Immunohistochemical study of matrix metalloproteinases and their tissue inhibitors in pulmonary Langerhans' cell granulomatosis

OBJECTIVE: To evaluate the role of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in the pathogenesis of the lesions of pulmonary Langerhans' cell granulomatosis. DESIGN: Immunohistochemical and confocal microscopic studies were made of lung biopsy specimens from five patients with pulmonary Langerhans' cell granulomatosis. RESULTS: The reactivity of Langerhans' cells was moderate to intense for MMP-2, weaker for MMP-9, and faint for TIMP-1 and TIMP-2. Type IV collagen colocalized with MMP-2 in areas of damage to epithelial basement membranes, a finding that emphasizes the potential importance of this enzyme in the pathogenesis of the destructive lesions of pulmonary Langerhans' cell granulomatosis. In the more advanced fibrotic lesions, TIMP-2 colocalized with basement membranes and with fibrillar collagen, suggesting that it contributes to the permanence of the fibrosis. CONCLUSION: These results indicate an important role for MMPs and TIMPs in pulmonary Langerhans' cell granulomatosis.     

Denervation, but not decentralization, reduces nerve growth factor content of the mesenteric artery

In the present study we applied an improved nerve growth factor (NGF) extraction method to examine the effects of denervation and sympathetic decentralization on NGF levels in vascular tissue. Adult male Wistar Kyoto rats underwent mesenteric arterial denervation or splanchnic nerve transection. Four days after operation, animals were killed, and the mesenteric artery and coeliac-superior mesenteric ganglia were removed. The arterial adventitia was stripped from the media to measure NGF levels in nerve and smooth muscle separately. A high concentration of NGF was detected in the normal artery, 90% of which was in the adventitial layer. Surgical denervation significantly reduced the NGF levels in the artery and ganglia by 78 and 71%, respectively. However, within the artery the level of NGF was reduced in the adventitia but not in the media. Thus, the large reduction of NGF content resulted from the loss of nerve plexus from the artery. In contrast, decentralization did not alter the NGF content in the artery, in either the adventitia or media. Our results are in marked contrast to previous studies reporting elevated levels of NGF following denervation. This discrepancy is explained by the ability of our new procedure to extract much greater amounts of NGF from the tissue.     

Some ionospheric factors affecting the coverage of an HF/VHF direct broadcasting satellite service

A study has been undertaken to assess the effects of the ionosphere on the performance of a direct broadcasting satellite service operating in the high frequency (HF) band. Results relating to two issues of performance are presented: 1) determining under what conditions a frequency allocated to the broadcasting service can be expected to reach the surface of the earth from a satellite and 2) the loss of signal strength due to passage through the ionosphere, it was found that if high frequency broadcast services are to be provided on a worldwide basis using satellite platforms, the satellites need to be optimally configured for the intended service area. Also, a 3 dB loss of signal strength is expected due to ionospheric absorption.     

Cocaine improves inhibitory control in a human model of response conflict.

The present study was designed to test the acute effects of cocaine on behavioral control in the presence and absence of motivational conflict. Adults (N=14) with a history of stimulant use received oral cocaine hydrogen chloride (0, 100, 200, and 300 mg) and performed a cue-dependent go/no-go task to measure inhibitory and activational mechanisms of behavioral control either with or without motivated conflict between the inhibition and the activation of responses. Cocaine improved response inhibition in both conflict conditions, as evident by a decrease in inhibitory failures following active doses. The current study provides a useful model to investigate the effects of other drugs reported to have performance-enhancing effects. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sample matrix effects on glycopeptide stability by high performance capillary electrophoresis

High performance capillary electrophoresis (CE) of glycoprotein digests frequently reveals extensive microheterogeneity associated with specific protein glycosylation sites. The choice of the sample matrix can influence the electrophoretic migration time, peak shape and resolution, as well as the physical stability of the product glycopeptides. Acetic acid is a frequently employed sample matrix for both capillary electrophoresis and electrospray ionization-mass spectrometry (ESI-MS). Acetic acid appears to enhance the spontaneous hydrolysis of sialic acids from the nonreducing termini of glycopeptides in a time- and concentration-dependent manner, even at 5 degrees C, as evidenced by changes in the electrophoretic mobility and ESI-MS spectra of the resulting glycopeptides. The observed parallel electrophoretic mobility changes for specific glycoforms are consistent with the induction of peptide structure with time. Asialoglycopeptide mobilities were stable in acetic acid. Electrophoretic mobilities can be stabilized with propionic acid sample matrix with no apparent structural changes observed by ESI-MS within 31 h. Migration time reproducibility was in the range of 0.1% relative standard deviation (N = 7) with excellent peak shapes and enhanced glycopeptide resolution.     

Nutritional alterations and the effect of fish oil supplementation in dogs with heart failure

Alterations in body composition and nutritional status are common in humans with heart failure and are related, in part, to increases in cytokine concentrations. Cytokines have not been studied previously in dogs with naturally occurring cardiac disease nor has fish oil administration been used in this population to decrease cytokine production. The purposes of this study were to characterize nutritional and cytokine alterations in dogs with heart failure and to test the ability of fish oil to reduce cytokines and improve clinical outcome. Body composition, insulinlike growth factor-1, fatty acids, and cytokines were measured in 28 dogs with heart failure and in 5 healthy controls. Dogs with heart failure then were randomized to receive either fish oil or placebo for 8 weeks. All parameters were measured again at the end of the study period. At baseline, 54% of dogs with heart failure were cachectic and the severity of cachexia correlated with circulating tumor necrosis factor-alpha concentrations (P = .05). Cytokine concentrations at baseline, however, were not significantly increased in dogs with heart failure compared to controls. Baseline plasma arachidonic acid (P = .02), eicosapentaenoic acid (P = .03), and docosahexaenoic acid (P = .004) concentrations were lower in dogs with heart failure than in controls. Fish oil supplementation decreased interleukin-1 beta (IL-1) concentrations (P = .02) and improved cachexia (P = .01) compared to the placebo group. The mean caloric intake of the heart failure dogs as a group was below the maintenance energy requirement (P < .001), but no difference was found in food intake between the fish oil and placebo groups. Insulinlike growth factor-1 concentrations (P = .01) and reductions in circulating IL-1 concentrations over the study period (P = .02) correlated with survival. These data demonstrate that canine heart failure is associated with cachexia, alterations in fatty acids, and reduced caloric intake. Fish oil supplementation decreased IL-1 concentrations and improved cachexia. In addition, reductions in IL-1 predicted survival, suggesting that anticytokine strategies may benefit patients with heart failure.     

Cytologic evaluation of bronchoalveolar lavage fluid from horses with recurrent airway obstruction after aerosol and parenteral administration of beclomethasone dipropionate and dexamethasone, respectively

OBJECTIVE: To determine cytologic changes in horses with recurrent airway obstruction (heaves) after administration of aerosolized beclomethasone dipropionate and dexamethasone parenterally. ANIMALS: 6 horses with inducible and reversible heaves. PROCEDURE: Episodes of heaves were induced by exposure to moldy hay and straw for 7 days. Horses were assigned to treatment groups (aerosolized beclomethasone, parenterally administered dexamethasone, aerosolized propellant), and pulmonary inflammation was evaluated by serial cytologic examination of bronchoalveolar lavage (BAL) fluid samples obtained on days 0, 7, 10, 14, and 21. Total and differential cell counting and phenotypic analysis of lymphocyte subpopulations in BAL fluid were performed. RESULTS: 7 days of natural challenge induced neutrophilic inflammation. Neutrophil counts in BAL fluid were reduced in beclomethasone- and dexamethasone-treated horses on days 10 and 14 but rebounded to pretreatment values on day 21. The proportion of proinflammatory lymphocyte subpopulations (CD4+ and B+) and MHC class-II antigen expression were increased on days 14 and 21 in propellant-treated horses, compared with beclomethasone- and dexamethasone-treated horses. CONCLUSIONS: Aerosolized beclomethasone attenuated neutrophilic pulmonary inflammation and prevented alteration in lymphocyte subpopulations in horses with heaves. Results were similar to the response associated with parenterally administered dexamethasone. Short-term administration of aerosolized beclomethasone without minimizing environmental allergen exposure is not expected to provide prolonged anti-inflammatory benefit for horses with heaves.