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Biomedical subjects

I Brodsky

Publications and source records attributed to I Brodsky.

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

Platelet DNA polymerase levels in CML: implications for oncogenesis.

Partially purified platelet DNA polymerase (PDP) was able to synthesize DNA transcripts of platelet polyadenylated RNA. PDP was elevated in the earliest stages of CML and PV. In PV, successful chemotherapy resulted in rapid return of PDP to normal levels while in CML this was not the case. An hypothesis is presented proposing that PDP contributes to oncogenesis by regulating the expression of oncogenes.

Blood Platelets↗
PubMed1984

Antiproliferative effect of natural beta interferon on fresh tumor cells analyzed in a clonogenic assay.

Natural beta interferon (beta IFN), derived from diploid fibroblasts, has been evaluated for its antiproliferative activity using a panel of twelve different histologic types of fresh human tumor cells. Thirty-nine percent (9/23) of the tumors showed a 70% or greater decrease in colony formation following exposure to 500 international reference units per ml of natural beta IFN, a concentration which is in the clinically achievable range. Interesting, is that leiomyosarcoma, a tumor relatively resistant to conventional chemotherapy, was uniformly sensitive (3/3) to natural beta IFN. Indeed, the antiproliferative activity of beta IFN was consistently superior (in 19/20 comparative assays) to the other conventional chemotherapeutic drugs evaluated for leiomyosarcomas. This study, which suggests that natural beta IFN exhibits significant antiproliferative activity on a variety of fresh human tumor cells, may be useful in orienting clinical trials with natural beta IFN (still in limited supply because of its unique physicochemical nature) to the more susceptible human malignancies.

Cell Division↗
PubMed1984

Low natural cytotoxicity of peripheral blood mononuclear cells in individuals with high familial incidences of cancer.

The possible role that natural cell-mediated cytotoxicity may play as a host defense mechanism against malignant tumors was investigated. We measured natural cell-mediated cytotoxicity (51Chromium released) in 79 normal individuals using K562 leukemia cells as targets in quadruplicate assays after 3, 4, and 5 hr of incubation using three different effector:target cell ratios (6.2:1, 25:1, and 50:1). Natural cell-mediated cytotoxicity was significantly lower (p less than 0.005) in each of the nine separate assay conditions for individuals with a high familial incidence of cancer compared to individuals with a low incidence of cancer. Moreover, natural cell-mediated cytotoxicity inversely correlated with the number of family members with cancer. The relationship between high familial cancer incidence and low natural cell-mediated cytotoxicity was observed in males as well as in females and in nonsmokers as well as in smokers. The same conclusion was reached whether the data were expressed as percentage of 51Chromium released, as lytic units per 10(7) mononuclear cells, or as lytic units per ml of peripheral blood. Thus, defects in natural cell-mediated cytotoxicity may play a role in the initial stages of human tumorigenesis. It may also be possible to identify individuals at increased risk of cancer development.

Adult↗
PubMed1983

Monocyte markers and the common acute lymphoblastic leukemia antigen on chronic lymphocytic leukemia cells.

The mononuclear cells from 42 patients with chronic lymphocytic leukemia (CLL) were analyzed for surface markers using monoclonal antibodies and flow cytofluorimetry. All 42 CLLs were Ig+HLA.DR+OKT3-OKT4-OKT6-OKT8- and monoclonal with respect to light chain type. Thirty of the 42 tumors expressed the common acute lymphocytic leukemia antigen, and cells from 18 leukemias stained with the antibodies OKM1 and 63D3, which are specific for different antigens characteristic of myeloid cells. Eight of the leukemias failed to stain with PI153, which has been reported to recognize all B-cell CLLs.

Antibodies, Monoclonal↗
PubMed1983

Extremely high levels of natural killer cells in angioimmunoblastic lymphadenopathy.

Analysis of peripheral blood leukocytes from a patient with angioimmunoblastic lymphadenopathy using monoclonal antibodies and the fluorescence-activated cell sorter showed an unusually high proportion of cells that were OKT10+OKM1+63D3-. Since a large proportion of the large granular lymphocytes associated with natural killing in humans bears this surface phenotype, both blood and lymph node cells were subsequently tested for cell-mediated cytotoxicity in natural killer (NK)-cell assays. Following chemotherapy, both cells bearing the NK surface phenotype and the NK cytotoxicity disappeared and a population of cells, bearing none of the typical lymphocyte or monocyte markers, became dominant. At this point the patient was diagnosed as having immunoblastic sarcoma and shortly thereafter succumbed to his disease. In the few cases where extremely high levels of NK activity have been reported, the tumor cells themselves have been responsible for cell-mediated cytotoxicity. In this case, the final tumor population had no NK activity. Thus either a subpopulation of cytotoxic tumor cells was destroyed by chemotherapy or the patient had expanded numbers of NK cells reacting against his tumor prior to therapy.

Antibodies, Monoclonal↗
PubMed1983

4'-(9-acridinylamino)methane-sulfon-m-anisidide (m-AMSA) and 5-azacytidine (AZA) in the treatment of relapsed adult acute leukemia.

Between March 1980 and December 1981, 22 patients were treated with 4'(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA) and 5-azacytidine (AZA), each given by I.V. push in a dosage of 150 mg/m2 for 5 days. Seven of 12 prior-remitting, acute nonlymphoblastic leukemia (ANLL) patients achieved complete remission (58%). Six ANLL patients who failed to remit on standard daunorubicin-cytosine arabinoside programs also failed to remit on the m-AMSA-AZA combination. Two patients with relapsed acute lymphatic leukemia (ALL) also failed while two patients with chronic myelocytic leukemia (CML) in evolution were cytoreduced. The seven patients who achieved remission had additional relapse-free survival for a median of six months (range 1-23+ months). One patient obtained a second remission with m-AMSA-AZA after relapse which followed a 9-month period of nonmaintained remission. Most patients demonstrated mild to moderate nausea and vomiting. Hepatic toxicity was mild to infrequent. Only four patients showed cardiac toxicity which was not life-threatening. The most troublesome toxicity was mucositis and was seen in 11 patients; four whom required I.V. hyperalimentation. We conclude that this combination is an effective salvage program for relapsed prior-remitting ANLL. Future studies should be conducted in three areas. The first study might be a comparison of relapsed prior-remitting ANLL with single-agent m-AMSA. The second, in untreated ANLL, following induction with DAT, might use m-AMSA-AZA in consolidation and maintenance arms of future protocols. The final study should explore m-AMSA-AZA activity in evolved CML in a greater number of patients.

Acute Disease↗
PubMed1982

Quantitation of RNA-dependent platelet DNA polymerase in patients with myeloproliferative disorders.

Platelets from 28 patients with the myeloproliferative diseases (MPD) polycythaemia vera (9), essential thrombocythaemia (6), myelofibrosis with myeloid metaplasia (5) and chronic myelogenous leukaemia (8) were examined for an RNA-dependent DNA polymerase activity using standardized conditions permitting highly reproducible quantitation. Low levels of activity were detected in platelets of normal individuals, but platelets of nearly all MPD patients (25/28) possessed higher levels. The polymerase activity correlated with diagnosis (P = 0.001) and did not correlate with platelet counts (P greater than 0.2). Quantitation of this RNA-dependent DNA polymerase activity may be a useful parameter in the diagnosis of myeloproliferative disorders.

Blood Platelets↗
PubMed1982

Busulphan: effect on platelet RNA dependent DNA polymerase--implications in the treatment of polycythemia vera, thrombosis and atherosclerosis.

Analysis of controlled studies performed by the Polycythemia Vera Study Group (P.V.S.G.) and the European Organization for Research in Treatment of Cancer (E.O.R.T.C.) indicate that busulphan (Myleran) (BU) is the treatment of choice for polycythemia vera (PV). BU is particularly effective as compared to aspirin and dipyridamole (Persantine) or radioactive phosphorus (32P) in preventing the thrombotic and atherosclerotic complications of PV. In contradistinction to chlorambucil (CM), BU is not associated with an unacceptable increase in the incidence of leukemia. The pharmacology of BU remains unclear, but certainly it cannot be considered a classic alkylating agent. BU suppresses the activity of the reverse transcriptase-like RNA dependent DNA polymerase in the platelets of these patients. A clearer understanding of the role of BU in the treatment of the myeloproliferative disorders will provide important insights into the etiology and pathogenesis not only of preneoplastic states, but also thrombosis and atherosclerosis.

Arteriosclerosis↗
PubMed1981

Ocular manifestations of relapsing polychondritis.

The clinical, ultrasonographic, fluorescein angiographic, and immunological features of a case of relapsing polychondritis in a 46-year-old female are described. Acute bilateral sclerouveitis with multiple retinal pigment epithelial defects and sensory retinal detachment were present on initial examination. Antibodies to type II collagen were present in serum samples taken from the patient during the acute and convalescent phase of the disease. A possible relationship of this disorder to the phylogenetic development of the eye is discussed.

Antibodies↗
PubMed1979

Correlation of a specific chromosomal marker, 21q-, and retroviral indicators in patients with thrombocythemia.

A chromosomal anomaly, 21q-, has been found in association with retroviral indicators in patients with myeloproliferative disorders (MPD) including polycythemia vera (PV), essential thrombocythemia (ET), chronic myelocytic leukemia (CML) and acute non-lymphocytic leukemia (ANLL). The viral indicators are found in platelet homogenates of thrombocythemic patients. Evidence is presented from 2 laboratories (Philadelphia, USA and Bologna, Italy) for the 21q- deletion in MPD patients. Thirty patients evaluated for the presence of both viral and chromosomal markers in Philadelphia showed positive correlations.

Animals↗