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T Collins

Publications and source records attributed to T Collins.

At least 145 records · Page 8Linked to original sources
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↗
PubMed1992

Homeobox genes and congenital malformations.

In this review we have built a case for abnormal Hox gene expression in human congenital malformations without presenting any direct evidence of their involvement. This approach is justified by the dramatic advances in developmental genetics which emphasize the considerable similarity in the primary processes and molecules used to guide early morphogenesis in all species. Hox genes occupy a central role in this scheme, being activated in a specific rostral-caudal order after initial specification of the basic embryonic axes and, thereafter, specifying positional identity by influencing downstream "realizator" genes that carry out the position-specific program. These theoretical arguments, together with the dramatic results obtained in an evolutionarily similar organism (the mouse) using the transgenic and gene deletion approaches, make it highly likely that abnormalities in Hox gene structure and expression will soon be implicated in specific human congenital malformation syndromes. In parallel with this phenotypic analysis, we can expect that the animal models discussed in this review will provide greater detail regarding the upstream regulators and downstream targets of Hox gene products. Together these approaches promise to finally elucidate some of the underlying mechanisms responsible for human congenital malformations.

Animals↗
PubMed1991

Gene structure, chromosomal location, and basis for alternative mRNA splicing of the human VCAM1 gene.

Vascular cell adhesion molecule 1 (VCAM-1) is a cell surface glycoprotein adhesive for certain blood leukocytes and tumor cells, which is expressed by activated endothelium in a variety of pathologic conditions including atherosclerosis. Genomic clones encoding the VCAM1 gene were isolated and the organization of the gene was determined. The gene, which is present in a single copy in the human genome, contains 9 exons spanning approximately 25 kilobases of DNA. Exons 2-8 contain C2 or H-type immunoglobulin domains. At least two different VCAM-1 precursors can be generated from the human gene as a result of alternative mRNA splicing events, which include or exclude exon 5. A consensus TATAA element is located upstream of the transcriptional start site. The VCAM1 promoter contains consensus binding sites for NF-kappa B, the GATA family of transcription factors, as well as an AP1 site. The VCAM1 gene was assigned to the 1p31-32 region of chromosome 1 based on the analysis of human-mouse hybrid cell lines and in situ hybridization. Structural analysis of the human VCAM1 gene provides the basis for alternative mRNA splicing and an initial approach to elucidating the regulation of VCAM-1 expression.

Amino Acid Sequence↗
PubMed1991

Structure and chromosomal location of the gene for endothelial-leukocyte adhesion molecule 1.

Endothelial-leukocyte adhesion molecule 1 is a cell surface glycoprotein expressed by cytokine-activated endothelium that mediates the adhesion of blood neutrophils. Endothelial-leukocyte adhesion molecule 1 is a member of the selectin family of cell adhesion molecules each of which contain an amino-terminal lectin-like domain, followed by an epidermal growth factor-like domain and a variable number of short consensus repeats similar to those found in complement binding proteins. Genomic clones encoding the ELAM gene were isolated and the organization of the ELAM gene was determined. The gene, which is present in a single copy in the human genome, contains 14 exons spanning about 13 kilobases of DNA. The positions of exon-intron boundaries correlate with the putative functional subdivisions of the protein. Introns are found at similar positions in all of the six complement regulatory repeats, suggesting that these elements arose by internal gene duplication. A consensus TATAA element is located upstream of the transcriptional start site. The ELAM promoter contains an inverted CCAAT box and consensus NF-kappa B- and AP-1-binding sites. The ELAM gene was assigned to the q12 greater than qter region of human chromosome 1 by analysis of human-mouse hybrid cell lines. Two other members of the selectin gene family, the leukocyte adhesion molecule 1 (LAM-1, TQ1, LEC-CAM 1, or Leu-8) and the granule membrane protein 140 (GMP-140, PADGEM, or CD62) have been localized to the long arm of chromosome 1, as have the structurally related complement binding proteins, suggesting that these genes may share a common evolutionary history.

Amino Acid Sequence↗
PubMed1991

PDGF B-chain in neurons of the central nervous system, posterior pituitary, and in a transgenic model.

Platelet-derived growth factors (PDGFs) are growth-regulatory molecules that stimulate chemotaxis, proliferation, and increased metabolism of primarily connective tissue cells. In a survey of normal tissues, we found specific immunostaining for PDGF B-chain in neurons, principal dendrites, some axons, and probable terminals throughout the brain, in the dorsal horn of the spinal cord, and in the posterior pituitary of a nonhuman primate (Macaca nemestrina). PDGF activity was extracted from brain cortex and posterior pituitary, and ubiquitous expression of transcripts for the two chains of PDGF and both PDGF receptors was detected throughout the brain and posterior pituitary. A transgenic model was also evaluated in which the chloramphenicol acetyltransferase gene was placed under transcriptional control of the PDGF B-chain promoter. The transgene was preferentially expressed within neural cell bodies in the cortex, hippocampus, and cerebellum. PDGF may act as a neuronal regulatory agent. Neuronal release of PDGF could contribute to nerve regeneration and to glial proliferation that leads to gliosis and scarring.

Animals↗
PubMed1991

Structure of the murine c-sis proto-oncogene (Sis, PDGFB) encoding the B chain of platelet-derived growth factor.

The murine proto-oncogene c-sis (Sis, PDGFB), encoding the B chain of platelet-derived growth factor, has been cloned. Its structure, with seven exons spanning approximately 20 kb, closely resembles that of the human and feline homologs. The predicted amino acid sequence of murine PDGF-B has residues 89% identical to those of human PDGF-B. A noncoding region at the start of exon 7, which is deleted by alternative splicing during the generation of the viral v-sis oncogene, is highly conserved in human, mouse, and cat and may represent an important regulatory element.

Amino Acid Sequence↗
PubMed1991

Regulated expression of endothelin 1 in glomerular capillary endothelial cells.

Endothelin (ET)-1 is a powerful vasoconstrictor known to be produced and secreted by endothelial cells lining large vessels. Because ET-1 stimulates glomerular mesangial cell contraction, glomerular capillary endothelial cells (GEN), normally situated in close apposition to mesangial cells, were examined for potential ET expression and secretion. Cultured bovine GEN released ET in a time-dependent fashion. ET secretion was significantly stimulated by bradykinin, an agonist known to activate phospholipase C in these cells. Preproendothelin 1 (preproET-1) mRNA levels in GEN rose in a biphasic manner on stimulation with bradykinin. The early increments (at 30 min) were not dependent on new protein synthesis, whereas the late rise (6 h after addition of bradykinin) appeared to be protein synthesis dependent. Neither early or late bradykinin-stimulated preproET-1 mRNA expression in glomerular endothelial cells was due to inhibition of mRNA breakdown. Both phases of preproET-1 mRNA expression were observed with other glomerular endothelial cell calcium-mobilizing agonists, namely thrombin, and were mimicked by the calcium ionophore ionomycin. By contrast, the protein kinase C activator phorbol myristate acetate only enhanced preproET-1 mRNA expression at 30 min and suppressed expression thereafter. It is concluded that GEN have the potential to express and secrete ET-1 in a phospholipase C-regulated fashion. Furthermore, because glomerular mesangial cells respond to this peptide, the findings raise the possibility of paracrine regulation of mesangial cell tone by glomerular endothelial cell-derived ET-1.

Animals↗
PubMed1991

Effects of heterologous growth hormones on hypothalamic and pituitary function in transgenic mice.

The expression of the mouse metallothionein-I (mMT) promoter/human growth hormone (hGH) fusion gene in transgenic mice leads to female sterility and major alterations in the function of the hypothalamic-adenohypophyseal system. These alterations include increases in median-eminence norepinephrine turnover and plasma LH levels, and a decrease in plasma prolactin levels in intact males, and an increase in median-eminence dopamine turnover combined with the suppression of plasma prolactin levels in ovariectomized females. To further characterize these changes and to determine whether they are due to the lactogenic or somatotropic activity of hGH, we have studied hypothalamic and pituitary function in transgenic mice expressing mMT/hGH, mMT/hGH.B 'variant', or mMT/bGH fusion genes. In males, the expression of the hGH.B gene was associated with a reduction in pituitary prolactin release in vitro and an increase in LH response to LHRH stimulation, while the bGH transgene did not affect any of the examined parameters of LH and prolactin release. Median-eminence norepinephrine turnover was increased in each of the three lines of transgenic males, while median-eminence dopamine turnover was reduced only in animals expressing the hGH.B gene. In ovariectomized females, plasma LH was suppressed by hGH variant expression, while median-eminence norepinephrine turnover was suppressed in both hGH.B and bGH animals. The turnover of dopamine was increased in the median eminence of females expressing either of the human genes (hGH or gHG.B) and reduced in the median eminence of ovariectomized bGH females. We conclude that the hGH.B gene is weakly lactogenic in mice, and that the chronic stimulation of either GH receptors (by bGH) or both GH and prolactin receptors (by hGH or hGH.B) can lead to profound alterations in the metabolism of hypothalamic neurotransmitters and pituitary hormone release.

Animals↗
PubMed1991

Mental illness and psychotropic medication use in the nursing home.

The authors examined mental illness and psychotropic medications use among nursing home residents. Data were drawn from the Texas Long-Term Care Reimbursement Project, a 1986 study of nearly 2,000 residents in 49 nursing homes. The study measured the use of antipsychotics and other psychotropic medications, physical health conditions, mental illness diagnoses, behavior, and nursing and other direct-care time for sampled residents. The findings indicated that 45% of the sample was receiving an antipsychotic or other psychotropic medication. Although psychotropics were prescribed more extensively for those with a psychiatric diagnosis, nearly one half of persons without a psychiatric diagnosis were receiving psychotropic medications at the time of the survey. Moreover, psychotropics were quite prevalent among those with unstable medical conditions and/or severe activities of daily living impairment. Neither a mental illness diagnosis, evidence of a behavioral problem, nor use of psychotropics was significantly correlated with the amount of nursing or other direct-care time received by residents. The findings raise concerns about the widespread prescribing of these medications, especially among residents who have no supporting psychiatric diagnosis and/or who have physical health conditions making them vulnerable to adverse drug effects.

Drug Utilization↗
PubMed1991

Alternative splicing of human VCAM-1 in activated vascular endothelium.

Vascular cell adhesion molecule 1 (VCAM-1)/inducible cell adhesion molecule 110 is a mononuclear leukocyte-selective adhesion molecule, expressed on vascular endothelium following activation by certain cytokines or endotoxin. This inducible transmembrane protein and member of the immunoglobulin gene superfamily was previously reported to contain six immunoglobulinlike domains. Using the polymerase chain reaction, a VCAM-1 cDNA was obtained from mRNA of interleukin-1 (IL-1)-treated cultured human umbilical vein endothelial cells (HUVEC). The cDNA clone contained an additional 276 base-pair (bp) domain, located between domains 3 and 4. This new domain is most homologous to the existing N-terminal domain (domain 1). The internal 276-bp region is encoded by a single exon of the human VCAM-1 gene, indicating that the two forms of mRNA arise by alternative splicing. Both forms of VCAM-1 mRNA were detected by polymerase chain reaction in IL-1-stimulated HUVEC, although the seven-domain form appeared predominant. On the surface of HUVEC only a 110-kd polypeptide, consistent with the seven-immunoglobulinlike domain form of VCAM-1, was detectable by immunoprecipitation. Alternative splicing of the VCAM-1 gene in cytokine-activated endothelium may generate functionally distinct cell-surface adhesion molecules.

Amino Acid Sequence↗
PubMed1991

Aminoglycosides versus beta-lactams in gram-negative pneumonia.

Newer beta-lactam antibiotics with high levels of activity against gram-negative aerobic bacilli (including Pseudomonas aeruginosa) such as cefoperazone, ceftazidime, imipenem, and aztreonam may be suitable for monotherapy of gram-negative pneumonia. Aminoglycoside antibiotics (gentamicin, tobramycin, amikacin are also highly active against these same organisms and have been more extensively used, but are both ototoxic and nephrotoxic. Key therapeutic questions are whether beta-lactams can safely replace aminoglycosides for the treatment of gram-negative pneumonia, and whether monotherapy or aminoglycoside and beta-lactam combination antibiotic treatment is superior. There is remarkably little definitive clinical data in the literature to answer these questions, but available studies suggest that beta-lactam monotherapy may be adequate for Escherichia coli and Klebsiella pneumoniae pneumonias, but that combination therapy may be preferred for Pseudomonas aeruginosa, Serratia sp, Enterobacter sp, and Acinetobacter sp, largely based on rates of bacterial persistence and emergence of resistance. At this time, there are more data available to support aminoglycoside monotherapy than beta-lactam monotherapy in gram-negative pneumonia and remarkably little data to suggest superiority of two antibiotics over single agents when they have been compared prospectively. Thus, combination therapy remains a conservative recommendation until better studies are available.

Aminoglycosides↗
PubMed1990

Increased platelet-derived growth factor A-chain expression in human uterine smooth muscle cells during the physiologic hypertrophy of pregnancy.

Platelet-derived growth factor (PDGF) has been implicated in the cell proliferation and directed cell movement in various physiologic and pathologic processes. To explore the role of PDGF in a reversible physiologic process, adaptation of the uterus to pregnancy, expression of PDGF in tissue sections of human gestational myometrium was demonstrated by immunohistochemical techniques and confirmed by nuclease protection analysis. Commensurate with an increase in immunoreactive PDGF expression in the myometrial smooth muscle cells, increased levels of PDGF A-chain mRNA, but not PDGF B-chain or PDGF B-type receptor transcripts, were seen in the gravid uterus relative to the nongravid uterus. The amount of A-chain transcript increased during gestation and diminished during the puerperium. These observations demonstrate PDGF polypeptide expression in situ and implicate PDGF in a normal physiologic process--uterine expansion during pregnancy.

Exons↗
PubMed1990

Parent-professional relationships in the treatment of seriously emotionally disturbed children and adolescents.

The principle of parent-professional collaboration in responding to the needs of seriously emotionally disturbed children has been articulated in both policy and program guidelines. Research suggests that parents have not yet been integrated into the system of care for their children. This article reviews parents' concerns about their interactions with professionals and analyzes factors that may impede an improved relationship between the two groups. It suggests that a feminist/empowerment conceptualization of practice with parents of seriously emotionally disturbed children may be conducive to the attainment of full parent involvement in the system of care.

Adolescent↗
PubMed1990

Alternatively spliced platelet-derived growth factor A-chain transcripts are not tumor specific but encode normal cellular proteins.

Two platelet-derived growth factor A-chain proteins, termed short and long A chains, are generated as a result of alternative mRNA splicing of exon 6 of the A-chain gene. S1 nuclease mapping and polymerase chain reaction analyses demonstrate that both short and long A-chain transcripts are expressed in a variety of normal tissues. In addition, immunohistochemical localization of long A-chain protein reveals a cellular distribution identical to that observed with platelet-derived growth factor heteroserum.

Amino Acid Sequence↗
PubMed1990

Neuroendocrine function in transgenic male mice with human growth hormone expression.

The neuroendocrine effects of human growth hormone (hGH) secretion were studied in adult male mice into which an hGH gene fused with mouse metallothionein 1 (mMT-1) promoter had been introduced. Intact transgenic mice had significantly greater plasma luteinizing hormone (LH) levels than did normal littermate controls. Castration increased LH levels in normal mice but was without effect on plasma LH levels in the transgenic mice. In vitro LH secretion and pituitary LH content were higher in the intact transgenic mice than in intact controls, while there was no significant difference in pituitary LH levels and in vitro LH secretion between the 2 groups of castrate animals. Intact transgenic mice exhibited a greater median eminence (ME) norepinephrine (NE) turnover than control animals, but ME NE turnover did not increase after castration in the transgenic animals as was the case in control mice. Castrate mice expressing the hGH gene had plasma levels of prolactin (PRL) similar to those seen in castrate controls, which was unexpected based on a previous study showing greatly attenuated PRL levels in intact hGH mice when compared to intact controls from the same line. Dopamine (DA) turnover in the ME was not significantly affected by the presence of the hGH gene, suggesting that the difference in plasma PRL levels between normal and transgenic mice is mediated through changes in PRL-regulating factors other than DA. In conclusion, the expression of the mMT-1/hGH hybrid gene in male mice leads to major alterations in LH secretion and lesser changes in PRL secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗