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991.
Ronald B. Moss Francois Ferre Alexandra Levine John Turner Fred C. Jensen Anne E. Daigle Steven P. Richieri Allison Truckenbrod Richard J. Trauger Dennis J. Carlo Jonas Salk 《Journal of clinical immunology》1996,16(5):266-271
Two trials of subjects inoculated with the inactivated, gp120-depleted HIV-1 Immunogen are reported. In one study, in which 19 subjects received ZDV and 8 subjects received ddI, treatment with the HIV-1 Immunogen did not affect the pharmacokinetic parameters of the antiviral drugs. In another study, 65 subjects who were previously immunized with the HIV-1 Immunogen over a mean period of 4.0 years (range, 1.2–5.4 years) received inoculations at 0 and 6 months. At some point during this 48-week study, 72% of the subjects (47/65) were receiving antiviral drug therapy. The HIV-1 DNA load in CD4 cells and CD4 percentage were found to be stable over the 48-week period. Delayed-type hypersensitivity to HIV-1 antigens increased after two inoculations with the HIV-1 Immunogen. In these two trials, no serious treatment-related adverse events were documented in the subjects. The two studies presented herein are the first to suggest that an immune-based therapy such as the HIV-1 Immunogen can be combined safely with antiviral drugs, supporting further study to evaluate the clinical utility of this approach. 相似文献
992.
Yang AH Chen JY Chen BF 《Virchows Archiv : an international journal of pathology》2004,445(3):305-314
While diffuse mesangial sclerosis is traditionally described as being the glomerulopathy of Denys–Drash syndrome (DDS), the podocyte proliferative lesions may be overlooked in these DDS cases. In the present study, an evolving process is extrapolated from a selected case of DDS that demonstrated glomerulopathy with conspicuous podocyte proliferation. The observation that podocytes express proliferation markers (Ki67, proliferating-cell nuclear antigen and topoisomerase II) in non-proliferative, mature-looking glomeruli suggests an initial pathogenic act to activate or to keep podocytes from quiescence. The subsequent proliferation of podocytes is in keeping with downregulation of WT1 and cyclin kinase inhibitors of p16 and p21. The emergence of cytokeratin-positive cells in glomeruli that show typical mesangial sclerosis implies elimination of podocytes and replacement with tubular and/or parietal epithelial cells. The final scene of evolving glomerulopathy displays apoptosis and expression of Fas-L and Bax in sclerotic mesangial lesions, which eventually end up with global sclerosis. This novel concept of DDS glomerulopathy implies complex molecular mechanisms involved in glomerular injury. 相似文献
993.
Previous results indicated that the herpes simplex virus 1 (HSV-1) U(L)31 gene is necessary and sufficient for localization of the U(L)34 protein exclusively to the nuclear membrane of infected Hep2 cells. In the current studies, a bacterial artificial chromosome containing the entire HSV-1 strain F genome was used to construct a recombinant viral genome in which a gene encoding kanamycin resistance was inserted in place of 262 codons of the 306 codon U(L)31 open reading frame. The deletion virus produced virus titers approximately 10- to 50-fold lower in rabbit skin cells, more than 2000-fold lower in Vero cells, and more than 1500-fold lower in CV1 cells, compared to a virus bearing a restored U(L)31 gene. The replication of the U(L)31 deletion virus was restored on U(L)31-complementing cell lines derived either from rabbit skin cells or CV1 cells. Confocal microscopy indicated that the majority of U(L)34 protein localized aberrantly in the cytoplasm and nucleoplasm of Vero cells and CV1 cells, whereas U(L)34 protein localized at the nuclear membrane in rabbit skin cells, and U(L)31 complementing CV1 cells infected with the U(L)31 deletion virus. We conclude that rabbit skin cells encode a function that allows proper localization of U(L)34 protein to the nuclear membrane. We speculate that this function partially complements that of U(L)31 and may explain why U(L)31 is less critical for replication in rabbit skin cells as opposed to Vero and CV1 cells. 相似文献
994.
Interleukin-15 is not required for the induction or maintenance of orally induced peripheral tolerance 下载免费PDF全文
Orally induced tolerance is a physiologically relevant form of peripheral tolerance, which is believed to be important for the prevention of pathological immune responses in the gut. Of several mechanisms proposed to mediate oral tolerance, one that has received much attention recently is the concept of regulatory CD4+ T cells. As recent studies have suggested that interleukin (IL)-15 may be important for the differentiation and maintenance of regulatory CD4+ T cells, we have examined the role of IL-15 in oral tolerance, using a soluble form of the IL-15 receptor (sIL-15R) which blocks the biological effects of IL-15 in vivo. Oral tolerance induced by feeding mice ovalbumin (OVA) in a low-dose regimen believed to induce regulatory T cell activity was not affected by the administration of sIL-15R during either the induction or maintenance phase of tolerance. Thus, oral tolerance does not involve an IL-15-dependent mechanism. 相似文献
995.
Jean‐Marie Raquez Philippe Dege Ramani Narayan Philippe Dubois 《Macromolecular chemistry and physics.》2004,205(13):1764-1773
Summary: Various poly(ε‐caprolactone‐block‐1,4‐dioxan‐2‐one) (P(CL‐block‐PDX)) block copolymers were prepared according to the living/controlled ring‐opening polymerization (ROP) of 1,4‐dioxan‐2‐one (PDX) as initiated by in situ generated ω‐aluminium alkoxides poly(ε‐caprolactone) (PCL) chains in toluene at 25 °C. 1 1H NMR, PCS and TEM measurements have attested for the formation of colloids attributed to a growing PPDX core surrounded by a solvating PCL shell during the polymerization of PDX promoted by ω‐Al alkoxide PCL chains in toluene. The thermal behavior of the P(CL‐block‐PDX) copolymers was studied by DSC; showing two distinct melting temperatures (as well as two glass transition temperatures) similar to those of the respective homopolyesters. Finally, the thermal degradation of the P(CL‐block‐PDX) block copolymers was investigated by TGA simultaneously coupled to a FT‐IR spectrometer and a mass spectrometer for evolved gas analysis (EGA). The degradation occurred in two consecutive steps involving a first unzipping depolymerization of the PPDX blocks followed by the degradation of the PCL blocks via both ester pyrolysis and unzipping reactions.
996.
997.
Stopfer P Obermeier F Dunger N Falk W Farkas S Janotta M Möller A Männel DN Hehlgans T 《Clinical and experimental immunology》2004,136(1):21-29
The lymphotoxin-beta receptor (LTbetaR) pathway is critical for maintenance of organized lymphoid structures and is involved in the development of colitis. To investigate the mechanisms by which LTbetaR activation contributes to the pathology of chronic inflammation we used a soluble LTbetaR-Ig fusion protein as a competitive inhibitor of LTbetaR activation in the mouse model of chronic colitis induced by oral administration of dextran sulphate sodium. Strong expression of LTbeta which constitutes part of the LTalpha(1)beta(2) ligand complex was detected in colonic tissue of mice with chronic colitis. Treatment with LTbetaR-Ig significantly attenuated the development and histological manifestations of the chronic inflammation and reduced the production of inflammatory cytokines such as TNF, IL-1beta, and IL-6. Moreover, LTbetaR-Ig treatment significantly down-regulated mucosal addressin cell adhesion molecule-1 (MAdCAM-1) expression, leading to reduced leucocyte rolling and sticking in postcapillary and collecting venules and reduced extravasation into the intestinal mucosa as quantified by in vivo fluorescence microscopy. Thus, LTbetaR pathway inhibition ameliorates DSS-induced experimental chronic colitis in mice by MAdCAM-1 down-regulation entailing reduced lymphocyte margination and extravasation into the inflamed mucosa. Therefore, a combined treatment with reagents blocking T cell-mediated perpetuation of chronic inflammation such as LTbetaR-Ig together with direct anti-inflammatory reagents such as TNF inhibitors could constitute a promising treatment strategy for chronic colitis. 相似文献
998.
The HIV-1 Vpr protein harbors a nuclear localization signal in its N-terminal domain. A peptide bearing this domain and which is designated VprN has been used as a target to screen a phage display single chain Fv (scFv) library. Here we report the isolation of anti-VprN scFv fragments from this library. The purified scFv fragments were able to bind the VprN peptide in an ELISA-based system and to inhibit VprN-mediated nuclear import in permeabilized as well as in intact microinjected cells. Furthermore, the anti-VprN scFv fragments recognized the full-length recombinant Vpr protein and inhibited its nuclear import. The same scFv fragments did not inhibit nuclear import mediated by the nuclear localization signal of the SV40 large T-antigen demonstrating a specific effect. The use of the described inhibitory anti-VprN scFv fragments to study nuclear import of viral karyophilic proteins and their therapeutic potential is discussed. 相似文献
999.
Nonulcerative penile mass lesions are rare. Pathological diagnosis of these lesions would traditionally be a biopsy. We report two such primary penile lesions which were diagnosed by fine-needle aspiration cytology (FNAC). Both lesions were present in the shaft and were diagnosed as squamous cell carcinoma (SCC). The first patient had a recurrence on the penile stump of partial amputation without any ulceration. The second had a primary urethral carcinoma on the terminal penile shaft infiltrating the corpora cavernosa dorsally. Open biopsies were avoided in both cases. FNAC was associated with very little and tolerable discomfort. There were no complications. The aspirate yield was sufficient for cytological diagnosis. FNAC of nonulcerated penile lesions is safe, well tolerated, and capable of providing a cytological diagnosis. Hence, it is a very useful outpatient procedure and could be the procedure of choice for diagnosis. 相似文献
1000.
Yoshihiro Kikkawa Hideki Abe Masahiro Fujita Tadahisa Iwata Yoshio Inoue Yoshiharu Doi 《Macromolecular chemistry and physics.》2003,204(15):1822-1831
Direct visualization of crystal growth in poly(L ‐lactide) thin films was carried out by using a temperature‐controlled atomic force microscopy (AFM). At the initial stage of crystallization, edge‐on lamellar crystals have nucleated and elongated. Subsequently, the edge‐on lamellar crystals showed S‐shaped morphology and changed their orientation from edge‐on manner to flat‐on one. The curvature of edge‐on lamellar crystal has been discussed in terms of inclination and distortion of polymer chains in the crystal. In addition, mechanism on the formation of flat‐on crystal from edge‐on lamellae was proposed as derivative growth on the basis of in situ AFM observation of crystal growth and enzymatic degradation.