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Biomedical subjects

H Kumada

Publications and source records attributed to H Kumada.

At least 127 records · Page 7Linked to original sources
PubMed1994

A detection method for point mutation in the precore region of human hepatitis B virus (HBV)-DNA using mutation-site-specific assay.

In the natural progression of acute active hepatitis and chronic active hepatitis in human hepatitis B virus (HBV)-infected patients, inactive hepatitis develops by seroconversion, which can be explained by the disappearance of HBe antigen. However, it has been found that in some patients with hepatitis, alanine aminotransferase levels undergo fluctuation even though their serum is negative for HBe antigen. In these patients, HBV-DNA has been detected in the serum and the HBV-DNA so detected has been considered a cause of worsening liver function. Most HBV-DNA detected in these cases has a point mutation from G to A at the 83rd base in the precore region. As a result of this point mutation, HBV is unable to produce HBe antigen. We have devised a sensitive polymerase chain reaction (PCR) method, a mutation-site-specific assay, for the detection of point mutations at the 83rd base in the precore region using a specific mutation-trapped oligonucleotide primer for the mutant HBV genome.

Base Sequence↗
PubMed1994

Imaging diagnosis of small hepatocellular carcinoma.

To elucidate the detectability of small hepatocellular carcinoma by various imaging modalities, we performed digital subtraction angiography, computed tomographic arterioportography and carbon dioxide-enhanced ultrasonography. Of 76 patients with a small hepatocellular carcinoma of 2 cm or less in maximum diameter, 61 underwent digital subtraction angiography, computed tomographic arterioportography and enhanced ultrasonography at the same time. Concerning the 61 patients undergoing all the procedures, the characteristics of hepatocellular carcinoma were found in 57.4% (35 of 61) by digital subtraction angiography, 75.4% (46 of 61) by computed tomographic arterioportography and 72.1% (44 of 61) by enhanced ultrasonography. Among them, four hepatocellular carcinomas were detected only by enhanced ultrasonography, three were diagnosed only by computed tomographic arterioportography and two were diagnosed by both of them. Except for six hemangioma nodules that were easily diagnosed only with angiography, four of 55 benign hepatic nodules (7.3%) showed false-positive findings suggestive of hepatocellular carcinoma with either computed tomographic arterioportography or enhanced ultrasonography. In conclusion, computed tomographic arterioportography and enhanced ultrasonography could complementarily detect a small hepatocellular carcinoma more sensitively than digital subtraction angiography.

Adult↗
PubMed1994

Nucleotide sequence of hepatitis C virus (type 3b) isolated from a Japanese patient with chronic hepatitis C.

The genomic sequences of many hepatitis C virus (HCV) isolates have been reported and a variety of virus genotypes have been classified based on homology in the conserved regions. We have previously identified five distinct genotypes (1a, 1b, 2a, 2b and 3b) in Japanese patients with chronic HCV infection by comparing the sequences of the NS5 region. The complete nucleotide sequence for five genotypes (1a, 1b, 1c, 2a and 2b) have already been reported and we report here the complete nucleotide sequence of genotype 3b. The isolate (HCV Tr) was 9439 nucleotides long, excluding the poly(U) tract at its 3' end, and encodes a single long open reading frame of 3023 amino acids. Total nucleotide sequence homologies were 68.4 to 68.7%, 68.3 to 69.0%, 67.2%, 65.8% and 65.6% compared with type 1a, 1b, 1c, 2a and 2b genomes, respectively. The amino acid sequences of these five genotypes were highly homologous in the core, NS3 and NS5B regions, but the E2/NS1 region, which contains hypervariable regions 1 and 2, and the NS5A region were poorly conserved. Although it was possible to detect antibody against the relatively homologous core and NS3 regions by ELISA, the presence of divergent protein structures must be taken into account in the development of a vaccine.

Amino Acid Sequence↗
PubMed1994

Small hepatocellular carcinoma: evaluation of portal blood flow with CT during arterial portography performed with balloon occlusion of the hepatic artery.

PURPOSE: To evaluate portal blood flow in small hepatocellular carcinomas (HCCs) by means of computed tomography during arterial portography (CTAP) and CTAP with hepatic arterial obstruction (CTP-HAO) achieved by means of balloon occlusion. MATERIALS AND METHODS: Thirteen patients with small HCC (< 20 mm in diameter) underwent CTAP, CTP-HAO, carbon dioxide-enhanced ultrasound (CEUS), and digital subtraction angiography (DSA). The imaging findings were correlated with histologic features. RESULTS: The first group of patients (n = 3) had tumors with portal blood flow at both CTAP and CTP-HAO and no hypervascularity at CEUS. The second group (n = 3) had tumors with portal blood flow at CTP-HAO but not at CTAP and hypervascularity at CEUS only. The third group (n = 7) had tumors without portal blood flow at CTAP or CTP-HAO and hypervascularity at DSA and CEUS. The first and second groups had well-differentiated HCCs; six of seven patients in the third group had moderately differentiated HCCs. CONCLUSION: Lack of portal blood flow was reversible in well-differentiated HCCs but irreversible in the other tumors.

Carcinoma, Hepatocellular↗
PubMed1994

The effect of root conditioning with minocycline HCl in removing endotoxin from the roots of periodontally-involved teeth.

Noting the acid-conditioning effect of minocycline on the root surface, we investigated the ability of minocycline to remove endotoxin on untreated, diseased cementum in vitro. Root surface specimens affected by periodontal disease were immersed in minocycline solution (10 mg/ml, 50 micrograms/ml, and 5 micrograms/ml) for 10 minutes, 1 day, 3 days, and 7 days, and endotoxin eluted was determined by the limulus amoebocyte lysate (LAL) assay. Specimens serving as controls were treated by immersion in pyrogen-free water, agitation, polishing, or exposure to citric acid (pH 1.0) for 3 minutes. When the period of immersion was the same, the root treatment with minocycline (10 mg/ml) yielded a significantly higher rate of neutralization of endotoxin than that with a 5 micrograms/ml or 50 micrograms/ml solution. However, the detoxifying effect of this method was less adequate than that of polishing or treatment with citric acid solution. There was variability in the effects of polishing among the teeth tested. To obtain the expected effect of the root treatment with minocycline solution; i.e., removal of the endotoxin, the combining of minocycline with a mechanical root preparation, such as polishing or root planing, seems to be effective.

Analysis of Variance↗
PubMed1994

[Examination in clinical course of HCV in interferon treatment].

We treated 812 patients who had chronic hepatitis C with interferon (IFN) and studied the effects of interferon. We defined complete response as normalization of amino-transferase more than 6 months after termination of IFN. Complete response by means of IFN therapy is dependent to some factors, that is HCV-genotype, quantity of HCV-RNA, histology. Cases of HCV genotype III or IV, CH2A, less than 10(5) copy/ml of HCV-RNA are effective in treatment of IFN. On the other hand, cases of HCV genotype II, CH2B, more than 10(6) copy/ml of HCV-RNA are effective in treatment of IFN.

Genotype↗
PubMed1994

[The diagnosis of hepatocellular carcinoma determined by pattern of AFP bands separated by Con A affinity electrophoresis].

We analyzed the Con A affinity of serum AFP in patients with a serum AFP concentration greater than 50ng/ml by antibody affinity electrophoresis and Western blotting to distinguish hepatocellular carcinoma (HCC) from benign chronic liver diseases (CLD). Of 164 patients with HCC, 48 (29.3%) had a single band, while 116 (70.7%) had multiple bands. All but three of 65 patients with cirrhosis had a single band. All but one of 32 patients with chronic hepatitis had a single band. We concluded that multiple AFP bands are diagnosis of HCC. This method is a useful assay for distinguishing HCC from CLD.

Adult↗
PubMed1994

[Long-term prognosis of liver cirrhosis].

In order to elucidate the long-term prognosis of liver cirrhosis, we analyzed a total of 795 consecutive patients with viral or alcoholic cirrhosis prospectively. During the observation period (median, 5.8 yr), hepatocellular carcinoma (HCC) developed in 221 patients. Cumulative appearance rates of HCC were 19.4%, 44.3%, and 58.2% at the end of the 5th, 10th, and 15th year, respectively. When classified by the state of hepatitis virus infection, the appearance rates of HCC in 180 patients with only hepatitis B surface antigen and in 349 patients with only anti-hepatitis C virus (anti-HCV) were 14.2% and 21.5% at the 5th year, 27.2% and 53.2% at the 10th year, and 27.2% and 75.2% at the 15th year, respectively. Cox proportional hazard model identified that alpha-fetoprotein (p = 0.00001), age (p = 0.00067), positive anti-HCV (p = 0.00135), total alcohol intake (p = 0.00455), and indocyanine green retention rate (p = 0.04491) were independently associated with the appearance rates of HCC. The survival rates of patients with cirrhosis were 84.1%, 57.0%, and 30.9% at the end of the fifth, tenth, and fifteenth year, respectively.

Adult↗
PubMed1994

A multicenter study on the prognosis of fulminant viral hepatitis: early prediction for liver transplantation.

To determine the risk of death at an early stage of fulminant viral hepatitis, we created severity indexes drawn from clinical data on the day of development of encephalopathy in 128 patients with fulminant hepatitis B and 103 with fulminant hepatitis non-A, non-B. In fulminant hepatitis B, the risk score was 2.75 x BL + 2.75 x BR + 2.7 x AG + 2.3 x WB + 1.67 x CD + 1.56 x AL - 0.098 x PR - 0.88, where BL is 1 if total bilirubin is higher than 20 mg/dl, BR is 1 if the ratio of total to direct bilirubin exceeds 2.2, AG is 1 if age is above 40 yr, WB is 1 if white blood cell count is less than 4,000 cells/mm3 or more than 18,000 cells/mm3, CD is 1 if a hazardous disease coexists and AL is 1 if ALT is less than 100 times the upper limit of normal (otherwise all are 0), and PR is prothrombin time (percentage of normal value). Using a cutoff score of 0, we found the positive predictive value, negative predictive value and predictive accuracy to be 0.90, 0.86 and 0.89, respectively. Sensitivity and specificity were 0.94 and 0.77, respectively. In fulminant non-A, non-B hepatitis, the risk score was 2.66 x BR + 2.25 x BL + 2.24 x DI + 2.05 x AL +/- 1.38 x AG + 0.00021 x WB - 6.33.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Chemical structure of the 2-keto-3-deoxyoctonate region of lipopolysaccharide isolated from Porphyromonas (Bacteroides) gingivalis.

Structural analysis of the 2-keto-3-deoxyoctonate region of lipopolysaccharide (LPS) isolated from Porphyromonas (Bacteroides) gingivalis was carried out. The substitution of the polysaccharide portion on the KDO was determined by gas chromatography/mass spectrometry of the product obtained by sequential derivatization of the LPS, including dephosphorylation, permethylation, carboxyl reduction, partial hydrolysis, carbonyl reduction, complete hydrolysis and O-acetylation. It was revealed that the KDO carries the polysaccharide on its position C5 and is phosphorylated on either position C7 or C8, although its exact position is not determined. The structure of the KDO region of P. gingivalis LPS in Gram-negative bacterial LPS had not hitherto been elucidated.

Gas Chromatography-Mass Spectrometry↗
PubMed1993

Risk factors for tumor recurrence and prognosis after curative resection of hepatocellular carcinoma.

METHODS: Eighty-three patients with hepatocellular carcinoma (HCC) were treated with curative surgical resection during the past 8 years. RESULTS: No operative deaths occurred. The cumulative recurrence rates after resection at the ends of years 1, 2, and 3 were 37.0%, 57.1%, and 71.6%, respectively. After adjusting the imbalance in clinical factors among patients by using a Cox proportional-hazards model, it was shown that multiplicity, histologic classification, and absence of antibody to hepatitis C virus were associated significantly with recurrence after resection. The size of the tumor did not affect the incidence of recurrence. Thirty-eight of 41 patients with intrahepatic tumor recurrence had undergone at least one of the following three therapies against HCC: surgical reresection, percutaneous ethanol injection (PEI), and transcatheter arterial embolization (TAE). The most significant factor affecting the survival time of patients with tumor recurrence was the total number of tumor nodules at the time of recurrence. Although surgery and PEI were thought to be more effective treatments than TAE in prolonging life, multivariate analysis showed that they were not significant factors of survival time because choices in the method of treatment were correlated closely with the number of cancer nodules. A 65.3% 5-year survival rate from the time of first surgery was accomplished through vigorous therapy when tumors recurred. CONCLUSION: In conclusion, despite the high recurrence rate after resection of HCC, the use of multiple therapies can achieve increased survival rates.

Adult↗
PubMed1993

Effect of lymphoblastoid alfa-interferon in patients with chronic hepatitis C having different genotypic subtype of hepatitis C virus.

Five subtypes of hepatitis C virus (Pt[I], K1[II], K2a[III], K2b[IV] and Tr[V]) have been suggested based on the nucleotide sequence of the non-structural five region. To assess the susceptibility of each subtype to interferon therapy, we developed a one-step method which allows quick determination of subtype using polymerase chain reaction with a mixed primer set deduced from the sequence of each subtype. We were able to determine the subtype of 69 of 80 (86.3%) Japanese patients who received natural alfa-interferon treatment. The incidence of each subtype was K1: 53 (76.8%), K2a: 14 (20.3%), K2b: 3 (4.3%) and Tr: 1 (1.4%). Interferon was administered to these patients and found to be effective in 28 of 51 (54.9%) patients with K1 subtype and in 16 of 18 (88.9%) patients with other subtypes (P < 0.01). These data show that K1 is a major subtype in Japan and relatively resistant to interferon treatment.

Adult↗
PubMed1993

Expression of monocyte chemoattractant protein 1 (MCP-1) in adult periodontal disease: increased monocyte chemotactic activity in crevicular fluids and induction of MCP-1 expression in gingival tissues.

The present study shows that monocyte chemotactic activity in crevicular fluids increases with severity of the disease and that a monocyte chemoattractant, monocyte chemoattractant protein 1 (MCP-1), is expressed as the predominant cytokine of gingival tissues and their fibroblasts treated with Porphyromonas (Bacteroides) gingivalis lipopolysaccharide (P-LPS). High monocyte chemotactic activity in the crevicular fluids was neutralized significantly by antiserum specific for the JE/MCP-1 protein. Marked expression of the MCP-1 gene was observed in the gingival tissues of all adult periodontal patients tested, but not in those of healthy subjects. Monocyte chemotactic activity was observed in culture supernatants of human normal gingival tissues treated with P-LPS, and the chemotactic activity increased in a dose-related manner. Expression of MCP-1 in P-LPS-treated human gingival fibroblasts was further examined. P-LPS induced the MCP-1 gene expression in a dose- and treatment time-dependent manner. The MCP-1 gene product in the culture supernatant was detected as two forms with molecular masses of 11,000 and 15,000 Da by immunoprecipitation with the specific antiserum. The MCP-1 gene expression was induced in the fibroblasts treated with interleukin-1 beta and tumor necrosis factor alpha, but not with interleukin-6. These results suggest that gingival fibroblasts can participate in monocyte recruitment in gingival tissues of adult periodontal patients via the MCP-1 gene product and that MCP-1 plays an important role in the inflammatory reaction in the disease.

Adult↗
PubMed1993

[Studies on the treatment of chronic hepatitis C with interferon. Assessment of treatment regimens and response to treatment].

The difference in response rate to interferon (IFN) among several treatment regimens was assessed retrospectively in 48 HCV-RNA positive patients with chronic hepatitis C. The study focused on patients' pretreatment profiles and response to treatment, histological findings before and after the treatment and the significance of HCV-RNA detection in evaluating the outcome. A complete response (CR) evaluated by the outcome of alanine aminotransferase (ALT) was obtained in 16 of 25 patients (64.0%) treated with IFN in doses of 3 to 6 million units daily for the first 4 or 8 wks and subsequent dosing twice or three times weekly for the following 8 to 146 wks. In contrast, CR was obtained in only 7 of 16 patients (43.8%) treated with the regimen in which patients received IFN in doses of 1 to 6 million units daily for 4 to 8 wks and no subsequent IFN. In comparing the responders to IFN (25 cases) and the non responders (19 cases), there were no significant differences regarding patients' age, sex, the presence or absence of history of blood transfusion, pretreatment ALT values or histological magnitude, or total doses of IFN administered. When the basal and final biopsy samples were compared, Knodell's index of histological activity had decreased significantly in the responders but not in the non responders. In 24 of the 25 responders, HCV-RNA had disappeared from their serum at the end of treatment, and in 23 it remained undetectable 6 months after treatment. In contrast, in 6 of the 19 non responders HCV-RNA had become negative at the end of treatment but was detectable in all cases 6 months after treatment. Thus, it is concluded that (1) a regimen of daily administration for the first 4 or 8 wks with subsequent dosing twice or three times weekly was preferable in terms of obtaining frequent CR, (2) response to IFN cannot be predicted by a patient's pretreatment profile, (3) in responders, histological activity decreases, and (4) in responders, HCV-RNA becomes undetectable not only at the end of treatment but also 6 months after treatment.

Adult↗
PubMed1993

A multivariate analysis of risk factors for hepatocellular carcinogenesis: a prospective observation of 795 patients with viral and alcoholic cirrhosis.

To elucidate the appearance rates of hepatocellular carcinoma in cirrhosis and to assess the risk factors for hepatocellular carcinogenesis, we prospectively studied 795 consecutive patients with viral or alcoholic cirrhosis for 2 to 17 yr (median of 5.8 yr). During the observation period, hepatocellular carcinoma developed in 221 patients. Cumulative appearance rates of hepatocellular carcinoma were 19.4%, 44.3% and 58.2% at the end of the fifth, tenth and fifteenth years, respectively. When classified by the type of hepatitis virus infection, the appearance rates of hepatocellular carcinoma in 180 patients with only HBsAg and in 349 patients with only antibodies to hepatitis C virus were 14.2% and 21.5% at the fifth yr, 27.2% and 53.2% at the tenth yr and 27.2% and 75.2% at the fifteenth yr, respectively. Cox proportional hazard model identified that alpha-fetoprotein levels (p = 0.00001), age (p = 0.00067), positive hepatitis C virus antibodies (p = 0.00135), total alcohol intake (p = 0.00455) and indocyanine green retention rate (p = 0.04491) were independently associated with the appearance rates of hepatocellular carcinoma. Whereas age and indocyanine green retention rate were independent predictors for the appearance rate of liver tumor in the subgroup of HBsAg-positive patients, alpha-fetoprotein levels, age and past alcohol consumption were independent predictors in the group of hepatitis C virus antibody-positive patients. These epidemiological results suggest that some differences exist in the activity and modes of cancer promotion between hepatitis B virus infection and hepatitis C virus infection.

Adult↗
PubMed1993

Diagnosis and follow-up of small hepatocellular carcinoma with selective intraarterial digital subtraction angiography.

To clarify the angiographic features of small hepatocellular carcinoma, we performed digital subtraction angiography in 91 patients with hepatocellular carcinomas of 2 cm or less. Repeated digital subtraction angiography studies were performed in 25 patients whose first angiograms showed no tumor staining. Digital subtraction angiography showed hypervascular tumor staining in only 51 patients (56.0%). We found that the smaller a tumor nodule was, the lower the detection rate of tumor stain on digital subtraction angiography. The detection rate of hypervascularity was closely correlated with the grading of histological differentiation of the tumors: well-differentiated hepatocellular carcinomas more often showed negative tumor staining. Repeated digital subtraction angiography studies showed alteration of tumor staining from isovascular to hypervascular in 6 of 6 patients with tumors that became larger than 2 cm and in 12 of 19 patients with tumors that remained 2 cm or smaller. Conversion of vascularity is commonly found in the early stage of small hepatocellular carcinoma, and the process is usually slow, taking approximately 1 yr.

Adult↗
PubMed1992

Alanine aminotransferase and HCV-RNA responses following interferon therapy of HCV-RNA positive chronic hepatitis.

Interferon (IFN) has been shown to be effective for chronic hepatitis C. This study investigated changes of alanine aminotransferase (ALT) and HCV-RNA in chronic hepatitis C patients treated with alpha-IFN. IFN was given to 73 patients with HCV-RNA positive chronic hepatitis C. The pattern of changes in ALT activity after IFN administration was classified into five types. Type 1 was characterized by normalization of ALT (< or = 25 K.U) during IFN administration and sustained normalization after the IFN therapy. Type 2 involved a rebound of ALT after termination of IFN therapy and subsequent normalization. Type 3 had no ALT normalization during IFN administration, with normalization after the completion of the therapy. Type 4 involved transient normalization of ALT level during IFN therapy, with a subsequent reversion to abnormal levels after the termination of IFN therapy. Type 5 showed sustained abnormally high levels of ALT activity both during and after treatment. Twenty four patients (32.9%) had sustained normalization ALT (< or = 25 K.U) after the termination of IFN treatment. The HCV-RNA negative rate at 6 months after IFN therapy in patients with sustained normalization of ALT was 87.5% (21/24).

Adult↗