Search PubMed⌕ Search

Biomedical subjects

Z Halpern

Publications and source records attributed to Z Halpern.

120 records · Page 7Linked to original sources

An increased familial frequency of gallstones.

Despite the very high prevalence of gallstone disease, studies of familial factors are very few, and asymptomatic family members were not studied. We studied, in a prospective manner, the frequency of gallstones in 171 first-degree relatives of patients with proven gallstones compared with 200 matched controls. All subjects were studied by oral cholecystography, and their height, weight, blood glucose, cholesterol, and other parameters were measured. Gallstones were found in 20.5% of the family group and in 9.0% of the control group. Gallstones were found in 22.8% of the female and 16.7% of the male family members as opposed to 10.3% of the female and 8.0% of the male controls. All these differences were statistically significant. Known risk factors, such as Ashkenazi community group, higher age, and overweight, were more frequent in the control group, as were blood glucose and cholesterol. These findings strengthen the validity of the twofold higher frequency of gallstones found in the family group and are likely to be due to genetic factors. A formal genetic family study of gallstone disease is now indicated, using the ultrasonic method.

Adult↗

Isolated colonic loop in the rabbit: an in vivo system for studying intestinal mucus.

A method for preparing an isolated colonic loop (Thiry-Vella) in a living rabbit is described. The loop, with its intact neurovascular supply, continues to secrete clear colonic mucus for more than 2 months. The chemical composition of the mucus, collected daily for 2 months, was analyzed and shown to be a high molecular weight glycoprotein composed of approximately equimolar amounts of protein and carbohydrate. The main sugars found were N-acetylgalactosamine, N-acetylglucosamine, galactose, and sialic acid. The most prominent amino acids were threonine, aspartic acid, glycine and serine. A considerable flattening and atrophy of the glandular structure of the isolated colonic loop was observed during the 2 months. This fact did not markedly affect the amount and chemical composition of the mucus that was collected daily from this loop. This model can be used in vivo to investigate colonic mucus in normal and diseased animals, or even following the administration of various drugs.

Animals↗

Manometric study during endoscopic retrograde cholangiopancreatography--a new technique for the evaluation of pathology in the pancreatic and biliary systems.

During endoscopic retrograde cholangiopancreatography, pressures of the common bile duct, the pancreatic duct and the sphincter of Oddi were recorded in 64 patients with various diseases of the pancreaticobiliary system. The manometric study was found to be helpful in the diagnosis of papillary dysfunction and in the assessment of the adequacy of papillotomy and the size of a choledochoduodenostomy. Furthermore, it is possible that nitrates may be effective in the treatment of patients with papillary dysfunction.

Aged↗

Frequency of papillary dysfunction among cholecystectomized patients.

Four hundred and fifty-four consecutive patients who had had their gallbladder removed were interviewed to determine the presence of upper abdominal pain, increased serum alkaline phosphatase and/or serum amylase activity. Patients with unexplained upper abdominal pain and/or enzyme abnormalities were offered endoscopic retrograde cholangiopancreatography (ERCP) and manometric evaluations. Dysfunction of the sphincter of Oddi diagnosed by ERCP manometry may account for the abdominal pain seen in 14% of the patients with postcholecystectomy syndrome. It may rarely be the cause of an elevated serum alkaline phosphatase and/or amylase when abdominal pain is not present. Papillary dysfunction is seen in less than 1% of the patients who have had their gallbladders removed. ERCP manometry is recommended in cholecystectomized patients with unexplained abdominal pain suggesting pancreaticobiliary origin.

Aged↗

Cholesterol nucleation from its carriers in human bile.

This study was performed to determine whether biliary cholesterol nucleates primarily from vesicles or micelles. Twenty gallbladder biles and 12 hepatic biles from patients with gallstones as well as 16 model biles were examined. The nucleation times (days) of the biles as well as their isolated vesicular and micellar fractions were determined and their lipid composition was analyzed. In 41 of 46 comparisons, cholesterol nucleated faster from vesicles than micelles; in only one case was the opposite found. The mean (+/- S.D.) nucleation times of vesicles and micelles in gallbladder biles were 8.9 +/- 5.4 vs. 15.4 +/- 8.6, in hepatic biles 14.6 +/- 9.4 vs. 20.6 +/- 9.1, and in model biles 9.0 +/- 3.7 vs. 18.9 +/- 9.1 days, respectively. All these differences were significant (p less than 0.005). Gallbladder biles (n = 7) devoid of vesicles nucleated more slowly (9.0 +/- 9.5 days), as compared to gallbladder biles (n = 13) containing vesicles (3.8 +/- 2.2 days). The nucleation time of gallbladder and hepatic biles was significantly correlated with the nucleation time of the vesicles from these biles (r = 0.847, p less than 0.05). There was no correlation with the nucleation time of micelles from the same biles. The percentage of cholesterol carried by vesicles in bile was positively correlated to the molar percentage of biliary cholesterol and the cholesterol saturation index and negatively correlated to the molar percentage of bile salts. Our data suggest that phospholipid vesicles are the major vehicle for cholesterol precipitation in bile as well as an important determinant of the nucleation time of bile.

Bile↗

Hepatocyte-derived soluble factors regulate proliferation and autocrine growth factor expression in colon cancer cell lines of varying liver-colonizing capability.

We investigated the role of hepatocyte-derived soluble growth factors on cell proliferation and expression of growth factors and their receptors in four colon cancer cell lines of varying liver-colonizing ability. Cocultures of hepatocytes and colon cells and cultures of colon cells with hepatocyte-conditioned medium resulted in growth inhibition of both weakly and strongly metastatic cell lines. Growth inhibition was accompanied by a reduced expression of erb-B2 in the colon cells after 4 days in the presence of hepatocytes. In LS174T and LiM6 cells, there was a dramatic reduction in heregulin-alpha levels in the presence of hepatocytes. Interestingly, after 2 days in culture, hepatocyte-derived soluble factors increased the mRNA levels for the EGF family members amphiregulin and cripto. These studies show an inhibitory effect of hepatocyte-derived soluble factors on the proliferation of colon cell lines, mediated in part by changes in the expression of autocrine growth factors and receptors of the EGF and heregulin family.

Amphiregulin↗

The use of synthetic analogues of Arg-Gly-Asp (RGD) and soluble receptor of tumor necrosis factor to prevent acute and chronic experimental liver injury.

In chronic viral hepatitis, autoimmune hepatitis, and some chronic cholestatic liver diseases, T-lymphocytes serve as effector cells of the immunostimulatory processes. Cellular interactions of immune cells with extracellular matrix (ECM) components are regulated primarily via the beta 1 subfamily of integrin receptors. The target epitope of several such integrin receptors is the Arg-Gly-Asp (RGD) sequence, a cell adhesion motif shared by several matrix-associated adhesive glycoproteins. We review the use of synthetic nonpeptidic analogues of RGD and of soluble receptor of tumor necrosis factor (TNF)-alpha in the prevention of immune-mediated, concanavalin A-induced liver damage in mice and of RGD analogues in inhibiting the development of liver cirrhosis in rats. The concanavalin A-induced elevation of serum transaminases and TNF-alpha, and the infiltration of liver tissue by inflammatory cells, were inhibited by pretreatment of the mice with the synthetic RGD mimetics and soluble TNF receptor. In rats, the progression of thioacetamide-induced liver cirrhosis was markedly inhibited by the coadministration of the RGD mimetic SF-6,5. The compounds described here may be examined therapeutically for pathological conditions in the liver, manifested as necroinflammation, cholestasis and fibrosis.

Animals↗