PubMed Health⌕ Search

Biomedical subjects

J A George

Publications and source records attributed to J A George.

17 recordsLinked to original sources

Two retrotransposons maintain telomeres in Drosophila.

Telomeres across the genus Drosophila are maintained, not by telomerase, but by two non-LTR retrotransposons, HeT-A and TART, that transpose specifically to chromosome ends. Successive transpositions result in long head-to-tail arrays of these elements. Thus Drosophila telomeres, like those produced by telomerase, consist of repeated sequences reverse transcribed from RNA templates. The Drosophila repeats, complete and 5'-truncated copies of HeT-A and TART, are more complex than telomerase repeats; nevertheless, these evolutionary variants have functional similarities to the more common telomeres. Like other telomeres, the Drosophila arrays are dynamic, fluctuating around an average length that can be changed by changes in the genetic background. Several proteins that interact with telomeres in other species have been found to have homologues that interact with Drosophila telomeres. Although they have hallmarks of non-LTR retrotransposons, HeT-A and TART appear to have a special relationship to Drosophila. Their Gag proteins are efficiently transported into diploid nuclei where HeT-A Gag recruits TART Gag to chromosome ends. Gags of other non-LTR elements remain predominantly in the cytoplasm. These studies provide intriguing evolutionary links between telomeres and retrotransposable elements.

Animals↗

Conserved features at the 5 end of Drosophila R2 retrotransposable elements: implications for transcription and translation.

R2 non-LTR retrotransposable elements insert site-specifically into the 28S ribosomal genes of insects. The sequence of the 5' end of full-length R2 elements from thirteen species of Drosophila were compared. Sequences within the 5' untranslated region (5' UTR) revealed little to suggest the presence of a promoter. Protein translation initiates within the 5' UTR and requires the bypassing of a highly conserved termination codon preceding the single R2 open reading frame. This bypassing probably involves a conserved RNA secondary structure which brings a potential initiation codon into close proximity to this termination codon. The most highly conserved sequence within the 5' UTR has properties similar to internal ribosomal entry sites. Based on these findings, we propose that R2elements are co-transcribed with the 28S gene and are translated as part of a large ribosomal subunit.

5' Untranslated Regions↗

Prediction of well-conserved HIV-1 ligands using a matrix-based algorithm, EpiMatrix.

This preliminary study was undertaken to identify new human leucocyte antigens (HLA) ligands from human immunodeficiency virus type 1 (HIV-1) which are highly conserved across HIV-1 clades and which may serve to induce cross-reactive cytotoxic T lymphocytes (CTLs). EpiMatrix was used to predict putative ligands from HIV-1 for HLA-A2 and HLA-B27. Twenty-six peptides that were both likely to bind and also highly conserved across HIV-1 strains in the Los Alamos HIV sequence database were selected for binding assays using the T2 stabilization assay. Two peptides that were also highly likely to bind (for A2 and B27, as determined by EpiMatrix) and well conserved across HIV-1 strains, and had previously been described to bind in the published literature, were also selected to serve as positive controls for the assays. Ten new major histocompatibility complex (MHC) ligands were identified among the 26 study peptides. The control peptides bound, as expected. These data confirm that EpiMatrix can be used to screen HIV-1 protein sequences for highly conserved regions that are likely to bind to MHC and may prove to be highly conserved HIV-1 CTL epitopes.

Algorithms↗

Co-infection with Mycobacterium tuberculosis and HIV in high risk clinical care setting in Rhode Island.

We assessed the extent to which co-infection with HIV and Mycobacterium tuberculosis (Mtb) was diagnosed at several high risk clinical care sites from 1992 to 1994 to determine whether surveillance for co-infection was performed. Information on PPD skin testing, HIV status, and HIV risk exposures was extracted from records at HIV clinics in Rhode Island and a large database (HIV sites) and from records at the state TB clinic and the Rhode Island Health Department (TB sites). At the HIV sites, 34 of 1,408 HIV infected subjects were newly diagnosed with Mtb infection in the study period. At the TB sites, 16 of 1,389 subjects with newly diagnosed Mtb infection or disease were identified as HIV infected. Eighty per cent of the records reviewed for this study were incomplete. Hispanic subjects were at higher risk of being identified as co-infected at the HIV sites. At the TB sites, US-born subjects were at higher risk of being identified as co-infected Recommendations for high risk individuals include yearly tuberculosis skin testing. Adherence to these guidelines in selected high-risk clinical care sites in Rhode Island was substandard during the study period; the importance of Mtb screening was demonstrated in this study. Identification of groups that are at higher risk of having HIV and Mtb co-infection identified may enable health care providers to improve testing and prevention of tuberculosis at high risk clinical care settings.

AIDS-Related Opportunistic Infections↗

Analysis of the 5' junctions of R2 insertions with the 28S gene: implications for non-LTR retrotransposition.

R2 elements are non-long terminal repeat retrotransposable elements that insert into 28S rRNA genes of most insect species. The single open reading frame of R2 encodes a protein with both endonuclease activity, which cleaves the target site, and reverse transcriptase activity, which uses this cleavage to prime reverse transcription. This target-primed reverse transcription mechanism is also used by group II introns. Little is known of the mechanism by which the 5' end of R2 is integrated after reverse transcription. We have determined the 5' junction sequence of 94 R2 elements from 14 different species of Drosophila. Only 37% of the full-length elements contained precise 5' junctions; the remainder contained deletions of the 28S gene and/or insertions of additional sequences. Because the 5' junctions of truncated copies were similar to full-length elements, no sequences at the 5' end of R2 appear to be required for element integration. A model in which the R2 reverse transcriptase is capable of switching templates from the R2 RNA transcript to the upstream 28S gene can best explain the observed 5' junction sequences. This template jumping is analogous to the template switching of retroviral reverse transcriptases during formation of the double-stranded integration products.

Animals↗

Tracheobronchial epithelium in the adult rhesus monkey: a quantitative histochemical and ultrastructural study.

Previous studies of the intrapulmonary conducting airways of sheep and rabbit have demonstrated marked diversity in the epithelial populations lining them. Because studies of trachea and centriacinar regions of macaque monkeys suggested that primates may be even more diverse, the present study was designed to characterize the epithelial population throughout the airway tree of one primate species, the rhesus monkey. Trachea and intrapulmonary airways of the right cranial and middle lobes of glutaraldehyde/paraformaldehyde-infused lungs of five adult rhesus monkeys were microdissected following the axial pathway. Each branch was assigned a binary number indicating its specific location within the tree. The trachea and six generations of intrapulmonary airway from the right cranial lobe were evaluated for ultrastructure and quantitative histology as were those of the right middle lobe for quantitative carbohydrate histochemistry. Four cell types were identified throughout the tree: ciliated, mucous goblet, small mucous granule, and basal. The tallest epithelium lined the trachea; the shortest, the respiratory bronchiole. The most cells per unit length of basement membrane were in proximal intrapulmonary bronchi; the least, in the respiratory bronchiole. The nonciliated bronchiolar epithelial or Clara cell was restricted to respiratory bronchioles. Sulfomucins were present in the vast majority of surface goblet cells in the trachea and proximal bronchi. In proximal bronchi, neutral glycoconjugates predominated in glands and acidic glycoconjugates in surface epithelium. In terminal and respiratory bronchioles the ratio of acidic glycoconjugate to neutral glycoconjugate equaled that in proximal bronchi, although glands were not present. Sulfomucins were minimal in terminal airways. We conclude that the characteristics of the epithelial lining of the mammalian tracheobronchial airway tree are very species-specific. The lining of the rhesus monkey does not have the diversity in cell types in different airway generations observed in sheep and rabbit. Also, the populations lining these airways in the rhesus are very different from either the sheep or rabbit in number, proportions of different cell types, glycoconjugate content, and distribution of specific cell types.

Animals↗

A hospital throughput model in the context of long waiting lists.

In a public health system, one of the problems is the size of the waiting list for admission to hospital. This research involves establishing a method of analysing the general surgery waiting list problem at hospital and district level. While there are many aspects to such a study, this paper concentrates on a linear programming model to plan the aggregate throughput of the general surgical department. Preliminary results from applying the techniques to actual health districts in the United Kingdom are reported.

Appointments and Schedules↗

Phaeohyphomycosis of the eye caused by Exserohilum rostratum in India.

A 40-year-old woman developed a corneal ulcer with hypopyon following a traumatic episode. In a KOH mount dematiaceous, septate, branched hyphae were demonstrated, and heavy growth of Exserohilum rostratum was obtained in culture. No bacterial pathogens were isolated. The patient was treated with natamycin and subsequently with ketoconazole. In spite of antimycotic therapy a descemetocele of the eye remained. This observation represents the first documented case of an Exserohilum infection in India.

Adult↗