Preheparin serum lipoprotein lipase mass is negatively related to coronary atherosclerosis.

In preheparin serum, there exists lipoprotein lipase (LPL) mass with little activity. The clinical significance of this preheparin serum LPL mass (preheparin LPL mass) is unclear. We studied the levels of preheparin LPL mass in patients with coronary atherosclerosis, comparing the results with those in healthy men. We also evaluated the correlation between preheparin LPL mass and the severity of coronary atherosclerosis by comparing with other risk factors such as age, smoking, family history, hypertension, hyperuricemia, diabetes mellitus, total cholesterol, triglyceride, high density lipoprotein-cholesterol and body mass index. The subjects, 70 men presenting with symptoms of coronary artery disease, underwent coronary angiographic examination. Significant narrowness was defined as > or = 75%. Control group comprised 77 men who had annual health checks and showed no abnormal findings. Preheparin LPL mass in the stenosis group was lower than normal coronary group and also than the control group. Multivariate analysis showed that preheparin LPL mass had the highest t-value (-2.53) for the number of lesions among the risk factors listed above. These results suggest that low preheparin LPL mass may be deeply involved in the progression of coronary atherosclerosis.

Two human papillomavirus DNAs molecularly cloned from a patient with epidermodysplasia verruciformis: restriction maps.

Two distinct human papillomavirus (HPV) DNAs (MY-1 and MY-2) were molecularly cloned from the benign skin lesions of a patient with epidermodysplasia verruciformis. The restriction map of MY-1 was the same as that of HPV 3a. The map of MY-2 appeared to be different from those of any HPVs reported in the literature. MY-2 did not cross-hybridize with MY-1 or the DNAs of HPV types 1, 2 and 4 under stringent conditions.

Molecular characteristics and physical state of human papillomavirus DNA change with progressing malignancy: studies in a patient with epidermodysplasia verruciformis.

In order to establish the role of human papillomavirus (HPV) in carcinogenesis of epidermodysplasia verruciformis (EV), the presence, the molecular characteristics and the physical state of HPV DNA in a benign lesion, a primary carcinoma and a metastatic carcinoma developing in the same EV patient were studied and compared. Of the 2 HPV DNAs isolated from benign macular lesions, only one (a subtype of HPV 5) was detected in both primary and metastatic tumors. Only one normal species of viral DNA molecule was detected in the benign lesion, whereas most, if not all, viral DNA molecules present in the carcinoma (both primary and metastatic) were aberrant ones. The major viral DNA molecule in the primary carcinoma was a large HPV DNA with duplicated 40% subgenomic segments, and was present as free episomes. The major viral DNA molecule in the metastatic carcinoma was the 40% subgenomic segment itself, lacking the remaining 60% segment of the viral genome, and was integrated within cellular DNA. Thus, HPV DNA was present in tumors at any stage of malignancy, and its molecular characteristics and physical state changed not only with the development but also with the enhancement of malignancy, consistently conserving its defined 40% subgenomic segment as the predominant viral sequences. Our results suggest that HPV 5 may be actually involved in carcinogenesis in EV patients.

A subtype of human papillomavirus 5 (HPV-5b) and its subgenomic segment amplified in a carcinoma: nucleotide sequences and genomic organizations.

A subtype of human papillomavirus 5 (HPV-5b) is closely associated with carcinomas in the disease epidermodysplasia verruciformis (EV). The complete genome was cloned from virus particles in benign lesions of a patient with EV and sequenced: it was 7779 nucleotides long and consisted of six open reading frames (ORFs) (E6, E7, E1, E2, E4, and E5) in the early region, three ORFs (L2, L3, and L1) in the late region, and a noncoding region, all existing on one DNA strand. The 40% segment of the HPV-5b genome specifically amplified in carcinomas was cloned from a primary carcinoma of the same EV patient and sequenced: it was 3143 nucleotides long and corresponded to a segment of the original HPV-5b genome containing the entire sequences of E6, E7, and the noncoding region and portions of E1 and L1. Compared to the whole genomic DNA, no mutations were detected in this probable malignancy-associated viral subgenomic segment cloned from carcinoma. These results suggest that amplification of the viral segment containing E6, E7, and the noncoding region may play a role in the malignant conversion of HPV-5b-infected benign lesions and that mutations in these genes or regions are not necessarily required.

Clinical significance of preheparin serum lipoprotein lipase mass in coronary vasospasm.

The present study investigated the clinical significance of preheparin serum lipoprotein lipase (LPL) mass in coronary vasospasm by examining its relationship with the acetylcholine-induced coronary artery response in patients without angiographically demonstrable atherosclerotic coronary artery disease (CAD). The subjects were 39 men who had suspected CAD and who underwent coronary angiography. Coronary vasospasm was defined as a marked luminal narrowing or total occlusion provoked by the intracoronary administration of acetylcholine. Preheparin LPL mass was lower (p<0.05) in 25 subjects in whom vasospasm was induced by the acetylcholine provocation test than in the 14 subjects with a negative response. As regards preheparin LPL mass, the subjects with multiple vessel spasm had significantly low concentrations (p<0.05) compared with single vessel spasm, although serum lipid levels were not significantly different. Multiple regression analysis revealed only preheparin LPL mass had a significant absolute t-value (2.016) among the coronary risk factors. Low preheparin LPL mass is interpreted as reflecting an impaired acetylcholine-induced coronary relaxation in coronary vasospasm and preheparin LPL mass may be useful as a marker of early stage coronary atherosclerosis that is not detectable by angiography.

[Effects of repetitive myocardial ischemia on collateral circulation, ST deviation and epicardial wall motion].

The effects of repetitive myocardial ischemia on collateral circulation, ST deviation and epicardial wall motion were examined in 12 patients undergoing percutaneous transluminal coronary angioplasty (PTCA) for single left anterior descending artery disease. Rentrop collateral filling grade was assessed using contrast injection to the contralateral artery during the first and final episodes of coronary occlusion. ST deviation was measured by intracoronary electrocardiography. Epicardial wall motion (%pre PTCA) was measured by guide wire motion analysis according to the centerline method. Collateral filling grade was assessed 30 sec after balloon inflation. The ST segment and the epicardial wall motion were measured 60 sec after balloon inflation and deflation, respectively. There was no change in the collateral filling grade between the first and final episode of coronary occlusion. Patients with collateral filling grade I (R-I group, n = 4), II (R-II group, n = 3) and III (R-III group, n = 5) during coronary occlusion showed mean ST segment shifts of 13.2, 9.4, and 0.9 mm, respectively, and mean epicardial wall motion of 41.4%, 67.2%, and 78.5%, respectively. The collateral filling grade correlated with ST deviation and epicardial wall motion, and there was a significant correlation between epicardial wall motion and ST deviation (r = -0.67). Comparison of the R-I group or severe ischemia (n = 4) and the R-III group or slight ischemia (n = 4) during coronary occlusion for the fourth time showed the effect of preconditioning was obtained in R-I group. More R-III group patients than R-I group had hyperkinetic epicardial wall motion during coronary reperfusion. Stunned myocardium was demonstrated in both R-I group and R-III group patients. Epicardial wall motion was poorer in the R-I group than R-III group. We concluded the following: There is no change in the grade of collaterals during repetitive coronary occlusion, and there is a relationship between the grade of collateral and degree of myocardial protection; there is good correlation between ST segment and epicardial wall motion; ischemic preconditioning is obtained during repetitive severe myocardial ischemia; recovery from brief episodes of slight myocardial ischemia is associated with hyperkinesia of epicardial wall motion; the reduction of stunned myocardium is related to the degree of premyocardial ischemia; preconditioning is sufficient to cause myocardial stunning, but myocardial stunning is insufficient to cause preconditioning.

Preventive effects of an antiallergic drug, pemirolast potassium, on restenosis after percutaneous transluminal coronary angioplasty.

BACKGROUND: We recently confirmed that pemirolast potassium, an antiallergic agent, markedly inhibits migration and proliferation of vascular smooth muscle cells. It has also been reported that pemirolast inhibits intimal hyperplasia in animal experiments. METHODS AND RESULTS: To elucidate the preventive effects of pemirolast on restenosis after percutaneous transluminal coronary angioplasty (PTCA), 227 patients were enrolled in this prospective, randomized trial. A total of 205 patients who were compatible with the protocol were analyzed (pemirolast group, 104 patients with 140 lesions; control group, 101 patients with 133 lesions). Patients in the pemirolast group received 20 mg/d of pemirolast from 1 week before PTCA until the time of follow-up angiography (4 months after PTCA). Angiographic restenosis was defined as diameter stenosis >/=50% at follow-up. Restenosis rates were significantly lower in the pemirolast group than in the control group (24.0% vs 46.5% of patients, 18.6% vs 35.3% of lesions, P <.01, respectively). During 8 months of follow-up, there were no coronary events (death, myocardial infarction, coronary artery bypass surgery, or repeated PTCA) in 81.7% of the pemirolast group and in 63.4% of the control group (P =.013). CONCLUSIONS: This study suggested that pemirolast would be useful in the clinical setting to prevent restenosis after PTCA.

Percutaneous dye image cardioscopy for detection of endocardial lesions.

Endocardial lesions are caused not only by inflammatory processes but also by myocardial ischemia, resulting in endocardial thrombosis and cerebral embolism. We deviced a method for direct visualization of endocardial damages by a novel dye image cardioscopy with Evans blue and examined its feasibility in patients with heart disease. The dye was injected into the left ventricle before and after endomyocardial biopsy. Endocardial surface was stained in dark blue in 63% of patients with angina pectoris before biopsy. After biopsy, the biopsied portions were stained in blue in all. The results indicate that endocardium is damaged even in apparently intact LV in patients with ischemic heart disease and that endomyocardial biopsy causes severe endocardial damages.

Angioscopic evaluation of stabilizing effects of bezafibrate on coronary plaques in patients with coronary artery disease.

Background Since long-term administrations of anti-hyperlipidemic agents result in reduction in % stenosis or increase in minimum lumen diameter (MLD) of stenotic coronary segments, it is generally believed that anti-hyperlipidemic agents stabilize vulnerable coronary plaques. However, recent pathologic and angioscopic studies revealed that vulnerability of coronary plaques is not related to severity of stenosis and the rims rather than top of the plaques disrupt, and therefore, angiography is not adequate for evaluation of vulnerability.Angioscopy enables macroscopic pathological evaluation of the coronary plaques. Therefore, we carried out a prospective angioscopic open trial for evaluation of the stabilizing effects of bezafibrate on coronary plaques.Methods From April, 1997 to December, 1998, 24 patients underwent coronary angioscopy of the plaques in the non-targeted vessels during coronary interventions and 6 months later. The patients were divided into control (10 patients, 14 plaques) and bezafibrat (14 patients, 21 plaques) groups. Oral administration of bezafibrate (Bezatol SR, 400mg/day) was started immediately after the interventions and was continued for 6 months. The vulnerability score was determined based on angioscopic characteristics of plaques and it was compared before and 6 months later.Results Six months later, vulnerability score was reduced (from 1.6 to 0.8;p < 0.05) in bezafibrate group and unchanged (from 1.4 to 1.3; NS) in control group. In bezafibrate group, the changes in vulnerability score was not correlated with those in % stenosis or MLD. Conclusion The results indicate that bezafibrate can stabilize coronary plaques.