Evaluation of epithelial and mesenchymal cell markers in canine urinary bladder transitional cell carcinoma.

Canine transitional cell carcinoma (cTCC) is the most common malignant tumour in the urinary bladder: it is highly invasive and exhibits metastatic characteristics. Inflammation is also strongly related to cTCC. Epithelial tumours often exhibit a mesenchymal cell phenotype during tumour invasion and metastasis owing to epithelial-mesenchymal transition (EMT), which is often induced in chronic inflammation. The aim of this retrospective study was to investigate the expression of epithelial and mesenchymal cell markers in tumour cells and to evaluate its relationship with prognosis of cTCC. In this study, 29 dogs with cTCC who underwent surgical treatment were enrolled. Clinical parameters were reviewed using medical records. Tissue expression of epithelial and mesenchymal markers was evaluated by immunohistochemical analysis. The association between the expression of mesenchymal cell markers and clinical parameters, including prognosis, was statistically examined. In five normal bladder tissues used as controls, no expression of mesenchymal markers was observed, except for one tissue that expressed fibronectin. Conversely, epithelial tumour cells expressed vimentin and fibronectin in 23/29 and 19/28 cTCC tissues, respectively. Regarding clinical parameters, vimentin score in Miniature Dachshunds was significantly higher than those in other dog breeds (P < 0.001). Multivariate survival analyses revealed that age>12 years was related to shorter progression-free survival (P = 0.02). Higher vimentin score, lower fibronectin score, and advanced clinical T stage were significantly correlated with shorter median survival time (P < 0.05). The results of this study indicate that vimentin expression was associated with cTCC progression. Further studies are needed to examine the incidence and relevance of EMT in cTCC.

Proteolysis of insulin-like growth factor-binding protein-3 is increased in urine from patients with diabetic nephropathy.

The insulin-like growth factor (IGF) system has been implicated in the development of experimental diabetic nephropathy. IGF-binding protein-3 (IGFBP-3) modulates IGF actions, and proteolysis decreases its binding affinity for IGFs. The aim of this study was to explore the possibility that proteolysis of IGFBP-3 may be altered in diabetic nephropathy and may therefore modify the intrarenal effects of IGFs. IGFBP-3 proteolysis in urine from diabetic patients with normo- [albumin excretion rate (AER), <20 microg/min], micro- (AER, 20-200 microg/min), and macroalbuminuria (AER, >200 microg/min) was studied in 34 patients with noninsulin-dependent diabetes mellitus (NIDDM), 14 patients with insulin-dependent diabetes mellitus, and 9 controls. Urine samples were analyzed by Western ligand blotting and IGFBP-3 immunoblotting. Protease activity was quantitated using [125I]IGFBP-3 as a substrate. WLB showed three main bands (40-46, 35, and 26 kDa) in control urine and a fainter 18-kDa band. All but the 35-kDa band were immunoreactive with the IGFBP-3 antiserum. The same pattern of IGFBPs was seen in urine from normoalbuminuric diabetic patients. However, the urine of diabetic patients with micro- and macroalbuminuria contained little or no intact 40- to 46-kDa IGFBP-3. In patients with noninsulin-dependent diabetes mellitus, urinary IGFBP-3 protease activity in micro- (n = 13) and macroalbuminuric patients (n = 12; mean +/- SD[SCAP], 75 +/- 25% and 84 +/- 24%) was significantly higher than that in normoalbuminuric patients (29 +/- 9%; P = 0.0001). Similar results were observed in patients with insulin-dependent diabetes mellitus. Proteolytic activity in diabetic urine was due to a serine protease. In conclusion, diabetic nephropathy was associated with IGFBP-3 proteolysis in urine. As similar changes were not observed in patients' sera, this is likely to reflect changes in the kidney or urinary tract, resulting in increased local IGF bioavailability, and therefore may contribute to the structural changes of diabetic nephropathy.

Rapid changes in concentrations of essential elements in organs of rats exposed to methylmercury chloride and mercuric chloride as shown by simultaneous multielemental analysis.

An in vivo study of rats given a dominant lethal dose of methylmercury chloride (MMC) or mercuric chloride (HgCl2) was conducted to elucidate the rapid biotransformation of essential elements. The elements were measured by inductively coupled plasma atomic emission spectrometry. For the rat brain Zn concentrations were higher in the MMC group than in the HgCl2 and control groups. The highest Cu concentration was found in HgCl2 dosed rat liver. For the rat kidney the highest Zn concentration was seen in the MMC group. From principal component analysis on the time dependent behaviour of each element in rat organs, characteristics specific to Cu in the liver and kidney and Mn in the brain were found after exposure to HgCl2 and Ca and Zn in the brain after exposure to MMC.

Concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans from chemical manufacturers and waste disposal facilities.

Polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) were measured in various source and environmental samples obtained from eight chemical manufacturers producing agricultural chemicals, synthetic dye, or resin and eight chemical waste disposal facilities. The concentrations of PCDDs and PCDFs ranged from 3.0 to 3504 ng/g for PCDDs and from 1.2 to 1668 ng/g for PCDFs in fly ash. Their concentrations in emission were in the ranges of 21.8 to 3205 ng/m3 for PCDDs and not detected to 4344 ng/m3 for PCDFs. PCDD and PCDF concentrations were higher in fly and bottom ashes and in emissions from two manufacturers that incinerate waste plastics than in those from other manufacturers. For emission and liquid samples from the manufacturers. For emission and liquid samples from the manufacturers of agricultural chemicals, significantly high concentrations of tetra-CDDs were detected. Furthermore, the high concentrations of PCDFs, especially hepta- and octa-CDF congeners, existed in emissions from waste incinerators that manufacture rubber. Among manufacturers and disposal facilities, the total emission equivalent (2.94 ng/m3) of PCDDs and PCDFs was highest for a certain manufacturer of agricultural chemicals, showing that more 2,3,7,8-chlorine-substituted PCDDs and PCDFs were present in their emissions.

The tissue distribution of 2,3,7,8-chlorine substituted dibenzo-p-dioxins in humans who died of cancer.

The tissue distribution of 2,3,7,8-chlorine substituted dibenzo-p-dioxins was conducted in 11 patients who died of cancer. The concentration of octachlorodibenzo-p-dioxin (octa-CDD) was the highest in each organ and tissue and hepta-CDD was also found at relatively high levels, second only to OCDD. The levels of 1,2,3, 7,8-penta-CDD and 1,2,3,6,7,8-hexa-CDD in the spleen were the highest, respectively. 2,3,7,8-Tetra-CDD was also detected and its concentration was the highest in the gonad (0.8-3.2 pg/g-range). From the 2,3,7,8-TCDD toxic equivalent calculations, the highest equivalent value was obtained from a 54-year-old female who died of cancerous goiter. This individual had the highest concentrations of 2,3,7,8-substituted penta- and hexa-CDDs among the 11 patients.

[Effect of mercuric chloride on phospholipid peroxidation in rat].

Individual molecular species of mercuric chloride induced phospholipid peroxide formed in rat brain, liver and kidney were determined using the multi-channel UV-high-performance liquid chromatography (HPLC) combined with potentiometric determination. Mercuric chloride (0.5 mg/kg/day) was administered subcutaneously to rats for 3 days. In accordance with a specified time schedule following administration (0.5, 1, 3 and 5 days), rats were decapitated and the phospholipids of brains, livers and kidneys were extracted and purified. The samples were then injected into the HPLC and the ratio (235 nm/203 nm) of peak area of each phospholipid was calculated. The peroxide value of each sample was determined using the calibration curve of the auto-oxidized standard phospholipids which were analyzed by both potentiometric determination and UV HPLC. Kidney phospholipid peroxides were easier induced than those in other organs reached their maximum peak (20.5 meq./kg) at 1 day after initial administration. Phospholipid peroxides in kidney and brain showed similar movement, while those in liver showed their maximum peak 3 days later. Of the phospholipids, phosphatidylserine and phosphatidylethanolamine seemed to be more susceptible to lipid peroxidation induced by mercuric chloride, the common feature of these two phospholipids being that both of them have primary amine group(s) on their polary heads and both are located on the cytosolic side of cell membrane. These results may be explained by mechanisms that relate to the interaction between mercurials and cell membranes or that between mercurials and primary amine groups of phospholipids. Further study is necessary to clarify the specific mechanisms involved in the induction of lipid peroxidation by mercurials and the interaction of mercurials with phospholipids.

[A report of renal cell carcinoma in a horseshoe kidney].

A case of renal cell carcinoma associated with horseshoe kidney is reported. The patient was a 67 years old man with the chief complaints of dull pain of right upper abdomen. Ultrasonography (US) revealed horseshoe kidney and abnormal mass sign at the right isthmus of the kidney. By the computed tomography (CT) and angiography, renal cell carcinoma associated with horseshoe kidney was diagnosed. Only 18 cases of this rare disease have been reported in Japan. The diagnostic procedures are discussed and the usefulness of selective arteriography of the isthmus is emphasized, as the presentation of vascular anatomy is of great value for diagnosis, surgical treatment and preoperative arterial embolization.

Enhancement of interferon-gamma production in glycyrrhizin-treated human peripheral lymphocytes in response to concanavalin A and to surface antigen of hepatitis B virus.

The effects of glycyrrhizin, a component of licorice (Glycyrrhiza glabra) roots, on the production of interferon-gamma in human peripheral lymphocyte-macrophage cultures by concanavalin A (Con A) was examined. Interferon-gamma production in normal lymphocyte-macrophage cultures treated with 10 to 100 micrograms/ml of glycyrrhizin at 37 degrees C for 12 hr or longer, and then treated with 10 micrograms/ml of Con A, was enhanced four to eight times compared to control cell cultures. Lymphocyte-macrophage cultures treated with 10 to 100 micrograms/ml of glycyrrhizin alone did not produce interferon. No significant difference in the adsorption of [3H]Con A to glycyrrhizin-treated and control lymphocyte-macrophage cultures was found, but RNA and protein synthesis of the treated lymphocytes was increased compared to control cells; DNA synthesis, however, was reduced. Collaboration between enriched T-lymphocytes and macrophages, both treated with glycyrrhizin, was needed for the enhancement of interferon-gamma production. A smaller increase in interferon production was also observed in the glycyrrhizin-treated peripheral lymphocyte-macrophage cultures derived from an asymptomatic carrier of hepatitis B virus, in response to Con A and surface antigen of hepatitis B virus.