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Biomedical subjects

T Saheki

Publications and source records attributed to T Saheki.

At least 91 records · Page 5Linked to original sources
PubMed1992

Serum calcium-decreasing factor (caldecrin) from porcine pancreas has proteolytic activity which has no clear connection with the calcium decrease.

We purified a serum calcium-decreasing factor, which showed chymotrypsin-like protease activity, from porcine pancreas to homogeneity. The factor administered to mice intravenously at a dose of 20 micrograms/kg b.w. decreased serum calcium by 15%. Treatment of the factor with the serine protease inhibitor, PMSF, caused a leftward shift in the dose-response curve, showing strengthened activity. It also caused a decrease in serum calcium and hydroxyproline levels in rats. At a dose of 10 ng/ml, the factor inhibited 45Ca release from cultured fetal long bone stimulated by parathyroid hormone (PTH) and PTH-related protein, but not by interleukin-1 alpha, prostaglandin E1 and 1,25-dihydroxy vitamin D3. No other well-known pancreatic proteases had these effects. In view of the results of experiments using protease inhibitor and pancreatic proteases, and in view of the specificity of this factor in vitro, we propose that the factor exerts its serum calcium-decreasing activity most probably not through proteolytic degradation of PTH, but through an inhibition of PTH action on bones by a yet undefined mechanism.

Animals↗
PubMed1992

Carnitine administration to juvenile visceral steatosis mice corrects the suppressed expression of urea cycle enzymes by normalizing their transcription.

Previous studies in our laboratories have revealed that juvenile visceral steatosis mice show suppressed transcription of urea cycle enzyme genes during development and are systemically deficient in carnitine. It has not yet been explained, however, how this carnitine deficiency relates to the abnormal gene expression. We investigated the effect of carnitine on abnormal gene expression, growth retardation, and fatty liver. Carnitine administration relieved the suppression of the developmental induction of two urea cycle enzymes examined, carbamoyl-phosphate synthetase and argininosuccinate synthase, and kept the activities of enzymes normal. However, carnitine did not reduce accumulated lipid in the liver to the normal level. These results suggest that carnitine deficiency plays an important role in the abnormal expression of urea cycle enzyme genes and that the abnormal expression of the genes is not directly caused by lipid accumulation in the liver.

Aging↗
PubMed1992

Abnormal expression of urea cycle enzyme genes in juvenile visceral steatosis (jvs) mice.

Juvenile visceral steatosis (jvs) mice from the C3H-H-2 degrees strain have markedly low levels of all the hepatic urea cycle enzymes (Imamura et al. (1990) FEBS Lett. 260, 119-121). The steady state levels of messenger RNA for the four urea cycle enzymes examined and also for albumin and serine dehydratase were severely reduced in the liver. The levels of mRNA for other liver-specific enzymes including aldolase B and phospho enol pyruvate carboxykinase did not vary significantly from normal littermates. As for extrahepatic expression of the urea cycle enzymes, only argininosuccinate synthetase in the kidney was decreased. Nuclear run-on experiments showed reduced transcription of the corresponding genes, which mostly accounts for the low mRNA levels. Furthermore, the time-course of mRNA accumulation from 5 days of age showed that the developmental induction of hepatic carbamyl phosphate synthetase and argininosuccinate synthetase mRNAs was strongly suppressed. These results suggest that jvs affects not only the regulation of the tissue-specific expression of the urea cycle enzymes but also the regulation of their developmental induction.

Animals↗
PubMed1992

Orthotopic liver transplantation for urea cycle enzyme deficiency.

Hyperammonemia, abnormalities in plasma amino acids and abnormalities of standard liver functions were corrected by orthotopic liver transplantation in a 14-day-old boy with carbamyl phosphate synthetase-I deficiency and in a 35-yr-old man with argininosuccinic acid synthetase deficiency. The first patient had high plasma glutamine levels and no measurable citrulline, whereas citrulline values were markedly increased in Patient 2. Enzyme analysis of the original livers showed undetectable activity of carbamyl phosphate synthetase-I in Patient 1 and argininosuccinic acid synthetase in Patient 2. Both patients were comatose before surgery. Intellectual recovery of patient 1 has been slightly retarded because of a brain abscess caused by Aspergillus infection after surgery. Both patients are well at 34 and 40 mo, respectively, after surgery. Our experience has shown that orthotopic liver transplantation corrects the life-threatening metabolic abnormalities caused by deficiencies in the urea cycle enzymes carbamyl phosphate synthetase-I and argininosuccinic acid synthetase. Seven other patients--six with ornithine transcarbamylase deficiency and another with carbamyl phosphate synthetase-I deficiency--are known to have been treated elsewhere with liver transplantation 1 1/2 yr or longer ago. Four of these seven recipients also are well, with follow-ups of 1 1/2 to 5 yr. Thus liver transplantation corrects the metabolic abnormalities of three of the six urea cycle enzyme deficiencies, and presumably would correct all.

Adult↗
PubMed1992

Argininosuccinate synthetase gene expression in leukemias: potential diagnostic marker for blastic crisis of chronic myelocytic leukemia.

Argininosuccinate synthetase (ASS) activity is hardly detected in human lymphocytes. In this study, we examined the ASS gene expression of various leukemia cells by a polymerase-chain-reaction method. We demonstrate here that (a) acute lymphocytic and acute myelocytic leukemia cells exhibit the highly elevated expression of the ASS gene and (b) chronic myelocytic leukemia (CML) in blastic crisis also exhibits the increase of ASS gene expression while CML in chronic phase, chronic lymphocytic leukemia and adult T leukemia cells show the similar level to that of normal lymphocytes. These results suggest that the ASS gene expression is of value as a diagnostic marker of acute type leukemia, particularly for blastic crisis of CML.

Adult↗
PubMed1991

Immunocytochemical localization of argininosuccinate synthetase in the rat brain.

The neuronal distribution of argininosuccinate synthetase (ASS) was mapped in the rat brain. Argininosuccinate synthetase is one of the enzymes of the arginine metabolic pathway and catabolizes the synthesis of argininosuccinate from aspartate and citrulline. Since arginine is the precursor of nitric oxide, argininosuccinate synthetase may act as part of the nitric oxide producing pathway. Argininosuccinate is also suggested to have a messenger function in the nervous system. Therefore, the localization of ASS is of great interest. Polyclonal antisera against purified rat liver argininosuccinate synthetase revealed a characteristic distribution pattern of argininosuccinate synthetase-like immunoreactivity: (1) many neurons with strong argininosuccinate synthetase-like immunoreactivity were observed in the septal area, basal forebrain, anterior medial and premammillary nuclei of the hypothalamus, anterior and midline thalamic nuclei, dorsal endopiriform nucleus of the amygdala, basal nucleus of Meynert, subthalamic nucleus, laterodorsal tegmental nucleus, raphe nuclei, nucleus ambiguus, and the area postrema, (2) neuropile staining was dense in the septal areas, hypothalamus, area postrema, nucleus of the solitary tract, and the laminae I and II of the caudal subnucleus of the spinal trigeminal nucleus and the spinal dorsal horn, (3) relay nuclei of the specific sensory systems such as the dorsal lateral geniculate nucleus and the ventral nuclei of the thalamus were devoid of argininosuccinate synthetase-like immunoreactivity, (4) no staining was seen in the large white matter structures such as the internal capsule, corpus callosum, and the anterior commissure, and (5) most of the neurons stained were small or medium in size and appeared to be interneurons. The results suggest that argininosuccinate synthetase affects the widely distributed, neuromodulatory system in the brain.

Animals↗
PubMed1991

Structure of the bovine atrial natriuretic peptide receptor (type C) gene.

The bovine gene encoding the type C atrial natriuretic peptide (ANP) receptor was isolated and characterized. The gene appears to exist as a single copy in the haploid genome and is comprised of eight exons distributed over more than 85 kilobases. The transcription start site was identified by primer extension and ribonuclease protection assay. A "TATA" box-like sequence was found just upstream of the start site (at position -32); however, no CAAT box was apparent. Exon boundaries of the ANP receptor gene correlated well with the functional domain boundaries of the receptor protein; for example, exon 1 contains coding information for a large proportion of the ANP-binding domain and the transmembrane and cytoplasmic domains are encoded by separate exons, namely by exon 7 and exon 8, respectively. These structural features suggest that the organization of the ANP receptor gene reflects the domain structure of the receptor.

Amino Acid Sequence↗
PubMed1991

The alpha-ketoacid dehydrogenase complexes. Sequence similarity of rat pyruvate dehydrogenase with Escherichia coli and Azotobacter vinelandii alpha-ketoglutarate dehydrogenase.

The pyruvate dehydrogenase complex and the alpha-ketoglutarate dehydrogenase complex are multienzyme complexes consisting of three different enzymes. No significant similarity has been reported among the dehydrogenases which are component enzymes of these complexes, despite the presence of homology among the other component enzymes. Here we isolated cDNAs for the alpha and beta subunits of rat pyruvate dehydrogenase and they exhibited a significant similarity of the amino acid sequences among rat pyruvate dehydrogenase, 2-oxoisovalerate dehydrogenase (which is a dehydrogenase component of branched chain alpha-ketoacid dehydrogenase complex) and alpha-ketoglutarate dehydrogenase, suggesting that they have been derived from a common ancestral dehydrogenase. Our results suggested that the alpha and beta subunits of the pyruvate and 2-oxoisovalerate dehydrogenases have been derived by the cleavage of the alpha-ketoglutarate dehydrogenase. However, we could not find significant homology between rat pyruvate dehydrogenase and Gram-negative bacterial pyruvate dehydrogenase.

Amino Acid Sequence↗
PubMed1991

Correction of ornithine transcarbamylase (OTC) deficiency in spf-ash mice by introduction of rat OTC gene.

We introduced rat ornithine transcarbamylase (OTC) gene into OTC-deficient spf-ash mice by mating spf-ash heterozygotes with transgenic mice which carried recombinant DNA composed of 1.3 kb of the 5' flanking region of the gene fused onto rat OTC cDNA. The liver OTC activity of hemizygous spf-ash mice which carried the transgene was about twice that of nontransgenic spf-ash mice, and the small intestinal OTC activity was 6 times higher; the values being 12% and 27% of the control levels, respectively. The transgenic spf-ash mice showed normal hair growth without sparse fur, nearly normalized urinary orotic acid excretion and normalized serum citrulline concentration.

Animals↗
PubMed1991

Animal model of systemic carnitine deficiency: analysis in C3H-H-2 degrees strain of mouse associated with juvenile visceral steatosis.

We analyzed carnitine profiles in C3H-H-2 degrees strain of mouse associated with fatty liver, hyperammonemia and hypoglycemia (Koizumi et al., 1988). Carnitine levels in serum, liver and muscle of mouse with fatty liver were markedly decreased in comparison with those of control mouse (littermates without fatty liver). This is a useful animal model to analyze the role of carnitine in lipid, amino acid and carbohydrate metabolism.

Aging↗
PubMed1991

L-argininosuccinate modulates L-glutamate response in acutely isolated cerebellar neurons of immature rat.

Fura-2 microfluorometry revealed that as little as 10(-13) M L-argininosuccinate, an intermediate of the L-arginine synthesizing pathway, is sufficient to reduce the increase in intracellular free calcium produced by L-glutamate in the acutely isolated cerebellar neurons of immature rats. In these neurons L-argininosuccinate also reduced the response to quisqualate, but not the response to kainate or N-methyl-D-aspartate. The results suggest that L-argininosuccinate may function as a transmitter or modulator in the brain.

Animals↗
PubMed1991

A case of citrullinemia with abnormal messenger RNA for argininosuccinate synthetase.

A male neonate, thus far healthy and fed with breast milk, developed rapidly increasing apathy on the third day of life. Sucking became poor and hyperhidrosis was present. Hyperammonemia (3,305 micrograms/dl) was noted. He became comatose and died on the fourth day. There was a profound derangement of amino acid concentration in the body fluids, with highly elevated citrulline levels (4.70 mumols/ml in serum and 8.47 mumols/ml in urine). Autopsy showed diffuse pulmonary bleeding, as the only noteworthy pathological finding. The liver contained no detectable argininosuccinate synthetase (ASS) activity. The defect of ASS in the present case was not due to a reduced amount of ASSmRNA, but its structure was found to be abnormal; it was approximately 1.57 kb in length due to a defect of about 0.1 kb near the 3' end of the coding region.

Amino Acid Metabolism, Inborn Errors↗
PubMed1991

Distribution of argininosuccinate synthetase-like immunoreactive neurons in the rat myenteric plexus: a whole mount study.

The distribution of argininosuccinate synthetase (ASS)-like immunoreactive neurons in the myenteric plexus of the rat alimentary tract were immunocytochemically studied using whole-mount tissues. The present study revealed ASS-like immunoreactive meshworks of ganglia and interconnecting nerve strands in the myenteric plexus of almost all parts of the alimentary tract. ASS-like immunoreactive neurons constituted about 11% of the myenteric cell.

Animals↗
PubMed1990

Differential cellular localization of enzymes of L-arginine metabolism in the rat brain.

Polyclonal rabbit antisera specific to argininosuccinate synthetase (ASS), argininosuccinate lyase and arginase revealed that these enzymes of L-arginine metabolism are generally localized in different cells of the rat brain. In the main olfactory bulb and the cerebellar cortex the three immunoreactivities were localized in different cells: in the somatic motor nuclei ASS-like immunoreactivity was localized in incoming fibers, and the other two enzymes were found in the motor neurons. The results suggest that L-argininosuccinate and/or L-arginine may be transcellularly transported in the nervous system.

Animals↗
PubMed1990

Urea cycle disorder in C3H-H-2 degree mice with juvenile steatosis of viscera.

We determined the activities of urea cycle enzymes in the liver of C3H-H-2 degree-jsv mice. The activities of all urea cycle enzymes decreased in the latter period of lactation. The activities of carbamylphosphate synthetase and ornithine transcarbamylase in some affected mice were undetectable. On the other hand, the activities of enzymes other than urea cycle enzymes were normal. We consider that the decrease in the urea cycle enzymes is caused by an abnormality in the mechanism of gene expression.

Ammonia↗
PubMed1990

Clearance of argininosuccinate synthetase from the circulation in acute liver disease.

Argininosuccinate synthetase is an enzyme which has been found to be a specific marker for liver damage. In patients with acute hepatitis, the concentration in serum increases at the onset of the disease, but later decreases more quickly, so that the time required for normalization is shorter than that of alanine aminotransferase. This is probably caused by rapid clearance of argininosuccinate synthetase from the serum. Rapid clearance was demonstrated in experimental animals given purified enzymes intravenously. Argininosuccinate synthetase disappeared from the serum with a half life of about 15 min, while the half lives of alanine aminotransferase and aspartate aminotransferase were 4 and 5 h, respectively, under the same conditions.

Acute Disease↗