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Biomedical subjects

M Lipkin

Publications and source records attributed to M Lipkin.

At least 163 records · Page 9Linked to original sources
PubMed1984

12-O-Tetradecanoylphorbol-13-acetate stimulation of DNA synthesis in cultured preneoplastic familial polyposis colonic epithelial cells but not in normal colonic epithelial cells.

We have developed a method for the routine primary culture of human colonic epithelial cells. Cultured cells exhibited characteristic epithelial structures, including a brush border and junctional complexes. Flask-like goblet cells containing mucus were also seen within the epithelial monolayer. [3H]Thymidine labeling indices were used to distinguish between cultured cells from familial polyposis patients, other patients at high risk to develop colon cancer, and low-risk control subjects. 12-O-Tetradecanoylphorbol-13-acetate (TPA) at 10 ng/ml enhanced DNA synthesis an average of 8-fold when assayed by labeling index in colonic epithelial cells from five of six familial polyposis patients. No such stimulation by TPA was seen in cells from 13 high-risk patients without familial polyposis or in cells from five low-risk subjects. Hundreds of benign polyps can be found in the colons of familial polyposis patients. One such benign tubular adenoma exhibited the same enhancement of DNA synthesis by TPA as normal-appearing epithelial cells from a biopsy adjacent to that polyp. Mitogenic response to TPA had been seen earlier in cells from each of four tubular adenomas (Friedman, E. Cancer Res., 41: 4588-4599, 1981). Both familial polyposis epithelial cells and adenoma cells are considered preneoplastic, but they are not identical because their patterns of actin cytoskeletal organization differ. These results imply that familial polyposis epithelial cells are precursors of tubular adenoma cells, and their transition to the more advanced preneoplastic cells of this benign tumor is influenced by endogeneous tumor promoters.

Cells, Cultured↗
PubMed1984

Classification and risk assessment of individuals with familial polyposis, Gardner's syndrome, and familial non-polyposis colon cancer from [3H]thymidine labeling patterns in colonic epithelial cells.

A probabilistic analysis has been developed to assist the binary classification and risk assessment of members of familial colon cancer kindreds. The analysis is based on the microautoradiographic observation of [3H]thymidine-labeled epithelial cells in colonic mucosa of the kindred members. From biopsies of colonic mucosa which are labeled with [3H]thymidine in vitro, the degree of similarity of each subject's cell-labeling pattern measured over entire crypts was automatically compared to the labeling patterns of high-risk and low-risk reference populations. Each individual was then presumptively classified and assigned to one of the reference populations, and a degree of risk for the classification was provided. In carrying out the analysis, a linear score was calculated for each individual relative to each of the reference populations, and the classification was based on the polarity of the score difference; the degree of risk was then quantitated from the magnitude of the score difference. When the method was applied to kindreds having either familial polyposis or familial non-polyposis colon cancer, it effectively segregated individuals affected with disease from others at low risk, with sensitivity and specificity ranging from 71 to 92%. Further application of the method to asymptomatic family members believed to be at 50% risk on the basis of pedigree evaluation revealed a biomodal distribution to nearly zero or full risk. The accuracy and simplicity of this approach and its capability of revealing early stages of abnormal colonic epithelial cell development indicate potential for preclinical screening of subjects at risk in cancer-prone kindreds and for assisting the analysis of modes of inheritance.

Colonic Neoplasms↗
PubMed1983

Natural antibodies in human sera directed against blood-group-related determinants expressed on colon cancer cells.

Sera from 136 normal males and 33 members of families at high risk for colon cancer were tested for reactivity with six colon cancer cell lines by the protein A-mixed hemadsorption assay. Ninety-one sera had antibodies to colon cancer cell line HT-29. In 89 cases the antibodies were absorbed by human A and B erythrocytes or sheep erythrocytes. Antibodies in the remaining two sera, which were from sisters in the high-risk group, were not absorbed by red cells but could be absorbed by tumor cells expressing A or B blood-group determinants. Their reactivity was inhibited by some soluble blood-group glycoproteins. One serum (No. 4) was inhibited by A-active glycoproteins from human saliva and ovarian cyst fluids and from porcine mucosa, as well as by a polysaccharide derived from gastric cancer; it has an anti-A-like specificity. The other serum (No. 6) was inhibited by A and B glycoproteins, by a blood group precursor glycoprotein and by the same gastric cancer polysaccharide; it seems to have a wider specificity directed towards both A- and B-like structures. It is not known what caused production of these antibodies but it may be significant that they occurred in members of a family at high risk for developing colon cancer.

Absorption↗
PubMed1983

Expression of gastric-associated antigens by human premalignant and malignant colonic epithelial cells.

A rabbit antiserum prepared to 2nd-trimester fetal organ extracts and absorbed with adult tissue (anti-STFa) was used to detect antigens common to 2nd-trimester fetal large bowel, normal adult stomach, several colon carcinoma cells (in primary and established cultures) and epithelial cells cultured from benign colonic polyps. The frequency of anti-STFa-positive cells was highest in cultures derived from benign tumors known to be associated with a greater degree of premalignancy. Thus, the percentage of antigen-positive cells increased from 18 and 43% to 70% of cultures from tubular, villotubular and villous adenomas, respectively. Considerable heterogeneity in the distribution of antigen-containing cells was evident within any given area of a positive culture. Absorption experiments, using a spectrum of fetal and normal adult tissue extracts, indicated that the adenoma-carcinoma specificity resides in fetal, but not adult, large bowel and normal adult stomach.

Adenoma↗
PubMed1983

Reduced capacity for DNA repair synthesis in patients with or genetically predisposed to colorectal cancer.

Peripheral resting mononuclear leukocytes were compared for their capacities to repair DNA lesions induced by a 1-hour exposure to a standardized 10-microM dose of N-acetoxy-N-2-fluorenylacetamide (N-AcO-2-FAA). Leukocytes from the following 3 groups were studied: 39 control subjects, 40 patients after colonic resection because of colorectal cancer (disease-free at the time of this study), and 28 individuals with a hereditary predisposition to colorectal cancer. Although the level of N-AcO-2-FAA that bound to mononuclear leukocyte DNA was the same for the various population groups, the level of N-AcO-2-FAA-induced unscheduled DNA synthesis (UDS) was significantly reduced in the mononuclear leukocytes of individuals who had had colorectal cancer or a genetic predisposition for the disease. These findings indicate that a deficiency in mononuclear leukocyte DNA repair synthesis is associated with the development of colorectal cancer in these populations. Our observation of this nonspecific UDS deficiency (relating to colorectal cancer) was not explained by experimental variations among the sampled groups with regard to individual differences in lymphocyte heterogeneity, age, sex, smoking habits, or blood pressure.

Acetoxyacetylaminofluorene↗
PubMed1982

Differential response of familial polyposis fibroblasts to two bifunctional alkylating agents.

Skin fibroblasts from three subjects with familial polyposis coli, a hereditary disorder predisposing to colon cancer, exhibited an unexpected insensitivity to mitomycin C (MMC). Sister chromatid exchanges (SCEs) were either reduced or unchanged after exposure to MMC, while another bi-functional alkylating agent, diepoxybutane (DEB), induced an increase in SCE level at a low, equitoxic dosage in parallel experiments. Increased sensitivity to MMC as assayed by colony formation was, however, shown by one of the subjects with polyposis. These cells with the familial polyposis genotype may have a deficiency in the DNA repair system handling MMC-induced alkylation damage yet remain capable of repairing damage induced by DEB alkylation. This deficiency may contribute to the increased frequency of neoplastic transformation known to occur in these cells in vivo.

Alkylating Agents↗
PubMed1982

Cell proliferation in explant cultures of human colon.

Biopsy specimens of human colonic mucosa taken from the rectosigmoid of 12 normal subjects were maintained in explant culture for 4 days. Histological, microautoradiographic and chemical measurements were carried out to evaluate cell replication, the effect of deoxycholic acid, and the incorporation of uridine and leucine into RNA and protein. Active cell replication was shown to be greatest during the first day of organ culture, and the number of cells that synthesized DNA also increased when deoxycholic acid was added to the culture medium. At later times, with morphological evidence of tissue viability, the synthesis of DNA, RNA, and protein within colonic epithelial cells decreased, and the total number of cells in the crypt columns declined. Findings indicate good maintenance of metabolic activities of colonic epithelial cells in short-term explant culture, and the utility of both cell-kinetic and morphological observations in assessing the status of colonic explants at early and late intervals.

Autoradiography↗
PubMed1982

The couvade syndrome: an epidemiologic study.

A tracer condition, to be used for clinical epidemiologic examination of psychosociogenic illness, must be common and clearly identifiable, distinguishable from concomitant physical problems, and found in general care. These criteria are met by couvade syndrome, the seeking of care for pregnancy-related symptoms by the mates of expectant women. Records of the mates of 267 postpartum women, representing a systemic sample of all births in a health maintenance organization of 36,000, were rated for the presence of nausea, vomiting, anorexia, abdominal pain, abdominal bloating, and other symptoms. Each patient was his own control. Sixty men (225 of 1000) sought care for couvade syndrome; they had a twofold increase in visits (p less than 0.001); had four times more symptoms than during control periods (p less than 0.001); and received twice as many prescriptions for medication as the men without this syndrome (p less than 0.05). The health care providers did not tend to recognize the "expectant" status of these patients or note the presence of the syndrome.

Adult↗
PubMed1981

Tissue culture of human epithelial cells from benign colonic tumors.

Human colonic epithelial cells from three classes of benign tumors have been reproducibly cultured free of fibroblasts for 8 wk using a supplemented Medium 199 (M 199S). The cultured colonic cells were identified as epithelial by the presence of junctional complexes (tight junctions, gap junctions, and desmosomes), a brush border on the apical surface, keratin fibrils, and by both a close-packed columnar or cuboidal morphology and the capability to transport water and ions to form hemicysts. Colony formation was initiated by groups of epithelial cells, not by single cells, and was inhibited by cocultivation with either lethally irradiated 3T3 cells or human diploid fibroblasts. Enhancement of epithelial colony formation was observed following culture on nonadherent, "floating" substrates compared with substrates attached directly to the bottom of the culture dish. Replication of epithelial cells in M 199S from the class of benign colonic tumors least prone to malignancy, the tubular, was significantly enhanced by epidermal growth factor (EGF). In contrast, EGF did not stimulate the growth of cells in M 199S from the other classes of benign tumors, the villotubular and the villous, which exhibit more malignant potential. These data imply that premalignant colonic epithelial cells lose responsiveness to growth modulation by EGF as they progress toward frank carcinoma.

Adenoma↗
PubMed1981

Transplantation of adenomatous polyps, normal colonic mucosa and adenocarcinoma of colon into athymic mice.

Fragments of benign colonic adenomatous polyps of man, adenocarcinoma of the colon of man, and normal colonic mucosa of man and rodent were transplanted under the kidney capsule of athymic mice. Benign human adenomatous cells survived for periods of up to 28 days, normal rodent colonic epithelial cells for 45 days and colonic carcinoma cells for 43 days. This was demonstrated by morphologic criteria, and by the incorporation of tritiated thymidine into DNA of the epithelial cells. The transplantation technique can supplement organ culture methods for the maintenance of adenomatous tissue derived from human colonic mucosa, in order to facilitate studies of growth characteristics and transformation of the cells.

Adenocarcinoma↗
PubMed1981

Nondegradation of fecal cholesterol in subjects at high risk for cancer of the large intestine.

In previous studies subjects with familial polyposis, the autosomal dominant disease leading to colon cancer, excreted higher levels of fecal cholesterol than normal subjects, with decreased conversion to degradation products. Findings suggested fecal cholesterol degradation as a marker of hereditary predisposition to colon cancer. Current measurements now have shown that affected individuals and asymptomatic progeny in a second population group with inherited predisposition to colon cancer are low converters of fecal cholesterol. The latter group consisted of highly colon cancer prone families without polyposis, in which patterns of inheritance similar to the autosomal dominant pattern of familial polyposis were observed. 24-h stool collections were obtained from 72 subjects who consumed mixed western diets. Mean percent degradation of fecal cholesterol to coprostanol, coprostanone, cholestanol, and cholestanone revealed significant decreases in fecal cholesterol conversion in affected and asymptomatic subjects in colon cancer prone families without polyposis (P < 0.001) compared to controls. This is in addition to those with familial polyposis (P < 0.001), and extends this marker of colon cancer susceptibility to a second population group with hereditary predisposition to colonic neoplasia.

Cholesterol↗
PubMed1981

Genetic counseling for beta-thalassemia trait following health screening in a health maintenance organization: comparison of programmed and conventional counseling.

Providing adequate counseling of patients identified in genetic screening programs is a major responsibility and expense. Adults in a health maintenance organization, unselected for interest, were screened for beta-thalassemia trait as part of preventive health care. Counseling was provided by either a trained physician (conventional counseling) or by a videotape containing the same information followed by an opportunity to question a trained physician (programmed counseling). Immediately before and after counseling, knowledge of thalassemia, knowledge of genetics, and mood change were assessed by questionnaire. Comparable mood changes and similar learning about thalassemia and genetics occurred with both counseling methods. Thus, as judged by immediate effects on knowledge and mood, videotaped instruction can greatly reduce professional time required for genetic counseling and facilitate the incorporation of genetic screening into primary health care.

Adult↗
PubMed1980

Organization of actin-containing cables in cultured skin fibroblasts from individuals at high risk of colon cancer.

Actin-containing cables were examined by immunofluorescence in cultured skin fibroblasts from individuals genetically prone to colon cancer. The study confirmed our earlier finding of an altered distribution of actin-containing cables in skin fibroblasts of patients with hereditary adenomatosis of the colon and rectum (ACR) (Kopelovich et al., 1977). Abnormalities were also found in about one-half of the asymptomatic offspring at risk for ACR, while a polyposis-free branch of one ACR family showed a normal pattern of actin-containing cables. Persons from colon cancer-prone (CCP) families without polyposis, and normal controls, showed no disturbance in the actin patterns. The results suggest that this phenotypic marker may be useful in identifying ACR gene carriers and in probing cellular controls of carcinogenesis.

Actins↗