The effect of hemin on globin synthesis and iron uptake by reticulocytes of the Belgrade rat.
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Biomedical subjects
Publications and source records attributed to J A Edwards.
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Fasting serum cholesterol and triglyceride levels were measured in 131 randomly selected adult members of a Lebanese Community of Western New York. Mean cholesterol levels (males, 217 mg%; females 234 mg%) were higher than those reported from the Lebanon but similar to those reported in most other populations. Mean triglyceride levels (males, 153 mg%; females, 115 mg%) were higher than those reported in most other populations. Twenty-three subjects were hyperlipidemic on the basis of age and frequency distribution adjusted serum lipid levels above the 90th percentile. Clinical and family studies carried out on 13 of these 23 hyperlipidemic subjects suggested that 77% had monogenic hyperlipidemia and 23% primary non-monogenic hyperlipidemia. A high frequency of familial hypercholesterolemia (minimum estimate 0.7%) was found, in keeping with the high frequency of the disorder in Lebanon. The study serves to emphasize the difficulties in defining hyperlipidemia, in establishing a specific diagnosis in the individual patient, and in distinguishing between optimum and normal serum lipid levels.
The duodenal mucosa of genotypically normal iron replete and iron deficient mice and mice with sex-linked (sla) and microcytic anemias (mk) was examined for the presence of iron-binding proteins. Following continuous, 15 or 120 minute, in vivo intraenteric exposure of a closed duodenal loop to 59Fe, a high speed supernatant of homogenized mucosal tissue was chromatographed on G-200 Sephadex. Two major peaks of 59Fe activity were observed. The molecular weight, and immunological properties of peak I were similar to ferritin whilst those of peak II were similar to transferrin. The distribution of 59Fe between peaks I and II in mk/mk animals was similar to that in genotypically normal iron deficient animals indicating that the intramucosal mechanisms for iron transport were reacting appropriately to the iron deficient state of mice with microcytic anemia. In contrast, the distribution of 59Fe between peaks I and II in sla/Y animals was the reverse of that found in genotypically normal iron deficient animals suggesting the possibility of an intramucosal iron binding protein defect in sex-linked anemia.
Erythroid cell iron uptake and globin synthesis were studied in the anemia of the Belgrade Laboratory rat (gene symbol, b), an autosomal recessive trait characterized by hypochromia and hyperferrinemia. Reticulocyte protein and globin synthesis, as measured in vitro by the incorporation of 3H-L-leucine, were significantly diminished in b/b animals, although no major imbalance between alpha-and beta-chain production was observed in b/b reticulocytes. The incorporation in vitro of 3H-L-methionine into marrow cell globin demonstrated no difference between b/b animals and +/? control animals in the proportion of alpha-to beta-chain production. The transfer of iron from plasma to reticulocytes, as measured in vitro by the uptake of 59Fe, was significantly decreased in b/b animals; Sephadex G 200 chromatography of b/b red cell lysates did not reveal the accumulation of 59Fe in nonhemoglobin fractions found when heme synthesis was inhibited with isoniazid. The magnitude of the reticulocyte iron-uptake defect was greater than the reticulocyte globin-synthesis defect, suggesting that the former is the primary lesion.
The synthesis of cephalosporin derivatives possessing a 3-substituted prop-1-enyl group at the 3 position is described. This was achieved using the reaction of vinylmagnesium chloride with the 3-formyl derivatives 1 to give a vinylcarbinol which readily underwent allylic rearrangements to give the desired side chains. The new derivatives exhibited potent in vitro and in vivo antibacterial activity.
The ferritin concentration of duodenum, liver, and spleen and the incorporation of L-leucine-3H into immunoprecipitated duodenal and liver ferritin was measured in genotypically normal (+/Y) mice and mice with sex-linked anemia (sla/Y), an X-linked recessive trait determined by a defect in intestinal iron absorption. Liver and splenic ferritin concentration was lower in sla/Y animals than in +/Y animals. Parenteral iron administration produced an increase in the duodenal, liver, and splenic ferritin concentration in both sla/Y and +/Y animals that was most striking in the case of the liver. Duodenal ferritin synthesis, both in vivo and in vitro, was increased in iron-deficient sla/Y animals and decreased in iron-deficient +/Y animals. In contrast, liver ferritin synthesis was decreased in both sla/Y and +/Y iron-deficient animals. In sla/Y animals fed an iron-deficient diet, duodenal ferritin synthesis decreased to near normal levels. These results indicating a high level of duodenal ferritin synthesis in standard-fed mice with sex-linked anemia suggest that the primary genetic defect is more likely a disorder of intramucosal iron transport than a primary disturbance of ferritin metabolism.
Lipoprotein-X is no longer detectable in serum by either the agar gel-electrophoresis/polyanion precipitation technique or immunoelectrophoresis with specific antiserum after in vitro addition of oleic acid. Evidence is presented which indicates that this ostensible loss is due not to its destruction, but rather to altered electrophoretic mobility. The findings suggest an explanation for the well known post-heparin "disappearance" of lipoprotein-X, and indicate that caution may be needed in the interpretation of such lipoprotein-X testing of sera from subjects with increased concentrations of lysolipids in their blood.
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The effect of 8 dyes on the electrophoretic mobility of normal human serum alpha-1 lipoprotein has been examined. The two characteristics of increase in anodal mobility, and conformational changes of the immunoelectrophoretic precipitin arc suggesting polymorphism, were found to vary independently among the dyes tested. The results suggest that dye induced electrophoretic mobility alteration may represent a useful tool for examination of heterogeneity of alpha-1 lipoprotein.
Three siblings with retinitis pigmentosa, deafness and mental retardation were studied. Physical abnormalities included nystagmus, acanthosis nigricans and multiple keloids. The two male siblings had gynecomastia, small testes and mild subvirilization whereas the only indication of hypogonadism in the female sibling was oligomenorrhea. Testosterone levels in the males, which were in the low to low normal range, were increased by the administration of large doses of chorionic gonadotropin. The two affected males had elevated plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels which were decreased by the administration of testosterone and increased by the administration of clomiphene. One sibling had mild obesity and diabetes mellitus, one had moderate obesity, normal glucose tolerance and hyperinsulinism and the third had abnormal glucose tolerance and hyperinsulinism. This familial syndrome is distinct from either the Laurence-Moon, Bardet-Biedl or Alström disorders and provides further evidence of genetic heterogeneity in this group of autosomal recessive traits.
This study tested one of the basic propositions of dual-process theory (Groves and Thompson, 1970) that 'dishabituation' results from an independent, superimposed process of excitation and not from disruption of the habituation process as proposed by Sokolov (1963). Skin conductance level (SCL) was employed as a measure of sensitization. On the basis of dual-process theory, it was hypothesized that if sensitization produced by the 'dishabituating' stimulus has decayed prior to re-presentation of the habituating stimulus, skin conductance response (SCR) amplitude to the habituating stimulus will not differ from that displayed by a control group which did not receive presentation of the 'dishabituating' stimulus. In experiment 1 (N = 10), subjects received 13 presentations of a 1000 Hz, 70 dB tone of 3 sec duration with interstimulus intervals of 40, 50 and 60 sec. Between trials 11 and 12, there was one presentation of a dishabituating (light) stimulus. Analysis of SCL indicated that an interval of 50 sec between trials 12 and 13 was sufficient to allow sensitization to decline to the pre-light level. The experimental conditions in experiment 2 (N = 32) were the same as in experiment 1 except that only half the subjects received presentation of the dishabituating stimulus. The results indicated that although there were no group differences in SCR amplitude on trials 1-11, experimental subjects displayed significantly larger responses on trial 13 than did control subjects. These results suggest that interpolation of a different stimulus in an habituation series does, in fact, disrupt the habituation process.
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A new tricyclic agent with an allenyl side chain experimentally shows antidepressant activity similar to amitriptyline and imipramine but also exerts marked CNS depression. Such dual activity should be of clinical interest for treatment of mixed anxiety and depression.
This trial has investigated the value of gentamicin therapy in patients requiring biliary surgery. One hundred consecutive patients were randomly allocated to receive either gentamicin or no antibiotic. Post-operative infection was assessed by an independent observer. Cultures and gentamicin assays were performed on bile and blood sampled during and after operation. The minimum inhibitory concentrations of gentamicin were measured with isolated bacterial. In 80 per cent of patients biliary organisms were inhibited by 2 mug/ml of gentamicin. Twice this concentration was found in the serum at operation in 88 per cent, but in the bile in only 18 per cent. Nevertheless, gentamicin lowered the incidence of bacteria in the bile from 42 to 25 per cent. There was a reduction in wound sepsis from 21 to 6 per cent (P less than 0-05). Bacteriaemia was demonstrated in only 1 patient receiving gentamicin compared with 5 controls and 1 death occurred from endotoxaemia in the control group. These data suggest that gentamicin will reduce the morbidity of biliary surgery, particularly in patients in whom the bile is infected at operation.
This study has investigated the relationship between duodenogastric reflux, gastritis and certain symptoms 6-12 months after three operations for uncomplicated duodenal ulcer. The operations studied were proximal gastric vagotomy (PGV, 20 cases), truncal vagotomy and pyloroplasty (TV+P, 22 cases) and truncal vagotomy and antrectomy (TV+A, 21 cases). Duodenogastric reflux was assessed both by a radiological technique and by measuring the concentration of bilirubin in the gastric aspirate before and after operation. Incidence and severity of postoperative gastritis were determined by endoscopic biopsy. Symptoms were assessed by symptomatic score and Visick grading. There was a significant correlation between duodenal reflux and histological evidence of both severe superficial gastritis and glandular atrophy (P less than 0-01). There was also a close association between the degree of reflux and the presence of severe heartburn, epigastric pain and bile vomiting after operation. The amount of reflux did not differ before operation. There was significantly less reflux following PGV than after either TV+P (P less than 0-025) or TV+A (P less than 0-001). The results indicate that an operation which preserves an innervated and intact antrum and pylorus will protect against postoperative duodenogastric reflux, gastritis and symptoms.
A study of plasma concentration (P1T, ng/ml), metabolic clearance rate (MCRT, L/day) and blood production rate (PBT, mg/day) was done on seven XYY subjects of various ages and four pair-matched control XY subjects by a radioinfusion technique of 1,2-3H-testosterone. Although MCRT showed no significant difference between the groups, P1T and PBT were significantly lower (P less than 0.05) in XYY subjects. Therefore, increased aggressive behavior of the XYY subjects can not be attributed to increased levels or production rates of testosterone.
1. Human hepatic "acid" beta-galactosidase preparations, which had been purified approximately 250-fold, were examined for activities toward 4-methylumbelliferyl beta-galactosylceramide, lactosylceramide, galactosyl-N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosyl-glucosylceramide(GM1-ganglioside) and galactosyl-N-acetylgalactosaminyl-galactosyl-glucosylceramide (asialo GM1-ganglioside). 2. The enzyme was active toward the synthetic substrate, GM1-ganglioside and asialo GM1-ganglioside but was inactive toward galactosylceramide. Under our assay conditions, optimized for lactosylceramidase II, the preparations were as active toward lactosylceramide as toward GM1-ganglioside or its asialo derivative. The apparent Km values for the three natural substrates were similar. When determined by the assay system of Wehger, D.A., Sattler, M., Clark, C. and McKelvey, H. (1974) Clin. Chim Acta 56, 199-206, lactosylceramide-cleaving activity was 0.2% of that determined by our assay system. This confirmed our previous suggestion that the Wenger assay system determines exclusively the activity of lactosylceramidase I, which is probably identical with galactosylceramide beta-galactosidase. 3. Crude sodium taurocholate was far more effective than pure taurocholate in stimulating hydrolysis of the three glycosphingolipids by the beta-galactosidase. However, crude taurocholate could largely be replaced by smaller amounts of sodium taurodeoxycholate, suggesting that the unique activating capacity of the crude taurocholate might be due to taurodeoxycholate present as the major impurity. 4. Cl- was generally stimulatory for hydrolysis of the natural glycosphingolipids by our enzyme preparation. Effects of additional oleic acid and Triton X-100 were generally minor in either direction. 5. When the enzyme preparation was diluted with water, activity toward the synthetic substrate declined rapidly while those toward the natural substrates were essentially stable. Activity toward the synthetic substrate remained much more stable when the enzyme was diluted with 0.1 M sodium citrate/phosphate buffer, pH 5.0. 6. These observations provide insight into the complex relationship among the human hepatic beta-galactosidases.
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