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Biomedical subjects

T Collins

Publications and source records attributed to T Collins.

At least 127 records · Page 7Linked to original sources
PubMed1993

Detection of latent cytomegalovirus DNA in diverse organs of mice.

Latency is essential to the pathogenesis of cytomegalovirus (CMV) infection and disease. A survey of mouse organs that might contain latent murine CMV (MCMV) DNA was conducted using nested enzymatic amplification of a 200-bp region of exon 4 of the major immediate early gene 1. MCMV DNA was detected in diverse organs including the heart, kidney, liver, lung, spleen, brain, and salivary glands. The total number of organs in which latent MCMV DNA was detected was significantly greater in mice infected at 4 weeks of age (64/70) than in mice infected at 7 weeks of age (40/69). This phenomenon was associated with greater viral replication in the same organs during acute infection. These results indicate that latent MCMV infection is distributed much more widely than previously suspected and is directly correlated with the extent of viral replication during acute infection.

Age Factors↗
PubMed1993

Differential regulation of vascular cell adhesion molecule 1 gene expression by specific NF-kappa B subunits in endothelial and epithelial cells.

Vascular cell adhesion molecule 1 (VCAM-1) is expressed in both endothelial and epithelial cell types, where it contributes to lymphocyte migration to sites of inflammation. Its expression is regulated by cytokines, in part through two kappa B-like regulatory elements. Because NF-kappa B can be composed of multiple alternative subunits with differential effects on gene expression, the role of different specific NF-kappa B family members subunits in VCAM-1 regulation is unknown. In this report, we define the contribution of different NF-kappa B family members to VCAM-1 gene regulation. We show that both kappa B sites in the VCAM-1 enhancer are required to optimally stimulate gene expression, but the enhancer is differentially regulated by specific combinations of NF-kappa B subunits. At low concentrations, RelA(p65) acted in concert with the approximately 50-kDa product of p105 NF-kappa B, NF-kappa B1(p50), to stimulate transcription, and at high concentrations, RelA(p65) alone stimulated the VCAM-1 promoter. In contrast, NF-kappa B2 inhibited functional activation of the VCAM reporter by p65. Consistent with this finding, an additional binding complex was detected by using recombinant NF-kappa B2(p49)/RelA(p65) with radiolabeled VCAM kappa B site probes. Interestingly, the human immunodeficiency virus enhancer responded differently to stimulation by NF-kappa B subunits, with optimal response to p49(100)/p65. Analysis of NF-kappa B mRNA in human umbilical vein endothelial cells revealed that nfkb1, nfkb2, and relA NF-kappa B but not c-rel were induced by tumor necrosis factor alpha and lipopolysaccharide, which also induce VCAM-1. These data suggest that specific subunits of NF-kappa B regulate VCAM-1 and differentially activate other genes in these cells.

Animals↗
PubMed1993

Nd:YAG laser as a therapeutic option in the management of gastrointestinal cancer.

We report the use of ELT utilizing an Nd:YAG laser in a group of patients with cancer who represented a significant surgical risk. Effective palliation was achieved, with minimal morbidity, and the quality of life of most of our patients was preserved or enhanced, at a minimal physiologic cost. In carefully selected patients, ELT has proved to be a safe and highly effective procedure for the management of gastrointestinal cancers. It should be considered a valuable addition to the treatment armamentarium of the practicing clinician dealing with patients with advanced cancers or patients with significant medical conditions precluding surgical resection.

Aged↗
PubMed1993

Expression of VCAM-1 and E-selectin in an in vivo model of endothelial activation.

Vascular cell adhesion molecule 1 (VCAM-1) and E-selectin (or endothelial-leukocyte adhesion molecule 1) are inducible endothelial cell adhesion molecules that play a role in the recruitment of leukocytes into sites of inflammation. Information about the spatial and temporal pattern of induced expression of these leukocyte adhesion molecules in vivo is limited. This study reports the expression profile of VCAM-1 and E-selectin in various mouse tissues after lipopolysaccharide administration. Using rat complementary DNA probes for VCAM-1 and E-selectin, Northern blot analysis showed a marked increase in transcript levels for both adhesion molecules in lung, heart, and kidney. Maximal transcript levels for both VCAM-1 and E-selectin were observed at 3-6 hours and declined to low, constitutive levels of expression at 48 hours. Consistent with the Northern blot results, immunoperoxidase analysis revealed focal endothelial cell expression of VCAM-1 in control animals. Following lipopolysaccharide administration, VCAM-1 expression increased dramatically in all vascular beds examined, although the response was heterogeneous. Widespread induced expression of VCAM-1 on cells other than vascular endothelium was not seen. Neither basal nor induced expression correlated with leukocyte adhesion. Signals other than the expression of endothelial leukocyte adhesion molecules are required in vivo for leukocyte infiltration in this murine model of systemic endothelial activation.

Amino Acid Sequence↗
PubMed1993

Endothelial nuclear factor-kappa B and the initiation of the atherosclerotic lesion.

The genes for several endothelial-leukocyte adhesion molecules implicated in the initiation of the atherosclerotic lesion contain functional NF-kappa B binding sites which are required for cytokine induction in endothelial cells. Activation of this pleiotropic family of transcription factors may explain in part the diversity of growth factor and cytokine gene expression associated with dysfunctional endothelium, as well as the increased endothelial cell replication observed at lesion prone anatomic sites. Endothelial oxidant stress and activation of the NF-kappa B family of transcription factors may link the otherwise seemingly diverse risk factors associated with the initiation of the atherosclerotic lesion into a final common pathway for induced endothelial gene activation.

Arteriosclerosis↗
PubMed1992

Functional analysis of the human vascular cell adhesion molecule 1 promoter.

The vascular cell adhesion molecule 1 (VCAM-1) is a 110-kD member of the immunoglobulin gene superfamily expressed on the surface of interleukin 1 beta- or tumor necrosis factor alpha (TNF)-stimulated endothelial cells. The cell surface protein functions as an inducible adhesion receptor for circulating mononuclear leukocytes and some tumor cells. We have previously characterized the genomic organization of the VCAM1 gene and described its chromosomal localization. In this report, the promoter of the VCAM1 gene is characterized. New transcription of the VCAM1 gene occurred when endothelial cells were treated with TNF. Fusion plasmids containing the 5' flanking sequence of the VCAM1 gene and the chloramphenicol acetyltransferase reporter gene were used to identify cis-acting sequences that direct the cytokine-induced transcription. When transfected into bovine aortic endothelial cells, constructs containing 755 bp of the 5' flanking sequence were induced by TNF. Within the cytokine-responsive region of the core promoter were functional NF-kappa B and GATA elements. Upstream of the core promoter, the VCAM1 5' flanking sequence contained a negative regulatory activity. NF-kappa B-mediated activation of VCAM1 gene expression may lead to endothelial expression of a mononuclear leukocyte adhesion molecule associated with initial events in the development of an atherosclerotic lesion.

Animals↗
PubMed1992

Human platelet-derived growth factor A chain is transcriptionally repressed by the Wilms tumor suppressor WT1.

Wilms tumor, an embryonic kidney malignancy, accounts for approximately 6% of all pediatric neoplasms. A gene implicated in the genesis of this tumor, the Wilms tumor suppressor gene (WT1), encodes a zinc-finger DNA-binding protein (WT1) that functions as a transcriptional repressor. In certain Wilms tumors, the platelet-derived growth factor A chain (PDGF-A) is overexpressed; it has therefore been suggested that it may play an autocrine role in development of these neoplasms. Since the PDGF-A promoter contains putative binding sites for WT1, we explored the role of WT1 in regulating A-chain expression. The major PDGF-A promoter activity was localized in transient transfection assays to a region spanning from -643 to + 8 relative to the transcription start site. WT1 bound to several sites in this region of the promoter, as demonstrated by gel-shift analysis and DNase I footprinting, and functioned as a powerful repressor of PDGF-A transcription in vivo. Maximal repression (> 50-fold) of the PDGF-A promoter was dependent on the presence of multiple WT1 binding sites in transient transfection assays. Our observations suggest a mechanism for normal downregulation of a growth factor gene and of an autocrine growth process of import in kidney development and other biological systems.

3T3 Cells↗
PubMed1992

Nucleotide sequence of rat vascular cell adhesion molecule-1 cDNA.

Vascular cell adhesion molecule 1 (VCAM-1) is an inducible transmembrane protein which is expressed by vascular endothelium following cytokine activation. VCAM-1 mediated the adhesion of certain blood leukocytes and tumor cells via the interaction with its counter-receptor, the integrin VLA4. When initially cloned from interleukin-1 (IL-1) stimulated human umbilical vein endothelial cells, VCAM-1 was reported to contain six immunoglobulin-like domains. However, subsequent cDNA clones and structural analysis of the human gene evealed an alternatively spliced seventh immunoglobulin domain. This seven domain form appears to be the predominant transcript in IL-1 activated endothelium. In this report, the cloning and nucleotide sequence of rat VCAM-1 is described.

Amino Acid Sequence↗
PubMed1992

Nucleotide sequence of endothelin-1 cDNA from rabbit endothelial cells.

A cDNA encoding rabbit endothelin-1 (ET-1) was isolated by plaque hybridization from a rabbit inferior vena caval endothelial cell lambda gt11 cDNA library using human ET-1 cDNA as the hybridization probe. DNA sequence analysis indicates that mature 21 amino acid rabbit ET-1 is derived from a 202 amino acid precursor, via a 39 amino acid intermediate 'big' ET-1.

Amino Acid Sequence↗
PubMed1992

Colocalization of thrombospondin and syndecan during murine development.

Thrombospondin is an adhesive glycoprotein that is thought to play a role in tissue genesis and repair. We have used a monoclonal anti-thrombospondin antibody, designated 5G11, to localize thrombospondin in paraformaldehyde fixed, paraffin-embedded sections of developing mouse embryos. Thrombospondin expression is observed in uterine smooth muscle, endometrial glands, the decidua, and trophoblastic giant cells during the initial phase of post-implantation development in the embryo. Cardiac myocytes and neuroepithelial cells show positive staining for thrombospondin at day 8.5 of gestation, and this expression continues throughout the development of the myocardium and central nervous system. Strong staining for thrombospondin is seen in developing bone and in the liver. Thrombospondin is also observed in developing smooth muscle and skeletal muscle, as well as in a variety of epithelia, including the epidermis, small intestinal epithelium, lens epithelium, renal tubular epithelium, and the epithelium of the developing tooth. Comparison of thrombospondin staining with that of two known cell surface receptors for thrombospondin, syndecan and the vitronectin receptor, reveals remarkable colocalization of thrombospondin and syndecan in all tissues, but almost no coexpression with the vitronectin receptor. Coexpression of thrombospondin and syndecan may play an important role in cell-cell or cell-matrix interactions during development.

Animals↗
PubMed1992

Platelet-derived growth factor A chain: confirmation of localization of PDGFA to chromosome 7p22 and description of an unusual minisatellite.

The human PDGFA gene, encoding the A chain of platelet-derived growth factor, has been previously cloned and characterized, but two conflicting chromosomal localizations have been presented. To resolve this controversy, we have now performed nonisotopic in situ hybridization using new genomic PDGFA subclones and analyzed somatic cell hybrid DNAs for the presence of human PDGFA by polymerase chain reaction. The results confirm our previous assignment of PDGFA to chromosome 7p22. New sequence data from the PDGFA locus have been obtained and analyzed. An unusual minisatellite, which includes an evolutionarily conserved protein-coding region of exon 4, was found within IVS4. The minisatellite includes an embedded polymorphic pentanucleotide microsatellite repeat. Analysis of this polymorphism and in situ hybridization both locate PDGFA outside the monosomic region in a patient with a de novo deletion of the short arm of chromosome 7 [del (7)(p22.1-pter)].

Amino Acid Sequence↗
PubMed1992

Human HOX4E: a gene strongly expressed in the adult male and female urogenital tracts.

Homeobox-containing genes (Hox genes) are believed to play a fundamental role in development and positional identity. Four homologous Hox gene complexes are found in humans and mice. Genes at the 3' ends of these complexes tend to be expressed rostrally while those at the 5' end are expressed caudally. Whereas complete open reading frames have been reported for rostrally expressed 3' Hox genes, structural information is lacking for the more 5' genes. Genomic and cDNA clones containing the human HOX4E (also known as human Hox 4.5) gene were isolated. The gene contains two exons and spans about 5 kb of DNA. The N-terminal portion of the HOX4E activation domain contains several consensus sequence elements also found in other mammalian AbdB family genes. Further downstream, however, HOX4E contains a novel 37-amino-acid stretch containing 30% acidic residues. Northern blot analysis of HOX4E expression in adult tissues showed a major human transcript of 1.8 kb, the expression of which was largely limited to tissues of the male and female urogenital tracts. Expression was particularly strong in the uterus. This suggests that aside from its effects during embryogenesis, the HOX4E gene may play a continuing role in adult genitourinary tract function.

Adult↗
PubMed1992

The use of discriminant analysis to guide palliative treatment for lung cancer patients.

The aim of this study was to develop a prognostic index for patients with inoperable non-small cell lung cancer which could predict survival to 3 months. This would enable less radiation dose to be given to patients where prognosis is limited by occult metastases, giving rise to less treatment morbidity and raising the therapeutic ratio. Data on 18 known prognostic factors were collected on 96 patients. Performance status, lymphocyte count, weight loss and extent of disease were the most predictive factors and were combined into an index. Logistic discriminant analysis was employed to give a numerical score of likelihood of survival to 3 months, ranging from 0 (not likely) to 1 (certain). In this first set of 96 patients, 16 deaths were observed before 3 months, of which 6 were predicted. There was one false positive prediction. Overall accuracy of prediction was therefore 89% with 99% specificity. The same 4 prognostic factors were measured on a second set of 80 patients. Nineteen died before 3 months, of which 5 were predicted with 2 false positives, giving an overall accuracy of 80% and 97% specificity. A probability of survival of less than or equal to 0.2, although highly specific, was only applicable to 9% of patients and this was the limiting factor in the clinical usefulness of the test. A 16-branch tree diagram allows any patient to be assigned a risk factor based on the four predictive factors at the first clinic attendance. Use of the index could encourage more rational prescribing of radiation dose.

Activities of Daily Living↗
PubMed1992

Children with Haemophilus influenzae bacteremia initially treated as outpatients: outcome in 85 American Indian children.

Eighty-five American Indian children less than 16 years of age with Haemophilus influenzae bacteremia were retrospectively determined to have been treated as outpatients after their initial evaluation. We hoped to determine the proportion that developed new foci, the time interval to this development and whether age or temperature at presentation predicted outcome. Fifty-one (60%) presented with nonfocal findings. Seventy-two (85%) were treated with antibiotics at the initial visit. Although 49 (58%) of the patients were never hospitalized, a new focus was identified in 25 (29%), including 13 (15%) with a final diagnosis of meningitis. The new foci were identified within 6 days of presentation (median, 2 days). An additional 15 (18%) patients had no new focus but were febrile and/or ill at follow-up. All patients with meningitis or a second positive culture were hospitalized at the first follow-up visit. Age and temperature at presentation did not help predict outcome. All patients with H. influenzae bacteremia require prompt reevaluation and close follow-up by an experienced physician.

Ambulatory Care↗
PubMed1992

Effects of interferon-gamma on nitric oxide synthase activity and endothelin-1 production by vascular endothelial cells.

Given the pivotal role suggested for IFN-gamma in immune diseases of the vascular wall, we investigated the effects of IFN-gamma on nitric oxide (NO) and endothelin-1 (ET-1) expression in bovine aortic endothelial cells (BAEC). We have previously reported that TNF-alpha enhanced NO synthase activity in BAEC as assessed by quantifying release of bioactive NO with reporter monolayers and measuring conversion of L-[14C]arginine to L-[14C] citrulline. In murine macrophages IFN-gamma synergizes with TNF-alpha or lipopolysaccharide to induce robust increases in calcium-independent NO synthase activity. In this study we have found that IFN-gamma alone failed to have a significant effect on NO synthase activity in BAEC. In contrast to murine macrophages, IFN-gamma inhibited TNF-alpha-stimulated induction of endothelial NO synthase activity in a concentration-dependent manner. This observation suggests that there is major difference in the response of BAEC and murine macrophages to IFN-gamma. A second major aim of this study was to determine the effect of IFN-gamma on preproET-1 mRNA expression and ET-1 secretion rates in BAEC. IFN-gamma alone had little or no effect on ET-1 mRNA levels and basal ET release when measured for 8 h. However, cotreatment with IFN-gamma potentiated the stimulatory effect of TNF-alpha on BAEC ET-1 mRNA transcript levels and ET release. In contrast, pretreatment of cells with IFN-gamma for 16-24 h blunted the stimulatory effect of TNF-alpha. These findings suggest that endothelial cell expression of vasoactive mediators is modified by the temporal interplay of at least two immune mediators, IFN-gamma and TNF-alpha.

Amino Acid Oxidoreductases↗