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Biomedical subjects

C Sato

Publications and source records attributed to C Sato.

At least 109 records · Page 6Linked to original sources
PubMed1998

Interferon therapy for chronic hepatitis C in hemodialysis patients: increased serum levels of interferon.

BACKGROUND/AIMS: The efficacy and side effects of interferon (IFN) therapy have not been well clarified in hemodialysis patients with chronic hepatitis C. METHODS: In 6 of 9 hemodialysis patients with chronic hepatitis C, 3 million units (MU) or 6 MU of recombinant IFN-alpha2b or natural IFN-alpha were administered intramuscularly daily for the first 2 weeks, followed by three times a week for 22 weeks. In the remaining 3 patients, 3 MU of IFN-alpha2b were given three times a week for 24 weeks. Serum concentrations of IFN-alpha2b were measured sequentially after the injection of interferon. Responders were defined as the patients with normal serum aminotransferase and negative serum HCV RNA 6 months after the cessation of IFN therapy. RESULTS: Three of the 6 patients who were administered IFN daily in the first 2 weeks were responders, while the other 3 withdrew from the therapy due to serious adverse events such as depression, loss of consciousness and persistence of high-grade fever. Serious adverse events were not observed in the 3 patients without daily administration. Half-lives of IFN-alpha2b in hemodialysis patients were significantly longer than those in nonuremic patients (10.0 vs. 6.0 h, p < 0.05). Moreover, the areas under the serum concentration curve of the hemodialysis patients were significantly larger than those of nonuremic patients (756 +/- 223 vs. 324 +/- 223 IU.h/ml, p < 0.05), despite the fact that the dose of IFN-alpha administered to hemodialysis patients was half that administered to nonuremic patients. CONCLUSIONS: In hemodialysis patients with chronic hepatitis C, pharmacokinetic parameters of IFN may be different from those in nonuremic patients, and daily or high-dose administration of IFN may lead to serious adverse events in those patients.

Adult↗
PubMed1998

Local anti-inflammatory activity and systemic side effects of NM-135, a new prodrug glucocorticoid, in an experimental inflammatory rat model.

The local anti-inflammatory activity and systemic side effects of NM-135 (6alpha,9-difluoro-11beta-hydroxy-16alpha-methyl-21[[2 ,3,4,6-tetrakis-O-(4-methylbenzoyl)-beta-D-glucopyranosyl]oxy]-pregna-1, 4-diene-3,20-dione) in croton oil-induced granuloma pouches and ear edema in rats were studied. The local anti-inflammatory activity of NM-135 was stronger than that of betamethasone 17-valerate (BV). As to systemic side effects, BV and diflucortolon valerate (DFV) caused thymolysis at the doses required for the anti-inflammatory activity. In contrast, no clear systemic side effect was observed in rats administered NM-135 at the dose producing the anti-inflammatory activity. These results suggest that NM-135 is a drug exhibiting a high degree of dissociation between the local anti-inflammatory activity and systemic side effects.

Animals↗
PubMed1998

Effect of pravastatin on plasma ketone bodies in diabetics with hypercholesterolemia.

Hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) is a common intermediate metabolite of cholesterol synthesis and ketone formation in the liver. In order to study the effect of HMG-CoA reductase inhibitor (pravastatin) on ketone formation, changes in the plasma levels of ketone bodies by treatment with pravastatin were studied in 18 non-insulin dependent diabetics with hypercholesterolemia. Body mass index, diabetic control, and plasma free fatty acid levels were not changed during the study, and the plasma levels of cholesterol decreased significantly from 250 +/- 25 to 211 +/- 34 mg/100 ml after 6 months of pravastatin treatment. The plasma levels of acetoacetic acid also significantly decreased from 37.7 +/- 22.6 to 28.4 +/- 13.4 mumol/l, and those of 3-hydroxybutyric acid and total ketone bodies also tended to decrease after pravastatin treatment. These results suggest that pravastatin decreases ketone formation in hepatic mitochondria besides cholesterol synthesis in hepatic microsome.

3-Hydroxybutyric Acid↗
PubMed1998

[Clarion 16 cochlear implant (System introduction and use experience in Japan].

The Clarion cochlear implant was developed in the USA and received FDA approval in August 1996. It consists of an implantable cochlear stimulator (ICS), speech processor with headpiece, and in addition, a clinician's programming system and portable cochlear implant tester. One of the features of the device is its stimulation-coding process for which two methods of continuous interleaved sampling (CIS) and compressed analogue (CA) are applicable. Regardless of which is used, stimulation can be provided over 8 channels. The device was used in 2 cases. Both patients were operated on in October 1996, and 16 electrodes in 8 pairs were mounted in the cochlea. Mapping, performed 3 weeks after the operation, showed good speech perception in both patients with only a cochlear implant in the "open-set" status. CIS was used as the stimulation-coding method. CA has yet to be applied.

Cochlear Implantation↗
PubMed1998

The selected information sources on poisoning and toxicology.

The third leading cause of unintentional injury death in 1993 was poisoning by solids and liquids, just behind motor vehicle accidents and falls. Poisoning and toxicology impacts all health care professionals. Physicians and emergency medicine professionals manage acute care, health educators address prevention and public education, and researchers focus on advancements. This article is an introduction to selected basic through advanced print and electronic information sources for anyone interested in poisoning and toxicology. All sources are available through the Hawaii Medical Library.

Computer Communication Networks↗
PubMed1997

Multivariate analysis of the association of bromocresol purple anion with bovine serum albumin.

The interaction of bromocresol purple (BCP) anions with bovine serum albumin (BSA) was investigated by principal factor analysis method, and reaction model, the number of molecular species and spectra of each component present in the reaction mixture were determined. The number of molecular species concerning the absorption intensity was three, including free BCP anion. Most part of the spectral change could be explained by the monomer binding of bromocresol purple anion (D) to serum albumin (P), a simple one step equilibrium, P + D = PD. A second type of association of BCP anions with serum albumin was also present, though in a small amount. Of six models tested which consisted of three or four molecular species, the sequential two step reaction model, P = PD = PD2, was the best model to explain the spectral data, and an existence of BCP anions as a dimer on the serum albumin was demonstrated. The dissociation constants were estimated at K1 = 1.6 x 10(-6) M for the first step and K2 = 1.2 x 10(-5) M for the second step.

Bromcresol Purple↗
PubMed1997

Molecular cloning and characterization of a putative neural calcium channel alpha1-subunit from squid optic lobe.

The complete amino acid sequence of a putative calcium channel alpha1-subunit, SQCC1, from the optic lobe of the squid Loligo bleekeri has been deduced by cloning and sequence analysis of the complementary DNA. The open reading frame encodes 2206 amino acids, which corresponds to a molecular weight of 251,451. The deduced amino acid sequence shares general structural features with the other voltage-dependent calcium channels; it consists of four repeated units of homology. Each motif has five hydrophobic segments and one positively charged segment. The transcriptional products were detected in all nervous systems examined; optic lobe, cerebral ganglia and giant stellate ganglia. However, it was not detected in the mantle muscle, heart and stomach, indicating SQCC1 is a calcium channel alpha1-subunit specific for squid nervous system. SQCC1 is more closely related in its amino acid sequence patterns to dihydropyridine-insensitive calcium channels rather than dihydropyridine-sensitive ones.

Amino Acid Sequence↗
PubMed1997

Analysis of genotypes and amino acid residues 2209 to 2248 of the NS5A region of hepatitis C virus in relation to the response to interferon-beta therapy.

In chronic hepatitis C virus (HCV) infection, genotypes other than genotype 1b of HCV (HCV-1b) and low serum HCV-RNA levels are known to be associated with favorable outcome of interferon alfa (IFN-alpha) therapy. In addition, we recently reported a close correlation between the number of mutations in amino acid sequences 2209 to 2248 of the nonstructual protein 5A gene (NS5A2209-2248) of HCV-1b and the response to IFN-alpha. In the present study, we analyzed these viral factors in relation to the efficacy to IFN-beta, another type I IFN. The pretreatment sera of 40 patients treated with IFN-beta intravenously at 6 MU daily for 42 days were studied. HCV genotypes, serum HCV-RNA levels, and the amino acid sequence of NS5A2209-2248 in HCV-1b were determined. A sustained complete response to IFN therapy occurred in none of the ten patients with the wild-type HCV-1b who had an NS5A2209-2248 sequence identical to the prototype HCV-1b and in none of the six patients with the intermediate-type HCV-1b that had 1 mutation. In contrast, complete responses occurred in the following: 4 of 6 patients with the mutant-type HCV-1b that had five to ten mutations; 6 of 13 patients with genotype 2a of HCV (HCV-2a); and 2 of 5 patients with genotype 2b of HCV (HCV-2b). Among patients with the mutant-type HCV-1b or genotype 2 of HCV (HCV-2) the rate of complete response was significantly higher (12 of 24 vs. 0 of 16 patients, P < .001) and HCV-RNA levels were significantly lower (4.5 [4.0-6.5] vs. 6 [4.5-6.5] log copies/mL, median [range]; P < .001) compared with patients with the wild- or the intermediate-type HCV-1b. Patients with the mutant-type HCV-1b or HCV-2 whose HCV-RNA levels were lower than 6 log copies/mL had a complete response rate of 75% (12 of 16 patients) in contrast to 0% (0 of 24 patients) of the others (P < .001). These results indicate that the mutant-type HCV-1b or HCV-2 are sensitive to IFN-beta as well as IFN-alpha. In conclusion, the determination of HCV genotypes, NS5A2209-2248 of HCV-1b and serum HCV-RNA levels may facilitate the selection of patients with a high likelihood of response to IFN-beta.

Amino Acid Sequence↗
PubMed1997

Nucleotide sequence variations in the internal ribosome entry site of hepatitis C virus-1b: no association with efficacy of interferon therapy or serum HCV-RNA levels.

The extreme 5'-proximal sequences of the hepatitis C virus (HCV) genome including the 5'untranslated region (5'UTR) and the first 30 nucleotides of the core region are highly conserved, and serve as an internal ribosome entry site (IRES) that initiates the cap-independent translation of HCV polyprotein. Mutations in the IRES sequence have been shown to cause changes in the efficiency of protein translation in vitro. However, the significance of genetic variations in the IRES is not fully known in clinical settings. Pretreatment sera of 25 patients with HCV-1b infection who were treated with interferon were amplified by polymerase chain reaction (PCR), and the IRES sequence was directly sequenced. Correlation of interferon responses or other clinical features with IRES sequence variability was studied. Eleven of 25 patients were sustained responders (SR) of interferon treatment (negative serum HCV RNA and normal alanine transaminase levels for 6 months after the end of interferon treatment), and the other 14 patients were nonresponders ([NR], defined as any patient with positive serum HCV RNA within 6 months after the end of interferon therapy). In each patient, one to four nucleotide substitutions were found compared with the consensus sequence of HCV-1b genotype. There were no differences in the number of nucleotide substitutions between either SR and NR (mean, 1.8 in SR, 2.1 in NR; P = .30), and no specific variations associated with SR or NR were observed. Although NR had significantly higher serum levels of pretreatment HCV RNA than SR (median, 16 vs. <0.5 Meq/mL; P = .02), there was no correlation between the HCV-RNA level and the number of nucleotide substitutions in the IRES (mean, 1.9 nucleotide substitutions in 12 patients with HCV RNA <0.5 Meq/ mL vs. 2.1 nucleotide substitutions in 13 patients with HCV RNA >0.5 Meq/mL; P = .61). Sequence variability of the IRES has no influence on interferon efficacy or serum HCV-RNA concentrations in patients with chronic HCV-1b infection.

Adult↗
PubMed1997

p53 and HER-2 alterations in renal cell carcinoma.

OBJECTIVES: To investigate protein expression and genetic aberrations of p53 and HER-2 in renal cell carcinoma (RCC) as well as possible association of p53 and HER-2 abnormalities with the tumor behavior of RCC. METHODS: Formalin-fixed and paraffin-embedded tissue blocks from 70 patients with RCC were studied. Protein expression of p53 and HER-2 was assessed immunohistochemically. Following deoxyribonucleic acid extraction from the paraffin sections using a microdissection technique, p53 gene mutations within exons 5 to 8 were examined by polymerase chain reaction (PCR) single-strand conformation polymorphism and HER-2 gene amplification by a differential PCR. RESULTS: Of the 70 RCCs, 16 (22.9%) showed protein expression of p53, with 7 (10%) demonstrating mutations within exons 5 to 7. Additionally, 28 RCCs (40%) displayed protein expression of HER-2, with 12 (17.1%) demonstrating gene amplification. All cases showing p53 mutations or HER-2 amplification represented protein expression of p53 or HER-2, respectively. No cases with negative immunostaining for p53 or HER-2 protein displayed positive results at gene level. Statistical analysis revealed a close relationship between p53 protein expression and the tumor grade, as well as a significant association of HER-2 protein expression and gene amplification with the tumor stage of RCC. CONCLUSIONS: Our observations suggest that the abnormalities of p53 and HER-2 may be involved in the pathogenesis of RCC and that other mechanisms leading to protein expression of p53 and HER-2 may coexist within a single tumor in addition to the genetic aberrations.

Adult↗
PubMed1997

ATP release and contraction mediated by different P2-receptor subtypes in guinea-pig ileal smooth muscle.

1. The present study was addressed to clarify the subtypes of P2-purinoceptor involved in ATP release and contraction evoked by alpha, beta-methylene ATP (alpha, beta-mATP) and other P2-agonists in guinea-pig ileum. 2. alpha, beta-mATP 100 microM produced a transient and steep contraction followed by ATP release from tissue segments. These maximum responses appeared with different time-courses and their ED50 values were 5 and 25 microM, respectively. The maximum release of ATP by alpha, beta-mATP was markedly reduced by 250 microM suramin, 30 microM pyridoxal-phosphate-6-azophenyl-2',5'-disulphonic acid (PPADS) and 30 microM reactive blue 2 (RB-2), P2-receptor antagonists. However, the contractile response was inhibited by suramin, tetrodotoxin and atropine, but not by PPADS and RB-2. 3. Although the contraction caused by alpha, beta-mATP was strongly diminished by Ca(2+)-removal and nifedipine, and also by tetrodotoxin and atropine at 0.3 microM, the release of ATP was virtually unaffected by these procedures. 4. UTP, beta, gamma-methylene ATP (beta, gamma-mATP) and ADP at 100 microM elicited a moderate release of ATP. The release caused by UTP was virtually unaffected by RB-2. However, these P2-agonists failed to elicit a contraction of the segment. 5. The potency order of all the agonists tested for the release of ATP was alpha, beta-mATP > UTP > beta, gamma-mATP > ADP. 6. In superfusion experiments with cultured smooth muscle cells from the ileum, alpha, beta-mATP (100 microM) enhanced the release of ATP 5 fold above the basal value. This evoked release was inhibited by RB-2. 7. These findings suggest that ATP release and contraction induced by P2-agonists such as alpha, beta-mATP in the guinea-pig ileum result mainly from stimulation of different P2-purinoceptors. P2Y-like purinoceptors on the smooth muscles and, probably, P2X-purinoceptors on cholinergic nerve terminals, respectively. However, the ATP release may also be mediated, in part, by P2U-receptors, because UTP caused RB-2-insensitive ATP release.

Adenosine Triphosphate↗
PubMed1997

Occurrence of terminal alpha 2-->8-linked disialylated poly-N-acetyllactosamine chains with Le(X) and I antigenic glycotopes in tetraantennary arms of an N-linked glycoprotein isolated from rainbow trout ovarian fluid.

The Pronase digestion of a 54K glycoprotein present in ovarian fluid of rainbow trout yielded a major glycopeptide. Carbohydrate compositional analysis revealed that this glycopeptide was likely to possess a single large N-glycan chain having low molecular weight oligomers of N-acetylneuraminic acid (oligoNeu5Ac). Structural studies of this glycopeptide revealed novel alpha 2-->8-linked disialylated poly-N-acetyllactosamine chains with Le(X) and I antigenic determinants on the N-linked tetraantennary core glycan. In our recent studies (Kitazume,S., Kitajima,K., Inoue,S., Inoue,Y. and Troy,F.A. (1994) J. Biol. Chem. 269, 10330-10340) we presented evidence that synthesis of alpha 2-->8-linked polysialic acid (polySia) chains is a two-step process in which chain initiation is catalyzed by an alpha 2-->8-sialyltransferase (alpha 2-->8-ST; initiase) that catalyzes synthesis of the first Sia alpha 2-->8-linkage, forming the disialic acid (diSia) unit, Sia alpha 2-->8-Sia alpha 2-->6-Gal-. Chain polymerization is then postulated to be catalyzed by a second enzyme, an alpha 2-->8-polyST ("polymerase") that converts the diSia units to polySia chains. The present structural studies leading to the discovery of alpha 2-->8-linked disialylated units that terminate poly-N-acetyllactosamine chains in an N-linked glycoprotein is further evidence in support of our hypothesis that more than one sialyltransferase activity is required for polySia chain synthesis and polymerization.

Animals↗
PubMed1997

Nonalcoholic steatohepatitis masquerading as autoimmune hepatitis.

Nonalcoholic steatohepatitis is an increasingly recognized clinicopathologic condition. We report two cases of nonalcoholic steatohepatitis in middle-aged Japanese women whose clinical and laboratory data mimicked autoimmune hepatitis. Histologic findings of both cases were definite steatohepatitis with portal and pericellular fibrosis. Both patients' HLA-DR haplotypes were DR4 and DR2, which are frequently observed in Japanese patients with autoimmune hepatitis. Our cases suggest a diversity in the pathogenesis of nonalcoholic steatohepatitis.

Adult↗
PubMed1997

Comparison of an improved AFP kit with the intra-amniotic PSP dye-injection method in equivocal cases of preterm premature rupture of the fetal membranes.

OBJECTIVE: We developed an improved AFP kit for detecting AFP in leaked amniotic fluid. We studied the relationship between the results of the improved AFP kit and those of the intra-amniotic PSP dye-injection test (PSP test), and compared the results of two tests with the prognosis for subsequent pregnancy outcome, in order to know the diagnostic value of the two tests for preterm PROM, especially in equivocal cases. METHODS: We compared the results of the AFP kit test with those of the PSP test in 8 equivocal cases of preterm PROM (18th to 34th weeks of gestation). RESULTS: The results of the AFP kit test coincided with those of the PSP test in all 8 equivocal cases of preterm PROM. The 4 cases that tested positive resulted in preterm deliveries; and the other 4 cases that tested negative resulted in full-term deliveries. CONCLUSION: The use of the AFP kit test is useful in assessing the prognosis for subsequent pregnancy in equivocal cases of preterm PROM. The rapid and accurate AFP kit test for diagnosing preterm PROM can be substituted for the PSP test in bedside and outpatient-clinic assessments.

Adult↗