Slow and Prolonged Activation of the p47 Protein Kinase during Hypersensitive Cell Death in a Culture of Tobacco Cells

To investigate the involvement of protein kinases in the signaling cascade that leads to hypersensitive cell death, we used a previously established system in which a fungal elicitor, xylanase from Trichoderma viride (TvX), induces a hypersensitive reaction in tobacco (Nicotiana tabacum) cells in culture (line XD6S). The elicitor induced the slow and prolonged activation of a p47 protein kinase, which has the characteristics of a family member of the mitogen-activated protein kinases. An inhibitor of protein kinases, staurosporine, and a blocker of Ca channels, Gd3+ ions, both of which blocked the TvX-induced hypersensitive cell death, inhibited the TvX-induced activation of p47 protein kinase. Moreover, an inhibitor of serine/threonine protein phosphatase alone induced both rapid cell death and the persistent activation of the p47 protein kinase. Thus, the p47 protein kinase might be a component of the signal transduction pathway that leads to hypersensitive cell death, and the regulation of the duration of activation of the p47 protein kinase might be important in determining the destiny of tobacco cells.

Obese gene expression: reduction by fasting and stimulation by insulin and glucose in lean mice, and persistent elevation in acquired (diet-induced) and genetic (yellow agouti) obesity.

Mutations in the obese (ob) gene lead to obesity. This gene has been recently cloned, but the factors regulating its expression have not been elucidated. To address the regulation of the ob gene with regard to body weight and nutritional factors, Northern blot analysis was used to assess ob mRNA in adipose tissue from mice [lean, obese due to diet, or genetically (yellow agouti) obese] under different nutritional conditions. ob mRNA was elevated in both forms of obesity, compared to lean controls, correlated with elevations in plasma insulin and body weight, but not plasma glucose. In lean C57BL/6J mice, but not in mice with diet-induced obesity, ob mRNA decreased after a 48-hr fast. Similarly, in lean C57BL/6J controls, but not in obese yellow mice, i.p. glucose injection significantly increased ob mRNA. For up to 30 min after glucose injection, ob mRNA in lean mice significantly correlated with plasma glucose, but not with plasma insulin. In a separate study with only lean mice, ob mRNA was inhibited >90% by fasting, and elevated approximately 2-fold 30 min after i.p. injection of either glucose or insulin. These results suggest that in lean animals glucose and insulin enhance ob gene expression. In contrast to our results in lean mice, in obese animals ob mRNA is elevated and relatively insensitive to nutritional state, possibly due to chronic exposure to elevated plasma insulin and/or glucose.

Prolonged survival of pancreatic islet allografts mediated by adenovirus immunoregulatory transgenes.

The adenovirus (Ad) early region 3 (E3) genes code for at least four proteins that inhibit the host immune responses mediated by cytotoxic T lymphocytes and tumor necrosis factor alpha. To evaluate the potential use of these immunoregulatory viral functions in facilitating allogeneic cell transplantation, the Ad E3 genes were expressed in pancreatic beta cells in transgenic mice under control of the rat insulin II promoter. Transgenic H-2b/d (C57BL/6 x BALB/c) islets, expressing the Ad E3 genes, remained viable for at least 94 days after transplantation under the kidney capsule of BALB/c (H-2d) recipients. Nontransgenic H-2b/d control islets were rejected as anticipated between 14 and 28 days. Histological analysis of the transplanted transgenic islets revealed normal architecture. Immunohistochemical studies with antisera to islet hormones revealed the presence of both beta and non-beta islet cells, suggesting a propagation of the immunosuppressive effect of Ad proteins from beta cells to other islet cells. The use of viral genes, which have evolved to regulate virus-host interactions, to immunosupress the anti-genicity of donor transplant tissue suggests additional ways for prolonging allograft survival. In addition, these findings have implications for designing Ad vectors for gene therapy.

Examining Adolescent Sport Dropout and Prolonged Engagement from a Developmental Perspective

This study examined youth sport dropout and prolonged engagement from a developmental perspective focusing on physical and psychosocial factors. Twenty-five dropout and 25 engaged adolescent swimmers, matched on key demographic variables, participated in a retrospective interview. Results indicated that dropouts were involved in fewer extra-curricular activities, less unstructured swimming play, and received less one-on-one coaching throughout development. Dropouts reached several developmental milestones (i.e., started training camps, started dry land training, and were top in club) earlier than engaged athletes. Dropouts were more likely to have had parents who were high-level athletes in their youth, were more likely to be the youngest in their training group, and were less likely to have a best friend at swimming. Findings are discussed in relation to past research; future directions and implications for researchers, sport programmers, coaches, and parents are suggested.

Understanding Dropout and Prolonged Engagement in Adolescent Competitive Sport

Objectives: The purpose of this study is to gain understanding of training patterns and roles of significant others (i.e. coaches, parents, peers, and siblings) in adolescent swimmers’ sport participation patterns. Design: The developmental model of sport participation [Côté, J., Baker, J., & Abernethy, B. (2003). From play to practice: A developmental framework for the acquisition of expertise in team sport. In J. Starkes, & K. A. Ericsson (Eds.), Recent advances in research on sport expertise (pp. 89–114). Champaign, IL: Human Kinetics; Côté, J., & Fraser-Thomas, J. (2007). Youth involvement in sport. In P. R. E. Crocker (Ed.), Introduction to sport psychology: A Canadian perspective (pp. 266–294). Toronto: Pearson Prentice Hall] was used as a framework. Method: Ten dropout and 10 engaged swimmers, matched on key demographic variables participated in a semi-structured qualitative interview. Results: Groups had many similar experiences (e.g. early training, supportive and unsupportive coaches, involved parents). However, only dropouts spoke of early peak performances, limited one-on-one coaching, pressuring parents during adolescence, lack of swimming peers during adolescence, and sibling rivalries. In contrast, only engaged athletes spoke of clubs’ developmental philosophies, coaches’ and parents’ open communication, school friends’ support, and siblings’ general positive influences. Conclusions: Findings highlight the importance of appropriately structured programs and the fragility of athletes’ relationships with significant others during the adolescent years. Implications for sport programmers, coaches, and parents are discussed.

The fast way to health; being, as to the first part, an exposition of the fasting cure and its application to the prevalent disorders, and, as to the second part, a treatise on food, together with diets for the well.

Mode of access: Internet.

The effect of severe and prolonged muscular work on food consumption, digestion, and metabolism,

Mode of access: Internet.

Improving modern apparatuses for prolonged artificial respiration,

"Translation of an article ... in the Russian-language journal vestnik khirurgii (Herald of surgery), vol. 90, no. 3, March 1963, pages 81-87."

Feasts and fasts; an essay on the rise, progress, and present state of the laws relating to Sundays and other holidays, and days of fasting;

"List of abbreviations employed, and of editions referred to": p.[xv]-xviii.

Prolonged Duration of Sciatic Nerve Blockade in the Elderly after Foot and Ankle Surgery

1.1 Background and Objectives: Perioperative morbidity related to anesthesia renders elderly patients vulnerable because age related factors affect medication effects, clearance and metabolism. Regional anesthesia within a multimodal regimen reduces opioid adverse effects in the elderly and improves immediate analgesia but not long term recovery and prolonged nerve blockade has been reported. The purpose of this study was to assess analgesic effects of sciatic nerve blockade in the elderly. 1.2 Methods: Postoperative sciatic nerve blockade was administered for foot and ankle surgery to patients over age 18 years. Preoperative, post-anesthesia unit and 24 hour postoperative pain scores and opioid doses for these same intervals were recorded. 1.3 Results: 47 patients enrolled and 12 (25.5%) were over age 70. Preoperative, immediate and 24 post-operative pain scores and total intraoperative and immediate postoperative opioid doses were lower in the elderly. The total 24 hour postoperative opioid doses in the elderly were lower compared to the younger group. 1.4 Conclusions: Total 24 hour postoperative cumulative opioid doses after sciatic nerve blockade in patients over 70 are lower than in younger patients. Further observations in greater numbers of patients and improved ultrasound to assess sciatic nerve structure in the elderly are warranted to study this effect.

Secondary prevention of cardiovascular events with long-term pravastatin in patients with diabetes or impaired fasting glucose - Results from the LIPID trial

OBJECTIVE- Diabetes, a major health problem worldwide, increases the risk of cardiovascular disease and its associated mortality. Evidence of the overall benefits of lipid modification in this area is needed. RESEARCH DESIGN AND METHODS- The Long-Term Intervention with Pravastatin in Ischemic Disease (LIPID) trial showed that cholesterol-lowering treatment with pravastatin reduced mortality and coronary heart disease (CHD) events in 9,014 patients aged 31-75 years with CHD and total cholesterol 4.0-7.0 mmol/l. We measured the effects of pravastatin therapy, 40 mg/day over 6.0 years, on the risk of CHD death or nonfatal myocardial infarction and other cardiovascular outcomes in 1,077 LIPID patients with diabetes and 940 patients with impaired fasting glucose (IFG). RESULTS- in patients allocated to placebo, the risk of a major CHD event was 61% higher in patients with diabetes and 23% higher in the IFG group than in patients with normal fasting glucose, and the risk of any cardiovascular event was 37% higher in the diabetic group and 19% higher in the IFG group. Pravastatin therapy reduced the risk of a major CHD event overall from 15.9 to 12.3% (relative risk reduction [RRR] 24%, P < 0.001) and from 23.4 to 19.6% in the diabetic group (19%, P = 0.11); in the diabetic group, the reduction was not significantly different from the reductions in the other groups. Pravastatin reduced the risk of any cardiovascular event from 52.7 to 45.2% (21%, P < 0.008) in patients With diabetes and from 45.7 to 37.1% (26%, P = 0.003) in the IFG group. Pravastatin reduced the risk of stroke from 9.9 to 6.3% in the diabetic group (RRR 39%, Cl 7-61%, P = 0.02) and from 5.4 to 3.4% in the IFG group (RRR 42%, Cl -9 to 69%, P = 0.09). Pravastatin did not reduce the incidence of diabetes. Over 6 years, pravastatin therapy prevented one major,CHD event (CHD death or nonfatal myocardial infarction) in 23 patients with IFG and 18 patients with diabetes. A meta-analysis of other major trials confirmed the high absolute risks of diabetes and IFG and the absolute benefits of statin therapy in these patients. CONCLUSIONS- Cholesterol-lowering treatment with pravastatin therapy prevents cardiovascular events, including stroke, in patients with diabetes or IFG and established CHD.