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G Nicholas

Publications and source records attributed to G Nicholas.

8 recordsLinked to original sources
PubMed2006

Actions of short-term fasting on human skeletal muscle myogenic and atrogenic gene expression.

BACKGROUND: Skeletal muscle mass is governed by multiple IGF-1-sensitive positive regulators of muscle-specific protein synthesis (myogenic regulatory factors which includes myoD, myogenin and Myf5) and negative regulators, including the atrogenic proteins myostatin, atrogin-1 and muscle ring finger 1 (MuRF-1). The coordinated control of these myogenic and atrogenic factors in human skeletal muscle following short-term fasting is currently unknown. METHOD: Healthy adults (n = 6, age 27.6 years) undertook a 40-hour fast. Skeletal muscle biopsy (vastus lateralis) and venous blood samples were taken 3, 15 and 40 h into the fast after an initial standard high-carbohydrate meal. Gene expression of the myogenic regulator factors (myoD, myogenin and Myf5) and the atrogenic factors (myostatin, atrogin-1 and MuRF-1) were determined by real-time PCR analysis. Plasma myostatin and IGF-1 were determined by ELISA. RESULTS: There were no significant alterations in either the positive or negative regulators of muscle mass at either 15 or 40 h, when compared to gene expression measured 3 h after a meal. Similarly, plasma myostatin and IGF-1 were also unaltered at these times. CONCLUSIONS: Unlike previous observations in catabolic and cachexic diseased states, short-term fasting (40 h) fails to elicit marked alteration of the genes regulating both muscle-specific protein synthesis or atrophy. Greater periods of fasting may be required to initiate coordinated inhibition of myogenic and atrogenic gene expression.

Adult↗
PubMed1992

Risk factors for stroke after coronary artery bypass.

To determine the prevalence of stroke after coronary artery bypass grafting and to evaluate risk factors, we reviewed the records of 1000 patients undergoing coronary bypass within a 1-year time period. Demographic and perioperative data were evaluated by chi 2 analysis. A history of diabetes, evidence of mural thrombus, positive oculopneumoplethysmography findings, increased age, aortic calcification, and postoperative arrhythmias all correlated with increased risk of permanent neurologic deficit for the patient undergoing coronary bypass. Risk factors were analyzed with stepwise logistic regression. A history of diabetes, presence of mural thrombi, and aortic calcification carried a higher probability that the patient would have a permanent neurologic deficit.

Aged↗
PubMed1987

Triazene metabolism. VI. 3-Azidomethyl-3-alkyl-1-aryltriazenes, a new class of anti-tumour triazene with potential pro-drug applications.

The synthesis of a new series of 3-azidomethyl-3-methyl-1-aryltriazenes is described. 3-Acetoxymethyl-3-methyl-1-aryltriazenes react with a large molar excess of sodium azide in aqueous acetone to afford the 3-azidomethyltriazenes in high yield. The rate of formation of the azidomethyltriazene increasing azide concentration, suggesting either an SN2 mechanism or a significant ionic strength effect on an SN1 reaction. In the absence of azide ion, the acetoxymethyltriazene undergoes a slow hydrolysis to give a bis-anilinomethane, which presumably arises via hydrolysis of the triazene to the aniline followed by condensation with formaldehyde released during the hydrolysis. The azidomethyltriazenes undergo facile hydrolysis in aqueous buffer solution with identical kinetic parameters to those of the hydrolysis of hydroxymethyltriazenes, suggesting that the azides may be good pro-drugs for the cytotoxic monomethyltriazene, the hydrolysis product derived from the hydroxymethyltriazene. Indeed, the azidomethyltriazenes have comparable anti-tumour activity against the P388 and PC6 tumours to other triazenes in this series. Furthermore, the azidomethyltriazenes display selective toxicity towards a human tumour cell line (the BE cell line) which is deficient in the repair of O6-methylguanine lesions, suggesting that these triazenes are capable of generating the monomethyltriazene without the need for metabolic activation.

Antineoplastic Agents↗
PubMed1975

Twenty-one years' experience with ruptured abdominal aortic aneurysms.

The surgical experience with 107 ruptured abdominal aortic aneurysms at this hospital during the years 1953 to 1975 has been reviewed. The operative mortality rate during the first ten years of this study was 86 per cent, but since 1966, it has fallen to 40 per cent. These improved mortality statistics are related primarily to improved techniques for controlling operative blood loss and minimizing the time of aortic cross clamping. The use of an intra-aortic balloon has been useful in this regard. Twenty-four additional patients died from ruptured aneurysms without undergoing operation, all before 1966. Only seven had a correct diagnosis prior to death, and these seven serve to emphasize the importance of being alert to the diagnosis of ruptured aneurysm which often masquerades as urologic or orthopedic problems because of the frequent symptoms of back, abdominal, flank or groin pain. Since the operative mortality rate for elective resection of the aneurysm has been less than 1 per cent at this institution during the last eight years, we believe we are justified in encouraging prompt resection of aneurysms on an elective basis to eliminate the high mortality rate that still accompanies rupture of the aneurysm.

Adult↗