Kinetic study of racemization of aspartyl residues in synthetic elastin peptides.

We previously reported that biologically uncommon D-aspartyl residues are present in sun-damaged skin from elderly people, possibly in elastin. Here, we report the kinetics of Asp racemization in model peptides corresponding to elastin sequences from exons 6 and 26. We estimated the activation energy (E) of racemization of Asp residues, the racemization rates (RR) at 37 degrees C and the time (t) required for the D/L ratio of Asp to approximate to 1.0 (D/L ratio of Asp=0.99) at 37 degrees C. For an exon 6 peptide, E=29.0 kcal/mol, RR=2.59 x 10(-2)/yr and t=101.0 yr. For an exon 26A peptide E=26.2 kcal/mol, RR=4.27 x 10(-2)/yr and t=61.3 yr; and for a second exon 26A peptide E=25.7 kcal/mol, RR=5.55 x 10(-2)/yr and t=47.0 yr. These results suggest that racemization of Asp residues in elastin could occur within a human life span. We propose that D-Asp could be a useful molecular indicators of aging.

Comparison of post-translational modifications of alpha A-crystallin from normal and hereditary cataract rats.

In order to investigate the relationship between lens opacities and the various modifications of lens proteins, we analyzed and compared the properties of lens proteins of 85-day old normal Wistar rats and the hereditary cataract model, ICR/f rats. The present study identified many differences between normal and mutant lens proteins. In the ICR/f mutant rats, the relative amounts of gamma-crystallin decreased and high molecular weight (HMW) protein increased. Racemization and isomerization of Asp-151 of alpha A-crystallin was observed in the mutant ICR/f rats, and Met-1 of alpha A-crystallin was oxidized to methionine sulfoxide. These modifications were not found in the age-matched normal rats. These tendencies are consistent with aged and cataractous human lenses.

[An experimental study on the influence of surgical injuries to the internodal conduction tracts on supraventricular arrhythmias associated with intraatrial operations].

In this study, the relationship between injuries to the internodal conduction tracts and supraventricular dysrhythmias was investigated in 30 adult mongrel dogs. Conduction time from the SA node to the vicinity of the AV node and isochronous activation sequences were examined by endocardial mapping during cardiopulmonary bypass before and after surgical injury to the anterior, middle or posterior internodal tracts. Prior to injury, the impulse from the SA node was conducted rapidly along the crista terminalis and the anterior arch of the crista. Only when the anterior internodal tract was injured, regardless of the location and the numbers of injuries, the conduction time from the SA node to the vicinity of the AV node was prolonged significantly, about 15 msec. After sequential division of the tracts, the cardiac rhythm was observed: Division of the anterior and posterior internodal tracts, or all the three tracts resulted in the absence of sinus rhythm and the appearance of brady-arrhythmias such as AV junctional rhythm in about fifty percent of the dogs. These findings suggest the importance of preservation of the anterior or posterior internodal tracts during intraatrial operation.

Electrophysiologic study of dysrhythmias after atrial operations in dogs.

Experiments were conducted with 159 dogs to investigate the mechanism of persistent dysrhythmias clinically encountered after atrial-level operations. Those found after incisions to the internodal pathways (INPs) of the right atrium were analyzed using cardiac mapping in an anesthetized or extracorporeally perfused state. Longitudinal incisions of the posterior INP often allowed inducible sustained atrial flutter, with circus movement of excitation around the right atrium near the tricuspid orfice. Sustained atrial flutter thus produced was modified in cycle length by coexisting division of the middle INP but inhibited by that of the anterior INP. Its incidence increased at chronic stage, with marked cicatricial changes. The disrupted anterior INP markedly prolonged conduction time to the atrioventricular node and A-H interval compared with the other disruptions. Persistent atrioventricular junctional rhythm developed in about 50% of the animals after disruption of all three INPs or anterior and posterior INPs; division of the anterior INP was the common potent factor, although no single blocked INP produced persistent junctional rhythm. Our results support the "summation theory." The incidence of junctional rhythm and hypoxia of the sinoatrial node (flow rate of less than 10 mL.100 g-1.min-1) were markedly enhanced by coexisting blockade of atrial feeding arteries in addition to division of the anterior INP. In conclusion, massive posterior INP disruption is a potent anatomic substrate in producing sustained atrial flutter, middle INP division a modifier, and anterior INP division an inhibitor. Division of the anterior INP is a potent anatomic substrate in producing junctional rhythm, and hypoxia involving the sinoatrial node reacts as its synergic factor.

[A study of valve replacement in the elderly].

From March 1982 to June 1989, 42 valve replacements were performed in 41 consecutive elderly patients (age 60 years and older, mean age 76.0 years). Main etiology of their diseases is calcific AS 7 (4: bicuspid valve), degenerative AR 4, rheumatic AS/AR 5, AAE 2, MR due to MVP or chordal rupture 13, rheumatic MS/MR 13. Operative methods are AVR 14, MVR 22, DVR 6. Cumulative follow-up was 99.2 patient-years (mean 30.5 months). Operative deaths were 2 cases (4.8%) due to left ventricular ruptures after MVR. There were 4 late deaths (9.5%). Actuarial survival rate at 7 years was an overall of 70 +/- 12%. Most common early postoperative complication was AV conduction disturbances. Continuous III degrees AV Block 1, transient III degrees AVB 3 and transient II degrees AVB 1 occurred in 7 calcified AS cases with calcific deposition to the attachment of anterior half of the noncoronary cusp. Valve related late complications were thromboembolism (7%/patient-year) and prosthetic valve endocarditis (3%/patient-year). Actuarial incidence of event free survival among hospital survivors at 7 years was 55 +/- 11%. It is our belief that surgical treatment for elders should be rather positively done when medical therapy has not met desired effects, under well evaluation of senile weakness for each case.