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41.
D. G. Robertson D. A. Warrell Jan S. Newton-Howes C. M. Fletcher 《BMJ (Clinical research ed.)》1969,3(5665):269-271
The change in specific airway conductance produced by smoking a cigarette under standard conditions was measured in 91 heavy smokers. Subsequently 19 of the most reactive subjects smoked two cigarettes with different filters and another containing cigar tobacco. The results indicated that reactivity to cigarette smoke was reduced significantly by increasing the retention efficiency of the filter and that reactivity to inhaled cigar-tobacco smoke was no less than that to cigarette smoke. 相似文献
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45.
K A Moore F A Fletcher R L Alford D K Villalon D H Hawkins G R MacGregor C T Caskey J W Belmont 《Génome》1989,31(2):832-839
Somatic gene transfer offers a possible new approach for treatment of human genetic disease. Defects affecting blood-forming tissues are candidates for therapies involving transfer of genetic information into hematopoietic stem cells. Adenosine deaminase (ADA) deficiency is being used as a model disease for which gene transfer techniques can be developed and evaluated. We describe here the construction and testing of 20 retroviral vectors for their ability to transfer and express human ADA in vitro and in vivo via a mouse bone marrow transplantation model. After infection of primary bone marrow with one fo these vectors (p delta NN2ADA), human ADA was detected in 60-85% of spleen colonies at day 14 and maintained long term in the blood of fully reconstituted mice. This system offers the opportunity to assess methods for increasing efficiency of gene transfer, for regulation of expression of foreign genes in hematopoietic progenitors, and for long-term measurement of the stability of expression in these cells. 相似文献
46.
P. M. Dodson M. Beevers R. Hallworth M. J. Webberley R. F. Fletcher K. G. Taylor 《BMJ (Clinical research ed.)》1989,298(6668):227-230
OBJECTIVE--To determine the effect of moderate dietary sodium restriction on the hypertension of non-insulin-dependent (type II) diabetes. DESIGN--Randomised parallel controlled study of moderate sodium restriction for three months compared with usual diabetic diet, followed by randomised double blind crossover trial of sustained release preparation of sodium for one month versus placebo for one month in patients continuing with sodium restriction. SETTING--Patients attending diabetic outpatient clinic of city hospital. PATIENTS--Thirty four patients with established type II diabetes complicated by mild hypertension (systolic blood pressure greater than 160 mm Hg or diastolic pressure greater than 95 mm Hg on three consecutive occasions). Patients already taking antihypertensive agents (but not diuretics) not barred from study provided that criteria for mild hypertension still met. Conditions precluding patients from study were diabetic or hypertensive nephropathy, cardiac failure, and pregnancy. INTERVENTIONS--After run in phase with recordings at seven weeks, three weeks, and time zero patients were allocated at random to receive moderate dietary sodium restriction for three months (n = 17) or to continue with usual diabetic diet. Subsequently nine patients in sodium restriction group continued with regimen for a further two months, during which they completed a randomised double blind crossover trial of sustained release preparation of sodium (Slow Sodium 80 mmol daily) for one month versus matching placebo for one month. END POINT--Reduction in blood pressure in type II diabetics with mild hypertension. MEASUREMENTS AND MAIN RESULTS--Supine and erect blood pressure, body weight, and 24 hour urinary sodium and potassium excretion measured monthly during parallel group and double blind crossover studies. After parallel group study sodium restriction group showed significant reduction in systolic blood pressure (supine 19.2 mm Hg, erect 21.4 mm Hg; p less than 0.001) and mean daily urinary sodium excretion (mean reduction 60 mmol/24 h). There were no appreciable changes in weight, diabetic control, or diastolic pressure. No significant changes occurred in controls. In double blind crossover study mean supine systolic blood pressure rose significantly (p less than 0.005) during sodium supplementation (to 171 mm Hg) compared with value after three months of sodium restriction alone (159.9 mm Hg) and after one month of placebo (161.8 mm Hg). CONCLUSIONS--Moderate dietary restriction of sodium has a definite hypotensive effect, which may be useful in mild hypertension of type II diabetes. 相似文献
47.
Increases in tyrosine phosphorylation are detectable before phospholipase C activation after T cell receptor stimulation. 总被引:70,自引:0,他引:70
C H June M C Fletcher J A Ledbetter L E Samelson 《Journal of immunology (Baltimore, Md. : 1950)》1990,144(5):1591-1599
Antiphosphotyrosine immunoblots were used to characterize tyrosine phosphorylated proteins after stimulation of the human TCR. Increased tyrosine phosphorylation was evident on at least 12 substrates within 2 min after ligation of the TCR with mAb. Analysis of the time course for increased tyrosine phosphorylation revealed distinct patterns. Increased phosphorylation of 135-kDa and 100-kDa substrates was evident within 5 s, whereas increased phosphorylation of the TCR-zeta-chain required several minutes after treatment with anti-CD3 mAb. This rapid cellular tyrosine phosphorylation occurred independent of the cell cycle, as it occurred after stimulation of resting T cells, T cell blasts, and the Jurkat T cell leukemia line. When the TCR complex was cross-linked together with the CD4 receptor by heteroconjugate anti-CD3/CD4 mAb, an increased magnitude of tyrosine phosphorylation occurred, although no new substrates could be detected. The increased tyrosine phosphorylation of the 135-kDa and 100-kDa substrates was specific in that anti-HLA class I, anti-CD6, anti-CD7, and anti-CD28 antibodies did not cause increased tyrosine phosphorylation. Anti-CD4 stimulation of resting T cells did not cause increased tyrosine phosphorylation of pp100 and pp135, suggesting that the CD4-associated kinase, lck, does not account for the tyrosine phosphorylation observed after TCR stimulation. Similarly, pharmacologic treatment of cells with phorbol ester and calcium ionophore did not cause increased tyrosine phosphorylation of these substrates, indicating that activation of protein kinase C or phospholipase C does not account for these early increases in tyrosine phosphorylation. The time of onset of pp100 phosphorylation, and the magnitude of phosphorylation correlated with the magnitude of calcium mobilization when cells were stimulated with different forms of TCR stimulation. When cells were labeled with [3H]myoinositol and analyzed after stimulation by anti-CD3 mAb, increased tyrosine phosphorylation of the 135-kDa and 100-kDa substrates preceded the activation of phospholipase C, as measured by the appearance of inositol 1,4,5-trisphosphate. This occurred in both T cell blasts and in the Jurkat T cell line. Thus, these findings show that increased tyrosine phosphorylation is the earliest yet detected signal observed after ligation of the TCR complex, and furthermore suggest that tyrosine phosphorylation might link the TCR to the phosphatidylinositolbisphosphate hydrolysis signaling pathway. 相似文献
48.
Testicular development and maturation of the hypothalamic-pituitary-testicular axis in the male tammar, Macropus eugenii 总被引:1,自引:0,他引:1
Testicular growth and maturation of the hypothalamic-pituitary-testicular axis were assessed in male tammars from 12 to 25 months of age to establish the time of sexual maturity. The testicular dimensions and body weights of 20 male tammars, approximately 12 months of age at the beginning of the study, were measured monthly for 1 year. Groups of 3 animals were castrated at 13, 19 and 25 months of age and their testes sectioned for histological examination. Testicular volume increased between 12 and 24 months of age and was highly correlated with body weight (r = 0.91). In the 13-month group the seminiferous tubules were closed with few mitotic figures. Spermatogenesis had begun in 2 of the 19-month animals. All stages of spermatogenesis were present in the other 19-month male, and in all of the 25-month males. Basal FSH concentrations increased with the age of the animal (21.0 +/- 32.48, 94.40 +/- 55.18 and 193.05 +/- 40.21 ng/ml (mean +/- s.d.) at 19, 20 and 25 months respectively) while basal LH concentrations were similar at 20 months and 25 months (0.43 +/- 0.18 and 0.58 +/- 0.25 ng/ml respectively). Basal testosterone concentrations were also similar 0.11 +/- 0.04, 0.35 +/- 0.16 and 0.22 +/- 0.10 ng/ml in 13-, 19- and 25-month-old animals. LHRH injection in tammars at 13, 19 and 25 months of age induced release of both LH and testosterone 10-30 min after injection. The hormone concentrations increased in both magnitude and duration with increasing age.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
49.
Uniconazole reduced growth of etiolated mung bean seedlings and increased lateral root formation. Ethylene production for whole seedlings was reduced by 80% within 24 h after treatment and 1-aminocyclopropane-1-carboxylic acid concentrations were reduced by approximately 40% in 12 h. Uniconazole treatment increased spermine levels by 100% by day 4, whereas spermidine and putrescine levels were not affected. Uniconazole, by inhibiting ethylene synthesis, may be increasing spermine levels, which in turn stimulate formation of root primordia. 相似文献
50.
The potential protective effect of immunization with outer-membrane protein I from Neisseria gonorrhoeae 总被引:9,自引:0,他引:9
Immunization of rabbits with outer membranes (OM) of Neisseria gonorrhoeae produced antibodies directed against outer-membrane proteins PI and PIII. The antibodies directed against PIII reacted equally well on Western blots with all strains tested, but antibodies directed against PI reacted only with the homologous strain. When purified PIB was used for immunization the immune response was quite different: the sera obtained reacted with both homologous and heterologous PIB types and also reacted with strains expressing PIA. Western blotting of peptides produced by sequential cleavage of PIB revealed that the antigenic determinants recognized by anti-OM sera were predominantly located in the central surface-exposed region of PIB, as is the epitope recognized by the protective anti-PIB monoclonal antibody SM24. In contrast antibodies produced by immunization with purified PI reacted with antigenic determinants in the N-terminal portion of PIB. Nevertheless these determinants are accessible to immune attack on the native protein since the anti-PI sera were opsonic and were strongly bactericidal for both PIA- and PIB-expressing strains. 相似文献