A genome-wide association study of periodontitis in a Japanese population.

Periodontitis is a multifactorial disease in which bacterial, lifestyle, and genetic factors are involved. Although previous genetic association studies identified several susceptibility genes for periodontitis in European populations, there is little information for Asian populations. Here, we conducted a genome-wide association study and a replication study consisting of 2,760 Japanese periodontitis patients and 15,158 Japanese controls. Although single-nucleotide polymorphisms that surpassed a stringent genome-wide significance threshold (P < 5 × 10(-8)) were not identified, we found 2 suggestive loci for periodontitis: KCNQ5 on chromosome 6q13 (rs9446777, P = 4.83 × 10(-6), odds ratio = 0.82) and GPR141-NME8 at chromosome 7p14.1 (rs2392510, P = 4.17 × 10(-6), odds ratio = 0.87). A stratified analysis indicated that the GPR141-NME8 locus had a strong genetic effect on the susceptibility to generalized periodontitis in Japanese individuals with a history of smoking. In conclusion, this study identified 2 suggestive loci for periodontitis in a Japanese population. This study should contribute to a further understanding of genetic factors for enhanced susceptibility to periodontitis.

Lipoprotein(a) is a potential coronary risk factor.

Lipoprotein(a) (Lp(a)) is recognized as a new coronary risk factor, but few studies have quantitatively assessed the relationship of serum Lp(a) levels with other coronary risk factors in many patients undergoing coronary cineangiography. Seventeen coronary risk factors were quantified (i.e., age, gender, hypertension, impaired glucose tolerance, cerebrovascular accident, hyperuricemia, smoking, family history of ischemic heart disease (IHD), history of hyperlipidemia, Lp(a), total cholesterol, high density lipoprotein (HDL)-cholesterol, triglyceride, low density lipoprotein-cholesterol, apolipoproteins(apo)A-I,B, E) to determine their relationship with the numbers of involved coronary vessels using multiple regression test in 1,006 patients who underwent coronary cineangiogram (280 non-IHD patients: 144 men, 136 women; 726 IHD patients: 460 men, 266 women; age 16-84 years, mean 60.5+/-0.3). Multiple regression test indicated R = 0.506 and items that showed high beta weight and significant p level were age, Lp(a), impaired glucose tolerance, total cholesterol, cerebrovascular accidents, HDL-cholesterol, smoking, gender, family history of IHD, and apo-A-I (0.221, p<0.001; 0.174, p<0.001; 0.616, p<0.001; 0.138, p<0.001; 0.122, p<0.001; -0.12, p<0.001; 0.092, p<0.01; 0.091, p<0.01; 0.067, p<0.05; -0.065, p<0.05; respectively). It was concluded that Lp(a) is an independent, potential, and modifiable coronary risk factor, and that reduction of serum Lp(a) is important in the clinical management of patients with IHD.

Microvascular sites and mechanisms responsible for reactive hyperemia in the coronary circulation of the beating canine heart.

Our aim was to elucidate the site and mechanism responsible for reactive hyperemia in coronary circulation. In in vivo beating canine hearts, microvessels of the left anterior descending coronary artery (LAD) were observed through a microscope equipped with a floating objective. Flow velocity of the LAD was measured with a suction-type Doppler probe. The LAD was occluded for 20 or 30 seconds and then released, and reactive hyperemia was observed before and after 8-phenyltheophylline (7.5 mg/kg i.v.) or glibenclamide (200 micrograms/kg into the LAD) infusion. During the occlusion, only arterial microvessels smaller than 100 microns in diameter dilated. Dilation of those vessels was partially attenuated by 8-phenyltheophylline and completely abolished with glibenclamide. In the early phase of reactive hyperemia, all arterial microvessels dilated, and the magnitude of peak dilation was greater in vessels smaller than 100 microns compared with those larger than 100 microns. Vasodilation during reactive hyperemia ceased within 60 seconds in vessels smaller than 100 microns but was sustained for more than 120 seconds in those larger than 100 microns. 8-Phenyltheophylline did not change peak dilation of arterial microvessels but reduced dilation after the peak. Glibenclamide remarkably attenuated dilation of all arterial microvessels in the whole phase of reactive hyperemia. These results indicate that all arterial microvessels are responsible for reactive hyperemia after coronary artery occlusions of 20-30 seconds, but there is greater participation of vessels smaller than 100 microns in the early phase of reactive hyperemia. Dilation of vessels larger than 100 microns assumes an important role in the later phase. ATP-sensitive K+ channels mediate dilation of arterial microvessels both in brief ischemia and reactive hyperemia.

Phasic blood flow velocity pattern in epimyocardial microvessels in the beating canine left ventricle.

We quantitated phasic epimyocardial microcirculatory coronary blood flow velocity patterns in the beating left ventricle. Using a newly developed floating objective and high-speed cinematography, red cell velocities in small arterioles, capillaries, and small venules and microvascular diameters in the superficial layer of the epimyocardium of beating left ventricle were determined throughout the entire cardiac cycle in open-chest anesthetized dogs. Heart rate was maintained at 140 beats/min by means of left atrial pacing. Peak red cell velocity was observed in midsystole in small arterioles and capillaries, and in late systole in small venules. Abrupt decline in red cell velocity and, in many cases, a momentary cessation or reverse of flow, was observed in these microvessels during the pre-ejection period. The internal diameter of small venule was increased in late systole, while that of small arteriole remained almost constant during the cardiac cycle. Furthermore, in these epimyocardial microvessels, a higher percentage of the total area under the velocity curve occurred during the ejection phase; 51% in small arterioles, 43% in capillaries, and 40% in small venules. These findings indicate that the phasic blood flow pattern is markedly different in the subepimyocardial microvessels from that in the large epicardial artery and the septal artery. During vasodilation following dilazep (50 micrograms/kg, i.v.), an adenosine potentiator, red cell velocity increased throughout the entire cardiac cycle in epimyocardial microvessels with significant increases in the total area under the velocity curves accompanied by significant dilation of the arterioles. The present data will provide information useful in predicting or simulating transmural differences in the phasic blood flow pattern.

Effect of diltiazem, a calcium antagonist, on myocardial ischemia.

In line with studies on the metabolism of the ischemic myocardium, the effectiveness of diltiazem hydrochloride, a potent calcium antagonist, in reducing the effects of ischemia was evaluated. Nonischemic and ischemic tissue samples were examined in two groups of dogs--Group I, dogs receiving no drug and killed after 60 minutes of regional ischemia, and Group II, dogs given diltiazem after 10 minutes of ischemia and killed 50 minutes later. Administration of diltiazem proved beneficial in several ways: The decrease in adenosine-5'-triphosphate in the ischemic region was halved, inhibition of anaerobic glycolysis was reduced, tissue levels of lactic acid and free fatty acids were lowered and the contractility of glycerinated heart muscle fibers was improved. However, administration of the drug did not influence mitochondrial function. Mitochondrial oxygen consumption and respiratory control were reduced by equal amounts in both groups, as was mitochondrial calcium ion binding. These observations demonstrate that diltiazem is capable of minimizing the consequences of acute ischemic, although the beneficial effects do not extend to all aspects of myocardial metabolism.

Bile duct carcinoma associated with an anomaly in the bile duct.

This paper reports a case of bile duct carcinoma associated with an extra-hepatic bile duct anomaly. In the present case, the anomaly induced an uncorrect preoperative diagnosis and obliged to change the surgical procedures during operation. A correct preoperative diagnosis was difficult to make in the present case, when the anomaly in the biliary system was not kept in mind.

Interaction in culture between mouse ascites hepatoma (MH-134) cells and lymphoid cells of isologous mice.

Thymocytes or lymphocytes of mesenteric lymph nodes were obtained from mice bearing subcutaneously mouse ascites hepatoma MH-134 for 5 to 40 days. These lymphoid cells were added into the cultures of MH-134 cells. Morphological changes of cells in the mixed cultures were observed by time-lapse cinemicrography for the period of 4 weeks. Lymphoid cells were phagocytosed by MH-134 cells, and, in most cases, the tumor cells did not undergo any damage due to the phagocytosis. The exceptional cases were as follows: When MH-134 cells were mixed with thymocytes from mice bearing MH-134 tumor for 5 days, MH-134 cells phagocytosed thymocytes but some of them died later. In the mixed cultures of MH-134 cells and thymocytes or mesenteric lymph node lymphocytes from mice bearing MH-134 for 14 or 15 days, MH-134 cells phagocytosed lymphoid cells but died later by the burst of cytoplasm. By the burst many lymphoid cells phagocytosed appeared from the broken cytoplasm of MH-134 cells and, in some cases, the lymphoid cells looked to be alive. These findings suggest the possibility that lymphoid cells attack tumor cells not only from the cell surface but also from the inside being phagocytosed by tumor cells.

Interaction in culture between mouse ascites mammary carcinoma (MM2) cells and lymphoid cells of isologous mice.

MM2 cells, ascitic tumor originated from spontaneous mammary carcinoma of C3H/He mouse, were mix-cultured with lymphoid cells of thymus or mesenteric lymph nodes from isologous animals of the same sex. The interaction in culture between these cells was examined by time-lapse cinemicrography. In single culture, thymocytes, mesenteric lymph node lymphocytes and MM2 cells were kept for 7 days with little change in cell population. Lymphocytes of both sources showed a marked decrease in cell number when cultured together with MM2 cells, being evidently phagocytosed by MM2 cells. Lymphocytes from MM2-bearing mice or mice sensitized with deoxycholate-extracted MM2 antigen were also all phagocytosed. MM2 cells exhibited no sign of damage or degeneration due to the phagocytosis. Thymocytes were not phagocytosed by histiocytes obtained from ascitic fluid 3 days after i.p. injection of 5% starch suspension. Phagocytosis of erythrocytes or lymphoid cells from spleen by MM2 cells was not detected.