Biomedical subjects

K Katayama

Publications and source records attributed to K Katayama.

At least 253 records · Page 14Linked to original sources

PubMed1994

Complete 5' noncoding region is necessary for the efficient internal initiation of hepatitis C virus RNA.

The mechanism of translational initiation by the 5' noncoding region (5'NCR) of hepatitis C virus (HCV) genome was analyzed. Using an in vitro translation system with artificial RNA containing a modified 5' NCR of HCV under the various KCl conditions, nucleotides (nt.) 62 to 341 of the HCV 5'NCR were not functional as an internal ribosome entry site (IRES). However, the full-length 5'NCR (nt. 1 to 341) produced an efficient internal initiation. To identify the essential region of the HCV-IRES, various mutants were produced in which stem-loops, predicted by secondary structure analysis of the HCV 5'NCR, were deleted. These constructs were analyzed by in vitro translation. Comparison of translation efficiency among these mutants suggested that the alpha- or both alpha- and beta-branches of domain II are essential for efficient translation. Moreover, the formation of correct secondary structure of IRES seems to be stabilized by the presence of domain I in 5'NCR. Furthermore, the uncapped 5'NCR of HCV promotes translation more efficiently than capped truncated 5'NCR constructs. Our results strongly suggested that complete 5'NCR containing all stem-loop structures is necessary for initiation by HCV-IRES.

Base Sequence↗

PubMed1994

Serial quantitative analysis of serum hepatitis C virus RNA level in patients with acute and chronic hepatitis C.

To examine changes in the serum level of hepatitis C virus RNA in acute and chronic phases of hepatitis C virus infection, we tested serial serum samples of six patients with acute hepatitis C (posttransfusion: three; sporadic: three) and 11 patients with chronic hepatitis C using a competitive reverse transcription and polymerase chain reaction assay. The internal standard consisted of known amounts of synthetic mutated RNA. No patient with acute hepatitis showed resolution during the follow-up period (24-57 weeks). In posttransfusion cases, titers of hepatitis C virus RNA (log10[hepatitis C virus RNA copies/ml serum]) rose to a high level (7.5-9.5) in the early phase of infection (4-12 weeks after the transfusions) in association with the first serum alanine aminotransferase peaks. Titers of hepatitis C virus RNA then decreased, while serum alanine aminotransferase levels fluctuated with multiple peaks. In sporadic cases, titers of hepatitis C virus RNA had already reached a high level (7.0-7.5) at the first alanine aminotransferase peaks 2-3 weeks after the clinical onset. In chronic hepatitis C virus infection, titers of hepatitis C virus RNA remained high for follow-up periods of 6-12 years in patients with chronic active hepatitis. These results indicate that the replication of hepatitis C virus rose to a high level in the early phase of infection and that a high replicative level of hepatitis C virus might be related with progression of liver disease in the chronic phase of infection.

Acute Disease↗

PubMed1994

IgG and IgM core antibodies and viral replication in hepatitis C virus carriers.

We studied IgG and IgM antibodies to hepatitis C virus core protein (anti-HCVcore) in relation to serum virus RNA levels in 71 hepatitis C virus carriers. Viremic levels ranged from 10(4)-10(9) copies/ml and were high in 34 chronic active hepatitis patients compared with 17 asymptomatic carriers and 20 cases of chronic persistent hepatitis (p < 0.01). IgG anti-HCVcore was found in 67/71 (94%), but four asymptomatic carriers with low levels of viremia (10(4)-10(5.5) copies/ml) tested negative. IgM anti-HCVcore was found in patients with high levels of viremia (10(8)-10(9) copies/ml), and one (6%) asymptomatic carrier and nine (26%) chronic active hepatitis patients tested positive. In chronic hepatitis patients, viremic levels were significantly higher in cases positive for IgM anti-HCVcore than in negative ones (p < 0.01). However, no correlation was found between the occurrence of IgM anti-HCVcore and serum aminotransferase levels or the histologic activity index. These findings suggest that although IgG anti-HCVcore is sensitive, low viremic patients can escape this screening, and that the IgM anti-HCVcore is induced in association with high levels of virus replication.

Adult↗

PubMed1994

Kinetic analysis of neuromuscular blockade. I. Relationship between twitch depression and stimulation frequency after d-tubocurarine administration.

The degree of twitch depression induced by nondepolarizing neuromuscular blocking drugs is known to be dependent on the stimulation frequency employed. Train-of-four (TOF) stimulations with different frequencies (0.67, 1.33 and 2.0 Hz) were delivered to a sciatic nerve of a rat and series of four twitch heights of a tibialis anterior muscle were measured after d-tubocurarine (d-TC) administration. With a decrease of stimulus interval, twitch heights were intensely depressed. We hypothesized that the oservations are due to the changes of released amount of neuromuscular transmitter, acetylcholine, dependent on stimulus interval, and a pharmacokinetic/pharmacodynamic model based on the hypothesis was proposed. The model allowed simultaneous fitting of the twitch height depression after d-TC administration. It also could give a rationale to the fact that TOF stimulation at 2.0 Hz is a more sensitive monitoring method of neuromuscular function than single twitch stimulation (0.1-0.2 Hz).

Acetylcholine↗

PubMed1994

Kinetic analysis of neuromuscular blockade. II. Train-of-four fade induced by d-tubocurarine and alpha-bungarotoxin.

The degree of train-of-four (TOF) fade, i.e., the reduction of the fourth to the first twitch height in a train, induced by d-tubocurarine (d-TC) and alpha-bungarotoxin (alpha-BX) was investigated. The fade induced by d-TC was pronounced in comparison with that by alpha-BX, and the difference was analyzed using a kinetic model. Based on the assumptions: (1) Acetylcholine (ACh) binds to the nicotinic receptor and evokes twitch response. (2) The amount of released ACh is dependent on stimulus interval. (3) d-TC interacts competitively with the receptor. (4) alpha-BX interacts irreversibly with the receptor. It was suggested that the fade by d-TC and alpha-BX can be explained by the difference of the receptor occupancy by ACh which was caused by different interaction mechanisms of the two muscle relaxants with receptors.

Acetylcholine↗

PubMed1994

In vitro-in vivo correlation of percutaneous absorption: isosorbide dinitrate and morphine hydrochloride.

The potential of an in vitro skin preparation as a model for predicting in vivo percutaneous absorption of drugs was examined. In vitro and in vivo skin permeation data for two model drugs with different lipophilicity, isosorbide dinitrate (ISDN) and morphine hydrochloride (MPH), were compared using pharmacokinetic techniques. In vitro permeation data published previously were analyzed based on a single pathway model, and permeation parameters were obtained. The disposition parameters were estimated from the plasma concentration profiles after i.v. administration. The plasma concentrations after topical application were then simulated using the obtained permeation and disposition parameters, and the values were compared with the corresponding observed ones. Although the simulated plasma concentration curves were not greatly different from those observed, there were some differences in the time course-pattern. Causes for these in vitro-in vivo differences were discussed.

Animals↗

PubMed1994

Effects of hepatitis B virus antigens on interferon-gamma production of peripheral blood mononuclear cells from hepatitis B virus carriers and healthy individuals.

BACKGROUND: Although the precise mechanisms of persistent infection by hepatitis B virus are not yet known, several lines of studies suggest that hepatitis B e antigen in sera might modulate the immune response of the host. The aim of this study was to clarify the effects of hepatitis B virus antigen on cytokine production of lymphocytes. METHODS: We studied the effects of recombinant hepatitis B core antigen and surface antigen on interferon-gamma production of phytohemagglutinin-stimulated peripheral blood mononuclear cells from hepatitis B virus carriers and healthy individuals. Hepatitis B core antigen used in this study shared the antigenic site responsible for hepatitis B core and e antigen. RESULTS: Although pre-incubation of peripheral blood mononuclear cells with hepatitis B core/e antigen followed by stimulation with phytohemagglutinin significantly reduced the production of interferon-gamma, pre-incubation with hepatitis B surface antigen did not affect them. CONCLUSIONS: These results indicate that hepatitis B core/e antigen has the ability to inhibit interferon-gamma production of lectin-stimulated peripheral blood mononuclear cells in vitro, suggesting that secretion of hepatitis B e antigen into sera might be how hepatitis B virus escapes the immuno-surveillance system of the host.

Adult↗

PubMed1994

Immunohistochemical detection of Fas antigen in liver tissue of patients with chronic hepatitis C.

Apoptosis is a type of cell death that occurs in acute or chronic hepatitis. It has been suggested to be mediated through Fas antigen. To evaluate the role of apoptosis on liver injury of chronic hepatitis C, we studied the expressions of Fas antigen and hepatitis C virus antigen (core antigen) immunohistochemically. Forty liver biopsy samples from patients with type C chronic liver disease were immunostained for Fas antigen and hepatitis C virus antigen. Expression of Fas antigen was found mainly in the cytoplasm of hepatocytes, and these positive cells were found particularly among infiltrating lymphocytes at the advancing edges of "piecemeal necrosis." The histological activity index showed inflammation of both portal and periportal areas to be more severe in the Fas antigen-positive samples than in the Fas antigen-negative ones (p < 0.05 and p < 0.001, respectively). Furthermore, semiquantitative analysis revealed more expression of Fas antigen in the liver tissues with active inflammation than in those without it (p < 0.01). The prevalence of Fas antigen expression in the hepatitis C virus antigen-positive group was higher than that in the hepatitis C virus antigen-negative group (p < 0.05). Our findings suggest that Fas antigen expression (apoptosis) plays an important role in inflammation in the hepatitis C virus-infected liver, particularly in the active inflammation of chronic hepatitis C.

Adolescent↗

PubMed1994

Increased serum hepatitis C virus RNA levels among alcoholic patients with chronic hepatitis C.

Hepatitis viruses and alcohol are major causes of liver disease. This study was aimed at investigating the effect of alcohol intake on the replication of hepatitis C virus and the efficacy of interferon therapy. Fifty-three patients who were histologically proved to have chronic hepatitis C were tested. Of these, 16 were diagnosed as habitual drinkers whose cumulative total consumption of alcohol was more than 100 kg or who had consumed at least 60 gm of ethanol daily for at least 5 yr. The quantities of hepatitis C virus RNA in serum were measured with a competitive assay that combined reverse transcription and polymerase chain reaction. The subjects received a 26-wk course of interferon-alpha therapy. There were no significant differences in age and ALT levels between habitual drinkers and nonhabitual drinkers. The titer of viral RNA (logarithmic transformed copy numbers per milliliter of serum) of habitual drinkers (8.5 +/- 0.5) was higher than that of nonhabitual drinkers (7.7 +/- 0.8) (p < 0.01). Neopterin levels in serum, a marker for the activation of cell-mediated immunity, were lower for habitual drinkers (5.7 +/- 1.5 pmol/ml) than for nonhabitual drinkers (8.1 +/- 5.0 pmol/ml) (p < 0.01). Eleven of the nonhabitual drinkers (30%) were long-term responders whose alanine aminotransferase levels remained within normal range during the 24 wk after interferon therapy, whereas only one (6%) of the habitual drinkers was a long-term responder (p = 0.06). These findings suggest that alcohol intake increases hepatitis C virus RNA levels in serum--at least in part--impairment of cellular immunity, and modulates the efficacy of interferon therapy.

Adult↗

PubMed1994

Distinctive functional properties of the neuronal BII (class E) calcium channel.

Functional diversity of voltage-dependent calcium channels (VDCC) is primarily due to the existence of six distinct genes of the channel-forming subunit alpha 1, which can be further classified into the L-type and neuronal non-L-type subfamilies. We have examined functional properties of the calcium channel BII expressed from the cloned cDNA, in Xenopus oocytes, and compared the results with the other members of the non-L-type subfamily, the BI and BIII channels. The BII channel is a high voltage-activated calcium channel pharmacologically features by its unique sensitivity to the inorganic blocker Ni2. The decaying component of the BII current shows high sensitivity to Ni2+ similar to that of the low voltage-activated channels and the R-type channel in cerebellar granule cells, whereas the sustained component is relatively resistant to Ni2+ as are the other high voltage-activated calcium channels. Dihydropyridines, omega-CgTx-GVIA, and omega-Aga-IVA, which have been used to discriminate L-, N-, and P-types, do not affect the BII current. The mode of modulation of the BII channel by auxiliary subunits is strikingly different from that observed in the L-type channels. Both activation and inactivation rates of the BII current are decelerated by coexpression of the beta subunit, and this effect is cancelled by further coexpression of the alpha 2 subunit. In situ tissue distribution studies indicate a higher level of BII mRNA expression in the hippocamus compared to other brain regions, revealing important difference in the relative abundance of BI, BII, and BIII channels in brain tissues. Overall, the results suggest that the BII channel forms a novel functional category of VDCC that is different from T-, L-, N-, and P-type.

Animals↗

PubMed1994

Expression of the c-met protooncogene in human hepatocellular carcinoma.

The c-met protooncogene is a growth factor receptor with tyrosine kinase activity. Recently the hepatocyte growth factor was identified as the ligand for this receptor. Because the hepatocyte growth factor is a most potent mitogen in hepatocytes, possible involvement of c-met expression in hepatocarcinogenesis is suspected. In this study, we examined c-met expression in 23 hepatocellular carcinoma cases by means of Northern-blot analysis and an immunohistochemical study. Northern-blot analysis revealed c-met mRNA expression in the tumors of 6 of 19 patients (31.6%); in the immunohistochemical study, c-met protein was detected in 16 of 23 patients (69.6%). With both methods, c-met was found to be overexpressed in hepatocellular carcinoma compared with the surrounding normal liver. Comprehensive analysis showed that c-met protein expression was correlated with poor-to-moderate differentiation of cancer cells (p < 0.05). Tumor proliferative activity of hepatocellular carcinoma was evaluated by means of Ki-67 labeling index. All cases with increased tumor proliferative activity showed c-met protein expression, although the elevation of proliferative activity in the c-met-positive group was not statistically significant. These data suggest that the overexpression of c-met plays an important role in the development of hepatocellular carcinoma.

Adult↗

PubMed1994

Successful peritransplant therapy in children with active hepatosplenic candidiasis.

Two pediatric leukemic patients with hepatosplenic candidiasis during multidrug antileukemic chemotherapy successfully underwent bone marrow transplantation (BMT) after aggressive antifungal chemotherapy employing fluconazole and amphotericin B with or without splenectomy. One patient received allogeneic marrow graft and the other received an autologous graft. One patient has been disease-free for more than 21 months after BMT without any recurrence of Candida infection. The other patient showed tentative reactivation of hepatic lesions just after BMT by CT scanning, but these lesions disappeared again by continuous administration of the antifungal agents. The second patient died of leukemia relapse without recurrence of fungal infection. Our cases indicate the possibility of successful BMT once a fungal infection is well controlled by antifungal chemotherapy and surgical resection.

Amphotericin B↗

PubMed1994

Serum hepatitis C virus RNA levels and liver injury in volunteer blood donors.

OBJECTIVES: Liver histology in volunteer blood donors positive for serum hepatitis C virus RNA was investigated in relation to hepatitis C virus viremia levels. METHODS: Twenty-one volunteer blood donors positive for serum hepatitis C virus RNA by polymerase chain reaction were monitored for at least 1 yr by monthly routine liver function tests and underwent liver biopsy. Liver histology findings were correlated with hepatitis C virus viremia levels assessed by a quantitative branched DNA assay. RESULTS: Liver histology showed the features of chronic hepatitis in 20 (95%) patients. Only one of the seven patients with persistently normal aminotransferase levels during follow-up had normal liver histology, and the others had chronic hepatitis. Sera obtained the same day of the liver biopsy were shown to contain hepatitis C virus RNA of 10(5.7)-10(7.6) equivalent/ml (median 10(6.7)). The total histological activity index score (median 2, range 0-15) and the scores of portal inflammation (median 1, range 0-3), lobular inflammation (median 1, range 0-4) and piecemeal necrosis (median 0, range 0-5) correlated with viremia levels (r = 0.64, p < 0.01; r = 0.60, p < 0.01; r = 0.48, p < 0.05; and r = 0.49, p < 0.05, respectively). CONCLUSIONS: These findings suggest that chronic hepatitis is frequently caused by hepatitis C virus infection irrespective of the serum aminotransferase levels, and high level hepatitis C virus replication is a contributory cause for liver injury in volunteer blood donor populations.

Alanine Transaminase↗

PubMed1994

[Juvenile muscular atrophy of the bilateral upper limbs associated with peculiar transformation of the dural tube induced by neck flexion].

We described an 18-year-old man with slowly progressive muscular atrophy in upper limbs on both sides. Regarding muscular atrophy, sensory disturbances in both palms were disproportionally very mild. Electrophysiological study suggested involvement of anterior horn restricted to the cervical cord, which resembled juvenile muscular atrophy of unilateral upper limb (Hirayama's disease). This patient, however, was unique in that the atrophy was bilateral and wider distribution of a lesion from C5 to T1 segments unlike Hirayama's disease. Neuroradiological findings in neutral position of the neck showed no abnormalities, but in flexion there was a characteristic change of the cervical cord and the posterior wall of dural canal. On myelography in flexion, anterior-posterior diameter of the middle and lower cervical dural canal decreased presumably due to an anterior shift of the dorsal part of dura mater. CT-myelography in neck flexion showed characteristic folding of the dorsal part of dura mater whose median portion seemed to intrude anteriorly and consequently concave the spinal cord. Anterior shift of the dorsal part of dura mater is known to occur in Hirayama's disease, but the folding is a peculiar finding in this patient. After laminectomy and laminoplasty of vertebrae from C3 to C7, his symptoms improved a little. On palpating the dorsal surface of dural canal, its median portion was harder than the lateral portion. A small fraction of the dura mater which was removed from hard median portion was thick, but showed no histological abnormalities. In normal functioning anatomy the dural canal is lengthened more posteriorly than anteriorly with neck flexion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1994

[Early phase II study of MST-16 (sobuzoxane) for breast cancer].

An early phase II study of MST-16 for breast cancer was conducted with the participation of 9 hospitals. MST-16 was administered at three doses; 1) 1,600 mg/body for 5 consecutive days repeating every 4 weeks, 2) 1,200 mg/body for 10-14 consecutive days every 5 weeks, and 3) 1,200 mg/body daily for at least 4 weeks. A total of 28 patients were entered, and 27 cases were eligible. Twenty-five cases were evaluated for efficacy and 27 cases for safety. One patient achieved complete response, 2 patients attained partial response, and the response rate thus obtained was 12.0%. Major side effects observed were myelosuppression represented by leukopenia (69.2%) followed by gastrointestinal disorders. These symptoms, however, were reversible by the cessation of administration.

Adult↗

PubMed1993

A novel peptide from funnel web spider venom, omega-Aga-TK, selectively blocks, P-type calcium channels.

In the course of purification of omega-Aga-IVA, a specific P-type calcium channel blocker, from the venom of Agelenopsis aperta we discovered a novel peptide. This peptide, named omega-agatoxin Tsukuba (omega-Aga-TK), also blocked P-type channels and was twelve times more abundant in the venom than omega-Aga-IVA. omega-Aga-TK was purified to homogeneity by a two-step reverse-phase HPLC procedure. Its amino acid sequence is 71% identical to that of omega-Aga-IVA. omega-Aga-TK has a negatively charged N-terminus, whereas omega-Aga-IVA has a positively charged one. Electrophysiological data indicate that omega-Aga-TK is a potent and selective inhibitor of P-type channels.

Agatoxins↗

PubMed1993

Combination of arachidonic acid and guanosine 5'-O-(3-thiotriphosphate) induce translocation of rac p21s to membrane and activation of NADPH oxidase in a cell-free system.

The superoxide-generating NADPH oxidase system in phagocytes consists of membrane-associated cytochrome b558 and three cytosolic components named p67-phox, p47-phox, and rac p21s. In a cell-free system consisting of membrane and cytosol, the oxidase can be activated with guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) and an unsaturated fatty acid such as arachidonic acid (AA). Incubation of cytosol and membrane with AA alone caused clear translocation of p47-phox and p67-phox to the membrane, but only slight translocation of rac p21s. GTP gamma S alone did not significantly induce the translocation of rac p21s. However, GTP gamma S in combination with AA markedly augmented rac p21s translocation to the membrane. The translocation of rac p21s is not induced by GDP or GDP beta S. These results indicate that the GTP-bound active form of rac p21s is the entity that is translocated to the membrane by the action of AA.

Amino Acid Sequence↗

PubMed1993

A pentapeptide from type I procollagen promotes extracellular matrix production.

The NH2 and COOH propieces of fibril-forming collagens are cleaved off extracellularly and have been implicated in feedback regulation of their own synthesis. Recently, we showed that a subfragment of the carboxyl-terminal propeptide of type I collagen (residues 197-241) dramatically augments extracellular matrix production in subconfluent fibroblasts. This stimulation of type I collagen, type III collagen, and fibronectin production occurred in a dose- and time-dependent manner with no effect on total protein synthesis or on the ratio of secreted proteins to cell-associated proteins (Katayama, K., Seyer, J.M., Raghow, R., and Kang, A.H. (1991) Biochemistry 30, 7097-7104). In the present report, we have extensively dissected this subfragment of the propeptide and found that the pentapeptide Lys-Thr-Thr-Lys-Ser (residues 212-216) is the minimum sequence necessary for potent stimulation of collagen and fibronectin production in a variety of mesenchymal cells. We postulate that the extracellular matrix production in fibroblasts may be subject to either positive or negative feedback regulation depending on the repertoire of specific proteases during postinflammatory tissue regeneration and fibrosis.

Amino Acid Sequence↗