Biomedical subjects
Publications and source records attributed to S Fischer.
The basal and the NaF-stimulated activities of human red blood cell membrane adenylate cyclase were found to be 5.3 +/- 0.8 (SE) and 219 +/- 76 (SE) pmol . mg-1 . min-1, respectively. Both activities were increased in nine patients with homozygous sickle-cell disease. There was no apparent correlation between this increase and the increase in the reticulocyte count.
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125I-labelled transferrin has been covalently linked to proteins of rabbit reticulocyte membranes using three different cross-linking reagents: (a) bis(methyl) suberimidate (b) 4-methyl mercaptobutirimidate and (c) Cu-o-phenanthroline. Analysis of the products of the cross-linking reactions by SDS polyacrylamide gel electrophoresis revealed three radioactively labelled components. The major component corresponds to non-cross-linked transferrin while a second smaller component represents a complex (125 000 daltons) of membrane protein and transferrin. A third component (210 000 daltons) was observed when 4-methyl mercaptobutirimidate was used as a cross-linking reagent. The possibility that the two higher molecular weight complexes contain the receptor protein for transferrin is discussed.
Techniques of cell separation were used to isolate murine erythroid cells at different stages of maturation. The number of transferrin receptors in these cell populations was assayed by measuring binding of 125I-labelled transferrin. Nearly 23 times as many receptors were found in the least mature cells, chiefly pronormoblasts, as in reticulocytes. Iron transport, determined by measurement of the rate of 59Fe uptake from 59Fe-labelled transferrin, was proportional to the number of receptors at all stages of differentiation. Electron microscope radioautographic studies of the interaction of 125I-labelled transferrin with erythroid precursor cells demonstrated that 15-33% of cell associated transferrin was intracellular in erythroid precursors.
The development pattern of one class of plasma membrane proteins, the external surface proteins, was examined in neoplastic and nonneoplastic differentiating murine erythroid cells. Neoplastic erythroid precusor cells were obtained from spleens of CD-1 mice after infection with Friend erythroleukemia virus while the nonneoplastic ellls were obtained from spleens of mice with phenylhydrazine-stimulated erythroid hyperplasia. Erythroid precursors at different stages of development were isolated from these erythroid cell populations by sedimentation at unit gravity. The surface proteins were labeled by lactoperoxidase-catalyzed iodination, solubilized in sodium dodecyl sulfate, and separated by sodium dodecyl sulfate gradient gel electrophoresis. Multiple labeled bands were found at all stages of neoplastic and nonneoplastic erythroid differentiation examined. The pattern of external membrane proteins labeled in nonneoplastic erythrocytes and in reticulocytes from peripheral blood were qualitatively similar and not altered by infection with Friend virus. The nucleated precursor cells from noninfected mice exhibited distinct differences from erythrocytes, and with increaseing differentiation an evolutionary pattern of several minor proteins was seen. Clear-cut differences in lactoperoxidast-reactive proteins were also observed between neoplastic and nonneoplastic precursors. The most marked differences were observed between the most immature cells. The youngest neoplastic cells from CD-1 mice possessed a protein with a molecular weight of 8000 not seen in normal erythroid cells. Additionally, there was an absence of a normally occurring protein with a molecular weight of 13,000 and increased amounts of a protein with a molecular weight of 140,000. With increasing maturation of the neoplastic cells, labeling of the protein with a molecular weight of 8,000 decreased while the protein with a molecular weight of 13,000 became apparent, so that a labeling pattern similar to that of nonneoplastic cells was obtained. These studies deomnstrate both distinct alterations of lactoperoxidase-reactive surface membrane proteins in nonneoplastic erythroid cells druring cell maturation in neoplastic erythroid cells as compared with nonneoplastic erythroid cells at similar stages of development.
For characterizing glucose-6-phosphate dehydrogenase variants 10 functional parameters are generally used. As additional tests the determination of Km and Ki at different pH values, the limiting Km for both substrates, isoelectric focusing and electrophoresis of enzyme subunits have been recommended. Most of the variants with favourable kinetic properties do not produce chronic haemolysis. As an exception G6PD Aarau is quoted. Sporadic cases and deficiency conditions with manifest chronic nonspherocytic haemolytic anaemia should be selected for complete enzyme characterization. Individual and public health aspects are of primary importance for screening programs. Among 28,367 blood samples 424 cases with G6PD deficiency have been found in Switzerland.
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The effect of low concentrations of a specifically designed sterol-24-transmethylase inhibitor, 25-aza-24, 25-dihydrozymosterol (10) on sterol production in Saccharomyces cerevisiae was examined. The synthesis of cholesta-5,7,22,24-tetraen-3beta-ol (4), its 7,22,24 analog (15) and the 7,24 analog (5) coupled with the availability of zymosterol (6) and cholesta-5,7,24-3beta-ol (3) derivatives facilitated a search for these sterols in cultures treated with this inhibitor. When S. cerevisiae was grown in the presence of 1.3 and 5 muM 10, it produced no ergosterol but accumulated zymosterol (6), cholesta-5,7,22,24-tetraen-3beta-ol (4) and related C27 sterols (3 and 5). These results indicate blockage of the side chain methylation that normally occurs during the biosynthesis of ergosterol in yeast by compound 10 is efficient. The cholesta-5,7,22,24-tetraen-3beta-ol is a close structural analog of provitamin D3 (7-dehydrocholesterol). The inhibited yeast thus provides a source of a potentially new provitamin D3 substitute.
This paper reports on an analysis of psychiatric population. 55 female patients with breast cancer were matched with non-cancer patients on age, year of admission, psychiatric diagnosis, race, and religion. Reserpine use was examined for yearly use by each year preceding the diagnosis of breast cancer, by cumulative yearly use, and by other defined time periods. Regardless of the definition of reserpine user, there were no significant increased relative risks of breast cancer for those women on reserpine. There was a fairly low proportion of patients from each group who were on the drug in any given year, and a fairly wide range of total dosage received. Over half of the women used reserpine at some time during their hospital stay.
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The binding of hemoglobins A, S, and A2 to red cell membranes prepared by hypotonic lysis from normal blood and blood from persons with sickle cell anemia was quantified under a variety of conditions using hemoglobin labelled by alkylation with 14C-labelled Nitrogen Mustard. Membrane morphology was examined by electron microscopy. Normal membranes were found capable of binding native hemoglobin A and hemoglobin S in similar amounts when incubated at low hemoglobin: membrane ratios, but at high ratios hemoglobin saturation levels of the membranes increased progressively for hemoglobin A, hemoglobin S and hemoglobin A2, respectively, in order of increasing electropositivity. Binding was unaffected by variations in temperature (4-22 degrees C) and altered little by the presence of sulfhydryl reagents, but was inhibited at pH levels above 7.35; disrupted at high ionic strength; and dependent on the ionic composition of the media. These findings suggest that electrostatic, but not hydrophobic or sulfhydryl bonds are important in membrane binding of the hemoglobin under the conditions studied. An increased retention of hemoglobin in preparations of membranes from red cells of patients with sickle cell anemia (homozygote S) was attributable to the dense fraction of homozygote S red cells rich in irreversibly sickled cells, and the latter membranes had a smaller residual binding capacity for new hemoglobin. This suggests that in homozygote S cells which have become irreversibly sickled cells in vivo, there are membrane changes which involve alteration and/or blockade of hemoglobin binding sites. These findings support the notion that hemoglobin participates in the dynamic structure of the red cell membrane in a manner which differs in normal and pathological states.
A total of 2672 cases with thalassemia syndromes observed in the period from 1 January 1968 to 30 April 1974 are classified according to type of thalassemia and the patient's country of origin. During the past 15 years some 10 patients annually with classical heterozygous beta-thalassaemia have been found to be of purely Swiss origin. Due to increased immigration from Mediterranean countries the Swiss patients represent only 2.6 percent of all cases at the present time, a marked decrease from the earlier 30 percent. Since 1968 2260 cases of thalassemia syndrome have been found in Italian patients. Smaller groups of patients originate from Greece, Spain and Turkey. Homozygous beta-thalassemia was observed in 56 cases. Ranking third among thalassemia syndromes is the Hb Lepore trait found in 16 cases. The increase in thalassemia syndromes due to population migration over the past 10 years has resulted in the finding of rare types in Switzerland: 8 patients with HbS-beta-thalassemia, 2 with HbC-beta-thalassemia, 3 cases of HbH-alpha-thalassemia and 2 cases of Hb Bart's-alpha-thalassemia are reported. The difficulty of diagnosing deltabeta-thalassemia and alpha-thalassemia is emphasized.