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Biomedical subjects

Y Takeda

Publications and source records attributed to Y Takeda.

At least 217 records · Page 12Linked to original sources
PubMed2000

Effects of chronic neutral endopeptidase inhibition in rats with cyclosporine-induced hypertension.

OBJECTIVE: Cyclosporine (CysA), a potent immunosuppressant, is associated with hypertension and nephrotoxicity. Neutral endopeptidase (NEP) degrades vasoactive peptides, including the natriuretic peptides and endothelin-1 (ET-1). We conducted the present study to determine whether or not the NEP inhibitor, ecadotril, prevents cyclosporine-induced hypertension and to clarify the mechanisms responsible for the hypotensive effects of ecadotril. DESIGN AND METHODS: We studied the chronic effects of ecadotril (30 mg/kg per day) on blood pressure; the production of ET-1 and C-type natriuretic peptide (CNP); endothelial nitric oxide synthase (eNOS) activity; and the expression of messenger RNA (mRNA), for each substance in blood vessels of CysA-induced hypertensive rats. RESULTS: CysA (25 mg/kg per day) given for 4 weeks increased the blood pressure from 116 +/- 14 mmHg to 159 +/- 15 mmHg, in rats. This increase was blunted by the co-administration of ecadotril (blood pressure: 134 +/- 14 mmHg). CysA increased plasma NEP activity. CysA increased the production of ET-1 and the expression of ET-1 mRNA without affecting CNP synthesis and endothelin converting enzyme (ECE)-1 mRNA expression. CysA decreased the eNOS activity and eNOS mRNA levels. Addition of the NEP inhibitor decreased the synthesis of ET-1 and ET-1 mRNA levels and increased the eNOS activity and the eNOS mRNA levels. Vascular CNP synthesis and ECE-1 mRNA expression in rats treated with ecadotril did not differ from those in rats treated with CysA and ecadotril. CONCLUSION: These results indicate that chronic NEP inhibition may prevent the CysA-induced hypertension by decreasing local ET-1 synthesis and partly increasing vascular nitric oxide production.

Animals↗
PubMed2000

Threshold of ischemic depolarization for neuronal injury following four-vessel occlusion in the rat cortex.

Previous studies have indicated that prolonging the onset of ischemic depolarization reduces neuronal damage. However, the relationship between the duration of ischemic depolarization and its histological outcome has not been quantitatively evaluated. Rats were anesthetized (with 1% halothane), intubated, and placed in a stereotaxic frame. Direct current (DC)-potential in the 5th layer of the parietal cortex was measured. Changes in cerebral blood flow (CBF) were monitored by a laser-Doppler flow probe placed adjacent to the DC-electrode. Animals were subjected to four-vessel occlusion for 5 minutes, 10 minutes, or 20 minutes. The histological outcome was evaluated at the DC-recorded site 7 days after the insult. Initiation of ischemia reduced CBF to 9%-28% of the preischemic value. Initial DC-deflection (14+/-3 mV), indicating ischemic depolarization, was observed at 172+/-112 seconds after the onset of ischemia. Total durations of ischemic depolarization were 6.4+/-1.5 minutes, 10.6+/-3.5 minutes and 19.8+/-4.6 minutes in rats in which ischemia was induced for 5 minutes, 10 minutes, and 20 minutes, respectively. The regression curve showed that there was a close relationship between percentage of damaged neurons and duration of ischemic depolarization (r2 = 0.80, P = .001). The durations of ischemic depolarization for neuronal injury in 30%, 50%, and 70% of pyramidal neurons in the parietal cortex were 15.6 minutes (95% confidence interval, 14.2-17.0 minutes), 20.3 minutes (18.5-22.7 minutes) and 25.0 minutes (22.7-28.5 minutes), respectively. It is thought that shortening the duration of ischemic depolarization is a rational approach for reducing the severity of ischemic injury.

Animals↗
PubMed2000

Mutation analysis of the PTEN / MMAC1 gene in Japanese patients with Cowden disease.

Cowden disease (CD), also known as multiple hamartoma syndrome, is an autosomal dominant cancer syndrome associated with high risk of breast and thyroid cancer. Recently, germline mutations in PTEN / MMAC1, which has nine exons encoding a dual specificity phosphatase with homology to tensin and auxilin, have been identified on chromosome 10q23 in some 40 to 80% of CD patients. Our polymerase chain reaction amplification and sequence analysis of all coding regions identified five different mutations including four novel germline mutations among 5 of 12 unrelated Japanese CD patients. The novel findings included a missense mutation (G --> T) at nucleotide 1004 in exon 8 resulting in an arginine-to-leucine change at codon 335 (R335L), two novel splice-site mutations (209 + 1delGT and 209 + 1delGTAA) in intron 3, and insertion of G at nucleotide 632 in exon 6 (632insG). We also detected a nonsense mutation (C --> T) at nucleotide 697 producing R233X in exon 7, which has been reported previously. From reported phenotypic data concerning CD patients from five different families who had the R233X mutation, it may be suggested that R233X mutation correlates with macrocephaly. Although previous reports have implicated exon 5 as a "hot spot," we found no mutation in exon 5.

Adult↗
PubMed2000

Clinical implications of TT virus superinfection in patients with chronic hepatitis C.

OBJECTIVE: TT virus (TTV) has been identified as a candidate agent of non-A-E hepatitis virus. We investigated superinfection of TTV in patients with chronic hepatitis C and studied the susceptibility to interferon (IFN) treatment and its association with liver disease caused by hepatitis C virus (HCV). METHODS: TTV DNA was examined using the seminested polymerase chain reaction (PCR), and its virus level was measured by the real-time fluorometric PCR. RESULTS: TTV DNA was detected in 20 of 102 (19.6%) patients examined. There was no significant difference in the alanine aminotransferase (ALT) level between patients with or without TTV DNA. Quantitative analysis of HCV RNA and TTV DNA revealed no correlation between virus levels in HCV/TTV-coinfected patients. Both TTV and HCV were sensitive to IFN therapy. Complete response to IFN with a sustained loss of viremia for 24 wk after completion of IFN treatment was found in 11 of 20 (55%) patients with respect to TTV DNA and in five of 20 (25%) patients with respect to HCV RNA. The mean pretreatment HCV RNA level was significantly lower in the complete-response cases than in the no-response cases, but there was no significant difference in the pretreatment TTV DNA levels between them. ALT normalization resulting from IFN therapy was not attributable to the eradication of TTV DNA but was attributable to that of HCV RNA. Superinfection by TTV did not influence the effect of IFN against HCV. No specific TTV genotype correlating with IFN sensitivity was found. CONCLUSIONS: These results suggest that TTV infection stands independent of HCV infection, with no influence on liver injury as a result of HCV infection.

Adolescent↗
PubMed2000

[Future direction of medical care system for patients with infectious disease and the new infectious diseases control law in Japan--centering around a category 1 hospital].

As of April 1, 1999, the new Infectious Diseases Control Law became effective in Japan. Under the new law, there are three types of category for medical care systems such as "Specified Infectious Disease Medical Hospital", "Category 1 Infectious Disease (Ebola virus hemorrhagic fever, Marburg disease, Lassa fever, Crimean-Congo hemorrhagic fever and plague) Designated Hospital" and "Category 2 Infectious Disease (Cholera, Sigellosis, Typhoid fever, Paratyphoid fever, Poliomyelitis and Diphtheria) Designated Hospital". In these categories, "Category 1 Infectious Disease Designated Hospital" should be designated by prefectural governments, one hospital per prefecture. Recently some papers indicated that (1) whether each government should arrange a category 1 hospital, (2) whether strict isolation with precautions against airborne spread including negative air pressure with anterior-room should be required, (3) plague is not a dangerous disease and the patient with plague is not required of Category 1 hospital but Category 2 hospital for medical care and infection control. The purpose of this article is, including a counterargument for these opinion, to summarize the point of view for the new medical care system under the new law and to search for the future medical care system in Japan. First of all, medical care for patients with infectious diseases should not be a special one but the extension of the general one. Second, we understand that one of the purposes for Category 1 hospital is the core hospital concerning the therapy, pre/post education and research for infectious diseases in each prefectures. Third, the constructive standard for Category 1 hospital should be a strict one including negative air pressure rooms with an anterior-room and an outside hall, and the air should not be recirculated. Under the big chance of enforcement of this new Infectious Diseases Control Law in Japan, we should try to restruct about medical care system for patients with infectious diseases in a long-range plan.

Hospital Design and Construction↗
PubMed2000

Virulence genes in environmental strains of Vibrio cholerae.

The virulence of a pathogen is dependent on a discrete set of genetic determinants and their well-regulated expression. The ctxAB and tcpA genes are known to play a cardinal role in maintaining virulence in Vibrio cholerae, and these genes are believed to be exclusively associated with clinical strains of O1 and O139 serogroups. In this study, we examined the presence of five virulence genes, including ctxAB and tcpA, as well as toxR and toxT, which are involved in the regulation of virulence, in environmental strains of V. cholerae cultured from three different freshwater lakes and ponds in the eastern part of Calcutta, India. PCR analysis revealed the presence of these virulence genes or their homologues among diverse serotypes and ribotypes of environmental V. cholerae strains. Sequencing of a part of the tcpA gene carried by an environmental strain showed 97.7% homology to the tcpA gene of the classical biotype of V. cholerae O1. Strains carrying the tcpA gene expressed the toxin-coregulated pilus (TCP), demonstrated by both autoagglutination analysis and electron microscopy of the TCP pili. Strains carrying ctxAB genes also produced cholera toxin, determined by monosialoganglioside enzyme-linked immunosorbent assay and by passage in the ileal loops of rabbits. Thus, this study demonstrates the presence and expression of critical virulence genes or their homologues in diverse environmental strains of V. cholerae, which appear to constitute an environmental reservoir of virulence genes, thereby providing new insights into the ecology of V. cholerae.

Amino Acid Sequence↗
PubMed2000

Cell vacuolation, a manifestation of the El tor hemolysin of Vibrio cholerae.

Culture supernatants of nontoxigenic nonepidemic clinical strains of Vibrio cholerae belonging to diverse serogroups were found to induce vacuolation of nonconfluent HeLa cells. The vacuoles became prominent 18 h after introduction of culture supernatant, and vacuolated cells survived for 48 h and then died. Only a fraction of the vacuolated cells took up neutral red dye, implying that there were differences in the vacuolar microenvironment. Further tests showed that the factor responsible for vacuolation was heat labile and proteinaceous. Vacuolating activity was completely neutralized by antibody to hemolysin of V. cholerae but not by antibody to vacuolating cytotoxin of Helicobacter pylori. Partial purification of the vacuolating factor led to elution of fractions, which showed both hemolytic and vacuolating activity. PCR amplification and cloning of the hemolysin structural gene (hlyA) into Escherichia coli DH5alpha led to isolation of clones producing cell vacuolating factor in a cell-associated form. Further, a null insertion mutation in the hlyA gene of a high-vacuolating-factor-producing strain led to complete abolition of both cell vacuolating and hemolytic activities. These analyses establish vacuolation as a potentially important but previously unrecognized property of V. cholerae El Tor hemolysin.

Animals↗
PubMed2000

Emergence of Vibrio cholerae O1 biotype El Tor serotype Inaba from the prevailing O1 Ogawa serotype strains in India.

The toxigenic Inaba serotype of Vibrio cholerae O1 biotype El Tor reappeared in India in 1998 and 1999, almost 10 years after its last dominance in Calcutta in 1989. Extensive molecular characterization by ribotyping, restriction fragment length polymorphism, and pulsed-field gel electrophoresis indicated that recent Inaba strains are remarkably different from the earlier Inaba strains but are very similar to the prevailing V. cholerae O1 Ogawa El Tor biotype strains. The antibiograms of the Inaba strains were also similar to those of the recent V. cholerae Ogawa strains. These V. cholerae O1 Inaba strains appear to have evolved from the currently prevailing Ogawa strains and are likely to dominate in the coming years.

Anti-Bacterial Agents↗
PubMed2000

Agonist-induced isometric contraction of smooth muscle cell-populated collagen gel fiber.

String-shaped reconstituted smooth muscle (SM) fibers were prepared in rectangular wells by thermal gelation of a mixed solution of collagen and cultured SM cells derived from guinea pig stomach. The cells in the fiber exhibited an elongated spindle shape and were aligned along the long axis. The fiber contracted in response to KCl (140 mM), norepinephrine (NE; 10(-7) M), epinephrine (10(-7) M), phenylephrine (10(-6) M), serotonin (10(-6) M), and histamine (10(-5) M), but not acetylcholine (10(-5) M). Phentolamine (10(-7) M) produced a parallel rightward shift of the NE dose-response curve. Moreover, NE-induced contraction was partially inhibited by nifedipine and completely abolished by the intracellular Ca(2+) chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester, the myosin light chain kinase inhibitor ML-9, the Rho kinase inhibitor Y-27632, and papaverine. A [(3)H]quinuclidinyl benzilate binding study revealed that the loss of response to acetylcholine was due to the loss of muscarinic receptor expression during culture. The expression of contractile proteins in the fibers was similar to that in cultured SM cells. These results suggest that, although the fiber is not a model for fully differentiated SM, contractile mechanisms are maintained.

Acetylcholine↗
PubMed2000

Cardiac aldosterone production in genetically hypertensive rats.

Aldosterone is synthesized in extra-adrenal tissues, both blood vessels and brain. We undertook the present study to determine whether the rat heart produces aldosterone and to investigate the effects of adrenalectomy, ACE inhibition, and angiotensin II on aldosterone synthesis in the heart. To clarify the pathophysiological role of cardiac aldosterone in the hypertensive heart, we compared the synthesis of aldosterone in the hearts of stroke-prone spontaneously hypertensive rats (SHRSP) with that in Wistar-Kyoto rats. The effects of the aldosterone antagonist spironolactone on myocardial hypertrophy in adrenalectomized SHRSP were also studied. Isolated rat hearts were perfused for 2 hours, and the perfusate was analyzed with HPLC and mass spectrometry. The activity of aldosterone synthase was estimated on the basis of the conversion of [(14)C]deoxycorticosterone to [(14)C]aldosterone. The levels of aldosterone synthase gene (CYP11B2) mRNA were determined with competitive polymerase chain reaction. Aldosterone production, the activity of aldosterone synthase, and the expression of CYP11B2 mRNA were increased in hearts from adrenalectomized rats and rats treated with angiotensin II. ACE inhibitors decreased cardiac aldosterone synthesis. Cardiac aldosterone, aldosterone synthase activity, and CYP11B2 mRNA levels in hearts from 2- and 4-week-old SHRSP were significantly greater than those of age-matched Wistar-Kyoto rats. Spironolactone prevented cardiac hypertrophy in adrenalectomized SHRSP. These results suggest that the rat heart produces aldosterone and that endogenous cardiac aldosterone may affect cardiac function and hypertrophy in hypertension in rats.

Adrenalectomy↗
PubMed2000

Sodium-induced cardiac aldosterone synthesis causes cardiac hypertrophy.

High sodium intake causes cardiac hypertrophy independently of increases in blood pressure. Aldosterone is synthesized in extraadrenal tissues such as blood vessels, brain, and heart. Effects of 8 weeks of high sodium intake on cardiac aldosterone synthesis, as well as cardiac structure, mass, and aldosterone production, levels of mRNA coding for aldosterone synthase (CYP11B2) and the angiotensin II AT1 receptor, were studied in normotensive Wistar-Kyoto (WKY) rats. Isolated rat hearts were perfused for 2 hr, and the perfusate was analyzed by high-performance liquid chromatography and mass spectrometry. Aldosterone synthase activity was estimated from the conversion of [14C]deoxycorticosterone to [14C]aldosterone. Levels of mRNA for CYP11B2 and AT1 receptor were determined by competitive polymerase chain reactions. A high sodium intake for 8 weeks produced left ventricular hypertrophy without elevation of blood pressure. Plasma aldosterone concentrations and plasma renin concentrations were decreased by high sodium intake. Aldosterone production, activity of aldosterone synthase, and expression of mRNA for CYP11B2 and AT1 receptor were increased in hearts of rats with high sodium intake. These results suggest that high sodium intake increases cardiac aldosterone synthesis, which may contribute to cardiac hypertrophy independently of the circulating renin-angiotensin-aldosterone system.

Aldosterone↗
PubMed2000

Isolation of lignan glucosides and neolignan sulfate from the leaves of Glochidion zeylanicum (Gaertn) A. Juss.

Six lignan and neolignan derivatives (1-6) were isolated from the n-BuOH-soluble fraction of a MeOH extract of the leaves of Glochidion zeylanicum. On the basis of spectral data, their structures were elucidated to be (+)-isolarisiresinol 3a-O-beta-glucopyranoside (1), dihydrodehydrodiconiferyl alcohol 4-, 9- and 9'-O-beta-D-glucopyranosides (2-4, respectively), (+)-isolarisiresinol 2a-O-beta-D-glucopyranoside (5), and dihydrodehydrodiconiferyl alcohol 9-O-sulfate (6), and 5 and 6 were new compounds.

Euphorbiaceae↗
PubMed2000

Labdane diterpenoids from Marrubium globosum ssp. globosum.

A new labdane type diterpenoid, marrubiglobosin, was isolated from the aerial parts of Marrubium globosum ssp. globosum together with the known diterpenoids, marrubiin and marrubinone B. The structure of this new compound was elucidated by spectral methods.

Diterpenes↗
PubMed2000

Megastigmane, benzyl and phenethyl alcohol glycosides, and 4,4'-dimethoxy-beta-truxinic acid catalpol diester from the leaves of Premna subscandens MERR.

Extensive isolation work on the n-BuOH-soluble fraction obtained from the leaves of Premna subscandens, collected on Ishigaki island, Okinawa, afforded six compounds. Two were identified as megastigmane glucosides, 7-(3,5-dihydroxy-1,1,5-trimethylcyclohexylidene)-9-methylprop++ +-8-enyl 9-O-beta-D-glucopyranoside and 3-hydroxy-5,6-epoxy-beta-ionol 9-O-beta-D-glucopyranoside. The structures of the remaining four new compounds were elucidated to be a 2'-O-beta-D-apiofuranosyl derivative of 3-hydroxy-5,6-epoxy-beta-ionol 9-O-beta-D-glucopyranoside, named premnaionoside, benzyl alcohol beta-D-(2'-O-beta-D-xylopyranosyl)glucopyranoside, phenethyl alcohol beta-D-(2'-O-beta-D-glucopyranosyl)glucopyranoside, and 4,4'-dimethoxy-beta-truxinic acid catalpol diester by spectroscopic analyses.

Acetylation↗
PubMed2000

Glochidionolactones A-F: butenolide glucosides from leaves of Glochidion zeylanicum (GAERTN) A. JUSS.

From the leaves of Glochidion zeylanicum, six new butenolide glucoside, named glochidionolactones A-F, were isolated along with a known related compound, phyllanthurinolactone. The structures of glochidionolactones A-D and F were elucidated mainly by spectroscopic analyses. The absolute stereochemistry of glochidionolactone E was established by X-ray crystallographic analysis.

Crystallography, X-Ray↗
PubMed2000

Development of non-bacterial thrombotic endocarditis after percutaneous transvenous mitral commissurotomy for severely calcified mitral stenosis.

We encountered a case of mitral stenosis, complicated with non-bacterial thrombotic endocarditis, that developed after percutaneous transvenous mitral commissurotomy (PTMC). A 71-year-old female Japanese patient had severe congestive heart failure and underwent PTMC for critical and severely calcified mitral stenosis. Four weeks later, the echocardiogram demonstrated a highly echoic protrusion in the postero-medial commissure of the mitral valve. There was little evidence of inflammation at that time. She had been anticoagulated adequately since she was admitted. The patient underwent replacement of the mitral valve. She did not show any evidence of systemic embolization. Microscopic evaluation showed only organized thrombus but no evidence of inflammation in the mitral valve. Silent development of non-bacterial thrombotic endocarditis after PTMC should be recognized as a rare but potentially lethal complication of PTMC.

Aged↗