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Biomedical subjects

P Taylor

Publications and source records attributed to P Taylor.

At least 289 records · Page 16Linked to original sources
PubMed1994

Immediate-early gene expression in response to hypertrophic and proliferative stimuli in pulmonary arterial smooth muscle cells.

Remodeling of the pulmonary vascular tree in pulmonary hypertension is associated with hypertrophy and proliferation of smooth muscle cells. Since the stimuli and signaling pathways for these processes are not well understood, we used a rat pulmonary arterial smooth muscle cell line (PAC1) to examine the effects of thrombin and platelet-derived growth factor (PDGF) on cellular growth and immediate-early gene expression. Over 72 h, thrombin (1 unit/ml) caused hypertrophy as reflected by a 102 +/- 12% increase in protein synthesis and a 49 +/- 11% increase in protein content per cell, but no change in cell number. PDGF (2.5 ng/ml) stimulated proliferation as evidenced by an increase in cell number (doubling in 5 days), but no significant change in protein content per cell. Immediate-early gene expression was examined by Northern blotting: both thrombin and PDGF induced egr-1, c-fos, c-jun, junB, and fra-1 mRNAs within 15 min; the response was maximal at 30-60 min (increases ranging from 2.9- to 9.3-fold over control serum-deprived cells) and returned to base-line levels within 2-4 h. Neither agent affected junD mRNA levels. However, thrombin but not PDGF, caused an increase in fosB mRNA levels (7.7 +/- 4.0-fold higher than control, n = 12, p < 0.0005). The immediate-early gene response to both agonists was generally dependent on extracellular Ca2+, Na2+/H+ exchange, and protein kinase C activation, but not on cAMP. The exception was c-jun mRNA, the levels of which were not affected by inhibition of protein kinase C, but decreased significantly by prevention of cAMP formation. Thapsigargin-sensitive intracellular Ca2+ stores were necessary for the response to thrombin, but not to PDGF. These results demonstrate that thrombin is a hypertrophic agent and that PDGF is a proliferative agent in PAC1 cells. These two agonists stimulate increases in a variety of immediate-early gene mRNAs, but only thrombin induces fosB mRNA.

Animals↗
PubMed1994

Identification of amino acid residues involved in the binding of Huperzine A to cholinesterases.

Huperzine A, a potential agent for therapy in Alzheimer's disease and for prophylaxis of organophosphate toxicity, has recently been characterized as a reversible inhibitor of cholinesterases. To examine the specificity of this novel compound in more detail, we have examined the interaction of the 2 stereoisomers of Huperzine A with cholinesterases and site-specific mutants that detail the involvement of specific amino acid residues. Inhibition of fetal bovine serum acetylcholinesterase by (-)-Huperzine A was 35-fold more potent than (+)-Huperzine A, with KI values of 6.2 nM and 210 nM, respectively. In addition, (-)-Huperzine A was 88-fold more potent in inhibiting Torpedo acetylcholinesterase than (+)-Huperzine A, with KI values of 0.25 microM and 22 microM, respectively. Far larger KI values that did not differ between the 2 stereoisomers were observed with horse and human serum butyrylcholinesterases. Mammalian acetylcholinesterase, Torpedo acetylcholinesterase, and mammalian butyrylcholinesterase can be distinguished by the amino acid Tyr, Phe, or Ala in the 330 position, respectively. Studies with mouse acetylcholinesterase mutants, Tyr 337 (330) Phe and Tyr 337 (330) Ala yielded a difference in reactivity that closely mimicked the native enzymes. In contrast, mutation of the conserved Glu 199 residue to Gln in Torpedo acetylcholinesterase produced only a 3-fold increase in KI value for the binding of Huperzine A.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholinesterase↗
PubMed1994

Endothelium-dependent relaxation of human resistance arteries in pregnancy.

OBJECTIVE: Reduced peripheral vascular resistance is an integral component of vascular adaptation in pregnancy. The precise mediators of the reduced resistance are unknown, however, and are often assessed by indirect means. In this study we investigated endothelium-dependent relaxation directly by examining acetylcholine-mediated relaxation in small arteries dissected from the subcutaneous fat layer undergoing biopsy at the time of gynecologic surgery and cesarean section. STUDY DESIGN: By means of a small vessel myograph we measured tension in resistance arteries of normal pregnant (n = 22) and nonpregnant (n = 10) women and assessed the contributions of vasodilatory prostanoids and endothelium-derived relaxing factor on endothelium-dependent relaxation, as elicited by acetylcholine (1 nmol/L to 10 mumol/L) after precontraction with 3 mumol/L norepinephrine. RESULTS: Endothelium-dependent relaxation was similar in arteries of pregnant and nonpregnant women. Sodium nitroprusside-induced relaxation was similar in arteries of pregnant and nonpregnant women. CONCLUSION: This study fails to demonstrate any increase in acetylcholine-induced endothelium-dependent relaxation in small subcutaneous arteries in pregnancy.

Acetylcholine↗
PubMed1994

Expression and ligand specificity of acetylcholinesterase and the nicotinic receptor: a tale of two cholinergic sites.

The functional design of the nAChR and AChE rather than their recognition capacities requires divergence in structure of the two binding sites. The receptor requires co-operativity to link ligand occupation to the response, rapid conformational transitions of activation, and slower transitions of desensitization. Hence, its binding sites have evolved at subunit interfaces. By contrast, AChE functions with a large kcat and a comparatively large Km. To do so, it must force acetylcholine through a low-energy transition site that features tetrahedral rather than the ground-state, trigonal conformation around the carbonyl carbon. This requires a high affinity (KD approximately 10(-17) M) for the enzyme complex of the transient transition state. Interestingly, the three-finger peptide toxins (alpha-bungarotoxin and fasciculin), though closely homologous, use different interaction sites on the receptor (the agonist recognition site) and AChE (a peripheral site). Finally, although the two proteins show co-ordinated expression during muscle differentiation, the receptor relies primarily on transcriptional control while AChE expression is post-transcriptional, being controlled by mRNA stability.

Acetylcholinesterase↗
PubMed1994

Occupational asthma and the chemical properties of low molecular weight organic substances.

Various low molecular weight substances cause occupational asthma, and there is scope for studying their chemical properties in relation to their propensity to cause this condition. Twenty-nine organic substances (molecular weight < 250), with or without oxygen or nitrogen atoms, were compared to control hazardous substances obtained from the list of occupational exposure limits. There were significantly more reactive groups in the active chemicals than in the controls. Carbon to nitrogen double bonds were also significantly over-represented in the active chemicals. If confirmed in a fuller study, these data could yield useful information on the causation of occupational asthma and on the hazard assessment of novel chemical entities.

Air Pollutants↗
PubMed1994

Quality of life after multiple trauma requiring intensive care.

A prospective observational study using structured interviews was used to assess changes in quality of life experienced by surviving trauma victims after management on a general intensive therapy unit in a district general hospital. Each patient's age, distribution of injuries, severity of illness on admission and duration of management were recorded. Deaths in the study group were excluded by examining the Hospital's 'Patient Administrative System'. Three attempts were then made to contact all known survivors and to assess their quality of life using three previously recognised and validated methods. Eighty-three survivors of multiple trauma were discharged but 19 were not studied. Of the remaining 64, 42 patients completed the questionnaire. After multiple trauma, patients reported significant decreases in their quality of life in relation to their overall health, happiness, ability to think and to pursue leisure activities, their income and their employment. Their mean Perceived Quality of Life Score decreased by 13% (95% confidence intervals 7.5-19.5%). Sixty-two percent of survivors experienced severe social disability and a modest or severe impairment at work. The Nottingham Health Profile identified major changes in 'psychological' aspects of quality of life, namely energy and emotional reactions.

Adult↗
PubMed1994

Dosimetric parameters of a modified set of wedges for use with asymmetric fields of a 6 MV linear accelerator.

A set of standard wedge filters has been modified for use with half-collimated beams of a 6 MV linear accelerator. The position of the standard size wedge filter has been shifted as far to one side of the wedge plate to ensure optimum half-collimated field coverage (up to 20 x 30 cm) required in certain clinical situations. Dosimetric parameters were normalized at 1.5 cm depth and at an off-axis reference point (3.5 cm from the central axis of the collimator at 100 cm SSD. The shapes of the wedged profile and isodose curves of the modified wedges remained similar to those of standard wedges. Data presented include wedge transmission factors, wedge angles, beam profiles, and isodose distributions. The clinical advantages of using modified wedge filters (larger field size, larger transmission, and smaller weight) over standard large wedges is discussed.

Humans↗
PubMed1994

Augmented responses to intrathecal nicotinic agonists in spontaneous hypertension.

Abnormal central cholinergic activity has been reported to be responsible in part for the pathogenesis of high blood pressure in spontaneously hypertensive rats (SHR). Administration of cholinergic agonists in brain and spinal cord results in exaggerated pressor responses in SHR. Studies to date have focused largely on the muscarinic cholinergic system. Recently, we demonstrated that intrathecal administration of nicotinic agonists results in pressor, tachycardic, and irritation responses. In the present study we examine the cardiovascular and behavioral responses to nicotine and cytisine administered intrathecally in La Jolla strain (LJ) SHRLJ and age-matched Wistar-Kyoto (WKYLJ) rats. Nicotinic agonists produced augmented pressor, heart rate, and irritation responses in SHRLJ compared with normotensive rats. In both SHRLJ and WKYLJ rats, cytisine elicited a greater nociceptive response and greater spinobulbar component to the pressor response than nicotine. SHRLJ and WKYLJ rats also differ in that the SHRLJ strain shows a diminished tendency for desensitization to cytisine. As in Sprague-Dawley rats, in SHRLJ and WKYLJ rats the cardiovascular and behavioral responses to intrathecal nicotine were significantly inhibited by mecamylamine, dihydro-beta-erthyroidine, and methyllycaconitine. However, methyllycaconitine, which effectively blocked cytisine-elicited cardiovascular and behavioral responses in Sprague-Dawley and WKYLJ rats, was unable to inhibit the maximal rise in cystine-elicited blood pressure, heart rate, and irritation responses in SHRLJ. In contrast to the heightened cardiovascular and behavioral responses, the number of nicotinic binding sites in spinal cord membranes was significantly decreased in the hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Aconitine↗
PubMed1994

Measuring image texture to separate "difficult" from "easy" mammograms.

We are investigating computerized techniques for sorting mammograms according to whether the breast tissue is fatty or dense. The hypothesis is that areas of dense tissue are a major factor in making certain mammograms harder for both radiologists and computers to interpret. Being able to identify dense mammograms automatically could permit better use of the time and skills of expert radiologists by allowing the difficult mammograms to be examined by the most experienced readers. In addition, the scope for computer-aided detection of abnormalities might be increased by concentrating on the easier, fatty mammograms. The mammograms used in the experiment were classified independently by two radiologists, who agreed in almost all cases. A number of local statistical and texture measures were then computed for patches from digitizations of these mammograms. One of the measures (local skewness in tiles) gives a good separation between fatty and dense patches. This measure has been incorporated into an automated procedure that separates off approximately two thirds of the fatty mammograms. This finding has been replicated on mammograms taken from a UK screening programme. The relationship between the fatty/dense distinction and the classification proposed by Wolfe is discussed.

Adipose Tissue↗
PubMed1994

Fortification of precooked maize flour with coarse defatted maize germ.

The possibility of improving the dietary value of precooked maize flour through fortification with 11% coarse defatted maize germ was investigated. The results of tests in humans presented here show that the total iron absorption from the fortified preparation is similar to that from the precooked maize alone, but with the advantage of being richer in several nutrients: protein (25%), zinc (61%), potassium (47%) and magnesium (112%), as well as fiber (34%). Fortification lowers (by 20%) rather than raises the cost of the flour, and may be an important contribution to the diet of those populations where maize bread is a major component of the diet.

Absorption↗
PubMed1994

[A rare cause of hyponatremia during introductory treatment of acute lymphoblastic leukemia in an infant: inappropriate secretion of atrial natriuretic factor?].

BACKGROUND: --Hyponatremia is frequently seen during the treatment of acute lymphoblastic leukemia: its causes are numerous. This work aims to present a case in whom hyponatremia was possibly due to an increased secretion of atrial natriuretic factor. CASE REPORT: --A 3 week-old baby was admitted because of malignant hemopathy. A diagnosis of acute lymphoblastic leukemia was rapidly made and the patient was firstly given alkaline diuresis, urate-oxidase and corticosteroids. Vincristine and daunorubicin were associated one week later. Insertion of a central intravenous line in the right subclavicular artery failed so that this catheter was finally inserted into the left jugular vein. Natremia was 126 mmol/l at that time and dramatically decreased within 24 hours to 109 mmol/l without net changes in water and electrolytic input. At that time, sodium urinary excretion was 6 mmol/kg/day (diuresis: 420 mlF/day). There was no hemodynamic changes, nor digestive or cardiac manifestations. Ultrasonography showed that the left superior cava vein drained into the right cardiac atrium. The catheter was withdrawn and the patient was given sodium supplementation permitting complete and definitive cure of hyponatremia within 2 days. CONCLUSIONS: --All usual causes of hyponatremia having been ruled out in this patient, we postulate that hyponatremia was due to direct stimulation of atrial natriuretic peptide through an increase in atrial pressure secondary to the catheter insertion near the cardiac atrium.

Atrial Natriuretic Factor↗
PubMed1994

Stimulatory pathways and sites of action of intrathecally administered nicotinic agents.

Intrathecal (i.t.) administration of nicotinic agonists to rats elicits a receptor-mediated pressor response, a heart rate increase and irritation-nociceptive behavior. We examined the stimulatory pathways and sites of action of spinally administered nicotinic agonists. The thoracic region appears more sensitive to nicotine-elicited pressor actions than the lumbar or cervical regions of the spinal cord. Nicotinic receptors evoking a nociceptive response appear to be located over an area extending from the lumbar rostrally to the thoracic region. Similar to the pressor response, the thoracic spinal cord is the most sensitive region to nicotine in producing the heart rate increase. The cervical region is the least responsive to nicotine, suggesting sites of actions caudal to the brain stem. Intravenous infusion of trimethaphan inhibited the nicotine-elicited pressor response and tachycardia without affecting the irritation response. This suggests that the cardiovascular responses to spinal nicotinic agonists result from enhanced sympathetic outflow. Intrathecal morphine and MK-801 block spinal nicotine-elicited irritation and tachycardia but not the pressor response, indicating that pressor and irritation responses involve independent receptor-mediated pathways. Tachycardia may be associated with the irritation response. In contrast to nicotine, both pressor and irritation responses to cytisine were blocked by morphine with no effect on heart rate. Spinal transection at the T1-2 level eliminated the nociceptive response to nicotine but not the pressor response. Cytisine responses were similar to nicotine; however, cytisine was significantly less potent as a pressor agent in the transected compared with intact animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaloids↗
PubMed1994

How disease prevention fails without good communication.

Even where resources are plentiful, efforts to achieve full immunization coverage fail if staff and users are misinformed and unmotivated. A highly practical study in Lagos pinpoints some of these failures and suggests ways of overcoming them.

Adult↗
PubMed1994

Cytokine involvement in predicting clinical graft-versus-host disease in allogeneic bone marrow transplant recipients.

An in vitro skin explant model has been used to predict the severity of acute graft-versus-host disease (GVHD) in 34 HLA-identical bone marrow transplant recipients (correlation coefficient 0.6 p < 0.001). Supernatants from HLA-matched patient/donor mixed lymphocyte cultures (MLCs) were analysed for levels of tumour necrosis factor alpha (TNF alpha) and interferon gamma (IFN gamma). High levels of both cytokines correlated with the development of GVHD grades II or above (p < 0.05). The supernatants were also tested for induction of class II MHC antigen expression on third party skin and results correlated with clinical outcome in 17 of 22 cases (77%) (correlation coefficient 0.65, p < 0.001). The results suggest that measurement of both TNF alpha and IFN gamma in HLA-matched MLC supernatants is of predictive value and that the skin explant model is a useful model for studying the aetiology of GVHD in humans.

Adolescent↗