PubMed Health⌕ Search

Biomedical subjects

D Morgan

Publications and source records attributed to D Morgan.

At least 145 records · Page 8Linked to original sources
PubMed1996

Site-directed mutagenesis of the N-linked glycosylation site in platelet-derived growth factor B-chain results in diminished intracellular retention.

Pulse-chase analysis of human platelet-derived growth factor (PDGF) B-chain was conducted in stably transfected Chinese hamster ovary cells to determine precisely the kinetics of processing, intracellular trafficking and secretion. Newly synthesized 31 kDa monomers of the B-chain (p31) dimerized rapidly via disulfide bonds to a p54 species (t1/2 < 30 min). The p54 dimer was processed to a group of intracellular, cell surface (suramin-releasable) and secreted forms whose rates of appearance and disappearance from the cell were measured over a 48 h period. The newly synthesized p31 species was quantitatively converted to p27 by treatment with endoglycosidase H, consistent with efficient N-glycosylation at a site in the N-terminal propeptide region (Asn63-Met64-Thr65). Interruption of B-chain glycosylation by oligodeoxynucleotide-directed mutagenesis resulted in a significant increase in suramin-releasable forms at the cell surface (p34-38) and a concomitant decrease in accumulation of an intracellular p24 species. The glycosylation-defective mutant exhibited slight increases in receptor binding and mitogenic activity. Our results suggest that N-linked glycosylation of the B-chain is not important for formation of mitogenically active protein, but that it plays a role in early intracellular sorting and proteolytic processing events.

Animals↗
PubMed1996

Increased amyloid-beta42(43) in brains of mice expressing mutant presenilin 1.

Mutations in the genes encoding amyloid-beta precursor protein (APP), presenilin 1 (PS1) and presenilin 2 (PS2) are known to cause early-onset, autosomal dominant Alzheimer's disease. Studies of plasma and fibroblasts from subjects with these mutations have established that they all alter amyloid beta-protein (beta APP) processing, which normally leads to the secretion of amyloid-beta protein (relative molecular mass 4,000; M(r) 4K; approximately 90% A beta1-40, approximately 10% A beta1-42(43)), so that the extracellular concentration of A beta42(43) is increased. This increase in A beta42(43) is believed to be the critical change that initiates Alzheimer's disease pathogenesis because A beta42(43) is deposited early and selectively in the senile plaques that are observed in the brains of patients with all forms of the disease. To establish that the presenilin mutations increase the amount of A beta42(43) in the brain and to test whether presenilin mutations act as true (gain of function) dominants, we have now constructed mice expressing wild-type and mutant presenilin genes. Analysis of these mice showed that overexpression of mutant, but not wild-type, PS1 selectively increases brain A beta42(43). These results indicate that the presenilin mutations probably cause Alzheimer's disease through a gain of deleterious function that increases the amount of A beta42(43) in the brain.

Amyloid beta-Peptides↗
PubMed1996

Effects of long-term cigarette smoking on endothelium-dependent responses in humans.

Endothelial injury is a central feature of vascular disease induced by cigarette smoking and may act as a precursor for future atherosclerosis. Using forearm occlusion plethysmography, we studied the vascular responses to methacholine (an endothelium-dependent vasodilator) and sodium nitroprusside (an endothelium-independent vasodilator) infused into the brachial artery of 35 long-term cigarette smokers and 16 nonsmoking subjects. NG-monomethyl-L-arginine (L-NMMA), a stereospecific inhibitor of nitric oxide production, was used to inhibit synthesis of nitric oxide in the endothelium. The reactive hyperemic response at peak and during recovery to the temporary interruption of forearm blood flow was also compared between groups. Smokers had elevated carboxyhemoglobin levels compared with nonsmokers (5.1 +/- 2.1% vs 0.8 +/- 0.4%; p < 0.001). No differences were found in the peak or late hyperemic responses between groups. In smokers, the incremental infusions of methacholine and sodium nitroprusside increased forearm blood flow from 3.6 +/- 1.2 to 12.9 +/- 9.0 ml.min-1 x 100 ml-1 and from 4.0 +/- 1.5 to 9.3 +/- 4.0 ml.min-1 x 100 ml-1, respectively, compared with 3.2 +/- 1.0 to 13.5 +/- 5.6 ml.min-1 x 100 mL-1 and from 2.9 +/- 0.7 to 8.6 +/- 4.2 ml.min-1 x 100 ml-1 in nonsmoking subjects (p = NS). L-NMMA (4 mumol/min for 5 minutes) significantly reduced forearm blood flow in both smokers and nonsmokers from 4.1 +/- 1.4 to 3.4 +/- 1.2 ml.min-1 x 100 ml-1 and 3.8 +/- 0.7 to 2.3 +/- 0.5 mL.min-1 x 100 ml-1, respectively (p < 0.01 for both); and the decrement in forearm blood flow in nonsmokers was significantly greater than that recorded in smoking subjects (p < 0.05). In this study, long-term cigarette smokers exhibited an impairment in basal, but not stimulated, nitric oxide-mediated vasodilation.

Adult↗
PubMed1996

Collaborative care receives stamp of approval in CMA, CNA study involving HIV/AIDS.

The CMA wants to work with national health care groups, such as the Canadian Nurses Association (CNA), to explore ways providers can work collaboratively to provide quality health care. A joint working group of the CMA and the CNA recently examined collaborative care, focusing on examples provided in HIV/AIDS care. The group developed principles to help people work collaboratively in a variety of settings.

Canada↗
PubMed1996

An international investigation of an outbreak of Legionnaires disease among UK and French tourists.

Five cases of legionnaires disease and one death were associated with four members of a tour group from the United Kingdom (UK) and one French tourist who all visited Spain in the spring of 1993. The UK group stayed at four hotels, one of which was also used by the French tourist. Phenotypic and genotypic comparison of isolates of Legionella pneumophila obtained from one of the UK cases and the French patient demonstrated that they were indistinguishable from each other and from environmental isolates obtained from the water supply of the hotel at which all five cases had stayed. A cohort study of the UK tour group was carried out to determine the extent of the outbreak and showed that three further members of the group had respiratory illness but were serologically negative to legionella infection. International participation in this investigation has highlighted the value of a European surveillance scheme and the benefit of microbiological collaboration between legionella reference laboratories in Europe.

Aged↗
PubMed1996

Effects of the delta opioid against BW373U86 in pigeons trained to discriminate fentanyl, bremazocine and water in a three-choice drug discrimination procedure.

The delta opioid agonist BW373U86 was examined alone and in combination with mu agonists in pigeons trained to discriminate the mu agonist fentanyl (0.056 mg/kg), the kappa agonist bremazocine (0.017 mg/kg), and distilled water in a three-choice drug discrimination procedure. BW373U86 (0.01-10 mg/kg) produced a dose-dependent increase in fentanyl-appropriate responding and complete generalization to fentanyl in four of five subjects. BW373U86 did not elicit bremazocine-appropriate responding in any of the subjects. Fentanyl-appropriate responding elicited by BW373U86 was antagonized by the delta selective antagonist naltrindole (0.1-10 mg/kg) but not by the mu selective antagonist naloxone (0.1-30.0 mg/kg). When BW373U86 was administered in combination with the mu agonists fentanyl, morphine and nalbuphine, a low dose of BW373U86 (0.01 mg/kg) that elicited primarily water-appropriate responding when administered alone did not produce a significant change in the ED50 values for fentanyl, morphine or nalbuphine. Higher doses of BW373U86 (0.1-1.0 mg/kg) increased levels of fentanyl-appropriate responding elicited by low doses of fentanyl, morphine and nalbuphine to levels similar to those produced by BW373U86 alone. These results indicate that BW373U86 shares discriminative stimulus properties with the mu agonist fentanyl in pigeons, possibly by acting at delta opioid receptors. However, BW373U86 does not potentiate the discriminative stimulus effects of mu agonists or share discriminative stimulus effects with the kappa agonist bremazocine.

Analgesics↗
PubMed1996

Neointimized Gore-Tex graft for ureteral prosthesis in the dog.

OBJECTIVES: To determine the feasibility of replacing a ureteral segment with a neointimized Gore-Tex graft. METHODS: Seven adult mongrel dogs underwent a two-stage operative procedure. The first procedure involved arterializing the graft to stimulate spread of a luminal neoendothelium by transmural capillary growth. Eight weeks after the initial procedure, a segment of the ipsilateral ureter was replaced with a segment of the neointimized graft. RESULTS: Histologic evaluation of a portion of the graft removed during the second procedure demonstrated transmural neocapillary ingrowth in all grafts; however, there was no neoendothelial growth on the luminal surface. In 5 dogs the graft was occluded with blood clot and was not suitable for a ureteral prosthesis. In 2 dogs the graft was patent and was successfully incorporated into the urinary system. After 1 year of observation, both of these dogs maintained a patent ureter and had no evidence of hydronephrosis on intravenous urogram. CONCLUSIONS: These data demonstrate that a Gore-Tex graft can be used as a ureteral prosthesis in the dog. The importance of preliminary arterialization, however, remains to be determined.

Animals↗
PubMed1996

Development of minimally differentiated acute myeloblastic leukemia with novel isochromosome 18p and antecedent aplastic anemia.

We describe a case of acute myeloblastic leukemia with a novel isochromosome 18, i(18)(p10), preceded by aplastic anemia for six months. The patient is a cotton grower chronically exposed to pesticides. The significance of this chromosomal abnormality is unknown. The possible relationship to the preceding history of aplastic anemia and occupational pesticide exposure is speculated on. The possible mechanism of the association of acute leukemia and aplastic anemia is discussed.

Agricultural Workers' Diseases↗
PubMed1996

Salmonella virchow PT 26 infection in England and Wales: a case control study investigating an increase in cases during 1994.

An increase in the number of human isolates of Salmonella virchow phage type (PT) 26 in England and Wales during 1994 was investigated. A national case control study was conducted which included 88 cases and 182 controls. The cases were mostly young adults (median age 26) and 13 (15%) were admitted to hospital. Acquisition of S. virchow PT 26 was associated with the consumption of any chicken (OR 2.5, CI 1.1-5.8), of chicken curry from restaurants and take aways (OR 2.9, CI 1.4-6.1), and of some other diverse types of pre-prepared chicken (OR 3.8, CI 1.9-7.6). Halal chicken was associated (P = 0.006) with illness in a subset. There were negative associations with contact with animals (OR 0.47, CI 0.23-0.95) and with the consumption of chicken cooked whole (OR 0.37, CI 0.21-0.66). The increase in S. virchow PT 26 may be due to changing epizoology and may be an indicator of what will become the dominant salmonella strain in poultry in future years. The increasing incidence of S. virchow PT 26 is of particular concern because of its association with more invasive disease in humans.

Adolescent↗
PubMed1996

X-linked anhidrotic (hypohidrotic) ectodermal dysplasia is caused by mutation in a novel transmembrane protein.

Ectodermal dysplasias comprise over 150 syndromes of unknown pathogenesis. X-linked anhidrotic ectodermal dysplasia (EDA) is characterized by abnormal hair, teeth and sweat glands. We now describe the positional cloning of the gene mutated in EDA. Two exons, separated by a 200-kilobase intron, encode a predicted 135-residue transmembrane protein. The gene is disrupted in six patients with X;autosome translocations or submicroscopic deletions; nine patients had point mutations. The gene is expressed in keratinocytes, hair follicles, and sweat glands, and in other adult and fetal tissues. The predicted EDA protein may belong to a novel class with a role in epithelial-mesenchymal signalling.

Adult↗
PubMed1996

Perception of emotion from dynamic point-light displays represented in dance.

It is well known that biological motion, as produced by point-light displays on a human body, gives a good representation of the represented body-eg its gender and the nature of the task which it is engaged in. The question is whether it is possible to judge the emotional state of a human body from motion information alone. An ability to make this kind of judgment may imply that people are able to perceive emotion from patterns of movement without having to compute the detailed shape first. Subjects were shown brief video clips of two trained dancers (one male, one female). The dancers were aiming to convey the following emotions: fear, anger, grief, joy, surprise, and disgust. The video clips portrayed fully lit scenes and point-light scenes, with thirteen small points of light attached to the body of each dancer. Half the stimuli were presented the right way up, while half were inverted. The subjects' task was to judge which emotion was being portrayed. Full-body clips gave good recognition of emotionality (88% correct), but the results for upright biological-motion displays were also significantly above chance (63% correct). Inversion of the display reduced biological-motion (but not full-body) performance to close to chance but still significantly above chance. A space-time analysis of the motion of the points of light was carried out, and was related to the discriminability of the different emotions. Biological-motion displays, which convey no information while static, are able to give a rich description of the subject matter, including the ability to judge emotional state. This ability is disrupted when the image is inverted.

Analysis of Variance↗
PubMed1996

High cellular concentration of peripheral blood progenitor cells during cryopreservation adversely affects CFU-GM but not hematopoietic recovery.

The effects of bone marrow (BM) and peripheral blood progenitor (PBPC) concentration during cryopreservation on subsequent hematopoietic engraftment following high-dose chemotherapy were studied in 24 patients. Seventeen BM harvests and 71 PBPC collections were performed between July 1991 and June 1994. The PBPC were frozen at significantly higher cellular concentrations than the BM (medians of 243 x 10(6)/ml versus 73 x 10(6)/ml respectively, p = 0.0003). The recovery of committed progenitor cell colonies (CFU-GM) was significantly lower from PBPC frozen at concentrations above the median, compared with 116% from those frozen at concentrations below the median (p = 0.0467). This phenomenon was not seen in BM, which was generally frozen at a threefold lower concentrations. Despite the lower recovery of CFU-GM when PBPC were frozen at a higher concentration, the patients receiving these grafts achieved good hematopoietic recovery. The higher number of PBPC probably compensated for the loss, and the patients still received a substantial number of clonogenic hematopoietic precursors.

Adolescent↗
PubMed1996

Acute hemodynamic and neurohoromonal effects of furosemide in critically ill pediatrics patients.

OBJECTIVES: To study the acute hemodynamic effects of furosemide in critically ill pediatrics patients, the temporal relationship between hemodynamic changes and changes in neuroendocrine axis, and the temporal relationship between hemodynamic changes and urine output. DESIGN: Prospective study. SETTING: Pediatric intensive care unit in a tertiary care university center. PATIENTS: Fourteen critically ill pediatric patients who clinically required diuretic therapy. INTERVENTIONS: Before and after furosemide administration, hemodynamic and neurohormonal measurements were taken. MEASUREMENTS AND MAIN RESULTS: Hemodynamic and neurohormonal responses to acute diuretic therapy were measured in 14 pediatric patients treated with furosemide (1 mg/kg/dose). Cardiac index deteriorated by 10 mins after drug administration (-9.4+/-3.9%, p<.05) and was associated with an increase in systemic vascular resistance (17.1+/-4.8%, p<.05). There was a subsequent increase in cardiac index (20+/-4.9%, p<.05) at 30 mins, with a decrease in systemic vascular resistance (-11.5+/-5.2%, p<.05). These hemodynamic changes were associated with marked increases in renin and norepinephrine concentrations and an increase in urinary prostaglandin release. The hemodynamic and neurohormonal effects had their onset before maximum diuresis. CONCLUSION: Intravenous furosemide administration in acutely ill pediatric patients results in an acute but transient deterioration in cardiac function that appears to parallel the neuroendocrine changes rather than the acute diuresis.

Adolescent↗
PubMed1996

Respect for autonomy: is it always paramount?

Following the argument proposed by Tschudin in 1986 that many nurses do not have the skills for ethical decision-making, this article identifies and discusses one ethical problem from practice. The problem concerns an extremely obese patient who refuses to be moved by a hoist. The nurse acquiesce to the patient's wishes and she is moved manually by four members of staff. The issues identified for discussion are: the paramountcy of the principle of respect for the patient's autonomy; the rights and obligations of the nurses; and the justification for influencing patient choice. The approach used by the ward nurses is analysed and the value of using an ethical decision-making model is considered.

Aged↗