Increased Ca2+-sensitivity of the contractile apparatus in end-stage human heart failure results from altered phosphorylation of contractile proteins.

OBJECTIVE: The alterations in contractile proteins underlying enhanced Ca(2+)-sensitivity of the contractile apparatus in end-stage failing human myocardium are still not resolved. In the present study an attempt was made to reveal to what extent protein alterations contribute to the increased Ca(2+)-responsiveness in human heart failure. METHODS: Isometric force and its Ca(2+)-sensitivity were studied in single left ventricular myocytes from non-failing donor (n=6) and end-stage failing (n=10) hearts. To elucidate which protein alterations contribute to the increased Ca(2+)-responsiveness isoform composition and phosphorylation status of contractile proteins were analysed by one- and two-dimensional gel electrophoresis and Western immunoblotting. RESULTS: Maximal tension did not differ between myocytes obtained from donor and failing hearts, while Ca(2+)-sensitivity of the contractile apparatus (pCa(50)) was significantly higher in failing myocardium (deltapCa(50)=0.17). Protein analysis indicated that neither re-expression of atrial light chain 1 and fetal troponin T (TnT) nor degradation of myosin light chains and troponin I (TnI) are responsible for the observed increase in Ca(2+)-responsiveness. An inverse correlation was found between pCa(50) and percentage of phosphorylated myosin light chain 2 (MLC-2), while phosphorylation of MLC-1 and TnT did not differ between donor and failing hearts. Incubation of myocytes with protein kinase A decreased Ca(2+)-sensitivity to a larger extent in failing (deltapCa(50)=0.20) than in donor (deltapCa(50)=0.03) myocytes, abolishing the difference in Ca(2+)-responsiveness. An increased percentage of dephosphorylated TnI was found in failing hearts, which significantly correlated with the enhanced Ca(2+)-responsiveness. CONCLUSIONS: The increased Ca(2+)-responsiveness of the contractile apparatus in end-stage failing human hearts cannot be explained by a shift in contractile protein isoforms, but results from the complex interplay between changes in the phosphorylation status of MLC-2 and TnI.

Effect of spectral flash on readaptation time.

The effects of an adapting flash of different colors on human vision were investigated with various flashes and target luminances. The readaptation time (RAT) was measured using optokinetic nystagmus elicited by a projected moving striped pattern in a hemisphere. The RATs were recorded from 26 subjects with a multichannel pen recorder. Two target luminances (1.1 X 10(-5) cd/m2 and 2.6 X 10(-5) cd/m2) and 12 flash wavelengths (449 nm, 456 nm, 468 nm, 477 nm, 498 nm, 502 nm, 520 nm, 565 nm, 580 nm, 591 nm, 622 nm, and 703 nm) were used. A spectral RAT curve was obtained, which showed that the chromatic response of RAT follows this order: green greater than blue greater than yellow greater than red. A larger influence of the variation of the target luminance on the RAT was demonstrated at shorter wavelengths. The results also showed that the energy density of the flash has a larger variation with the RAT in blue and green than in red.

[Occupational vitiligo caused by para-tertiary-butylphenol, a trias of vitiligo, hepatosis and struma]. / Berufsbedingte Vitiligo durch para-tertiär-Butylphenol, eine Trias von Vitiligo, Hepatose und Struma

In the period between 1956-1974 twelve cases of occupational vitiligo due to para-tertiary butylphenol were observed. In addition another 12 cases of vitiligo of other etiology occurred. Occupational vitiligo cannot be distinguished from ordinary vitiligo. 21 patients had, aside from their leukodermia a normal thyroid function, and 18 patients showed symptoms of chronic liver damage. The trias of vitiligo, hepatic disease and struma euthyreotica was noticeable. Autoimmunisation tests were positive in cases of vitiligo of unknown etiology. The localization of vitiligo may be compared to viscero-cutaneous reflexes.