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Biomedical subjects

B Scott

Publications and source records attributed to B Scott.

At least 109 records · Page 6Linked to original sources
PubMed1990

Early deletion and late positive selection of T cells expressing a male-specific receptor in T-cell receptor transgenic mice.

The ontogeny of T cells in T-cell receptor (TCR) transgenic mice, which express a transgenic alpha beta heterodimer, specific for the male (H-Y) antigen in association with H-2Db, was determined. The transgenic alpha chain was expressed on about 10% of the fetal thymocytes on day 14 of gestation. About 50% of day-15 fetal thymocytes expressed both alpha and beta transchains and virtually all fetal thymocytes expressed the transgenic alpha beta heterodimer by day 17. The early expression of the transgenic TCR on CD4-8- thymocytes prevented the development of gamma delta cells, and led to accelerated growth of thymocytes and an earlier expression of CD4 and CD8 molecules. Up to day 17, no significant differences in T-cell development could be detected between female and male thymuses. By day 18 of gestation, the male transgenic thymus contained more CD4-8- thymocytes than the female transgenic thymus. The preponderance of CD4-8- thymocytes in the male transgenic thymus increased until birth and was a consequence of the deletion of the CD4+8+ thymocytes and their CD4-8+ precursors. By the time of birth, the male transgenic thymus contained half the number of cells as the female transgenic thymus. The deletion of autospecific precursor cells in the male transgenic mouse began only at day 18 of gestation, despite the fact that the ligand could already be detected by day 16. The preferential accumulation of CD4-8+ T cells, which expressed a high density of the transgenic TCR, occurred only after birth and was obvious in 6-week-old female thymus. These data support the hypothesis that the positive selection of T cells expressing this transgenic heterodimer may involve two steps, i.e., the commitment of CD4+8+ thymocytes to the CD4-8+ lineage following the interaction of the transgenic TCR with restricting major histocompatibility molecules, followed by a slow conversion of CD4+8+ thymocytes into CD4-8+ T cells. In normal mice, the precursors of CD4+8+ and single positive thymocytes have the CD4-8- CD3-J11d+ (or M1/69+) phenotype. Because of the early expression of the transgenic alpha beta heterodimer, this population was not detected in adult transgenic mice. All CD4-8- M1/69+ cells expressed the transgenic receptor associated with CD3 and could be readily grown in media containing T-cell lectins and interleukin 2.

Animals↗
PubMed1990

Predictors of tinnitus discomfort, adaptation and subjective loudness.

In a nation-wide investigation, covering all the hearing centres in Sweden, a study was made of adaptation processes, subjective discomfort from tinnitus, subjective loudness of tinnitus and psychological complaints in 3372 subjects by means of a questionnaire. The most important predictors of discomfort from and adaptation to tinnitus were found to be the controllability and the degree of maskability by external sounds, i.e. the subject's coping abilities or internal-external locus of control. Increased control and masking effects from the environment imply a decrease in discomfort and better adaptation. The most important predictor of worsened subjective loudness of tinnitus was the duration of the tinnitus. That is, subjects who had had tinnitus for a longer time perceived the loudness as more intense. The psychosomatic factors which most strongly predicted increased discomfort from and decreased tolerance to tinnitus were depression and insomnia. These findings have theoretical and practical implications for the management and treatment of tinnitus.

Adaptation, Psychological↗
PubMed1990

Investigation and outcome of 121 infants and children requiring Nissen fundoplication for the management of gastroesophageal reflux.

In a 6.5 year period starting January 1982, 121 patients (74 male, 47 female; 1.6:1) with complicated gastroesophageal reflux referred to Alberta Children's Hospital, University of Calgary, required a Nissen fundoplication at a mean age of 35.5 months (range 3 weeks to 18 years). The median age of onset of symptoms was less than 1 month. Symptoms and indications for surgery included regurgitation (88%), failure to thrive (52%), reflux-associated pulmonary symptoms and aspiration (48%), biopsy evidence of esophagitis (35%) with heartburn (17%), dysphagia (18%), hematemesis (17%), anemia (13%), and hypoproteinemia (22%). Sixty-four percent of the patients had a syndrome or chromosomal abnormality, respiratory disease, or neuromuscular disorder. The barium contrast upper-gastrointestinal radiographic series, performed in all patients, identified structural [gastric outlet obstruction (2%), esophageal stricture (11%), erosive esophagitis (9%)], and functional abnormalities [gastroesophageal reflux (90%), barium aspiration (8%), esophageal hypoperistalsis (30%), delayed gastric emptying (4%)]. Barium contrast upper gastrointestinal radiographic series identified gastroesophageal reflux with a sensitivity of 90% (compared to history), was 50% sensitive and 92% specific for erosive esophagitis (compared to biopsy), was 59% sensitive and 74% specific for esophageal dysmotility (compared to esophageal manometry), and there was a significant (p less than 0.01) association between barium aspiration and prior evidence of aspiration pneumonitis. Esophageal manometry demonstrated a significantly (p less than 0.001) lower esophageal sphincter pressure in patients compared with controls, but no significant correlation with failure to thrive, aspiration pneumonia, biopsy evidence of esophagitis, or parameters of the 24-hour esophageal pH study. Twenty-four hour pH monitoring showed significantly (p less than 0.05) more reflux episodes than in asymptomatic controls and there was significant (p less than 0.05) correlation between the percentage of time pH was less than 4 and the presence of hypoalbuminemia, and biopsy-proven erosive esophagitis or Barrett's esophagus. Endoscopic appearance was 91% sensitive and 60% specific for esophagitis when compared to biopsy. Nissen fundoplication was completely effective at resolving gastroesophageal reflux in 83%, and associated with marked improvement in 15%. No patient died as a result of fundoplication. Major complications included: recurrence of symptoms requiring reoperation (2%), subsequent mechanical bowel obstruction (8%), wound infection or pneumonia (12%).

Adolescent↗
PubMed1989

The generation of mature T cells requires interaction of the alpha beta T-cell receptor with major histocompatibility antigens.

THE T-cell repertoire within an individual is biased to recognize antigen in the context of self major histocompatibility complex (MHC) antigens. This is thought to depend on a process of positive selection during development. Support for this notion has recently been obtained in experiments using transgenic mice bearing genes for T-cell receptors (TCR) of defined specificity: T cells expressing the introduced genes form the main part of the mature T-cell population only in mice that express the appropriate MHC product. We have now extended these observations using TCR transgenic mice homozygous for the severe combined immunodeficiency (SCID) mutation which are defective in the rearrangement of both TCR and immunoglobulin genes. In this case mature thymocytes develop only in transgenic mice that express the MHC product which restricts the specificity of the transgenic TCR. This shows that the interaction of the alpha beta TCR with thymic MHC antigen is essential for the development of mature T cells. Furthermore, the peripheral lymph nodes of such mice are underdeveloped, suggesting that the peripheral expansion of mature T cells may require interactions with other lymphocytes expressing a range of receptors.

Animals↗
PubMed1989

Deletion of autospecific T cells in T cell receptor (TCR) transgenic mice spares cells with normal TCR levels and low levels of CD8 molecules.

Transgenic mice that carry on a large fraction of their T cells an alpha/beta T cell receptor that recognizes the male antigen in the context of H-2Db molecules were constructed. An mAb specific for the transgenic receptor was developed and used to analyze T cell subsets in male transgenic H-2b mice. The vast majority of immature CD4+8+ T cells that express the transgenic TCR were deleted in the male transgenic mouse. Nevertheless, the majority of T cells spared by this deletion process expressed a high level of the transgenic TCR. These T cells, however, had an abnormal CD4/CD8 phenotype in that they expressed either no CD8 molecules or only low levels.

Animals↗
PubMed1989

Dietary fat influences electric membrane properties of neurons in cell culture.

1. SJL/J mice were maintained on semipurified diets which differed in the ratio of polyunsaturated/saturated fatty acid content (P/S). Exposure was from conception and was maintained for periods ranging from 6 to 34 weeks. 2. Neural cell cultures were prepared from dorsal root ganglia (DRG). After 6 and 20 days of culture, neuronal electric membrane properties were determined quantitatively by intracellular recording. 3. A number of significant differences were observed for the two dietary conditions. DRG from mice on the low-P/s diet had an increase in the rate of fall of both phases of repolarization which, in conjunction with the reduced action potential overshoot, led to a reduced action potential duration. This shift to shorter-duration action potentials was accompanied by a shift to more monophasic falling phases. The low-P/S neurons also exhibited a decreased afterhyperpolarization, decreased specific membrane resistance, and decreased membrane electrical time constant compared to high-P/S neurons. 4. It was concluded that the P/S ratio in the diet can have a significant effect on the electric properties of neurons. The high-P/S neurons tended to have action potentials with biphasic repolarizations and longer durations. In contrast, the low-P/S neurons tended to have action potentials with monophasic repolarizations and shorter durations. Moreover, the known ionic dependence of these two types of action potentials suggested that the low-P/S diet resulted in action potentials with a more exclusive Na dependence, while the high-P/S diet resulted in action potentials with both Na and Ca dependence.

Action Potentials↗
PubMed1989

The psychological treatment of tinnitus: an experimental evaluation.

Disabling tinnitus in 27 patients was treated in an experimental setting with two different type of therapy aiming at the development of coping behaviour. One was focused on behavioural control procedures, while the other aimed at more cognitive control methods such as distraction. The results of the two forms of therapy were compared with each other and with observations of the untreated control subjects. Assessments of subjective loudness, discomfort from tinnitus and controllability were made on analogue scales and at a questionnaire follow-up. Psychoacoustic measures such as personal loudness units (PLU) were used in connection with these self-recordings and for evaluation of treatment effects. The results confirmed favourable reports on behavioural methods in tinnitus. However, no differences were found between therapies. The results are discussed in the light of the coping and adaptation theory.

Adult↗
PubMed1989

Gastroenterology services: a regional review of changes over a five year period (1981-86).

A survey of all gastroenterologists in the Trent region showed that the number of upper GI endoscopies had doubled to 7.6 per 1000 of the population from 1981 to 1986, equalling the number of barium meals. Colonoscopies had increased from 0.39 to 0.94 per 1000 of the population. There had been a large increase in the proportion of endoscopies done by surgeons. There were 0.37 ERCP examinations per 1000 of the population done in six of the 12 districts, and 0.17 variceal sclerotherapy procedures per 1000 of the population done in five districts. There was widespread dissatisfaction with the provision of facilities and staff for endoscopy. From 1981 to 1986 the number of consultants with an interest in gastroenterology had increased from 20 to 25, but none of these appointments had been anticipated in 1981. All eight senior registrars in gastroenterology in 1981 had achieved consultant status - three in the region, four in the NHS outside the region, and one abroad.

Consumer Behavior↗
PubMed1989

T-cell and plasma cell populations in coeliac small intestinal mucosa in relation to dermatitis herpetiformis.

Differential lymphocyte and plasma cell counts and measurements of mucosal architecture were studied in small intestinal biopsies from 17 controls and 17 patients with untreated uncomplicated coeliac disease of whom five also had dermatitis herpetiformis. Intraepithelial T-cell and plasma cell counts and measurements of mucosal architecture were not significantly different in the two coeliac groups but both groups differed from the controls. Lamina propria T-cell counts were significantly higher in the patients who also had dermatitis herpetiformis than in uncomplicated coeliac disease, with a significant increase in the Leu 2 (CD8) positive (cytotoxic/suppressor) T-cell subset. This suggests a specific abnormality of T-cell control of immune responsiveness in the pathogenesis of the skin manifestations of dermatitis herpetiformis which is not found in uncomplicated coeliac disease.

Adolescent↗
PubMed1988

Thymic major histocompatibility complex antigens and the alpha beta T-cell receptor determine the CD4/CD8 phenotype of T cells.

T-cell receptors and T-cell subsets were analysed in T-cell receptor transgenic mice expressing alpha and beta T-cell receptor genes isolated from a male-specific, H-2Db-restricted CD4-8+ T-cell clone. The results indicate that the specific interaction of the T-cell receptor on immature thymocytes with thymic major histocompatibility complex antigens determines the differentiation of CD4+8+ thymocytes into either CD4+8- or CD4-8+ mature T cells.

Animals↗
PubMed1988

Effects of aging on neuronal electrical membrane properties.

The electric membrane properties (EMP) of dorsal root ganglion (DRG) neurons in cell cultures prepared from control mice (8-14 weeks) and old mice (90-92 weeks) were compared. The old neurons had a number of significant alterations in EMP compared to controls including decreased electrical excitability, increased action potential duration and more pronounced biphasicity of the repolarization phase. The old neurons also had larger action potential overshoot and afterhyperpolarization. The pattern of altered electric membrane properties was consistent with an age-induced shift from voltage-sensitive sodium channels to less excitable voltage-sensitive calcium channels and also a decrease in potassium permeability during the repolarizing phase of the action potential.

Aging↗
PubMed1988

Early expression of a T-cell receptor beta-chain transgene suppresses rearrangement of the V gamma 4 gene segment.

beta transgenic mice have a T-cell receptor beta-chain gene that is prematurely expressed on the surface of CD4- CD8- thymocytes and paired with an uncharacterized non-T-cell receptor alpha-chain polypeptide. The rearrangement of the T-cell receptor variable region gamma chain gene segment V gamma 4, a component of the gamma-chain gene that is rearranged and expressed preferentially on thymocytes of normal adult mice, is severely repressed in beta transgenic mice. Consequently no gamma delta T-cell receptor heterodimers are detectable on the surface of adult thymocytes or splenic T cells. These results indicate that cells expressing alpha beta or gamma (V gamma 4)-delta TCRs originate from a common precursor in which the first productive rearrangement of either the beta or gamma locus determines the further differentiation pathway into either alpha beta or gamma delta T cells. The repression of V gamma 4 rearrangement by a preexisting beta-chain gene may be indicative of one of several mechanisms which ensure that gamma delta and alpha beta receptors do not as a rule appear on the surface of the same cell.

Alleles↗
PubMed1988

Behavioural therapy in the clinical management of tinnitus.

Behavioural therapy was given to reduce discomfort and annoyance associated with severe tinnitus in 75 consecutive patients. Treatment was conducted within the routine clinical management. It included information and discussion about tinnitus, behavioural analysis and relaxation training combined with various cognitive strategies. The method of treatment was thus a form of coping technique. Self-recordings showed significant reductions of 'discomfort from tinnitus' as well as significant elevations in 'general mood' over a 3-month follow-up period. Interview findings indicated strong overall positive effects of treatment, as well as other positive side-effects on complaints such as tension headaches, dizziness, muscle tension and sleep disturbances. Implications for the clinical management of tinnitus sufferers are discussed.

Adult↗