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Biomedical subjects

R Connor

Publications and source records attributed to R Connor.

At least 19 recordsLinked to original sources
PubMed2002

The genome sequence of Schizosaccharomyces pombe.

We have sequenced and annotated the genome of fission yeast (Schizosaccharomyces pombe), which contains the smallest number of protein-coding genes yet recorded for a eukaryote: 4,824. The centromeres are between 35 and 110 kilobases (kb) and contain related repeats including a highly conserved 1.8-kb element. Regions upstream of genes are longer than in budding yeast (Saccharomyces cerevisiae), possibly reflecting more-extended control regions. Some 43% of the genes contain introns, of which there are 4,730. Fifty genes have significant similarity with human disease genes; half of these are cancer related. We identify highly conserved genes important for eukaryotic cell organization including those required for the cytoskeleton, compartmentation, cell-cycle control, proteolysis, protein phosphorylation and RNA splicing. These genes may have originated with the appearance of eukaryotic life. Few similarly conserved genes that are important for multicellular organization were identified, suggesting that the transition from prokaryotes to eukaryotes required more new genes than did the transition from unicellular to multicellular organization.

Base Sequence↗
PubMed2002

Sumatriptan challenge in bipolar patients with and without migraine: a neuroendocrine study of 5-HT1D receptor function.

An association between bipolar disorder and migraine has been lately recognized and an abnormality of central serotonergic function is suggested as the underlying neurophysiological disturbance. To examine the role of serotonin in bipolar disorder and migraine, we used the neuroendocrine challenge paradigm, and we chose sumatriptan, a 5HT1D agonist, as the pharmacological probe. We studied nine bipolar patients with migraine, nine bipolar patients without it, seven migraine patients, and nine matched normal controls. A post-hoc analysis showed subsensitivity of serotonergic function, reflected in a blunted growth hormone response to sumatriptan challenge in bipolar patients who also suffered from migraine.

Adult↗
PubMed2001

Massive gene decay in the leprosy bacillus.

Leprosy, a chronic human neurological disease, results from infection with the obligate intracellular pathogen Mycobacterium leprae, a close relative of the tubercle bacillus. Mycobacterium leprae has the longest doubling time of all known bacteria and has thwarted every effort at culture in the laboratory. Comparing the 3.27-megabase (Mb) genome sequence of an armadillo-derived Indian isolate of the leprosy bacillus with that of Mycobacterium tuberculosis (4.41 Mb) provides clear explanations for these properties and reveals an extreme case of reductive evolution. Less than half of the genome contains functional genes but pseudogenes, with intact counterparts in M. tuberculosis, abound. Genome downsizing and the current mosaic arrangement appear to have resulted from extensive recombination events between dispersed repetitive sequences. Gene deletion and decay have eliminated many important metabolic activities including siderophore production, part of the oxidative and most of the microaerophilic and anaerobic respiratory chains, and numerous catabolic systems and their regulatory circuits.

Animals↗
PubMed2001

An invitation for medical educators to focus on ethical and policy issues in research and scholarly practice.

Medical education research and medical education practice both involve being methodical, innovative, self-observing, forward-looking, and open to peer review, and both are scholarly activities. For these reasons, distinguishing between these two activities is often difficult. There are three important reasons to clarify the distinctions: the moral difference between education research and education practice; federal regulations governing education research that require more safeguards than often exist in education practice; and the fact that student participants in research have characteristics in common with members of special populations. The authors explain why attention to issues of safeguards in education research and practice is likely to grow at academic health centers, yet maintain that these issues are neglected in the medical education literature. They demonstrate this with findings from their review of 424 education research reports published in 1988 and 1989 and in 1998 and 1999 in two major medical education journals. Each article was evaluated for documentation of six ethically important safeguards and features (e.g., informed consent). The rates of reporting the six features and safeguards were relatively low (3-27%). Nearly half (47%) of the empirical reports offered no indication of ethically important safeguards or features, and no article mentioned all six. Furthermore, those rates did not increase substantially after ten years. The authors discuss a number of implications of their findings for faculty, training institutions, students, and editors and peer reviewers, and conclude with the hope that their findings will raise awareness of these neglected issues in medical education and will stimulate all those involved to reflect upon the issues and set standards on the ethical aspects of research and scholarly practice.

Academic Medical Centers↗
PubMed2001

Cytopathicity of human immunodeficiency virus type 1 primary isolates depends on coreceptor usage and not patient disease status.

It has been hypothesized that human immunodeficiency virus type 1 (HIV-1) evolves toward increased cytopathicity in conjunction with disease progression in infected patients. A viral property known to evolve in some but not all patients is coreceptor utilization, and it has been shown that a switch in coreceptor utilization is sufficient for the development of increased cytopathicity. To test the hypothesis that the evolution of other viral properties also contributes to accelerating cytopathicity in vivo, we used human lymphoid tissue explants to assay the cytopathicity of a panel of primary HIV-1 isolates derived from various stages of disease characterized by the presence or absence of changes in coreceptor preference. We found no evidence of coreceptor-independent increases in cytopathicity in isolates obtained either before coreceptor preference changes or from patients who progressed to AIDS despite an absence of coreceptor evolution. Instead, the cytopathicity of all HIV-1 isolates was determined solely by their coreceptor utilization. These results argue that HIV-1 does not evolve toward increased cytopathicity independently of changes in coreceptor utilization.

CD4-Positive T-Lymphocytes↗
PubMed2000

Eph receptors and ephrin expression in cranial motor neurons and the branchial arches of the chick embryo.

Cranial motor axons navigate along a variety of pathways to their targets in the periphery of the head. Whereas somatic motor axons innervate tongue and eye muscles, visceral motor axons innervate parasympathetic ganglia, and branchiomotor axons innervate the branchial arches. The formation of these diverse pathways must depend upon molecules present in the environment traversed by growing axons. We have analyzed the potential roles of the ephrin ligands and their Eph tyrosine kinase receptors during cranial motor neuron development and axon pathfinding, by investigating expression patterns of these molecules at relevant stages in the chick. We detected expression of EphA3 and EphA4 among trigeminal and facial motor neurons, at times when these neurons are projecting to their muscle targets in the branchial arches. Corresponding ephrin-A ligands for these receptors were found to be expressed in specific regions of the arches during the same period, implicating ephrin-mediated interactions in cranial motor axon pathfinding.

Animals↗
PubMed2000

Chronic sclerosing sialadenitis of the submandibular and parotid glands: a report of a case and review of the literature.

Chronic sclerosing sialadenitis (also known as Küttner tumor) is a chronic inflammatory condition of the salivary glands, first described by Küttner in 1896. Clinically, the disease cannot be distinguished from a true neoplasm. The submandibular gland is affected more commonly than any other salivary gland. This report is of a case of widespread swelling of the salivary glands in which histologic features of chronic sclerosing sialadenitis were seen in the submandibular and parotid glands. The etiology, pathogenesis, and differential diagnosis of this disease and the clinical outcome of this case are discussed and presented.

Aged↗
PubMed2000

In vitro fusion of human inguinal hernia with associated epithelial transformation.

The processus vaginalis (PV) is a peritoneal diverticulum which forms to allow descent of the fetal testis to the scrotum. During human development fusion and obliteration of the PV often fails to occur with the result that inguinal hernias are the most prevalent congenital abnormality requiring surgery in childhood. Androgen is proposed to regulate testicular descent via the genitofemoral nerve which releases the neuropeptide calcitonin gene-related peptide (CGRP). It is possible that subsequent fusion of the PV and tissue remodelling following descent is indirectly controlled by androgen via CGRP action. An organ culture assay was developed to assess fusion of the PV taken from inguinal herniotomy in infants. Fusion was induced in vitro by CGRP but not by CGRP 8-37, CGRP 27-37 or dihydrotestosterone in equimolar concentrations. Fusion was accompanied by transformation of the epithelium, as shown by staining of intermediate filament proteins, cytokeratin and vimentin. Localization studies for CGRP receptors on 25 specimens indicated CGRP acts on mesenchymal fibroblasts but not directly on PV epithelium suggesting an indirect pathway. Hepatocyte growth factor/scatter factor was found to induce fusion of PV and may be involved as an intermediate molecule in the fusion cascade. This study represents the first approach to understanding the humoral control and underlying mechanism by which the PV fuses.

Animals↗
PubMed1999

Comparison of restimulation methods to elicit SIV specific cytotoxic T-lymphocytes (CTL) in vitro: Staphylococcal enterotoxin B (SEB) provides a novel method for the quantification of SIV specific CTL precursors.

Most investigators believe that an effective HIV-1 vaccine will have to induce high levels of HIV-1 specific cytotoxic T-cells (CTL). The macaque SIV challenge/protection model system has been used to test candidate vaccines, but quantitative immunogenicity measurements are difficult due to technical limitations of the assays available. The quantification of SIV specific CTLp is crucial to understanding correlates of immunity for these vaccines, but are difficult to measure. We have compared various methods to quantify SIV specific CTLp, and describe a novel method of SIV specific CTL in vitro stimulation using the superantigen Staphylococcal enterotoxin B (SEB). SEB can stimulate high levels of CTLp in vitro, and provides an alternative method to induce SIV specific CTL.

Animals↗
PubMed1999

Expression and use of human immunodeficiency virus type 1 coreceptors by human alveolar macrophages.

Human immunodeficiency virus type 1 (HIV-1) requires, in addition to CD4, coreceptors of the CC or CXC chemokine families for productive infection of T cells and cells of the monocyte-macrophage lineage. Based on the hypothesis that coreceptor expression on alveolar macrophages (AM) may influence HIV-1 infection of AM in the lung, this study analyzes the expression and utilization of HIV-1 coreceptors on AM of healthy individuals. AM were productively infected with five different primary isolates of HIV-1. Levels of surface expression of CCR5, CXCR4, and CD4 were low compared to those of blood monocytes, but CCR3 was not detectable. mRNA for CCR5, CXCR4, CCR2, and CCR3 were all detectable, but to varying degrees and with variability among donors. Expression of CCR5, CXCR4, and CCR2 mRNA was downregulated following stimulation with lipopolysaccharide (LPS). In contrast, secretion of the chemokines RANTES, MIP-1alpha, and MIP-1beta was upregulated with LPS stimulation. Interestingly, HIV-1 replication was diminished following LPS stimulation. Infection of AM with HIV-1 in the presence of the CC chemokines demonstrated blocking of infection. Together, these studies demonstrate that AM can be infected by a variety of primary HIV-1 isolates, AM express a variety of chemokine receptors, the dominant coreceptor used for HIV entry into AM is CCR5, the expression of these receptors is dependent on the state of activation of AM, and the ability of HIV-1 to infect AM may be modulated by expression of the chemokine receptors and by chemokines per se.

CD4 Antigens↗
PubMed1998

Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence.

Countless millions of people have died from tuberculosis, a chronic infectious disease caused by the tubercle bacillus. The complete genome sequence of the best-characterized strain of Mycobacterium tuberculosis, H37Rv, has been determined and analysed in order to improve our understanding of the biology of this slow-growing pathogen and to help the conception of new prophylactic and therapeutic interventions. The genome comprises 4,411,529 base pairs, contains around 4,000 genes, and has a very high guanine + cytosine content that is reflected in the biased amino-acid content of the proteins. M. tuberculosis differs radically from other bacteria in that a very large portion of its coding capacity is devoted to the production of enzymes involved in lipogenesis and lipolysis, and to two new families of glycine-rich proteins with a repetitive structure that may represent a source of antigenic variation.

Chromosome Mapping↗
PubMed1997

The nucleotide sequence of Saccharomyces cerevisiae chromosome IX.

Large-scale systematic sequencing has generally depended on the availability of an ordered library of large-insert bacterial or viral genomic clones for the organism under study. The generation of these large insert libraries, and the location of each clone on a genome map, is a laborious and time-consuming process. In an effort to overcome these problems, several groups have successfully demonstrated the viability of the whole-genome random 'shotgun' method in large-scale sequencing of both viruses and prokaryotes. Here we report the sequence of Saccharomyces cerevisiae chromosome IX, determined in part by a whole-chromosome 'shotgun', and describe the particular difficulties encountered in the random 'shotgun' sequencing of an entire eukaryotic chromosome. Analysis of this sequence shows that chromosome IX contains 221 open reading frames (ORFs), of which approximately 30% have been sequenced previously. This chromosome shows features typical of a small Saccharomyces cerevisiae chromosome.

Base Composition↗
PubMed1997

The nucleotide sequence of Saccharomyces cerevisiae chromosome XIII.

Systematic sequencing of the genome of Saccharomyces cerevisiae has revealed thousands of new predicted genes and allowed analysis of long-range features of chromosomal organization. Generally, genes and predicted genes seem to be distributed evenly throughout the genome, having no overall preference for DNA strand. Apart from the smaller chromosomes, which can have substantially lower gene density in their telomeric regions, there is a consistent average of one open reading frame (ORF) approximately every two kilobases. However, one of the most surprising findings for a eukaryote with approximately 6,000 genes was the amount of apparent redundancy in its genome. This redundancy occurs both between individual ORFs and over more extensive chromosome regions, which have been duplicated preserving gene order and orientation. Here we report the entire nucleotide sequence of chromosome XIII, the sixth-largest S. cerevisiae chromosome, and demonstrate that its features and organization are consistent with those observed for other S. cerevisiae chromosomes. Analysis revealed 459 ORFs, 284 have not been identified previously. Both intra- and interchromosomal duplications of regions of this chromosome have occurred.

Base Composition↗
PubMed1996

Effect of patient wear and extent of protein deposition on adsorption of Acanthamoeba to five types of hydrogel contact lenses.

Attachment of Acanthamoeba species to hydrogel contact lenses is a possible route of infection in Acanthamoeba keratitis. In this study, Acanthamoeba adsorption was compared with extent of lens deposition in worn lenses of different hydrogel polymers. After wear, lenses (80 lenses of 5 different types) were analyzed for total protein, surface area of deposition, and Acanthamoeba castellani trophozoite and cyst adsorption. Adsorption of Acanthamoeba trophozoites to worn lenses was greater than adsorption to unworn lenses for four of the five lens polymers (p < 0.01). Adsorption of cysts was greater for one of the five lens polymers (p < 0.001); all other adsorption assays showed no change with wear (p > 0.05). Adsorption was affected by both the water content and ionicity of the lens polymer. These results show that adsorption of Acanthamoeba to worn hydrogel contact lenses is greater than or equal to adsorption to unworn lenses.

Acanthamoeba↗
PubMed1996

Evaluation of oxygen delivery with the use of nasopharyngeal catheters and nasal cannulas.

The purpose of this pilot study was to examine the differences between nasopharyngeal catheter and nasal cannula oxygen delivery systems in infants. Eleven subjects requiring supplemental oxygen were enrolled in the study. All infants received both therapies at three separate gas flow rates (0.5, 0.3, and 0.2 liters per minute). Infants had higher heart rates when receiving nasal cannula oxygen than when receiving nasopharyngeal catheter oxygen (p < .05). There were no significant differences between the two therapies when comparing pulmonary mechanics, hypopharyngeal oxygen concentrations, and respiratory rates. However, when oxygen was delivered at the higher flow (0.5 liters), heart rate, tidal volume, and oxygen concentration were higher, and respiratory rates were decreased for both methods (p < .05). Because minimal differences were found between these two methods, either may be an appropriate choice for delivering supplemental oxygen.

Heart Rate↗
PubMed1990

A WAIS-R marker for accelerated aging and dementia, Alzheimer's type? Base rates of the Fuld formula in the WAIS-R standardization sample.

Recent reports have provided evidence that a WAIS-R marker for dementia of the Alzheimer's type (DAT) may have value in differential clinical diagnosis. Using the Fuld (1984) formula, this study investigated the prevalence of the WAIS-R marker in the WAIS-R standardization sample (N = 1,880), whose members range in age from 16 to 74 years. The results from the WAIS-R sample suggest no significant age differences in the occurrence of this marker when age-corrected scaled scores are employed. Across age, the occurrence of this marker is about 6.2%. Although there were no significant effects according to race, there were significant sex (males = 7.34%; females = 5.11%) and education effects. For individuals aged 65-74 with some post high school education, the base rate was about 14%. These findings are discussed as they relate to the potential clinical usefulness of this marker in the differential diagnosis of DAT.

Adolescent↗