Experimental induction of uterine cancer in rats by N-ethyl-N'-nitro-N-nitrosoguanidine dissolved in polyethylene glycol

In the present experiment we attempted to experimentally induce uterine cancer in rats by injecting into the uterine cavity N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) dissolved in polyethylene glycol (PEG). Fifty-nine female F-344 rats, 7-8 weeks old, were divided into three groups and each received in the left uterine cavity with laparotomy a single dose of ENNG dissolved in PEG according to the following schedule: Group 1 received 75 mg ENNG/kg body wt.; Group 2 had 20 mg ENNG/kg body wt.: and Group 3 was given only PEG. In Group 1 it was observed that adenocarcinoma and sarcoma were present in the uterine corpus while squamous cell carcinoma occurred in the uterine cervix. In Group 2, although tumors such as adenocarcinoma, adenoma and sarcoma were observed in the uterine corpus, no tumor was present in the uterine cervix. No tumor growth whatsoever was observed in Group 3. From the above results it is apparent that the present method is an efficient means for experimentally inducing uterine cancer and that the site of tumor generation varies according to the concentration of ENNG administered.     

Probable implication of mutations of the X open reading frame in the onset of fulminant hepatitis B

A pathogenic role of precore-defective mutation in the onset of fulminant hepatitis B has been suggested. However, precore-defective mutants do not always cause fulminant hepatitis B and are not always isolated from affected patients. These findings strongly suggest the presence of some additional important mutations outside the precore region in fulminant hepatitis. In the present investigation an attempt was made to sequence the X open reading frame of hepatitis B virus DNA isolated from seven patients with fulminant hepatitis B and five patients with acute hepatitis B. The latter were used as controls. Since the X open reading frame encodes the X protein and contains the core promoter/enhancer II complex, some critical mutations may enhance or disrupt the replication and expression of hepatitis B virus DNA leading to fulminant hepatitis. A C-to-T substitution was found at nucleotide (nt) 1655, an A-to-T substitution at nt 1764 and a G-to-A substitution at nt 1766 in 4, 5 and 5 patients, respectively, out of the seven with fulminant hepatitis. These substitutions were not recognized in the patients with acute hepatitis. These mutations might change the function of the X protein and core promoter/enhancer II complex. It is suggested, therefore, that these mutations, as well as the precore-defective mutation, may play an important role in the pathogenesis of fulminant hepatitis. © Wiley-Liss, Inc.     

Immune Abnormalities Induced by Human Endogenous Retroviral Peptides: With Reference to the Pathogenesis of Systemic Lupus Erythematosus

P15E is a specific sequence among the envelope gene (env)-encoded transmembrane proteins of exogenous and endogenous retroviruses. A synthetic peptide (CKS-17) that shows homology to this p15E region in several species of retrovirus is known to induce immune abnormalities. In this study, we examined the effect of a synthetic peptide derived from a region of human endogenous retrovirus (HERV) clone 4-1 ( 4-1) similar to sequences of CKS-17 on the induction of systemic lupus erythematosus (SLE)-related immune abnormalities. Our results indicated that this peptide could induce T-cell activation and anergy in normal peripheral blood mononuclear cells, and the peptide could also promote the production of interleukins IL-6 and IL-16. These phenomena are representative immune abnormalities observed in SLE patients. Thus, our findings support the possibility that HERV acts as a pathogen in human SLE.     

Glomerulosclerosis develops in Thy-1 nephritis under persistent accumulation of macrophages

To clarify the relationship between macrophages and development of glomerulosclerosis, the authors developed a new experimental nephritis model with macrophages persisting in Thy-1 nephritis. Methyl-cellulose was administered intraperitoneally in addition to the intravenous injection of the anti-Thy-1 antibody to Wistar rats. Foamy macrophages influxed into the lytic mesangium and stayed to form nodular aggregates. Mesangial cells proliferated with the formation of extracellular matrices around these nodular aggregates of macrophages. Immunohistochemical analyses revealed that alpha-smooth muscle actin (alpha-SMA) was expressed in the proliferative area around these nodules of foamy macrophages from day 7. Type I collagen and type IV collagen were also expressed around the foamy macrophages in correspondence with alpha-SMA expression from day 7. The electron microscopic study revealed that collagen fibrils were formed around the transformed mesangial cells. The expression of platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31), a marker of glomerular vasculature endothelial cells, was not found in the area occupied by the foamy macrophages, suggesting the impairment of glomerular reconstruction. Macrophages may participate in the progression of glomerulosclerosis in Thy-1 nephritis by enhancing the production of the extracellular matrix through transformed mesangial cells and preventing reconstruction of the capillary network.     

Dioxygen sensitivity of a photoexcited thin film of phthalocyanine dispersed in poly(N-vinylcarbazole)

Thin films (thickness 0,3 μm) of a mixture of phthalocyaninatozinc(II) ( 1 ) and poly(1-vinylcarbazole) ( 2 ) are prepared by coating from a solution on ITO glass. The blue coloured films are investigated in an electrochemical cell under irradiation with visible light. In the presence of dioxygen from air the films exhibit an intensive cathodic photocurrent. The action spectrum of the photocurrent corresponds to the absorption spectrum of the phthalocyanine. The results show a device which can be switched by air and visible light.