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Biomedical subjects

S Ohta

Publications and source records attributed to S Ohta.

At least 703 records · Page 39Linked to original sources

[Choleretic effects of methanol extracts obtained from various Chinese traditional medicine].

Choleretic effects of 60 kinds of Chinese traditional medicine frequently used in clinical practice were investigated. Consequently, significant effects of choleretics were found in the methanol extracts of Ko-so-san, Intinko-to, Saiko-seikan-to, Hange-koboku-to, Antyu-san, Syo-kankyo-to, Keisi-syakuyaku-timo-to, Senkan-meimoku-to, Bohu-tusyo-san, Juzen-taiho-to, Jumi-haidoku-to Kami-syoyo-san and Hange-syasin-to. Water extracts of these Chinese traditional medicine had no such effect. Alteration of excretion of various biliary components after administration of the methanol extracts with the choleretic effect was examined, and with all medicines, bile acid excretion decreased and sodium and potassium excretions increased. Therefore, a medicine inducing choleresis involves some selective increases in the bile acid-independent fraction of bile flow. And after administration of methanol extracts of Keisi-syakuyaku-timo-to and Bohu-tusyo-san, lithogenic index, an index of saturation level of cholesterol, decreased significantly. Therefore, with these medicines, a dissolving effect on cholesterol gallstone is expected.

Animals↗

Teratogenic effects of carboplatin, an oncostatic drug, administered during the early organogenetic period in rats.

In the preceding study, no teratological effects against rat fetuses were observed when carboplatin, an oncostatic platinum coordination complex, was dosed to their dams from days 7 to 17 of gestation at a dose level of 4 mg/kg/day. However, there are a few reports which show the teratogenic action of carboplatin injected from days 6 to 15 of pregnancy at a dose level of 6 mg/kg/day. In the present study, carboplatin was administered intravenously to pregnant female Crj: CD (Sprague-Dawley) rats from days 6 to 9 or 7 to 10 of gestation at a dose level of 6 mg/kg/day in order to know the teratogenicity of this drug. Carboplatin were highly embryolethal in dams when dosed from days 6 to 9 of gestation, but not in animals when injected from days 7 to 10 of pregnancy. Carboplatin also produced external, internal and skeletal anomalies in fetuses such as gastroschisis, dilatation of cerebral ventricles, cleft sternum, fused ribs, malformed thoracic vertebra when administered from days 6 to 9 of gestation, but not in conceptuses when dosed from days 7 to 10 of pregnancy. However, the delayed ossification which was ascribed to the fetal growth retardation was observed in rats treated with this drug during both administration periods. These results suggest that carboplatin is embryotoxic, inducing intrauterine death and congenital malformations in rats, when injected during the early stages of gestation including day 6 of pregnancy.

Abnormalities, Drug-Induced↗

[The effect of acute hypocarbia on human auditory brainstem responses].

The effect of acute hypocarbia on auditory brainstem responses (ABRs) was studied in nine patients scheduled for cranioplasty under N2O/O2/fentanyl anesthesia. PaCO2 was allowed to stabilize for 15 min before ABR recordings were obtained during normocarbia [N] (PaCO2 = 40.8 +/- 1.9 mmHg), hypocarbia [H] (PaCO2 = 25.9 +/- 0.8 mmHg), and after return to normocarbia [NR]. No significant change in the absolute or interpeak latencies of waves I, III, and V was observed between during [N] and [H]. On return to normocarbia, the absolute latencies of waves I, III, and V increased slightly but significantly when compared with [N] or [H], although the interpeak latencies were unchanged. It is concluded that the latencies of ABR are unaffected directly by acute hypocarbia to a PaCO2 of 25 mmHg. The increase of absolute latencies on return to normocarbia may be explained by increased middle ear pressure with N2O and/or increased intracranial pressure.

Brain Stem↗

[Evaluation of toxic effects on yusho causal substances by chick embryo hepatic microsomal enzymes activities].

PCBs, non-ortho chlorine substituted PCBs (Co-PCBs), PCQs and (PCDFs + PCDDs), all of which contained similar compositions of those corresponding in yusho oil, were prepared from a PCB preparation used as a heat exchanger fluid. After dissolved in 1, 4-dioxane, they were applied into the air sac of white leghorn eggs incubated for 16.5 days at 37.5 degrees C. Forty eight hours after injection, the hepatic benzo(a)pyrene hydroxylase (AHH) and 7-ethoxyresorufin deethylase (EROD) activities were assayed. The average relative potencies of induction for the two microsomal drug metabolizing enzymes by (PCDFs + PCDDs), Co-PCBs, PCBs and PCQs were 100, 13.4, 0.0006 and 0.0004, respectively. The toxic effects for yusho disease by these substances were calculated from the relative enzyme induction potencies and the average concentrations in yusho oils with the production dates of February 9 and 10, 1968. Consequently, the relative toxicities of (PCDFs+PCDDs), Co-PCBs, PCBs and PCQs were 100, 13.2, 0.06 and 0.12, respectively. This result, as well as our previous investigations using rats and monkeys, insists that (PCDFs+PCDDs) are the primary causal agents for yusho disease. However, the Co-PCBs, which were recently detected in the yusho oils by us, were revealed to be fairly effective in yusho manifestation. In addition, it was cleared that the hepatic enzyme induction by the Co-PCBs fraction, which contained other several PCB isomers, was almost completely contributed by only Co-PCBs such as 3,4,3',4'-tetra- 3,4,5,3',4'-penta- and 3,4,5,3',4',5'-hexachlorinated biphenyls present in the fraction. A chemical uptake rate from the air sac by the chick embryo decreased significantly in the cases of extremely high doses of PCBs (10,000 micrograms/egg) and PCQs (3,333 and 10,000 micrograms/egg), and result the elevations of hepatic enzymes activities were depressed, indicating that the suitable chemical dose amount to be less than about 1,000 micrograms/egg.

Animals↗

Defective gene in lactic acidosis: abnormal pyruvate dehydrogenase E1 alpha-subunit caused by a frame shift.

A patient with lactic acidosis showed a lowered pyruvate dehydrogenase E1 activity and fatigued on slight exercise. The cDNA encoding the pyruvate dehydrogenase E1 alpha-subunit from his lymphocytes, transformed by infection of Epstein-Barr virus, was cloned and sequenced. The nucleotide sequence determination revealed that the gene had a deletion of four nucleotides at the second codon upstream from the termination codon. This deletion would lead to a reading-frame shift and make a new termination codon at the 33d codon downstream from the "normal" termination codon. An S1 nuclease-protection experiment confirmed the presence of mRNA with its deletion in the patient. Amplification, by the polymerase chain reaction method, of the genomic-DNA region from his peripheral blood cells showed that the deletion was localized in an exon and that it was not caused by an abnormal splicing at the intron/exon junction. This is the first report on cloning a defective gene of the pyruvate dehydrogenase complex.

Acidosis, Lactic↗

[The hepatic hemodynamic response to intra-arterial infusion of vasoactive agents--Part 2. Blood flow measurements in rats with liver cancer].

The tissue blood flow (TBF) of primary liver cancer and normal live in 54 rats were measured following infusion of vasoactive agents into the celiac axis under continuous recording of blood pressure. Angiotensin II (AT) (1.0 micrograms/kg/min) and Prostaglandin F2 alpha (PGF) (1.0 micrograms/kg/min) were used. The former increased TBF of the tumor and blood pressure and the latter reduced TBF of the tumor with no remarkable change of the blood pressure, but both drugs made little or no influence on TBF of the normal liver. Dibutyryl cyclic AMP (DBcAMP) (2.0 mg/kg/hr) infusion increased TBF of the both tumor and normal liver with no significant change of blood pressure. PGF (1.0 micrograms/kg/min) infusion after preinfusion of DBcAMP did not cause the decrease of TBF of the tumor.

Angiotensin II↗

[Kappa-type opioid receptor in human placental membrane].

Since many opioid receptor preparations are heterogeneous systems containing multiple types of receptor, characterization of each type of the receptor is influenced by contamination with other types of receptor. Demonstrating kappa receptor proved more difficult owing to the ability of kappa ligands to interact with a number of receptor classes and to the lack of the homogeneous preparation. It has been reported that kappa ligands selectively bind to human placental membrane. To establish homogeneous kappa receptor preparation, the kappa binding to human placenta was characterized. The portion which was predominantly villus tissue was removed from freshly collected placenta, and the P3-membrane fraction was prepared. Kappa opioid agonist, such as 3H-Dynorphin A, 3H-ethylketocyclazocine and 3H-U-69593, bound to the human placental membrane fraction in a manner of single class of binding site (Bmax: approximately 40 fmol.mg-1 protein). In contrast, 3H-dihydromorphine, 3H-DAGO (mu agonist), 3H-DADLE (delta agonist) or 3H-SKF-10047 (sigma agonist) showed no binding activity. The specific binding of 3H-diprenorphine was displaced only by kappa-selective ligand (U-50488H, dynorphin, butorphanol). These results suggest that opioid binding in human placental membrane is specific for kappa opioid.

Humans↗

[Tetrahydroisoquinolines in connection with Parkinson's disease].

Tetrahydroisoquinoline (TIQ) derivatives have been assumed to be substances closely related to parkinsonism because of their structural similarity to MPTP, which induces parkinsonism. TIQ and 1-methyltetrahydroisoquinoline (1MeTIQ) could be detected in human brains. The 1MeTIQ content in the frontal lobe of parkinsonian cases was markedly reduced than in non-parkinsonian cases. In addition, it could be recognized that 1MeTIQ content was decreased with aging both in the control and parkinsonians. It can be presumed that 1MeTIQ plays a role in protecting the brain from parkinsonism or aging processes. TIQ and 1MeTIQ were also present in a number of foods. It can be pointed out the possibility of TIQ intake from some foods. Metabolism of TIQ was defective in female DA, rat an animal model of a poor debrisoquine metabolizer. The female DA rat showed significantly higher brain accumulation of TIQ. These results suggest that the metabolic detoxication process is depressed and TIQ accumulation in the brain is enhanced in a poor debrisoquine metabolizer, which may be one possible explanation for poor debrisoquine metabolizers being susceptible to Parkinson's disease.

Aging↗

[A case report of reflex sympathetic dystrophy treated with nifedipine].

Reflex sympathetic dystrophy (RSD) refers to a symptom complex observed after nerve injury and consists primarily of severe burning pain associated with sensory, vasomotor and trophic phenomena. A 54-year-old male had undergone nephrectomy. At surgery left XIth intercostal nerve had been injured by cautery. After a few weeks following surgery, the patient developed progressive deep burning pain, stabbing sensation and dysesthesia in the left abdominal region. Analgesics and narcotics were ineffective. We diagnosed his case as RSD. He received nifedipine 10mg sublingually. Pain relief was obtained within 10min and lasted for 6hs. Consequently, nifedipine therapy was started at a daily dose of 30 to 60mg. His symptoms were markedly improved within 4 weeks. After 3 months his pain resolved. At the present, some pain often returns, but nifedipine is effective. Nifedipine may be useful as a drug for the management of reflex sympathetic dystrophy.

Humans↗

[Total anomalous pulmonary venous connection in adult: report of a case].

Total anomalous pulmonary venous connection (TAPVC) is a cardiac disorder that seldom permits survival into adulthood without surgical correction in infancy. We reported a successful total correction in a 47-year-old man with TAPVC. Cardiovascular angiography demonstrated the features of Darling I a type TAPVC. Cardiac catheterization showed Qp/Qs: 5.8, Pp/Ps: 0.31, Rp/Rs: 0.06 and mild pulmonary hypertension. On operation, the posterior wall of left atrium anastomosed to the common pulmonary vein over 4 cm length, ASD (5.0x3.8 cm) was closed with patch, and the communicating vein was ligated. The patient made uneventful postoperative recovery and is well 3 months following surgery.

Anastomosis, Surgical↗

Complete cDNA encoding a putative phospholipase C from transformed human lymphocytes.

Phosphoinositide-specific phospholipase C (PLC) is a crucial enzyme in transmembrane signaling. A cDNA encoding the putative phospholipase C was cloned from human lymphocytes that were transformed by infection with Epstein-Barr virus. The deduced amino acid sequence of the cDNA accounted for 146.1 kDa of the molecular mass of the complete enzyme and showed 50.2% sequence similarity to bovine brain PLC. This cDNA contained regions, the sequences of which were similar to those of some tyrosine kinase-related oncogene products. Northern blotting demonstrated that the mRNA for this PLC is expressed in human promyelocytic leukemia cells (HL-60). Since the other cloned cDNAs for PLCs could not hybridize with the RNA from this cell, it is strongly suggested that the gene obtained here encodes an additional isozyme of PLC in blood cells.

Amino Acid Sequence↗

N-terminal amino acid sequence of the deep-sea tube worm haemoglobin remarkably resembles that of annelid haemoglobin.

The deep-sea giant tube worm Lamellibrachia, belonging to the phylum Vestimentifera, contains two extracellular haemoglobins, an Mr 3,000,000 haemoglobin and an Mr 440,000 haemoglobin. The former has a hexagonal bilayer structure and consists of six polypeptide chains (AI-VI); a study of its haem content shows that not all of the chains contain haem. The Mr 440,000 haemoglobin consists of four haem-containing chains (BI-IV). We isolated most of the chains by reverse-phase chromatography and determined the amino acid sequences of the 21-45 N-terminal residues. Eight chains (AI-IV and BI-IV) showed significant homology with haem-containing chains of annelid giant haemoglobin. The highest homology was found between Lamellibrachia chain AI and Tylorrhynchus chain I; surprisingly, 18 out of the 20 N-terminal residues are identical. On the other hand, chain AV, with an unusual Mr of 32,000, showed a rather different sequence and is likely to be a non-haem chain which might act as a linker protein in the assembly of the haem-containing chains. From these results, we conclude that the tube worm Mr 3,000,000 haemoglobin is highly homologous with annelid haemoglobin.

Amino Acid Sequence↗

Gene structure of the human mitochondrial adenosine triphosphate synthase beta subunit.

The mitochondrial ATP synthase beta subunit is encoded by a nuclear gene and assembled with the other subunits encoded by both mitochondrial and nuclear genes. As the next step in the analysis of the molecular mechanisms coordinating the two genetic systems, the gene for the human beta subunit was cloned, and its structure was determined. The gene contains 10 exons, with the first exon corresponding to the noncoding region and most of the presequence which targets this protein to the mitochondria. Eight Alu repeating sequences including inverted repeats were found in the 5' upstream region and introns. An S1 nuclease protection experiment revealed two initiation sites for the transcription. A typical TATA box was not present at about 30 base pairs upstream from either initiation site. Three CAT boxes (CCAAT) were found between the two initiation sites. In addition, one CAT box was found 41 base pairs upstream from the first initiation site. Two GC boxes (potential Sp1 binding sites) were located in the 5' upstream region, one of them linked to Alu repeating sequences. For determination of the promoter activity, fragments of various length from the 5' upstream region were fused to a chloramphenicol acetyltransferase gene and transfected into cultured cells. This experiment showed the existence of an enhancing, structure(s) for transcription between nucleotide -400 and -1100 in the upstream region.

Amino Acid Sequence↗

Sequence and over-expression of subunits of adenosine triphosphate synthase in thermophilic bacterium PS3.

The primary structures of all the subunits of thermophilic ATP synthase were determined, and its alpha, beta and gamma subunits could be over-expressed in Escherichia coli, because these subunits were stable and reconstitutable. DNA of 7500 base pairs in length was found to contain a cluster of nine genes for subunits of ATP synthase. The order of their reading frames (size in base pairs) was: I(381): a(630): c(216): b(489): delta(537): alpha(1507): gamma(858): beta(1419): epsilon(396), I being a gene for a small hydrophobic, basic protein expressed in vitro. All the termini of TF0F1 subunits were confirmed by peptide sequencing. Large quantities of the overexpressed thermophilic alpha, beta and gamma subunits were prepared from the extract of E. coli, by a few purification steps.

Amino Acid Sequence↗