NMR spectroscopy of human post mortem cerebrospinal fluid: distinction of Alzheimer''s disease from control using pattern recognition and statistics

Mutations of ras oncogenes in 37 human stomach cancers and 13 adenomas were investigated with regard to the histological phenotypes using polymerase chain reaction (PCR), allele-specific oligonucleotide hybridization and/or direct sequencing of the PCR products. The ras mutation was found only in one case (2.7%), the histology of which was poorly differentiated adenocarcinoma. We found no mutation in stomach adenomas. The mutation consisted of a guanine-to-adenine transition in the first base of codon 13 of c-Ki-ras which replaced wild-type glycine with serine, indicating that a putative glycine-to-aspartic acid change is not necessarily the critical event for c-Ki-ras gene activation in codon 13. These results further confirm the infrequency of ras mutation in stomach tumors and also suggest that ras mutations are not specific to the differentiated type of stomach cancer.     

Prospective study of effect of switching from cigarettes to pipes or cigars on mortality from three smoking related diseases

OBJECTIVE: To estimate the extent to which cigarette smokers who switch to cigars or pipes alter their risk of dying of three-smoking related diseases-lung cancer, ischaemic heart disease, and chronic obstructive lung disease. DESIGN: A prospective study of 21520 men aged 35-64 years when recruited in 1975-82 with detailed history of smoking and measurement of carboxyhaemoglobin. MAIN OUTCOME MEASURES: Notification of deaths (to 1993) classified by cause. RESULTS: Pipe and cigar smokers who had switched from cigarettes over 20 years before entry to the study smoked less tobacco than cigarette smokers (8.1 g/day v 20 g/day), but they had the same consumption as pipe and cigar smokers who had never smoked cigarettes (8.1 g) and had higher carboxyhaemoglobin saturations (1.2% v 1.0%, P < 0.001), indicating that they inhaled tobacco smoke to a greater extent. They had a 51% higher risk of dying of the three smoking related diseases than pipe or cigar smokers who had never smoked cigarettes (relative risk 1.51; 95% confidence interval 0.96 to 2.38), a 68% higher risk than lifelong non-smokers (1.68; 1.16 to 2.45), a 57% higher risk than former cigarette smokers who gave up smoking over 20 years before entry (1.57; 1.04 to 2.38), and a 46% lower risk than continuing cigarette smokers (0.54; 0.38 to 0.77). CONCLUSION: Cigarette smokers who have difficulty in giving up smoking altogether are better off changing to cigars or pipes than continuing to smoke cigarettes. Much of the effect is due to the reduction in the quantity of tobacco smoked, and some is due to inhaling less. Men who switch do not, however, achieve the lower risk of pipe and cigar smokers who have never smoked cigarettes. All pipe and cigar smokers have a greater risk of lung cancer than lifelong non-smokers or former smokers.     

Angiotensin II receptor type 1 mRNA is upregulated in atria of patients with end-stage heart failure

There is increasing evidence that pathological changes in the myocardium during chronic heart failure (CHF) are partly regulated through the activation of the renin-angiotensin system (RAS), an effect mediated by the angiotensin II type 1 receptor (AT1R). We examined the expression of cardiac AT1R mRNA in normal (atria, n=7; ventricle, n=3) and end-stage CHF human hearts (atria, n=8; ventricle, n=14). Tissue was snap-frozen immediately after explantation during orthotopic cardiac transplantation; control specimens were obtained from healthy donor hearts rejected for technical reasons. Northern blots of purified total mRNA from each tissue were hybridized with a random primed radiolabeled probe for the coding sequence of AT1R. Stringent conditions were used for both hybridization (5X SSC, 65 degrees C) and washing (0.5X SSC, 0.1% SDS, 65 degrees C) of the membrane. Left and right atrial tissue showed low levels of AT1R mRNA expression in the controls, with statistically significant upregulation of expression in tissue from pathological hearts; CHF atria 1.28+/-0.86 optical density (OD) units, control atria 0.56+/-0.31 OD units, P=0.05 (mean+/-s.d.). There were undetectable levels in ventricles from either control (2/2) or dilated hearts (7/7). The results were independent of the etiology of the heart failure and suggest that increased levels of atrial AT1R mRNA may occur in response to elevated atrial pressures in heart failure.