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T Takemoto

Publications and source records attributed to T Takemoto.

At least 73 records · Page 4Linked to original sources
PubMed1994

Novel potassium-channel openers: preparation and pharmacological evaluation of racemic and optically active N-(6-amino-3-pyridyl)-N'-bicycloalkyl-N"-cyanoguanidine derivatives.

The previous paper reported on the synthesis and pharmacological evaluation of N-(6-amino-3-pyridyl)-N'-bicycloalkyl-N"-cyanoguanidine derivatives, from among which three compounds were selected as potent potassium-channel openers. In the present study, selected compounds were tested for antagonism of potassium-induced contraction of rat aorta, hypotensive activity in normotensive rats, and diuretic activity in spontaneously hypertensive rats. This led to further evaluation of compound (+/-)-10 and selection of (+)-N-(6-amino-3-pyridyl)-N'- [(1S,2R,4R)-bicyclo- [2.2.1]hept-2-yl]-N"-cyanoguanidine ((+)-10) (AL0670) for development as an antihypertensive agent. Although AL0670 is regarded as a pinacidil-type K(+)-channel opener, it showed different pharmacological and conformational profiles from pinacidil.

Animals↗
PubMed1994

Novel potassium channel openers: synthesis and pharmacological evaluation of new N-(substituted-3-pyridyl)-N'-alkylthioureas and related compounds.

This report describes the synthesis and pharmacological evaluation of a series of novel potassium channel openers related to the pinacidil-type compounds. Thioureas, cyanoguanidines, and pyridine N-oxides were systematically evaluated for their effects on both the inhibition of spontaneous mechanical activity in rat portal vein (in vitro) and their antihypertensive activity (in vivo), and the structure-activity relationship for this series of compounds was discussed. Good correlation between in vitro and iv antihypertensive activity was observed for these compounds. Among them, cyanoguanidines bearing a conformationally rigid unit such as a norbornyl group generally possessed potent activity in both in vitro and in vivo studies. Especially, N-(6-amino-3-pyridyl)-N'-cyano-N"-(1-methyl-2-norbornyl)guanidine (23d) was identified as a more potent potassium channel opener in vitro (EC100 = 3 x 10(-8) M) than pinacidil (EC100 = 10(-7) M).

4-Aminopyridine↗
PubMed1994

Helicobacter pylori infection in Japan: current status and future options.

BACKGROUND: The combination of the high prevalence of Helicobacter pylori infection in Japan and the availability of methods to diagnose and treat the infection suggest that elimination of the infection from the population might be beneficial. Therefore we reviewed the epidemiology, consequences and possible benefits of elimination of H. pylori in Japan. RESULTS: H. pylori infection has been etiologically linked to peptic ulcer disease, gastric carcinoma and gastric B-cell lymphoma. The cumulative risk of those with H. pylori infection for developing peptic ulcer disease is 15-20%, with 0.01-0.1% developing gastric carcinoma. Twenty to thirty per cent of those infected suffer mortality or morbidity related to H. pylori infection. Recommendations were made concerning the elimination of this infection. CONCLUSIONS: Eradication of H. pylori should largely eliminate peptic ulcer disease with all its costs and complications, while rapidly changing the risk of developing gastric cancer.

Helicobacter Infections↗
PubMed1994

Role of oxygen-derived free radicals in the mechanism of cysteamine-induced duodenal ulcer in rats.

In this study, the possible role of oxygen-derived free radicals in cysteamine-induced duodenal ulcers in rats was investigated. Separate groups of rats were treated with 350 mg/kg cysteamine subcutaneously. Superoxide dismutase (SOD) activity and thiobarbituric acid (TBA) reactants in the duodenal mucosa were analyzed one, three, six, 12 and 24 hours after treatment, respectively. Cu,Zn-SOD activity significantly decreased from 41.79 +/- 3.53 NU/mg protein to 29.56 +/- 3.62, 27.23 +/- 3.02 and 24.64 +/- 3.07 NU/mg protein at three, six and 12 hours, respectively. TBA reactants, indicators of tissue injury by oxygen-derived free radicals, significantly increased from 0.18 +/- 0.10 nmol/mg protein to 1.31 +/- 0.12 and 1.57 +/- 0.09 nmol/mg protein at six and 12 hours after cysteamine treatment, respectively. We conclude that an increase of oxygen-derived free radicals and a decrease of Cu,Zn-SOD activity in the duodenal mucosa may be involved in the pathogenesis of cysteamine-induced duodenal ulcers in rats.

Animals↗
PubMed1994

[Assessment of QOL in cancer drug therapy using 22-item questionnaire].

In order to integrate quality of life as the end point in the cancer drug therapy, a questionnaire form has been developed over the past four years by a Grant-in-Aid for Cancer Research from the Ministry of Health and Welfare, Japan. Fifty-one items generated by questionnaires were forwarded to oncologists, nurses, psychologists and 121 patients. Then questionnaires were scaled down to 36 items based upon factor analysis considering correlation to State-Trait Anxiety Inventory (STAI) and Self-rating Depression Scale (SDS). These 36 items were administered to 536 patients. Finally, a 22-item questionnaire was completed by rechecking correlations with PS, STAI, SDS and Cronbach's alpha. It includes such components as physical activities (6 items), psychological (5 items) and social variables (5 items), symptoms (5 items) and global well-being (1 item: face scale). In our treatment of G. I. cancer by chemotherapy, NC patients showed improvement (+1.56 score), especially in physical functions (+2.43 score), but with slight deterioration (-0.25 score).

Female↗
PubMed1993

Structure determination of glycosphingolipids of cultured human keratinocytes.

From cultured human keratinocytes, seven glycolipid fractions were isolated by DEAE and silica-gel column chromatographies, and further by HPLC on a silica-gel column. By means of 1H-NMR spectroscopy, fast atom bombardment mass spectrometry and GLC-mass spectrometry, one fraction was determined to contain acylglucosylceramides, which consist of amide linked omega-hydroxy fatty acids (C30:0, C30:1, C32:1 and C34:1), fatty acids linked to the omega-hydroxy fatty acids through ester linkages (C14:1, C16:1, C18:1 and C18:2), a long-chain base (d18-sphingenine), and beta-glucose. Five of the other fractions contained glucosylceramides, and the seventh fraction contained a mixture of glucosylceramides and galactosylceramides. Glucosylceramides containing long-chain omega-hydroxy fatty acids, which are assumed to be immediate precursors of the acylglucosylceramides, were hardly detected in these glycolipid fractions. Six glucosylceramide fractions were separated due to differences in their fatty acids and sphingosines. On comparison with the results reported in our previous paper, the acylglucosylceramide content of the cultured human keratinocytes was about half that of human epidermis. Under the culture conditions used, the human keratinocytes did not differentiate into granular or horny cells. Taken together, the results suggest that the synthesis of acylglucosylceramides is not activated much in the cultured keratinocytes, but would be more activated in differentiated cells.

Adult↗
PubMed1993

The relationship between endoscopic findings of gastric ulcer scar and ulcer relapse.

Regenerated mucosal patterns that appeared during the healing of chronic gastric ulcers were observed and assessed in detail by magnifying endoscopes. Three patterns of ulcer scarring were distinguished: Sa with central depression, Sb with a coarse regenerated mucosal pattern, and Sc with a fine mucosal pattern. From a study on the relationship between the depth of ulcer confirmed histologically and the endoscopic findings of the scar, a clear distinction could be made endoscopically between U1-IV scar with a well-demarcated scarring zone, U1-III scar with an unclear boundary, and U1-II scar without a distinct scar area. Scar patterns were also related to ulcer depth. Analysis of the relationship between an ulcer relapse and the scar pattern demonstrated that the ulcer relapse rate over a 2-year follow-up period was 84% in Sa, 33% in Sb, and 0% in Sc.

Adult↗
PubMed1993

Lipid analysis of Helicobacter pylori.

Lipids from Helicobacter pylori were extracted, isolated by conventional DEAE-Sephadex and silica gel column chromatography, and then purified by preparative thin-layer chromatography. Simple and phospholipids were analyzed by HPTLC and quantitatively determined by densitometry scanning. The fatty acid compositions of simple lipids were estimated by gas-liquid chromatography. The simple lipid composition of H. pylori consisted of wax ester (2.5%), triglycerides (4.9%), free fatty acids (30.0%), cholesterol (6.9%), diacylglycerol (29.1%), and monoacylglycerol (2.6%). The neutral phospholipid composition consisted of phosphatidyl ethanolamine (79.1%), lysophosphatidyl ethanolamine (16%), and phosphatidyl choline (1.9%). That of acidic phospholipids consisted of phosphatidic acid (52.7%) and phosphatidyl serine (47.3%). The major fatty acids of crude lipid, wax, free fatty acids, triglycerides, diacylglycerides, and monoacyl glycerides were C19:1 (cyclo), C18:2, C16:0, C19:1 (cyclo), C22h:0, and C18:0, respectively. These results are new findings and suggest significant characteristics from the metabolic, physiologic, and chemotaxonomic point of view.

Chromatography, Gas↗
PubMed1993

Difference of the 28-item general health questionnaire scores between Japanese high school and university students.

The General Health Questionnaire (GHQ) with 28 items was tested in Nagasaki city on 138 senior students in a prefectural high school and 685 freshmen in a national university to evaluate the degree of students' mental stress due to the highly competitive entrance examination for university. The average GHQ score tested on high school students was 5.33 for males and 7.07 for females, and 3.99 for males and 4.42 for females on university students. It showed that high school students were under greater pressure than university students and female students were in a higher tension compared with male students. The factor analysis showed that the primary and secondary factor of high school students were "severe depression" and "anxiety and insomnia," while "somatic symptoms" were the primary factor causing stress in university students.

Adolescent↗
PubMed1993

Purification of arginine-sensitive hemagglutinin from Fusobacterium nucleatum and its role in coaggregation.

Hemagglutinin of Fusobacterium nucleatum was extracted from Triton X-100-pronase P-treated cell envelopes, and was purified by affinity chromatography on L-arginine agarose. The hemagglutinin was inactivated by heating at 70 degrees C for 1 min. The activity was inhibited by L-arginine but was not affected by any sugars or by EDTA. The hemagglutinin aggregated 14 out of 17 strains of oral streptococci tested, and the bacterial aggregating activity was also inhibited by L-arginine. The results indicate the dominant role of this hemagglutinin in the adherence of this bacterium both to host cells and to other bacteria.

Arginine↗
PubMed1993

[A comparative study of chemosensitivity tests in vitro for AUC-dependent drugs focusing on the usefulness of MTT assay with drug washout and additional incubation (M-MTT)].

Although many in vitro chemosensitivity tests for anticancer agents have been reported, no scientific assessment of the optimum exposure time and dose of anticancer drugs for such tests has been established. We assessed the cytotoxicity of 4 anticancer agents (CDDP, CBDCA, ADM, MMC) by analyzing the relationships between the IC50 values and the drug exposure time in a study using PC-14 cells. The clinical AUC (Area Under the Curve) of each drug was compared with the dose giving 50% inhibition of the control level for cell growth (IC50) in a conventional MTT assay (C-MTT). A modified MTT assay, which involved washing out of the drugs and additional incubation (M-MTT) and a HTCA (Human Tumor Clonogenic Assay) was also carried out with PC-9 and PC-14 cells. The results suggested that all of 4 anticancer drugs were AUC-dependent agents. The HTCA was considered to be the assay giving results closest to the doses effective in clinical practice among the 3 assays tested, while the C-MTT gave a much higher AUC than the clinical AUC. It is suggested the reason is that in the C-MTT all the cells are viable at the end of drug exposure. Thus, not only viable cells with the potential of proliferate but also those without this potential are included in the results. On the other hand, viable cells with a proliferative potential are better assessed by the M-MTT, which has an additional incubation time. This study indicated that the C-MTT was unsuitable in vitro chemosensitivity tests for new AUC-dependent drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Agents↗
PubMed1992

Conformational feature of neuroactive domoic acid: X-ray structural comparison with isodomoic acid A and alpha-kainic acid.

As an aid for developing a new type of potent insecticide acting on the neuromuscular junction, conformational characteristics of domoic acid and isodomoic acid A, the naturally occurring glutamate agonists, were investigated by X-ray crystal analyses. Conformational comparison with a neuroactive alpha-kainic acid provides information concerning the stereochemical feature responsible for the biological activity.

Insecticides↗
PubMed1992

Application of ultrasonic probes prior to endoscopic resection of early gastric cancer.

The development of a new strip biopsy technique for endoscopic mucosectomy utilizing endoscopic saline injection and a double-channel endoscope permits the safe and simple resection of superficial type early gastric cancer which has been difficult to perform with conventional polypectomy techniques. Preresection assessment of the depth of invasion and postresection assessment of efficacy are important with regard to treatment of early gastric cancer, but conventional endoscopic ultrasonography employed for this purpose requires special equipment and involves intricate procedures. An ultrasonic probe which can be used endoscopically has recently been developed and is currently in the trial stage. The authors have conducted studies with respect to a 7.5 MHz radial scanning type Miniature Ultrasonic Probe as well as a 20 MHz manual linear scanning type Sonoprobe System. Experimental studies indicated that the former type is capable of delineating postresection ulcers, while the latter permitted delineation of tumors as hypoechoic images in 9 of 11 cases of early gastric cancer.

Adenocarcinoma↗
PubMed1992

Ecological structure and incidence rates of schizophrenia in Nagasaki City.

The purpose of this study was to investigate the relationship between incidence rates of schizophrenia and residential features in Nagasaki City, Japan. Social features of residents in 259 areas in the Nagasaki City ecological structure were determined using the results of the 1980 national census. Six residential factors--employment status, occupational and academic career, household status, length of residence, housing tenure and young male predominance--were selected as factors that clearly reflect residential differentiation of residents. Contrary to the findings of many other studies conducted in Western cities, no statistically significant differences were observed, although it seemed that incidence rates were comparatively higher in the lower social classes. These results possibly reflect differences in cultural and social values and structures.

Adult↗
PubMed1992

[Endoscopic treatment of early colorectal cancer].

Early cancer of the colon and rectum is currently treated by endoscopic or surgical resection. We studied the indications for endoscopic treatment of early colorectal cancers (80 lesions) in relation to the size and macroscopic findings. The endoscopic treatment consists of polypectomy for a pedunculated or a sessile polyp and strip biopsy for a plaque-like or a depressive lesion. Microscopic or most small cancers were completely treated endoscopically. From macroscopic findings of the early cancers, type Ip (less than 2cm and 2cm in diameter) was completely treated by polypectomy, type I s and type II a (less than 1cm and 1cm in diameter) by polypectomy or strip biopsy, and type II c (less than 0.5cm and 0.5cm in diameter) by strip biopsy.

Colonic Neoplasms↗