Maternal antibody repertoire restriction modulates the development of lupus-like disease in BXSB offspring.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease that has a strong preference for women of child-bearing age. Maternal factors play an essential role in shaping the immune system of the newborn, yet it is unknown whether maternal factors could modulate the development of SLE in the offspring. Activation-induced cytidine deaminase (AID) is an enzyme required for somatic hypermutation and class switch recombination. Given that IgG and IgA isotypes account for the vast majority of passive immunity in rodents, our previously established AID-deficient BXSB mice provide a model in which maternal antibodies that can be transferred to the offspring are greatly diminished and have restricted repertoire. In this study, we compared genotypically identical mice born to either AID-sufficient dams or AID-deficient dams and evaluated the effects of maternal antibodies in disease progression. Offspring from knockout dams developed disease at a faster rate, as shown by more severe nephritis and elevated pathogenic autoantibodies compared to their counterparts born to wild-type dams. When immune competent pups were cross fostered onto AID-deficient dams, these mice exhibited more severe disease characteristics, including exacerbated lupus nephritis, increased levels of circulating antinuclear antibodies, and more activated T cells. These results suggest that a protective antibody effect contributes to the modulation of SLE progression in postnatal period. Overall, these findings highlight the importance of maternal antibodies in programming the immune system and altering SLE development in offspring.

The Role of the Urinary Bladder in the Diagnosis of Abdominal Compartment Syndrome: A Prospective Study in Trauma Patients.

Purpose The aim of this study was to evaluate the accuracy of bladder pressures in the diagnosis and management of abdominal compartment syndrome (ACS). Methods After Institutional Review Board (IRB) approval, nine operative abdominal trauma patients were prospectively studied over an 18-month period. Bladder pressures were compared to pressures obtained from intra-operatively placed electronic transducer located in the pelvis. Statistical analysis was performed using methods described by Bland and Altman. Results A Bland-Altman plot was used to assess the differences between bladder and transducer pressures. There was little agreement between the two methods at low (10-15 mmHg) and high (30-70 mmHg) pressures. At higher pressures, there was a notable difference between these two types of pressure. No patients required repeated operation. One patient died from severe traumatic brain injury. Conclusion Measurements obtained from the urinary bladder did not agree well with those obtained from within the peritoneal cavity. Furthermore, abdominal pressures greater than 20 mmHg did not show signs of ACS in this selected population, raising doubts about the utility of using abdominal pressures alone in the management of ACS.

Recurrent left chest mass: a case report.

Empyema necessitans is a rare complication of untreated pleural space infections. Untreated empyema that spontaneously burrows through the parietal pleura can present with a subcutaneous abscess. In the following case report, we present a 55 year old male who presented with an intermittent left chest mass later to be diagnosed as empyema necessitans. The patient suffered from a hemothorax treated by tube thoracostomy three years prior. The patient had been seen several times and no mass could be appreciated. The patient was diagnosed with empyema necessitans on computed tomography and treated with a left thoracotomy. Empyema necessitans can develop if pleural infections are left untreated. We present an unusual presentation of this rare complication. Empyema necessitans should be kept in the differential diagnosis of patients with left chest masses or abscesses.

Lactic acidosis after resuscitation with sodium acetate.

BACKGROUND: At our institution, we began using sodium acetate for resuscitation of trauma patients in 2005. Sodium acetate is used as an alternative to normal saline to help prevent hyperchloremic metabolic acidosis as well as to help buffer metabolic acidosis. DISCUSSION: Here we present a case of a 29-year-old trauma patient who began to have severe lactic acidosis after the infusion of sodium acetate. This is the first reported case of lactic acidosis caused by sodium acetate infusion. Up to this point, we have not experienced any adverse events and patients have tolerated sodium acetate well. CONCLUSION: This unique case report presents the first case of lactic acidosis from sodium acetate infusion. The lactic acidosis seen in this patient reminds us of the complex regulation of pyruvate dehydrogenase and the potential for down regulation of the enzyme shunting substrates to formation of lactate.

Ceramide signaling in fenretinide-induced endothelial cell apoptosis.

Stress stimuli can mediate apoptosis by generation of the lipid second messenger, ceramide. Herein we investigate the molecular mechanism of ceramide signaling in endothelial apoptosis induced by fenretinide (N-(4-hydroxyphenyl)retinamide (4-HPR)). 4-HPR, a synthetic derivative of retinoic acid that induces ceramide in tumor cell lines, has been shown to have antiangiogenic effects, but the molecular mechanism of these is largely unknown. We report that 4-HPR was cytotoxic to endothelial cells (50% cytotoxicity at 2.4 microm, 90% at 5.36 microm) and induced a caspase-dependent endothelial apoptosis. 4-HPR (5 microm) increased ceramide levels in endothelial cells 5.3-fold, and the increase in ceramide was required to achieve the apoptotic effect of 4-HPR. The 4-HPR-induced increase in ceramide was suppressed by inhibitors of ceramide synthesis, fumonisin B(1), myriocin, and l-cycloserine, and 4-HPR transiently activated serine palmitoyltransferase, demonstrating that 4-HPR induced de novo ceramide synthesis. Sphingomyelin levels were not altered by 4-HPR, and desipramine had no effect on ceramide level, suggesting that sphingomyelinase did not contribute to the 4-HPR-induced ceramide increase. Finally, the pancaspase inhibitor, t-butyloxycarbonyl-aspartyl[O-methyl]-fluoromethyl ketone, suppressed 4-HPR-mediated apoptosis but not ceramide accumulation, suggesting that ceramide is upstream of caspases. Our results provide the first evidence that increased ceramide biosynthesis is required for 4-HPR-induced endothelial apoptosis and present a molecular mechanism for its antiangiogenic effects.