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M Uzuki

Publications and source records attributed to M Uzuki.

28 records · Page 2Linked to original sources

Mixed osteoclastic/pleomorphic-type giant cell tumor of the pancreas with ductal adenocarcinoma: histochemical and immunohistochemical study with review of the literature.

We described a rare form of giant cell tumor of the pancreas composed of mixed osteoclastic/pleomorphic-type giant cell tumor with ductal adenocarcinoma. Immunohistochemical study showed positive staining of cytokeratin and epithelial membrane antigen for pleomorphic-type giant cells and ductal adenocarcinoma but negative for osteoclastic-type giant cells. Vimentin stained positive in both types of giant cells but negative in adenocarcinoma. Osteoclastic-type giant cells were strongly positive for CD68 and tartarate-resistant acid phosphatase was present in these cells, suggesting the osteoclast-like character. CD68 was negative for both pleomorphic-type giant cells and ductal adenocarcinoma. From these findings, we consider that this tumor might be a carcinosarcoma-like neoplasm consisting of both an epithelial and a histiocytic-mesenchymal component.

Aged↗

Aromatase in human bone tissue.

Peripheral aromatization of androgens exert estrogenic actions in many tissues. Recently in situ production of estrogens by aromatase was detected in human bone and cultured osteoblasts and has been proposed to participate in the maintenance of bone mass. We examined aromatase expression by immunohistochemistry and mRNA in situ hybridization in 16 cases of tibia (female 2 male, 14 female, 62 +/- 5.2 years old) and quantified the level of aromatase mRNA in 28 cases of rib, femur, and lumbar vertebrae (16 male, 12 female, 58.0 +/- 11.3 years old) by reverse transcriptase-polymerase chain reaction (RT-PCR) in order to study whether or not and in which cell types aromatase was expressed in human bone tissues. We also studied alternative use of multiple exons 1 of its gene and immunolocalization of type I 17 beta-hydroxysteroid dehydrogenase (HSD), which converts estrone produced by aromatase to estradiol. Strong aromatase immunoreactivity and mRNA hybridization as well as type I 17 beta-HSD immunoreactivity were detected in lining cells, osteoblasts, chondrocytes of articular cartilage, and adipocytes adjacent to bone trabeculae in all the cases examined. Amounts of aromatase mRNA varied greatly among the subjects (11.25 +/- 9.77, 0.61-42.84 attomol/ng of total RNA). The amount of aromatase expression was not correlated with age or gender of the subjects but positively correlated with the degree of osteroporotic changes evaluated by radiological findings of lumbar vertebrae. Analysis of multiple exons 1 revealed that 1b or fibroblast type was predominantly (23/26) utilized as a promoter of aromatase gene expression. These results demonstrated that aromatase is expressed widely in human bone tissue and may play important roles in maintenance of human bone tissue.

17-Hydroxysteroid Dehydrogenases↗

[Expression of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) in joint tissues of rapidly destructive coxarthropathy (RDC), analyzed by immunohistochemical study].

OBJECTIVE: Rapidly destructive coxarthropathy (RDC) is characterized by rapid destruction of hip joints, but its pathogenetic mechanism is still obscure. Matrix metalloproteinases (MMPs) are possibly one of the candidates concerning with this mechanism. We attempted histochemical investigation to demonstrate MMPs and tissue inhibitor of metalloproteinases (TIMPs) in joint tissues obtained from RDC patients to clarify their roles in the destruction mechanism. MATERIALS AND METHODS: Joint tissues including synovia and cartilage-bone tissues were obtained from RDC patients at total hip replacement (THR). After fixation with 4% paraformaldehyde, cartilage-bone tissues were partly decalcified. We performed histochemical study for paraffin sections of these tissues by using avidin-biotin method. Antibodies used in this study were monoclonal antibodies to MMP-1, MMP-2, MMP-7, MMP-8, MMP-9, TIMP-1, TIMP-2 and polyclonal antibody to MMP-3. RESULTS: Histological feature of RDC was severe destruction of cartilage and bone by invasion of non-specific granulation tissues composed of many small vessels, macrophages and fibroblastic cells. At the same time, RDC showed apparently fewer lymphocytic cells in these granulation tissues compare with rheumatoid arthritis. MMP-2 and MMP-9 were expressed most demonstrably in synovia and destructive regions of femoral heads, especially in osteoclasts, macrophages, and fibroblastic cells, while MMP-1, MMP-3, were slightly expressed only in the superficial layer of synovia in limited cases. MMP-8, usually contained in neutrophils, was not present in RDC. On the other hand TIMP-1 and TIMP-2 were presented throughout the synovia and destructive regions of femoral heads including fibroblastic cells, macrophages, osteoblasts and osteocytes. CONCLUSION: Immunohistochemical study revealed obvious presence of MMP-2 and MMP-9 in synovia and destructive regions of femoral heads in RDC. Those evidence suggest that MMP-2 and MMP-9 share very important role in the destructive mechanism of RDC, possibly under imbalance between TIMPs.

Aged↗

In situ hybridization of stromelysin mRNA in the synovial biopsies from rheumatoid arthritis.

We examined the expression of stromelysin mRNA (SL mRNA) in synovial biopsy specimens from 12 cases of rheumatoid arthritis (RA) and 2 cases of osteoarthritis (OA) using in situ hybridization. The study demonstrated that positive cells with high levels of SL mRNA were mostly (85%) found in the synovial lining layer. The positive cells were abundant in the synovium of RA which presented well developed lymphoid follicles with massive inflammatory cells. On the other hand, the synovium of OA contained no positive cells for SL mRNA. In addition, low yet positive levels of SL mRNA were detected in the endothelial cells and vascular myocytes, and interstitial cells in the deeper layer of the synovium. Karyometric studies showed that cells positive for SL mRNA had significantly larger and more spherical nuclei than weakly positive or negative cells. The SL mRNA positive cells did not demonstrate any immunoreactivity to markers of bone marrow origin, such as Leu M1, Leukocyte Common Antigen (LCA) and lysozyme antigen. Electron microscopy of a case with many SL mRNA positive cells showed that most had well developed rough endoplasmic reticulum and numerous processes on the cell surface, and some had also well developed rough endoplasmic reticulum but without processes indicating that they may be AB and/or B synoviocytes.

Adult↗

Double cancer in a 74-year-old woman: a case report with genetic findings.

An autopsy case of double cancer is reported. The patient had undergone right hemicolectomy for colon carcinoma in 1982, and the second cancer was detected in the pancreas in April 1989, which was diagnosed as intraductal papillary adenocarcinoma that is known for its favorable prognosis after surgical resection. However, as the patient did not consent to the operation, she died in August 1994, five years after the diagnosis of the second cancer. Histopathological study revealed neither recurrence nor metastasis of colon carcinoma. The pancreatic carcinoma metastasized to the lung, liver, and peritoneum. DNAs were extracted from paraffin-embedded tissue for molecular pathological examinations. Different mutations were found at codon 12 of the K-ras gene by nucleotide sequencing analysis: one in the colon and the other in the pancreas and lung. Over-expression of p53 protein was also detected in the colon by immunostaining. Replication error was not observed in these three tumors suggesting that a factor(s) other than genetic instability was playing a role in the development of double cancer in this patient.

Aged↗

Determination of interstitial collagenase (MMP-1) in patients with rheumatoid arthritis.

OBJECTIVES: To investigate whether interstitial collagenase (MMP-1) concentration in synovial fluid can be useful as a marker for disease activity in rheumatoid arthritis (RA), to determine the main route by which collagenase degrades the matrix of articular cartilage, and to investigate if an imbalance between metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMP) is responsible for the activity of MMPs in RA. METHODS: Collagenase concentrations were measured in synovial fluid and paired serum samples using a specific sandwich enzyme linked immunosorbent assay. Collagenase activities were also assayed in synovial fluid samples. Synovial tissues obtained from the same patient were examined by immunohistochemical staining and the numbers of cells expressing collagenase were counted. RESULTS: Collagenase concentrations in synovial fluid did not correlate with C reactive protein and collagenase levels in serum, but did correlate positively with the degree of synovial inflammation, and increased with increasing numbers of cells identified as expressing collagenase in synovial tissue. Collagenase activities did not correlate with TIMP-1 concentrations, but did correlate strongly with the ratios of collagenase concentration to TIMP-1 (r = 0.73). CONCLUSION: The collagenase concentration in synovial fluid cannot be used as a marker for systemic disease activity, but can be used as a marker for the degree of synovial inflammation in the joint from which the sample is aspirated. In advanced RA, most of the collagenase is probably produced in synovial lining cells and released into synovial fluid, where it degrades the matrix of articular cartilage. An imbalance between MMP and TIMP may be of importance in the degradation of extracellular matrix of articular cartilage in RA.

Adult↗

Kidney disease in systemic lupus erythematosus (SLE) of children--morphometric analysis of kidneys from autopsy cases.

We have investigated the histopathological changes of kidney from 16 autopsy cases of children with systemic lupus erythematosus (SLE) using morphometric and immunohistochemical methods. These 16 cases accounted for 61% of the child autopsy cases with SLE registered in the data base "Annual of the Pathological Autopsy Cases in Japan" during the nine years from 1984 to 1992. Based on the histologic and morphometric findings, we divided the SLE-associated renal disease into three types: glomerular (3 cases), vascular (3 cases) and non-renal (10 cases) types. The glomerular and vascular types had renal lesions, while in the non-renal the main changes were found in extrarenal tissues. Of the 16 cases examined, three showed diffuse proliferative glomerulonephritis, with one of the three having crescentic formations in the glomeruli. Two of the three had wire-loop lesions. Recently the crescentic or wire-loop lesions are rarely experienced even in renal biopsy and autopsy of adult cases. The vascular type was characterized by necrotizing angiitis (1 case) and severe intimal thickening of interlobular arteries (2 cases), but they had no advanced glomerular lesion. Morphometric methods allowed us to demonstrate that the severity of arterial lesions, especially intimal thickening, does not correlate with that of glomerular lesions in children.

Adolescent↗

[Matrix metalloproteinase (MMP-9) in patients with rheumatoid arthritis].

MMP-9 degrades type IV collagen, gelatin, type V collagen, and type XI collagen. We measured proMMP-9 and proMMP-9/TIMP-1 complex in sera and joint fluids by sandwich ELISA, and examined immunohistochemically the expression of these proteins in joint tissue from patients with rheumatoid arthritis (RA). ProMMP-9 was purified by the three chromatographic steps from the culture medium of HT1080 cells. Purified proMMP-9 and activated MMP-9 by APMA showed a single band of Mr92000, Mr67000, resectively on gelatin-zymography. We raised two monoclonal antibody colones 2G9, 8G7 against proMMP-9 with BALB/c mice. 2G9 and 8G7 reacted with proMMP-9 on Western blotting, and these clones reacted proMMP-9 and proMMP-9/TIMP-1 complex on sandwich ELISA, specifically. ProMMP-9 concentration in 86 sera (749.4+/-940.2 ng/ml) and 54 joint fluids (4539.9+/-7681.5 ng/ml) from patients with RA was significantly higher than those of patients with osteoarthritis and control. Immunohistochemistry with 2G9 showed that in rheumatoid synovium proMMP-9 localized in neutrophils and monocytes diffusely infiltrated the sublining layer. In addition, osteoclasts in rheumatoid subchondral bone were intensively stained. ProMMP-9 concentration in joint fluids from 39 RA patients was not correlated to stage and class of Steinbrocker and to clinical laboratorial data. But, it was positively correlated to the number of proMMP-9 positive cells in RA synovium (r=0.607) and the score of Roony's diffuse infiltrates of lymphocytes (r=0.720). Our results suggest a role of MMP-9 in joint destraction of RA throughout neutrophils and monocytes, and a regulation of this enzyme by lymphocytes.

Adult↗

[Increased levels of circulating hyaluronate in the sera of patients with rheumatoid arthritis with special reference to joint destruction].

We sought to assess whether serum levels of hyaluronate (HA) in patients with rheumatoid arthritis (RA) are elevated and correlated with grade of joint destruction and with laboratory data. Circulating HA levels were determined by protein binding assay of serum from 236 patients and 19 healthy controls. The greatest elevations of HA were seen in RA patients (350.7 +/- 689.5 ng/ml) than controls (33.7 +/- 24.2 ng/ml). Their levels showed only weak correlation values of CRP in laboratory data. Although HA levels of sera in stage III and IV in Steinbrocker's classification revealed significantly higher on average than ones in stage I and II (p < 0.01), there were many cases with low HA levels even in stage III and IV. Comparing HA levels between the cases with progressive and non-progressive type of hip or knee joint destruction within a year, the former (1143.6 +/- 1746.0 ng/ml median 480.1 ng/ml) presented significantly higher HA levels than the latter (245.3 +/- 255.8 ng/ml median 140.0 ng/ml) (p < 0.01). Further, one of 7 cases followed by 4 years with extremely high levels of HA showed progression of joint destruction from grade III to IV in Larsen Grade in bilateral knee joints during these times, though there were no significant correlations between HA levels and laboratory data. From above results, levels of circulating HA in the sera of patients with RA correspond to the joint destruction, not to a result of one.

Aged↗