Search PubMed⌕ Search

Biomedical subjects

H Newmark

Publications and source records attributed to H Newmark.

At least 37 records · Page 2Linked to original sources
PubMed1995

Calcium and the prevention of colon cancer.

Chemoprevention studies utilizing calcium have now progressed from basic measurements to clinical trials. Calcium's effects on epithelial cells have demonstrated decreased proliferation and induced cell differentiation with increasing levels of calcium in vitro, similar in vivo effects in rodent and human colon, and decreased carcinogen-induced colonic tumor formation in rodents. Current studies are attempting to inhibit colonic adenoma formation in human subjects. Most but not all epidemiologic studies also link increased dietary calcium with a decreased risk of colon cancer. In animal models, supplemental dietary calcium has decreased mammary epithelial cell hyperplasia and hyperproliferation and colonic cell hyperproliferation when the latter was induced by bile acids, fatty acids, and partial resection of the small intestine. Supplemental dietary calcium also decreased carcinogen-induced colonic tumors in several rodent models. In normal mice, and in mice carrying a targeted apc gene mutation, we recently increased colonic polypoid hyperplasias by a Western-style diet containing low calcium and vitamin D. In human subjects at increased risk for colon cancer, oral calcium supplementation significantly reduced colonic epithelial cell proliferation in most of the studies, including four randomized clinical trials. These studies have now progressed to short-term human clinical trials, including trials that measure the regrowth of transformed adenoma cells. Short-term adenoma-regrowth clinical trials, however, are limited in their ability to measure whether chemopreventive agents inhibit early genotoxic events, abnormal cellular metabolic activities involved in tumor promotion over many years, or the progression of adenoma cells to carcinoma.

Adenoma↗
PubMed1994

Protective effects of rutin against hemoglobin oxidation.

A prooxidant drug, primaquine (PQ) was used to produce oxidative stress in human red blood cells (RBC) in vitro. Rutin, a plant flavonoid, did not prevent PQ-induced cell lysis but protected against hemoglobin (Hb) oxidation inside RBC. After PQ removal, rutin failed to reduce preformed met-Hb indicating that the rutin protective effect manifests only in the presence of PQ. Since H2O2 was proved to mediate PQ-induced Hb oxidation, authentic Hb was studied for its reaction with H2O2 and rutin in solution. Rutin partially protected oxy-Hb against H2O2-induced oxidation and heme loss. Rutin was also shown to delay H2O2-induced met-Hb oxidation to ferryl-Hb. Rutin directly reduced ferryl-Hb to met-Hb in stoichiometric (1:1) reaction characterized by a rate constant of 100 to 130/M/sec. It is assumed that by reducing ferryl-Hb, rutin prevents oxy-Hb from reacting with ferryl-Hb (comproportionation reaction), thus preventing half of the oxy-Hb molecules from being converted to met-Hb. This mechanism is consistent with 50% inhibition by rutin (at the maximum of its activity) of PQ-induced oxy-Hb oxidation in RBC. The present results demonstrate new antioxidant properties of rutin that may be useful in diminishing oxidative damage to pathological red blood cells.

Antioxidants↗
PubMed1994

Mammary ductal epithelial cell hyperproliferation and hyperplasia induced by a nutritional stress diet containing four components of a western-style diet.

We have studied effects of several nutrients on the proliferation of mammary ductal epithelial cells in C57BL/6J virgin female mice, using morphometry and [3H]dT in vivo labeling. A nutritional stress diet was given based on the AIN-76A semi-synthetic diet modified to contain four significant risk factors of a Western-style diet: high fat and phosphate and decreased calcium and vitamin D. The numbers of large, intermediate and terminal ducts and proliferating epithelial cells in mammary glands were assayed in control and stress diet groups. An increased number of mammary ducts and increased number of proliferating cells were found at the level of the small terminal ducts, a cancer-prone region in the mammary gland in the stress diet group compared to the control group after 20 weeks of diet administration. Thus, mammary terminal ductal hyperproliferation, expansion in the size of the proliferative epithelial cell compartment and excessive duplication of mammary ductal epithelial cells were found after this Western-style diet containing decreased dietary calcium and vitamin D. These changes are similar to those developing in colonic epithelium of mice maintained on the same diets and during chemically induced colonic carcinogenesis.

Animals↗
PubMed1992

Inhibitory effect of topical application of a green tea polyphenol fraction on tumor initiation and promotion in mouse skin.

A green tea polyphenol fraction was evaluated for its ability to inhibit tumor initiation by polycyclic aromatic hydrocarbons and tumor promotion by a phorbol ester in the skin of CD-1 mice. Topical application of the green tea polyphenol fraction inhibited benzo[a]pyrene- and 7,12-dimethylbenz[a]-anthracene-induced tumor initiation as well as 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced tumor promotion. Topical application of the green tea polyphenol fraction also inhibited TPA-induced inflammation, ornithine decarboxylase activity, hyperplasia and hydrogen peroxide formation. Studies with individual polyphenolic compounds in green tea indicated that topical application of (-)-epigallocatechin gallate, (-)-epigallocatechin and (-)-epicatechin gallate inhibited TPA-induced inflammation in mouse epidermis.

9,10-Dimethyl-1,2-benzanthracene↗
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

Fecal diglycerides as selective endogenous mitogens for premalignant and malignant human colonic epithelial cells.

Diglycerides (DGs) have been found in fecal extracts at concentrations which induce mitogenesis of adenoma and some carcinoma cells but not normal cells in primary culture. DGs containing stearic, oleic, palmitic, and myristic acid side chains were found in fecal extracts from each of eight subjects. Synthetic 1,2-DGs, containing the fatty acids found in endogenous fecal DGs, induced mitogenesis in cultures of premalignant cells from each of 13 adenomas, covering all histological classes, and in cultures from two of four carcinomas. The potent adenoma mitogen, dimyristin, had no mitogenic activity on cultures of normal colonic epithelial cells from seven different subjects. These results suggest DGs may act as endogenous mitogens in the development of human colon cancer. The extent of adenoma mitogenesis was correlated with the chain length of the saturated R-groups: 16 greater than 14 greater than 12 greater than 10 greater than 8 much greater than 18. DGs with oleic acid residues, C18:1, were among the most active, while substitution of even one fatty acid residue with a stearic acid residue, C18:0, reduced or eliminated mitogenic activity. Dimyristin also induced enhanced levels of urokinase secretion from carcinoma cells, in parallel to the phorbol ester tumor promoter, 12-O-tetradecanoylphorbol-13-acetate. These results imply that DGs found in the colon induce a selective growth of benign colonic tumors and some carcinomas, and may enhance the invasive capacity of carcinomas, while leaving normal cells unaffected.

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↗
PubMed1987

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↗
PubMed1986

Computed tomography of acute cervical spine tendinitis.

The authors present the first case of acute calcific tendinitis of the neck seen on computed tomography. Although clinical presentation and routine radiographs suggested the diagnosis, computed tomography established it by illustrating calcification of the longus colli muscle that was not seen on the radiographs. The illustrations and interesting aspects of the case are described.

Acute Disease↗