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Biomedical subjects

C S Johnson

Publications and source records attributed to C S Johnson.

At least 127 records · Page 7Linked to original sources
PubMed1984

Mechanical properties of oxygenated red blood cells in sickle cell (HbSS) disease.

Little data exist for the mechanical properties of individual irreversible or reversible sickle cells (ISC and RSC, respectively), nor is the process of ISC formation well understood. For oxygenated ISC and density-fractionated RSC, we have used micropipette techniques to measure cell surface area (SA) and volume (V), membrane shear elastic modulus (mu), time constant for viscoelastic shape recovery (tc), and hence to calculate membrane surface viscosity (eta = mu X tc). Volume loss associated with increasing cell density was accompanied by a proportionately smaller surface area decrease; SA/V ratio thus increased for denser cells, with ISC having the highest values. Membrane area loss by fragmentation must thus be accompanied by an accelerated decrease in cell volume. ISC had relatively rigid membranes (mu 130% above normal controls) and tc close to normal values, so that their effective membrane viscosity was more than double control. RSC had viscoelastic properties close to control, but showed wider variation between sickle cell donors and within samples. Measurements on density-separated RSC showed that, on average, mu was nearly constant, but that tc was longer for the densest cells, with their eta approaching ISC levels. A small subpopulation of RSC were found that had mu close to ISC values. Hypotonically swollen ISC (with internal hemoglobin concentration decreased to normal levels) retained their increased membrane stiffness but had markedly decreased tc, so that their eta approached normal values. The results show that elevated hemoglobin concentration influences the viscoelastic behavior of ISC and RSC, but that an irreversible change in membrane elasticity also occurs for ISC. These data suggest that ISC formation occurs via a two-stage process: (1) accelerated volume loss leading to increased cytoplasmic and effective membrane viscosity; (2) a sharp rise in membrane rigidity, presumably linked to membrane structural alteration.

Adolescent↗
PubMed1983

Thalassemia minor: routine erythrocyte measurements and differentiation from iron deficiency.

The clinical differentiation of the causes of microcytosis is difficult because of the lack of a method for the diagnosis of alpha thalassemia. A number of laboratory tests have been proposed for the differentiation of alpha thalassemia from iron deficiency, including decision functions based on the red blood cell indices generated by electronic cell counters. The accuracy of these screening methods was assessed in 93 patients with microcytosis known to be secondary to either iron deficiency or beta thalassemia minor and, prospectively, in 26 patients with microcytosis in whom globin chain synthesis ratio was used to diagnose thalassemia. The functions evaluated were: RBC volume distribution curve; osmotic fragility; erythrocyte count; discriminant function = MCV - (5 X Hgb) - RBC - 8.4; ratio of MCH/RBC; ratio of MCV/RBC; and 0.01 X MCH X (MCV)2. A simplified method of measuring anisocytosis using the RBC volume distribution curve was significantly more accurate (P less than 0.01) in distinguishing iron deficiency from thalassemia than any of the other decision functions. Analysis of red blood cell volume distribution, although not sufficiently accurate for definitive diagnosis, appears to be a useful technic in the initial screening of patients with microcytosis and in determining which additional testing should be done.

Adult↗
PubMed1983

The first example of a deletion in the human alpha chain: hemoglobin Boyle Heights or alpha 2 6 (A4) Asp----to O beta 2.

Hemoglobin Boyle Heights (alpha 6 (A4) Asp leads to O) is the first observed variant with a deletion in the alpha chain. The variant, which was detected in a 39-year-old man of Mexican descent, constitutes 14% of the total hemoglobin and is associated with microcytosis, heat instability, and increased oxygen affinity. It migrates between Hb F and Hb S on cellulose acetate and starch gel electrophoresis and with Hb A on citrate agar gel electrophoresis. Identification was done by high performance liquid chromatographic procedures. Residue Asp alpha 6 is neither a heme nor an interchain contact, but does have intrachain contacts. Like Hb Sawara (alpha 6 Asp leads to Ala), Hb Boyle Heights has increased oxygen affinity. It is likely that the Bohr effect will be altered because the deletion in Hb Boyle Heights should alter the configuration of Val alpha 1 and influence its participation in the Bohr effect.

Adult↗
PubMed1983

The effect of fetal hemoglobin on the sickling dynamics of SS erythrocytes.

A reaction-limited flow system was used to study the effects of several hematological variables on the sickling dynamics of homozygous SS erythrocytes. Sudden deoxygenation was achieved via a zero oxygen tension sodium dithionite solution; the erythrocytes were recorded on video tape and sickling was identified by morphologic criteria. Two indices of the sickling process were determined: t50, the time at which 50% of the initially discoid cells had sickled; %3sec, the percentage of sickled cells 3 s after the start of deoxygenation. The percentage of fetal hemoglobin (Hb F) significantly influenced these indices with increasing levels of Hb F yielding longer t50 times and smaller %3sec values. Calculated values of percentage F-erythrocytes also showed significant correlations with the two sickling indices. Neither single nor stepwise multiple regression techniques demonstrated any significant effects of percentage hemoglobin A2, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration or mean corpuscular volume. The non-significant effects of these variables may be related to their somewhat narrow range observed in the patient population and to the dominating influence of Hb F levels.

Adolescent↗
PubMed1983

Yta isoimmunization in pregnancy. A case report.

A case of isoimmunization with anti-Yta occurred. Despite transplacental passage of IgG antibody, no hemolysis of fetal cells was noted. The potential for hemolysis of cells transfused to an adult is unclear. Alternatives exist for securing compatible cells for possible maternal transfusion.

Adult↗
PubMed1982

High concentration active enzyme centrifugation studies with pig kidney phosphofructokinase. Detection of 9.8 S, 25 S, and 53 S active polymeric forms.

This laboratory has carried out the first detailed studies of the active polymeric forms of phosphofructokinases over the concentration region of 1 to 1200 micrograms/ml. This includes the concentration range in which the enzymes exist in vivo and the concentration range in which their association-dissociation equilibria shift to yield various polymeric forms. Previously, active enzyme centrifugation experiments were limited to the concentration range below a few micrograms per ml. The present experiments were made possible by the recent development in this laboratory of a new technique called high concentration active enzyme centrifugation (Wei, G. J., and Deal, W. C., Jr. (1979) Biochemistry 18, 1129). We report here three new active polymeric forms of pig kidney phosphofructokinase which have been observed in high concentration active enzyme centrifugation experiments. These include: 1) a 9.8 S form (Mr = 2.6 X 10(5)); 2) a 25 S form (Mr = 1.01 X 10(6)); and 3) a 53 S form (too asymmetric to estimate Mr). In addition, a 5.4 S form is predicted from the Mr (8.8 X 10(4)) of the polypeptide chain obtained from sodium dodecyl sulfate gel electrophoresis; it is not known whether or not it is active. The 9.8 S value is the limiting sedimentation coefficient value observed in active enzyme centrifugation experiments. The 25 S form is indicated by a plateau in the 50 to 200 micrograms/ml region of the s versus c curve. The 53 S form is observed as a plateau in the 600 to 1000 micrograms/ml region of the s versus c curve.

Animals↗
PubMed1982

alpha-Thalassemia: prevalence and hematologic findings in American Blacks.

alpha-Thalassemia is common in southeast Asia and the Mediterranean, where the predominant lesion seems to be a deletion of one or more of the four gene loci responsible for alpha-globin chain production. In the United States, the prevalence of alpha-thalassemia in blacks was once thought to be low, but more recent studies show that the prevalence of alpha-thalassemia is high. We measured the globin chain synthetic rations in 144 black Americans to determine the prevalence and hematologic manifestations of alpha-thalassemia in this population. There were 120 subjects with a mean synthetic ration of 0.986 +/- 0.04, with a range of 0.90 to 1.06; these were classified as normal. Five subjects were found to have beta-thalassemia; 19 subjects had mild alpha-thalassemia. The overall gene frequency for alpha-thalassemia was estimated to be 0.07 in this population. The hemoglobin values of subjects with mild alpha-thalassemia were not statistically significantly different from normal black or white control subjects of the same sex, but there was a significant decrease in the mean corpuscular volume and in the mean corpuscular hemoglobin value.

Adult↗
PubMed1982

Identification of eleven human hemoglobin variants by high-performance liquid chromatography: additional data on functional properties and clinical expression.

Eleven abnormal hemoglobins were detected in the course of cord blood screening or in the evaluation of evident hematological problems in individual cases. Identification of the variant in each case was done by high-performance liquid chromatography (HPLC); HPLC provides a rapid, sensitive means for the examination of abnormal hemoglobins. Some of the 11 variants that were identified have been described repeatedly and are included to provide information on the HPLC behavior of tryptic peptides. Others are much rarer. Additional information is provided about the hematological and clinical expression as well as ethnic and geographical distribution of the abnormal hemoglobin.

Chromatography, High Pressure Liquid↗
PubMed1982

Tracer diffusion coefficients of oxyhemoglobin A and oxyhemoglobin S in blood cells as determined by pulsed field gradient NMR.

It is demonstrated that tracer diffusion coefficients can be determined for oxyhemoglobin A (HbA-O2) and oxyhemoglobin S (HbS-O2) in intact blood cells by means of pulsed field gradient NMR (PFG-NMR). This is possible because the method discriminates between both rapidly moving water molecules and molecules having small proton transverse relaxation times (T2). The results indicate that only hemoglobin molecules contribute to the echo signals when large field gradients are used. The dependence of the measured diffusion coefficients on osmolarity and pH are attributed to changes in hemoglobin concentration resulting from changes in cell volume.

Anemia, Sickle Cell↗
PubMed1982

Functional properties of Hb Pasadena, alpha 2 beta 2 75(E 19) Leu replaced by Arg.

Functional properties of Hb Pasadena (beta 75[E19]Leu replaced by Arg) as well as correlations of its structure-function relationships with those of normal hemoglobin are presented. The homeotropic and heterotropic properties of the isolated variant were investigated by automatic recording oxygen equilibrium analysis. These studies indicate an increase of 02 affinity but normal cooperativity. The decrease of 02 affinity in response to organic phosphate (DPG and IHP) was found to be normal. However, the cooperativity of Hb Pasadena is less affected by IHP than is that of Hb A. The alkaline Bohr effect was found to be somewhat decreased, although the temperature effect is nearly normal. The autoxidation rate is increased by a factor of nearly 2 compared to normal. These observations are consistent with the conclusion that the beta (E19)75 leucyl hydrophobic residue of Hb A associates with beta (A8)11 Val, beta (A12)15 Trp and beta (H11)133 Val to form a hydrophobic cluster between the A, E and H helics which thereby stabilizes the heme of the beta chain in the deoxy ferrous state. The experimental results also suggest that the amino acid substitution in Hb Pasadena mainly disrupts the interior conformation of the beta subunit without affecting subunit interfaces. Thus it is predicted that Hb Pasadena should have a normal crystal structure in either the liganded (R) or unliganded (T) state. Its increased 02 affinity can be explained partially by a decrease of proton binding and partially by a shift of the R:T equilibrium towards the R conformation.

Female↗
PubMed1982

Effect of C-reactive protein on granulocyte-macrophage progenitor cells.

Pathophysiological concentrations of CRP inhibited the in vitro clonal proliferation of CFU-C's. CRP inhibition was specific for normal CFU-C's committed to the mononuclear phagocyte lineage. Macrophage progenitor cells stimulated by an inflammatory response were unaffected by CRP. CFU-C's which were committed to the granulocyte lineage, those which gave rise to both macrophages and granulocytes, and erythroid progenitor cells were also not affected by CRP. Only macrophage CFU-C's that possessed Fc receptors and were in S-phase at the time at CRP exposure were susceptible to inhibition of colony formation. The data suggest that CRP functions as a regulator of the cellular composition of an inflammatory response.

Animals↗
PubMed1982

Inhibition of normal erythropoiesis in mice with Friend virus induced erythroleukemia.

Mice in which erythroleukemia was induced by the Friend murine leukemia virus produced inhibitors of normal erythropoiesis. The inhibitors were released into media conditioned by bone marrow cells from leukemic, but not normal mice. The inhibitors were active at high dilution against normal erythroid progenitors (CFUE) in S-phase. Colony formation by CFUE from leukemic mice was stimulated by the same preparations of inhibitor. Fractionation of inhibitory media by gel filtration chromatography revealed 2 protease-sensitive, macromolecular components and a small molecular weight species. The cells responsible for production of the CFUE inhibitors were adherent, possessed macrophage but not T or B cell markers, and did not express viral antigens. The CFUE inhibitors were distinguishable from the previously described inhibitor of granulocyte-macrophage precursors, CFUC LIA, by antigenic specificity and cellular origin.

Animals↗
PubMed1981

Catalysis of the disproportionation of superoxide by metalloporphyrins. III.

An assay based on the use of an oxygen electrode has been used to determine the superoxide dismutase-type activity of several metalloporphyrins. Both the iron(III) and manganese(III) derivatives of tetrakis-(4-N-methylpyridyl)porphine were shown to have comparable activity, about 2-3% of that of the enzyme. Comparisons are made between this assay method and the more standard one which depends on the conversion of nitroblue tetrazolium to formazan.

Copper↗