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Biomedical subjects

G Casey

Publications and source records attributed to G Casey.

At least 109 records · Page 6Linked to original sources

Amplification of human int-2 in breast cancers and squamous carcinomas.

Murine int-2 is one of the genetic loci implicated in the induction of mouse breast cancers by murine mammary tumor virus. An homologous gene has recently been identified in the human genome (Casey et al., 1986). The human int-2 locus was found to be amplified 7- to 25-fold in 4 of 46 infiltrating ductal breast cancers and 30- to 60-fold in 2 of 8 squamous carcinomas of the head and neck region, but not in other cancers. All of the involved tumors had metastasized to regional lymphatics at the time of analysis and five exhibited clinically aggressive behavior.

Breast Neoplasms↗

Energy expenditure of autoperfusing heart-lung preparation.

The autoperfused heart-lung preparation was developed as a method for extending the acceptable donor-to-recipient interval in clinical heart-lung transplantation. Metabolic substrate enhancement has been shown to be necessary for the survival and homeostasis of the functioning preparation. To define basic metabolic requirements and to determine the resting energy expenditure of the working canine heart-lung preparation, two groups were studied. Ten canine heart-lung blocks were placed in a normothermic autoperfusion circuit. In Group 1 (n = 5), a hyperalimentation solution of balanced substrate was infused (15% dextrose, 4.25% amino acids, 8 meq magnesium sulfate, 30 IU/dl insulin, and 10% lipids). In Group 2 (n = 5), no substrate was given. The preparations were ventilated with a mixture of room air and 5% CO2 at a rate of 4 breaths/min to maintain physiological pH. Myocardial function was assessed by cardiac output determinations and mixed venous gases. Pulmonary function was assessed with arterial blood gases. The oxygen consumption (VO2) and carbon dioxide production (VCO2) were measured with a Metabolic Cart, and the resting energy expenditure was calculated. The mean survival time for Group 1 was 360 minutes, and all preparations were terminated electively. The mean survival time for Group 2 was 219 +/- 43 minutes (p less than 0.01) with congestive heart failure as the common terminal event. All parameters of cardiac function and blood gases remained within physiological limits without significant differences between groups. The resting energy expenditure, a measure of metabolic rate, was 2.5 +/- 0.3 kcal/hr in Group 1 and 1.0 +/- 0.2 in Group 2 at termination (mean +/- SD) (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Sequence, topography and protein coding potential of mouse int-2: a putative oncogene activated by mouse mammary tumour virus.

A major proportion of carcinomas induced by mouse mammary tumour virus (MMTV) show evidence for proviral activation of a cellular gene, int-2, on chromosome 7. The sequence of 7869 bp of DNA spanning the transcription unit of int-2 was determined and compared with that of a series of int-2-specific cDNA clones derived from mammary tumour RNA. The predicted positions of intron-exon boundaries, established by alignment of cDNA and chromosomal DNA sequences, indicate that the gene comprises at least three exons. An open reading frame capable of encoding a protein of 245 amino acids with an estimated mol. wt of 27 kd, is flanked by substantial non-coding segments at both 5' and 3' ends. Comparison of the chromosomal DNA sequence and the predicted amino acid sequence with available data-bases has revealed no homology to other known genes. These results are discussed in relation to the status of int-2 as a candidate proto-oncogene.

Amino Acid Sequence↗

Characterization and chromosome assignment of the human homolog of int-2, a potential proto-oncogene.

int-2 is one of two cellular genes (int-1 and int-2) currently implicated in the genesis of mammary carcinomas by mouse mammary tumor virus and may constitute a novel cellular proto-oncogene. Using low-stringency hybridization with mouse int-2 probes, we established that homologous genes exist in a variety of mammalian species, including humans, but failed to detect related sequences in other classes and phyla. Recombinant bacteriophage clones and a single cosmid encompassing the human int-2 gene were isolated and characterized by restriction enzyme mapping. A survey of nine primary human breast tumors, three breast tumor cell lines, and three normal individuals revealed no evidence for gross amplification or rearrangement of the int-2 locus. Three distinct restriction fragment length polymorphisms were observed which could prove useful in future linkage studies. By a combination of in situ hybridization of metaphase chromosomes and somatic cell genetics, the human int-2 gene was mapped to chromosome 11, band q13.

Animals↗

Long-term effects of chemotherapy on lymphocyte chromosomes from patients treated for gestational trophoblastic tumours.

A cytogenetic follow-up study of patients treated with chemotherapy for gestational trophoblastic tumours was undertaken. In some cases, high levels of chromosome damage were found to persist in lymphocytes for several years after completion of therapy. These results are compared with those found in similar studies of non-malignant and other malignant diseases. The relevance of these findings to the risk of subsequent chemotherapy-induced malignancy is discussed.

Adult↗

Long-term cytogenetic follow-up study of patients with uveitis treated with chlorambucil.

We have studied the long-term effects of chlorambucil treatment on the chromosomes of peripheral blood lymphocytes from patients with uveitis. Amounts of chromosome damage (breaks and rearrangements) were found to vary between individuals, but tended to increase with the cumulative dose. Some patients were found to have persistently high levels of chromosome damage many years after treatment had been completed.

Chlorambucil↗

Correlation of differentiation state and silver staining of nucleolar organizers in the promyelocytic leukemia cell line HL-60.

We have applied nucleolar organizer region (NOR) silver staining to the promyelocytic leukemia cell line HL-60, before and after dimethylsulfoxide (DMSO) mediated differentiation. The results demonstrated a gradual suppression of rDNA transcription during terminal maturation of these bone-marrow-derived cells and support our hypothesis that there are characteristic NOR staining profiles for different bone marrow cell types.

Cell Cycle↗

Sister-chromatid exchange and cell kinetics in CHO-K1 cells, human fibroblasts and lymphoblastoid cells exposed in vitro to asbestos and glass fibre.

Possible mutagenic activity of the asbestos dusts crocidolite and chrysotile, and fine and coarse glass, was assessed in CHO-K1 cells, human fibroblasts and human lymphoblastoid cells using the sister-chromatid exchange assay and by examining the effects on cell kinetics. Asbestos caused no dose-related increase in sister-chromatid exchange levels in any of the cell types. However, mitotic delay was induced in CHO-K1 cells and human fibroblasts. The order of magnitude of induced delay in CHO-K1 cells was chrysotile greater than fine glass greater than crocidolite greater than coarse glass. Mitotic inhibition was more pronounced in these cells if they were still in suspension when initially exposed to the dusts compared with 1 h after plating.

Animals↗

The prevalence of neural tube defects among ethnic groups in Brooklyn, New York.

Records of almost 174,000 consecutive births at six Brooklyn hospitals during the years 1968-1976 were reviewed for congenital neural tube defects. Prevalence of anencephaly, myelomeningocele and occipital encephalocele combined was significantly higher in infants delivered to mothers born in Puerto Rico than in offspring of non-Puerto Rican whites or blacks. The association of prevalence rates with ethnicity remained significant after adjustment for several variables. However, when adjustment was made for private or service status the difference between Puerto Ricans and whites, although still appreciable, was no longer statistically significant. No significant differences in prevalence rates between whites and blacks were observed. Sex ratios of affected infants were close to unity in each ethnic group. Statistically significant associations were found between the prevalence of neural tube defects and parity, gravidity and economic status. The patterns of these associations varied among the ethnic groups. A declining trend in the prevalence of myelomeningocele was observed for all ethnic groups.

Black People↗

A comparison of the cytogenetic response to asbestos and glass fibre in Chinese hamster and human cell lines. Demonstration of growth inhibition in primary human fibroblasts.

Asbestos and fine glass fibre, which induce high levels of chromosome aberrations and polyploidy in Chinese hamster permanent cell lines, were found to cause no increase in chromosome damage or polyploidy in primary human fibroblasts or in human lymphoblastoid lines. In common with permanent cell lines of hamster or human origin, treatment of primary human fibroblasts with higher doses of asbestos or fine glass resulted in almost total growth inhibition, showing that the primary cells are not unaffected by these agents. The reason for lack of evident cytogenetic damage in primary cells may lie in the greater spontaneous karyotype instability of transformed (permanent) cell lines or may be connected with the less efficient DNA repair capacity of Chinese hamster ovary cells.

Animals↗

Variations in the activity of nucleolar organizers in different tissues, demonstrated by silver staining of human normal and leukemic cells.

A simple silver-staining technique that demonstrates those nucleolar organizing regions of metaphase chromosomes which are transcriptionally active during the preceding interphase (AgNORs) has been applied to cells obtained from the bone marrow and mitogen-stimulated peripheral blood lymphocyte cultures of hematologically normal individuals and patients with various forms of leukemia. In the majority of bone marrow cells from the normal controls and many of the patients, the number of cells with detectable AgNORs, and the staining intensities in those cells which were Ag+, were markedly reduced compared with the levels found in blood lymphocytes. The numbers of cells having satellite associations and the numbers of chromosomes participating in these associations also generally reflected the proportions of AgNORs present. When patterns of bone marrow silver staining were compared between patients with leukemia, distinct differences were found which could be correlated with cytology. It is suggested that different cell types have characteristic AgNOR staining profiles, reflecting specific regulation of ribosomal RNA synthesis in particular cell lineages. AgNOR staining may indicate, therefore, the predominant cell types that divide in the bone marrows of patients with different forms of leukemia.

Bone Marrow Cells↗

Growth, DNA repair, sister chromatid exchange and chromosome studies in fibroblasts from Huntington's disease patients.

Fibroblast cultures from six unrelated Huntington's Disease (HD) patients and controls and one affected relative of an HD patient were used in studies of cell growth, DNA repair, sister chromatid exchange (SCE) and chromosome aberrations. There were no significant differences in background levels of SCEs or of chromosome aberrations between HD cultures and controls. Preliminary results using epidermal growth factor indicated that HD cells may have a lowered relative response to this polypeptide hormone. Cell growth studies showed no correlation between growth rate and HD. Increased cell saturation density was recorded in cell lines from four of the HD patients; the remaining three lines from affected individuals (two of them related) were indistinguishable from control cultures. This variation may reflect genetic heterogeneity in HD. An apparent deficiency in DNA repair capacity following UV irradiation in cultures from three HD patients was subsequently shown to be the result of the increased cell saturation densities in these cultures.

Adult↗

The epidemiology of congenital hydrocephalus. A study in Brooklyn, N.Y. 1968--1976.

In a hospital-based study of almost 174,000 total births during 1968--1976, the authors found the incidence of congenital hydrocephalus to be 66 cases per 100,000 births. There was a significantly higher frequency in children born to mothers who themselves had been born in Puerto Rico but no significant difference in incidence between whites and blacks. The influences of maternal age, previous pregnancies, socioeconomic status, temporal and other factors are assessed and compared to previous reports.

Ethnicity↗

Hepatitis B virus infection in dentists.

To evaluate viral hepatitis as a hazard in general dentistry, we surveyed participants in an annual health-screening program at the 1972 American Dental Association session. Of 1245 practitioners, 0.9 per cent were positive for hepatitis B surface antigen, and 12.7 per cent were antibody positive. Of those who had had clinical hepatitis while studying or practicing dentistry, 43 per cent were seropositive. The frequency of evidence for prior infection with hepatitis B virus increased uniformly with increasing years of professional experience. The proportion of seropositive dentists did not vary with geographic region of the United States, or size of community. Only 10.5 per cent recognized illicit self-injection among patients, and their infection rate was not increased. These data indicate an increased frequency of infection with hepatitis B virus among general dentists, and are compatible with relatively uniform endemicity of subtype/ad strans of that agent in the general population for several decades.

Adult↗