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Biomedical subjects

M Mizokami

Publications and source records attributed to M Mizokami.

At least 127 records · Page 7Linked to original sources

Perforated acute appendicitis in a patient with AIDS/HIV infection: report of a case.

We report herein the case of a 40-year-old man with AIDS who was admitted to hospital with severe abdominal pain, fever, and chills. He underwent an emergency laparotomy which revealed a perforated appendix with suppurative peritonitis. An appendectomy with peritoneal drainage was carried out, but the postoperative course was complicated by fever without leukocytosis; however, he gradually improved following treatment with intravenous antibiotics, granulocyte colony-stimulating factor (G-CSF) and immunoglobulins, and made a complete recovery. His postoperative course demonstrates the effectiveness of this treatment regimen for patients with AIDS complicated by infection without an increase in the white blood cell count (WBC).

AIDS-Related Opportunistic Infections↗

Significance of hepatic expression of hepatitis C viral antigens in chronic hepatitis C.

To determine the significance of hepatic expression of hepatitis C viral (HCV) antigens, HCV core and NS4 antigens were detected by immunohistochemistry in 46 patients with chronic HCV infection. Serum HCV RNA was quantitated by branched DNA assay in 41 and HCV genotype determined in 30 patients. HCV core and NS4 antigens were detected exclusively in the cytoplasm of hepatocytes in 83% and 61% of patients, respectively. There was no correlation between the expression of HCV antigens and clinical, biochemical, histological parameters and HCV genotype. Hepatic expression of HCV antigens was positively associated with serum HCV-RNA levels (P < 0.02). At the end of interferon-alpha (IFN) therapy, expression of HCV antigens remained either unchanged or decreased in 11/12 patients studied (undetectable in all four patients who had complete and sustained response). We conclude that hepatic expression of HCV core and NS4 antigens parallels serum HCV-RNA levels and IFN therapy reduces hepatic expression of these viral antigens.

Female↗

Genotype distribution in Nagoya and new genotype (genotype 3a) in Japanese patients with hepatitis C virus.

We evaluated hepatitis C virus (HCV) genotype distribution among Japanese patients in the city of Nagoya and the possible existence of any other genotype not determined by Okamoto's method. Eighty-five of 93 (91.4%) anti-HCV-positive patients had detectable HCV RNA. The genotype of the HCV isolate was determined in 84 of 85 (98.8%) of these HCV RNA-positive patients by Okamoto's method but determination was not possible in one (1.2%). Genotype 1b was detected in 58 of the 85 patients (68.2%), genotype 2a in 20 (23.5%), genotype 2b in 3 (3.5%), and genotype 1b + 2a in 3 (3.5%). In the remaining 1 patient in whom the genotype could not be determined, we determined the nucleotide sequence of the core region in HCV RNA extracted from this patient and evaluated it by molecular evolutionary analysis. This HCV isolate was then classified as genotype 3a. These results suggest that genotype 3a is rare among Japanese patients with HCV; thus, when classifying Japanese isolates, we should take more care because genotype 3a is not determined by current typing systems.

Amino Acid Sequence↗

Classification of hepatitis C virus into major types and subtypes based on molecular evolutionary analysis.

Molecular evolutionary analysis was applied to determine the number of hepatitis C virus (HCV) types and subtypes based on all the HCV nucleotide sequences available from the DNA data banks (DDBJ, GenBank (NCBI), EMBL) and the literature. There was an excellent concordance among the types and subtypes assigned based on different HCV genomic regions. Only one HCV isolate was assigned to different HCV types based on the 5' non-coding (NC) and envelope 1 (E1) regions. The 5' NC region was well conserved and could be used to assign only types and not subtypes. From the sequence data available there were 13 subtypes based on the core region and 14 subtypes based on the E1 and non-structural protein 5 (NS5) regions.

Biological Evolution↗

Simple fluorescent enzyme immunoassay for detection and quantification of hepatitis C viremia.

The viral load of hepatitis C virus, as reflected by hepatitis C virus viremia, has been shown to have important clinical implications. In this study the hepatitis C virus core protein level in serum was evaluated for the detection and quantification of hepatitis C virus viremia. Hepatitis C virus core protein in serum was detected using a simple and sensitive fluorescent enzyme immunoassay. Hepatitis C virus core protein was quantitated in 100 healthy subjects, 258 patients with hepatitis C virus infection and 108 patients with non-hepatitis-C-virus-related chronic liver diseases. HCV-RNA was determined using the branched DNA (bDNA) assay and reverse-transcription polymerase chain reaction. The detection limit of this fluorescent enzyme immunoassay was found between 10(4) - 10(5) copies/ml HCV-RNA equivalent. There was a good correlation between the core protein and bDNA assay results (p <0.01). Hepatitis C virus core protein was detected in 81% of patients with hepatitis C virus infection (acute hepatitis 4/5, chronic hepatitis 85/104, cirrhosis 64/73 and hepatocellular carcinoma 56/76) but in none of the healthy subjects and patients with non-hepatitis C virus chronic liver diseases. The amount of hepatitis C virus core protein in patients with hepatitis-C-virus-related hepatocellular carcinoma was lower compared to chronic hepatitis and cirrhosis (p <0.05). All 26 patients treated with interferon-alpha showed parallel changes between HCV-RNA and core protein levels. This fluorescent enzyme immunoassay is simple and quick (assay time <3 h) with sensitivity at least matching the bDNA assay. Similar levels of hepatitis C virus core protein were detected in patients with chronic hepatitis and cirrhosis, but patients with hepatocellular carcinoma tended to have a lower level of hepatitis C virus core protein.

DNA, Viral↗

HCV RNA monitoring for tailored regimens of interferon therapy in hepatitis C.

Sustained non-viraemia is prerequisite for a virological cure of hepatitis C virus (HCV) disease. We monitored serum HCV RNA in our patients during interferon therapy and for 6 months of follow-up. The rate of sustained responders (RNA-negative at the end of follow-up) differed significantly by whether or not RNA became sero-negative within 24 weeks of the initiation of therapy (71% vs 7%); and also by whether or not the RNA-seronegativity lasted for 12 weeks during therapy (88% vs 11%). Thus, by monitoring viraemia in individual patients, we can tailor the duration of therapy and minimize waste of interferon.

Follow-Up Studies↗

Relationships between serotypes and genotypes of hepatitis B virus: genetic classification of HBV by use of surface genes.

Hepatitis B virus (HBV) surface antigen (HBsAg), which is encoded by the HBV S gene, is conventionally classified into 4 serological subtypes, adw, adr, ayw and ayr. To determine the relationship between the HBsAg seroreactivity and the nucleotide sequence diversity of the HBV S gene, the nucleotide sequences of S genes for HBV isolates reported so far were aligned with each other. The numbers of nucleotide substitutions were then estimated by the 6-parameter method, and a phylogenetic tree was constructed by the unweighted paired grouping method with arithmetic mean (UPGMA) and the neighboring-joining (NJ) method. The phylogenetic trees constructed showed that all isolates were grouped into 4 genotypes (gyw, gdw-1, gdw-2, and gdr). More importantly, the genotypes did not necessarily correspond to the conventional serotypes. In particular, serotype 'adw' can be any of genotypes gdw-1, gdw-2, or gdr. Thus, genotyping by S genes gives more accurate information about genetic variation of HBV.

Amino Acid Sequence↗

Application of six hepatitis C virus genotyping systems to sera from chronic hepatitis C patients in the United States.

Serum samples from 139 US patients with chronic hepatitis C virus (HCV) infection were studied using six different genotyping systems, including both molecular and serologic methods, to determine the applicability of these approaches and the prevalence of various HCV subtypes. The concordance of genotyping results based on the various systems (except for core polymerase chain reaction genotyping) was good (93.5%). Subtypes 1a and 1b were prevalent (37.4%). Subtypes 2a (2.2%), 2b (8.6%), and 3a (5.8%) were less common. HCV genotypes could not be determined in 3.4%-16.5% of samples depending on the method used. HCV type 2 was associated with greater histologic activity but lower serum HCV RNA levels (P < .05), whereas type 3 was associated with lower serum alanine aminotransferase levels (P < .05). These data demonstrate a high concordance between HCV genotyping systems and provide a foundation for comparison of genotyping data between studies using different systems. HCV types 1a and 1b are both prevalent in the United States.

Adult↗

Hepatitis C virus genotypes 1 and 2 respond to interferon-alpha with different virologic kinetics.

Responses of patients infected with chronic hepatitis C virus (HCV) to interferon-alpha (IFN-alpha) treatment were studied. HCV genotypes were determined by molecular and serologic techniques. Levels of HCV viremia were determined by quantitative reverse transcription-polymerase chain reaction. Infection with HCV genotype 2 or low pretreatment HCV viremia levels in subjects infected with genotype 1 were associated with favorable (complete and sustained) responses (CR-SR; P < .001) to IFN-alpha treatment. HCV viremia levels in genotype 2 infection were significantly lower (P < .05) than in genotype 1 infection. The reduction rates of serum HCV RNA levels were four times higher in patients with genotype 2 infection than in those infected with genotype 1. The proportion of patients with CR-SR who experienced virologic relapse after completion of IFN-alpha treatment was higher for those infected with genotype 1. The proportion of patients with CR-SR and genotype 1 infection increased linearly in accordance with increases in single or total IFN-alpha dose.

Adult↗

Frequent detection of hepatitis C virus subtype 3a (HCV-3a) isolates in Thailand by PCR using subtype-specific primers.

By means of a polymerase chain reaction (PCR) method using subtype-specific primers for hepatitis C virus (HCV) subtypes 1a, 1b, 2a, 2b and 3a, the prevalence of each subtype among HCV isolates in Chiang Mai, Thailand, was determined. HCV-3a appeared to be the most common subtype in blood donors, and was also frequently found in patients with liver disease. HCV-1b, but not HCV-2a or -2b, was also commonly found in this area, while a considerable percentage of the total HCV isolates still remained unclassifiable by the above methods. Serotype analysis of the HCV isolates using C14-1 and C14-2 recombinant peptides revealed that HCV-3a was likely to carry an antigenic determinant(s) different from those of the major types 1 (HCV-1a and -1b) and 2 (HCV-2a and -2b).

Adult↗

Variations of hepatitis C virus NS5B sequence (nucleotides 8261-8566) do not correlate with response to interferon-alpha therapy.

Hepatitis C virus (HCV) is an RNA virus with the NS5B gene encoding an RNA-dependent RNA polymerase. Interferon-alpha (IFN-alpha) is effective against HCV and its effect is believed to be related to its antiviral activity. To determine whether sequence variations of the HCV NS5B region correlate with response to IFN therapy, pretreatment serum samples from 40 patients with chronic HCV infection who were subsequently treated with IFN (> or = 3 MU thrice weekly for 24 weeks) and had well-characterized biochemical responses were studied. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to generate an approximately 365-bp fragment from which nucleotide sequence and genotypes were determined. By comparing the nucleotide sequences and the encoded amino acid sequences of samples from each group, no response group-specific nucleotide or encoded amino acid substitution was identified. Most of the substitutions identified were synonymous (usually by changes at the third position of the codon). These data suggest that these substitutions were selective rather than spontaneous events. Of the few non-synonymous substitutions identified, none was correlated with subsequent response to IFN, either within or across genotypes.

Adult↗

Clearance of serum hepatitis C virus RNA after interferon therapy in relation to virus genotype.

The effect of recombinant interferon-alfa on serum HCV RNA levels in Japanese patients with chronic hepatitis C was investigated. At 24 weeks of treatment, 41 (32.5%) of 126 patients lost HCV RNA from serum, and aminotransferases were normalized in 31 (75.6%) of these 41 cases. HCV genotypes were categorized into four types (Type I, II, III, IV); the frequencies among the patients were: Type I: 0%, Type II: 70.6%, Type III: 20.6%, and Type IV: 6.3%. At the end of the 24-week treatment, HCV RNA levels were remarkably decreased in Type III patients and became undetectable in 18 (69.2%) of 26. In contrast, only 18 (20.2%) of 89 patients with Type II and two of eight with Type IV lost HCV RNA from sera. The relation between HCV genotype (Type III) and response to IFN therapy was also confirmed using a logistic regression model. HCV genotype seems to be an important factor in determining the response to IFN in patients with chronic hepatitis C.

Alanine Transaminase↗

Clinical evaluation of intramuscular administration of natural interferon-gamma in the treatment of chronic hepatitis B.

Natural interferon-gamma at a dose of 0.5 x 10(6) or 1 x 10(6) IU daily was intramuscularly administered daily for 4 weeks to 15 patients with chronic hepatitis B. The efficacy and safety of the treatment were evaluated for 24 weeks following the completion of the 4-week treatment period. Persistent disappearance of HBeAg was observed in 5 of 15 patients. Serum hepatitis B virus (HBV)-related DNA polymerase disappeared in 5 of 13 patients at the end of interferon therapy. On the other hand, serum ALT and beta 2-microglobulin levels showed a significant increase during the interferon therapy period. The side effects were completely reversible. These findings suggest that interferon-gamma has an antiviral effect in patients with chronic hepatitis B and that the main mechanism of the therapeutic effect may be associated with the elimination of HBV-infected hepatocytes due to the immunopotentiating effect of the substance.

Adult↗