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Biomedical subjects

C Hall

Publications and source records attributed to C Hall.

At least 235 records · Page 13Linked to original sources

Effect of n-3 and n-6 dietary fats on the lipoxygenase products from stimulated rat neutrophils.

Fish oil was fed to rats in combination with an equal amount of olive, sunflower or linseed (flax) oil in semisynthetic diets for 3 weeks. Following stimulation of isolated neutrophils with calcium ionophore the levels of leukotrienes (LT) were determined by HPLC. Graphical presentation of the resultant data show a direct linear relationship between LTB production and substrate concentration with no preferential conversion of n-3 or n-6 substrates. In addition the results highlighted the greater conversion of eicosapentaenoic acid (EPA) and arachidonic acid (AA) to 5-hydroxy metabolites in stimulated neutrophils. There is no suggestion in our results of inhibition of any of the enzymatic conversion steps between EPA or AA and LTB production by any of the dietary fatty acids except by altering the EPA/AA ratio in neutrophil membranes.

Animals↗

Subclinical central nervous system infection with JC virus in patients with AIDS.

Immunocompromised patients, particularly those with AIDS, develop progressive multifocal leukoencephalopathy (PML) due to central nervous system infection with JC virus (JCV). It is unknown whether JCV infection in the central nervous system can occur in the absence of PML symptoms. To address this question, autopsy specimens from patients with AIDS were examined. The brains of a group of patients without AIDS or central nervous system disease were also examined. JCV DNA was detected by the polymerase chain reaction in brain tissue from 4 (31%) of 13 human immunodeficiency virus (HIV)-positive patients. JCV was also detected in 1 elderly HIV-negative patient but not in the 11 other control brains. JCV was not detected in 22 myocardial specimens obtained at autopsy from HIV-negative patients nor 10 peripheral blood specimens from HIV-positive patients. The presence of JCV in brains of patients without clinically evident PML suggests that JCV may be present in the central nervous system without clinical disease.

Acquired Immunodeficiency Syndrome↗

Plasma concentrations of atrial peptides ANF(1-98) and ANF(99-126) after intravenous infusion: effect of infusate temperature.

Atrial peptides ANF(1-98) and ANF(99-126) were measured in plasma before and after infusion of Ringer-Acetate solution in healthy volunteers. The solution was infused over a 45 min period in an amount equal to 20 per cent of estimated extra-cellular volume. We found that the increase in atrial peptide immunoreactivity after infusion depended on the temperature of the infusate. The molar increase in ANF(1-98) was much larger than the increase in ANF(99-126). We speculate that plasma levels of ANF(1-98) may be a clinically useful parameter of atrial distension secondary to hypervolaemia.

Adult↗

Crypt cell production rates at various sites around the colon in Wistar rats and humans.

The crypt cell production rate (CCPR) is considered the most robust estimate of cell turnover. The CCPR was determined at various sites around the colon in the Wistar rat (using an in vivo technique) and in six healthy humans (using in vitro organ culture). In both the rat and human colon, the CCPR increased proximally from the rectum to the caecum. The caecum had a significantly higher cell turnover than any other site in the colon (p < 0.05 in the rat, p < 0.01 in humans, Student's t test). These findings are of interest when considering cellular proliferation studies in both inflammatory bowel disease and colorectal cancer, and draw attention to the importance of choosing a constant reference site for comparative studies. This is the first time the CCPR had been measured along the length of the human colon.

Adult↗

Relation of diagnostic serum amylase levels to aetiology and severity of acute pancreatitis.

The sensitivity of diagnostic serum amylase (greater than 1000 iu/l) was assessed in 417 patients with acute pancreatitis as a result of gall stones (258), alcohol (104), or miscellaneous causes (55), of whom 111 (27%) had a clinically severe attack (including 34 deaths). On hospital admission, an amylase value diagnostic of pancreatitis was found in 96.1% of all mild cases and in 87.4% of severe cases (p less than 0.001); at 48 hours these values were 33.3% and 48.2% respectively (p = 0.026). Diagnostic amylase levels for alcoholic patients were found in 86% of mild cases on admission and in 76% of severe cases (p less than 0.001, compared with other groups). The diagnostic levels were also significantly lower at 24 hours for both the alcoholic and miscellaneous groups compared with the gall stone group (p less than 0.001). Eight of 27 (30%) patients with a serum amylase activity less than 1000 iu/l had pancreatic necrosis compared with 12 of the remaining 390 (3.1%) patients (p less than 0.001); the mortality was also significantly different (44% v 5.6% respectively, p less than 0.001). These data support the view that more sensitive tests for acute pancreatitis are needed for routine use especially in those whose disease has an alcoholic aetiology.

Acute Disease↗

Imagery and the acquisition of motor skills.

This paper examines the relationship between imagery and the acquisition of motor skills. Since most of the research in the motor domain has considered imagery under the topic of mental practice, a comparison between imagery and mental practice is first drawn. Then the basic mental practice paradigm is outlined and research on the effects of imagery is summarized. Factors influencing the use of imagery are considered, including the task, the imagery instructions, and individual imagery abilities. Implications for employing imagery in the teaching of motor skills are discussed and, finally, an approach to studying imagery and motor skills is put forward.

Cognition↗

Pharmacokinetics and pharmacodynamics of labetalol in the pregnant sheep.

The maternal-fetal disposition of labetalol, a combined alpha-1 and beta adrenergic blocker, and its pharmacodynamics in pregnancy are not well understood. This study describes the pharmacokinetics, cardiovascular and metabolic effects of labetalol in the mother and in utero fetus after a 100-mg maternal i.v. bolus administration, in the chronically instrumented pregnant sheep. Labetalol shows a triexponential decline in the mother with a total body clearance of 30.8 +/- 3.83 ml/min/kg, an apparent steady-state volume of distribution (nonparametric) of 3.02 +/- 0.18 liters/kg and terminal elimination half-life of 2.79 +/- 0.66 hr. These estimates are similar to the reported values in pregnant women. Labetalol rapidly crosses the sheep placenta. The peak fetal plasma concentration was 33.7 +/- 5.8 ng/ml, the fetal exposure to labetalol as calculated by the fetal to maternal area under the curve ratio was 14.37 +/- 1.54% and the apparent fetal elimination half-life was 3.71 +/- 0.5 hr. Labetalol persists in the amniotic and fetal tracheal fluids up to 24 hr with concentrations reaching 2- to 4 times the fetal plasma concentration. Whereas there were no significant maternal or fetal cardiovascular effects, some very significant metabolic effects were observed, including fetal and maternal lactic acidosis and hyperglycemia. Lactic acid accumulates in the fetal blood and amniotic fluid with peak concentrations (6.0 +/- 0.31 and 5.5 +/- 0.26 mM, respectively) showing a more than 300% increase over control values. The exact mechanism by which labetalol causes these metabolic effects is not clear, but it may involve its partial beta-2 agonist activity.

Animals↗

Bcr encodes a GTPase-activating protein for p21rac.

More than thirty small guanine nucleotide-binding proteins related to the ras-encoded oncoprotein, termed Ras or p21ras, are known. They regulate many fundamental processes in all eukaryotic cells, such as growth, vesicle traffic and cytoskeletal organization. GTPase-activating proteins (GAPs) accelerate the intrinsic rate of GTP hydrolysis of Ras-related proteins, leading to down-regulation of the active GTP-bound form. For p21ras, two GAP proteins are known, rasGAP and the neurofibromatosis (NF1) gene product. There is evidence that rasGAP may also be a target protein for regulation by Ras and be involved in downstream signalling. We have purified a GAP protein for p21rho, which is involved in the regulation of the actin cytoskeleton. Partial sequencing of rhoGAP reveals significant homology with the product of the bcr (breakpoint cluster region) gene, the translocation breakpoint in Philadelphia chromosome-positive chronic myeloid leukaemias. We show here that the carboxy-terminal domains of the bcr-encoded protein (Bcr) and of a Bcr-related protein, n-chimaerin, are both GAP proteins for the Ras-related GTP-binding protein, p21rac. This result suggest that Bcr could be a target for regulation by Rac and has important new implications for the role of bcr translocations in leukaemia.

Amino Acid Sequence↗

Colon perforation during colonoscopy: surgical versus conservative management.

A survey of endoscopy units in the West Midlands, UK, was undertaken to ascertain the management of colonic perforation during colonoscopy. Fifteen perforations were reported from a total of 17,500 colonoscopies performed in 14 units (a rate of 0.09 per cent). In seven patients the diagnosis was suspected or diagnosed immediately and in the remaining eight 2-72 h later. Four patients with associated pathology (carcinoma, Crohn's disease, ulcerative colitis and a polyp) had resection and primary anastomosis. Seven patients had a simple oversew, four of these having had a delayed diagnosis. In four cases the site of perforation was not identified, but only one patient had conservative treatment. Three patients had drainage and a defunctioning colostomy. There was no significant morbidity following treatment. It is recommended that patients who have had a good bowel preparation should be treated conservatively unless there is a large perforation or an underlying carcinoma.

Adult↗

Requirements for cell surface expression of the human TCR/CD3 complex in non-T cells.

The T-cell antigen receptor (TCR) consists of a glycoprotein heterodimer (alpha/beta or gamma/delta) which is non-covalently associated with at least four or five invariant polypeptides (CD3 gamma, delta, epsilon, zeta and eta). In T-cell variants lacking TCR alpha, beta or zeta, it has been shown that incomplete TCR/CD3 complexes are retained within the cell. To examine requirements for cell surface expression of TCR/CD3, we transfected COS monkey kidney cells with cDNAs encoding TCR alpha, beta and CD3 gamma, delta, epsilon and zeta. We report that cell surface appearance of TCR/CD3 on COS cells requires coordinate expression of all six proteins. In the absence of the zeta chain, subcomplexes comprising from two to five chains were readily demonstrable in COS cells, but they failed to reach the cell surface or to acquire N-linked oligosaccharide side chains indicating failure to reach the medial Golgi. Pulse-chase metabolic labelling of transfected COS cells showed that three chains (CD3 gamma, CD3 epsilon, and zeta) were stable while three (TCR alpha, TCR beta and CD3 delta) were rapidly degraded. In two- and three-chain co-transfections specific intracellular subcomplexes were formed between TCR alpha and CD3 gamma, TCR alpha and CD3 delta, or TCR beta and CD3 epsilon. Binary subcomplexes having at least one stable chain (CD3 epsilon - TCR beta) were stable while one formed by two unstable chains (TCR alpha - CD3 delta) was still degraded. Assembly of the TCR/CD3 complex in COS cells thus appears centered around the metabolically stable CD3 gamma and CD3 epsilon proteins. Site-specific mutations of the negatively-charged transmembrane amino acid of residues of the CD3 chains to alanines served to either abolish (for TCR alpha - CD3 delta and TCR beta - CD3 epsilon) or diminish (for TCR alpha -CD3 gamma) these TCR-CD3 interactions. These mutations had no effect, however, on CD3-CD3 interactions or upon synthesis, metabolism, or intracellular distributions of the CD3 proteins. The transmembrane domains of CD3 gamma, delta, and epsilon thus appear to play a major role in associations of CD3 with TCR chains.

Animals↗

Endocrine responses to positive end-expiratory pressure ventilation in patients who have recently undergone heart surgery.

The effect of positive end-expiratory pressure ventilation (PEEP) on angiotensin II and atrial natriuretic factor (ANF) was studied postoperatively following heart surgery. In nine patients pressures were recorded in the radial artery, pulmonary artery and the right atrium. PEEP of 5 cmH2O (0.5 kPa) and 10 cmH2O (1 kPa) increased angiotensin II from 38.8 +/- 20.3 (mean +/- s.e.mean) to 56.7 +/- 29.6 (n.s.) and 66.7 +/- 28.7 (P less than 0.05) pmol/l, respectively. Plasma-ANF showed no significant changes during PEEP. Pulmonary artery wedge pressure increased from 12.9 +/- 2.0 to 14.1 +/- 2.0 (n.s.) and 18.5 +/- 2.1 (P less than 0.01) mmHg, and right atrial pressure from 8.3 +/- 1.7 to 9.8 +/- 1.7 (n.s.) and 12.9 +/- 1.7 (P less than 0.01) mmHg with 5 and 10 cmH2O (0.5 and 1.0 kPa) of PEEP, respectively. Systemic blood pressure tended to decrease (n.s.) with PEEP. In conclusion, PEEP markedly increased angiotensin II. This may represent an important compensatory mechanism, helping to prevent reduction in aortic pressure during PEEP. ANF, however, did not change with PEEP of 5 or 10 cmH2O (0.5 and 1.0 kPa).

Anesthesia, General↗

The relationship between atrial pressure, atrial dimensions and atrial natriuretic factor during pacing tachycardia in dogs.

Acute supraventricular tachycardia is known to increase the plasma level of atrial natriuretic factor (ANF). The purpose of these experiments was to investigate if such an increase in plasma-ANF could be ascribed to changes in atrial pressure and atrial dimensions. Eight anaesthetized dogs were instrumented with atrial pressure catheters and sonomicrometers to measure left and right auricular and atrial free wall dimensions. An acute increase in atrial rate from 150 to 200 min-1 for 10 min did not change plasma-ANF or atrial haemodynamic variables. A further increase in atrial rate to 250 or 300 min-1 increased right and left atrial intracavitary pressures (P less than 0.01), both auricular diameters and right atrial free wall segment length (P less than 0.05). Left atrial free wall segment length remained unchanged. Plasma-ANF increased in all dogs (P less than 0.01). The change in plasma-ANF correlated well with changes in atrial pressures as well as with changes in atrial dimensions. These results support the hypothesis that release of ANF during acute atrial tachycardia may in part be attributed to atrial dilatation.

Animals↗

Rate-induced increase in plasma atrial natriuretic factor can occur independently of changes in atrial wall stretch.

Tachycardia is known to increase the plasma level of atrial natriuretic factor (ANF). The aim of the study was to determine whether such release of ANF can occur independently of increased atrial wall stretch. Seven anesthetized dogs were instrumented with pressure catheters and sonomicrometer crystals to measure left and right auricular and atrial free wall dimensions. During atrial pacing, the measured atrial dimensions were kept constant by adjusting vascular constrictors placed around the great vessel trunks. When atrial rate was increased progressively by pacing at 150, 200, and 250 min-1, plasma ANF increased from 40.8 +/- 5.4 to 43.0 +/- 6.0 (P = NS) and 103.1 +/- 17.6 (SE) pmol/l (P less than 0.05), respectively. Repeating the pacing sequence at two different levels of elevated left atrial pressure caused at each level a similar increase in plasma ANF at 250 min-1. The relationship between plasma ANF and atrial dimensions was shifted upward by pacing, such that ANF was higher for any given atrial dimension. In conclusion, pacing tachycardia elevates plasma ANF in the presence of constant atrial dimensions. These results support the hypothesis that chronotropic stimulation can cause release of ANF by a mechanism that is independent of atrial stretch.

Animals↗

Blood volume changes in liver and spleen during cardiogenic shock in dogs.

Changes in vascular capacitance of the liver and spleen were studied in seven anesthetized dogs during cardiogenic shock induced by coronary microembolization. Left ventricular end-diastolic pressure increased from 2 +/- 2 to 28 +/- 4 mmHg (P less than 0.001), and mean aortic pressure decreased from 111 +/- 7 to 56 +/- 9 mmHg (P less than 0.001). Hepatic venous pressure increased from 1.8 +/- 0.6 to 5.0 +/- 1.0 mmHg (P less than 0.05). Portal venous pressure did not change. Blood volume changes were assessed from sonomicrometric measurements of organ diameters. Hepatic diameter increased after embolization, corresponding to an estimated 54 +/- 14 ml increase of hepatic blood volume (P less than 0.01). Splenic diameter gradually decreased during shock until an estimated 33 +/- 12 ml of blood had been released (P less than 0.05). Occlusion of hepatic venous outflow by a balloon catheter was used to cause ramp changes in hepatic volume and hepatic venous pressure so that a pressure-volume curve could be estimated. Analysis of the hepatic curves showed an increase in unstressed volume with no change in vascular compliance during shock. The blood volume increase could in part be attributed to increased outflow pressure, but active dilation of hepatic capacitance vessels probably contributed. Splenic curves were shifted downward, suggesting expulsion of blood by active contraction.

Animals↗

Splanchnic vascular capacitance and positive end-expiratory pressure in dogs.

We have investigated the effect of positive end-expiratory pressure ventilation (PEEP) on regional splanchnic vascular capacitance. In 12 anesthetized dogs hepatic and splenic blood volumes were assessed by sonomicrometry. Vascular pressure-diameter curves were defined by obstructing hepatic outflow. With 10 and 15 cmH2O PEEP portal venous pressure increased 3.1 +/- 0.3 and 5.1 +/- 0.4 mmHg (P less than 0.001) while hepatic venous pressure increased 4.9 +/- 0.4 and 7.3 +/- 0.4 mmHg (P less than 0.001), respectively. Hepatic blood volume increased (P less than 0.01) 3.8 +/- 0.9 and 6.3 +/- 1.4 ml/kg body wt while splenic volume decreased (P less than 0.01) 0.8 +/- 0.2 and 1.3 +/- 0.2 ml/kg body wt. The changes were similar with closed abdomen. The slope of the hepatic vascular pressure-diameter curves decreased with PEEP (P less than 0.01), possibly reflecting reduced vascular compliance. There was an increase (P less than 0.01) in unstressed hepatic vascular volume. The slope of the splenic pressure-diameter curves was unchanged, but there was a significant (P less than 0.05) decrease in unstressed diameter during PEEP. In conclusion, hepatic blood volume increased during PEEP. This was mainly a reflection of passive distension due to elevated venous pressures. The spleen expelled blood and thus prevented a further reduction in central blood volume.

Animals↗

Effect of catheter size on pressures recorded in small pulmonary veins in dog lung.

Controversy continues about the contribution of the veins to pulmonary vascular resistance. From data obtained in studies using intravascular catheters, it appears that a major fraction (up to 44%) of the total pulmonary vascular pressure drop resides in larger (greater than 1.0 mm diam) veins, whereas micropuncture data and various models give much less pressure drop. Theoretically, artifactual pressure drops can be obtained if an intravascular catheter partly obstructs the vessel. We made measurements of pressure in the same lung vein with two different-sized catheters (1.2 and 0.6 mm OD, respectively). In paired experiments the larger catheter always measured a higher pressure than the smaller one, except close to the large lobar vein outlet. In some of the experiments we measured the diameter of the vessel containing the indwelling catheter by freezing the lung and then serial-sectioned the frozen lung. From these data we could infer that the range of vein diameter in the which the smaller catheter measured a lower pressure was 1.5-4 mm. We conclude that the larger catheter overestimated the pressure because of greater obstruction. The pressures obtained with the smaller catheter suggest that little (less than 10%) of the total pulmonary vascular resistance resides in veins larger than approximately 1 mm diam under zone 3 baseline conditions.

Animals↗