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Biomedical subjects

T Ohtani

Publications and source records attributed to T Ohtani.

At least 91 records · Page 5Linked to original sources

Synthesis of possible metabolites of 1-cyclopropyl-1,4-dihydro-6-fluoro-5-methyl-7-(3-methyl-1-piperazinyl)- 4-oxo-3-quinolinecarboxylic acid (Grepafloxacin, OPC-17116).

Grepafloxacin (1-cyclopropyl-1,4-dihydro-6-fluoro-5-methyl-7-(3-methyl-1-piperazinyl )-4-oxo-3-quinoline-carboxylic acid, OPC-17116) (1) exhibits potent and broad-spectrum in vitro and in vivo antibacterial activity. In order to identify the structures of the metabolites of grepafloxacin, 17 possible metabolites were prepared. Among them, 6 compounds were found to be actual metabolites (2a, b, 4a, b and 6a, b) of grepafloxacin in rats, dogs and/or humans. The antibacterial activities of these metabolites were found to be weaker than that of grepafloxacin.

Animals↗

Synthesis of 4-(phenylamino)quinoline-3-carboxamides as a novel class of gastric H+/K+-ATPase inhibitors.

In search for inhibitors of gastric H+/K+-ATPase, 4-(phenylamino)quinoline-3-carboxamides were synthesized and evaluated for antisecretory activity against histamine-induced gastric acid secretion in rats. These compounds were synthesized by condensation of aniline derivatives with N-substituted 4-chloroquinoline-3-carboxamides, which were obtained from treatment of 4(1H)-quinolinone-3-carboxylic acid with thionyl chloride. Most of the compounds inhibited histamine-induced gastric acid secretion in rats. Among them, N-allyl-4-(2-ethylphenylamino)quinoline-3-carboxamide (4h) was the most potent inhibitor and had the best profile as a candidate antiulcer agent. This compound showed reversible, K+-competitive gastric H+/K+-ATPase inhibitory activity.

Animals↗

[A controlled study of AO-90, a methionine-free intravenous amino acid solution, in combination with 5-fluorouracil and mitomycin C in advanced gastric cancer patients (internal medicine group evaluation)].

The results of recent preclinical and clinical studies suggest that AO-90, a methionine-free intravenous amino acid solution (7.43%), potentiates the antitumor effect of 5-fluorouracil (5-FU). In the present multi-center, randomized, controlled study conducted at the internal medicine departments of 24 institutions between July 1991 and May 1993, patients with advanced gastric cancer were randomly allocated to receive either AO-90 (500-750 mL/day, AO/MF group) or Amiparen, a commercial intravenous amino acid solution (600-800 mL/day, C/MF group) by total parenteral nutrition for 14 days. Both groups received MF therapy which consisted of a continuous infusion of 5-FU at 350 mg/m2/day for 14 days and an i.v. push of mitomycin C 7 mg/m2 on days 7 and 14 (one course). Additional treatment courses were initiated after a withdrawal period when appropriate. Of the 53 subjects enrolled, 52 (98.1%) were eligible and 47 (88.7%) completed the scheduled treatment (AO/MF group: 23, C/MF group: 24). Although there were significant differences for age and sex between the groups, the Mantel-Haenszel test showed that these unevenly distributed characteristics did not affect the study results. The overall clinical response rates in the completed cases were 30.4% (7/23) in the AO/MF group and 16.7% (4/24) in the C/MF group. In particular, the response rate in the inoperable advanced cases with liver metastases, ascites or distant metastases was 45.5% (5/11) in the AO/MF group versus 16.7% (2/12) in the C/MF group. The treatment-related adverse reactions observed were mainly hematologic and subjective/objective symptoms, such as decreased leukocyte count, hemoglobin level and platelet count, nausea/vomiting, diarrhea, stomatitis, and fever. The differences in the incidence were not significant between the groups. These results show that AO-90 in combination with MF therapy is efficacious in the treatment of patients with gastric cancer.

Adolescent↗

[A cooperative late phase II trial of l-leucovorin and 5-fluorouracil in the treatment of advanced gastric cancer. l-Leucovorin and 5-FU Study Group (Japan Western Group)].

A multicenter cooperative study was conducted to evaluate the clinical efficacy of l-leucovorin (l-LV) and 5-fluorouracil (5-FU) treatment in 69 cases of advanced gastric cancer. l-LV was administered intravenously by a 2-hour infusion at a dosage of 250 mg/m2 and 5-FU at a dosage of 600 mg/m2, intravenously via bolus one hour after administration of l-LV had been started. The combination was given weekly for 6 weeks followed by a 2-week rest period. Patients were evaluated for response after the sixth dose. Nineteen PRs were noted in the 55 patients for an overall response rate of 34.5%. Median survival time was 190 days for eligible cases, and 448 days for PR cases. Age and performance status (PS) appeared to influence clinical response. Patients aged 49 years or younger showed a significantly higher PR rate than those aged 50 years or older. The PR rate was significantly higher in the patients of PS 0-1 than those of PS 2. Diarrhea and leukopenia were experienced in 46.7% and 65% of patients, respectively. Patients who had severe toxicities required discontinuity of treatment. After recovery, treatment was repeated. The clinical results are promising for patients with advanced gastric cancer, particularly middle-aged patients. However, whether the l-leucovorin and 5-FU combination therapy will ultimately produce superior results in middle-aged patients awaits the results of Phase III trials.

Adult↗

Hardness of denture reline materials polymerized with different techniques.

Two kinds of hard type self-cured denture reline materials were polymerized using three different techniques: (1) on a surface of glass plate, (2) under water, (3) under water with some hardening agent. Hardness of specimens were measured longitudinally during three weeks periods of storage in water at 37 degrees C. Results of our study indicated that the specimen cured with the special hardening agent showed the higher hardness than those cured only in water. Most of the hardness changes took place during first three days of the experiment period.

Acrylic Resins↗

Characterization of a species of non-specific cross-reacting antigen (NCA) expressed by human monocytic cell lines: structure and expression during cell differentiation.

It has been documented that human monocytes/macrophages are reactive with antibodies directed to carcinoembryonic antigen (CEA) and non-specific cross-reacting antigens (NCAs), a group of glycoproteins antigenically cross-reactive with CEA, yet the molecules responsible for this antigenic activity have not been fully clarified. In the present study, among 7 myelomonocytic cell lines tested, 2 monoblastoid lines, U-937 and THP-1, were found to express NCA-50/90, a glycosylphosphatidylinositol-anchored cell-adhesion molecule chiefly expressed on granulocytes. The 2 cell lines showed a reaction pattern with 5 distinct anti-CEA and anti-NCA monoclonal antibodies, similar to that of CHO transfectants expressing recombinant NCA-50/90. Immunoprecipitation and SDS-PAGE analyses identified glycoproteins of about 95 and 55 kDa in U-937 and THP-1 cells, respectively. Deglycosylation of the 2 antigens with N-glycanase gave the same apparent molecular mass of about 45,000, which was also the same as that of the deglycosylated form of the recombinant NCA-50/90. Upon Northern-blot analysis, only one band of approximately 2.5 kb was detected in both cell lines with a cDNA probe for NCA-50/90, which has a broad specificity to the CEA gene family members. cDNA cloning demonstrated that the 2.5-kb clones encode the peptide of NCA-50/90. The expression of NCA-50/90 by U-937 and THP-1 was down-regulated at both the protein and mRNA levels during cell differentiation from monoblastoid to monocyte/macrophage-like cells induced by stimulation with phorbol 12-myristate 13-acetate. Our observations suggest that NCA-50/90 is a differentiation antigen of cells of the monocyte/macrophage lineage as well as of the granulocyte lineage.

Antigens, Differentiation, Myelomonocytic↗

Systolic anterior motion of the mitral valve associated with acute myocardial infarction in a 62-year-old patient.

A 62-year-old patient was admitted to our hospital for treatment of early gastric cancer. After total gastrectomy, he suffered from anteroseptal myocardial infarction. Systolic anterior motion of the mitral valve which was not observed before surgery was observed during the acute phase of myocardial infarction and completely disappeared 3 weeks after the onset of myocardial infarction. Systolic anterior motion of the mitral valve in this patient may have been caused by changes in left ventricular wall motion during the acute phase of myocardial infarction.

Echocardiography↗

Reconstruction of the extensor apparatus of the knee with the Leeds-Keio ligament.

We describe a new method for the reconstruction of ruptures of the patellar ligament or the quadriceps tendon, using the flexible open-weave polyester Leeds-Keio prosthetic ligament. Of 25 operations performed since 1985, we were able to review 18 patients (19 knees) with a mean follow-up of 3.5 years (3 to 6.5). No patient had required immobilisation of the knee after operation and the average period to return to normal activities without a walking aid was 10.5 weeks. The average range of motion was 146 degrees, and four patients could squat fully in the Japanese style. There was an extension lag (< 10 degrees) in only four patients; eight patients had some patellar crepitus which was mildly painful in three. There were no cases of infection, persistent joint effusion or rerupture of the extensor apparatus.

Adult↗

The association between extrahepatic biliary carcinoma and the junction of the cystic duct and the biliary tree.

OBJECTIVE: To establish accurately the sites of primary extrahepatic biliary carcinomas, so that optimal treatment may be given. DESIGN: Retrospective study. SETTING: University department of surgery. SUBJECTS: 120 patients with 121 primary extrahepatic biliary carcinomas. MAIN OUTCOME MEASURES: Site of tumour (primary site being geometric centre of tumour) and distance from junction of cystic duct and the biliary tree on histological examination of the resected specimen. RESULTS: 64 of the tumours (53%) were within 5 mm of the junction; 14 were proximal to the junction, 32 distal, and 18 within the cystic duct itself. CONCLUSIONS: Over half the primary extrahepatic biliary tumours were within 5 mm of the junction of the cystic duct and the rest of the biliary tree. Further investigations are required to find out if any particular aetiological factor can be identified.

Adenocarcinoma↗

Distinct subdomains of human endothelin receptors determine their selectivity to endothelinA-selective antagonist and endothelinB-selective agonists.

The endothelin (ET) family of peptides acts via two subtypes of G-protein-coupled heptahelical receptors termed ETA and ETB, which have distinct rank orders of affinity to endothelin receptor agonists and antagonists. To delineate which portions of the receptor molecules determine ligand selectivity, we have constructed a series of chimeras between human ETA and ETB receptors and characterized the chimeric receptors expressed in heterologous cell lines by competitive radioligand binding analysis and by measuring agonist-induced transients of intracellular Ca2+. We demonstrate that the binding determinant for the ETB-selective agonists ET-3, BQ3020, and IRL1620 residues within the region spanning the putative transmembrane helices IV-VI and the adjacent loop regions. In contrast, the transmembrane helices I, II, III, and VII plus the intervening loop regions specify the selectivity for BQ123, an ETA-selective antagonist. BQ123 exhibited no detectable agonistic activity in all wild-type and chimeric receptors tested. A chimeric receptor that has the transmembrane helices IV-VI (and adjacent loops) from the ETB receptor inserted into the remaining regions from the ETA receptor binds both the ETA- and ETB-selective ligands with high affinities. Moreover, BQ123 competitively inhibits the binding of the amino-terminally truncated ETB agonists, 125I-BQ3020 and 125I-IRL1620, to this chimeric receptor, suggesting that BQ123 is a mimic of the carboxyl-terminal linear portion of endothelins. These findings indicate that there are at least two separable ligand interaction subdomains within the endothelin receptors.

Amino Acid Sequence↗

Percutaneous transhepatic cholecystostomy for acute acalculous cholecystitis.

The effectiveness and long-term results of percutaneous cholecystostomy for acute acalculous cholecystitis are evaluated. Fifteen patients with acute acalculous cholecystitis were treated prospectively by this procedure, using a pigtail catheter successfully placed under ultrasonographic and fluoroscopic guidance. Prompt relief of the signs and symptoms of cholecystitis was achieved in 14 patients. One required emergency cholecystectomy for uncontrolled bleeding after drainage. Another patient underwent prophylactic cholecystectomy before further chemotherapy for leukaemia. The remaining 13 patients required no further surgery. Morbidity and mortality rates were 13 per cent and nil respectively. Long-term follow-up showed no recurrence of cholecystitis after removal of the catheter. Percutaneous cholecystostomy is a safe, effective and usually definitive procedure for the treatment of acute acalculous cholecystitis.

Acute Disease↗

Activation of anthocyanin synthesis genes by white light in eggplant hypocotyl tissues, and identification of an inducible P-450 cDNA.

Eggplant seedlings (Solanum melongena) grown under red light irradiation showed a normal morphology with green, fully expanded cotyledons. When the seedlings grown under red light were irradiated with ultraviolet-containing white light, anthocyanin synthesis was induced in the hypocotyl tissues, especially when a UV light supplement was added. The accumulation of pigments was closely associated with the expression of genes involved in flavonoid synthesis. These genes include chalcone synthase (CHS) and dihydroflavonol 4-reductase (DFR). Using subtracted probes, which had been enriched for the accumulated mRNA, one white light-responsive cDNA was identified as being a P450 gene by comparison with database sequences. The maximal amino acid homology this cDNA had with other P450s was 36%. This was with CYP71 from avocado (Persea americana). Thus it represents a new P-450 family, which has been named CYP75. The mRNA of this gene was localized in the hypocotyl tissues of eggplant seedlings, which had been white light-irradiated. The transcript was accumulated by changing the light source, as in the case of other flavonoid biosynthesis genes. In delphinidin producing petunia plants, the mRNAs corresponding to the eggplant P-450 and flavonoid biosynthesis genes such as CHS and DFR were most abundant during the mid stage of flower bud development, but could not be detected in leaf tissues. These results suggest that this P-450 gene encodes a hydroxylating enzyme involved in flavonoid biosynthesis.

Amino Acid Sequence↗

Contact sensitivity and cross-reactivity of budesonide.

5 cases of allergic contact dermatitis due to budesonide are described. We studied the antigen determinant structures in these cases by applying patch tests with several substances related to budesonide. 2 cases showed cross-reactions to both amcinonide and prednisolone acetate. The antigen determinant structure is also discussed.

Adult↗

Neurological manifestations of hemorrhagic colitis in the outbreak of Escherichia coli O157:H7 infection in Japan.

An outbreak of hemorrhagic colitis associated with Escherichia coli O157:H7 occurred in a kindergarten in Saitama, Japan from September to November, 1990. Seven patients admitted to our hospital showed neurological manifestations: generalized seizures, impaired consciousness, urinary incontinence, gaze nystagmus, phrenic nerve palsy, action tremor and vertigo. Two patients died. On the basis of the clinical courses and laboratory findings of the seven patients and postmortem findings of one case, these neurological symptoms were suspected to be induced by the verotoxin elaborated by Escherichia coli O157:H7.

Bacterial Toxins↗

Carcinoma of the gallbladder: CT evaluation of lymphatic spread.

PURPOSE: To clarify the computed tomographic (CT) characteristics of positive nodes and to assess the ability of CT to demonstrate lymphatic spread. MATERIALS AND METHODS: CT findings of lymph nodes in 51 patients with histologically proved gallbladder carcinoma were correlated with pathologic findings retrospectively. RESULTS: Thirty-one of 51 patients (61%) had a total of 157 positive nodes, 60 (38%) of which were depicted at CT. A positive node was defined at CT as a soft-tissue mass with an anteroposterior dimension of at least 10 mm that showed ringlike or heterogeneous enhancement. These criteria had a positive predictive value of 75% for cystic nodes, 90% for pericholedochal nodes, 100% for posterosuperior pancreatoduodenal nodes, 100% for retroportal nodes, 88% for right celiac nodes, 100% for hepatic nodes, 100% for superior mesenteric nodes, and 83% for interaortocaval nodes. CONCLUSION: CT does not reliably demonstrate all regional nodes of gallbladder carcinoma, but the criteria of size and pattern of enhancement reliably indicate lymphatic spread, which has an important bearing on disease staging and treatment planning.

Carcinoma↗

Measurement of cardiac chamber volumes by cine magnetic resonance imaging.

Cardiac chamber volumes (both atria and ventricles) in 19 healthy volunteers were measured noninvasively by cine magnetic resonance imaging (MRI). First, cardiac localization was determined from the coronal image by 0.5-T superconducting magnetic imager. Then, transaxial ECG gated multislice spin echo images were obtained from the bottom to the top of the heart. In the last step, cine MRI was performed at each level of all these transaxial spin echo MR images involving the heart. Each cardiac chamber volume at the same phase was calculated by adding chamber areas in each anatomic section multiplied by slice thickness. Left ventricular (LV) end-diastolic volume (EDV) 132.0 +/- 26.9 mL) and LV end-systolic volume (ESV) (47.8 +/- 13.9 mL) were smaller than right ventricular (RV) EDV (141.1 +/- 24.8 mL) and RVESV (57.0 +/- 12.6 mL), respectively (p < 0.01). LV stroke volume (84.3 +/- 17.9 mL) was equivalent to RV stroke volume (84.2 +/- 17.6 mL) (r = 0.91, p < 0.01). Left atrial (LA) and right atrial (RA) maximal volumes were 75.8 +/- 15.4 mL and 84.4 +/- 18.7 mL, respectively. LA minimal volume (37.5 +/- 10.7 mL) was smaller than RA minimal volume (47.8 +/- 12.2 mL). These values measured by cine MRI are satisfactory and cine MRI will be a useful method of determining cardiac chamber volumes, especially atrial volumes.

Adult↗