Angiotensin-converting enzyme gene polymorphisms and prognosis in chronic thromboembolic pulmonary hypertension.

BACKGROUND: Angiotensin-converting enzyme (ACE) plays an important role in vascular remodeling in pulmonary hypertension, and ACE gene polymorphism is associated with exercise-induced pulmonary hypertension in Japanese patients with chronic obstructive pulmonary disease. The present study was designed to investigate if ACE-insertion (I)/deletion (D) polymorphism might be related to the susceptibility, severity, and disease outcome in chronic thromboembolic pulmonary hypertension (CTEPH). METHODS AND RESULTS: ACE-I/D genotypes were determined in 95 consecutive CTEPH patients (46 underwent surgery, 49 received medical treatment) and 97 controls. The frequencies of genotypes and alleles were not significantly different between patients and controls. Clinical characteristics were compared among ACE genotypes (II, ID, DD). ACE D allele carrier (ID plus DD) was associated with a lower 6-min walk test distance compared with D allele non-carrier (II) (330+/-102 (mean +/- SD) vs 381 +/-85 m, p=0.046). Kaplan-Meier analysis in the medically treated group showed significantly deteriorated survival for D allele carriers compared with D allele non-carriers (p=0.0389). Multivariate analysis revealed that age (p=0.013), pulmonary vascular resistance (p=0.008), and D allele carrier status (p=0.021) were independent predictors of survival. CONCLUSION: ACE D allele carrier is possibly one of the prognostic factors for medically treated CTEPH patients.

Oncolytic viral therapy for cervical and ovarian cancer cells by Sindbis virus AR339 strain.

PURPOSE: Recently, the application of replication-competent viruses has been studied as anticancer agents. Sindbis virus (SIN) is an RNA virus that belongs to the Alphavirus genus in the Togaviridae virus family. The AR339 strain of SIN has not been reported to induce any serious disease to humans. EXPERIMENTAL DESIGN: In this study, we evaluated the feasibility of the replication-competent SIN AR339 strain as an agent for cervical and ovarian cancer therapy. RESULTS: SIN infection was able to induce cytopathic effects and apoptosis in two cervical cancer cells (HeLaS3 and C33A) and three ovarian cancer cells (HOC-1, HAC-2, and OMC-3) but not in normal human keratinocytes in vitro. The analysis of cell viability, virus protein synthesis, and viral growth showed the cancer-specific cytotoxicity and virus growth of SIN. In nude mice, i.t. and i.v. inoculation of SIN resulted in significant regression of established cervical tumors implanted at their backs. Histologic studies revealed that systemic treatment with the single injection of SIN induces necrosis within tumors at a remote site. In the metastasis model of ovarian cancer, suppression of ascites formation was observed in nude mice with i.p. SIN treatment. By using an in vivo green fluorescent protein imaging system, we also showed that systemic treatment with SIN targeted tumors specifically. CONCLUSIONS: Our study suggested that SIN AR339 strain has a possibility as a novel agent for human cervical and ovarian cancer therapy.

Lymphangioleiomyomatosis with a giant bulla: report of a case.

We report a case of lymphangioleiomyomatosis (LAM) with a giant bulla. A 33-year-old woman was referred to our department for treatment of dyspnea. Chest computed tomography showed a giant bulla with many smaller bullae. To obtain a definitive diagnosis and relieve the dyspnea, we performed a lung biopsy and bullectomy, after which her symptoms and pulmonary function improved remarkably. She was commenced on progesterone, which improved her condition even further. This case report retrospectively follows the progression of her disease from the onset of symptoms 5 years before she was referred to us for treatment.

A case of bronchiolitis obliterans organizing pneumonia syndrome with preceding radiation pneumonitis after breast-conserving therapy.

Recent case series have demonstrated that bronchiolitis obliterans organizing pneumonia (BOOP) after radiation therapy to the breast is a distinct clinicopathological entity. Most of the investigators speculated that radiation may prime the development of BOOP through an unidentified immunological process; however, none of them showed the relationship between direct radiation injury and BOOP. We report herein a case of a 67-year-old female with BOOP following direct radiation damage confined to the irradiated area after breast-conserving therapy. This is the first case demonstrating that BOOP after breast-conserving therapy arises from direct radiation injury.

Plasma orexin-A levels in obstructive sleep apnea-hypopnea syndrome.

STUDY OBJECTIVES: Orexin and orexin receptors are present in the CNS. The effects of orexin peptides have been uniformly reported as excitatory, and the posterior hypothalamus containing orexin neurons has been implicated in arousal state control. Therefore, it is probable that the orexin system may have a neuromodulatory effect on arousal states. The aim of the present study was to investigate the relationship between plasma orexin-A levels and arousals from sleep in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). DESIGN: An analysis was conducted in 30 male patients with OSAHS, which had been diagnosed by polysomnography by the presence of an apnea-hypopnea index (AHI) of > 5, and 20 male age-matched and body mass index (BMI)-matched control subjects. RESULTS: Plasma orexin-A levels were higher in patients with OSAHS compared with those in control subjects (p < 0.05). Plasma orexin-A levels correlated positively, but weakly, with the arousal index (r = 0.51; p < 0.05) and the AHI (r = 0.52; p < 0.05). However, plasma orexin-A levels did not relate to age, BMI, Epworth sleepiness scale, PaO(2), PaCO(2), minimum arterial oxygen saturation (SaO(2)) during sleep, or mean SaO(2) during sleep. Plasma orexin-A levels can be a measure of both AHI and arousal index. CONCLUSION: These results suggested that the orexin system may be involved in arousal mechanisms in patients with OSAHS.