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Biomedical subjects

M Morimatsu

Publications and source records attributed to M Morimatsu.

At least 145 records · Page 8Linked to original sources

Development-related changes in matrix metalloproteinase expression in human aortic smooth muscle cells.

BACKGROUND: It is known that extracellular matrix-degrading enzymes play an important role in tissue remodeling and that large amounts of structural proteins including types I, III, IV, and V collagens and elastin are produced by smooth muscle cells (SMC) in the arterial wall. We have recently shown that matrix metalloproteinases (MMPs) produced by human aortic medial smooth muscle cells are closely related to the proliferation of the cells, leading to the formation of atherosclerotic plaques, characteristic of intimal remodeling. For a better understanding of the mechanism of atherogenesis, therefore, it is important to clarify the relationship between the production of matrix-degrading enzymes and artery development. EXPERIMENTAL DESIGN: In vivo or in vitro synthesis of MMPs by SMC was analyzed by immunohistochemistry and immunoblotting. Elastase activity in the culture medium was also estimated. RESULTS: Production of proMMP 1, 2, and 3 was detected in cultured SMC isolated from the aortas of both neonates and fetuses; in medial SMC cultured from young individuals, production of proMMP-1 and -3 was extremely decreased, but was apparent in intimal SMC. Immunohistochemical observation indicated that in the media of fetal or neonatal aorta, SMC synthesized large amounts of the three proMMPs; in aortas from older individuals, proMMP-2, but not proMMP-1 and -3, was detected in the media, and relatively large amounts of proMMP-1, -2, and -3 were produced by SMC in the slightly thickened intima. Assay of elastase activity in the culture medium gave results similar to those for MMPs. CONCLUSIONS: We conclude that the production of proMMP-1 and -3 is associated with phenotypic modulation of SMC to a "synthetic" state, and that the ability of SMC to produce MMPs plays an important role in the development and/or aging of the human aorta through remodeling of the extracellular matrix; furthermore elastase is also involved in these processes in the arterial wall.

Adolescent↗

[A case of anti-glomerular basement membrane antibody (AGBMA) nephritis associated with myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)].

A 68-year-old patient visited our hospital, because of progressive renal failure. Laboratory data were serum creatinine 13.3 mg/dl, BUN 74.3 mg/dl, AGBMA 134U, MPO-ANCA 37% and CIC 1.6 g/dl. Hemodialysis was performed on admission and renal biopsy was conducted. Though the histological findings showed fibrocellular crescents and global sclerosis in many glomeruli, renal function was gradually ameliorated by administration of prednisolone (40 mg/day) and cyclophosphamide (50 mg/day). After 3 weeks of therapy, hemodialysis was withdrawn temporarily. Because of the complication of pneumocystis carini, prednisolone and cyclophosphamide were discontinued, and maintenance hemodialysis was resumed. In spite of progressed histological findings, hemodialysis was withdrawn at least temporarily through the use of pharmacological therapy. Thus, the presence of ANCA may indicate a relatively good prognosis of AGBMA nephritis.

Aged↗

[A study on the distribution of metastases at autopsy in 70 patients with ovarian cancer].

A total of 6,457 autopsy protocols were reviewed to identify 70 women who died of ovarian cancer. 1. Epithelial tumors were the most common tumor (74%). Twenty% were germ cell tumors. There were two cases each of sarcoma and stromal cell tumors. 2. The patients with germ cell tumors were younger than those with epithelial tumors. The duration of the epithelial tumor disease was longer than that of germ cell tumor. 3. The most common mechanism of death was carcinomatosis (69%). Eight of 70 patients (11%) had respiratory failure. One case of subacute cor pulmonale was due to tumor embolization. One case had a rupture of the portal vein. 4. The peritoneum was most frequently involved in every tumor (87%). The liver was the second most frequent site (73%). Other frequent metastatic sites included the lungs (44%), and spleen (47%). Lymph nodes including the paraaortic, pelvic and mesenteric were also very frequent metastatic sites. 5. CDDP containing regimens were used in 33 cases (47%). FAMT regimen was the second most common treatment (15.7%). Another common treatment is whole abdominal radiotherapy (14%). The patients treated with the CDDP containing regimen had a significantly longer survival time (23.4 months) than those treated with FAMT (19.2 months) and others (13.6 months). 6. For metastasis to the lungs, spleen and mesenteric lymph nodes the patients treated with the CDDP containing regimen were more numerous than those treated without CDDP. For metastasis to the kidneys, the patients treated without CDDP were more numerous than those treated with CDDP containing regimens.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Effects of lipid peroxide on production of matrix metalloproteinase 1 (tissue collagenase) and 3 (stromelysin) and tissue inhibitor metalloproteinase 1 by human rheumatoid synovial fibroblasts.

The effects of linoleic acid hydroperoxide on the production of matrix metalloproteinases (MMPs) including MMP-1 (tissue collagenase), -2 ("type IV collagenase"), and -3 (stromelysin) and of tissue inhibitor of metalloproteinase 1 (TIMP-1), as well as DNA synthesis were investigated in rheumatoid synovial fibroblasts. Our results demonstrated that the levels of proMMP-1 and -3 and TIMP-1 were extremely elevated when 0.5-2.0 nmole/ml of linoleic acid hydroperoxide was added to cultures of rheumatoid synovial fibroblasts. DNA synthesis, however, was inhibited by linoleic acid hydroperoxide. These results indicate that lipid peroxide causes the disruption of extracellular matrix macromolecules and the inhibition of cell repair in synovial tissue. Therefore, they also suggest that an elevated level of oxygen free radical and/or lipid peroxides in synovial fluid may play an important role in the process of rheumatoid arthritis, resulting in the disruption of the joint.

Arthritis, Rheumatoid↗

Effect of linoleic acid hydroperoxide on production of matrix metalloproteinases by human aortic endothelial and smooth muscle cells.

The effect of linoleic acid hydroperoxide on the production of proforms of matrix metalloproteinase-1, -2, and -3 (proMMP-1, -2, and -3) in cultured human arterial endothelial and smooth muscle cells was investigated. Upon cultivation of the endothelial cells in the absence of the hydroperoxide, only proMMP-1 was detected, and its amount was increased by cultivation with the hydroperoxide. In the cultures of the intimal smooth muscle cells in the absence of the hydroperoxide, a large amount of proMMP-2 and small amounts of proMMP-1 and -3 were detected, and the hydroperoxide treatment increased remarkably the amounts of proMMP-1 and -3, but rather decreased the amount of proMMP-2. In the cultures of the medial smooth muscle cells, the same tendency was observed. However, the amounts of these proenzymes found in the intimal smooth muscle cells exceeded those found in the medial smooth muscle cells, both in the absence and in the presence of the hydroperoxide. Possible involvement of these phenomena in atherogenesis was discussed.

Aorta, Thoracic↗

Avidity of antibody and agglutinability of antibody-sensitized latex in latex agglutination test.

This paper describes the avidity of IgG antibody used for preparation of latex sensitized with IgG antibody (IgG-sensitized latex) and the agglutinability of IgG-sensitized latex in slide reversed passive latex agglutination (RPLA). Using immunodiffusion techniques, it was found that anti-canine C-reactive protein (CRP) sera from four rabbits immunized with canine CRP had the same antibody titers. However, the antibodies had different levels of avidity. When lattices were sensitized under the same condition with the IgG antibodies of different avidity levels separated from the above-mentioned antisera using Protein A and canine CRP-Sepharose 4B immunosorbent, these demonstrated different patterns of agglutinability in slide RPLA. The latex sensitized with IgG antibody of higher avidity demonstrated a stronger agglutinability.

Agglutination↗

Efficient preparation of monospecific anti-canine C-reactive protein serum and purification of canine C-reactive protein by affinity chromatography.

The canine C-reactive protein (CRP) fraction isolated from canine acute-phase serum on a phosphorylcholine-Sepharose 4B column was further subjected to Sephacryl S-300 gel filtration. A canine CRP fraction not containing IgM was then obtained. The antisera, obtained after several immunizations with this canine CRP fraction, contained nonspecific antibodies that reacted with albumin, transferrin and IgG in addition to CRP. This antiserum could be easily changed to monospecific canine CRP serum, when it was subjected to absorption for only 15 min using glutaraldehyde-insolubilized normal canine serum protein containing 3.5 micrograms ml-1 of CRP. Pure canine CRP was isolated with a recovery rate of 95% from canine acute-phase serum by affinity chromatography using specific anti-canine CRP antibody.

Acute-Phase Reaction↗

Induction of acute phase protein by recombinant human interleukin-6 (IL-6) in calves.

Interleukin-6 (IL-6) is a major inducer of acute phase proteins in human and murine species. However, the effects of IL-6 have not yet been investigated in cattle. Following continuous infusion of recombinant human IL-6, serum concentrations of bovine haptoglobin and fibrinogen increased in a manner similar to those in cattle with acute phase reaction. In contrast, C-reactive protein and alpha 1-acid glycoprotein, as well as the other hematologic parameters, did not change significantly. Intravenous administration of recombinant human IL-6 resulted in only a mild and transient increase of bovine haptoglobin. These results suggest that the regulation of acute phase protein production in cattle is similar, but not identical, to that observed in human and murine species.

Acute-Phase Proteins↗

Production of matrix metalloproteinase 9 (92-kDa gelatinase) by human oesophageal squamous cell carcinoma in response to epidermal growth factor.

We demonstrated that four human oesophageal squamous cell carcinoma cell lines (TE8, TE9, TE10 and TE11) produced matrix metalloproteinase-1 (proMMP-1/tissue collagenase), 2 (ProMMP-2/'type IV collagenase'), 3 (proMMP-3/stromelysin), and 9 (proMMP-9/92-kDa gelatinase) as members of a matrix metalloproteinase (MMP) family, which degrades extracellular matrix macromolecules. Under normal culture conditions, in immunoblot analysis, proMMP-1 of M(r) = 53,00 was detected in one cell line (TE8), proMMP-2 of M(r) = 72,000 in three cell lines (TE9, TE10, and TE11), and proMMP-3 of M(r) = 57,000 in all four cell lines. In addition to these enzymes, in enzymography, a gelatinolytic activity around M(r) = 92-kDa, likely to be proMMP-9, was detected in only one cell line (TE10) under normal culture conditions. When these cell lines were treated with epidermal growth factor (EGF), however, the agent stimulated three cell lines (TE8, TE10 and TE11) to produce proMMP-9 in a dose-dose dependent manner. Oesophageal carcinoma-conditioned medium stimulated oesophageal fibroblasts to produce proMMP-1, -2, and -3, suggesting that the interaction between oesophageal carcinoma and stromal fibroblasts also plays a role in the production of MMPs by the latter. Our present study illustrates that oesophageal squamous cell carcinoma produces a variety of MMPs including proMMP-1, -2, -3, and -9 in vitro, suggesting that the ability of MMP production of the tumour may play an important role in its malignant behaviour and that the production of proMMP-9 may be regulated by EGF via overexpression of EGF receptors.

Carcinoma, Squamous Cell↗

Expression of matrix metalloproteinase-2 related to lymph node metastasis of oral squamous cell carcinoma. A clinicopathologic study.

To investigate the effect of matrix-degrading enzymes on the malignant potential of oral squamous cell carcinoma, the expression of matrix metalloproteinase-2 (MMP-2/72-kD gelatinase/type IV collagenase) in 46 patients who had neck surgery for oral cancer was studied immunohistochemically. In 20 of 26 patients (76.9%) with lymph node metastases, proMMP-2 was strongly expressed, whereas the production of proMMP-2 in tissue was detected only in 5 of 20 patients (25%) who had no lymph node metastases. In tissue specimens, proMMP-2 was expressed in a diffuse invasive mode and in the advancing front of cancer. Because MMP-2 can degrade type IV collagen composed of basement membrane, these results suggest that the in vivo production of the enzyme by cancer is an indicator of the degree of malignancy, and that the analysis of proMMP-2 expression is useful to evaluate the malignant potential in individual oral squamous cell carcinoma.

Adult↗

Porcine vascular smooth muscle cells immortalized with SV40 ori-defective DNA: characteristics of cell growth and collagen synthesis.

A cell line derived from medial smooth muscle cells (SMC) was established from the porcine coronary artery by transfection with ori-defective simian virus 40 plasmid DNA (SV40 DNA). The characteristics of transfected cells (SV40-SMC) such as cell growth, collagen and non-collagen syntheses were investigated. SV40-SMC expressed SV40 large T antigen, c-myc and c-myb encoded proteins in the nuclei. SV40-SMC demonstrated a 'hills and valleys'-like arrangement in overconfluence and actin filaments upon immunofluorescent staining. Under electron microscopic observation, SV40-SMC had larger amounts of synthetic organelles and smaller amounts of filament bundles than those of SMC. SV40-SMC demonstrated three times higher growth activity and 4.4 times greater cellular density than SMC. Smooth muscle cells did not grow in media containing 5% plasma derived serum (PDS) instead of normal serum, whereas SV40-SMC proliferated in this medium. SV40-SMC did not grow in soft agar gel, while HeLa S3 cells, a cell line of human cervical carcinoma, formed colonies in this gel. By immunofluorescent (IF) staining, collagen phenotypes I, III, IV and V were detected in both SV40-SMC and SMC. However, protein synthesis including collagen and non-collagen was higher in SV40-SMC than in the control sample. It was concluded that SV40-SMC were a continuous cell line for vascular SMC regarding morphological characteristics, and demonstrated a higher growth activity, with increased collagen and non-collagen syntheses. This cell line is useful for the investigation of atherogenesis in relation to a proliferation of SMC and an accumulation of extracellular matrices in vascular intima.

Agar↗

Induction of gelatinolytic neutral proteinase secretion by lipid peroxide in cultured mesangial cells.

To investigate whether lipid peroxides in tissue and/or blood play an important role in the injury to mesangial cells and glomerular structural proteins, we studied the effect of linoleic acid hydroperoxide (LHO) on mesangial cells cultured from rat kidneys. When 1.0-3.0 nmol/ml of LHO were added to the culture, the production of 70-kDa gelatinolytic neutral proteinase by mesangial cells was enhanced without morphological damage. The production of the enzyme, however, was inhibited by an addition of 4.0 or 5.0 nmol/ml of LHO and a microscopic examination also demonstrated marked injury to mesangial cells in the presence of these concentrations of LHO. These data suggest that there is a possibility that increased lipid peroxides in tissue and/or blood play a role in the injury to mesangial cells and glomerular structural proteins leading to mesangiopathy.

Animals↗

Purification and identification of a serum protein increased by anthelmintic drugs for Dirofilaria immitis in dogs.

Polyacrylamide gel electrophoretic analysis of canine serum protein has revealed that the administration of anthelmintics elicits an increase in a certain serum protein. This protein, named PT60, was partially purified by ammonium sulfate fractionation and preparative electrophoresis. The purified PT60 gave a single band with the molecular size of 53 kDa in sodium dodecyl sulfate-polyacrylamide gel electrophoresis under non-reducing conditions. After reduction with 2-mercaptoethanol, two bands appeared at 35 kDa and 17 kDa, indicating that PT60 consists of two subunits which are linked with each other by disulfide bonds. PT60 had the capacity to bind to hemoglobin. In an immunodiffusion test, an antiserum against PT60 cross-reacted with canine haptoglobin (Hp). N-terminal amino acid sequences of two PT60 subunits were identical to those of alpha and beta subunits of canine Hp, respectively. Thus, PT60 was identified as Hp.

Amino Acid Sequence↗

Down-regulation in the production of matrix metalloproteinase 1 by human aortic intimal smooth muscle cells.

Effects of dexamethasone, retinoic acid, prostaglandin E2 (PGE2), and Iloprost as a agonist of prostacyclin (A-PGI2) on DNA synthesis and production of a precursor of matrix metalloproteinase 1 (tissue procollagenase/proMMP-1) by human aortic smooth muscle cells were investigated. When after treatment with platelet-derived growth factor (PDGF), these agents were added to the cultures, DNA synthesis and production of proMMP-1 were inhibited in a dose-dependent manner. These results suggest that these agents are negative regulators of PDGF. Since these agents are present in the blood or produced in the blood wall, in addition, since PDGF plays the most important role in the process of atherosclerosis, we propose that these agents function in vivo as a systems of protection against atherosclerosis.

Aorta↗

[A case of isolated adrenocorticotropic hormone deficiency with adrenocorticosteroid-responsive brain edema and repeated confusions].

A 60-year-old man developed confusional state with severely abnormal electroencephalogram and brain edema on computed tomography (CT) of brain. Adrenocorticosteroid therapy was dramatically effective for the confusional state and brain edema. The reduction of adrenocorticosteroid induced confusional states, and they disappeared with the increase of adrenocorticosteroid. When brain edema on CT disappeared, T 2-weighted magnetic resonance imagings revealed diffuse high signal in the white matter. A diagnosis of isolated adrenocorticotropic hormone deficiency was made by endocrinological examinations and clinical features. We suggest that brain edema in this patient is due to deficiency of glucocorticoid. High intensity area in the white matter may show the degeneration of the white matter following brain edema.

Adrenocorticotropic Hormone↗

[MRI and SPECT of adrenoleukodystrophy (cerebello-brainstem dominant form)--a case report].

We reported a 28-year-old man with adrenoleukodystrophy showing neurological features of olivopontocerebellar atrophy. He had a 11-year history of Addison's disease. ACTH stimulation produced no rise in the plasma cortisol level. The ratios of C24:0/C22:0, C25:0/C22:0, and C26:0/C22:0 in fatty acids of sphingomyelin from plasma were all increased. MRI showed the atrophy of brainstem and cerebellum and the abnormal hyperintense lesions of the bilateral pyramidal tracts in the brainstem and internal capsule. 99mTc-HM PAO SPECT showed hypoperfusion of the deep white matter, frontal lobes, temporal lobes, and cerebellum. We suggest that SPECT may be useful for detection of subclinical lesions in ALD.

Adrenoleukodystrophy↗