PubMed Health⌕ Search

Biomedical subjects

T Ohmori

Publications and source records attributed to T Ohmori.

At least 127 records · Page 7Linked to original sources
PubMed1994

A novel antitumor antibiotic, KW-2189 is activated by carboxyl esterase and induces DNA strand breaks in human small cell lung cancer cells.

KW-2189 has been selected as a lead compound for clinical trial among duocarmycin derivatives with structural similarity to CC-1065, a cyclopropylpyrroloindole. The purpose of this study was to examine the DNA-binding potency and the mechanisms of cytotoxicity of KW-2189. In order to analyze DNA-binding activity of KW-2189, plasmid pBR322 was treated with KW-2189 with or without pretreatment with carboxyl esterase, which we demonstrated to be an activating enzyme, and the products were examined by agarose gel electrophoresis and restriction enzyme analysis. Cytotoxic activity was examined by exposing a human small cell lung cancer cell line, NCI-H69 to KW-2189 with or without carboxyl esterase. Alkaline elution was performed to examine whether KW-2189 induces DNA strand breaks. DNA treated with KW-2189 and carboxyl esterase migrated faster than KW-2189-treated DNA, which migrated at the same rate as untreated DNA. In addition DNA treated with esterase-activated KW-2189 was protected from digestion by some restriction enzymes. KW-2189 showed concentration- and time-dependent growth inhibitory effect with IC50 values (drug concentration required for 50% growth inhibition) of 58 nM (96 h) to 1900 nM (1 h) in H69 cells. The IC50 values of 4-h exposure of H69 to KW-2189 with 0, 26, 130, 650 mU/ml carboxyl esterase were 460, 120, 30, and 7 nM, respectively. Time-dependent enhancement of cytotoxicity by carboxyl esterase was also observed. KW-2189 induced DNA strand breaks in H69 cells in a concentration-dependent manner around the IC50 value. We conclude that 1) KW-2189 is activated by carboxyl esterase to its active form(s), 2) activated KW-2189 has a stronger DNA-binding activity and cytotoxicity than KW-2189, 3) DNA cleavage is one of the major mechanisms of KW-2189-mediated cytotoxicity.

Antibiotics, Antineoplastic↗
PubMed1994

Hepatitis C virus antibodies, viral RNA and genotypes in sera from patients on maintenance haemodialysis.

Patients on maintenance haemodialysis in four dialysis centres were tested for markers of hepatitis C virus (HCV) infection. Antibody to HCV (anti-HCV) was detected by the second-generation enzyme immunoassay in 142 (26%) of the 543 patients and HCV RNA in 117 (22%) of whom four were without detectable anti-HCV in serum. Seventy-seven (66%) were infected with HCV of genotype II/1b, 31 (27%) with genotype III/2a and eight (7%) with genotype IV/2b, in a distribution similar to that in blood donors who carried HCV asymptomatically. Haemodialysis patients had high HCV RNA titres comparable to those of patients with chronic hepatitis C. HCV RNA was detected in 96 (26%) of the 365 patients with a history of transfusion more frequently than in 21 (12%) of the 178 without previous transfusion (P < 0.001). In transfused patients, frequencies of anti-HCV and HCV RNA increased in parallel with the duration of haemodialysis. The frequency of anti-HCV in non-transfused patients, however, did not change appreciably with the duration of haemodialysis up to 22 years. The patients with anti-HCV had a higher frequency of HCV RNA in serum than symptom-free blood donors with anti-HCV (113/142 or 80% vs 109/166 or 66%, P < 0.01) and the patients with HCV RNA had a lower frequency of elevated aminotransferase levels than blood donors with HCV RNA (5/113 or 4% vs 27/109 or 25%, P < 0.001). These results indicate that transfusion is a significant cause of HCV infection in patients on maintenance haemodialysis, and that these patients are prone to establish the HCV carrier state after infection.

Adult↗
PubMed1994

CA125-producing adenocarcinoma of the seminal vesicle.

A case of primary seminal vesicle carcinoma is reported. The tumor was a CA125-producing adenocarcinoma consisting of fine papillary-tubular, intricate branching or anastomosing glandular structures and was composed of small cuboidal, but occasionally hobnailed, cells with mostly clear, but occasionally granular, cytoplasm. Some tumor cells showed evidence of secretion of seromucinous materials into the interpapillary and cystic space. Immunohistochemically, almost half of the tumor cells expressed a positive reaction with anti-CA125, a common serological marker for ovarian epithelial carcinomas; however, no tumor cells expressed any other serological tumor markers such as carcinoembryonic antigen, alpha-fetoprotein, human chorionic gonadotropin, prostatic specific acid phosphatase, or prostatic specific antigen. The patient showed a high level of serological CA125, which fluctuated parallel with the growth, removal and recurrence of the tumor. The morphological and immunohistochemical findings suggested a close relationship between the present tumor and clear cell carcinoma of the ovary, which is thought to be of a Müllerian-Wolfian duct origin.

Adenocarcinoma↗
PubMed1994

Aminopeptidase P, capable of hydrolyzing oligoproline, from bovine brain.

An aminopeptidase P, capable of hydrolyzing oligoproline, was isolated from the homogenate of bovine brain. The molecular mass of the enzyme was 140 kDa by gel filtration. The enzyme was activated by Mn2+ and inhibited by o-phenanthroline. The enzyme hydrolyzed substrates such as Pro-Pro-Pro-Pro, Pro-Pro-Pro, and Pro-Pro to proline, and cleaved N-terminal amino acids from peptides containing penultimate prolines such as bradykinin and neuropeptide Y.

Amino Acid Sequence↗
PubMed1994

Platelet-activating factor (PAF) concentration and PAF acetylhydrolase activity in cerebrospinal fluid of patients with subarachnoid hemorrhage.

The authors studied the sequential changes in platelet-activating factor (PAF) and PAF acetylhydrolase in the cerebrospinal fluid (CSF) of patients with subarachnoid hemorrhage (SAH). Levels of PAF in CSF showed a gradual increase after the onset of SAH, with a subsequent decrease. The PAF concentration between 5 and 9 days after SAH was greater in patients with cerebral infarction due to vasospasm than in patients without infarction. Conversely, PAF acetylhydrolase activity decreased gradually after SAH, then increased. The enzyme activity for the same period was smaller in patients with cerebral infarction than in patients without infarction. The distribution of the days of maximum PAF concentration and minimum PAF acetylhydrolase activity did not differ significantly between the two groups. The CSF as a source of PAF acetylhydrolase activity gave an apparent Michaelis constant value of 90.8 microM and a maximum velocity of 0.2 nmol/min/mg. The optimum pH level for the PAF acetylhydrolase activity obtained from CSF was 6.5. The enzyme activity of CSF increased, depending on the incubation temperature, ranging from 25 degrees to 45 degrees C. Ethylene-glycol tetra-acetic acid (1 mM) was found to inhibit PAF acetylhydrolase activity in CSF obtained from patients with SAH. Unaltered PAF acetylhydrolase activity was inhibited by adding an aliquot of CSF and minimum PAF acetylhydrolase activity decreased following SAH. Two peaks of inhibitory activity were detected on Sephacryl S-200 HR gel filtration: one was eluted in void volume and the other with an apparent molecular mass of 13 kD. The inhibitory activity was very labile and was lost completely within 3 days of incubation at 4 degrees C. The regulation of the PAF concentration in the CSF of SAH patients is discussed.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1994

Effects of diet high in medium-chain triglyceride on plasma ketone, glucose, and insulin concentrations in enterectomized and normal rats.

The effects of dietary medium-chain triglyceride (MCT) on the concentration of plasma ketone bodies in enterectomized and normal rats were examined, together with the effects on plasma glucose, plasma immuno-reactive insulin, and liver function. Four groups of enterectomized rats and four groups of normal rats were fed experimental diets containing 0, 6, 11, or 21% of MCT by weight for 6 days. All animals including normal rats received meal-feeding for 3 h once a day. On day 3, concentration of plasma ketone bodies in enterectomized rats increased dose-dependently with dietary MCT and the level was higher than that in normal rats. However, all the values in enterectomized rats never exceeded 2 mM, the maximum physiological concentration. In contrast, plasma glucose in the enterectomized rats showed a tendency to decrease more clearly and dose-dependently with dietary MCT, followed by a marked increase of insulin secretion compared with those in normal rats. On the final day, no significant differences in the results of liver function tests were observed among these groups. These results indicate that the MCT-induced ketosis was within an acceptable range, and dietary MCT is useful for the suppression of increase in plasma glucose following a surgical operation without any disadvantageous effects on liver function.

Animals↗
PubMed1994

[A case of liver cirrhosis presenting with right pleural fluid without ascites].

A 80-year-old man was admitted to our hospital complaining of appetite loss, dry cough, and dyspnea on exertion. Chest X-ray film showed massive right pleural effusion. On physical examination, the right thorax was dull to percussion, and breath sounds of the right lung field were diminished. Examination of the cardiovascular system was unremarkable. Hepatosplenomegaly and ascites were not evident. The character of the pleural fluid was transudative. Cytological findings were negative and culture of the pleural fluid was normal. First, the pleural fluid was diminished by thoracic drainage. But, after the cessation of drainage, the pleural fluid soon reaccumulated. Abdominal ultrasonography showed typical liver cirrhosis pattern without ascites. An intraperitoneal injection of 99mTc-sulfur colloid was followed by positive uptake of radioactivity in the right pleural cavity from 1 hour after the injection, demonstrating the existence of a direct perito-pleural communication. Thus, the diagnosis of liver cirrhosis presenting with right pleural fluid, without ascites was made. This case indicates that the absence of ascites cannot exclude cirrhosis as the etiologic cause of pleural effusion.

Aged↗
PubMed1994

Multiple ileal carcinoids and appendiceal endocrine carcinoma in association with Meckel's diverticulum. A histochemical and immunohistochemical study.

An unusual case of multicentric ileal carcinoids and appendiceal endocrine carcinoma in association with Meckel's diverticulum was studied, with special attention given to the histogenesis of these neoplasms. A total of six ileal carcinoids, the largest of which was located in the wall of Meckel's diverticulum, were macroscopically and microscopically confirmed to be multicentric and revealed no visceral metastases. The histochemical and immunohistochemical profiles of the ileal carcinoids and the appendiceal carcinoma differed considerably: the former resembled subepithelial neuroendocrine cells and the latter resembled epithelial nonmucous cells and Paneth cells. The appendiceal carcinoma exhibited signs of endocrine differentiation, expressing somatostatin and vasoactive intestinal polypeptide, and secreted mucus. The tumor had metastasized to various organs. The carcinoids exhibited signs of neuroendocrine and glandular differentiation, expressing neuron-specific enolase, serotonin, chromogranin A, and endocrine granule constituent, and secreted little mucus. The data suggest different tumor cell origins or different grades of differentiation of the two types of intestinal endocrine cell tumor.

Aged↗
PubMed1993

Modulation of cisplatin sensitivity and accumulation by amphotericin B in cisplatin-resistant human lung cancer cell lines.

To ascertain whether resistance to cis-diamminedichloroplatinum(II) (cisplatin) could be overcome, we determined the effects of amphotericin B (AmB), an antifungal agent, on cisplatin cytotoxicity, cisplatin-induced DNA interstrand cross-links formation, and cellular accumulation of cisplatin in human lung cancer cell lines, PC-9, PC-14, PC-7, and H69 and their corresponding respective cisplatin-resistant sublines PC-9/CDDP, PC-14/CDDP, PC-7/CDDP, and H69/CDDP in vitro. In PC-9/CDDP but not PC-9 cells, augmentation of cytotoxicity was observed when a nontoxic concentration (10 micrograms/ml) of AmB was combined with cisplatin, cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II), and cis-diammine(glycolato)platinum(II). Sensitizing effects of AmB of varying magnitudes on cisplatin cytotoxicity also were observed in all the other cell lines except PC-14. AmB-induced increases in cisplatin-induced interstrand cross-links formation were observed, the magnitudes of which corresponded to the magnitudes of AmB-augmented cisplatin cytotoxicity. Increased intracellular cisplatin accumulation was observed in the presence of AmB in all the cells that were sensitized to cisplatin by AmB. Therefore, the increases in cisplatin accumulation were considered to be responsible, at least in part, for the mechanism of the sensitizing effect. Further experiments using other human lung cancer cell lines showed that cells that were more resistant to cisplatin were more sensitized to cisplatin by AmB than cells that were cisplatin-sensitive.

Amphotericin B↗
PubMed1993

B-HT 920, a dopamine D2 agonist, in the treatment of negative symptoms of chronic schizophrenia.

A prospective, nonblind 8-week trial of talipexole dihydrochloride (B-HT 920), a dopamine D2 agonist, was conducted in 15 schizophrenic patients with predominantly negative symptoms. B-HT 920 was initiated at 0.15 mg/day and then adjusted at 0.15-2.4 mg/day on the basis of clinical response and side effects. Dosage of concurrent neuroleptics was fixed at least 3 weeks prior to the trial and was unchanged throughout the study period. In addition to clinical assessment, levels of plasma homovanillic acid (pHVA), a potential index of central dopamine turnover, were measured. There was a small but significant (p < 0.01, Wilcoxon test) reduction in total scores of the Scale for the Assessment of Negative Symptoms or in a cluster score of three negative items (Emotional Withdrawal, Blunted Affect, and Psychomotor Retardation) of the Brief Psychiatric Rating Scale (BPRS). No change was observed in cluster scores of positive items of BPRS. There was a weak negative correlation between pHVA levels and the cluster scores of negative items of BPRS both at weeks 0 and 8 of the trial. The clinical results suggest that activation of D2 receptors was related to partial amelioration of the negative symptoms. The clinical and biochemical findings are consistent with a hypothesis that decreased dopaminergic activity may be related to the etiology of negative symptoms of schizophrenia.

Arousal↗
PubMed1993

Apoptosis of lung cancer cells caused by some anti-cancer agents (MMC, CPT-11, ADM) is inhibited by bcl-2.

To determine whether the apoptotic cell death induced by anti-cancer agents could be inhibited by bcl-2, we established a bcl-2-transfected human small cell lung cancer cell line, SBC-3/Bcl2. SBC-3/Bcl2 showed higher resistance to ADM, CPT-11 and MMC compared with the parental line SBC-3, with relative resistance values of 3.4, 7.6 and 5.7, respectively. However, there was no difference in sensitivity to CDDP, VP-16, ACNU, MTX and taxol between SBC-3 and SBC-3/Bcl2. Agarose gel electrophoresis showed typical DNA fragmentation of SBC-3 following treatment with CPT-11 or MMC, in a concentration-dependent manner. In contrast, the same concentration of the drugs did not induce DNA fragmentation in SBC-3/Bcl2. Treatment with CDDP resulted in the same degree of DNA fragmentation in SBC-3 and SBC-3/Bcl2. These studies indicate that bcl-2 can modulate the cytotoxicity of some anti-cancer agents by inhibiting the process of apoptosis.

Animals↗
PubMed1993

Competitive and noncompetitive N-methyl-D-aspartate antagonists protect dopaminergic and serotonergic neurotoxicity produced by methamphetamine in various brain regions.

Protective effects of NMDA antagonists on dopaminergic and serotonergic neurotoxicity produced by methamphetamine (MA) were examined. Four injections of MA (7.5 mg/kg, s.c., at 2 h intervals) caused significant decrements (40-60% of control values) in levels of dopamine (DA) and its metabolites in the rat striatum and levels of serotonin (5-HT) and its metabolite in the medial prefrontal cortex, nucleus accumbens, striatum, anterior hypothalamus, amygdala and hippocampus. These decreases in DA, 5-HT and their metabolites were prevented by pretreatment with MK-801, a noncompetitive N-methyl-D-aspartate (NMDA) antagonist, or D-CPP-ene (SDZ EAA 494), a competitive NMDA antagonist. The results suggest that NMDA receptors play a role for MA-induced serotonergic damage in various brain regions as well as dopaminergic damage in the striatum.

Animals↗
PubMed1993

Immunocytochemical localization of copper-zinc superoxide dismutase in mouse olfactory mucosa.

Copper-zinc superoxide dismutase (Cu-Zn SOD) has been localized in mouse nasal mucosa. Immunocytochemical staining using polyclonal antibody against Cu-Zn SOD revealed endogenous Cu-Zn SOD in sustentacular cells in the olfactory area, and in ciliated epithelial cells in the respiratory area of the olfactory mucosa. Since these cells are located in the superficial portion of the olfactory mucosa, Cu-Zn SOD may serve as an intracellular antioxidant.

Animals↗
PubMed1993

CO-N reaction--a new serological activity index--on Wegener's granulomatosis.

Cordyceps ophioglossoides is one of the Japanese old 'Kanpoh' drugs used for metrorrhagia as a decoction. We found that CO-N, a galactosaminoglycan from Cordyceps ophioglossoides, reacted with sera from patients with some collagen diseases. By using CO-N, we made a new serological activity index (CO-N reaction). In the present study, we investigated CO-N reaction on patients with Wegener's granulomatosis (WG). The aggregation titres of CO-N (CO-N numbers) displayed a possible correlation with their clinical activity. CO-N reaction might also serve an important role in supporting the diagnosis of active WG and in helping to assess the degree of disease activity. The purpose of this report is to introduce this new serological activity index for Wegener's granulomatosis.

Adolescent↗
PubMed1993

Characterisation of a vindesine-resistant human small-cell lung cancer cell line.

We established a vindesine-resistant (x 11.6) human small-cell lung cancer cell line (H69/VDS) by stepwise exposure of parent line H69 to vindesine. H69/VDS showed cross-resistance to taxol (x 10.1), vincristine (x 6.9) and colchicine (x 3.4) but not to doxorubicin, cisplatin or etoposide. There was no significant difference in intracellular [3H]-vincristine and doxorubicin accumulation between H69 and H69/VDS cells. The human mdr1 mRNA was not detected in either of the cell lines. These results indicated that H69/VDS did not express a typical multidrug resistant phenotype. Addition of 20 microM verapamil enhanced the growth inhibitory effect of vindesine on both H69/VDS (x 12.0) and H69 cells (x 3.8). The amount of total tubulin in H69/VDS cells was lower than that in the H69 parental cells. No significant increase was observed in the amount of total and polymerised tubulins of H69 cells. In H69/VDS cells, however, verapamil increased the amount of total tubulin to the level of parental cells, but decreased the amount of polymerised tubulin. Modulation of tubulin may play a role in the resistance to vindesine.

Antineoplastic Agents↗