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981.
CE Canman DS Lim KA Cimprich Y Taya K Tamai K Sakaguchi E Appella MB Kastan JD Siliciano 《Canadian Metallurgical Quarterly》1998,281(5383):1677-1679
The p53 tumor suppressor protein is activated and phosphorylated on serine-15 in response to various DNA damaging agents. The gene product mutated in ataxia telangiectasia, ATM, acts upstream of p53 in a signal transduction pathway initiated by ionizing radiation. Immunoprecipitated ATM had intrinsic protein kinase activity and phosphorylated p53 on serine-15 in a manganese-dependent manner. Ionizing radiation, but not ultraviolet radiation, rapidly enhanced this p53-directed kinase activity of endogenous ATM. These observations, along with the fact that phosphorylation of p53 on serine-15 in response to ionizing radiation is reduced in ataxia telangiectasia cells, suggest that ATM is a protein kinase that phosphorylates p53 in vivo. 相似文献
982.
Cardiomyocytes isolated from rabbit hearts were preconditioned in vitro by 10 min of ischemia or treatment with 100 microM adenosine. Protection was assessed as average integrated mortality following osmotic swelling and determination of viability by trypan blue exclusion over 60-180 min ischemia. Repetitive sub-maximal stimulations with 1 microM adenosine amplified the protective response. Treatment with adenosine only at the onset of prolonged ischemia afforded a dose-dependent protection. The PKC inhibitor calphostin C (500 nm) blocked preconditioning and, when added during ischemic incubation of non-preconditioned cells, significantly increased injury. The memory of adenosine-induced preconditioning decayed over a 60 min post-incubation period. Light activation of calphostin C initially added to preconditioned ischemic cells in the dark indicated that a 10 min period of PKC activity at the onset of ischemia affords full protection. The reversible PKC inhibitors chelerythrine (5 microM) or staurosporine (100 nM) added only to bracket induction of ischemia, reduced but did not abolish protection. Protection was abolished when either drug was present during induction and a subsequent 30 min post-incubation period. Staurosporine included during initiation and post-incubation but washed out in the final 5 min of post-incubation allowed significant protection to occur. It is concluded that a single adenosine receptor-stimulation induces protection as it preconditions, and PKC activity appears to be required for both induction and protection. Memory may reside in post-receptor amplification of an initial protective response. 相似文献
983.
984.
ZC Wen SA Chen CT Tai CE Chiang CW Chiou MS Chang 《Canadian Metallurgical Quarterly》1998,98(24):2716-2723
BACKGROUND: The vagal maneuvers used for termination of paroxysmal supraventricular reentrant tachycardia (PSVT) appear to involve more complex mechanisms than we have known, and further study should be done to explore the possible mechanisms. METHODS AND RESULTS: In this study, 133 patients with PSVT and 30 age- and sex-matched control subjects were included. We assessed the effects of different vagal maneuvers on termination of PSVT and compared baroreflex sensitivity and beta-adrenergic sensitivity between the patients with PSVT and control subjects. Out of 85 patients with atrioventricular reciprocating tachycardia (AVRT), vagal maneuvers terminated in 45 (53%). Of these, 28 (33%) terminated in the antegrade limb and 17 (20%) terminated in the retrograde limb. Out of 48 patients with atrioventricular nodal reentrant tachycardia (AVNRT), vagal maneuvers terminated the tachycardia in the antegrade slow pathway (14%) or in the retrograde fast pathway (19%). Baroreflex sensitivity was poorer but isoproterenol sensitivity test better in patients with AVNRT. Poorer antegrade atrioventricular node conduction properties and better vagal response determined successful antegrade termination of AVRT by vagal maneuvers. Poorer retrograde accessory pathway conduction property but better vagal response determined successful retrograde termination of AVRT. Better sympathetic and vagal response associated with poorer retrograde atrioventricular node conduction determined retrograde termination of AVNRT by the Valsalva maneuver. CONCLUSIONS: Both the vagal response and conduction properties of the reentrant circuit determine the tachycardia termination by vagal maneuvers. Improved understanding of the interaction of autonomic and electrophysiological mechanisms in maintaining or terminating PSVT may provide important insight into the pathophysiology of these two tachycardias. 相似文献
985.
986.
987.
CJ Knott-Craig CE Howell BD Parsons SM Paulsen BR Brown RC Elkins 《Canadian Metallurgical Quarterly》1997,63(5):1405-9; discussion 1409-10
BACKGROUND: Perioperative mortality and morbidity after lung resection for carcinoma are generally reported to be 3% to 6% and 15% to 30%, respectively, and higher in the elderly and those with limited cardiopulmonary reserve. METHODS: To minimize this risk and extend the surgical option to more high-risk patients, we adopted a protocol in 1991 that included preoperative digitalis, subcutaneous heparin and venoocclusive stockings, aggressive perioperative pulmonary toilet, and video-directed limited resections for many patients with limited pulmonary reserve. In October 1996, we reviewed our results with 173 consecutive patients (median age, 60 years; range, 17 to 89 years) undergoing operation for suspected lung carcinoma. Forty-one patients were 70 years old or older, and 70 patients were considered high risk on the basis of advanced age (> or = 70 years), poor cardiac or pulmonary reserve, or serious medical comorbidity. Procedures included pneumonectomy (n = 31), lobectomy (n = 83), bilobectomy (n = 12), and limited resection (n = 45). Two patients had unresectable disease. RESULTS: Hospital mortality was 1.6% (3/173) and morbidity was experienced by 15% (26/173). Among the high-risk subgroup mortality was 4.2% (3/70) and morbidity was 20% (14/70; p < 0.03). For the older patients these values were 4.8% (2/41) and 17.9% (7/41), respectively. CONCLUSIONS: Morbidity and mortality from lung resections may be minimized with the perioperative management strategy outlined above. This would allow more high-risk patients to benefit from surgical resection, and do so with an acceptably low risk. 相似文献
988.
The causes of visual loss in 1411 children attending schools for the blind in different geographical areas in India are described. Ninety-three percent (1318) of the children were severely visually impaired (SVI) or blind (i.e. corrected acuity in the better eye of <20/200 [<6/60]). In 60% of SVI/blind children vision loss was attributable to factors operating in the prenatal period, in 47% the prenatal factors were known and definite, and in 13% prenatal factors were the most probable causes. Hereditary retinal dystrophies and albinism were seen in 19% of SVI/blind children and 23% had congenital ocular anomalies. There were variations in the relative importance of different causes by state. The observed pattern of causes of visual loss is intermediate between those seen in industrialised countries and in the poorest developing countries. This suggests that strategies to combat childhood blindness in India need to address concurrently both preventable and treatable causes. The need for aetiological studies, particularly on anophthalmos and microphthalmos, is highlighted. 相似文献
989.
OBJECTIVE: The present study investigated the associations of stature, lower leg length (LLL) and demi-arm span (demi-AS) with major predisposing cardiovascular risk factors and coronary heart disease. STUDY DESIGN AND SUBJECTS: Cross-sectional study set at Glasgow Royal Infirmary of a subsample of 543 men and 646 women aged 25-66 y from the random MONICA sample. ASSOCIATED MEASURES: LLL, demi-AS, blood pressure, plasma total cholesterol, diabetes mellitus and coronary heart disease (angina, angioplasty, heart attack, and coronary artery bypass graft). RESULTS: The numbers (and proportions) of men and women, respectively, with hypertension were 126 (23.6%) and 80 (14.0%), hypercholesterolaemia 155 (29.0%) and 171 (30.1%), coronary heart disease 53 (10.1%) and 47 (8.4%), and diabetes 15 (2.9%) and 9 (1.6%). Results were adjusted for age, social class and smoking. Analysis of variance showed that in men, shortness of height, LLL or demi-AS were all associated significantly (P < 0.05) with hypercholesterolaemia. Long LLL, high ratios of LLL:height or LLL:demi-As were associated significantly (P < 0.05) with diabetes mellitus. In women, shortness of height or LLL were associated with significantly (P < 0.05) with coronary heart disease. High ratio of demi-AS:height or low ratio of LLL:demi-AS was associated significantly (P < 0.05) with coronary heart disease. CONCLUSIONS: Short stature and limb lengths, and also altered skeletal proportions, which may reflect interrupted early growth, are associated with several metabolic disorders. Skeletal disproportion associates with diabetes in men and coronary heart disease in women. 相似文献
990.
Reactive free oxygen radicals are known to play an important role in the pathogenesis of various lung diseases such as idiopathic pulmonary fibrosis (IPF), adult respiratory distress syndrome (ARDS) or cystic fibrosis (CF). They can originate from endogenous processes or can be part of exogenous exposures (e.g. ozone, cigarette smoke, asbestos fibres). Consequently, therapeutic enhancement of anti-oxidant defence mechanisms in these lung disorders seems a rational approach. In this regard, N-acetyl-L-cysteine (NAC) and ambroxol have both been frequently investigated. Because of its SH group, NAC scavenges H2O2 (hydrogen peroxide), .OH (hydroxol radical), and HOCl (hypochlorous acid). Furthermore, NAC can easily be deacetylated to cysteine, an important precursor of cellular glutathione synthesis, and thus stimulate the cellular glutathione system. This is most evident in pulmonary diseases characterized by low glutathione levels and high oxidant production by inflammatory cells (e.g. in IPF and ARDS). NAC is an effective drug in the treatment of paracetamol intoxication and may even be protective against side-effects of mutagenic agents. In addition NAC reduces cellular production of pro-inflammatory mediators (e.g. TNF-alpha, IL-1). Also, ambroxol [trans-4-(2-amino-3,5-dibromobenzylamino)-cyclohexane hydrochloride] scavenges oxidants (e.g. .OH, HOCl). Moreover, ambroxol reduces bronchial hyperreactivity, and it is known to stimulate cellular surfactant production. In addition, ambroxol has anti-inflammatory properties owing to its inhibitory effect on the production of cellular cytokines and arachidonic acid metabolites. For both substances effective anti-oxidant and anti-inflammatory function has been validated when used in micromolar concentrations. These levels are attainable in vivo in humans. This paper gives an up-to-date overview about the current knowledge of the hypothesis that oxidant-induced cellular damage underlies the pathogenesis of many human pulmonary diseases, and it discusses the feasibility of anti-oxidant augmentation therapy to the lung by using NAC or ambroxol. 相似文献