Rheumatoid arthritis (RA) is an autoimmune disease hallmarked by aberrant cellular homeostasis, resulting in hyperactive CD4+ T cells that are more resistant to apoptosis. Both hyperactivation and resistance to apoptosis may contribute to the pathogenicity of these T cells in the autoimmune process. A better knowledge of the mechanisms determining such impaired homeostasis could contribute significantly to both the understanding and the treatment of the disease. Here we investigated whether autophagy, is dysregulated in CD4+ T cells of RA patients, resulting in disturbed T cell homeostasis. We demonstrate that the rate of autophagy is significantly increased in CD4+ T cells from RA patients, and that increased autophagy is also a feature of in vitro activated CD4+ T cells. The increased apoptosis resistance observed in CD4+ T cells from RA patients was significantly reversed upon autophagy inhibition. These mechanisms may contribute to RA pathogenesis, as autophagy inhibition reduced both arthritis incidence and disease severity in a mouse collagen induced arthritis mouse model. Conversely, in Atg5flox/flox-CD4-Cre+ mice, in which all T cells are autophagy-deficient, T cells showed impaired activation and proliferation. These data provide novel insight into the pathogenesis of RA and underscore the relevance of autophagy as a promising therapeutic target.

The induction of intracranial neoplasms following the intracerebral inoculation of avian sarcoma virus (ASV) in neonatal mammals is well established. The present study demonstrates the susceptibility of adult rats and compares the incidence and morphology of tumors induced by a uniform inoculum of the Bratislava-77 strain of ASV in adult, neonatal, and fetal Fischer 344 rats. Post-inoculation mortality varied significantly between groups inoculated at 1, 10 and 100 days and was most precipitous in perinatally inoculated rats. Percentage of tumor induction declined from 100% among rats inoculated at 1 day of age to 50% among rats inoculated at 100 days of age. The mean number of tumors/animal was inversely proportional to the logarithm of the age at inoculation. A large majority of tumors in each group were glial; the remainder were mesenchymal and mixed glial and mesenchymal. Neuroglial tumors included: mixed gliomas with oligodendroglial and astrocytic elements; and gemistocytic, pilocytic, fibrillary, anaplastic and protoplasmic astrocytomas. Tumors induced in perinates were more heterogeneous in histological pattern while tumors induced in perinates were more heterogeneous in histological pattern while tumors induced in older animals tended to be purely astrocytic and of uniform cell type. Mesenchymal tumors occurred primarily in the meninges and were common among animals inoculated perinatally but were rare among animals inoculated as adults. No neuronal tumors were encountered even among rats inoculated as early as 16 days of gestation.

Treatment with an air-circulating cooling blanket did not effectively reduce body temperature in febrile neuro-ICU patients treated with acetaminophen. More effective interventions are needed to maintain normothermia in patients at risk for fever-related brain damage.

A 37-year-old white woman presented with progressive visual loss in the right eye. The diagnostic evaluation suggested a tumor in the suprasellar area. At operation an isolated melanoma was found just superior to the sella turcica. No evidence of other intracranial lesions was present and complete diagnostic studies failed to reveal any other primary site. The patient subsequently underwent a second neurosurgical procedure in an effort to remove the tumor completely. This was followed by recurrent symptomatology and she was then treated with a combination of multiple drug chemotherapy and immunotherapy. Approximately 3 years after her initial operation the patient succumbed secondary to her disease. The autopsy findings were consistent with a primary melanoma of the leptomeninges in the area just above the sella turcica. This unusual presentation is discussed and plausible hypotheses are given.