Search PubMed⌕ Search

Biomedical subjects

M Lipkin

Publications and source records attributed to M Lipkin.

At least 109 records · Page 6Linked to original sources
PubMed1991

Correlations between rectal mucosa cell proliferation and the clinical and pathological features of nonfamilial neoplasia of the large intestine.

An in vitro study of proliferative activity as shown by immunohistochemical detection of the uptake of bromodeoxyuridine was run on rectal biopsies from 400 patients with nonfamilial large bowel neoplasia: 200 adenoma; 150 adenocarcinoma; 50 adenoma plus adenocarcinoma. The controls were 400 subjects with negative personal and family histories of colorectal neoplasia. The number and height distribution of bromodeoxyuridine positive cells were determined by dividing the crypt into five longitudinal compartments. The total labeling index and the labeling index of each compartment were higher in all three groups compared with the controls. In subjects with adenoma, total labeling index and labeling index values were correlated with tumor size and decreased in function of the duration of the polyp-free colon state. The major zone of DNA synthesis had shifted to the intermediate and surface crypt compartments in all three groups. This stage II abnormality was more marked in adenoma patients with a high degree of dysplasia and in those with adenoma plus adenocarcinoma. Hyperproliferation and the proliferative compartment shift are cytokinetic abnormalities that coexist in the flat rectal mucosa of patients with colorectal neoplasia. Nonetheless, they are independent, controlled by different factors, and are expressions of different biological aspects of large bowel carcinogenesis.

Adenocarcinoma↗
PubMed1991

Lectin soybean agglutinin: measurements in colonic epithelial cells of human subjects following supplemental dietary calcium.

A biomarker of cell differentiation was analyzed in normal and abnormal colonic epithelial cells. Soybean agglutinin (SBA) lectin which binds to specific carbohydrate residues was studied in normal human colonic epithelial cells, in epithelial cells in transitional colonic mucosa adjacent to carcinomas, and in colonic carcinomas. Findings revealed that increased SBA binding occurred maximally in normal, well-differentiated colonic epithelial cells, and least in colonic carcinomas. Further quantitation of SBA lectin binding also was carried out before and after supplemental dietary calcium. Findings revealed that in subjects whose colonic crypt biopsies had normal SBA lectin binding before calcium supplementation, SBA remained unchanged after calcium supplementation. However, in subjects whose biopsies initially had reduced SBA binding, the SBA increased after calcium and became more characteristic of that observed in normal colonic epithelium. In subjects receiving calcium for less than 3 months, the increased SBA was not statistically significant; but when subjects received calcium for durations of 3 months or longer SBA lectin binding was significantly increased, changing towards that observed in normal mucosa containing greater numbers of well-differentiated colonic epithelial cells.

Adenocarcinoma↗
PubMed1991

Application of intermediate biomarkers to studies of cancer prevention in the gastrointestinal tract: introduction and perspective.

In this article, abnormalities in the proliferation and differentiation of gastrointestinal cells are described in diseases that increase predisposition to gastrointestinal cancer. Recent findings related to the effects of calcium on gastrointestinal cell proliferation, differentiation, and tumor occurrence in rodent models and in human subjects are summarized.

Animals↗
PubMed1991

Colonic hyperproliferation induced in rats and mice by nutritional-stress diets containing four components of a human Western-style diet (series 2).

In a previous study colonic hyperplasia and hyperproliferation were induced in mice and rats by a nutritional-stress diet, based on the AIN-76A semisynthetic diet modified to contain four suggested high-risk components of the human Western-style diet: increased fat and phosphate and decreased calcium and vitamin D contents. In this study the effect of raising calcium alone to near the median level (0.22 mg/kcal) and to a high level (1.3 mg/kcal), comparable to adult human dietary intake, was tested in mice and rats while retaining the three other high-risk components. With median calcium intake the nutritional-stress diet induced hyperproliferation of epithelial cells in colonic crypts, with increased numbers of proliferating cells in crypt columns in sigmoid colon of mice (P less than 0.001) and rats (P = 0.02) and in the ascending colon of mice (P = 0.01). With high calcium intake, hyperproliferation was reduced almost to control amounts in the presence of unchanged fat, phosphate, and vitamin D.

Animals↗
PubMed1991

Sex differences in patients' and physicians' communication during primary care medical visits.

This study reports on the analysis of audiotapes of 537 adult, chronic disease patients and their 127 physicians (101 men and 26 women) in a variety of primary care practice settings to explore differences attributable to the effects of the patient's and the physician's sex on the process of communication during medical visits. Compared to male physicians, women conducted longer medical visits (22.9 vs 20.3 minutes; F(1,515) = 7.9, P less than .005), with substantially more talk F(1,518) = 19.5, P less than .000. Differences were especially evident during the history segment of the visit when female physicians talked 40% more than male physicians (F(1,518) = 20.1, P less than .000) and when patients of female physicians talked 58% more than male physicians' patients (F(1,448) = 24.4, P less than .000). Compared to male physicians, female physicians engaged in more positive talk, partnership-building, question-asking, and information-giving. Similarly, when with female compared to male physicians, patients engaged in more positive talk, more partnership-building, question-asking, and information-giving related to both biomedical and psychosocial topics.

Adult↗
PubMed1990

Labeling index and labeling distribution of cells in esophageal epithelium of individuals at increased risk for esophageal cancer in Huixian, China.

The pattern of proliferation of epithelial cells in esophageal epithelium was studied by means of [3H]deoxythymidine labeling of esophageal epithelium in subjects from Huixian, Henan Province, China, a high-risk geographical region for esophageal cancer. Comparisons were made among patterns of cell proliferation observed in normal esophagus, in hyperplasia, in mild dysplasia, and in moderate dysplasia in a total of 118 subjects. The amount of cell proliferation observed was lowest in normal esophageal epithelium and increased progressively in subjects having hyperplasia, mild dysplasia, and moderate dysplasia. The location of proliferating cells was limited mainly to the base of the esophageal epithelium in normal esophagus, but expanded toward the surface of the esophageal lining in individuals with hyperplasia and dysplasia. The larger total numbers of proliferating cells in the esophageal epithelium and the progressive expansion of the proliferative compartment toward the epithelial surface found in hyperplasia and in dysplasia could both facilitate the screening of subjects for esophageal cancer risk and serve as intermediate biomarkers in prophylactic dietary or pharmacological intervention studies.

Cell Count↗
PubMed1990

Injury induced by fatty acids or bile acid in isolated human colonocytes prevented by calcium.

Measurement of the modulation of the growth fraction of isolated normal colonocytes from adult subjects in primary monolayer culture was used as a sensitive quantitative assay to evaluate toxic effects of several endogenous compounds found within the colon. This assay was used to study the role of CaCl2 in blocking cell injury. When added simultaneously with the injurious agent, 5-10 mM CaCl2 blocked the toxicity of physiological concentrations of deoxycholic acid, oleic acid, palmitic acid and linoleic acid.

Calcium Chloride↗
PubMed1990

Colonic hyperplasia and hyperproliferation induced by a nutritional stress diet with four components of Western-style diet.

We studied the effects of specific nutritional modifications on colonic epithelial cell proliferation in mice and rats. The nutritional stress diet developed for this study was based on the AIN (American Institute of Nutrition)-76A semisynthetic diet, modified to contain four suggested risk factors of the human Western-style diet: increased fat and phosphate and decreased calcium and vitamin D content. We fed diets to mice and rats for 12 weeks beginning at 3 weeks of age. Hyperplasia developed in both sigmoid and ascending colon of mice and rats with lengthening of colonic crypts. Hyperproliferation developed in the sigmoid colon of mice and rats, and in the ascending colon of rats, with increased [3H]thymidine-labeling of epithelial cells. Thus, in colonic mucosa, the nutritional stress diet, which included risk factors of a Western-style diet, induced changes that occur in carcinogen-induced rodent models and in humans who are at increased risk for colonic neoplasia.

Animals↗
PubMed1990

Primary care internal medicine: a challenging career choice for the 1990s.

A career in primary care internal medicine can be challenging and rewarding, yet during the last decade fewer medical students have selected training in internal medicine. We wish to inform medical students, their advisors, and other physicians about the field of primary care internal medicine. We define the discipline, compare it with traditional internal medicine and with family practice, and describe features of strong primary care internal medicine training programs. We discuss common misconceptions and concerns about training programs and the career and give examples of career paths chosen by graduates of primary care programs. We encourage students to consider the option of primary care internal medicine when making career decisions and provide faculty advisors unfamiliar with primary care internal medicine training programs with a reference resource.

Career Choice↗
PubMed1990

Expression of mitochondrial cytochrome c oxidase in human colonic cell differentiation, transformation, and risk for colonic cancer.

In a panel of eight cloned complementary DNA sequences whose level of expression characterize colon cells as transformed in vivo and in vitro, one which may also serve as a marker of risk in familial polyposis and familial colon cancer flat mucosa has been identified as mitochondrial cytochrome c oxidase subunit 3. Mean level of expression of cytochrome c oxidase subunit 3 decreases progressively in colon adenomas and carcinomas relative to normal mucosa in vivo, and returns to higher levels present in biopsies of normal mucosa when the HT29 human colonic adenocarcinoma cell line is induced to differentiate with sodium butyrate. Quantitation of cytochrome c oxidase subunit 3 DNA by dot blots indicated that these changes in expression were not associated with alterations in the number of mitochondrial genomes.

Adenomatous Polyposis Coli↗
PubMed1990

Dietary calcium and chronic diseases.

The Agricultural Revolution was almost certainly associated with a substantial decrease in human calcium intake. Calcium intakes typical of contemporary humans may well be inadequate for many individuals. Various slowly developing chronic disorders such as osteoporosis, hypertension, hyperlipidemia, and colon cancer may be induced or exaggerated by the current low level of dietary calcium intake in Western societies. We propose two hypotheses relating calcium intake to diverse diseases: first, the adaptation required to adjust to low intakes is inadequate to maintain critical components of cellular calcium regulation; second, the constant, forced adaptive response to low intake itself produces untoward consequences.

Adaptation, Physiological↗
PubMed1990

AE1 cytokeratin reaction patterns in different differentiation states of squamous cell carcinoma of the esophagus.

Anticytokeratin antibody AE1 was studied immunohistochemically in 56 surgical specimens of esophageal carcinoma. Relationships between morphologic characteristics and AE1 reaction patterns were analyzed in carcinomas and adjacent epithelium. Infiltrating carcinomas had three types of AE1 patterns that paralleled degrees of differentiation. Type 1 pattern was present in well-differentiated carcinomas characterized by cytoplasmic staining of polyhedral cells. Types 2 and 3 were seen in poorly differentiated and undifferentiated carcinomas in different percentages, characterized by all cancer cells stained, with cellular membrane and cytoplasm stained or all unstained, respectively. In normal esophageal epithelium, basal cells were the major population that was AE1 positive. In hyperplasia basal cells showed two kinds of changes, either reduced/lost AE1 staining accompanied by AE1 expression in spinous cells or retained/increased AE1 reactivity. In dysplasia and carcinoma in situ, abnormal cells had reaction patterns in which they lost or increased AE1 expression. Findings indicate that different degrees of differentiation of infiltrating esophageal carcinoma cells have differing expressions of cytokeratins and that monoclonal antibody AE1 can serve as a biomarker identifying early abnormalities in esophageal epithelial cells having increased predisposition to malignancy. Molecular mechanisms of AE1 cytokeratin expression in esophageal epithelium are also discussed.

Antibodies, Monoclonal↗
PubMed1989

Heterogeneity in the response of familial polyposis epithelial cells and adenomas to increasing levels of calcium in vitro.

A biomarker of increased risk for colon cancer is abnormally high proliferation of colonic epithelial cells. The authors developed an in vitro assay that measures the ability of human colonic epithelial cells that are in progressive stages of abnormal development to respond to direct application of calcium as the chloride in tissue culture medium. Incorporation of 3H-thymidine and autoradiography in situ was employed to measure the number of proliferating cells cultured at 0.1 mM CaCl2, the optimum level for growth, and 2.2 to 5 mM, both levels achievable in the colonic lumen. Abnormal cell proliferation was reduced in biopsies from 13 of 14 patients without familial polyposis but at increased risk for colon cancer because of previous colonic neoplasms or familial association; in cells from three of four asymptomatic individuals in familial polyposis families at risk for that disease; and in cells of three of ten patients symptomatic with familial polyposis. Growth of tubular adenoma cells from two of seven familial polyposis patients was also inhibited by calcium. Growth inhibition was not observed in more advanced colon tumors including eight adenomas, either villotubular or villous, and five carcinomas. These findings indicate heterogeneity within the familial polyposis phenotype for the normal cellular response to growth inhibition by calcium, and a further loss of response to calcium as these cells progress toward malignancy.

Adenoma↗
PubMed1989

Colonic epithelial cell proliferation in responders and nonresponders to supplemental dietary calcium.

Supplemental dietary calcium decreased and normalized hyperproliferation of colonic epithelial cells in individuals in familial colon cancer kindreds, measured by rates and patterns of [3H]thymidine labeling of epithelial cells in colonic crypts. In whole colonic crypts hyperproliferation was decreased to lower levels in over one-half of the subjects individually studied during the course of the calcium supplementation regimen. The remaining familial colon cancer subjects did not show reductions in cell proliferation measured over the whole crypt. However, when their cell-labeling data were analyzed in regions of the colonic crypt, the size of the proliferative compartment decreased and contracted towards the crypt base after calcium, a pattern typical of individuals at decreased risk for colonic cancer. This contraction of the proliferative region of the crypts occurred through decreased cell labeling in the two crypt compartments closest to the luminal surface and increased cell labeling in the second crypt compartment nearest to the base of the crypt. Following in vitro exposure of colonic epithelial cells to increasing physiological amounts of calcium, cell proliferation in familial colon cancer subjects decreased uniformly and greater heterogeneity in responsiveness was observed in cells from individuals with familial polyposis.

Adenomatous Polyposis Coli↗
PubMed1989

Reactivity of a human monoclonal antibody against carcinomas and other lesions of the colon.

To identify tumor-associated antigens that may be immunogenic to man, human monoclonal antibodies (human mAb) were generated by fusing nonsecreting mouse myeloma cells with lymphocytes from regional mesenteric nodes of patients with adenocarcinomas of the colon. One IgG1 human mAb, designated as 14-31-10, was identified by its reactivity against human tumor xenografts. We have studied the reactivity of mAb 14-31-10 with formalin-fixed, paraffin-embedded specimens of human colon. A total of 86 cases were studied, including normal adult and fetal colons, adenocarcinomas of the colon, and a variety of colonic inflammatory diseases and preneoplastic lesions. Intense reactivity was found in 15 of 18 adenocarcinomas of the colon, but not in 10 specimens of normal adult or 4 specimens of fetal colonic mucosa. Interestingly, in four cases of carcinoma, reactivity was also observed in histologically normal mucosa situated 10 cm or more from the primary lesion. On the other hand, no staining was detected in any of the 16 inflammatory lesions. Of the 38 preneoplastic lesions, only 6 showed staining by the mAb: 1 of 5 benign tubular adenomatous polyps, 3 of 9 villous adenomas and tubovillous polyps, 1 of 5 specimens of ulcerative colitis and 1 of 19 specimens of familial polyposis. However, the intensity of staining was only moderate in those cases. Our data, therefore, suggest that the epitope identified by the human mAb 14-31-10 shows preferential expression in preneoplastic and neoplastic lesions of the colon, and in ostensibly normal mucosa at some distance from a primary colonic carcinoma. In all instances, the staining was cytoplasmic, suggesting a cytoplasmic or internal membrane location of the target antigen. This antigen appeared to be distinct from carcinoembryonic antigen, since staining by 14-31-10 was consistently different from that of a mouse monoclonal antibody to carcinoembryonic antigen in serial sections of the same specimens. The restricted reactivity of 14-31-10 suggests its potential application in immunohistochemistry. Moreover, the epitope identified by mAb 14-31-10 may be expressed during the progression of normal mucosa to neoplasia.

Animals↗
PubMed1989

Decreased content of the 35 kDa cytoskeletal protein p35 in Friend erythroleukemia cells exposed to dimethyl sulfoxide and retinoic acid is associated with entrance into a quiescent substrate.

1. The effect of all-trans-retinoic acid (RA) on cell cycle kinetics, RNA content, and expression of the 35 kDa cytoskeletal protein p35 in exponentially-growing Friend erythroleukemia (FL) cells was compared with the prototypic differentiation-inducer dimethylsulfoxide (DMSO). 2. Two G1 phase populations of RA-treated FL cells were identified: one with an intermediate RNA content (T-cells) similar to G1 cells in near-plateau-phase control cultures and the other with a very low RNA content (Q-cells) similar to DMSO-differentiated cells; although quiescent, RA-treated cells remained undifferentiated as evidenced by the absence of late-stage markers of erythroid maturation. 3. Decreases in the cellular content of p35 occurred in both DMSO- and RA-treated FL cells, correlating with the onset of accumulation of cells into G1, and stabilized by 48 hr after initial exposure to either inducer. 4. Down-regulation in the cellular p35 content, thus, appears to be linked to entrance of FL cells into a quiescent substrate and independent of the subsequent capacity for erythroid differentiation.

Animals↗
PubMed1989

Hypersegmented neutrophils and vitamin B12 deficiency. Hypersegmentation in B12 deficiency.

The sensitivities and specificities of the mean cell volume (MCV), the red cell distribution width (RDW), and blood smear hypersegmentation for B12 deficiency were reviewed in 515 patients whose B12 levels were determined. 61 patients had B12 levels less than 200 pg/ml. 43 patients were defined as B12 deficient (n = 13) or non-B12 deficient (n = 30). Hypersegmentation was more sensitive (91%) than MCV greater than 95 fl (62%) or RDW greater than 15% (54%) in detecting B12 deficiency. The MCV and the RDW should not be relied on when screening for B12 deficiency; examination of the blood smear for hypersegmentation is essential.

Anemia↗