Hepatitis C virus is a more likely cause of chronic liver disease in the Japanese population than hepatitis B virus.

508 Japanese patients with chronic liver disease, including chronic hepatitis, cirrhosis and hepatocellular carcinoma, and 500 controls matched for sex and age were studied. Antibody to hepatitis C virus (anti-HCV) alone was found in 233 (45.9%) patients and hepatitis B surface antigen (HBsAg) alone was present in 128 (25.2%) patients. Both anti-HCV and HBsAg were present in 18 (3.5%) patients. Anti-HCV was found in 8 (1.6%) controls and HBsAg was present in 4 (0.8%) controls. The prevalence of anti-HCV alone was 36.9% in chronic hepatitis, 49.0% in cirrhosis and 67.0% in hepatocellular carcinoma, respectively. The prevalence of anti-HCV increased with the progress of severity of liver disease. Anti-HCV was more prevalent than HBsAg both in cirrhosis and hepatocellular carcinoma (p less than 0.001). The prevalence of anti-HCV increased with age. Among patients under age 39 years, HBsAg was detected more often than anti-HCV, however, in those over age 50 years, anti-HCV was detected more often than HBsAg (p less than 0.001). It would appear that hepatitis C virus more than hepatitis B virus is a prominent cause of chronic liver disease among Japanese patients.     

Thioredoxin levels in the sera of untreated viral hepatitis patients and those treated with glycyrrhizin or ursodeoxycholic acid

Thioredoxin (TRX), a thiol-containing protein, is induced by various oxidative stresses. Serum TRX levels were measured with a sandwich enzyme-linked immunosorbent assay kit in 210 hepatitis C virus (HCV)-infected patients, 39 hepatitis B virus (HBV)-infected patients, and 17 healthy volunteers. The effects of hepatoprotective drugs on TRX levels were also examined. The median TRX levels were significantly higher in HCV-infected patients than in controls (34.2 vs. 23.5 ng/ml, respectively; p < 0.005), but were not elevated in HBV-infected patients (26.7 ng/ml). The TRX levels were significantly correlated with serum lipid peroxide levels and indocyanine green exclusion test values, and were markedly decreased following treatment with Stronger Neo-Minophagen C or ursodeoxycholic acid. In conclusion serum TRX levels, a marker of oxidative stress, were higher in patients with HCV infection than those with HBV infection and healthy controls. The therapeutic efficacy of hepatoprotective drugs may be connected with the decrease in oxidative stress in hepatitis patients.     

Histamine synthesis by non-mast cells through mitogen-dependent induction of histidine decarboxylase.

Culture of spleen cells of C57BL/6 mice led to a spontaneous increase in activity of histidine decarboxylase (HDC) in the cell and the medium. Concomitantly histamine increased in the cells and, especially, in the medium. Addition of concanavalin A (Con A) or lipopolysaccharide (LPS) to the culture enhanced these processes. There was also a significant Con A-dependent increase in HDC activity and histamine biosynthesis in the culture of spleen cells of genetically mast-cell deficient W/Wv mice. Peritoneal macrophages of C57BL/6J mice had constitutively 11-19-fold as much HDC as T and B lymphocytes when compared on the basis of same number of cells. Con A had no effect on HDC activity when the macrophages were cultured alone. However, co-culture with T lymphocytes, separated from macrophages by a millipore filter membrane (pore size, 0.45 micron), rendered the macrophages responsive to Con A, leading to a notable increase in HDC activity in the cell. Addition of LPS caused a small but significant increase in HDC activity in macrophages, even when the cells were cultured alone. Co-culture with T or B cells enhanced the LPS-dependent increase in HDC activity in macrophages. In contrast, the HDC activity in T and B lymphocytes did not change essentially in the presence of any of these mitogens, even when they were co-cultured with macrophages. These results suggest that histamine is synthesized by non-mast cells through HDC.     

Genome-wide array-based comparative genomic hybridization of natural killer cell lymphoma/leukemia: different genomic alteration patterns of aggressive NK-cell leukemia and extranodal Nk/T-cell lymphoma, nasal type

Natural killer (NK) cell lymphomas/leukemias are highly aggressive lymphoid malignancies, but little is known about their genomic alterations, and thus there is an urgent need for identification and analysis of NK cell lymphomas/leukemias. Recently, we developed our own array-based comparative genomic hybridization (array CGH) with an average resolution of 1.3 Mb. We performed an array CGH analysis for 27 NK-cell lymphoma/leukemia cases that were classified into two disease groups based on the World Health Organization Classification (10 aggressive NK-cell leukemia cases and 17 extranodal NK/T-cell [NK/T] lymphomas, nasal type). We identified the differences in the genomic alteration patterns of the two groups. The recurrent regions characteristic of the aggressive NK-cell leukemia group compared with those of the extranodal NK/T lymphoma, nasal-type group, were gain of 1q and loss of 7p15.1-p22.3 and 17p13.1. In particular, gain of 1q23.1-24.2 (P = 0.041) and 1q31.3-q44 (P = 0.003-0.047), and loss of 7p15.1-p22.3 (P = 0.012-0.041) and 17p13.1 (P = 0.012) occurred significantly more frequently in the former than in the latter group. Recurrent regions characteristic of the extranodal NK/T lymphoma, nasal-type group, compared with those of the other group were gain of 2q, and loss of 6q16.1-q27, 11q22.3-q23.3, 5p14.1-p14.3, 5q34-q35.3, 1p36.23-p36.33, 2p16.1-p16.3, 4q12, and 4q31.3-q32.1. Our results can be expected to provide further insights into the genetic basis of lymphomagenesis and the clinicopathologic features of NK-cell lymphomas/leukemias.     

Evaluation of immunochromatographic assay systems for rapid detection of hepatitis B surface antigen and antibody, Dainascreen HBsAg and Dainascreen Ausab.

We evaluated two immunochromatographic assays (ICAs), Dainascreen HBsAg for detecting human hepatitis hepatitis B surface antigen (HBsAg) and Dainascreen Ausab for detecting human hepatitis B surface antibody (anti-HBs) in human serum. The ICA systems are composed of a comb-shaped device that contains nitrocellulose strips on which complexes of HBsAg and anti-HBs can be visualized. The results can be read within 15 min of incubation. The limit of detection for HBsAg was 3.1 ng/ml and that for anti-HBs was 42 mIU/ml. Results of HBsAg detection agreed completely with those of conventional enzyme immunoassays (EIAs) and showed a 100% sensitivity (158 of 158 samples) and a 100% specificity (304 of 304 samples). The Dainascreen Ausab detected 184 of the 199 EIA-positive samples (sensitivity, 92.5%) and yielded 6 positive results among the 281 EIA-negative samples (specificity, 97.9%). The ICA systems are rapid and sensitive methods for detecting HBsAg and anti-HBs. They are low-cost systems that need no complex instrumentation for analysis and can be recommended for routine use in clinical microbiology laboratories.     

Feeding with powdered diet after weaning increases visuospatial ability in association with increases in the expression of N-methyl-D-aspartate receptors in the hippocampus of female rats

We determined whether feeding with powdered diet improved the visuospatial ability in female rats by checking the expression of N-methyl-D-aspartate receptor (NMDAR) subunit 1 (NR1) mRNA in the hippocampus. In rats fed standard pelleted diet, males performed better than females in a radial 8-arm maze task as we reported previously. We found that the expression of NR1 mRNA, which may be the key mediator in visuospatial ability in the hippocampus, was also higher in males than in females. However, in rats fed powdered diet, no sex difference was seen in the radial 8-arm maze task and the expression of NR1 mRNA in the hippocampus, since feeding with powdered diet improved the visuospatial ability with increases in the expression of NR1 mRNA in the hippocampus in females. We suggest that the sex difference in visuospatial ability is at least in part due to feeding conditions.     

Identification and characterization of the scl gene encoding a group A Streptococcus extracellular protein virulence factor with similarity to human collagen

Group A Streptococcus (GAS) expresses cell surface proteins that mediate important biological functions such as resistance to phagocytosis, adherence to plasma and extracellular matrix proteins, and degradation of host proteins. An open reading frame encoding a protein of 348 amino acid residues was identified by analysis of the genome sequence available for a serotype M1 strain. The protein has an LPATGE sequence located near the carboxy terminus that matches the consensus sequence (LPXTGX) present in many gram-positive cell wall-anchored molecules. Importantly, the central region of this protein contains 50 contiguous Gly-X-X triplet amino acid motifs characteristic of the structure of human collagen. The structural gene (designated scl for streptococcal collagen-like) was present in all 50 GAS isolates tested, which together express 21 different M protein types and represent the breadth of genomic diversity in the species. DNA sequence analysis of the gene in these 50 isolates found that the number of contiguous Gly-X-X motifs ranged from 14 in serotype M6 isolates to 62 in a serotype M41 organism. M1 and M18 organisms had the identical allele, which indicates very recent horizontal gene transfer. The gene was transcribed abundantly in the logarithmic but not stationary phase of growth, a result consistent with the occurrence of a DNA sequence with substantial homology with a consensus Mga binding site immediately upstream of the scl open reading frame. Two isogenic mutant M1 strains created by nonpolar mutagenesis of the scl structural gene were not attenuated for mouse virulence as assessed by intraperitoneal inoculation. In contrast, the isogenic mutant derivative made from the M1 strain representative of the subclone most frequently causing human infections was significantly less virulent when inoculated subcutaneously into mice. In addition, both isogenic mutant strains had significantly reduced adherence to human A549 epithelial cells grown in culture. These studies identify a new extracellular GAS virulence factor that is widely distributed in the species and participates in adherence to host cells and soft tissue pathology.