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Biomedical subjects

B Ramot

Publications and source records attributed to B Ramot.

At least 91 records · Page 5Linked to original sources

Effect of cardiac operation on platelets.

The effect of extracorporeal circulation on platelet count and size (mean platelet volume) was studied in 65 patients (nine bleeders and 56 nonbleeders). In addition to the above, in 20 of the patients platelet aggregation response to adenosine diphosphate, collagen, and ristocetin was measured. Platelet counts dropped postoperatively both in the bleeder and in the nonbleeder groups. The difference between them was not significant. However, the bleeders had a significantly lower mean platelet volume (7.7 +/- 0.84 versus 8.68 +/- 1.1 fl) and lower volume percentage of platelets in whole blood (0.075% +/- 0.02% versus 0.116% +/- 0.04%) (p less than 0.05) than the nonbleeders. None of the bleeders had a volume percentage of platelets in whole blood higher than 0.095%. All 20 patients studied for platelet functions had an abnormal postoperative aggregation response to adenosine diphosphate, collagen, and ristocetin. Three patterns of disturbed response to ristocetin were observed: grade I, delayed onset (14 patients); grade II, incomplete aggregation (five patients); and grade III, total lack of aggregation (one patient). All patients with delayed-onset response to ristocetin had a normal bleeding time, whereas the six patients with grade II and III responses had prolonged bleeding times and three of them had clinically significant bleeding. Factor VIII procoagulant activity, factor VIII-related antigen, factor VIII-ristocetin cofactor, and factor VIII two-dimensional electrophoresis were found normal, which suggests that the von Willebrand-like reaction to ristocetin observed in this study was caused by a defect in platelet membrane rather than by factor VIII changes.

Adolescent↗

Platelet size and mass as an indicator for platelet transfusion after cardiopulmonary bypass.

Platelet count, mean platelet volume (MPV), and plateletcrit (PCT) were studied in 51 patients after cardiopulmonary bypass (CPB). MPV was significantly lower in 10 patients who developed postoperative bleeding (bleeders) compared to 41 with no significant bleeding (nonbleeders) (7.7 +/- 0.86 vs 8.5 +/- 1.2 fl, p less than .05). Postoperative platelet count was significantly lower in the group of bleeders (93.3 +/- 22.4 vs 127.5 +/- 43 X 10(9)/liters, p less than .02). A cutoff point of MPV or platelet count that would include bleeders and exclude nonbleeders could not be found due to the large overlap between the two groups. However, such a cutoff point does exist for PCT (PCT = total platelet mass). PCT was significantly lower among the bleeders (0.072 +/- 0.02% vs 0.108 +/- 0.036%, p less than .05) and a cutoff point of PCT less than 0.1% included all the bleeders and excluded 65% of nonbleeders. The low PCT and bleeding tendency can be corrected by platelets transfusion. In 15 patients (eight bleeders and seven nonbleeders) with low postoperative PCT (0.078 +/- 0.014), transfusion of 10 platelet units increased platelet count from 101 +/- 32 to 169 +/- 22 X 10(9)/liter, increased PCT to 0.128 +/- 0.2%, and stopped bleeding in all bleeders. A finding of PCT less than 0.1% after CPB is a clear indication for platelet transfusion in patients who develop post-CPB bleeding. This supports the observation that large platelets are more active than smaller ones, and that PCT, rather than PLT counts, predicts the risk of bleeding in patients with thrombocytopenia.

Adolescent↗

Production of burst-promoting activity by monoclonal antibody defined malignant T lymphocytes from patients with lymphocytic leukemia and lymphoma.

We tested conditioned media from 12 patients with T lymphocyte neoplasms and four T cell lines for their ability to stimulate the in vitro growth of erythroid-burst-forming units (BFU-E) from bone marrow mononuclear cells in a methylcellulose culture system. Nine patients suffered from acute lymphocytic leukemia, two from chronic lymphocytic leukemia, and one from non-Hodgkin's lymphoma. The T lymphocytes were characterized by a series of monoclonal antibodies and their stage of development was correlated with their ability to produce burst-promoting activity (BPA). Conditioned media from cells classified as prothymocytes (three cases), common thymocytes (one case), mature thymocytes (three cases), and mature lymphocytes of the helper subtype (two cases) increased BFU-E proliferation four- to 19-fold over control values using normal bone marrow as target cells. Conditioned media from OKT8+ malignant T lymphocytes (three cases) did not enhance BFU-E proliferation. Conditioned media from cells classified as immature T cells stimulated CFU-GM proliferation in only one of seven cases even though they secreted BPA. Conditioned media from three of the four cell lines stimulated by phytohemagglutinin, enhanced BFU-E growth. Our results indicate that malignant cells that have characteristics of immature T cells are able to produce BPA. Studies using techniques to isolate homogeneous populations of normal T cell subsets are required to determine whether normal immature T lymphocytes have the same capability.

Antibodies, Monoclonal↗

Production of colony-stimulating activity (CSA) by T-chronic lymphocytic leukemia cells.

T-lymphocytes are probably involved in regulating myelopoiesis. We show that homogeneous populations of leukemic T-lymphocytes freshly obtained from two patients with T cell chronic lymphocytic leukemia produce colony-stimulating activity. The cells from both patients showed the antigenic and biochemical phenotype of the mature T-lymphocyte of the helper subset. This adds further support to the view that helper T-lymphocytes may regulate hematopoiesis in addition to their role in the immune function.

Adenosine Deaminase↗

Amodiaquine-induced agranulocytosis: drug inhibition of myeloid colonies in the presence of patient's serum.

We report a patient who developed agranulocytosis following exposure to three drugs: amodiaquine, pyrimethamine and dipyrone. The combination of amodiaquine with the patient's serum, obtained during the agranulocytosis, inhibited in vitro granulocyte-monocyte colony-forming unit (CFU-GM) growth of autologous and allogeneic marrow. These results support the view that amodiaquine-induced agranulocytosis is immune in nature. This in vitro approach may be used to study the mechanism of drug-induced agranulocytosis, especially when patients are exposed to multiple drugs.

Agranulocytosis↗

Transformation of chronic lymphocytic leukemia to plasmacytoma.

In a woman with chronic lymphocytic leukemia (CLL), a maxillary plasmacytoma developed after 8 years. The membrane-bound immunoglobulin of the leukemic lymphocytes, the cytoplasmic immunoglobulin of the plasma cells, the serum monoclonal protein and the urine Bence-Jones protein had the same heavy and light chains--mu kappa. This suggests that the leukemic cells transformed to plasma cells. This very rare event is a complete reversal of the more common transformation that occurs in CLL and manifested by de-differentiation. Only in one case out of the 20 previously reported patients with CLL and multiple myeloma there was evidence, like in the current case, of a common clonal origin of the two B-cell neoplasms.

Adult↗

The epidemiology of childhood acute lymphoblastic leukemia and non-Hodgkin's lymphoma in Israel between 1976 and 1981.

n epidemiologic survey of childhood acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL) occurring in Israel, Judea, Samaria and the Gaza Strip between the years 1976 and 1981, revealed 205 cases of ALL and 69 of NHL. The mean annual incidence of lymphatic malignancies was 3.1/10(5) in the Israeli Jews, 2.3/10(5) in the Israeli Arabs and 2.5/10(5) in the Gaza Strip. In the Jewish population there was a peak in the incidence of lymphatic malignancies at the 2-5 years age group, while in the Israeli Arabs this was less prominent. There were no significant differences in the incidence or type of lymphatic malignancies in the various Jewish or Arab groups but there was a trend for a high leukemia to lymphoma ratio (LLR) in the patients from the Gaza Strip. A relatively higher LLR was observed in families of a high socioeconomic status, but it did not reach statistical significance. T-cell ALL comprised about a third of the typed ALL cases. A high proportion of the patients with ALL belonged to the high-risk category: 46% of the Jewish children and 76% of the Gaza Strip children. White blood cell count above 100,000/mm3 were found at presentation in 36.7% of the Gaza Strip patients but only in 9.4% of the Jewish patients. In spite of that, the survival at 4 years of the Jewish and Arab patients was similar. However, the patients with T-cell ALL had a significantly worse survival than the standard risk or the non-T high-risk group: 43.3 +/- 9.7, 66.6 +/- 7.1 and 63.6 +/- 10.4%, respectively. Compared to a previous study conducted in this country in the sixties it appears that the epidemiologic differences that were observed at that time between the various Jewish ethnic groups have practically disappeared.

Adolescent↗

Expression of HLA-DR alloantigens on acute lymphoblastic leukemia lymphoblasts.

We have described the expression of HLA-DR alloantigens on the surface of lymphoblasts from patients with acute lymphoblastic leukemia (ALL). The patient groups included 49 acute lymphoblastic leukemia (ALL) patients (15 common ALL [CALLA +]; 11 "Null" ALL [CALLA-]; 19 T-Cell ALL; 4 Pre-B ALL, and one patient with hairy cell leukemia (HCL). Thirty one of these patients, who exhibited Ia-like antigens demonstrable by monoclonal antibodies, expressed HLA-DR utilizing alloantisera to Class II histocompatibility alloantigens (25/26 non-T-ALL; 2/4 Pre-B ALL; 3/19 T-ALL, and one HCL). The expression of HLA-DR on lymphoblasts was confirmed by family studies of five patients, indicating that ALL lymphoblasts can be used to perform HLA-DR phenotyping or genotyping of such patients. Another important finding was the coexpression on T-cell ALL lymphoblasts of markers for T-helper, T-supressor/cytotoxic, and thymic differentiation marker T6, together with Ia-like and HLA-DR, in one patient, and markers for T-helper, T6, and CALLA in another patient.

Adolescent↗

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↗

IgE induces secretion of prostaglandin E2 by human monocytes.

IgE was isolated from a patient with the hyper IgE, recurrent infection syndrome by immunoadsorption on sepharose bound goat anti-human IgE. Addition of this IgE to a monolayer culture of human monocytes resulted in a dose-dependent increase in PGE2 secretion. The addition of F(ab')2 fraction of goat anti-human IgE in the presence of sub-stimulating doses of IgE markedly increased PGE2 secretion; whereas addition of F(ab')2 fragment of irrelevant goat IgG had no effect. Similar activation of monocytes which could be enhanced by anti IgE was observed in the presence of the patient's serum. No such effect was seen in the presence of normal human serum. These results indicate that IgE may activate human monocytes and induce PGE secretion.

Adolescent↗

Results of treatment of high risk childhood acute lymphoblastic leukemia.

Sixteen children with high risk acute lymphoblastic leukemia (ALL) who had one or more of the following risk factors: white cell count over 50 X 10(9)/liter, mediastinal mass, age under 2 or over 10 years, extramedullary involvement, or T-cell markers, were treated by a new protocol. All attained complete remission and 11 are still in their continuous first remission for 6-53 months. High activity of adenosine deaminase (ADA) in the leukemic cells seems to be an independent risk factor, as in the high ADA level group, 4 out of 7 patients relapsed and died, while none of the 8 patients with low ADA levels relapsed or died.

Adenosine Deaminase↗

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↗

Phenotypic characterization of acute leukemia with monoclonal antibodies using the microlymphocytotoxicity assay.

Surface antigens of lymphoblasts from 56 pediatric ALL patients were studied with a set of complement fixing monoclonal antibodies. This group of lymphoblasts was comprised of 22 T-cell ALL, 22 CALLA+ Ia+ ALL and 12 non-T-non-B, CALLA- Ia+ ALL. For comparison, two adult T-cell CLL and six B-cell CLL were also studied. It was found that by using the microlymphocytotoxicity technique, the lymphoblasts can be assigned their immunophenotype and thus be classified into their respective lineage and stage of differentiation. In the samples tested, concordant reactivity was observed when FACS fluorescence profile was compared with that of microlymphocytotoxicity suggesting that the latter can be used especially when qualitative estimates are required.

Acute Disease↗

Studies on human milk macrophages: effect of activation on phagocytosis and secretion of prostaglandin E2 and lysozyme.

Breast milk macrophages cultured in vitro synthesized and secreted increasing amounts of protein, lysozyme, and prostaglandin E2(PGE2) into the extracellular medium. These cells were also shown to actively phagocytose labeled zymosan particles in culture. Morphologic characteristics, phagocytosis, and secretory responses of the macrophages were altered depending on the presence of various stimuli in the culture. Concanavalin A, endotoxin and zymosan particles, but not latex particles, all resulted in an increased PGE2 secretion into the medium. Although total protein synthesis was not altered by any of these stimuli, Concanavalin A and endotoxin resulted in a decreased lysozyme concentration in the extracellular medium. Concanavalin A enhanced, whereas endotoxin and prior phagocytosis of latex particles inhibited phagocytosis of labeled zymosan particles. These findings indicate that phagocytosis and secretions of milk macrophages may be altered depending on the nature of the stimulating agent.

Concanavalin A↗