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Gemcitabine is a deoxycytidine analogue that has a broad spectrum of antitumour activity in many solid tumours including pancreatic cancer. We have recently carried out a pharmacogenomic study in cancer patients treated with gemcitabine, and found that one genetic polymorphism of an enzyme involved in gemcitabine metabolism can cause interindividual variations in the pharmacokinetics and toxicity of this agent. In this paper, we review recent genetic studies of gemcitabine, and discuss the possibility of individualised cancer chemotherapy based on a pharmacogenomic approach.British Journal of Cancer (2007) 97, 145–151. doi:10.1038/sj.bjc.6603860 www.bjcancer.com Published online 26 June 2007 [ABSTRACT FROM AUTHOR]

We sought to clarify the incidence and role of Helicobacter pylori ( H. pylori) seropositivity in patients with hepatitis C virus (HCV) infection and the effect of coinfection on interferon- α and ribavirin therapy. The presence of H. pylori was tested using a commercially available enzyme immunoassay in serum samples from 93 patients with chronic hepatitis C. Clinical features, HCV markers and response of HCV to interferon- α and ribavirin were compared between H. pylori-positive and H. pylori-negative patients. Anti- H. pylori antibody was detected in 45 (48%) of the 93 patients, whose median HCV-RNA level (495 vs 760 kIU/mL; P = 0.013) and platelet count (128 vs 158 × 103/ μL; P = 0.009) were significantly lower than in patients with HCV infection alone. Anti- H. pylori antibody levels were found to be significantly correlated with fibrosis score ( P = 0.0083, r = 0.33) but inversely related to platelet count ( P = 0.0037, r = −0.34). The sustained response rate for HCV clearance following interferon- α and ribavirin treatment did not differ between patients with and without anti- H. pylori seropositivity. The presence of H. pylori [odds ratio (OR) 8.61; 95% confidence interval (CI) 1.59–46.70] and fibrosis score (OR 30.13; 95% CI 5.44–166.78) were found by multivariate analysis to be associated with the decrease of platelet count during therapy. Coexistent H. pylori infection does not demonstrably influence the clinical course of chronic hepatitis C. A possible connection between H. pylori coinfection and thrombocytopenia was found during the treatment course, suggesting that preemptive eradication of H. pylori may facilitate completion of treatment and increased sustained virological response. [ABSTRACT FROM AUTHOR]

Background: Autoimmune pancreatitis is a unique form of chronic pancreatitis characterized by high serum IgG4 concentrations and abundant IgG4-bearing plasma cell infiltration in the pancreatic lesion, and it has been reported to be associated with a variety of extrapancreatic lesions, leading us to postulate the concept of a systemic inflammatory disease. To confirm this, we clarified the exact distribution of these extrapancreatic lesions and provide a panoramic view of them.Methods: The frequency, distribution, clinical characteristics, and pathology of five extrapancreatic lesions were determined in 64 patients with autoimmune pancreatitis by examining clinical and laboratory findings.Results: The most frequent extrapancreatic lesion was hilar lymphadenopathy (80.4%), followed by extrapancreatic bile duct lesions (73.9%), lachrymal and salivary gland lesions (39.1%), hypothyroidism (22.2%), and retroperitoneal fibrosis (12.5%). No patients had all five types of lesions. Patients with hilar lymphadenopathy or lachrymal and salivary gland lesions were found to have significantly higher IgG4 levels than those without (P = 0.0042 and 0.0227, respectively). Patients with three lesions were found to have significantly higher IgG4 levels than those with no lesion, suggesting that patients with multiple extrapancreatic lesions have active disease. Similar to pancreatic lesions, extrapancreatic lesions have a characteristic histological finding of abundant IgG4-bearing plasma cell infiltration, and they respond favorably to corticosteroid therapy.Conclusions: Autoimmune pancreatitis was recognized as a systemic inflammatory disease. Furthermore, recognition of these characteristic findings will aid in the correct diagnosis of this disease. [ABSTRACT FROM AUTHOR]

Pancreatic adenocarcinoma is an aggressive human malignancy and is characterized by resistance to apoptosis. Recently, NADPH oxidase (Nox) 4-mediated generation of intracellular reactive oxygen species (ROS) was proposed to confer antiapoptotic activity and thus a growth advantage to pancreatic cancer cells. The signaling mechanism by which Nox4 transmits cell survival signals remains unclear. Here, we show that both a flavoprotein inhibitor, diphenylene iodonium (DPI), and small interfering RNAs designed to target Nox4 mRNA (siNox4RNAs) inhibited superoxide production in PANC-1 pancreatic cancer cells, and depletion of ROS by DPI or siNox4RNAs induced apoptosis. Parallely, DPI treatment and siNox4RNA transfection blocked activation of the cell survival kinase AKT by attenuating phosphorylation of AKT. Furthermore, AKT phosphorylation of apoptosis signal-regulating kinase 1 (ASK1) on Ser-83 was reduced by DPI and siNox4RNAs. When ASK1Ser83Ala (an AKT phosphorylation-defective ASK1 mutant) was introduced into PANC-1 cells, this mutant alone induced apoptosis. But, addition of DPI or co-transfection of siNox4RNA had no additive effect, indicating that the mutant can substitute for these reagents in apoptosis induction. Taken together, these findings suggest that ROS generated by Nox4, at least in part, transmit cell survival signals through the AKT–ASK1 pathway in pancreatic cancer cells and their depletion leads to apoptosis.Oncogene (2006) 25, 3699–3707. doi:10.1038/sj.onc.1209406; published online 13 March 2006 [ABSTRACT FROM AUTHOR]

We report a 72-year-old female on long-term hemodialysis, who was admitted to the hospital because of hematemesis. On emergency laparotomy, pylorogastrectomy was performed. The resected specimen showed a giant hematoma and traversing fissure along the lesser curvature of the body of the stomach. Histologically, the specimen showed wide hematoma formation and amyloid deposits in the submucosal layer, especially in the wall of blood vessels. These deposits reacted positively to antihuman β2- microglobulin antibody. The post-operative course was favorable, and the patient was discharged on the 35th hospital day. In this case, the laceration site on the gastric mucosa was almost intact and did not demonstrate ischemic change, suggesting that the giant hematoma was caused by submucosal vessel rupture, which led to the gastric mucosa laceration. To our knowledge, this is the first case of gastric mucosa laceration associated with dialysis-related amyloidosis. [ABSTRACT FROM AUTHOR]

We investigated the presence of antibodies to hepatitis E virus (anti-HEV) and hepatitis A virus (anti-HAV) by enzyme immunoassays in sera from 1015 individuals collected in 1974, 1984 and 1994. Age-specific profiles of anti-HEV remained unchanged with a peak at 40–49 years, while those of anti-HAV started to increase in individuals aged 20–29 years in 1974, 30–39 years in 1984 and 40–49 years in 1994. These results suggest that a silent HEV infection has been taking place in the last 20 years or so in Japan, while HAV infection has been terminated at least since 1974. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cell-type lymphoproliferative diseases of granular lymphocytes can be subdivided into aggressive NK cell leukemia (ANKL) and chronic NK cell lymphocytosis (CNKL). One reason for the poor outcome in ANKL is leukemic infiltration into multiple organs. The mechanisms of cell trafficking associated with the chemokine system have been investigated in NK cells. To clarify the mechanism of systemic migration of leukemic NK cells, we enrolled nine ANKL and six CNKL cases, and analyzed the expression profiles and functions of chemokine receptors by flowcytometry and chemotaxis assay. CXCR1 was detected on NK cells in all groups, and CCR5 was positive in all ANKL cells. Proliferating NK cells were simultaneously positive for CXCR1 and CCR5 in all ANKL patients examined, and NK cells with this phenotype did not expand in CNKL patients or healthy donors. ANKL cells showed enhanced chemotaxis toward the ligands of these receptors. These results indicated that the chemokine system might play an important role in the pathophysiology of ANKL and that chemokine receptor profiling might be a novel tool for discriminating ANKL cells from benign NK cells.Leukemia (2005) 19, 1169–1174. doi:10.1038/sj.leu.2403732 Published online 19 May 2005 [ABSTRACT FROM AUTHOR]

Thymalfasin (thymosin alpha-1; Tα1) is a 28-amino acid polypeptide that has shown efficacy in the treatment of chronic hepatitis B virus (HBV) infection. The objective of this study was to evaluate the long-term, dose-related efficacy and safety of Tα1 treatment in chronic hepatitis B patients with positive HBV-DNA and abnormally high alanine aminotransferase (ALT) levels. A total of 316 patients were randomized to receive either 0.8 or 1.6 mg of Tα1 monotherapy for 24 weeks. At the end of the 72-week observation period (12 months after cessation of therapy), 36.4% of patients in the 1.6-mg treatment group achieved normalization of ALT, 30% achieved clearance of HBV-DNA by branched DNAvs15% by transcription-mediated amplification, and 22.8% achieved clearance of HBe-antigen. Patients in the 0.8-mg treatment group achieved similar efficacy rates, although patients with advanced fibrosis demonstrated a significantly better response rate when treated with 1.6 mg of Tα1 monotherapyvs0.8 mg (as determined by intragroup analysis; patients were not stratified by liver biopsy). All adverse drug reactions were mild and most involved the fluctuation of liver enzymes, which was most likely related to the positive immune effects caused by the response to Tα1 treatment. Adverse event incidence was similar in the 1.6- and 0.8-mg treatment groups. In conclusion, Tα1 at doses of 0.8 and 1.6 mg exhibits long-term efficacy against hepatitis B with a good safety profile. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) causes persistent infection in most patients. To clarify the mechanisms underlying establishment of this persistent infection, nucleotide sequences of the E1/E2 region were characterized in 5 patients with acute and chronic HCV infection. We used direct DNA sequencing methods to identify the major sequence of HCV in each patient. Each HCV genome displayed a high frequency of nucleotide sequence variation in the hypervariable region (HVR) of E2. However, patient-specific conserved nucleotide sequences were identified in the E1/E2 region during the course of infection and conserved the higher-order protein structure. In the acute phase HCV infection, amino acid substitution in HVR-1 as the monthly rate of amino acids substitution per site (%) between each point exceeded 10.2%. In the chronic phase HCV infection, a significantly lower rate of amino acid substitution was observed in patients. The host immune responses to HVR-1 of each HCV isolates from all clinical courses were characterized using synthetic peptides and ELISA. One chronic patient serum (genotype 1b) did not react at all to its own HVR-1 peptides, however another patient (genotype 2b) reacted to all clinical course. These results indicated that HVR-1 might not always exhibit neutralizing epitopes of HCV infection. The sequence variation in HVR-1 may instead indicate the existence of various clones in acute phase infection and the adaption of these clones is thought to have caused persistent and chronic infection in each patient. [ABSTRACT FROM AUTHOR]

BACKGROUND: A prospective study was conducted to evaluate the influence of host factors, including human leukocyte antigen (HLA), and viral factors, including hepatitis C virus (HCV) core antigen, on the response to interferon (IFN)-Alpha. METHODS: Natural IFN-Alpha was given to 66 patients with chronic hepatitis C at a dose of 9 million units per day for 2 weeks, followed by 9 million units three times a week for 22 weeks. RESULTS: Sustained virological response without detectable HCV RNA in serum 24 weeks after the end of IFN therapy was achieved in 21 patients, while it was not in 32 patients; the remaining 13 patients were not evaluated. HCV core antigen and HCV RNA started to decrease 1 and 4 weeks, respectively, after the commencement of IFN in responders ( P = 0.02 and P = 0.05, respectively). On univariate analysis, age of 50 years or less ( P < 0.001); lack of HLA DR6 ( P = 0.018) or DR52 ( P < 0.041); platelets more than 14 x 10(4)/mm(3) ( P = 0.031); HCV core antigen 500 fmol/l or less ( P = 0.001); and HCV RNA 100 KIU/ml or less were predictive of response. On multivariate analysis, age 50 years or less (odds ratio [OR], 4.009; P = 0.039); lack of HLA DR6 (OR, 8.130; P = 0.027); IFN-naive (OR, 11.63; P = 0.016); HCV core antigen 500 fmol/l or less (OR, 10.61; P = 0.007); and genotypes other than 1b (OR, 8.929; P = 0.010) were predictive of response. CONCLUSIONS: Lack of HLA DR6 determined the response to IFN. HCV core antigen was useful in predicting and monitoring the response to IFN. [ABSTRACT FROM AUTHOR]

Interferon therapy for chronic hepatitis C reduces the risk of hepatocellular carcinoma, especially among virological and biochemical responders. However, little is known about the effect of interferon therapy on mortality. We studied the long-term effect of interferon therapy on mortality in patients with chronic hepatitis C. For this retrospective cohort study, 2954 patients with chronic hepatitis C were recruited, of whom 2698 received interferon therapy and 256 did not. The effect of interferon therapy on survival was assessed by standardized mortality ratio (SMR) based on published mortality data for the general Japanese population and by risk ratio calculated by proportional hazard regression. Over 6.0 ± 2.2 years follow-up, death from liver-related diseases was observed in 69 (68%) of 101 deaths among interferon-treated patients and in 42 (81%) of 52 deaths among untreated patients. Compared with the general population, overall mortality was high among untreated patients (SMR: 2.7; 95% CI: 2.0–3.6) but not among interferon-treated patients (SMR: 0.9; 95% CI: 0.7–1.1). Liver-related mortality was extremely high among untreated patients (SMR: 22.2; 95% CI: 16.0–30.0) and less among interferon-treated patients (SMR: 5.5; 95% CI: 4.3–6.9). The risk of death from all causes was lower for interferon-treated than untreated patients (risk ratio: 0.47; 95% CI: 0.261–0.836; P = 0.01). The risk of death from liver-related diseases was significantly lower for sustained virological responders (risk ratio: 0.04; 95% CI: 0.005–0.301; P = 0.002) compared with untreated patients, but not for nonsustained virological responders. Sustained biochemical responders (risk ratio: 0.03; 95% CI: 0.004–0.230; P < 0.001) and transient biochemical responders (risk ratio: 0.18; 95% CI: 0.063–0.532; P = 0.002) showed a significantly reduced risk of death from liver-related death, whereas biochemical nonresponders did not. Hence interferon treatment improved survival in chronic hepatitis C patients showing a biochemical as well as a virological response by preventing liver-related deaths. [ABSTRACT FROM AUTHOR]

Summary. We aimed to assess the clinical performance of a newly developed chemiluminescence enzyme immunoassay (CLEIA) for the detection of hepatitis B virus (HBV) core-related antigen (HBcrAg) in patients with chronic HBV infection. A total of 82 patients with chronic HBV infection and 167 HBV-negative controls were studied. HBcrAg was measured by CLEIA with monoclonal antibodies to hepatitis B e antigen (HBeAg) and hepatitis B core antigen (HBcAg), and HBV DNA was measured by transcription-mediated amplification assay (TMA) and in-house real-time detection polymerase chain reaction (RTD-PCR). The HBcrAg assay detected viremia in 189 of 216 samples (88%) collected from 72 patients whilst the TMA assay detected viremia in 178 of the 216 samples (82%) (P = 0.019). The HBcrAg concentration correlated linearly with the HBV DNA concentration (P < 0.001) over a range which varied 100 000-fold. The accuracy in the measurement of the patients’ HBV load obtained using the HBcrAg assay was not affected by the absence of hepatitis B e antigen from the serum or the presence of precore mutations in the HBV genome. In patients without anti-viral drugs, changes in their serum HBcrAg concentration over time corresponded to their HBV DNA concentration. In six additional patients who were later treated with lamivudine, HBV DNA concentration declined more rapidly than their HBcrAg concentration. Three months after treatment commenced, the ratio of HBcrAg: HBV DNA had increased in all six patients (P = 0.031). The HBcrAg assay is a sensitive and useful test for the assessment of a patient's HBV load. When monitoring the anti-viral effect of lamivudine, HBcrAg provides a viral marker which is independent of HBV DNA. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) causes various grades of chronic liver disease, ranging from an asymptomatic state to cirrhosis. To assess genetic factors of disease severity, we selected two HCV patient groups according to the following stringent criteria: (i) asymptomatic carrier state (ASC) defined by HCV infection for more than 20 years, normal alanine aminotransferase levels for the past 5 years as well as normal liver histology and/or shape and (ii) liver cirrhosis (LC) as diagnosed by clinical symptoms, liver biopsy and/or ultrasonography. A total of 103 chronically infected Japanese HCV patients (43 ASC and 60 LC) were analyzed. HLA class I and II alleles were established using low resolution DNA typing. HLA-DRB1 and DQB1 genotypes were inferred upon polymerase chain reaction-restriction fragment length polymorphism analysis. Two hundred and one anti-HCV-negative ethnically matched controls were included. The frequencies of DRB1*12 (*1201 and *1202), DQB1*0301 and DRB3*03 alleles were higher in patients with ASC than in those with LC (odds ratio (OR) 11.23, OR 4.25, and OR 3.22, respectively). The frequency of DQB1*0503 were lower in ASC patients compared to LC patients (OR 0.05). No significant differences between groups were observed for age, sex, source of infection, HCV genotype or viral loads. Our findings establish that certain HLA class II alleles strongly influence disease progression following HCV infection. [ABSTRACT FROM AUTHOR]

Discusses the case of an 83-year-old female patient presenting with low grade mucosa associated lymphoid tissue (MALT) lymphoma of the esophagus. Clinical signs and symptoms; Genetic features of MALT-type lymphoma; Disease background.

Background: Type A hepatitis is still a considerable problem in both underdeveloped and developed countries. Why some patients progress to fulminant type A hepatitis and others do not is unclear. Aims: To determine if nucleotide differences in the genome of hepatitis A virus (HAV) are responsible for the range of clinical severities, we analysed the 5' non-translated region (5'NTR) of the HAV genome, which has an internal ribosomal entry site and is important for cap independent translation of the viral message. Methods: Serum samples from 84 Japanese patients with sporadic type A hepatitis from five distant regions of Japan, comprising 12 patients with fulminant hepatitis (FH), 13 with severe acute hepatitis (AHs), and 59 with acute hepatitis (AH), were examined for HAV RNA. The fragment between nucleotides 75 and 638 of the 5'NTR was amplified by reverse transcription-polymerase chain reaction, and the nucleotide sequence was determined by direct sequencing. Results: Comparison of sequences of the 5'NTR revealed relatively fewer nucleotide substitutions in FH and AHs patients compared with the considerable sequence variations found in strains of AH. This tendency was most prominent between nucleotides 200 and 500. Strains from FH and AHs cases had fewer nucleotide substitutions (p<0.001) in this region. Conclusions: Nucleotide variations in the central portion of the 5'NTR of HAV may influence the severity of type A hepatitis. [ABSTRACT FROM AUTHOR]

Background: To study the association, clinical significance, and impact of hepatitis C virus (HCV) co-infection in patients with schistosomal liver disease (SLD).Methods: A total of 240 patients with chronic liver diseases encountered consecutively were enrolled in the study. Fifty volunteer blood donors were enrolled as controls. HCV antibody determination (enzyme-linked immunosorbent assay), qualitative and quantitative HCV RNA assay (reverse transcriptase polymerase chain reaction), and HCV genotyping (line probe assay) were performed.Results: Twenty-eight patients had SLD alone, 60 had both SLD and chronic hepatitis C (CH-C), 120 had CH-C alone, and 32 had other liver diseases. The positivity rates for HCV antibody (76% vs 20%; P < 0.001) and HCV RNA (59% vs 10%; P < 0.001) were significantly higher in the patients with SLD (n = 88) than in the volunteer blood donors (n = 50). Complications of liver cirrhosis were more common in patients with concomitant SLD and CH-C than in those with either SLD or CH-C alone. The mean levels of alanine aminotransferase (77 +/- 42 vs 93 +/- 55 IU/l; P = 0.049) and HCV RNA concentrations (3.5 +/- 1.0 vs 4.2 +/- 1.0 log copy/ml; P < 0.001) were significantly lower in patients with concomitant SLD and CH-C than in those with CH-C alone. HCV genotype 4 predominated in both these groups (93% and 98%).Conclusions: SLD in Egypt is significantly associated with HCV infection, with the predominance of genotype 4. Concurrent HCV infection and SLD result in much more severe liver disease than that seen with either disease alone. However, the activity of HCV infection seems to be partially suppressed in patients with SLD. [ABSTRACT FROM AUTHOR]

A feature of hepatocellular carcinoma (HCC) is that antecedent liver cirrhosis and chronic hepatitis are common precursor conditions and during transition to malignancy some patients develop autoantibodies which were not present during the preceding chronic liver disease phase. Serum samples from such patients can be used to immunoscreen cDNA expression libraries to identify genes encoding the new autoantigens. We demonstrate here the de novo appearance of antibodies to p62, a cytoplasmic protein which has been shown to bind to a developmentally regulated fetal species of insulin-like growth factor II (IGF-II) mRNA. Another antibody appearing during the transition period was against CENP-F, a cell cycle-related nuclear protein with maximum expression in the G2 and M phases of the cell cycle and previously shown to have a high association with malignancy. In three additional patients in whom serial serum samples were examined, new appearance of anti‐p62 was detected in two patients and anti-CENP-F in one patient. This study demonstrates that transition to malignancy can be associated with autoantibody responses to certain cellular proteins which might have some role in tumorigenesis. [ABSTRACT FROM AUTHOR]

Background. Steroids have been used for patients with some histologic groups of lupus nephritis with/without nephrotic-range proteinuria. However, many patients exhibit steroid-resistance, steroid-dependence, and/or frequent relapse, and there are many adverse effects. Recently, cyclosporin (CsA) has been reported to be effective for steroid-resistant nephrotic syndrome; however, with high-dose use, it produces specific adverse effects, especially nephrotoxicity. Here, we report results with the administration of low-dose CsA to patients with systemic lupus erythematosus (SLE). Methods. We treated three patients with steroid-resistant lupus nephritis with CsA (80–100 ng/ml blood trough level) for 6 months, and investigated the effect of CsA on lupus nephritis and SLE activity. Results. Mean pretreatment and posttreatment values for both 24-h urine protein excretion and total protein improved after treatment. Furthermore, SLE disease activity index scores, and levels of complements, anti-unclear antibody (ANA), anti-DNA antibody, and immune complexes in the three patients also improved. Conclusions. Our results support the idea that low-dose CsA is effective for nephrotic-range proteinuria caused by lupus nephritis, and show that this treatment may decrease SLE activity, without producing severe adverse effects. [ABSTRACT FROM AUTHOR]

Examines the characteristics on T cells in patients with chronic hepatitis C (CHC). Role of T cells in the immunopathogenesis of hepatic inflammation; Analysis of the complementarity-determining region 3 size lengths of T cell receptor; Pathogenesis of hepatocyte destruction in CHC.

AbstractTo facilitate pancreatic stone retrieval, four patients with chronic pancreatitis and pancreatic stones underwent endoscopic pancreatic sphincter balloon dilation (EPSBD) rather than pancreatic sphincterotomy. Extracorporeal shock wave lithotripsy combined with endoscopic removal was carried out in three patients. Stone removal following EPSBD was completely successful in all four patients. Patients showed no severe complications during the dilation procedure. In one patient, to prevent pancreatitis, an endoscopic nasopancreatic drain was placed for 1 week after EPSBD. Compared with pancreatic sphincterotomy, EPSBD can be performed safely in patients with chronic pancreatitis to assist in the extraction of pancreatic duct stones. Use of the EPSBD procedure in cases of chronic pancreatitis provides a useful approach to improve endoscopic clearance of pancreatic duct stones. [ABSTRACT FROM AUTHOR]

To study the prevalence and clinical significance of TT virus (TTV) infection in hemodialysis patients, we tested for TTV DNA in serum, using the nested polymerase chain reaction. The prevalence of TTV DNA in 352 hemodialysis patients was 32%, significantly higher than that in 50 healthy blood donors (12%). The prevalence increased with age (P = 0.0098): it was 20% (22/110) in patients aged less than 49 years, 37% (69/188) in those aged 50-69 years, and 41% (22/ 54) in those aged over 70 years. Other clinical features and the prevalence of other hepatitis viral markers tested did not differ between patients with TTV DNA and those without it. The detection rate of hepatitis C virus (HCV) and hepatitis G virus (HGV) viremias increased with duration of hemodialysis and with the number of blood transfusion units, but the prevalence of TTV viremia did not. Twenty-nine of 91 patients followed for 5 years were initially positive for TTV DNA. Of these 29 patients, 17 (59%) carried this viremia for at least 5 years. Fourteen of the 62 patients (23%) who were initially negative for TTV DNA acquired TTV viremia. Serum alanine aminotransferase (ALT) levels were elevated in patients with HCV viremia but not in patients with HGV or TTV viremia. However, the mean ALT level in patients with all three viremias (HCV, HGV, and TTV) was significantly higher than that in patients with one or two of the viremias. More than 30% of the hemodialysis patients had TTV viremia and the carrier state was maintained for years. The hemodialysis procedures, including blood transfusion, did not seem to be crucial for the transmission of TTV. The pathogenic effects of TTV on hepatitis appear to be limited. [ABSTRACT FROM AUTHOR]

Key words: ascites; Crow-Fukase syndrome; immunoadsorption plasmapheresis; interleukin-6 [ABSTRACT FROM PUBLISHER]

A fluorescence enzyme immunoassay (FEIA) for the quantitative measurement of hepatitis C virus (HCV) core protein has recently been developed. In this study, we studied the clinical usefulness of this measurement in patients with acute hepatitis C. Eighteen patients with post-transfusion acute hepatitis C were enrolled in the study; 5 patients showed resolution of hepatitis with disappearance of HCV viremia, while the remaining 13 patients did not. A second generation HCV antibody, HCV RNA, and HCV core protein were measured in serial serum samples taken within 1 month of the onset of acute hepatitis and 3, 6, 12, 24, and 36 months after onset. Within the first month after disease onset, the positivity rates of HCV RNA (100%; P = 0.0014) and HCV core protein (89%; P = 0.0300) were both significantly higher than that of HCV antibody (56%). Six months after disease onset, the positivity rate of HCV antibody had increased, to 100%, and the positivity rates of HCV RNA and HCV core protein began to decrease. HCV core protein levels did not differ between patients with resolved and unresolved disease in the first month after disease onset. These findings indicate that FEIA, a simple assay, for the measurement of HCV core protein was useful for the early diagnosis of acute hepatitis C. [ABSTRACT FROM AUTHOR]

Two patients with acute hepatitis B with suggested sexual transmission of hepatitis G virus (HGV) are reported. A total of 18 patients with community acquired acute hepatitis B were analyzed in this study. Two of the 18 patients (patients 1 and 2) were positive for serum HGV RNA at the initial consultation. Both patients had had sexual contact with prostitutes several weeks before the onset of acute hepatitis, and hepatitis B virus (HBV) was suggested to be infected through the sexual contacts. These patients showed no other history of exposure to possible transmission routes for blood-borne hepatitis viruses. Patient 1 was diagnosed as with acute HGV infection because the antibody to HGV envelope-2 protein seroconverted to positive during the course of acute hepatitis. HGV RNA was negative in a serum sample collected from patient 2 before the onset of acute hepatitis, also suggesting acute HGV infection. These results indicate that in patients 1 and 2 HGV was infected along with HBV through sexual contact. The clinical manifestations of acute hepatitis in the two patients with HGV co-infection did not differ from those in the 16 patients with HBV infection alone. [ABSTRACT FROM AUTHOR]

Assessment of anti-proliferative effects of unmodified antisense oligodeoxynucleotides targeted against c-raf mRNA. Actions to unrelated antisense mechanism; Independence of the effects of phosphorothioate and phosphodiester; Modification of synthetic carriers.

The salt-tolerant alga Chara longifolia (Robinson) is capable of regulating its turgor in response to hypotonic pressure of the medium. This regulatory process takes only 40 min in small cells (length &les; 10 mm), but requires 3 d in large cells (length &ges; 30 mm). Turgor regulation in small cells is comprised of two phase is inhibited by reducing the contration of Ca2+ in the external medium from 4.6 to 0.01 mol m-3; the first phase is less affected by the reduction of Ca2+. In the first 5 min of stress, the membrane depolarizes in a voltage-dependent transiently and cytoplasmic streaming is inhibited. When the external Ca2+ concentration is lowered, conductance does not increase and streaming continues unaffected. In the medium for turgor regulation. To test the hypothesis that there is increased Ca2+ entry from the medium during turgor regulation, we measured the influx of 45Ca2+ into the cell. We found an increased influx of Ca2+, from 18 to 36 nol m-2 s-1 during the first 30 to 90 s following osmotic stress. This increase was evident only in cells below about 7 mm in length, and was more marked in smaller cells. [ABSTRACT FROM AUTHOR]

Survival and death of Chara internodal cells were investigated in one of the alkali metal salts KCl, some of the alkali earth metal salts CaCl2, Ca(NO3)2, MgCl2, Mg(NO3)2, SrCl2, Sr(NO3)2, BaCl2, and Ba(NO3)2, potassium phosphate pH buffer solution (pH 7.0). Tris-maleate pH buffer solution (pH 7.0), HEPES (N-2-hydroxyethylpiperazine-N'-2- ethancsulphonic acid)-KOH (pH 7.0) pH buffer solution, calcium buffer solutions, and deionized water. Most of the internodal cells died within a day or a few days in KCl, MgCl2, Mg(NO3)2, BaCl2, and Ba(NO3)2, solutions of higher concentrations, calcium butler solutions of pCa 6.0, 10.0 mol m-3 potassium phosphate pH buffer solution and 10.0 mol m-3. Tris-maleate pH buffer solution. However, all of the internodal cells survived more than 10 d in deionized water, 80.0 mol m-3 CaCl2, 80.0 mol m-3 Ca(NO3)2, 80.0 mol m-3 SrCl2. 80.0 mol m-3 Sr(NO3)2, calcium buffer solutions of pCa 4.0 and pCa 5.0, and 10.0 mol m-3 HEPES-KOH (pH 7.0) pH buffer solution. Addition of Ca2+ or Sr2+ to K+, Mg2+ and Ba2+ salt solutions increased the survival rates of the internodal cells. Calcium release from the internodal cell wall was measured in deionized water, KCI, NaCI, MgCl2, CaCl2, SrCl2 and BaCl2 solutions. Except in deionized water and CaCl2, solution, most of the calcium binding to the cell wall was released within one or a few hours in respective electrolyte solutions. Thus, survival and death of the internodal cells in the electrolyte solutions tested were interpreted in terms of the calcium release from the cell wall and the cell membrane, and intrinsic ability of Sr2+ to maintain the cell membrane normal. [ABSTRACT FROM AUTHOR]

A 58-year-old woman who had undergone resection of insulinoma 14 year earlier visited our clinic complaining of abdominal discomfort. Computerized tomographic scan showed multiple liver tumors, and a diagnosis of metastatic tumor of malignant islet cell tumor was confirmed histologically. No oversecretion of hormones or hypoglycemic episode was observed on readmission. Thus, the insulinoma seemed to have transformed to a clinically non-functioning tumor. The patient was treated with transcatheter arterial embolization, resulting in clinical improvement with marked reduction in tumor size. Features of interest in this case included; (1) transformation to non-functioning metastatic liver tumor 14 years after resection of insulinoma, (2) the usefulness of transcatheter arterial embolization for multiple metastatic tumor of malignant islet cell tumor. [ABSTRACT FROM AUTHOR]

The characteristic features of a 48-year-old male presenting with isolated acromegaly caused by a GRH-producing pancreatic endocrine tumor bearing no relation to MEN1 was reported. The clinical features, laboratory findings, and sellar enlargement were improved after removal of the pancreatic tumor. The resected pancreatic tumor showed positive GRH immunoreactivity and contained abundant GRH mRNA. This tumor is extremely rare and to date only 10 cases have been reported. In the management of acromegaly, the measurement of GRH is recommended and the search for an ectopic source will prevent unnecessary and potentially ineffective pituitary surgery. [ABSTRACT FROM AUTHOR]

Tenascin, an extracellular matrix glycoprotein, has been reported to be expressed predominantly on glioma tissue in the CNS, both in a cell associated and an excreted form. Recently, a highly sensitive sandwich type enzyme immunoassay for quantitative determination of tenascin was developed. In the present study, the amount of tenascin in CSF was measured. An increase of tenascin in CSF (> 100 ng/ml) was found in patients with an astrocytic tumour. The concentration was significantly higher (> 300 ng/ml) in high grade astrocytoma (anaplastic astrocytoma and glioblastoma) and a further increase (> 1000 ng/ml) was found in cases of CSF dissemination of high grade astrocytoma. On the other hand, tenascin concentrations were less than 100 ng/ml in non-astrocytic tumours and non-neoplastic neurological diseases, except meningeal dissemination of tumour cells, meningeal stimulation by infection, and subarachnoid haemorrhage. In cases of treated astrocytomas in remission, tenascin was negligible (< 100 ng/ml) in the CSF. The measurement of tenascin in CSF is useful for differential diagnosis of brain tumours and monitoring of astrocytic tumours. [ABSTRACT FROM AUTHOR]

The localization of hepatitis C virus (HCV) in the liver has not been well clarified. We report successful indirect immunoperoxidase staining of the HCV core antigen using polyclonal antibodies raised in rabbits and conventional formalin-fixed, paraffin-embedded needle biopsy sections of liver. The core antigen was distributed in a fine granular pattern diffusely, perisinusoidally, or focally within the hepatocellular cytoplasm of livers from patients with HCV infection. The staining tended to show a more heterogeneous pattern in terms of intensity and distribution in cases of more advanced disease. Hepatocellular carcinoma cells were also frequently stained. HCV immunostaining will provide important information on the pathogenesis and treatment of HCV-related liver diseases. [ABSTRACT FROM AUTHOR]

Three patients with hepatitis C virus (HCV)-related chronic liver disease were shown to have autoantibodies strongly reacting with cytoskeletal fibres of non-muscle cells. The heavy chain of non-muscle myosin microfilament was the main target for those autoantibodies. as determined by (I) cell and tissue immunofluorescence studies showing colocalization with an anti-myosin antibody prototype; (ii) primary reactivity in immunoblotting with a 200-kD protein, using either MOLT-4 cells, human platelets, or affinity-purified non-muscle myosin as antigen extract: and (iii) immunoblotting of similar immunoreactive fragments in papain-digested MOLT-4 cell extracts, by using those human sera and antibody prototype. Autoantibodies to non-muscle myosin heavy chain were not previously reported in patients with chronic liver diseases, especially in those associated with HCV infection. [ABSTRACT FROM AUTHOR]