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Biomedical subjects

Ryukichi Kumashiro

Publications and source records attributed to Ryukichi Kumashiro.

At least 19 recordsLinked to original sources
PubMed2006

Granulocytapheresis (GCAP) for severe alcoholic hepatitis-A preliminary report.

AIM: To evaluate the efficacy of granulocytapheresis therapy in alcoholic hepatitis. METHODS: We attempted to trap leukocytes in the peripheral circulation using the granulocytapheresis (GCAP) technique in patients with severe alcoholic hepatitis who showed a marked elevation of peripheral leukocytes. Corticosteroids were co-administered. RESULTS: The Maddrey's indices for these patients varied between 42 and 117 and MELD scores for alcoholic hepatitis (Mayo) ranged from 20 to 44. Survival rate was 50% (3/6), which is better than the results reported recently for similar patients in a national survey (29%). The effect of GCAP was reflected in decreases in interleukin-6 and interleukin-8 levels as well as in serum concentrations of soluble intercellular adhesion molecule. White blood cell counts were not affected. In the surviving patients, the Maddrey's indices and MELD scores for alcoholic hepatitis varied between 49 and 67, and 20 and 22, respectively, showing that GCAP is effective in patients with disease of moderate severity. Hemolytic anemia occurred in one patient after GCAP therapy. Other events such as pancreatitis, pneumonia, and cerebral hemorrhage were considered to be related to the alcoholic hepatitis itself. CONCLUSION: GCAP therapy deserves further evaluation as a new therapeutic modality for a moderately severe alcoholic hepatitis.

Journal Article↗
PubMed2006

A decrease in AFP level related to administration of interferon in patients with chronic hepatitis C and a high level of AFP.

It is known that there is a very high incidence of hepatocellular carcinoma (HCC) among patients with type C chronic hepatitis and cirrhosis, and alpha -fetoprotein (AFP) has been widely used as a diagnostic marker for HCC. However, there are some patients showing continuous high AFP values but no evidence of HCC, and some studies have defined such patients as a high-risk group for HCC. In vitro study has shown that interferon (IFN) inhibits cell proliferation and enhances apoptosis as well as specific cytotoxic T lymphocytes against HCC, resulting in direct anticancer actions. In this study, we investigated the effect of IFN on AFP changes in chronic hepatitis C patients. Of 40 patients with chronic hepatitis C in whom diagnostic imaging confirmed the absence of HCC, 24 patients showed high pretreatment AFP values (high AFP group: AFP level > 10 ng/dl; mean +/- SD, 46.3 +/- 41.5 ng/dl) and 16 showed low pretreatment AFP values (low AFP group: pretreatment AFP level < or = 10 ng/dl; mean +/- SD, 5.3 +/- 2.2 ng/dl). Pretreatment clinical parameters were statistically evaluated in relation to the AFP value. In the high AFP group, the platelet count, albumin level, and prothrombin (%) were significantly lower (P = 0.047, P = 0.0002, and P = 0.044, respectively), suggesting that AFP value increases with advancing liver disease. Subsequently 27 patients were administered IFN (IFN group), and the remaining 13 patients were administered Stronger Neo-minophagen C (SNMC), a glycyrrhizin preparation (SNMC group), as a control group receiving liver-protective therapy. Alanine aminotransferase was reduced in both the IFN and the SNMC group (mean, 132.56 to 60.07 mg/ml [P < 0001] and 147.85 to 56.23 mg/ml [P = 0.0240], respectively). AFP was significantly reduced in the IFN group (mean, 30.03 to 12.65 ng/ml; P = 0.0034), but there was no significant change in AFP in the SNMC group (mean, 29.70 to 39.17 ng/ml). AFP is useful for diagnosing HCC; however, some patients show a persistently high AFP level in the absence of HCC, and these patients have been described as a high-risk group for HCC. In this study, we found that IFN therapy but not SNMC universally reduced the AFP baseline. Since AFP is a significant predictor for HCC, therapeutic strategies for hepatitis C, e.g., long-term low-dose IFN treatment, may reduce hepatocarcinogenesis.

Aged↗
PubMed2006

Endothelial progenitor cell transplantation improves the survival following liver injury in mice.

BACKGROUND & AIMS: Neovascularization, which is vital to the healing of injured tissues, recently has been found to include both angiogenesis, which involves in mature endothelial cells, and vasculogenesis, involving endothelial progenitor cells. The aim of this study was to clarify the possible roles of endothelial progenitor cells during postnatal liver regeneration. METHODS: To determine how endothelial progenitor cells participate in liver regeneration, human or mouse endothelial progenitor cells were transplanted into the mice with carbon tetrachloride-induced acute liver injury. Survival rate of the mice in endothelial progenitor cell-transplanted and control groups was calculated. Separately, livers removed temporally from both groups were examined. RESULTS: At an early stage, transplanted human endothelial progenitor cells were seen mainly surrounding hepatic central veins where hepatocytes showed extensive necrosis; later, the transplanted cells formed tubular structures. More of these cells were observed along hepatic sinusoids. Transplantation of human or mouse endothelial progenitor cells improved survival of the mice following liver injury (from 28.6% to 85.7%, P < .0005 and from 33.3% to 80.0%, P < .001, respectively), accompanied by greater proliferation of hepatocytes. Human endothelial progenitor cells produced several growth factors, such as hepatocyte growth factor, transforming growth factor-alpha, heparin-binding epidermal growth factor-like growth factor, and vascular endothelial growth factor, and also elicited endogenous growth factors. CONCLUSIONS: Endogenous and exogenous growth factors and direct neovascularization after endothelial progenitor cell transplantation promoted liver regeneration, thus improving survival after liver injury. Transplantation of endothelial progenitor cells could represent a new therapeutic strategy for promoting liver regeneration.

Animals↗
PubMed2006

Gene transfer of kringle 1-5 suppresses tumor development and improves prognosis of mice with hepatocellular carcinoma.

BACKGROUND & AIMS: Recent studies indicate that kringle 1-5 has a potent and specific antiangiogenic activity. Here, we investigated the antitumor effect of kringle 1-5 gene transfer on hepatocellular carcinoma in mice. METHODS: The inhibitory effect of kringle 1-5 protein on proliferation of bovine capillary endothelial cells was evaluated by a tetrazolium-based assay. To study tumor growth, intrahepatic metastasis, and survival, liposome/kringle 1-5 complementary DNA complexes were injected intravenously in nude mice preimplanted with 1 of 3 hepatoma cell lines into the liver. Production of kringle 1-5 was tested by immunohistochemistry and Western blotting. Intratumoral vessel density was quantified. Expression of vascular endothelial growth factor, angiopoietin-1, and angiopoietin-2 in tumors was examined by Western blotting. Serum alanine aminotransferase and alpha-fetoprotein levels and body weights were measured. RESULTS: Proliferation of bovine capillary endothelial cells was inhibited by purified kringle 1-5 in a dose-dependent manner. Gene transfer of kringle 1-5 caused a significant reduction in vessel density with suppression of tumor growth of the 3 hepatoma cell lines and serum alpha-fetoprotein levels, prolonged the survival period, and reduced the number of intrahepatic metastases. Among the analyzed angiogenic factors, kringle 1-5 reduced angiopoietin-2 expression levels. Expression of kringle 1-5 protein was detected on hepatoma cells and hepatocytes in the liver. However, it did not alter serum alanine aminotransferase levels and body weights, suggesting kringle 1-5 lacks severe side effects. CONCLUSIONS: Antiangiogenic gene therapy with kringle 1-5 complementary DNA is a promising safe and effective strategy for suppression of growth of hepatocellular carcinoma.

Alanine Transaminase↗
PubMed2006

Late-onset ornithine transcarbamylase deficiency in male patients: prognostic factors and characteristics of plasma amino acid profile.

BACKGROUND: The occurrence of male patients with ornithine transcarbamylase (OTC) deficiency during adolescence or in adulthood has now been recognized. The aim of this study was to determine the prognostic factors that affect the prognosis of life, to explore a basis for therapeutic strategy. METHODS: In 10 patients, nine of whom carried the R40H mutation and the other one carrying the Y55D mutation in the OTC gene, 32 demographic and laboratory data were first compared between survivors and non-survivors, using the unpaired t-test. The factors with significant difference were then subjected to multiple regression analysis. RESULTS: The factors that exhibited significant difference were: age at onset, concentration of plasma ammonium, blood pH, and concentrations of six amino acids in plasma. The multiple regression analysis then revealed concentrations of ammonium, leucine, lysine, isoleucine, phenylalanine, glutamine and proline to be significant prognostic factors. The amino acid profile in the 10 patients showed increases in glutamine, proline, lysine, valine and methionine, and decreases in serine, ornithine and arginine. There was an inverse correlation between the age at onset and the level of the residual hepatic OTC activity. CONCLUSION: The results implied that: (i) the plasma amino acid profile was unique, in comparison to other liver diseases; (ii) the plasma concentration of each of the (mentioned above) six amino acids was a significant predictor of prognosis; and (iii) suppression of protein catabolism, as suggested by the higher concentrations in isoleucine and leucine in the non-survivors, prevention of glutamine-induced brain edema, correction of alkalosis, and supplementation with ornithine or arginine may improve the prognosis of life.

Adolescent↗
PubMed2006

Value of fusing PET plus CT images in hepatocellular carcinoma and combined hepatocellular and cholangiocarcinoma patients with extrahepatic metastases: preliminary findings.

BACKGROUND/AIMS: This study aimed to evaluate the usefulness of (18)F-fluoro-2-deoxy-d-glucose positron emission tomography (PET) and PET plus computed tomography (CT) fusion images for the detection of extrahepatic metastases of hepatocellular carcinoma (HCC) and combined hepatocellular and cholangiocarcinoma (combined HCC/CC). METHODS: Twenty-one patients with HCC and combined HCC/CC were enrolled in the study from December 2004 to February 2005. In all patients, PET and CT of the chest to pelvis region were performed. The sensitivity of PET plus CT fusion images was compared with the sensitivity of PET, CT, and bone scintigraphy. RESULTS: In 14 patients, a total of 58 extrahepatic metastases were diagnosed. The detection rate of PET plus CT fusion images, PET, CT, and bone scintigraphy was 98.2% (57 of 58 metastases), 89.6% (52 of 58 metastases), 91.2% (52 of 57 metastases), and 68.7% (11 of 16 bone metastases), respectively. No extrahepatic metastases were detected in the other seven patients. The detection rate of PET was 10/18 (55.6%) for intrahepatic lesions of HCC and combined HCC/CC. CONCLUSIONS: The fusion of PET plus CT images is useful in detecting extrahepatic metastases in HCC and combined HCC/CC patients.

Adult↗
PubMed2006

Antibody to hepatitis B core antigen is associated with the development of hepatocellular carcinoma in hepatitis C virus-infected persons: a 12-year prospective study.

Several studies have reported that antibody to hepatitis B core antigen (anti-HBc) positivity may influence the development of hepatocellular carcinoma (HCC) in chronic hepatitis C patients, but the evidence is still not conclusive. In this study, we examined whether the presence of anti-HBc positive was associated with the development of HCC in hepatitis C virus (HCV)-infected subjects among the residents in an HCV hyperepidemic area who were followed up for 12 years. In an HCV hyperendemic area (positive rate of anti-HCV: 23.4%), 509 residents were examined by health screening in 1990. After 12 years of follow-up, we evaluated the risk factors for HCC. The incidence of HCC was compared between anti-HBc positive and anti-HBc negative subjects after 12 years of prospective observation. Univariate and multivariate analyses were conducted to determine risk factors for the development of HCC. The incidence of HCC was significantly higher in the anti-HBc positive group (13 subjects) than in the anti-HBc negative group (0 subjects) (P=0.012). Multivariate analysis identified positivity for anti-HBc and HCV RNA, history of icterus, and female gender as independent determinants of the development of HCC. Our findings provide clear evidence in a prospective study that presence of anti-HBc, that is, past hepatitis B virus (HBV) infection, is a risk factor for the development of HCC in HCV-infected people.

Aged↗
PubMed2005

Timing of interferon therapy and sources of infection in patients with acute hepatitis C.

BACKGROUND/AIMS: Controversy over the selection of patients and optimum therapeutic method for acute hepatitis C has continued. The aims of this study were to investigate the source of infection, and to evaluate the timing of interferon (IFN) therapy in patients with acute hepatitis C in Japan. METHODS: The records of 102 patients from 12 facilities in Japan who developed acute hepatitis C after 1990 were investigated. In the patients treated with IFN, we performed multivariate analysis to investigate factors related to sustained virological response (SVR). RESULTS: Medical procedure was the most common source of infection, accounting for 32.4% in the 102 patients (33/102). Of 81 patients treated with IFN, 71 patients were followed after IFN therapy, and 57/71 (80.3%) had SVR. The SVR rate was significantly higher in patients treated with IFN within 24 weeks from onset of symptoms than the SVR rate in those treated after 25 weeks (P=0.0016). Multivariate analysis revealed that only the duration between onset of symptoms and initiation of IFN therapy (within 24 weeks) was related to SVR. CONCLUSIONS: Our multicenter cooperative survey revealed that medical procedure was the most frequent source of infection in acute hepatitis C. As concerns the therapy, interferon treatment should be initiated within 24 weeks after onset of symptoms.

Journal Article↗
PubMed2005

Clinical course of patients with chronic hepatitis B with viral breakthrough during long-term lamivudine treatment.

BACKGROUND: We evaluated the clinical course of patients with chronic hepatitis B who showed viral breakthrough during long-term lamivudine therapy. METHODS: We initially studied 141 patients treated with lamivudine for 1 year or more, and 49 patients who showed viral breakthrough were the subjects of this study. Their mean lamivudine administration period was 2.3 +/- 0.9 years. RESULTS: After viral breakthrough, breakthrough hepatitis occurred in 47 patients (95.9%), but did not occur in the other 2 (4.1%). Four of the 47 patients with breakthrough hepatitis were observed without further treatment, and the alanine transferase (ALT) level was normalized in 2 of them but fluctuated in the other 2. Breakthrough hepatitis was treated by injection of glycyrrhizin or ursodeoxycholic acid administration in 36 of the remaining 43 patients, and by antiviral drug administration in the other 7 (entecavir in 2 patients, adefovir in 2, and interferon in 3). The ALT level was normalized in 5 of the 36 patients treated with glycyrrhizin or ursodeoxycholic acid, but persistently fluctuated in the other 31. In those with normalized ALT after the occurrence of breakthrough hepatitis, the peak ALT level at that point was significantly lower (86 +/- 47 IU/l) than that in the patients without normalization (206 +/- 167 IU/l). CONCLUSIONS: These results showed that there were a few patients who did not develop breakthrough hepatitis after showing viral breakthrough, and some who showed normalization of the ALT level after the occurrence of breakthrough hepatitis, but in many patients, ALT continuously fluctuated.

Administration, Oral↗
PubMed2005

Exacerbation of oral erosive lichen planus by combination of interferon and ribavirin therapy for chronic hepatitis C.

Hepatitis C virus (HCV) induces extrahepatic manifestations such as oral lichen planus (OLP) as well as chronic liver diseases. The treatment of HCV-related chronic liver disease has evolved from the use of a single agent, mainly interferon (IFN), to the combination of IFN and ribavirin. We present a case of erosive OLP, cutaneous lichen planus (CLP), and leukoplakia of the vocal cord in a man with chronic hepatitis C infection treated with IFN and ribavirin. A 65-year-old man suffered from OLP before undergoing combination of IFN and ribavirin therapy for chronic hepatitis C. He was initially treated with IFNbeta (6 million units (MU) /day for 2 weeks), then a combination of IFNalpha-2b (6 MU/day for 2 weeks and 3 times a week for 14 weeks) and ribavirin (400-600 mg/day). The OLP lesion was not aggravated by application of steroids during the 7 weeks after the treatment, but after 18 weeks, the combination of IFN and ribavirin was stopped because of aggravation of the OLP. Elevated aminotransferase levels returned to normal during the therapy. But 7 weeks after discontinuation, aminotransferase levels rose to 10 times the normal range. Five months after discontinuation, the papules of CLP appeared. Eight months after discontinuation, the OLP erosion had gradually reduced, but some erosion remained. Aminotransferase levels were decreased, but serum HCV RNA had not disappeared. Caution should be exercised when IFN or ribavirin therapy is given to chronic hepatitis C patients with prior erosive OLP.

Aged↗
PubMed2005

Causal relationship between hepatitis C virus core and the development of type 2 diabetes mellitus in a hepatitis C virus hyperendemic area: a pilot study.

Hepatitis C virus (HCV) infection may contribute to the development of type 2 diabetes mellitus. However, this association at the population level remains unclear. The aim of this pilot study is to examine the relationship between HCV infection and the development of type 2 diabetes mellitus in an HCV hyperendemic area where we conducted health screenings in 1995. After 7 years of follow-up, we evaluated the relative risk of the development of type 2 diabetes mellitus in anti-HCV-inhabitants. Among 71 subjects free of diabetes mellitus in 1995, 7 developed type 2 diabetes mellitus during the 7-year follow-up evaluation. Overall, anti-HCV-positive subjects were nearly 3-fold as likely as anti-HCV-negative subjects to develop diabetes mellitus, but this difference was not statistically significant (p=0.08). After stratification of the anti-HCV-positive group according to serum HCV core titer, a significant increase in the incidence of diabetes was seen in subjects with high titer of HCV core compared to anti-HCV-negative subjects (p=0.02; relative hazard, 5.60; 95% confidence interval, 1.41 to 37.42). In conclusion, HCV infection potentially has a significant role in the development of type 2 diabetes mellitus at the population level. Further large-scale studies are needed to confirm these preliminary findings.

Diabetes Mellitus, Type 2↗
PubMed2005

Extrahepatic manifestations and insulin resistance in an HCV hyperendemic area.

Hepatitis C virus (HCV) causes extrahepatic manifestations as well as liver diseases, and contributes to insulin resistance and type 2 diabetes mellitus. The purpose of the present study was to evaluate the relationship of extrahepatic manifestations and insulin resistance in an HCV hyperendemic area. We investigated the incidence of extrahepatic manifestations among 139 inhabitants living in an HCV hyperendemic area in 2002 and compared it to 1999 data for the same inhabitants. Insulin resistance was tested for some non-HCV or HCV-infected inhabitants we had identified during mass screenings in 1999 and 2002. For some of the inhabitants in 2002, we examined records on the prevalence of insulin resistance seven years earlier. The prevalence of extrahepatic manifestations among individuals with positivity for anti-HCV antibodies was higher than among those without HCV in both 1999 and 2002. The prevalence of each extrahepatic manifestation which we identified in 2002 was higher than in 1999. Moreover, in some non-HCV or HCV-infected inhabitants, insulin resistance in 2002 was significantly higher than in 1999. Among inhabitants who had HCV infection with extrahepatic manifestations, fasting insulin levels or HOMA-IR findings seven years prior was significantly higher than for inhabitants who had neither HCV infection nor extrahepatic manifestations (p = 0.03, p = 0.01, respectively). Insulin resistance induces HCV infection, which causes an increase in the incidence of extrahepatic manifestations in HCV-infected individuals.

Aged↗
PubMed2004

Predicting relapse after cessation of Lamivudine monotherapy for chronic hepatitis B virus infection.

There have been reports of relapse after cessation of lamivudine monotherapy for hepatitis B virus (HBV) infection. The aim of this study was to examine factors that predict posttreatment relapse. Comparison 22 patients who experienced relapse with 11 who did not after cessation of therapy showed that predictive factors for nonrelapse were hepatitis B e antigen seroconversion and duration of undetectable HBV DNA load (<0.7 log IU/mL), as determined by HBV real-time detection direct testing. However, 7 of 12 patients with seroconversion experienced relapse after cessation of therapy. Multivariate analysis revealed that the duration of an undetectable HBV DNA load was the only independent predictive factor for nonrelapse (odds ratio, 0.50; 95% confidence interval, 0.27-0.9). More-prolonged lamivudine therapy is required after seroconversion, and persistent duration of an HBV DNA level of <0.7 log IU/mL for >6 months can more accurately aid in the decision of when to stop lamivudine therapy.

Adult↗
PubMed2004

Genetic heterogeneity of the precore and the core promoter region of genotype C hepatitis B virus during lamivudine therapy.

It has been reported that spontaneous or interferon (IFN)-induced hepatitis B e (HBe) seroconversion has usually been associated with the development of a stop codon in the precore region. However, the difference between lamivudine-induced seroconversion and spontaneous or IFN-induced seroconversion is not known. The aim of this study was to investigate the correlation between the evolution of the precore and core promoter mutations and lamivudine-induced seroconversion. Forty-five patients with chronic hepatitis B virus (HBV) infection who were treated with lamivudine for more than 1 year were enrolled. The nucleotide sequence of the precore and core promoter region was determined before and after treatment with lamivudine for 1 year. Among 29 patients who were hepatitis B e antigen (HBeAg)-positive before treatment, 12 (41.3%) lost HBeAg during the course of treatment for 1 year. Of these, eight patients (66.7%) still had precore wild type HBV after 1 year. After 1 year, reversion to precore wild type HBV was detected in 11 (64.7%) of 17 patients who had precore mutant HBV before treatment. Twelve (70.6%) of 17 patients who were persistently HBeAg-positive had precore wild type HBV before and after treatment for 1 year. Despite the loss of HBeAg, two thirds of the patients still had precore wild type HBV after the 1-year treatment. It is suggested that lamivudine-induced seroconversion differs from spontaneous or IFN-induced seroconversion in the change of nucleotides in the precore region. The reversion in the precore region may be caused by the difference of drug-susceptibility to lamivudine. The antiviral effect of lamivudine may be more effective in the precore mutant HBV than in the precore wild type HBV.

Adult↗
PubMed2004

Analysis of approach to therapy for chronic liver disease in an HCV hyperendemic area of Japan.

In 1990, we conducted an epidemiological study of 509 residents in a hepatitis C virus (HCV) hyperendemic area in Japan. The purpose of the present study was to examine the approach to therapy for liver diseases accompanied by HCV and hepatitis B virus (HBV) infections among the surviving residents in the town after 12 years. Fifty-three with HCV or HBV infections among 385 people who resided in the town were clearly analyzed in 2002. The number of persons diagnosed with the liver diseases was as follows: HCV-related asymptomatic healthy carrier (1), past history of HCV infection (15), chronic hepatitis C (22), HCV-related liver cirrhosis (6), HCV-related hepatocellular carcinoma (HCC) (5), and HBV-related asymptomatic healthy carrier (4). HCC was detected in residents who did not have periodic regular hospital checkups. Only 19% of the 53 inhabitants consulted liver medical specialists, and 75% (3/4) who received interferon therapy received treatment from a liver medical specialist. It is necessary to provide continuous medical treatment to HCV carriers, minimizing difference in treatment quality in different medical institution. An efficient HCV medical checkup and a program of subsequence health management are important problems to be solved for improved health care.

Journal Article↗
PubMed2004

Development of quantitative neuropsychological tests for diagnosis of subclinical hepatic encephalopathy in liver cirrhosis patients and establishment of diagnostic criteria-multicenter collaborative study in Japanese.

At present, there are no generally accepted diagnostic criteria or methods for subclinical hepatic encephalopathy (SHE) associated with liver cirrhosis. We therefore developed an easily conducted computer-aided quantitative neuropsychiatric function test system for use in routine medical practice. We established normal values in healthy Japanese subjects and determined differences between healthy persons and liver cirrhosis patients without clinical encephalopathy in a multi-center clinical trial. The test system consists of eight tests: number connection tests A and B, a figure position test, a digit symbol test, a block design test, and reaction time tests A, B and C. The test results were affected by age, but not by gender or facility. No learning effect was noted. The results were therefore reported by 5-year quartile ranges and differences were evaluated between 542 healthy subjects and 292 cirrhotic patients. When the cut-off value was set at the 10th/90th percentile of the results in healthy subjects, the results of each of the 8 tests were abnormal in about 25% of cirrhotic patients, and at least 1 of the 8 tests gave values greater than the 10th/90th percentile cut-off value in 58.2% of the 292 liver cirrhosis patients. SHE patients were thought to be included in these 58.2% of patients. The developed test makes it possible to quantitatively assess neuropsychiatric function, and the results obtained can be used as a basis for the diagnosis of SHE.

Journal Article↗