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Biomedical subjects

D Meytes

Publications and source records attributed to D Meytes.

At least 55 records · Page 3Linked to original sources

Lymphocyte subsets in habitual abortion.

Lymphocyte subpopulations were characterized by means of monoclonal antibodies in 25 women with habitual abortion and 21 multiparous normal women. Compared to nonpregnant women (N = 8), pregnant normal women were associated with significantly lower helper-to-suppressor ratios (1.71 +/- 0.41 versus 2.37 +/- 0.66). In contrast in pregnant women with habitual abortion (N = 13) the ratio remained high (2.32 +/- 0.73). Failure to increase the number of suppressors and a significant rise in helpers caused this increased ratio. We discuss the possible mechanisms and etiological importance of this finding in habitual abortion.

Abortion, Habitual↗

Heparin-induced thrombocytopenia and recurrent thrombosis in pregnancy. A case report.

Heparin-induced thrombocytopenia with thromboembolism calls for an immediate substitution of the heparin with other potent anticoagulants, such as coumarin derivatives. The occurrence of this adverse effect in pregnancy poses an additional dilemma because the use of coumarin derivatives is not acceptable during pregnancy, while other medications may not be as effective. In a pregnant patient treated with mucous sodium heparin for deep vein thrombosis, recurrent heparin-induced thrombosis and disseminated intravascular coagulation (DIC) occurred. Replacing the heparin with a different brand of the same drug resulted in reversal of the DIC and in clinical improvement. If severe heparin-induced thrombosis occurs in a patient in whom anticoagulation with other drugs is contraindicated, substituting one brand of heparin for another could be of value.

Adult↗

Coexistence of nonsecreting and nonproducing light chain multiple myeloma.

A 61-year-old female patient presented with osteolytic skeletal lesions. Open rib biopsy disclosed tumor tissue which consisted of two types of cells: massive infiltrates of poorly differentiated lymphoplasmacytic cells were surrounded by large deposits of differentiated plasma cells. Serum immunoglobulins were normal. No light chains could be found in the urine. An immunoperoxidase technique was employed to detect intracellular immunoglobulins. While the partially differentiated cells were negative, the plasma cells were stained strongly positive for kappa light chains.

Female↗

Measurement of human erythroid burst-promoting activity by a specific cell culture assay.

A two-stage cell culture assay specific for human erythroid burst-promoting activity (BPA) is described. Human peripheral blood mononuclear cells were cultured in suspension with or without a BPA test sample for two days, then transferred to methylcellulose medium with added erythropoietin (EPO) and incubated for ten more days, and finally BFU-E-derived colonies were scored. An increase in number of colonies due to the presence of BPA was observed that was proportional to the concentration of BPA in the test sample. This response was linear with respect to number of cells plated between 2 and 5 X 10(5)/ml. The system was standardized with a partially purified human urinary BPA preparation. Dose responses to urinary protein preparations, plasma, and serum were parallel. The assay system was found to be nonresponsive to highly purified EPO and to bacterial endotoxin. It was determined that BPA action was confined to the suspension culture stage of the assay, while EPO presence was an absolute requirement during methylcellulose culture. In the two-stage assay optimal amounts of BPA caused up to 358% increases of BFU-E-derived colonies; the same amounts of BPA added to conventional methylcellulose cultures caused only up to 54% increases over the number of colonies obtained with EPO alone. Plasma and serum BPA levels of hematologically normal and abnormal individuals showed no correlation with EPO levels and hemoglobin (Hb) concentrations. This seems to rule out the possibility that BPA elaboration is regulated by oxygen availability or the amount of EPO circulating in an organism.

Anemia, Aplastic↗

Human bone marrow fibroblast proliferation and GM-CFC colony formation in patients with acute leukemia.

The proliferation of bone marrow (BM)-derived fibroblasts and granulocyte-macrophage progenitors (GM-CFC) was studied in culture in 23 patients with acute leukemia (AL). The number of GM-CFC colonies was significantly lower in patients with infiltrated BM when compared to those in remission: 17 +/- 12 vs. 125 +/- 35 colonies per 2 X 10(5) cells (p less than 0.005). The proliferation of fibroblasts derived from leukemic BM was significantly more active in acute nonlymphocytic (ANLL) than in acute lymphoblastic leukemia (ALL): 6.8 +/- 3.2 X 10(5) vs. 2.8 +/- 1.8 X 10(5) fibroblasts per flask (p less than 0.05). The reduced GM-CFC colony formation correlated significantly (r = 0.84; p less than 0.02) with the reduced fibroblast proliferation in patients with ALL but not in those with ANLL. Supernatants from fibroblast monolayers stimulated additionally normal GM-CFC cultured in the presence of a potent conditioned medium as the source of colony stimulating activity. Fibroblast supernatants derived from BM with leukemic infiltrates, stimulated the incorporation of 3H-thymidine by monolayers of normal bone marrow fibroblasts but had no effect on ANLL fibroblasts.

Acute Disease↗

Chemotherapy related leukemogenesis.

Administration of aggressive chemotherapy to patients with cancer has considerably improved their outlook for effective palliation or cure. However, a hitherto unappreciated complication consisting of a secondary malignancy, in particular acute leukemia, has emerged. Prolonged therapy with alkylating agents and chemotherapy plus radiotherapy are associated with an increased risk of this complication. The disease evolves through a preleukemic phase of pancytopenia and sideroblastic refractory anemia. The median onset from the initiation of chemotherapy is about 5 years with an increasing incidence with time. Myelomonocytic, monocytic and erythroleukemia with atypical features and resistance to conventional therapy predominate. Hyploidy and aberrations involving chromosomes 5 and 7 are frequent. Alkylating agents are carcinogenic in laboratory animals. Although the pathway to leukemogenesis in humans is unknown, a multistep evolution is envisaged. This involves: 1) initiation through induction of errors in DNA, 2) promotion related to stem cell replication following chemotherapy-induced aplasia and 3) propagation related to immunosuppression. It is possible that, as in myeloproliferative disorders, an underlying tendency for leukemia is present in patients with cancer. This may be accentuated by chemotherapy, and more frequently observed due to the longer survival of such patients. The crucial role of chemotherapy in leukemogenesis is evident from data accumulated in non-malignant conditions such as rheumatoid arthritis.

Alkylating Agents↗

The relationship between human spleen and blood erythroid burstforming units (BFU-E).

The influence of splenectomy on erythroid burst colony formation by peripheral blood mononuclear cells from 10 patients (four with hereditary spherocytosis, two with beta-thalassaemia major, two with Hodgkin's disease and two with idiopathic thrombocytopenic purpura) was studied. In every instance splenectomy was followed by a lowering of blood BFU-E. The post-splenectomy levels ranged from 0 to 30% of the preoperative levels. Mononuclear cells from the spleens of eight patients were cultured and found to contain numerous BFU-E. The total quantity of BFU-E in the whole blood and in the spleen of the patients was generally of the same order of magnitude. The number of splenic BFU-E did not correlate with spleen size. Splenic BFU-E differed from peripheral blood BFU-E in that they were more sensitive to erythropoietin (Ep) and in that they failed to respond to burst promoting activity (BPA) produced by preincubating the spleen mononuclear cells with phytohaemagglutinin M (PHA). In contrast, media conditioned by PHA-treated spleen cells contained BPA active on peripheral blood BFU-E from normal individuals. These data suggest that the spleen may have an influence on the numbers and functional properties of BFU-E.

Adolescent↗

Cyclic leukocytosis and long survival in chronic myeloid leukemia.

A patient with an unusually prolonged course of Ph' positive chronic myeloid leukemia is presented. His disease was marked by cyclic leukocytosis, various chromosomal aberrations and secondary thrombasthenia. In vitro culture studies and granulocyte-macrophage colony stimulating factor (GM-CSF) production were consistent with responsiveness of the leukemic clone to GM-CSF. The possible relationship between the long survival and the feedback regulation of leukopoiesis is raised.

Blood Platelets↗

Effect of parathyroid hormone on erythropoiesis.

Inhibitors of erythropoiesis have been found in the blood of uremic patients but their nature has not been identified. These patients have excess blood levels of parathyroid hormone (PTH) and it is possible that PTH inhibits erythropoiesis. The present study was undertaken to examine the effect of intact PTH molecules and some of its fragments on human peripheral blood and mouse bone marrow burst-forming units-erythroid (BFU-E), on mouse bone marrow erythroid colony-forming unit (CFU-E), and granulocyte macrophage progenitors (CFU-GM), and evaluate the interaction between PTH and erythropoietin (Ep) on human BFU-E. Intact PTH (1-84 bPTH) in concentrations (7.5-30 U/ml;) comparable to those found in blood of uremic patients produced marked and significant (P less than 0.01) inhibition of BFU-E and mouse marrow GFU-GM, but not of mouse marrow CFU-E. Inactivation of 1-84 bPTH abolished its action on erythropoiesis. Increasing the concentration of Ep in the media from 0.67 to 1.9 U/ml overcame the inhibitory effect of 1-84 bPTH on BFU-E. The N-terminal fragment of PTH (1-34 bPTH) and 53-84 hPTH had no effect on BFU-E. The results demonstrate that (a) either the intact PTH molecule or a C-terminal fragment(s) bigger than 53-84 moiety exerts the inhibitory effect on erythropoiesis, and (b) adequate amounts of Ep can overcome this action of PTH. The data provide one possible pathway for the participation of excess PTH in the genesis of the anemia of uremia.

Animals↗

Biological properties of a human urinary protein fraction with burst promoting activity.

Urinary proteins from patients with iron deficiency anemia and acquired aplastic anemia were fractionated by chromatography on QAE-Sephadex A-50 and Sephadex G-25. Fractions containing erythroid burst promoting activity (code named regulatory protein RP) were separated from erythropoietin. Mouse bone marrow cells were preincubated for one day in suspension culture, in the presence or absence of RP, transferred to a methylcellulose based system and incubated for six more days with erythropoietin (EPO). It was found that the presence of RP in the preincubation medium had a 2 to 4 fold enhancing effect on subsequent erythroid burst colony formation. However, when RP was added to methylcellulose based cultures simultaneously with EPO, the erythroid burst response was reduced or abolished. Addition of RP to marrow cell suspension cultures increased the number of self replicating, pluripotent (erythroid/granuloid, E/G ratio = 3) spleen colony forming units (CFU-S) found at the end of 2 days incubation 3-5 fold over their number in control cultures incubated without the factor. In marked contrast to this, addition of EPO to the cultures caused an increased persistence of CFU-S with a predominantly erythroid commitment (E/G ratio = 19) and a low self replicating ability, as measured by retransplantation of spleen cells into secondary recipients. These observations are compatible with the presence in RP of a factor, or factors, capable of maintaining the size of certain early precursor cell compartments.

Anemia, Aplastic↗

Constancy of erythroid burst forming unit (BFUE) levels in the blood of hematologically normal individuals.

Repeated determination of circulating blood BFUE levels in 7 hematologically normal individuals, during a 6 to 16 month period, showed their respective levels to be maintained within narrow limits (coefficient of variation did not exceed 15.1%). However, males differed from each other 3-fold and females as much as 12-fold in the number of BFUE/ml blood. These differences may reflect various sizes of the early erythroid progenitor compartment, which in the presence of different levels of humoral regulators of erythropoiesis are capable of maintaining a normal rate of red cell production. Our findings suggest that the observation of changes of the blood BFUE level of individuals, over a period of time, may be indicative of a change in their erythropoiesis and may shed some light on the physiological role of the peripheral blood BFUE.

Blood Physiological Phenomena↗

Human erythroid burst-promoting activity produced by phytohemagglutinin-stimulated, radioresistant peripheral blood mononuclear cells.

The regulation of erythroid burst-colony formation was studied in cultures of human peripheral blood mononuclear cells. Numbers of erythropoietin-stimulated colonies obtainable from the cells in response to various treatments were compared. One-day preincubation of the cells with phytohemagglutinin (PHA) doubled the yield of colonies. Irradiation of the cells with 3000 rad eliminated their ability to form erythroid bursts, but did not impair the ability of PHA-treated cells to enhance burst formation when added to a fresh batch of cells. This was due to a humoral factor, since media conditioned by PHA-treated washed cells were as effective as the cells themselves. When cells were separated into subpopulations by an adherence procedure and according to their ability to form rosettes with sheep red blood cells, it was found that the PHA-dependent burst-promoting activity released into the medium originated in a nonadherent, nonrosetting (T-cell depleted) cell population.

Cell Adhesion↗

The relation between therapy and herpes zoster in Hodgkin's disease.

The rate of occurrence of herpes zoster (HZ) was analyzed by the life table method in 108 Hodgkin's disease (HD) patients, diagnosed and treated during the years 1969 to 1976. Three groups, divided according to the degree of severity of the disease, were compared. The cumulative rate of occurrence of HZ at the end of the third year after diagnosis was higher in the group with intermediately extensive disease than in that with the most extensive disease (35 vs. 23%), but the difference was not significant. At the end of the fifth year, the rate was almost identical in both groups (35.3 and 35.6%, respectively). The group with the least severe form of HD had a very low HZ rate (2.2%), which was significantly different from the other two groups and close to the rate reported for normal populations. The five-year mortality rate was 0.0, 20.3 and 40.6%, respectively, in the three groups. These findings were interpreted to mean that in more advanced stages of HD, therapy and not the severity of the disease is the main factor determining the incidence of HZ. Extended field irradiation followed by a few courses of combined chemotherapy appear to have an effect similar to that of prolonged chemotherapy.

Adolescent↗