Respiratory symptoms and cigarette smoking in 3,197 pulmonologist-based asthmatic patients with a highly prevalent use of inhaled corticosteroid.

The relation between smoking and risk of asthma has been well-examined; however little attention has been paid to the correlation between smoking and asthma symptoms. The aims of this study were to examine respiratory symptoms in asthmatics with a highly prevalent use of inhaled corticosteroid (ICS) and to assess the effects of smoking and its cessation. A cross-sectional study of pulmonologist-based 3197 asthmatics (men 45.2%, ages 20-97) was performed using a questionnaire about smoking habits, the incidence and frequency of symptoms (sputum, cough and wheezing, night symptoms, and shortness of breath), physical activity interference, and medication. Although 81.4% of the patients used ICS according to the international guideline, 14.9% had activity interference, and daily symptoms remained in 43.3%. At the time of the questionnaire, 21.6% were current and 25.1% were ex-smokers. In multiple logistic regression analysis, the factors of significance (p < 0.0001) were (1) smoking; for all four symptoms, (2) age and duration of asthma; for shortness of breath. Current smokers were at a risk of sputum (age-adjusted odds ratio 2.32 [95% confidence interval 1.73-3.11]; 2.09 [1.57-2.79]), of cough and wheezing (2.38 [1.81-3.14]; 1.78 [1.35-2.36]), of night symptoms (1.95 [1.41-2.60]; 1.47 [1.09-1.98]), and of shortness of breath (1.70 [1.26-2.28]; 1.30 [0.97-1.75]) in men and women, respectively. These ratios in ex-smokers decreased to the level similar to nonsmokers. Although 81.4% of asthmatic patients used ICS, 43.3% complained of daily respiratory symptoms, especially sputum. It is suggested that the effects of ICS on asthma symptoms may be interfered with by smoking and therefore more emphasis should be placed on cessation of smoking.     

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.     

Classification of human liver transplant recipients by their preoperative CD8+ T cell subpopulation and its relation to outcome.

The primed status of T cells is markedly different among liver transplant recipients, due to a lifetime of antigen exposure and reduced thymopoiesis by aging, and diseases. This study aims to characterize the preoperative immunological status of CD8+ T cell subpopulations and relate it to the outcome for liver transplant recipients. We classified 112 liver transplant recipients into 5 groups, based on hierarchical clustering of the CD8+CD45 isoform proportion of T cells. In Groups I and II (pediatric), the naive T cell proportion was more than 50%. In adult recipients, Group III was characterized by a naive T cell proportion of 50%, Group IV had the greatest effector/memory T cells (EM), and Group V had the greatest proportion of effector T cells. In Groups IV and V, the effector T cell proportion was considerably higher, and was accompanied by marked downregulation of the CD27+CD28+ subsets and upregulation of interferon gamma (IFN)-gamma, tumor necrosis factor-alpha, and perforin expression. Group V recipients tended to be complicated postoperatively, with a significantly reduced survival rate (1 yr, 66.8%) and markedly reduced Eastern Cooperative Oncology Group performance status.     

Acute hemorrhagic colitis induced by the neuraminidase inhibitor oseltamivir]

A 23-year-old woman had lower abdominal pain, diarrhea and bloody stool was admitted and given a diagnosis of influenza B. Her home doctor had started treatment by neuraminidase inhibitor (oseltamivir) the previous day. Colonoscopic examination revealed an area of hemorrhage and erosion in the left transverse colon. After halting oseltamivir treatment these symptoms disappeared and her colonoscopic findings improved. A drug-induced lymphocyte stimulation test was positive for oseltamivir. This case is the first reported case of acute hemorrhagic colitis induced by oseltamivir.     

Improved expression of gamma-aminobutyric acid receptor in mice with cerebral infarct and transplanted bone marrow stromal cells: an autoradiographic and histologic analysis.

Recent studies have indicated that bone marrow stromal cells (BMSC) have the potential to improve neurologic function when transplanted into animal models of central nervous system disorders. However, how the transplanted BMSC restore the lost neurologic function is not clear. In the present study, therefore, we aimed to elucidate whether BMSC express the neuron-specific gamma-aminobutyric acid (GABA) receptor when transplanted into brain that has been subjected to cerebral infarction. METHODS: The BMSC were harvested from green fluorescent protein-transgenic mice and were cultured. The mice were subjected to permanent middle cerebral artery occlusion. The BMSC or vehicle was transplanted into the ipsilateral striatum 7 d after the insult. Using autoradiography and fluorescence immunohistochemistry, we evaluated the binding of 125I-iomazenil and the expression of GABA receptor protein in and around the cerebral infarct 4 wk after transplantation. RESULTS: Binding of 125I-iomazenil was significantly higher in the periinfarct neocortex in the BMSC-transplanted animals than in the vehicle-transplanted animals. Likewise, the number of the GABAA receptor-positive cells was significantly higher in the periinfarct neocortex in the BMSC-transplanted animals than in the vehicle-transplanted animals. A certain subpopulation of the transplanted BMSC expressed a neuron-specific marker, microtubule-associated protein 2, and the marker protein specific for GABAA receptor in the periinfarct area. CONCLUSION: These findings suggest that BMSC may contribute to neural tissue regeneration through migrating toward the periinfarct area and acquiring the neuron-specific receptor function.     

Histological changes in the midbrain around the aqueduct in congenital hydrocephalic rat LEW/Jms

Primary aqueductal stenosis is one of the main causes of congenital hydrocephalus in humans and experimental models. The congenitally hydrocephalic rat strain LEW/Jms is one such model. In this report, we describe further detailed histological features of periaqueductal structure, including the posterior commissure, subcommissural organ (SCO), and ependyma, and discuss the changes in these structures in relation to the cause of hydrocephalus. Coronal sections of the aqueduct in normal rats showed that the usual ependyma was absent in the center of the base facing the dorsal side, which was replaced by tall columnar cells. On the other hand, in hydrocephalic rats the ependyma encircled the aqueductal cavity. In midline sagittal sections, normal and hydrocephalic rats showed the SCO, although the SCO in hydrocephalic rats was shorter than in normal rats. There was also a marked difference between normal and hydrocephalic rats in the dorsoventral dimension of the rostral midbrain. In hydrocephalus, this dimension was large in comparison with normal rats. The superior collicular commissure located caudal to the posterior commissure ran along the ventral side of the midbrain in rats with hydrocephalus, and there was a cell-depleted area just dorsal to the superior collicular commissure. The same findings were observed from the 17th day of gestation until the postnatal period. Although the role of the SCO has been widely discussed from the viewpoint of secretory function, the present study indicated that this organ might be involved in the formation of the shape of the aqueduct.     

Polymorphisms in ADAM33 are associated with allergic rhinitis due to Japanese cedar pollen

BACKGROUND: A recent report provided evidence that a disintegrin and metalloprotease domain 33 (ADAM33), a member of the ADAM family, is a novel susceptibility gene in asthma linked to bronchial hyper-responsiveness. However, there has been no investigation of the genetic role of ADAM33 variants in nasal allergy. OBJECTIVE: The purpose of this study was to test the association between ADAM33 polymorphisms and Japanese cedar pollinosis (JCPsis), a most common seasonal allergic rhinitis in Japan. METHODS: We conducted a case-control association study among a Japanese population, involving 95 adult individuals with JCPsis and 95 normal healthy controls. A total of 22 single-nucleotide polymorphisms (SNPs) in ADAM33 were genotyped using PCR-based molecular methods. RESULTS: Six SNPs of ADAM33 gene, three in introns (7575G/A, 9073G/A and 12540C/T) and three in the coding region (10918G/C, 12433T/C and 12462C/T), were strongly associated with JCPsis (P = 0.0002-0.022 for absolute allele frequencies) and most of the SNPs were in linkage disequilibrium with each other. A higher frequency of the common alleles of these SNPs was noted for the subjects with JCPsis in comparison with healthy controls. We also identified a haplotype associated with the disease susceptibility. In addition, associations were found between ADAM33 polymorphisms and various cedar pollinosis phenotypes including clinical severity, eosinophil counts in nasal secretion and allergen-specific IgE levels in sera, but not total serum IgE levels. CONCLUSION: These results indicate that polymorphisms in the ADAM33 gene are associated with susceptibility to allergic rhinitis due to Japanese cedar pollen, but the functional relationship still needs clarification.