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Biomedical subjects

S Selig

Publications and source records attributed to S Selig.

At least 19 recordsLinked to original sources
PubMed2000

HIV-1 envelope induces activation of caspase-3 and cleavage of focal adhesion kinase in primary human CD4(+) T cells.

Binding of HIV type 1 (HIV-1) envelope glycoproteins to the surface of a CD4(+) T cell transduces intracellular signals through the primary envelope receptor, CD4, and a coreceptor, either CCR5 or CXCR4. Furthermore, envelope-CD4(+) cell interactions increase rates of apoptosis in peripheral blood mononuclear cells (PBMCs). We demonstrate that in primary T lymphocytes, recombinant HIV-1 envelope proteins induce the activation of caspase-3 and caspase-6, which belong to a family of cysteine proteases that, upon activation, promote programmed cell death. Envelope-mediated activation of caspase-3 and caspase-6 depended on envelope-CD4 receptor interactions; CCR5-utilizing as well as CXCR4-utilizing envelopes elicited this response. Focal adhesion kinase (FAK) is a substrate of both caspase-3 and caspase-6, and inactivation of FAK by these caspases promotes apoptosis. En-velope treatment of lymphocytes led to the cleavage of FAK in a manner consistent with caspase-mediated cleavage.

Apoptosis↗
PubMed1999

Position effect of human telomeric repeats on replication timing.

Telomeres are distinct structures, composed of short, repeated sequences, at the ends of all eukaryotic chromosomes. Telomeres have been shown in yeast to induce late replication in S phase and to silence transcription of neighboring genes. To examine the possibility of similar effects in human chromosomes, we studied cells from a subject with a microdeletion of 130 kb at the end of one copy of chromosome arm 22q, repaired by the addition of telomere repeats. Using fluorescence in situ hybridization of S phase nuclei, a distinct difference was found in the replication timing of the breakpoint region between the intact and truncated copies of chromosome 22. This difference was evident as a shift from middle to late replication time of the breakpoint region adjacent to the repaired telomere. This finding suggests that the human telomere sequence influences activation of adjacent replication origin(s). The difference in replication timing between the two chromosomes was not associated with differences in sensitivity to digestion by DNase I or with methylation of regions immediately adjacent to the breakpoint. Furthermore, both alleles of arylsulfatase A, a gene located at a distance of approximately 54 kb from the breakpoint, were expressed. We conclude that as in yeast, the proximity of telomeric DNA may induce a positional effect that delays the replication of adjacent chromosomal regions in humans.

Cell Line↗
PubMed1997

Molecular characterization of Br-cadherin, a developmentally regulated, brain-specific cadherin.

Cadherins are a family of transmembrane proteins that play a crucial role in cell adhesion and in morphogenesis. Several of the cadherins are expressed in the nervous system, but none is neuron-specific. We characterize a new member of the cadherin family, Br-cadherin, which is present exclusively in the central nervous system. Although the Br-cadherin protein is confined to the central nervous system, its mRNA is present in several additional tissues, suggesting that there is posttranscriptional control of this gene's expression. Within the central nervous system, Br-cadherin appears to be expressed specifically by neurons. In the mouse, its expression becomes detectable during the first postnatal week, which corresponds temporally to the onset of synaptogenesis and dendrite outgrowth in the brain. This pattern of expression is consistent with a role for Br-cadherin in neuronal development, perhaps specifically with synaptogenesis.

Aging↗
PubMed1996

Girl Talk: development of an intervention for prevention of HIV/AIDS and other sexually transmitted diseases in adolescent females.

The number of adolescent females between the ages of 13 and 19 who are contracting sexually transmitted diseases (STDs) is rising at an alarming rate. Although the issue of STDs has been overshadowed by continued public debate over adolescent pregnancy and childbearing, it demands attention. Particularly concerning is the fact that STDs increase the likelihood of transmitting HIV (N.E. MacDonald et al., 1990). To offset the growing incidences of STDs among female adolescents, gender-specific interventions are needed. Following is a description of the theoretical underpinnings that informed and guided the development of a gender-specific intervention titled Girl Talk. A two-stage creation and review process was used to design this 2.5-hr, four-session intervention. An overview of the quasi-experimental design that compared a nonequivalent comparison and two intervention groups (peer led and adult led) is presented. Baseline characteristics of the three groups are reported. Also described is how participant feedback and a design content analysis are used to evaluate the appropriateness of the intervention for adolescent females.

Adolescent↗
PubMed1995

Expressed cadherin pseudogenes are localized to the critical region of the spinal muscular atrophy gene.

Low-copy repeats have been associated with genomic rearrangements and have been implicated in the generation of mutations in several diseases. Here we characterize a subset of low-copy repeats in the spinal muscular atrophy (SMA) region in human chromosome 5q13. We show that this repeated sequence, named c41-cad, is a highly expressed pseudogene derived from an intact neuronal cadherin gene, Br-cadherin, situated on 5p13-14. Br-cadherin is expressed specifically in the brain, whereas the c41-cad transcripts are 10-15 times more abundant and are present in all tissues examined. We speculate that the c41-cad repeats, separately or in concert with other repeats in the SMA region, are involved in the pathogenesis of SMA by promoting rearrangements and deletions.

Amino Acid Sequence↗
PubMed1995

Dp140: a novel 140 kDa CNS transcript from the dystrophin locus.

We have identified a 7.5 kb transcript from the dystrophin locus which encodes a novel 140 kDa protein (Dp140). Based on immunoblotting Dp140 consists of the distal rod domain and C-terminus of 427 kDa dystrophin and is found throughout the CNS. This protein is transcribed from an alternative promoter in the dystrophin locus upstream to exon 45. The unique 5' first exon is conserved between rat and human. The transcript has a 1 kb 5' untranslated region, and the first methionine initiation codon occurs in exon 51, predicting a protein of 140 kDa. Several studies report that Duchenne dystrophy patients with deletions in the exon 45-52 region have an increased incidence of cognitive impairment. Such deletions would affect expression of 427 kDa dystrophin and this shorter 140 kDa isoform but not the recently described small distal transcripts Dp116 or Dp71, suggesting particular importance to CNS function.

Amino Acid Sequence↗
PubMed1995

Refinement of the spinal muscular atrophy locus by genetic and physical mapping.

We report the mapping and characterization of 12 microsatellite markers including 11 novel markers. All markers were generated from overlapping YAC clones that span the spinal muscular atrophy (SMA) locus. PCR amplification of 32 overlapping YAC clones shows that 9 of the new markers (those set in italics) map to the interval between the two previous closest flanking markers (D5S629 and D5S557): cen-D5S6-D5S125-D5S435-D5S1407- D5S629-D5S1410-D5S1411/D5S1412-D5S1413- D5S1414-D5Z8-D5Z9-CATT1-D5Z10/D5Z6- D5S557-D5S1408-D5S1409-D5S637-D5S351-MA P1B-tel. Four of these new markers detect multiple loci in and out of the SMA gene region. Genetic analysis of recombinant SMA families indicates that D5S1413 is a new proximal flanking locus for the SMA gene. Interestingly, among the 40 physically mapped loci, the 14 multilocus markers map contiguously to a genomic region that overlaps, and perhaps helps define, the minimum genetic region encompassing the SMA gene(s).

Base Sequence↗
PubMed1994

Cloning of human basic A1, a distinct 59-kDa dystrophin-associated protein encoded on chromosome 8q23-24.

Duchenne and Becker muscular dystrophies are caused by defects of dystrophin, which forms a part of the membrane cytoskeleton of specialized cells such as muscle. It has been previously shown that the dystrophin-associated protein A1 (59-kDa DAP) is actually a heterogeneous group of phosphorylated proteins consisting of an acidic (alpha-A1) and a distinct basic (beta-A1) component. Partial peptide sequence of the A1 complex purified from rabbit muscle permitted the design of oligonucleotide probes that were used to isolate a cDNA for one human isoform of A1. This cDNA encodes a basic A1 isoform that is distinct from the recently described syntrophins in Torpedo and mouse and is expressed in many tissues with at least five distinct mRNA species of 5.9, 4.8, 4.3, 3.1, and 1.5 kb. A comparison of our human cDNA sequence with the GenBank expressed sequence tag (EST) data base has identified a relative from human skeletal muscle, EST25263, which is probably a human homologue of the published mouse syntrophin 2. We have mapped the human basic component of A1 and EST25263 genes to chromosomes 8q23-24 and 16, respectively.

Amino Acid Sequence↗
PubMed1993

Replication structure of the human beta-globin gene domain.

The animal cell genome is organized into a series of replicons with an average size of 50-300 kilobases; each of these units is characterized by its own origin of replication which serves as the point of initiation for DNA synthesis. In animal viruses, origin usage can be regulated by cis-acting elements, and in some cases, replication may be cell-type specific. Little is known, however, about the organization and control of endogenous tissue-specific gene replication. To understand this process, we have used a replication direction assay to examine DNA fragments covering more than 200 kilobases of the human beta-like globin domain, and have identified a single bidirectional origin located upstream of the beta-globin itself. This locus is used to initiate DNA synthesis in expressing cells, where the globin domain replicates early, and in non-expressing cells, which are characterized by late replication of the same region. Deletion of this origin sequence, as occurs in the haemoglobin Lepore syndrome, cancels bidirectional DNA synthesis at this site and leads to a striking reversal of replication direction upstream to the locus. This represents the first genetic proof of the existence of specific, discrete origins of replication in animal cells.

Cell Line↗
PubMed1993

Allele-specific replication timing of imprinted gene regions.

Several lines of evidence suggest that the paternal and maternal genomes may have different expression patterns in the developing organism and this has been confirmed by the identification of endogenous genes that are parentally imprinted in the mouse. Little is known about the precise mechanisms involved in the process, but structural differences between the two alleles must somehow provide cis-acting signals for directing parental-specific transcription. Cell-cycle replication time is one parameter that has been shown to be associated with both tissue-specific gene expression and the allele-specific transcription patterns of the X chromosomes in female cells. For this reason we have examined the replication timing patterns for the chromosomal regions containing the imprinted genes Igf2, Igf2r, H19 and Snrpn in the mouse. At all of these sites, and their corresponding positions in the human genome, the two homologous alleles replicate asynchronously and it is always the paternal allele that is early-replicating. Thus imprinted genes appear to be embedded in large DNA domains with differential replication patterns, which may provide a structural imprint for parental identity.

Alleles↗
PubMed1992

Delineation of DNA replication time zones by fluorescence in situ hybridization.

Fluorescence in situ hybridization has been used to visualize specific genomic DNA sequences in interphase nuclei. In normal diploid cells, unreplicated DNA segments give singlet hybridization signals while replicated loci are characterized by doublets. The distribution of these two patterns in unsynchronized cell populations can be used to determine the S phase replication time of any DNA sequence. The validity of this approach was established by analyzing genes whose replication profiles in expressing and non-expressing cells had been determined previously by conventional methods. Using this technique it has been possible to map the replication timing topography of the DNA within and flanking the cystic fibrosis (CF) gene locus on chromosome 7. The gene itself is located within a defined time zone which is approximately 500 kb in length and is under developmental control. It is early replicating in cells which express CF but late replicating in other cell types. These time zones probably represent basic units of chromosome structure.

Bromodeoxyuridine↗
PubMed1991

Chromosome structure and eukaryotic gene organization.

The DNA in the eukaryotic nucleus is highly compacted but well organized into distinct regional units. Chromosomal bands are characterized by their structure and distinctive replication time. They are subdivided into chromatin loops which serve as functional domains that have discrete boundary elements and can be regulated during development.

Animals↗
PubMed1991

Ethical dimensions of intergenerational reciprocity: implications for practice.

This paper reviews the moral and ethical context of family relationships and caregiver stress, with an emphasis on the implications for professional interventions. Three views of filial responsibility are presented: parental reverence, a debt of gratitude, and caregiving as an expression of friendship and love. Case studies are presented to illustrate how an exploration of ethically defensible limits to caregiving might proceed.

Adult↗
PubMed1989

Keeping volunteers in EMS* (*emergency medical services).

The EMS system is widely dependent on the use of volunteers. This report of a study of EMS in Genesee County, Michigan, covers the volunteers' point of view on their attraction to the field and job satisfaction as well as the agency's response to recruitment and retention issues.

Data Collection↗