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Biomedical subjects

E B Brown

Publications and source records attributed to E B Brown.

At least 37 records · Page 2Linked to original sources

Tissue effects of iron deficiency in the rat.

Measurements of succinate dehydrogenase and mitochondrial glycerol-3-phosphate dehydrogenase activities, iron, cytochrome c and myoglobin, were made on various hind-leg muscles, fast-twitch red and white muscle and heart and liver of male Wistar rats fed an iron-deficient diet on weaning. Rats fed the same diet and given 20 mg iron intraperitoneally as iron-dextran (Imferon) served as controls. For iron-repletion studies anemic rats (hemoglobin less than 7 g/dl) were given a single injection of 10 mg iron (Imferon) and the time course of change in the above parameters was followed up to 22 days after injection. The iron concentration of most iron-deficient muscles dropped to approx. 35% of control, the heart to 60% and liver to 13%. On repletion, the iron concentration of all tissues increase significantly by 4 days. While the levels of cytochrome c and myoglobin approximated the iron levels in muscle, they did not change significantly in the heart. Succinate dehydrogenase activity dropped profoundly in muscle, to 10-30% of control; on repletion, the activity increased significantly. Mitochondrial glycerol-3-phosphate dehydrogenase activity showed only small changes in iron-deficient tissues.

Anemia, Hypochromic↗

Electron microscopy of influenza haemagglutinin-monoclonal antibody complexes.

The molecular locations of antibody binding sites on the haemagglutinin of influenza virus X-31 were investigated by electron microscopy of haemagglutinin-monoclonal antibody complexes. Evidence was obtained for different sites of binding of different antibodies and direct correspondence was observed between these sites and the locations of antigenic sites A, B, and E (D. C. Wiley, I. A. Wilson, and J. J. Skehel (1981). Nature (London) 289, 373-378) defined by determining the amino acids recognized by the specific antibodies.

Amino Acids↗

Effect of body temperature on salicylate-induced hyperventilation.

Hyperventilation and hyperpyrexia occur simultaneously during acute salicylate intoxication. The present experiments were designed to investigate the stimulatory effect of increased body temperature on respiration in this pathological state. Acute salicylate intoxication was produced in mongrel dogs by intravenous infusion of 200 mg sodium salicylate/kg body weight, and the effect of body temperature on salicylate-induced hyperventilation was studied by comparing the respiration of hyperthermic animals with the respiration of animals maintained normothermic during acute salicylate intoxication by bathing them in cold water. The minute volume of ventilation increased greatly over control levels in both normothermic and hyperthermic animals, but this increment was much larger in hyperthermic animals. The increase in ventilation of normothermic animals can be explained as a rise in alveolar ventilation which results in hypocapnia despite large increases in carbon dioxide production and oxygen consumption during acute salicylate intoxication. The further augmentation of ventilation in hyperthermic animals can be explained as a rise in deadspace ventilation in response to increased body temperature during acute salicylate intoxication.

Animals↗

Thalassemia.

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Chelating Agents↗

Changes in the conformation of influenza virus hemagglutinin at the pH optimum of virus-mediated membrane fusion.

A conformational change in the hemagglutinin glycoprotein of influenza virus has been observed to occur to pH values corresponding to those optimal for the membrane fusion activity of the virus. CD, electron microscopic, and sedimentation analyses show that, in the pH range 5.2-4.9, bromelain-solubilized hemagglutinin (BHA) aggregates as protein-protein rosettes and acquires the ability to bind both lipid vesicles and nonionic detergent. Trypsin treatment of BHA in the pH 5.0-induced conformation indicates that aggregation is a property of the BHA2 component and that the conformation change also involves BHA1. The implications of these observations for the role of the glycoprotein in membrane fusion are discussed.

Bromelains↗

Psychological changes during a controlled trial of rehabilitation in chronic respiratory disability.

Thirty-four men with chronic respiratory disability took part in a randomised, controlled trial of physical training. The control group also undertook exercise training after their control period. During the study measurements were made of exercise tolerance (12-minute walking distance) and the men completed two psychology questionnaires. Walking distance improved significantly more in the treatment group than in the control group. Both groups recorded scores suggesting psychological "improvement" and the changes in the two groups were not significantly different from each other. There were no consistent associations between the increase in walking distance and changes in psychological scores. Initial psychological scores were not useful in predicting changes in walking distance. The results suggest that the effect of treatment on walking distance was not psychological.

Clinical Trials as Topic↗

Physiological and biochemical effects of iron deficiency on rat skeletal muscle.

Young rats were made iron deficient by feeding them a low-iron diet for 8 wk. Iron deficiency resulted in a 50% decrease in cytochrome c and cytochrome oxidase and a 26% decrease in mitochondrial glycerol-3-phosphate dehydrogenase activity in skeletal muscle. Respiratory capacity of muscle homogenates was reduced 55%. After 8 days of iron treatment, respiratory capacity, cytochrome c, cytochrome oxidase, and glycerol-3-phosphate dehydrogenase had returned 50% toward normal. Maximum O2 uptake of contracting hindlimb muscles averaged 8.5 mumol O2.min-1.g-1 in control, 4.3 mumol O2.min-1.g-1 in iron-deficient, and 6.2 mumol O2.min-1.g-1 in the 8-day-iron-repleted rats. Muscle fatigue during 10 min of stimulation was greater in the iron-deficient group. Lactate concentration in red muscle was higher in iron-deficient than in control rats after stimulation. The muscle fatigue and lactate responses returned 50% toward normal during 8 days of iron treatment. We conclude that iron deficiency results in a decrease in skeletal muscle capacity for aerobic metabolism and, by this mechanism, increases susceptibility to fatigue.

Animals↗

Transferrin receptors on the human placental microvillous membrane.

A preparation of microvillous membrane vesicles from human placental syncytiotrophoblast binds transferrin to specific transferrin receptors. Transferrin binding to placental receptors is rapid, saturable, reversible, and specific. Approximately 2.5 X 10(13) receptors are present per milligram of membrane protein; the apparent association constant of transferrin for the placental receptor is 2.2 X 10(7) X M-1. No evidence for removal of iron from transferrin bound to intact membrane receptors was observed in these studies. Nonionic detergent solubilization and partial purification of the microvillous membrane transferrin receptor were carried out with preservation of the functional properties of the receptor.

Female↗

Neurological, neuropsychological, and behavioral correlates of Klinefelter's syndrome.

Neuropsychological assessment is a rapidly expanding discipline combining skills from clinical psychology and neurology. Although neuropsychological correlates have been reported for a wide variety of clinical syndromes, little investigation of this kind has been done in the area of genetic abnormalities. The present case study concerned a child with a variant of Klinefelter's syndrome, genotype XXYY. Results of extensive neurological, psychological, and neuropsychological evaluations are presented and discussed. In addition, educational achievement and personality correlates of the syndrome are reported. Combined evaluation from all disciplines presented a picture of diffuse cortical impairment with slightly greater left hemisphere involvement, resulting in retardation. Previously proposed personality correlates of passivity, shyness, and dependency were also in evidence. On recommendation of the treatment team the child was placed in an educable mentally retarded classroom and a 6-month follow-up showed him to be adjusting socially and functioning well in this setting. Although conclusions cannot be drawn from the study of a single case, data such as these may serve as a basis for future multidisciplinary approaches studying genetic abnormalities.

Child↗

The effect of acid pH and citrate on the release and exchange of iron on rat transferrin.

The effect of acid pH and citrate on the exchange of iron between binding sites of rat transferrin has been studied. In the absence of citrate, diferric transferrin shows stepwise loss of iron atoms with the first atom of iron released at approximately pH 5.2. Citrate at physiologic concentrations (1.10(-3) M) or greater allows random iron removal at pH 6.5 or less. Iron dissociation from monoferric transferrin at acid pH, with or without citrate, is a random process. At pH 7.4, randomization of iron on transferrin takes from 3 to 6 h in the presence of millimolar concentrations of citrate. We conclude that at acid pH and in the presence of citrate concentrations likely to occur in vivo in the rat there is little scrambling of iron bound to transferrin.

Animals↗

In vivo evidence for the functional heterogeneity of transferrin-bound iron. IV. Selective uptake by erythroid precursors of radioiron from portal vein plasma transferrin during intestinal iron absorption.

In addition to the previously demonstrated selective tissue uptake of iron from the two binding sites of transferrin, the Fletcher-Huehns hypothesis predicts that iron absorbed by the intestine is delivered selectively to the erythroblast-oriented iron-binding site of transferrin in portal plasma. We have tested this prediction in rats by measuring in vitro the rate and amount of radioiron taken up by reticulocytes and bone marrow erythroblasts from selectively labeled portal plasma and randomly labeled peripheral plasma. Portal plasma transferrin was significantly more effective than peripheral plasma in delivering radioiron to both reticulocytes and marrow erythroblasts; on a per-cell basis the erythroblasts took up about five times more radioiron. Iron-deficient reticulocytes were more avid but less discriminating than iron-replete reticulocytes in uptake of iron from the two plasma sources. When injected into normal test rats in vivo, radioiron from portal plasma was preferentially removed by red cell precursors and preferentially incorporated into heme extracted from marrow and spleen. These results support the concept of selective release of iron to erythroblast-oriented binding sites of portal plasma transferrin by intestinal cells during absorption. Combined with previously demonstrated selective tissue uptake of iron from transferrin, these experiments offer strong support for the active role of transferrin in the internal iron exchange of the rat.

Anemia↗

Quantification of wear, hemolysis and coagulation deficits in patients with Beall mitral valves.

Fifty-five patients (35 females and 20 males) were studied by noninvasive means 3.5-8.6 years after isolated mitral valve replacement with Models 103 and 104 Beall prostheses. History and physical exams by three physicians, complete hemograms, SMA 18, iron excretion rates, and coagulation profiles were performed. Additionally, electrocardiograms, echocardiograms, phonocardiograms, cardiac series, and high-speed cinefluorography of the prostheses were obtained. Valve wear was assessed by the disc/cage ratio measured from a "three-legged view" with magnification. At a mean duration of 5.85 years after operation, the entire group had a mean disc/cage ratio of operation, the entire group had a mean disc/cage ratio of 0.906 +/- 0.031 vs a normal value of 0.944 +/- 0.014. The group was mildly anemic and had a urinary iron loss that was 40 times normal. The lactic dehydrogenase (LDH) concentration was more than five times normal. The coagulation profiles were abnormal with respect to the bleeding and stypven times, antiheparin activity, fibrin degradation products, and megathrombocyte index. These abnormalities were unrelated to sex, degree of valve wear, and history of thromboembolism. Males were less anemic and had higher urine iron losses than females. Nine patients with severe valve wear (disc/cage ratio less than or equal to 0.87) were significantly more anemic with large urine iron losses and had elevated total bilirubin, serum glutamic oxaloacetic transaminase, and LDH concentrations (ninefold), when compared to nine patients with minimal wear (disc/cage ratio greater than or equal to 0.925). It is emphasized that the findings of a significant anemia, an LDH concentration greater than 1500 mU/ml, and a disc/cage ratio of less than 0.87 in a patient with an isolated Beall mitral valve prosthesis are indicators for the need to replace the prosthesis in the near future. Re-replacement is urged before significant clinical deterioration.

Adult↗