Search PubMed⌕ Search

Biomedical subjects

T Ishihara

Publications and source records attributed to T Ishihara.

At least 199 records · Page 11Linked to original sources
PubMed1998

Circadian blood pressure and heart rate profiles in normotensive patients with mild hyperthyroidism.

We investigated the influence of thyroid hormones on the circadian blood pressure (BP) and heart rate (HR) variations in 12 normotensive subjects and 12 normotensive patients with mild hyperthyroidism. BP and HR were monitored every 30 minutes for 48 h, and electrocardiograms (ECGs) were recorded to measure the RR interval of the ECGs. We analyzed the circadian BP and HR variations, HR variability, and the morning rise in BP and HR. There was no significant difference in the average 24 h BP between groups. HR and pulse pressure were higher in the hyperthyroid group than in the control group. Though the circadian BP pattern was similar in both groups, HR decreased at night in the control group, but not in the hyperthyroid group. Spectrum analysis of the RR interval showed no increase in the high-frequency (HF) component at night in patients with hyperthyroidism. The HR did not show a morning rise in the hyperthyroid group. These findings indicate that the circadian rhythm of HR was not preserved in patients with mild hyperthyroidism. The circadian BP rhythm was similar in normotensive subjects and normotensive patients with mild hyperthyroidism, suggesting that it resulted from factors other than thyroid hormone.

Adult↗
PubMed1998

Ultrastructural evidence for the formation of amyloid fibrils within cardiomyocytes in isolated atrial amyloid.

Isolated atrial amyloid (IAA) frequently affects elderly human hearts in which only the atria are involved by the deposits. Biochemical analysis has indicated that the major subunit protein of IAA is alpha-human atrial natriuretic peptide (alpha-ANP), which is synthesized by the atrial muscle cells. To define the exact location of the formation of IAA fibrils, right atria from 25 patients undergoing cardiac surgery have been examined by an immunohistochemistry and immunoelectron microscopy with anti-alpha-ANP, apolipoprotein E, amyloid P component, transthyretin, and cathepsin B antisera. Of 25 patients, 19 were involved with IAA deposits which reacted with anti-alpha-ANP, apolipoprotein E, amyloid P component antisera but not with anti-transthyretin antiserum. In 8 of them, amyloid fibrils were seen not only in the interstitium of the atrial myocardium but also in the dilated transverse tubules of the cardiomyocytes. In some cardiomyocytes, amyloid fibrils were also demonstrated within the organelles such as coated and uncoated secretory vesicles or lysosomes. These findings lead to the inescapable conclusion that the polymerization of amyloid fibrils in IAA occurs within the cytoplasm of cardiomyocytes under some conditions.

Adult↗
PubMed1998

[Differences in exercise blood pressure response between dipper and non-dipper elderly patients with essential hypertension].

We evaluated the circadian variation and exercise stress response patterns of blood pressure (BP) in elderly patients with essential hypertension. Ambulatory BP monitoring for 48 hours every 30 minutes, and treadmill exercise test using a Bruce protocol at PM 3 to 5 were performed in 49 untreated patients with hypertension. Mean daytime (awake), and night-time (sleeping) systolic BP (SBP) and diastolic BP (DBP) values were analyzed by reviewing the patients' diaries, and the nocturnal reduction rate (NRR) of SBP and DBP were calculated according to the following formula. NRR (%) = [(daytime mean-nighttime mean)/daytime mean] x 100. The patients were divided into two groups according to the presence (dipper, n = 25) or absence (non-dipper, n = 24) of a reduction in both SBP and DBP during the night by an average of more than 10% of the daytime BP. Mean values of SBP and DBP measured over 48 hours in the dipper and non-dipper groups were similar. Responses of SBP to dynamic exercise at 2 to 5 minutes in the non-dipper group were significantly smaller than those in the dipper group (p < 0.05). Non-dipper patients with hypertension responded to dynamic exercise stress with smaller increases in SBP than did those in the dipper group. The differences in BP responses to exercise may affect the circadian blood pressure profile in dipper and non-dipper elderly patients with essential hypertension.

Aged↗
PubMed1998

[Pharmacokinetic and clinical evaluation of tazobactam/piperacillin in the pediatric field].

Pharmacokinetic and clinical evaluation was conducted on the combination drug, tazobactam/piperacillin (TAZ/PIPC, YP-14), of newly developed beta-lactamase inhibitor, tazobactam (TAZ), and antibiotic agent of penicillin group for injections, piperacillin (PIPC), and the following results were obtained. 1. Absorption and excretion Both serum levels of TAZ and PIPC after the intravenous drip infusion for 30 minutes at the dose of 25 mg/kg or 50 mg/kg of TAZ/PIPC showed peaks at the end of the intravenous drip infusion (in 30 minutes after the commencement of the administration) with the levels of 11.93 or 26.05 micrograms/ml for TAZ and 49.80 or 107.50 micrograms/ml for PIPC. The halflife times were 0.51 or 0.67 hours for TAZ and 0.51 or 0.54 hours for PIPC. The serum level of desethyl-piperacillin (DEt-PIPC), an active metabolite of PIPC, showed a peak one hour after the end of the intravenous drip infusion (in 90 minutes after the commencement of the administration) with the level of 0.79 or 1.47 micrograms/ml. On the other hand, cumulative recovery ratios into urine were 41.3% or 40.4% for TAZ and 38.7% or 37.8% for PIPC. The recovery ratio for DEt-PIPC, an active metabolite of PIPC, was 1.9% or 0.3%. 2. Clinical evaluation TAZ/PIPC was administered to 47 cases (pneumonia: 25 cases, bronchitis: 16 cases, cutaneous soft tissue infection: 3 cases, urinary tract infection: 2 cases and lymphadenitis: 1 case). Clinical efficacy evaluation was conducted in 45 cases, excluding one case with bronchitis complicated by measles and other one case with left cervical cellulitis complicated by mumps. Good or more efficacy was observed in the all cases (excellent efficacy: 28 cases and good efficacy: 17 cases). The eradication rate in 31 cases where the pathogenic bacteria were identified and bacteriological efficacy was revealed was 93.5% (29/31 cases). Out of them, bacterial replacement was observed in 5 cases. Decrease in bacteria (including partial eradication) was observed in the remaining 2 cases. Adverse reactions were not reported in any cases. Abnormal values of clinical laboratory examination were reported in 5 cases (increase in platelet count: 2 cases, decrease in leukocyte count: 2 cases and increase in eosinophil count: 1 case). However, there was no case requiring any treatment.

Bacteria↗
PubMed1998

Purification and characterization of a novel dipeptidase from carp ordinary muscle.

A novel dipeptidase was purified to homogeneity from the crude extract of carp ordinary muscle with an increase in specific activity of 4041-fold and a 4% recovery rate. The enzyme was determined to have molecular weights of 54,000 after reduction and 106,000 without reduction, indicating that it is composed of two sulfide-linking molecules of subunit peptide chains of identical molar size. The optimum hydrolysis pH and temperature of the enzyme were evaluated by l-leucine-glycine to be pH 8.5 and 40 degreesC, respectively, and it was markedly stable in the weak alkaline region and at temperatures below 30 degreesC. Dipeptide hydrolysis of the enzyme was inhibited by metalloprotease inhibitors, sulfide-specific reagents, metal chelating reagents and reductants. In addition, sulfide-affinity bivalent metals potently inactivated the enzyme, while Mg2+ and Mn2+ activated it to different extents, and Mn2+ was also effective on the restoration of the nearly completely inactivated enzyme. The enzyme had a broad range of action on dipeptides that are composed of only l-amino acids, such as l-leucine, l-methionine, l-phenylalanine, and l-valine at the C-terminal and l-alanine, l-leucine, l-methionine, and l-valine at the N-terminal, but it had no catalytic action on dipeptides containing l-proline and d-amino acids, tripeptides, and peptide derivatives.

Journal Article↗
PubMed1998

Distinctive catalytic actions of carp dipeptidases from ordinary muscle and intestine.

Although carp muscular and intestinal dipeptidases are metalloenzymes acting only on dipeptides, some structural and enzymatic differences occur between them. The present study verifies distinctive actions during dipeptide hydrolysis by these enzymes in terms of their kinetic characterization. The intestinal enzyme was differentially inhibited by EDTA and 1,10-phenanthroline, whereas these compounds induced a similar level inhibition of the muscular enzyme. The Km and Vmax values of both enzymes for l-leucine-glycine hydrolysis varied during incubations with 1,10-phenanthroline and EDTA, and the Km or Vmax values of the intestinal enzyme increased or remained the same with increasing concentrations of 1,10-phenanthroline, respectively. Analysis of the kinetic parameters indicated that Co2+ and Mn2+ had noncompetitive effects on the muscular enzyme and that a noncompetitive activation on the intestinal enzyme was stimulated by 1.5 mM of Mg2+ and with increasing concentrations of Mn2+. The muscular enzyme acted on a wide range of l-configuration dipeptides, whereas the intestinal enzyme acted only on a select range of dipeptides with a hydrophobic amino acid at the N-terminal position. The Kcat/Km values of both enzymes for dipeptide hydrolysis showed that highly hydrophobic dipeptides served as their preferential substrates. Other kinetic parameters demonstrated distinctive hydrolytic action of the two enzymes on these dipeptides: a strong affinity of the low catalytic rate muscular enzyme, and a weak affinity of the high catalytic rate intestinal enzyme.

Journal Article↗
PubMed1998

[Primary Sjögren's syndrome with pulmonary hypertension].

A 50-year-old woman was admitted to our hospital because of dyspnea on exertion. A chest X-ray film showed cardiomegaly and echocardiography revealed right-heart overload. Right heart catheterization studies revealed pulmonary hypertension and no signs of pulmonary embolism or vasculitis. The patient had complained of Raynaud's phenomenon since 6 years before admission. She did not notice eye or mouth dryness, but examination of a lip-biopsy specimen showed infiltration of lymphocytes into the salivary glands. Laboratory findings showed hypergammaglobulinemia and hemolytic anemia. Primary Sjögren's syndrome with pulmonary hypertension was diagnosed. Her general condition improved with steroid pulse therapy followed by oral administration of corticosteroids and cyclophosphamide.

Anemia, Hemolytic↗
PubMed1998

[Clinical application of multi-shot diffusion EPI in neurological disease].

Using the multi-shot EPI method we investigated the clinical application of diffusion weighted imaging (DWI) in the diagnosis of neurological disease. The multi-shot method provided better susceptibility artifact-free DWI than the single-shot method particularly in the region of the posterior cranial fossa. DWI using the multi-shot EPI method readily shows the pyramidal tract extending from the internal capsule to the brainstems which is inaccessible by the conventional single-shot EPI method, and providing three-dimensional and distinct images of pyramidal tract changes in amyotrophic lateral sclerosis or cerebral infarction with pyramidal tract disturbance. Our findings suggest that the use of DWI with the multi-shot EPI method would provide a technique for the easy diagnosis and evaluation of various neurological diseases.

Amyotrophic Lateral Sclerosis↗
PubMed1998

Fibrilization in mouse senile amyloidosis is fibril conformation-dependent.

Amyloidosis refers to a group of diseases characterized by tissue deposition of amyloid fibrils. A single intravenous injection of a very small amount of the native mouse senile amyloid fibrils (AApoAII) induced severe systemic amyloid deposition in young mice having the amyloidogenic apoA-II gene (Apoa2c). After AApoAII injection, amyloid deposition occurred rapidly and advanced in an accelerated manner, as observed in spontaneous senile amyloidosis in mice. However, the injection of denatured AApoAII, native apoA-II in high-density lipoprotein (HDL), and denatured apoA-II monomer, which have the same primary structure but without a fibril conformation, did not induce amyloidosis. No amyloid deposition was observed in mice having an amyloid-resistant apoA-II gene (Apoa2b) even 3 months after AApoAII injection. Significantly less amyloid deposition was observed in mice having both types of apoA-II genes heterozygously (Apoa2b/c). These findings suggest that the nucleation-dependent polymerization found in vitro also occurs in vivo, and that the fibril conformation is required for the injected amyloid fibrils to act as seeds in vivo. Fibril conformation-dependent fibrillization is proposed as a general model of the pathogenesis of various kinds of amyloidosis occurring in vivo; it may be useful in both elucidating the pathogenesis of amyloidosis and developing effective therapeutic modalities to treat this disease.

Aging↗
PubMed1997

Alterations of calmodulin and its mRNA in rat brain after acute and chronic administration of methamphetamine.

The effect of acute and chronic administration of methamphetamine (METH) on the levels of calmodulin (CaM) and its mRNAs has been investigated in rat brain using antisense oligonucleotides to three distinct rat CaM genes (CaM I, CaM II, CaM III). CaM I mRNA was reduced in the striatum and nucleus accumbens within 2 h of acute administration of 4 mg/kg METH, but returned to the control level by 6 h. The CaM content in both the cytosolic and membrane fractions of the striatum was reduced 0.5, 2, and 6 h after acute administration of METH. In the chronic experiments, rats were treated with either 4 mg/kg METH or saline once daily for 14 days. This was followed by a withdrawal period of 28 days, and thereafter, the animals were challenged with either METH (4 mg/kg, i.p.) or saline. All the animals were decapitated 6 h after this injection. There were four treatment groups: METH-METH (MM); METH-saline (MS); saline-METH (SM); and saline-saline (SS). There was a significant decrease in the mRNA for CaM I and CaM II in the striatum, and CaM II and CaM III in the nucleus accumbens in the MS group and the MS and MM groups, respectively, when compared to the SS group. The CaM content in the striatal membrane fraction decreased in both the SM and MS groups but not in the MM group. In contrast, the CaM content in the membrane fraction of the mesolimbic area showed a significant increase in the MM group. The CaM content in the cytosolic fraction of these brain areas decreased in both the SM and MM groups. The total CaM decreased significantly in the SM and MM groups of the striatum, but increased significantly in the MM group of the mesolimbic area. The mRNA for CaM I and CaM III decreased significantly in the MM group, and in the SM and MM groups, in the substantia nigra pars compacta (SNC) and ventral tegmental area (VTA), respectively. The CaM content in both the cytosolic and membrane fractions and total CaM content of the SN/VTA decreased significantly in the SM, MS and MM group as compared with the SS group. In the medial prefrontal cortex and hippocampus the significant increase of CaM content in the membrane fraction of the MM group was also found, but neither the CaM content in the cytosol fraction nor total CaM content changed. These results suggest that chronic METH administration leads to a translocation of CaM from the cytosolic to membrane fractions; these may underlie METH-induced behavioral sensitization.

Animals↗
PubMed1997

Inhibition of smooth muscle cell migration by the p21 cyclin-dependent kinase inhibitor (Cip1).

In vascular smooth muscle cells (SMCs), proliferation and migration contribute to lesion formation after arterial injury. In the cell cycle, several cyclin-dependent kinases (cdks) inhibitors are implicated in the regulating of cyclin-cdk activity such as p21Cip1, p16Ink4 and p27Kip1. Although Cip1 inhibits SMC proliferation, its effects on SMC migration are unknown. To test the hypothesis that Cip1 inhibits SMCs migration and proliferation, we transfected the Cip1 gene into a strain of rabbit aortic SMCs (SM3 cells). Both the spreading and the attachment of Cip1-transfected SM3 cells to extracellular matrices (ECMs) were inhibited compared to that of vector-transfected cells. In the modified Boyden's chamber assay the effect of fibronectin on the migratory activity of Cip1-transfected SM3 cells was significantly less than that of vector transfected cells in response to PDGF-BB. These data suggested that Cip1 inhibited both the migration and proliferation of SMC.

Actins↗
PubMed1997

Substituted 3-(phenylsulfonyl)-1-phenylimidazolidine-2,4-dione derivatives as novel nonpeptide inhibitors of human heart chymase.

A series of 3-(phenylsulfonyl)-1-phenylimidazolidine-2,4-dione derivatives have been synthesized and evaluated for their ability to selectively inhibit human heart chymase. The structure-activity relationship studies on these compounds gave the following results. The 1-phenyl moiety participates in a hydrophobic interaction where an optimum size is required. At this position, 3,4-dimethylphenyl is the best moiety for inhibiting chymase and showed high selectivity compared with chymotrypsin and cathepsin G. A 3-phenylsulfonyl moiety substituted with hydrogen-bond acceptors such as nitrile and methoxycarbonyl enhances its activity. Molecular-modeling studies on the interaction of 3-[(4-chlorophenyl)sulfonyl]-1-(4-chlorophenyl)-imidazolidine-2,4-dione (29) with the active site of human heart chymase suggested that the 1-phenyl moiety interacts with the hydrophobic P1 pocket, the 3-phenylsulfonyl moiety resides in the S1'-S2' subsites, and the 4-carbonyl of the imidazolidine ring and sulfonyl group interact with the oxyanion hole and the His-45 side chain of chymase, respectively. The complex model is consistent with the structure-activity relationships.

Binding Sites↗
PubMed1997

Molecular genetic evidence of clinical heterogeneity in Fukuyama-type congenital muscular dystrophy.

Fukuyama-type congenital muscular dystrophy (FCMD) is an autosomal recessive severe muscular dystrophy associated with brain malformation. The gene responsible for FCMD was mapped to chromosome 9q31, a region in which convincing evidence of strong linkage disequilibrium between FCMD and mfd220 (D9S306) was recently found. FCMD is also characterized clinically by a peak motor function which, at best, allows patients to sit unassisted or slide on the buttocks. However, a small fraction of patients acquire the capacity to walk unassisted. Whether such ambulant cases belong to the FCMD spectrum or to a different disease entity has been a topic of considerable debate. We performed linkage analysis for ten families with ambulant cases using DNA markers flanking the FCMD locus. The mfd220 locus yielded a significant lod score of 3.09 for ambulant FCMD. We also found evidence for linkage disequilibrium between ambulant FCMD and mfd220. We further conducted haplotype analysis in FCMD siblings with different phenotypes, one of whom was ambulant while the other was not. The results indicate that the FCMD siblings share exactly the same haplotype at nine marker loci spanning 23.3 cM surrounding the FCMD locus. On the basis of these results, we conclude that, genetically, ambulant cases are, in fact, part of the FCMD spectrum.

Adolescent↗
PubMed1997

Production of adrenomedullin in human vascular endothelial cells.

To examine the production of adrenomedullin (AM) in human vascular endothelial cells, AM concentrations in cultured endothelial cells derived from the human umbilical vein and the conditioned media of the cells were measured in the present study. The cultured endothelial cells secreted immunoreactive AM (ir-AM) into the medium at a rate of 14.7 +/- 3.0 fmol/10(6) cells/24 h with an intracellular ir-AM of 5.2 +/- 0.8 fmol/l0(6) cells. Analysis by reverse phase high performance-liquid chromatography (HPLC) showed that ir-AM in both the cells and the conditioned medium eluted at the position identical to that of human AM(1-52). Treatment with dexamethasone significantly augmented the secretion of ir-AM from the cells without any effect on the intracellular ir-AM concentration. Northern blot analysis showed not only the presence of the 1.6 kb human AM precursor mRNA in the endothelial cells, but also its increased expression in the dexamethasone-treated cells. Thus, AM was synthesized and secreted by the human endothelial cells of the umbilical vein, and glucocorticoid augmented the AM production. These findings suggest not only the role of AM as a local modulator of the vascular tone but also the possibility that endothelial cells contribute to circulating AM in the human blood.

Adrenomedullin↗
PubMed1997

Simple preparation of nanoparticles coated with carbohydrate-carrying polymers.

Nanoparticles bearing carbohydrate chains on the surface can be prepared by the simple diafiltration method. The nanoparticles prepared by the present method displayed high yield, no-aggregation formation, small size, narrow size distribution, and one-step procedure. Also, the high density carbohydrate chains on the particles can be recognized by liver cells.

Animals↗