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Biomedical subjects

S Murakami

Publications and source records attributed to S Murakami.

At least 217 records · Page 12Linked to original sources
PubMed1999

A phase II trial of low dose administration of 5-fluorouracil and cisplatin in patients with advanced and recurrent gastric cancer.

The clinical efficacy of chemotherapy for patients with advanced gastric cancer has not been established. We investigated in a phase II study the combination chemotherapy of low dose 5-fluorouracil (5-FU) and cisplatin (low dose FP) to evaluate its clinical efficacy in terms of response, quality of life and survival in 43 gastric cancer patients including 29 advanced and 14 recurrent cases. The administration of 5-FU was done by continuous intravenous infusion for 28 consecutive days with a dose of 250 mg/m2, while the administration of cisplatin was done by 1-h intravenous drip-infusion for 5 consecutive days and 2-day intervals per week with a dose of 3.5 mg/m2, that was repeated for 4 weeks in one cycle. The response rate in advanced cases was 48.3%, evaluated in 14 cases of partial response (PR), whereas its response rate in recurrent cases was 35.7%, evaluated in 5 cases of PR. The most effective lesions for low dose FP chemotherapy were primary lesion and lymph node metastasis. The quality of life assessed by performance status and oral intake was improved in 13.8% and 37.9% of advanced cases, and 21.4% and 28.6% of recurrent cases, respectively, as compared to those of pretreatment. The median survival time and 1-year survival rate were 6 months, 21.6% in advanced cases and 10 months, 28.8% in recurrent cases, respectively. The major adverse effect was observed in gastrointestinal toxicity and leukopenia, and the all toxicities were less than grade 2, that were controllable during the treatment. These results indicated that the combination chemotherapy of low dose administration of 5-FU and cisplatin might have therapeutic efficacy in tumor response and offer improvement in quality of life in patients with advanced and recurrent gastric cancer.

Adult↗
PubMed1999

[Electroconductive lithotripsy: clinical results of the Sonolith sigma].

The electroconductive lithotripter (ECL) is a new concept for shockwave generation in which a highly conductive solution channels the discharge between the anode and cathode. Out of 152 patients treated, complete follow up data were available on 151 patients. The average number of shocks per treatment was 2,138. At 3 months the overall stone-free rate was 73.5%. Success rate, defined as stone-free or asymptomatic residual fragments measuring 4 mm or less, was 84.9% for renal and 94.9% for ureteral calculi. The overall success rate for all calculi was 89%.

Adult↗
PubMed1999

[Preliminary survey of illegal drug misuse among Japanese high school students].

For several years, amphetamine misuse by high school students has been increasing in Japan. The Japanese National Police Agency announced that the third widespread use of amphetamines has started, especially among adolescents. However, there are few data on misuse of amphetamines or other substance abuse among high school students except for solvent inhalation. This is a preliminary survey report concerning substance abuse and substance-related problems among high school students. We surveyed 3393 high school students from 8 high schools in Kanagawa Prefecture and Kyushu Area on drinking and smoking status, and experience of illegal substance use. The results showed that 5.1% of the high school students had experiences of solvents inhalation, 1.1% of marijuana use, and 0.8% of amphetamine use. Around these illegal drug misusers, there were many reserves, such as students who experienced temptation to use solvents (13.6%), marijuana (2.4%), and amphetamines (2.5%), and those who responded that they wanted to use solvents (3.7%), marijuana (3.5%), and amphetamines (2.4%) if they were tempted. The prevalence of illegal drug misusers and reserves was not significantly different between male and female students, and they were concentrated among problem drinkers by the QF Scale and among current smokers. Prevalence of illegal drug misuse among Japanese high school students can not be estimated from the results of the survey because the subjects were limited to two areas and a small number of schools.

Adolescent↗
PubMed1999

Prevention of atherosclerotic lesion development in mice by taurine.

The antiatherosclerotic effects of taurine were evaluated in two murine models. In C57BL/6J mice fed a high-fat diet, 6-month treatment with taurine decreased serum atherogenic low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) cholesterol by 44%. The same treatment increased antiatherogenic high-density lipoprotein (HDL) cholesterol by 25%. Hepatic cholesterol content was also decreased by taurine. Taurine improved the area of oil red O positive arterial lipid accumulation by 20%. Hepatic cholesterol 7 alpha-hydroxylase activity, a rate-limiting enzyme of bile acid synthesis from cholesterol, was doubled in taurine-treated mice, suggesting stimulation of cholesterol catabolism to bile acid as the cholesterol-lowering mechanism seen with taurine. Thus, taurine prevented the progression of atherosclerotic lesions, and concomitantly improved the serum lipoprotein profile. In another murine model, in apolipoprotein-E-deficient mice fed regular chow, a 3-month treatment with taurine prevented accumulation of arterial lipids by 31%, despite a significant increase in serum LDL and VLDL cholesterol levels. Serum thiobarbituric acid reactive substances (TBARS) in apolipoprotein-E-deficient mice were significantly higher than those in wild type mice and treatment with taurine lowered serum TBARS level by 26%. Thus, taurine prevents the development of atherosclerotic lesions and this antioxidative effect may play an important role in the antiatherosclerotic effect that is unrelated to serum cholesterol levels.

Animals↗
PubMed1999

[Small cell lung cancer associated with paraneoplastic cerebellar degeneration and Lambert-Eaton myasthenic syndrome].

A 57-year-old man was admitted to our hospital in November 1997 because of dysarthria, progressive ataxia, generalized weakness, and incoordination in both hands. He had been aware of the dysarthria 6 months earlier. Chest roentgenograms and computed tomographic films disclosed a 5 cm x 6 cm mass in the left S3b. The patient was given a diagnosis of small cell lung cancer (T3N2M0, stage IIIA) associated with paraneoplastic cerebellar degeneration (PCD). Three courses of chemotherapy (carboplatin and etoposide) eliminated the tumor and slightly alleviated the PCD symptoms. In March 1998, electromyograms revealed a fall in the single-stimulated M wave and a waxing phenomenon that had not been observed on admission. Anti-P/Q type voltage gated calcium channel antibody was detected in serum samples obtained on admission and after chemotherapy. These findings confirmed an association with Lambert-Eaton myasthenic syndrome. No relapse of the tumor has been observed 15 months after the last course of chemotherapy.

Autoantibodies↗
PubMed1999

HBV X protein (HBX) interacts with general transcription factor TFIIB both in vitro and in vivo.

OBJECTIVE: In order to demonstrate the binding of HBV X protein (HBX) with the general transcription factor TFIIB. METHODS: In vitro glutathion S-transferase (GST) resin Pull-Down assay and Far-Western Blotting assay, in vivo Co-immunoprecipition assay were used. RESULTS: The X199 (51-99) domain of HBX is reponsible for HBX binding to TFIIB. While the d10 domain (125-295) of TFIIB is required for TFIIB binding to HBX. When the two basic amino acids (K) at position 178 and 189 of TFIIB were substituted by neutral amino acids (L), the binding of TFIIB K178L and K189L to HBX was siginificantly reduced. When the the basic amino acids were substituted by the acidic amino acids (E), the binding of TFIIB K178E and K189E to HBX were almost lost. In vitro results of HBX binding to TFIIB were further confirmed by in vivo co-immunoprecipitation assay. Our results also indicated that the Woodchuck hepatitis virus X protein (WHX) interacts with TFIIB. CONCLUSION: These results suggested that the communication between HBX and general transcription factor TFIIB is one of the mechanisms which account for its transcriptional transactivation.

Binding Sites↗
PubMed1998

The hepatitis B virus X protein is a co-activator of activated transcription that modulates the transcription machinery and distal binding activators.

Hepatitis B virus X protein (HBx) transactivates viral and cellular genes through a wide variety of cis-elements, but the mechanism has not been well elucidated. Evidence for nuclear events in HBx transactivation has been reported. Here we examine the role of HBx in modulation of transcription with a transient transfection system and an in vitro transcription assay. Reporters bearing Gal4-binding sites were applied to avoid the effects of endogenous transcription factors with or without signaling processes. The Gal4-DNA binding domain fused form of HBx exhibited no effect on Gal4-responsive reporters. However, HBx augmented activated transcription by transcriptional activators, suggesting HBx retains a co-activator but not a transcriptional activator function. The functional domain for co-activation was the same as that for HBx transactivation, and the transcription factor IIB- and RNA polymerase II subunit 5-interacting sites of HBx, which were critical for HBx transactivation, were shown to be crucial for the co-activation function. Importantly, HBx stimulated transcription on templates bearing the X responsive elements in vitro with endogenous activators. These results imply that HBx acts as a co-activator that modulates transcriptional machinery and distal-binding activators, which may explain one of the mechanisms of transactivation by HBx when localized in nuclei.

DNA-Directed RNA Polymerases↗
PubMed1998

Life extension and stress resistance in Caenorhabditis elegans modulated by the tkr-1 gene.

The nematode Caenorhabditis elegans is widely used to study aging, development, behavior and other basic metazoan processes [1-3]. The only mutants directly identified on the basis of their extended longevity in any metazoan have been isolated in C. elegans [4,5]. All life-extension mutants (Age mutants) previously identified in C. elegans result from hypo-morphic or nullo-morphic mutations. We have identified a new class of gerontogene (a gene whose alteration causes life extension) that increases life span when overexpressed. The first gene in this class has been designated tyrosine kinase receptor-1 (tkr-1); it encodes a putative receptor tyrosine kinase. Overexpression of tkr-1 in transgenics increases longevity 40-100% (average 65%), confers increased resistance to heat and ultraviolet (UV) irradiation in transgenic nematodes, and does not alter development or fertility. Unlike previously identified gerontogenes, tkr-1 positively modulates stress resistance and longevity. These results further support the positive relationship between increased stress resistance and increased longevity seen in all previously studied longevity mutants. This transgenic system is an effective means for identifying overexpression gerontogenes.

Adaptation, Physiological↗
PubMed1998

RNA-dependent RNA polymerase activity of the soluble recombinant hepatitis C virus NS5B protein truncated at the C-terminal region.

The hepatitis C virus (HCV) NS5B protein encodes an RNA-dependent RNA polymerase (RdRP), which is the central catalytic enzyme of HCV replicase. We established a new method to purify soluble HCV NS5B in the glutathione S-transferase-fused form NS5Bt from Escherichia coli which lacks the C-terminal 21 amino acid residues encompassing a putative anchoring domain (anino acids 2990-3010). The recombinant soluble protein exhibited RdRP activity in vitro which was dependent upon the template and primer, but it did not exhibit the terminal transferase activity that has been reported to be associated with the recombinant NS5B protein from insect cells. The RdRP activity of purified glutathione S-transferase-NS5Bt and thrombin-cleavaged non-fused NS5Bt shares most of the properties. Substitution mutations of NS5Bt at the GDD motif, which is highly conserved among viral RdRPs, and at the clustered basic residues (amino acids 2919-2924 and 2693-2699) abolished the RdRP activity. The C-terminal region of NS5B, which is dispensable for the RdRP activity, dramatically affected the subcellular localization of NS5B retaining it in perinuclear sites in transiently overexpressed mammalian cells. These results may provide some clues to dissecting the molecular mechanism of the HCV replication and also act as a basis for developing new anti-viral drugs.

Amino Acid Sequence↗
PubMed1998

LHRH neurons migrate into the trigeminal nerve when the developing olfactory nerve fibers are physically interrupted in chick embryos.

Most LHRH neurons actively migrate from the olfactory epithelium to the forebrain during embryonic days (ED) 3.5-8. When a small piece of the membrane filter was placed on the central course of the olfactory nerve in ED 3.5-5 chick embryos, LHRH neurons deviated from their regular migratory course at ED 6.5-7.5 to follow a route along the PSA-NCAM-positive medial and lateral nasal branches of the ophthalmic nerve of the trigeminal nerve. The olfactory nerve fibers which were specifically immunoreactive for somatostatin also deviated into the ophthalmic nerve. Enzymatic removal of PSA using endoneuraminidase did not interfere with the migration of LHRH neurons into the ophthalmic nerve bundle of the trigeminal nerve. The presence of structural supports seems to be primarily of importance in the migration of LHRH neurons along the olfactory and trigeminal nerve bundles. PSA may be less important for the migration of the LHRH neurons along peripheral neural elements.

Animals↗
PubMed1998

Properties of repeat domain found in a novel protective antigen, SpaA, of Erysipelothrix rhusiopathiae.

Erysipelothrix rhusiopathiae is a small gram-positive rod bacterium that causes erysipelas in swine and a variety of diseases in other animals and humans. Although live-attenuated or bacterin vaccines are effective in protecting against erysipelas, the genetic construction of their active antigen has not been identified. To clarify the surface antigen(s) involved in protective and arthritic response, using monoclonal antibody I2A against the surface proteins of E. rhusiopathiae, we identified a protective antigen, which consists of 606 amino acids. Analysis of deletion derivatives of the gene, spaA(surface protective antigen), showed that the SpaA protein binds tightly to the bacterial cell surface via eight repeat units with a GW-module consisting of 20 amino acids at the C-terminus. Although DeltaSpaA lacking their repeat units lost its ability to induce protection against E. rhusiopathiae infection, intact SpaA protein showed the protection. We conclude that the presence of repeat units is essential both for the binding of SpaA to the bacterial cell surface and for protection. We believe that the repeat region at the C-terminus should be a candidate for a subunit vaccine against erysipelas.

Amino Acid Sequence↗
PubMed1998

Metabolism of 2-aminophenol by Pseudomonas sp. AP-3: modified meta-cleavage pathway.

A novel pathway for 2-aminophenol metabolism by Pseudomonas sp. AP-3 is proposed. The proposed pathway is similar to that known for meta-cleavage of catechol except that one of the hydroxyl groups on the metabolites is replaced by an amino group. During the degradation of 2-aminophenol, 2-amino-2,4-pentadienoic acid is the last metabolite containing an amino group. We, therefore, propose a modified meta-cleavage pathway for the 2-aminophenol metabolism.

Aminophenols↗
PubMed1998

Molecular cloning and nucleotide sequence of the pyruvate kinase gene of an actinomycete Microbispora thermodiastatica.

The gene for the thermostable pyruvate kinase of Microbispora thermodiastatica IFO 14046, a moderate thermophilic actinomycete, was cloned in Escherichia coli. This gene consists of an open reading frame of 1422 nucleotides and encodes a protein of 474 amino acids with molecular mass of 50,805 Da. The open reading frame was confirmed as the pyruvate kinase gene by comparison with the N-terminal amino acid sequence of the purified pyruvate kinase from M. thermodiastatica.

Actinomycetaceae↗
PubMed1998

Astrocytic plaques and tufts of abnormal fibers do not coexist in corticobasal degeneration and progressive supranuclear palsy.

Corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) are characterized by their unique clinical features and neuronal pathology. Although astrocytic plaques and tufts of abnormal fibers have been suggested to be specific histopathologic markers, recent studies have revealed significant clinicopathologic overlap between CBD and PSP. Based on the distinctive camera lucida profile of astrocytic inclusions on Gallyas-Braak silver staining, we found that astrocytic plaques and tufts of abnormal fibers did not coexist in the same patient among 30 cases of clinically diagnosed CBD, PSP and atypical Parkinson's disease. Using Tau immunohistochemistry it was difficult to verify the absence of tufts of abnormal fibers. A morphometric analysis revealed that the two groups classified by the presence or absence of astrocytic plaques and tufts of abnormal fibers exhibited significant differences in the density of ballooned neurons and neurofibrillary tangles and degeneration of the subcortical nuclei. Assessment using the NINDS neuropathologic criteria revealed that the cases with astrocytic plaques and tufts of abnormal fibers closely correspond to CBD and typical PSP, respectively. In addition, the cases lacking either of these two astrocytic inclusions had atypical PSP according to the NINDS criteria, and were associated with novel tau-positive astrocytes (spiny astrocytes). We thus conclude that astrocytic plaques and tufts of abnormal fibers are highly characteristic structures for CBD and typical PSP, respectively. We emphasize the importance of strict differentiation between different astrocytic inclusions not only for diagnosis, but also for further studies for elucidation of their role in the disease mechanisms of CBD and PSP.

Aged↗
PubMed1998

Combined schedule of 7-valent pneumococcal conjugate vaccine followed by 23-valent pneumococcal vaccine in children and young adults with sickle cell disease.

We compared the immunogenicity of 7-valent pneumococcal-conjugate vaccine plus 23-valent pneumococcal vaccine to immunization with 23-valent vaccine only in individuals > or = 2 years of age with sickle cell disease. IgG pneumococcal antibody concentrations were higher in the combined schedule group with no increase in side effects observed after immunization with 23-valent vaccine.

Adolescent↗