In situ evaluation of podocin in normal and glomerular diseases

In situ evaluation of podocin in normal and glomerular diseases.BackgroundMutations of the NPHS2 gene are responsible for autosomal-recessive steroid-resistant nephrotic syndrome. Its product, podocin, faces the slit diaphragm area with its two ends in the cytoplasm of foot processes.MethodsWe generated rabbit polyclonal antibodies against conjugated peptides from human podocin N- and C-termini, and studied podocin and synaptopodin using kidney tissues of normal humans and those with glomerular diseases.ResultsAntipodocin antibodies detected the original 42 kD fragment and an extra smaller fragment by Western blot analysis using human isolated mature glomeruli. RNA analysis showed two bands, the original and the other of a decreased length. Immunohistochemically, podocin was detected in a linear pattern along the glomerular capillary loop. Antipodocin antibody (C-terminal) stained the smooth muscles of renal arterioles and aorta. Among 42 patients, podocin was normally expressed in glomeruli in purpura nephritis, IgA nephropathy (IgAN), and minimal-change disease (MCD), while it was either decreased or absent in most subjects with focal segmental glomerulosclerosis (FSGS). The expression of synaptopodin was similar to that of podocin, although some discrepancy existed.ConclusionAlthough indirect, our data suggest the existence of a vascular isoform of podocin with a different molecular mass. We propose that examination of podocin expression may help differentiate MCD from FSGS

Phase I/IIa Study of Low Dose Subcutaneous Interleukin-2 (IL-2) for Treatment of Refractory Chronic Graft Versus Host Disease

Chronic graft versus host disease (cGVHD) remains a major problem for long survivors after allogeneic hematopoietic stem cell transplantation (HSCT). Currently, corticosteroid therapy is effective for cGVHD as the first line therapy. However, prolonged therapy with corticosteroids causes various severe adverse events. To develop the new therapeutic strategy of cGVHD, we have launched a multicenter phase I/IIa clinical trial of low dose subcutaneous interleukin-2 (IL-2) for treatment of steroid refractory cGVHD, which is constituted of 2 sequential phases (induction phase and maitanance phase). This study will provide the new therapeutic option for patients with refractory cGVHD after allogeneic HSCT

Brain Metastasis from Gastrointestinal Stromal Tumor: A Case Report and Review of the Literature

Metastasis of gastrointestinal stromal tumor (GIST) into the central nervous system is extremely rare. We report a patient with synchronous GIST and brain metastasis. At disease onset, there was left hemiplegia and ptosis of the right eyelids. Resection cytology of the brain tumor was reported as metastasis of GIST. After positron emission tomography examination, another tumor in the small bowel was discovered, which suggested a small bowel GIST associated with intracranial metastasis. Immunohistochemical analysis of the intestinal tumor specimen obtained by double balloon endoscopy showed a pattern similar to the brain tumor, with the tumors subsequently identified as intracranial metastases of jejunal GIST. After surgical resection of one brain tumor, the patient underwent whole brain radiation therapy followed by treatment with imatinib mesylate (Gleevec; Novartis Pharma, Basel, Switzerland). Mutational analysis of the original intestinal tumor revealed there were no gene alterations in KIT or PDGFRα. Since the results indicated the treatment had no apparent effect on either of the tumors, and because ileus developed due to an intestinal primary tumor, the patient underwent surgical resection of the intestinal lesion. However, the patient's condition gradually worsen and she subsequently died 4 months after the initial treatment

Identification of biomarkers in ductal carcinoma in situ of the breast with microinvasion

<p>Abstract</p> <p>Background</p> <p>Widespread use of mammography in breast cancer screening has led to the identification of increasing numbers of patients with ductal carcinoma <it>in situ </it>(DCIS). DCIS of the breast with an area of focal invasion 1 mm or less in diameter is defined as DCIS with microinvasion, DCIS-Mi. Identification of biological differences between DCIS and DCIS-Mi may aid in understanding of the nature and causes of the progression of DCIS to invasiveness.</p> <p>Methods</p> <p>In this study, using resected breast cancer tissues, we compared pure DCIS (52 cases) and DCIS-Mi (28 cases) with regard to pathological findings of intraductal lesions, biological factors, apoptosis-related protein expression, and proliferative capacity through the use of immunohistochemistry and the TdT-mediated dUTP-biotin nick end labeling (TUNEL) method.</p> <p>Results</p> <p>There were no differences in biological factors between DCIS and DCIS-Mi, with respect to levels of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor type 2. The frequency of necrosis and positive expression ratio of survivin and Bax were significantly higher in DCIS-Mi than in DCIS. In addition, apoptotic index, Ki-67 index, and positive Bcl-2 immunolabeling tended to be higher in DCIS-Mi than in DCIS. Multivariate analysis revealed that the presence of necrosis and positive survivin expression were independent factors associated with invasion.</p> <p>Conclusion</p> <p>Compared with DCIS, DCIS-Mi is characterized by a slightly elevated cell proliferation capacity and enhanced apoptosis within the intraductal lesion, both of which are thought to promote the formation of cell necrotic foci. Furthermore, the differential expression of survivin may serve in deciding the response to therapy and may have some prognostic significance.</p

Intravascular Papillary Endothelial Hyperplasia Associated with Venous Pool Arising in the Lower Lip: A Case Report

Intravascular papillary endothelial hyperplasia is a benign nonneoplastic vascular lesion that consists of endothelial cells with abundant vascular tissue with papillary proliferation. An adult female had a painless growing dark red nodule on the left side of the lower lip and often touched and gnawed at it for more than 4 years. The lesion was a tender, smooth mass approximately 1 cm in diameter without discoloration reaction. Magnetic resonance imaging of the lesion showed specific findings. She was diagnosed clinically as having mimicked hemangioma, and the lesion was totally excised under local anesthesia. Histopathological examination revealed that papillary proliferated endothelial cells with venous pool, and the lesion was diagnosed as intravascular papillary endothelial hyperplasia associated with venous pool. There has been no recurrence for more than 1 year. Despite the benign nature of this lesion, it could have been mistaken for a malignant tumor because of its clinical course and radiologic findings. Copyright © 2009 Hisanobu Yonezawa et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 1

Y: Spatiotemporal pattern of the mouse chondromodulin-I gene expression and its regulatory role in vascular invasion into cartilage during endochondral bone formation

ABSTRACT During endochondral bone formation, vascular invasion into cartilage initiates the replacement of cartilage by bone. Chondromodulin-I, a 25 kDa glycoprotein purified from bovine epiphyseal cartilage, was recently identified as a novel endothelial cell growth inhibitor. Here we cloned the mouse chondromodulin-I cDNA from a mouse whole embryo cDNA library. Northern blot analysis revealed that the chondromodulin-I transcripts were expressed in association with the formation of cartilage expressing type II collagen from days 11 to 17 of gestation in mouse embryos, at which time cartilaginous bone rudiments were gradually replaced by bone. Chondromodulin-I mRNA was also detected in the thymus and eyes at a lower level. In situ hybridization revealed significant expression in all cartilaginous tissues in the embryos at days 13.5 and 16 of gestation. However, the expression was completely abolished in the hypertrophic cartilage zone prior to calcification. Upon chondrogenic differentiation of mouse ATDC5 cells in vitro, the expression of chondromodulin-I transcripts was induced concomitantly with the formation of type II collagenexpressing chondrocytes. The expression of the transcripts then declined as type X collagenexpressing hypertrophic chondrocytes appeared in the culture. Purified chondromodulin-I protein inhibited the vascular invasion into cartilage ectopically induced by demineralized bone matrix in nude mice, leading to the suppression of bone formation in vivo. These results suggest that chondromodulin-I is involved in the anti-angiogenic property of cartilage, and that the withdrawal of its expression allows the vascular invasion which triggers the replacement of cartilage by bone during endochondral bone development