PubMed Health⌕ Search

Biomedical subjects

M Lishner

Publications and source records attributed to M Lishner.

At least 73 records · Page 4Linked to original sources
PubMed1995

Fluorescence in situ hybridization (FISH) for retrospective detection of trisomies 3 and 7 in multiple myeloma.

The malignant plasma cells of multiple myeloma (MM) have a low proliferative activity and therefore cytogenetic studies of the disease have been severely limited. We evaluated the role of fluorescence in situ hybridization (FISH) in the detection of numerical chromosomal abnormalities in early stages of myeloma and the applicability of the method to stored archival slides. Old air-dried bone marrow smears from 15 myeloma patients obtained at presentation were probed with alpha satellite DNA sequences to chromosomes 3 and 7. Numerical chromosome aberrations were found in eight (53%) of the patients, including six (of 12) with trisomy 7, and two (of eight) with trisomy 3. This study demonstrates that FISH is a sensitive method for the detection of numerical aberrations in myeloma and for the study of old slides for retrospective analysis.

Aged↗
PubMed1995

The BCL-1, BCL-2, and BCL-3 oncogenes are involved in chronic lymphocytic leukemia. Detection by fluorescence in situ hybridization.

The putative oncogenes BCL-1, BCL-2, and BCL-3 are commonly rearranged by translocations to the immunoglobulin genes in B-cell malignancies. However, Southern blotting rarely detected their involvement in chronic lymphocytic leukemia (CLL). This discrepancy could stem from some unique features of the oncogenesis of CLL or be due to shortcomings of Southern blotting. We have therefore evaluated the role of fluorescence in situ hybridization (FISH) in the detection of these oncogenes in CLL. Twenty consecutive CLL patients were studied by FISH for the detection of BCL-1, BCL-2, or BCL-3 rearrangement and for the presence of trisomy 12. Selected patients were also evaluated by classical cytogenetic techniques and by Southern blot analysis. Juxtaposition of JH and BCL-1 was demonstrated in 10 (50%), BCL-2 in three (15%), and BCL-3 in four (20%) of the patients. Trisomy 12 was detected by FISH in 11 (55%) patients. The coexistence of trisomy 12 and translocation of the BCL-1 oncogene was common. Three of the patients had chromosomal aberrations compatible with those detected by FISH. In contrast, in none of the five patients selected by their positive FISH findings was a rearrangement demonstrated by Southern blotting. We conclude that FISH is a sensitive method for the detection of oncogene involvement in CLL. Mainly BCL-1, but also BCL-2 and BCL-3, are commonly translocated to the immunoglobulin heavy chain locus on chromosome 14. These translocations are often associated with trisomy 12. These findings indicate that the BCL oncogenes are commonly involved in CLL and lend support to the multi-hit theory of cancer development.

Aged↗
PubMed1995

Plasma lipids and the progression of nephropathy in diabetes mellitus type II: effect of ACE inhibitors.

Ninety-four normotensive type II diabetics with normal renal function and microalbuminuria were randomized to receive enalapril 10 mg/day or placebo and were followed for five years. In the patients treated by enalapril plasma creatinine values and albuminuria remained stable throughout the observation period. Their plasma total cholesterol decreased from an initial value of 245 +/- 27 mg/dl to mean study value of 236 +/- 29 mg/dl, and to a fifth year value of 232 +/- 27 mg/dl (P < 0.001). The changes in HDL cholesterol and triglyceride values were nonsignificant. In the placebo group there was a significant increase in albuminuria and a mean decline of 13% in reciprocal creatinine values during the five years. Plasma total cholesterol increased from an initial mean value of 246 +/- 24 to a mean study value of 252 +/- 25 mg/dl, and to a fifth year mean value of 259 +/- 32 mg/dl (P < 0.001). There was a significant correlation between both initial and mean plasma total cholesterol values, and the decline in renal function and the rise in albuminuria in the placebo treated patients. This correlation persisted after stratification for blood pressure. Treatment with enalapril did not eliminate these correlations. Cholesterol may be an additional risk factor for diabetic nephropathy. ACE inhibitors may have a modest cholesterol lowering effect in diabetic patients mediated, in part, through the decline in albuminuria.

Adult↗
PubMed1995

Monoclonal lymphocyte proliferation and bcl-2 rearrangement in essential mixed cryoglobulinaemia.

A patient with essential mixed cryoglobulinaemia (EMC) type II and hepatitis C virus (HCV) infection, in whom immunophenotypic and genotypic studies demonstrated a clonal proliferation of B lymphocytes, is described. Fluorescent in situ hybridization with probes to Ig heavy chain gene and to the oncogene bcl-2 demonstrated a translocation of bcl-2 to the immunoglobulin heavy chain locus on chromosome 14. A sharp rise in the level of the monoclonal IgM was associated with a second genetic aberration [t(8:22) (q24:q11)]. No other clinical evidence of disease progression could be demonstrated. Low grade lymphoproliferative disorder with typical cytogenetic abnormalities developed on the background of EMC and HCV. Clinical progression was associated with a second genetic abnormality involving the myc oncogene. It is possible that HCV chronic infection may indirectly influence oncogenes associated with lymphoma.

Adult↗
PubMed1995

Growth modulation and differentiation of acute myeloid leukemia cells by jaspamide.

We have examined the effect of Jaspamide, a peptide isolated from the marine sponge Hemiastrella minor, on in vitro proliferation and differentiation of leukemic cell lines and blast cells of three AML patients and compared it to that of cytosine arabinoside (ARA-C). The biological properties were studied in two complementary culture methods. The first is a clonogenic assay that supports colony formation in agar and reflects terminal divisions. The second is a suspension assay in which clonogenic cells increase exponentially and which reflects self-renewal. Jaspamide, at micromolar concentrations and in a dose-dependent manner, suppressed both primary colony formation in agar and the recovery of clonogenic cells from suspension culture in the investigated cell lines and in fresh blasts. Furthermore, Jaspamide was more effective in inhibiting clonogenic cells grown in suspension than primary colonies grown in agar. In addition, Jaspamide, similarly to ARA-C, was able to induce immunophenotypic maturation of leukemic cell lines (upregulation of CD14 and CD11 and downregulation of CD34 antigens). Our results indicate that Jaspamide significantly inhibits the self-renewal capacity of leukemic progenitors and may provide a new useful tool for the treatment of acute myeloid leukemia (AML) patients.

Antigens, CD↗
PubMed1995

Sensitivity of hematopoietic progenitors of acute myeloblastic leukemia to new compounds derived from marine organisms.

Results of chemotherapy in acute myeloid leukemia (AML) have improved slowly or not at all in the last decade. We evaluated the effect of Eilatin and Norsegoline, two new aromatic alkaloids derived from the Red Sea purple tunicate Eudistoma sp., on in vitro proliferation and differentiation of leukemic cell lines and blast cells of three AML patients. These biological properties were studied in two complementary culture methods. The first is a clonogenic assay that supports colony formation in agar and reflects terminal divisions. The second is a suspension assay where clonogenic cells increase exponentially and reflects self-renewal. Eilatin and Norsegoline, at micromolar concentrations, suppressed, in a dose-dependent manner, both primary colony formation in agar and the recovery of clonogenic cells from suspension culture in the investigated cell lines and in fresh blasts. Furthermore, both alkaloids were more effective in inhibiting clonogenic cells grown in suspension than primary colonies grown in agar. In addition, these agents were able to induce immunophenotypic maturation of leukemic cell lines (upregulation of CD14 and CD11 and down-regulation of CD34 antigens). Our results indicate that Eilatin and Norsegoline significantly inhibit self-renewal capacity of leukemic progenitors and may provide a useful new tool for the treatment of AML patients.

Alkaloids↗
PubMed1995

Eilatin: a novel marine alkaloid inhibits in vitro proliferation of progenitor cells in chronic myeloid leukemia patients.

We examined the effect of Eilatin, a novel marine product, on the survival of human myeloid progenitor cells (CFU-C) isolated from normal individuals and from 12 patients with Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) in chronic phase and blastic crisis. We compared its effect to the effect of interferon-alpha (IFN-alpha) and cytosine arabinoside (Ara-C). Eilatin, IFN-alpha, and Ara-C inhibited the proliferation of CFU-C from normal individuals and CML patients in a dose-dependent manner. The percent survival of colony-forming units from bone marrow (BM) of seven CML patients in chronic phase exposed for 16 hours to Eilatin (10(-7) and 10(-6) M), IFN-alpha (500 U/mL), or Ara-C (10(-9) M and 10(-8) M) was found to be statistically lower (p < 0.05) than the percent survival of myeloid progenitors from normal individuals. A 16-hour exposure of CD34+ cells isolated from peripheral blood (PB) of three CML patients in blastic crisis and from BM of two patients in chronic phase to Eilatin 10(-7) M, IFN-alpha 500 U/mL, Ara-C 10(-9) M resulted in a marked inhibition in the ability of the cells to proliferate in liquid culture and a reduction in CFU-C content. Using fluorescent in situ hybridization (FISH), we evaluated detection of the BCR/ABL fusion product in the CD34+ cells. All five patients were 100% Ph+ at diagnosis. BCR/ABL translocations were detected in 94.6 +/- 0.6% of CD34+ cells after growth in liquid culture for 7 days. The level of BCR/ABL fusion signals detected after exposure of CD34+ cells for 16 hours to Eilatin 10(-7) M, IFN-alpha 500 U/mL, or Ara-C 10(-9) M were 54.5 +/- 5%, 63.6 +/- 5%, and 70 +/- 4%, respectively (mean +/- SE, n = 5). Our data indicate that Eilatin, a substance isolated from the Red Sea purple tunicate Eudistoma sp., has an antileukemic effect against in vitro Ph+ cells and may be used in conjunction with currently available agents for ex vivo purging of BM and/or PB of CML patients in conjunction with autologous bone marrow transplantation.

Adolescent↗
PubMed1995

Potent antileukemic activity of the novel agents norsegoline and dibezine.

We examined the effect of norsegoline, a natural marine product, and dibezine, a synthetic product, on the survival of human myeloid progenitor cells [colony-forming unit-cells (CFU-C)] from normal individuals and from 10 patients with Philadelphia-positive chronic myelogenous leukemia (CML) in chronic phase and blastic crisis. We compared their effect to the effect of IFN-alpha. Norsegoline, dibezine, and IFN-alpha inhibited the proliferation of CFU-C in a dose-dependent manner. The number of CFU-C from bone marrow (BM) of five CML patients in chronic phase exposed for 16 h to norsegoline (10(-8)-10(-6)M), dibezine (10(-8)-10(-6)M), and IFN-alpha (500 units/ml) was found to be statistically lower (P < 0.05) than the number of CFU-C derived from normal individuals. A 16-h drug exposure of CD34(+) cells isolated from the peripheral blood of three CML patients in blastic crisis and from BM of two patients in chronic phase resulted in a marked inhibition in the ability of the cells to proliferate in liquid culture and a reduction in CFU-C content. Using the fluorescent in situ hybridization technique, we evaluated detection of the BCR/ABL fusion product in the CD34(+) cells. All five patients were 100% Philadelphia positive at diagnosis. BCR/ABL translocations were detected in 94.6 +/- 0.6% of cells following their growth in liquid culture for 7 days. Following exposure of CD34(+) cells to norsegoline, dibezine, or IFN-alpha, BCR/ABL fusion signals could be detected in 73 +/- 11%, 66.5 +/- 4. 7%, and 66.0 +/- 2.5% of cells from BM and 72.3 +/- 5%, 68.8 +/- 7%, and 60.6 +/- 6.8% of peripheral blood, respectively. Our data indicate that norsegoline and dibezine have in vitro an antileukemic effect against Philadelphia-positive cells and may be used in conjunction with currently available agents for ex vivo purging of BM and/or peripheral blood of CML patients in conjunction with autologous bone marrow transplantation.

Adolescent↗
PubMed1994

Delta-T-lymphocytosis in a patient with thymoma.

BACKGROUND: Malignant thymoma is composed of neoplastic epithelial cells and small lymphocytes. Rarely, patients also may have peripheral T-lymphocytosis. These lymphocytes have been considered nonneoplastic because of their microscopic appearance and immunophenotype, as well as gene rearrangement studies. METHODS: A 42-year-old man developed lymphocytosis 3 years after the completion of intensive combined chemoradiotherapy protocol for lymphocytic thymoma. These peripheral blood lymphocytes were evaluated phenotypically and genotypically. RESULTS: Immunophenotyping established that the cells were CD3 positive, CD4 negative, CD8 negative, T-cell receptor (TCR)-alpha/beta negative, and TCR-gamma/delta positive. Gene rearrangement studies with TCR-delta probe confirmed the monoclonality of these cells. Chromosome analysis showed deletion of chromosome Y. The clinical course was progressive and had the features of malignant lymphoma. CONCLUSIONS: To the authors' knowledge, this is the first report of a patient with thymoma in whom monoclonal proliferation of T-gamma/delta peripheral blood lymphocytes was confirmed immunophenotypically and genotypically. These monoclonal TCR-gamma/delta lymphocytes may belong to the malignant clone of the thymoma; however, the possibility that they represent an evolution of a second lymphatic malignancy cannot be excluded.

Adult↗
PubMed1994

Angiotensin-converting enzyme inhibitors and cough: a prospective evaluation in hypertension and in congestive heart failure.

Angiotensin-converting enzyme inhibitors (ACE-I) have become the mainstem of antihypertensive therapy and first-choice agents for vasodilatation in congestive heart failure (CHF). A typical dry cough is the main cause for discontinuation of ACE-I therapy. Data about the incidence, course, and clinical significance of this side effect are conflicting. This study determined the incidence of cough in ACE-I treated patients with hypertension and with CHF and to appreciate its clinical significance; 268 ACE-I treated patients, 164 with hypertension and 104 with CHF were prospectively followed for at least 1 year and specifically questioned about cough and other side effects. In those in whom cough developed, a second and then a third ACE-I were tried. Cough developed in 50 (18.6%) of the 268 patients; 23 patients with hypertension (14%) had coughs 24.7 +/- 17.1 (SD) weeks after initiation of therapy; 27 patients with CHF (26%) had coughs 12.3 +/- 12 (SD) weeks after the start of ACE-I therapy (P = 0.005). All but three patients had coughs also on the second and third ACE-I. The time from the beginning of therapy to the onset of cough was significantly shorter with the second than the first drug. ACE-I agents had to be discontinued in 50% of the patients in whom coughs developed, most of them in the CHF group. In the others, cough was well tolerated or disappeared during subsequent months. The incidence of cough, which necessitated discontinuation of ACE-I treatment, was 4% among patients with hypertension and 18% among patients with CHF (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Detection of bcl rearrangements in B-CLL by fluorescence in situ hybridization.

Data concerning oncogene activation in CLL are very limited. When studied by Southern blot, rearrangements of bcl-1, bcl-2, and bcl-3 have been only infrequently reported. We evaluated the role of fluorescence in situ hybridization (FISH) in the detection of gene rearrangements in two CLL patients. We used multiple DNA probes, including those of chromosome 12, immunoglobulin heavy and light chains, and the oncogenes bcl-1, bcl-2, and bcl-3. Additionally, routine cytogenetic study was performed. In one patient, trisomy 12 and bcl-2 translocation were demonstrated by both methods, while trisomy 12 and bcl-1 translocation were seen in the second patient, who had a normal karyotype. Larger studies should evaluate the role of FISH in the detection of oncogene involvement in CLL and compare it with other molecular methods.

Aged↗
PubMed1994

Fibrosing alveolitis associated with primary antiphospholipid syndrome.

The spectrum of the primary antiphospholipid syndrome has expanded in recent years. It has been associated with a number of non-thrombotic syndromes such as pulmonary hypertension, adrenal insufficiency, chorea and avascular necrosis of bone. Yet, it has not been described in association with inflammatory pulmonary disease. We describe a young male with definite primary antiphospholipid syndrome who developed insidious diffuse pulmonary infiltrates. The histopathologic examination of the involved lung demonstrated alveolitis and fibrosis. We suggest that this pulmonary involvement may represent another manifestation of the primary antiphospholipid syndrome.

Adult↗
PubMed1994

Aplastic anemia induced by cyclohexylchloroethylnitrousurea.

We report a patient who developed aplastic anemia after three courses of cyclohexylchloroethylnitrousurea (CCNU), procarbazine and oncovine administered after craniotomy and irradiation for brain astrocytoma. To the best of our knowledge, aplastic anemia following CCNU has not been reported previously. The unique course of the disease and implications of this complication are discussed.

Adult↗
PubMed1994

Non-Hodgkin's lymphoma and pregnancy.

Non-Hodgkin's lymphoma (NHL) is infrequently diagnosed during pregnancy. Most NHL's complicating pregnancy are aggressive and disseminated. This presentation together with the possible teratogenecity of diagnostic methods dictate a limited staging workup during pregnancy. Although prognosis had been reported to be poor, there is recent evidence to suggest that when properly treated, pregnancy does not affect the course of lymphoma. The risk to the fetus can also be reduced by an appropriate therapeutic approach.

Female↗
PubMed1994

The response of diffuse large cell and other intermediate grade non-Hodgkin's lymphomas to adriamycin containing combination chemotherapy.

Adriamycin containing combination chemotherapy (ACCC) is usually delivered to patients with stages III, IV diffuse large cell (DLCL) non-Hodgkin's lymphoma (NHL). Although this mode of therapy is also commonly used in other intermediate grade lymphomas, it's role in the latter subset of patients is not well defined. In a retrospective analysis we evaluated and compared the outcome of previously untreated DLCL and non-DLCL intermediate grade lymphoma patients who received as initial therapy, "first generation" ACCC. No differences in response and relapse rates between these subgroups were observed. The trend towards the survival advantage observed for the non-DLCL patients, is probably due to a lower mortality over 5-8 years, for complete responders.

Actuarial Analysis↗
PubMed1994

Long-term effect of ACE inhibition on development of nephropathy in diabetes mellitus type II.

Ninety-four normotensive, type II diabetics with microalbuminuria and normal renal function were randomized to receive enalapril or placebo and were followed for five years. In the patients treated with enalapril, albuminuria decreased initially from 143 +/- 64 (mean +/- SD) mg/24 hours to 122 +/- 67 mg/24 hours, then a slow increase was observed to 140 +/- 134 mg/24 hours after five years. In the placebo group albuminuria increased from 123 +/- 58 mg/24 hours to 310 +/- 167 mg/24 hours after five years. The difference between the rates of change in albuminuria over time in the two groups was highly significant (P < 0.005). Kidney function, expressed as mean reciprocal creatinine, declined by 13% in the placebo group and remained stable (-1%) in the enalapril group (P < 0.05). The initial value of daily albuminuria was a good predictor of the subsequent decline in renal function (r = 0.86, P < 0.001 and r = 0.72, P < 0.001 for the enalapril and the placebo groups, respectively). Initial and subsequent mean values of cholesterol and LDL were lower in the enalapril than in the placebo group. There was a close correlation between mean cholesterol values and the decline in renal function (r = -0.58, P < 0.001). The mean blood pressure was stable in the enalapril group (initial group mean 99 +/- 2.1 mmHg, fifth year mean 100 +/- 3.2 mmHg) and increased in the placebo group from 97 +/- 3.2 mmHg to 102 +/- 3.4 mm Hg at the end of the study (P = 0.082).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗