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B Ruebner

Publications and source records attributed to B Ruebner.

27 records · Page 2Linked to original sources

A methodology for the analysis of the preneoplastic antigen.

A highly sensitive assay for the epoxide hydrolase activity associated with the preneoplastic antigen (PNA) has been developed based on the synthesis of cis-stilbene oxide labeled with tritium at approximately 15 Ci/mmol. This assay allows the detection of elevated epoxide hydrolase activity in the serum of humans and rodents as well as in the culture medium bathing isolated hepatocytes. The integrity of the enzymatic assay was confirmed in rodents by precipitating the serum PNA activity using an antibody raised against the rat microsomal epoxide hydrolase. Methodology for the detection of PNA in serum will facilitate evaluation of this antigen as a marker for hepatic neoplasia in man and in experimental animals.

Acetaminophen↗

Microsomal and cytosolic epoxide hydrolases in rhesus monkey liver, and in normal and neoplastic human liver.

The cytosolic epoxide hydrolase (EH-LC) was observed in rhesus monkey liver cytosol, and in both normal and neoplastic human liver. Microsomal epoxide hydrolase (EH-LM) was detected not only in the microsomes of normal and neoplastic human liver and normal rhesus monkey liver, but also in the cytosol of these tissues. No apparent differences were observed between the EH-LM in liver cytosol and that in microsomes. No major differences were observed between the levels of EH-LM in the cytosol of normal and that in neoplastic human liver.

Animals↗

Anti-mu induces lymphoma in germfree congenitally athymic (nude) but not in heterozygous (nu/+) mice.

To further our understanding of the role of host immunity in the development of lymphoid neoplasia, groups of germfree BALB/c nude and nu/+ mice were either followed unmanipulated or were treated, beginning at birth, with anti-mu, normal goat IgG or with lipopolysaccharide (LPS). The survival and development of neoplasia of all groups of animals were monitored up to 2 yr. Nude mice, under germfree and specific pathogen-free (spf) conditions, had a higher incidence of lymphoid neoplasia and reduced survival when compared to nu/+ littermates. The incidence of lymphoid tumors in nude mice under spf or germfree conditions was 7.2 and 8.7%, respectively, in comparison to 0% in nu/+ animals. Treatment of germfree nude mice with anti-mu, but not with goat IgG, increased the incidence of lymphoid tumors to 39%. Anti-mu did not significantly change the incidence of lymphoid neoplasia in nu/+ animals. Treatment of nu/nu and nu/+ mice with LPS, however, led to a several-fold increase in the appearance of neoplasia, to values of 25.4% in nude and 10% in nu/+ mice. Lymphoid neoplasia found in either unmanipulated, anti-mu, or IgG-treated germfree or spf mice included Thy-1.2+, surface IgM+, and IgG+ tumors. In contrast, all the lymphomas found in LPS-treated mice were surface IgM+. Thus, whereas LPS may have generated a relatively homogeneous group of tumors, anti-mu may have randomly increased the normal incidence of spontaneous tumors. Moreover, although there was significant variation in the histologic appearance of tumors, both within treatment groups as well as in different areas of the same animal, only LPS-treated mice were regularly noted to have distant nonlymphoid involvement, with lesions found in liver, lung, and kidney. In contrast, the incidence of nonlymphoid neoplasia was similar and was less than 2.5% in all groups.

Aging↗

Conjugated and unconjugated bilirubins in bile of humans and rhesus monkeys. Structure of adult human and rhesus-monkey bilirubins compared with dog bilirubins.

1. Bilirubin-IXalpha, -IXalpha diglucuronide, -IXalpha monoglucuronide, -IXalpha monoglucoside -IXalpha monoxyloside, a bilirubin-IXalpha diconjugate containing glucose and another unknown compound, and bilirubin-IXbeta are present in gall-bladder bile of adult human, rhesus monkey and dog. Dog bile normally also contains other bilirubin-IXalpha diconjugates, i.e. compounds containing two conjugating sugars such as glucuronic acid and glucose, glucuronic acid and xylose and glucose xylose. 2. Azopigments alphaF, alphaO, alpha2, alpha3, betax and delta derived from human and rhesus-monkey bilirubins are identical in their chemical composition with those obtained from the dog. 3. Azopigments alphaF and betax found in diazotized biles of adult humans, rhesus monkeys and dogs are products of unconjugated bilirubin-IXbeta. 4. Technical modifications of previously published procedures [Heirwegh, Fevery, Michiels, Van Hees & Compernolle, (1975) Biochem. J. 145, 185-199] were introduced which make it possible to separate the bilirubins, diazotize the separated bilirubins, extract the azopigments and chromatograph them in one working day (6-8h).

Adult↗

Jejunal perfusion of simple and conjugated folates in celiac sprue.

The intestinal absorption of [3H]-pteroylmonoglutamate (simple folic acid) and pteroyl-micron[14C]glutamyl-gamma-hexaglutamate ([14C]PG-7, conjugated folic acid) was assessed by the method of jejunal perfusion in five patients with proven celiac sprue who were studied after a gluten-containing or a gluten-free diet, and in nine normal subjects. The luminal disappearance of each folate was markedly impaired after exposure of the patients to dietary gluten and improved by gluten restriction, but not to within the range found in the normal subjects. The luminal disappearance of each folate was markedly impaired after exposure of the patients to dietary gluten and improved by gluten restriction, but not to within the range found in the normal subjects. In each experiment, column chromatography of the luminal aspirates revealed similar spectra of hydrolytic products of [14C]PG-7, whereas the fraction of the distal aspirate chromatogram appearing as pteroyl-micron[14C]glutamyl-gamma-monoglutamate ([14C]-PG-1) was similar in all three groups. By accounting for the variable effects of absorption on the luminal appearance of [14C]PG-1 and by correcting for mucosal hydrolysis which was not followed by release of [14C]PG-1 to the luminal contents, the calculated rate of in vivo hydrolysis of [14C]PG-7 to [14C]PG-1 was found impaired in both celiac sprue groups, with significant improvement on treatment. In mucosal biopsies from the sprue patients, the in vitro activity of folate conjugase in whole homogenates was higher and the activity of disaccharidase lower than in a group of 12 normal mucosal biopsies. These in vitro data suggest that the predominant cellular location of mucosal folate conjugase is different from that of disaccharidase, whereas comparison with the results of in vivo hydrolysis suggests that measurement of the enzyme in whole mucosal homogenates overestimates its significant digestive activity. The present studies indicate that (a) the mucosal lesion of celiac sprue significantly limits the intestinal absorption of both simple and conjugated folate, and (b) malabsorption of conjugated folate results from a combination of impaired hydrolysis and decreased mucosal uptake of hydrolytic product.

Adult↗

Fatal hepatocerebral syndrome in siblings discordant for exposure to valproate.

Occurrence of a progressive encephalopathy with seizures in siblings was associated with hepatic pathology. One of these patients was exposed to valproate (VPA) and developed hepatic necrosis, confirmed at autopsy. The other had not been exposed to VPA, and her hepatic lesions at autopsy were less severe. The liver pathology in both was within the range described in previous cases of liver disease attributed to VPA. These facts and the otherwise similar course of their disease suggests that in these patients, and probably in other cases of fatal liver failure attributed to VPA, the drug actually either had no effect or acted only to increase the severity of the preexisting hepatic component of the hepatocerebral disorder.

Child, Preschool↗