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Biomedical subjects

H Miyoshi

Publications and source records attributed to H Miyoshi.

At least 55 records · Page 3Linked to original sources
PubMed2001

Kupffer cell-derived cyclooxygenase-2 regulates hepatocyte Bcl-2 expression in choledocho-venous fistula rats.

We have previously demonstrated that after bile duct ligation hepatocytes express Bcl-2, although the mechanisms regulating Bcl-2 expression were not identified. Our aim was to determine if biliary constituents induce hepatocellular expression of Bcl-2 by a cyclooxygenase-2 (COX-2)-dependent mechanism. We used the choledocho-venous fistula (CVF) rat model for these studies and inhibited COX-2 by feeding the animals nimesulide, a selective inhibitor of COX-2 activity. Serum bile acids were 70-fold greater in CVF animals compared with controls, although liver histology and serum alanine aminotransferase values remained normal for the duration of the study. Neither Bcl-2 nor COX-2 was detected in sham-operated animals. However, Bcl-2 was expressed in hepatocytes but not in other liver cells in the CVF animals. In contrast, COX-2 protein was identified in Kupffer cells but not in hepatocytes of CVF animals. Hepatic Bcl-2 protein expression was fourfold lower in the livers from nimesulide-treated CVF rats. In conclusion, high circulating concentrations of biliary constituents are associated with stimulation of de novo hepatocyte expression of Bcl-2 and Kupffer cell expression of COX-2. These data suggest Kupffer cell-derived prostanoids may regulate Bcl-2 expression in the hepatocyte.

Anastomosis, Surgical↗
PubMed2001

Analysis of the isoform of Xenopus euakryotic translation initiation factor 4E.

We have found two isoforms of the eukaryotic translation initiation factor 4E (eIF4E) in Xenopus laevis. These proteins differ in length by 18 amino acids. Overexpression of either of the two eIF4E proteins modestly increase translation in Xenopus oocytes. The results suggest that both of these two isoforms function in translation.

Amino Acid Motifs↗
PubMed2001

Regional myocardial function at the papillary muscle insertion site.

The importance of the mitral apparatus to the global left ventricular (LV) function has been suggested in several clinical studies. One recent study reported that chordal transsection induced an unloading of myocardium at the papillary muscle insertion site. We hypothesized that the regional response for afterloading at this site with intact mitral apparatus was different from that at the free wall. We investigated the end-systolic pressure-regional segment length relations (ESPLR) in two anterior LV sites, free wall (FREE) and the papillary muscle insertion site (PAP), during an increasing afterload by aortic occlusion in 7 anesthetized open-chest dogs. To measure the regional segment length at FREE and PAP, two sets of the pair of sonomicrometer crystals were implanted in the same midwall depth at the same circumferential hoop by using an echocardiographic guide. ESPLR both at FREE and PAP were always highly linear in a physiological range (r > or = 0.9). The slope of this relation at FREE (274 +/- 164 mmHg/mm) was significantly steeper than that at PAP (157 +/- 118 mmHg/mm) for each dog (p < 0.05). These data indicate that the regional response for afterloading at PAP loaded by chordal tension is different from that at FREE in the same heart.

Animals↗
PubMed2001

[Effects of dopamine and dobutamine on renal function and urinary excretion of prostaglandin E2 in elderly postoperative patients].

Effects of dopamine and dobutamine on renal function and urinary excretion of prostaglandin E2 (UPGE) were studied in 21 elderly patients who underwent abdominal surgery. Fractional sodium excretion (FeNa), creatinine clearance (Ccr), urinary volume (UV, ml.kg-1.min-1) and UPGE were measured on the first and second postoperative day. These patients were divided into three groups: i.e. C (control), DA (dopamine) and DB (dobutamine) groups. Group DA received dopamine 2 mcg.kg-1.min-1 beginning at six o'clock on the first postoperative day. Group DB received dobutamine 2 mcg.kg-1.min-1. There were no significant differences in UV and UPGE among these three groups. Ccr was significantly higher on the second postoperative day than that on the first postoperative day in DA group. FeNa in DA group was higher than in C group on the second postoperative day. The relationship between UPGE and UV was not determined. These results suggest that DA improve renal functions in the elderly.

Aged↗
PubMed2001

Accuracy of technetium-99m tetrofosmin myocardial perfusion imaging in the detection of spontaneous recanalization in patients with acute anterior myocardial infarction.

To avoid the haemorrhagic risk of unnecessary thrombolysis in acute myocardial infarction (MI), early and precise diagnosis of spontaneous recanalization (SR) of the infarct-related artery is required. To clarify the accuracy of technetium-99m tetrofosmin myocardial single-photon emission tomography (SPET) in the detection of SR in patients with acute anterior MI, electrocardiography (ECG), echocardiography and 99mTc-tetrofosmin SPET imaging were performed in 49 patients with acute anterior MI before emergency coronary angiography. Defect score was calculated as the sum of the perfusion defects of each segment: from 3 (complete defect) to 0 (normal perfusion). Echocardiographic asynergic score (the sum of asynergic grades) and the greatest ST elevation of the 12-lead ECG on admission were also measured. SR was defined as Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow on emergency coronary angiography. Defect score in 11 patients with SR (9.2 +/- 3.7) was significantly lower than that in 38 patients without SR (18.5 +/- 5.0) (P < 0.001), whereas there were no significant differences in asynergic score and ST elevation between the two groups. From the receiver operating characteristic curves, the optimal cut-off points of defect score, asynergic score and ST elevation for the detection of SR were calculated to be 12, 13 and 3.5, respectively. The sensitivity and specificity of the scintigraphic defect score (91% and 89%) were significantly higher than those of the asynergic score (64% and 68%) and ST elevation (73% and 71%). Thus, 99mTc-tetrofosmin SPET imaging on admission is a very accurate method for the detection of SR in patients with acute anterior MI.

Acute Disease↗
PubMed2001

Bid antisense attenuates bile acid-induced apoptosis and cholestatic liver injury.

Bile acids cause liver injury during cholestasis by inducing hepatocyte apoptosis by both Fas-dependent and -independent mechanisms. However, the Fas-independent apoptosis also appears to be death receptor-mediated. Because death receptor-mediated apoptosis in hepatocytes requires proapoptotic Bcl-2 BH3 domain only protein Bid, we postulated that Fas-independent but death receptor-mediated bile acid cytotoxicity would be Bid-dependent. We used Fas-deficient lymphoproliferative (lpr) mouse hepatocytes for these studies, and inhibited Bid expression using an antisense approach. Glychochenodeoxycholate (GCDC) was used to induce apoptosis. Bid cleavage and translocation to mitochondria was observed in GCDC-treated cells as assessed by immunoblot analysis and confocal imaging of Bid-green fluorescent protein, respectively. Bid translocation to mitochondria was associated with cytochrome c release. A Bid antisense 2'-MOE modified oligonucleotide inhibited Bid expression in hepatocytes and markedly attenuated hepatocytes apoptosis by GCDC. Treatment of lpr mice with Bid antisense also ameliorated liver injury following bile duct ligation of the mice, a model of extrahepatic cholestasis. These results suggest that bile acid cytotoxicity is Bid-dependent despite the absence of Fas. Bid antisense therapy is a promising approach for the treatment of cholestatic liver injury.

Animals↗
PubMed2001

[Long-term outcome after extracorporeal shock wave lithotripsy for gallstones].

We retrospectively reviewed 289 cases followed for a long time after extracorporeal shock wave lithotripy (ESWL) for gallstones. Follow-up periods ranged from 0.5 years to 9.2 years, with a median of 4.1 years. The complete resolution rate was 45.6%. A solitary gallstone, non-calcified gallstones on CT, and Tsuchiya's sonographic type Ia and Ib gallstones were found to be statistically significant variable for resolution of the disease. With a maximum follow-up period of 9 years, the cumulative recurrence rate was 30.7%. Among the 156 patients whose gallstones did not resolve, 70 were symptomatic and the other 86 were asymptomatic. Thirty-eight of the symptomatic patients (54.3%) became symptom-free, while 23 asymptomatic patients (29.1%) became symptomatic. The cumulative rate of occurrence of colic attacks and/or acute cholecystitis was significantly higher in the cases with lithotripsy fragments 4 mm or more in size than in the cases wih fragments 3 mm or less in size (51.8% vs. 16.7%; p < 0.05). ESWL was followed by surgery in 23.1% because symptoms developed or became aggravated after ESWL in 58.3% of them. Gallbladder cancer was discovered in one case. Patients undergoing ESWL should be followed by focusing on postoperative recurrence, symptoms, and gallbladder cancer.

Adult↗
PubMed2000

Definition of crucial structural factors of acetogenins, potent inhibitors of mitochondrial complex I.

Some natural acetogenins are the most potent inhibitors of bovine heart mitochondrial complex I. These compounds are characterized by two functional units (i.e. hydroxylated tetrahydrofuran (THF) and alpha,beta-unsaturated gamma-lactone ring moieties) separated by a long alkyl spacer. To elucidate which structural factors of acetogenins including their active conformation are crucial for the potent inhibitory effect, we synthesized a series of novel acetogenin analogues possessing bis-THF rings. The present study clearly demonstrated that the natural gamma-lactone ring is not crucial for the potent inhibition, although this moiety is the most common structural unit among a large number of natural acetogenins and has been suggested to be the only reactive species that directly interacts with the enzyme (Shimada et al., Biochemistry 37 (1998) 854-866). The presence of free hydroxy group(s) in the adjacent bis-THF rings was favorable, but not essential, for the potent activity. This was probably because high polarity (or hydrophilicity), rather than hydrogen bond-donating ability, around the bis-THF rings is required to retain the inhibitor in the active conformation. Interestingly, length of the alkyl spacer proved to be a very important structural factor for the potent activity, the optimal length being approximately 13 carbon atoms. The present study provided further strong evidence for the previous proposal (Kuwabara et al., Eur. J. Biochem. 267 (2000) 2538-2546) that the gamma-lactone and THF ring moieties act in a cooperative manner on complex I with the support of some specific conformation of the spacer.

Binding Sites↗
PubMed2000

The inhibitory effect of prostaglandin E1 on oxidative stress-induced hepatocyte injury evaluated by calpain-mu activation.

BACKGROUND: Prostaglandin E1 (PGE1) is known to inhibit ischemia-reperfusion injury of the liver. The calcium-dependent neutral proteinase, calpain-mu, is involved in oxidative stress-induced hepatocyte injury. We investigated the mechanisms of cytoprotection by PGE1, focusing on the elevation of intracellular calcium ([Ca2+]i), activation of calpain-mu, and calpain-mu-mediated activation of protein kinase C-alpha (PKC-alpha). METHODS: Cultured hepatocytes were treated with various amounts of PGE1 (0, 0.1, 1.0, 10, and 100 ng/ml) for 30 min and subsequently with 0.5 mM tert-butyl hydroperoxide (TBHP). Cell injury was evaluated by the release of lactate dehydrogenase. Plasma membrane bleb formation was examined by phase contrast microscopy. Activation of calpain-mu and limited degradation of PKC-alpha was evaluated by Western blotting using antibodies that specifically recognize the amino-terminal regions of calpain-mu and PKC-alpha. [Ca2+]i was measured by confocal microscopy using Fluo-3AM. RESULTS: LDH release from cells treated with 10 ng/ml PGE1 was significantly lower than from untreated cells (135 +/- 12 vs. 258 +/- 18 IU/L, respectively; P < 0.05). Morphologically, many blebs were observed in untreated cells, but very few were seen in those treated with 10 ng/ml PGE1. Western blotting revealed that the amount of activated calpain-mu and [Ca2+]i increased up to 1,300 nM at 35 min after the addition of TBHP (0.5 mmol/L) in control experiments (without PGE1). PGE1 (10 ng/ml) delayed the rise in [Ca2+]i for about 30 min, but did not suppress it completely. PKC-alpha decreased in experiments using PGE1 (10 ng/ml). CONCLUSION: PGE1 exerts its cytoprotective effect in TBHP-induced hepatocyte injury partly by inhibiting Ca2+-calpain-mu-mediated mechanisms.

Alprostadil↗
PubMed2000

Phosphorylation-dependent activation of TAK1 mitogen-activated protein kinase kinase kinase by TAB1.

TAK1 is a mitogen-activated protein kinase kinase kinase (MAP3K) that is involved in the c-Jun N-terminal kinase/p38 MAPKs and NF-kappaB signaling pathways. Here, we characterized the molecular mechanisms of TAK1 activation by its specific activator TAB1. Autophosphorylation of two threonine residues in the activation loop of TAK1 was necessary for TAK1 activation. Association with TAK1 and induction of TAK1 autophosphorylation required the C-terminal 24 amino acids of TAB1, but full TAK1 activation required additional C-terminal Ser/Thr rich sequences. These results demonstrated that the association between the kinase domain of TAK1 and the C-terminal TAB1 triggered the phosphorylation-dependent TAK1 activation mechanism.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Reactivation of human herpesvirus 6 by infection of human herpesvirus 7.

We have attempted to reactivate human herpesvirus 6 (HHV-6) by infection with HHV-7 using childhood exanthem subitum patients in vitro. Peripheral blood mononuclear cells (PBMCs) were collected from children who had a history of exanthem subitum(ES) by HHV-6 and were infected by human herpesvirus 7 (HHV-7) in vitro. The antigen positive rate to HHV-6 started to increase 7 days after the infection and reached a maximum by Day 15 using an immunofluorescence antibody test. The copy number of HHV-6 DNA also increased in the samples in 10 days after infection in vitro. No antigen or increase in DNA was detected in PBMCs, that were mock-infected or infected with supernatant of stock virus after ultracentrifugation, suggesting that an infection by HHV-7 is necessary to reactivate HHV-6. In the paired sera samples during the acute and the convalescent phases of ES, seven to ten bands, that were specific for HHV-6, were recognized in samples from the acute phase, and at least 5 dominant polypeptides were found more intensively after HHV-7 infection.

Blotting, Southern↗
PubMed2000

Disinfection potential of electrolyzed solutions containing sodium chloride at low concentrations.

Electrolyzed products of sodium chloride solution were examined for their disinfection potential against hepatitis B virus (HBV) and human immunodeficiency virus (HIV) in vitro. Electrolysis of 0.05% NaCl in tap water was carried out for 45 min at room temperature using a 3 A electric current in separate wells installed with positive and negative electrodes. The electrolyzed products were obtained from the positive well. The oxidation reduction potential (ORP), pH and free chlorine content of the product were 1053 mV, pH 2.34 and 4.20 ppm, respectively. The products modified the antigenicity of the surface protein of HBV as well as the infectivity of HIV in time- and concentration-dependent manner. Although the inactivating potential was decreased by the addition of contaminating protein, recycling of the product or continuous addition of fresh product may restore the complete disinfection against bloodborne pathogens.

Acids↗
PubMed2000

Splanchnic perfusion during controlled hypotension combined with acute hypervolemic hemodilution: a comparison with combination of acute normovolemic hemodilution-gastric intramucosal pH study.

STUDY OBJECTIVE: To evaluate the effect of controlled hypotension combined with acute hypervolemic or normovolemic hemodilution on the splanchnic perfusion in the clinical setting. DESIGN: Randomized, prospective study. SETTING: Inpatient surgery at Nagasaki Rosai Hospital. PATIENTS: 28 ASA physical status I and II patients scheduled for total hip arthroplasty. INTERVENTIONS: Patients were randomly divided into two groups. Group A (n = 14) received controlled hypotension with acute normovolemic hemodilution (ANH). Group B (n = 14) received controlled hypotension with acute hypervolemic hemodilution (HHD). ANH was produced by drawing approximately 1000 mL of blood and replacing it with the same amount of 6% hydroxyethyl starch solution (HES). HHD was produced by preoperative infusion of 1000 mL of 6% HES without removing blood. The final hematocrit values were 24+/-2% (mean +/- SD) in Group A and 25+/-3% in Group B. Controlled hypotension was induced with prostaglandin E1 (PGE1) to maintain mean arterial blood pressure at 55 mmHg for 80 minutes. MEASUREMENTS: Measurements included the gastric pH (pHi), the arterial blood pH (pHa), and plasma lactate. These indices were measured before hemodilution, after hemodilution, 80 minutes after starting hypotension, 60 minutes after recovery from hypotension, and on the first postoperative day. The value of pHi was measured by tonometric method. MAIN RESULTS: The pHa and lactate values showed no change in either group A or group B throughout the time course. Gastric pHi values in group A showed a significant decrease from 7.424+/-0.033 to 7.335+/-0.038 (p<0.05) after hemodilution, whereas it showed no further decrease at 80 minutes after starting hypotension and 60 minutes after recovery from hypotension. The pHi values in group B showed no significant decrease after hemodilution and no further change at 80 minutes after starting hypotension. CONCLUSIONS: HHD does not impair splanchnic perfusion, whereas ANH might cause impairment. Controlled hypotension with prostaglandin E1 would not impair splanchnic perfusion in combination with either HHD or ANH.

Aged↗
PubMed2000

Epidemiological study of human herpesvirus-6 and human herpesvirus-7 in pityriasis rosea.

BACKGROUND: Pityriasis rosea (PR) is a common papulosquamous skin disorder that is suspected to have an infectious aetiology. OBJECTIVES: We aimed to study the role of human herpesvirus (HHV)-7 and HHV-6 in the pathogenesis of PR. METHODS: We performed seroepidemiological studies (indirect immunofluorescence test) and polymerase chain reaction (PCR) analysis for HHV-6 and HHV-7 in patients with PR. Seventy-two serum samples and 37 samples of peripheral blood mononuclear cells (PBMC) from 44 patients with PR were obtained. Twenty-five patients with other skin disorders such as drug eruption, urticaria or herpes zoster were studied as controls in the PCR analysis. RESULTS: HHV-7 DNA was detected in 13 of 30 (43%) samples of PBMC of the patients with PR and 14 of 25 (56%) samples of PBMC of controls. HHV-6 DNA was detected in six of 29 (21%) patients with PR and nine of 23 (39%) controls. Thus there was no difference in the prevalence of HHV-6 or HHV-7 in PBMC between patients with PR and those with other skin disorders. In the seroepidemiological study, two cases of at least a fourfold rise in titre and five cases of a fourfold decrease in titre to HHV-7 antibody, and two cases of a fourfold rise in titre and two cases of a fourfold decrease in titre to HHV-6 antibody, were observed in 24 patients with PR. This seroepidemiological study revealed antibody responses consistent with active infection in several PR patients, but the greater proportion of the patients had no definite increase in the antibody titres. CONCLUSIONS: We conclude that HHV-7 and HHV-6 may play a part in some patients with PR, but that other causative agents may exist. Further analyses are needed to determine the causative agents of PR.

Adolescent↗
PubMed2000

Design syntheses and mitochondrial complex I inhibitory activity of novel acetogenin mimics.

Some natural acetogenins are the most potent inhibitors of mitochondrial complex I. These compounds are characterized by two functional units [i.e. hydroxylated tetrahydrofuran (THF) and alpha, beta-unsaturated gamma-lactone ring moieties] separated by a long alkyl spacer. To elucidate which structural factors of acetogenins, including their active conformation, are crucial for the potent inhibitory activity we synthesized a novel bis-acetogenin and its analogues possessing two gamma-lactone rings connected to bis-THF rings by flexible alkyl spacers. The inhibitory potency of the bis-acetogenin with bovine heart mitochondrial complex I was identical to that of bullatacin, one of the most potent natural acetogenins. This result indicated that one molecule of the bis-acetogenin does not work as two reactive inhibitors, suggesting that a gamma-lactone and the THF ring moieties act in a cooperative manner on the enzyme. In support of this, either of the two ring moieties synthesized individually showed no or very weak inhibitory effects. Moreover, combined use of the two ring moieties at various molar ratios exhibited no synergistic enhancement of the inhibitory potency. These observations indicate that both functional units work efficiently only when they are directly linked by a flexible alkyl spacer. Therefore, some specific conformation of the spacer must be important for optimal positioning of the two units in the enzyme. Furthermore, the alpha,beta-unsaturated gamma-lactone, the 4-OH group in the spacer region, the long alkyl tail attached to the THF unit and the stereochemistry surrounding the hydroxylated bis-THF rings were not crucial for the activity, although these are the most common structural features of natural acetogenins. The present study provided useful guiding principles not only for simplification of complicated acetogenin structure, but also for further wide structural modifications of these molecules.

Animals↗
PubMed2000

Regulation of human eIF4E by 4E-BP1: binding analysis using surface plasmon resonance.

The interaction between recombinant human eukaryotic initiation factor (eIF)4E and recombinant glutathione S-transferase (GST)-fused human 4E-binding protein (BP)1 was analyzed by using the surface plasmon resonance method. The association rate of 4E-BP1 with eIF4E increased by about two orders of magnitude in the presence of m7GTP (a model compound of mRNA cap structure), but the dissociation rate was scarcely affected, indicating the cap-dependent binding of 4E-BP1 to eIF4E. On the other hand, phosphorylation of 4E-BP1 weakened its interaction with eIF4E whether m7GTP was present or not. However, phosphorylation of 4E-BP1 already associated with eIF4E or its m7GTP complex did not cause any change of the association, probably because of incomplete phosphorylation. This suggests that the regulation of eIF4E by 4E-BP phosphorylation is performed at its free state, not when it is in the associated state with eIF4E. Given these results, we discuss how 4E-BP regulates eIF4E at the first step of translation initiation.

Adaptor Proteins, Signal Transducing↗