Lymphoid Neogenesis in Murine Cardiac Allografts Undergoing Chronic Rejection

Lymphoid neogenesis is the process by which ectopic lymphoid accumulations that resemble lymph nodes arise in nonlymphoid tissues. Such lymphoid accumulations, known as tertiary lymphoid organs (TLO), are observed in chronic autoimmunity and they propagate immune pathology by setting up local antigen presenting sites. Whether lymphoid neogenesis occurs in transplanted organs and contributes to rejection is not well understood. To begin to address this question, we retrospectively analyzed 319 murine cardiac allografts for microscopic evidence of lymph-node-like structures. We found 78 allografts that had either classical TLO, characterized by discrete T- and B-cell zones and high endothelial venules (HEV) expressing peripheral node addressin (PNAd) (n = 34), or PNAd(+) HEV without organized lymphoid accumulations (n = 44). These changes were present in both short- and long-lived allografts and were invariably associated with rejection. Importantly, they occurred in 78% of allografts undergoing chronic rejection (n = 85) but in only 7% of allografts undergoing primarily acute rejection (n = 184). These findings indicate that, like autoimmunity, alloimmunity is associated with lymphoid neogenesis in the target organ and suggest a role for local T-cell activation in chronic allograft rejection.     

Potential aripiprazole-mediated extrapyramidal symptoms in an adult with developmental disabilities.

PURPOSE: A case of extrapyramidal symptoms (EPS) following administration of aripiprazole to a man with developmental disabilities who had never received antipsychotic medications and had no history of movement disorders is presented. SUMMARY: The patient was a 40-year-old male with developmental disabilities. He was nonverbal, profoundly mentally retarded, and diagnosed with obsessive compulsive disorder (OCD) and orthopedic problems. He developed episodic movements possibly consistent with EPS secondary to aripiprazole usage. The patient was antipsychotic naive before initiation of aripiprazole 5 mg daily. Concurrent medications at the time of EPS onset included oxazepam, baclofen, and citalopram. Baclofen and oxazepam were prescribed secondary to right-sided hemiparesis contractures. Aripiprazole, 5 mg daily, was initiated in November 2004 as an augmentation strategy for the diagnosis of OCD. Facial, tongue, and arm movements were first reported approximately five weeks after the initiation of aripiprazole. Initial symptoms resolved after approximately 24 hours. The dosage was increased to 10 mg daily two weeks later. Dystonic episodes continued on an intermittent basis, and the patient presented with lower-lip thrusting and upper-limb athetosis. These movements interfered with the patient's eating, chewing, and holding of utensils. Several of the standard treatment strategies for EPS were used. Initially, diphenhydramine hydrochloride 25 mg was administered orally every six hours. The patient's movements resolved following diphenhydramine administration. Aripiprazole was subsequently discontinued secondary to its lack of efficacy for OCD and the development of a movement disorder. CONCLUSION: A patient with developmental disabilities who had no history of movement disorders developed EPS following initiation of aripiprazole.     

Transgenic mice expressing constitutive active MAPKAPK5 display gender-dependent differences in exploration and activity

Background  

The mitogen-activated protein kinases, MAPKs for short, constitute cascades of signalling pathways involved in the regulation of several cellular processes that include cell proliferation, differentiation and motility. They also intervene in neurological processes like fear conditioning and memory. Since little remains known about the MAPK-Activated Protein Kinase, MAPKAPK5, we constructed the first MAPKAPK knockin mouse model, using a constitutive active variant of MAPKAPK5 and analyzed the resulting mice for changes in anxiety-related behaviour.