Lifestyle intervention might easily improve blood pressure in hypertensive men with the C genotype of angiotensin II type 2 receptor gene

BACKGROUND/OBJECTIVESRecent studies have reported an association of the angiotensin II type 2 receptor (AT2R) 3123Cytosine/Adenine (3123C/A) polymorphism with essential hypertension and cardiovascular diseases. The purpose of the study was to investigate whether the AT2R 3123C/A polymorphism affects blood pressure for free-living hypertensive men during a 5-month intervention period.SUBJECTS/METHODSThe subjects were free-living hypertensive Japanese men aged 40 to 75 years who agreed to intervention in the period from 2004 to 2011. Detection of the AT2R 3123C/A polymorphism was determined by polymerase chain reaction. The dietary intervention was designed to decrease salt level and to increase potassium level through cooking instructions and self-monitoring of the diet. The exercise session consisted of activities such as stretching, resistance training, and walking. Blood pressure, urinary sodium and potassium excretion, dietary and lifestyle data, and non-fasting venous blood sample were collected at baseline and after the intervention period.RESULTSThirty nine subjects were eligible for participation and the follow-up rate was 97.4%. The C allele proportion was 57.9%. AT2R 3123C/A polymorphism was X-chromosome-linked, therefore we analyzed the C and A genotypes. At baseline, no significant differences were observed between the genotype groups. After the intervention, there were no significant differences in lifestyle habit between the groups. Nevertheless, the estimated salt excretion (g/day) was significantly decreased only in the C genotype (13.0-10.3, P = 0.031). No significant change was observed in systolic blood pressure (SBP) (mmHg) in the A genotype, but a significant decrease was observed in the C genotype (150.0-141.5, P = 0.024).CONCLUSTIONSIn the C genotype, it might be easy to improve SBP through lifestyle intervention in free-living hypertensive Japanese men, however generalization could not be achieved by the small sample size.     

Development of packaging cell lines for generation of adeno-associated virus vectors by lentiviral gene transfer of trans-complementary components

Adeno-associated virus (AAV) vector system has several useful advantages with regard to in vitro and in vivo gene transfer. However, their usages have been limited by cumbersome and labor-intensive vector production in the traditional method. To overcome limitations in AAV production, in this report, we explored the possibility of generating AAV packaging cell line, 293T R/C.VA.E2A.E4. cells, by using lentivirus-mediated transduction of Rep/Cap gene of AAV-2, VA RNA, E2A, and E4 genes of Ad5 into 293T cells. In packaging cell lines, it is important that supply of the AAV vector can be stably performed for long time. We showed that the 293T R/C.VA.E2A.E4. cells have stably maintained the transduced components after more than 10 passages and yielded high-titer AAV vectors, and the titer of AAV vectors did not decline even if culture of the packaging cells was continued for long time. The Rep/Cap and E4 gene products caused no remarkable cytotoxicity. The 293T R/C.VA.E2A.E4. cells might be able to tolerate the Rep/Cap and E4 gene products, or have less copy numbers of the Rep/Cap and E4 genes than the traditional method. Moreover, we showed that the AAV vectors derived from 293T R/C.VA.E2A.E4. cells infected the primary human CD34+ haematopoietic progenitor cells with high efficiency (50-70%). In the 293T R/C.VA.E2A.E4. cells, the AAV vectors can be generated by the transfection of one AAV vector plasmid, and large-scale AAV production can be easily achieved. It is important that cumbersome, variable, and costly transfection is avoided.     

Microscopic polyangiitis associated with diffuse panbronchiolitis

There are several case reports of systemic vasculitis associated with chronic suppurative lung diseases. We describe a 46-year-old female, previously diagnosed as having diffuse panbronchiolitis (DPB), presenting with hemosputum and dyspnea. Her serum titer of MPO-ANCA was positive together with a high titer of BPI-ANCA. Chest X-ray and chest CT scan showed pulmonary hemorrhage, and the renal biopsy specimen revealed necrotizing, crescentic glomerulonephritis. She was diagnosed as having ANCA-associated vasculitis, and more specifically, microscopic polyangiitis accompanied by DPB. She was treated with methylprednisolone pulse therapy, followed by intravenous cyclophosphamide. This case suggested a possible association with chronic bacterial infection, which may play a role in the pathogenesis of ANCA-associated vasculitis.     

Different hypersensitivities against homologous proteins of MGL_1304 in patients with atopic dermatitis

Background

Atopic dermatitis (AD) is exacerbated by sweating, and the skin of most patients with AD are resided by Malassezia (M.) fungi. Recently, MGL_1304 produced by Malassezia globosa was identified as the major histamine releasing antigen in human sweat.

Association between a variant of the glutathione S-transferase P1 gene (GSTP1) and hypertension in pregnancy in Japanese: interaction with parity, age, and genetic factors

Hypertension in pregnancy (HP), including preeclampsia (PE), is known to be a multifactorial disease. Recently, an Ile105Val variant of the glutathione S-transferase P1 gene ( GSTP1) was shown to be associated with PE in The Netherlands. We therefore performed an association study of the Ile105Val variant comparing 131 patients with HP and 327 normal pregnant controls in Japan. We analyzed the data in the context of other risk factors before pregnancy. The frequency of the Ile/Val+Val/Val genotype of the GSTP1 was not significantly different between the HP (26%) patients and the controls (28%). However, in primiparous patients, the frequency was significantly different in elderly pregnancy (63% in severe HP vs. 18% in controls; P < 0.05), in the subgroup with the MM+MT genotypes of the angiotensinogen gene (50% in severe HP vs. 26% in controls; P < 0.05), and in the subgroup with the GA+AA genotypes of the endothelial nitric oxide synthase gene (42% in severe HP vs. 13% in controls; P < 0.05). These results suggest that this variant of the GSTP1 may play a role in the manifestation of HP together with other independently and/or synergistically acting factors, particularly in primiparous pregnancy.     

Intermittent bundle branch blocks in a patient with uncommon-type atrioventricular nodal reentrant tachycardia and enhanced atrioventricular nodal conduction

We report on a patient with uncommon-type atrioventricular (AV) nodal reentrant tachycardia with a short tachycardia cycle length (235-270 ms), in whom transient wide QRS tachycardia with both left bundle branch block and right bundle branch block aberrancy were followed by narrow QRS complexes. In addition, His-ventricular (H-V) block and a sudden prolongation of the H-V interval occurred during the tachycardia. As the determinant of these unusual findings, the possibility that the anterograde limb of the reentry circuit has an enhanced AV nodal conduction property is discussed, as is the clinical significance of this type of tachycardia.     

Coronary sinus pacing initiates counterclockwise atrial flutter while pacing from the low lateral right atrium initiates clockwise atrial flutter: Analysis of episodes of direct initiation of atrial flutter

Introduction: Rapid atrial pacing in sinus rhythm may directly induce atrial flutter without provoking intervening atrial fibrillation, or initiate atrial flutter indirectly, by a conversion from an episode of transient atrial fibrillation provoked by rapid atrial pacing. The present study was performed to examine whether or not the direct induction of clockwise or counterclockwise atrial flutter was pacing-site (right or left atrium) dependent. Methods and Results: We analyzed the mode of direct induction of atrial flutter by rapid atrial pacing. In 46 patients with a history of atrial flutter, rapid atrial pacing with 3 to 20 stimuli (cycle LENGTH = 500 − 170 ms) was performed in sinus rhythm to induce atrial flutter from 3 atrial sites, including the high right atrium, the low lateral right atrium, and the proximal coronary sinus, while recording multiple intracardiac electrograms of the atria. Direct induction of atrial flutter by rapid atrial pacing was a rare phenomenon and was documented only 22 times in 15 patients: 3, 11, and 8 times during stimulation, respectively, from the high right atrium, low lateral right atrium, and the proximal coronary sinus. Counterclockwise atrial flutter (12 times) was more frequently induced with stimulation from the proximal coronary sinus than from the low lateral right atrium (8 vs 1, P = .0001); clockwise atrial flutter (10 times) was induced exclusively from the low lateral right atrium (P = .0001 for low lateral right atrium vs proximal coronary sinus, P = .011 for low lateral right atrium vs high right atrium). Conclusions: Direct induction of either counterclockwise or clockwise atrial flutter was definitively pacing-site dependent; low lateral right atrial pacing induced clockwise, while proximal coronary sinus pacing induced counterclockwise atrial flutter. Anatomic correlation between the flutter circuit and the atrial pacing site may play an important role in the inducibility of counterclockwise or clockwise atrial flutter.