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Biomedical subjects

J Dyer

Publications and source records attributed to J Dyer.

At least 19 recordsLinked to original sources
PubMed1992

Image comparison techniques for use with megavoltage imaging systems.

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.

Algorithms↗
PubMed1991

Glucose/galactose malabsorption caused by a defect in the Na+/glucose cotransporter.

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.

Antisense Elements (Genetics)↗
PubMed1991

National Institute of Mental Health longitudinal study of chronic schizophrenia. Prognosis and predictors of outcome.

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.

Adult↗
PubMed1990

Glycyl-L-proline transport in rabbit enterocyte basolateral-membrane vesicles.

The properties of a peptide-transport system in rabbit enterocyte basolateral membrane were examined with glycyl-L-proline as the substrate. Basolateral-membrane vesicles prepared from rabbit proximal intestine were characterized in terms of both purity and orientation. Marker-enzyme assays show that the basolateral-membrane marker, ouabain-sensitive K(+)-activated phosphatase, is enriched 17-fold with respect to the initial homogenate. The activities of enzymes used as markers for other membranes and organelles are low, and contamination of the final membrane fraction with these is minimal. The use of immunoblotting techniques further confirms the absence of brush-border-membrane contamination. Proteins in the basolateral-membrane vesicle preparation gave no cross-reaction with antibodies against the 140 kDa antigen and the Na+/glucose-symport protein, markers specific to the brush-border membrane of the enterocyte. Conversely, antibodies raised against the classical basolateral-membrane marker, the RLA class I histocompatibility complex, reacted strongly with a 43 kDa basolateral-membrane protein. The orientation of the basolateral-membrane vesicles was shown to be predominantly inside-out on determination by two independent criteria. The uptake of [1-14C]glycyl-L-proline by these vesicles is stimulated by the presence of an inwardly directed pH gradient, and this stimulation can be abolished by the proton ionophores carbonyl cyanide p-trichloromethoxyphenylhydrazone (CCCP) and tetrachlorotrifluoromethylbenzimidazole (TTFB). Transport is also inhibited by HgCl2, thimerosal, Na+ and other glycyl dipeptides.

Amino Acids↗
PubMed1990

Preparation and properties of brush-border membrane vesicles from human small intestine.

This study describes a simple and rapid method for the preparation of brush-border membrane vesicles from intestinal biopsies. The specific activities of sucrase, amino peptidase N, and alkaline phosphatase in these vesicles were the same as those in vesicles prepared from intestinal segments. The vesicles from all the regions of the small intestine can transport D-glucose in an Na+-dependent manner. The rates of transport of D-glucose presented here are far higher than previously reported. The method should have a wide applicability to studies of transport mechanisms and the distribution of transport processes within the intestine.

Adult↗
PubMed1989

Changes in the functions of the intestinal brush border membrane during the development of the ruminant habit in lambs.

1. Brush border membrane vesicles were prepared from lamb enterocytes. These were used to study the changes in the enzyme contents and the transport capacities which occur during the change from a milk to a roughage diet. 2. Na+-dependent transport of D-glucose was present in all regions of the small intestine of pre-ruminant lambs and absent in ruminants. 3. Na+-dependent transport of L-proline was present in all regions of the small intestine irrespective of the age of the animal. 4. Phosphate transport was seen only in the presence of a transmembrane pH gradient (acid outside). The transport was not stimulated by either Na+ or K+. The transport capacity increases 2-fold as the animal becomes ruminant. 5. The activities of lactase and maltase diminished with age. Alkaline phosphatase and aminopeptidase N activities remain constant. Sucrase activity cannot be detected in lambs of any age.

Alkaline Phosphatase↗
PubMed1987

IgE-immunotoxins. I. IgE-intact ricin.

An IgE immunotoxin consisting of rat IgE myeloma protein, IR 162, conjugated via the heterobifunctional linking agent N-succinimidyl-3-(2-pyridyldithio)propionate to intact ricin was synthesized and evaluated. The capacity of this IgE-immunotoxin to bind to rat basophilic leukemia cells (RBL cells) and to inhibit RBL cell incorporation of [3H]leucine was assessed. The IgE-intact ricin conjugate sensitized RBL cells for histamine release after treatment with anti-IgE with a time-course of sensitization and dose-response equivalent to native IgE. Intact ricin and IgE-intact ricin were both cytotoxic to RBL cells as assessed by [3H]leucine incorporation. Lactose (50 mM) competed with intact ricin binding and toxicity such that more than 100 ng/ml ricin (8 times its IC50 in the absence of lactose) was required for ricin to kill RBL cells in the presence of lactose. Lactose (50 mM) was not able to fully inhibit 1-100 ng/ml IgE-ricin immunotoxin killing of RBL cells. Saturation of RBL cell IgE receptors by preincubation with IgE totally inhibited IgE-intact ricin-induced toxicity, in the presence of lactose, indicating that toxicity required IgE Fc receptor binding.

Animals↗