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Biomedical subjects

C Sullivan

Publications and source records attributed to C Sullivan.

At least 19 recordsLinked to original sources
PubMed2001

The role of IL-4 in Heligmosomoides polygyrus-induced alterations in murine intestinal epithelial cell function.

IL-4 and IL-13 promote gastrointestinal worm expulsion, at least in part, through effects on nonlymphoid cells, such as intestinal epithelial cells. The role of IL-4/IL-13 in the regulation of intestinal epithelial function during Heligmosomoides polygyrus (Hp) infection was investigated in BALB/c mice infected with Hp or treated with a long-lasting formulation of recombinant mouse IL-4/alphaIL-4 complexes (IL-4C) for 7 days. Separate groups of BALB/c mice were drug-cured of initial infection and later reinfected and treated with anti-IL-4R mAb, an antagonist of IL-4 and IL-13 receptor binding, or with a control mAb. Segments of jejunum were mounted in Ussing chambers, and short circuit current responses to acetylcholine, histamine, serotonin, PGE2, and glucose were determined. Although only modest changes in epithelial cell function were observed during primary Hp infection, IL-4C or a secondary Hp infection each induced more dramatic changes, including increased mucosal permeability, reduced sodium-linked glucose absorption, and increased Cl- secretory response to PGE2. Some, but not all, effects of IL-4C and Hp infection were dependent on enteric nerves. Hp-induced changes in epithelial function were attenuated or prevented by anti-IL-4R mAb. Thus, IL-4/IL-13 mediate many of the effects of Hp infection on intestinal epithelial cell function and do so both through direct effects on epithelial cells and through indirect, enteric nerve-mediated prosecretory effects. These immune system-independent effector functions of IL-4/IL-13 may be important for host protection against gastrointestinal nematodes.

Animals↗
PubMed2001

PDGF-D, a new protease-activated growth factor.

Platelet-derived growth factor (PDGF) has been directly implicated in developmental and physiological processes, as well as in human cancer, fibrotic diseases and arteriosclerosis. The PDGF family currently consists of at least three gene products, PDGF-A, PDGF-B and PDGF-C, which selectively signal through two PDGF receptors (PDGFRs) to regulate diverse cellular functions. After two decades of searching, PDGF-A and B were the only ligands identified for PDGFRs. Recently, however, database mining has resulted in the discovery of a third member of the PDGF family, PDGF-C, a functional analogue of PDGF-A that requires proteolytic activation. PDGF-A and PDGF-C selectively activate PDGFR-alpha, whereas PDGF-B activates both PDGFR-alpha and PDGFR-beta. Here we identify and characterize a new member of the PDGF family, PDGF D, which also requires proteolytic activation. Recombinant, purified PDGF-D induces DNA synthesis and growth in cells expressing PDGFRs. In cells expressing individual PDGFRs, PDGF-D binds to and activates PDGFR-beta but not PDGFR-alpha. However, in cells expressing both PDGFRs, PDGF-D activates both receptors. This indicates that PDGFR-alpha activation may result from PDGFR-alpha/beta heterodimerization.

3T3 Cells↗
PubMed2001

Human angiopoietin gene expression is a marker for severity of pulmonary hypertension in patients undergoing pulmonary thromboendarterectomy.

OBJECTIVE: A consistent pathologic feature seen in lungs of patients with pulmonary hypertension from thromboembolic disease is hyperplasia of the media of pulmonary arterioles. The molecular factors responsible for these vessel wall changes are unknown. Angiopoietin-1 is a gene responsible for the formation of the media of blood vessels in utero. We hypothesized that aberrant expression of the angiopoietin-1 gene in the adult lung would be a major contributing factor in the development of pulmonary hypertension. METHODS: From April 1999 to March 2000, a total of 35 patients (18 men, 17 women, mean age 52 years) with pulmonary hypertension and pulmonary vascular resistance ranging from 407 to 2006 dynes x sec x cm(-5) underwent pulmonary endarterectomy at our institution. Before cardiopulmonary bypass, lung biopsy specimens were taken from each patient. Biopsy specimens were also obtained from 10 patients (5 women, 5 men, mean age 55 years) undergoing lung resection for causes other than pulmonary hypertension. All specimens were blindly scored by a pathologist for degree of medial hyperplasia. Quantitative reverse transcriptase-polymerase chain reaction, Western blot, and immunohistochemistry were used to quantitate angiopoietin-1 messenger RNA and protein in each sample. RESULTS: Lung specimens from all patients with pulmonary hypertension demonstrated up-regulation of angiopoietin-1 at the messenger RNA level. The degree of angiopoietin-1 transcription was directly proportional to the preoperative pulmonary vascular resistance and medial wall hyperplasia/hypertrophy in each patient. By immunohistochemistry, angiopoietin-1 protein was confined to the media of pulmonary arterioles. Lung biopsy specimens from patients without pulmonary hypertension had no detectable expression of angiopoietin-1 at the messenger RNA or protein level. CONCLUSION: Angiopoietin-1, a gene responsible for vessel development in the embryonic lung, is up-regulated in the lung parenchyma of patients with pulmonary hypertension. The level of expression of angiopoietin-1 at messenger RNA and protein levels correlates to the severity of pulmonary hypertension in patients with thromboembolic disease and serves as a target for strategies to treat this disease.

Adult↗
PubMed2001

Inferring population history from microsatellite and enzyme data in serially introduced cane toads, Bufo marinus.

Much progress has been made on inferring population history from molecular data. However, complex demographic scenarios have been considered rarely or have proved intractable. The serial introduction of the South-Central American cane toad Bufo marinus in various Caribbean and Pacific islands involves four major phases: a possible genetic admixture during the first introduction, a bottleneck associated with founding, a transitory population boom, and finally, a demographic stabilization. A large amount of historical and demographic information is available for those introductions and can be combined profitably with molecular data. We used a Bayesian approach to combine this information with microsatellite (10 loci) and enzyme (22 loci) data and used a rejection algorithm to simultaneously estimate the demographic parameters describing the four major phases of the introduction history. The general historical trends supported by microsatellites and enzymes were similar. However, there was a stronger support for a larger bottleneck at introductions for microsatellites than enzymes and for a more balanced genetic admixture for enzymes than for microsatellites. Very little information was obtained from either marker about the transitory population boom observed after each introduction. Possible explanations for differences in resolution of demographic events and discrepancies between results obtained with microsatellites and enzymes were explored. Limits of our model and method for the analysis of nonequilibrium populations were discussed.

Animals↗
PubMed2001

Cigarette smoking in the Oregon Air National Guard: findings from a health promotions survey.

The purpose of this study was to assess the prevalence of smoking among demographic subgroups in the Oregon Air National Guard (ORANG), examine demographic predictors of current smoking, and describe interest in smoking cessation classes. During the autumn of 1995, 1,000 surveys were distributed through unit medical liaisons to ORANG personnel. A total of 589 (59%) surveys were returned. Overall smoking prevalence was 19%. The percentage of smokers who reported heavy smoking (one or more packs per day) was highest among enlisted personnel in the middle (46.9%) and highest (71.4%) pay grades and in the oldest age group (63.4%). Cigarette consumption per day was significantly higher in the oldest age group (F = 3.92, df = 3/107, p < 0.01). In separate logistic regression models, neither age, full-time technician vs. traditional National Guard status, nor pay grade were significant predictors of smoking in either enlisted or officer personnel. Substantial interest in smoking cessation programs was identified.

Adult↗
PubMed2000

The mode selection trial (MOST) in sinus node dysfunction: design, rationale, and baseline characteristics of the first 1000 patients.

BACKGROUND: More than 200,000 permanent pacemakers will be implanted in the United States in 2000 at a cost of more than $2 billion. Sick sinus syndrome (SSS) will likely account for approximately half of all cases necessitating implantation. Pacemaker technology permits the selection of ventricular (single-chamber) or dual-chamber devices. However, clinical and outcomes data are inadequate to support a clear recommendation that one or the other type of device be used. METHODS: The Mode Selection Trial (MOST) is a single-blind study supported by the National Heart, Lung, and Blood Institute designed to enroll 2000 patients with SSS. All patients will receive a DDDR pacemaker programmed to VVIR or DDDR before implantation. The average time of follow-up will be 3 years. MOST has a >90% power to detect a 25% reduction in the primary end point-nonfatal stroke or total (all cause) mortality-in the DDDR-treated group. Secondary end points will include health-related quality of life and cost effectiveness, atrial fibrillation, and development of pacemaker syndrome. Prespecified subgroups for analysis will include women and the elderly. Enrollment was completed in October 1999, with a total of 2010 patients. RESULTS: The median age of the first 1000 enrolled patients is 74 years, with 25% of patients 80 years or older. Women comprise 49%, and 17% are nonwhite, predominantly black (13%). Before pacemaker implantation, 22% of patients reported a history of congestive heart failure, 11% coronary angioplasty, and 25% coronary bypass surgery. Supraventricular tachycardia including atrial fibrillation was present in 53% of patients. A prior stroke was reported by 12%. Antiarrhythmic therapy was in use in 18% of patients. CONCLUSIONS: MOST will fill the clinical need for carefully designed prospective studies to define the benefits of dual-chamber versus single-chamber ventricular pacing in patients with SSS. The MOST population is typical of the overall pacemaker population in the United States. Thus the final results of MOST should be clinically generalizable.

Aged↗
PubMed2000

Effect of delivery temperature on endocrine stimulation of thermoregulation in lambs born by cesarean section.

We examined the hypothesis that exogenous stimulation with physiological doses of 3,5,3'-triiodothyronine (T(3)) and/or norepinephrine at birth can improve thermoregulation in near-term lambs delivered by cesarean section. This was achieved by investigating the effect of delivery temperature [i.e., warm (30( degrees )C) vs. cool (15( degrees )C) ambient temperatures] on hormonal stimulation on uncoupling protein-1 (UCP1) abundance in brown adipose tissue. In vivo measurements of temperature control (i. e., colonic temperature, oxygen consumption, and incidence of shivering) were made over the first 2.5 h after birth. Each lamb was injected with saline with or without T(3), norepinephrine, or T(3) plus norepinephrine. Irrespective of delivery temperature, abundance of UCP1 increased and incidence of shivering decreased by all hormonal treatments, but this only reduced the rate of decline in colonic temperature of cool-delivered lambs. Oxygen consumption was higher in cool-delivered lambs that were able to fully restore body temperature, an adaptation not observed in controls or any warm-delivered groups. Exogenous administration of endocrine stimulatory factors can enhance the abundance of UCP1 in cesarean-section-delivered lambs with the magnitude of thermoregulatory response being greater at cool than warm delivery temperatures.

Adipose Tissue↗
PubMed2000

A child with neurofibromatosis-1 and a lumbar epidural arteriovenous malformation.

A 10-year-old child with neurofibromatosis-1 was evaluated for progressive lumbar scoliosis, back pain, and foot numbness. Magnetic resonance imaging showed several lumbar intraspinal and extraspinal masses consistent with neurofibromas. The mass at L3-L5 compressed the thecal sac and was thought to be the source of the symptoms. On operative exploration, a lumbar epidural arteriovenous malformation was found, which was removed in its entirety. The child's back pain and foot numbness resolved. Epidural arteriovenous malformations in patients with neurofibromatosis-1 are rare and have been reported only in the cervical spine. Our finding of a lumbar epidural arteriovenous malformation in a child with neurofibromatosis-1 demonstrates that vascular anomalies can be present throughout the spine of patients with neurofibromatosis-1 and should be considered in the differential diagnosis of any neurofibromatosis-1-related epidural mass.

Arteriovenous Malformations↗
PubMed2000

Effect of maternal nutrition on brown adipose tissue and its prolactin receptor status in the fetal lamb.

We investigated the influence of maternal nutritional enhancement during the second half of gestation on prolactin receptor (PRLR) abundance in fetal brown adipose tissue (BAT) and liver close to term (i.e. 141-144 d gestation). Ewes were provided with 100% (i.e. control; n = 8) or 150% (i.e. well-fed; n = 7) of their metabolic requirements from 80 to 144 d gestation. Crude plasma membranes were prepared from fetal BAT and hepatic tissue, and individual molecular weight isoforms for the long and short forms of the PRLR were detected by immunoblotting. Mitochondrial preparations were prepared from BAT to measure the amount of the BAT-specific mitochondrial uncoupling protein-1 and its thermogenic activity (i.e. guanosine 5'-diphosphate binding). Fetuses sampled from well-fed ewes were heavier (controls, 3927 +/- 196 g; well-fed, 4783 +/- 219 g; p = 0.01) but possessed less BAT per kilogram body weight (controls, 5.92 +/- 0.43 g/kg; well-fed, 3.85 +/- 0.19 g/kg; p = 0.001), which had a greater uncoupling protein-1 abundance (controls, 56 +/- 5% of reference; well-fed, 78 +/- 9% of reference; p < 0.01) and higher thermogenic activity (controls, 157 +/- 41 pmol guanosine 5'-diphosphate per milligram mitochondrial protein; well-fed, 352 +/- 36 pmol guanosine 5'-diphosphate per milligram mitochondrial protein; p < 0.01) than controls. Multiple isoforms of the long and short forms of the P1LR were detected in all tissues. BAT from well-fed fetuses had a higher abundance of the 15-kD isoform of the long form of the PRLR (controls, 1.6 +/- 0.4 densitometric units; well-fed, 16.3 +/- 2.0 densitometric units; p < 0.001). This isoform was not detected in hepatic tissue. Maternal nutrient intake had no effect on any other isoforms of the PRLR in BAT or liver. In conclusion, increasing the quantity of feed provided in late gestation acts to promote fetal weight and BAT maturation, the combination of which will enhance neonatal viability.

Adipose Tissue, Brown↗
PubMed2000

Canadian study shows promising results on home care cost effectiveness.

Researcher Marcus Hollander, PhD, a former director of continuing care in British Columbia, is leading a national effort to compare costs of providing treatment at home to alternative settings including hospitals and nursing homes. The first study compared costs incurred by home care clients to costs incurred by similar persons in skilled nursing facilities and found home care costs were significantly less for home care. The average savings ranged from 25% to 60%. The first of 15 planned research projects on the cost effectiveness of home care to be released during 2000 offers evidence of significant savings associated with providing services in the home as compared to long-term institutions.

British Columbia↗
PubMed2000

Acute spinal cord injury. Nursing considerations for the first 72 hours.

The effects of spinal cord injury can be devastating. An understanding of spinal anatomy and the mechanisms of injury provide the basis for correlating presenting signs and symptoms with the extent of neural damage. Understanding the principles of acute care management will help guide the nurse in executing interventions aimed at preservation of neurologic functions. Research must continue to focus on quality-of-life issues and methods of preventing both primary and secondary injuries.

Acute Disease↗
PubMed1999

Identification of a cytokine-induced repressor of interleukin-1 stimulated expression of stromelysin 1 (MMP-3).

Stromelysin 1 (MMP-3) is a matrix metalloproteinase with broad substrate specificity that has been linked to joint and tissue destruction associated with chronic inflammatory diseases such as rheumatoid arthritis and periodontitis. Transcription of the stromelysin gene is induced by inflammatory cytokines such as interleukin 1 (IL-1) and tumor necrosis factor as well as a number of other cytokines and mitogens, but the exact mechanisms involved in its regulation are not fully understood. To identify transcription factors and cis elements potentially involved in the IL-1 induction of stromelysin, the human stromelysin 5'-flanking region was screened by electrophoretic mobility shift assay for IL-1-induced DNA-binding complexes in human synovial and gingival fibroblasts. Here we report the identification of such a complex binding to the region -1614 to -1595 (5'-G(T)TTTTTCCCCCCATCAAAG-3') termed the stromelysin IL-1 responsive element site. Binding to this site is also induced by tumor necrosis factor but not by platelet-derived growth factor or interleukin 4. UV cross-linking demonstrates that there are at least two DNA-binding proteins involved, of approximately 48 and 52 kDa. Transient transfection experiments in human foreskin fibroblasts demonstrate that proteins binding to this site act as a repressor of IL-1-induced expression of the stromelysin gene.

Base Sequence↗
PubMed1999

Pheromones and novel male-induced pregnancy disruptions in mice: exposure to conspecifics is necessary for urine alone to induce an effect.

Previous research indicates a role of pheromones in novel male-induced early pregnancy disruptions. Although some reports suggest that urine alone is sufficient to produce this effect, others raise procedural concerns and fail to replicate such effects. On Days 1 to 5 after insemination, female CF-1 mice had their nasal regions repeatedly painted with water, urine from males housed in isolation, or urine from males housed in proximity to females. Almost all (87.5%) of the control females delivered litters. There was a small nonsignificant reduction in proportion parturient (78.5%) among females exposed to urine of males housed without social contact. The proportion of females parturient (57.1%) after treatment with urine from males housed in proximity to females was significantly different from controls. The magnitude of the effect of socially stimulated male urine is substantially less than that recorded when males are housed directly above inseminated females separated by a wire-mesh grid. These data suggest that production of pregnancy-disrupting male pheromones is stimulated by contact with conspecifics.

Animals↗
PubMed1999

Haemodynamic responses to obstructive sleep apnoeas in premenopausal women.

OBJECTIVES: Obstructive apnoeas during sleep are associated with marked cyclical blood pressure fluctuations in men with obstructive sleep apnoea (OSA). Haemodynamic responses to OSA in women are largely unknown. We aimed to investigate haemodynamics during apnoeic events in women with OSA and to assess the influence of the menstrual cycle on these responses. DESIGN AND METHODS: Full overnight polysomnography and continuous non-invasive blood pressure monitoring was performed in 13 women with OSA during follicular and luteal phases of the menstrual cycle. Change in blood pressure (deltaBP) from pre- to post-apnoea termination was measured for each apnoeic cycle. RESULTS: Only 10 of 13 subjects ovulated. In women who ovulated, pressor responses to apnoea termination occurred in both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep, but substantially increased during the luteal phase of ovulatory cycles [NREM change in mean arterial pressure (deltaMAP) 12 +/- 3 mmHg during the follicular phase and 20 +/- 3 mmHg during the luteal phase, P < 0.001; REM deltaMAP 11 +/- 3 mmHg during the follicular phase and 23 +/- 3 mmHg during the luteal phase, P < 0.001]. Sleep apnoea severity did not change during the cycle in NREM sleep, but was reduced in REM during the luteal phase. Changes in pressor responses were absent in non-ovulating subjects. CONCLUSIONS: Obstructive apnoeas in women were associated with marked blood pressure changes, similar to those previously reported in men. While respiratory events improved slightly in the luteal phase, blood pressure responses to these events increased by approximately 100%. Thus, the menstrual cycle has discordant effects on the respiratory and cardiovascular effects of OSA in women.

Adult↗
PubMed1999

A fully-automated environmental chamber for examination of long-term effects of intermittent hypoxia on medium-size animals.

We describe the design and construction of a fully-automated environmental chamber for the simultaneous exposure of up to four medium-size laboratory animals to long-term intermittent hypoxia. The air-sealed automated environmental chamber consists of a box equipped with a ventilation fan and three electrically-activated solenoid valves. Our system was used to expose four rabbits to 12 h of repetitive episodes of hypoxia (environmental O2 concentration 12-13%) lasting 45 min followed by breathing room air for 15 min. During environmental hypoxia, the mean arterial PaO2 and PaCO2 were 41 +/- 3.0 and 24 +/- 0.7 mmHg (mean +/- SEM), respectively. In this system, opening and closing of the solenoid valves is fully computerized to allow different settings of the duration and severity of hypoxia. The chamber is safe and fully automated and cost-effective for studying the effects of long-term intermittent hypoxemia in medium-size animals.

Animals↗
PubMed1998

Normative oxygen saturation values for pregnant women at sea level.

Objective: To develop normative ranges of maternal arterial oxygen saturation (SpO(2)) for women residing at sea level throughout gestation and postpartum.Materials and Methods: Healthy, nonsmoking, non-laboring pregnant women, with no obstetrical risk factors, were recruited into this longitudinal study performed at The Stamford Hospital (elevation sea level). Maternal SpO(2) was measured in the dominant index finger while breathing room air with a Nelcor N-200 pulse oximeter and DS-100A sensor (Nellcor Puritan Bennett, Pleasanton, CA) at set antepartum (AP) and postpartum (PP) intervals. Oxygen saturation was measured in the following positions: sitting, lying on the left then right side, knee-chest, and supine. Five minutes were allowed between measurements. Measurements were taken at 12, 24, and 36 weeks of gestation and then at 12 weeks postpartum for each patient.Results: Thirty-six patients were initially enrolled. Three were excluded from this study, secondary to loss of follow-up (1), preterm delivery at 35 weeks (1), and complicated placenta previa (1). Of the 33 patients who remained in the study 5 have delivered and undergone postpartum evaluation. SpO(2) values (%) are summarized as mean +/- 2 SD in the Table.Conclusion: Preliminary data in this ongoing descriptive longitudinal study suggest that maternal SpO(2) is at least 97% throughout pregnancy for healthy, non-smoking women residing at sea level. These normative data may be useful in managing pregnant women at risk for hypoxia.

Journal Article↗
PubMed1998

Masoprocol (nordihydroguaiaretic acid): a new antihyperglycemic agent isolated from the creosote bush (Larrea tridentata).

An ethnomedically-driven approach was used to evaluate the ability of a pure compound isolated from the creosote bush (Larrea tridentata) to lower plasma glucose concentration in two mouse models of type 2 diabetes. The results indicated that plasma glucose concentration fell approximately 8 mmol/l in male C57BL/ks-db/db or C57BL/6J-ob/ob mice following the oral administration of masoprocol (nordihydroguaiaretic acid), a well known lipoxygenase inhibitor. The decline in plasma glucose concentration following masoprocol treatment in the mice was achieved without any change in plasma insulin concentration. In addition, oral glucose tolerance improved and the ability of insulin to lower plasma glucose concentrations was accentuated in masoprocol-treated db/db mice. These data raise the possibility that masoprocol, or other lipoxygenase inhibitors, represents a new approach to the pharmacological treatment of Type 2 diabetes.

Animals↗