PubMed HealthSearch

Biomedical subjects

B Scott

Publications and source records attributed to B Scott.

At least 19 recordsLinked to original sources

Antisense oligonucleotides specific for transforming growth factor beta2 inhibit the growth of malignant mesothelioma both in vitro and in vivo.

Transforming growth factor beta (TGF-beta) is a potent growth-regulatory and immunomodulatory cytokine that exerts a diverse range of effects on many types of cells. High levels of TGF-beta are produced by several human and mouse malignant mesothelioma (MM) cell lines, and it is known to act as a growth factor for these cells. Antisense oligonucleotides (ODNs), targeted against specific TGF-beta mRNA, were used to block TGF-beta production from MM cells in vitro and in vivo. TGF-beta antisense ODNs were encapsulated in liposomes and transfected into MM cells or delivered intratumorally. TGF-beta2 mRNA levels, assessed by semiquantitative PCR, and TGF-beta2 protein secretion were reduced after TGF-beta2 antisense ODN transfection. MM cell proliferation, assessed by tritiated thymidine uptake, was specifically inhibited by both TGF-beta1- and TGF-beta2-specific antisense ODNs. In vivo administration of TGF-beta2 antisense ODNs, delivered locally, reduced tumor growth. These data show that the blockade of TGF-beta2 within this tumor reduces tumor growth and raises the possibility that TGF-beta2 antisense ODNs may be useful as a therapy for this disease.

Animals

The influence of vertigo, hearing impairment and tinnitus on the daily life of Menière patients.

The aim of this questionnaire study was to investigate the impact of the symptoms in Meniere's disease on the daily life of patients and to analyse the relationships between the cardinal symptoms and environmental, emotional and activity factors. The study comprised 514 patients, recruited from two different sources. The results showed that vertigo, hearing impairment and tinnitus had a strong negative influence on the daily life of patients. Seventy-five percent of the subjects avoided certain everyday activities or situations because of the disease. However, the correlation between discomfort and reported satisfaction with life was moderate. Most of the subjects experienced premonitory symptoms of the attacks and 80% reported relations between external factors and vertigo attacks.

Adaptation, Psychological

CD8(+) T cell-mediated spontaneous diabetes in neonatal mice.

Transgenic mice that express the influenza virus hemagglutinin (HA) on pancreatic islet beta cells (ins-HA) demonstrate tolerance of HA even after immunization with influenza virus. Surprisingly, when Ins-HA mice were mated with a transgenic mouse expressing a TCR specific for an epitope of HA that is restricted by MHC class I H-2Kd (Clone-4 TCR), the resulting double transgenic (Ins-HA x Clone-4 TCR)F1 neonates developed spontaneous autoimmune diabetes immediately after birth and died within 10 days. This represents a unique situation in which all safeguards within the immune system that normally maintain tolerance of self-antigens in the neonate are insufficient.

Animals

An evaluation of a behavioural treatment approach to hearing impairment.

Twenty-four elderly hearing impaired Ss participated in an experimental treatment study and received either behavioural group treatment or served as untreated controls. The treatment package included applied relaxation, video self-modelling, exposure, information and various coping skills. Assessments (pre-post) were conducted using a structured video-interview measuring coping behaviour. In order to evoke behavioural compensation small acoustic provocations were included in the interview. The edited videos were then rated blindly by two trained observers. Pre-post assessments also included daily registered hearing problems on visual analogue scales and a questionnaire. Finally, a one month follow-up blind telephone interview was conducted. Results showed significant beneficial effects in favour of the treatment package and support the implementation of a behavioural approach in audiological rehabilitation research.

Activities of Daily Living

Development of a short scale for self-assessment of experiences of hearing loss. The hearing coping assessment.

A short scale for self-assessment of experiences of hearing impairment--the Hearing Coping Assessment (HCA) was developed and administered to 114 consecutive hearing-impaired patients at a Swedish hearing centre. The scale was evaluated in terms of descriptive statistics, reliability, principal components analysis, and validity. The results showed high internal consistency, high split-half correlation, and high item-total correlations. Significant correlations were found between the HCA questionnaire and measures of optimism, depressive syndrome, and audiogram (PTA). The principal component analysis showed two meaningful factors. The first mainly represents disability, and the second emotional reactions due to hearing loss. Aspects of handicap were present in both factors. The subjects in this study were no less optimistic nor did they show more signs of depressive syndrome than comparable norm groups. Still, optimists reported fewer hearing problems as measured by the HCA. The HCA is proposed as a suitable assessment scale in studies on the effects of counselling.

Adaptation, Psychological

A two-year follow-up examination of a behavioural treatment approach to hearing tactics.

Twenty elderly hearing impaired patients participated in a two-year follow-up study on the effects of behavioural treatment aimed at increasing coping with hearing impairment. Subjects who had received treatment were compared with untreated controls using the Hearing Coping Assessment (HCA) and the Communication Strategies Subscale of the Communication Profile for the Hearing Impaired (CPHI-CSS). The group treatment package included applied relaxation, video self-modelling, exposure, information, and the teaching of hearing tactics. Results showed some effects in favour of the treatment on the HCA at post-treatment, but no differences at follow-up. The results on the CPHI-CSS using pre-treatment HCA scores as covariate showed significant multivariate effects on the subscales measuring maladaptive behaviours, non-verbal strategies, and on the CPHI-CSS total score. No significant multivariate effect was found for the verbal strategies subscale. As no pre-treatment data were available, results on the CPHI-CSS should be interpreted with caution. Overall, the results from this study give some support for the implementation of behavioural treatment in audiological rehabilitation.

Adaptation, Psychological

Secretion of thermostable DNA polymerase using a novel baculovirus vector.

Baculovirus-mediated expression has become a powerful tool for the high yield production of functionally active recombinant proteins. In order to further enhance the utility of this expression system, we constructed versatile transfer vectors that facilitate the secretion of recombinant proteins from host insect cells by inserting functional secretory leader sequences down-stream of the polyhedrin promoter. In-frame insertion of cDNA sequences results in the synthesis of fusion proteins containing a heterologous signal sequence which directs the recombinant protein to the secretory pathway. Human and insect leader sequences were successfully tested with a number of proteins including the thermostable Pyrococcus furiousus (Pfu) DNA polymerase in an effort to maximize secretion of heterologous proteins from insect cells. The human placental alkaline phosphatase signal sequence (MLGPCMLLLLLLLGLRLQLSLG) proved to be optimal for the secretion of not only this thermostable bacterial enzyme but also for the secretion of other biologically active polypeptides.

Amino Acid Sequence

2,3,7,8-Tetrachlorodibenzo-p-dioxin reduces the number, size, and organelle content of Leydig cells in adult rat testes.

Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters testicular steroidogenesis and reduces total Leydig cell volume in the testis. However, its effect on Leydig cell number, size, and organelle content had not been determined in adult rats. Adult male rats received a single intraperitoneal injection of TCDD at a dose of 0, 12.5, 25.0, or 50.0 micrograms/kg body weight. Testicular tissues were obtained from rats 4 weeks after treatment. Testes were vascularly perfused with glutaraldehyde, embedded in Epon 812, sectioned at 0.5 micron, stained with toluidine blue, and evaluated by stereology for number and size of Leydig cells. Specimens from control and high dose groups were prepared for electron microscopy to quantify Leydig cell organelle content. TCDD treatment reduced (P < 0.01) body weight in a dose-dependent fashion. Testicular weight was not significantly reduced by TCDD treatment. The volume of Leydig cell cytoplasm per testis was reduced (P < 0.01) four weeks after treatment. Reduction in total Leydig cell volume resulted from a reduced (P < 0.05) number of Leydig cells and a reduced (P < 0.01) size of individual Leydig cells. However, the volume density (percentage) of Leydig cells occupied by specific organelles was not influenced by TCDD treatment. As a result of reduced total Leydig cell volume with no change in volume density of organelles in Leydig cells, the volumes per testis of smooth endoplasmic reticulum and mitochondria were reduced (P < 0.01) by TCDD treatment. In conclusion, the TCDD-induced reduction in Leydig cell volume per testis is explained by reduced number and size of individual Leydig cells and resulted in a significant reduction in total volume of both Leydig cell smooth endoplasmic reticulum and mitochondria per testis. Reduction in content of organelles that are responsible for various key steps in steroidogenesis, could explain TCDD-reduced production of testosterone in rats.

Animals

Early identification and isolation of inpatients at high risk for tuberculosis.

BACKGROUND: Although it has been recommended that all patients suspected of having tuberculosis be placed in isolation, the feasibility of this recommendation has not been investigated. METHODS: Forty-three patients with pulmonary tuberculosis were compared with 43 control subjects. The control subjects had submitted expectorated sputum, and were culture negative. Variables included chest roentgenogram results, and risk factors used by the Centers for Disease Control and Prevention (Atlanta, Ga) to identify patients at increased risk for tuberculosis. RESULTS: Potential control subjects outnumbered patients by 92:1. Although a positive tuberculin skin test, foreign birth, and weight loss were more common in the patients, 86% of the control subjects had at least one risk factor for tuberculosis. Chest roentgenograms consistent with tuberculosis (cavities or apical or nodular infiltrates) were found in 86% of the patients, but in only 16% of the control subjects (odds ratio, 31.7; 95% confidence interval, 8.6 to 127.7). The positive and negative predictive values of a consistent chest roentgenogram were 6% and 99.8%, respectively. The sensitivity of testing a single sputum specimen was 81%, yet almost half of the control subjects had only one specimen submitted. Of the inpatient cases, 58% were not identified on admission with a median delay of 13 days before isolation. CONCLUSIONS: Isolating all the patients at the time sputum is submitted for testing is not practical and would have resulted in a 92-fold overuse of isolation rooms. The chest roentgenogram was of great value in identifying patients who did not require isolation and was the best available means of identifying inpatients at high risk for active pulmonary tuberculosis.

Adult

On the various manifestations of spontaneous autoimmune diabetes in rodent models.

Autoimmune (type 1) diabetes mellitus in mouse, rat, and humans shares several features, including T lymphocyte infiltration into pancreatic islets and a dependence on permissive class II major histocompatibility complex (MHC) alleles. We report here on an experimental model involving mice that express influenza hemagglutinin (HA) under the control of the insulin promoter and, at the same time, a transgenic class II MHC-restricted T cell receptor (TcR) specific for an HA peptide. These mice spontaneously develop islet infiltrates resembling those found in NOD mice and most animals become diabetic within 8 weeks of age. Because of the availability of a clonotypic TcR antibody, we can be confident that the Ins-HA transgene does not induce any measurable alterations in the vast majority of T cells with the transgenic TcR in primary and secondary lymphoid organs. Continuous export of large numbers of HA-specific lymphocytes from the thymus was not required for the manifestation of the disease since mice thymectomized at 3 days after birth still developed the disease albeit with smaller infiltrates.

Animals

Integrative transformation of the mycotoxin-producing fungus, Penicillium paxilli.

A high frequency transformation system has been developed for Penicillium paxilli using pAN7-1. Up to 44% of the primary transformants were heterokaryons. Loss of hygromycin resistance was observed in primary transformants that were sub-cultured on non-selective media, but single spores of these primary transformants were mitotically stable on both selective and non-selective media. A molecular analysis of the transformants generated showed that 78% had single-site integrations, with half of these containing a single copy of pAN7-1. CHEF-gel electrophoresis showed that P. paxilli has at least six chromosomes with a total genome size of about 23.4 Mb.

Chromosomes, Fungal

A role for non-MHC genetic polymorphism in susceptibility to spontaneous autoimmunity.

Peripheral immunological tolerance is traditionally explained by mechanisms for deletion or inactivation of autoreactive T cell clones. Using an autoimmune disease model combining transgenic mice expressing a well-defined antigen, influenza hemagglutinin (HA), on islet beta cells (Ins-HA), and a T cell receptor transgene (TCR-HNT) specific for a class II-restricted HA peptide, we demonstrate that the conventional assumptions do not apply to this in vivo situation. Double transgenic mice displayed either resistance or susceptibility to spontaneous autoimmune disease, depending on genetic contributions from either of two common inbred mouse strains, BALB/c or B10.D2. Functional studies on autoreactive CD4+ T cells from resistant mice showed that, contrary to expectations, neither clonal anergy, clonal deletion, nor receptor desensitization was induced; rather, there was a non-MHC-encoded predisposition toward differentiation to a nonpathogenic effector (Th2 versus Th1) phenotype. T cells from resistant double transgenic mice showed evidence for prior activation by antigen, suggesting that disease may be actively suppressed by autoreactive Th2 cells. These findings shed light on functional aspects of genetically determined susceptibility to autoimmunity, and should lead to new therapeutic approaches aimed at controlling the differentiation of autoreactive CD4+ effector T cells in vivo.

Animals

Sperm motility, morphology, hyperactivation, and ionophore-induced acrosome reactions after overnight incubation with mycoplasmas.

OBJECTIVE: To evaluate the effect on the function on human sperm of overnight incubation with mycoplasma species. DESIGN: Prospective controlled in vitro study. SETTING: Community-based sperm bank and andrology laboratory. INTERVENTIONS: Percoll-separated sperm were incubated overnight with a low densities of Myco-plasma hominis and Ureaplasma urealyticum serotypes. MAIN OUTCOME MEASURES: Motility, midpiece and tail morphology, hyperactivation after overnight capacitation, and acrosome status after incubation with calcium ionophore. RESULTS: Overnight incubation with mycoplasma species resulted in small but highly statistically significant differences in motility, morphology, hyperactivation after overnight capacitation, and proportion acrosome reacted after incubation with calcium ionophore compared with controls. CONCLUSIONS: Incubation with mycoplasma species impairs sperm physiology. Identification and treatment of mycoplasma may augment a physiology-based infertility evaluation.

Acrosome