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Biomedical subjects

D Welsh

Publications and source records attributed to D Welsh.

At least 19 recordsLinked to original sources
PubMed2003

A retrospective review comparing the use of Gonal-F and Metrodin-HP for in-vitro fertilisation (IVF).

All cycles of IVF with pituitary down-regulation (n = 57) done at the Damansara Fertility Centre in the year 2000 were studied. All the 57 patients had controlled ovarian hyperstimulation, either using Metrodin HP (n = 27) or Gonal-F (n = 30). Of these, 53 patients reached oocyte pick-up, 26 patients in Metrodin HP group and 27 patients in Gonal-F group. Gonal-F resulted in a higher clinical pregnancy rate of 66.6% compared to Metrodin HP 38.5% (p < 0.05). The live birth rate tends to be higher in Gonal-F group (40.7%) compared to Metrodin HP (30.8%), (p > 0.05).

Adult↗
PubMed2002

Ambulatory pulmonary artery pressure monitoring during sleep and exercise in normal individuals and patients with COPD.

BACKGROUND: Pulmonary hypertension is a common complication of chronic obstructive airways disease (COPD) and its presence implies a poor prognosis. However, it is difficult to measure and its specific contribution to symptoms is difficult to quantify. A micromanometer tipped pulmonary artery catheter was used to measure pulmonary artery pressure (PAP) during sleep and on exercise. METHODS: Ten patients (five with COPD receiving long term oxygen therapy and five normal individuals) were studied. Pulmonary artery pressure was recorded continuously during two periods of sleep (breathing oxygen followed by air for the COPD group) and during exercise. RESULTS: In the COPD group PAP during sleep on oxygen was significantly lower than PAP during sleep breathing air (mean (SD) difference 9.6 (5.3) mm Hg, 95% CI 4.9 to 14.3, p= 0.016). PAP during exercise was not significantly different from PAP during sleep breathing air (mean (SD) difference 0.8 (8.9) mm Hg, 95% CI -7.0 to 8.6, p= 0.851). In normal individuals the group mean (SD) PAP was 15 (5.9) mm Hg for the first nocturnal period and 15 (5.7) mm Hg for the second nocturnal period. PAP during exercise was not significantly different from PAP during sleep breathing air (mean (SD) difference 3.3 (2.2) mm Hg, 95% CI 1.1 to 5.5, p= 0.061). CONCLUSION: In patients with COPD, PAP rose significantly during sleep to levels similar to those measured during exercise, but this could be reversed with oxygen.

Adult↗
PubMed2001

Genome-wide gene expression profiles of the developing mouse hippocampus.

We have analyzed the developmental molecular programs of the mouse hippocampus, a cortical structure critical for learning and memory, by means of large-scale DNA microarray techniques. Of 11,000 genes and expressed sequence tags examined, 1,926 showed dynamic changes during hippocampal development from embryonic day 16 to postnatal day 30. Gene-cluster analysis was used to group these genes into 16 distinct clusters with striking patterns that appear to correlate with major developmental hallmarks and cellular events. These include genes involved in neuronal proliferation, differentiation, and synapse formation. A complete list of the transcriptional changes has been compiled into a comprehensive gene profile database (http://BrainGenomics.Princeton.edu), which should prove valuable in advancing our understanding of the molecular and genetic programs underlying both the development and the functions of the mammalian brain.

Animals↗
PubMed2001

Pulmonary hypertension associated with HIV infection.

Pulmonary hypertension occurs with increased frequency among patients with human immunodeficiency virus (HIV) infection. Although the pathogenesis of HIV-associated pulmonary hypertension remains unknown, it appears to occur independently of other risk factors associated with pulmonary vasculopathy, such as chronic hepatitis C infection and intravenous drug use. Signs and symptoms are typical of those immunocompetent patients with primary pulmonary hypertension, but because many HIV-infected patients are receiving intensive medical supervision, the diagnosis of pulmonary hypertension is often made at an earlier stage. Acute responses to epoprostenol are similar to those among non-HIV-infected individuals, but the benefits of long-term, intravenous treatment with epoprostenol in HIV-infected patients is unknown. Future investigations should define the true incidence of pulmonary hypertension and the long-term effects of epoprostenol on survival among HIV-infected individuals. Physicians should be alert to possible pulmonary hypertension in persons infected with HIV.

Antihypertensive Agents↗
PubMed1998

Hypoxic stimulation of the stress-activated protein kinases in pulmonary artery fibroblasts.

Pulmonary hypertension in response to chronic hypoxia is invariably accompanied by remodeling of the pulmonary vessels but the mechanism by which hypoxia increases the replication of vascular cells is unknown. To investigate the hypothesis that hypoxia stimulates intracellular kinase cascades we measured the activity of "classic" mitogen-activated protein (MAP) kinase pathways and "stress- activated" MAP kinase pathways in bovine pulmonary artery fibroblasts subjected to hypoxia for up to 30 h. Hypoxia (1% O2) stimulated strongly the stress-activated protein kinases, c-Jun NH2-terminal kinase (JNK) and p38 MAP kinase. Two peaks of p38 MAP kinase activity at 6 and 24 h were associated with an increase in the activity of mitogen-activated protein kinase-activated protein (MAPKAP) kinase-2, the immediate downstream target of p38 MAP kinase. Furthermore, the second phase of p38 MAP kinase activity could be reversed if cells were reoxygenated after 12 h. These data suggest that hypoxic stimulation of pulmonary artery cells is mediated by activation of the stress-activated protein kinases.

Animals↗
PubMed1998

Developmental stages and spiritual coping responses among economically impoverished women living with HIV disease.

Identifies environmental markers, situational appraisals, perceived ability to mediate situations and outcomes, primary coping strategies, and purposes served by religion and spirituality in 10 HIV-positive women recruited from a regional health care clinic. Findings indicated that the women experienced a disintegration of family during their early developmental years, yielding feelings of hopelessness and isolation; that their sexual development was marked by rape and incest, and their early adulthood was characterized by failed relationships, pregnancies, drugs, and alcohol. Reports that the women's religious influences were predominantly maternal and provided a model for intercessory prayer. Notes that prior to their diagnosis of HIV, participants described their coping as escapist, while after diagnosis they believed there was a divine intercession renewing their spiritual growth and connectedness with others. Reports that the women's personal spirituality was greatly influenced by prayer, television ministries, and reading the Bible. Suggests the interventions that actively recruit women into social support services, health care systems, and faith congregations are needed and that television ministries may serve as access points for connecting women with necessary services.

Adaptation, Psychological↗
PubMed1997

Palliation of a malignant gastrocolic fistula by endoscopic human fibrin sealant injection.

We report the case of a female patient with Hodgkin's disease resistant to therapy who developed a gastrocolic fistula as a consequence of her disease, leading to distressing faeculent vomiting. This was not considered to be amenable to surgical resection and her symptoms were successfully palliated endoscopically using injection of human fibrin sealant into the gastric and colonic aspect of the fistula tract. Both mechanical sealing and promotion of healing by human fibrin sealant are likely to be responsible for its efficacy.

Adult↗
PubMed1996

Molecular cloning of the cDNA and chromosome localization of the gene for human ubiquitin-conjugating enzyme 9.

We report a novel human gene whose product specifically associates with the negative regulatory domain of the Wilms' tumor gene product (WT1) in a yeast two-hybrid screen and with WT1 in immunoprecipitation and glutathione S-transferase (GST) capture assays. The gene encodes a 17-kDa protein that has 56% amino acid sequence identity with yeast ubiquitin-conjugating enzyme (yUBC) 9, a protein required for cell cycle progression in yeast, and significant identity with other subfamilies of ubiquitin-conjugating enzymes. The human gene fully complements yeast that have a temperature-sensitive yUBC9 gene mutation to fully restore normal growth, indicating that we have cloned a functionally conserved human (h) homolog of yUBC9. Transcripts of hUBC9 of 4.4 kilobases (kb), 2.8 kb, and 1.3 kb were found in all human tissues tested. A single copy of the hUBC9 gene was found and localized to human chromosome 16p13.3. We conclude that hUBC9 retains striking structural and functional conservation with yUBC9 and suggest a possible link of the ubiquitin/proteosome proteolytic pathway and the WT1 transcriptional repressor system.

Amino Acid Sequence↗
PubMed1994

Contaminants in eggs of aquatic birds from the grasslands of central California.

Eggs were collected from the Grasslands of western Merced County, California, during 1986 and 1987, and at the Mendota Wildlife Area in Fresno County in 1987, as part of a reproductive study of nesting ducks and shorebirds. The eggs were analyzed to evaluate the effects of contaminants in agricultural drainwater on avian reproduction. Agricultural drainwater was the major source of water for irrigation and fall flooding in the Grasslands until the fall of 1985 when drainwater was mostly replaced by uncontaminated water. Drainwater had not been used at Mendota. Concentrations of arsenic and boron in eggs from all sites were lower than those known to harm avian reproduction. However, mean concentrations of selenium, a trace element known to impair avian reproduction at high dietary levels, were higher in eggs from the Grasslands than in eggs from the uncontaminated site. Although some selenium concentrations were as high as those found to have caused death or deformities at other sites, reproductive impairment was not observed in any ducks or shorebirds nesting in the Grasslands in 1986 or 1987.

Animals↗
PubMed1994

The 1993 Walter Hubert Lecture: the role of the p53 tumour-suppressor gene in tumorigenesis.

The p53 tumour-suppressor gene is mutated in 60% of human tumours, and the product of the gene acts as a suppressor of cell division. It is thought that the growth-suppressive effects of p53 are mediated through the transcriptional transactivation activity of the protein. Overexpression of the p53 protein results either in arrest in the G1 phase of the cell cycle or in the induction of apoptosis. Both the level of the protein and its transcriptional transactivation activity increase following treatment of cells with agents that damage DNA, and it is thought that p53 acts to protect cells against the accumulation of mutations and subsequent conversion to a cancerous state. The induction of p53 levels in cells exposed to gamma-irradiation results in cell cycle arrest in some cells (fibroblasts) and apoptosis in others (thymocytes). Cells lacking p53 have lost this cell cycle control and presumably accumulate damage-induced mutations that result in tumorigenesis. Thus, the role of p53 in suppressing tumorigenesis may be to rescue the cell or organism from the mutagenic effects of DNA damage. Loss of p53 function accelerates the process of tumorigenesis and alters the response of cells to agents that damage DNA, indicating that successful strategies for radiation therapy may well need to take into account the tissue of origin and the status of p53 in the tumour.

Animals↗
PubMed1993

Intravascular ultrasound study of angiographically mildly diseased coronary arteries.

OBJECTIVES: We hypothesized that intravascular ultrasound may identify significant coronary artery narrowing in the mildly diseased coronary artery of patients with insignificant or one- or two-vessel coronary artery disease. BACKGROUND: Necropsy studies have revealed that coronary angiography may underestimate stenosis severity in vessels that appear mildly diseased. Intravascular ultrasound has been shown to detect atherosclerotic changes in angiographically normal coronary arteries and to correlate better with histologic findings. METHODS: In 20 patients, we performed intravascular ultrasound imaging (3.5F catheter, 30-MHz transducer) in 37 coronary arteries that were considered mildly diseased (<50% diameter narrowing) by qualitative angiography. The angiographic diagnosis was no significant coronary artery disease in eight patients, one-vessel disease in seven and two-vessel disease in five. Each vessel, except for the left main coronary artery, was divided into proximal, mid and distal segments. Percent area narrowing and minimal lumen diameter were subsequently quantified by both ultrasound and quantitative angiography. RESULTS: Mean maximal arterial area narrowing by ultrasound in the 67 segments studied was 36 +/- 20% (range 0% to 80.2%) and 19 +/- 23% (range 0% to 82%) by quantitative angiography of these same segments (p < 0.001, paired t test). Mean minimal lumen diameter of the segment was 3.3 +/- 0.9 mm by ultrasound and 2.7 +/- 0.8 mm by quantitative angiography. In 10 patients there were 19 angiographically mildly diseased segments where the percent arterial area narrowing by ultrasound was > or = 50%. Intravascular ultrasound revealed that the more proximal (reference) segment had > 25% intimal thickening in 12 of the 19 underestimated segments. In six stenosed segments (32%), total vessel area increased compared with that of the adjacent proximal vessel segment because of compensatory dilation. CONCLUSIONS: Intravascular ultrasound identifies potentially significant coronary artery disease in vessels that appear to be only mildly diseased by angiography.

Constriction, Pathologic↗
PubMed1990

A stereotactic technique for volumetric interstitial implantation in the brain.

Stereotaxis, a method of localizing a specific point using three dimensional coordinates, has greatly improved since the advent of computed tomography (CT). A simple, noninvasive stereotactic system which enables rapid, parallel placement of multiple interstitial catheters for treatment of malignant brain tumors has been developed. Departing from traditional stereotactic methods, the implantation procedure is performed in one stage--entirely in the CT suite. Perioperative nursing responsibilities include mastering the technical aspect of a high precision system as well as meeting the special needs of the patient undergoing this procedure. Initially developed for use in volumetric interstitial brachytherapy, the procedure is now being used in Phase II clinical trials of volumetric interstitial hyperthermia in the management of patients with intracranial malignancies.

Brachytherapy↗
PubMed1988

Effect of running wheel availability on circadian patterns of sleep and wakefulness in mice.

Sleep/wake expression in mice varies predictably with circadian phase. Such circadian rhythms are known to depend on intact suprachiasmatic nuclei (SCN) in the hypothalamus, but the mechanism by which SCN activity modulates sleep/wake expression is unknown. This paper examines the possibility that circadian patterns of sleep/wake derive partly from circadian timing of waking behaviors that are incompatible with sleep, such as locomotor activity. Voluntary locomotor activity was restricted in five mice adapted to a running wheel by locking the wheel in place. Continuous electrographic monitoring of sleep and wakefulness over multiple circadian cycles revealed: (1) during the active phase, shorter wake bouts and more frequent bouts of sleep, resulting in greater sleep/wake fragmentation and more time spent asleep; (2) during the rest phase, a small compensatory reduction in NREM sleep; (3) reduced amplitude of circadian sleep/wake rhythms and a greater amount of sleep overall. Thus, voluntary locomotor activity has an important influence on sleep/wake expression in mice, and the normal circadian pattern of sleep/wake depends on circadian timing of activity. Previous reports of damped circadian sleep/wake rhythms in rodents may therefore be explained by coincident diminutions in locomotor activity associated with age or health status. Our results also support analogous findings in human subjects, and we propose that elderly humans may benefit from therapies that augment daytime activity.

Animals↗
PubMed1988

CheA protein, a central regulator of bacterial chemotaxis, belongs to a family of proteins that control gene expression in response to changing environmental conditions.

During bacterial chemotaxis, the binding of stimulatory ligands to chemoreceptors at the cell periphery leads to a response at the flagellar motor. Three proteins appear to be required for receptor-mediated control of swimming behavior, the products of the cheA, cheW, and cheY genes. Here we present the complete nucleotide sequence of the Salmonella typhimurium cheA gene together with the purification and characterization of its protein product. The protein is a 73,000 Mr cytoplasmic constituent. Amino acid-sequence comparisons indicate that it belongs to a family of bacterial regulatory proteins including the products of the cpxA, dctB, envZ, ntrB, phoR, phoM, and virA genes. Each member of this family has a conserved domain of approximately equal to 200 residues within its C terminus. We have previously shown that another chemotaxis protein, CheY, represents a domain of protein structure that has been conserved within a second large family of bacterial regulatory proteins. Each protein of the CheA family seems to function as a regulator of a different CheY homologue. Although each pair of proteins appears to produce a specialized response to a distinct type of stimulus, the relationships in primary structure suggest that a similar molecular mechanism may be involved.

Amino Acid Sequence↗
PubMed1987

The use of measured genotype information in the analysis of quantitative phenotypes in man. II. The role of the apolipoprotein E polymorphism in determining levels, variability, and covariability of cholesterol, betalipoprotein, and triglycerides in a sample of unrelated individuals.

Recent advances in molecular biology provide measures of genotypes at loci involved in lipid metabolism. Genotypes for apolipoprotein E (apo E) and quantitative levels of total plasma cholesterol, betalipoprotein, and triglycerides were measured in a sample of 223 unrelated individuals from Nancy, France. The frequencies of the epsilon 2, epsilon 3, and epsilon 4 alleles are 0.13, 0.74, and 0.13, respectively, in this sample. Significant differences among apo E genotypes were detected for these lipoprotein phenotypes. The average effect of the epsilon 2 allele was to reduce total plasma cholesterol and betalipoprotein levels by 0.52 mmol/L and 0.98, respectively, while the epsilon 4 allele raised these levels by 0.26 mmol/L and 0.61, respectively. Apo E genotype specific correlations suggest that this locus also has an effect on the coordinated metabolism between cholesterol and triglycerides. We infer that approximately 17% of the genetic variability in total plasma cholesterol may be attributable to this apo E polymorphism. No other single locus has been identified with such a large contribution to cardiovascular disease risk factors in the general population.

Alleles↗