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T Yanagawa

Publications and source records attributed to T Yanagawa.

At least 73 records · Page 4Linked to original sources
PubMed1997

Antiandrogenic natural Diels--Alder-type adducts from Brosimum rubescens.

The isolation and structure elucidation of five novel natural Diels--Alder-type adducts, named palodesangrens A-E (1-5), from the Peruvian folk medicine known as "palo de sangre" (Brosimum rubescens) is described. The structures of the Diels--Alder adducts, consisting of chalcone derivatives and a prenylcoumarin, were elucidated by analysis of spectroscopic data including 2D NMR. Some of these compounds showed potent inhibitory activity towards 5 alpha-dihydrotestosterone (DHT) binding with an androgen receptor to form a DHT-receptor complex that causes androgen-dependent diseases.

5-alpha Reductase Inhibitors↗
PubMed1997

Blood pressure, insulin, and haematocrit values in Japanese subjects over 60 years of age.

Many studies have suggested an association between blood pressure (BP) and both insulinaemia and haematocrit values in Western populations. However, relatively few data regarding such associations for the Japanese population are available. We investigated the relationship between BP and various parameters, including insulin and haematocrit, in 269 healthy Japanese individuals (113 men and 156 women) over 60 years of age. The data were analysed by stepwise multiple regression analysis. In men, the most important determinant of systolic BP (SBP) and diastolic BP (DBP) was the plasma insulin concentration (beta = 0.32, F = 12.4, P < 0.001 and beta = 0.32, F = 13, P < 0.001, respectively), and haematocrit was found to be associated with DBP (beta = 0.21, F = 5.3, P < 0.05). In women, fasting insulins were unrelated to BP, but fasting plasma glucose and triglyceride concentrations and age were associated with SBP (beta = 0.29, F = 15.5, P < 0.001, beta = 0.27, F = 14.3, P < 0.001, and beta = 0.2, F = 7.8, P < 0.01, respectively), and haematocrit, fasting plasma glucose concentration and age were associated with DBP (beta = 0.29, F = 14, P < 0.001, beta = 0.2, F = 6.9, P < 0.01 and beta = 0.2, F = 6.3, P < 0.05, respectively). These results suggest that the insulin-BP associations in healthy Japanese subjects over 60 years of age differ according to sex, and that haematocrit is an important determinant of DBP in both sexes in our population.

Aged↗
PubMed1997

CTLA4 gene polymorphism confers susceptibility to Graves' disease in Japanese.

Susceptibility to Graves' disease (GD) is determined by environmental and genetic factors. The genetic susceptibility to GD is conferred by genes in the human leukocyte antigen (HLA), and several other genes unlinked to HLA are thought to contribute to the development of GD. Three recent papers described the association of GD with the CTLA-4 gene. CTLA-4 is a candidate gene for T-cell mediated autoimmune diseases because it is a negative regulator of T-cell proliferation. As CTLA-4 association with GD may be influenced by the racial composition of the population, it is important to study it in other ethnic groups. We investigated the distribution of CTLA-4 gene polymorphism in 153 Japanese patients with GD (35 males and 118 females) and 200 controls (96 males and 104 females). An A/G transition at position 49 of exon 1 was analyzed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The distribution of genotype frequencies differs between GD and controls (chi2 = 9.46, 2 degrees of freedom, p < 0.01). The presence of at least one G allele (GG or AG) conferred an odds ratio of 2.64 (95% CI = 1.92-3.36). The present study supported the association of the CTLA-4 gene with GD in Japanese and showed that the CTLA4 gene could be one of the non-HLA linked susceptibility genes for GD.

Abatacept↗
PubMed1997

Identification of mutations in the hepatocyte nuclear factor (HNF)-1 alpha gene in Japanese subjects with IDDM.

One form of maturity-onset diabetes of the young, MODY3, is characterized by a severe insulin secretory defect, compared with MODY2, a glucokinase-deficient diabetes. It has recently been shown that mutations of the gene encoding the transcription factor hepatocyte nuclear factor (HNF)-1 alpha cause MODY3. Because of the rapid progress to overt diabetes and the high prevalence of required insulin treatment in patients with MODY3, we screened the HNF-1 alpha gene for mutations in Japanese subjects with IDDM. Ten exons and flanking introns of the HNF-1 alpha gene in these subjects were amplified by polymerase chain reaction and direct sequencing of the products. Mutations were identified in three (5.5%) of the 55 unrelated subjects with IDDM. A missense mutation of R272H (replacement of Arg by His in codon 272) in the DNA binding domain of HNF-1 alpha was found in a subject who developed IDDM 1 year after diagnosis of NIDDM at 8 years of age. A frameshift mutation of P291 fsinsC (insertion of a C in a polyC tract around codon 291 for Pro), which would generate a mutant truncated protein of 340 amino acids, was found in a subject who started insulin treatment when hyperglycemia and ketonuria were noticed at 13 years of age. A missense mutation of R583G (replacement of Arg by Gly in codon 583) in the transactivation domain of HNF-1 alpha was found in a subject with sudden-onset IDDM at 20 years of age. None of these mutations were present in 100 nondiabetic subjects (200 normal chromosomes). These results indicate that the HNF-1 alpha gene defects could lead to the development of not only early-onset NIDDM but also IDDM, implicating the importance of subclassification of HNF-1 alpha-deficient IDDM from a classical type of autoimmune-based IDDM in Japanese.

Adolescent↗
PubMed1997

[Labor status of anesthesia in general hospitals in Japan Committee on Human Resources, the Japan Society of Anesthesiology].

AIMS: Investigating the labor by anesthetists in general hospitals with more than 600 beds during the month of September 1995. METHOD: Using MS/EXCEL spread sheet soft wear, we have analyzed daily OR anesthesia activities in 33 hospitals based on personal attendance of anesthesiologists. We defined anesthesia performing hours i.e. actual working hours as the time between the onset and the end of anesthesia for each anesthetist. RESULTS: An average number of monthly anesthesia cases was 961 in the first 10 hospitals we surveyed. We obtained two frequency graphs on weekly 5-day working 138 anesthetists whose anesthesia performed, and their occupied hours were as shown in fig. 1 and 2. for those who worked other less than 5 days per week, they showed the shorter hours on the frequency distribution graph as shown in fig. 3 to 7. The 5-day working anesthetists have spent more than 5 hours giving anesthesia in the 93.2% of all anesthesia times in the first 10 hospitals, while 28.1% of the times in the last 10 hospitals. There were an average of 11.6 operating tables, in the first 10 hospitals. And we have analyzed ratios of the number of 5 day working persons to the number of operating tables. The ratio was 0.86 in the first 10 hospitals, while 0.21 in the last 10 hospitals. CONCLUSIONS: There must be overwork of 5-day working anesthetists, who are working for too many hours for anesthesia. It is necessary to have better quality service in the OR.

Anesthesia↗
PubMed1997

Antiandrogenic phenolic constituents from Dalbergia cochinchinensis.

Four new compounds, 9-hydroxy-6,7-dimethoxydalbergiquinol, 6-hydroxy-2,7-dimethoxyneoflavene, 6,4'-dihydroxy-7-methoxyflavan and 2,2',5-trihydroxy-4-methoxybenzophenone, in addition to eight known phenolic compounds including 7-hydroxy-6-methoxyflavone, have been isolated from the stems of Dalbergia cochinchinensis. Their structures were established by spectroscopic techniques including one- and two-dimensional NMR methods. The first two compounds showed potent inhibitory activity towards 5 alpha-dihydrotestosterone (DHT) which binds with an androgen receptor to form a DHT-receptor complex that causes androgen-dependent disease.

5-alpha Reductase Inhibitors↗
PubMed1996

Murine peritoneal macrophages induce a novel 60-kDa protein with structural similarity to a tyrosine kinase p56lck-associated protein in response to oxidative stress.

Using differential screening we have cloned a cDNA encoding a novel oxidative stress protein designated A170 from murine peritoneal macrophages. It has a Zn-finger domain, a PEST domain and several potential phosphorylation sites for kinases. Treatments with oxidative stress agents such as diethyl maleate and paraquat increased a 2.0-kilobase A170 mRNA about twofold in the macrophages after 12 hours in culture. However, H2O2 or glucose/glucose oxidase did not increase the level of the A170 mRNA. Using an A170-specific antibody we have detected in the macrophages a 60-kDa protein that was induced 5 to 10 hours after the addition of the oxidative stress agents. A search of sequence databases revealed that the A170 protein is roughly 90% identical to a human protein that binds to the Src homology 2 domain of the T-cell-specific tyrosine kinase p56lck. These features suggest that the A170 protein plays a significant role in oxidative stress-responsive signal transduction in macrophages.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Body surface distribution of significant changes in QRST time-integral values after radiofrequency catheter ablation in patients with Wolff-Parkinson-White syndrome.

We analyzed 87-lead body surface QRST time-integral values (QRST values) in 29 patients with Wolff-Parkinson-White syndrome (group A, 17 patients with manifest left-sided accessory pathway; group B, 6 patients with manifest right-sided accessory pathway; and group C, 6 patients with concealed left-sided accessory pathway), before, 1 day after, and 1 week after radiofrequency catheter ablation (RCA). The number of leads with abnormal QRST values was significantly lower 1 week after RCA compared with those before RCA and 1 day after RCA in groups A and B (p < 0.05); there was no significant difference in QRST values before and 1 day after RCA in groups A and B. The QRST values over areas with preexisting repolarization abnormalities were significantly altered 1 week after RCA compared with before and 1 day after RCA in groups A and B (p < 0.01). However, there was no significant difference in the QRST values over areas without preexisting abnormalities before RCA. In group C, there were no significant differences in the QRST values or the number of leads with abnormal QRST values before, 1 day and 1 week after RCA. In conclusion, RCA did not significantly influence repolarization properties over areas without preexisting abnormalities, but gradually reduced preexisting repolarization abnormalities, which were closely related to the location of the accessory pathway in patients with manifest Wolff-Parkinson-White syndrome. Our results suggest that body surface QRST values are useful for assessment of repolarization abnormalities during the periablation period.

Adolescent↗
PubMed1996

Relationship between QRS duration and repolarization abnormalities in patients with Wolff-Parkinson-White syndrome.

Marked T wave abnormalities in 12-lead electrocardiograms often appear after radiofrequency ablation in patients with Wolff-Parkinson-White (WPW) syndrome. Durations of the QRS complex before ablation have been reported to be significantly greater in patients with repolarization abnormalities after ablation than in those with normal repolarization. However, there has been no report concerning the relationship between QRS duration and repolarization abnormalities before ablation. It has been reported that QRST isointegral maps are dependent on local cellular repolarization properties but largely independent of activation sequence, and that they provide quantitative information about repolarization abnormalities. Isointegral maps were constructed from data recorded in 34 patients with WPW syndrome and QRS durations of 0.1 second or longer (21 patients with left-sided accessory pathways and 13 with right-sided pathways) in order to investigate the relationship between QRS duration and abnormalities in repolarization properties during preexcitation. Body surface ECGs were recorded with an 87-lead system at a sampling interval of 1 ms. The QRST values (mean +/- 2SD) from 607 normal individuals were taken to represent the normal range. The area with abnormally low QRST values was designated as the -2SD area and the sum of the QRST values (sigma QRST) in this area was calculated. The QRS duration was found to be significantly related to sigma QRST. These results demonstrate that the patients with WPW syndrome had abnormalities in local repolarization properties that were significantly related to QRS duration during preexcitation. The degree of preexcitation may be important in producing these abnormalities in patients with manifest WPW syndrome. This may result in T wave abnormalities after ablation of the accessory pathway attributable to cardiac memory.

Adolescent↗
PubMed1996

Drug sensitivity testing for clinical samples from oesophageal cancer using adhesive tumour cell culture system.

A total of 83 specimens of surgically resected tumours from 78 patients with oesophageal cancer were assayed for drug sensitivity using an adhesive tumour cell culture system (LifeTrac CSA assay). Seventyone of 83 specimens had a sufficient number of cells to permit growth in culture and 57 of 71 (80%) were evaluable for drug response. Cells (3 x 10(3) ml-1 well-1) were cultured for 14 days and exposed to drugs on days 3-8. Growing cells were confirmed as cancer cells by immunohistochemical staining. IC90 values against several anti-cancer drugs were determined and population distributions of IC90 for each drug served as the basis for judging sensitivity. The 10th percentiles of IC90 (microgram ml-1) for CDDP, 5-FU, DOX, CPM, MTX, VP16, IFOS, VDS, BLM and CDDP + 5-FU were 0.3, 0.16, 0.005, 0.9, 0.006, 0.09, 0.8, 0.006, 0.04 and 0.15 + 0.09 respectively. The population distribution of IC90 against each drug showed a specific pattern that was very similar among histopathological gradings and stages of the disease. This system appeared to be a clinically applicable drug sensitivity test for human oesophageal cancer.

Antineoplastic Agents↗
PubMed1996

HLA class II associations in African-American female patients with Graves' disease.

Graves' disease (GD) is an autoimmune thyroid disease. Development of the disease phenotype is believed to be dependent on environmental factors and the action of several genes either in concert or in independent groups. Genes of, or closely associated to, the human leukocyte antigen (HLA) complex are important in determining genetic predisposition to GD in various ethnic groups. We previously reported that no significant HLA class I or -DR associations were detected in the total group of African-American patients with GD. To further investigate the associations of GD with HLA class II alleles, 52 unrelated African-American female patients with GD and 55 controls were typed for HLA-DRB1, -DQA1, and -DQB1, using sequence-specific oligonucleotide probes to analyze polymerase chain reaction amplified DNA. There were no significant differences in HLA distribution between patients and controls. These findings indicate that the contribution of HLA-DR and DQ regions to susceptibility to GD is small in African-American women.

Adult↗
PubMed1996

T-cell recognition of residue 158-176 in thyrotropin receptor confers risk for development of thyroid autoimmunity in siblings in a family with Graves' disease.

Twenty-two subjects in a family with Graves' Disease and 20 normal subjects unrelated to the family were examined for T-cell responses to rec h TSHR-ECD and its synthetic peptides. Seven of the family members and none of the controls responded positively to rec h TSHR-ECD. Peptide 158-176 was the only residue that showed a high percentage of response among family members, no responses in spouses, and a significant difference compared to unrelated controls. Family members under age of 6 did not differ from spouses in response to rec h TSHR-ECD or any individual peptide. Family members ages 6-12 years were significantly different from spouses in response to peptides 30-49, 158-176, and 172-186. The reactivity of adult family members including 3 Graves' patients was significantly different from spouses in response to peptides 44-62, 132-150, 158-176, and 248-263. The responses of female members of the family were higher than that of the male members and significantly different for peptide 272-291. These data suggest that recognition of peptide 158-176 may be an early event in the pathogenesis of the disease and that recognition of both 158-176 and 248-263 residues may be the cornerstone for establishment of the disease.

Adolescent↗
PubMed1996

Establishment of anaplastic thyroid carcinoma cell lines useful for analysis of chemosensitivity and carcinogenesis.

Anaplastic thyroid carcinoma (ATC) is usually associated with a poor prognosis, with most patients dying within a few months. The mechanism of its carcinogenesis is unclear, and its rapid growth and spread often prevent effective surgical therapy. Thus, chemotherapy is necessary. However, ATC is often resistant to anticancer drugs. Therefore, prediction of chemosensitivity is important in selecting appropriate treatment. In this study, after the establishment of three cell lines (K119, KOA2, and IAA) from patients with ATC, we analyzed them for abnormalities in certain oncogenes (myc, ras, ret, and c-erbB2) and the p53 tumor suppressor gene. Only one of three cell lines (KOA2) had a N-ras mutation [codon 61 CAA(Gln)-->CGA(Arg)] and a p53 gene mutation [exon 6 codon 192 Caa(Gln)-->TAG(stop)]. We also investigated their in vitro drug sensitivity and compared it with clinical chemosensitivity, retrospectively. In vitro drug sensitivity was determined using an adhesive tumor cell culture system. Only the K119 cells were sensitive to adriamycin and cisplatin in vitro. The other two were resistant to them in vitro. These results paralleled the clinical responses. We also evaluated the in vitro drug sensitivity of a poorly differentiated thyroid carcinoma cell line (SMP) and papillary thyroid carcinoma cell lines (NPA). None of the five cell lines expressed the multidrug resistance gene (mdr-1). In conclusion, we established ATC cell lines that are suitable models for characterizing the nature of multidrug resistance and carcinogenesis.

Aged↗
PubMed1996

[Outcome in patients with interstitial lung disease and polymyositis-dermatomyositis--a subgroup with poor prognosis].

To determine the role of interstitial lung disease (ILD) in the outcome of polymyositis-dermatomyositis (PM/DM), we studied 41 patients who had radiographic evidence of ILD among 51 patients with PM/DM. The patients were divided into 3 groups according to therapy: progressive, no change, or improved. Those classified as progressive had significantly higher rates of skin and lung symptoms, milder muscle symptoms, and lower levels of muscle enzymes than the other 2 groups, and none was positive for the anti-Jo-1 autoantibody. Nine patients with DM died of respiratory failure; they had low serum creatine kinase levels, no anti-Jo-1 antibodies, and a rapidly progressive course before death. Autopsy findings were obtained in 7 patients, and all had diffuse alveolar damage as the main pulmonary histological finding. A subgroup of patients with PM/DM-ILD have a poor prognosis, and ILD in PM/DM is an important prognostic factor.

Dermatomyositis↗
PubMed1996

[Importance of interstitial lung disease in collagen vascular disease: analysis of outcome].

We studied length of survival and related clinical findings in 715 inpatients with collagen-vascular diseases (1984 through 1994), the diagnostic Kaplan-Meier analysis showed that patients with polymyositis/dermatomyositis and those with systemic sclerosis did not survive as long as those with other types of collagen-vascular disease. Of the patients who died 37% died of respiratory failure due to interstitial lung disease. Patients with interstitial lung disease had better outcomes than did those with idiopathic interstitial pneumonia: they were younger, had higher initial vital capacities, and fewer episodes of acute exacerbation of lung disease than did those with idiopathic interstitial pneumonia. Among patients with interstitial lung disease, those who died of polymyositis/dermatomyositis did so within 1 year, but those who died of systemic sclerosis lived longer. Interstitial lung disease is an important prognostic factor in collagen-vascular disease, and needs further evaluation.

Cause of Death↗