Modulation of mucus production by interleukin-13 receptor alpha2 in the human airway epithelium.

BACKGROUND: IL-13 induces goblet cell hyperplasia and mucus overproduction in airway epithelial cells. IL-13 receptor alpha2 (IL-13Ralpha(2)) has been suggested to act as a 'decoy receptor' in the airway epithelium by inhibiting the IL-13 signal. However, the regulatory mechanisms for mucus production by IL-13Ralpha(2) remain unclear. OBJECTIVE: The aim of this study was to examine the role of IL-13Ralpha(2) in goblet cell hyperplasia and mucus overproduction by IL-13. METHODS: Bronchi were obtained from patients who underwent a lung resection due to lung cancer or benign lung tumours. Normal human bronchial epithelial cells (NHBECs) were isolated and cultured using an air-liquid interface (ALI) method. RESULTS: The number of periodic acid-Schiff's (PAS)-positive cells, goblet cells and MUC5AC-positive cells increased after adding IL-13 into NHBECs. The concentrations of MUC5AC protein in the supernatant and the mRNA expression of MUC5AC significantly increased after adding IL-13, and returned to control levels at 21 days. The mRNA expression of IL-13Ralpha(2) significantly increased at 7 days and then continuously increased up to 21 days. The protein of a soluble form of IL-13Ralpha(2) in the supernatants significantly increased at 14 and 21 days. Anti-IL-13Ralpha(1) antibody and recombinant IL-13Ralpha(2) reduced the number of PAS-positive cells, goblet cells and MUC5AC-positive cells, and MUC5AC mRNA, while the anti-IL-13Ralpha(2) antibody increased the number of these cells and MUC5AC mRNA. The concentration of MUC5AC protein in the supernatant induced by IL-13 was reduced by anti- IL-13Ralpha(1) antibody and recombinant IL-13Ralpha(2). IL-13-induced signal transducer and activator of transcription (STAT) activation was inhibited by anti-IL-13Ralpha(1) antibody and recombinant IL-13Ralpha(2). In contrast, the IL-4-induced mucus production, mucus secretion and STAT activation were not inhibited by recombinant IL-13Ralpha(2). CONCLUSION: The soluble form of IL-13Ralpha(2) may therefore modulate mucus overproduction by IL-13 through the pathway including IL-13Ralpha(1) in NHBECs.

Egg lectin of Rana japonica and its receptor glycoprotein of Ehrlich tumor cells.

Egg lectin of Rana japonica, which specifically agglutinates transformed cells but does not agglutinate nontransformed cells and erythrocytes, has been isolated by gel filtration and successive ion-exchange chromatographies on diethylaminoethyl cellulose and carboxymethylcellulose columns and has been characterized as a homogeneous carbohydrate-free protein with a relative molecular weight of 13,500. The lectin, at a concentration of 1 microgram/0.1 ml, causes obvious cytoagglutination of various transformed and tumor cell. The receptor of the Erlich ascites tumor cells which inhibits the lectin-induced agglutination of the Ehrlich ascites tumor cells has been isolated and characterized. The receptor was solubilized from Ehrlich ascites carcinoma cells by treating a tumor cell suspension with insolubilized trypsin, and the solubilized receptor was isolated by gel filtration through Sephadex G-100, followed by ion-exchange chromatography on diethylaminoethyl cellulose. The receptor was identified as a homogeneous glycoprotein having about 25% carbohydrate. The receptor, at a concentration of 4 microgram/0.1 ml, completely inhibited the cytoagglutination of the Ehrlich carcinoma cells caused by three agglutination doses (about 3 microgram/0.1 ml) of the R. japonica lectin.

Identification of the inferior salivatory nucleus in the cat as studied by HRP bathings of the transected glossopharyngeal nerve root.

The localization of the inferior salivatory nucleus that gives rise to parasympathetic fibers to the parotid gland was identified by means of horseradish peroxidase (HRP) method in the cat. The inferior salivatory nucleus does exist in the medulla oblongata and is situated in the dorsal part of the reticular formation. The nucleus is well-circumscribed caudally but rostrally the nucleus becomes scattered within the wide area of the dorso-lateral reticular formation. The inferior salivatory nucleus, demonstrated by the present study is composed of medium-sized multipolar neurons with well-developed slender dendrites and densely stained Nissl substance.

Identification of the superior salivatory nucleus in the cat as studied by the HRP method.

Using horseradish peroxidase (HRP) bathing of either the intermediofacial nerve or the chorda tympani, the localization of the superior salivatory nucleus that gives rise to parasympathetic fibers to the submandibular and sublingual glands was identified in the cat. The superior salivatory nucleus demonstrated by this study does not exist in the pons but does exist in the dorsal part of the reticular formation of the rostral medulla oblongata. Neurons of this nucleus were generally medium-sized and multipolar, with densely stained Nissl substance.

Sacral spinal innervations of the rectal and vesical smooth muscles and the sphincteric striated muscles as demonstrated by the horseradish peroxidase method.

To investigate the central organization of efferent neurons innervating the rectal and vesical smooth muscles and the sphincteric striated muscles in the cat, horseradish peroxidase (HRP) was injected into each of these structures and retrogradely labeled neurons were identified in the sacral spinal cord. Following HRP injections into these smooth muscle structures, labeled neurons were found in the intermediolateral and intermediolateral cell columns, the cell group X of Onuf and the nucleus myoleioticus medialis of the sacral cord. HRP injections into the external anal sphincter and bulbospongiosus muscles showed labeled neurons in the cell group X of Onuf and some in the nucleus myoleioticus medialis.

Prognostic value of carotid angiography in severe head injury.

Seventy-seven carotid angiograms in patients with severe head injuries were reviewed. The prognostic value of angiographic findings was evaluated. We were particularly concerned with midline shift, extracerebral avascular area, cerebral circulation time, phlebographic index, and distance between insula and inner table of the skull. Poor visualization of the internal cerebral and the thalamostriate veins, and prolongation of the arterial circulation time were significantly related to a poor prognosis.

Cerebellar hemorrhage associated with moyamoya disease.

A 60-year-old female was admitted with complaints of severe headache, nausea, and vomiting. Computed tomography demonstrated a right cerebellar hematoma, which was surgically removed. Bilateral carotid angiography showed occlusions of the anterior and middle cerebral arteries, and abnormal vascular networks. Vertebral angiography showed a well developed posterior pericallosal artery. Left encephalo-duro-arterio-synangiosis was performed. No cerebral vascular incident has been observed for 32 months.

[In vitro study on efficacy of combination use of aspoxicillin and beta-lactam preparations (ceftazidime, cefmetazole and aztreonam) against bacteria isolated from abdominal infections].

An in vitro study was done to evaluate combination use of aspoxicillin (ASPC) with each of 3 beta-lactam preparations, ceftazidime (CAZ), cefmetazole (CMZ) and aztreonam (AZT). The results obtained are summarized as follows: 1. ASPC has strong activity against Gram-positive bacteria and anaerobic bacteria, while CMZ and CAZ have strong activity against Gram-negative bacteria. 2. Rates of beta-lactamase producing strains among the isolated bacteria (a total of 383 isolates) were 4.4% among Gram-positive bacteria, 71.6% among Gram-negative bacteria and 89.3% among anaerobic bacteria. The overall rate of beta-lactamase secreting strains among all isolates was 46.5%. 3. Efficacies of combination uses were studied using the FIC index. Combination of ASPC and CAZ was effective against 95.0% of the isolates, ASPC and AZT against 85.7%, and ASPC and CMZ against 83.5%. Combination of ASPC and CMZ showed antagonism in 12.8% of the isolates. In conclusion, combination use of ASPC with any one of CMZ, AZT or CAZ proved to be highly effective. In particular, combination of ASPC and CAZ appeared to be the best in view of complementing antibacterial spectra.

[A case of stage IV (A3) cervical and upper thoracic esophageal adenocarcinoma successfully treated with concurrent chemoradiotherapy].

We report a case of cervical and upper thoracic esophageal adenocarcinoma with tracheal stenosis and bilateral recurrent nerve palsy. A 64-year-old man with unresectable esophageal cancer (A3, N1, M0) was treated with concurrent chemoradiotherapy. A dose of 67.4 Gy was irradiated to the cervical and upper thoracic area where the primary tumor and lymph node metastases were located, and six courses of 5-FU (250 mg/24 h/day 1-5) and CDDP (5 mg/1 h, just before radiation/day 1-5) were delivered concurrently. The esophageal tumor showed a complete response (CR), and the paratracheal lymph node metastases showed partial responses (PR). The reason these therapies were more effective against the tumor than the lymph node metastases is uncertain. The patient is no longer required to stay in the hospital, and his QOL has been improving. His condition has been maintained for 4 months, so this type of concurrent chemoradiotherapy may be recommended for cervical and upper thoracic esophageal adenocarcinoma.

Usefulness of elastica-van Gieson stain for the pathomorphological diagnosis of a cutaneous electric mark--a fatal electrocution case during arc welding.

Identification of an electric mark on a body is required for a precise diagnosis of electrocution at the time of forensic autopsy. We applied Elastica-van Gieson (EVG) stain as a means of obtaining the pathomorphological diagnosis of a cutaneous electric mark in relation to a fatal electrocution case. Using EVG stain, the characteristic findings of electric marks, such as elongation of basal-cell nuclei and vacuolation of cells within the epidermis, were clearly observed, while in addition, disarrangement of elastic fibers in the connective tissues within the dermis was also demonstrated. EVG staining was considered to be useful in enabling pathomorphological observations of a cutaneous electric mark to be made.

[Pathogenesis of black gallstones associated with hemolytic disease].

In order to investigate the pathogenesis of black gallstones associated with hemolytic disorders, experimental and clinical studies were performed. Firstly, a one-shot injection of bilirubin and hemolyzed blood, and a continuous injection of bilirubin were performed in mongrel dogs with the aim to analyze the changes of hepatic and gallbladder bile composition. Secondly, gallbladder bile obtained intraoperatively from the patients with black gallstones associated with hemolytic disease, patients with black stones not associated with hemolytic disease and patients with gallbladder polyp were analyzed in order to compare the characteristics of hemolytic patients' bile with those of the model animals. High concentration of total bilirubin and increased proportion of bilirubin monoconjugate (BMC) fraction was observed in the bile of patients with black stone associated with hemolytic disease compared with the bile of the patients of other two groups. Bile pH, total calcium concentration and ionized calcium concentration were similar in all the groups. Total bile lipid concentration of hemolytic patients was decreased but the ratio of total bile acid to total lipid was increased. Both bolus injection of bilirubin and hemolyzed blood produced an increase of total bilirubin concentration and BMC in hepatic bile. Continuous bilirubin injection for 7 days induced an increase of total bilirubin and BMC in both hepatic and gallbladder bile. These results suggest that the conjugating capacity of the hepatocyte is surpassed by the excessive amount of bilirubin produced after hemolysis, producing therefore, an increased BMC and unconjugated bilirubin content in bile. This increased content can precipitate in bile as black gallstones.

[Surgery for cholelithiasis in cirrhotic patients].

Although biliary tract surgery for cholelithiasis is performed frequently, cirrhotic patients require special consideration. The prevalence of postoperative severe complications, such as hepatic failure and biliary peritonitis caused by insufficient fistula formation after removal of the T-tube, is higher than non-cirrhotic patients. We suggest that definitive surgery can be carried out safely, in Child's A and B cirrhotic patients, either electively or as an emergency. However, a more conservative approach is advisable in Child's C patients with acute conditions and definitive surgery is recommended as an elective procedure after liver function has improved. And for the treatment of choledocholithiasis in patients with severe cirrhosis, avoiding surgical intervention through the use of such techniques as endoscopic papillotomy is recommended whenever possible.

[Investigation of papillary insufficiency in dogs by monitoring the manometry of the biliary tract with the saline perfusion method].

In order to establish the animal model of papillary insufficiency, 10% formalin solution (0.5-1.0 ml) was injected into duodenal papillae just after cholecystectomy in ten dogs. The bile duct pressure of the dogs was monitored by the manometer utilizing the saline perfusion system. Persistent dilatation of the bile duct was observed postoperatively. Two weeks after operation, the maximum dilatation of the bile duct was observed. The bile duct pressure of the dogs showed several characteristic changes: 1) the perfused pressure increased rapidly just after saline perfusion and then became stable, 2) the dumping time was shorter than that of the control dogs, 3) the residual pressure was lower than that of the control dogs. A metal sound, 4mm in diameter, was passed through the duodenal papillae of the dogs with ease. After injection of 10% formalin solution, macroscopic findings of the duodenal papillae revealed the diminish of their protrusions. These results demonstrated that the pathophysiology of the duodenal papillae treated with 10% formalin solution in this animal model is quite similar to that of human papillary insufficiency.

[Crystal morphology of cholesterol monohydrate in cholesterol gallstones and gallbladder bile].

To understand the pathogenesis of cholesterol gallstones from a crystallographic point of view, we investigated gallstones and precipitates in gallbladder bile by the optical method used in crystallography. First, ground thin sections of cholesterol gallstones in 28 cases were examined by a polarizing microscope. The crystalline fragments which were peeled off from gallstones by sonication were also examined in the same manner. Secondly, the cholesterol monohydrate crystals in gallbladder bile were examined by a polarizing and phase contrast microscope. The bile samples were obtained from 15 patients with cholesterol gallstones by the needle puncture of gallbladder during surgery. The results of observation were as follows. 1) The cholesterol gallstones were composed of many small plated cholesterol monohydrate crystals aggregated radially. 2) Each small plated crystal was grown by the lateral growth mechanism in bile. Spiral growth patterns were often observed on the (001) faces. 3) The cholesterol gallstones were formed by two successive mechanisms: The aggregation of cholesterol monohydrate crystals and the lateral growth of each single crystal.

[Three-dimensional morphology of intrahepatic bile ducts in patients with intrahepatic gallstones].

Eight livers surgically resected for intrahepatic gallstones were submitted to graphic reconstruction from serial histological sections to correlate the peculiar ductal changes with the pathogenetic aspects of this disease. Reconstruction was aided by a microcomputer system we have developed. Further, morphometric analysis was added to relate the obstruction of portal veins with parenchymal atrophy. Three-dimensionally, the ducts in these livers were strikingly transformed into a chain of ampullar dilatations interposed by either bending or strictures. Morphometrically, even a stenotic segment was wider than a corresponding normal one, showing that it was a relative stricture. The parenchymal lobule was atrophic or even completely destroyed due to the frequent thrombotic obstruction of portal veins about 0.5mm diameter. These 3-D morphology of intrahepatic bile ducts provided little evidence of congenital bile duct anomaly for the origin of intrahepatic gallstones. The basic ductal changes were dilations, alternated with "stenoses" that were more apparent than real. On the other hand, both the frequent obstruction of small portal veins and the lobular atrophy reflected a severely reduced portal blood flow. Not only the recurrent cholangitis that is apt to occur upon dilated ducts, but this functional incompetence of a stone-harboring, atrophic liver lobe strongly suggests a surgical indication for hepatic resection.

[Post-gastrectomy gallstone disease].

Biliary tree of gastrectomized patients was examined with ultrasonography to investigate the factors affecting post-gastrectomy gallstone formation. Only gallbladder stone was found in 57 (18.9%). In 11 (20.0%) of 55 patients, stones had developed within 2 years after surgery, but no difference in incidence were observed by sex and age. Sixty four gastrectomized gallstone patients were examined in respect to the kind of gallstone. Patients with cholesterol gallstones were 18 (28.1%), patients with black gallstones were 29 (45.3%) and patients with calcium bilirubinate gallstones were 17 (26.6%). The incidence rate of cholesterol gallstones was lower and the rate of black gallstones and calcium bilirubinate gallstones was higher than that of non-gastrectomized patients. In conclusion, the incidence of pigment gallstones is very high in gastrectomized patients.