Integrin α11 in non–small cell lung cancer is associated with tumor progression and postoperative recurrence

Integrins are transmembrane proteins that mediate cell adhesion to the extracellular matrix. Integrin α11 (ITGA11) is not expressed in normal alveolar epithelial cells and is a known receptor for collagen. While integrin α11β1 overexpression in the tumor stroma has been associated with tumor growth and metastatic potential of non–small cell lung cancer (NSCLC), little is known about the role of ITGA11 in tumor cells. Thus, we examined the RNA expression of ITGA11 by quantitative RT‐PCR in 80 samples collected from NSCLC patients who had undergone surgical resection and analyzed the clinical outcomes. We found that high expression of ITGA11 was associated with lower recurrence‐free survival in all NSCLC patients (P = 0.043) and in stage I NSCLC patients (P = 0.049). These results were consistent with in silico analyses of the Cancer Genome Atlas database. We also analyzed cell proliferation, migration and invasion capacity in lung cancer cell lines after overexpression of ITGA11. Overexpression of ITGA11 in lung cancer cell lines had little effect on cell proliferation but resulted in increased migration and invasion capacity. Our findings suggest that ITGA11 plays a significant role in cancer migration and invasion, leading to higher recurrence. ITGA11 expression may be a predictor of poor prognosis in patients with surgically resected NSCLC.     

Spontaneous subcapsular hepatic hemorrhage associated with pregnancy: Report of a case

We report herein a case of spontaneous subcapsular hepatic hemorrhage which occurred in a 33-year-old woman 1 day after she had been delivered of her second child by cesarean section following an uneventful pregnancy. She complained of right upper quadrant pain on the 1st postoperative day, and computed tomography (CT) showed subcapsular low-density masses in both liver lobes, while extravasation was demonstrated by CO₂ intraarterial digital subtraction angiography (IADSA). The hemorrhage was successfully controlled by transcatheter arterial embolization (TAE). However, on the 3rd day after TAE, an exploratory laparotomy was performed to establish an exact diagnosis to explain the persistent abdominal pain and abnormal liver function tests. Subcapsular hematomas in both lobes were confirmed and no visible laceration was present. The patient recovered gradually by spontaneous absorption of the hematomas and was discharged on the 22nd postoperative day. Spontaneous hepatic hemorrhage associated with pregnancy is a very rare complication, and establishing a correct diagnosis and initiating appropriate therapy are essential for this life-threatening disease.     

Changes of acinar cells in the pancreato-biliary duct ligation with exocrine pancreatic stimulation model in rats; protective effects of a new potent protease inhibitor, ONO3307]

To evaluate the changes of pancreatic acinar cells in the pancreatic duct obstructed animals as well as the protective effects of a new potent protease inhibitor, ONO3307, we measured the serum amylase levels, pancreatic water content, histological changes, lysosomal fragility in in-vitro incubation, cathepsin B distribution in acinar cells, and cathepsin B and amylase output into pancreatic juice after short-termed (3 hrs) pancreatic duct obstruction with caerulein (0.2 micrograms/kg.hr) infusion in rats. Serum amylase levels, pancreatic water content, and lysosomal fragility in duct obstructed with caerulein infused animals were significantly increased compared with the control groups, and remarkable shift of cathepsin B from lysosomal fraction to zymogen fraction was observed in this group. These changes tended to continue 24 hours after removal of duct obstruction. But with infusion of ONO3307, these changes observed in duct-obstructed with caerulein infusion groups were significantly, almost completely attenuated. These results indicate the intimate relationship between the pathogenesis of acute pancreatitis and lysosomes and some known proteases which are inhibited by ONO 3307 and suggest the usefulness of such a kind of protease inhibitor in the treatment of acute pancreatitis.     

Comparative study on the macroscopic and histopathological diagnosis of lymph node metastases in cancer patients

Macroscopic diagnosis for lymph node metastases was compared with histopathological diagnosis in 444 patients with carcinoma of the esophagus, stomach, colon, thyroid and breast. The former indicated lymph node metastases in 181 patients. In all of them, none or less than five node metastases were proven by routine histopathological diagnosis. Detailed histological study revealed lymph node metastases in 25 out of 263 patients with macroscopically negative nodes, the rate of false negative being 9.5 per cent. The study also demonstrated no lymph node metastases in 51 of 181 patients with macroscopically positive nodes. Three additional specimens were obtained from originally examined 693 lymph nodes and reexamined microscopically in these 51 patients. Involvement by cancer cells was detected in 9 nodes (1.3 per cent) in 8 patients. Metastases were found from additional specimens in 7 of 9 nodes, indicating that metastatic carcinoma had been overlooked in the remaining two nodes. Additional specimens or embedding-techniques were recommended in such cases as macroscopic metastases were strongly suspected or lymph vessel invasions were remarkable. In 24 patients with esophageal cancer, one to one correspondence was available in the analysis of macroscopic diagnosis. Seventy-eight out of 108 involved nodes were macroscopically judged as involved (sensitivity; 72.2 per cent), and 1166 out of 1260 nodes without macroscopical metastases were judged as cancer-free (specificity; 92.5 per cent). Overestimation of macroscopic diagnosis was due to thickened capsule, fibrosis, inflammation and enlargement in size more than 10 mm in diameter of the nodes. Underestimation was observed in case of nodes with metastatic area less than one-third and with smaller size less than 5mm in diameter.     

Cisplatin-induced long-term dynorphin A-immunoreactivity in cell somata of rat area postrema neurons

We evaluated long-term dynorphin A-immunoreactivity in the rat area postrema (AP) after the administration of cisplatin. First, rats were given 1, 5 and 10 mg/kg body weight cisplatin (i.p.) and their behavior was monitored for 72 h. We observed a delayed increase in pica 24-72 h after injection, compared to the 24 h before injection. We attributed this to the cisplatin injection. Pica was defined as an increase in the intake of non-nutritional matter such as kaolin. Administration of 1, 5 and 10 mg/kg cisplatin led to an increase in kaolin intake on day 1. Administration of 5 and 10 mg/kg of cisplatin led to decreased intake of laboratory chow (MF) on days 1–3, but 10 mg/kg cisplatin causes an excessive aggravation of their condition. Following this behavioral experiment, we immunohistochemically examined the induction of dynorphin A in the AP at 24, 48 and 72 h post-administration of 1 and 5 mg/kg cisplatin. Administration of 5 mg/kg cisplatin caused dynorphin A to accumulate gradually in the neurosoma of the AP neurons, and the numbers of positive AP neurosomata at 48 and 72 h post-administration were higher than following an equal dosage of 0.9% NaCl. These findings suggest that dynorphin A increases in the central nervous system for a long time following administration, and causes certain behavioral and clinical changes, including those related to appetite and nausea.     

A novel Fc receptor for IgA and IgM is expressed on both hematopoietic and non-hematopoietic tissues

By contrast to well-defined Fc gamma and Fc epsilon receptors, the structural and functional characteristics of Fc mu receptor are unclear. We have recently described a novel mouse Fc receptor, designated Fc alpha/mu receptor, and its human homologue, which bind both IgM and IgA. Here we show that the Fc alpha/mu receptor is expressed on mature, but not immature, B lymphocytes and acquires the ability to bind IgM and IgA antibodies after stimulation of B lymphocytes. Moreover, stimulation with phorbol 12-myristate 13-acetate increased endocytosis of IgM-coated microparticles mediated by the Fc alpha/mu receptor expressed on pro-B cell line Ba/F3 cells. We also show that the Fc alpha/mu receptor is expressed in secondary lymphoid organs, such as lymph node and appendix, kidney and intestine, suggesting an important role of the receptor for immunity in these organs.     

Operation for adult patent ductus arteriosus using cardiopulmonary bypass

Background. Surgical repair of adult patent ductus arteriosus is more hazardous than when performed on young patients.

Methods. Nine adult patent ductus arteriosus patients underwent surgical repair between January 1986 and December 1998. There were 3 male and 6 female patients (mean age 55.0 years). The ratio of pulmonary blood flow to systemic flow was 2.40 ± 0.95, and pulmonary arterial pressure was 56.0 ± 26.4 mm Hg. The operation was performed using transpulmonary approach under total cardiopulmonary bypass. Balloon occlusion method was also utilized.

Results. Direct closure was made in 5 and patch closure in 4 patients. Cardiopulmonary bypass and balloon occlusion were safely established. Cardioplegic arrest was not required in the 2 most recent patients. No operative death has occurred. Pulmonary arterial systolic pressure decreased to 35.3 ± 6.6 mm Hg at 6 months after operation. The mean follow-up period for all patients is 55 months. To date, neither recannalization of the ductus nor pseudoaneurysm has been recognized.

Conclusions. Cardiopulmonary bypass with balloon occlusion provides a safe operation for adult patients with complicated patent ductus arteriosus.     

Distal arch aneurysm repair using stent-grafting and ascending aorto-left axillary bypass

Background. Transcatheter application of a stent-graft to the angulated aortic segments with critical side branches poses some problems. We report our technique of distal arch aneurysm repairs using stent-grafts inserted through the aortic arch and ascending aorto-axillary bypass.

Patients and Results. Three patients underwent successful distal arch aneurysm repair using a homemade semiflexible stent-graft placed under hypothermic circulatory arrest. The left subclavian artery was reconstructed by an extraanatomic bypass grafting between the ascending aorta and left axillary artery. Postoperative imaging demonstrated reduction of aneurysm size and no endoleaks from an intercostal artery.

Conclusions. Our technique seems to be useful for repair of distal arch aneurysms and is a less invasive procedure.     

Influx and efflux transport of H1-antagonist epinastine across the blood-brain barrier.

We investigated influx and efflux transporters involved in blood-brain barrier transport of the nonsedative H1-antagonist epinastine. The basal-to-apical transport of [14C]epinastine was markedly higher than that in the opposite direction in LLC-GA5-COL150 cells stably transfected with human multidrug resistance (MDR)1 gene. The brain-to-plasma concentration ratio of [14C]epinastine in mdr1a/b(-/-) mice was 3.2 times higher than that in wild-type mice. The uptake of both [3H]mepyramine and [14C]epinastine into immortalized rat brain capillary endothelial cells (RBEC)1 showed temperature and concentration dependence. The kinetic parameters, K(m), V(max), and uptake clearance (V(max)/K(m)), of the initial uptake of [3H]mepyramine and [14C]epinastine by RBEC1 were 150 microM, 41.8 nmol/min/mg protein, and 279 microl/min/mg protein for mepyramine and 10.0 mM, 339 nmol/min/mg protein, and 33.9 microl/min/mg protein for epinastine, respectively. The uptake of [3H]mepyramine and [14C]epinastine by RBEC1 was inhibited by organic cations such as quinidine, amantadine, and verapamil, but not by other organic cations, tetraethyl ammonium, guanidine, and carnitine. Organic anions such as benzoic acid, estrone-3-sulfate, taurocholate, and neutral digoxin were not inhibitory. Furthermore, some cationic H1 antagonists (chlorpheniramine, cyproheptadine, ketotifen, and desloratadine) inhibited the [3H]mepyramine and [14C]epinastine uptake into RBEC1. In conclusion, the present study demonstrated that the combination of efficient efflux transport by P-glycoprotein and poor uptake by the influx transporter, which is identical with that responsible for the uptake of mepyramine, account for the low brain distribution of epinastine.