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Biomedical subjects

D H Alpers

Publications and source records attributed to D H Alpers.

At least 145 records · Page 8Linked to original sources
PubMed1984

Induction of rat hepatic and intestinal alkaline phosphatase activity produced by bile from bile duct-ligated animals.

Bile duct ligation caused a threefold elevation of not only hepatic but also intestinal alkaline phosphatase. The increase was transient in intestinal mucosa and peaked at 12 h. Hepatic phosphatase levels reached a plateau by 36 h. Intraperitoneal injection of bile from ligated animals into normal rats produced qualitatively similar results. Studies were performed to further characterize the induction of phosphatase activity in both tissues. The addition of bile from ligated animals to organ explants of liver and intestine produced a two- and threefold rise in activity, respectively. Therefore, neural and hormonal factors are not essential in producing this induction. The increased activity produced in vitro in both tissues was due to heat-stable and dialyzable factor(s) and was blocked by inhibitors of protein synthesis. In the intestine activity occurred over the entire brush border as demonstrated by electron microscopic histochemistry. In the liver, increased activity was noted over the entire plasma membrane and was not localized to the canalicular membrane. Tunicamycin treatment of liver and intestinal explants markedly suppressed the induced phosphatase activity. Simultaneous treatment with protease inhibitors restored some of the phosphatase activity. These findings suggest that glycosylation of the alkaline phosphatase might provide at least partial protection from proteolysis.

Alkaline Phosphatase↗
PubMed1984

Metabolism of human isoamylases in the rabbit.

Human isoamylases were purified from pancreas and saliva with separation of salivary isoenzymes into glycosylated and nonglycosylated forms. After iodination, bolus injection of each purified isoamylase into conscious rabbits revealed biexponential disappearance from plasma. Glycosylated salivary amylase had a metabolic clearance (t 1/2 = 35 min) that was three to four times faster than nonglycosylated salivary (t 1/2 = 139 min) or pancreatic (t 1/2 = 111 min) amylase. In contrast to our previous studies on homologous (rabbit) isoamylases, human pancreatic isoamylase was excreted into urine as protein-bound radioactivity more readily than salivary isoamylase. No organ contained more than 18% of the injected dose of radioactivity except for a striking accumulation of radioactivity in the liver after injection of 125I-labeled glycosylated salivary amylase. We concluded that 1) human nonglycosylated salivary amylase and pancreatic amylase are cleared from the rabbit circulation at rates comparable with those reported for homologous isoamylases in the rabbit and baboon, 2) the rabbit kidney excretes human pancreatic amylase into urine more readily than human salivary isoamylases, and 3) with the notable exception of glycosylated salivary isoamylase, human isoamylases do not appear to be metabolized primarily by any single organ.

Animals↗
PubMed1984

Hepatic clearance of rat plasma intestinal alkaline phosphatase.

The mechanism and route of clearance of intestinal alkaline phosphatase from plasma have been studied in rats to define the magnitude of hepatic extraction and biliary excretion of the enzyme. Plasma clearance, tissue distribution, and biliary excretion of enzyme were followed after intravenous administration of physiological amounts of 125I-labeled rat intestinal alkaline phosphatase. The plasma disappearance curve was biphasic; the initial phase was rapid, during which 50% of injected enzyme was selectively extracted by the liver over 5 min. Less than 4% of total hepatic radioactivity was excreted into bile over 80 min; this was shown by chromatographic analysis to be degraded enzyme only. Rapid clearance of enzyme could be significantly slowed by injection of large amounts of mannan or N-acetylglucosamine-bovine serum albumin, but not by desialylated fetuin, demonstrating that clearance was probably mediated by mannose/N-acetylglucosamine-specific receptors. It is concluded that, under physiological conditions, rat plasma intestinal alkaline phosphatase is rapidly cleared from the circulation by the liver. However, biliary excretion of undergraded enzyme is negligible, and a physiologically significant enterohepatic circulation seems most unlikely.

Alkaline Phosphatase↗
PubMed1984

A study of the association between Crohn's disease and psychiatric illness.

This study is an examination of the association between Crohn's disease and psychiatric illness using careful gastrointestinal evaluation, a structured psychiatric interview of known reliability and validity, and explicit diagnostic criteria for psychiatric illness. A proband sample of 50 subjects with Crohn's disease was obtained from a university clinic and a private clinic. Fifty control subjects with chronic medical illnesses obtained from the same two clinic sources were also examined. Compared with controls, a significantly greater number of the patients with Crohn's disease met criteria for some psychiatric disorder at some time in their lives, and a significantly greater number had a diagnosis of depression. A greater number of the probands reported obsessional or phobic symptoms, and the mean number of obsessional symptoms was higher in probands than in controls. We found no evidence of an interaction between psychiatric disorder and Crohn's disease. The significance of the discovered association for the treatment and natural history of Crohn's disease is discussed.

Adult↗
PubMed1983

Binding of intrinsic factor to ileal brush border membrane in the rat.

The rat ileal brush border membrane binds both free [125I]-intrinsic factor (IF) and the IF-[57Co]cobalamin (cbl) complex. This binding is observed with IF isolated from rat stomach, but not from IF isolated from hog, canine and human stomachs. The binding of rat-IF[57Co]cbl can be blocked with free rat IF but not with hog IF. The IF-cbl complex binds at a higher affinity (Ka = 0.15 X 10(9) M-1) compared to that of free IF (Ka = 0.9 X 10(9) M-1). Rat IF-cbl also binds efficiently to human and canine ileal membranes. While antibody to the canine ileal receptor blocks the binding of rat, human or hog IF-[57Co]cbl to human and canine ileal membranes, it does not affect the binding of rat IF-[57Co]cbl to rat ileal membranes. These findings demonstrate that the rat ileal receptor is different from canine and human ileal receptors.

Animals↗
PubMed1983

The nucleotide sequence of rat liver fatty acid binding protein mRNA.

Rat liver fatty acid binding protein mRNA is present in both liver and intestinal epithelium. It is the most abundant mRNA in the small intestinal mucosa. We have determined the sequence of this mRNA from cloned cDNA. It consists of a 5'-nontranslated domain at least 39 nucleotides long, a coding region which specifies a 127-amino acid, 14,184-dalton polypeptide, and a 3'-nontranslated region 68 nucleotides long. An AAUAAA sequence begins 21 nucleotides before the 3'-terminal poly(A) tail. The derived protein sequence was verified by automated sequential Edman degradation of (i) the primary translation product of the mRNA and (ii) a cyanogen bromide peptide generated from the mature liver protein. Evidence is presented which suggests that this protein is targeted to the cytoplasm. The NH2 terminus of the primary translation product is acetylated in vitro. No cleavable signal peptide sequence or internal signal sequence equivalent was detectable in a co-translational cleavage assay. Cloned cDNA was used to establish that this mRNA was 12 times more abundant in intestinal epithelial than in liver RNA.

Amino Acid Sequence↗
PubMed1983

Fate of circulating isoamylases in the rabbit.

Amylase purified from the pancreas and parotid gland of rabbits was labeled with 125I. Plasma disappearance was biexponential after bolus injection. Half-time of metabolic clearance was 97 and 95 min, respectively, for pancreatic and salivary 125I-amylase. About 20 and 30% of the injected pancreatic and salivary 125I-amylase, respectively, appeared intact in the urine within 24 h. Organs were assayed for radioactivity at specified times. No organ at any time contained more than 20% of injected radioactivity. At 24 h, more than 90% of radioactivity in organs was acid soluble. Bilateral nephrectomy significantly slowed plasma disappearance, although 90% hepatectomy did not. These studies in the rabbit indicate that 1) homologous isoamylases are cleared from plasma at rates comparable with those reported in primates; 2) in contrast to primates, urinary excretion of salivary amylase is greater than pancreatic amylase; and 3) within 24 h, virtually all of injected 125I-labeled isoamylases were catabolized or excreted.

Amylases↗
PubMed1983

Effect of bile and bile acids on binding of intrinsic factor to cobalamin and intrinsic factor-cobalamin complex to ileal receptor.

Human bile or commercially available bile acids bind [57Co]cobalamin (Cbl) due to the presence of "R"-type binders, which are normally present in the former and present as a contaminant in the latter. The competition of these R proteins for the binding of Cbl by intrinsic factor (IF) could explain the in vivo inhibition attributed previously to the bile acids themselves. R protein seems to be involved in the inhibition of Cbl binding because protease digestion of either bile or bile acid abolishes the Cbl binding ability. Moreover, antibody to R protein abolishes the inhibition. Bile or bile acids do not have a direct effect on either purified IF or the IF-Cbl receptor molecule, even though bile acids increase the attachment of IF-[57Co]Cbl to ileal brush-border membranes. These data demonstrate two steps where components of bile could affect Cbl absorption: the binding of Cbl to IF and of IF-Cbl to its ileal receptor. It is not clear whether these in vitro phenomena are important for the normal absorption of Cbl in vivo.

Animals↗
PubMed1982

Cloning of a complementary deoxyribonucleic acid encoding a portion of rat intestinal preapolipoprotein AIV messenger ribonucleic acid.

Apolipoprotein AIV is one of the principal apolipoproteins synthesized by the rat small intestine. We have cloned a cDNA encoding a portion of preapolipoprotein AIV mRNA. A kinetically fractionated cDNA probe highly enriched for the abundant intestinal mucosal mRNA sequences was used to screen a library of recombinants containing cDNA generated from total intestinal epithelial mRNA. The abundant class of mRNA sequences was defined by hybridization analyses. This frequency class had an aggregate complexity of 5300 nucleotides and represented 25% of accumulated mRNA sequences.l The mRNAs comprising this class were identified by in vitro translation and included preapolipoprotein AIV, preproapolipoprotein AI, intestinal fatty acid binding protein, and liver fatty acid binding protein. A cDNA-containing clone derived from preapolipoprotein AIV mRNA was identified among probe-positive recombinants. This cDNA was used to establish that apolipoprotein AIV mRNA has a mass of 550000 daltons (equivalent to 1780 nucleotides) and represents 0.013% of total cellular RNA in the fasting state. Acute feeding with triglyceride-rich meals resulted in a 2-fold increase in preapolipoprotein AiV mRNA after 4 h.

Animals↗
PubMed1982

Proteolytic processing of the primary translation product of rat intestinal apolipoprotein A-IV mRNA. Comparison with preproapolipoprotein A-I processing.

Total cellular RNA, isolated from rat intestinal epithelium, was translated in a wheat germ cell-free system, and the primary translation product of apolipoprotein A-IV mRNA was purified by immunoprecipitation with monospecific antibody. NH2-terminal sequence analyses of mature rat plasma high density lipoprotein-associated A-IV and the cell-free product revealed that A-IV is initially synthesized with a 20-amino-acid NH2-terminal extension. Co-translational cleavage of the primary translation product indicated that the entire NH2-terminal extension behaved as a prepeptide. The prepeptides of intestinal apolipoproteins A-I and A-IV have 59% sequence homology. However, A-IV does not possess the unusual propeptide previously identified in intestinal A-I (Gordon, J. I., Smith, D. P. Andy, R., Alpers, D. H. Schonfeld, G., and Strauss, A. (1982) J. Biol. Chem. 257, 971-978). Therefore it appears that proteolytic processing of these two apolipoproteins differs significantly.

Amino Acid Sequence↗
PubMed1982

The primary translation product of rat intestinal apolipoprotein A-I mRNA is an unusual preproprotein.

We have characterized the NH2-terminal sequence of the primary translation product of intestinal apolipoprotein A-I mRNA. Co-translational cleavage of this in vitro product and NH2-terminal sequence analysis of plasma high density lipoprotein-associated apolipoprotein A-I showed that it is initially synthesized as a preproprotein. The 24-amino-acid NH2-terminal extension consists of an 18-amino-acid presegment; Met-Lys-Ala-Ala-Val-Leu-Ala-Val-Ala-Leu-Val-Phe-Leu-Thr-Gly-Cys-Gln-Ala, and a hexapeptide prosegment; -X-Glu-Phe-X-Gln-Gln, followed by the NH2 terminus of the "mature" plasma protein: Asp-Glu-Pro-Gln-X-Gln-Trp-Asp-Arg-Val-Lys-Asp-Phe-Ala-X-Val-Tyr-X-Asp-Ala-Val. Although the prepeptide resembles other signal peptides, the prosegment differs from other propeptides in that it does not terminate with paired basic amino acid residues. These results suggest that translocation of nascent preproapolipoprotein A-I is similar to that of other secretory proteins. However, post-translational proteolytic processing of proapolipoprotein A-I must be unique, and could play a role in the formation of nascent high density lipoprotein particles.

Amino Acid Sequence↗
PubMed1982

A controlled study of the association between ulcerative colitis and psychiatric diagnoses.

Fifty consecutive patients with ulcerative colitis were personally examined to determine the lifetime prevalence of specific psychiatric diagnoses. A personality assessment and a tabulation of recently occurring stressful events were done. A matched control sample with chronic nongastrointestinal medical illnesses was evaluated in the same way. The two groups were compared so as to quantify the relative association and impact of psychiatric disorder in ulcerative colitis. We found no greater frequency of diagnosable psychiatric disorder in ulcerative colitis patients than in the control population. Those with ulcerative colitis and a psychiatric illness did not appear to have more serious gastrointestinal involvement, nor did severity of the ulcerative colitis predict more frequent or more serious psychiatric disorder. Personality profiles were similar in probands and controls, and there was no correlation between the frequency of potentially stressful life events within the six months prior to interview and severity of ulcerative colitis at the time of interview. We did find slightly higher levels of obsessional symptomatology in ulcerative colitis cases, but this association appeared to be weak and unrelated to the severity of the gastrointestinal disorder. Despite the fact that more than a quarter of the ulcerative colitis patients had some diagnosable psychiatric illness, the occurrence of psychiatric disorder was rarely documented in the medical charts.

Adult↗
PubMed1982

The effects of fat feeding on apolipoprotein AI secretion from rat small intestinal epithelium.

The small intestine is known to be an important synthetic site for certain apolipoproteins, which are subsequently secreted from the enterocyte into the mesenteric lymph. We have studied apolipoprotein AI and CIII content of the enterocyte during the course of fat feeding in order to determine their relative synthetic and secretory rates. Rat intestinal enterocytes were isolated from the entire jejunal villus after fat feeding in vivo. The apo AI content fell 50% as determined by RIA one and two hours after fat feeding. By four hours, the intracellular cellular levels had returned to prefeeding levels. These changes in apolipoprotein AI levels were not seen in the terminal ileum. Apolipoprotein CIII levels remained unchanged afer fat feeding. To determine the effect of free fatty acids on apolipoprotein AI secretion, organ culture explants were incubated for four hours in the presence and absence of 360 microM oleic acid bound to albumin. Apolipoprotein AI detected in the incubation media reflected release from the lamina propria (which was not colchicine sensitive), and secretion from the enterocyte (which was inhibited by colchicine). In the absence of oleic acid, enterocyte secretion of apolipoprotein AI accounted for about half of the apo AI recovered in the medium. In the presence of oleic acid, the total apolipoprotein AI content of the tissue increased by 50 percent. A similar increase in colchicine sensitive secretion was observed. The secretion of apolipoprotein AI from explants was more rapid in the presence of oleic acid and began without the half hour lag noted when oleic acid was absent. The mid intestine was most active in the secretion of apolipoprotein AI. These data are consistent with the hypothesis that in the first few hours after feeding the rate of secretion of apolipoprotein AI exceeds the synthetic capacity of the small intestinal epithelium.

Animals↗