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Biomedical subjects

M Lipkin

Publications and source records attributed to M Lipkin.

At least 127 records · Page 7Linked to original sources

Six primary cancers in individuals. Report of four cases.

Four patients who had six or more primary cancers are described in this article. Two of the patients had seven cancers each; the most frequent cancer site was the colon. These patients were young at the onset of their first cancer and had a long survival. All the patients had a strong family history of cancer, especially colon cancer. We found that family members of individuals with multiple cancers should be considered to have an increased risk for the development of cancer.

Adult↗

Red cell distribution width, mean corpuscular volume, and transferrin saturation in the diagnosis of iron deficiency.

The usefulness of the red cell distribution width, mean corpuscular volume, and the transferrin saturation in diagnosing iron deficiency anemia were evaluated in a retrospective study of 247 anemic hospitalized patients, many of whom had chronic liver disease. A red cell distribution width greater than 15% had a sensitivity of 71% and a specificity of 54% for iron deficiency as diagnosed by a low serum ferritin or bone marrow examination. A mean corpuscular volume less than 80 femtoliters had a sensitivity of 53% and a specificity of 84%. Transferrin saturation less than 16% had a sensitivity of 61% and a specificity of 86%. Because the sensitivities and specificities of these tests are less than reported in studies of healthier populations, they cannot be relied on for screening for iron deficiency in sick hospitalized patients.

Anemia, Hypochromic↗

Expression of cloned sequences in biopsies of human colonic tissue and in colonic carcinoma cells induced to differentiate in vitro.

A computer-based scanning and image-processing system has been developed to quantitate the relative level of expression of each of 4000 cloned complementary DNA sequences in small biopsies routinely removed from the mucosa of normal and neoplastic human large intestine. Individuals have been studied from well-defined population groups in which colonic epithelial cells have progressed to increasingly advanced stages of neoplastic transformation. Comparison of normal colonic mucosa to colonic carcinomas demonstrated alterations in expression of approximately 7% of the cloned sequences; fewer changes were found between benign colonic adenomas and either normal colonic mucosa or carcinomas. A subset of the sequences which change in expression during progression from normal mucosa, to adenoma, to carcinoma showed complementary changes when colon carcinoma cells were induced to differentiate in vitro with sodium butyrate; quantitative correlations between in vivo and in vitro results were highly significant. Comparison of normal colonic mucosa with mucosa from patients with the autosomal dominant disease familial polyposis revealed more extensive alterations in gene expression involving approximately 25% of the clones screened. Flat colonic mucosa in familial polyposis is therefore markedly aberrant and may be highly dedifferentiated, suggesting several possible mechanisms for the very high incidence of cancer that develops in this epithelium.

Adenoma↗

Tritiated-thymidine labeling of rectal epithelial cells in 'non-prep' biopsies of individuals at increased risk for colonic neoplasia.

Recent measurements have shown increased proliferation of colonic epithelial cells in individuals at heightened risk for cancer of the large intestine. This biomarker has facilitated measurements of the effects of nutritional intervention in studies that are attempting to inhibit tumor development in high-risk individuals. In this study, further measurements were made of the proliferation of rectal epithelial cells, when biopsies were removed from mucosa that had not previously been disturbed by any tapwater or other enema preparations. Progressive increases were found in the numbers of [3H]dThd-labeled epithelial cells in rectal crypts, and in labeling index profiles, in patients having previous sporadic adenomas or colon cancer, compared to individuals who had not developed colonic neoplasms. The most quiescent proliferative equilibrium was found in individuals without previous colonic disease. Findings indicated that 'non-prep' rectal biopsies obtained from the most accessible region of the large intestine, show modifications in the biomarker of cell proliferation paralleling colon cancer risk.

Aged↗

Colonic cell proliferation in familial polyposis.

Methods are presented for measuring cell proliferation in inherited gastrointestinal polyposis syndromes and related diseases. Future studies should be aimed at the identification of potentially susceptible individuals and interventions to inhibit tumor development.

Adenomatous Polyposis Coli↗

Evaluation of current criteria used to measure vitamin B12 levels.

Because of recent improvements in the serum vitamin B12 assay, literature criteria based on prior assay methods used in measuring B12 levels were evaluated. Of 1,708 B12 levels measured at Bellevue Hospital in a six-month period, 137 in 124 patients were below 200 pg/ml. Contrary to expectations, 81.6 percent of patients with low B12 levels had a mean corpuscular volume (MCV) below 95 fl. Literature-derived criteria missed 30 percent of patients with low B12 levels. Only three of 12 patients with megaloblastic bone marrow or an abnormal Schilling result had B12 levels that were low (below 100 pg/ml), and nine had values in an intermediate range (100 to 200 pg/ml). This suggests that the use of an MCV below 95 fl and a B12 level below 100 pg/ml as abnormal values may not detect clinically important B12 deficiency.

Adolescent↗

Multiple primary malignant tumors.

Members of colon cancer-prone nonpolyposis families who had multiple primary malignant tumors were analyzed to determine the frequencies, locations, and stages of their cancers, and the duration of their survival. Colon cancers tended to be more proximal, were in a less advanced stage than in the general population, and in a majority of instances were associated with colonic adenomas. The multiple primary malignant tumors were more common in women, and occurred at a younger age than in the general population. Six or more multiple primary malignant tumors occurred in each of 4 patients. All patients survived for more than 10 yr after the diagnosis of the first cancer. Extracolonic cancers were most frequent in the breast and endometrium.

Actuarial Analysis↗

Proliferation of esophageal epithelial cells among residents of Linxian, People's Republic of China.

Histopathologic and tritiated thymidine labeling subjects were carried out on esophageal biopsy specimens of 44 human subjects with cytologic evidence of dysplasia from Linxian, People's Republic of China, a high-risk area for esophageal cancer. With the use of histopathologic criteria, 10 cases showed evidence of dysplasia, 20 hyperplasia, and 14 a near-normal morphology when compared with 21 normal cases studied previously from Jiaoxian, a low-risk area for esophageal cancer in the People's Republic of China. Significantly increased labeling indices were found in the esophageal mucosa of the dysplasia and hyperplasia subjects. There was a gradient of increased expansion in the basal layer of proliferating cells progressing from normal to hyperplasia to dysplasia, with the expansion twice as high in the epithelial cell lining in dysplasia when compared with the findings in the normal and near-normal groups. The correlation of proliferative abnormalities with the severity of precancerous lesions of the esophagus indicates that labeling studies may provide a sensitive adjunct to evaluate risk status and any modifications that might result from nutritional intervention.

Biopsy↗

Genetic counseling of asymptomatic carriers in a primary care setting. The effectiveness of screening and counseling for beta-thalassemia trait.

In a prospective, controlled, stratified, experimental effectiveness study of screening and counseling, 25 000 consecutive adults were screened for thalassemia trait. Eight hundred forty-three adults had a mean corpuscular volume less than 77 fL; 192 (22% of those with microcytosis) had hemoglobin A2 greater than 3.5%, proving beta-thalassemia trait. Video-program, neutral-educational, and patient-centered counseling methods produced equal levels of learning, retention, psychologic impact, and effects on life adjustment immediately and at 2 and 10 months after counseling. Ninety-nine percent of the patients told other persons about the counseling, and 43% had 106 others screened. Factors related to having someone else screened included plans to have children (p less than 0.002), being younger (p less than 0.0025), better education (p less than 0.05), and having high knowledge of thalassemia (p = 0.05). For maximum effectiveness, screening and counseling programs should focus on patients for whom a positive result has high significance.

Adolescent↗

Expression of murine gamma fetal antigen in adult hematopoietic tissue and during induced differentiation of Friend erythroleukemia cells.

Quantitative analysis of extracts of various normal adult CD-1 mouse tissues indicated that the serologically defined murine gamma fetal antigen (gamma-FA) was expressed at high levels in hematopoietic tissue in general and in bone marrow (BM) in particular. Metabolic labeling of isolated BM cells indicated that the BM was a site of gamma-FA synthesis in the adult animal. The size(s) of the antigen immunoprecipitated from labeled BM cells (35 and 27 kilodaltons) with anti-gamma-FA serum correlated well with molecular weight estimates of fibrosarcoma-fetal mouse-associated gamma-FA, as determined by molecular sieve chromatography. For ascertainment of the relationship between hematopoietic cell differentiation and gamma-FA content, a multiparameter flow cytometric approach was used to evaluate gamma-FA levels in Friend erythroleukemia (FL) cells as a function of growth state (blast or dimethyl sulfoxide-differentiated) and cell-cycle compartment. Differentiated G1-arrested FL cells (G1D) possessed significantly lower gamma-FA-associated immunofluorescence as compared to control cells in the G0-G1 substate. Remaining S- and G2 + M-phase cells in differentiated populations demonstrated an even greater reduction in gamma-FA content relative to control cells in the corresponding cell-cycle phases. The available data support the tentative classification of gamma-FA as a murine differentiation antigen.

Actins↗

Inhibition of human colonic epithelial cell proliferation in vivo and in vitro by calcium.

Nine patients at high risk of developing colon cancer were placed on daily p.o. supplementation of 1500 mg of calcium for 4-8 weeks. The colonic epithelial cells in six of these patients showed a statistically significant decrease in their [3H]thymidine labeling indices in tissue culture so that they resembled those of patients at low risk of developing colon cancer. The three nonresponders had similar labeling indices before and after calcium supplementation. Biopsies from each of nine high-risk patients exhibited a decrease in proliferation when they were cultured in vitro with a high level of CaCl2 (2.2 mM compared with the 0.1 mM optimum value for proliferation). Two adenomas and two carcinomas showed a different pattern of response than normal cells, exhibiting no inhibition of growth at 2.2 mM CaCl2. These data indicate that the growth inhibition induced by high levels of extracellular calcium levels is lost at a stage in tumor development before cells become malignant.

Calcium, Dietary↗

Effect of added dietary calcium on colonic epithelial-cell proliferation in subjects at high risk for familial colonic cancer.

We studied the frequency and distribution of proliferating epithelial cells lining colonic crypts in 10 subjects at high risk for familial colonic cancer, before and after oral supplementation of their conventional diets with 1.25 g of calcium as calcium carbonate. Patterns of cell proliferation were defined by dividing the colonic crypt into longitudinal compartments and comparing the numbers and fractions of tritiated thymidine--labeled epithelial cells in the various compartments. Before dietary supplementation with calcium, the profile of proliferating epithelial cells in the colonic crypts was comparable to that previously observed in subjects who had had familial colonic cancer. Two to three months after supplementation had been started, proliferation was significantly reduced and the profile of the colonic crypts approached that previously observed in subjects at low risk for colonic cancer. Our findings indicate that oral calcium supplementation induces a more quiescent equilibrium in epithelial-cell proliferation in the colonic mucosa of subjects at high risk of colon cancer, similar to that observed in subjects at low risk.

Calcium, Dietary↗