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.

Primary invasive micropapillary carcinoma of the colon.

AIMS: Invasive micropapillary carcinoma (IMPC) is associated with frequent lymph node metastasis and adverse clinical outcome. IMPC has been reported in breast, urinary bladder, ureter, lung and parotid gland but not in colon. We present the clinicopathological features of three cases of primary IMPC of the colon with a review of the literature. METHODS AND RESULTS: The patients (one man and two women) were 53, 67 and 68 years old, respectively. The size of the tumour ranged from 20 to 100 mm in diameter. Histologically, all cases were composed predominantly of papillary tumour cell clusters with spaces in a background of fine fibrocollagenous stroma. One of the tumours (case 1) was nearly completely composed of IMPC, but the other two were associated with foci of adenocarcinoma and concurrent mucinous carcinoma, respectively. MUC1 was positive in all cases, suggestive of reverse cell orientation which is responsible for its unique histological features. CONCLUSIONS: We report three cases of primary IMPC of the colon. Its clinical significance remains undetermined but the presence of this component may represent a poor prognostic factor.

Regulation of asialoglycoprotein receptor expression in the proliferative state of hepatocytes.

It is necessary to proliferate hepatocytes and to increase the number of hepatocytes for development of bioartificial liver (BAL) and reconstitutive therapy. But usually the cell has a precarious balance between proliferation and differentiation: as the cell proliferation increases, functional differentiation decreases. Therefore, it is desirable for the hepatocytes to be functional by differentiation as a material for such clinical use not to be proliferative. In this study, we investigated the background of hepatocyte proliferation for the springboard of control between proliferation and differentiation of hepatocytes, and we focused attention to the asialoglycoprotein receptors (ASGP-R) of the hepatocytes. Partially hepatectomized (PH) rats were used as a model animal. When the isolated hepatocytes were plated onto the artificial extracellular matrix of poly-(N-p-vinylbenzyl-O-beta-d-galactopyranosyl-d-gluconamide) (PVLA) having galactose residues as cell-specific ligand, the rate of adhesion was decreased along with liver regeneration. Interestingly, the release of the ASGP-R from hepatocytes in serum after PH in vivo and reduction of ASGP-R of the hepatocytes in the proliferative state occurred due to cell growth in vitro. It is suggested that the ASGP-R on the hepatocyte surface during the differentiation was released in the proliferative state.

Low asialoglycoprotein receptor expression as markers for highly proliferative potential hepatocytes.

Development of a reliable method to isolate highly proliferative potential hepatocytes will provide insight into the molecular mechanisms of liver regeneration, as well as proving crucial for the development of a biohybrid artificial liver. The aim of this study is to isolate highly proliferative, e.g., progenitor-like, hepatocytes. To this end, we fractionated hepatocytes expressing low and high levels of the asialoglycoprotein receptor (ASGP-R) based on the difference in their adhesion to poly[N-p-vinylbenzyl-O-beta-d-galactopyranosyl-(1-->4)-d-gluconamide] (PVLA), and examined the proliferative activity and gene expression of these fractionated hepatocytes. The results showed that approximately 0.5 to 1% of the total number of hepatocytes, which showed low adhesion to PVLA, expressed low levels of the ASGP-R, while the rest of hepatocyte population with high adhesion to PVLA expressed high levels of the ASGP-R. Interestingly hepatocytes with low ASGP-R expression levels had much higher DNA synthesizing activity (i.e., are much more proliferative) than those with high ASGP-R expression levels. Moreover, hepatocytes with low ASGP-R expression levels expressed higher levels of epidermal growth factor receptor (EGF-R), CD29 (beta1 integrin) and CD49f (alpha6 integrin) and lower levels of glutamine synthetase than those with high ASGP-R expression. These findings suggested that hepatocytes with low adhesion to PVLA due to their low ASGP-R expression could be potential candidates for progenitor-like hepatocytes due to their high proliferative capacity; hence, the low expression of the ASGP-R could be a unique marker for progenitor hepatocytes. The isolation of hepatocytes with different functional phenotypes using PVLA may provide a new research tool for a better understanding of the biology of hepatocytes and the mechanisms regulating their proliferation and differentiation in health and disease.

Metastatic colon carcinoma found within an inguinal hernia sac: report of a case.

We report herein the case of a patient in whom metastatic colon carcinoma was found within an inguinal hernia sac. According to Lejar's classification, colon carcinomas within inguinal hernias are categorized as intrasaccular- and saccular-type tumors. In our patient, asymptomatic transverse colon carcinoma was the primary lesion, and to the best of our knowledge, this is only the fourth case of such a saccular-type tumor to be reported in the literature. To date, 21 cases of intrasaccular tumors have been reported, and saccular-type tumors are considered to be an even rarer entity, unless the patients have obvious ascites, indicating peritonitis carcinomatosa. Histologic examination of the hernia sac is recommended for male patients of advanced age with an inguinal hernia, especially those who have previously undergone surgery for colorectal carcinoma.

Hand-assisted laparoscopic digestive surgery provides safety and tactile sensation for malignancy or obesity.

BACKGROUND: Some of the persistent problems associated with laparoscopic surgery stem from the inability of the surgeon to palpate the abdominal contents during the operation. This lack of tactile sensation can lead to poor abdominal exploration, difficulty in extracting the organs, and a relatively long operation time compared to conventional procedures. The Dexterity Pneumo Sleeve is a new device that allows the surgeon to insert his or her hand into the abdominal cavity through a small incision while preserving the pneumoperitoneum. METHODS: Recently, 13 of our patients underwent hand-assisted advanced laparoscopic surgery using this device. In this series, we had two cases of gastrectomy, two cases of gastric bypass for morbid obesity, two Whipple cases for periampullary tumor, and seven cases of bowel resection. On the basis of this series, we were able to assess the utility of this device. RESULTS: Satisfactory pneumoperitoneum was maintained in 12 of 13 cases. The length of the skin incision was 7.8 cm on average, which was almost the same size as surgeon's glove. The device proved to be very useful for tissue retraction and abdominal exploration in all cases and for intracorporeal knot tying in some cases. CONCLUSIONS: We found that the device permitted an easier dissection, resection, and anastomosis. It also helped to decrease the operation time.

[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.

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.

Simple and rapid determination of enflurane in human tissues using gas chromatography and gas chromatography-mass spectrometry.

A simple, rapid and reliable method was devised to determine the levels of enflurane in human tissues, using gas chromatography and gas chromatography-mass spectrometry. 1,4-Dioxane was used as an internal standard (I.S.). Enflurane and the I.S. were extracted from 0.25 g of body tissues using an automatic headspace sampler and 1 ml of headspace gas was injected into the gas chromatograph. Enflurane was analyzed qualitatively by gas chromatography-mass spectrometry and quantitatively by gas chromatography with a flame-ionization detector. The calibration curves in all tissues examined were linear in the concentration range 1-100 microg/0.25 g. The lower limit of detection was 200-300 ng/0.25 g. The accuracy and precision of this method were evaluated at two different concentrations, 1 and 20 microg/0.25 g. The coefficient of variation ranged from 3.4-13.4%. We used this method to determine the presence of enflurane in tissues from an autopsied individual who died suddenly during extirpation of a malignant tumor.

[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.

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.

Duodenal but not gastric transection disturbs motility of the sphincter of Oddi in the dog.

The aim of the present study was to elucidate the effect of gastric and duodenal transection on biliary manometry in anesthetized dogs. The basal biliary pressure and increase in pressure during saline perfusion at rates of 1.0 and 1.5 ml/min were studied in intact controls, during infusion of cholecystokinin (CCK) alone, and after gastric and duodenal transection. CCK dose-dependently lowered the basal pressure and the increase in pressure during perfusion. Gastric transection 1.5 cm proximal to the pylorus did not affect these parameters. In contrast, duodenal transection 1.0 cm distal to the pylorus significantly increased these parameters compared to all other groups. These observations suggest that the proximal duodenal transection, as performed during conventional distal gastrectomy, may contribute to the pathogenesis of postgastrectomy gallstone formation by altering motor function of the sphincter of Oddi.

Design and synthesis of new mitochondrial cytotoxin N-thiadiazolylanilines that inhibit tumor cell growth.

New N-thiadiazolylanilines were designed and synthesized to develop mitochondrial cytotoxins superior to SF 6847. The mitochondrial cytotoxin N-thiadiazolylanilines, TX-108 and TX-109, inhibited EMT6/KU mammary sarcoma cell growth at a low micromolar concentration. Their inhibitory activities were parallel to their mitochondrial cytotoxicity, such as uncoupling oxidative phosphorylation and inhibiting ATP synthesis. This report also supports the notion that the inhibition of tumor cell growth of inhibitor of protein tyrosine kinase AG17, which is identical to SF 6847, may be due to its mitochondrial cytotoxicity.

[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.