Left Ventricular Mass Regression After Implantation of St. Jude Medical Cardiac Valves in Small Aortic Roots

In this study, we analyzed the extent of regression of left ventricular hypertrophy in patients who received small St. Jude Medical (SJM) aortic valves and compared the results with those of another group receiving larger valves. Eighty-eight patients received either 19 or 21 mm valves (Group 1, 25 patients) or either 23 or 25 mm valves (Group 2, 53 patients). Echocardiographic studies were done before the operation and 5 years postoperatively. At follow-up a significant reduction in the left ventricular mass was found for both patient groups (p < 0.0001). Doppler echocardiography derived pressure gradients for both groups were obtained during the follow-up period. As expected, the patients in Group 1 had higher peak pressure gradients than did those in Group 2. However, there was no significant difference between the 2 groups or any significant correlations between peak pressure gradients and body surface area (BSA). Actuarial survival was 84.7% at 15 years for Group 1 and 85.9% at 17 years for Group 2. Actuarial freedom from valve related events was 91.4 % at 15 years for Group 1 and 82.7% at 17 years for Group 2. There was no significant difference in survival or valve related event free curves between the 2 groups. After implantations of SJM valves in small aortic roots, significant left ventricular mass regression was obtained, and the results were comparable to those for valves of other sizes. The long-term performance of aortic valve replacement with small valves was satisfactory as judged by improvement in the functional class of patients and survival statistics, the durability of the prosthesis, and valve related morbidity comparable to that of valves of other sizes.     

Preparation and Properties of Thyroxine-Binding Alpha Globulin (TBG)

Thyroxine-binding alpha globulin (TBG) in human serum was isolated from Cohn fractions IV-5,6 and IV-4 by (1) chromatography on carboxymethyl (CM) cellulose, (2) gel filtration on Sephadex G-200, (3) chromatography on diethylaminoethyl-Sephadex, (4) a novel procedure of "double-gel" electrophoresis, and (5) preparative polyacrylamide gel electrophoresis. The protein was homogeneous by analytical disc gel electrophoresis, immunoelectrophoresis, and ultracentrifugal analyses (sedimentation velocity and sedimentation equilibrium), and after addition of thyroxine-(125)I showed a constant specific radioactivity on polyacrylamide electrophoresis. The sedimentation and diffusion coefficients were s(20, w), 3.0 x 10(-13) sec, and D(20, w), 8.05 x 10(-7) cm(2).sec(-1), and the molecular weight obtained by sedimentation equilibrium was 36,500. Gel filtration studies on Sephadex G-200 demonstrated that the protein had the same elution volume as that of native TBG in serum, apparently excluding the possibility of a subunit of the native protein. Chemical composition was ascertained by amino acid and carbohydrate analyses. The maximal thyroxine (T4)-binding capacity measured by reverse flow paper electrophoresis was 15,000 mug per g of protein, representing more than 2100 times that of the starting material, or about 5000 times that of whole serum. Based on the molecular weight obtained, the TBG preparation could bind 0.7 mole T4 per mole of protein, suggesting a single binding site. The association constant for T4 was estimated to be of the order of 10(10) by competitive binding studies employing TBG and T4-binding prealbumin (TBPA).     

Loss of p21WAF1/CIP1 expression in invasive fronts of oral tongue squamous cell carcinomas is correlated with tumor progression and poor prognosis

The clinicopathological significance of cell-cycle proteins has remained unclear in oral tongue squamous cell carcinomas (OTSCC). In the current study, we evaluated several cell-cycle proteins in relation to clinicopathological parameters and disease outcome for OTSCC. A total of 123 previously untreated patients with OTSCC, who underwent surgical treatment, were enrolled. Tumor specimens were examined for expression of p21, p27, p16, p53, and p63 using immunohistochemistry, with reference to clinicopathological factors and disease outcome. It is noteworthy that differences in p21 immunoreactivity were evident between the shallow region and invasive front of tumors within the same specimens. Loss of p21 expression in invasive fronts was found to be associated with clinicopathological factors of tumor progression and poor prognosis. p21 expression in invasive fronts is a significant indicator for impact on survival. Moreover, p21 is one of the important factors that regulate the progression of malignant cells in OTSCC.     

Nicorandil inhibits serum starvation-induced apoptosis in vascular endothelial cells

The Impact Of Nicorandil in Angina (IONA) randomized trial showed a significant reduction in coronary events, in patients with stable angina treated with a KATP channel opener, nicorandil. However, the impact of nicorandil on endothelial apoptosis remains to be examined. We tested the hypothesis that nicorandil has anti-apoptotic effects in endothelial cells (ECs). Apoptosis was induced by serum starvation in the culture media in human umbilical vein endothelial cells. We examined the effects of nicorandil on endothelial cell apoptosis. Cell viability after serum starvation was significantly higher in the nicorandil-treated group compared with the control group (81 +/- 8% vs. 63 +/- 3%, P < 0.01). Apoptosis, as detected by caspase 3 activation and Hoechst 33258 assay, induced by serum starvation was also effectively abrogated by the treatment of nicorandil (100 muM). The protective effects of nicorandil on endothelial survival were significantly inhibited by a specific mitochondrial KATP channel blocker, 5-Hydroxydecanoic acid. A mitochondrial permeability transition pore activator significantly abolished the anti-apoptotic effect of nicorandil in endothelial cells, indicating that the mechanism of protective effect of nicorandil is involved in the mitochondrial apoptotic pathway although it affects neither Bcl-2 nor Bax protein expression levels. In conclusion, nicorandil inhibits serum starvation-induced endothelial cell apoptosis possibly through mitochondrial KATP channels.     

Role of positive selection of thymoma-associated T cells in the pathogenesis of myasthenia gravis

BACKGROUND: A human thymoma is a thymic epithelial neoplasm and is characterized by its frequent association with myasthenia gravis. The histological characteristic of thymoma is coexistence of a large number of lymphocytes, including CD4(+)CD8(+) double positive T cells, phenotypes of the cortical thymocytes. To elucidate the role of these T lymphocytes in the pathogenesis of thymoma-associated myasthenia gravis, we examined the usage of alphabeta or gammadelta T cell receptor of the T lymphocytes in thymoma in conjunction with the positive selection event. MATERIALS AND METHODS: Thymomas were obtained from 28 patients. Nine patients were associated with myasthenia gravis. Lymphocytes were freshly isolated from the tumor tissue and were subjected to four-color flow cytometric analysis. RESULTS: The average proportion of TCRalphabeta(+) cells in thymomas associated with myasthenia gravis was 47.0% and was significantly higher (P = 0.0008) than that without myasthenia gravis (23.4%). Positive selection event was then examined in terms of CD69, a positive selection marker. The mean proportion of TCRalphabeta(+)CD69(+)CD4(+)CD8(-) cells in the myasthenic thymomas (8.22%) was significantly greater (P = 0.015) than the nonmyasthenic thymomas (2.99%). On the other hand, there was not a significant difference in the mean proportion of TCRalphabeta(+)CD69(+)CD4(-)CD8(+) cells between the myasthenic and the nonmyasthenic thymomas. CONCLUSIONS: The possible role of development of TCRalphabeta(+) T cells, especially the role of positive selection of TCRalphabeta(+)CD4(+)CD8(-) T cells in thymoma, was suggested in the pathogenesis of thymoma-associated myasthenia gravis.