Peripheral noxious stimulation induces CREM expression in dorsal horn: involvement of glutamate

Thermal washout curves have been proposed as noninvasive tools for analysing lower airway dimensions and pulmonary blood flow, but how upper airway heat transfer affects these washout curves is unclear. The present study was designed to compare extrathoracic and tracheobronchial contributions to thermal washout curves. Respiratory frequency, air ambient temperature, and body core temperature (tc) were varied in six male subjects before and after immersion in cold (1.1 degrees C) water for up to 2 h under three conditions: 1) control: ambient temperature (tamb) = 25 degrees C, rectal temperature change (delta tre) = 0 degrees C; 2) pre-immersion: tamb = 4 degrees C, delta tre = 0 degrees C; and 3) post-immersion: tamb = 25 degrees C, delta tre = -0.7 degrees C. Both peak expiratory nasal (tpn) and oral (tpo) airstream temperatures were measured. Each subject was tested twice. Expiratory tpo was generally higher than tpn in all conditions. Increasing breathing rates lowered tpn and tpo in the control and cold air environments. Orifice temperatures, which are presumed to reflect upper airway blood temperatures, correlated with both tpn and tpo. Lowering tc had no effect on washout curves during quiet breathing and affected only tpn during rapid breathing. The results suggest that while tracheobronchial conditions may contribute to thermal washout curves, extrathoracic conditions predominate. Strong correlations between orifice temperatures, peak expiratory nasal temperatures and peak expiratory oral temperature demonstrate the dominant role of upper airway heat exchange in determining thermal washout curves.     

Sarcoplasmic reticular Ca2+ pump ATPase activity in congestive heart failure due to myocardial infarction

OBJECTIVE: Earlier studies have shown a depression in the sarcoplasmic reticular (SR) Ca2+ uptake and gene expression in Ca2+ pump ATPase protein in congestive heart failure subsequent to myocardial infarction. It is the objective of this study to understand further the mechanisms of depressed SR Ca2+ pump activity in the failing heart. METHODS: Heart failure in rats was induced by occluding the left coronary artery for 16 weeks and the viable left ventricle was processed for the isolation of SR membranes. Sham-operated animals were used as control. The characteristics of SR Ca2+ pump ATPase in the presence of different concentrations of K+, Ca2+ and ATP were examined and the purity of these membranes was monitored by determining the marker enzyme activities. In addition to measuring changes in cyclic adenosine monophosphate (cAMP) protein kinase and Ca(2+)-calmodulin induced phosphorylation, alterations in SR phospholipid composition as well as sulfhydryl (SH) group content were investigated. RESULTS: Ca(2+)-stimulated ATPase activity, unlike Mg(2+)-ATPase activity, was depressed in the left ventricular SR from failing hearts as compared to control. The decrease in Ca(2+)-stimulated ATPase activity was seen at different concentrations of Ca2+, K+ and ATP but no changes in the affinities of the enzyme for Ca2+ and ATP were evident. The SR Ca(2+)-stimulated ATPase activities in the presence of both cAMP-dependent protein kinase and Ca(2+)-calmodulin were markedly decreased in the failing hearts when compared to control preparations. Furthermore, the 32P incorporation in the presence of cAMP-dependent protein kinase or Ca(2+)-calmodulin was also reduced in the experimental heart SR membranes. The phospholipid composition of the SR membranes from the failing heart was markedly altered. No changes in SH-group or the degree of cross contamination with other membranes were apparent in the failing heart SR. CONCLUSIONS: These results suggest that abnormalities in membrane phospholipid composition and phosphorylation of the enzyme may partly explain the observed depression in SR Ca2+ pump ATPase activity in heart failure following myocardial infarction.     

K-ras gene mutations: an unfavorable prognostic marker in stage I lung adenocarcinoma

Activation of K-ras gene by point mutations, a common finding in lung adenocarcinomas, has been suggested to decrease patient survival. We investigated 109 lung adenocarcinomas, mostly small, peripheral, stage I tumours (81/109) for presence of K-ras gene mutations at codons 12 and 13. Mutations were detected by denaturing gradient gel electrophoresis analysis of specific sequences amplified by polymerase chain reaction from DNA extracted from archival pathological material. Thirty-three of 109 (30.3%) tumours showed mutations at codon 12 (28/33, 84.8%) or 13 (5/33, 15.2%) of the gene. Mutations and type of nucleotide substitutions were differently distributed among cytological subtypes, being more prevalent among less differentiated (G2 and G3) tumours and among bronchial than bronchiolo-alveolar type adenocarcinomas. Survival analysis showed an adverse effect of K-ras mutation on survival, restricted to stage I tumours. Median survival for 81 stage I patients was 30 months for non-mutated tumours versus 20 months for mutated tumours (p = 0.016). Multivariate analysis showed that age of patient (p = 0.001) and K-ras mutation status (p = 0.04) were the only independent factors influencing survival significantly. These data strengthen the hypothesis that K-ras gene mutations may be useful in identifying a subgroup of patients with poor outcome.     

Long-term progression in chronic manganism: ten years of follow-up

We studied the long-term clinical course of five patients with chronic manganese intoxication. The mean scores of the King's College Hospital Rating Scale for Parkinson's disease increased from 15.0 +/- 4.2 in 1987 to 28.3 +/- 6.70 in 1991 and then to 38.1 +/- 12.9 in 1995. The deterioration was most prominent in gait, rigidity, speed of foot tapping, and writing. Tissue concentrations of manganese in blood, urine, scalp hair, and pubic hair returned to normal. Follow-up MRIs did not show paramagnetic high-signal intensity on T1-weighted images. The data indicate that clinical progression in patients with manganese parkinsonism continues even 10 years after cessation of exposure.