Effects of recombinant bovine interferon gamma on Strongyloides papillosus infection in calves.

The effects of interferon (IFN) gamma on the course of infection with Strongyloides papillosus in calves were investigated. Calves (N = 7 each) were inoculated with recombinant bovine IFNy or control solution daily from day 0 to day 15 following S. papillosus infection. Treatment with IFN-gamma induced an increase in faecal egg output in the peak stage of infection. The IFNgamma-treated animals harboured more worms, especially more immature worms, in the small intestine than control animals at necropsy on day 17, with no decreases in intestinal mucosal mast cells. Both animal groups had similar small numbers of intestinal worms at necropsy on day 26. All control animals developed peripheral blood eosinophilia on day 7, while five of seven IFN-gamma-treated animals did not. Serum alpha1-acid glycoprotein concentrations increased on day 7 in both animal groups, with higher values in control animals than in IFNgamma-treated animals. Control animals mounted a predominant IgG1 response to S. papillosus from day 10, while IFNgamma-treated animals did from day 22. These data suggested that IFNgamma inhibited some host protective responses to S. papillosus migrating larvae, resulting in an improvement of worm survival after a period when protective responses should be activated during the early stage of infection. The effects of IFNgamma on intestinal worm expulsion should be confirmed by further experiments.

Effect of combination therapy with matrix metalloproteinase inhibitor MMI-166 and mitomycin C on the growth and liver metastasis of human colon cancer.

Several synthetic inhibitors of matrix metalloproteinases (MMPs) show antitumor, antimetastasis and antiangiogenesis effects in various models. Synergistic effects of combinations with conventional cytotoxic agents were reported previously. In this study, we examined the effects of a new selective MMP inhibitor, MMI-166, on tumor growth, angiogenesis and metastasis in a liver metastatic model of human xenotransplanted colon cancer (TK-4). We also investigated the synergistic effects of MMI-166 and a conventional cytotoxic agent, mitomycin C (MMC), in this model. Mice transplanted orthotopically with TK-4 were divided into 4 groups; a control group (treated with vehicle solution), an MMI-166 group in which MMI-166 was orally administered (p.o.) at a dose of 200 mg / kg, 6 days / week for 5 weeks, an MMC group in which MMC was administered intraperitoneally (i.p.) at a dose of 2 mg / kg / week for 5 weeks, and a combination group (treated with MMI-166 and MMC). MMI-166 did not inhibit transplanted tumor growth, but significantly inhibited liver metastasis compared with the control group and MMC group (P < 0.01). Significant antitumor and antimetastatic effects of the combination therapy were demonstrated. The microvessel density (MVD) detected by immunohistochemical staining with ER-MP12 antibody tended to be lower in the MMI-166 and the combination groups. These results suggest that MMI-166 has potential antimetastatic ability and a synergistic effect with MMC.

Identification and characterization of membrane cofactor protein (CD46) in the human kidneys.

Membrane cofactor protein (MCP, CD46) is an integral protein that serves as a cofactor for factor I in inactivating C3b/C4b deposited on the same cell membrane as C3bi/C4c+C4d. This C3b/C4b inactivation is closely associated with self-protection of host cells from autologous complement attack. We have studied the distribution and properties of MCP in the normal human kidney by immunohistochemical and immunoblotting methods using monoclonal antibodies against MCP. MCP was predominantly expressed on the juxtaglomerular apparatus. Glomerular capillary walls, mesangial areas, and tubulus were also MCP positive. Glomerulus MCP was composed of two major bands of 45-65 kDa, which were similar to those of lymphocyte MCP. The proportion of the high and low molecular weight components in glomerulus MCP, however, was considerably different from that of lymphocyte MCP among the individual samples tested. Glomerular epithelial cells and mesangial cells from an individual having equal amounts of high and low molecular weight components in the lymphocytes were cultured separately and the properties of their MCP investigated. MCP in the mesangial cells and glomerular epithelial cells showed profiles in which the upper band was predominant. The results may explain the unique distribution of the high and low molecular weight forms in the glomerulus. These forms of MCP together with factor I were all capable of inactivating C3b to C3bi. Message analysis suggested that glomerular epithelial cells and mesangial cells synthesized a single species of mRNA of 4.2 kb from which the polymorphic MCP species were generated. Flow cytometric analysis suggested that MCP was minimal in mesangial cells. These results, taken together with the previous reports on the distribution of other complement regulatory proteins, infer that the distribution profile of MCP is rather similar to that of DAF but differs from those of CD59 and CR1 in the normal human kidney; this may reflect the differences between their roles or functional properties in renal tissue.

Interleukin-8 in chronic renal failure and dialysis patients.

A total of 105 patients participated in this study, including 10 with chronic glomerulonephritis with normal renal function (CGN patients), 36 uraemic patients (CRF patients), 19 continuous ambulatory peritoneal dialysis patients (CAPD) without peritonitis, three CAPD patients with peritonitis, 37 patients undergoing chronic haemodialysis (HD) divided into short-term HD, 15 patients; medium-term HD, 12 patients; and long-term HD, 10 patients. IL-8 and two other proinflammatory cytokines, IL-6 and TNF alpha were tested using a specific immunoassay. IL-8, IL-6, and TNF alpha serum levels were significantly increased in patients with chronic renal failure compared to their levels in normal individuals (P < 0.0001, P < 0.05 and P < 0.0001 respectively). The most pronounced increment in IL-8, IL-6 and TNF alpha serum levels was observed in CAPD patients (P < 0.0001). CAPD patients without peritonitis showed relatively low levels of IL-8 or IL-6 in peritoneal dialysate effluents (PDE), whereas PDE-TNF alpha were not detectable in almost all patients tested. Patients with peritonitis showed very high serum and PDE levels of IL-8, IL-6 and TNF alpha. The clinical recovery from peritonitis was characterized by a rapid fall in IL-8, IL-6 and TNF alpha in serum and dialysate. HD patients showed a significant increase in serum levels of IL-8 and also IL-6 and TNF alpha compared to normal individuals (P < 0.05, P < 0.05 and P < 0.01 respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

[A case of pulmonary lymphangiomyomatosis induced by pregnancy].

A 35-year-old primigravida was admitted to the Department of obstetrics complaining of dyspnea and left back pain at 21 weeks' gestation. Chest roentgenogram revealed diffuse reticulonodular shadows predominantly in both lower lung fields and arterial hypoxemia was present. Pulmonary function tests showed restrictive impairment and decreased carbon monoxide diffuse capacity. From these results, interstitial pneumonia was suspected and she was first treated with prednisolone. However during her pregnancy, spontaneous pneumothorax occurred. Following spontaneous delivery of healthy infant at 37 weeks, left chylothorax occurred, and pleurodesis was performed with OK432. Thereafter the histological diagnosis of pulmonary lymphangiomyomatosis was made by transbronchial lung biopsy and treatment of prednisolone was stopped. She was treated with tamoxifen. In addition, progesterone-receptor was detected in the pulmonary tissue obtained at open lung biopsy. She was treated with cyclophosphamide in addition to tamoxifen. At present, shortness of breath has decreased slightly in comparison with one year previously, but no improvement has been seen in lung function tests or chest roentgenogram.