[Endoscopic stent insertion for decompression of pancreatic duct stenosis].
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Chronic Disease↗
Biomedical subjects
Hiromitsu Saisho
Publications and source records attributed to Hiromitsu Saisho.
Bezafibrate treatment: a new medical approach for PBC patients?
BACKGROUND: A new medical approach to primary biliary cirrhosis (PBC) has been desired. We investigated the feasibility of using combination ursodeoxycholic acid (UDCA)-bezafibrate therapy in patients with PBC nonresponsive to UDCA monotherapy. METHODS: During a 6-month period, 22 PBC patients with elevated serum alkaline phosphatase (ALP) despite UDCA monotherapy received either UDCA at 600 mg/day (control group) or UDCA at 600 mg/day plus bezafibrate at 400 mg/day (bezafibrate group). Each patient underwent detailed clinical and biochemical evaluation. RESULTS: During treatment, changes in ALP level were greater in the bezafibrate group than in the control group (P< 0.01). During and at the end of treatment, serum ALP levels were significantly lower than those before treatment in patients receiving UDCA plus bezafibrate (P< 0.05). At the end of the 6 months, normalization of serum ALP was observed in 5 of 11 (45.4%) patients given bezafibrate and in 2 of 11 (18.1%) patients not given bezafibrate (P< 0.16). Bile acid proportions during the combination therapy did not change. Pruritus disappeared in 1 of 7 bezafibrate-group patients with this symptom. CONCLUSIONS: UDCA at 600 mg/day plus bezafibrate at 400 mg/day may be considered as a new therapeutic option for patients with PBC.
Alkaline Phosphatase↗
Prevention of gallstones by ursodeoxycholic acid after cardiac surgery.
BACKGROUND: One of the problems in prosthetic-valve recipients is the development of gallstones. We suggested that the use of a heart-lung machine may be closely related to gallstone formation. The objective of this study was to clarify the efficacy of ursodeoxycholic acid (UDCA) in the prevention of gallstone formation after open cardiac surgery. METHODS: One hundred and six patients without gallstones who underwent cardiac surgery in which a heart-lung machine was used were randomly divided into two groups: group A, comprising 54 patients who did not receive UDCA, and group B, comprising 52 patients who received UDCA (600 mg daily for 6 months from 1 week before surgery). Both groups were followed by ultrasonography for 60 months. Blood markers of hemolysis (hemoglobin, reticulocyte count, haptoglobin, total bilirubin, and lactate dehydrogenase) were evaluated before, immediately after, and at 3 weeks and 3, 6, 12, 24, and 60 months after surgery. RESULTS: In groups A and B, cumulative incidence rates for gallstone formation were 15.1% and 0% at 3 months, 23.0% and 0% at 6 months, 29.2% and 2.0% at 12 months, 29.2% and 8.4% at 24 months, and 29.2% and 8.4% at 60 months, respectively. In regard to the composition of the gallstones, they were considered to be mainly black pigment stones. CONCLUSIONS: The prophylactic administration of UDCA resulted in a significant decrease in the incidence of gallstones after open cardiac surgery.
Adolescent↗
The copper/zinc ratio in patients with hepatocellular carcinoma.
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Biomarkers, Tumor↗
Hemodynamic response of the left gastric vein to glucagon in patients with portal hypertension and esophageal varices.
Flow direction and flow velocity of the left gastric vein (LGV) and the portal vein (PV) were examined by a Doppler sonographic machine in 33 patients with esophageal varices, before and after venous injection of glucagon (1 mg). In two patients with hepatopetal blood flow in the LGV, the flow direction changed to hepatofugal after injection of glucagon. In 31 patients with hepatofugal blood flow in the LGV, a significant increase of flow velocity was observed in the LGV in 18 patients (58.1%) and the changes (26.4 +/- 24.6%) were significantly larger than those in the PV (7.9 +/- 16.0%). The changes in flow velocity decreased in the LGV as the diameter of the LGV and the size of varices increased. In conclusion, glucagon increased collateral blood flow in the LGV in portal hypertension. However, the grade of the response decreased as the grade of portal hypertension increased.
Aged↗
Analysis of the genotype-determining region of hepatitis A viral RNA in relation to disease severities.
Although hepatitis A is still a considerable problem in Japan, correlation of genomic differences of hepatitis A virus (HAV) and the clinical status of hepatitis A has not been studied. To examine whether the HAV genotype is associated with the disease severity, we analyzed the HAV genotype-determining region in sera from patients with hepatitis A of various clinical degrees. Serum samples from 47 Japanese patients with sporadic hepatitis A from 4 different areas in Japan, including 8 with fulminant hepatitis, 11 with severe acute hepatitis (AHs), and 28 with AHs, were examined for HAV RNA. The 168 base pair sequence of the genotype-determining region, which is located at the VP1/2A junction, was amplified by reverse transcription-polymerase chain reaction, and the nucleotide sequence was determined by direct sequencing. By comparing sequences for VP1/2A, we determined that 44 of 47 cases examined were of subgenotype IA, two were of subgenotype IB, and one was of subgenotype IIIA. With respect to subgenotype IA strains, individuals who were infected between 1990 and 1996 tended to show similar sequences, whereas those infected between 1997 and 1999 showed sequences slightly different from those of the 1990-1996 cases. There were no apparent associations between disease severity and sequences of the genotype-determining region. Hepatitis A of our study was caused by a variety of subgenotype IA strains, consistent with the sporadic spread of infection. Disease severity was not associated with the nucleotide sequence of the HAV genotype-determining region.
Journal Article↗
Significance of prior hepatitis B virus infection in the development of hepatocellular carcinoma in patients with chronic hepatitis C.
To clarify the clinical significance of prior hepatitis B virus (HBV) infection in the development of C-viral hepatocellular carcinoma (HCC), we conducted two studies: (1) Two hundred thirty-four patients with C-viral HCC and 320 patients with C-viral chronic liver disease without HCC admitted to our hospital between 1990 and 1994 were analyzed for the association of hepatitis B core antibody (HBcAb) positivity with HCC by multivariate logistic regression analysis, and this revealed HBcAb positivity as an independent risk factor for development of HCC adjusted for age and sex. (2) Four hundred fifty-nine patients with biopsy-proven hepatitis C virus-related chronic liver disease between 1986 and 1998 were enrolled in the cohort study and followed for the development of HCC. During an average follow-up of 6.6 +/- 3.3 years, HCC developed in 63 patients, 37 of 160 patients positive for HBcAb and 26 of 299 patients negative for HBcAb. Multivariate Cox proportional regression analysis showed that the incidence of HCC increased by age, advanced stage of liver fibrosis, mean alanine aminotransferase value of more than 80 IU/liter, and positivity of HBcAb. Sustained virological responders after interferon therapy revealed a reduced risk for HCC development. In conclusion, prior HBV infection was shown to be one of the independent risk factors for development of HCC in C-viral chronic liver disease.
Carcinoma, Hepatocellular↗
Successful clearance of hepatitis B virus after allogeneic stem cell transplantation: beneficial combination of adoptive immunity transfer and lamivudine.
We report a 38-yr-old male with acute lymphocytic leukemia (ALL), whose serological tests for the hepatitis B virus (HBV) before transplantation showed a chronic carrier status, and a liver biopsy specimen revealed chronic liver injury because of HBV. The patient underwent allogeneic peripheral blood stem cell transplantation (PBSCT) from his sibling who was hepatitis B surface antibody (HBsAb) positive. He had received lamivudine treatment for the prophylaxis of HBV reactivation during cytotoxic chemotherapy, and lamivudine administration continued after transplantation. Successful engraftment was documented 3 wk after PBSCT, and clearance of the hepatitis B surface antigen (HBsAg) was observed 2 months after PBSCT. Liver function tests transiently showed a mild elevation of aminotransferases on day 25, although this returned to normal after the dose escalation of the immunosuppressive agent. We presume that the combination of adoptive immunity transfer by bone marrow transplantation (BMT) from an HBsAb-positive donor and antiviral drugs such as lamivudine is beneficial in clearing HBV in chronic carriers.
Adult↗
Expression of the interleukin-21 gene in murine colon carcinoma cells generates systemic immunity in the inoculated hosts.
Interleukin-21 (IL-21) is a novel cytokine that can induce proliferation of activated T cells and maturation of natural killer (NK) cells. We therefore examined whether expression of the IL-21 gene in tumor cells could generate antitumor responses. Murine colon carcinoma Colon 26 cells that were transduced with the mouse IL-21 gene (Colon 26/IL-21) were rejected in syngeneic mice and the mice subsequently acquired protective immunity. The growth of Colon 26/IL-21 tumors developed in nude mice was retarded compared with that of parent tumors, and this growth suppression was not observed in nude mice that were treated with anti-asialo GM(1) antibody. Spleen cells from the mice that had rejected Colon 26/IL-21 cells showed cytotoxic activity to Colon 26 but not to irrelevant tumor cells, and produced larger amounts of interferon-gamma upon stimulation with irradiated Colon 26 cells. Spleen cells from Colon 26/IL-21-tumor- but not parent-tumor-bearing mice had lytic activity to YAC-1 cells. These data suggest that expression of IL-21 in tumors induces T- and NK-cell-dependent antitumor effects.
Animals↗
Transduction of the IL-21 and IL-23 genes in human pancreatic carcinoma cells produces natural killer cell-dependent and -independent antitumor effects.
We examined whether novel cytokines, interleukin (IL)-21 and IL-23, that were expressed in tumors could produce antitumor effects in the inoculated mice. Human pancreatic cancer AsPC-1 cells were retrovirally transduced with murine IL-21 or IL-23 (p19-linked p40) gene (AsPC-1/IL-21, AsPC-1/IL-23) and were injected into nude or severe combined immunodeficiency (SCID) mice. Although the proliferation in vitro of the transduced cells remained the same as that of parent cells, growth of AsPC-1/IL-21 and AsPC-1/IL-23 tumors developed in nude mice was retarded compared with that of parent tumors. Treatment of nude mice with anti-asialo GM(1) antibody temporally abrogated the growth retardation of AsPC-1/IL-21, but not AsPC-1/IL-23 tumors; however, the growth of AsPC-1/IL-21 tumors came to be retarded thereafter with the regeneration of natural killer (NK) cells. The growth of AsPC-1/IL-21 tumors developed in SCID mice was also retarded compared with parent tumors and the growth retardation was abrogated by treatment with anti-asialo GM(1) antibody. The growth of AsPC-1/IL-23 tumors in SCID mice was not different from that of parent tumors. Cytotoxic activity and secretion of interferon-gamma in response to AsPC-1 cells were induced in spleen cells of the mice bearing AsPC-1/IL-21 or AsPC-1/IL-23 tumors. When nude mice were injected with a mixed population of AsPC-1/IL-21 and AsPC-1/IL-23 cells, no synergistic effects were observed. These data collectively suggest that expression of IL-21 and IL-23 in tumors can produce NK cell-dependent and -independent antitumor effects in an alpha beta T cell-defective condition, respectively.
Animals↗
Severe hepatotoxicity associated with Chinese diet product 'Onshidou-Genbi-Kounou'.
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Adult↗
Assessment of cancer cell differentiation in small hepatocellular carcinoma by computed tomography and magnetic resonance imaging.
AIM: To study whether cancer cell differentiation in small hepatocellular carcinoma (HCC) can be assessed by computed tomography (CT) and magnetic resonance (MR) imaging. METHODS: We retrospectively evaluated the relationship between cancer cell differentiation in 127 HCC 3 cm or less in diameter (113 patients) and CT and MR images. Images were reviewed in a consensus conference by three authors (SA, TY, and ME). Histopathological diagnosis of HCC was made from liver specimens obtained by sonographically guided biopsy. RESULTS: The degree of histological differentiation of cancer cells was significantly different between HCC that were isodense with liver parenchyma in both artery-dominant and equilibrium phases in contrast-enhanced CT and tumors that were hyperdense in the artery-dominant phase and iso- or hypodense in the equilibrium phase (P = 0.0054), as well as tumors that were iso- or hypodense artery-dominant and hypodense equilibrium (P = 0.0002). Histological differentiation of lesions that were hyperintense in T1-weighted images and hypointense in T2-weighted images differed significantly from those with the opposite MR characteristics (P = 0.0122). In T1-weighted fat-suppression images and T2-weighted images, respectively, the degree of histological differentiation was significant between the hypointense/hyperintense and the hyperintense/hypointense patterns (P < 0.0001), as well as the hyperintense/isointense (P = 0.0296), the hyperintense/hyperintense (P = 0.0434), and the isointense/hyperintense (P = 0.0171). Using these differences an equation was developed that could determine with 76% accuracy whether the tumors were well or less-well differentiated. CONCLUSION: CT and MR imaging patterns were useful in predicting the degree of histological differentiation of cancer cells in HCC.
Adult↗
N-nitroso-fenfluramine hepatotoxicity resembling chronic hepatitis.
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Chemical and Drug Induced Liver Injury↗
Predominant role of FcgammaRIII in the induction of accelerated nephrotoxic glomerulonephritis.
BACKGROUND: Nephrotoxic glomerulonephritis is induced by the administration of antibody against the glomerular basement membrane (GBM). We demonstrated previously that Fc receptors for immunoglobulin G (IgG) (FcgammaR) play crucial roles in the induction of accelerated nephrotoxic glomerulonephritis by using FcRgamma-deficient (-/-) mice. Since FcRgamma-/- mice lack the cell surface expression of two activating FcgammaRs, FcgammaRI and FcgammaRIII. The present study aims to identify the FcgammaR responsible for the induction of nephrotoxic glomerulonephritis. METHODS: Accelerated anti-GBM glomerulonephritis was induced in FcgammaRI-/-, FcgammaRIII-/-, and FcRgamma-/- mice by preimmunization with rabbit IgG followed by inoculation of rabbit anti-GBM antibody. Histologic analysis and immunostaining of renal sections were performed. RESULTS: FcgammaRI-/- mice as well as wild-type mice showed severe glomerulonephritis with hypernitremia by the administration of anti-GBM antibody. In contrast, FcgammaRIII-/- mice showed much milder renal involvement, similar to FcRgamma-/- mice. Histologically, FcgammaRI-/- mice showed intracapillary proliferation, glomerular thrombosis, and crescent formation, whereas FcgammaRIII-/- mice showed only glomerular hypercellular changes. The depositions of anti-GBM antibodies, autologous antibodies and complement C3 along the GBM were equally observed among all three FcR-/- mouse types by immunostaining. CONCLUSIONS: Accelerated nephrotoxic glomerulonephritis is induced predominantly through FcgammaRIII but not FcgammaRI.
Albuminuria↗
Influence of hepatitis B virus genotypes on the progression of chronic type B liver disease.
To investigate the hepatitis B virus (HBV) genotype-related differences in the progression of liver disease, 585 patients with chronic HBV infection including 258 with histologically verified chronic liver disease (CLD) and 74 with hepatocellular carcinoma (HCC) were examined. The mean ages of both patients with advanced fibrosis (F3 or F4) and with HCC were significantly older in genotype B than in genotype C patients (P =.018, P =.024, respectively). Both the hepatitis B e antigen (HBeAg) negativity rate at biopsy and the cumulative HBe seroconversion rate in patients with CLD were significantly higher in genotype B patients than genotype C patients (P <.01, P =.022, respectively). Multivariate analysis revealed that genotype B, presence of precore mutation, high ALT levels, and severe histologic activity were independent factors for HBe seroconversion. Among all the biopsy-proven CLD patients, the ratio of patients with advanced fibrosis in genotype B was significantly lower than that in genotype C (4/30 vs. 74/224, respectively; P =.034). This difference was more remarkable in younger patients (< or =45 years; 1/25 vs. 47/180, respectively; P =.020), and there was no difference in older patients (>45 years). The distribution of each genotype between CLD and HCC was very similar (B and C: 11.2% and 87.0% vs. 10.8% and 89.2%, respectively). In conclusion, our results suggest that, although the patients with genotype B experience earlier HBe seroconversion, slower progression of liver fibrosis, and slower development of HCC, the life-long risk of progression to advanced fibrosis and development of HCC may not differ among genotypes B- and C-related chronic liver disease.
Adult↗
Favorable prognosis of chronic hepatitis C after interferon therapy by long-term cohort study.
The prognosis of patients with chronic hepatitis C after interferon (IFN) therapy is still poorly defined. The present study evaluated the effect of IFN therapy on survival in a cohort of such patients. The study included 459 patients with biopsy-proven C-viral chronic liver disease who were followed for 8.2 +/- 2.9 years (range, 7-183 months). Survival status was examined by medical records or direct questionnaires. Fifteen (14%) of 104 IFN-untreated patients and 33 (9%) of 355 patients treated with IFN died during follow-up. Among the treated patients, 4 (3%) of 116 with sustained virologic response and 29 (12%) of 239 without sustained virologic response died. Liver-related death was shown in 32 (67%) patients, and hepatocellular carcinoma (HCC) caused 25 (52%) of the 48 deaths. Multivariate Cox proportional regression analysis revealed that IFN treatment decreased the risk ratio for overall death to 0.521 (confidence interval [CI]: 0.263-1.034) and for liver-related death to 0.208 (CI: 0.088-0.495) compared with untreated patients, and sustained virologic response showed a decrease in the risk ratio for overall death to 0.219 (CI: 0.068-0.710) and for liver-related death to 0.030 (CI: 0.003-0.267). IFN treatment showed no association with liver-unrelated death. Furthermore, the standardized mortality ratios for all causes of death and liver-related death were reduced in IFN-treated patients compared with untreated patients (1.4 vs. 2.0 for total death and 7.9 vs. 19.7 for liver-related death). In conclusion, the present data suggest that IFN therapy has a long-term clinical benefit for patients with chronic hepatitis C patients by reducing liver-related death, especially in patients with sustained virologic response.
Adult↗
Early endoscopic treatment of intramural hematoma of the esophagus.
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Biopsy↗
Induction of apoptosis and ubiquitin hydrolase gene expression by human serum factors in the early phase of acute myocardial infarction.
The physiologic events leading to apoptosis in myocardial infarction and the molecules involved in the death process have not been clarified unequivocally. We developed a method to search for serum factors that induce apoptosis of human cells, using serum obtained from patients within 1 day of the onset of acute myocardial infarction (AMI). Serum factors were found to have the ability to increase the caspase-3 activity levels in human RSa cells, which are susceptible to apoptosis inducers. The factors obtained from AMI patients by elution at about 0.5 mol/L KCl from a dye-ligand column were named AMI-SFs (serum factors from AMI). Electrophoretic analysis showed DNA fragmentation in AMI-SF-treated RSa cells, but not in RSa cells treated with fractions from AMI patients 1 week after clinical onset of illness. AMI-SF-induced DNA fragmentation was also demonstrated by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling analysis, whereas a suppression of fragmentation was seen in RSa cells treated with AMI-SFs in combination with a caspase-3 inhibitor. The increase in caspase-3 activity was not inhibited by neutralizing antibodies to tumor necrosis factor-alpha, interleukin-6, human interferon-beta, or interferon-gamma. Polymerase chain reaction-based messenger RNA differential display and Northern blotting revealed an increase in the messenger RNA expression level of human ubiquitin hydrolase in AMI-SF-treated RSa cells. Antisense oligonucleotides for ubiquitin hydrolase inhibited the increase in caspase-3 activity. These findings suggested that serum from AMI patients in the acute phase contains factors that induce apoptosis, possibly by inducing the expression of the ubiquitin hydrolase gene, at least in the human cells tested.
Adult↗