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Biomedical subjects

H Ohkubo

Publications and source records attributed to H Ohkubo.

At least 181 records · Page 10Linked to original sources

Role of portal and splenic vein shunts and impaired hepatic extraction in the elevated serum bile acids in liver cirrhosis.

To study the mechanism for the elevation of serum bile acids in liver cirrhosis, bile acid concentrations were measured in the portal, superior mesenteric, and splenic veins, using percutaneous transhepatic catheterization, and compared with those of peripheral veins in 41 patients with mild to moderately advanced cirrhosis. The demonstrated gradient of bile acid concentration was superior mesenteric vein greater than portal vein greater than peripheral vein nearly equal to splenic vein, suggesting that the superior mesenteric vein is the main route of transport for the intestinally absorbed bile acids. Bile acid concentrations in peripheral vein were correlated with the measured portal and splenic vein shunt indexes. The ursodeoxycholic acid oral tolerance test carried out in 10 patients during portal vein catheterization demonstrated that hepatic extraction of this bile acid was correlated with indocyanine green clearance and that it was inversely correlated with portal vein shunt index. These findings are consistent with the view that distorted hepatic blood flow has a significant role in elevating serum bile acid, at least in patients with moderately advanced liver cirrhosis.

Adolescent↗

Recurrent laryngeal nerve paralysis. A 10-year review of 564 patients.

A retrospective review of the clinical records of 564 patients with recurrent laryngeal nerve paralysis examined at the Department of Otolaryngology, Kurume University Hospital during the 10-year period from 1971 to 1980 was completed. The results are summarized as follows: 1) Two-hundred and ninety-three patients were male and 271, female. The incidence was high in old age groups. 2) Idiopathic paralysis (233 cases) was the most frequent and paralysis caused by thyroid surgery (68 cases) and endotracheal intubation (63 cases) came next. 3) The lesion was unilateral in 519 patients (right to left = 148 to 371) and bilateral in 45. 4) The paralytic vocal fold was fixed in the paramedian position in the majority of the patients. A limited movement of the paralytic fold was observed in some cases, especially those of paralysis caused by endotracheal intubation and idiopathic paralysis. 5) A compensatory overcrossing of the unaffected vocal fold was found in 41 patients. It developed within six months from the onset in most cases. 6) Spontaneous recovery and improvement of mobility took place in 54 of the 165 patients who could be followed up for 1 year or longer. Paralysis caused by endotracheal intubation showed the best prognosis and idiopathic paralysis came next. 7) Spontaneous voice recovery and improvement occurred in 183 of the 240 patients whose voice outcome was determined. 8) Phonosurgical treatments yielded good results in most cases. Some patients, however, had their voice receded later.

Adolescent↗

Non-specific granuloma of the larynx. A 10-year review of 63 patients.

During the 10 years from 1971 to 1980, 63 cases of non-specific granuloma of the larynx were examined at the Department of Otolaryngology, Kurume University Hospital. Of the entire 63 cases, 51 were intubation granulomas, 5, contact granulomas and 7, granulomas of unknown etiology. A review of the clinical records of these patients was completed. The results are summarized as follows; 1) In intubation granulomas, there was a significant preponderance of females over males (43 to 8). The age ranged from 9 to 72 years. The lesion was bilateral in 21 cases and unilateral in 30. All the granulomas but one were located at the cartilaginous portion. Twenty-one (75%) of the 28 cases which were surgically treated got healed, 6 (21%) developed a recurrence and 1 was lost to follow up. 2) All 5 patients with contact granulomas were males. Their lesions were unilateral. Three patients were surgically treated. Two of these 3 had no recurrence while the other developed a recurrence, which disappeared following conservative treatments. One patient was successfully treated with conservative modalities. 3) Granulomas of unknown etiology were found in 5 males and 2 females. Their age ranged from 19 to 70 years. The lesion was unilateral in all 7 cases. Three patients were surgically treated. Two of these 3 required repeated surgeries. One patient was successfully treated by means of conservative therapy.

Adolescent↗

Cloning and sequence analysis of cDNA for human renin precursor.

The primary structure of human renin precursor has been deduced from its cDNA sequence. A library of cDNA clones was constructed from human kidney poly(A)+ RNA by applying the vector/primer method of Okayama and Berg. The library was screened for human renin sequences by hybridization with the previously cloned mouse renin cDNA. Of the 240,000 colonies screened, 35 colonies that were positive for hybridization were isolated. Two recombinant plasmids containing long inserts of about 1,300 and 1,600 base pairs were selected for sequence analysis. The amino acid sequence predicted from the cDNA sequence shows that the human renin precursor consists of 406 amino acids with a pre and a pro segment carrying 20 and 46 amino acids, respectively. A high degree of sequence homology was found upon comparison of the mouse and human renins. Close similarities were also observed in the primary structures of renin and aspartyl proteinases that have known three-dimensional structures, suggesting a similar tertiary structure for renin.

Amino Acid Sequence↗

Cloning and sequence analysis of cDNA for rat angiotensinogen.

A mixture of tetradecamer oligodeoxyribonucleotides complementary to the codons specifying the carboxyl-terminal sequence, Ile-His-Pro-Phe-His, of angiotensin was chemically synthesized as two pools and used for the isolation of a cDNA clone specific for angiotensinogen from a cDNA bank of rat liver mRNA sequences. The two pools (oligo 1 and oligo 2), each containing 24 oligodeoxyribonucleotides, were first used as primers to initiate reverse transcription of rat liver mRNA. One of the pools (oligo 1) was found to prime a specific 32P-labeled cDNA of approximately 160 nucleotides that contained the anticoding sequence corresponding exactly to the amino acid sequence of rat angiotensin. This cDNA, in turn, was used to rescreen cDNA clones that were isolated by initially selecting the rat liver cDNA bank by hybridization with the oligo 1 mixture. One clone thus obtained, designated pRag16, was subjected to nucleotide sequence analysis and verified to contain a nearly full-length cDNA sequence coding for rat angiotensinogen precursor. The deduced amino acid sequence indicates that the precursor molecular consists of angiotensinogen of 453 amino acid residues and a putative signal peptide of 24 amino acid residues. The predicted molecular weight and amino acid composition of angiotensinogen agree well with those determined by using the purified protein. An angiotensin moiety is located at the amino-terminal part of angiotensinogen, preceded directly by the signal peptide and followed by a large carboxyl-terminal sequence that contains two internally homologous sequences and three potential glycosylation sites.

Amino Acid Sequence↗

KC-404: a potential anti-allergic agent with antagonistic action against slow reacting substance of anaphylaxis.

The mode of action of a novel compound, 3-isobutyryl-2-isopropylpyrazolo [1,5-a]pyridine (KC-404), as a potential anti-allergic agent has been investigated. KC-404 was shown to have a direct bronchodilator activity in guinea pig trachea in vitro and in anesthetized guinea pig in vivo. In addition, KC-404 had a fairly selective antagonistic action against slow reacting substance of anaphylaxis (SRS-A) on guinea pig ileum in vitro. In anesthetized guinea pigs, ED50 values for intravenously and intraduodenally injected KC-404 to inhibit SRS-A-induced bronchoconstriction were 0.0014 and 0.0065 mg/kg, respectively. Much higher doses were required to inhibit bronchospasms produced by histamine or particularly by acetylcholine. Orally administered KC-404, 0.001 to 0.1 mg/kg, also showed a selective inhibitory effect on increased vascular permeability by intradermal SRS-A in guinea pigs and rats. KC-404 inhibited the immunological release of mediators, notably SRS-A from sensitized guinea pig chopped lung in vitro at 10(-8) to 10(-4) g/ml. In vivo, the release of SRS-A, but not of histamine, mediated by a nonreaginic antibody in the peritoneal cavity of sensitized rats was inhibited by KC-404 at oral doses above 3 mg/kg. In a similar anaphylactic reaction but mediated by a reaginic antibody, KC-404 also inhibited SRS-A release at intraperitoneal doses of 2.5 to 10 mg/kg. The inhibitory activity on histamine release was less than half of that on SRS-A release. These results indicate that KC-404 is an orally active compound with a unique mode of action to inhibit preferentially both the effects and immunological release of SRS-A.

Animals↗

Angiotensinogen and kininogen: cloning and sequence analysis of the cDNAs.

The primary structures of the angiotensinogen precursor and the low molecular weight (LMW) kininogen precursors have been deduced by determining the nucleotide sequences of cloned DNAs complementary to their mRNAs. The angiotensinogen precursor consists of a mature angiotensinogen of 453 amino acid residues and a putative signal peptide of 24 amino acid residues. An angiotensin moiety is located at the amino-terminal part of angiotensinogen, preceded directly by the signal peptide and followed by a large carboxyl-terminal sequence that contains two internally homologous sequences and three potential glycosylation sites. The LMW kininogen precursors are encoded by two very similar but distinct mRNAs and composed of 436 and 434 amino acid residues. Both kininogens contain two internally homologous sequences in which all amino acid differences between the two kininogens are located. This suggests that these homologous regions may be biologically significant in relation to the existence of two LMW kininogens.

Amino Acid Sequence↗

Unusual methylation pattern of the alpha 2 (l) collagen gene.

We studied the methylation pattern of the alpha 2 (type 1) collagen gene in DNA from five cell types with varying rates of type I collagen synthesis: chick embryo fibroblast (CEF), CEF transformed by Rous sarcoma virus, erythrocyte, brain and sperm. The methylation-sensitive restriction enzymes, Msp I, Hpa II, Ava I and Sma I were used to detect methylation in three regions of the alpha 2 (type I) collagen gene: a 5.7 kb region, which includes the start site of transcription and the first two exons of the collagen gene; a 5.2 kb region containing exons in the middle of the gene; and a 3.5 kb region containing exons in the 3' portion of the gene. The DNA around the start site of transcription is not methylated whether or not the cells synthesize collagen. In contrast, the DNA from the central and 3' region of the gene is methylated to about the same extent whether or not the cells make collagen. Our data indicate that a gene that is methylated can be actively transcribed and that the level of expression of the alpha 2 (type I) collagen gene seems to be independent of methylation.

Animals↗

Developmental changes of brainstem auditory evoked potentials (BAEPs) in normal human subjects from infants to young adults.

BAEP has been found to be useful for assessment of subcortical maturation. However, the precise maturational changes of the peripheral and central transmission in normal human subjects are still open to controversy. We obtained a total of 200 BAEPs from 165 normal human subjects ranging from infants to young adults. Electrodes were placed at both mastoids and the reference at the vertex. 85 dB SL click stimuli were presented binaurally at a rate of 13/sec and 2,048 responses were summated on line with an averager. Investigation of the maturation of the transmission time indicated that the peripheral auditory apparatus attains functional maturity during the first 2 months of life, whereas the central transmission time shortens up to the age of 5 to 8 years. III-II and V-IV interpeak latencies (IPLs) showed maturational changes similar to those of V-I IPLs, in contrast II-I and IV-III showed little changes. A clear increase of the amplitude of peak V up to 4 years of age and a subsequent decreasing tendency was observed. The V-I IPLs of males were longer than those of females in each age group. Females also displayed larger BAEPs for wave V than males after 2 years of age. These data indicate that it is worthwhile to have separate latency and amplitude norms for males and females from infants to adults for attaching diagnostic significance to BAEP measures.

Adolescent↗

Peripheral neuropathy in children on long-term phenytoin therapy.

Nerve conduction studies of the ulnar, median, posterior tibial, peroneal and sural nerves were performed in 21 epileptic children aged 6 to 17 years on long-term phenytoin therapy. Auditory brain stem evoked responses were obtained in 16 patients to evaluate the effect of phenytoin on central nervous system synapses. Of the 21 patients examined, 15 (71.4%) showed abnormal findings. The most frequent abnormality was slowed motor conduction velocity of the ulnar nerve (33.3%) and posterior tibial nerve (23.8%), followed by slowed sensory conduction velocity of the sural nerve (20%), lowered H/M ratio (14.3%), slowed motor conduction velocity of the peroneal nerve (14.3%) and of the median nerve (14.2%). A significant correlation was noted between the total dosage and duration of therapy with PHT and the reduction of motor conduction velocity in the posterior tibial nerve. Auditory brain stem evoked responses showed no significant differences in each peak latency between the patients and the normal control group. The study indicates that long-term phenytoin therapy can cause latent impairment of peripheral nerve function in children with no clinical evidence of peripheral neuropathy.

Adolescent↗

Structure of the promoter for chicken alpha 2 type I collagen gene.

The chicken alpha 2 type I collagen gene is 38 kilobases long and its coding information is subdivided into more than 50 exons. In the current study, we used primer extension and S1 nuclease mapping to determine the sequence of the 5' end of alpha 2 collagen mRNA and to locate the start site for transcription of the alpha 2 collagen gene. The DNA sequence around the start site for transcription shows a typical Goldberg-Hogness sequence, 5' T-A-T-A-A-A-T 3', between -33 and -26 and a 5' G-C-C-C-A-T-T 3' sequence ("CAT" box) between -84 and -78. Three AUGs are found in the initial portion of the mRNA, the first from +54 to +56, the second from +117 to +119, and the third from +134 to +136. The first two AUGs are followed by short coding sequences that could specify a hexapeptide a tetrapeptide, respectively. Only the third AUG is followed by an open reading frame coding for a sequence that presents considerable homology with the previously determined amino acid sequence of prepro alpha 1 collagen. In the promoter region sequence there are several extensive dyads of symmetry. Three of these inverted repeats which precede the start site for transcription overlap each other and may have a role in the developmental regulation of this gene.

Animals↗