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Biomedical subjects

Kazuhisa Yamamoto

Publications and source records attributed to Kazuhisa Yamamoto.

10 recordsLinked to original sources

In vivo immunization by vaccine therapy following virus suppression by lamivudine: a novel approach for treating patients with chronic hepatitis B.

BACKGROUND: Both the hepatitis B virus (HBV) and the immune response of the hosts to HBV play important roles in the pathogenesis of chronic hepatitis B (CHB). Lamivudine is a potent antiviral agent with minimal immune modulator capacity. Moreover, lamivudine causes severe side effects like breakthrough of HBV DNA and breakthrough hepatitis in patients with CHB. On the other hand, vaccine therapy, a recently-developed immune therapy, exhibits potent immune modulatory potentials and almost no side effects, but possesses little antiviral capacity in patients with CHB. OBJECTIVES: The aim of this clinical trial is to evaluate the efficacy of a combination therapy of lamivudine and vaccine in patients with CHB. STUDY DESIGN: Seventy-two patients with CHB (hepatitis B e antigen (HBeAg)-positive, 40; antibody to HBeAg (anti-HBe)-positive, 32). All patients received lamivudine at a dose of 100 mg daily for 12 months. Fifteen patients (HBeAg+, 9; anti-HBe+, 6) receiving oral lamivudine were also given a vaccine containing 20 microg of hepatitis B surface antigen, intradermally, once every 2 weeks for 12 times (combination therapy). RESULTS: Twelve months after the start of therapy, serum HBV DNA became negative in 9 of 9 (100%) HBeAg+ CHB patients receiving combination therapy and in 15 of 31 (48%) HBeAg+ CHB patients receiving lamivudine monotherapy (P < 0.05). The rate of seroconversion from HBeAg to anti-HBe was also significantly higher in patients receiving combination therapy (56% versus lamivudine monotherapy, 16%, P < 0.05). Of the 57 patients receiving lamivudine monotherapy, breakthrough of HBV DNA was found in 10 and breakthrough hepatitis was found in 4; however, these were not seen in any patient receiving combination therapy. CONCLUSIONS: Combination therapy represents a better therapeutic regimen with few complications in patients with CHB.

Adult↗

Infectious source factors affecting the severity of sexually transmitted acute hepatitis due to hepatitis B virus genotype C.

OBJECTIVE: The aim of this study was to identify clinical features and virological aspects of infectious sources that are related to the severity of sexually transmitted acute hepatitis B virus (HBV) infection in patients, especially in cases of genotype C. METHODS: Nineteen patients with acute HBV infection, 10 classified with severe acute hepatitis (SH) (prothrombin time; PT <40%) and 9 with typical acute hepatitis (AH) (PT >40%), and their infectious sources (all were sexual partners) were studied. Infectious source factors were analyzed in relation to the severity of hepatitis in the patients' partners. RESULTS: The nucleotide homology of HBV-DNA between each pair was >/=98.9%. Sixteen were infected with HBV genotype C. Among the 16 infectious sources, age, numbers with elevated alanine aminotransferase (ALT, 7/9 vs. 1/7), anti-HBe positivity (8/9 vs. 1/7) and core promoter mutations at nt 1762 (7/9 vs. 1/7), nt 1764 (8/9 vs. 1/7) and precore mutation at nt 1896 (8/9 vs. 1/7) were significantly higher in the sources of SH than in those of AH. CONCLUSION: Higher age, elevated ALT, anti-HBe positivity and core promoter/precore mutations were possible risk factors for an infectious source of the severe form of sexually transmitted acute hepatitis due to HBV genotype C.

Acute Disease↗

Efficacy of lamivudine therapy for decompensated liver cirrhosis due to hepatitis B virus with or without hepatocellular carcinoma.

The prognosis for patients with decompensated hepatitis B virus (HBV) related liver cirrhosis (LC-B), especially for those with LC-B complicated with hepatocellular carcinoma (HCC), is poor. We investigated the effects of lamivudine in patients with decompensated LC-B, with and without HCC. Decompensated LC-B patients (n=55) with Child-Pugh classification scores (CPS) >7 points were enrolled. All were admitted to the hospitals of the authors between January 1997 and December 2004. Decompensated cases due to a severe exacerbation of hepatitis with CH-B and patients with HCC showing an extra hepatic metastasis or portal vein tumor thrombus were excluded. Some 19 cases (including 5 cases complicated with HCC at the start of therapy) were treated with lamivudine at 100 mg/day (L group), and 36 (including 7 cases with HCC at time of admittance) were treated without lamivudine (non-L group). The median of CPS points in the L group was higher than that of non-L group (11 points versus 9 points, p<0.02). Prothrombin time (%), albumin, ascites, CPS, and HBV-DNA quantity were each significantly improved after 6 months in the L group (p<0.05). A mutation in the YMDD motif was observed in 5 patients in the L group, however liver function did not deteriorate. Further, the survival rate was significantly higher in the L group (p<0.05). HCC was found in 3 L group and 4 non-L group patients during the study. In the L group, all patients complicated with HCC were treated repeatedly or until cured, whereas 91% of those in the non-L group could not be treated (p<0.01). Our results suggest that lamivudine is a useful and important therapy for patients with decompensated LC-B with and without HCC, as well as those who are restricted from having liver transplantation.

Adult↗

Efficient 340-nm light generation by a ridge-type waveguide in a first-order periodically poled MgO:LiNbO3.

Quasi-phase-matched (QPM) UV second-harmonic generation (SHG) in a periodically poled MgO:LiNbO3 waveguide is presented. A ridge-type waveguide with high nonlinearity and strong resistance to photorefractive damage was achieved by use of an ultraprecision machining technique. By use of this waveguide in 1.4-microm periodically poled MgO:LiNbO3, a first-order QPM SHG device for 340-nm UV radiation was demonstrated. In a single-pass configuration, continuous-wave 22.4-mW UV light was generated for a fundamental power of 81 mW, corresponding to a normalized conversion efficiency of 340%/W.

Journal Article↗

Generation of 360-nm ultraviolet light in first-order periodically poled bulk MgO:LiNbO3.

Ultraviolet second-harmonic generation in first-order periodically poled MgO:LiNbO3 is presented. Using a high-voltage multipulse application method, we fabricated a first-order nonlinear grating with a period of 1.8 microm and depth of approximately 150 microm over 10-mm interaction length in a 1-mm-thick MgO:LiNbO3 substrate. In a single-pass configuration, continuous-wave 30-mW UV light at 362.5 nm was generated for a fundamental power of 522 mW, corresponding to a normalized conversion efficiency of 11%/W.

Journal Article↗

Change of acute hepatitis B transmission routes in Japan.

BACKGROUND: Many years have passed since various prophylactic policies for preventing hepatitis B virus (HBV) transmission were begun. We studied the chronological alterations in HBV infectious routes in patients with acute hepatitis B in the past 27 years. METHODS: Seventy-two patients with acute HBV infection who were admitted to our hospital during the period 1976 to 2002 were enrolled in this study. This study was divided into two periods (first period, 1976-1990; and second period, 1991-2002), and the HBV infectious routes were studied. RESULTS: Infectious routes have been changing. Posttransfusion hepatitis was seen only in the first period. In the second period, sexual transmission was the major infectious route (68%), followed by infection at a medical facility or occupational exposure such as needlestick injury (8%). CONCLUSIONS: Transmission from sexual contact has become the main infectious route of HBV in Japan.

Acute Disease↗

Complete genome sequence of hepatitis B virus (HBV) from a patient with fulminant hepatitis without precore and core promoter mutations: comparison with HBV from a patient with acute hepatitis infected from the same infectious source.

BACKGROUND/AIMS: There is a paucity of information regarding hepatitis B virus (HBV) from patients with fulminant hepatitis (FH) without precore (pre-C, nt 1896) and core promoter (CP, nt 1762, 1764) mutations. METHODS: Pre-C and CP mutations were studied in eight patients with FH and 26 patients with acute hepatitis (AH) due to HBV. One patient with FH (FH1) was infected with HBV without these mutations. Interestingly, the sera of the infectious source (IS1) and of a patient with AH (AH1) infected from IS1 were available. Complete HBV genomes from these three patients were analyzed. RESULTS: These mutations were found in seven of eight FH and five of 26 AH (P<0.01). HBV from FH1, IS1 and AH1 belonged to genotype D. Nucleotide difference between FH1 and AH1 was six of 3182 bases (nt 493, 998, 1173, 2928, 3067, and 3078). Two and five substitutions of deduced amino acid sequences were found in the pre-S1 and polymerase regions, respectively. The same nucleotide substitutions at nt 493, 1173, 2928 and 3067 were found in several patients with FH in our laboratory or GenBank. CONCLUSIONS: These six nucleotide substitutions of HBV DNA could be candidates of mutations relating to FH.

Acute Disease↗

Autoimmune hepatitis associated with Graves' disease.

A 31-year-old woman with Graves' disease with a 12-month-history of propylthiouracil intake and autoantibodies in the sera was admitted to our hospital. The differential diagnosis between autoimmune hepatitis and propylthiouracil-induced hepatitis was intractable. Steroid therapy was started and she showed a complete response to the treatment. Liver biopsy demonstrated acute hepatitis and plasma cell infiltration. A second liver biopsy, which was performed 10 months after starting steroid therapy, showed some inflammatory cells in the portal tracts. These findings suggest that she had been suffering from autoimmune hepatitis.

Adult↗

Drug-induced hepatitis with autoimmune features during minocycline therapy.

A 25-year-old woman with no history of liver disease developed liver dysfunction associated with severe jaundice and general malaise following a prolonged therapy with minocycline for acne vulgaris. Serum anti-nuclear antibody was detected and immunoglobulin G level was elevated. Symptoms resolved and liver function normalized following minocycline discontinuation and corticosteroid administration. Our diagnosis was drug-induced hepatitis with autoimmune features, as liver histology revealed acute hepatitis. Drug-induced hepatitis should be considered when liver dysfunction or systemic symptoms develops during long-term minocycline therapy.

Acne Vulgaris↗