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Biomedical subjects

B Lubin

Publications and source records attributed to B Lubin.

At least 127 records · Page 7Linked to original sources

Increased IgG molecules bound to the surface of red blood cells of patients with sickle cell anemia.

We have used the complement-fixing antibody consumption ( CFAC ) test to detect small concentrations of IgG on red blood cells from patients with hemolytic anemias that are not thought to be caused by an immune mechanism. Although patients with hereditary spherocytosis, pyruvate kinase deficiency, and mechanical hemolytic anemias generally had normal concentrations of IgG bound to their red cells (less than 25 molecules IgG per red cell), we found that 39/62 (63%) patients with sickle cell anemia had elevated values. These 39 patients had a mean of 195 and a maximum of 890 molecules of IgG per red cell. None of the patients had been transfused within the previous 90 days, and some had never been transfused. Direct antiglobulin tests were positive in only two instances and autoantibodies were not found in the serum of any patient. However, eluates from the red cells of 6 of 23 patients demonstrated antibody activity against all of a panel of normal red cells by the indirect antiglobulin test. There was no correlation between the number of IgG molecules on patients' red cells and the severity of their anemia, the incidence of painful sickle cell crises, the reticulocyte count, or with blood transfusion history. We conclude that further study of immunohematologic abnormalities in patients with sickle cell anemia is warranted, especially in view of previous reports in this population of patients with red cell autoantibodies, autoimmune hemolytic anemia, hemolytic transfusion reactions without detectable alloantibodies, and an association of some episodes of pain crises with immunologically mediated red cell destruction.

Adolescent↗

Accelerated transbilayer movement of phosphatidylcholine in sickled erythrocytes. A reversible process.

The transbilayer mobility of phosphatidylcholine (PC) molecules in the membrane of homozygous reversible sickle cells (RSCs) was studied using a PC-specific exchange protein from beef liver. In deoxygenated RSCs, all of the PC present in the membrane of the intact cell is rapidly available for exchange, mediated by this protein. Since a substantial amount of the PC is present in the inner membrane leaflet of these cells, this observation implies that the PC molecules in their membranes do experience rapid transbilayer movements. To determine the actual rate of transbilayer movement of the PC, radioactive PC was introduced into the outer monolayer of oxygenated RSCs using the PC-specific exchange protein. Subsequently, the cells were incubated at 37 degrees C under oxy- and deoxygenating conditions to enable the PC to equilibrate within the bilayer. At various time intervals, samples were taken and treated with phospholipase A2, which selectively degrades the PC in the outer monolayer. Analysis of the specific radioactivities of the lyso-PC thus produced, as well as of the residual PC, enabled us to follow the fate of the radioactive PC previously introduced into the outer membrane layer. The half-time value for transbilayer equilibration of the PC in deoxygenated RSCs was determined to be 3.5 h, which is about four times lower than that for oxygenated RSCs. This increased transbilayer mobility of PC, observed in deoxygenated RSCs, is immediately restored to the normal low rate upon reoxygenation of the cells, indicating a complete reversibility of this phenomenon.

Androgen-Binding Protein↗

Interaction of phosphatidylserine-phosphatidylcholine liposomes with sickle erythrocytes. Evidence for altered membrane surface properties.

The sickle erythrocyte (RBC) is a pathologic RBC that contains multiple membrane abnormalities. Some of these abnormalities have been implicated in the pathophysiology of vasoocclusive crises characteristic of sickle cell disease; others have yet to be defined in terms of their clinical significance. Recent information has shown that sickle RBC adhere abnormally to cultured endothelial cells yet little is known about the ways in which sickle cells interact with model membranes of defined size and lipid composition. We investigated this phenomenon by interacting sickle RBC with artificial lipid vesicles (liposomes) containing acidic phospholipids. Our results demonstrate that sickle disease (hemoglobin SS) RBC bind more of these liposomes than do normal or sickle trait (hemoglobin AS) RBC and that these differences are accentuated by hypoxia-induced sickling. Binding of liposome phospholipid to sickled RBC was not attributable to phospholipid exchange between liposomes and RBC and was consistent with a mechanism involving both membrane fusion and a stable reversible adhesion of liposomes to the RBC membrane.Investigations into the mechanism(s) underlying increased liposome binding to sickled RBC suggested that the known reversible translocation of aminophospholipids, phosphatidylserine (PS) and phosphatidyl-ethanolamine (PE), from the inner to the outer leaflet of the reversibly sickled RBC (RSC) plasma membrane during sickling may be a component of increased liposome binding to RSC. This idea was supported from results of experiments in which normal RBC were treated with diamide resulting in the expression of outer leaflet PE and PS and a stimulation of liposome binding to these cells. However, sickle RBC separated according to cell density on stractan gradients showed that irreversibly sickled RBC (ISC) were less capable of liposome binding than were discoid RSC. Since ISC are known to contain elevated levels of outer leaflet aminophospholipids, such a result suggests that other changes in the plasma membrane of sickle cells, in addition to phospholipid reorganization, are probably involved in enhanced liposome binding to these cells. In other experiments, we showed that liposomes containing l-phenylalanine were capable of delivering this antisickling agent into intact sickle RBC as demonstrated by the partial inhibition of hypoxia-induced sickling in vitro. Our results suggest that liposomes can be used as sensitive probes for investigating changes in RBC membrane properties, especially those that affect intermembrane interactions, and that liposomal transport systems may have significant implications in the therapy of sickle cell disease.

Anemia, Sickle Cell↗

Alteration of membrane phospholipid bilayer organization in human erythrocytes during drug-induced endocytosis.

Our plan was to evaluate the potentially important role of phospholipids in erythrocyte shape alterations by determining if their orientation was altered during endocytosis. Stomatocytosis and endocytosis were induced in normal intact human erythrocytes by incubation with three agents: primaquine, vinblastine, and chlorpromazine, each of which has its own requirements and time course for producing endocytosis. The organization of the phospholipid bilayer was assessed by measuring the extent of degradation of phophatidylcholine (PC), phophatidylethanolamine (PE), phosphatidylserine (PS), and sphingomyelin (SM) produced by exposure of erythrocytes to a nonpenetrating protease-free phospholipase A2 alone or in combination with a purified sphingomyelinase as well. The induction of stomatocytosis did not change this orientation. However, correlating with the onset of endocytosis but not its extent, there was an increase in PE degradation, which could be detected regularly only by use of phospholipase A2 alone. Use of the combination of phospholipase A2 and sphingomyelinase showed that the extent and course of endocytosis was paralleled by an apparent movement of PC and SM from the outer to the inner half of the lipid bilayer. Since no further PE was hydrolyzed and because no PS was ever degraded, this inward movement of PC and SM did not represent the establishment of complete symmetry in the membrane. By adjusting the experimental design it was possible to implicate the endocytic process, and not insertion of drug in the membrane, as the cause of the alterations in phospholipid organization seen. Our findings indicate that the phospholipid orientation is very closely involved in the endocytosis process and that specific states of phospholipid asymmetry may be related to identifiable membrane events.

Chlorpromazine↗

Response manipulation on the depression Adjective Check List.

Explored response manipulation on the Depression Adjective Check List (DACL) in a 2 (trials) x 3 (instructions to fake) x 2 (sex) x 2 (order) mixed factorial, counterbalanced design in which 240 college students, 120 males and 120 females, were assigned randomly to one of six conditions with 20 males and 20 females per condition. For conditions 1, 2, and 3, each session consisted of two trials. In trial 1, Ss completed DACL, E, F, and G as they actually felt and in trial 2 they were instructed to either "fake good," "fake bad," or "fake average." The order of "actual" and "faked" trials was reversed for conditions 4, 5, and 6. The significant findings for "fake bad" and "fake good" were discussed in terms of the ability of an examiner to detect the manipulative set by means of the grossly deviant scores.

Adult↗

Peroxidation, vitamin E, and sickle-cell anemia.

In summary, we propose the following scheme (Figure 5) to describe the role of peroxidation in the pathophysiology of SCA. Sickle erythrocytes are more susceptible to peroxidation than are normal erythrocytes. This increased susceptibility to peroxidation is, in part, due to decreased blood vitamin E levels and abnormal membrane phospholipid organization induced by sickling. The peroxidative damage of sickle erythrocytes may accelerate or contribute to loss of cell deformability and to chronic hemolysis. Peroxidative damage can produce abnormal cellular properties, such as potassium leak and reduced filterability, and contribute to formation of ISCs. Increased red cell rigidity can initiate episodes of capillary obstruction, leading to vasoocclusive painful crises and to tissue infarction. Liver dysfunction as well as increased production of bilirubin secondary to hemolysis could result in bile sludging and decreased secretion of bile salts into the intestinal lumen. Reduced bile salt secretion leads to partial fat and vitamin E malabsorption. Vitamin E deficiency enhances red cell susceptibility to peroxidation and promotes a vicious cycle in SCA. Although we have not studied factors that might initiate peroxidative damage, sickle hemoglobin and excess body iron should be considered as potential sources. Our studies suggest that vitamin E supplementation to sickle-cell patients could be of clinical benefit.

Anemia, Sickle Cell↗

Properties of vitamin E-deficient erythrocytes following peroxidant injury.

Several membrane properties of vitamin E-deficient and normal erythrocytes were studied after incubation of these cells with hydrogen peroxide. Measurements of mean corpuscular volume, cation permeability, membrane Na+, K+ ATPase activity, red cell filterability through 5 mu millipore filters, and membrane protein pattern on sodium dodecyle sulfate-gel electrophoresis revealed marked alterations before lysis. Vitamin E sufficient cells were unaffected by a similar incubation with hydrogen peroxide. We speculate that the changes in membrane function, which follow peroxidant injury, contribute to the shortened red cell survival in the vitamin E deficient state.

Cell Membrane Permeability↗

Comparison of response formats for the Depression Adjective Check Lists.

Studied potential checking and response bias on the Depression Adjective Check Lists (DACL) by comparing the scores of 144 college students on three administration formats: True-false, forced-choice, and standard format. The DACL scores on the three formats were interrelated significantly with one another as well as with an independent measure of state depression of college students (CID). Correlations between the number of depressive adjectives checked and the depression score were significant in the true-false format, but not in the standard format. This argues against the use of the true-false format of the DACL. However, in demonstrating only a weak social desirability response bias, and in failing to reveal the existence of a checking bias, the results give further credence to the use of the standard format.

Depressive Disorder↗

Validation of individual items of the Depression Adjective Check List (Form E) across three populations.

Investigated the individual item response patterns of the Depression Adjective Check List (DACL) from E across three study populations by means of 34 stepwise regression analyses where the DACL adjectives were the dependent variables and the population group, sex, race, age and education were the independent variables. The study groups were: An area probability sample of Kansas City residents (N = 3,313), adult applicants to an urban community mental health center (N = 1,087) and a national probability sample (N = 3,007). Thirty-two of the 34 analyses produce the population as the most significant contribution to the prediction equation. Additional findings are discussed.

Adult↗

Norms for the revised Hebrew version of the Depression Adjective Check List.

In order to reduce the readability level of the Hebrew version of the DACL, a new list of words with high frequency of usage in the Hebrew language was created from the translations of E, F, and G. Ninety-four Ss completed the revised form and the translated standard form E in randomized order; the correlation was .90 (p less .001). Split-half reliability for the revised form was .83 (N = 1,230, p less than .001). The revised DACL was included in a national probability sample survey (N = 1253; 699 females and 544 males). T score and percentile norm distributions are skewed toward the left. Raw scores above 20 are rare.

Adolescent↗

Correlates of depression in chronic dialysis patients: morbidity and mortality.

A group of 74 end-stage renal disease outpatients on dialysis completed on of seven forms of the Depression Adjective Check List (DACL) (Lubin, 1981) once a month over a 12-month period. Patient cooperation in filling out the DACL was 95%, indicating patient's acceptance of this fairly unobtrusive instrument. The distribution of usable DACL scores of 53 patients was trifurcated: high = one SD above the mean; medium +/- one SD from the mean; and low = more than one SD below the mean. A one-way ANOVA on the mean number hospitalizations during the 12-month period for each group was significant, F (2,50) = 8.11, p less than .01. The mean number of hospital admissions was highest for the high depression group and lowest for the low depression group. DACL scores of seven patients who died were significantly higher than for the 46 survivors, t (60) = 4.44, p less than .01.

Depression↗