Reduced transforming growth factor-beta signaling in cartilage of old mice: role in impaired repair capacity

Osteoarthritis (OA) is a common joint disease, mainly effecting the elderly population. The cause of OA seems to be an imbalance in catabolic and anabolic factors that develops with age. IL-1 is a catabolic factor known to induce cartilage damage, and transforming growth factor (TGF)-beta is an anabolic factor that can counteract many IL-1-induced effects. In old mice, we observed reduced responsiveness to TGF-beta-induced IL-1 counteraction. We investigated whether expression of TGF-beta and its signaling molecules altered with age. To mimic the TGF-beta deprived conditions in aged mice, we assessed the functional consequence of TGF-beta blocking. We isolated knee joints of mice aged 5 months or 2 years, half of which were exposed to IL-1 by intra-articular injection 24 h prior to knee joint isolation. Immunohistochemistry was performed, staining for TGF-beta1, -2 or -3, TGF-betaRI or -RII, Smad2, -3, -4, -6 and -7 and Smad-2P. The percentage of cells staining positive was determined in tibial cartilage. To mimic the lack of TGF-beta signaling in old mice, young mice were injected with IL-1 and after 2 days Ad-LAP (TGF-beta inhibitor) or a control virus were injected. Proteoglycan (PG) synthesis (³⁵S-sulfate incorporation) and PG content of the cartilage were determined. Our experiments revealed that TGF-beta2 and -3 expression decreased with age, as did the TGF-beta receptors. Although the number of cells positive for the Smad proteins was not altered, the number of cells expressing Smad2P strongly dropped in old mice. IL-1 did not alter the expression patterns. We mimicked the lack of TGF-beta signaling in old mice by TGF-beta inhibition with LAP. This resulted in a reduced level of PG synthesis and aggravation of PG depletion. The limited response of old mice to TGF-beta induced-IL-1 counteraction is not due to a diminished level of intracellular signaling molecules or an upregulation of intracellular inhibitors, but is likely due to an intrinsic absence of sufficient TGF-beta receptor expression. Blocking TGF-beta distorted the natural repair response after IL-1 injection. In conclusion, TGF-beta appears to play an important role in repair of cartilage and a lack of TGF-beta responsiveness in old mice might be at the root of OA development.     

Mixed osteoclastic/pleomorphic giant cell tumor of the pancreas: a case report

BACKGROUND: Mixed giant cell tumor (MGCT) of the pancreas is a rare malignant neoplasm. The tumor contains pleomorphic giant cells (PGC), pleomorphic mononuclear cells (PMC) and osteoclastic giant cells (OGC). We describe the first fine needle aspiration biopsy (FNAB) diagnosis of this tumor. CASE: A 76-year-old woman was discovered (on imaging studies) to have an apparently inoperable mass in the head of the pancreas. Computed tomography-guided FNAB showed a malignant neoplasm with features of an MGCT. PGC/PMC, OGC and spindle cells were present. The PGC/PMC expressed epithelial antigens, pancytokeratin, CAM 5.2, AE1/AE3 and epithelial membrane antigen (EMA). The spindle cells focally stained for EMA. OGC were negative for the epithelial antigens. OGC, PGC/PMC and the spindle cells were positive for the mesenchymal marker vimentin. CONCLUSION: FNAB was instrumental in making the diagnosis of a rare pancreatic tumor, MGCT. Immunocytochemistry was helpful in making a definitive diagnosis and suggested that MGCT is a carcinosarcoma like neoplasm. The morphology and immunocytochemical profile raise the possibility that osteoclastic giant cell tumor and pleomorphic giant cell tumor may be different morphologic and biologic expressions of the same tumor.     

Free-pool amino acids in Biomphalaria glabrata infected with Echinostoma caproni as determined by thin-layer chromatography

Thin-layer chromatography was used to analyze the free-pool amino acids of the digestive gland-gonad complex (DGG) of Biomphalaria glabrata infected with Echinostoma caproni and uninfected (control) snails. Qualitative analysis revealed the presence of histidine, lysine, serine, alanine, valine, and isoleucine or leucine in all samples. Quantitative analysis of lysine and valine gave mean weight percentages of 0.00699 +/- 0.0022 and 0.00174 +/- 0.00056, respectively, in the DGG of uninfected snails, and 0.00504 +/- 0.0014 and 0.00254 +/- 0.00033, respectively, in the DGG of infected snails. The differences in values between infected and uninfected snails were not statistically significant (Student's t-test, P > 0.05).