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Biomedical subjects

K Katayama

Publications and source records attributed to K Katayama.

At least 217 records · Page 12Linked to original sources
PubMed1996

Inhibitory effect of E3330, a novel quinone derivative able to suppress tumor necrosis factor-alpha generation, on activation of nuclear factor-kappa B.

(2E)-3-[5-(2,3-Dimethoxy-6-methyl-1,4-benzoquinoyl)]-2-nonyl-2- propenoic acid (E3330), is a novel agent with hepatoprotective activity. We report the effect of E3330 on transcriptional activation of tumor necrosis factor (TNF)-alpha gene and on nuclear factor (NF)-kappa B activation. Nuclear run-on experiments showed that E3330 decreases transcriptional activation of TNF-alpha gene induced by lipopolysaccharide (LPS) stimulation in human peripheral monocytes. To investigate the inhibitory mechanisms, we constructed a secreted-type placental alkaline phosphatase (PLAP) reporter gene whose transcription is controlled by a 1.4-kb human TNF-alpha promoter. A stable transformant of the PLAP reporter gene derived from human monocytic cell line showed very little activity on the promoter before stimulation, whereas LPS stimulation led to a dramatic increase in PLAP activity. E3330 inhibited this induced promoter activity in a dose-dependent manner. There are four putative NF-kappa B binding sites (kappa B-1, kappa B-2, kappa B-3, kappa B-4) in human TNF-alpha promoter. By using mutated promoter-PLAP plasmids, we established that these NF-kappa B sites were necessary for induction of TNF-alpha transcription on stimulation with LPS. A gel retardation experiment with synthetic double-stranded oligonucleotides showed that activated NF-kappa B consisting of p50/p65 heterodimer bound to all four putative NF-kappa B DNA probes, suggesting that all four putative NF-kappa B recognition sites play an important role in inducible TNF-alpha expression. E3330 decreased activated NF-kappa B in nuclei, suggesting that E3330 inhibits NF-kappa B activation and/or translocation of the nuclei. Western blotting analysis with anti-I kappa B-alpha antibody indicated that E3330 inhibited degradation of I kappa B-alpha, which is an inhibitory protein of NF-kappa B, in LPS-stimulated monocytes. E3330 may suppress the production of active oxygen species serving as common messengers to activate NF-kappa B.

Alkaline Phosphatase↗
PubMed1996

[Liver resection in a case of multiple liver metastases of gastric cancer following hepatic arterial infusion chemotherapy].

A 61-year-old-man underwent subtotal gastrectomy (D2) for advanced gastric cancer with multiple liver metastases. After the operation, repeated hepatic arterial infusion chemotherapy was performed employing implantable catheter and port system with CDDP and MMC. The result was that the liver tumors showed a remarkable regression in size, and the serum CA 19-9 level decreased within normal range. But the tumor in the lateral segment grew and the CA 19-9 level increased again. There was no evidence of metastasis or recurrence except in the liver, and the metastatic tumors in right lobe became smaller by hepatic arterial infusion chemotherapy at this time. Therefore, lateral segment resection was performed for reductive surgery 14 months after the first operation. After that, the liver tumors did not grow and CA 19-9 kept within the normal range, while hepatic arterial infusion chemotherapy could be given. Thus, it seems that liver resection for reduction surgery following hepatic arterial infusion chemotherapy should be considered as a treatment for multiple liver metastases.

Adenocarcinoma↗
PubMed1996

Modulation by dihydropyridines and protein kinases of the recombinant cardiac L-type Ca channel with multiple unitary current amplitudes.

The cloned cardiac L-type Ca channel current expressed in baby hamster kidney (BHK) cells was characterized at the single channel level. After transfection of cDNA of the cardiac alpha 1 subunit along with skeletal beta, alpha 2/delta and gamma subunits to this cell line, recombinant Ca channels could be observed at high density over extended times. The properties of cloned Ca channels were almost identical with those of native cardiac L-type Ca channels, with respect to voltage dependence of activation, unitary conductance (25 pS with 100mM Ba2+ as the charge carrier and the modulation by a dihydropyridine (DHP) Ca channel agonist and an antagonist, or by 8Br-cAMP and phorbol esters. As in native cardiac Ca channels, changes in kinetic behavior during 8Br-cAMP application included increased number of channel openings and increased duration of open times. Phorbol esters also increased the number of openings with long duration. In 27 out of 37 patches in the presence of BayK8644, small amplitude openings of several levels were observed. These openings behaved similarly to the predominant 25 pS openings during DHP and 8Br-cAMP application, with infrequent transitions to and from the predominant level. We conclude that BHK cells provide a useful expression system where the modulations and biophysical aspects of Ca channels can be studied at the single channel level.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1996

[Effective transcatheter arterial embolization for hepatic metastasis in a case of AFP producing gastric cancer].

We experienced a case of effective transcatheter arterial embolization (TAE) for hepatic metastasis in a AFP producing gastric cancer. A 51-year-old man with 2 type gastric cancer (H0) underwent subtotal gastrectomy (D2). The serum AFP level was 134.3 ng/ml, and AFP positive tumor cells were detected by PAP method. After the operation, the serum AFP level initially decreased but re-increased on the 7th postoperative month, and metastatic lesions of the liver were detected by CT scan. After the patient was treated 4 times by TAE, the serum AFP level returned within normal range and the metastatic tumors of the liver decreased markedly. Therefore liver resection was performed at the 28th month after the first operation. Total necrosis of metastatic liver lesions was confirmed. This patient has been well without recurrence signs for 10 years since operation. It is concluded that TAE should be used to treat hepatic metastasis in the case of an AFP producing gastric cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Two types of calcium channels sensitive to omega-agatoxin- TK in cultured rat hippocampal neurones.

We characterized the electrophysiological properties of calcium channels in cultured rat hippocampal neurones using omega-agatoxin-TK (omega-Aga-TK) and compared them with those of the P-type channel and the BI (alpha 1A) channel which resembles the Q-type channel. Two types of omega-Aga-TK-sensitive calcium channels were detected in hippocampal neurones. The first type showed slow inactivation, high sensitivity to omega-Aga-TK and low reversibility from omega-Aga-TK-induced block, resembling the P-type channel. The second type showed fast inactivation, low sensitivity to omega-Aga-TK and high reversibility from omega-Aga-TK-induced block. These results suggest that the second type of calcium channel (Q-type-like) plays a prominent role in the hippocampal synaptic transmission.

Agatoxins↗
PubMed1995

Isolation and characterization of a peptide isomerase from funnel web spider venom.

A novel peptide isomerase was purified from the venom of funnel web spider, Agelenopsis aperta. The complete primary structure of the isomerase has been established by sequence analyses of polypeptide chains, assignments of disulfide bridges, carbohydrate analyses, and mass spectrometry of sugar chains. The isomerase was found to be a 29-kDa polypeptide that consists of an 18-residue light chain and a 243-residue heavy chain connected by a single disulfide bridge. The heavy chain contains three intramolecular disulfide bridges and one N-linked oligosaccharide chain with a simple trimannosyl core structure. A sequence homology search showed a significant similarity of the enzyme with serine proteases, particularly around a putative catalytic triad of the isomerase. The isomerase specifically interconverts the configuration of Ser46 of a 48-amino-acid peptide, omega-agatoxin-TK, and the conversion rate from L-Ser to D-Ser was approximately two times faster than the reverse reaction.

Amino Acid Isomerases↗
PubMed1995

Spectral analyses of R-R interval and systolic blood pressure in diabetic autonomic neuropathy.

We studied autonomic nervous system function using the principle of maximum entropy (ME) to perform spectral analyses of the R-R interval and systolic blood pressure in 32 diabetic patients and 40 healthy controls. The R-R interval and systolic blood pressure were measured using a continuous, noninvasive monitoring system. The power spectra of both the R-R interval (RR) and systolic blood pressure (SYS) were obtained using ME and the areas of two frequency components were measured: a low- (LFC) and a high-frequency component (HFC). The RR-LFC, RR-HFC and SYS-LFC of diabetic patients were significantly smaller than those of healthy controls. The results of the spectral analyses in diabetic patients correlated with neither disease duration nor nephropathy, while the SYS-LFC showed significant correlations with both retinopathy and the delay in median motor nerve conduction velocity. In the mild autonomic neuropathy group, the RR-LFC and SYS-LFC were not differ from those of healthy controls or patients without autonomic neuropathy. However, the RR-HFC was significantly smaller than that of healthy controls or patients without atonomic neuropathy. In the setting of mild diabetic autonomic neuropathy, it was suggested that cardiac parasympathetic dysfunction preceded both alpha and beta sympathetic dysfunction.

Adult↗
PubMed1995

Clinical characteristics and antibody profiles of chronic hepatitis C patients: relation to hepatitis C virus genotypes.

Genotyping of 179 consecutive Japanese chronic hepatitis C patients was carried out based on the variation in the hepatitis C virus (HCV) core gene. The results were correlated with clinical features and antibody responses toward specific HCV proteins deduced from the nucleotide sequence of genotype I/1a. Genotypes II/1b, III/2a, and IV/2b were identified in 138 (77%), 24 (13%), and 12 (7%) patients, respectively. Five patients had double infections. Genotype dependence was observed only for antibody response toward the NS4 (5-1-1) protein, which was infrequent in genotype III/2a patients (33%) compared with genotype II/1b (81%; P < 0.01) and genotype IV/2b (75%; P < 0.05). Following interferon-alpha therapy, sustained amniotransferase normalisation was achieved by 89% (eight of nine) patients without antibody to the 5-1-1 protein and 33% (17 of 51) with it (P < 0.01). These findings indicate that absence of antibody response to the 5-1-1 protein is frequent in genotype III/2a HCV carriers and may serve to predict responses to interferon therapy.

Adult↗
PubMed1995

Serial density analysis of hepatitis C virus particle populations in chronic hepatitis C patients treated with interferon-alpha.

In interferon treatment of chronic hepatitis C patients, the biochemical and virological responses mostly parallel each other. However, some patients who show persistent ALT normalization display continued viremia after cessation of therapy. High-density hepatitis C virus (HCV) particles, which are immune complex forms, are reported to be less infectious both in vitro and in vivo. To assess whether high-density HCV contributes to the response discrepancies and to clarify the association with patient outcome, sera were examined from chronic hepatitis C patients who were treated with interferon-alpha. This study included 10 sustained responders with viremia (SR + ve), 5 SR without viremia, 3 transient responders (TR), and 3 nonresponders (NR). The SR + ve patients were defined as those with continued ALT normalization and serum HCV-RNA positivity at 24 weeks after therapy completion. Serum samples obtained before and 24 weeks after therapy were ultracentrifuged on 35% sucrose. The ratio between high-density and low-density HCV was determined by quantification of HCV-RNA titers in the bottom and top fractions by competitive reverse transcription and by the polymerase chain reaction, and expressed as the bottom/top (B/T) ratio. The B/T ratios before therapy were 1:1 in all groups of patients, and 1:1 after therapy in TR and NR groups. Five out of 6 SR + ve patients who showed 1:1 ratio after therapy relapsed within 1 year. In contrast, all SR + ve patients whose ratios were 10-100:1 continued to show ALT normalization. These findings demonstrate that patients who have high-density HCV dominance after therapy show persistent ALT normalization despite viremia, which can be explained by predominance of the neutralized immune complex.

Adult↗
PubMed1995

Long-term follow-up of hepatitis B virus and hepatitis C virus replicative levels in chronic hepatitis patients coinfected with both viruses.

Dual infection with hepatitis B and C viruses is often encountered in endemic areas of both viruses. However, understanding of the clinical and virological implications is limited. The aim of this study was to investigate the role of each virus in liver injury and the interaction between the two viruses in dual infection with hepatitis B and C viruses. Three patients who had chronic infection with both hepatitis B and C viruses were examined, and a longitudinal study of both serum hepatitis B virus DNA and hepatitis C virus RNA levels over 4 years was undertaken. The results were correlated with serum alanine aminotransferase levels. Serum alanine aminotransferase values showed a relationship with hepatitis B virus replicative levels, but not with hepatitis C virus replicative levels in all 3 patients. Serial changes of replicative levels of both viruses were studied, and it was found that hepatitis C virus replicative levels were enhanced after the decline of hepatitis B virus replication in 1 of the 3 patients. In the remaining 2 patients, a transient rise of hepatitis C virus replicative levels in association with a decrease of hepatitis B virus replication was also observed during part of the follow-up period. These findings indicate that hepatitis B virus may play a dominant etiological role in liver injury, and that a suppressive action between hepatitis B and C viruses may occur in dual infection with both viruses.

Adult↗
PubMed1995

Tumor necrosis factor-alpha and interferon-gamma inhibit synergistically viral replication in hepatitis B virus-replicating cells.

The effects of tumor necrosis factor-alpha and/or interferon-gamma on the replication of hepatitis B virus were examined using HB611 cells. These cells were derived from human hepatoblastoma cells, Huh6, by integrating hepatitis B virus DNA, and produce hepatitis B virus continuously. Each of the cytokines inhibited hepatitis B virus replication in the cells assessed as the amount of episomal hepatitis B virus DNA, without a decrease in cell viability. When the two cytokines were administered together, the inhibitory effect became greater. Incubation of the cells with 1,000 U/ml tumor necrosis factor-alpha decreased HBV DNA replicative intermediates by 55%, and that with 1,000 U/ml interferon-gamma decreased these by 51%. Furthermore, incubation with 1,000 U/ml tumor necrosis factor-alpha and 1,000 U/ml interferon-gamma in combination decreased HBV DNA replicative intermediates by 71%. In contrast, the amount of hepatitis B virus RNA and secretion of hepatitis B e antigen were not apparently reduced by the cytokines, and 2',5'-oligoadenylate synthetase activity was not detected in the supernatant. These results suggest that tumor necrosis factor-alpha and interferon-gamma inhibit hepatitis B virus replication by blocking some step in reverse transcription and that the 2',5'-oligoadenylate synthetase is not involved in the mechanism underlying the inhibition by these two cytokines.

2',5'-Oligoadenylate Synthetase↗
PubMed1995

Adhesive substrates influence acid-productive activities of cultured rabbit osteoclasts: cultured osteoclasts with large vacuoles have enhanced acid-productive activities.

Since acid secretion of polarized osteoclasts on the bone surface has an important role in bone resorption, we examined the acid-productive activities of osteoclasts by measuring the pH of acidic organelles such as endosomes, lysosomes, and vacuoles in cultured rabbit osteoclasts with FITC-dextran as a fluorescent pH probe. The average pH value of acidic organelles of osteoclasts cultured on plain glass coverslips was 5.3 +/- 0.2. The pH of the acidic organelles correlated well with the size and amount of the vacuoles in the cells. Using this FITC-dextran method, we also examined the effects of adhesive substrates, such as type I collagen, vitronectin, and dentine, on the acid-productive activities of osteoclasts and found that the pH value of acidic organelles of osteoclasts cultured on dentine slices was significantly lower than that of osteoclasts cultured on plain glass coverslips. Likewise, in the case of the osteoclasts cultured on type I collagen- or vitronectin-coated glass coverslips, the pH values of acidic organelles were slightly lower and the proportion of osteoclasts having large vacuoles was increased compared with the cells cultured on the plain glass coverslips. These results indicate that osteoclasts containing large vacuoles have high acid-productive activities, and adhesive substrates such as type I collagen and vitronectin influence the formation of large vacuoles in cultured osteoclasts.

Acids↗
PubMed1995

Comparison of the entire nucleotide and deduced amino acid sequences of the attenuated hog cholera vaccine strain GPE- and the wild-type parental strain ALD.

We have determined the complete nucleotide sequences of a live attenuated hog cholera virus (HCV) and its progenitor strain. The viral RNA of each strain consisted of 12,298 nucleotides including untranslated regions of 373 and 228 bases at the 5' and 3' end, respectively. There was a single large open reading frame spanning 11,697 nucleotides which could encode a large protein of 3,899 amino acids with a calculated molecular weight of 438-kDa. We have found 225 nucleotide difference between the two strains, of which six were located in the untranslated region. Four-sixths of these differences resulted in amino acid substitutions.

Amino Acid Sequence↗
PubMed1995

Characterization of the hog cholera virus 5' terminus.

Hog cholera virus (HoCV) 5' terminus of the ALD and GPE(-) strains were analyzed by using rapid amplification of cDNA end method (5'RACE). An additional nine nucleotides were found at the 5' termini of genomic RNA in the ALD and GPE(-) strains of HoCV. These nine nucleotides were also conserved in BVDV and were suggested to form a hairpin structure at the 5' terminus by computer-assisted analysis. It seems possible that the secondary structure and/or the 5' terminus sequence has a significant role in the HoCV virus genome.

Animals↗
PubMed1995

Regional diastolic function in effort angina pectoris: assessment with biplane left ventriculography.

To investigate left ventricular (LV) regional diastolic function in effort angina pectoris (AP), we performed left ventriculography in 14 patients with AP and isolated left anterior descending artery disease and in 9 normal subjects (N). LV volume (V), regional area (S) [anterior, apex, and inferior], and the first derivative of V and S (dV/dt, dS/dt) were derived from analysis of the left ventriculogram. Normalized peak filling rate (nPFR) and peak atrial filling rate (nPAFR) were derived from dV/dt. The ratio of filling volume to stroke volume during rapid filling and atrial contraction were defined as rapid filling fraction (RFF) and atrial filling fraction (AFF). Similarly, peak area changing rate (PACR), peak area changing rate during atrial contraction (PACRac), rapid area changing fraction (RACF), and atrial area changing fraction (AACF) were derived from S and dS/dt. We also calculated the time constant of LV relaxation (T), and LV global and regional compliance during atrial contraction [(dV/VdP)ac, (dS/SdP)ac]. The LV global diastolic function (T increases, nPFR decreases) was impaired in the angina patients. LV regional diastolic function (nPACR decreases, RACF decreases) was also impaired in the affected region of the AP group. While their rapid filling was impaired, nPACRac was maintained and AACF was increased in the affected region. Furthermore, nPACR and RACF each showed a significant inverse correlation with AACF in the anterior region [r = -0.57 (P < 0.01), r = -0.92 (P < 0.001)]. In the affected region of the patients with AP, (dS/SdP)ac was increased, but not significantly. Thus, LV global and regional diastolic functions were simultaneously impaired in patients with isolated left anterior descending artery disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Pretreatment viral load and response to prolonged interferon-alpha course for chronic hepatitis C.

BACKGROUND/AIMS: We investigated the clinical benefit of long-term interferon therapy in chronic hepatitis C in relation to the pretreatment viral load and genotypes. METHODS: Chronic hepatitis C patients were randomly assigned to receive 28-week (n = 45) or 52-week (n = 43) courses of interferon-alpha. The responses were correlated with pretreatment viremic levels assessed by a branched DNA assay and genotypes. RESULTS: After the 28-week interferon-alpha course, sustained aminotransferase normalization showed correlation with a lower initial viral load. The normalization was achieved by 78% (7/9) of the low viremic (branched DNA-negative) patients, but only 22% (8/36) of the highly viremic (branched DNA-positive) patients (p < 0.01). Treatment with the 52-week interferon-alpha course increased the incidence of a sustained response in highly viremic patients and led to a decrease in relapse after therapy withdrawal (p < 0.05). Thus, 75% (6/8) of the low viremic patients and 49% (17/35) of the highly viremic patients showed a sustained response. The data further showed that frequent sustained responses in patients with genotypes III and IV were associated with a low initial viral load. CONCLUSIONS: These findings suggest that although the pretreatment viral load is an important virological factor for predicting responses to interferon in chronic hepatitis C, relapse in highly viremic patients may be prevented by long-term therapy.

Adult↗
PubMed1995

Involvement of P-type calcium channels in high potassium-elicited release of neurotransmitters from rat brain slices.

Several types of voltage-dependent calcium channels appear to occur in neurons, although coupling of the particular subtype of calcium channels to the release of neurotransmitter has not been clearly understood. We have examined the effects of subtype-specific inhibitors of the calcium channels on depolarization-induced release of endogenous neurotransmitters from brain slices. High potassium-induced release of glutamate and aspartate from hippocampal and striatal slices was almost completely inhibited by a P-type channel blocker, omega-agatoxin IVA. omega-Agatoxin IVA also completely inhibited the release of serotonin from the hippocampal slices with almost the same potency as in the case of glutamate, whereas the potency in blocking the release of serotonin and dopamine from striatal slices was lower than that from the hippocampal slices. Another calcium channel blocker, omega-agatoxin TK, that was recently found to block P-type channels with very similar selectivity and potency to omega-agatoxin IVA, also inhibited the release of amino acid transmitters and monoamines, though its potency was lower than that of omega-agatoxin IVA. An N-type channel blocker, omega-conotoxin GVIA, partially inhibited the neurotransmitter release, but an L-type channel blocker, nifedipine was ineffective. We propose that the activation of P-type calcium channels makes a major contribution to depolarization-elicited neurotransmitter release in the CNS and that multiple P-type channels sensitive to omega-agatoxin IVA and omega-agatoxin TK modulate the neurotransmitter release.

Analysis of Variance↗