Biomedical subjects

K Chayama

Publications and source records attributed to K Chayama.

At least 91 records · Page 5Linked to original sources

PubMed2000

MEKK2 gene disruption causes loss of cytokine production in response to IgE and c-Kit ligand stimulation of ES cell-derived mast cells.

Ligation of the high-affinity IgE receptor (FcepsilonRI) or of c-Kit stimulates cytokine production in mast cells. We show that MEK kinase 2 (MEKK2), a MAPK kinase kinase (MAP3K) that regulates the JNK and ERK5 pathways, is required for cytokine production in embryonic stem (ES) cell-derived mast cells (ESMC). Targeted disruption of the MEKK2 or MEKK1 gene was used to abolish expression of the respective kinases in ESMC. Transcription of specific cytokines in response to IgE or c-Kit ligand was markedly reduced in MEKK2(-/-) ESMC relative to wild-type ESMC. Cytokine production in MEKK1(-/-) ESMC was similar to that of wild-type ESMC, demonstrating the specificity of MEKK2 in signaling cytokine gene regulation. MEKK2(-/-) ESMC also lost receptor-mediated stimulation of JNK. In contrast, JNK activation in response to UV irradiation was normal, showing that MEKK2 is required for receptor signaling but not for cellular stress responses. MEKK2 is the first MAP3K shown to be required for mast cell tyrosine kinase receptor signaling controlling cytokine gene expression.

Animals↗

PubMed2000

Incidence of primary cholangiocellular carcinoma of the liver in japanese patients with hepatitis C virus-related cirrhosis.

BACKGROUND: Hepatitis C virus (HCV) infection is a major risk factor for the development of hepatocellular carcinoma. However, the risk factors for primary cholangiocellular carcinoma of the liver (PCC-L) have not been fully investigated. The authors determined the incidence of PCC-L in patients with HCV-related cirrhosis. METHODS: Between 1980 and 1997, the authors prospectively studied 600 consecutive patients for the appearance of PCC-L; these patients were positive for HCV and later developed cirrhosis. The follow-up period ranged from 0 to 18.5 years (median, 7.2 years). RESULTS: During the observation period, PCC-L developed in 14 patients (2.3%). Among these, 11 (1.8%) had cholangiocellular carcinomas and the other 3 (0.5%) had a combined type of hepatocellular and cholangiocellular carcinoma. Within the same period, hepatocellular carcinoma (HCC) developed in 206 patients (34.3%). The cumulative rates of newly diagnosed PCC-L were 1.6% at 5 years and 3.5% at 10 years, which was about 1000 times higher than the estimated incidence of PCC-L in the general population of Japan. PCC-L was treated by surgical resection in 3 patients who survived for > 3 years. However, the other 11 patients received palliative therapy or chemotherapy. The survival rates among PCC-L patients were 39.3%, 23. 6%, and 16.5% at the end of 1, 3, and 5 years, respectively, and were significantly lower than those of HCC (P = 0.0001). CONCLUSIONS: The results of this study show a relatively high incidence of PCC-L in patients with HCV-related cirrhosis, and also show that this type of liver cancer is associated with a relatively poor prognosis. These results indicate that HCV-related cirrhosis is a major risk factor for PCC-L in Japanese patients.

Adult↗

PubMed2000

Fluctuation patterns of HCV-RNA serum level in patients with chronic hepatitis C.

The serum level of hepatitis C virus (HCV)-RNA is clinically important as a predictor of the response to interferon (IFN) therapy in patients with chronic hepatitis C. If serum HCV-RNA levels fluctuate during follow-up, and IFN therapy is begun at the time of a low HCV-RNA level, the IFN therapy may be more effective. We evaluated the fluctuation of HCV-RNA serum levels for 2 years in 212 patients with chronic hepatitis C, untreated with IFN who had HCV genotype 1b and an HCV-RNA level of 10 Meq/ml or more at first consultation. The HCV-RNA level was measured monthly for 2 years with an HCV branched DNA probe assay (b DNA probe assay). We classified HCV-RNA patterns into three types by the ratio of maximum HCV-RNA level (a) to minimum HCV-RNA level (b). In pattern 1 (constant type, 151 patients; 71.2%) the a/ b ratio was 1-5. In pattern 2 (slight fluctuation type, 46 patients; 21.7%) the a/b ratio was 5-10. In pattern 3 (severe fluctuation type, 15 patients; 7.1%), the a/b ratio was 10 or more. Next, we evaluated the factors associated with the three patterns. Acute exacerbation of chronic hepatitis was regarded as an increase in serum alanine aminotransferase (ALT) level to more than 250 IU/l. The incidence of acute exacerbation for a 2-year follow-up was 13.9% (21/151) in pattern 1, 19.6% (9/46) in pattern 2, and 53.3% (8/15) in pattern 3. Multivariate analysis showed that acute exacerbation was the most important factor in the manifestation pattern 3. In conclusion, we found that: (1) about 70% of patients had a constant HCV-RNA levels for 2 years. (2) A few patients had severe fluctuation of serum HCV-RNA level after acute exacerbation of chronic hepatitis.

Adult↗

PubMed2000

Hepatic vascular side effects of styrene maleic acid neocarzinostatin in the treatment of hepatocellular carcinoma.

Styrene-maleic acid neocarzinostatin (SMANCS) sometimes causes hepatic vascular side effects, including arterial stricture, obstruction, and arterio-portal shunt. A total of 128 intra-arterial SMANCS injection treatments, performed for 89 patients with hepatocellular carcinoma, were analyzed to determine the relationship between angiographic findings and subsequent hepatic vascular injuries. After SMANCS therapy, hepatic arterial stricture or obstruction occurred in 5 patients (5/128; 3.9%), arterio-portal shunting in 12 (12/128; 9.4%), liver shrinkage in 4 (4/128; 3.1%), and cholangitis or biloma in 2 (2/128; 1.6%). Among 23 patients whose plain abdominal X-ray films just after SMANCS injection showed Lipiodol retention in the hepatic artery, 5 patients developed arterial obstruction, 10 developed arterio-portal shunt, and 2, cholangitis or biloma. Among 26 patients with Lipiodol retention in the portal vein, 4 developed hepatic lobe atrophy with aggravation of liver function. Among 3 patients with Lipiodol retention in both the hepatic artery and the portal vein, 1 developed arterio-portal shunt. In 76 treatments without excessive Lipiodol retention, only 1 of the patients developed arterio-portal shunt. Excessive retention of Lipiodol in hepatic vascular beds just after SMANCS therapy was significantly associated with future vascular side effects (22/52 vs 1/76; P < 0.0001). Lipiodol retention in arteries just after SMANCS injection was closely associated with subsequent arterial obstruction or arterio-portal shunt, and Lipiodol retention in the portal vein was related to subsequent hepatic lobe atrophy.

Adult↗

PubMed2000

Progressive and sufficient decrease of hepatitis B core antibody can predict the disappearance of hepatitis B virus DNA in Japanese patients with hepatitis B surface antigen clearance.

The aim of this study was to elucidate the relationships among serum levels of hepatitis B virus (HBV) DNA, periods after hepatitis B surface (HBs) antigen clearance, and the titer of hepatitis B core (HBc) antibody in 200-fold diluted serum. Twelve patients who had clearance of HBs antigen from serum were studied. Five patients had not received any treatment (group A), and seven had received prednisolone withdrawal therapy. The patients in groups A and B were followed up for 86 months and 108 months (median), respectively. Serum HBV was measured by the nested polymerase chain reaction method. In both groups, serum HBV tended to become gradually undetectable after HBs antigen clearance. The positive rate of HBV in the sera 5 years or more after HBs antigen clearance was significantly lower than that in the sera at less than 5 years, both in group A (P = 0.004) and group B (P = 0.010). In both groups, the titer of HBs tended to decline every year after HBs antigen clearance. HBV was still detectable in the sera of some patients for a long period of time after they showed seroconversion to HBs antibody. The results suggest that detection of HBV was difficult in sera with an HBc titer of 30% or lower and at more than 5 years after HBs antigen clearance in both groups. It is important to note that HBV DNA rarely exists in the serum, even when HBs antigen and HBc are both negative.

Adolescent↗

PubMed2000

Increased response rate to interferon therapy after a second course in hepatitis C patients who show relapse after the initial course.

Some patients with chronic hepatitis C become HCV-RNA seronegative during interferon (IFN) therapy. However, about one-half of these patients show a relapse, evident by high serum alanine aminotransferase (ALT) level. In some patients with biochemical relapse, the serum HCV-RNA level becomes low immediately after the ALT relapse. Here, we assessed the changes in serum HCV-RNA level in patients with ALT relapse after IFN therapy, and evaluated the efficacy of a second course of IFN, started at the recovery stage after ALT relapse. Two hundred and seventy-seven patients who showed HCV-RNA seronegativity by reverse transcription nested-polymerase chain reaction (RT nested-PCR) and normalization of ALT during the initial IFN therapy, and had positive HCV-RNA with ALT relapse (> 100 IU/l) within 3 months after completion of the initial IFN course were enrolled in this retrospective study. Two hundred and sixty patients were followed-up without further IFN retreatment after the ALT relapse (group 1), and 17 patients received another 6-month course of IFN after the ALT relapse (group 2). The median level of serum HCV-RNA, determined with a branched DNA probe assay (version 1; Chiron-Dai-ichi Kagaku Tokyo, Japan), in group 1 was 3.1 Meq/ml before IFN therapy, 1.3 Meq/ml at the time point of the ALT peak after the completion of IFN therapy, and 0.7 and 2.6 Meq/ml at 2-4 and 6-8 weeks after the ALT peak, respectively. The serum HCV-RNA level at 2-4 weeks after the ALT peak was lower than that before IFN therapy. The eradication rate of HCV-RNA (complete response; CR) in group 2 (47.1%; 8/17) was significantly higher than that in group 1 (1.5%; 4/260; P < 0.001). In conclusion, our data suggested that: (1) patients who showed biochemical relapse after initial IFN therapy had a significantly lower serum HCV-RNA level at recovery after ALT relapse compared with that before initial IFN therapy. (2) A high response rate was noted after a second course of IFN administered at the recovery stage of the ALT relapse, compared with patients without IFN retreatment.

Adult↗

PubMed2000

Splenectomy may improve the glomerulopathy of type II mixed cryoglobulinemia.

Many patients with type II mixed cryoglobulinemia have been shown to be infected with hapatitis C virus (HCV). Therefore, interferon-alfa has become the first choice of treatment for patients with HCV-associated cryoglobulinemia. However, the disease often relapses after the discontinuation of interferon therapy. The long-term effect of interferon therapy is controversial. Therefore, a more effective therapy needs to be developed. A 62-year-old Japanese woman was admitted to our hospital for the examination of abnormal liver function tests, severe edema, and purpura in her lower extremities. Glomerulopathy secondary to HCV-related cryoglobulinemia was suspected. Her serum creatinine was increased to 2.1 mg/dL. Interferon therapy was considered initially. However, because of pancytopenia caused by liver cirrhosis and splenomegaly, splenectomy was performed in February 1997, before the start of interferon therapy. Renal biopsy specimen taken at the time of the splenectomy showed typical cryoglobulinemic glomerulonephritis. Gradually, after surgery, the patient's thrombocytopenia and anemia improved, her proteinuria and hematuria were decreased, her cryocrit dropped from 15% to 5%, the Ccr increased from 21.1 mL/min to 48.8 mL/min, and the purpura in her lower extremities disappeared. A repeat renal biopsy performed in May 1998 showed marked histological improvement. Splenectomy is not widely accepted as a treatment for cryoglobulinemia. Our case suggests the possibility that the monoclonal-IgM component of the type II cryoglobulin may be formed in the spleen. In conclusion, splenectomy may be an effective therapy for cryoglobulinemia in patients with HCV-positive liver cirrhosis and pancytopenia secondary to splenomegaly.

Anemia↗

PubMed2000

Distinction between chronic hepatitis and liver cirrhosis in patients with hepatitis C virus infection. Practical discriminant function using common laboratory data.

In order to distinguish patients with cirrhosis from those with chronic hepatitis, multivariate discriminant analysis was performed using common laboratory data. A total of 205 consecutive patients were diagnosed by peritoneoscopy and biopsy as having chronic liver disease caused by hepatitis C virus (HCV), 168 with chronic hepatitis and 37 with cirrhosis. Twenty variables and their natural logarithmic transformation were employed in the multivariate analysis. After stepwise variable selection, the following function was finally obtained to discriminate the disease severity, z=0.120xgamma-globulin (%)+0.423xln (hyaluronate) (µg l(-1))-0.059xplatelet (x10(4) counts per mm(3))-0.364xsex (male, 1; female, 2)-3.953. Since the function contained an expression of logarithm and was slightly troublesome to apply, we prepared another discriminant function composed of usual figures without logarithmic transformation, z=0.124x(gamma-globulin (%))+0.001x(hyaluronate) (µg l(-1))-0.075x(platelet (x10(4) counts per mm(3)))-0.413xgender (male, 1; female, 2)-2.005. When a positive result is calculated in the latter equation, the diagnosis of the liver disease indicates cirrhosis, and negative result chronic hepatitis. Accuracy of the two discriminant functions was 90.3 and 91.2%, respectively. A concise linear discriminant function could successfully differentiate liver cirrhosis from chronic hepatitis with an accuracy of 91.2%.

Journal Article↗

PubMed2000

Association of amino acid sequence in the PKR-eIF2 phosphorylation homology domain and response to interferon therapy.

Hepatitis C virus (HCV) genotype 1b and high pretreatment virus load are well known predictive factors of poor response to interferon (IFN) therapy. In addition, a sparsity of amino acid substitutions in the interferon sensitivity determining region (ISDR) is also predictive of a poor response to IFN in patients with genotype 1b, although this issue is still controversial. Recently, a 12 amino acid domain in the E2 protein of HCV (PKR-eIF2 alpha phosphorylation homology domain [PePHD]) has been reported to bind with and block the virus replication inhibition ability of PKR, suggesting that the interaction of E2 and PKR may be one mechanism by which HCV circumvents the antiviral effect of IFN. To clarify the significance of amino-acid sequences in this domain in predicting the effect of IFN therapy, we analyzed 82 patients with genotype 1b. Eleven patients (13.4%) responded to treatment whereas the remaining 71 patients (86.6%) were nonresponders. Multivariate analysis showed that only HCV load and amino-acid substitutions in the ISDR were predictive of sustained response to IFN. Amino-acid substitutions in the PePHD were detected in only eight of 82 patients (9.8%), and did not correlate with the therapeutic effect of IFN. However, amino-acid-sequence analyses of quasispecies before and after 1 week of IFN therapy showed elimination of clones with substitutions in this domain. Our results suggest that amino-acid sequences of the PePHD domain may be related to viral resistance to IFN but do not predict the outcome of IFN therapy as amino-acid substitutions in this domain are rare.

Adult↗

PubMed2000

Interferon beta prevents recurrence of hepatocellular carcinoma after complete resection or ablation of the primary tumor-A prospective randomized study of hepatitis C virus-related liver cancer.

Because hepatocellular carcinoma often recurs after surgical resection or ethanol injection therapy, we conducted a prospective randomized controlled trial of interferon (IFN) in patients with chronic liver disease caused by hepatitis C virus (HCV). Twenty eligible patients with cirrhosis were randomized into two groups: 10 patients treated with 6 million units of natural IFN-beta twice a week for 36 months and 10 patients without IFN therapy. One patient within the treatment group discontinued interferon therapy after 19 months of treatment because of a mild degree of retinopathy. None of the patients in either group lost HCV-RNA until the end of the observation. Although 7 (70.0%) of 10 patients in the nontreatment group showed tumor recurrence, only 1 (10.0%) of 10 patients with IFN therapy developed tumor recurrence during a median observation period of 25.0 months. Cumulative recurrence rates of the treated and untreated groups were 0% and 62.5% at the end of the first year, and 0% and 100% at the second year, respectively (log-rank test, P =.0004). In conclusion, intermittent administration of IFN suppressed tumor recurrence after treatment with surgery or ethanol injection in patients with HCV-related chronic liver disease.

Aged↗

PubMed2000

Detection of hantaviral antibodies among patients with hepatitis of unknown etiology in Japan.

Hantaviral antibodies were detected in the sera from patients with hepatic disease of unknown etiology in Japan by several different serological diagnostic methods. A total of 105 sera from diseased patients which were negative to A-G hepatitis virus infections in the Tokyo area were tested. Among them, 3 out of 73 sera from patients with chronic hepatic disease were positive to hantaviral antibody by enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescent antibody assay (IFA) and Western blot analysis (WB). Neutralizing antibody titers of the 3 sera to Seoul virus (SEO) were 4 to 8 times higher than those to Hantaan virus (HTN). However, all of the 32 sera from patients with acute hepatitis were negative for hantaviral antibody. Among the 60 patients with chronic hepatitis in Hokkaido which were serologically negative to B and C hepatitis virus infection, one was positive for hantaviral antibody by ELISA and WB. In contrast, the sera from healthy adults in Japan, 550 from the Honshu and Kyushu regions, and 1,000 from the Hokkaido region, were negative for hantavirus antibody. These results show that hantaviral antibodies are more frequently detected in patients with hepatic disease than in healthy adults. However, the observation that no positive sera were detected from patients with acute hepatitis implies that hantavirus might not be directly related to hepatitis.

Acute Disease↗

PubMed2000

Relationship between five-year histological outcome and serial changes in serum alanine aminotransferase in patients with biochemical and virological relapse after interferon treatment for chronic hepatitis C.

OBJECTIVE: The aim of this study was to assess the correlation between serial changes in serum alanine aminotransferase (ALT) levels and histological outcome 5 years after treatment of patients with chronic hepatitis C with interferon (IFN). METHODS: We retrospectively evaluated 61 consecutive patients who underwent two liver biopsies, just before and 5 years after a 6-month course of IFN therapy, and who showed a relapse after therapy. The extent of liver fibrosis was estimated using a scale with seven grades. RESULTS: At the end of 6-month IFN therapy, 40 (65.6%) patients had normal serum ALT concentrations. However, 13 of the 40 patients relapsed within 6 months after IFN therapy. The average ALT during 5 years in 40 patients was less than or equal to 75 IU/l, while in the other 21 patients it was more than 75 IU/l. Among the 40 patients with a mean ALT less than 75 IU/l, 13 (33%) patients showed histological improvement, 26 (65%) showed no changes and only 1 patient (2%) showed worsening of liver fibrosis. On the other hand, among the 21 patients with a mean ALT of more than 75 IU/l, only 1 (5%) patient showed improvement, 8 (38%) showed no changes and 12 patients (57%) showed worsening of liver fibrosis. CONCLUSION: There is a significant relationship between 5-year histological outcome and serial changes in serum ALT in patients with biochemical and virological relapse after IFN treatment for chronic hepatitis C.

Adult↗

PubMed1999

Application of capillary electrophoresis to the analysis of inorganic ions in environmental samples.

A comprehensive review is presented of the state-of-the-art of capillary electrophoresis for application to the analysis of inorganic species, mainly ions, in environmental samples. This brief review covers the developments principally in sensitivity and matrix interference for the determination of inorganic ions in the following samples: drinking, mineral, surface, and ground waters, rainwater, snow, seawater, brine and waste waters, aerosol, and others. References published mainly from 1995 to 1997 were summarized in this review.

Aerosols↗

PubMed1999

Mitogen-activated protein kinase activation through Fc epsilon receptor I and stem cell factor receptor is differentially regulated by phosphatidylinositol 3-kinase and calcineurin in mouse bone marrow-derived mast cells.

Aggregation of high affinity FcR for IgE (Fc epsilon RI) on mast cells activates intracellular signal transduction pathways, including the activation of protein tyrosine kinases, phosphatidylinositol 3-kinase (PI3-kinase), and protein kinase C. Binding of stem cell factor (SCF) to its receptor (SCFR, c-Kit) on mast cells also induces increases in intrinsic tyrosine kinase activity and activation of PI3-kinase. Although ligation of both receptors induces Ras and Raf-1 activation, the downstream consequences of these early activation events are not well defined, except for the activation of extracellular signal-regulated kinases (ERK). Addition of Ag (OVA) to mouse bone marrow-derived mast cells (BMMC) sensitized with anti-OVA IgE triggers the activation of three members of the mitogen-activated protein (MAP) kinase family, c-Jun amino-terminal kinase (JNK), p38 MAP kinase (p38), and extracellular signal-regulated kinases. SCF similarly activates all three MAP kinases. Wortmannin, an inhibitor of PI3-kinase, inhibited both Fc epsilon RI- and SCFR-mediated JNK activation and partially inhibited Fc epsilon RI, but not SCFR-mediated p38 activation. Cyclosporin A inhibited Fc epsilon RI-mediated JNK and p38 activation, but did not affect the activation of these kinases when stimulated through the SCFR. Wortmannin and cyclosporin A inhibited Fc epsilon RI-mediated production of TNF-alpha and IL-4 in addition to serotonin release in BMMC. These results indicate that both PI3-kinase and calcineurin may contribute to the regulation of cytokine gene transcription and the degranulation response by modulating JNK activity in BMMC.

Amino Acid Sequence↗

PubMed1999

Fluctuations of hepatitis C virus load are not related to amino acid substitutions in hypervariable region 1 and interferon sensitivity determining region.

Hepatitis C virus (HCV) load is one of the most important predictive factors of response to interferon treatment. However, little is known about the mode and determinants of viremia. The mode of viremia was investigated in 78 patients with chronic HCV genotype 1b infection during 1-2 years follow up. Virus load, determined by a branched chain DNA amplification assay, was stable in 73 of 78 (93.6%) patients, whereas 5 (6.4%) showed marked fluctuation (from undetectable level to more than 10 Meq/ml) in viral titer. To study the mechanisms mediating fluctuations in viral titer, amino acid sequences of two regions were examined; hypervariable region (HVR) 1 and the interferon sensitivity determining region (ISDR). Multiple amino acid substitutions were observed in HVR 1 but no relationship was evident between substitutions and virus titers. In contrast, no amino acid substitutions were observed in the ISDR in any patients with stable virus titer during a follow-up period of 12-24 months (7-24 samples) or in one patient who was observed for 15 years. Interestingly, multiple amino acid substitutions in the ISDR appeared in only two of the five patients with marked titer fluctuation, when the virus decreased markedly. Alanine aminotransferase levels in these five patients correlated with viral load. The data suggest that amino acid substitutions in HVR1 and ISDR are not essential for changes in viral titer. Possible mechanisms of fluctuations of viral titer and amino acid substitutions in the ISDR accompanying marked reductions in viral load are discussed.

Alanine Transaminase↗

PubMed1999

Effect of interferon therapy on hepatocellular carcinogenesis in patients with chronic hepatitis type C: A long-term observation study of 1,643 patients using statistical bias correction with proportional hazard analysis.

The activity of interferon (IFN) is not elucidated from the viewpoint of cancer prevention in chronic hepatitis C patients en masse. The hepatocellular carcinogenesis rate was analyzed statistically in 1,643 patients with chronic hepatitis C: 1,191 patients with IFN therapy and 452 without IFN therapy. Hepatocellular carcinogenesis rates in the treated and untreated groups were 2.1% and 4.8% at the end of the 5th year, and 7.6% and 12.4% at the 10th year, respectively (P =.0036). Multivariate analysis showed that IFN slightly decreased the risk of carcinogenesis by 33%, compared with that of untreated patients (P =. 14), adjusting for the confounding effects of age, fibrotic stage, gender, and gamma-glutamyl transpeptidase (GGTP) value. Among 1,191 patients with IFN, 461 patients attained persistent loss of hepatitis C virus (HCV) RNA, and the other 145 patients retained normal alanine transaminase (ALT) values without loss of HCV RNA. The hazard of carcinogenesis in these 606 patients with persistent normal ALT with or without HCV-RNA clearance was significantly lower than that of untreated patients (hazard ratio: 0.32; P =.012) and that of the abnormal aminotransferase group. Among patients with chronic hepatitis C, IFN significantly decreased the hepatocellular carcinogenesis rate in those patients with normal or persistent low ALT values.

Adolescent↗

PubMed1999

Predictive value of different hepatitis C serological assays in the treatment of chronic hepatitis C with interferon alpha.

In order to predict the complete response rate of natural interferon-alpha (nIFN-alpha) treatment in patients with chronic active hepatitis C, we examined the predictive value (PV) of different hepatitis C serological assays. We performed first generation (ver.1) and second generation (ver.2) hepatitis C virus (HCV) branched DNA-probe assays (bDNA-probe), HCV core protein assay (core protein), HCV Amplicor Monitor assay (amplicor monitor), and HCV competitive polymerase chain reaction (competitive PCR) assay, using serum samples collected immediately before initiation of treatment. For each marker, we studied, in patients stratified by serological group (Gr), which predictive value (PV) of the HCV titers showed association with the therapeutic effect. In 59 Gr 1 patients, complete response to nIFN-alpha treatment was predicted from the following PVs for each marker: 0.5 Meq/ml or less (odds ratio 11.7: P = 0.0010) with ver.1, 1.0 Meq/ml or less (odds ratio 5.3; P = 0.0119) with ver.2 of the bDNA-probe, 50 pg/ml or less (odds ratio 10.3; P = 0.0062) with core protein, 200 x 10(3) copy/ml or less (odds ratio 7.8; P = 0.0031) with amplicor monitor, and 10(4) copy/ml or less (odds ratio 6.2; p = 0.8395) with competitive PCR. In 27 Gr 2 patients, the PV for each marker indicating complete response was as follows: There was no relationship between PV and therapeutic effect with ver.1 of the bDNA-probe, while the PVs for the other markers were 0.2 Meq/ml or less (odds ratio 2.2; P = 0.3788) with ver.2, 20 pg/ml or less (odds ratio 5.6; P = 0.0597) with core protein, 400 x 10(3) copy/ml or less (odds ratio 4.0; P = 0.2965) with amplicor monitor, and 10(5.5) copy/ml or less (odds ratio 29.2; P = 0.0096) with competitive PCR. Our findings showed that complete response to the treatment may be predicted using the appropriate PV for each marker.

Adult↗

PubMed1999

Enzyme-linked immunosorbent assay to detect hepatitis C virus serological groups 1 to 6.

By conventional serological grouping methods, it is possible to determine hepatitis C virus (HCV) serological groups for genotypes 1a, and 1b, and genotypes 2a, and 2b, but not for other genotypes, i.e., 3a, 3b, 4a, 5a, and 6a. In this study, we attempted to serologically group HCV with the Murex HCV serotyping 1 to 6 assay (Murex Diagnostics, Kent, UK), using an enzyme-linked immunosorbent assay (ELISA) based on genotype-specific peptides from the NS4 region. The subjects of this study were 365 patients infected with HCV of genotype 1a, 1b, 2a, 2b, 3a, or 3b. The sensitivity of the assay was 100% in patients with genotype 1a, 82.7% in those with 1b, 68.5% in those with 2a, 84.2% in those with 2b, 50.0% in those with 3a, and 76.5% in those with genotype 3b. The overall sensitivity was 78.4%. The specificity of the assay was 100% in the subjects with genotype 1a, 98.8% in those with 1b, 98.4% in those with 2a, 96.9% in those with 2b, 100% in those with 3a, and 100% in those with genotype 3b. The overall specificity was 98.6%. The concordance of the assay was 100% in subjects with genotype la, 81.7% in those with 1b, 67.4% in those with 2a, 81.6% in those with 2b, 50.0% in those with 3a, and 76.5% in those with genotype 3b. The overall concordance was 77.5%. We believe it would be better to serotype with the Murex HCV serotyping 1 to 6 assay, if other than serological group (Gr) 1 or Gr 2 is suspected in particular ethnic groups or in subjects with an indeterminate result with the Immucheck HCV Gr assay (Kokusai, Kobe, Japan), assuming that the genotype must be other than 1a, 1b, 2a, or 2b.

Enzyme-Linked Immunosorbent Assay↗