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H Koike

Publications and source records attributed to H Koike.

At least 91 records · Page 5Linked to original sources

Susceptibility of TT virus to interferon therapy.

TT virus (TTV) is a newly identified single-stranded DNA virus. We retrospectively analysed serum samples from sixteen patients, infected with both hepatitis C virus (HCV) and TTV, and who had been treated with interferon. An elevated serum alanine aminotransferase level after interferon was associated with persistence of HCV (abnormal in five of seven patients with persistence of HCV compared with normal in all nine patients who showed eradication of HCV) irrespective of persistence of TTV. Comparison of partial viral DNA nucleotide sequences and phylogenetic analysis showed that viral strains that had a high identity to the prototype virus were more resistant to interferon than those showing low nucleotide sequence identity. Although we observed no liver cell injury caused by persistent TTV infection, the mechanism(s) of TTV resistance to interferon should be further investigated for a better understanding of viral diseases and establishment of therapy.

Alanine Transaminase↗

Alcohol consumption enhances liver metastasis in colorectal carcinoma patients.

BACKGROUND: It is important to identify risk factors for liver metastasis in patients with colorectal carcinoma because the liver is the most common site of recurrence. Alcohol consumption reportedly is associated with hematogenous metastasis in certain animal models. Furthermore, some studies have shown that carmofur, a derivative of 5-fluorouracil, is particularly effective as adjuvant chemotherapy for colorectal carcinoma, and may even suppress liver metastasis, although the mechanism by which this occurs remains unknown. In addition, carmofur is known to inhibit alcohol metabolism. To the authors' knowledge, the relation between liver metastasis in colorectal carcinoma and alcohol consumption has not been examined previously. Therefore, the authors studied the relations between liver metastasis in colorectal carcinoma and various clinicopathologic factors including alcohol consumption status. METHODS: This study was comprised of 133 colorectal carcinoma patients with invasion beyond the submucosal layer who had undergone surgical resection. The subjects were examined and divided into two groups according to the occurrence or absence of liver metastasis. The relations between liver metastasis and other clinicopathologic factors were analyzed by univariate and multivariate statistical methods. RESULTS: Univariate analysis showed alcohol consumption (P=0.0021) and blood vessel invasion (P=0.0045) were correlated with liver metastasis. Multivariate analysis showed both to be independent risk factors for liver metastasis. CONCLUSIONS: Alcohol consumption is an independent risk factor for liver metastasis in colorectal carcinoma patients. Therefore, patients with colorectal carcinoma who drink alcohol require intensive examination and follow-up with respect to liver metastasis. Further study is necessary to confirm the effect of adjuvant chemotherapy using carmofur in colorectal carcinoma patients.

Adult↗

1.8 A crystal structure of the major NAD(P)H:FMN oxidoreductase of a bioluminescent bacterium, Vibrio fischeri: overall structure, cofactor and substrate-analog binding, and comparison with related flavoproteins.

We have solved the crystal structure of FRase I, the major NAD(P)H:FMN oxidoreductase of Vibrio fischeri, by the multiple isomorphous replacement method (MIR) at 1.8 A resolution with the conventional R factor of 0.187. The crystal structure of FRase I complexed with its competitive inhibitor, dicoumarol, has also been solved at 2.2 A resolution with the conventional R factor of 0.161. FRase I is a homodimer, having one FMN cofactor per subunit, which is situated at the interface of two subunits. The overall fold can be divided into two domains; 80% of the residues form a rigid core and the remaining, a small flexible domain. The overall core folding is similar to those of an NADPH-dependent flavin reductase of Vibrio harveyi (FRP) and the NADH oxidase of Thermus thermophilus (NOX) in spite of the very low identity in amino acid sequences (10% with FRP and 21% with NOX). 56% of alpha-carbons of FRase I core residues could be superposed onto NOX counterparts with an r.m.s. distance of 1.2 A. The remaining residues have relatively high B-values and may be essential for defining the substrate specificity. Indeed, one of them, Phe124, was found to participate in the binding of dicoumarol through stacking to one of the rings of dicoumarol. Upon binding of dicoumarol, most of the exposed re-face of the FMN cofactor is buried, which is consistent with the ping pong bi bi catalytic mechanism.

Amino Acid Sequence↗

A transcription frame-based analysis of the genomic DNA sequence of a hyper-thermophilic archaeon for the identification of genes, pseudo-genes and operon structures.

An algorithm for identifying transcription units, independently regulated genes and operons, and pseudo-genes that are not expected to be expressed, has been developed by combining a system for predicting transcription and translation signals, and a system for scoring the triplet periodicity in ORF candidates. By using the algorithm, the 1.09 Mb sequence that covers approximately 60% of the genome of Pyrococcus sp. OT3 has been analyzed. The identified ORFs show the expected biological and physical characteristics, while the rejected ORF candidates do not. Frequent use of operon structures for transcription, and gene duplication followed by mutation or termination of the duplicated genes, are discussed.

Base Composition↗

Emergence and takeover of YMDD motif mutant hepatitis B virus during long-term lamivudine therapy and re-takeover by wild type after cessation of therapy.

Treatment of hepatitis B virus (HBV) with lamivudine is effective in suppressing virus replication and results in reduced inflammatory activity. However, the emergence of lamivudine-resistant mutant virus, with amino acid substitution in the YMDD motif of DNA polymerase, has been reported. We report the emergence and takeover of YMDD mutant and re-takeover by wild type during and after long-term lamivudine therapy. YMDD mutants were detected in five patients who showed DNA breakthrough (HBV DNA becoming detectable after a period of DNA negativity), which occurred after 9 to 14 months of lamivudine therapy. Four of five mutants had amino acid sequence YIDD, and the remaining mutant had YVDD. Patients with high HBV-DNA titer and/or hepatitis B e antigen tended to develop breakthrough (P = .038). Using a sensitive and specific polymerase chain reaction (PCR)-based method developed in this study, the emergence of YMDD mutants was detected 1 to 4 months before DNA breakthrough, but not detected in any of the pretreatment sera. The mutants were predominant at breakthrough, but were replaced by wild-type virus 3 to 4 months after cessation of therapy in the two patients who discontinued therapy. One of these patients had a relapse of hepatitis. Mutant continued to replicate in the remaining three patients who continued to receive treatment, and relapse occurred in only one of these patients. Our results suggest that the replication of YMDD mutant viruses is less than wild type and is re-overtaken by wild type after cessation of therapy. Re-administration of lamivudine, possibly combined with other antiviral therapy, might be useful in some patients experiencing hepatitis with lamivudine-resistant variants.

Adult↗

Usefulness of hepatitis C virus RNA counts by second generation HCV bDNA-probe in chronic hepatitis C based on the HCV genotype.

Detection of hepatitis C virus (HCV) RNA by a second generation (ver 2) HCV bDNA-probe method (bDNA-probe) was compared with detection by the first generation (ver 1) assay. The two assays were performed simultaneously with the same serum samples of HCV genotypes 1b, 2a, 2b, 3a, and 3b. The positive rates with ver 1 were 82% for HCV genotype 1b (type 1b), 57.6% for HCV genotype 2a (type 2a), 75.0% for HCV genotype 2b (type 2b), 55.6% for HCV genotype 3a (type 3a), and 93.8% for HCV genotype 3b (type 3b). The positive rates with ver 2 were 95.0% for type 1b, 93.9% for type 2a, 83.3% for type 2b, 100% for type 3a, and 93.8% for type 3b. With Fisher's exact test, the detection rate for type 2a was significantly higher (P = 0.001) with ver 2 than with ver 1. We obtained regression lines using the HCV counts measured by bDNA-probe on the y axis and the HCV counts obtained by an HCV reverse transcriptase (RT)-competitive polymerase chain reaction method (competitive PCR) on the x axis. The gradients for types 1b, 2a, and 3b were greater with ver 2 compared to ver 1. The gradients for types 2a and 3b were the highest: for type 2a, y = 0.135x + 0.6 with ver 1 and y = 0.248x + 0.1 with ver 2; for type 3b, y = 0.366x + 0.1 with ver 1 and y = 0.727x + 0.3 for ver 2. In addition, HCV-RNA counts for all the genotypes tested in this study were significantly higher with ver 2 than with ver 1. Hence, we conclude that ver 2 of the bDNA-probe measures HCV-RNA counts closer to those obtained with competitive PCR than the ver 1 assay.

DNA Probes↗

Simultaneous resection of gastric carcinoma and splenectomy in a patient with polycythemia vera: report of a case.

We report herein the case of a 57-year-old man who underwent resection of gastric carcinoma after being treated for polycythemia vera (PV) for 16 months. He was admitted with gastrointestinal bleeding; barium meal roentogenogram and endoscopic examination subsequently revealed a Borrmann type II carcinoma in the cardia of the stomach with extension into the lower esophagus. Thus, a lower esophagogastrectomy, distal pancreatectomy, splenectomy, and lymph node dissection were performed. Although an insufficiency of the esophagojejunal anastomosis occurred, the patient suffered no hematologic complications in the setting of careful myelosuppressive and antiplatelet coagulation therapy. He is currently doing well 5 years after his operation, with grade 1 performance status and no signs of recurrence or any hematologic complications.

Cardia↗

Use of the harmonic scalpel for nephron sparing surgery in renal cell carcinoma.

PURPOSE: The harmonic scalpel is a new tool for excising and coagulating tissue with ultrasound using higher frequencies than an ultrasonic aspirator. We evaluated the usefulness of the harmonic scalpel in nephron sparing surgery. MATERIALS AND METHODS: We used the harmonic scalpel to incise the renal parenchyma during nephron sparing surgery in 10 patients with renal cell carcinoma. RESULTS: Bleeding from the renal parenchyma was minimal but hemostasis of the larger vessels was not obtained even when the harmonic scalpel was used at maximal coagulation power. The cut surface of the kidneys, especially the vessels, were more clearly recognized than if an ultrasonic aspirator had been used, enabling hemostasis by figure-of-8 suture. CONCLUSIONS: The harmonic scalpel is useful for obtaining a clear parenchymal stump and hemostasis during nephron sparing surgery, although complete hemostasis of the arcuate or larger vessels cannot be achieved.

Carcinoma, Renal Cell↗

Proximal cis-regulatory elements of sea urchin arylsulfatase gene.

Expression of the arylsulfatase (HpArs) gene in the sea urchin, Hemicentrotus pulcherrimus, is regulated in spatially, as well as temporally, during development. To address the cis-regulatory elements involved in this regulation, we performed reporter assays using variously deleted or mutated promoter and regulatory elements of the HpArs gene, accompanied by gel mobility shift assay and foot printing. Results show that two regions, PU1 (-72 b.p. to -56 b.p.), which is similar to SpZ12-1 and/or Oct-1 motif, and the PD1 site (+133 b.p. to +142 b.p.), which is homologous to the binding sites of Rel family transcription factors and/or AGIE-BP1, are related to the regulation of expression of the HpArs gene. Furthermore, an HpArs enhancer element called C15, which is located 3 kb.p. downstream from the transcription start site, activates the HpArs promoter. We also report that the enhancer activity of the C15 fragment was mediated by elements, PU1 and PD1.

Animals↗

Pedunculated esophageal leiomyosarcoma: a case report.

We report a case of esophageal leiomyosarcoma that possibly arose from the muscularis mucosae, thereby showing a particularly unusual appearance. A large polypoid intraluminal lesion in the distal esophagus was found on an endoscopic examination of a 68-year-old man with a 3-month history of dysphagia. Although the histological examination of biopsy specimens clearly revealed leiomyosarcoma, the absence of an exophytic component on computed tomography (CT) scan caused us to suspect that the tumor was carcinosarcoma. The tumor was resected by a subtotal esophagectomy. Microscopic evaluation revealed no involvement in the layer of the muscularis propria and no component of carcinoma. Clinical features of the pedunculated esophageal leiomyosarcoma shown in this case and three additional cases previously reported in the literature are reviewed.

Aged↗

Polypeptide composition of envelopes of spinach chloroplasts: two major proteins occupy 90% of outer envelope membranes.

Outer and inner envelope membranes of spinach chloroplasts were isolated using floatation centrifugation followed by sedimentation sucrose density gradient centrifugation after disruption of intact chloroplasts by freezing and thawing. Two major fractions with buoyant densities of 1.11 and 1.08 g cm-3 and a minor fraction with a density of 1.15 g cm-3 were obtained. They were identified as inner and outer envelope and thylakoid fractions, respectively by analyzing their polypeptide composition by high-resolution SDS-PAGE and the N-terminal sequences of their protein components. Due to the refinement of the isolation procedure, most of the ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO), which had always been observed as a contaminant, was eliminated from the outer envelope fraction. Application of high-resolution SDS-PAGE revealed that this fraction was rich in the low-molecular-mass outer envelope protein, E6.7 [Salomon et al. (1990) Proc. Natl. Acad. Sci. USA 87: 5778] and a protein with a molecular mass of 15 kDa which is homologous to the 16 kDa outer envelope protein of pea [Pohlmeyer et al. (1997) Proc. Natl. Acad. Sci. USA 94: 9504]. The two proteins account for 90% of the total proteins present in outer envelope membranes. Proteins which are suggested to function in translocation of nuclear-encoded polypeptides were not identified in the envelopes from spinach in the present study. Differences in the protein composition of outer envelope membranes are discussed based on the developemental stages of chloroplasts.

Amino Acid Sequence↗

Involvement of platelet-derived 5-hydroxytryptamine in thromboxane A2-induced aggregation in cat platelets.

The present study was undertaken to examine the involvement of platelet-derived serotonin (5-hydroxytryptamine; 5-HT) in thromboxane A2 (TXA2)-induced platelet aggregation. Pharmacological experiments with 5-HT2 and TXA2 inhibitors were conducted on platelet aggregation in platelet-rich plasma from cats. Exogenously added 5-HT, U-46619 (a stable TXA2 analogue) and collagen caused platelet aggregation in a concentration-dependent manner. The combination of low concentrations of 5-HT and U-46619 caused full platelet aggregation, whereas each agent alone, at these concentrations, caused a transient aggregation. 5-HT-induced aggregation was inhibited by ketanserin (0.01-0.3 micromol/l), a 5-HT2 receptor antagonist, in a concentration-dependent manner. Collagen-induced platelet aggregation was also inhibited by ketanserin, whereas the inhibition by indomethacin was modest even at the highest concentration tested (300 micromol/l). U-46619 triggered platelet aggregation in a biphasic manner. Ketanserin inhibited only the second phase of the aggregation. The inhibition of U-46619-induced aggregation by ketanserin occurred at a concentration range similar to that for 5-HT-induced platelet aggregation. Likewise, platelet aggregation induced by the combination of low concentrations of 5-HT and U-46619 was fully inhibited by ketanserin. These data suggest a major involvement of platelet-derived 5-HT in TXA2-dependent aggregation in cat platelets.

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

Predictive factors in eradicating hepatitis C virus using a relatively small dose of interferon.

Interferon (IFN) can reduce hepatitis C virus load and even eliminate the virus in 30-40% of patients. Several predictive factors for eradication of the virus have been reported and a higher dose of IFN tends to result in elimination of the virus. However, a small dose of IFN sometimes is as effective as a large dose in eradicating the virus. The predictive factors for such a response are not well established. We retrospectively analysed 50 patients with chronic hepatitis C who were treated with relatively small amounts of IFN (equal or less than 252 million units). Eleven patients were responders (elimination of hepatitis C virus (HCV) and normalization of alanine amino transferase (ALT) for at least 6 months), but the remaining 39 were non-responders. Multivariate analysis showed that the pretreatment viral load and total dose of IFN per kilogram of bodyweight were significant predictive factors of response to therapy. We also assessed the amino acid substitutions in the IFN sensitivity determining region (ISDR), NS5A codon 2209-2248, of HCV in serum samples obtained from 31 patients with HCV genotype 1b. The presence of more than one amino acid substitution in the ISDR tended to correlate with HCV genotype 1b elimination. As IFN is expensive and has a number of serious side effects, our study suggests that the optimal dose of IFN may vary from one patient to another and that more stringent criteria should be used to select the optimal dose for therapy.

Adult↗

Biochemical and histological features of hepatitis G virus infection.

To assess the biochemical and histological characteristics of hepatitis G virus (HGV) infection, we examined four patients who were infected with HGV only (HGV group), and compared them with 16 patients infected with both HGV and hepatitis C virus (HCV; HGV + HCV group) and 18 patients infected with HCV only (HCV group). Biochemical examination showed a significantly low level of serum alanine aminotransferase (ALT) in the HGV group, and that the gamma-glutamyl transpeptidase (gamma-GTP)/ALT ratio in the same group was significantly higher than in the other two groups. Although all three patient groups had a similar degree of liver fibrosis, both the degree of periportal inflammation and total histological activity index were significantly lower in the HGV group than in the other two groups. Fibrous enlargement of the portal tract without lymphoid infiltration and thin fibrous septa was characteristically observed in the HGV group. No significant difference was found between the HGV + HCV group and HCV group. Our results suggest that biochemical and histological changes in HGV infection are very mild and quite different from those of HCV infection.

Adult↗

Inhibition of rat platelet aggregation by mycalolide-B, a novel inhibitor of actin polymerization with a different mechanism of action from cytochalasin-D.

In vitro effects of mycalolide-B (MB), isolated from marine sponge, were investigated with regard to the activation of rat platelets. Collagen-induced platelet aggregation in platelet-rich plasma (PRP) was slightly but significantly potentiated by lower concentrations of MB (0.3 and 1 microM) but was inhibited by higher concentrations (3 and 10 microM). ADP-induced platelet aggregation in PRP was also significantly prevented by MB (1-10 microM). Potentiation of ADP-induced aggregation by MB (0.3 microM) was hardly observed. G-actin contents, determined by DNase I inhibition assay, were increased in resting washed platelets incubated with MB (3 microM). In contrast, cytochalasin-D (CD) at 3 microM slightly reduced G-actin contents in resting platelets. After platelet aggregation with collagen (3 microg/ml) or ADP (10 microM), G-actin contents in platelets were reduced, indicating de novo actin polymerization. MB (3 microM) and CD (3 microM) abolished both ADP (10 microM)- and collagen (3 microg/ml)-induced platelet aggregation and actin polymerization in washed platelets. MB (1-10 microM) had no effects on intracellular Ca2+ concentrations in ADP (10 microM)-stimulated platelets. [125I]-fibrinogen binding to activated platelets with ADP (10 microM)(was inhibited by MB (0.3-3 microM) in a concentration-dependent manner. Thrombin-induced platelet-fibrin clot retraction was inhibited by MB (1 and 10 microM). These results suggest that MB inhibits platelet activation by interfering with actin polymerization through a different mechanism of action from CD. MB may be a useful tool for studying the role of actin polymerization in various cells.

Actins↗

[A successfully procedure for the high risk redo-aortic valve replacement under profound hypothermic circulatory arrest and selective cerebral perfusion].

A 45-year-old female with atypical coactation of aorta and aortic regurgitation was treated with aortic valve replacement and extra-anastomic bypass between the ascending aorta and the left common iliac artery using a 12 mm woven dacron graft in 1978. She had complained of palpitation and shortness of breath six years after surgery, cinefluoroscopy demonstrated prosthetic valve dysfunction. Thrombolytic therapy was carried out to improve the valve function, but it did not result in improvement. Therefore, we decided to proceed with re-surgery. During a median sternotomy, massive bleeding from the substernal graft occurred. Therefore, we abandoned the re-surgery at that time. Then, her general condition was getting worse and she had occasional pulmonary edema fifteen years after the initial surgery. She finally underwent redo-aortic valve replacement with the aid of profound hypothermic circulatory arrest and selective cerebral perfusion. There was no cerebral complication after the re-surgery and she is now leading normal life. A median sternotomy under profound hypothermic circulatory arrest and selective cerebral perfusion was a very useful and safe procedure for patients who had risks of inadvertent injury to the aorta or the heart during the re-surgery.

Aortic Coarctation↗

Carbon monoxide controls the proliferation of hypoxic vascular smooth muscle cells.

Excess vascular smooth muscle cell (VSMC) proliferation and contractility are key events in the pathophysiology of vascular disorders induced by hypoxia. We have recently reported that carbon monoxide (CO), produced by VSMC under conditions of hypoxia, can be a modulator of cGMP levels in both endothelial and smooth muscle cells. In this respect, some of the physiologic effects of CO in the vasculature parallel those of nitric oxide (NO), a well characterized regulator of vascular tone. We report here that under hypoxia, VSMC-derived CO is an important regulator of VSMC proliferation. Inhibiting CO formation or scavenging CO with hemoglobin increased VSMC proliferation in response to serum or to mitogens such as endothelin, whereas increasing CO production or exposing cells to exogenous CO lead to a markedly attenuated growth response. The effects of CO on VSMC proliferation correlated with changes in E2F-1 expression, the prototype member of a family of transcription factors that participate in the control of cell cycle progression. CO significantly suppressed E2F-1 expression, whereas, removal of CO from the cultures with hemoglobin lead to increased E2F-1 gene transcription, mRNA, and protein production as well as mRNA levels of c-myc, a target gene of E2F-1. Moreover, the actions of CO were mediated by the second messenger molecule, cGMP. Limiting VSMC growth by increasing the release of CO may represent a key event in the body's compensatory responses to hypoxia.

Animals↗