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Biomedical subjects

M Lipkin

Publications and source records attributed to M Lipkin.

At least 199 records · Page 11Linked to original sources
PubMed1976

Appearance of rapidly labeled, high molecular weight RNA in nuclear ribonucleoprotein. Release from chromatin and association with protein.

Chromatin and nuclear ribonucleoprotein (nRNP) have been prepared from a human carcinoma cell line. Following a 1-hour (3H)uridine pulse, 60 to 70% of the nuclear radioactivity, after removal of nucleoli, was found in the chromatin, the balance in nRNP. This was true whether the chromatin and nRNP were separated by velocity centrifugation or by isopycnic centrifugation on Metrizamide gradients. Radioactivity in chromatin and nRNP was found in high molecular weight RNA, with mean sedimentation coefficients of 20 S and 15 S, respectively, as determined on sodium dodecyl sulfate-sucrose gradients. Experiments on the kinetics of appearance of radioactivity in the RNA of the two fractions suggest that some of the chromatin-associated RNA is precursor to nRNP-RNA. The proteins of nRNP are complex as revealed by sodium dodecyl sulfate gel electrophoresis. The contamination by chromatin protein was estimated to be 5%. Experiments involving short pulses of (3H)tryptophan, and pulse-chase, suggested that the rapidly turning over proteins of nRNP were not complexed with RNA while still associated with chromatin. However, it was also shown that the radioactivity in nRNP following short pulses of (3H)tryptophan did not correspond to the major bands seen on stained sodium dodecyl sulfate gels. It is therefore concluded that the protein of nRNP consists of two classes: species present in large amounts, possibly common to all RNA in nRNP, which are relatively stable and may be complexed to RNA still associated with chromatin; and a large number of rapidly turning over species, each present in small amounts and associated with nRNP only after its release from chromatin.

Cell Line↗
PubMed1976

Fecal bile acids and neutral sterols in patients with familial polyposis.

Fecal neutral steroids and bile acids were measured in patients with familial polyposis, family controls who are immediate relatives of patients, and controls other than relatives. All subjects were consuming a mixed Western diet at the time of collection of stool specimens. Although the total fecal neutral sterol concentrations were not different between the groups, the patients with familial polyposis excreted a high amount of cholesterol and low levels of coprostanol and coprostanone compared with other groups. Patients with familial polyposis excreted levels of total bile acids in their feces comparable to those excreted by controls; lithocholic acid excretion was decreased in patients with familial polyposis. These findings suggest that analysis of stools for cholesterol and its metabolites be useful in screening the siblings of polyposis families for latent disease.

Adolescent↗
PubMed1976

Growth abnormalities of cultured human skin fibroblasts derived from individuals with hereditary adenomatosis of the colon and rectum.

A heritable propensity to develop malignant lesions is found in individuals with familial adenomatosis of the colon an rectum (ACR) and the Gardner's syndrome variant, an autosomal dominant trait. In the present study, the growth characteristics of cultured skin fibroblasts (SF) derived from normal-appearing flat skin biopsies of ACR families, representing all phenotypes, and appropriate controls were investigated. SF were obtained from stocks between the second and fifth passages and growth to confluency in Eagle's Minimal Essential Medium (EMEM) supplemented with 15% fetal calf serum (FCS). Following trypsinization, cells were replanted in EMEM supplemented with either 1% or 15% FCS at an initial density of 4 x 10(3) cells/cm2 and counted daily for five days. Normal SF representing several age groups (both sexes) and those obtained from non-afflicted individuals of ACR families grew only in 15% FCS. In contrast, SF from ACR subjects and from embryonal skin grew both in 1% and 15% FCS. SF from several clinically asymptomatic adults, children or ACR patients, grew in 1% FCS as well. Cell cultures from ACR individuals showed regions of criss-crossed arrays and multilayered pattern. These growth properties were not observed in normal cell cultures. The SF from ACR individuals did not grow in methocel, nor did they form tumors in athymic mice. These results suggest the occurrence of previously undetected biochemical alterations in SF taken from ACR genotypes.

Animals↗
PubMed1976

Recent studies on the identification of proliferative abnormalities and of oncogenic potential of cutaneous cells in individuals at increased risk of colon cancer.

This recent study describes the growth characteristics of ACR skin fibroblasts in culture and their differential susceptibility to transformation by Kirsten murine sarcoma virus (Ki-MSV). The SF were derived from normal appearing subepidermoid biopsies of ACR individuals, their progeny and ocntrols. Normal SF were contact-inhibited and grew only in 15% FCS. SF of ACR subjects, and some asymptomatic ACR progeny were not contact inhibited, grew in both 1% and 15% FCS and were considerably more susceptible to transformation by Ki-MSV than were control SF. The virally transformed SF showed a loss of anchorage dependency in methylcellulose and formed tumors in athymic mice. The results suggest the presence of early and previously undetected metabolic lesions in SF from clinically asymptomatic subjects. These phenotype markers are currently evaluated for their utility in the clinical diagnosis of individuals with latent ACR and those at increased risk for colon cancer. SF from ACR individuals have been recently shown to contain significant alterations in the intracellular distribution of actin (R. Pollack and L. Kopelovich, in preparation), and elevated levels of plasminogen activator (L. Kopelovich).

Cell Transformation, Neoplastic↗
PubMed1976

Early proliferative changes in intestinal cells.

Early lesions in the colonic mucosa of humans and rodents are characterized by similar proliferative changes within their epithelial cell population. Progressive phases of abnormal cell development appear during the evolution of neoplastic transformation in colonic cells of rodents exposed to chemical carcinogens and in humans highly susceptible to gastrointestinal cancer. Identification and classification by phenotype of cells of these individuals at increased risk for colon cancer are leading to new methods to improve the detection and diagnosis of neoplasia in high risk individuals and families. An analytical system of precise numerical definitions is aiding an approach to modify the evolution of advanced stages of neoplasia.

Adolescent↗
PubMed1975

Proliferative patterns in colonic mucosa in familial polyposis.

Microautoradiographic measurements of TdR3H incorporation into epithelial cells of colonic biopsies were compared in normal and eight index cases with familial polyposis, an inherited trait characterized by the development of colonic polyps and carcinomas. Colonic epithelial cells normally synthesized DNA synthesis was proliferated in the deeper two-thirds of the crypts, while DNA synthesis was repressed in the upper one-third. Patients with familial polyposis and patients with isolated single polyps incorporated TdR into epithelial cells lining the surfaces of polyps and occasionally into surface cells of intervening flat mucosa. Symptom-free members of polyposis families also demonstrated TdR3H incorporation into surface epithelial cells in biopsies of morphologically flat mucosa. The findings indicate similar proliferative behavior of epithelial cells in the formation of all adenomas, be they single isolated polyps or multiple familial adenomatous polyps. A sequence of changes occurs involving a loss of the cells' ability to repress DNA synthesis and the appearance of cells with persistent DNA synthesis at the surface and along the upper portion of colonic crypts. These defects are focal and widespread in the colonic mucosa of those with familial polyposis and are expressed at early age.

Adolescent↗
PubMed1975

Biology of large bowel cancer. Present status and research frontiers.

Man and laboratory rodents exposed to chemical carcinogens both show changes in growth characteristics of colonic epithelial cells during neoplastic transformation. Progressive phases of abnormal cell development appear in colonic epithelial cells which gain an increased ability to proliferate and accumulate in the mucosa. These phases in the expression of neoplastic transformation of colonic cells are best defined in the dominant inherited disease of man as adenomatosis of the colon and rectum. Individuals with inherited adenomatosis and those in lesser risk categories can be classified by cell phenotype based on changes in the proliferation and maturation of colonic and other cells. These classifications are leading to new predictive indices which identify heightened degrees of susceptibility of individuals who are at increased risk for colon cancer, and the stage of development of their disease. The indices also are being used to study the contribution of specific elements in the enviroment that modify or accelerate the progression of disease.

Adenoma↗