Antigenic homogeneity among the adenovirus hexon types of subgenus C

Summary Antigenic relationships of hexons of human adenovirus (Ad h) types 1, 2, 5 and 6 of subgenus C were studied with 61 monoclonal antibodies (MAbs) raised against human Ad h1, Ad h35 and bovine adenovirus 2. The reactivity pattern (RP) and the titers of the MAbs were determined in indirect ELISA. In previous experiments with hexons of different subgenera 49 MAbs displayed numerous different intertype specificities besides genus specific and type specific ones. With the four hexon types of subgenus C all MAbs gave identical RPs except the type specific ones. Data reveal the existence of a remarkable homogeneity in the antigenic structure among the hexon types of subgenus C defined by the presence of identical or closely related intertype specific epitopes on the surface of the hexons. The possible significance of the results in the experimental gene therapy is discussed.     

Inhibitory activity of a series of coumarins on leukocyte eicosanoid generation

Sixteen plant-derived or synthetic coumarins with different patterns of substitution were tested for their capacity to modify A23187-induced synthesis of leukotriene B₄ and thromboxane B₂ via the 5-lipoxygenase and cyclooxygenase pathways of arachidonate metabolism in rat peritoneal exudate leukocytes. Five of the 16 coumarins inhibited LTB₄ production: all containortho-dihydroxy substitutions (approximate IC₅₀ values 8–100 M). The mechanism is likely to depend upon a combination of the coumarins' iron-chelating and iron ion-reducing abilities, properties which also confer beneficial activities of these compounds as scavengers of reactive oxygen species (Payá et al., Biochem. Pharmacol.44, 205–214 (1992)). Inhibition of the cyclooxygenase pathway was only demonstrated by one compound, 5,7-dihydroxy-4-methylcoumarin, which did not inhibit 5-lipoxygenase, indicating that the cyclooxygenase inhibitory mechanism is different. Similar effects of the active coumarins were obtained using arachidonic acid as substrate for rat leukocyte eicosanoid generation, confirming that they act at the 5-lipoxygenase/cyclooxygenase level. The same profile of activity was also shown when the coumarins were tested against 5-lipoxygenase in human polymorphonuclear neutrophils. Taken together, these antioxidant and anti-eicosanoid properties of coumarins could be exploited for the design of potentially valuable non-toxic anti-inflammatory agents for treating diseases in which eicosanoid generation and the production of reactive oxygen species are involved.     

Lack of correlation between impaired Interferon production and natural killer activity of lymphocytes in multiple sclerosis

Summary The ability of lymphocytes from patients with multiple sclerosis (MS) to produce Interferon (IFN-) in response to Newcastle Disease Virus (NDV) was studiedin vitro. The correlation between individual IFN- titers and natural killer (NK) cell activity and the presence of HLA system antigens associated with MS (B-7 and DRW-2) was also investigated.Lymphocytes from MS patients showed a significantly impaired capacity to synthesize IFN-in vitro when compared to lymphocytes from healthy donors (mean titers: 85.9 I.U. and 268.2 I.U., respectively). Marked differences in IFN- titers were observed in the group of MS patients.The production of IFN- by the patients' lymphocytes did not correlate with either the activity of NK cells or with their stimulation by exogenous IFN-. There was also no correlation between IFN- production by lymphocytes from MS patients and the presence or absence of B-7 and DRW-2 antigens.With 3 Figures     

Favorably tipping the balance between cytopathic and regulatory T cells to create transplantation tolerance

Therapeutic application of broadly reactive anti-T cell antibodies can lead not only to potent immunosuppression but also to profound and long-lived T cell depletion. We reasoned that a strategy that almost exclusively targets activated cytopathic donor reactive T cells and spares immunoregulatory networks might prove to be an exceptionally potent and highly selective means of producing long-term engraftment and tolerance. Herein we show that the combined administration of rapamycin and agonist IL-2- and antagonist IL-15-related cytolytic fusion proteins provides for long-term engraftment/tolerance in exceptionally stringent allotransplant models by (1) limiting the early expansion of activated T cells, (2) preserving and even exaggerating their subsequent apoptotic clearance, and (3) further amplifying the depletion of these activated T cells by antibody-dependent mechanisms, while (4) preserving CD4+CD25+ T cell-dependent immunoregulatory networks.     

Botryoid-type of embryonal rhabdomyosarcoma of renal pelvis in an adult. A case report and review of the literature

A case of botryoid-type embryonal rhabdomyosarcoma of the renal pelvis in a 49-year-old woman is reported. The tumor led to hydronephrosis. The surgical resection specimen disclosed a translucent, polypoid mass attached to the wall of the renal pelvis by thin stalk. Light-microscopic examination revealed a large exophytic polypoid tumor with intact surface epithelium, which was negative for dysplasia or carcinoma in situ. There was a condensation of epithelioid to spindle cells underneath the basement membrane, forming a cambium layer. The core of the lesion contained interspersed epithelioid to spindle cells with myxoid change and edema. Cells of the cambium layer as well as interspersed cells in the core exhibited marked cytologic atypia with mitotic figures. Immunohistochemical stains for cytokeratin, S-100 and myoglobin were negative, stains for desmin and actin were positive. Although botryoid-type embryonal rhabdomyosarcomas have been reported to occur at various sites in the genital tract and lower urinary tract, to our knowledge, this is the first reported case of the tumor within the renal pelvis. Also, the occurrence of these tumors in adults is quite rare.     

High co-prevalence of genogroup 1 TT virus and human papillomavirus is associated with poor clinical outcome of laryngeal carcinoma

BACKGROUND: The aetiology and factors leading to the progression of laryngeal cancer are still unclear. Although human papillomavirus (HPV) has been suggested to play a role, reports concerning the effect of HPV infection on tumour development are controversial. Recently, transfusion transmitted virus (TTV) was suggested to play a role in certain infections as a causative or coinfecting agent. AIMS: To investigate whether the development and progression of laryngeal squamous cell carcinoma is associated with coinfection with TTV and HPV. METHODS: The prevalence of TTV and HPV was investigated using the polymerase chain reaction in tissue samples from 40 healthy individuals, 10 patients with recurrent papillomatosis, five patients with papillomatosis with malignant transformation, and 25 patients with laryngeal carcinoma. The obtained prevalence data were compared and analysed statistically. RESULTS: In the 11 patients with carcinoma who had metastasis or relapse there was a high rate of coinfection with genogroup 1 TTV and HPV (eight of 11), whereas in the 14 without tumour progression no coinfection was found. Coinfection was associated with significantly lower tumour free survival in patients with carcinoma (p < 0.001). Furthermore, four of five patients who had papillomatosis with malignant transformation were coinfected with genogroup 1 TTV and HPV. CONCLUSIONS: Although the nature of cooperation between HPV and TTV needs to be investigated further, coinfection with genogroup 1 TTV and HPV appears to be associated with poor clinical outcome in laryngeal cancer.     

Monoclonal antibodies to three distinct epitopes on human IgE: their use for determination of allergen-specific IgE

Three different monoclonal antibodies (MAb) against human immunoglobulin E have been obtained which specifically bind to human myeloma and polyclonal IgE. The antibodies showed high avidities for soluble IgE (0.7 X 10(9) to 3.3 X 10(9) M-1). These MAb defined three distinct epitopes on IgE. A mixture of these antibodies in combination with an 125I-labelled anti-mouse Kappa chain MAb has been used to measure allergen-specific IgE. This determination was performed by a solid-phase radioimmunoassay using allergen extracts coated to either chemically activated paper discs or to polyvinyl chloride wells. This method is 4-10 times more sensitive than other previously reported procedures. A similar technique has also been applied to detect individual allergens in immunoblots of allergen extracts.