Influence of SNPs in cytokine-related genes on the severity of food allergy and atopic eczema in children

Although many single nucleotide polymorphism (SNP) studies have reported an association of atopy, allergic diseases and total serum immunoglobulin E (IgE) levels, almost all of these studies sought risk factors for the onset of these allergic diseases. Furthermore, many studies have analyzed a single gene and hardly any have analyzed environmental factors. In these analyses, the results could be masked and the effects of other genes and environmental factors may be decreased. Here, we described the correlation between four genes [interleukin (IL)-4 (C-590T), IL-4 receptor (A1652G), FCER1B (G6842A) and STAT6 (G2964A)] in connection with IgE production; the role of IL-10 (C-627A) as a regulatory cytokine of allergy; and the severity of food allergy (FA) and atopic eczema (AE) in 220 Japanese allergic children. In addition to these SNPs, environmental factors, i.e., patient's attitude, indoor environment, and so on, were also investigated in this study. Our study was retrospective, and the correlation was analyzed by our defined clinical scores divided into three terms: worst symptoms, recent symptoms and general amelioration at the most recent examination during the disease course. Our results indicated that IL-10 AA, the genotype with lower IL-10 production, is associated with higher IgE levels in the serum (p < 0.0001, estimate; 0.912). Marginal liver abnormalities were observed in the subject group with both FA and AE (p < 0.1191, estimate; 0.1490). Our defined clinical scores enabled evaluation of various aspects of disease severity. Based on the scores, while no single SNP selected in this study determined severity, the combination of the SNP with laboratory data and environmental factors appeared to determine severity.     

St. Jude Medical valve replacement: clinical experience with 1,039 patients

St. Jude Medical valve replacement was performed in 1,039 patients; 320 had aortic (AVR), 543 mitral (MVR), and 176 had double valve replacement (DVR). There were 44(4.2%) early deaths. Follow-up extended in 995 patients from 10 to 130 months, with a cumulative period of 2,730 patients-years. The overall survival rates of AVR, MVR, and DVR patients at 10 years were 60.5%, 89.6%, 90.3% respectively. The linearized incidences of valve thrombosis, thromboembolism, anticoagulation-related hemorrhage, prosthetic valve endocarditis, and significant hemolysis were as follows: 0.11%/pt-yr, 1.33%/pt-yr, 0.04%/pt-yr, 0.18%/pt-yr, and 0.11%/pt-yr, respectively. There were no structural failure after 10 years follow-up. Reoperation (explant and re-replacement or suture repair) was required in 10 patients. Seven of them had periprosthetic leakage, 2 had valve thrombosis, and one underwent reoperation because of a technical error. Actuarially over 98% of patients were free of valve-related mortality at 10 years. St. Jude Medical valve is an excellent alternative for use in the surgical treatment of valvular heart disease.     

Fractalkine and inflammatory diseases]

The migration of leukocytes into inflamed peripheral tissues and lymphoid organs involves a cascade of molecular events finely regulated by cell adhesion molecules and chemokines. Fractalkine/CX3CL1 is a membrane-bound chemokine that functions not only as a chemoattractant but also as an adhesion molecule, and is expressed on endothelial cells activated by proinflammatory cytokines. The fractalkine receptor, CX3CR1, is expressed on cytotoxic effector lymphocytes including NK cells and cytotoxic effector T cells (T(CE)), mature monocytes/macrophages, and mucosal dendritic cells, all of which play important roles in elimination of pathogens and cancer cells. Recently, accumulating evidence in both clinical studies and animal disease models has shown that fractalkine is also involved in the pathogenesis of various chronic inflammatory diseases, such as rheumatoid arthritis and atherosclerosis. This article reviews the unique functions of fractalkine and its pathophysiological roles in various clinical conditions.     

Hydrolysis of phenyl esters in cyclodextrin-polymer systems

The catalytic hydrolysis of phenyl esters in systems containing ß-cyclodextrin (ß-CD) and polyelectrolytes was investigated. Poly(methacrylic acid) was found to exhibit an inhibition effect on the hydrolysis, while poly(sodium styrenesulfonate) (NaPSS) shows a pronounced acceleration effect on the hydrolysis: the larger the molecular weight and the lower the degree of substitution, the greater is the acceleration effect. On the other hand, sodium ethylbenzenesulfonate and sodium dodecylbenzenesulfonate inhibit the reaction. The acceleration of the reaction in presence of NaPSS is attributed to the concentration of ß-CD and the substrate esters near to the chain of the macromolecule, through inclusion effects and hydrophobic interactions.     

Case of dermatomyositis complicated with massive pleural effusion that preceded the myopathy]

A 36-year-old man was admitted to a hospital with complaints of fever, polyarthralgia and dyspnea. Erythema was observed on his face, extensor surface of the fingers and extremities, and a chest X-ray revealed massive bilateral pleural effusion. He had no sign of myopathy at this point. Pleural fluid was proved to be exudative and contained extremely high levels of hyaluronic acid. He was also complicated with interstitial pneumonitis and was given a pulse therapy with methyl prednisolone followed by daily administration of 55 mg prednisolone (PSL). Twenty days after the commencement of the therapy, pleural effusion decreased but muscle weakness gradually appeared, accompanied by elevation of myogenic enzymes. Myogenic changes on electromyogram, and irregularity of the muscle fibers with slight inflammatory cell infiltrates in a biopsy specimen were demonstrated. He was transferred to our hospital, and a diagnosis of dermatomyositis was made. Later, pleural effusion waxed and waned depending on the dosage of PSL, but no other causative disorder was demonstrated by extensive examinations. This case indicates that the pleuritis could be one of the vasculitic manifestations of dermatomyositis.     

NEW METHOD OF STENTING TREATMENT FOR MALIGNANT DUODENAL STENOSIS: USING DOUBLE‐BALLOON ENTEROSCOPY

Recently, a self‐expandable metallic stent has been recognized for treatment of malignant duodenal stenosis. But the complications by stenting are important problems even now. In the present study, we report our new method of duodenal stenting by using of double‐balloon enteroscopy considered safe and effective.     

Small extra-adrenal pheochromocytoma causing severe hypertension in an elderly patient.

We report the case of a 67-year-old woman with severe hypertension caused by an extra-adrenal pheochromocytoma. The tumor was detected by 131I metaiodobenzylguanidine scintigraphy and it was found to be small (2 cm ?) by enhanced CT. After the extirpation of the tumor, the blood pressure of the patient immediately normalized. It should be taken into account that a small extra-adrenal pheochromocytoma can be one of the causes of secondary hypertension in elderly patients. Since small extra-adrenal pheochromocytomas are difficult to detect, it is also important to perform suitable examinations to establish the diagnosis. Furthermore, we emphasize the importance of an accurate diagnosis in elderly patients with pheochromocytoma, for they often have less symptomatology and more severe cardiovascular complications due to refractory hypertension than younger patients.     

Inhibition of inward rectifier K+ currents by angiotensin II in rat atrial myocytes: lack of effects in cells from spontaneously hypertensive rats.

We examined the effects of angiotensin II (Ang II) on inward rectifier K+ currents (IK1) in rat atrial myocytes. [125I]Ang II-binding assays revealed the presence of both Ang II type 1 (AT1) and type 2 (AT2) receptors in atrial membrane preparations. Ang II inhibited IK1 in isolated atrial myocytes with an IC50 of 46 nmol/l. This inhibition was abolished by the AT, antagonist RNH6270 but not at all by the AT2 antagonist PD123319. Treatment of cells with pertussis toxin or a synthetic decapeptide corresponding to the carboxyl-terminus of Gialpha-3 abolished the inhibition by Ang II, indicating the role of a Gi-dependent signaling pathway. Accordingly, Ang II failed to inhibit IK1 in the presence of forskolin, dibutyryl-cAMP or protein kinase A catalytic subunits. In spite of the increased binding capacities for [125I]Ang II, Ang II failed to affect IKI in cells from spontaneously hypertensive rats (SHR). AT, immunoprecipitation from atrial extracts revealed decreased amounts of Gialpha-2 and Gialpha-3 proteins associated with this receptor in SHR as compared with controls. The reduced coupling of AT, with Gialpha. proteins may underlie the unresponsiveness of atrial IK1 to Ang II in SHR cells.