Effect of intranasal fluticasone proprionate on the immediate and late allergic reaction and nasal hyperreactivity in patients with a house dust mite allergy

Background Patients with perennial allergic rhinitis develop nasal symptoms not only after allergen exposure, but generally also after non-specific stimuli. Objective To evaluate the effect of 2 week's treatment with fluticasone propionate aqueous nasal spray (FPANS) on the nasal clinical response, inflammatory mediators and nasal hyperreactivity. Methods Twenty-four rhinitis patients allergic to house dust mite (HDM). participated in a douhle-blind. placebo-controlled crossover study. After 2 week's treatment with placebo or 200 μg FPANS twice daily, patients were challenged with HDM extract. Symptoms were recorded and nasal lavages were collected for up to 9.5 h after challenge. Nasal hyperreaclivity was determined by histamine challenge 24 h later. Results Because of a carry-over effect for the immediate symptom score, for this variable only the data from the first treatment period were used. FPANS treatment resulted in a significant decrease of nasal symptoms with 70%. 69% and 63% after 100. 1000 and 10000 Biological Units (BU)/mL of HDM extract respectively. Active treatment resulted in a 76% decrease of the late-phase symptoms. FPANS treatment significantly reduced albumin influx after HDM 1000 BU/mL with 62% and tended to reduce tryptase release after HDM 1000 BU ml. (P 0.0629). During the late phase FPANS treatment reduced albumin influx with 67% and eosinophil cationic protein (ECP) release with 83%. No effect of FPANS was seen on histamine levels. FPANS significantly decreased histamine-induced symptom score with 34%, secretion with 32%, and sneezes with 41%. Conclusion FPANS significantly inhibits the immediate and late allergic response, and nasal hyperreactivity, probably by suppressing mast cells and eosinophils in the nasal mucosa.     

Monocyte chemotactic protein-3 (MCP3) interacts with multiple leukocyte receptors: binding and signaling of MCP3 through shared as well as unique receptors on monocytes and neutrophils

The diversity of monocyte chemotactic protein (MCP)3 target cell types, as well as the capacity of MCP3 to desensitize leukocyte responses to other CC chemokines, suggested that MCP3 may interact with multiple CC chemokine receptors. The purpose of this study is to establish how MCP3 binds and activates monocytes and neutrophils. We show that human monocytes exhibit high-affinity binding for ¹²⁵I-MCP3 with an estimated Kd of 1–3 nM and about 10000 binding sites/cell. The binding of ¹²⁵I-MCP3 to monocytes was progressively less well competed by CC chemokines macrophage inflammatory protein (MIP)lα (Kd = 5–10 nM), RANTES (Kd = 5–10 nM), MCP1 (monocyte chemoattractant and activating factor, or MCAF) (Kd = 60 nM) and MIP1β (Kd > 100 nM). On the other hand, unlabeled MCP3 displaced the binding of radiolabeled MIP1α, RANTES, MCP1 and MIP1β as effectively as the isologous CC chemokines. In agreement with the binding data, pretreatment of monocytes with MCP3 completely desensitized the calcium flux in response to MIP1α and RANTES. However, MIP1α and RANTES failed to desensitize the response of monocytes to MCP3. MCP3 and MCP1 partially desensitized each other's effects on monocytes. These binding and cross-desensitization results suggest that MCP3 binds and signals through other binding sites in addition to those shared with MIP1α, RANTES and MCP1. The unidirectional competition for MIP1β binding and signaling by MCP3 suggests the existence of an as-yet unidentified site for MCP3 shared with MIP1β. The existence of another unique binding site(s) for MCP3 was further shown by the failure of any of the other CC chemokines to compete effectively for MCP3 binding on neutrophils. MCP3 in our study was also the only human CC chemokine that consistently chemoattracted neutrophils. These results suggest that MCP3 is a ligand that can bind and activate a broad range of target cells through receptors shared by other CC chemokines as well as its own receptor.     

Secretion of γ-Interferon at the Cellular Level

Using a haemolytic plaque assay for gamma-interferon (IFN-gamma) secretion we found that in vitro Epstein-Barr virus (EBV) exposure of peripheral blood mononuclear cells from EBV immune individuals led to IFN-gamma secretion, which was apparent within 6 h after virus contact and peaked 12-24 h after induction. Live, ultraviolet-light-irradiated and heat-inactivated virions all caused IFN-gamma secretion. In contrast, blood mononuclear cells from EBV non-immune adults or neonates could not be activated to IFN-gamma production by EBV.     

Analysis of the Expression of I-Ak-like Antigens in Murine Fetal and Adult Tissues with the Monoclonal Antibody 10–2.16

The expression of I-Ak antigens in normal C3H/FeJ adult and 15-day embryonic mice has been investigated by indirect immunofluorescence staining of tissue cryostat sections with the anti I-Ak antigen monoclonal antibody 10-2.16. In adult mice I-Ak antigens were expressed in Langerhans-like cells in the skin, epithelium of the gastrointestinal tract, endometrium, thymic reticuloepithelial cells, and several capillary endothelia. On the other hand, these antigens were not detected in Kupffer cells, alveolar macrophages, brain or mammary gland. In 15-day-old embryos the expression of Ia-like antigens was restricted to thymic reticuloepithelial cells, isolated spleen cells, and capillaries of the gastrointestinal tract.     

Elaboration of lymphotoxin by cultured human peripheral blood leucocytes stimulated with dental-plaque deposits

Leucocyte cultures from subjects with periodontal disease when stimulated by human dental-plaque deposit material, or phytohaemagglutinin, produce a soluble factor, lymphotoxin, which is cytotoxic for fibroblasts in vitro. The cytotoxic effect was determined from the degree of inhibition of incorporation of ¹⁴C-labelled L-leucine by in vitro cultures of human gingival or mouse L-fibroblasts exposed to supernatants from such cultures. Inhibition of protein synthesis by the fibroblasts was not due to either depletion of nutrients or direct toxicity of the antigenic dental-plaque material. Both plaque-stimulated leucocyte culture supernatants from clinically normal subjects and unstimulated leucocyte culture supernatants from subjects with periodontal disease were significantly less inhibitory than supernatants of plaque-stimulated leucocyte cultures from subjects with periodontal disease. This production of lymphotoxin by leucocytes stimulated with antigen(s) present in dental plaque-deposits may reflect a mechanism of tissue destruction by sensitized lymphocytes present in the tissues of subjects with periodontal disease.     

Enhancement of the primary antibody response by 2-mercaptoethanol is mediated by its action on glutathione in the serum

2-Mercaptoethanol (2-ME) is widely used in rodent lymphoid cell cultures as an enhancer of multiple cellular functions. We have confirmed that the action of 2-ME must be on a serum component(s), rather than a direct action on the cells. The serum component(s) is contained within the dialyzable fraction of fetal calf serum (FCS) since: (a) dialysis of FCS diminished the ability of FCS to support an antibody response even in the presence of 2-ME; and (b) FCS dialysate, pulsed with 2-ME, restored the ability of dialyzed FCS to support an antibody response. Diminution of the reduced glutathione content of FCS by heating reduced the capacity of FCS to support an antibody response, whereas addition of 2-ME-pulsed glutathione restored the supportive capacity of heated FCS. Conversely, oxidized glutathione inhibited the antibody response in the absence of 2-ME, but that inhibition was not seen in the presence of 2-ME. We have concluded that reduced glutathione is an essential component in FCS in order for 2-ME to produce its enhancing effect. The most plausible explanation for the enhancement of antibody responses, in vitro, by 2-ME is the concomitant reversal of the inhibitory effect of oxidized glutathione and the increased availability of reduced glutathione which can scavenge oxygen-derived radicals, thus protecting macrophages and lymphocytes from the deleterious effects of oxygen-derived free radicals.     

Ventricular tachycardia as a complication of annular subvalvular ventricular aneurysm in a Caucasian woman

A Caucasian female patient with repetitive attacks of ventriculartachycardia and fibrillation caused by annular submitral leftventricular aneurysm is reported. During a follow-up periodof six years after aneurysmectomy, the patient remained symptom-free.     

Osteosarcomatosis

A review of the 690 cases of osteosarcoma in the radiographic file of the Armed Forces Institute of Pathology revealed 29 cases of "osteosarcomatosis" (multiple skeletal sites of osteosarcoma). Fifteen of these patients were 18 years old and under and manifested rapidly appearing, usually symmetric, sclerotic metaphyseal lesions. The remaining 14 patients were more than 18 years old and had fewer, asymmetric sclerotic lesions. In most patients (28 of 29), a radiographically dominant skeletal tumor was seen. Pulmonary metastases occurred in the majority of patients and were detected at the same time as the bone lesions. These 29 patients were studied with regard to demographic data and skeletal distribution and radiographic appearance of their lesions. As a result of the findings, a metastatic origin from a primary dominant osteosarcoma is favored over a multifocal origin as the basis for osteosarcomatosis. Osteosarcomatosis is more commonly encountered in the mature skeleton than has been previously recognized.