Prevention of murine antiphospholipid syndrome by BAFF blockade

OBJECTIVE: This study was undertaken to determine whether BAFF blockade can be used to prevent or treat antiphospholipid syndrome in a mouse model. METHODS: Eight- and 12-week-old (NZW x BXSB)F(1) mice were treated with BAFF-R-Ig or TACI-Ig alone or in addition to a short course of CTLA-4Ig. Mice were monitored for thrombocytopenia and proteinuria. Sera were tested for anticardiolipin antibodies (aCL), BAFF levels, and levels of soluble vascular cell adhesion molecule and E-selectin. Mice were killed at 17, 22, or 32 weeks of age, and kidneys and hearts were subjected to histologic examination. Spleen cells were phenotyped and enzyme-linked immunospot assays for autoantibody-producing B cells were performed. RESULTS: Both BAFF-R-Ig and TACI-Ig prevented disease onset and significantly prolonged survival. Treated mice had significantly smaller spleens than controls, with fewer B cells and fewer activated and memory T cells. BAFF blockade did not prevent the development of aCL, and there was only a modest delay in the development of thrombocytopenia. However, treated mice had significantly less nephritis and myocardial infarcts than did controls. CONCLUSION: Our findings suggest that aCL are generated in the germinal center, which is relatively independent of BAFF. Effector function of antiplatelet antibodies was only modestly affected by BAFF blockade. In contrast, myocardial infarctions were prevented, suggesting that triggering of thromboses requires both autoantibodies and mediators of inflammation. Similarly, renal damage requires both immune complexes and effector cells. The dissociation between autoantibody production and inflammation that may occur with B cell-depleting therapies underscores the role of B cells as effector cells in the autoimmune response.     

Unusual presentations of aorto-enteric fistula

BACKGROUND: Aorto-enteric fistula is rare but can result in exsanguination without timely surgery or endovascular stent placement. METHODS: Four cases of aorto-enteric fistula were reviewed in which the presentation was unusual and diagnosis difficult. OBSERVATIONS: The first patient had an aorto-sigmoid fistula in the setting of an aorto-bi-femoral graft. Two patients had a primary aorto-enteric fistula, one to the stomach from a suprarenal aortic aneurysm, and the other, to the duodenum in the setting of retroperitoneal spread of renal cancer. The aortoduodenal fistula recurred in the 4th patient within 3 months of surgical repair; this patient is the only one who survived long term. CONCLUSIONS: When presentation is atypical, the diagnosis of aorto-enteric fistula can be extremely difficult. Because investigative studies are not consistently useful in making a definitive pre-operative diagnosis, a strong index of clinical suspicion and a willingness to consider surgical exploration are essential for timely and successful management.     

Water quality criteria assessment for chlorinated benzenes using the quantitative structure activity relation approach and porphyrogenic endpoint in rats

Sub‐chronic toxicity data on rats for various chlorobenzenes have been utilized to show a high correlation between log dose porphyria and log P, the log of the octanol:water partition coefficient. Various predictive equations were calculated as a function of log P (log P)² log P + (log P)² log 1/S_W and (log 1/S_w)². All have good correlations except for the case of (log 1/S_w)². The calculated log criterion values obtained from predicted dose for porphyria in rats were regressed against log P and the log of the bioconcentration factor (log B) and various single and multi‐parameter regression equations were found. Criteria predicted from log P values and sub‐chronic toxicity data tended to be between 10–100 times larger than criteria calculated by other means (chronic toxicity, carcinogenicity or organoleptic). This quantitative structure activity relation approach has the advantage of providing criteria for all congeners in a series, whether or not they have been tested for carcinogenicity.     

Triangulating stapling technique: An alternative approach to colorectal anastomosis

The triangulating stapling technique was employed to perform colorectal anastomosis in 259 patients. In 220 patients, the anastomosis was performed between the colon and nonperitonealized rectum. This anastomotic technique is safe and reliable and is an effective alternative to a circular stapling device, with minimal morbidity. The incidence of leak rate is comparable to anastomoses created by a circular stapling device. The main advantage seems to be the very low incidence of anastomotic stenosis.     

Effect of methylmercuric chloride on gene expression in neuroblastoma and glioma cells after acute and chronic treatments

To understand the cellular and molecular mechanisms ofmethylmercuric chloride (CH₃HgCl)-induced damage to nerve tissue, monolayer cultures of glioma cells (C-6) and of neuroblastoma cells (NBP2) were used in this study. Chronic (6–8 weeks) and acute (5 days) treatment of glioma cells with low concentrations (0.05 to 0.1 μM) of CH₃HgCl produced marked increases and decreases in the amounts and net phosphorylation profiles of specific proteins. Chronic treatment of neuroblastoma cells (0.1 and 0.2 μM) did not produce any significant alterations in the amounts of specific proteins, but it caused marked changes in the phosphorylation levels of cellular proteins. The morphology and doubling time of chronically treated glioma and neuroblastoma cells did not change. Adenosine 3',5'-cyclic monophosphate (cyclic AMP)-stimulating agents produced morphological changes in chronically treated glioma and neuroblastoma cells similar to those produced in untreated cells.     

Chloramine-T as a potential scrubbing agent: Removal of odorous sulfur-containing environmental pollutants

Conclusion A detailed study of the reaction of thioacetamide, thiobenzamide, thiobenzoic acid, thiophenol and ethanethiol (emitted from industrial stacks or as industrial wastewater effluents and ultimately becoming environmental pollutants) with Chloramine-T has been made. Odor studies based on the sensory approach, have been performed on the reactants as well as the reaction mixtures containing the oxidation products, using odor test panels to determine the odor threshold levels. In all cases the median odor threshold concentration has been raised substantially by reaction with CAT. From the preliminary studies it is concluded that this oxidative technique has potential application in air and water pollution odor control.