Search PubMed⌕ Search

Biomedical subjects

H Ohkubo

Publications and source records attributed to H Ohkubo.

At least 199 records · Page 11Linked to original sources

Ursodeoxycholic acid oral tolerance test in patients with constitutional hyperbilirubinemias and effect of phenobarbital.

An oral tolerance test using a 25-mg dose of ursodeoxycholic acid was carried out in 46 patients with constitutional hyperbilirubinemias: 26 with Gilbert's syndrome, 9 with Dubin-Johnson syndrome, 7 with Rotor Syndrome, 3 with constitutional indocyanine green intolerance, and 1 with Crigler-Najjar syndrome type II; they were compared with 14 healthy control subjects. The integrated area under the curve of increments of serum UDCA above the base line between 0 and 2 h after oral administration was significantly increased in patients with Gilbert's syndrome and Dubin-Johnson syndrome, whereas it was normal in patients with Rotor syndrome and constitutional indocyanine green intolerance. As the area under the curve reflects the hepatic clearance of intestinally absorbed ursodeoxycholic acid and therefore gives a quantitative estimate of hepatic ursodeoxycholic acid clearance, the hepatic clearance of ursodeoxycholic acid seems to be impaired in patients with Gilbert's syndrome and Dubin-Johnson syndrome. Administration of phenobarbital, 100 mg/day for 2 wk, improved the ursodeoxycholic acid tolerance test in concordance with the reduction in serum bilirubin in 9 patients with Gilbert's syndrome studied. If the turnover of ursodeoxycholic acid is representative of that of other bile acids, these findings suggest that the hepatic transport of bile acid is impaired like other anions in patients with certain constitutional hyperbilirubinemias.

Administration, Oral↗

The collagen gene: evidence for its evolutinary assembly by amplification of a DNA segment containing an exon of 54 bp.

We have determined the size and sequence of 8 exons in the gene that specifies chick type 1 alpha 2 collagen. These 8 exons represent three different segments of the gene, but all encode information for the helical portion of the protein. Seven exons have a length of 54 bp, and the 8th has a size of 99 bp. The sequences within these exons vary except for th glycine codons, which occur every third triplet. Each exon begins with a glycine codon and ends with a triplet that precedes a glycine codon. The size and the sequences of the introns do not show any homology except at their ends. Of 7 introns examined the first six bases at the 5' end of 5 of these are identical. The sequences at the 3' end of the introns also show homologies. Our results imply that the ancestral gene for collagen arose by multiple duplications of a single genetic unit containing a 54 bp condig segment. The sequences within these exons drifted by successive point mutations and in some cases by additions or deletions of 9 bp or multiples of 9 bp.

Animals↗

Isolation and characterization of overlapping genomic clones covering the chicken alpha 2 (type I) collagen gene.

A series of overlapping recombinant clones, which cover the alpha 2 (type I) collagen gene, have been isolated by stepwise screening of two libraries of chicken genomic DNA fragments. The first genomic clone was isolated by using a cloned cDNA containing alpha 2 collagen DNA sequences as hybridization probe. The other clones were obtained by a sequence of screenings using defined fragments of the successive genomic clones as hybridization probes. Several types of experiments indicated that the DNA of these clones are truly overlapping and span 55 kilobase pairs of contiguous DNA sequences in the chicken genome. Sequence analysis of small DNA segments of some of these clones confirm that they contain coding sequences which specify alpha 2 collagen. Electron microscopic analysis of hybrids between type I alpha 2 collagen mRNA and the overlapping genomic clones indicates that the chicken alpha 2 collagen gene has a length of at least 37 kilobases, about 7.4 times longer than the corresponding translatable cytoplasmic mRNA. The coding information for alpha 2 collagen is distributed in more than 50 coding sequences which are interrupted by intervening sequences of various sizes. The structure of the gene implies that the conversion of precursor RNA to mature mRNA for alpha 2 collagen includes at least 50 splicing events.

Animals↗

Studies on nicotinic acid interaction with bilirubin metabolism.

The mechanism by which intravenous administration of nicotinic acid (NA) increases serum unconjugated bilirubin in patients with the Gilbert's syndrome has been investigated. Studies using the technique of percutaneous transhepatic catheterization of the splenic vein and coil planet centrifuge suggested that following intravenous injection of NA some of the circulating erythrocytes were rendered osmotically fragile and trapped by the spleen and that unconjugated bilirubin increased in the splenic vein blood. In patients with liver cirrhosis, the increments of unconjugated bilirubin were closely correlated with the weights of the spleens removed for the management of varices. In rats, intravenous NA injection enhanced heme oxygenase activities in the spleen, but not uridine-5'-diphosphate (UDP)-glucuronyltransferase activity in the liver. These results are consistent with the hypothesis that NA-induced unconjugated hyperbilirubinemia is a result of complex reactions which include increased erythrocyte fragility, increased splenic heme oxygenase activity, and increased formation of bilirubin in the spleen.

Adult↗

Effects of caloric restriction on the kinetics of indocyanine green in patients with liver diseases and in the rat.

The effect of caloric restriction on the hepatic uptake and excretion of indocyanine green (ICG) was studied in man as well as in rats. It was demonstrated that following a 72-hr caloric restriction in man, the plasma clearance rate for ICG was increased significantly at the low dose of 0.5 mg/kg, and transport maximum was increased without a significant change of storage capacity. In rats, the maximal biliary excretion was significantly increased after 48-hr fast, but neither maximal hepatic uptake (Vmax) nor hepatic ICG content was altered. The evidence is consistent with the view that fasting increases the ICG plasma clearance at low doses by enhancement of excretory steps at the bile canalicular membrane.

Adult↗

Isolation and characterization of a plaque-forming lambda bacteriophage carrying a ColE1 plasmid.

A plaque-forming lambdaimm434 bacteriophage carrying the entire genome of colicinogenic factor E1 has been isolated and characterized. This phage, lambdaimm434ColE1, can lysogenize as a stable plasmid within a recombination-deficient Escherichia coli cell that lacks the normal attachment site for lambda phage. Furthermore, it has been found that lambdaimm434ColE1 phage carrying amber mutations in the O and P genes of the lambda genome, i.e., lambdaimm434OamPamColE1, behaves as a plaque-forming phage, and this finding suggests that the ColE1 factor DNA permits replication of the DNA of the plaque-forming phage.

Bacteriocin Plasmids↗

Effects of 1-methyl-5-chloroindoline methylbromide (S-6) on Renshaw cells of cats.

Effects of 1-methyl-5-chloroindoline methylbromide (S-6) on Renshaw cells were investigated in cats anesthetized with pentobarbital sodium. S-6 proved to have little effect on spike discharges of Renshaw cells when administered intravenously, but the agent electrophoretically applied revealed excitatory effects which resembled the action of methacholine and such effects were blocked by intravenous administration of atropine. It was conlcuded that (1) S-6 is impermeant to the blood brain barrier and (2) the excitatory action of S-6 on Renshaw cells is muscarinic in nature.

Acetylcholine↗

Marked delay in indocyanine green plasma clearance with a near-normal bromosulphophthalein retention test: a constitutional abnormality?

Five patients showing a normal to near-normal BSP test and a marked delay in ICG plasma clearance, and two families with clustering of the same abnormality, are described. Two had Gilbert's syndrome, one was convalescing from acute hepatitis, and the other two had no detectable liver abnormality. Measured indices of ICG metabolism indicated a marked reduction in the hepatic uptake, storage capacity, biliary transport maximum, and an increased reflux into plasma. Biochemical studies on the binding of ICG by plasma proteins failed to demonstrate any difference from normal controls. Thus, the primary defect seems to be in the transport of ICG by the hepatocyte. Although the relationship of the defect in ICG metabolism to other constitutional hyperbilirubinaemias is not clear, it is possible that the defect in these patients is a constitutional one involving some steps in the hepatic disposal of organic anions.

Adult↗

Relationship between the levels of intracellular cyclic nucleotides and mechanical responses induced by drugs.

The tracheal smooth muscle dissected free from connective tissues was used as a test preparation, since isoprenaline caused a decrease in cyclic GMP in the muscle while it caused an increase in cyclic GMP in the remaining tracheal tissue. Acetylcholine, histamine and papaverine increased both cyclic AMP and cyclic GMP levels in the tracheal muscle. Isoprenaline increased the cyclic AMP level but decreased the cyclic GMP level. However, when tracheal muscle was incubated with isoprenaline in the presence of acetylcholine, isoprenaline did not cause a decrease in cyclic GMP but rather a significant increase in cyclic AMP after only 1 min incubation. These results indicate that the relaxation of the tracheal muscle by isoprenaline is initiated by the increase in cyclic AMP but is not associated with the change in cyclic GMP.

Acetylcholine↗