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.     

Suppressive effect of leflunomide metabolite (A77 1726) on metalloproteinase production in IL-1beta stimulated rheumatoid synovial fibroblasts

Leflunomide, an isoxazol derivative structurally unrelated to other immunomodulatory drugs, has proven to be efficacious in the treatment of rheumatoid arthritis (RA). This study was conducted to elucidate the mechanism by which leflunomide mediated antirheumatic effects. We investigated the effects of A77 1726, leflunomide's active metabolite, on mitogen-activated protein kinase (MAPK) activation in IL-1beta-stimulated rheumatoid synovial fibroblasts. The effects of A77 1726 on the secretion of matrix metalloproteinases (MMPs) from rheumatoid synovial fibroblasts were also examined. A77 1726 partially suppressed IL-1beta-induced ERK1/2 and p38 kinase activation. In contrast, A77 1726 efficiently suppressed IL-1beta-stimulated JNK1/2 kinase activation. Although no suppressive effect was demonstrated on MMP-2, A77 1726 markedly inhibited MMP-1, 3, and 13 secretions from IL-1beta-stimulated rheumatoid synovial fibroblasts. Tissue inhibitor of metalloproteinases-1 (TIMP-1) was constitutively produced from rheumatoid synovial fibroblasts and the suppressive effects of A77 1726 on TIMP-1 production were minimal. Our results suggest that the suppression of the MAPK signalling pathway and MMP synthesis in rheumatoid synovial fibroblasts is a possible mechanism for the inhibitory activity of leflunomide against rheumatoid arthritis.     

A case of primary sarcoma of the pulmonary artery.

A 39-year-old male was admitted complaining of nonproductive cough and dyspnea on exertion. Death occurred eight months after onset of the symptoms. Autopsy examination showed that the pulmonary trunk and left main pulmonary artery were markedly dilated and completely occluded by a tumor. The tumor had infiltrated into the left upper lobe and mediastinal lymph nodes, and metastatic nodules were found in both lungs and in the left adrenal gland. Small foci of infarction were noted in the lower lobes of both lungs. The tumor cells were of two types; pleomorphic spindle cells and bizarre multinucleated giant cells. Immunohistochemically, they were positive for vimentin, myosin, and lysozyme, but negative for desmin and muscle-specific actin. The cytoplasm of the tumor cells was showed by electron microscopy to contain microfilaments, dense bodies, and pinocytotic vesicles. We diagnosed this case as undifferentiated sarcoma of the pulmonary artery. Approximately 100 cases of pulmonary artery sarcoma have been reported. Histopathologically, almost all of the reported cases showed both spindle cells and pleomorphic giant cells, indicating a biologically anaplastic neoplasm.     

The evolutionary origin of the major histocompatibility complex: Polymorphism of class II α chain genes in the cartilaginous fish

T cells recognize antigen (Ag) in the form of peptides bound to the major histocompatibility complex (MHC) molecule. One of the important issues in evolutionary immunology is to identify the stage in phylogeny when this mode of Ag recognition emerged. At present, there is a considerable controversy as to whether the cartilaginous fish have the bona fide MHC. In our previous study, we showed that the nurse shark, a member of the cartilaginous fish, has (a) gene(s) capable of encoding MHC class II a chains. In the present study, we examined the polymorphism of nurse shark MHC class II a chain genes designated Gici-DAA and Gici-DBA using the polymerase chain reaction. The Gici-DAA and Gici-DBA genes had six and five alleles, respectively, and individual alleles usually differed by multiple nucleotides. In addition, most of the nucleotide substitutions were located at the putative Ag-binding sites, where non-synonymous substitutions occurred more frequently than synonymous substitutions. The fact that the Gici-DAA and Gici-DBA genes display a polymorphism pattern essentially similar to that of mammalian MHC genes playing a major role in Ag presentation suggests that the cartilaginous fish have the bona fide MHC. Thus, the MHC-peptide-based T cell recognition system appears to have arisen at or before the emergence of the cartilaginous fish.     

The polypeptides of adenovirus. V. Young virions, structural intermediate between top components and aged virions

The turnip yellow mosaic virus (TYMV) RNA-replicase bound to the chloroplast fraction of a participate cell-free preparation isolated from TYMV-infected Chinese cabbage leaves catalyzes the synthesis of RNA of the viral type, “plus” RNA, in the absence of added “minus” RNA template. Addition of TYMV-RNA does not stimulate RNA synthesis. The complex formed by the replicase bound to “minus” RNA template can be removed from the chloroplast fraction by solubilization with a non-ionic detergent, Lubrol W, and separated from insoluble material by centrifugation. The resulting supernatant contains the template-bound replicase as well as a small proportion of template-free replicase molecules. Treatment of this preparation with a polyethylene glycol-dextran two-phase aqueous system at high salt concentration removes the replicase from the template and yields, after centrifugation, a polyethylene glycol upper phase containing the template-free replicase molecules (PEG-enzyme) and a lower dextran phase containing a small proportion of replicase molecules still bound to their template. The soluble PEG-enzyme is markedly stimulated by added RNA. With TYMV-RNA as the added RNA, the product synthesized by the enzyme is RNA complementary to TYMV-RNA, i.e., “minus” RNA, indicating the enzyme uses the viral RNA as template. The “minus”-RNA synthesized remains hydrogen bonded to the viral RNA template and forms a RNase resistant, double-stranded structure. Chromatography on cellulose CF 11 column reveals two different double-stranded structures, one, fully double-stranded, in which the synthesized “minus” RNA strand is hydrogen bonded to template RNA of equal length, and one partly double-stranded and partly single-stranded in which probably the template RNA is very much longer than the synthesized “minus” RNA. The PEG-enzyme seems to be sensitive to high ionic strength since its activity can be completely suppressed by various salts; removal of the salts restores the activity.     

Congenital spongiform change in the brain stem nuclei of a domestic kitten

This report describes a novel spongiform change in the brain stem nuclei of a 9-month-old mixed breed kitten with neurological signs. Histologically, vacuoles were found in perineuronal spaces and neuropil, with mild to moderate astrocytosis in the brain stem nuclei. Vacuoles were not observed in the cytoplasm of neurons and no evidence of neuronal loss was found. Ultrastructurally, there were intramyelinic vacuoles with separation of lamellae at intraperiod lines and larger spaces formed by coalescence of ruptured vacuoles. Immunohistochemically, abnormal accumulation of prion protein (PrP) was not detected in the brain stem lesions. This is, to our knowledge, the first report of a feline spongiform change localized in the brain stem nuclei.     

Genetic association between interleukin-10 gene promoter region polymorphisms and type 1 diabetes age-at-onset

This study investigated whether interleukin-10 (IL-10) gene promoter region polymorphisms are associated with susceptibility to or clinical presentation of type 1 diabetes. The frequency of -1082G/A, -819C/T, and -592C/A polymorphisms was analyzed in 128 Japanese patients with type 1 diabetes and in 107 healthy control subjects in a case-controlled study. The allelic and haplotypic frequencies of the IL-10 gene promoter region polymorphisms were similar in patients with type 1 diabetes and in control subjects. However, the -819T and -592A allele were associated with adult-onset (>18 years) of the disease (p = 0.037). Furthermore, the frequency of ATA haplotype was increased in adult-onset patients than that in early-onset patients (< or =18 years; p = 0.037). Among the genotypes comprising ATA haplotype, the frequency of ATA/ATA was significantly higher in adult-onset patients than in early-onset patients (p = 0.004). These results suggest that the IL-10 gene promoter polymorphisms are associated with the age-at-onset in Japanese patients with type 1 diabetes.     

The action of BDNF on GABAA currents changes from potentiating to suppressing during maturation of rat hippocampal CA1 pyramidal neurons

During the development of the hippocampus, the action of GABA shifts from depolarizing to hyperpolarizing, and brain-derived neurotrophic factor (BDNF) has important roles in GABAergic transmission. We demonstrate that BDNF (20 ng ml⁻¹) rapidly and reversibly potentiates postsynaptic GABA_A receptor-mediated currents (by 80.5 ± 14.3 %, n = 10) in hippocampal CA1 pyramidal neurons isolated from postnatal day (P)6 rats, using nystatin-perforated patch-clamp recordings. This potentiation is caused by an elevation of intracellular Ca²⁺ that occurs in response to the activation of Trk B receptor tyrosine kinase and phospholipase C-γ. The modulation of the GABA_A responses by BDNF in hippocampal CA1 pyramidal neurons isolated from P10 rats was more diverse (from potentiating to inhibitory), and at P14, BDNF induced a long-lasting inhibition. In addition, Ca²⁺/calmodulin-dependent protein kinase 2 plays important roles in the potentiating, but not in the inhibitory effect, of BDNF on the GABA_A responses. These results suggest that changes in the intracellular signalling pathway could contribute to the developmental shift of the actions of BDNF on inhibitory systems.     

Abnormalities of fecal flora in patients with acrodermatitis enteropathica

Fecal flora in two female patients with acrodermatitis enteropathica (AE) were investigated in connection with the efficacies of zinc sulfate and Entero-Vioform (EV). The following results were obtained.

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