Elevated Levels of VE-Cadherin-Positive Endothelial Microparticles in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease

ObjectivesThe purpose of this study was to examine whether CD144-EMP (endothelium-derived microparticles) is useful as a specific marker of endothelial cell (EC) dysfunction and to determine whether plasma levels of circulating CD144-EMP predicted coronary artery disease (CAD) in patients with type 2 diabetes mellitus (DM).BackgroundEndothelial cell dysfunction is involved in atherogenesis; however, the quantitative assessment of EC dysfunction has yet to be established clinically. Endothelium-derived microparticles are small, membrane-shed vesicles that are generated from the EC surface in response to cellular dysfunction and/or injury. Diabetes mellitus is known to be associated with EC dysfunction and accelerated atherosclerosis.MethodsWe characterized EMP using anti-CD144 (VE-Cadherin) antibody in various atherosclerosis-related cells and investigated the association between the levels of CD144-positive microparticles and hydrogen-peroxide-induced EC injury and acetylcholine-induced coronary vasomotion. Furthermore, we evaluated plasma CD144-EMP levels in patients with and without DM.ResultsWe demonstrated that CD144-positive microparticles were derived selectively from human EC. The levels of CD144-EMP reflected the degree of in vitro hydrogen-peroxide-induced EC injury and impairment of in vivo endothelium-dependent coronary vasodilation (p < 0.01). Plasma CD144-EMP levels were increased significantly in DM patients compared with patients without DM (p < 0.001). In DM patients, the elevated levels of CD144-EMP were the most significant risk factor for CAD relative to all other traditional risk factors (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.8 to 6.9, p < 0.001). Notably, plasma CD144-EMP identified a subpopulation of established CAD patients in DM subjects without typical anginal symptoms (OR 10.6, 95% CI 3.9 to 29.5, p < 0.001).ConclusionsThe CD144-positive EMP exist in human plasma, and plasma CD144-EMP levels can be a clinically specific and quantitative marker of EC dysfunction and/or injury. Measurement of CD144-EMP, by providing a quantitative assessment of EC dysfunction, may be useful for identifying DM patients with increased risk of CAD

Branched-chain Sugars. XX. Kinetic Studies on the Epimerization of 1,2 : 5,6-Di-O-isopropylidene-3-C-nitromethyl-α-D-allofuranose

A study was made on the kinetics of the epimerization of 1,2: 5,6-di-O-isopropylidene-3-C-nitromethyl-α-D-allofuranose in nitromethane to its 3-epimer in the presence of a small amount of sodium methoxide. The activation energy was found to be 75±8 kJ/mol, the intermediate in epimerization being 1,2: 5,6-di-O-isopropylidene-α-D-ribo-hexofuranos-3-ulose with use of the labelled compound

Decreasing the Pressure Gradient of the Left Ventricular Outflow Tract by Single-lead VDD Pacing in a Patient with Hypertrophic Obstructive Cardiomyopathy

A 59-year-old woman with hypertrophic cardiomyopathy of 8 years duration, who had been taking ﾎｲ-blocker, was admitted to our hospital for exertional dyspnea and previous syncope. Cardiac catheterization showed a prominent left-ventricular outflow tract (LVOT) pressure gradient, and hypertrophic obstructive cardiomyopathy (HOCM) was diagnosed. To reduce LVOT obstruction, we implanted a single-lead VDD-mode pacemaker. Cardiac catheterization after the implantation revealed a remarkable decrease in the LVOT pressure gradient with short atrioventricular delay, 80 msec, and her symptoms disappeared. A singlelead VDD pacemaker is also a useful treatment for an HOCM patient due to the relative ease with which it can be implanted

Synthetic emmprin peptides with chitobiose substitution stimulate MMP-2 production by fibroblasts

<p>Abstract</p> <p>Background</p> <p>Emmprin, a glycoprotein containing two Ig domains, is enriched on tumor cell surfaces and stimulates matrix metalloproteinase (MMP) production by adjacent stromal cells. Its first Ig domain (ECI) contains the biologically active site. The dependence of emmprin activity on N-glycosylation is controversial. We investigated whether synthetic ECI with the shortest sugar is functionally active.</p> <p>Methods</p> <p>The whole ECI peptides carrying sugar chains, a chitobiose unit or N-linked core pentasaccharide, were synthesized by the thioester method and added to fibroblasts to examine whether they stimulate MMP-2 production.</p> <p>Results</p> <p>ECI carrying a chitobiose unit, ECI-(GlcNAc) ₂, but not ECI without a chitobiose unit or the chitobiose unit alone, dose-dependently stimulated MMP-2 production by fibroblasts. ECI with longer chitobiose units, ECI-[(Man)₃(GlcNAc)₂], also stimulated MMP-2 production, but the extent of its stimulation was lower than that of ECI-(GlcNAc)₂.</p> <p>Conclusions</p> <p>Our results indicate that ECI can mimic emmprin activity when substituted with chitobiose, the disaccharide with which N-glycosylation starts.</p

Effect of Coexisting Gases on NO Removal Using Corona Discharge

Effects of H_2O, CO_2, CH_4 and C_2H_4 contained in automotive exhaust gas on NO removal by using a DC corona discharge were investigated experimentally. In this experiment, N_2/O_2/NO mixture was used as a base gas of the simulated exhaust gas. To clarify the effect of the individual coexisting gas on NO removal, each coexisting gas was added to the base gas. The results showed that the existence of H_2O or C_2H_4 was effective for NO removal with low energy density. Also, when negative corona discharge was applied to the simulated exhaust gas (N_2/O_2/NO/H_2O/CO_2/C_2H_4 mixture), the efficiency of DeNOx was more than 90%. However, the by-products such as CO, O_3, HNO_3 and N_2O increased with increasing the energy density. It was found that the optimum energy density of corona discharge was about 250J/L for DeNO_x of simulated exhaust gas

Radon Therapy for Autoimmune Diseases Pemphigus and Diabetes: 2 Case Reports

We report on the application of radon therapy to relieve the suffering of 2 patients with autoimmune diseases, one with pemphigus with an old myocardial infarction and diabetes mellitus and the other with type I diabetes. We include a lengthy discussion of the biological mechanisms that we believe produced the observed benefits. During the 6 to 9 months of the treatments, the marker values decreased to the upper limit of their normal ranges and the symptoms of the diseases were alleviated. Disorders of Th1/Th2 balance are implicated in the onset of many diseases, including autoimmune diseases. Our decision to give radon ( 222 Rn) therapy to these patients was based on the results of 2 similar case reports and our earlier mouse experiments, which indicated that low doses of radiation induce regulatory T cells. Regulatory T cells regulate the T helper 1 cell and the T helper 2 cell balance. There are more than 80 different autoimmune diseases that are treated with anti-inflammatory agents or immune-suppressing drugs because the exact causes of these diseases and the cures are unknown. These and other case reports indicate that proper radon therapy is an effective treatment. We urge physicians to consider radon as a standard therapy for refractory autoimmune diseases

Present and Future Prospects of Radiation Therapy Using α-Emitting Nuclides

Therapy with α-radiation has issues associated with internal exposure; its clinical use has been avoided. However, phase III clinical tests of the α-emitting nuclide 223 Ra on patients with cancer have been conducted, and results were reported in 2011 to 2012. Since then, research has being carried out on targeted internal therapy by introducing α-emitting nuclides directly into the cancers. For many decades, nontargeted radon therapy has been carried out and is controversial because its mechanism of action is stimulation. The low-level radiation sends powerful signals to upregulate many biological protection systems, which protect against the effects of radiogenic and nonradiogenic toxins. These vital systems prevent, repair, and remove DNA and other biomolecular damage being produced endogenously at a very high rate by the very abundant reactive oxygen species associated with aerobic metabolism. Stimulation of protection systems results in beneficial effects, including a lower risk of cancer. This article reports the results of treatments on 4 patients with cancer and reviews the clinical use of α-radiation from 223 Ra and radon. It discusses the prospect of using the novel 225 Ac-prostate-specific membrane antigen ligand-617 ligand as a therapeutic agent for prostate cancer. It presents a new treatment system that we developed, α-Radiorespir o-Rn , which seems to be extremely effective in treating cancer

A Patient With Progressive Myelopathy and Antibodies to Human T-Cell Leukemia Virus Type I and Human Immunodeficiency Virus Type 1 in Serum and Cerebrospinal Fluid

• A 52-year-old human immunodeficiency virus type 1-seropositive bisexual black man was evaluated at UCLA because of the recent onset of progressive lowerextremity weakness. Initial neurologic examination showed that the patient's distal weakness was greater than his proximal weakness, with bilateral foot drop and electrophysiologic evidence of denervation in the distal lower extremities. Magnetic resonance imaging of the brain and spinal cord disclosed no abnormalities. Subsequent neurologic evaluation 8 months later showed a myelopathy, with progression of lower-extremity weakness, spasticity, and flexor spasms, and urinary incontinence, as well as the peripheral neuropathy noted previously. A second magnetic resonance imaging scan of the brain showed patchy foci of increased signal intensity in white matter and cortex, with mild generalized cerebral and cerebellar atrophy and no lesions in the spinal cord. Specimens of the patient's serum and cerebrospinal fluid contained antibodies to human immunodeficiency virus type 1. Additionally, specimens of his serum and cerebrospinal fluid were tested for antibody to human T-cell leukemia virus type I by Western blotting and radioimmunoprecipitation, and found to be positive for human T-cell leukemia virus type I gag, env, and tax antibodies. The primary cause of severe myelopathy in this patient may be infection with human T-cell leukemia virus type I rather than with human immunodeficiency virus type 1. Treatment with prednisolone resulted in improvement of the lower-extremity weakness, reduction in flexor spasms, and slower but significant improvement in urinary symptoms. Patients who are infected with human immunodeficiency virus type 1 and have unusual motor findings should be tested for concomitant human T-cell leukemia virus type I infection