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Biomedical subjects

M Shaklai

Publications and source records attributed to M Shaklai.

At least 91 records · Page 5Linked to original sources
PubMed1984

Monoclonal gammopathy in patients with chronic and acute myeloid leukemia.

Monoclonal IgG components were found in the serum of 5 of 40 patients with chronic myelocytic leukemia (12.5%), as well as in 2 of 15 patients with acute myelocytic leukemia (13.3%). These findings may represent an involvement of the lymphoplasmacytic system in myeloproliferative disorders. The significance of this association is discussed.

Adult↗
PubMed1984

The interaction of hemin with skeletal muscle actin.

The ability of actin to interact with hemin was studied. It was found that the Soret absorption band of hemin changes in the presence of actin and that hemin is capable of quenching the fluorescence intensity of actin. These findings were indicative of hemin binding to actin. The binding constant for the high affinity site was calculated to be 5.3 X 10(6) M-1. The amounts of native G- and F-actin were estimated by their DNAase I inhibition activity. It was observed that the binding of hemin to G-actin is followed by a slow decrease in the ability of actin to inhibit DNAase I activity and to polymerize upon addition of salts. Binding of hemin to F-actin resulted in a gradual depolymerization of the filaments, to an inactivated form, as expressed by a reduction in the ability of hemin-bound F-actin to inhibit DNAase I activity in the absence as well as in the presence of guanidine-HCl. Electron microscopy studies further corroborated these findings by demonstrating that: (1) hemin-bound G-actin failed to show formation of polymers when salts were added; (2) a marked reduction in the amount of actin polymers was observed in the specimens examined 24 h after mixing with hemin. It is suggested that the elevated amounts of free hemin formed under pathological conditions, might be toxic to cells by interfering with actin polymerization cycles.

Actins↗
PubMed1984

Glycine pools and turnover rates in leukaemia patients measured with [15N]glycine.

Turnover parameters for plasma glycine were measured by administration of a single dose of [15N]glycine to overnight fasted healthy volunteers, nine patients with chronic leukaemia, one patient with acute monocytic leukaemia and one patient with chronic myeloid leukaemia before and after chemotherapy. Gas chromatography-mass spectrometry was used to determine plasma [15N]glycine enrichment. Pool sizes and turnover rate constants were estimated from time-decay curves for isotope enrichment. Turnover rate constants and metabolic clearance rates of plasma glycine in leukaemia patients were elevated in comparison with data for healthy volunteers. The increased rates of glycine disappearance from the circulation were not accompanied by a depletion in glycine pool size. Turnover rate constants fell during chemotherapy and were within the normal range during remission. There was a significant positive correlation between glycine turnover rate constants and leucocyte counts. The increase in glycine turnover rate constants may be related to proliferation of the neoplastic cells.

Female↗
PubMed1984

Interaction of spectrin with hemin disaggregates spectrin associations.

Crude spectrin preparations were extracted from red cell membranes either in dimeric or tetrameric forms and incubated at 4 degrees C with hemin. The mixtures were subjected immediately or after 18 hours to nondenaturing electrophoresis. It was found that immediately after addition of 0.3 mM hemin, the fraction of spectrin complexed with other skeletal proteins, disaggregated to tetramer and dimer forms. After incubation for 18 hours at 4 degrees C most of the spectrin appeared in two additional bands which contained more hemin and migrated on the gels as molecular weight forms smaller than the dimers. Since SDS electrophoresis showed that spectrin subunits retained their integrity in these mixtures, it was concluded that hemin bound spectrin dissociates with time into monomers. It is suggested that there are pathophysiological implications to the disaggregation of spectrin complexes in the cytoskeleton by hemin.

Erythrocyte Membrane↗
PubMed1983

Erythrocyte uroporphyrinogen synthase activity as a possible diagnostic aid in the diagnosis of lymphoproliferative diseases.

Patients with active lymphoproliferative diseases were shown to have high activity of erythrocyte uroporphyrinogen synthetase (URO-S), the enzyme which converts porphobilinogen to uroporphyrinogen. In a few patients examined the lymphocyte URO-S was markedly increased. No correlation was found between the high URO-S activity and the degree of anemia, reticulocytosis, or the presence of hemolysis. Patients with epithelial malignancies and with some common viral diseases had normal erythrocyte URO-S values. Three patients with nonalcoholic cirrhosis also had high erythrocyte URO-S activities. The determination of erythrocyte and lymphocyte URO-S activity may be of aid in the diagnosis of lymphoproliferative diseases. It may also indicate whether remission has been achieved and whether treatment should be continued or reinstituted. These preliminary observations justify the investigation of a larger patient and control material.

Adult↗
PubMed1982

Homogeneous populations of macrophages from histiocytic lymphoma patients as a source for macrophage subpopulations which differ in immunoregulatory properties.

The existence of subpopulations of macrophages which express a variety of regulatory activities of other branches of the immune system is suggested in a comparative study of a human macrophage long term culture ZI and a macrophage cell line DAB-1. Both cell cultures were derived from pleural effusions of patients with diffuse histiocytic lymphoma. DAB-1 cells were found to secrete factors which strongly suppress the response of normal T and B lymphocytes to the mitogens PHA, Con-A and pokeweed mitogen (PWM) (by 96-98%) and to stimulate the cytotoxic activity of NK cells. ZI cells secrete factors which have a mild inhibitory effect on the response of lymphocytes to the T-cell mitogens PHA and Con-A and a stimulatory effect on the response to PWM, whereas very little effect could be detected on the activity of NK cells. While DAB-1 cells form large clusters during growth in culture, and are capable of inducing the formation of lymphocyte rosettes around the tumor cells, ZI cells grow as a homogeneous monolayer and could not be shown to form such rosettes. The differences in the behavior of the two cell populations suggest that the malignant transformation may have affected different subsets of macrophages in each case. Cells from histiocytic lymphoma patients may therefore be a source for homogeneous subpopulations of macrophages and their isolation and propagation in culture is one approach by which such subsets can be defined characterized and classified. The biological characterization of macrophage subsets may also be of clinical importance since a transformed subset with broad suppressory activities may lead to a violet and rapidly deteriorating course of disease, as was in the case of the patient from whom the DAB-1 cell line was derived.

Adult↗
PubMed1982

Absence of predictive parameters for CNS involvement in adult non-lymphocytic leukaemia at time of diagnosis.

13 patients with adult non-lymphocytic leukemia (ANLL) who developed central nervous system (CNS) involvement during the course of their illness are reported and compared with a control group of 26 ANLL patients without CNS involvement. The incidence of CNS involvement was 13/510 patients (2.5%). Initial symptoms and signs and routine laboratory data were not helpful in predicting which patients would ultimately develop CNS involvement. Almost 1/2 of the patients were in clinical and haematological remission at the time of the diagnosis of CNS involvement. Specific treatment to the CNS including intrathecal cytotoxic drugs and/or radiotherapy failed to increase the survival rate significantly. Whether the establishment of an early diagnosis of CNS involvement and the institution of appropriate treatment may improve the prognosis of this complication is a question which presently remains unanswered.

Adult↗
PubMed1982

Familial multiple myeloma. A review of thirty-seven families.

The review of the pertinent literature disclosed 36 reports of familial multiple myeloma, described mostly in siblings, to which the authors add one more family. These patients did not differ significantly from those with non-familial myeloma with regard to sex, age, distribution of monoclonal proteins, clinical and laboratory data, and the course and prognosis of the disease. An increased incidence of immunoglobulin abnormalities was observed in healthy relatives of patients affected with familial myeloma. In most cases the time interval of the diagnosis of myeloma in a family member of a known patient was under 4 years. These observations, in conjunction with reports of myeloma occurring in clusters in a community and the appearance of myeloma in spouses raise the possibility of an environmental factor (virus?) which may contribute to the pathogenesis of myeloma in genetically predisposed individuals. Multiple myeloma should be added to the list of neoplastic diseases in which the family history is relevant and in which genetic and possibly environmental factors may be pathogenetically involved.

Aged↗
PubMed1982

Morphological platelet anomalies in thrombotic thrombocytopenic purpura.

A patient with thrombotic thrombocytopenic purpura was treated with 8 U of fresh frozen plasma, resulting in a rapid improvement in her condition and subsequently followed by a prolonged clinical remission. The transmission and scanning electron microscopic examinations of the platelets performed before treatment demonstrated marked anomalies of the platelet morphology, namely, an increased number of abnormally elongated pseudopods with terminal knobs, a decreased number of platelet granules and excess of glycogen and marked anisocytosis. These anomalies remained unchanged when reexamined 2 months after the achievement of the clinical remission. The question whether these platelet abnormalities are an integral part of thrombotic thrombocytopenic purpura and play a role in its pathogenesis, is raised.

Blood Coagulation Factors↗
PubMed1982

Lanthanum as an electron microscopic stain.

Applications of lanthanum as an electron microscopic tracer have been reviewed. This electron-dense trivalent cation, which binds avidly to calcium binding sites, can be used as tracer for delineating extracellular spaces and intercellular junctions. It has served as a basis for classification of junctional structures. It can also be used as a calcium probe, a tracer in studying the permeability of barriers, as an intracellular marker and as an electron microscopic stain for such membrane components as surface glycoprotein. Each of these applications may require a different methodology. Thus methodological considerations in the use of this tracer have also been reviewed. The recent recognition that lanthanum is more than a passive tracer and that by reacting with different cell components may serve as a true stain, will extend the use of lanthanum in electron microscope histochemistry.

Animals↗
PubMed1982

Production of a colony-inhibitory factor by ethylamine in continuous, long-term marrow culture.

The effect of ethylamine (EA), a simple alkylamine, on continuous, long-term marrow culture was studied in the mouse. EA reduced the granulocyte-monocyte progenitor cell (CFU-c) activity in the supernatant of these cultures in a dose-dependent fashion. This inhibitory effect persisted even after the EA was completely removed from the culture. Moreover, the cell-free supernatant showed inhibitory activity on the growth of CFU-c using freshly isolated target cell. This inhibitory effect also persisted after the EA was completely removed from the culture. Thus, EA appeared to induce changes in these cultures not only by interfering with their potential to maintain the CFU-c but also by releasing a factor in the supernatant that was inhibitory to the CFU-c growth derived from fresh bone marrow. Electron microscopy indicated profound alterations in lysosomal structures. The selective accumulation of this weakly basic substance in the lysosomes may lead to elaboration and release of a colony-inhibitory factor in the supernatant. This effect of EA appears to be independent of its effect on receptor-mediated endocytosis.

Animals↗
PubMed1982

Gaucher's disease: a disease with chronic stimulation of the immune system.

Concentrations of IgA, IgG, and IgM were measured in 25 patients with Gaucher's disease. The mean of each was significantly higher than that generally observed in healthy adults. A direct correlation was noted between IgA and IgG concentrations and age. Patients who underwent splenectomy had IgM concentrations significantly lower than those of persons who did not. In two of 25 patients, multiple myeloma of the nonsecretory type developed. The migration inhibition factor (MIF) test performed with the lymphocytes of our patients was positive to glucocerebroside in four of 17 patients, to glucocerebrosidase in four of 19 patients, and to the extracts of the spleen of a patient with Gaucher's disease in three of eight patients. The results of al MIF tests were negative in six control subjects with splenomegaly of other causes. Our results suggest that in Gaucher's disease there is chronic stimulation of the humoral immune system. The first expression of this stimulation is the production of polyclonal immunoglobulins and, in due time, the development of monoclonal immunoglobulin as well as multiple myeloma.

Adult↗
PubMed1982

The mechanism of benign hereditary neutropenia.

Benign familial (hereditary) leukopenia and neutropenia (BFLN) have been reported in some ethnic groups, including black Americans and Yemenite Jews. The bone-marrow response of 34 Yemenite Jews (with and without neutropenia) to an intravenous injection of 200 mg of hydrocortisone sodium succinate was studied and compared with the response of 18 healthy control subjects. The mean +/- SEM of the increments in polymorphonuclear cells (PMNs) following injection of hydrocortisone in Yemenite Jews (2,413 +/- 245/mm3 in neutropenic subjects and 2,187 +/- 343/mm3 in nonneutropenic subjects) were significantly lower than in the control subjects (4,431 +/- 467/mm3), without significant differences among the subgroups of the Yemenite Jews. The decreases in monocytes, lymphocytes, and eosinophils were similar in all groups. No correlation was found between baseline PMN levels and the increments following hydrocortisone administration. These results suggest a lowered bone-marrow response to hydrocortisone in subjects with BFLN, indicating some defect in PMNs release from the bone-marrow storage pool to the peripheral blood. It seems that this defect characterizes all members of the ethnic group, whether they have "overt" neutropenia or not.

Adult↗