Cell cycle aberrations by alpha-synuclein over-expression and cyclin B immunoreactivity in Lewy bodies.

alpha-Synuclein is a presynaptic protein that accumulates abnormally in Lewy bodies of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Its physiological function and role in neuronal death remain poorly understood. Recent immunohistochemical studies suggest that cell cycle-related phenomena may play a role in the pathogenesis of Alzheimer's disease and perhaps other neurodegenerative disorders. In this investigation, we examined the effects of alpha-synuclein expression levels on cell cycle indices in PC12 cells engineered to conditionally induce alpha-synuclein expression upon withdrawal of doxycycline. Over-expression of alpha-synuclein resulted in enhanced proliferation rate and enrichment of cells in the S phase of the cell cycle. This was associated with increased accumulation of the mitotic factor cyclin B and down-regulation of the tumor suppressor retinoblastoma 2. Additionally, ERK1/2, key molecules in proliferation signaling, were highly phosphorylated. Immunohistochemical studies on postmortem brains revealed intense cyclin B immunoreactivity in Lewy bodies in cases with DLB and to a lesser extent in PD. We propose that elevated expression of alpha-synuclein causes changes in cell cycle regulators through ERK activation leading to apoptosis of postmitotic neurons. These changes in cell cycle proteins are also associated with ectopic expression of cyclin B in Lewy bodies.

[Acquired sideroblastic anemia and cholestasis in a hyperthyroid patient treated with methimazole and atenolol]. / Anemia sideroblástica adquirida y colestasis en un paciente hipertiroideo tratado con metimazol y atenolol.

The authors describe a 62 year-old white male who was diagnosed as autoimmune hyperthyroidism and treated with methimazole and atenolol. Ten days later he showed itching, jaundice and choluria. All drugs were discontinued. The patient was given radioactive iodine. Two months later direct serum bilirubin levels reached 35 mg%. Endoscopic retrograde cholangiogram evidenced normal extrahepatic biliary ducts. The percutaneous liver biopsy showed marked cholestasis specially in the centrolobular zone with a slight infiltrate of mononuclear cells in the portal areas. Together with the liver disease the patient presented an anemic syndrome. Bone marrow aspiration showed rich cellularity, Perls staining showed 70% sideroblasts, with 10% ringed sideroblasts and increased extracorpuscular iron. The patient's evolution was satisfactory. Twenty months after the beginning of the disease clinical and biochemical tests were normal. A new bone marrow aspiration rendered normal. Hepatic cholestasis suffered by our patient was probably due to an adverse reaction of methimazole. Physiopathology of reversible sideroblastic anemia is discussed.

Anemia sideroblástica adquirida y colestasis en un paciente hipertiroideo tratado con metimazol y atenolol. / [Acquired sideroblastic anemia and cholestasis in a hyperthyroid patient treated with methimazole and atenolol]

The authors describe a 62 year-old white male who was diagnosed as autoimmune hyperthyroidism and treated with methimazole and atenolol. Ten days later he showed itching, jaundice and choluria. All drugs were discontinued. The patient was given radioactive iodine. Two months later direct serum bilirubin levels reached 35 mg

. Endoscopic retrograde cholangiogram evidenced normal extrahepatic biliary ducts. The percutaneous liver biopsy showed marked cholestasis specially in the centrolobular zone with a slight infiltrate of mononuclear cells in the portal areas. Together with the liver disease the patient presented an anemic syndrome. Bone marrow aspiration showed rich cellularity, Perls staining showed 70

sideroblasts, with 10

ringed sideroblasts and increased extracorpuscular iron. The patients evolution was satisfactory. Twenty months after the beginning of the disease clinical and biochemical tests were normal. A new bone marrow aspiration rendered normal. Hepatic cholestasis suffered by our patient was probably due to an adverse reaction of methimazole. Physiopathology of reversible sideroblastic anemia is discussed.

Assessment by planimetry of Langerhans' cell density in penile epithelium with human papillomavirus infection: changes observed after topical treatment.

Langerhans' cells could have an important role in the immune surveillance for the malignant transformation associated with certain viral infections. A planimetric study of Langerhans' cells was performed on epithelial sheets obtained from male and female patients who presented with human papillomavirus-induced condylomata. Preliminary epidemiological studies have indicated that after a human papillomavirus infection the risk of malignant transformation is higher in the cervix than in the penis. Our study was designed in such a way that the Langerhans' cell density observed in condylomata could be compared to that detected in adjacent normal areas from the same patients. The results showed that a highly significant decrease in Langerhans' cells occurred in male and female human papillomavirus infected genital tracts. In the penis the local treatment with 5-fluorouracil restored the normal Langerhans' cell density. The significance of these findings in relationship with malignant transformation is discussed.