly reproducible model for the study of the pathogenesis of and mechanisms of immunity to this virus.
Age Factors↗
Production and characterization of monoclonal antibodies to tetanus toxin.
Monoclonal antibodies against tetanus toxin were produced to obtain highly specific antisera. Ten hybridoma cell lines producing monoclonal antibodies were derived from the fusion of rat myeloma cells and spleen cells from rats immunized with tetanus toxoid. Eight produced monoclonal antibodies specific for determinants on toxin and toxoid, whereas two were specific only for determinants on the toxoid. The antibodies produced by hybridomas were characterized by determination of the class of light and heavy chain components, epitope specificity, toxin neutralization, and subunit specificity. All of the antibodies contained kappa light chain, eight contained the gamma 1 heavy chain, and the remaining two contained the gamma 2a heavy chain. Five distinct epitopes were indicated by competition assay of paired monoclonal antibodies, and 4 of the 10 monoclonal antibodies neutralized the in vivo activity of tetanus toxin. The four neutralizing monoclonal antibodies and one other were specific for the C fragment of the heavy chain of the toxin molecule.
Animals↗
Good health is good business.
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Health Education↗
Monoclonal antibodies protect against respiratory syncytial virus infection in mice.
Twenty-five monoclonal antibodies (Mab) to respiratory syncytial virus (RSV) and two to hepatitis B virus were inoculated intravenously into mice. Twenty-four hours later the mice were challenged intranasally with RSV. Eleven of 14 Mab against fusion protein and four out of six Mab against a larger glycoprotein (GP84) significantly reduced the titre of RSV in the lungs when mice were killed 5 days later. Five Mab against three other RSV proteins and two Mab against hepatitis B virus had no significant effect on RSV infection. These results indicated that serum IgG against one epitope on the fusion protein and another on the larger glycoprotein (GP84) will completely protect mice against challenge. These epitopes are primary candidates for an RSV vaccine produced by techniques of gene cloning and peptide synthesis.
Animals↗
Globin chain precipitation, deranged iron metabolism and dyserythropoiesis in some thalassaemia syndromes.
Electron microscope studies of the erythropoietic cells have revealed two morphologically distinct types of intracellular inclusion in homozygous beta-thalassaemia and HbH disease, presumably reflecting different appearances of precipitated alpha- and beta-chains, respectively. Inclusions resembling those seen in homozygous beta-thalassaemia are also seen in HbE/beta-thalassaemia and to a lesser extent in heterozygous beta-thalassaemia. Dyserythropoietic changes including those indicative of deranged iron metabolism, are seen in some erythropoietic cells in all of the above-mentioned thalassaemia syndromes. Several of these changes are most prominent in homozygous beta-thalassaemia and HbE/beta-thalassaemia, less marked in heterozygous beta-thalassaemia and least prominent in HbH disease. There are gross disturbances of proliferation and protein biosynthesis in erythroblasts in homozygous beta-thalassaemia but not in HbH disease and this difference is reflected in a much greater degree of ineffective erythropoiesis in the former than in the latter. Results of studies into the relationship between the extent of alpha-chain precipitation in individual cells and both the disorder of proliferation and of protein biosynthesis are consistent with the view that these functional disturbances are related to the presence of precipitated alpha-chains and/or an expanded intracellular soluble alpha-chain pool. Some alpha-chains precipitate on centrioles and, presumably, thereby interfere with mitosis. The biochemical changes in the cell membrane of thalassaemic erythroblasts which result in their recognition and phagocytosis by macrophages remain to be determined.
Autoradiography↗