Crystal structures of two H-2Db/glycopeptide complexes suggest a molecular basis for CTL cross-reactivity.

Two synthetic O-GlcNAc-bearing peptides that elicit H-2Db-restricted glycopeptide-specific cytotoxic T cells (CTL) have been shown to display nonreciprocal patterns of cross-reactivity. Here, we present the crystal structures of the H-2Db glycopeptide complexes to 2.85 A resolution or better. In both cases, the glycan is solvent exposed and available for direct recognition by the T cell receptor (TCR). We have modeled the complex formed between the MHC-glycopeptide complexes and their respective TCRs, showing that a single saccharide residue can be accommodated in the standard TCR-MHC geometry. The models also reveal a possible molecular basis for the observed cross-reactivity patterns of the CTL clones, which appear to be influenced by the length of the CDR3 loop and the nature of the immunizing ligand.

Effect of serine O-glycosylation on cis-trans proline isomerization.

In order to examine the ability of an O-glycosylated serine residue preceding proline to stabilize a cis amide conformation in a fashion similar to that observed with aromatic amino acid residues, we prepared a series of glycosylated analogs of a small linear peptide which we have previous reported to contain a cis conformation of an amide bond between tyrosine and proline. The glycopeptides were prepared by incorporating glycosylated N alpha- (fluoren-9-yl) methoxycarbonyl (Fmoc) amino acids into a standard solid phase peptide synthesis protocol. The peptides and glycopeptides were analyzed using 2-dimensional NMR spectroscopy. Unlike the case where the residue preceding proline was tyrosine, no signals corresponding to a cis proline conformation were detected in the spectra of the two glycopeptides containing serine O-glycosylated with either beta-linked N-acetyl glucosamine or alpha-linked N-acetyl galactosamine in the position preceding proline.

The Cornell Medical Index as a predictor of health in a prospective cardiovascular study in Taiwan.

As part of a prospective study of cardiovascular disease (CVD) in middle-aged Chinese men in Taiwan, 1820 Chinese males, aged 40--59 years, from the middle and upper socioeconomic classes, were characterized at study entry by a history and physical examination with particular reference to cardiovascular status and by the Cornell Medical Index (CMI). Disease occurrence in the 1820 participants was observed over a seven-year period. Comparison of CMI test performance by specific disease incidence categories showed no group mean differences. In examining total disease occurrence in the form of prevalence, incidence of major morbidity and mortality and no illness occurrence, however, the authors found significant differences using the CMI. The highest scoring group on the CMI was non-survivors who had chronic illness at study entry, followed closely by those subjects who also had a chronic illness at study entry but who survived. Scoring lower than those with chronic illness at study entry, but significantly higher than the group remaining disease-free, were the subjects who incurred a major illness event and/or developed a chronic disease. The authors conclude that the CMI diffentiated between those who stayed healthy and those who died or incurred a major illness in this study population. Therefore, this study supports the use of the CMI as a measurement of general health, as well as a predictor of future health status, and suggests that it may be used in other cultures than the one in which it was developed.

Near-maximal exercise responses in health and disease in middle-aged Chinese men.

Cardiovascular, aerobic, and ventilatory responses to a multistage treadmill test of near-maximal exercise were determined in 208 middle-aged Chinese men to provide standards in health, and to identify differences in relation to hypertension, coronary heart disease, chronic pulmonary disease and stroke. Except in patients with hypertension, exercise duration was shortened and symptom-limited oxygen uptake was reduced in all disease groups. Unexpectedly, stroke patients exhibited lower heart rate responses to exercise than did patients with coronary heart disease.

Polarcardiographic criteria for myocardial infarction in Chinese men.

Polarcardiograms (PCG) derived from xyz leads of the Frank electrocardiogram (ECG) were recorded in the supine position in 1264 initially healthy middle-aged Chinese men who had been under continuing medical surveillance and were re-examined seven years later. Polarcardiographic criteria for myocardial infarction (MI) were demonstrated in 97 men (7.7%), but only 15 of them showed diagnostic Q waves in the electrocardiogram (ECG). Polarcardiographic criteria for MI were independent of age, but ranged from 4.3% in 464 apparently normal men to 38% in 21 men with manifestations of ischemic heart disease. The possible association of polarcardiographic criteria and a history of smoking was limited to those with clinical evidence of heart disease. The "false positive" rate of 4.3% in clinically normal men was similar to that reported in younger Canadians and in Cretan population samples.

Seven-year follow-up of cardiovascular study and maximal exercise of Chinese men.

A seven-year follow-up in 1973 of a prospective cardiovascular study of 1820 initially, healthy, middle-aged Chinese men of 40-59 years of age identified 1745 (95.9%) known survivors, 49 (2.7%) interim deaths, and 26 (1.4) who could not be traced. Of the survivors, 1462 (83.8%) were re-examined, 292 (16.7%) had another treadmill test of maximal exercise, and 283 (16.2%) failed to return for re-examination. On the basis of interim surveillance of hospital admissions, questionnaires and re-examination, a greater incidence of noncardiovascular events (338 or 18.6%) than evidence of cardiovascular disease (220 or 12.1%) was found while the majority (1021 or 56.1%) remained healthy. Total mortality was 0.29 for men under 50 and 0.76 per 100 person-years for men of 50 or more years of age. Only nine, or 18.4% of the deaths were due to cardiovascular causes, and unexpectedly for this population sample, only three were attributed to stroke. When cardiovascular morbidity was related to presence of ST depression after maximal exercise, to hypertension at rest by WHO criteria, to both findings, or to absence of either on initial intake examination, incidence increased from 2.3% for NEITHER group, to 5.7% for ST group, to 11.9% for HT group, and to 25.0% for BOTH groups. Re-examination revealed more evidence of cardiovascular disease than did surveillance of hospital admissions. Additional to effects of aging and mild adiposity, longitudinal changes in blood pressure and ST depression, increasing in the NEITHER group, but less frequent in the other groups, showed some evidence of regression toward the mean, as well as emerging disease and the confounding effects of uncontrolled treatment of hypertension in many. The potential for prediction of subsequent cardiovascular morbidity or mortality appeared stronger for hypertension than for postexertional ST depression, although the two were additive in this population, which is more prone to hypertension and stroke but now is developing clinical manifestations of coronary heart disease more frequently.