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Biomedical subjects

R Ehrlich

Publications and source records attributed to R Ehrlich.

At least 145 records · Page 8Linked to original sources
PubMed1995

Selective mechanisms utilized by persistent and oncogenic viruses to interfere with antigen processing and presentation.

Cell-mediated immunity is effective against cells harboring active virus replication, and is critical for the elimination of ongoing infections, regression of virus-associated tumors, and reducing or preventing the reactivation of persistent viruses. The capacity of persistent and oncogenic viruses to maintain a long-term relationship with their host presupposes viral mechanisms for circumventing antiviral defenses. By suppressing the expression of molecules associated with antigen processing and presentation, viruses abrogate the major immune mechanism that deals with the elimination of infected and tumor cells. This is accomplished either by transcriptional downregulation of genes encoding class I MHC antigens, peptide transporter molecules, and the proteasome-associated LMP subunits, or by interfering with transport of class I molecules to the cell surface. In some cases viruses shut off the expression of most viral proteins during latency or express mainly nonimmunogenic or antagonistic peptide epitopes. This review describes selective mechanisms utilized by viruses for interference with antigen processing and presentation, and addresses their significance for in vivo viral persistence and tumor progression.

Animals↗
PubMed1995

Complications of laparoscopic nephrectomy in 185 patients: a multi-institutional review.

PURPOSE: We document the incidence of complications associated with laparoscopic nephrectomy in a multi-institutional study. MATERIALS AND METHODS: The study included the initial 185 patients undergoing laparoscopic nephrectomy at 5 centers in the United States between June 1990 and July 1993. RESULTS: A total of 30 patients (16%) had 34 complications. There was no mortality. Access-related complications included 2 cases of hernia formation at the trocar site, 1 abdominal wall hematoma and 1 trocar injury to a hydronephrotic kidney. Intraoperative complications included 5 cases of vascular injury, 1 splenic laceration and 1 pneumothorax. Postoperative complications involved the gastrointestinal tract in 6 cases, cardiovascular system in 6, genitourinary tract in 4, respiratory system in 4 and musculoskeletal system in 2. Miscellaneous complications occurred in 3 patients. Open surgical intervention was required electively in 8 patients and on an emergency basis in 2. The incidence of complications decreased with experience: 71% occurred during the initial 20 cases at each institution. CONCLUSIONS: In our early experience the complication rate for laparoscopic nephrectomy was 12% in patients with benign renal disease and 34% in those with renal cancer. Based on this collective experience, recommendations for prevention, recognition and treatment of complications are made.

Adult↗
PubMed1994

Downregulation of peptide transporter genes in cell lines transformed with the highly oncogenic adenovirus 12.

The expression of class I major histocompatibility complex antigens on the surface of cells transformed by adenovirus 12 (Ad12) is generally very low, and correlates with the high oncogenicity of this virus. In primary embryonal fibroblasts from transgenic mice that express both endogenous H-2 genes and a miniature swine class I gene (PD1), Ad12-mediated transformation results in suppression of cell surface expression of all class I antigens. Although class I mRNA levels of PD1 and H-2Db are similar to those in nonvirally transformed cells, recognition of newly synthesized class I molecules by a panel of monoclonal antibodies is impaired, presumably as a result of inefficient assembly and transport of the class I molecules. Class I expression can be partially induced by culturing cells at 26 degrees C, or by coculture of cells with class I binding peptides at 37 degrees C. Analysis of steady state mRNA levels of the TAP1 and TAP2 transporter genes for Ad12-transformed cell lines revealed that they both are significantly reduced, TAP2 by about 100-fold and TAP1 by 5-10-fold. Reconstitution of PD1 and H-2Db, but not H-2Kb, expression is achieved in an Ad12-transformed cell line by stable transfection with a TAP2, but not a TAP1, expression construct. From these data it may be concluded that suppressed expression of peptide transporter genes, especially TAP2, in Ad12-transformed cells inhibits cell surface expression of class I molecules. The failure to fully reconstitute H-2Db and H-2Kb expression indicates that additional factors are involved in controlling class I gene expression in Ad12-transformed cells. Nevertheless, these results suggest that suppression of peptide transporter genes might be an important mechanism whereby virus-transformed cells escape immune recognition in vivo.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Transcriptional regulation of class-I major histocompatibility complex genes transformed in murine cells is mediated by positive and negative regulatory elements.

The expression of class-I major histocompatibility complex (MHC) antigens on the surface of cells transformed by adenovirus 12 (Ad12) is generally very low or absent; a phenotype that correlates with the high tumorigenicity of these cell lines. In primary mouse embryonal fibroblasts (MEF) from class-I transgenic mice (PD1 transgenic mice), Ad12-mediated transformation results in down-regulation of both endogenous genes and the transgene. Functional analysis of class-I regulatory elements revealed that the suppression of a class-I promoter is mediated by two negative regulatory elements, one of which functions specifically in Ad12-transformed cells. In addition, Ad12-transformed cells produce only minute amounts of the nuclear factors that bind to the major class-I enhancer, RI (region I or H2TF1). A silencer element derived from the 5' region of the miniature swine class-I gene (PD1) is capable of competing for the binding of nuclear factors to a second enhancer, RII (region II or CREII), that is located upstream from RI in the class-I regulatory element (CRE). Based on these results, we propose that down-regulation of class-I genes in Ad12-transformed cells is mediated mainly by negative regulators.

Adenoviridae↗
PubMed1994

Environmental tobacco smoke and childhood asthma: comparing exposure metrics using probability plots.

This study demonstrates the use of probability plots for assessing exposure-disease relationships in case-control studies. We reanalyze data from a study of childhood asthma and exposure to environmental tobacco smoke, comparing alternative measures of smoking intensity. Previous analyses showed a higher mean urinary cotinine-to-creatinine ratio (CCR) in cases as compared with controls and a statistically significant odds ratio with exposure defined as 30 ng/mg CCR or higher. Using probability plots, we compare alternative exposure metrics and exposure cutpoints with respect to their ability to detect a statistically significant exposure-disease effect. A strong exposure-disease response is evident, overall, and the results are fairly robust to the choice of exposure cutpoint.

Adolescent↗
PubMed1994

De novo methylation of an MHC class I transgene following transformation with human adenoviruses is not correlated with its altered expression.

The biological importance of class I histocompatibility antigens in a large variety of immune mechanisms is widely recognized, and their role in tumor rejection has been proven in several experimental tumor systems. Reduced expression of class I antigens, which is correlated with enhanced tumorigenicity, was shown in these systems to be mainly the result of transcriptional down-regulation. Mouse embryonal fibroblasts expressing H-2 antigens and the product of a miniature swine class I transgene, transformed by adenovirus 12, exhibit low levels of all class I antigens on the cell surface. Half of the cell lines demonstrate a suppressed level of class I mRNAs. Cell lines derived from transformation with the early region of adenovirus 5 express a high level of class I antigens. DNAs from adenovirus-transformed cells are extensively hypermethylated both in the 5' and the coding regions of the transgene compared to DNAs from immortalized cell lines and primary embryonal fibroblasts. Nevertheless, hypermethylation of these sequences is not correlated with mRNA level or cell-surface expression of the transgene product. Treatment of the transformed cells with high concentration of 5-azacytidine (5 Aza-C) induced merely a minor enhancement in the expression of class I mRNAs and class I antigens. Thus, this system is a perfect example of where viral transformation is associated with induced methylation of a class I gene, but hypermethylation does not affect its expression. The role of de novo methylation of genes in this system might be associated with transformation, or generation of mutations in CpG-rich sequences.

Adenoviridae↗
PubMed1994

Chlorhexidine.

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Chlorhexidine↗