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Biomedical subjects

Y Bujanover

Publications and source records attributed to Y Bujanover.

At least 55 records · Page 3Linked to original sources

Alteration in the regulation of plasma membrane glycoproteins of the hepatocyte during ontogeny.

The expression of four integral membrane glycoproteins was examined in detail utilizing monospecific antibodies during liver development. These included asialoglycoprotein receptor, a hepatocyte glycoprotein residing in the sinusoidal domain, and three bile canalicular glycoproteins, leucine aminopeptidase, dipeptidyl peptidase IV, and a Mr 110,000 glycoprotein denoted GP 110. It was observed that asialoglycoprotein receptor, GP 110, and dipeptidyl peptidase IV were present in low amounts in fetal liver and reached adult levels between 1 to 3 weeks. In contrast, leucine aminopeptidase was present in nearly adult amounts in 18-day-old fetal livers. These observations were qualitatively confirmed by indirect immunofluorescent staining of frozen thin liver sections obtained from fetal and adult rats. Further, in fetal livers it was found that leucine aminopeptidase was not localized to typical bile canalicular areas. Immunoprecipitation studies performed in the presence of proteolytic inhibitors using detergent-solubilized extracts of metabolically labeled liver minces revealed that GP 110 was present in low amounts as Mr 110,000 and Mr 105,000 polypeptides in 17-day fetal livers but by 21 days of gestation the larger polypeptide was the major synthesis product. Conversely, the apparent molecular weights of leucine aminopeptidase and dipeptidyl peptidase IV were not altered during development. Experiments determining relative rates of synthesis using excess amounts of antibodies showed that the concentrations of the three bile canalicular glycoproteins in liver during ontogeny reflect their rates of synthesis. These results underscore that plasma membrane constituents of the hepatocyte undergo dramatic changes in expression and localization as the liver changes its physiological role at birth.

Aging↗

Nodular gastritis and Helicobacter pylori.

Numerous reports have established the association of Helicobacter pylori and peptic ulcer disease in adults. Recently, this association has also been demonstrated in children. We investigated 14 children and adolescents with recurrent abdominal pain. In six patients, endoscopy revealed gastritis and Helicobacter pylori was identified. Giemsa stain was more sensitive than culture or urease testing in identifying the bacteria. In four of the six, a nodular appearance of the antral mucosa was observed. The histological examination suggests lymphoid hyperplasia as the cause of the nodularity. All of the patients became symptomless after combined treatment with amoxicillin and bismuth subsalicylate. We conclude that nodular gastritis is a peculiar type of gastritis in children. It is frequently found in association with Helicobacter pylori infection.

Adolescent↗

Hepatomegaly as a single presenting sign of stage IV-S neuroblastoma.

This article presents the case of an infant who on routine physical examination at the age of 5 months was found to have hepatomegaly. The initial investigation revealed borderline liver function tests, and ultrasonography showed multiple space-occupying lesions. Further workup using different imaging techniques, urinary vanillylmandelic acid, serum catecholamines, and liver biopsy led to the diagnosis of stage IV-S neuroblastoma. No primary site outside of the liver could be demonstrated. The tumor regressed spontaneously.

Hepatomegaly↗

Isolation and characterization of a Mr = 110,000 glycoprotein localized to the hepatocyte bile canaliculus.

A Mr = 110,000 glycoprotein, GP 110, was partially purified using wheat germ agglutinin-Sepharose affinity chromatography from a bile canalicular-enriched membrane fraction denoted N2u of rat liver. This fraction was subjected to preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis and the Mr = 110,000 polypeptide was excised and used as an immunogen in rabbits. The antisera were found to specifically recognize a Mr = 110,000 polypeptide, named GP 110, in the N2u membrane fraction. In isolated hepatocytes, GP 110 was readily accessible to cell surface iodination catalyzed by lactoperoxidase at 4 degrees C and was judged by immunoprecipitation studies to contain about 2% of total radioactivity incorporated into externally oriented proteins of the cell. Immunoprecipitated GP 110 was shown by two-dimensional polyacrylamide gel electrophoresis to migrate with an approximate pI of 4.9. Indirect immunofluorescence on frozen liver sections demonstrated that GP 110 was primarily localized in the bile canaliculus. In corroborative studies employing subcellular fractionation, it was found that GP 110 was enriched nearly 19-fold in P2, a plasma membrane fraction primarily derived from the sinusoidal domain, and 44-fold in N2u. In contrast, only low levels of GP 110 were present in endoplasmic reticulum, mitochondrial, cytosolic, and nuclear-enriched fractions of liver. The physiological function of GP 110 is as yet unknown; antisera to it did not immunoprecipitate other known bile canalicular proteins of similar molecular weights. GP 110 was found to be extensively glycosylated relative to other known membrane proteins; approximately 33% of the apparent molecular weight appear to be carbohydrate. In agreement, limited removal of N-linked carbohydrate chains indicated that there are approximately eight chains/GP 110 polypeptide. Neuraminidase treatment of GP 110 resulted in a desialylated Mr = 85,000 polypeptide suggesting that the majority of carbohydrate chains on GP 110 are of the complex type.

Animals↗

Isolation of domains of the plasma membrane of hepatocytes.

Several recent studies have demonstrated the ability of techniques based on immunoadsorption to selectively isolate specialized subregions of membranes, termed domains, which are derived from a larger more complex parent membrane like the plasma membrane. The immunoadsorbent is directed against a specific antigen that resides exclusively or predominantly in the membrane domain to be isolated. Thus, a monospecific antibody to the domain-specific antigen is required. In the present study we developed a method employing a modified immunoblotting strategy which could utilize polyspecific antibodies to isolate membrane vesicles derived from a specific membrane domain of the hepatocyte plasma membrane. We also used specific cell surface labeling of the hepatocyte plasma membrane by lactoperoxidase-catalyzed iodination at 4 degrees C and preparation of different sized vesicles by sonication to facilitate isolation of the specific domain. For this study, polyspecific antisera were raised in goats against a membrane fraction, denoted N2u, which is enriched in bile canalicular proteins. This antiserum recognizes, among other antigens, a 110,000 Mr polypeptide previously shown to be localized in the bile canaliculus (J. Cook et al. (1983) J. Cell. Biol. 97, 1823-1833). A monospecific antiserum was raised in rabbits against the rat hepatocyte asialoglycoprotein receptor, a sinusoidal domain-specific set of glycoproteins whose major form has a Mr of 43,000. These antisera were each coupled indirectly to different pieces of nitrocellulose by the immunoblotting protocol and were used to isolate membrane vesicles from a crude extract of liver plasma membrane prepared by sonication. The ratio of iodinated asialoglycoprotein receptor to the 110,000 Mr polypeptide in vesicles isolated by the affinity nitrocellulose immunoadsorbent method indicate a 10- to 15-fold enrichment of sinusoidal-derived vesicles relative to bile canalicular-derived membrane vesicles. These results show that the affinity nitrocellulose immunoadsorbent method can be used to isolate domain-specific vesicles. Further, the affinity immunoadsorbent method described here for the isolation of domains of the plasma membrane is an integrative one allowing isolation of vesicles present in relatively small concentration in crude cell extracts and it requires minimal ultracentrifugation time.

Affinity Labels↗

Clinical and laboratory study in 22 patients with inherited hyperammonemic syndromes.

Twenty-two patients with inherited hyperammonemic syndromes are presented. These patients represent 22 different families. The diagnosis was based mainly on family history, blood ammonium levels, acid base balance, urinary orotic acid, urinary and plasma amino acids and organic acids. The final diagnosis was confirmed by determination of liver enzyme activity. In 12 patients (54%), the first clinical manifestations were noticed after the neonatal period; 7 patients (31%) were diagnosed after infancy, and 8 (23%) after the age of 8 years. Two patients who represent the late-onset group of inherited hyperammonemic syndromes are presented in detail. The three most common diagnoses were ornithine transcarbamoylase deficiency, carbamoyl phosphate synthetase deficiency, and lysinuric protein intolerance, which comprised 59% of the diagnosed patients. Our data, based on one of the largest series reported, reveal a relatively large percentage of late-onset inherited hyperammonemic syndromes as compared with previous reports.

Amino Acid Metabolism, Inborn Errors↗

Is human methane production affected by long-term occupational exposure to a methanogenic flora?

The factors determining human methane production or nonproduction are unknown. Exposure at a young age to a methanogenic flora is thought to be of significance. We examined whether long-term occupational exposure to methanogenic flora in adult life affects methane production. Among 38 subjects who worked in a cowshed for a mean period of 14 +/- 15 years, the proportion of methane producers was identical to that found in well-matched controls. The length of work in the cowshed had no effect on methane production.

Adolescent↗

Lactose malabsorption is not a cause of diarrhea during phototherapy.

Lactose malabsorption is not a cause of diarrhea during phototherapy. Jaundiced neonates under phototherapy develop diarrhea or loose stools during the treatment. These phenomena were attributed to an induced lactase deficiency caused by bilirubin breakdown products. We investigated lactose malabsorption in 59 neonates--29 normals and 30 jaundiced under phototherapy. Five-hour hydrogen breath tests were performed. Preprandial and postprandial (at 30, 60, 120, 180, 240, and 300 min) expired air samples were analyzed for hydrogen. Ten controls and five jaundiced neonates had positive hydrogen breath tests. Eighteen controls and 16 neonates under phototherapy had preprandial hydrogen (concentrations above 5 ppm). In our hands, lactase deficiency and lactose malabsorption were not induced by phototherapy. Lactase deficiency is therefore not the cause of diarrhea associated with phototherapy.

Breath Tests↗

The development of methane production in childhood and adolescence.

Methane concentration in the expired air was analyzed in 393 infants, children, and adolescents. There was no methane production below the age of 3 years. In the age group 3-4 years, 6.4% of the children produced methane. The percentages were 14.3-18.2% in children aged 7-14. A rise in methane production to 39.4-45.9% was recorded from age 14 to 18, as compared with 49.4% in adults in Israel. The reasons for these changes in methane production with age are not known. Alterations in the colonic flora or the production of a specific substrate(s) are the main possibilities. In our opinion, the latter possibility deserves further investigation.

Adolescent↗

Lactose malabsorption in Israeli children.

Lactose malabsorption during childhood was studied in 110 Jewish children in Israel, using the lactose hydrogen breath test. Sixty-eight subjects (61.8%) were lactose malabsorbers, 41 (60.3%) of whom were lactose-intolerant with symptoms evidenced during or following the tests, whereas 27 (39.7%) were symptom-free (tolerant malabsorbers). In the youngest age-group (4 months to 3 years), no lactose malabsorption was detected, whereas in the higher age-groups the prevalence of lactose malabsorption increased with age. The percentages of lactose malabsorption in the age-groups 3 to 6, 6 to 12 and 12 to 16 years were 56.5, 65.2 and 75.0%, respectively. The percentages of lactose-intolerant subjects also increased in the same age-group, to 26.5, 39.1 and 65.0%. There were no significant differences in lactose malabsorption and tolerance between the various ethnic groups tested. The peak values of breath hydrogen were higher in lactose-intolerant than in lactose-tolerant malabsorbers.

Adolescent↗

Campylobacter enteritis in normal and immunodeficient children.

Campylobacter fetus subspecies jejuni (CBJ) has been recently recognized as a common pathogen in bacterial gastroenteritis in children. During a period of 16 months, 51 cases of C fetus subspecies jejuni gastroenteritis were diagnosed. Five of the children in whom the cases were diagnosed were previously known to be immunodeficient: two had X-linked agammaglobulinemia, one had agammaglobulinemia, one had combined immunodeficiency, and one had transient hypogammaglobulinemia. Average duration of fever and diarrhea was longer in the five immunodeficient children (15 and 23 days, respectively) compared with the normal children (four and five days, respectively). Excretion of C fetus subspecies jejuni in stool persisted for 20 to 27 days in four of the immunodeficient children and for one year in the fifth, whereas normal children excreted C fetus subspecies jejuni for only four to 16 days. Campylobacter fetus subspecies jejuni may be added to the list of bacterial pathogens most likely to infect immunodeficient children, especially those with a defect of the humoral system.

Campylobacter Infections↗

99mTc-HIDA cholescintigraphy in children with Dubin-Johnson syndrome.

Tc-HIDA cholescintigraphy in Dubin-Johnson syndrome (DJS) demonstrates intense prolonged homogeneous visualization of the liver, together with delayed visualization of the gall bladder and extrahepatic ducts. Such a cholescintigram has not been described for any other hyperbilirubinemic state. Because it is a noninvasive and easy technique, it is recommended for the evaluation of children suspected of having DJS.

Bile Ducts↗

Development and regulation of bile salt sulfotransferase in rat liver.

Hepatic bile salt sulfotransferase activity was extremely limited in fetus, gradually increasing after birth. At puberty, enzyme activity declined in males but not in females, suggesting the influence of gonadal hormones associated with sexual maturation. Extremely high enzyme activity was found in pregnant rats at term. The neonatal bile salt sulfotransferase activity could be stimulated by bile acid feeding during pregnancy or maternal bile duct ligation. In contrast, a decrease in enzyme activity was detected in the treated pregnant females. Phenobarbital treatment during pregnancy also produced a 5-fold increase in neonatal enzyme activity. These results suggested that bile salt sulfation was regulated by chemical factors before maturity, and by gonadal hormones thereafter. Two fractions with bile salt sulfotransferase activity were separated from female liver by zone electrophoresis and DEAE-Sephadex A-50 chromatography, while a single active fraction was detected in male liver which corresponded to one of the active female fractions. The two active fractions in the female exhibited the same molecular weight (130 000), and different isoelectric points (6.8 and 5.3). The male fraction had a molecular weight of 130 000 and a pI of 5.3.

Aging↗