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Biomedical subjects

J Wilkinson

Publications and source records attributed to J Wilkinson.

At least 163 records · Page 9Linked to original sources
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↗
PubMed1989

A conserved tripeptide sorts proteins to peroxisomes.

The firefly luciferase protein contains a peroxisomal targeting signal at its extreme COOH terminus (Gould et al., 1987). Site-directed mutagenesis of the luciferase gene reveals that this peroxisomal targeting signal consists of the COOH-terminal three amino acids of the protein, serine-lysine-leucine. When this tripeptide is appended to the COOH terminus of a cytosolic protein (chloramphenicol acetyltransferase), it is sufficient to direct the fusion protein into peroxisomes. Additional mutagenesis experiments reveal that only a limited number of conservative changes can be made in this tripeptide targeting signal without abolishing its activity. These results indicate that peroxisomal protein import, unlike other types of transmembrane translocation, is dependent upon a conserved amino acid sequence.

Amino Acid Sequence↗
PubMed1988

European multicenter study of the TRUE Test.

A new, standardized, ready-to-apply patch test, the TRUE Test, has been evaluated on 698 consecutive patients with suspected contact dermatitis. The patients were tested with 12 different allergens. Simultaneously, the same 12 allergens in pet. (Trolab) were applied symmetrically to the opposite side of the upper back using the conventional Finn Chamber technique. There were positive test reactions to all 12 allergens tested in the patient group. The concordance of positive reactions between the TRUE Test and the Finn Chamber test was 67%; 13% of all positive reactions were recorded only for the TRUE Test and 20% only for the Finn Chamber method. The frequency of questionable and irritant reactions was of the same low order of magnitude for both test methods; such reactions were recorded in around 2% of all test patches.

Allergens↗
PubMed1987

The indirect flight muscle of Drosophila accumulates a unique myosin alkali light chain isoform.

Mapping of the 5' and 3' ends of the Drosophila myosin alkali light chain (MLC-ALK) mRNA by S1 nuclease and primer extension assays has shown that the primary transcripts are identical irrespective of the time in development that the RNA was prepared. As shown by S1 nuclease experiments these transcripts are alternatively spliced in a tissue-specific fashion generating mRNAs that encode tissue-specific protein isoforms. Antibodies were raised to synthetic peptides identical in sequence to the unique portion of each protein. Western blots of one-dimensional polyacrylamide gels using the type-specific antibodies confirmed and extended the results obtained from the S1 nuclease experiments. The indirect flight muscle is the only tissue in the adult that accumulates the alternatively spliced mRNA. The choice between splicing pathways involves the use of a nonconsensus 3' splice junction in larvae and in the tubular muscles of adults, whereas in the indirect flight muscle of the adult only consensus sequences are utilized. The involvement of a trans-acting factor to activate the nonconsensus splice site in the myotubes of larvae and the tubular myotubes of adults is proposed.

Animals↗
PubMed1987

Direct gene transfer into human cultured cells facilitated by laser micropuncture of the cell membrane.

The selective alteration of the cellular genome by laser microbeam irradiation has been extensively applied in cell biology. We report here the use of the third harmonic (355 nm) of an yttrium-aluminum garnet laser to facilitate the direct transfer of the neo gene into cultured human HT1080-6TG cells. The resultant transformants were selected in medium containing an aminoglycoside antibiotic, G418. Integration of the neo gene into individual human chromosomes and expression of the gene were demonstrated by Southern blot analyses, microcell-mediated chromosome transfer, and chromosome analyses. The stability of the integrated neo gene in the transformants was shown by a comparative growth assay in selective and nonselective media. Transformation and incorporation of the neo gene into the host genome occurred at a frequency of 8 X 10(-4)-3 X 10(-3). This method appears to be 100-fold more efficient than the standard calcium phosphate-mediated method of DNA transfer.

Animals↗