CHH with Early-Onset CAD

The patient with congenital hypogonadotropic hypogonadism (HH) shows low serum levels of androgen, which is a group of sex hormones including testosterone, caused by the decreased gonadotropin release in the hypothalamus. Recent reports showed androgens exert protective effects against insulin resistance or atherosclerotic diseases, such as diabetes mellitus or coronary artery disease. However, whether the juvenile hypogonadism affects the diabetes or cardiovascular disease is unclear. We report a case of a middle-aged man with congenital HH who had severe coronary artery disease complicated with metabolic disorders

The Lipid-Binding Defective Dynamin 2 Mutant in Charcot-Marie-Tooth Disease Impairs Proper Actin Bundling and Actin Organization in Glomerular Podocytes

Dynamin is an endocytic protein that functions in vesicle formation by scission of invaginated membranes. Dynamin maintains the structure of foot processes in glomerular podocytes by directly and indirectly interacting with actin filaments. However, molecular mechanisms underlying dynamin-mediated actin regulation are largely unknown. Here, biochemical and cell biological experiments were conducted to uncover how dynamin modulates interactions between membranes and actin in human podocytes. Actin-bundling, membrane tubulating, and GTPase activities of dynamin were examined in vitro using recombinant dynamin 2-wild-type (WT) or dynamin 2-K562E, which is a mutant found in Charcot-Marie-Tooth patients. Dynamin 2-WT and dynamin 2-K562E led to the formation of prominent actin bundles with constant diameters. Whereas liposomes incubated with dynamin 2-WT resulted in tubule formation, dynamin 2-K562E reduced tubulation. Actin filaments and liposomes stimulated dynamin 2-WT GTPase activity by 6- and 20-fold, respectively. Actin-filaments, but not liposomes, stimulated dynamin 2-K562E GTPase activity by 4-fold. Self-assembly-dependent GTPase activity of dynamin 2-K562E was reduced to one-third compared to that of dynamin 2-WT. Incubation of liposomes and actin with dynamin 2-WT led to the formation of thick actin bundles, which often bound to liposomes. The interaction between lipid membranes and actin bundles by dynamin 2-K562E was lower than that by dynamin 2-WT. Dynamin 2-WT partially colocalized with stress fibers and actin bundles based on double immunofluorescence of human podocytes. Dynamin 2-K562E expression resulted in decreased stress fiber density and the formation of aberrant actin clusters. Dynamin 2-K562E colocalized with alpha-actinin-4 in aberrant actin clusters. Reformation of stress fibers after cytochalasin D-induced actin depolymerization and washout was less effective in dynamin 2-K562E-expressing cells than that in dynamin 2-WT. Bis-T-23, a dynamin self-assembly enhancer, was unable to rescue the decreased focal adhesion numbers and reduced stress fiber density induced by dynamin 2-K562E expression. These results suggest that the low affinity of the K562E mutant for lipid membranes, and atypical self-assembling properties, lead to actin disorganization in HPCs. Moreover, lipid-binding and self-assembly of dynamin 2 along actin filaments are required for podocyte morphology and functions. Finally, dynamin 2-mediated interactions between actin and membranes are critical for actin bundle formation in HPCs

シンフゼン オ ガッペイ シタ ジンケッカンセイ コウケツアツ ニ タイスル ケイヒテキ ジンドウミャク ケイセイジュツ ノ ユウコウセイ

【Background】 Percutaneous transluminal renal angioplasty （PTRA） is recommended for patients with heart failure due to renovascular hypertension ; however, the clinical characteristics of the patients and the effects of PTRA on heart failure and cardiorenal function have not been elucidated. 【Methods】 We retrospectively analyzed data for 4 PTRA-treated patients （male/female, 1/3 ; mean age, 70.0±10 years ; mean left ventricular ejection fraction, 51.5±15.2％） with heart failure due to renovascular hypertension and evaluated the effects of PTRA on heart failure and cardiorenal function 6 months after treatment. 【Results】 All patients had pro-arteriosclerotic diseases including diabetes mellitus, essential thrombocythemia, heparin cofactor II deficency, metabolic syndrome, and familial hypercholesterolemia, and 3 patients had ischemic heart disease. No abdominal bruit was heard and mean plasma renin activity was 4.5±3.6 ng/ml/hr, which was not elevated, contrary to expectation. All contralateral kidneys of PTRA were nonfunctioning, suggesting bilateral kidneys were disturbed in all patients. In all patients, PTRA was successfully performed and resolved heart failure. PTRA resulted in decreases in systolic blood pressure from 157±18 to 124±8.6 mmHg, mean serum creatinine from 3.2±2.6 to 2.7±2.2 mg/dl, and mean BNP from 919±998 to 243±291 pg/ml at 6 months after treatment. PTRA did not change left ventricular ejection fraction, a parameter of systolic fraction evaluated by an echocardiogram ; however, PTRA improved E/e’, a parameter of left ventricular diastolic fraction, from 16.1±5.2 to 9.7±3.7. None of the patients were hospitalized due to heart failure during the 6-month period after PTRA. 【Conclusions】 Patients with heart failure with cardiovascular risk factors should be screened for renovascular hypertension regardless of abdominal bruit or plasma renin activity. PTRA is effective for resolving heart failure and for improving renal and cardiac diastolic functions in patients with renovascular hypertension complicated with heart failure

シロリムス ヨウシュツ ステント リュウチ 7ネンゴ ニ ハジメテ ゾウエイザイ ステント シュウイ シミダシゾウ オ ミトメタ イチレイ

A 74-year-old man who had a history of percutaneous coronary intervention ［left anterior descending coronary artery ＃6‐7, sirolimus eluting stent （SES） （Cypher stent,3.0×18mm）, left circumflex coronary artery ＃13, SES （Cypher stent, 2.5×23mm）］ for angina pectoris experienced chest pain on effort after seven years from the coronary intervention. He was introduced to our hospital and coronary angiography revealed late acquired peri-stent contrast staining （PSS）, which is defined as an angiographical finding of contrast medium stain outside the stent being ＞20％ of the stent diameter, in the SES of the left anterior descending artery. Drug-eluting stent （DES） significantly inhibits neointimal proliferation, thereby significantly reducing in-stent restenosis. However, the risk of very late stent thrombosis has become a major problem after the DES implantation against the bare-metal stent implantation. PSS has been reported that PSS after SES implantation could predict late stent thrombosis and incomplete stent apposition of the lesion with PSS. In this case, PSS was pointed out for the first time in seven years after SES implantation nevertheless it did not be pointed out in three years. The mechanism and prognosis of PSS is unclear. But, we found the increase in local coagulation at the coronary artery in this case and the degree of prothrombin fragment F1＋2, one of the coagulation marker, was greater in seven years after SES implantation than in three years. We thought these findings might reflect that PSS after SES implantation was associated with very late stent thrombosis. So we started the dual antiplatelet therapy for the prevention of stent thrombosis. Careful long-term observation might be recommended in patients with late acquired PSS and elevated local coagulation response following SES implantation

Tuberculosis infection among homeless persons and caregivers in a high-tuberculosis-prevalence area in Japan: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Tuberculosis (TB) is a major public health problem. The Airin district of Osaka City has a large population of homeless persons and caregivers and is estimated to be the largest TB-endemic area in the intermediate-prevalence country, Japan. However, there have been few studies of homeless persons and caregivers. The objective of this study is to detect active TB and to assess the prevalence and risk factors for latent TB infection among homeless persons and caregivers.</p> <p>Methods</p> <p>We conducted a cross-sectional study for screening TB infection (active and latent TB infections) using questionnaire, chest X-ray (CXR), newly available assay for latent TB infection (QuantiFERON-TB Gold In-Tube; QFT) and clinical evaluation by physicians at the Osaka Socio-Medical Center Hospital between July 2007 and March 2008. Homeless persons and caregivers, aged 30-74 years old, who had not received CXR examination within one year, were recruited. As for risk factors of latent TB infection, the odds ratios (OR) and 95% confidence intervals (95% CI) for QFT-positivity were calculated using logistic regression model.</p> <p>Results</p> <p>Complete responses were available from 436 individuals (263 homeless persons and 173 caregivers). Four active TB cases (1.5%) among homeless persons were found, while there were no cases among caregivers. Out of these four, three had positive QFT results. One hundred and thirty-three (50.6%) homeless persons and 42 (24.3%) caregivers had positive QFT results. In multivariate analysis, QFT-positivity was independently associated with a long time spent in the Airin district: ≥10 years versus <10 years for homeless (OR = 2.53; 95% CI, 1.39-4.61) and for caregivers (OR = 2.32; 95% CI, 1.05-5.13), and the past exposure to TB patients for caregivers (OR = 3.21; 95% CI, 1.30-7.91) but not for homeless persons (OR = 1.51; 95% CI, 0.71-3.21).</p> <p>Conclusions</p> <p>Although no active TB was found for caregivers, one-quarter of them had latent TB infection. In addition to homeless persons, caregivers need examinations for latent TB infection as well as active TB and careful follow-up, especially when they have spent a long time in a TB-endemic area and/or have been exposed to TB patients.</p