Age-related Changes in Bovine α-crystallin and High-molecular-weight Protein

The high-molecular-weight (HMW) protein from the lens is composed mostly of α-crystallin in a highly aggregated state. Bovine HMW protein was carefully separated from α-crystallin by size-exclusion chromatography. α-Crystallin has chaperone-like ability whereby it stabilizes other proteins under conditions of stress (e.g. heat). Comparison of bovine HMW protein and α-crystallin shows that the HMW protein has a markedly reduced chaperone ability compared to α-crystallin. However, in contrast to the results of other workers, we observe no alteration with age in the ability of α-crystallin to act as a chaperone. Using electrospray ionisation mass spectrometry, changes in the phosphorylation of the α-crystallin subunits with age have been quantified. Phosphorylation of α-crystallin occurs early in life but does not alter in proportion after about three years of age. In addition, phosphorylation of the A subunit of α-crystallin has little effect on its chaperone ability. As is found in the artificially prepared HMW complex of α- and γ-crystallin, NMR spectroscopy shows that in the naturally occurring HMW protein, the short C-terminal extension of the α_Bsubunit has lost its flexibility whereas the α_Asubunit extension is still flexible. Post-translational modifications therefore seem to have little effect on the chaperone action of α-crystallin, but alterations in the quaternary structure of α-crystallin via incorporation into the HMW aggregate, lead to major changes in the chaperone ability of the protein. The results are consistent with the notion that one of the contributing factors to cataract formation in the lens is the depletion of α-crystallin with age as it is converted into the HMW protein.     

Chrome congestive heart failure: Non-invasive measurement of cardiac output by a carbon dioxide rebreathing method at rest and during exercise

Cardiac output was measured in 11 patients undergoing routinecardiac catheterization using a carbon dioxide rebreathing techniqueand compared with cardiac output measured by direct Fick andthermodilution. The carbon dioxide rebreathing technique gaveconsistently lower values for cardiac output than the othertwo methods (mean difference –0·73, 95% CI –0·95to–0·511. min^–1 with the direct Fick and–0·72. 95% CI –1·19 to –0·261.min^–1 with thermodilution). The direct Fick and thermodilutionmethods gave similar results (mean dtfference –0·08,95% CI –0·32 to 0·16a. min^–1). Cardiacoutput was also measured in 10 healthy subjects at rest andduring two steady-state levels of exercise using the carbondioxide rebreathing technique. Measurements were made in triplicateon 3 separate days. The technique gave reproducible resultsbetween replicates at rest (coefficient of variation 91%) andbecame more reproducible on exercise (coefficients of variation56% and 54% respectively at each exercise level). There wasa good correlation between cardiac output and oxygen consumption(r=0·98 The carbon dioxide rebreathing technique is afeasible non-invasive way of measuring cardiac output. It tendsto underestimate cardiac output at rest but is reproducibleand becomes more so on exercise which is where it should beof most value.     

Novel techniques for the estimation of intracorneal cohesion in vivo*

Desquamation is the result of loss of cohesion between horny squames. This study is concerned with the in vivo measurement of intracorneal cohesion using three new techniques. A new instrument, the cohesograph, directly measures the force (g) required to distract a known area of partial thickness of stratum corneum in vivo. Sex and site differences were detected with this method. A surfometer was employed to measure the surface contours of the internal face of skin surface biopsies and when this measurement of the surface irregularity was compared to the ‘cohesograph’ reading for the same sites in 16 normal individuals a significant positive correlation of r = 0·79 was found between the two sets of results. It is therefore suggested that the surfometer provides indirect measure of horny layer cohesion. Desquamation has also been estimated by using a modified ‘scrub technique’. The scrub apparatus used is able to deliver a controlled stimulus to the skin surface to release horny cells. The light absorbance at 400 run of corneocyte suspensions was measured and found to correlate well (r = 0·96) with the numbers of squames released. It is suggested that the three techniques used in conjunction provide a profile of stratum corneum cohesion in vivo.     

Nationwide linkage analysis in Scotland implicates age as the critical overall determinant of mortality in ulcerative colitis

Aliment Pharmacol Ther 31 , 1310–1321

Summary

Background Recent data associated higher mortality with medical rather than surgical intervention in patients with ulcerative colitis who require hospitalization. Aim To examine factors influencing UC‐related mortality in Scotland. Method Using the national record linkage database 1998–2000, 3‐year mortality was determined after four admission types: colectomy‐elective or emergency; no colectomy‐elective or emergency. Results Of 1078 patients, crude 3‐year mortality rates were: colectomy elective 5.6% (n = 177) and emergency 9.0% (100); no colectomy elective 9.8% (244) and emergency 16.0% (557). Using elective colectomy as reference, multivariate analysis [OR (95% CI)] showed that admission age >50 years [OR 5.46 (2.29–11.95)], male gender [OR 1.92 (1.23–3.02)], comorbidity [OR 2.2 (1.38–3.51)], length of stay >15 days [OR 2.04 (1.08–3.84)] and prior IBD admission [OR 1.66 (1.06–2.61)] were independently related to mortality. Age was the strongest determinant. No patient <30 years died. Mortality of patients aged <50 years [10/587 (1.7%)] was significantly lower than mortality of those aged 50–64 years [26/246 (10.6%)] (χ² = 32.91; P < 0.0000001) and >65 [96/245 (39.2%)] (χ² = 218.2; P < 0.0000001). For those patients aged more than 65 years, mortality in the four groups was 29.4%, 33.3%, 28.1% and 44.7%– all greater than expected in the Scottish population on assessment of standardized mortality ratios. Conclusion Hospital admission in UC patients >65 is associated with high mortality. Management strategies should consider this by treatment in specialist units, early investigation, focused medical treatment and earlier surgical referral.     

DISTRIBUTION AND TURNOVER OF ACETALDEHYDE-MODIFIED PROTEINS IN LIVER AND BLOOD OF ETHANOL-FED RATS

Previous studies have shown that acetaldehyde (AcH)-modifiedproteins are formed in the liver and blood of rats fed ethanol-containingdiets. in this study we report the application of ELISA techniquesto study the subcellular distribution and turnover of AcH-modifiedproteins in ethanol-fed and control rats. Modified proteinswere found in liver mitochondrial, crude membrane and cytosolicfractions, as well as in plasma from ethanol-fed rats. No adductswere detected by our assay in haemolysates from the same animals.The rate of decline of AcH-modifled proteins after cessationof ethanol feeding was also examined. Modified liver cytosolicproteins were shown to decline with a half-life of 2.3 weeks,whereas modified plasma adducts declined with a half-life of4.8 weeks.     

Studies of Alpha-2-Adrenoceptor Function in Abstinent Alcoholics

Hormonal, haemodynamic and subjective psychological responses to the intravenous infusion of clonidine were investigated in nine male alcoholics who had been abstinent for 5 weeks, and were compared with those of nine healthy controls. The growth hormone response to clonidine was significantly blunted in the abstinent alcoholics. Both baseline cortisol levels and the clonidine-induced cortisol decrease were significantly greater in the alcoholics than in controls. Blood pressure, pulse rate and psychological responses to clonidine were similar in both groups. These results indicate that some aspects of alpha-2-adrenoceptor sensitivity are persistently abnormal in alcoholics at least 5 weeks into abstinence.     

Variable patterns of atrial natriuretic peptide secretion in man

Abstract Peripheral circulating levels of atrial natriuretic peptide may exhibit short-term variation compatible with a pulsatile pattern of secretion. We obtained samples every 2 min for 90 min from the antecubital vein of 16 patients with chronic cardiac failure and 13 controls. Overall levels were higher in the patients (median and quartiles 230 (125,325) vs. 26 (16,48) ng l^-1; P <0·001). In both groups there was considerable variability, with 10 (2–12) peaks, 9 (7–15) troughs (both defined as >2 SD from the mean) and 16 (13–18) pulses (defined by computer) during the sampling period in controls, and a similar number in patients. We then carried out simultaneous sampling in the pulmonary artery, femoral artery and peripheral vein in eight subjects with normal cardiac function and six patients with impaired function due to valvular heart disease. The pattern of variability was preserved in all three sites in both groups, suggesting intermittent secretion rather than variable breakdown of the peptide in the lung. No changes in right atrial pressure or heart rate were observed to coincide with the variations, but levels of the peptide in the pulmonary artery correlated with right atrial pressure in patients (r = 0·87; P <0·05). The mechanism of such periodicity and its pathophysiological importance remain unknown.