ABSTRACT
The endoplasmic reticulum (ER) stress results from disrupted protein folding triggered by protein mutation or oxidation, reduced proteasome activity, and altered Ca2+ homeostasis. ER stress is accompanied by activation of the unfolded protein response (UPR) and cell death pathway. We examined if the UPR and cell death pathway would be activated in Alzheimer's disease (AD). RT-PCR experiments revealed increased splicing of X-box binding protein-1 (XBP-1), an UPR transcription factor, in AD compared with age-matched control. Among target genes of XBP-1, expression of protein disulfide isomerase (PDI), but not glucose-regulated protein 78 (GRP78), was increased in AD, suggesting disturbed activation of the UPR in AD. C/EBP homologous protein (CHOP), caspase-3, caspase-4, and caspase-12, downstream mediators of cell death pathway, were activated in AD. Neither the UPR nor cell death pathway was induced in aged Tg2576 mice, a transgenic mouse model of Alzheimer's disease that reveals both plaque pathology and some cognitive deficits. The present study suggests that disturbed induction of the UPR and activation of the pro-apoptotic proteins contribute to neuropathological process in AD irrespective of amyloid beta and senile plaque.
ABSTRACT
BACKGROUND: Hypoplastic acute leukemia is rare and most cases reported were of older age group. We reviewed our cases of hypoplastic acute leukemia and their hematologic and clinical findings. METHOD: The bone marrow biopsy slides and the reports of patients diagnosed as having acute leukemia during recent ten years were reviewed. The medical records of patients who had blast cells of greater than 30% and marrow cellularity less than or equal to 50% were reviewed. RESULTS: Of 308 patients analyzed, 17 (5.5%) fulfilled the above mentioned criteria. Ten patients were women and seven men. The median age was 44 with a range of 18-71. Chief complaints were fever, headache, general weakness and abdominal pain. Two patient presented hepatomegaly. One patient was diagnosed as granulocytic sarcoma. Ten patients were pancytopenic with median leukocyte count of 1,500/ L, hemoglobin of 8.3 g/dL, and platelet count of 27,000/ L. Circulating blast cells were 0-76%. FAB classification revealed one to be M0, three M1, seven M2, three M4, one M5, one M6 and one L1. Seven patients were not followed, and three were treated conservatively. Of seven patients receiving chemotherapy, four achieved durable complete remission. One achieved complete remission by using G-CSF. CONCLUSION: Most cases of reported hypoplastic acute leukemia were acute myelogenous leukemia of older age but our cases included leukemia of younger age and one acute lymphoblastic leukemia. Of seven patients who received chemotherapy, four achieved complete remission and one showed complete remission only by G-CSF.