HepG2 cell binding activities of different hepatitis b virus isolates: inhibitory effect of anti-HBs and anti-preS1(21–47)

The antigenic relationships among different hepatitis B virus (HBV) isolates were investigated by using monoclonal antibodies (MAbs) specific for HBs, preS2 (pHSA binding site), and preS1 (hepatocyte receptor-binding site) epitopes in a double immunoradiometric assay. In order to define possible functional differences resulting from structural and antigenic differences in the HBV env protein, the HBV isolates were compared in an in vitro cell-binding assay based on the attachment of 125I-labeled HBV to human hepatoma HepG2 cells. We provided evidence for a variability of the expression of preS1 and preS2 specificities in the peplomer (glyco)protein of HBV depending on d/ysubtype of HBsAg, which could affect the viral infectivity. We showed that the integrity of the HBV envelope structure associated with a large expression of preS1(21–47) epitopes is an essential factor for effective binding to HepG2 cells. Interestingly, the HBs-specific MAbs directed to disulfide-bond-dependent epitopes were found to be the best inhibitors of the preS1-HepG2 cell interaction (>50% at the final concentration of 0.5 μg/ml). The MAb F35.25 directed to the preS1(21–47) sequence corresponding to the hepatocyte receptor recognition site was, however, also found to inhibit binding. Thus, our results demonstrate the abilities of both anti-HBs and anti-preS(21–41) to block the attachment of complete HBV particles to HepG2 cells, suggesting that these antibodies should be virus neutralizing and would be expected to confer protection against reinfection.     

Balancing the bipotential gonad between alternative organ fates: a new perspective on an old problem.

The embryonic gonads give rise to one of two morphologically and functionally different organs, a testis or an ovary. Sex determination is the embryonic process that determines the developmental fate of the gonad. In mammals, sex determination is regulated by a DNA binding protein encoded on the Y chromosome, Sry, and it's downstream mediator, Sox9, which trigger testis determination in the bipotential gonad. However, evidence suggests that the extracellular signals. Fgf9 and Wnt4, are also required to establish divergent organogenesis of the gonad. In this review, we discuss how these extracellular signals interface with cell-autonomous factors to determine the fate of the mammalian gonad, and we derive a model that could provide a molecular explanation for testis determination in vertebrates where Sry is absent.     

Monoclonal antibody (WT 1) directed against a T cell surface glycoprotein: characteristics and immunosuppressive activity

WT 1, an IgG2a subclass monoclonal antibody, recognizes a human T lineage specific antigen (mol. wt 40,000). This antigen is strongly expressed on thymic T blasts, and on peripheral T cells activated by phytohaemagglutinin, whereas cortical thymocytes and peripheral T cells are moderately positive for WT 1. In contrast, B lymphocytes, myeloid and erythroid cells, including the progenitor cells of these lineages, and terminal deoxynucleotidyl transferase positive cells in the bone marrow, are all WT 1 negative. Binding of WT 1 to T cells is blocked by a previously described antibody (3A1) suggesting that both antibodies bind to the same antigen present on human T cells. WT 1, however, is also reactive with T lymphocytes from rhesus monkeys whereas 3A1 is not. Therefore, the biological effects of WT 1 could be studied in a monkey model. In a skin allograft model, WT 1 was immunosuppressive and induced a marked prolongation of graft survival.     

The blocking effect of antibodies against the products of the H-2 gene complex on lymphocyte complement (C3d) receptors. complement dependence and specificity

Antisera against the products of the major histocompatibility system (MHS), produced by immunization between congenic mouse strains differing only at that segment of the 17th chromosome rosettes which bears the H-2gene complex, exert a reproducible blocking effect on formation of with EACm (C3d rosettes). In many instances this effect is probably due to specific antibodies reactive with the lymphocytes, as indicated by immunochemical and adsorption experiments. Purified antibodies from the C3H anti-C3H.B10 immune ascites failed to exert this blocking effect. The blocking capacity can be restored, however, by addition of fresh normal mouse, rabbit or fetal calf serum, but not by heat inactivated serum. These experiments show that the presently defined H-2K, H-2D and H-2L antigens as well as some Ia antigens are themselves not the C3d receptors. The blocking effects observed in the presence of complement are possibly due to the proximity of H-2 or Ia molecules and C3d receptors, or to a rearrangement of membrane components after reaction with anti-MHC anti-MHC antibodies and complement.     

Respiratory function changes after asbestos pleurisy.

Six patients with radiographic evidence of diffuse pleural thickening after industrial asbestos exposure are described. Five had computed tomography of the thorax. All the scans showed marked circumferential pleural thickening often with calcification, and four showed no significant evidence of intrapulmonary fibrosis (asbestosis). Lung function testing showed reduction of the inspiratory capacity and the single-breath carbon monoxide transfer factor (TLCO). The transfer coefficient, calculated as the TLCO divided by the alveolar volume determined by helium dilution during the measurement of TLCO, was increased. Pseudo-static compliance curves showed markedly more negative intrapleural pressures at all lung volumes than found in normal people. These results suggest that the circumferential pleural thickening was preventing normal lung expansion despite abnormally great distending pressures. The pattern of lung function tests is sufficiently distinctive for it to be recognised in clinical practice, and suggests that the lungs are held rigidly within an abnormal pleura. The pleural thickening in our patients may have been related to the condition described as "benign asbestos pleurisy" rather than the interstitial fibrosis of asbestosis.     

An unusual intraventricular interthalamic vein: two anatomical case reports

Neurosurgeons use ventricular veins during an endoscopic third ventriculocisternostomy as landmark to progress in ventricles. In the current literature, there is lack of detailed intraventricular venous anatomy. Majority of those papers treats Monro’s foramen venous variations. There are no data of third ventricle venous anatomy and variations in the literature. We reported two cases of unusual interthalamic vein that we need to spare during endoscopy.     

Intra- and extracellular amyloid fibrils are formed in cultured pancreatic islets of transgenic mice expressing human islet amyloid polypeptide.

Islet amyloid polypeptide (IAPP) is the constituent peptide of amyloid deposits found in the islets of non-insulin-dependent diabetic patients. Formation of islet amyloid is associated with a progressive destruction of insulin-producing beta cells. Factors responsible for the conversion of IAPP into insoluble amyloid fibrils are unknown. Both the amino acid sequence of human IAPP (hIAPP) and hypersecretion of hIAPP have been implicated as factors for amyloid fibril formation in man. We have generated transgenic mice using rat insulin promoter-hIAPP or rat IAPP (rIAPP) gene constructs. No fibrillar islet amyloid was detectable in vivo in these normoglycemic mice, although small amorphous perivascular accumulations of IAPP were observed in hIAPP mice only. To determine the effects of glucose on IAPP secretion and fibrillogenesis, pancreatic islets from transgenic and control mice were examined in vitro. Islet IAPP secretion and content were increased in transgenic islets compared with control islets. IAPP-immunoreactive fibrils were formed at both intra- and extracellular sites in isolated hIAPP islets cultured with glucose at 11.1 and 28 mM for only 7 days. At 28 mM glucose, fibrils were present in deep invaginations of beta cells as observed in non-insulin-dependent diabetic patients. No fibrils were present at low glucose concentrations in hIAPP islets or at any glucose concentration in rIAPP or control islets. Thus, glucose-induced expression and secretion of hIAPP in transgenic mouse islets can lead to formation of amyloid fibrils similar to that found in non-insulin-dependent diabetes mellitus.