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Biomedical subjects

F Hecht

Publications and source records attributed to F Hecht.

At least 145 records · Page 8Linked to original sources
PubMed1986

Genetic control over fragile X chromosome expression.

The cytogenetic expression of fragile sites is highly variable. Sites are seen in differing proportions of cells. To determine if part of this variability is genetic, the proportions of lymphocytes manifesting the fragile X were examined in a large cohort of males with the fragile X chromosome. The number of fragile X cells was solely determined by genetic factors: the heritability as determined from the correlation between brothers as well as between cousins was 99.6% and 94.4%, respectively, as compared with 0% in unrelated males with the fragile X. This is consistent with pure genetic determination without any environmental influence over the expression of the fragile X chromosome in males.

Alleles↗
PubMed1986

Population cytogenetics of autosomal fragile sites.

The present investigation deals with a population chromosomal survey for autosomal fragile sites under conditions of folate deprivation in 405 mental retardates. A total of 13 ascertainments of folate sensitive autosomal fragile sites is observed, of which 10q23 fragility appears to be the most frequent. Further cytogenetic studies of normal and retarded individuals are required to help elucidate the possible phenotypic effect of these autosomal sites and mental retardation.

Chromosome Fragile Sites↗
PubMed1986

Congenital cutis laxa with retardation of growth and motor development: a recessive disorder of connective tissue with male lethality.

A syndrome of cutis laxa, ligamentous laxity and delayed motor development has been reported in 13 children. All are girls. Four are from Saudi Arabia. Another Saudi Arabian girl, the product of a consanguineous union, is described with intrauterine growth retardation, delayed closure of the anterior fontanel, slow motor development, cutis laxa and ligamentous laxity. The syndrome appears to be an autosomal recessive disorder of connective tissue, with male lethality.

Consanguinity↗
PubMed1986

13-cis retinoic acid treatment for myelodysplastic syndromes.

To test the biologic activity of 13-cis retinoic acid (13-CRA) in patients with myelodysplastic states (MDS), we administered 13-CRA orally (2.5 mg/kg/d initially, escalated to 4 mg/kg/d) for 8 weeks to 15 consecutive patients. Eight of 15 patients (53%) experienced an increase in peripheral granulocyte counts of greater than 20% (range, 22% to 700%). In five patients, the absolute increase in peripheral granulocyte count was greater than 500 cells/microL. Two of 15 patients experienced a decrease in the circulating granulocyte count of greater than or equal to 20%. Comparable values for peripheral platelet counts were 27% (4/15 patients) greater than 20% increase and 33% (5/15 patients) greater than 20% decrease. No patient experienced a major change in erythrocyte transfusion requirement while receiving 13-CRA in comparison with pretreatment status. Thirteen patients had morphologic and cytogenetic evaluation of marrow cells before 13-CRA treatment, and with one exception, marrow morphologic and cytogenetic abnormalities persisted following 13-CRA administration. The exception occurred in the patient with the most dramatic response, whose granulocyte count increased from 400 to 2,800 cells/microL along with a normalization of the leukocyte alkaline phosphatase score, a morphologic improvement in granulocyte maturation, and a disappearance of the initial chromosome abnormality. These changes did not persist after cessation of 13-CRA administration, but were reproduced following drug readministration. No patients experienced serious decrements in peripheral blood counts or leukemic transformation while receiving 13-CRA. All patients had mild to marked dermatologic toxicity (cheilosis, skin dryness). No other major toxicity was encountered. We conclude that 13-CRA may be safely administered and may increase peripheral granulocyte counts in a proportion of patients with MDS.

Adult↗
PubMed1986

Cytogenetic and immunophenotypic analysis of cell lines established from patients with T cell leukemia/lymphoma.

Cell lines were established from five patients with T cell malignancies. Two patients had T cell lymphoblastic lymphoma (T-LL), whereas three patients had T cell acute lymphoblastic leukemia (T-ALL). Both T-LL cell lines expressed cell surface antigens characteristic of midthymocytes (Leu 2, 3, 6+). One T-ALL cell line also expressed this immunophenotype, one expressed suppressor/cytotoxic antigens (Leu 2+; Leu 3, 6-), and one expressed antigens of a mature but uncommitted T cell (Leu 4+; Leu 2, 3, 6-). Cytogenetic analysis showed that each cell line had 46 chromosomes with pseudodiploidy. The three T-ALL cell lines had only a few chromosome changes; one cell line had one deletion, another had two deletions, and the third had a translocation and two deletions (including loss of part of 9p). In comparison, both T-LL cell lines had complex chromosome changes, including most notably a rearrangement of band 14q11.2. The immunophenotypes and chromosome breakpoints showed patterns of interlock between the T-LL and T-ALL cell lines because common abnormalities occurred at six distinct chromosome sites. Cell lines with limited and specific chromosomal abnormalities are important because they can provide the basic material for molecular genetic studies that could elucidate the genetic mechanisms involved in neoplasia.

Adolescent↗
PubMed1986

Responses of hemopoietic precursors to 13-cis retinoic acid and 1,25 dihydroxyvitamin D3 in the myelodysplastic syndromes.

To determine the effects of the "maturation-inducing" agents 13-cis retinoic acid and 1,25 dihydroxyvitamin D3 on marrow cells from normal individuals and patients with myelodysplastic syndromes (MDS), we assessed marrow hemopoietic clonogenicity and differentiation response patterns to these agents. These vitamins caused increased proliferation in vitro of normal clonogenic marrow myeloid precursor cells (CFU-GM), decreased erythroid precursors (BFU-E), and no change in multipotent stem cells (CFU-GEMM). Marrow hemopoietic colony-forming cell incidence was generally subnormal in the 22 MDS patients evaluated. In vitro exposure to both agents caused various patterns of alteration of MDS hemopoietic colony and cluster formation, with similar but more pronounced effects evoked by retinoic acid. In the vast majority of MDS patients, enhanced marrow clonal granulocyte-monocyte differentiation and decreased BFU-E growth were noted after in vitro exposure to these vitamins. Correlation of biological effects was demonstrated between in vivo changes of peripheral neutrophil counts and in vitro responses of myeloid precursors for ten MDS patients treated with an eight-week therapeutic course of retinoic acid. Cytogenetic analyses indicated persisting aneuploidy or coexisting normal and aneuploid karyotypes in the cultured MDS myeloid cells and (with one exception) in native marrow cells from the treated patients. The varying responses of the MDS cells may monitor differing proportions of normal versus leukemic marrow cells susceptible to proliferative and differentiative expression on exposure to these agents.

Adult↗
PubMed1985

Nonreciprocal chromosome translocation t(5;14) in cancers of the kidney: adenocarcinoma of the renal parenchyma and transitional cell carcinoma of the kidney pelvis.

Chromosome studies were done on an adenocarcinoma of the kidney and a transitional cell carcinoma of the kidney. The adenocarcinoma was in the renal parenchyma, whereas the transitional cell carcinoma was in the kidney pelvis. The adenocarcinoma was moderately well differentiated, and the transitional cell tumor was poorly differentiated. The adenocarcinoma was hypotetraploid, with 69-75 chromosomes per cell, and the transitional cell carcinoma was pseudodiploid, with 46 chromosomes. Both tumors showed a nonreciprocal t(5;14) translocation that resulted in a 5q- and a 14q+ chromosome with loss of 14q material. The breakpoints were in bands 5q13 and 14q22. Both tumors also contained an extra 5q- chromosome. The oncogene c-fms is normally situated in band 5q34 and so may have been translocated onto 14q, although whether it has been activated is conjectural. The t(5;14) translocation may be another tissue-specific cancer chromosome change.

Adult↗
PubMed1985

Histiocytic lymphoma cell lines: immunologic and cytogenetic studies.

Cell lines were established from 15 patients with diffuse histiocytic lymphoma (DHL) of the intermediate grade, diffuse large cell (class G), and high-grade, large cell immunoblastic (class H) types. Immunologic studies indicated that 11 of the 15 DHL cell lines were B cell in origin, 2 were histiocytic, and 2 were null cell. Cytogenetic studies revealed 1 hypodiploid, 11 hyperdiploid, and 3 near-tetraploid cell lines. Chromosome #7 was trisomic in 3 lines, chromosomes #12 in 4 lines, and chromosome #13 in 3 lines. Chromosome #2 was monosomic in 3 lines, chromosome #8 was monosomic in 5 lines, chromosome #14 in 4 lines, and chromosome #22 in 6 cell lines. This is of special interest, as chromosomes #2, #8, #14, and #22 are clearly concerned with rearrangements in Burkitt's lymphoma and immunoglobulin expression. The most common rearrangement in the DHL cell lines involved chromosome #14 at band 14q32. However, in contrast to Burkitt's lymphoma, the pattern of translocation in DHL is between chromosome #14 and usually chromosome #11 or chromosome #18. The 14;18 translocation is not restricted to patients with low-grade follicular, small cleaved cell lymphomas, as has been reported. The 14q+ chromosome is characteristic of lymphoid malignancies in general. It is due, invariably, to a translocation with the breakpoint in band 14q32, which is the locus of the immunoglobulin heavy chain genes. We propose that in each translocation, for example, chromosomes #11 or #18, an oncogene may be transposed onto chromosome #14, and that each 14q+ translocation in DHL represents an event that transposes an oncogene from another chromosome to chromosome #14.

Cell Line↗
PubMed1985

The Philadelphia (Ph) chromosome in leukemia. I. A new mechanism due to interstitial deletion and insertion in chronic myelocytic leukemia.

The Philadelphia (Ph) chromosome in leukemia is invariably derived from chromosome #22. A break occurs in the long (q) arm of chromosome #22 and, in every case observed until now, all of the material from that breakpoint through the telomere of chromosome #22 has been reciprocally translocated to another chromosome, most often chromosome #9. With the t(9;22) translocation, the oncogene c-sis moves from chromosome #22 onto 9q and the oncogene c-abl moves reciprocally from chromosome #9 onto 22q. We report a new mechanism for the genesis of the Ph chromosome in chronic myelocytic leukemia (CML) involving interstitial deletion of chromosome #22 with insertion of the deleted material into another chromosome: 46,XX,dir ins(11;22)(q13;q11q13). The distal portion of chromosome #22, including the telomere, appeared to have been retained in the Ph chromosome. There was no visible involvement of chromosome #9. This insertional deletion is of potential importance in evaluating the roles of oncogenes such as c-abl and c-sis in the Ph rearrangement in the origin of leukemia.

Bone Marrow↗
PubMed1985

The Philadelphia (Ph) chromosome in leukemia. II. Variant Ph translocations in acute lymphoblastic leukemia.

Nearly 20 patients with a masked Philadelphia (Ph) translocation have been described in chronic myelocytic leukemia. We report two instances of acute lymphoblastic leukemia (ALL) with variant Ph translocations. One case, involving a 26-year-old male, was associated with a variant t(14;22)(q32;q11) translocation. The second case involved a 36-year-old male with a more complex translocation, t(9;15;22)(q12;q26;q11). In each case, cells with a masked Ph translocation were observed. These appear to be the first ALL cases reported with a masked Ph chromosome. The findings are discussed in relation to recent knowledge regarding the genesis of the Ph chromosome.

Adult↗
PubMed1985

The Philadelphia (Ph) chromosome in leukemia. III. Complex Ph translocation plus inversion in chronic myelocytic leukemia.

Remarkable chromosome abnormalities were observed in bone marrow cells from a woman with chronic myelocytic leukemia and atypical tuberculosis due to Mycobacterium avium-intracellulare infection. Four chromosome breaks occurred at bands 1p13, 1q32, 11p15, and 22q11. These breaks resulted in a complex Philadelphia (Ph) translocation between chromosomes #1, #11, and #22 and in an inversion of chromosome #1. Oncogenes on these chromosomes include N-ras and c-sk on chromosome #1, c-H-ras on chromosome #11, and c-sis on chromosome #22. Complex chromosome rearrangements may facilitate multiple oncogene changes, thereby permitting several steps in cancer development to occur simultaneously.

Adult↗
PubMed1985

Enhanced expression of chromosome fragile site 10q25 in chronic myelogenous leukemia.

Spontaneous expression of a BrdU-sensitive fragile site at 10q25 was observed in normal lymphocytes and malignant blood and bone marrow cells in chronic myelogenous leukemia (CML). The cells were marked by a Philadelphia chromosome rearrangement due to insertion of 22q11----q13 at 11q13. The fragile site at 10q25 was expressed in larger proportions of malignant than normal cells. Although this fragile site is not at a cancer chromosome breakpoint, malignancy enhanced its expression, consistent with a cascade effect.

Bone Marrow↗