Biomedical subjects

T Hashizume

Publications and source records attributed to T Hashizume.

At least 55 records · Page 3Linked to original sources

PubMed2000

[A case of pulmonary tuberculosis diagnosed by DNA amplification methods from transbronchial lung biopsy materials].

The hybridization assay using polymerase chain reaction (PCR) is useful for rapid detection of Mycobacterium tuberculosis (M. tuberculosis). A 77-year-old female was admitted to our hospital complaining of cough, and examination of the sputum culture showed M. tuberculosis. Her chest X-ray showed a variety of abnormal shadows, such as a cavity lesion, multiple coin lesions, and infiltrates. Malignant disease was also suspected to be involved, with the complication of pulmonary tuberculosis. Specimens were obtained by transbronchial lung biopsy (TBLB) from coin lesions. The hybridization assay using PCR on the TBLB specimens showed M. tuberculosis gene expression. She was treated with anti-tuberculous drugs. All shadows in her chest X-ray were improved six months after admission. She was remained well without recurrence for more than two years after admission. The hybridization assay using PCR with TBLB specimens is useful for the detection of M. tuberculosis.

Aged↗

PubMed1999

Oral administration of peptidergic growth hormone (GH) secretagogue KP102 stimulates GH release in goats.

To assess the oral activity of KP102 (also known GHRP-2) on growth hormone (GH) release in ruminant animals, 5 or 10 mg/kg body weight (BW) of KP102 dissolved in saline was orally administered twice at 2 hr-intervals to either 1- or 3-mo-old goats (n = 5-6). Plasma GH concentrations in the 1-mo-old goats were elevated at 15 min after the first administration of both 5 and 10 mg/kg BW of KP102. Significant elevation of GH concentrations continued until 180 min after 10 mg/kg BW of KP102, whereas the elevated GH levels after the administrations of 5 mg/kg BW of KP102 subsided to basal concentrations within 90 min. The second administration of 10 mg/kg BW of KP102 failed to elevate the GH concentration, but 5 mg/kg BW of KP102 abruptly stimulated GH release. Plasma GH concentrations in the 3-mo-old goats were also significantly elevated after the administration of both 5 and 10 mg/kg BW of KP102. The plasma GH responses to 5 and 10 mg/kg BW of KP102 were almost identical. The elevated GH levels after the first administration of KP102 tended to be maintained throughout the experiment, and a transient increase in plasma GH levels was observed after the second administration. However, the stimulatory effect of KP102 on GH release in the 3-mo-old goats was small and less abrupt than that in the 1-mo-old goats. The concentrations of insulin-like growth factor-I were not increased by KP102 during the brief sampling periods used in this experiment. These results show that the oral administration of the peptidergic GH secretogogue KP102 stimulates GH release in a ruminant species, and that the oral activity of KP102 on GH release is modified by the age.

Aging↗

PubMed1999

Clinical experiences in Sakai City Hospital during the massive outbreak of enterohemorrhagic Escherichia coli O157 infections in Sakai City, 1996.

In the middle of July, 1996, a massive outbreak of hemorrhagic colitis (HC) occurred among elementary schoolchildren in Sakai city. This is the most widespread outbreak of O157 infection ever experienced to our knowledge. Lunch foods supplied in the elementary schools in Sakai were contaminated by Escherichia coli (E. coli) O157. One hundred and twenty-one cases developed hemolytic uremic syndrome (HUS) from 12,680 symptomatic patients, including putative secondary infections, and three girls died during this outbreak. Sakai City Hospital is one of the core medical facilities in this community; hence, 425 children with HC were treated at the hospital. Antibiotics were used extensively on all patients. Among them, 12 children developed HUS. All 425 children, including the patients with HUS, recovered without significant sequelae. In the present paper, the clinical experiences during this massive outbreak of E. coli O157 infection in Sakai City Hospital are described.

Anti-Bacterial Agents↗

PubMed1999

Stimulation by ceramide of phospholipase A2 activation through a mechanism related to the phospholipase C-initiated signaling pathway in rabbit platelets.

To study the involvement of sphingolipids in glycerophospholipid metabolism, the contribution of ceramide to the activation of group IV cytosolic phospholipase A2 (cPLA2) was investigated in platelets using cell-permeable C6-ceramide (N-hexanoylsphingosine). The addition of ceramide led to potentiation of thrombin-induced activation of cPLA2 and mitogen-activated protein kinase (MAPK) as well as arachidonic acid release and lysophosphatidylcholine formation. However, ceramide by itself did not induce any response. The arachidonic acid release due to the synergistic action of ceramide and thrombin was inhibited by PD98059, a MAPK kinase inhibitor. Ceramide also stimulated thrombin-induced protein kinase C (PKC) activation, but ceramide by itself failed to do so. Furthermore, ceramide synergistically enhanced diacylglycerol (DAG) formation and Ca2+ mobilization with thrombin, and also DAG formation with Ca2+-ionophore A23187. The DAG formation in response to ceramide with thrombin or A23187, as well as arachidonic acid release with thrombin were completely inhibited by U73122, a phospholipase C (PLC) inhibitor. These results suggest that ceramide triggers PLC activation through its synergistic action with thrombin, and subsequently potentiates the sequential PKC-MAPK cascade-cPLA2 pathway, thus resulting in enhancement of arachidonic acid release.

Animals↗

PubMed1999

A new Ca-antagonist, azelnidipine, reduced blood pressure during exercise without augmentation of sympathetic nervous system in essential hypertension: a randomized, double-blind, placebo-controlled trial.

This study was carried out to evaluate the effect of a new long-acting calcium-channel antagonist, azelnidipine, on hemodynamic and neural responses to exercise. Ten patients (age, 36-69 years) with mild essential hypertension were enrolled in this study. A randomized, double-blind, crossover treatment of azelnidipine at a dose of 8.0 mg once daily for 4 weeks was performed. After a 4-week placebo period, the patients exercised in a submaximal test by using an ergometer with azelnidipine or placebo treatment. The changes caused by exercise in arterial blood pressure (BP), heart rate, cardiac output (CO), and systemic vascular resistance were evaluated. In addition, the plasma norepinephrine (NE), epinephrine (E), plasma renin activity, and plasma aldosterone concentration were determined at rest, at peak exercise, and at the recovery period. Both the SBP and diastolic (D) BP were decreased at rest by azelnidipine treatment (from 158 +/- 10/97 +/- 7 to 145 +/- 14/90 +/- 9 mm Hg). Azelnidipine significantly decreased both SBP and DBP during exercise (SBP, F = 6.09, p < 0.05, Fi = 0.612, NS; DBP, F = 17.78, p < 0.001, Fi = 0.298, NS). No significant changes in the resting heart rate and CO were observed, and the exercise-induced increase of these parameters was also not affected by azelnidipine. Azelnidipine produced no significant change of the resting plasma NE and E levels and an exercise-induced increase of plasma NE. In conclusion, these results indicate that azelnidipine, different from another dihydropyridine-type calcium channel antagonists, does not produce any changes in the hemodynamic and neurohumoral response to exercise, and it may be beneficial for patients with mild essential hypertension.

Adult↗

PubMed1999

Carbapenem derivatives as potential inhibitors of various beta-lactamases, including class B metallo-beta-lactamases.

A variety of 1beta-methylcarbapenem derivatives were screened to identify inhibitors of IMP-1 metallo-beta-lactamase, a class B beta-lactamase, in an automated microassay system using nitrocefin as a substrate. The structure-inhibitory-activity relationship study revealed that three types of 1beta-methylcarbapenems having benzothienylthio, dithiocarbamate, or pyrrolidinylthio moieties at the C-2 position showed good inhibitory activity. Among the compounds screened, J-110,441, having a benzothienylthio moiety at the C-2 position of 1beta-methylcarbapenem, was the most potent inhibitor of class B metallo-beta-lactamases with K(i) values of 0. 0037, 0.23, 1.00, and 0.83 microM for IMP-1 encoded by the bla(IMP) gene, CcrA from Bacteroides fragilis, L1 from Stenotrophomonas maltophilia, and type II from Bacillus cereus, respectively. In a further characterization study, J-110,441 also showed inhibitory activity against TEM-type class A serine beta-lactamase and chromosomal class C serine beta-lactamase from Enterobacter cloacae with K(i) values of 2.54 and 0.037 microM, respectively. Combining imipenem or ceftazidime with J-110,441 had a synergistic effect on the antimicrobial activity against beta-lactamase-producing bacteria. Against the isolates of IMP-1-producing Serratia marcescens, the MICs of imipenem decreased to levels ranging from 1/64 to 1/4 in the presence of one-fourth of the MIC of J-110,441. Against E. cloacae producing high levels of class C beta-lactamase, the MIC of ceftazidime decreased from 64 to 4 microg/ml in the presence of 4 microg of J-110,441 per ml. This is the first report to describe a new class of inhibitor of class B and class C beta-lactamases including transferable IMP-1 metallo-beta-lactamases.

Bacterial Proteins↗

PubMed1999

Ceramide enhances susceptibility of membrane phospholipids to phospholipase A2 through modification of lipid organization in platelet membranes.

The effects of ceramide on agonist-stimulated phospholipase A2 (PLA2) activity were studied in platelets. Cell-permeable C6-ceramide (N-hexanoylsphingosine) exogenously added to platelet suspension enhanced U46619-stimulated arachidonic acid release and lysophosphatidylcholine production. Treatment of platelets with sphingomyelinase also led to an enhancement of the release. The enhanced arachidonic acid release by exogenous ceramide was completely inhibited by methyl arachidonyl fluorophosphonate, a cytosolic PLA2 inhibitor. However, U46619-stimulated PLA2 activity was not significantly potentiated by ceramide. These results suggest that enrichment of ceramide in membranes causes modification of intermolecular organization, leading to increased susceptibility of substrate phospholipids to PLA2.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1999

Influence of cytoplasmic pH on the aggregation and Ca2+ mobilization in rabbit platelets.

The aggregability of rabbit platelets was studied under various cytoplasmic pHs (pHi). Nigericin, a K+/H+ ionophore, which can induce a decrease in pHi, at 2-10 microM in 2 min incubation reduced both platelet aggregation and an increase in cytoplasmic free Ca2+ concentration ([Ca2+]i) stimulated with thrombin or U46619. The reduced aggregability recovered 10 min after incubation with nigericin in parallel with an increase in pHi. In contrast, when pHi was increased by simultaneous addition of NH4Cl, methylamine or monensin, aggregation in response to a low concentration of thrombin, U46619, arachidonic acid or A23187 was enhanced significantly. The enhancing effect of NH4Cl was lowered by prolonged incubation with NH4Cl, by which the increased pHi was improved concomitantly. Indomethacin, an inhibitor of cyclooxygenase, failed to inhibit the enhancement of aggregation by NH4Cl under stimulation with U46619. In addition, treatment with NH4Cl enhanced an increase in [Ca2+]i in response to U46619 in a concentration-dependent manner, although the treatment by NH4Cl alone did not affect [Ca2+]i. When pHi was artificially altered during the ranges of 6.6-7.4 by treatment with nigericin in K+-rich medium, aggregation by low concentrations of thrombin was dependent on the pHi. These data indicate that pHi is an important factor for platelet activation including intracellular Ca2+ mobilization and aggregation.

Ammonium Chloride↗

PubMed1999

[A method for improving the accuracy in measurement of 99mTc-GSA liver uptake].

In order to improve the accuracy in the measurement of liver uptake rate of radioactivity at 15 minutes after injection of 99mTc-GSA, the corrected liver uptake rate (LU15VW) for tissue attenuation of gamma ray was measured. On the basis of the results of phantom studies, LU15VW was obtained as a ratio of the liver counts to the calculated counts of the injected dose supposed to homogeneously distribute in the liver of each patient and to decrease in count rate by the tissue attenuation of gamma ray, which was caused by the liver itself and body wall. The values of LU15VW were compared with those of the other 99mTc-GSA indices (LU15, LHL15, and HH15) and of the laboratory tests of liver function in 5 patients with chronic persistent hepatitis (CPH), 25 patients with chronic active hepatitis (CAH) 2A, 8 with CAH 2B, 8 with liver cirrhosis (LC), and 20 with hepatocellular carcinoma. LU15VW showed a good correlation with LU15, LHL15, and HH15 (r = 0.912, 0.864, and -0.869). The relationships between the results of LU15VW and the laboratory tests of liver function such as ICGR15, serum albumin, platelets counts, and hepaplastin test (r = -0.800, 0.684, 0.599, and 0.465) were more excellent as compared with those between the results of the other 99mTc-GSA indices and the laboratory tests. LU15VW was distinctly different in the mean values among the three groups of patients with CAH 2A, CAH 2B, and LC. These results indicated that LU15VW was an useful method for improvement of the accuracy in the measurement of liver uptake rate of 99mTc-GSA.

Humans↗

PubMed1998

Different effects of cell-permeable ceramide analogs on platelet activation.

The effects of cell-permeable ceramide analogs on platelet responses induced by agonists were investigated. When washed rabbit platelets were pretreated with ceramide and then stimulated with thrombin or U46619, C2-ceramide (N-acetylsphingosine) dose-dependently inhibited the aggregation and arachidonic acid liberation, whereas C6-ceramide (N-hexanoylsphingosine) and C8-ceramide (N-octanoylsphingosine) enhanced these responses. Furthermore, C6-ceramide, but not C2-ceramide, enhanced the increase in and prevented the progressive decrease in cytoplasmic free Ca2+ concentration induced by U46619. On the other hand, treatment with sphingomyelinase potentiated the aggregation in response to U46619. These results indicate that the effects of cell-permeable ceramide analogs on platelet activation vary with N-acyl chain length.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1998

Inhibitory effect of the leaf extract of Ginkgo biloba L. on oxidative stress-induced platelet aggregation.

The effect of the leaf extract of Ginkgo biloba L. on platelet aggregation induced by oxidative stress was studied. The extract caused a dose-dependent inhibition of platelet aggregation stimulated with tert-butyl hydroperoxide (t-BHP) and Fe2+. Similar inhibitory activity was observed when platelets were exposed to H2O2 and Fe2+. Synergistic aggregation induced by a combination of t-BHP and Fe2+ or H2O2 and Fe2+ in association with suboptimal concentration of collagen or U46619, was prevented by the extract. However, the extract failed to inhibit aggregation in response to collagen, thrombin or U46619. Ginkgolides A, B and C inhibited platelet-activating factor-induced aggregation, but not oxidant-induced aggregation. These data suggest that the suppressive effect of the extract is specific on platelet aggregation stimulated by oxidative stress, and that this effect is involved in the mechanism related to its protective effect upon cerebral or myocardial injuries.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1998

Tc-99m MIBI localization in bone marrow: a marker of bone marrow malignancy.

To determine the potential of Tc-99m MIBI for detecting bone marrow malignancy, MIBI imaging of the femur was evaluated. There was no detectable MIBI activity in 125 of 141 (89%) control patients. Clearly demonstrated focal or tubular MIBI activity indicating intramedullary accumulation was demonstrated in 44 of 45 (98%) patients with proven marrow malignancy: 9 patients with multiple myeloma, 10 patients with malignant lymphoma, 11 patients with acute leukemia, 1 patient with chronic leukemia, and 14 patients with skeletal metastases. No abnormal MIBI activity was observed in the femur in 19 of 22 (86%) patients who had no evidence of malignant involvement in the femoral marrow, in 3 patients with solitary plasmacytomas of the spine, sternum or iliac bone, or in 16 patients with malignant lymphoma. In 12 of 24 patients with acute leukemia in complete remission, no abnormal MIBI accumulation was shown in the femur, but in 12 patients, abnormal accumulation indicating residual leukemic activity was demonstrated. MIBI imaging correlated extremely well with MRI studies; 26 of 28 patients with focal or tubular increased MIBI activity in the femur showed decreased signal on T1-weighted images and a high signal on short inversion recovery images, and 11 patients with no abnormal activity showed a high signal on T1 images. MIBI imaging of the femoral bone marrow may be a new modality for detecting marrow malignancy.

Adult↗

PubMed1998

Intrahypothalamic perfusion of KP102 stimulates growth hormone release in goats.

The hypothalamic actions of KP102 (also called GHRP-2) on the release of GH were studied in female goats. KP102 (10(-5) M) was perfused into the goat hypothalamus through a microdialysis probe (CMA/10 probe with a 4 mm membrane length) at a rate of 4 microl/min for 90 min, and plasma GH concentrations before and after perfusion were measured. The intrahypothalamic perfusion of 10(-5) M KP102 significantly stimulated GH release in goats (P<0.05). The GH levels began to rise after commencement of perfusion, and reached a maximum mean value at 180 min. The concentrations of GH at 165, 180, 195, 210, 225 and 240 min after commencement of perfusion of KP102 were significantly higher than the corresponding values for control animals (P<0.05). KP102 had no effect on GH pulse frequency, but it significantly increased the GH pulse amplitude after the perfusion (P<0.05). In contrast to KP102, intrahypothalamic perfusion of 10(-5) M GHRH had no effect on the stimulation of GH release in goats even if intravenous injection of 10(-5) M GHRH significantly stimulated GH release (P<0.05). These results suggest that KP102 may act partly on the hypothalamus to stimulate GH release in goats.

Animals↗

PubMed1998

N-Dealkylation and hydroxylation of ebastine by human liver cytochrome P450.

Ebastine [4'-tert-butyl-4-[4-(diphenylmethoxy)piperidino]butyro phe- none] is a new-generation, nonsedative, H1 antihistamine. The present study was performed to characterize the cytochrome P450 (CYP) isoforms responsible for ebastine N-dealkylation and hydroxylation. Human liver microsomes metabolized ebastine to two major metabolites, i.e. a desbutyrophenone metabolite (des-BP) and hydroxyebastine (M-OH), and the ratio of Vmax values was 3:1. N-Dealkylation yielded des-BP, whereas M-OH, an hydroxylation product, could be further oxidized to the pharmacologically active carebastine. In a panel of 14 human liver microsomal preparations, the rate of dealkylation showed a highly significant correlation with CYP3A-mediated testosterone 6beta-hydroxylation but not with reactions of seven other CYP isoforms. However, there was no correlation between the two pathways for ebastine (dealkylation and hydroxylation). Differential chemical inhibition in liver microsomes, in which dealkylation was more sensitive than hydroxylation, was demonstrated with ketoconazole, troleandomycin, cyclosporin A, and midazolam. Anti-CYP3A antibodies markedly reduced the dealkylation rate (>95%) in liver microsomes but exhibited insignificant effects on hydroxylation (<5%). Among 12 cDNA-expressed human CYP isoforms, which account for up to 70% of the total CYP enzyme content in human liver, CYP3A4 alone metabolized ebastine; the ratio of des-BP to M-OH formation was 12:1. This ratio for metabolism by the pure enzyme was much larger than the ratio (3:1) observed for the microsomal reaction mixture. This change in ratio, which is attributed to a decrease in M-OH formation, indicates that, although ebastine is metabolized to two major metabolites, N-dealkylation to des-BP is mediated by CYP3A, whereas hydroxylation to M-OH appears to be mediated mainly by unidentified enzymes other than CYP3A.

Butyrophenones↗

PubMed1998

[Fulminant hepatic failure related to immunosuppressive therapy in an asymptomatic HBsAg carrier with idiopathic interstitial pneumonia].

A 72-year-old woman who was an asymptomatic HBsAg carrier was admitted because of productive cough and dyspnea on exertion. After close examination, she was given a diagnosis of idiopathic interstitial pneumonia (IIP), and treated with glucocorticoids and cyclophosphamide. However, fulminant hepatitis type B developed and the patient died of respiratory complications stemming from the acute exacerbation of IIP. To avoid such outcomes, extra caution should be taken when planning immunosuppressive therapy for HBsAg carriers.

Aged↗

PubMed1997

Biosynthesis of archaeosine, a novel derivative of 7-deazaguanosine specific to archaeal tRNA, proceeds via a pathway involving base replacement on the tRNA polynucleotide chain.

Archaeosine is a novel derivative of 7-deazaguanosine found in transfer RNAs of most organisms exclusively in the archaeal phylogenetic lineage and is present in the D-loop at position 15. We show that this modification is formed by a posttranscriptional base replacement reaction, catalyzed by a new tRNA-guanine transglycosylase (TGT), which has been isolated from Haloferax volcanii and purified nearly to homogeneity. The molecular weight of the enzyme was estimated to be 78 kDa by SDS-gel electrophoresis. The enzyme can insert free 7-cyano-7-deazaguanine (preQ0 base) in vitro at position 15 of an H. volcanii tRNA T7 transcript, replacing the guanine originally located at that position without breakage of the phosphodiester backbone. Since archaeosine base and 7-aminomethyl-7-deazaguanine (preQ1 base) were not incorporated into tRNA by this enzyme, preQ0 base appears to be the actual substrate for the TGT of H. volcanii, a conclusion supported by characterization of preQ0 base in an acid-soluble extract of H. volcanii cells. Thus, this novel TGT in H. volcanii is a key enzyme for the biosynthetic pathway leading to archaeosine in archaeal tRNAs.

Amino Acid Sequence↗

PubMed1997

Bilirubin oxidation provoked by endotoxin treatment is suppressed by feeding ascorbic acid in a rat mutant unable to synthesize ascorbic acid.

We examined the possibility that bilirubin oxidation is provoked in vivo by using scurvy-prone ODS-od/od rats treated with endotoxin (lipopolysaccharide). Recently, bilirubin oxidative metabolites were isolated from human urine and named biotripyrrin-a and biotripyrrin-b. In ODS-od/od rats fed an ascorbic-acid-free diet, the concentration of bilirubin metabolites in urine was increased 7.0-fold at 3 h after injection of lipopolysaccharide and 4.4-fold at 10 h compared to the control rats injected with saline. The dietary supplement of ascorbic acid, the physiological antioxidant, suppressed the increase in bilirubin metabolites in urine after lipopolysaccharide injection: concentrations of biotripyrrin-a and biotripyrrin-b in urine collected 6.5-10 h after the injection were lower in rats fed an ascorbic-acid-supplemented diet than in rats fed an ascorbic-acid-free diet. Moreover, feeding of ascorbic acid suppressed the hepatic mRNA level of heme oxygenase-1, the rate-limiting enzyme of bilirubin biosynthesis, in rats injected with lipopolysaccharide. These findings indicate that bilirubin oxidation is markedly stimulated in lipopolysaccharide-treated rats and suggest that bilirubin and ascorbic acid have physiologically protective effects against oxidative stress.

Animals↗

PubMed1997

Roles of the transforming growth factor beta 1 and its type I and II receptors in the development of a pulmonary adenocarcinoma: results of an immunohistochemical study.

BACKGROUND: In the United States, pulmonary adenocarcinomas have recently replaced squamous cell carcinomas as the most frequent type of lung cancer encountered. The incidence of pulmonary adenocarcinoma continued to increase worldwide. METHOD: To determine the roles of the transforming growth factor-beta 1 (TGF-beta 1), and TGF-beta type I receptor (T beta R-I), and the TGF-beta type II receptor (T beta R-II) in the progression of a pulmonary adenocarcinoma, their respective expressions have been immunohistologically studied in specimens from 120 pulmonary adenocarcinoma patients. RESULT: The overall prognosis was significantly poorer for patients showing positive TGF-beta 1, T beta R-I, T beta R-II expressions than for patients who were negative to all three immunostainings (P < 0.01). Our multivariate analysis also revealed that a positive TGF-beta 1 response significantly affect prognosis (P < 0.05). CONCLUSIONS: TGF-beta 1, T beta R-I, and T beta R-II play important roles in tumor progression, and a positive TGF-beta 1 expression can serve as a pulmonary adenocarcinoma marker. T beta R-I and T beta R-II expressions are necessary for TGF-beta signal transduction.

Activin Receptors, Type I↗