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Biomedical subjects

H Kumada

Publications and source records attributed to H Kumada.

At least 109 records · Page 6Linked to original sources

Hepatitis C virus subtype 3b infection in a hospital in Japan: epidemiological study.

To elucidate the epidemiology of infection with hepatitis C virus (HCV) subtype 3b (a rare subtype thought to have originated in Southeast Asia) in Japan, we examined the genotypic subtype in 1397 patients with HCV-related chronic liver diseases. Of 1330 patients with identified HCV RNA genotypes. 960 had subtype 1b, 243 had subtype 2a, 97 had subtype 2b, 14 (1.1%) had subtype 3b, and 16 had other types of HCV or mixed subtypes. The age, gender, and severity of liver disease in patients with HCV subtype 3b did not differ from these features in patients with other subtypes. Eleven of the 14 patients with the 3b subtype had once worked at Company A in Tokyo, Japan. Multivariate logistic analysis showed that working history at that company was independently associated with the incidence of the subtype; the risk ratio was 207.2 (P < 0.0001). All 11 patients from Company A had received medical services, between 1953 and 1981, at Clinic C, which undertook medical care of the company staff. All 11 patients had received repeated intramuscular or intravenous injections for treatment of various diseases or for preventive vaccination for contagious diseases. The rare HCV subtype 3b, appeared to have been transmitted among the employees of a company through the performance of certain medical practices.

Adult↗

A pilot study of corticosteroid priming for lymphoblastoid interferon alfa in patients with chronic hepatitis C.

Interferon treatment reduces the serum level of hepatitis C virus (HCV) and improves inflammatory activity, but relapse is frequently observed. In an attempt to develop a new therapeutic strategy that may reduce relapse and cure the disease, we evaluated the effect of corticosteroid priming on lymphoblastoid interferon alfa in an open randomized clinical trial. The level of HCV RNA increased significantly during corticosteroid priming (from 5.60 [median] to 21.0 x 10(5) Eq/mL; P = .0004) but decreased to the pretreatment level 4 weeks after cessation of corticosteroid (7.0 x 10(5) Eq/mL; P = .07). Sustained normalization of alanine transaminase (ALT) level and virus clearance, confirmed by negative results for HCV RNA using reverse-transcription nested polymerase chain reaction (PCR), were observed over a period of 6 months in 8 of 19 (42.1%) corticosteroid-primed patients, compared with 6 of 19 patients (31.6%) treated with interferon only. A "rebound" of ALT after the withdrawal of corticosteroid was observed in only 2 of 19 patients primed with corticosteroid, but both showed sustained responses. Multivariate analysis for factors predictive of the sustained response indicated that HCV titers measured immediately before interferon therapy and HCV genotype were statistically significant (P = .006 and P = .025, respectively). Our results indicated that corticosteroid priming has a marginal benefit over treatment with interferon alone and that large-scale clinical trials are necessary to determine whether interferon with corticosteroid priming is more effective than interferon alone.

Adult↗

Diagnosis of hepatocellular carcinoma by concanavalin A affinity electrophoresis of serum alpha-fetoprotein.

BACKGROUND: Concanavalin A (Con A) affinity electrophoresis of serum alpha-fetoprotein (AFP) can distinguish hepatocellular carcinoma (HCC) from other malignancies when the serum AFP concentration is elevated. However, Con A has not been able to distinguish HCC from benign chronic liver disease such as cirrhosis or chronic hepatitis. METHODS: The Con A affinity electrophoresis of serum AFP was analyzed in patients with a serum AFP concentration greater than 50 ng/mL by antibody affinity electrophoresis and Western blotting in an attempt to distinguish hepatocellular carcinoma from benign chronic liver disease. Before the assay, the serum AFP concentrations were adjusted between 100 ng/ml and 300 ng/ml by concentrating or diluting the samples. RESULTS: Of 180 patients with HCC, 44 (24%) had a single band and 91 (51%), 35 (19%), and 10 (6%) had 2, 3, and 4 bands, respectively. All 35 patients with chronic hepatitis had a single band. All but 1 of 72 patients with cirrhosis had a single band. Multiple AFP bands on Con A affinity electrophoresis appear to be diagnostic of HCC. This method has a sensitivity of 76%, a specificity of 99%, a positive predictive value of 99%, and a negative predictive value of 71% for detecting HCC. The number of AFP bands correlated with serum AFP concentration and tumor size in patients with HCC. CONCLUSIONS: This assay is useful for distinguishing HCC from benign chronic liver diseases.

Adult↗

Molecular analysis of intraspousal transmission of hepatitis C virus.

BACKGROUND/AIMS: Although intraspousal transmission of hepatitis C virus (HCV) has been speculated, there is no direct evidence. METHODS: To investigate whether transmission of HCV occurs by this route, 295 spouses of persons diagnosed with HCV were studied. Of these, 25 (8.8%) tested positive for anti-HCV. Next, the HCV genotype was determined by polymerase chain reaction using a mixed primer set, and cDNA was obtained in 17 of the 25 couples for comparison of the genotypes. RESULTS: Of these 17, 14 (82.4%) spouses were shown to be infected with HCV of the same genotype. Analysis of the nucleotide sequences of putative E1 gene of eight couples having the same HCV genotype revealed that five couples had remarkably high nucleotide sequence homologies (> 97%), whereas samples obtained from the remaining three couples showed relatively low homology (91-92%). Nucleotide sequence homologies were significantly higher between spouses than between non-spouse pairs of isolates. Phylogenetic analysis using the neighbor-joining method suggests that infection in these five couples probably occurred after marriage. Furthermore, none of the five couples had shared other possible transmission routes such as intravenous drug use, dental treatment or acupuncture. CONCLUSION: These data strongly suggest the occurrence of intraspousal transmission of HCV.

Adult↗

A prospective randomized evaluation of a compound of tegafur and uracil as an adjuvant chemotherapy for hepatocellular carcinoma treated with transcatheter arterial chemoembolization.

A prospective randomized trial was conducted to evaluate the efficacy of long-term oral administration of low-dose tegafur combined with uracil as an adjuvant chemotherapy, following transcatheter arterial embolization (TAE) in 40 patients with hepatocellular carcinoma (HCC). Forty eligible patients were randomized into two groups: 20 with TAE plus UFT (a compound of tegafur 200 mg and uracil 448 mg per day) and 20 with TAE alone. A good necrosis rate or decrease in size of more than 70% of the original tumor mass was attained in 10 by TAE plus UFT arm and in 12 by TAE arm alone. As for the "responded" patients, there was no significant difference in the time from tumor response to tumor regrowth between the two groups. The appearance rate of ascites and/or encephalopathy in patients with chemotherapy was slightly higher than that in control patients. The median survival time was 22.7 months for TAE plus UFT arm and 28.2 months for TAE arm alone. There was no significant difference in the cumulative survival curves. In conclusion, these results indicated no substantial benefit for this chemotherapy regimen, as an adjuvant therapy for patients with HCC during repeated TAE.

Adult↗

Quantitative analysis of the gastric ulcer healing process using video endoscopic pseudocolor imaging systems.

We developed an endoscopic pseudocolor imaging system in cooperation with Olympus Optical. This system was used for color processing of ulcer images observed over time using an electronic endoscope with measurement capability. The patients were receiving ranitidine (group R) or lansoprazole (group L) for ulcer treatment. By this method it is possible to differentiate between the types of healing tissue by their color. The total area of regions with a high degree of redness in the pseudocolor processed images was measured with a digitizer, and the hemoglobin-rich area (HA) in the regenerated epithelium was determined for the two groups. In the second week of drug administration, the HA was significantly larger in group L, at 170.70 +/- 64.70 mm2, than in group R, at 22.61 +/- 5.72 mm2 (p < 0.05). The hemoglobin rate was significantly higher in group L, at 0.90 +/- 0.02 (p < 0.01) at 2 weeks and 0.94 +/- 0.02 (p < 0.05) at 4 weeks, than in group R, at 0.72 +/- 0.06 and 0.86 +/- 0.05 at 2 and 4 weeks, respectively.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Inflammatory cytokine gene expression in human periodontal ligament fibroblasts stimulated with bacterial lipopolysaccharides.

The effects of Porphyromonas gingivalis lipopolysaccharide (P-LPS) and Escherichia coli lipopolysaccharide (E-LPS) on the gene expression and production of inflammatory cytokines of human periodontal ligament fibroblasts (HPLF) were examined by a Northern (RNA blot) assay and enzyme-linked immunosorbent assay, respectively. mRNAs for interleukin-6 (IL-6), IL-8, and transforming growth factor beta (TGF-beta) were detected in HPLF cells, but IL-1 alpha, IL-1 beta, tumor necrosis factor alpha, transforming growth factor alpha, and granulocyte-macrophage colony-stimulating factor were not detected by reverse transcription-PCR. The expression of TGF-beta mRNA was not influenced by either LPS. P-LPS (1 to 10 micrograms/ml) and E-LPS (100 micrograms/ml) markedly stimulated the expression of IL-6 and IL-8 mRNAs compared with the control. The synthesis of IL-6 and IL-8 was also stimulated by 10 and 100 micrograms of both LPSs per ml, but IL-8 synthesis was not stimulated with E-LPS at 1 microgram/ml. Secretion of IL-6 and IL-8 into the culture medium was detected at 6 and 3 h, respectively, after exposure to P-LPS (10 micrograms/ml). These findings suggested that P. gingivalis leads to periodontal tissue destruction and alveolar bone resorption through IL-6 and IL-8 released from HPLF cells stimulated with its LPS.

Alkaline Phosphatase↗

Structural study on the free lipid A isolated from lipopolysaccharide of Porphyromonas gingivalis.

The chemical structure of lipid A isolated from Porphyromonas gingivalis lipopolysaccharide was elucidated by compositional analysis, mass spectrometry, and nuclear magnetic resonance spectroscopy. The hydrophilic backbone of free lipid A was found to consisted of beta(1,6)-linked D-glucosamine disaccharide 1-phosphate. (R)-3-Hydroxy-15-methylhexadecanoic acid and (R)-3-hydroxyhexadecanoic acid are attached at positions 2 and 3 of the reducing terminal residue, respectively, and positions 2' and 3' of the nonreducing terminal unit are acylated with (R)-3-O-(hexadecanoyl)-15-methylhexadecanoic acid and (R)-3-hydroxy-13-methyltetradecanoic acid, respectively. The hydroxyl group at position 4' is partially replaced by another phosphate group, and the hydroxyl groups at positions 4 and 6' are unsubstituted. Considerable heterogeneity in the fatty acid chain length and the degree of acylation and phosphorylation was detected by liquid secondary ion-mass spectrometry (LSI-MS). A significant pseudomolecular ion of lipid A at m/z 1,769.6 [M-H]- corresponding to a diphosphorylated GlcN backbone bearing five acyl groups described above was detected in the negative mode of LSI-MS. Predominant ions, however, were observed at m/z 1,434.9 [M-H]- and m/z 1,449.0 [M-H]-, each representing monophosphoryl lipid A lacking (R)-3-hydroxyhexadecanoic and (R)-3-hydroxy-13-methyltetradecanoic acids, respectively. The presence of mono- and diphosphorylated lipid A species was also confirmed by LSI-MS of de-O-acylated lipid A (m/z 955.3 and 1,035.2, respectively).

Carbohydrate Sequence↗

Serial hemodynamic measurements in well-differentiated hepatocellular carcinomas.

We performed serial hemodynamics in 15 patients with 21 well-differentiated hepatocellular carcinomas. The total length of the observation period ranged from 129 to 678 days (median, 368). We investigated both arterial and portal blood flow at intervals of at least 4 months. Arterial blood flow was measured with carbon dioxide-enhanced ultrasonography (US), and portal blood flow was measured with computed tomographic arterial portography (CTAP). None of the tumors were hypervascular on the initial study; however, by the final study nine nodules (42.9%) had become homogeneously hypervascular, two (9.5%) had become partially hypervascular, and the others did not change. Of 10 nodules without portal blood supply on any study, 8 became hypervascular by the final study. Of 11 nodules with portal blood supply on the initial study, a follow-up study showed no change in portal flow in 6 and the loss of portal flow in 5. Four of these five became hypervascular, with a documented loss of portal flow before the increase in arterial flow. The doubling time of tumors with a homogeneous increase in arterial blood flow ranged from 89 to 333 days (median, 172), whereas the doubling time of other tumors ranged from 227 to 607 days (median, 392). Thus, growth rate and vascularity in well-differentiated hepatocellular carcinoma are closely correlated. When the well-differentiated hepatocellular carcinoma has portal blood flow and is not hypervascular, it grows slowly. On the other hand, when it loses portal blood flow and becomes hypervascular, it grows rapidly.

Adult↗

Serum des-gamma-carboxyprothrombin concentration determined by the avidin-biotin complex method in small hepatocellular carcinomas.

BACKGROUND: Des-gamma-carboxyprothrombin (DCP) is a useful tumor marker for hepatocellular carcinoma (HCC). The present method for measurement of DCP concentration, however, does not have adequate sensitivity to detect small HCCs. METHODS: The serum DCP concentration was investigated by the avidin-biotin complex (ABC) method in patients with an HCC smaller than 20 mm in maximum dimension. A serum DCP concentration greater than 4.0 arbitrary units per liter using the ABC method was considered abnormal. RESULTS: Of 115 patients with small HCC, 45 (39.1%) had an abnormal DCP concentration. Ten of 141 patients with chronic hepatitis (7.1%), 18 of 115 (15.7%) with cirrhosis, and 0 of 30 normal control patients had abnormal DCP concentrations. This method yielded a sensitivity of 39.1%, a specificity of 89.1%, a positive predictive value of 61.6%, and a negative predictive value of 76.5% for detection of small HCC. The detectability of HCC increased to 56.5% when alpha-fetoprotein (AFP) was was measured (> 40 ng/ml). Abnormal DCP concentrations were seen in 8 of 34 (23.5%), 24 of 42 (57.1%), and 5 of 7 (71.4%) patients with Edmondson's Grade I, II, and III tumors, respectively. There was a significant relationship between DCP concentrations and histologic grade (P = 0.0017), but there was no association between DCP concentration and other patient characteristics. Elevation of serum AFP concentrations in patients with hepatitis B surface antigen positivity, however, was more frequent than that in patients who were antihepatitis C virus (HCV) positive. Therefore, the measurement of serum DCP concentrations may be more useful than that of serum AFP concentrations in patients with anti-HCV positivity. CONCLUSIONS: The measurement of serum DCP concentrations by the ABC method is a useful diagnostic tool for the monitoring of small HCC.

Adult↗

Interferon retreatment of nonresponders with HCV-RNA-positive chronic hepatitis C.

Interferon has been shown to be an effective treatment for some patients with chronic hepatitis C. In this study, the value of retreatment of nonresponders to interferon was investigated. Thirty-eight patients with hepatitis C virus (HCV)-RNA-positive chronic hepatitis C who had been treated with beta-interferon but still showed an alanine aminotransferase (ALT) level > 50 KU upon completion of therapy were retreated with alpha-interferon. Eight patients (21.1%) had normalization of ALT levels for at least 6 months after the completion of retreatment. The factors related to normalization of ALT levels after interferon retreatment were studied. Of 16 patients with transient HCV-RNA negativity 1 month after the initial interferon therapy, 7 (43.8%) had a complete response, with normalization of ALT levels and undetectable HCV-RNA, more than 6 months after interferon retreatment. On the other hand, of the 22 patients with HCV-RNA activity 1 month after the initial interferon therapy, only 1 (4.5%) had a complete response. Multivariate analysis, using a multiple logistic model, indicated that a complete response to readministration of interferon was most strongly correlated to transient negative conversion for HCV-RNA after the initial course of treatment.

Alanine Transaminase↗

Prevalence of HCV genotype among patients with chronic liver diseases in the Tokyo metropolitan area.

We examined 613 Toranomon Hospital patients with HCV RNA-positive chronic liver disease to elucidate the viral genotype in the Tokyo metropolitan area. An epidemiological and clinical study was conducted in the 565 patients whose HCV genotype could be determined. The HCV genotypes found were type II, in 414 patients (67.5%); type III, in 103 (16.8%); type IV, in 37 (6.0%); type V, in 4 (0.7%); mixed genotype II and III, in 5 (0.8%); and mixed genotype II and IV, in 2 (0.3%). The HCV genotype could not be determined in 48 patients. Type II was most prevalent. The HCV genotype I was not found at all. There were no significant differences between genotypes in relation to sex, age, history of blood transfusion, or the progression of the disease. It was uncommon to find a history of blood transfusion in the patients with mixed genotypes; however, a high incidence of hepatic disorders was noted among the family members of these patients. Ninety-two percent of the patients with HCV genotype II tested positive for C100-3, while 70.9% of those with type III, and 43.2% of those with type IV tested positive for this antibody. HCV genotype II was most prevalent, and the positivity rate for anti C100-3 in patients with this HCV genotype was significantly higher (P < 0.00001) than that in patients with the other genotypes.

Adolescent↗