Maternal asthma is a risk factor for development of asthma in children, but mechanisms remain unclear. Offspring of asthmatic mother mice (sensitized and repeatedly exposed to OVA Ag) showed airway hyperresponsiveness and allergic pulmonary inflammation after an intentionally suboptimal OVA sensitization and exposure protocol that had little effect on normal offspring. Similar results were obtained when offspring of OVA-allergic mothers were exposed to an unrelated allergen, casein, indicating that the maternal effect is allergen independent and not transferred by OVA-specific Abs. Premating treatment with neutralizing anti-IL-4 Ab or reduction of maternal allergen exposure abrogated the maternal effect, showing a critical mechanistic role for IL-4 and suggesting an additional benefit of allergen avoidance.

Occurred in 32 patients (9.5%) with colorectal ESD; however, all cases had a good outcome with conservative management. Female sex, tumor location at the ascending colon and cecum, and resected specimen ≥40 mm were independently significant risk factors for PECS.

UEMR is efficacious for the treatment of small duodenal adenomas, but further large-scale trials are warranted to confirm these results.

Traction-assisted colorectal endoscopic submucosal dissection reduced the procedure time and increased the self-completion rate by the intermediates (UMIN000018612).

Sildenafil, an oral phosphodiesterase type-5 inhibitor, has vasodilatory effects through a cyclic guanosine 3', 5'-monophosphate-dependent mechanism, whereas beraprost, an oral prostacyclin analog, induces vasorelaxation through a cAMP-dependent mechanism. We investigated whether the combination of oral sildenafil and beraprost is superior to each drug alone in the treatment of pulmonary hypertension. Rats were randomized to receive repeated administration of saline, sildenafil, beraprost, or both of these drugs twice a day for 3 weeks. Three weeks after monocrotaline (MCT) injection, there was significant development of pulmonary hypertension. The increases in right ventricular systolic pressure and ratio of right ventricular weight to body weight were significantly attenuated in the Sildenafil and Beraprost groups. Combination therapy with sildenafil and beraprost had additive effects on increases in plasma cAMP and cyclic guanosine 3', 5'-monophosphate levels, resulting in further improvement in pulmonary hemodynamics compared with treatment with each drug alone. Unlike MCT rats given saline, sildenafil, or beraprost alone, all rats treated with both drugs remained alive during 6-week follow-up. These results suggest that combination therapy with oral sildenafil and beraprost attenuates the development of MCT-induced pulmonary hypertension compared with treatment with each drug alone.

We have tested the hypothesis that the CysLT(1) receptor is expressed by a variety of bronchial mucosal immune cells and that the numbers of these cells increase in asthma, when stable and in exacerbations. We have applied in situ hybridization and immunohistochemistry to endobronchial biopsy tissue to identify and count inflammatory cells expressing CysLT(1) receptor mRNA and protein, respectively, and used double immunohistochemistry to identify the specific cell immunophenotypes expressing the receptor. Double-labeling demonstrated that bronchial mucosal eosinophils, neutrophils, mast cells, macrophages, B-lymphocytes, and plasma cells, but not T-lymphocytes, expressed the CysLT(1) receptor. The numbers of CysLT(1) receptor mRNA and protein positive inflammatory cells in nonsmoking, nonatopic control subjects without asthma were 13 and 16 mm(-2), respectively (median values; n = 15), and were significantly greater in stable asthma (50 and 43 mm(-2), respectively; n = 17; P < 0.001). Compared with stable asthma, there were further significant increases in subjects hospitalized for a severe exacerbation of their asthma (mRNA: median = 113 and protein: 156 mm(-2); n = 15; P < 0.002). For the combined data of both asthma subgroups, there were strong positive correlations between the increased numbers of CD45+ leukocytes and the greater numbers of cells expressing CysLT(1) receptor (mRNA: r = 0.60, P < 0.001; protein: r = 0.73, P < 0.0001). In conclusion, a variety of immunohistologically distinct inflammatory cells express the CysLT(1) receptor in the bronchial mucosa and both these and the total number of leukocytes increase in mild stable disease and increase further when there is a severe exacerbation of asthma.

Antagonism of CCR5 and CXCR3 has a substantial therapeutic effect on inhibiting both acute and chronic allograft rejection. CCR5 and CXCR3 are functional in the process of allograft rejection and may be potential targets in clinical transplantation in the future.

Background: Although steroid injection prevents stricture after esophageal endoscopic submucosal dissection (ESD), some patients require repeated sessions of endoscopic balloon dilation (EBD). We investigated the risk for refractory stricture despite the administration of steroid injections to prevent stricture in patients undergoing esophageal ESD. Refractory stricture was defined as the requirement for more than three sessions of EBD to resolve the stricture. In addition, the safety of steroid injections was assessed based on the rate of complications. Patients and methods: We analyzed data from 127 consecutive patients who underwent esophageal ESD and had mucosal defects with a circumferential extent greater than three-quarters of the esophagus. To prevent stricture, steroid injection was performed. EBD was performed whenever a patient had symptoms of dysphagia. Results: The percentage of patients with a tumor circumferential extent greater than 75 % was significantly higher in those with refractory stricture than in those without stricture (P = 0.001). Multivariate analysis adjusted for age, sex, history of radiation therapy, tumor location, and tumor diameter showed that a tumor circumferential extent greater than 75 % was an independent risk factor for refractory stricture (adjusted odds ratio [OR] 5.49 [95 %CI 1.91 – 15.84], P = 0.002). Major adverse events occurred in 3 patients (2.4 %): perforation during EBD in 2 patients and delayed perforation after EBD in 1 patient. The patient with delayed perforation underwent esophagectomy because of mediastinitis. Conclusions: A tumor circumferential extent greater than 75 % is an independent risk factor for refractory stricture despite steroid injections. The development of more extensive interventions is warranted to prevent refractory stricture.