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Biomedical subjects

J Shaw

Publications and source records attributed to J Shaw.

At least 235 records · Page 13Linked to original sources
PubMed1988

A molecular-genetic analysis of cytotoxic T lymphocyte function.

Two genes that are specifically expressed in T cells with cytolytic activity were isolated from a CTL cDNA library by differential screening. Both appear to encode serine proteases, thus suggesting a cascade mechanism, similar to complement, in activated CTL. Both CTL-specific proteases have a number of unusual structural features that suggest that they will have novel substrate specificities. One of the proteins (CCPI) has been oriented to the granules found in the cytoplasm of CTL. Taken together, these data strongly suggest that these molecules play an important role in target-cell lysis by CTL. Furthermore, we believe that the detailed molecular knowledge being accumulated through these studies may lead to the development of innovative forms of immunotherapy.

Amino Acid Sequence↗
PubMed1988

Phorbol diester-inducible, cyclosporine-suppressible transcription from a novel promoter within the mouse mammary tumor virus env gene.

The mouse T-cell lymphoma cell line EL4.E1 constitutively synthesizes mouse mammary tumor virus (MMTV) transcripts encoding either the entire proviral genome or segments of it. In addition to these conventional mRNAs, however, an mRNA of about 1 kilobase accumulates after induction of these cells with phorbol myristate acetate (PMA). The accumulation of this transcript is strongly inhibited by the immunosuppressive agent cyclosporin A. Its pattern of induction by PMA and suppression by cyclosporin A is thus the same as seen for several lymphokine mRNAs in these cells, including interleukin-2 and granulocyte-macrophage colony-stimulating factor. The short MMTV transcript is the most abundant PMA-induced transcript in EL4.E1 cells, but was not found in a series of other leukocyte tumor cell lines. It is initiated from a novel promoter within the env gene, and a segment of 1,161 nucleotides is then spliced out. The major part of the transcript is a copy of the long terminal repeat (LTR) of MMTV. The MMTV proviral genomes in these cells, and the short transcript, contain a 491-nucleotide deletion in the LTR compared with the normal MMTV provirus. The resulting open reading frame could encode a protein of molecular weight 22,800, which is a likely candidate for an LTR-related protein with a similar molecular weight recently described in this system (J. Racevskis, J. Virol. 58:441-449, 1986).

Animals↗
PubMed1988

Cloning of cDNA for the bovine IL-2 receptor (bovine Tac antigen).

We have cloned the Tac analog of the bovine IL-2 receptor (IL-2R) cDNA. Using mouse and human cDNA probes, we isolated five bovine IL-2R clones from a lambda gt11 bovine long-term lymphocyte cDNA library. Three of the clones had inserts of 2600 base pairs (bp), the same size as the bovine IL-2R mRNA visualized on Northern blots. The full-length cDNA contain a 190-bp 5' untranslated region, followed by a 825-bp coding region, and a 3' untranslated region that contain 1600 bp. Comparison of the bovine and human IL-2R-coding sequences revealed 71% homology at the nucleotide level. The 3' and 5' non-coding regions were not as homologous, apart from a specific site in the 5'-untranslated region that contained a 5'-upstream start codon. In this region, 24 of 26 nucleotides were identical for the human and bovine cDNAs. Further analysis of the bovine IL-2R sequence also revealed the following: (i) the hydrophobic domains of the IL-2R protein were more conserved between species than the hydrophilic domains, (ii) the predominant site of intracellular IL-2R phosphorylation in mouse and human was a conserved Ser which was not conserved in the bovine sequence, and (iii) there exists a statistically significant amino acid homology with the AIDS gag protein.

Amino Acid Sequence↗
PubMed1987

Studies on alpha adrenoceptors in guinea-pig peripheral lung strips.

Contractile responses of guinea-pig peripheral lung strips to noradrenaline were determined in the presence of propranolol (2.5 X 10(-6) mol/l). All strips (n = 44) contracted to noradrenaline and a geometric mean EC50 of 1.4 X 10(-6) mol/l (1.1 X 10(-6) mol/l, 1.8 X 10(-6) mol/l 95% confidence limits) was obtained. Contractions were antagonised by phentolamine (5 X 10(-7)-10(-5) mol/l) and by prazosin (10(-8)-10(-7) mol/l). Dose-ratios (DR) were calculated and log (DR-1) was plotted against log concentration of antagonist to yield slopes (+/- SE) of 0.84 +/- 0.14 and 0.73 +/- 0.22 respectively which were not significantly different from unity. A pA2 value (+/- SE) of 6.7 +/- 0.2 was obtained for phentolamine and 7.5 +/- 0.1 for prazosin. Yohimbine (10(-7)-10(-5) mol/l) did not significantly affect the maximal tension generated or the EC50 values for noradrenaline. These results suggest that alpha 1 adrenoceptors are mediating the contractile responses to noradrenaline. In the presence of cocaine (10(-5) mol/l, n = 18), normetanephrine (2 X 10(-5) mol/l, n = 15), hydrocortisone (2.5 X 10(-5) mol/l, n = 15) and normetanephrine (2 X 10(-5) mol/l) plus cocaine (10(-5) mol/l, n = 15) pA2 values for phentolamine of 6.9, 6.7, 6.6, and 6.3 respectively were obtained. Since these pA2 values are not significantly different from 6.7, it is unlikely that this original pA2 value, which is lower than values obtained with phentolamine at alpha-adrenoceptors in other tissues, may be explained by neuronal or extraneuronal uptake of noradrenaline.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1987

Exclusion of the Friedreich ataxia gene from chromosome 19.

Friedreich ataxia, a progressive neurodegenerative disorder, is an autosomal recessive disease with a carrier frequency of 1/110 in the United Kingdom. The pathophysiological basis for the disease is not known and the chromosomal location of the mutation remains unidentified. As part of an attempt to map the mutation using linked DNA markers, we demonstrate that the Friedreich ataxia gene is excluded from human chromosome 19. This study also demonstrates that the insulin receptor, which maps to chromosome 19 and may be associated with abnormal biochemical features in some patients, is not the basic defect.

Alleles↗
PubMed1987

Cotinine validation of self-reported smoking in commercially run community surveys.

A validation study was carried out on self-reported smoking for 1177 people in Sydney and Melbourne in 1983. Because of its long half life and the fact that smoking is its only source in body fluids, saliva cotinine was chosen as the validation measure. Cotinine levels above 250 nmol/l were used to classify people as smokers. The sensitivity of self-reported smoking was 92.6% and the specificity was 93.4%. There was some evidence that people in the process of changing their smoking status might be slow in updating their self-classification. The smoking prevalence estimate based on cotinine levels was found to be 1.7% lower than that for self-reported smoking status. The small proportion of false negatives and false positives suggests that commercially collected data banks can be valid sources of prevalence data. Correlation between cotinine level and reported cigarette consumption was not affected by sample volume, and was similar to that achieved for carbon monoxide and thiocyanate at a low 0.34. Regression analysis using self-reported cigarette consumption filter/non-filter cigarettes, and time since last cigarette as predictors, explained 13.6% of the variance in cotinine level.

Adolescent↗
PubMed1987

Induction, suppression and superinduction of lymphokine mRNA in T lymphocytes.

The expression of several lymphokine gene is characterized by a common pattern of induction, suppression and superinduction. This pattern was studied at the level of cellular mRNA in the mouse T-lymphoma cell line EL4, the human T-leukemia line Jurkat and in normal human peripheral blood lymphocytes. Lymphokine mRNA was induced by stimulating the cells with the phorbol diester PMA (TPA), with or without T-lymphocyte mitogens. The induction of Interleukin-2, Interferon gamma and the Colony Stimulating Factor for granulocytes and macrophages was suppressed by Cyclosporin A at moderate concns. Furthermore, these mRNAs accumulated to extraordinarily high levels (superinduction) if the protein synthesis inhibitor cycloheximide was added during transcription. Superinduction was not due to an increased rate of transcription. CsA interrupted ongoing transcription of IL2 by a mechanism not dependent on the induction of a new protein. The co-ordinate regulation of these genes strongly suggests that common intracellular signals mediate their expression.

Animals↗
PubMed1987

Health beliefs, satisfaction and compliance.

Relationships were studied between measures of parents' Health Beliefs, satisfaction, and compliance in 174 children suffering from asthma. It was found that while concurrent measures of Health Belief Model (HBM) variables and compliance were significantly correlated, measures of HBM variables did not predict future compliance. Satisfaction measures, however, not only correlated with concurrent measures of compliance but also predicted future compliance. It is concluded that these findings are consistent with the view that in this sample health beliefs were reactive to compliance behaviours and that they did not have a casual effect on compliance.

Adolescent↗
PubMed1987

Prevalence of hepatitis B surface antigen and antibody (hepatitis B virus markers) in personnel at a children's hospital.

After two cases of acute hepatitis B infection occurred in phlebotomists at The Hospital for Sick Children in 1985, a seroprevalence survey of hepatitis B virus markers was undertaken. Directors in high-risk areas were advised by phone and memorandum to screen employees. Participation was entirely voluntary, and employees who did not respond were contacted six weeks after initial notification. Information obtained from each participant through a self-administered questionnaire included age, duration of employment in current pediatric occupation, history of blood transfusions, immune globulin prophylaxis, needlestick injury, and country of birth (North America/United Kingdom or other). Sera identified by code were tested by radioimmunoassay. Interactions were analyzed by using a multiple logistic regression model. A total of 10% of the personnel in high-risk areas, in which there was frequent exposure to blood or blood products, had hepatitis B markers in their blood, compared with 2% who did not have this exposure. Birthplace and occupation have independently significant effects on the likelihood of having hepatitis B markers. There appears to be an increased risk to employees in pediatric units, depending on the patient (and parent) population being served, although the risk may be lower than in adult hospitals.

Adult↗
PubMed1987

The effects of propranolol and metoprolol on skin blood flow in diabetic patients.

The effect of 2 weeks treatment with propranolol or metoprolol on skin blood flow (SBF) at rest was examined in 12 diabetic patients with essential hypertension in whom gross large vessel disease had been excluded. Neither drug significantly altered resting skin blood flow. However we cannot exclude an important difference between the two beta-adrenoceptor blockers because of the great variability of SBF within subjects. A larger study and/or more accurate methods of measuring SBF are needed to determine if beta 1-selective adrenoceptor antagonists differ from non-selective beta-adrenoceptor blockers with respect to skin blood flow.

Adult↗
PubMed1987

Structure and expression of a tandem gene pair in Leishmania donovani that encodes a protein structurally homologous to eucaryotic cation-transporting ATPases.

An oligonucleotide probe was used to clone a cation-transporting ATPase gene from the genome of Leishmania donovani. The nucleotide sequence of the gene contained a 2,922-base-pair open reading frame that was predicted to encode a 107,406-dalton protein composed of 974 amino acids. The predicted L. donovani protein contained all the structural and functional domains expected to be present in a cation-transporting ATPase of the aspartyl phosphate class. The nucleotide sequence encoding the ATPase gene was duplicated in tandem in the parasite genome. Partial sequenation of the second member of the tandem repeat, which lay 2 kilobase pairs downstream of the ATPase gene, indicated that it was either identical to the first gene or very closely related to it. RNA homologous to either the ATPase gene or its adjacent relative was 5 kilobases in size and was approximately equally abundant in both promastigote and amastigote forms of the organism.

Adenosine Triphosphatases↗
PubMed1987

Effects of aerosol antigen challenge in vivo on responsiveness of guinea pig tracheal and parenchymal strips in vitro to contractile agonists.

Guinea pigs sensitized to produce IgG-like antibodies were challenged with aerosol antigen in vivo. The following day responses in vitro to histamine and carbachol of tracheal and lung parenchymal strips (LPS) from challenged animals and unchallenged controls were compared. Responses of LPS to both histamine and carbachol were increased in challenged animals but tracheal strips from challenged guinea pigs did not display increased sensitivity to histamine or carbachol compared with controls. Moreover, the sensitivity of tracheal strips to carbachol decreased in challenged animals. The increased sensitivity of LPS from challenged animals may be due to the release of chemical mediators and down regulation of postsynaptic muscarinic receptors may account for the decreased sensitivity of tracheal strips.

Aerosols↗