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Biomedical subjects

Y Niv

Publications and source records attributed to Y Niv.

At least 19 recordsLinked to original sources

Mucin synthesis and secretion in relation to spontaneous differentiation of colon cancer cells in vitro.

The synthesis and secretion of mucin-like high-molecular glycoprotein was studied in 2 human colon cancer cell lines that spontaneously differentiate in culture (Caco-2 and T84) and in 2 cell lines that do not spontaneously differentiate (LS174T and HT29). Mucin, quantitated by 3H-glucosamine labelling and chromatography on Sepharose CL-4B was found to be produced by all 4 cell lines. The mucinous nature of the labelled high-molecular glycoprotein was verified by enzymatic degradation treatments (heparinase, hyaluronidase, chondroitinase ABC, and N-glycanase), alkaline-borohydride treatment, inhibition of labelling by the glycosylation inhibitor benzyl-alpha-GalNAc, and by CsCl-density-gradient centrifugation. In all 4 cell lines, an inverse correlation of mucin synthesis with cell density was demonstrated. In Caco-2 cells, the spontaneous post-confluent enterocytic differentiation with increased brush-border enzyme expression was associated with a decrease in mucin synthesis and in the activities of polypeptidyl GalNAc transferase and beta 1,3-galactosyltransferase activity. Using cDNA probes for 2 distinct human intestinal mucins (MUC2 and MUC3), we found that all 4 colon cancer cell lines expressed mucin message, but the types of mucin mRNA expressed differed. These data indicate that mucin-like glycoproteins can be synthesized by cell lines derived from non-mucinous colon cancer, whether or not they undergo spontaneous differentiation in culture. These cell lines may serve as in vitro models for studying apomucin heterogeneity and control of mucin gene expression.

Cell Differentiation

Does a risk questionnaire add anything to a colorectal screening project? Report of a 3-year screening experience.

A questionnaire to detect persons at high risk for colorectal cancer was used in conjunction with fecal occult blood tests in a 3-year screening program in Northern Israel. Screening was offered to 2,590 persons over 40 years of age and accepted by 1,797 (compliance of 69.4%). In the subsequent 2 years, occult blood testing (Hemoccult II) was offered to those who had had negative tests (compliance rate of 99.6% and 100%). Six hundred and thirty persons (35.1%) had risk factors according to the questionnaire, and 195 of them underwent colonoscopy, with a predictive value of 15.9% for a neoplastic lesion. The Hemoccult II test was positive in 71 participants (4.0%) of whom 67 were investigated with a similar predictive value for neoplastic lesion (16.4%). In the second and third annual screening, the fecal occult blood test was positive in 29 (2.6%) and 27 (2.5%), and had a two and three times higher predictive value for neoplastic lesions, respectively. This was accompanied by a decrease in the cost of discovery. In all three stages, an adenomatous polyp was found in 48, and cancer in 10 participants (2.6% and 0.5% of the 1,797 original participants). Although a questionnaire may be fruitful in colorectal cancer screening, the higher number of participants subjected to further examinations makes this approach very expensive. The annual stool examination for occult blood has a higher predictive value for colonic neoplasm and a lower cost than a one stage, broader population based, study.

Adult

Spontaneous nonfistulous barium reflux into the biliary tract: association with duodenal ulcer disease. A report of four cases.

Reflux of barium into the bile duct system during a barium study of the upper gastrointestinal tract is rare in the absence of spontaneous or postoperative fistula. We report four patients, three men and one woman, who had such reflux, associated with active duodenal ulcer disease, shown at radiologic and endoscopic investigation. Reflux of gastrointestinal contents into the biliary tract can result from peptic ulcer disease with duodenal involvement. The finding does not necessarily imply fistulous communication, ulcer perforation, or surgical emergency.

Adult

Open-access, flexible, fiberoptic sigmoidoscopy in a regional primary-care clinic.

We established an open-access, flexible, fiberoptic sigmoidoscopy service in an outpatient clinic in Kiriat-Shmona, Northern Israel. Twenty-eight general physicians in the city and in 41 surrounding rural residences (population 40,000) were encouraged to refer patients for sigmoidoscopy. In the first operative year, flexible sigmoidoscopy was performed on 255 patients (age range 10-90 years, mean 54). The male to female ratio was 123:132; women were slightly older than men (mean age 55.9 years vs. 51.1). Rectal bleeding and change in bowel habits were the most common indications. The sidmoidoscope was passed to the splenic flexure in 156 patients (61%). In five patients (2%) the instrument could not be inserted beyond the rectosigmoid junction. Excluding hemorrhoids and anal lesions, abnormalities were detected in 69 patients (27%). In 29 patients (11.4%) a cancer or polyp was found. Analysis of referral indications showed an increased positive predictive value for neoplastic lesions in patients referred for anemia (22.2%), weight loss (20.0%), abdominal pain (17.8%), and positive fecal occult blood test (15.4%). There were only two patients with polyp or cancer of 55 (3.6%) < 40 years of age, in contrast to 27 of 200 (13.5%) > 40 (p < 0.05). Sixty-six patients underwent further investigation, and 26 had positive results: colonic lesions were confirmed in 20 patients, sigmoid colon cancer was found on barium enema in one, and lesions outside the colon were detected in seven. Such open-access, flexible sigmoidoscopy gave higher yield for colorectal polyps or cancers than open-access or hospital-initiation barium enema.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

[Closure of postoperative anastomotic fistulas with a somatostatin analogue].

Postoperative gastrointestinal fistula formation is not rare, and is accompanied by considerable morbidity and mortality. Somatostatin, a potential, universal endocrine and exocrine inhibitor, is a peptide synthesized in the nervous system and the gastrointestinal tract. We describe 2 men, 58 and 53 years old, respectively, with postoperative fistulas, the first after pancreatic-jejunal and the second after jejunal anastomosis. 7 and 3 days, respectively, after starting a synthetic somatostatin analogue (SMS 201-995), discharge from the fistulas decreased and they closed completely.

Anastomosis, Surgical

Mouse splenic and bone marrow cell populations that express high-affinity Fc epsilon receptors and produce interleukin 4 are highly enriched in basophils.

Splenic and bone marrow cells from normal mice, and from mice that have been polyclonally activated by injection of anti-IgD antibody, contain cells that produce interleukin 4 (IL-4) in response to crosslinkage of Fc epsilon receptors (Fc epsilon R) or Fc gamma R or to ionomycin. Isolated Fc epsilon R+ cells have recently been shown to contain all of the IL-4-producing capacity of the nonlymphoid compartment of spleen and bone marrow. Here, purified Fc epsilon R+ cells are shown to be enriched in cells that contain histamine and express alcian blue-positive cytoplasmic granules. By electron microscopy, the vast majority of cytoplasmic granule-containing cells are basophils; they constitute approximately 25% and approximately 50%, respectively, of Fc epsilon R+ spleen and bone marrow cells from anti-IgD-injected mice. The Fc epsilon R- populations contain cells that form colonies typical of mast cells. The Fc epsilon R+ populations also contain cells that, upon culture with IL-3, form colonies of alcian blue-positive cells, but (in contrast to colonies derived from Fc epsilon R- populations) the colonies are small, and all the cells die within 2-3 weeks. The Fc epsilon R+ cells synthesize histamine during a 60-hr culture with IL-3, while the Fc epsilon R- cells do not. These results indicate that IL-4-producing Fc epsilon R+ cells are highly enriched in basophils.

Animals

The efficiency of cryopreserved semen versus fresh semen for in vitro fertilization/embryo transfer.

The efficiency of cryopreserved donor semen versus fresh donor semen in an in vitro fertilization/embryo transfer programme was evaluated. Thirty-nine in vitro fertilization/embryo transfer cycles were performed using fresh donor semen (group A) and 74 cycles were carried out using cryopreserved semen (group B). All patients underwent a uniform controlled ovarian hyperstimulation using high doses of human menopausal gonadotropins. Oocytes were retrieved transvaginally under ultrasound imaging. Semen (fresh or frozen-thawed) were prepared for insemination by a washing technique. Each ovum was inseminated with 500,000-600,000 motile spermatozoa. No significant difference was noted between the two groups regarding female age, duration of infertility, and number of ova retrieved per aspiration. Even though the fertilization rate in group B was significantly lower than in group A (55.5 +/- 3.8 vs 70.4 +/- 3.5, P = 0.008), pregnancy rates per embryo transfer were similar--39.3 and 38.5%, respectively.

Adult

Prevalence of ulcerative colitis in the Israeli kibbutz population.

We carried out an epidemiological study of ulcerative colitis in 279 Israeli kibbutzim (121,403 population). The prevalence on December 31, 1987 was 121.08 per 100,000 population. When the data were stratified according to ethnic groups, the highest point prevalence was found in Israeli-born Jews (220.56 per 100,000 population), more than in Asian-African-born, or European-American-born kibbutz members (139.20 and 78.73 cases per 100,000 population, respectively). There were 68 men and 78 women (ratio of 0.87). The average age of the patients in the year of this survey was 46 years; it was 35 years at the time of diagnosis. Proctitis was found in 57%, left-sided colitis in 12%, and substantial or total colitis in 31%. Relapse at pregnancy was demonstrated in seven patients, and remission in one. Family history of a first-degree relative with inflammatory bowel disease was documented in three patients (2%). Probable complications of ulcerative colitis were observed in 38 (26%), anemia in 13 (9%). One patient (0.7%) with rectal cancer, also had breast cancer. We suggest that the impressive increase in ulcerative colitis prevalence among Israeli and Asian-African-born, in comparison with European-American-born kibbutz members, points toward a role of environmental factors in the etiology of this disease.

Adult

Cystic changes in gastric glands after gastric surgery and in the intact stomach.

Cystic changes of gastric mucosal glands have been described mainly after gastric operations, and like intestinal metaplasia and dysplasia, they may represent a premalignant condition. Their association with gastritis raises the possibility of their being secondary to the inflammatory process. Enterogastric reflux of duodenal contents, local chronic ischemia, and inflammatory reaction as a result of gastric surgery and suture at gastroenterostomy have been considered responsible for this lesion. In 18 of 157 consecutive patients (11.5%) who underwent endoscopic gastric biopsy within a year we found cystic changes of gastric mucosal glands. Cystic changes were present in 43% of 30 patients after gastric operation for duodenal ulcer disease, within an average of 8.4 years in contrast to only 4% of patients with an intact stomach. This change is statistically significant (Z = 1.97, (p less than 0.05) and suggests that there is a cause-and-effect link between the operation and the development of cystic lesions. In three patients we traced the original operative specimen, and in none did we find cystic changes. All the cases were associated with chronic gastritis; mild dysplasia was found in four (22%). The cystic glands were shown (by alcian blue-periodic acid-schiff staining) to secrete neutral mucin like normal gastric glands, and unlike dysplastic glands or intestinal metaplasia where acid mucin is characteristic. Thus, our findings suggest an inflammatory cause for the cystic glandular change (reactive, hyperplastic change of glands), and suggest that it is probably not a preneoplastic state.

Adult

Mucin production by human colonic carcinoma cells correlates with their metastatic potential in animal models of colon cancer metastasis.

Patients with mucinous colorectal cancers characteristically present with advanced disease, however, the relationship between mucin production by colon cancer cells and their metastatic potential remains unclear. We therefore sought to define the relationship between mucin production by human colon cancer cells and metastatic ability by employing animal models of colon cancer metastasis. LS LiM 6, a colon carcinoma cell line with high liver metastasizing ability during cecal growth in nude mice produced twofold more metabolically labeled intracellular mucin and secreted four- to fivefold more mucin into the culture medium compared to poorly metastatic parental line LS174T. This was accompanied by a similar elevation in poly(A)+ RNA detected by blot hybridization with a human intestinal mucin cDNA probe, and increases in mucin core carbohydrate antigens determined immunohistochemically. Variants of LS174T selected for high (HM 7) or low (LM 12) mucin synthesizing capacity also yielded metastases after cecal growth and colonized the liver after splenic-portal injection in proportion to their ability to produce mucin. Inhibition of mucin glycosylation by the arylglycoside benzyl-alpha-N-acetyl-galactosamine greatly reduced liver colonization after splenic-portal injection of the tumor cells. These data suggest that mucin production by human colon cancer cells correlates with their metastatic potential and affects their ability to colonize the liver in experimental model systems.

Animals

Fecal occult blood test--the importance of proper evaluation.

Fecal occult blood testing is used worldwide to screen for early detection of colorectal neoplasia. Because processing Hemoccult II cards is not difficult, it is very easy for inexperienced personnel to perform, and opens a way to overdiagnose positive tests. This could be followed by unnecessary, expensive diagnostic procedures and a significant decline in the test specificity. In a prospective study of two similar populations (two kibbutzim of the Upper Galilee in northern Israel), I compared the impact of processing the Hemoccult II cards on their positive predictive value for colonic cancer and adenomatous polyps. The inexperienced processor increased overall screening positivity fourfold (25 versus 6%, p less than 0.01). This was accompanied by a sharp decrease in the predictive value for adenomas greater than 1 cm (6 versus 25%, p less than 0.05) with no change in the final screening yield: 1.58 versus 1.53% of the participants had adenomas in kibbutz A and kibbutz B, respectively. I recommend that the Hemoccult II cards be processed by experienced personnel only.

Adenocarcinoma

Treatment of duodenitis with cimetidine: a clinical, endoscopic, and histologic study.

We studied the effectiveness of cimetidine in the treatment of endoscopically diagnosed duodenitis. Sixty-nine patients with the solitary endoscopic finding of duodenitis (6% of 1,200 patients who underwent fiberoptic endoscopy of the upper gastrointestinal tract in our unit over 3 years) were studied retrospectively: a good clinical response was apparent in 45 of 69 patients treated with cimetidine (65%), and a fair response in another four (6%). In a controlled, randomized prospective study, we evaluated the effectiveness of cimetidine in duodenitis. Statistically significant improvement for the clinical and endoscopic scores was found in 10 patients treated with cimetidine (p less than 0.01). Improvement in the histologic score did not reach statistical significance. No such improvement was demonstrated in seven placebo-treated patients. We believe that duodenitis is a "peptic syndrome," has a good response to cimetidine treatment, and behaves much like duodenal ulcer disease.

Adult