Biomedical subjects
Publications and source records attributed to J Dyer.
A former amateur diver presented with a progressive paraparesis. Thirteen years previously he had developed acute spinal cord dysfunction immediately after dry hyperbaric exposure. He had completely recovered motor function in the intervening period. No alternative reason for the later decline emerged from detailed investigation.
Children with cystic fibrosis need support to benefit from a normal education. Liaison between the specialist nurse and school staff--teachers and nurses--can enable the school to provide this support.
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We have investigated the mechanisms of regulation of the Na+/glucose co-transporter (SGLT1) in a ruminant animal, which is an exceptional model system for studying intestinal glucose transport. Pre-ruminant lambs absorb glucose, produced by hydrolysis of the milk sugar lactose, in the intestine via apical SGLT1 and basolateral facilitative glucose transporters (GLUT2). Weaning coincides with the development of the rumen, and consequently the amount of hexoses reaching the small intestine of the ruminant sheep is undetectable. During development, SGLT1 activity and abundance in intestinal brush-border membranes decreased by over 200-fold, and either maintaining lambs on a milk replacer diet or infusing sheep intestine with D-glucose restored co-transporter activity and expression. We have measured ovine intestinal SGLT1 mRNA levels during development, with changes in diet and after direct infusion of D-glucose or methyl alpha-D-glucopyranoside into the intestinal lumen, in order to determine the level of regulation. During development, mRNA levels decreased only 4-fold. Lambs maintained on a milk replacer diet showed no change in mRNA levels relative to age-matched controls. Finally, upon infusion of the intestine of the ruminant sheep with sugars, D-glucose infusion increased SGLT1 mRNA, but only by 2-fold, compared with a 60-90-fold increase in co-transporter number and activity. Since the change in Na(+)-dependent glucose transport activity is correlated with SGLT1 protein abundance, and since changes in mRNA levels do not account for the dramatic changes in protein abundance, we conclude that the principal level of SGLT1 regulation by luminal sugar is translational or post-translational.
We have shown previously that the activity and abundance of the intestinal Na+/glucose cotransporter (SGLT1) declines dramatically during the postnatal development of lambs, and that it can be restored in the intestine of ruminant sheep by intra-luminal infusion of D-glucose. The work presented in this paper has followed the expression of the SGLT1 gene along the vertical and horizontal axes of the ovine small intestine during early development, using quantitative in situ hybridisation histochemistry. Along the vertical axis, SGLT1 mRNA was first detectable just below the crypt-villus junction and rose rapidly to a peak level approx. 150 microns above this point. After reaching a maximum, the amount of message gradually declined towards the villus tip. This pattern of mRNA accumulation along the crypt-villus axis was similar in all intestinal positions and age groups. Along the length of the small intestine (horizontal axis), a decline in the level of SGLT1 mRNA was observed first in the distal intestine. This decrease in SGLT1 mRNA was significant in the intestine (75% of length) of 5-week-old lambs when compared to tissue taken from 25 and 50% of length (P < 0.01 and P < 0.02, respectively). However, the observed fall in the expression of this gene during weaning did not coincide with the fall in activity and amount of SGLT1. In adult animals, where the activity of SGLT1 is very low, the amount of message was greatly reduced. This work supports the finding that the expression of SGLT1 is primarily controlled at the post-transcriptional level during the postnatal development of ovine intestine.
Planning and quality control procedures are described for a randomised trial designed to measure the effect on normal tissue toxicity of reducing the volume of normal tissue irradiated through the introduction of Beams-Eye-View designed customised blocks. Consideration is given to the accuracy with which blocks can be designed and to the potential application of multi-leaf collimator technology.
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A lead worker developed bilateral wrist drop. At first this seemed to be a lead neuropathy but all his screening tests for blood and urine toxicity had been within the accepted safety limit during employment. Detailed investigation showed that he had plumboporphyria (ALAD deficiency) which had been symptom free until he was exposed to lead. Details of his porphyrin metabolism are presented.
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In this paper we describe software facilities for enabling patient positioning studies using the megavoltage imaging system developed at the Royal Marsden Hospital and Institute of Cancer Research. The study focuses on the use of the system for three purposes: patient position verification (by comparing images taken at treatment simulation with megavoltage images taken at treatment time); reproducibility studies (by analysing a set of megavoltage images); and set-up correction (by adjusting the set-up until the megavoltage image obtained at treatment registers with the simulation image). The need is discussed for suitably presented simulator images, a method of determining field boundaries and the possibility of delineating soft-tissue interfaces. Several algorithms of different types, developed specifically for the purpose of intercomparison of planar projection images, are presented. The techniques employed and their usefulness, in both the qualitative and the quantitative sense, are discussed. The results are presented of a phantom and clinical study, to evaluate the rigour and reproducibility of the algorithms. These results indicate that measurements can be made to an accuracy of about 1-2 mm, with a similar value for interobserver reproducibility for the best image comparison techniques available.
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Glucose/galactose malabsorption (GGM) is an autosomal recessive disease manifesting within the first weeks of life and characterized by a selective failure to absorb dietary glucose and galactose from the intestine. The consequent severe diarrhoea and dehydration are usually fatal unless these sugars are eliminated from the diet. Intestinal biopsies of GGM patients have revealed a specific defect in Na(+)-dependent absorption of glucose in the brush border. Normal glucose absorption is mediated by the Na+/glucose cotransporter in the brush border membrane of the intestinal epithelium. Cellular influx is driven by the transmembrane Na+ electrochemical potential gradient; thereafter the sugar moves to the blood across the basolateral membrane via the facilitated glucose carrier. We have previously cloned and sequenced a Na+/glucose cotransporter from normal human ileum and shown that this gene, SGLT1, resides on the distal q arm of chromosome 22. We have now amplified SGLT1 complementary DNA and genomic DNA from members of a family affected with GGM by the polymerase chain reaction. Sequence analysis of the amplified products has revealed a single missense mutation in SGLT1 which cosegregates with the GGM phenotype and results in a complete loss of Na(+)-dependent glucose transport in Xenopus oocytes injected with this complementary RNA.
We performed a longitudinal study of chronic schizophrenic patients who were hospitalized for research purposes at the National Institute of Mental Health (NIMH) Intramural Program in the 1970s and early 1980s. We assessed present course, outcome and predictor data from the initial cohort of 58 young chronic schizophrenic patients who were followed up for 2 to 12 years following their NIMH index hospitalization. At follow-up, the sample showed substantial functional impairment and levels of symptoms with only about 20% of the sample demonstrating a good outcome. In addition, strong intercorrelation was noted among the symptom and functioning indexes at follow-up. Moreover, neuropsychologic tests of frontal cortical functioning were significantly correlated with outcome levels of negative symptoms and social functioning but not with levels of positive symptoms. During the period from the index hospitalization to the follow-up assessment, 78% of the sample suffered a relapse, 38% attempted suicide and 24% had episodes of major affective illness. Furthermore, levels of positive and negative symptoms ascertained when patients received optimal neuroleptic treatment during the index hospitalization significantly predicted outcome levels of symptoms and functioning and time spent hospitalized during the follow-up period. In contrast, levels of index positive and negative symptoms ascertained during the drug-free state did not predict outcome symptoms or functioning. These data suggest that treatment response is a critical predictor variable. We examined the implication of these data for the course of illness in schizophrenics.
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