Airway cough sensitivity to inhaled capsaicin and bronchial responsiveness to methacholine in asthmatic and bronchitic subjects

The objective of this study was to evaluate the effect of chronic airway inflammation on airway cough sensitivity and non-specific bronchial responsiveness, and the relationship between them. The capsaicin cough threshold, defined as the lowest concentration of capsaicin causing five or more coughs, and non-specific bronchial responsiveness, defined as the methacholine concentration causing a 20% fall in forced expiratory volume in 1 s (FEV1) (PC20-FEV1), were measured in 18 asthmatic, 13 bronchitic (sinobronchial syndrome) and 28 healthy non-atopic subjects. All subjects were non-smoking men. The geometric mean values (mumol) of the cough threshold were 18.9 (GSEM 1.29), 8.69 (GSEM 1.29) and 27.6 (GSEM 1.31) in asthmatic, bronchitic and normal subjects, respectively. The value in bronchitic subjects was significantly lower (P < 0.02) than that in normal subjects. The geometric mean value of PC20-FEV1 in asthmatic subjects (0.48 mg/ml (GSEM 1.38)) was significantly lower than that in bronchitic subjects (18.5 mg/ml (GSEM 1.75)) (P < 0.001). There was no correlation between cough threshold and PC20-FEV1 values (correlation coefficient (r) = 0.155). These results indicate that cough sensitivity is potentiated by chronic airway inflammation in bronchitis but not in asthma, and suggest that cough sensitivity and bronchial responsiveness may be independently potentiated by different mechanisms resulting from chronic airway inflammation.     

Bronchodilator effect of inhaled olprinone, a phosphodiesterase 3 inhibitor, in asthmatic patients.

The effect of topical administration of phosphodiesterase (PDE) 3 inhibitors on the airway is not clear. In order to examine the usefulness of inhaled PDE3 inhibitors in the treatment of asthma, we investigated the bronchodilator effect of inhaled olprinone, a newly developed PDE3 inhibitor, in nine asthmatic patients. On three separate study days, olprinone, salbutamol, or vehicle was administered in a double-blind and randomized fashion, and pulmonary functions were assessed over 60 min. Significant increases in FEV(1) were observed until 45 min after inhalation of olprinone without adverse cardiovascular effects. Mean maximal increases in FEV(1) were 16.0 +/- 4.0 and 20.5 +/- 4.2% with olprinone and salbutamol, respectively. The bronchodilator effect of olprinone was greater than that of salbutamol in four of the nine patients. These results suggest that the inhaled PDE3 inhibitor has a bronchodilator effect in asthmatic patients.     

Soluble type II transforming growth factor-beta receptor attenuates expression of metastasis-associated genes and suppresses pancreatic cancer cell metastasis

Pancreatic ductal adenocarcinoma (PDAC) is a deadly malignancy that frequently metastasizes and that overexpresses transforming growth factor-beta s (TGF-beta s). To determine whether TGF-beta s can act to enhance the metastatic potential of PDAC, PANC-1 human pancreatic cancer cells were transfected with an expression construct encoding a soluble type II TGF-beta receptor (sT beta RII) that blocks cellular responsiveness to TGF-beta 1. When injected s.c. in athymic mice, PANC-1 clones expressing sT beta RII exhibited decreased tumor growth in comparison with sham-transfected cells and attenuated expression of plasminogen activator inhibitor 1 (PAI-1), a gene associated with tumor growth. When tested in an orthotopic mouse model, these clones formed small intrapancreatic tumors that exhibited a suppressed metastatic capacity and decreased expression of plasminogen activator inhibitor 1 and the metastasis-associated urokinase plasminogen activator. These results indicate that TGF-beta s act in vivo to enhance the expression of genes that promote the growth and metastasis of pancreatic cancer cells and suggest that sT beta RII may ultimately have a therapeutic benefit in PDAC.     

Routine endoscopy using a magnifying endoscope for gastric cancer diagnosis

BACKGROUND AND STUDY AIMS: It has been reported that the fine mucosal patterns of the gastric pits can be observed with magnification and this may assist in preliminary evaluation prior to histological diagnosis. The aim of this prospective study was to clarify the relationship between the fine mucosal patterns of gastric lesions and histological findings, and also to evaluate the usefulness of magnifying endoscopy during routine endoscopy. PATIENTS AND METHODS: A recently developed magnifying video endoscope, which enables magnification up to 80 times, was used for gastrointestinal endoscopy in 318 patients between January 2000 and January 2001, at the National Shikoku Cancer Center. In total, 232 lesions were detected. However, patients diagnosed by conventional endoscopy as having advanced gastric cancer, malignant lymphoma, or submucosal tumor were excluded from the study. The endoscopic findings for 211 lesions included in this study were compared with the histological findings. RESULTS: Coarse and irregular mucosal patterns were observed in elevated-type cancers by magnifying endoscopy, and in depressed-type cancers there was a finer pit pattern than in the surrounding mucosa, destruction or disappearance of the mucosal microstructure, and abnormal capillary vessels. The magnifying endoscopy results were closely related to the mucosal microstructure observed by dissecting microscopy and to the histological features. The rate of presumptive diagnosis of small gastric cancers was significantly higher when a magnifying endoscope was used compared with conventional endoscopy. In this study, the sensitivity and specificity of magnifying endoscopy as a diagnostic method were 96.0% and 95.5%, respectively. CONCLUSIONS: The fine mucosal patterns and the features of capillary vessels, which were identified with the magnifying endoscope, correlated well with the pathological diagnosis. Magnifying endoscopy will be very useful in predicting the histological diagnosis during routine endoscopic procedures.     

Tenascin-C levels in the vitreous of patients with proliferative vitreoretinopathy

PURPOSE: To determine whether tenascin-C levels are elevated in the vitreous of patients with proliferative vitreoretinopathy (PVR). METHODS: We assayed tenascin-C levels in vitreous samples of 110 consecutive patients with PVR (30 eyes), rhegmatogenous retinal detachment (RRD; 32 eyes), and macular hole or idiopathic epiretinal membrane (controls, 48 eyes) using an enzyme-linked immunosorbent assay. RESULTS: Vitreous levels of tenascin-C (median [range]) were significantly greater in PVR (845.0 ng/ml [411.0-1,050.0]) than in RRD (21.9 ng/ml [13.2-127.0]) and in the controls (18.0 ng/ml [9.9-199.0]) (p < 0.0001). CONCLUSION: The results indicate the possibility that tenascin-C is involved in the pathogenesis of PVR.     

An analysis of the cellular DNA contents in lung-metastasized stomach cancers

A study has been conducted of the cellular DNA contents in the primary and metastatic lesions of 30 cases of lung-metastasized stomach cancers, in which each DNA Index (DI) was calculated and analysed comparatively. As a consequence, the rate of the diploid type in the nodular lung metastases was found to be higher than the rate of the others. Further, the DI's of 22 out of 30 (73%) metastatic lymph nodes corresponded with those of the primary lesions. Four lung metastatic lesions out of five differed from their primary lesions, but all five lesions simulated their metastatic lymph nodes. Thus understanding of the properties of the metastatic lymph nodes, rather than their primary lesions, would seen to be helpful in planning the therapy to combat recurrent cancers.     

Immunohistochemical evaluation of squamous cell carcinoma antigen and S-100 protein-positive cells in human malignant esophageal tissues

Localization and intensity of squamous cell carcinoma-related antigen (SCC-Ag) and infiltration of Langerhans' cells (LC) were investigated immunohistochemically, using anti-SCC-Ag and anti-S-100 protein antisera, respectively, in 36 cases of squamous cell carcinoma of the human esophagus. The SCC-Ag was an indicator of histologic differentiation of squamous cell carcinoma but not of malignant potential. The population density of LC correlated well with the histologic stage, vessel invasion, and postoperative survival time. In patients with a marked infiltration of LC, survival time was longer than for those in whom the infiltration was slight (P less than 0.05). The density of the LC can serve an indicator of defense of the host against the carcinoma. There was no correlation between SCC-Ag and S-100 protein-positive cells.     

A case of invasive lobular carcinoma of the breast first manifesting with duodenal obstruction

Lobular carcinoma of the breast presents with various clinical manifestations. Lobular carcinoma comprises about one fifth of cases of ductal carcinoma. Intestinal metastasis is dominant in cases of lobular carcinoma. Without a prior diagnosis of lobular carcinoma of the breast, the diagnosis of intestinal metastasis from breast cancer is difficult. A 52-year-old women underwent duodenogastrectomy for duodenal cancer. About 18 months later, she underwent mastectomy for lobular carcinoma of the breast. The duodenal cancer consisted mainly of malignant cells invading the submucosa that were identical to those in the breast. Immunohistochemical assays for estrogen receptor also confirmed breast cancer metastasis. Duodenal obstruction was the first sign of isolated metastatic lobular carcinoma of the breast in this case. The characteristic metastatic pattern of lobular carcinoma, which differs from that of ductal carcinoma, should be kept in mind to ensue proper diagnosis. Preceding breast surgery for lobular carcinoma should prompt investigation based on the typical metastatic pattern.     

Superior anti-tumor efficacy of bicalutamide 80 mg in combination with a luteinizing hormone-releasing hormone (LHRH) agonist versus LHRH agonist monotherapy as first-line treatment for advanced prostate cancer: interim results of a randomized study in Japanese patients

OBJECTIVES: To evaluate bicalutamide (Casodex) 80 mg as a component of maximum androgen blockade (MAB) in Japanese patients with previously untreated advanced prostate cancer. METHODS: 205 patients with previously untreated stage C/D prostate cancer were randomized (1:1) to receive once-daily bicalutamide 80 mg or placebo, each combined with a luteinizing hormone-releasing hormone (LHRH) agonist. Primary study variables were the 12 week prostate-specific antigen (PSA) normalization (i.e. PSA level 相似文献   

Relation between hormone dependency and the estrogen receptor of mammary carcinoma--comparative study of rat and human mammary tumors

A comparative study of rat and human mammary tumors was undertaken to clarify the mechanism of hormone dependency by the PAP method. In normal mammary glands, histological estrogen receptor ER (+) cells were observed in the ductal epithelium and acinal cells, while only ER (-) cells were noted in HAN. After overiectomy, 55.6% of the ER (+) cells changes to ER (-). Furthermore, histological changes were glandular atrophy, anaplastic changes, (with) the remaining ER (+) cells (being in the) insular group. Those ER (+) cancer cells seem to be different in hormone sensitivity. As for human mammary glands, proliferation of ER (+) cells was observed in papillary lesions as duct papillomatosis. In the cancer tissues as a whole, ER (+) and ER (-) cancer cells were mixed, showing a so-called mosaic pattern.