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Biomedical subjects

R Ehrlich

Publications and source records attributed to R Ehrlich.

At least 127 records · Page 7Linked to original sources
PubMed1996

LMP-associated proteolytic activities and TAP-dependent peptide transport for class 1 MHC molecules are suppressed in cell lines transformed by the highly oncogenic adenovirus 12.

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 in vivo oncogenicity of this virus. In primary embryonal fibroblasts (H-2b) that express transgenic swine class I antigen (PD1), Ad12-mediated transformation results in inhibition in transport of newly synthesized class I molecules, as well as significant reduction in transporter associated with antigen presentation (TAP) gene expression. In this report we show that reexpression of TAP molecules either by stable transfection of mouse TAP genes or by infection with recombinant vaccinia viruses expressing human TAP genes, only partially reconstitutes the expression and transport of the class I molecules. Further analysis of Ad12-transformed cells revealed that the expression of both LMP2 and LMP7, but not of other proteasome complex components, was downregulated, resulting in altered proteolytic activities of the 20S proteasomes. Reconstitution of both TAP and LMP expression resulted in complete restoration of PD1 cell surface expression and enhanced expression of the endogenous H-2D(b) molecules encoded by recombinant vaccinia viruses, in reconstituted Ad12-transformed cells, efficient transport of H-2 class I molecules could only be achieved by treatment of the cells with gamma-interferon. These data suggest that an additional factor(s) that is interferon-regulated plays a role in the biosynthetic pathway of the class I complex, and that its function is deficient in this cell system. Thus, Ad12 viral transformation appears to suppress the expression of multiple genes that are important for antigen processing and presentation, which allows such transformed cells to escape immune surveillance. This coordinate downregulation of immune response genes must likely occur through their use of common regulatory elements.

ATP-Binding Cassette Transporters↗
PubMed1996

Long-term sequelae of hearing impairment in congenital hypothyroidism.

Hearing loss and its functional consequences were evaluated retrospectively in children with congenital hypothyroidism. From a cohort of 101 children followed longitudinally to evaluate newborn screening, 75 with previous hearing tests were studied. Fifteen (20%) were found to have hearing problems. Of these, nine had unilateral or sensorineural loss mostly at high frequencies, five had a conductive loss, and one had both problems. Hearing impaired children differed from children with normal hearing in age of treatment onset (22 vs 14 days) but not disease severity or duration. A comparison of language and auditory processing skills at ages 3, 5, and 7 years revealed that early speech was delayed in hearing impaired children, whereas deficits persisted in later receptive language and auditory discrimination skills. Comparing hearing impaired children and children with normal hearing with matched control subjects at grade 3 showed that hearing impaired children were poorer readers because of less adequate phonologic processing skills.

Child↗
PubMed1996

Tubularized incised plate hypospadias repair: results of a multicenter experience.

PURPOSE: We report a multicenter experience using tubularized incised plate urethroplasty to correct distal hypospadias. MATERIALS AND METHODS: A total of 148 patients underwent repair by 6 pediatric urologists at different institutions in the United States and Europe. RESULTS: Tubularized incised plate repair created a functional neourethra with a vertically oriented meatus. Complications, including meatal stenoses and fistulas, occurred in 10 patients (7%). CONCLUSIONS: Tubularized incised plate urethroplasty can be performed in most cases of distal hypospadias. Cosmetic results are superior to those of other popular techniques.

Child↗
PubMed1996

Synonymous codon selection controls in vivo turnover and amount of mRNA in Escherichia coli bla and ompA genes.

A number of silent codon changes were made in two Escherichia coli genes. For the ompA gene, the replacement of seven consecutive frequently used codons with synonymous infrequently used codons reduced the ompA mRNA level and its half-life. For the bla gene, the exchange of 24 codons for the most frequently used synonymous codons extended the bla mRNA half-life. A modification of ribosome traffic could account for these observations.

Amino Acid Sequence↗
PubMed1996

A guide to spirometry as applied to occupational health.

In the context of occupational health, spirometric testing of respiratory function has a number of important applications. These applications can be expected to become more widespread in view of extensive changes to occupational health and compensation legislation in South Africa. Spirometry is an essential component of pre-assignment medical examinations at the commencement of employment; of medical surveillance of workers exposed to hazardous substances so as to intervene when early changes in pulmonary function are detected; of medical evaluation of functional impairment for appropriate job relocation or compensation; and of research. These applications of spirometry each have special considerations which are detailed.

Female↗
PubMed1995

Functional domain analysis of interferon consensus sequence binding protein (ICSBP) and its association with interferon regulatory factors.

Interferon consensus sequence binding protein (ICSBP) is a member of the interferon regulatory factor (IRF) family of proteins that include IRF-1, IRF-2, and ISGF3gamma which share sequence similarity at the putative DNA binding domain (DBD). ICSBP is expressed exclusively in cells of the immune system and acts as a repressor of interferon consensus sequence (ICS) containing promoters that can be alleviated by interferons. In this communication, we have searched for functional domains of ICSBP by dissecting the DBD from the repression activity. The putative DBD of ICSBP (amino acids 1-121) when fused in frame to the transcriptional activation domain of the herpes simplex VP16 (ICSBP-VP16) is a very strong activator of ICS-containing promoters. In addition, ICSBP-VP16 fusion construct transfected into adenovirus (Ad) 12 transformed cells enabled cell surface expression of major histocompatibility complex class I antigens as did treatment with interferon. On the other hand, the DBD of the yeast transcriptional activator GAL4 was fused in frame to a truncated ICSBP in which the DBD was impaired resulting in a chimeric construct GAL4-ICSBP. This construct is capable of repressing promoters containing GAL4 binding sites. Thus, ICSBP contains at least two independent domains: a DBD and a transcriptional repressor domain. Furthermore, we have tested possible interactions between ICSBP and IRFs. The chimeric construct GAL4-ICSBP inhibited the stimulated effect of IRF-1 on a reporter gene, implying for a possible interaction between IRF-1 and ICSBP. Electromobility shift assays, demonstrated that ICSBP can associate with IRF-2 or IRF-1 in vitro as well as in vivo. Thus, ICSBP contains a third functional domain that enables the association with IRFs. These associations are probably important for the fine balance between positive and negative regulators involved in the interferon-mediated signal transduction pathways in cells of the immune system.

Base Sequence↗
PubMed1995

Characterization of mature and immature RadLV-induced thymic T-cell lines for tumorigenesis and MHC-class-I gene expression.

Class-I-MHC molecules are divided into class-Ia molecules, which play major roles in recognition of virus-infected cells, graft rejection and immune responses against tumors, and class-Ib molecules, which are less polymorphic and may be responsible for presenting unique classes of peptides. Our report characterizes RadLV-induced thymic T-cell lines that differ both in their tumorigenic potential and in the level of protein for class-Ia and TL genes. The PD1.1 cell line is CD4-CD8+ and expresses relatively high levels of class-I as compared with the CD4+CD8+ PD1.2 cell line. These class-I-expression levels correlate with thymocytes and splenic T cells of the same phenotype, except that normal cells fail to express TL3b. Interferon-treated PD1.2 cells demonstrate significantly lower levels of class-I expression than do interferon-treated PD1.1 cells, and were shown to contain large amounts of degraded class-I mRNA, at least some of which was TL in origin. These RNA products were not detected in PD1.1 cells, suggesting the existence of a mechanism controlling cell-specific and gene-specific mRNA stability. Such RadLV-induced cell lines provide a means for obtaining stage-specific T cells, which can be used for studying the regulation of class-I gene expression during T-cell differentiation, as well as factors that differentially regulate class-Ia and class-Ib expression and are potentially useful for studying T-cell differentiation in general.

Animals↗