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M H Greene

Publications and source records attributed to M H Greene.

At least 37 records · Page 2Linked to original sources
PubMed1989

Mapping the gene for hereditary cutaneous malignant melanoma-dysplastic nevus to chromosome 1p.

We used molecular genetic techniques and multipoint linkage analyses to locate the gene responsible for cutaneous malignant melanoma-dysplastic nevus. We evaluated 99 relatives and 26 spouses in six families with a predisposition to melanoma. Thirty-four family members had cutaneous malignant melanoma, and 31 of these 34 also had histologically confirmed dysplastic nevi. Twenty-four family members had dysplastic nevi alone. An analysis of the cosegregation of the cutaneous malignant melanoma-dysplastic nevus trait with 26 polymorphic DNA markers on the short arm of chromosome 1 demonstrated the presence of a gene for susceptibility to melanoma. The gene was located between an anonymous DNA marker (D1S47) and the gene locus for pronatrodilatin, a commonly used reference gene (PND), in chromosome band 1p36. The odds were greater than 260,000:1 in favor of linkage at this location.

Adolescent↗
PubMed1989

Dysplastic naevi in a population-based survey.

The prevalence of dysplastic naevi was studied in a population-based survey of 380 30 to 39-year-old and 50 to 59-year-old non-Maoris in Milton, a small town in the south of New Zealand. Photographs of all pigmented naevi greater than or equal to 4 mm in diameter were taken during the survey and subsequently evaluated by two experienced reviewers. Nine percent of the group (95% CI, 6%-13%) were judged to have one or more dysplastic naevi. Interobserver agreement over the diagnosis of dysplastic naevi was 85% (kappa = 0.55). Dysplastic naevi were associated with higher counts of moles greater than or equal to 2 mm in diameter; 50 or more such moles increased the likelihood of having three or more dysplastic naevi about 40-fold. Naevi judged to be dysplastic were, therefore, relatively common and were associated with increased numbers of common moles.

Adult↗
PubMed1988

Relationship between sensitivity of cells from patients with hereditary cutaneous malignant melanoma to killing and mutations by 4-nitroquinoline 1-oxide and adduct formation.

Hereditary cutaneous malignant melanoma (HCMM) is an autosomal dominant disease and develops mostly in patients with the hereditary dysplastic nevus syndrome (DNS). A previous study from this laboratory showed that fibroblasts derived from skin biopsies of four HCMM/DNS patients and one DNS patient were significantly more sensitive to the cytotoxic and mutagenic effects of 4-nitroquinoline 1-oxide (4-NQO) than three fibroblast cell lines from normal newborn males and one from a 45-yr-old normal donor. The survival curves of the HCMM/DNS or DNS cell lines fell into two groups, one with a slope approximately twice as steep as the controls and one with a slope approximately 3 times as steep. This marked difference in survival curves disappeared if the same cell lines were exposed to 4-hydroxyaminoquinoline 1-oxide, a partially reduced metabolite of the parent compound, suggesting that the difference in sensitivity reflected a difference in the cells' ability to metabolize the parent compound into a more reactive form. To see if such increased sensitivity to the cytotoxic effect of 4-NQO was an identifying characteristic of cells from HCMM/DNS and DNS patients and whether cells derived from unaffected members of such families were also more sensitive to 4-NQO than the controls, the survival curves of a series of 40 coded cell lines, derived from patients, family members, or normal donors of various ages, were compared in a blind study. The slopes of the survival curves of all the HCMM/DNS and DNS cell lines proved to be 2- to 3-fold steeper than those of the four previously studied control cell lines, bringing the total to nine of nine and eight of eight, respectively. Ten of the 28 coded cell lines from nonaffected family members or normal, age-matched donors proved to be as resistant as the four previously studied control cell lines and another foreskin-derived control cell line, bringing the total of relatively resistant cell lines to 15 of 33. However, the rest were just as sensitive as the cells from the patients. Mutagenesis studies showed that increased sensitivity to killing by 4-NQO was accompanied by increased sensitivity to mutation induction. Relatively sensitive and relatively resistant cell lines were treated with tritiated 4-NQO and assayed for survival and for the number of 4-NQO residues bound to DNA. The relationship between the number of adducts formed and cell survival was linear, with the relatively sensitive cell lines exhibiting the higher level of residues.(ABSTRACT TRUNCATED AT 400 WORDS)

4-Nitroquinoline-1-oxide↗
PubMed1988

Trisomy 11 in myelodysplasia.

A case of pancytopenia with dysplastic changes in the bone marrow with trisomy 11 (+11) as the sole karyotypic anomaly in an adult male is described. The literature on +11, both as a primary (14 cases) and secondary (55 cases) cytogenetic event in hematologic disorders, is summarized and the findings are discussed. There is the possibility that +11 is a nonrandom chromosomal anomaly in some myelodysplastic disorders.

Aged↗
PubMed1988

Immunoglobulin allotypes and familial cutaneous malignant melanoma/dysplastic nevi. A family study.

Gm and Km allotypes were examined in 355 members of 14 large pedigrees segregating for autosomal dominant cutaneous malignant melanoma/dysplastic nevi. No evidence for linkage was found between the disease locus and the immunoglobulin loci. Furthermore, there was no association of G1m(2) or Gm(-1) with cutaneous malignant melanoma in the 14 independent family probands.

Chromosomes, Human, Pair 14↗
PubMed1987

Hypersensitivity to G2 chromatid radiation damage in familial dysplastic naevus syndrome.

Skin fibroblasts from 25 members of nine kindreds with familial dysplastic naevus syndrome (DNS), 12 apparently normal spouses, and 11 additional unrelated normal individuals were tested for G2 cell-cycle phase sensitivity to ionising radiation. The cells from individuals with DNS or hereditary cutaneous malignant melanoma with DNS (HCMM/DNS) had significantly more chromatid breaks and gaps when entering metaphase 0.5-1.5 h after G2 phase X-irradiation (1 Gy) than those from unaffected controls. In two cases, the test results positively identified individuals before the clinical diagnosis of DNS. A clinically normal obligate carrier of the HCMM/DNS gene showed the enhanced G2 radiosensitivity. Moreover, in a test on 1 proband, the sensitivity was apparent in peripheral blood lymphoblasts. Enhanced G2 chromatid radiosensitivity may be a marker of genetic susceptibility to HCMM/DNS.

Adult↗
PubMed1987

Clinical and laboratory observations in a lymphoma-prone family.

Three sisters developed non-Hodgkin's lymphoma (NHL). Thirteen maternal relatives had adenocarcinomas of various types, predominantly breast and large bowel. Detailed laboratory assessment of this family revealed a variety of immunologic abnormalities. Two lymphoma patients had elevated anti-early antigens (EA) Epstein-Barr virus (EBV) titers. One of the two also had a markedly elevated anti-viral capsid antigen (VCA) EBV titer. The two lymphoma patients were human leukocyte antigen (HLA)-identical, but two unaffected siblings shared the same HLA haplotypes. One of the lymphoma patients and four unaffected family members were anergic; and three unaffected family members had a decreased percentage of T-cells. These data suggest that a subtle disturbance in cellular immune functions may play a causal role in some familial aggregations of malignant lymphoma.

Aged↗
PubMed1987

Decreasing risk of leukemia with prolonged follow-up after chemotherapy and radiotherapy for Hodgkin's disease.

Acute nonlymphocytic leukemia is a recognized complication of combined chemotherapy and radiation treatment of patients with Hodgkin's disease. Previous studies have suggested that the risk of leukemia in these patients increases with time after treatment. We analyzed the occurrence of second neoplasms among 192 patients with Hodgkin's disease who were followed for a median of over 15 years. We originally planned to identify prospectively the morphologic changes in bone marrow that precede the development of acute leukemia. All 63 patients consenting to bone marrow aspiration had normal marrow morphology, and no case of acute leukemia occurred more than 11 years after treatment. Actuarial analysis revealed that the peak onset of leukemia-related complications was between three and nine years after first treatment. We conclude that there appears to be a period of increased risk in patients treated with chemotherapy and radiation, after which the risk of secondary leukemia decreases. Patients surviving for more than 11 years after treatment appear to be at no increased risk of acute leukemia.

Adult↗
PubMed1987

Cytogenetics in hereditary malignant melanoma and dysplastic nevus syndrome: is dysplastic nevus syndrome a chromosome instability disorder?

Analysis of peripheral blood lymphocyte Giemsa-banded karyotypes was performed on 163 family members from 13 melanoma-prone families. Patients were classified regarding the presence of cutaneous melanoma and dysplastic nevi (a well characterized melanoma precursor), and each karyotype was scored for the number of cells containing the following: major structural, minor structural, and numerical abnormalities. No clonal cytogenetic abnormalities were observed. Cutaneous malignant melanoma and dysplastic nevi syndrome patients each had increased abnormalities of all types combined, compared with pooled controls (i.e., normal family members, and spouses; respectively, chi 2 = 6.02, p = 0.01; chi 2 = 5.29, p = 0.02). There was a statistically significant p-value for major structural abnormalities for melanoma patients and numerical abnormalities for the dysplastic nevi patients. Minor structural abnormalities did not differ in any of the groups. In addition, studies of ultraviolet induced sister chromatid exchange, in vitro tetraploidy, and extended prophase banding were performed on a limited number of patients. No significant differences between cases and controls were observed in these tests. Our data suggest that a chromosome instability abnormality may contribute to the pathogenesis of hereditary melanoma.

Adult↗
PubMed1987

Hereditary melanoma and the dysplastic nevus syndrome: the risk of cancers other than melanoma.

We analyzed the prospective occurrence of cancers other than malignant melanoma in fourteen kindreds with hereditary cutaneous malignant melanoma and the dysplastic nevus syndrome. No significant excess of nonmelanoma cancers was documented, suggesting that hereditary cutaneous malignant melanoma/dysplastic nevus syndrome is not pleiotropic for other tumor types.

Dysplastic Nevus Syndrome↗
PubMed1987

Acute myeloid leukemia and other myelopathic disorders following treatment with alkylating agents.

Several large cohorts of patients treated with alkylating agents served as a means to review the clinical and pathologic features of 55 cases of myelopathic disorders that resulted. The incidence was 1.8% overall and consisted of five patients (9.9%) who developed bone marrow hypoplasia or aplasia, 15 (27.2%) who developed a myelodysplastic syndrome, and 35 cases of acute myeloid leukemia (62.9%). The median time to recognition of MPD was 14 months, following cessation of chemotherapy. The distribution of the treatment-related MDS cases was different than "de novo" MDS with a high percentage of RAEB-T, and with the treatment related AMLs, there were a higher percentage of patients with FAB M6 (erythroleukemia), and no cases of FAB M3 (hypergranular promyelocytic). The median survival of all patients was very brief.

Adolescent↗
PubMed1986

Melphalan may be a more potent leukemogen than cyclophosphamide.

We have evaluated the relation between alkylating agents and leukemic disorders in 3363 1-year survivors of ovarian cancer who were treated in five randomized clinical trials and at two large medical centers. Overall, 28 patients developed acute nonlymphocytic leukemia (expected, 1.2) and 7 developed preleukemia. A 93-fold increased risk for acute nonlymphocytic leukemia was seen in 1794 women treated with chemotherapy; the incidence of leukemic disorders was 7.7/1000 women per year. Risk was highest 5 to 6 years after the first treatment and appeared to decrease thereafter. The use of radiation therapy did not affect risk. The 10-year cumulative risk (mean +/- SE) of acquiring a leukemic disorder was 8.5% +/- 1.6% after treatment with any alkylating agent, 11.2% +/- 2.6% after treatment with melphalan, and 5.4% +/- 3.2% after cyclophosphamide treatment. A dose-response relationship was apparent in 605 women receiving melphalan and suggested in 333 women receiving cyclophosphamide. Women receiving melphalan were two to three times as likely to develop leukemic disorders than were women receiving cyclophosphamide. These data indicate that choice of chemotherapeutic agent and drug dosage may influence significantly the risk for long-term adverse effects of cancer therapy.

Acute Disease↗
PubMed1986

Cutaneous malignant melanoma and familial dysplastic nevi: evidence for autosomal dominance and pleiotropy.

Segregation of familial cutaneous melanoma has been shown to be compatible with autosomal dominant transmission with incomplete penetrance. However, the combined phenotype of melanoma and a known melanoma-precursor lesion, the dysplastic nevus (DN), has not previously been found to fit a Mendelian model of inheritance using complex segregation analysis. Employing a life-table and disease-free survival analysis approach, we estimated the lifetime incidence of melanoma in the sibs and offspring of DN-affected individuals to be 46%, consistent with a highly penetrant, autosomal dominant mode of inheritance. To further elucidate the relationship between the two traits, we conducted a linkage analysis between the melanoma locus and a hypothetical DN locus, and obtained a maximum lod score of 3.857 at theta = .08. Furthermore, all families giving evidence for linkage were in the coupling phase and the maximum likelihood estimate of theta was not significantly different from 0 (P = .1). This provides evidence that the DN and melanoma traits may represent pleiotropic effects of a single, highly penetrant gene behaving in an autosomal dominant manner.

Disease Susceptibility↗
PubMed1986

Hereditary dysplastic nevus syndrome: lymphoid cell ultraviolet hypermutability in association with increased melanoma susceptibility.

The hereditary dysplastic nevus syndrome (DNS) is a well-characterized disorder in which affected individuals have increased numbers of premalignant (dysplastic) nevi and a markedly increased risk of developing cutaneous melanoma. Seeking evidence of a systemic disorder in DNS, we examined the effect of ultraviolet radiation on cultured lymphoid cells. Epstein-Barr virus-transformed lymphoblastoid cell lines from patients with hereditary DNS had similar survival values following treatment with 2.3 to 9.0 J of 254-nm ultraviolet radiation per m2 as did lines from control individuals. Mutagenesis at the hypoxanthineguanine phosphoribosyltransferase locus was assessed by measuring the induction of resistance to thioguanine using a microtiter well assay. Three lymphoblastoid cell lines from patients with hereditary DNS and melanoma had a 2- to 3-fold greater frequency of induced mutants per clonable cell than three normal lines following exposure to 4.5 to 9.0 J of ultraviolet radiation per m2. Expanded clones of mutated DNS lymphoblastoid cell lines had less than 6% of normal hypoxanthine-guanine phosphoribosyltransferase activity. Inhibition and recovery of DNA synthesis following ultraviolet exposure were similar in 2 DNS and 2 normal lines. Repair by DNS lines of ultraviolet-induced DNA damage was in the normal range as measured by alkaline elution. Thus, hereditary DNS exhibits in vitro hypermutability which may reflect increased susceptibility to ultraviolet-induced somatic mutations in vivo. This abnormality may be related to the increased melanoma susceptibility of patients with hereditary DNS.

Adult↗