Hepatitis B surface antigen particles of subtypes adw and adr, and compound subtype (adwr) in symptom-free carriers in Japan.

Of sera from 1,878 Japanese blood donors who carried hepatitis B surface antigen (HBsAg), 420 were subtyped as adw (22.4%) and 1,443 as adr (76.8%); only 15 (0.8%) contained HBsAg of subtype ayw or ayr. Sera with HBsAg/adr had higher HBsAg titres than those with HBsAg/adw (geometric mean of haemagglutination titre: 10.1 +/- 2.4 vs. 9.7 +/- 2.4, p less than 0.01), and a higher prevalence of hepatitis B e antigen (24% vs. 13%, p less than 0.001). Carriers of HBsAg/adr progressively predominated over those of HBsAg/adw with increasing age. Of sera from 1,863 carriers of HBsAg/adw or HBsAg/adr, 182 (9.8%) contained HBsAg particles with both subtypic determinants in the w/r allele. The presence of w and r determinants on the same particles was ascertained by sandwiching them between monoclonal antibody with the specificity for w and that with the specificity for r. HBsAg particles of compound subtype (adwr) were found more often in sera with hepatitis B e antigen than those without it (145/403 [36.0%] vs. 37/1,460 [2.5%], p less than 0.001). Sera with HBsAg/adwr particles had HBsAg titres higher than those without them (12.4 +/- 1.9 vs. 9.7 +/- 2.3, p less than 0.001). HBsAg/adwr particles arise from phenotypic mixing of the S-gene product of wild-type virus and that of mutants with point mutations for subtypic changes. The results obtained indicated that HBV strains of subtype adr have a higher replicative activity than those of adw, and suggested that mutations in the S gene for subtypic changes would be associated with an active replication of hepatitis B virus.     

The loss of subtypic determinants in alleles, d/y or w/r, on hepatitis B surface antigen

Hepatitis B surface antigen possesses the group-specific determinant called a and one or another member from each of two pairs of allelic determinants, d and y as well as w and r, thereby creating the four major subtypes, adw, adr, ayw and ayr. In the sequence of major surface antigen polypeptides made of 226 amino acid residues, lysine or arginine at amino acid position 122 specifies d or y determinant, and lysine or arginine at position 160 specifies w or r determinant, respectively. By means of site-directed mutagenesis and expression of mutant genes in cultured cells, the mechanism for the loss of subtypic determinants on surface antigens was investigated at the molecular level. A rare sample of surface antigen of subtype ad, devoid of w or r determinant, had asparagine at position 160. When it was converted to lysine, the surface antigen of subtype adw was obtained. Two samples of surface antigen were subtyped as ar. They lacked d determinant, despite having lysine at position 122 which usually specified it. They differed from all reported sequences of surface antigen in amino acid 144 or 145. They displayed d determinant when amino acid 144 was converted from glutamic acid to aspartic acid, or when amino acid 145 was changed from alanine to glycine. These results indicate that the key amino acid residue at position 122 or 160 is indispensable for the expression of subtypic determinants and that some distant residues are also crucially involved in conforming them.     

Functional combination of tapering profiles and overlapping arrangements in nonspanning skeletal muscle fibers terminating intrafascicularly

Using digital image analysis and several anatomical methods, morphometric analysis of nonspanning fibers which had tapering profiles at their intrafascicular termination sites and represented overlapping arrangements within the fiber fascicles was performed in the rat rectus abdominis. Special emphasis was focused on dimensional relationships occurring between overlapping portions and tapering segments and sarcomere lengths in non- and overlapping portions. Nonspanning fibers were found to overlap each other for more than 40% of their length. In length, their overlapping portions generally corresponded to their tapering segments, which were also greater than 40% of the fiber length. In addition, despite the presence of overlapping linkages, nonspanning fibers maintained a fairly uniform length irrespective of their overlapping and non-overlapping portions. Overlapping linkages in fibers without tapering profiles have a larger cross-sectional area in the overlapping portion than in the non-overlapping one, resulting in a phenomenon which will cause different sarcomere lengths between the two portions during fiber stretching. The present results suggest that tapering profiles in the overlapping portion ensure uniform sarcomere lengths within nonspanning fibers, thereby providing mechanical stability in each fiber. © 1993 Wiley-Liss, Inc.     

Phenotypic modulation in lipocytes in experimental liver fibrosis

The presence of a-smooth muscle actin (smA)-positive cells has recently been reported in the fibrotic liver. Lipocytes have been considered to play important roles in hepatic fibrosis. However, the relation of the a-smA-positive cells and lipocytes has not been determined. The biological implication of a-smA expression remains unknown. To study these questions, we carried out double immunofluorescent staining of a-smA and desmin (a marker for lipocytes), or a-smA and collagen, and double immunohistochemical staining of a-smA and 5-bromo-2'-deoxyuridine (BrdUrd) in carbon tetrachloride-induced fibrotic rat livers. In normal and control livers, a-smA-positive cells were not seen in the lobules, whereas scattered desmin-positive cells were present. With the development of hepatic fibrosis, a-smA was expressed only in a portion of desmin-positive cells located predominantly around collagen bundles. A number of a-smA-positive cells in the lobules were labelled with BrdUrd. These results suggest phenotypic modulation in lipocytes and differentiation of lipocytes towards myofibroblast-like cells, since a-smA is expressed with desmin in myofibroblasts in scar tissue. The expression of a-smA may be related to events of the fibrotic process, such as tissue contraction or fibrogenesis per se.     

Association of single nucleotide polymorphisms of the interleukin-10 promoter gene and susceptibility to primary biliary cirrhosis: immunogenetic differences in Italian and Japanese patients

Several lines of data suggest that genetic factors play an important role in the onset and/or progression of primary biliary cirrhosis (PBC). Since PBC is an autoimmune disease, it is reasoned to assume that genes encoding cytokines may confer susceptibility to disease. Amongst these factors, interleukin-10 (IL-10) has received significant attention. The promoter region of IL-10 gene has three single nucleotide polymorphisms (SNPs) at positions -1082, -819 and -592. To elucidate the association of the three SNPs of IL-10 promoter region with susceptibility of PBC in two different genetic populations, 159 unrelated patients with PBC (94 Italian and 65 Japanese) and 143 local controls (72 Italian and 71 Japanese) were enrolled. SNPs were determined using allele-specific PCR/RFLP. In Italian PBC patients, the frequency of homozygosity for G/G at position -1082 was significantly higher than that of local controls (p < 0.041, OR = 2.44, 95% C.I.; 1.02-5.86). The frequencies of haplotype GCC in PBC patients, possibly linked to higher IL-10 production, were also significant higher than local controls (p < 0.033). However, in Japanese population, there were no significant differences in the three SNPs and haplotypes between PBC patients and controls. Excessive production of IL-10 may play an important role in some populations in modulating the onset of PBC. Further, immunogenetic studies of PBC should take into account ethnic and geographic variations; this makes such studies in heterogeneous population, like the USA, more difficult.     

Intraplacental choriocarcinoma with fetomaternal transfusion

Intraplacental choriocarcinoma is very rare, and is usually found only after maternal and fetal metastatic disease is identified. The purpose of this case report is to review the incidence and findings of intraplacental choriocarcinoma. A term placenta was investigated because the newborn was born with severe anemia (Hb 3.0 g/dL). A 2 cm nodule was noted on the surface of the amniotic membrane and grossly resembled an infarction. The tumor was examined microscopically with immunohistochemical staining for the alpha- and beta-human chorionic gonadotropin (alpha-hCG, beta-hCG) subunits, human placental lactogen (hPL) and Ki-67. Microscopically, the tumor consisted of necrotic areas with proliferation of atypical trophoblastic cells and destruction of the villi and capillaries. The cells were positive for the alpha-hCG, beta-hCG subunits, hPL and Ki-67, consistent with intraplacental choriocarcinoma. The mother and newborn were investigated for the presence of metastatic disease. Computed tomography scans and magnetic resonance imaging of the mother and infant were negative for metastatic disease. Choriocarcinoma, limited only to the placenta with no evidence of metastatic disease is very rare. Primary intraplacental choriocarcinoma may frequently be overlooked or missed, and choriocarcinoma may possibly arise in the placenta more often than in retained or persistent trophoblast following pregnancy.