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Biomedical subjects

M Lipkin

Publications and source records attributed to M Lipkin.

At least 145 records · Page 8Linked to original sources
PubMed1985

Hereditary nonpolyposis colorectal cancer (Lynch syndromes I and II). I. Clinical description of resource.

Hereditary nonpolyposis colorectal cancer (HNPCC) is comprised of the following: the cancer family syndrome (CFS), or Lynch syndrome II, which shows early-onset proximal colonic cancer predominance and other associated extracolonic adenocarcinomas, particularly endometrial carcinoma; and hereditary site-specific colon cancer (HSSCC), or Lynch syndrome I, which shows all of the same characteristics, except for extracolonic cancer. Nine families with CFS and two with HSSCC provided the resource that was tested for biomarkers (see companion article). All families were meticulously evaluated for genealogy and cancer verification. Biologic specimens were obtained during field visits to areas of closest geographic proximity to the families. Cancer education and recommendations for surveillance/management were provided to patients and their physicians. Additionally, 40 families (about 3000 individuals) with either CFS or HSSCC have been ascertained. Syndrome cancers were restricted to direct-line relatives as opposed to nonbloodline relatives, arguing against involvement of environmental factors. One documented clinical feature was a predilection for proximal versus distal colonic cancer in both CFS and HSSCC kindreds. This has important clinical significance in that it clarifies the need for instituting effective surveillance earlier to detect the predominantly proximal colonic cancers.

Adolescent↗
PubMed1985

Proliferative abnormalities of the oesophageal epithelium of Chinese populations at high and low risk for oesophageal cancer.

Studies on the pattern of proliferation of epithelial cells from the oesophagus of 33 individuals from Linxian, a high-risk area for oesophageal cancer in China, and of 22 subjects from Jiaoxian, a low-risk area for the same cancer in China, were performed using thymidine labelling. Oesophageal biopsies were obtained during endoscopic surveys carried out in these 2 populations. A clear difference was observed between the 2 groups; the high-risk group showed cell proliferation in the upper layers of the epithelium more often than the low-risk group. No difference was found in the cell proliferation patterns of subjects with oesophagitis and those without oesophagitis in the high-risk area. This finding could suggest that the tritiated thymidine assay may be a more sensitive method to characterize the precancerous lesions of the oesophagus in high- and low-risk populations than simple histological evaluation.

Adult↗
PubMed1985

Seventh-Day Adventist vegetarians have a quiescent proliferative activity in colonic mucosa.

The proliferation of epithelial cells in colonic mucosa was studied in humans at varying degrees of risk for colon cancer. Seventh-Day Adventist vegetarians, known to have significantly lower mortality from colon cancer than the general U.S. population, had the most quiescent proliferative activity of mucosal epithelial cells. Increased replication and expansion of the proliferative compartment accompanied increased colon cancer risk. The analytical methods of this study may be useful in assessing the influence of dietary components involved in the initiation, promotion or inhibition of colon cancer, and in developing strategies for nutritional intervention.

Adult↗
PubMed1985

Proliferative and antigenic modifications in human epithelial cells in chronic atrophic gastritis.

For the study of both proliferative and antigenic changes in epithelial cells in a disease predisposing to gastric cancer, endoscopic biopsy specimens were analyzed following removal from individuals with chronic atrophic gastritis (CAG); comparisons were made with specimens from normal gastric mucosa. All subjects were from Nariño, Colombia, the population of which has a high age-adjusted incidence of gastric cancer (150/100,000 population) occurring mainly in gastric antrum. After pulse incubation of biopsy specimens with tritiated thymidine ([3H]dThd), microautoradiographic distributions of [3H]dThd-labeled cells in the epithelial lining of gastric pits were correlated with expression of serologically defined gamma-fetal antigen (FA) as a second marker. Measurements were done both in gastric corpus and in antrum for entire gastric pits and over multiple gastric pit compartments. Total numbers of cells per gastric pit column did not differ between the normal and the CAG specimens either in corpus or in antrum; however, both in corpus and in antrum mean numbers of [3H]dThd-labeled cells per gastric pit column and labeling index were almost twice as large for the CAG population (P less than .006). Labeling index differences also were significant over most gastric pit compartments (P less than .02). In antrum gamma-FA-positive lesions had an expanded proliferative compartment with labeling indices significantly greater than those of antigen-negative lesions (P less than .02). This correlation did not extend to biopsy specimens obtained from corpus of stomach where the frequency of carcinoma is low. Findings indicate a hyperproliferative state in CAG compared to the proliferative state in normal gastric mucosa and, in gastric antrum, a further correlation with expression of gamma-FA in hyperproliferating cells. The two markers can be used to aid definition of the gastric mucosa in a disease associated with the development of gastric cancer and in prophylactic dietary intervention programs.

Antigens, Neoplasm↗
PubMed1985

Altered actin cytoskeletal patterns in two premalignant stages in human colon carcinoma development.

Primary culture of human colonic biopsies converts the single cell thick epithelial layer from a highly indented sheet in vivo into a flat patch on the surface of a Petri dish. Migration of cells from biopsies in a continuous sheet to form the patch cultures allows the cultured cells in large part to retain the junctional complexes and membrane interdigitations which connect adjacent cells in vivo and therefore to maintain their spatial relationships to neighboring cells. Migration of the cells onto a flat surface also allows visualization of their actin cables (E. Friedman, M. Verderame, S. Winawer, and R. Pollack, Cancer Res., 44: 3040-3050, 1984). Actin organization patterns have been studied in primary patch cultures of colonic epithelial cells from four stages in the development of colon cancer: normal tissue, normal-appearing but preneoplastic cells characteristic of familial polyposis patients, benign tumors or adenomas from familial polyposis patients, and benign and malignant tumors from patients in the general population. Carcinomas exhibited the least number of actin cables, while adenomas contained the greatest concentration. Similar actin patterns were seen in both familial polyposis and nonpolyposis adenomas. The preneoplastic prebenign tumor stage characteristic of familial polyposis patients had less actin cables than either normal cells or benign tumor cells. Thus actin organization loss characterized the transition from the normal colonic epithelial cell to the preneoplastic nontumor cell. The ability to form actin cables was then regained with the transition from the preneoplastic pretumor cell to the benign tumor cell and lost again with the benign tumor to malignant tumor transition. The complexity of these changes in actin organization during the step-wise transformation of colonic epithelial cells was not predicted from the simple model of actin cable loss accompanying fibroblast transformation.

Actins↗
PubMed1985

Studies on the identification of genetic risk for heritable colon cancer.

The limitations of the assignment of genetic risk status for colon cancer based on pedigree data are known. The purpose of this paper is to present two approaches being evaluated for the identification of genetic predisposition for colon cancer: in vivo studies on colonic mucosa and in vitro studies on dermal fibroblasts derived from high- and low-risk individuals.

Cells, Cultured↗
PubMed1984

Methionine dependence in skin fibroblasts of humans affected with familial colon cancer or Gardner's syndrome.

Reduced growth in methionine-deficient, homocysteine-, folic acid-, and vitamin B12-supplemented medium, a characteristic of tumor and transformed cell lines, was investigated in skin fibroblasts of patients affected with hereditary colon neoplasms. The presence or absence of this phenotype was studied in 37 cell lines from either low-risk subjects or members of families with Gardner's syndrome (GS) or familial colon cancer (FCC). Growth constants of skin fibroblasts of the low-risk group were not significantly different in the presence of methionine (Kme) or absence of methionine (Kho) (0.106 +/- 0.011 and 0.098 +/- 0.011, respectively). However, growth constants of skin fibroblasts of both GS and FCC were significantly reduced in the absence of methionine. In GS, Kho = 0.086 +/- 0.006 and Kme = 0.120 +/- 0.006 (P less than .01). In FCC, Kho = 0.048 +/- 0.007 and Kme = 0.084 +/- 0.009 (P less than .01). Thus the growth of skin fibroblasts from both GS and FCC was methionine dependent. This phenotype was expressed in skin fibroblasts of an individual several years before any clinical manifestation of GS. In all populations studied the phenotype was independent of the age or sex of the individuals, aging of the cell lines, low serum concentration, and acute carcinogen treatment. In addition, there is a significant correlation (r = -0.85, P less than .001) between the disorganization of actin cables of the skin fibroblasts and the ratio of the growth constants. These data constitute the first report demonstrating methionine dependence in cell lines that are not derived from transformed cells, tumor cells, or fetal cells but are derived from skin fibroblasts of patients with hereditary colonic neoplasms. Inasmuch as these cells are not target cells related to colon cancer, the phenotype appears to be the expression of an inherited autosomal dominant genotype related to the oncogenic transformation.

Adolescent↗
PubMed1984

Method of binary classification and risk assessment of individuals with familial polyposis based on [3H]TdR labelling of epithelial cells in colonic crypts.

An analysis has been developed to improve the quantitation of abnormal patterns of tritiated thymidine [(3H]TdR) labelling of colonic epithelial cells, in biopsy specimens removed from human subjects at varying degrees of risk for colon cancer. After pulse incubation of specimens of colonic mucosa with [3H]TdR, each subject's microautoradiographic epithelial cell labelling distribution was segregated into eleven compartments over entire colonic crypts. The findings of each subject were then analysed to determine their relative degree of similarity to the findings for two reference populations of interest, i.e. a high-risk and a low-risk population; the individual was then classified as being closer to one or the other of the reference populations. The analysis developed is based upon a comparison of multinomial probabilities for the distributions of the labelled cells within the crypts, and permits the routine categorization of uneven distributions of labelled cells. For each subject, certain linear scores, a prognostic index based on them, and a related presumptive risk, were calculated. The sensitivity with which individuals known to be symptomatic for polyposis, and the specificity with which individuals known to be at lower risk were determined, were 73 and 93% respectively. The results suggest that this method of distinguishing among integer distributions of [3H]TdR- labelled cells in biopsies of colonic mucosa, may provide a useful basis for identifying individuals with familial polyposis, by separating their labelling patterns from those of low-risk subjects.

Adolescent↗
PubMed1984

Fetal antigens in the precursor stages of gastric cancer.

Gastric epithelial cells, identified in biopsy specimens from individuals with varying degrees of gastritis and cellular atypia, were classified according to morphology and reactivity with an adult tissue-absorbed rabbit antibody to 2nd trimester human fetal tissue. Sections of stomach from normal individuals and patients with superficial gastritis were generally unreactive with this antibody as determined by immunoperoxidase microscopy. However, a progressive increase in the frequency of antigen-positive gastric epithelial cells was observed during the transition from superficial gastritis to mature metaplasia to dysplasia. Adjunct immunohistologic subclassification of gastric lesions, thus, appears to be possible using a suitably prepared antibody probe. This approach may provide additional parameters necessary for assessment of preneoplastic syndromes and contribute to clinical staging of gastric disease.

Antigens, Surface↗
PubMed1984

The medical interview: a core curriculum for residencies in internal medicine.

A core curriculum for teaching medical interviewing is presented that enhances the internist's skills in a broad range of interactions with patients. Learning these skills is now left to chance and is often deficient. Four objectives are developed: patient-centered interviewing and treatment; an integrated (biopsychosocial) approach to clinical reasoning and patient care; personal development of humanistic values; and psychosocial and psychiatric medicine. Teaching options include real and simulated encounters with patients, observation with discussion, and use of groups. A general strategy for implementing the curriculum at the local level requires the intellectual and financial support of the dean and department chairman, and a multidisciplinary faculty committed to developing, implementing, and evaluating the curriculum. At many programs, faculty development will be necessary.

Curriculum↗
PubMed1984

Proliferative and antigenic properties of rectal cells in patients with chronic ulcerative colitis.

Two markers related to preneoplasia were studied simultaneously in ulcerative colitis (UC). The renewal of the rectal epithelial cells together with expression of second-trimester fetal antigen (STFA) were evaluated in nine patients with UC and four healthy subjects. Endoscopic biopsies were incubated with tritiated thymidine. Cell renewal was studied with microautoradiography, and the antigenic properties of the cells were evaluated by indirect immunofluorescence. At the time of the study, all the UC patients were in a mildly active or in a quiescent stage of the disease; their biopsies did not show dysplastic or neoplastic changes in epithelial cells. STFA was expressed in five UC patients. The analysis of cell renewal in this group revealed a shift of the proliferative compartment towards the luminal surface of the colonic crypts. By contrast, the patient group with STFA-negative reactions showed a pattern of cell proliferation similar to that observed in the controls. These results suggest that the expression of STFA in colonic mucosa is associated with an expansion of the epithelial stem cell population or with arrested cell differentiation, and it may represent a phenotypic marker of proneness of the mucosa toward neoplastic development.

Adolescent↗
PubMed1984

The identification of high risk populations.

This presentation is concerned with the early identification of individuals at increased risk for cancer of the large intestine. To facilitate this work we developed a comprehensive register of individuals at high risk for colorectal cancer at Memorial Sloan-Kettering Cancer Center. The high risk groups are characterised by an hereditary predisposition to colorectal cancer, as suggested by familial associations or early ages of onset of neoplasia, or by the presence of a previous disease of the large intestine believed to be associated with premalignancy. Recent information on the biological characteristics of colonic mucosa, and related findings in individuals with increased susceptibility to colorectal cancer, are summarised in this review. Particular reference is made to proliferate abnormalities that develop during early stages of neoplastic cell transformation, and to new methods of measurement which facilitate the identification of early abnormalities.

Cell Division↗
PubMed1984

Screening and genetic counseling for beta-thalassemia trait in a population unselected for interest: comparison of three counseling methods.

We have assessed the effects of screening and genetic counseling for beta-thalassemia trait on knowledge, attitudes, and behavior in a prospective, controlled study of randomly selected adult members of a health maintenance organization. We report here that knowledge of manifestations and of inheritance of thalassemia, previously reported to be high immediately after counseling, were well maintained at 2 and 10 months following counseling. There was no detectable impairment of self-concept. Marital adjustment improved, and sexual activity increased significantly. Mood, assessed immediately before and after counseling, showed no undesirable changes. A patient-structured counseling method, designed to minimize negative psychological effects via discussion of feelings, was not superior to conventional and programmed methods, described in our previous reports, in terms of learning or attitude change.

Adolescent↗