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T Collins

Publications and source records attributed to T Collins.

At least 37 records · Page 2Linked to original sources
PubMed1997

Tumor necrosis factor alpha-induced E-selectin expression is activated by the nuclear factor-kappaB and c-JUN N-terminal kinase/p38 mitogen-activated protein kinase pathways.

E-selectin expression by endothelium is crucial for leukocyte recruitment during inflammatory responses. Transcriptional regulation of the E-selectin promoter by tumor necrosis factor alpha (TNFalpha) requires multiple nuclear factor-kappaB (NF-kappaB) binding sites and a cAMP-responsive element/activating transcription factor-like binding site designated positive domain II (PDII). Here we characterize the role of the stress-activated family of mitogen-activated protein (MAP) kinases in induced expression of this adhesion molecule. By UV cross-linking and immunoprecipitation, we demonstrated that a heterodimer of transcription factors ATF-2 and c-JUN is constitutively bound to the PDII site. TNFalpha stimulation of endothelial cells induces transient phosphorylation of both ATF-2 and c-JUN and induces marked activation of the c-JUN N-terminal kinase (JNK1) and p38 but not extracellular signal-regulated kinase (ERK1). JNK and p38 are constitutively present in the nucleus, and DNA-bound c-JUN and ATF-2 are stably contacted by JNK and p38, respectively. MAP/ERK kinase kinase 1 (MEKK1), an upstream activator of MAP kinases, increases E-selectin promoter transcription and requires an intact PDII site for maximal induction. MEKK1 can also activate NF-kappaB -dependent gene expression. The effects of dominant interfering forms of the JNK/p38 signaling pathway demonstrate that activation of these kinases is critical for cytokine-induced E-selectin gene expression. Thus, TNFalpha activates two signaling pathways, NF-kappaB and JNK/p38, which are both required for maximal expression of E-selectin.

Activating Transcription Factor 2↗
PubMed1997

Effect of gender on outcomes following renal artery stent placement for renovascular hypertension.

To study the effect of gender on outcome following renal artery stent placement for renovascular hypertension, we prospectIvely followed 66 patients (30 males, 36 females) who underwent Palmaz stent placement in 89 renal arteries. There was no difference in the incidence of procedure-related complications between males and females. At 6-mo follow-up, the decrease in systolic (35 +/- 30 mm Hg and 27 +/- 25 mm Hg) and diastolic (15 +/- 23 mm Hg and 14 +/- 14 mm Hg) blood pressures was similar in female and male patients, respectIvely. Late follow-up at 19 +/- 11 mo also showed no difference in blood pressure response. In 44 patients who underwent repeat angiography at a mean duration of 9.1 +/- 5.6 mo after stent deployment, the incidence of restenosis was 26% in females and 24% in males (P = 0.85). We conclude that gender has no effect on the incidence of complications, blood pressure response, or angiographic restenosis in patients undergoing renal artery stent placement.

Aged↗
PubMed1997

Endothelial gene regulation by laminar shear stress.

Endothelial cells, because of their unique localization, are constantly exposed to fluid mechanical forces derived by the flowing blood. These forces, and more specifically shear stresses; affect endothelial structure and function, both in vivo and in vitro, and are implicated as contributing factors in the development of cardiovascular diseases. We have demonstrated earlier that the shear stress selectively induces the transcription of several endothelial genes, and have defined a shear stress response element (SSRE) in the promoter of platelet-derived-growth-factor B (PDGF-B), that is shared by additional endothelial shear stress responsive genes. Here we further characterize this SSRE and the nuclear factors that bind to it, and imply the possible role of the endothelium cytoskeleton in transducing shear stress, leading to the expression of PDGF-B/SSRE constructs in transfected endothelial cells exposed to shear stress. We also present, yet a new shear stress response element in the Platelet Derived Growth Factor A promoter, that contains a binding site to the transcription factors egr1/sp1. These results further demonstrate the complexity of gene regulation by hemodynamic forces, and support the important part that these forces have in the physiology and pathophysiology of the vessel wall.

Animals↗
PubMed1997

Physician responses to an educational intervention on improving their long-term prescribing of sedatives.

The current study examined response forms returned by physicians in response to a Medicaid retrospective therapeutic intervention on the long-term use of sedatives. The educational intervention was designed to notify physicians about their patients' long-term use of sedatives and suggest that they reevaluate the patient's need for sedative hypnotic medication and decrease or discontinue prescribing the medication and/or suggest non-pharmacological alternatives if deemed appropriate. Forty-seven percent of physicians responded to the educational intervention. Nineteen percent of responding physicians planned to change the patient's medication in some way. The most common planned change was to decrease the dose. Physicians also stated that they would recommend one or more non-pharmacological alternatives to 17% of patients. Thirty-eight percent of physicians planned to monitor and/or counsel the patient. Over 40% of physicians reported planning no action after receiving the intervention. Twenty-six percent of physicians planned no action because of patient demand for the sedatives. The study concludes that physicians need to be better trained on how to: (1) discuss non-pharmacological treatments with patients and (2) deal with and respond to patients who demand controlled substances.

Adult↗
PubMed1997

Reappearance of the minor alpha-sarcomeric actins in postnatal muscle.

The postnatal expression profiles of alpha-sarcomeric actin transcripts and protein are quantified in mouse striated muscles from birth to postnatal day 56 by Northern and Western blot analyses. alpha-Cardiac actin (alpha-CA) transcripts transiently increase between 12 and 21 days after birth in the quadriceps muscle, reaching approximately 90% that found in the adult mouse heart. Although alpha-CA is the alpha-sarcomeric actin isoform expressed in the immature fiber, the expression profiles of other contractile protein isoforms indicate that this postnatal period is not reflective of an immature phenotype. alpha-Skeletal actin (alpha-SA) transcripts accumulate to approximately 32% of the total alpha-sarcomeric actin transcripts in the adult heart. Our study shows that 1) there is a simultaneous reappearance of alpha-CA and alpha-SA in postnatal skeletal and heart muscles, respectively, and 2) the contractile protein gene expression profile characteristic of adult skeletal muscle is not achieved until after 42 days postnatal in the mouse. We propose there is a previously uncharacterized period of postnatal striated muscle maturation marked by the reappearance of the minor alpha-sarcomeric actins.

Actins↗
PubMed1997

Inducible PDGF A-chain transcription in smooth muscle cells is mediated by Egr-1 displacement of Sp1 and Sp3.

Platelet-derived growth factor (PDGF) A-chain is expressed by vascular smooth muscle cells (SMC) in a variety of pathological settings. Phorbol 12-myristate 13-acetate (PMA) increases A-chain transcription and was used as a model agonist. Transient transfection analysis identified a region in the promoter that is required for inducibility, located between base pairs -71 and -55 from the transcription start site. This region contains overlapping recognition elements for members of the Sp and Egr families. Egr-1 transcript and protein increased after PMA treatment, whereas Sp1 and Sp3 levels remain unchanged. Egr-1 expression and PDGF A-chain promoter activity also increased in cells exposed to PDGF or mechanical injury. In vitro binding assays demonstrated that Egr-1, Sp1, and Sp3 can bind to this promoter region and that increasing Egr-1 can displace both Sp1 and Sp3. In an in vivo model of arterial injury, Egr-1 expression was induced concurrently with the expression of PDGF-A in SMC. Displacement of Sp1 and Sp3 by Egr-1 is correlated with inducible PDGF A-chain expression in the vessel wall.

Animals↗
PubMed1997

Egr-1 is activated in endothelial cells exposed to fluid shear stress and interacts with a novel shear-stress-response element in the PDGF A-chain promoter.

Exposure of vascular endothelial cells to fluid mechanical forces can modulate the expression of many genes involved in vascular physiology and pathophysiology. Here, we report that platelet-derived growth factor (PDGF) A-chain gene expression is induced at the level of transcription in cultured bovine aortic endothelial cells exposed to a physiologic level of steady laminar shear stress (10 dyn/cm2). 5' Deletion analysis of the human PDGF-A promoter revealed that a GC-rich region near the TATA box was required for shear-inducible reporter gene expression. This element conferred shear inducibility onto a heterologous promoter-reporter construct that was otherwise unresponsive to shear stress. The induction of PDGF-A expression by shear was preceded by rapid and transient induction in the expression of the immediate-early gene, egr-1, which binds to GC-rich sequences. Gel shift studies indicated that shear-induced Egr-1 bound to the proximal PDGF-A promoter in a specific and time-dependent manner, displacing Sp1 from their overlapping recognition elements. Overlapping consensus binding sites for Egr-1 and Sp1 also appear in the proximal promoters of several other endothelial genes, including transforming growth factor-beta 1 and tissue factor, whose expression is modulated by shear stress. These findings define the Egr-1 binding site in the proximal PDGF-A promoter as a shear-stress-responsive element and suggest that shear-stimulated Egr-1 gene expression may be a unifying theme in the induction of various other endothelial genes exposed to biomechanical forces.

Animals↗
PubMed1997

Managing TMD.

Explore the source record for details and available documents.

American Dental Association↗
PubMed1997

Seasonal differences in suicide birth rate in Alaska Natives compared to other populations.

Seasonal differences in suicide birth rates among Alaska Natives and for populations at different latitudes (residents of the Yukon, Saskatchewan, Montana, Wyoming, and Pennsylvania) were investigated. Seasonal birth rates for the general population were similarly examined. Suicide birth rates showed small seasonal variations for Alaska Natives with summer births showing more suicides. However, at lower latitudes, suicide birth rates among other populations showed no seasonal differences. Hours of daily sunlight at the summer and winter solstice correlated with the proportion of suicide victims born during those seasons. Seasonal differences in birth rates of suicide victims correlated strongly with latitude and seasonal differences in daylight. General population birth rates did not show significant seasonal differences, and did not correlate with differences in latitude or sunlight length at the summer or winter solstice.

Alaska↗
PubMed1997

HMGI(Y) expression in human uterine leiomyomata. Involvement of another high-mobility group architectural factor in a benign neoplasm.

Chromosomal rearrangements involving 6p21 have been observed in uterine leiomyomata and a variety of other benign tumors. The gene for HMGI(Y), a member of the high-mobility group (HMG) family of proteins, has been localized to 6p21. To determine whether rearrangements observed in this area alter HMGI(Y) expression, we analyzed HMGI(Y) DNA-binding activity in protein extracts from uterine leiomyoma and normal myometrium tissues. This report describes a uterine leiomyoma specimen with an inv(6)(p21q15). A genomic P1 clone that contains the HMGI(Y) region of chromosome 6 is found to span the inversion breakpoint by fluorescent in situ hybridization of metaphase chromosomes. Expression of HMGI(Y) protein in this leiomyoma specimen is increased dramatically as compared with the matching normal myometrial tissue. Elevated HMGI(Y) expression was also found in 8 of 16 leiomyomas without cytogenetically detectable chromosome 6p21 aberrations but not in any of the 9 matching myometrial tissues. Analysis of the genetic events involved in the pathobiology of these benign tumors will provide a basis for understanding the process of improper cellular growth and might be important in deciphering the multistep pathway of tumorigenesis.

Base Sequence↗
PubMed1997

N-acetyl cysteine blocks mesangial VCAM-1 and NF-kappa B expression in vivo.

Inducible vascular cell adhesion molecule-1 (VCAM-1) in glomerular mesangial cells (GMC) exposed to lipopolysaccharide (LPS) in vitro involves the activation of nuclear factor-kappa B (NF-kappa B) and its interaction with the proximal VCAM-1 promoter. We used a murine model to assess the effect of the antioxidant, N-acetyl cysteine on GMC activation in vivo. Single intraperitoneal administration of N-acetyl cysteine completely suppressed LPS-induced VCAM-1 expression on the GMC surface. When an oligonucleotide spanning the NF-kappa B binding region of the VCAM-1 promoter was incubated with extracts from the renal cortex of LPS-treated animals, a single nucleoprotein complex formed. This complex was composed of p50 and p65, but not p52, c-Rel, or RelB, and its formation was dramatically inhibited by pretreatment with N-acetyl cysteine, D,L-Buthionine-[S,R]-sulfoximide, a compound that depletes glutathione, augmented VCAM-1 expression inducible with a suboptimal amount of LPS to levels comparable with using 50 micrograms of LPS alone, D,L-Buthionine-[S,R]-sulfoximide also potentiated the p50-p65 binding activity induced with a suboptimal amount of LPS. These data provide a redox-sensitive, transcriptional link between NF-kappa B and VCAM-1 in GMC in vivo and implicate oxidative stress as an important regulatory signal in the pathogenesis of glomerular mesangial cell disorders.

Acetylcysteine↗
PubMed1996

Postinduction transcriptional repression of E-selectin and vascular cell adhesion molecule-1.

TNF-alpha induction of the E-selectin and vascular cell adhesion molecule-1 (VCAM-1) genes leads to transient accumulation of high levels of mRNA in endothelial cells. The increase in these mRNAs after induction is due to an increase in the rate of gene transcription, which is maintained for several hours in the continuous presence of cytokine. Cytokine-induced transcriptional activation of these genes requires the transcription factor, nuclear factor-kappaB. Following removal of TNF-alpha, there is rapid postinduction transcriptional repression common to both of these genes. The repression is protein synthesis dependent and correlates with protein synthesis-dependent loss of both the p50 and p65 subunits of nuclear factor-kappaB from the nucleus. IkappaBalpha is capable of specifically displacing endothelial-derived heterodimeric p50/p65 from the E-selectin and VCAM-1 kappaB elements, while having no effect on binding of p50 homodimer. In the presence of agents that block proteasomal degradation of IkappaBalpha, endogenous IkappaBalpha can be visualized in the nucleus of both resting and TNF-alpha-activated endothelial cells. Endogenous IkappaBalpha is readily detected in the nucleus of HeLa cells, and its nuclear localization is increased following removal of TNF-alpha. Repression of E-selectin and VCAM-1 transcription following cytokine removal requires the loss of nuclear p50 and p65, and involves IkappaBalpha. This postinduction transcription repression mechanism may be one component of a program that prevents inappropriate and prolonged expression of adhesion molecules.

Animals↗
PubMed1996

Chronic, topical exposure to benzo[a]pyrene induces relatively high steady-state levels of DNA adducts in target tissues and alters kinetics of adduct loss.

Carcinogen-DNA adduct measurements may become useful biomarkers of effective dose and/or early effect. However, validation of this biomarker is required at several levels to ensure that human exposure and response are accurately reflected. Important in this regard is an understanding of the relative biomarker levels in target and nontarget organs and the response of the biomarker under the chronic, low-dose conditions to which humans are exposed. We studied the differences between single and chronic topical application of benzo[a]pyrene (BAP) on the accumulation and removal of BAP-DNA adducts in skin, lung, and liver. Animals were treated with BAP at 10, 25, or 50 nMol topically once or twice per week for as long as 15 weeks. Animals were sacrificed either at 24, 48, or 72 hr after the last dose at 1 and 30 treatments, and after 24 hr for all other treatment groups. Adduct levels increased with increasing dose, but the slope of the dose-response was different in each organ. At low doses, accumulation was linear in skin and lung, but at high doses the adduct levels in the lung increased dramatically at the same time when the levels in the skin reached apparent steady state. In the liver adduct, levels were lower than in target tissues and apparent steady-state adduct levels were reached rapidly, the maxima being independent of dose, suggesting that activating metabolism was saturated in this organ. Removal of adducts from skin, the target organ, was more rapid following single treatment than with chronic exposure. This finding is consistent with earlier data, indicating that some areas of the genome are more resistant to repair. Thus, repeated exposure and repair cycles would be more likely to cause an increase in the proportion of carcinogen-DNA adducts in repair-resistant areas of the genome. These findings indicate that single-dose experiments may underestimate the potential for carcinogenicity for compounds that follow this pattern.

Administration, Topical↗
PubMed1996

Salicylates inhibit I kappa B-alpha phosphorylation, endothelial-leukocyte adhesion molecule expression, and neutrophil transmigration.

The expression of leukocyte adhesion molecules on endothelial cells is induced by TNF-alpha and other inflammatory cytokines. This induction of endothelial-leukocyte adhesion molecule-1, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 requires the transcription factor nuclear factor-kappa B (NF-kappa B). Recent work has suggested that some nonsteroidal anti-inflammatory agents, including sodium salicylate and aspirin, can inhibit NF-kappa B-dependent gene activation. We studied the effects of salicylates on expression of adhesion molecules in HUVECs. We found that sodium salicylate inhibited activation of NF-kappa B (p50/p65 and p65/p65) by preventing phosphorylation and subsequent degradation of the inhibitor 1 kappa B-alpha. Salicylate treatment had no effect on TNF-alpha-induced phosphorylation of the transcription factor ATF-2. Salicylate blocked the TNF-alpha-induced increase in mRNA levels of adhesion molecules and gave a dose-dependent inhibition of TNF-alpha-induced surface expression of vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 with higher doses required to inhibit endothelial-leukocyte adhesion molecule-1 expression. Indomethacin, a nonsalicylate cyclooxygenase inhibitor, had no effect on surface expression of adhesion molecules, suggesting that the effects were not due to inhibition of cyclooxygenase. Treatment of endothelial cell monolayers with sodium salicylate inhibited transendothelial migration of neutrophils but had no significant effect on neutrophil adhesion under flow conditions. The clinical importance of high-dose salicylates in inflammation may be due, in part, to the ability to prevent expression of inducible adhesion molecules and recruitment of leukocytes.

Base Sequence↗
PubMed1996

Egr-1-induced endothelial gene expression: a common theme in vascular injury.

A number of pathophysiologically relevant genes, including platelet-derived growth factor B-chain (PDGF-B), are induced in the vasculature after acute mechanical injury. In rat aorta, the activated expression of these genes was preceded by a marked increase in the amount of the early-growth-response gene product Egr-1 at the endothelial wound edge. Egr-1 interacts with a novel element in the proximal PDGF-B promoter, as well as with consensus elements in the promoters of other genes induced by endothelial injury. This interaction is crucial for injury-induced PDGF-B promoter-dependent expression. Sp1, whose binding site in the PDGF-B promoter overlaps that of Egr-1, occupies this element in unstimulated cells and is displaced by increasing amounts of Egr-1. These findings implicate Egr-1 in the up-regulated expression of PDGF-B and other potent mediators in mechanically injured arterial endothelial cells.

Animals↗
PubMed1996

Chondrodysplasia and neurological abnormalities in ATF-2-deficient mice.

Activating transcription factor-2 (ATF-2) is a basic region leucine zipper protein whose DNA target sequence is the widely distributed cAMP response element (CRE). We report here that mice carrying a germline mutation in ATF-2 demonstrated unique actions of ATF-2 not duplicated by other ATF/CREB family members. Mutant mice had decreased postnatal viability and growth, with a defect in endochondral ossification at epiphyseal plates similar to human hypochondroplasia. The animals had ataxic gait, hyperactivity and decreased hearing. In the brain, there were reduced numbers of cerebellar Purkinje cells, atrophic vestibular sense organs and enlarged ventricles. Unlike CREB alpha/delta-deficient mice whose main defect is in long-term potentiation, the widespread abnormalities in ATF-2 mutant mice demonstrate its absolute requirement for skeletal and central nervous system development, and for maximal induction of select genes with CRE sites, such as E-selectin.

Abnormalities, Multiple↗
PubMed1996

Missed injuries in a rural area trauma center.

BACKGROUND: Missed injuries can lead to delays. In the rural environment, where patients are frequently seen in multiple hospitals prior to reaching the trauma center, different problems arise. METHODS: Level-1 trauma center admissions from January 1993 through June 1995 were reviewed. Missed injuries were those not identified within 24 hours of injury. Data extracted included demographics, mechanism, severity and outcome. Comparisons were made between missed injury patients and typical trauma patients. RESULTS: Of 3,996 patients, 70 missed injuries were identified in 56 patients. Compared with typical trauma patients, missed injury patients suffered more blunt trauma, were more severely injured, had longer intensive care unit and hospital stays, and a lower mortality rate. Transferred patients accounted for 60% of missed injuries. CONCLUSIONS: Transferred patients with blunt injury have the highest risk for missed injury. Delayed transports and prior examination may contribute to complacency. All trauma patients must be repeatedly evaluated thoroughly, and all diagnostic studies reviewed for adequacy.

Adult↗