Clinical significance of triglyceride-rich lipoproteins in metabolic syndrome

Increase in triglyceride (TG) -rich lipoproteins is one of the symptoms clustered in metabolic syndrome and is associated with increased plasma free fatty acid level derived from central obesity and insulin resistance. Increase in triglyceride (TG) -rich lipoproteins is also related to several coronary risk factors such as remnant hyperlipidemia, decreased HDL-cholesterol, elevated small dense LDL, postprandial hyperlipidemia, and hypercoagulability. The first line of treatment for hypertriglyceridemia is the modification of individual life-style, among which, restriction of over-eating and practice of regular exercise are both essential. The consideration of dietary composition, not only the quantity but also the quality of nutrients, such as fat and carbohydrate, and behavior toward diet are also important to manage abnormal lipid profile. Statins, fibrates, nicotinic acid derivatives, and EPA are the drugs recommended for the treatment of dyslipidemias in metabolic syndrome.     

Fine assignment of beta-hexosaminidase A alpha-subunit on 15q23-q24 by high resolution in situ hybridization

Tay-Sachs disease results from mutation in the gene encoding beta-hexosaminidase A alpha-subunit. Although some reports have suggested the locus on 15q, we tried to determine the finer gene locus using high resolution in situ hybridization. cDNA probe, p beta H alpha-5, containing the full-length sequence for the enzyme subunit, was 3H-labeled within 1-4 x 10(7) cpm/micrograms of cDNA by nick-translation. After molecular hybridization and autoradiography, prometaphases were G-banded by Hoechst 33258, UV-exposure and Giemsa. A total of 227 silver grains on chromosomes within 115 prometaphase spreads were analyzed. The region 15q23-q24 had 27 grains, corresponding to 11.9% of the total grains and to 77.1% of the grains on chromosome 15. 20.9% of prometaphases were observed with a grain at 15q23-q24. According to several previous reports, the shortest region of overlap (SRO) of the locus has been 15q22-q25.1. Here we have assigned the gene locus to the narrower region 15q23-q24 by high-resolution in situ hybridization, which is one of the most powerful strategy for the completion of human gene map.     

Differential expression and cellular localization of activin and inhibin mRNA in the rainbow trout ovary and testis

An inhibin cDNA from rainbow trout consisted of 1305 bp, which coded for 352 amino acid residues. The deduced amino acid sequence of mature inhibin was 50 to 60% identical to mammalian sequences. Distribution of inhibin alpha and activin beta A and beta B in different ovarian and testis compartments was studied in rainbow trout by in situ hybridization with complementary RNA probes. In testis tissue, inhibin alpha and activin beta A and beta B were expressed only in the testicular interstitia between the seminal lobules, where Sertoli cells and Leydig cells are distributed. The localizations and intensities of the reactions were constant throughout the maturation of the testis. Within ovarian tissue, the theca cell layers of follicles showed strong reactions of Dig-labeled antisense mRNA probes hybridizing against inhibin alpha and activin beta A and beta B in all samples over the same sampling period. In regressing oocytes, a positive reaction was observed in the granular cell layer of the follicles.     

Association of Gln222Arg polymorphism in the deoxyribonuclease I (DNase I) gene with myocardial infarction in Japanese patients.

AIMS: We have recently reported that serum deoxyribonuclease I (DNase I) activity, which may be involved in apoptosis, increases abruptly in the early phase of acute myocardial infarction (MI) [Kawai Y, Yoshida M, Arakawa K, Kumamoto T, Morikawa N, Masamura K, Tada H, Ito S, Hoshizaki H, Oshima S, Taniguchi K, Terasawa H, Miyamori I, Kishi K, Yasuda T. Diagnostic use of serum deoxyribonuclease I activity as a novel early-phase marker in acute myocardial infarction. Circulation 2004;109:2398-2400]. Death of vascular smooth muscle cells, in part because of apoptosis, is postulated to heighten susceptibility to disruption of vulnerable plaque, resulting in onset of MI. The present study evaluated the possibility that Gln222Arg polymorphism of the DNase I gene may be one of the factors involved in predisposition to MI. METHODS AND RESULTS: We assessed 611 Japanese patients: 311 with MI and 300 with stable angina pectoris (AP). Three common phenotypes determined by two common codominant alleles, DNASE1*1 and *2, whose corresponding gene products exhibit different properties, were found in these patient groups. The prevalence of DNASE1*2 was significantly higher in patients with MI than in those with AP (0.543 vs. 0.428, P < 0.001), being confirmed by phenotyping of the second study population. Multiple logistic regression analysis showed that the odds ratio of DNASE1*2 was 1.51 [95% confidence interval (CI) 1.04-2.18]. The association of the DNASE1*2 allele with MI was statistically significant, being independent of other conventional risk factors. CONCLUSION: Our data demonstrate that Gln222Arg polymorphism in the DNase I gene is associated with MI in the Japanese patients.