Biomedical subjects

Naohisa Tomosugi

Publications and source records attributed to Naohisa Tomosugi.

7 recordsLinked to original sources

PubMed2004

Gene therapy via blockade of monocyte chemoattractant protein-1 for renal fibrosis.

Monocyte chemoattractant protein (MCP)-1, also termed monocyte chemotactic and activating factor (MCAF)/CCL2, plays an important role in progressive organ fibrosis. It was hypothesized that MCP-1, through its cognate receptor, CCR2, regulates the pathogenesis and is therapeutically of importance for renal fibrosis. To achieve this goal, the therapeutic efficacy and efficiency in renal fibrosis induced by a unilateral ureteral obstruction nephropathy model in mice by the blockade of MCP-1/CCR2 signaling was studied. The delivery of N-terminal deletion mutant of the human MCP-1 gene, 7ND, into a skeletal muscle ameliorated renal fibrosis by resulting in decrease in the deposit of type I collagen and in reduced expression of TGF-beta. Concomitantly, gene transfer of 7ND reduced the cell infiltration, most of which were CCR2-positive macrophages, followed by the decrease in MCP-1 expression in the diseased kidneys. These observations suggest that MCP-1 through CCR2 signaling is responsible for Mphi recruitment, which augments downstream events, resulting in renal fibrosis. Moreover, these findings imply that gene therapy against MCP-1/CCR2 signaling via the mutant gene transferred strategy may serve a beneficial therapeutic application for renal fibrosis.

Animals↗

PubMed2004

Bilateral epididymal sarcoidosis presenting without radiographic evidence of intrathoracic lesion: Review of sarcoidosis involving the male reproductive tract.

Sarcoidosis is a multisystem disorder that rarely involves the genitourinary tract. To date, only 59 cases of histologically proven sarcoidosis involving the male reproductive tract have been reported in the literature. We present here a case of bilateral epididymal sarcoidosis without radiographic evidence of intrathoracic lesion. A 46-year-old man presented with a one-week history of painless bilateral scrotal swellings. Physical examination detected multiple elastic firm nodules on both sides of the scrotum which showed no tenderness. The nodules seemed to involve the entire bilateral epididymides. Some irregularly shaped hypoechoic masses in the bilateral epididymides were identified on gray scale ultrasonography. On magnetic resonance images, the bilateral epididymides were seen to be enlarged, heterogeneous and nodular without any signs of testicular involvement. The lesion showed a slightly high signal intensity on the T2-weighted image. Pathological evaluation following bilateral epididymectomy found non-caseating epithelioid cell granulomas with giant cells in epididymal tissue, thus confirming a diagnosis of sarcoidosis. Gallium-67 scanning showed additional small hot spots in the anterior chest wall and extremities. Open biopsy of a superficial papular lesion in the dermis of the right upper arm was performed and pathological findings indicated sarcoid granulomas. This report also includes a review of the literature pertaining to sarcoidosis of the male reproductive tract.

Epididymis↗

PubMed2004

[Discovery of disease biomarkers by ProteinChip system; clinical proteomics as noninvasive diagnostic tool].

Biopsy-associated complications could not be eliminated in spite of recent refinement, although needle biopsy has been the standard test for diagnosis of renal diseases. The development of noninvasive diagnostic test that provides insights into the mechanisms of diseases would be expected in the field of laboratory medicine. Biological fluids potentially have important histological information whose determination could serve to detect early disease state. Recently the advent of SELDI-TOF-MS (surface-enhanced laser desorption/ionization time-of-flight mass spectrometry) has extended the application of mass spectrometry to the study of proteins in biological fluids. We applied a new protein-chip technology based on SELDI in a discovery of renal disease biomarkers. Proteomic patterns in serum by means of protein-chip were exemplified by elucidating a biomarker candidate for acute renal allograft rejection. SELDI protein-chip technology will be applied more frequently to a number of medical and basic research problems because of high resolution, high reproducibility, ease of use, and fentomole sensitivity.

Biomarkers↗

PubMed2003

Cystic renal cell carcinoma, suspected because of lack of regression of renal cysts after renal transplantation in a dialysis patient with acquired renal cystic disease.

A 34-year-old man who had been on dialysis for about 6 years, and had acquired renal cystic disease, received a renal transplantation. However, in spite of the success of the transplantation, one area without cyst regression was observed in the original kidney. Therefore, carcinoma was suspected and nephrectomy was performed. Histology revealed cystic renal cell carcinoma (RCC). No case of cystic RCC occurring in a dialysis patient has previously been reported. Cystic RCC should be suspected in a cystic mass in the original kidney which does not regress after successful renal transplantation.

Adult↗

PubMed2003

Gene therapy expressing amino-terminal truncated monocyte chemoattractant protein-1 prevents renal ischemia-reperfusion injury.

Ischemia-reperfusion is closely associated with tissue damage in various organs, including kidney. Despite clinical investigations, useful therapy for renal ischemia-reperfusion injury is not available so far. This study evaluated therapeutic effects of gene therapy expressing an amino-terminal deletion mutant of MCP-1 called 7ND to inhibit monocyte chemoattractant protein (MCP)-1/CCR2 signaling in vivo on renal ischemia-reperfusion injury. 7ND gene was transferred into the femoral muscle of Balb/c mice. Renal artery and vein of the left kidney were occluded with a vascular clamp for 60 min. A large number of infiltrated cells were observed, as was marked acute tubular necrosis in outer medulla after renal ischemia-reperfusion injury in control mice, while these lesions were significantly decreased in 7ND gene-transfected mice. Macrophages in the interstitial region, most of which were CCR2-positive, were markedly decreased in 7ND gene-transfected mice after reperfusion. Although macrophages infiltrated around MCP-1-positive cells in control mice, the smaller number of F4/80-positive cells could infiltrate into the neighbor of MCP-1-positive cells in 7ND-treated mice. These results provide evidence that gene therapy by 7ND is potentially a powerful therapeutic approach to inhibit MCP-1/CCR2 signaling, resulting in rescue from renal ischemia-reperfusion injury.

Animals↗

PubMed2002

[Not Available].

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Journal Article↗

PubMedDate not supplied

Diagnostic potential of tear proteomic patterns in Sjögren's syndrome.

Histological and functional changes of the lacrimal gland might be reflected in proteomic patterns in tear fluids. In this study, we carried out a determination of the disease biomarkers in tear fluid for Sjögren's syndrome (SS) and a performance of noninvasive diagnostic test based on the proteomic patterns. Thirty-one SS patients and 57 control subjects were enrolled to this study. Their details were 23 cases with primary SS, 8 with secondary SS, 14 with dry eyes, 22 with miscellaneous ocular diseases, and 21 of healthy volunteers. Protein profiling in tear fluids was identified by surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Multiple protein changes were reproducibly detected in the primary SS group, including 10 potential novel biomarkers. Seven of the biomarkers (2094, 2743, 14191, 14702, 16429, 17453, 17792 m/z) were down-regulated and 3 biomarkers (3483, 4972, 10860 m/z) were up-regulated in primary SS group, comparing to the protein profiles of control subjects. When cutoff value of SS down-score was set less than 0.5, this result yielded 87% sensitivity and 100% specificity. The positive predictive value for this sample set was 100%. There was a significant inverse correlation between SS down-scores and epithelial damages of the ocular surface in primary SS patients. These findings support the potential of proteomic pattern technology in tear fluids as the noninvasive diagnostic test for primary SS.

Biomarkers↗