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Biomedical subjects

E Shinar

Publications and source records attributed to E Shinar.

At least 55 records · Page 3Linked to original sources
PubMed1987

Erythrocyte membrane skeleton abnormalities in severe beta-thalassemia.

The protein composition of ghosts, inside-out vesicles (IOV), and membrane skeletons (MS) of erythrocytes (RBC) from splenectomized (spx) and nonsplenectomized (non-spx) patients with beta-thalassemia major and beta-thalassemia intermedia was determined. Ghosts from spx thalassemia intermedia patients had a significant increase in their globin content (which was mostly heme reactive) and contained extra polypeptides in the protein 4.2 to 5 and 6-globin areas. The Triton-extracted MS from all of the thalassemic patients showed two major abnormalities: they retained up to twice the amount of protein 3 when compared with controls; they had a significant increase in their globin content, the concentration of which was independent of their protein 3 content. Analysis of the IOV revealed no differences between those prepared from normal controls and those of the patients. MS from spx thalassemia intermedia patients were grossly abnormal when examined by scanning electron microscopy and they exhibited aggregates of material that on transmission electron microscopy suggested the presence of globin precipitates. We propose that, although the integral protein composition, as reflected in the IOV, from severely affected beta-thalassemics is intact, their MS assembly is deranged. The altered skeletal structure of thalassemic RBC could result from attachment of denatured globin to the skeleton components. These abnormalities may contribute to the premature cell death seen in severe beta-thalassemia.

Cytosol↗
PubMed1986

Managing the granulocytopenic patient with acute perianal inflammatory disease.

Acute perianal inflammation concomitant with a decrease in the number of circulating granulocytes developed in 15 patients with various hematologic disorders. The treatment included antibiotic coverage alone (11 patients) or combined with surgical drainage of the inflamed area (7 patients). Our study shows that surgical drainage during agranulocytosis resulted in slow healing of the wound, prolonged hospitalization, and a higher mortality rate, when compared with the group that received antibiotics alone (28 percent versus 18 percent). The preferred treatment for these patients is the administration of broad spectrum antibiotics without attempting drainage of the infected area.

Acute Disease↗
PubMed1985

Alterations in membrane protein and phosphorylation pattern in beta-thalassemic red blood cells.

The architecture and phosphorylation pattern of RBC membranes were studied in intact RBC and ghosts of patients with beta-thalassemia intermedia. Electron microscopic studies showed severe morphological alterations in ghosts from spx thalassemic patients. The polypeptide pattern obtained on SDS-PAGE revealed a fourfold increase in globin content of ghosts from spx patients. In addition, multiple protein bands were detected migrating below band 4.2, accompanied by alterations in the band 3 zone. When membrane protein phosphorylation was examined by SDS-PAGE and auto-radiography following incubation of intact RBC with [32P]Pi, a reduced labeling of the normally phosphorylated polypeptides was found in the thalassemic RBC. In addition, new phosphorylated peptides appeared in the region of band 3 and below band 4. On the other hand, phosphorylation of isolated membranes with [gamma-32P]ATP showed no major differences in the labeling of the major phosphorylated proteins. An analysis of the initial rate of spectrin-band 2.1 phosphorylation obtained by counting the excised bands from the SDS gels showed that there was a twofold increase in spectrin-band 2.1-phosphorylation rate catalyzed by cAMP-dependent protein-kinase in the thalassemic ghosts, although no differences were found in the extent of spectrin phosphorability. The results are consistent with major changes in membrane protein disposition in thalassemic RBC, most probably caused by the precipitation of excess globin chains.

Electrophoresis, Polyacrylamide Gel↗
PubMed1985

Predominant T cells in pleural effusion of a patient with B-cell CLL.

Pleural effusion is a relatively rare complication of chronic lymphatic leukemia (CLL). It can be the result of primary pleural involvement, central lymphatic blockage, infection or changes induced by previous irradiation or chemotherapy. When the effusion is caused by leukemic pleural infiltration, the lymphocytes are identical to those in the peripheral blood. We have recently treated a splenectomized patient with B-cell CLL who developed pleural effusion with predominant T cells. It is suggested that this might be due to a redistribution of the T cells in the recirculating lymphocytic pool in a patient who had undergone splenectomy in the past. The possible source of these cells in the pleural effusion is discussed.

B-Lymphocytes↗
PubMed1984

Lactobacillus plantarum endocarditis.

Subacute bacterial endocarditis developed in a 30-year-old male with rheumatic valve disease. The causative organism was identified as Lactobacillus plantarum. After three different antibiotic regimens had failed to control the infection, surgical replacement of the affected valve was curative.

Adult↗
PubMed1984

Pancytopenia with hypercellular bone marrow--a possible paraneoplastic syndrome in carcinoma of the lung: a report of three cases.

Three patients with idiopathic pancytopenia and hypercellular bone marrow who developed carcinoma of the lung within two years of diagnosis are reported. All three patients had macrocytic anemia associated with a megaloblastic marrow in the presence of normal serum vitamin B12 and folic acid levels. Neutropenia with monocytosis, elevated serum muramidase and LAP scores, and increased fetal hemoglobin levels were also found. In all cases Ham's tests were negative with a normal bone marrow karyotype. In all three patients, pancytopenia due to myelodysplasia, a probable preleukemic state, was diagnosed initially prior to the appearance of carcinoma of the lung. One of the patients showed improved leukocyte and platelet counts during chemotherapy, while the other two died before chemotherapy could be administered. In the light of the above findings we suggest that carcinoma of the lung may be the cause of a paraneoplastic syndrome with pancytopenia, particularly in patients with a hypercellular marrow with a normal karyotype.

Adenocarcinoma↗
PubMed1984

Impaired erythrocyte calcium homeostasis in beta-thalassemia.

Intracellular calcium (Ca) concentration in erythrocytes (RBCs) is controlled by a low passive influx through a relatively impermeable membrane and by active efflux catalyzed by Ca2+,Mg2+-ATPase. Since precipitation of alpha-globin chains in thalassemic RBCs may interfere with normal membrane function, we studied the RBC intracellular Ca content and the RBC membrane Ca2+,Mg2+-ATPase activity in two groups of patients with nonsplenectomized (n = 9) and splenectomized (n = 9) beta-thalassemia intermedia and in two groups of matched controls. The mean +/- SD Ca concentration in the nonsplenectomized (n = 12) and splenectomized (n = 6) controls were 6.1 +/- 6.0 and 5.8 +/- 3.4 mumol Ca per liter of RBCs, respectively, compared with 26.0 +/- 7.6 (P less than .001) and 85 +/- 24.4 (P less than .001) in the nonsplenectomized and splenectomized thalassemia patients, respectively. The mean +/- SD Ca2+,Mg2+-ATPase activity in the eight nonsplenectomized patients was 0.77 +/- 0.58 mumol inorganic phosphate (Pi) per milligram of protein per hour compared with 0.66 +/- 0.41 in the controls (P = NS). Similar values were obtained for the splenectomized patients and their controls. No correlation was found between either the intracellular Ca content or the Ca2+,Mg2+-ATPase activity with the peripheral nucleated RBC count. These findings suggest that there is a major defect in the membrane of the thalassemic RBC leading to an increased Ca content that is more pronounced in splenectomized patients.

Calcium↗
PubMed1984

Acridinyl anisidide (m-AMSA) therapy in 11 patients with refractory acute leukemia.

Eleven patients with acute leukemia, refractory to all previous chemotherapy, were treated with acridinyl anisidide (m-AMSA). Seven patients received m-AMSA i.v. as a single agent at 150 mg/m2 daily for 4 to 7 days, and 4 patients received m-AMSA at 90 mg/m2 daily for 3 days in combination with thioguanine and cytosine arabinoside. Four of the nine patients with acute nonlymphoblastic leukemia responded to the treatment, and complete remission was obtained in three of them. One of these patients remained in complete remission 5 months after therapy. Three of the four responding patients received m-AMSA as a single agent. Two patients with resistant acute lymphoblastic leukemia did not respond. As in earlier trials with m-AMSA reported by others, about one-third of our refractory patients responded, which justifies the future use of this agent in refractory leukemia and in other regimens for the induction of remission in acute leukemia. Despite minimal cardiotoxicity of the drug, evidence of its cardiotoxic potential is recorded.

Adolescent↗
PubMed1984

Acute electrocardiographic changes induced by amsacrine.

The ECG effect of amsacrine (m-AMSA) was evaluated in 12 consecutive patients with leukemia. m-AMSA induced a significant prolongation of the Q-T interval (msecs, mean +/- SE) before (448 +/- 13) and 1 hour after (512 +/- 12) treatment (P . 0.0001, paired t test), without concomitant changes in the P-R interval, QRS duration, and heart rate. This selective cardiotoxic effect appeared to be transient and was noted towards the end of the iv drug administration, but was not present 24 hours later. No cardiac arrhythmias were noted during continuous monitoring. Nevertheless, it is assumed that the prolongation of the Q-T interval may represent a state of increased vulnerability to rhythm disturbances. Special care should be taken to avoid factors that may prolong the Q-T interval (hypokalemia, ischemia, or premedication with phenothiazine) during the administration of m-AMSA.

Acute Disease↗
PubMed1983

The analogous mechanisms of enzymatic inactivation induced by ascorbate and superoxide in the presence of copper.

The mechanism of enzymatic inactivation of purified and membrane-bound acetylcholine esterase by ascorbate and copper was investigated. While the exposure of the enzyme to either ascorbate or copper did not cause enzymatic inactivation, the incubation of the enzyme with a combination of both ascorbate and copper resulted in a loss in acetylcholine esterase activity, which was time dependent. The enzymatic inactivation required either molecular oxygen or hydrogen peroxide under anaerobic conditions. Scavengers of hydroxyl radicals at concentrations of up to 100 mM did not provide protection to acetylcholine esterase. Only mannitol at very high concentrations (above 1 M) efficiently prevented the inactivation of the enzyme. The kinetics of the aerobic oxidation of reduced ascorbate in the presence of acetylcholine esterase and copper closely followed the rate of enzyme inactivation. Addition of the chelating agents EDTA and diethylenetriaminepentaacetic acid prevented both the oxidation of ascorbate and the inactivation of the enzyme. In the presence of low concentrations of histidine (0.5-2.0 mM), which forms high affinity complexes with copper, the rate of ascorbate oxidation was similar to that recorded in its absence. On the other hand, no enzyme inactivation was indicated in the presence of histidine. Low temperature EPR measurements have demonstrated the binding of copper to the enzyme, and have shown the reduction of the cupric enzyme to the corresponding cuprous complex. In view of these results, a general "site-specific" mechanism for biological damage can be offered, in which copper(II) ions are bound to enzymes or other biological macromolecules. Ascorbate plays a dual role: it reduces the cupric complex to the corresponding cuprous state and serves as a source for H2O2, which, in turn, reacts with the reduced copper complex, in a Fenton reaction. In this reaction, secondary hydroxyl radicals are site specifically formed, and react preferentially with the protein, at the site of their formation, causing its inactivation. This mechanism is analogous to that previously proposed (Samuni, A., Chevion, M., and Czapski, G. (1981) J. Biol. Chem. 256, 12632-12635) for the enhancement of the biological damage caused by superoxide in the presence of copper.

Acetylcholinesterase↗
PubMed1983

Neutropenic typhlitis. A plea for conservatism.

Neutropenic typhlitis is an acute inflammation of the cecum occurring in neutropenic patients. Two cases are described, both presenting typical features of the disease. It is our experience that the treatment approach should consist of bowel rest, fluid therapy, and massive administration of broad spectrum antibiotics. In some cases, full recovery will follow. If abdominal signs persist, surgery should be deferred until hematologic convalescence occurs. At this time, cecostomy and drainage should be adequate. Only in very severe cases, with wide-spread necrosis, should a right hemicolectomy be performed.

Acute Disease↗
PubMed1983

Alterations in structure, function, and Ca++ content of thalassemic red blood cells.

Dodge ghosts and their Triton extracted cytoskeletons (TS) were obtained from RBC of splenectomized (spx) and non-splenectomized (non-spx) patients with beta thalassemia intermedia. No major abnormalities were seen in the polypeptide pattern of Dodge ghosts of the thalassemic patients apart from increased globin content in the spx patients (P = 0.004). There was also a large increase of globin content in the TS of both spx and non-spx patients, while the spectrin content of the TS was markedly decreased from 22 +/- 2.8% in the spx patients compared to 39 +/- 2% in the controls (P = 0.006). At least part of the globin was not found at the normal band 3-binding site. The mean Ca++ content in spx and non-spx controls was approximately 6.0 micromoles ca/liter RBC, as compared to 26 +/- 7.6 (P less than 0.001) in the non-spx and 85 +/- 24 in the spx thalassemic patients (P less than 0.001). (Ca++Mg++)-ATPase activity was in the same range in RBC of patients and controls. Membrane protein phosphorylation was examined by incubation of intact cells with (32P)Pi. There was decreased labeling of several protein bands in thalassemic RBC which are labeled in normal RBC. New phosphorylation peptides also appeared. On the other hand, there were no major differences in the phosphorylation of isolated membranes including phosphorability of spectrin. The possible etiology and consequences of the newly described RBC membrane changes in thalassemia is discussed.

Blood Proteins↗
PubMed1983

Causes of agranulocytosis in a hospital population: identification of dipyrone as an important causative agent.

A population of patients with agranulocytosis admitted to a general hospital over a period of 12 yr was studied retrospectively in order to determine the causes of the disease. Of the 48 cases identified, 31 (65%) had drug-induced neutropenia, whereas 17 (35%) had chronic neutropenia unrelated to the use of drugs. Eight patients had an underlying hematological malignancy. Patients with agranulocytosis not induced by drugs more frequently had hepatomegaly, splenomegaly, enlarged lymph glands, or thrombocytopenia together with severe anemia. In contrast, drug-induced agranulocytosis was more severe, with a higher incidence of positive blood cultures, low cellularity of initial bone marrow aspirates, and a shorter duration of neutropenia. Dipyrone and methimazole were the drugs most commonly associated with agranulocytosis. Dipyrone was probably the causative agent in two of the seven drug-induced fatalities. In view of these findings, and those of several previous reports, it is proposed that the use of dipyrone in Israel be severely restricted or discontinued altogether.

Adolescent↗
PubMed1982

Coexistence of Gaucher Disease and Philadelphia positive chronic granulocytic leukemia.

A patient with coexistent Gaucher disease and Philadelphia positive chronic granulocytic leukemia (CGL), who subsequently developed myeloblastic leukemia, is described. The diagnosis of CGL was established according to standard clinical, morphological, biochemical, and cytogenetic data, while the diagnosis of true Gaucher disease was based on biochemical data and the presence of Gaucher cells with typical ultrastructural features in the bone marrow and spleen. Enzyme studies showed low activity of ceramide-beta-glucosidase in the patient's peripheral blood leukocytes, skin fibroblasts, and splenic tissue and the presence of increased amounts of ceramide-beta-glucoside in the spleen. This case is reported in order to draw attention to the possible coexistence of these two diseases in the same patient, as opposed to the well-recognized finding of "Gaucher-like" cells in the bone marrow of patients with CGL. Enzyme studies enable distinction between these two situations.

Chromosomes, Human, 21-22 and Y↗