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Biomedical subjects

J Wilkinson

Publications and source records attributed to J Wilkinson.

At least 19 recordsLinked to original sources
PubMed1992

Determination of the intracellular distribution and pool sizes of apolipoprotein B in rabbit liver.

We have investigated the intracellular distribution of apolipoprotein B (apo B) in rabbit liver by immunoblotting, radioimmunoassay (r.i.a.) and enzyme-linked immunoassay (e.l.i.s.a.). Apo B100 was detected in total microsomes, rough microsomes, smooth microsomes, trans-enriched Golgi and cis-enriched Golgi and membrane and cisternal-content subfractions prepared from these fractions. There was also evidence of degradation of apo B100 in the Golgi membrane fractions. The amount of apo B in the subcellular fractions detected by competitive r.i.a. or e.l.i.s.a. ranged from 1.5 micrograms/mg of protein in the rough endoplasmic reticulum to 13 micrograms/mg of protein in the trans-Golgi fraction. Using internal standards (NADPH-cytochrome c reductase for the endoplasmic reticulum and galactosyltransferase for the Golgi membranes) it was calculated that all the apo B of liver is recovered within the secretory compartment, with 63% of the total apo B in the endoplasmic reticulum and the remainder in the Golgi. When the subcellular fractions were separated into membranes and cisternal contents, 60%, 50%, 60% and 30% of the total apo B was recovered in the membrane of the rough microsomes, smooth microsomes, cis-Golgi and trans-Golgi respectively. Using competitive e.l.i.s.a. we found that the membrane-bound form of the apo B was exposed at the cytosolic surface of the intact subcellular fractions. These observations are consistent with a model for assembly of very-low-density lipoproteins (VLDL) in which newly synthesized apo B is incorporated into a membrane-bound pool and a lumenal pool. The membrane-bound pool not used for VLDL assembly may be degraded, possibly in the Golgi region.

Animals↗
PubMed1992

Membrane-bound apolipoprotein B is exposed at the cytosolic surface of liver microsomes.

We have used a competitive enzyme-linked immunoassay with a panel of monoclonal antibodies to probe the topography of the membrane-bound form of apolipoprotein B (apo B) in rabbit microsomes. All epitopes investigated were found to be expressed at the cytosolic side of the microsomal membrane under conditions in which the vesicles remained sealed. These results indicate that the membrane-associated form of apolipoprotein B is either at the cytosolic side of the endoplasmic reticulum membrane or integrated into the membrane. From this site apo B may be translocated to the lumen for assembly into VLDL or may be degraded.

Animals↗
PubMed1992

Dimensions of anger-hostility and cardiovascular reactivity in provoked and angered men.

This study investigated the relationship between two dimensions of anger-hostility--the expression of anger-hostility and the experience of anger-hostility--and cardiovascular reactivity in provoked and angered men. A serial subtraction task was administered to 41 male undergraduates who were provoked and angered. A measure of the expression of anger-hostility correlated positively and significantly with systolic and diastolic blood pressure (BP) reactivity. There were no significant correlations between a measure of the experience of anger-hostility and cardiovascular reactivity. The two types of anger-hostility were also found to relate differentially to life-style variables that have been identified as risk factors for coronary heart disease (CHD), with only the expression of anger-hostility showing positive relationships with these life-style CHD risk factors. These findings are discussed within the context of a similar differential relationship between the two dimensions of anger-hostility and CAD and CHD. Finally, significant negative relationships were obtained between the experience of anger-hostility and resting BP and heart rate levels. These findings are discussed within the context of other data suggesting that trait anxiety-neuroticism may have protective properties.

Adult↗
PubMed1992

Appropriate acid suppression for the management of gastro-oesophageal reflux disease.

Gastro-oesophageal reflux disease (GORD) results from an abnormally prolonged dwell time of acidic gastric contents in the oesophagus. Although GORD is primarily a motor disorder, the injurious effects of gastric acid are central to the pathogenic process of oesophagitis, and the severity of disease correlates with the degree and duration of oesophageal acid exposure. In the majority of patients with mild disease, oesophageal acid exposure occurs predominantly during post-prandial periods. Conventional doses of H2-receptor antagonists cannot overcome the integrated stimulus to acid secretion resulting from a meal, and are thus relatively ineffective in preventing daytime, post-prandial oesophageal acid exposure. In patients with more severe grades of oesophagitis, there are abnormally high levels of nocturnal acid exposure, with the intra-oesophageal pH being less than 4.0 for 36% of the time, compared with 5% of the time in patients with mild GORD. Control of nocturnal acid secretion thus becomes increasingly important. This may be made worse by relative gastric acid hypersecretion in some patients with severe GORD. The long duration of action and effective inhibition of meal-stimulated acid secretion probably explains the superiority of omeprazole in treating GORD. Preliminary meta-analysis shows that the healing rate of erosive oesophagitis at 8 weeks by antisecretory agents is directly related to the duration of suppression of gastric acid secretion achieved over a 24-hour period (r = 0.87; p less than 0.05).

Anti-Ulcer Agents↗
PubMed1992

Influence of bovine somatotropin on the composition and manufacturing properties of milk.

Three studies (84, 140, and 200 d) were performed to examine the effect of injecting dairy cows with various doses (0, 320, 640, or 960 mg/28 d; 0 or 640 mg/28 d; 0, 320 mg/14 d, or 320 or 640 mg/28 d) of bST on milk production, composition, and manufacturing properties. Mean bST response among studies on milk production varied from 0 (trial 1) to 7.3% (trial 2) and from 8.5 to 14.2% (trial 3) in relation to feeding conditions. Neither milk fat nor protein percentages in milk at time of maximum response were affected by the use of bST. Distribution of casein and protein in the whey was not affected by the treatments at any time. The nature of fatty acids varied more with time after injection than with bST doses. Neither coagulation time, standard curd firmness, nor soft or pressed cheese yields were affected by the treatments.

Animals↗
PubMed1992

The use of exit interviews in health service facilities.

Exit Interviews, also known as termination or separation interviews, are conducted in some hospitals and other health service agencies as a routine procedure when staff are ending their period of employment. The major purpose of these interviews is to elicit data regarding the employee's working experience in the organization and hence identify those factors that enhance retention of staff, for example, job satisfaction, study opportunity, challenging milieu, and those that are contributory factors to the decision to resign, such as, dissatisfaction due to poor standards of care becoming the norm and lack of autonomy in planning and implementing nursing care. As a recent study indicated, the hierarchical level of the Exit Interviewer could have a significant effect on the amount and accuracy of the data so obtained. While applicable to all departments of a facility, comments herein are largely concerned with nursing and are based on a thesis by the author.

Humans↗
PubMed1992

Sequential treatment with low dose almitrine bismesylate in hypoxaemic chronic obstructive airways disease.

Daily dose schedules of 100-200 mg of almitrine bismesylate improve arterial blood gases in patients with hypoxaemic chronic obstructive airways disease (COPD) but dose related side effects are evident. In the present study, daily doses approximately half of those previously used were employed in a randomised double blind manner in 85 patients (age 35-79 years) with hypoxaemic COPD. After a one month period to check stability of arterial blood gases, patients were allocated to almitrine (A) or placebo (P) using an unequal code (60% A, 40% P). Tablets, 50-100 mg daily were stopped for one month after 3, 6 and 9 months to counteract drug accumulation. 50 patients in group A and 35 in group P were comparable on entry; mean age 65 (SD = 8) yrs., Pao2 7.8 (0.7) kPa (58.3 (5.0) mmHg), PaCO2 5.8 (0.8) kPa (43.2 (6.0) mmHg), forced expiratory volume in one second--FEV1 0.89 (0.25) l and 6 minute walking distance 296 (97) metres. The improvement in baseline PaO2 values was the same 0.8-1.3 kPa (6-9.8 mmHg) as with previous higher dose therapy. Approximately one third of patients did not respond, defined as PaO2 elevation > 0.67 kPa (5 mmHg). The sequential dosing scheme stabilised blood levels of almitrine within the therapeutic range of 280-300 ng.ml-1. After withdrawal of therapy arterial blood gases and spirometry reverted to pre-treatment levels, suggesting no permanent reversal of pathophysiology. Dose related side effects of breathlessness, indigestion and peripheral neuropathy were not observed. Nerve conduction studies revealed no difference in peripheral nerve dysfunction in hypoxaemic COPD between active and placebo therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Comparison of radionuclide estimation of glomerular filtration rate using technetium 99m diethylenetriaminepentaacetic acid and chromium 51 ethylenediaminetetraacetic acid.

Simultaneous measurements of the clearance rates of technetium 99m diethylenetriaminepentaacetic acid (99mTc-DTPA) and chronium 51 ethylenediaminetetraacetic acid (51Cr-EDTA) were performed in 30 patients with a range of renal function (glomerular filtration rates between 9 and 120 ml/min). Using multiple blood samples, the two clearance values correlated well (r = 0.991, standard error 3.9 ml/min), but DTPA clearance was systematically higher by 7.6%. For each radiopharmaceutical, an equation was derived to correct clearance values obtained using only plasma samples taken at 2 and 4 h for the systematic error inherent in this technique compared with analysis of the complete plasma concentration-time curve. The root mean square error remaining after application of these equations was 1.9 ml/min for both the EDTA and DTPA data. The corresponding errors obtained using the equation derived by Brochner-Mortensen for EDTA plasma clearance were 2.2 ml/min and 1.9 ml/min, respectively, these values were not significantly different from those obtained using the equations derived in this study.

Adult↗
PubMed1991

Screening for undescended testes.

There is a general consensus among surgeons and paediatricians that cryptorchidism should be detected and treated by the age of 5 years, if not earlier. In reality, incomplete descent is often detected well beyond the age of 5. The effectiveness of local screening was assessed by reviewing the screening history and subsequent management of boys treated for undescended testes between 1983 and 1986. The detection rates for undescended testes in the boys under 5 years were low both for doctors and health visitors. In contrast, the school entry medical examination for 5 and 6 year olds had a higher screening yield. Over 40% of cases came to light as a result of parents recognising the condition and seeking medical opinion. Late detection had also occurred in some boys who had had previous genital surgery or examination. Methods to improve early detection and ways of monitoring proposed changes are discussed.

Age Factors↗
PubMed1990

Chromosomal translocation t(1;19) results in synthesis of a homeobox fusion mRNA that codes for a potential chimeric transcription factor.

The gene (E2A) for enhancer binding transcription factors E12 and E47 maps to the t(1;19) chromosomal translocation breakpoint in pre-B cell leukemias. Altered E2A transcripts lacking sequences coding for the helix-loop-helix DNA binding motif were detected in several t(1;19)-carrying cell lines. Fusion cDNAs that crossed the t(1;19) breakpoint were cloned and shown to code for an 85 kd protein consisting of the amino-terminal two-thirds of E2A fused to a chromosome 1-derived protein. The fusion protein has the features of a chimeric transcription factor in which the DNA binding domain of E2A is replaced by the putative DNA binding domain of a homeoprotein from chromosome 1 for which the name Prl (pre-B cell leukemia) is proposed. Identical E2A-prl mRNA junctions were detected by PCR in three t(1;19)-carrying cell lines, indicating that the fusion transcripts and predicted chimeric protein are a consistent feature of this translocation.

Amino Acid Sequence↗
PubMed1990

The effects of excitotoxic lesions of the basal forebrain on the acquisition, retention and serial reversal of visual discriminations in marmosets.

The effects of N-methyl-D-aspartate-induced lesions of the basal forebrain (which included the cholinergic cells of the nucleus basalis of Meynert) were studied on three aspects of visual discrimination; learning, retention and reversal performance, in the marmoset. Neurobiological investigations revealed that the lesion produced large reductions in choline acetyltransferase activity within anterior regions of cortex, particularly prefrontal. In Experiment 1 lesioned animals showed impaired retention, one week after surgery, of a visual discrimination learned immediately prior to surgery and subsequently showed impaired performance over a series of reversals. The reversal deficit could be characterized as a tendency to perseverate on the previously correct stimulus on the first reversal and as a failure to show serial reversal learning on subsequent reversals. Acquisition of a novel discrimination was not impaired five weeks after surgery. As time of testing may have been a confounding factor, in Experiment 2 the effects of the same lesion on new learning were examined immediately following surgery and the effects on retention a month later. The lesion was found to disrupt new learning but did not affect retention. From the two experiments it is clear that, whereas disruption of retention and new learning was relatively transient, the impairments in reversal performance were more long lasting. In addition, lesioned animals exhibited behavioural hyperactivity and elevations in consummatory and schedule-controlled licking. The disinhibitory and preservative effects observed following lesions of the basal forebrain in this study are similar to those following lesions of the orbitofrontal cortex while the disruption of serial reversal learning is commonly seen following damage to the amygdala. Therefore, these results are consistent with the hypothesis that the range of behavioural effects of the lesion result from damage to the cholinergic afferents to orbitofrontal cortex and to the amygdala, two structures intimately connected to one another.

Animals↗
PubMed1990

Effect of food and activity on the reproducibility of isotopic GFR estimation.

The reproducibility of the plasma clearance of 99Tcm DTPA was studied in 26 patients under standardized conditions with the subject fasting and at rest. The coefficient of variation of duplicate measurements in patients with glomerular filtration rates (GRF's) ranging from 11-103 ml min-1 was 8%. Mean GFR following a breakfast containing 670 kcal and 31 g protein was increased significantly from 40.7 +/- 28.1 ml min-1 to 43.6 +/- 30.8 ml min-1. When fasted but permitted free exercise there was no consistent trend in GFR but the coefficient of variation of duplicate estimates increased significantly to 12.1%. It is recommended that routine GFR measurement should be carried out fasting or following a light diet with restricted activity.

Food↗
PubMed1990

Effect of a practical neck cooling device on core temperature during exercise.

Previous studies have documented the effectiveness of combined head and neck cooling in reducing thermal stress during exercise. However, these studies investigated low intensity exercise and devices that are not practical for use on a widespread basis during recreational exercise. In the present study, we investigated the effect of a commercially available, practical neck cooling device on core temperature during strenuous exercise. In a randomized cross-over fashion, 10 male endurance athletes (age 29 +/- 2 yr) performed a 45-min submaximal run (Borg rating of perceived exertion approximately 15) at a constant speed, with and without neck cooling. Runs were conducted on an indoor track, where the ambient temperature was maintained at approximately 21 degrees C dry bulb and approximately 17 degrees C wet bulb. Exercise heart rates and subjective perception of effort were not significantly modified by neck cooling. In contrast, rectal temperature rises (by 0.21 degrees C or 9.5%, P less than 0.02) and sweat rates (by 92 ml.h-1 or 6.4%, P less than 0.02) were reduced by neck cooling. Our study therefore concludes that this practical neck cooling device is capable of inducing reductions in thermal stress during strenuous exercise that, although numerically small, are in a direction of potential benefit.

Adult↗
PubMed1989

Comparative effects of ibotenic acid- and quisqualic acid-induced lesions of the substantia innominata on attentional function in the rat: further implications for the role of the cholinergic neurons of the nucleus basalis in cognitive processes.

Two experiments examined the effects of excitotoxic lesions of the substantia innominata on cholinergic activity in the neocortex and on performance in a paradigm measuring selective attention in the rat. In Expt. 1, ibotenate-induced lesions produced approximately 30% reductions in cortical choline acetyltransferase (ChAT) activity, and damage to wide regions of the substantia innominata and ventral pallidum. The rats were impaired in their ability to localize brief visual targets in a serial reaction time task, as measured by reduced choice accuracy. This impairment was particularly evident at short stimulus durations, but the lesioned rats did not exhibit evidence of primary visual sensory dysfunction and exhibited only minor deficits when the stimuli were presented unpredictably. The deficit was exacerbated when distracting white noise was interpolated into the task. The rats with lesions were also slower to respond correctly, probably resulting partly from the adoption of a speed/error trade-off strategy, and were slower to collect earned food pellets, although they made no more errors of omission than controls. In Expt. 2, quisqualate-induced lesions produced fewer signs of non-specific damage and 50% reductions in cortical ChAT activity. This lesion produced generally qualitatively similar, but weaker effects to those of ibotenate-induced lesions. It was notable that many of the deficits following either ibotenate- or quisqualate-induced lesions lasted for several months after surgery. The results are discussed in terms of the cholinergic hypothesis of cognitive dysfunction. It is argued that lesions of the substantia innominata, including the magnocellular cholinergic neurons of the nucleus basalis of Meynert, produce deficits in attentional processing, which may not result from damage specifically to cholinergic cells. However, the longevity of the effects makes these preparations suitable for further exploration of the restorative effects of cholinergic treatments.

Animals↗