Biomedical subjects

Y Sasaguri

Publications and source records attributed to Y Sasaguri.

At least 73 records · Page 4Linked to original sources

PubMed1995

Expression of matrix metalloproteinase-3 in stage I and II squamous cell carcinoma of the oral cavity.

PURPOSE: The object of this study was to evaluate the significance of matrix metalloproteinase-3 (MMP-3) in tumor invasion and metastasis of early squamous cell carcinoma (SCC) of the oral cavity. MATERIALS AND METHODS: Surgical specimens from 65 patients with stage I and II SCC of the oral cavity were the subjects of this study. Tissue specimens were fixed in formalin and embedded in paraffin, and the sections were stained with monospecific antibodies against human MMP-3 by the avidin-biotin-peroxidase complex method. RESULTS: Of the 65 patients, 30 (46.2%) tested positive for MMP-3. Immunoreactivity revealed the expression of MMP-3 to be in the small cancer nests in the advancing front of invasion, but not in normal oral epithelium. MMP-3 expression was positively correlated with tumor size, depth of tumor invasion, diffuse invasive mode, and the high incidence of lymph node metastasis. CONCLUSION: MMP-3-containing tumors will invade adjacent normal tissues more aggressively, including lymphatic and blood vessels. Therefore, the examination of MMP-3 expression in biopsy specimens should provide information useful in predicting the malignant potential of early SCC of the oral cavity.

Adult↗

PubMed1995

Co-culture of human breast adenocarcinoma MCF-7 cells and human dermal fibroblasts enhances the production of matrix metalloproteinases 1, 2 and 3 in fibroblasts.

No measurable amounts of matrix metalloproteinases (MMPs) were produced by human breast adenocarcinoma cell lines MCF-7 and BT-20 in culture. When MCF-7 cells were co-cultured with human dermal fibroblasts enhanced production of precursors of MMP-1 (interstitial collagenase), MMP-2 (gelatinase A), MMP-3 (stromelysin 1) and tissue inhibitor of metalloproteinase type 1 (TIMP-1) was observed. Immunohistochemical studies indicated that these pro-MMPs originated primarily from the fibroblasts, suggesting that MCF-7 cells have a stimulatory effect on stromal cells to produce at least three pro-MMPs and TIMP-1. BT-20 cells also enhanced the production of pro-MMP-2 and TIMP-1 in the dermal fibroblasts, but not of pro-MMP-1 and pro-MMP-3. Normal mammary epithelial cells promoted only TIMP-1 production. To investigate further the stimulatory factors from MCF-7 cells, the conditioned medium and the cell membrane were prepared and examined. The cell membrane fraction enhanced the production of pro-MMP-1 and -3 and TIMP-1, but not of pro-MMP-2. The conditioned medium, on the other hand, augmented the production of all four proteins in the fibroblasts. These observations suggest that breast adenocarcinoma MCF-7 cells in culture produce both soluble and membrane-bound factor(s) which stimulate the production of pro-MMPs and TIMP-1 in neighbouring stromal cells, but the factor(s) released into the medium and that associated with cell membranes are probably different. Such communication between the normal and malignant cell types may, in part, assist the cancer cells to invade and metastasise.

Adenocarcinoma↗

PubMed1995

A novel adult T cell leukemia-derived cell line (SALT-3) susceptible to human immunodeficiency virus type 1 infection.

A novel human T cell line (SALT-3) was established from the pleural effusion of a patient with adult T cell leukemia (ATL) of lymphoma type. SALT-3 showed atypical T cell markers such as CD1-CD2-CD3-CD4+CD5+CD7+CD8-CD19-CD20-CD25+HLA-DR+. T cell receptor alpha/beta and gamma/delta were undetectable. Human T cell lymphotropic virus type 1 (HTLV-I) particles were seen on SALT-3 cells by electron microscopic analysis. HTLV-I gag p19, proviral DNA and mRNA of HTLV-I genes were also detected in the cells. Chromosome analysis showed abnormal karyotypes as 47, XY, partial trisomy of No.3 chromosome, and trisomy of No. 7 chromosome. Furthermore, SALT-3 were susceptible to the infection of human immunodeficiency virus type 1 (HIV-1) and the cells were rapidly killed after HIV-1 infection. This newly established HTLV-I-infected human T cell line would be a useful tool to study biological activities of atypical type of ATL cells and to examine the cytotoxic effects of HIV-1 and it's modulators.

Aged↗

PubMed1995

[Angiotrophic lymphoma in the paranasal sinuses].

Angiotrophic lymphoma (neoplastic angioendotheliosis) is a peculiar disease which increases large extraordinary sized cells originating from B lymphocytes, in the small blood vessels and the capillary vessels of each viscera of the whole body, including brain. This disease, which was first reported by Pfleger and Tappeiner in 1959, has many clinical manifestations. CNS, skin, lung, kidney, and adrenal gland are often damaged by the disease. A case of this disease appearing in the paranasal sinus with successful remission following chemotherapy is reported. The patient was a 78-year-old woman with bilateral occulomotor nervous paralysis. Ethmosphenoidectomy was conducted under a working diagnosis of pansinusitis following CT. The surgical specimens were studied histopathologically and diagnosed as angiotrophic lymphoma. Six courses of chemotherapy (THP-COP) were applied. This disease is not necessarily rare, but the possibility of its being overlooked without enough diagnosis and treatment is very high. If we detect and treat it at an early stage, recovery of the disease can be expected, as in the case described above.

Aged↗

PubMed1995

Myxoid and globular degeneration of nerves in the shoulder joint.

Characteristic degeneration of the nerves in shoulder joints was recognized in 26 of 35 capsules (74.3%) from 20 cadavers. No left or right or gender differences were found. Histologic features of the nerves were (1) thickening of the perineurium, (2) myxoid degeneration in the endoneurium, and (3) hyaline globular structures with a whorled, oligocellular appearance regarded as Renaut bodies. The results of histochemical and electron microscopic studies showed prominent degenerated collagen fibers in the globular areas. These features resembled those found in the fusiform swelling in the axillary nerve branch to the teres minor muscle, believed to be caused by chronic nerve compression. Sixty percent of the degenerated nerves occurred in the anteroinferior and posteroinferior portions of the capsule, an area that is considered to be innervated by the axillary nerve. No correlation between age and severity of these degenerative nerve changes was noted. Compression of the axillary nerve and inferior joint capsule caused by repetitive shoulder movement such as forward flexion, abduction, and external rotation of the humerus might result in this form of nerve degeneration found histologically over a lifetime without necessarily causing clinical symptoms.

Adolescent↗

PubMed1995

Effect of angiotensin II and thromboxane A2 on the production of matrix metalloproteinase by human aortic smooth muscle cells.

Angiotensin II (AGII) and thromboxane A2 (TXA2), potent vasoconstrictors, augmented the production of the precursor of tissue procollagenase/promatrixmetalloproteinase-1 (proMMP-1) and DNA synthesis in cultured human aortic smooth muscle cells (SMC) significantly compared with that in untreated SMC. Moreover, AGII and TXA2 stimulated hydrolysis of phosphoinositides and subsequent formation of inositol triphosphate (IP3), leading to an increase in the intracellular free Ca2+ concentration. These results suggest that the production of proMMP-1 increased by AGII and TXA2 in intimal SMC in relation to cell proliferation plays a role in arterial reconstruction in vascular diseases.

Angiotensin II↗

PubMed1995

Expression of the histamine H1 receptor gene in relation to atherosclerosis.

Histamine in serum and arterial tissue contributes to the pathogenesis of atherosclerosis and the formation of coronary artery vasospasm. As the effect of histamine at a given site will be mediated by its specific receptors, we investigated by in situ hybridization and Northern blot analysis the expression and localization of human histamine H1 receptor mRNA in the arterial wall and in cultured human aortic intimal smooth muscle cells (SMC) and immortalized SMC (ISS10) and endothelial cells (SE1). In situ hybridization showed that SMC and endothelial cells expressed H1 receptor mRNA in vivo and that the expression was increased in SMC in the thickened intima of atherosclerotic foci in both the aorta and coronary artery. By Northern blot analysis, we also detected histamine H1 receptor mRNA in cultured SMC, ISS10, and SE1 and found that platelet-derived growth factor stimulated SMC to increase their expression of the mRNA in vitro. These results suggest that up-regulation of histamine H1 receptor expression by platelet-derived growth factor plays an important role in the initiation and progression of cardiovascular diseases.

Aorta↗

PubMed1995

Establishment and characterization of immortalized human coronary endothelial cells.

We established an immortalized cell line from endothelial cells derived from a human coronary artery, isolated at autopsy from 76-year-old male, by transfecting the cells with origin-minus simian virus 40 DNA. These cells showed SV40 T antigen in the nuclei and Ulex europaeus I agglutinin and factor VIII-related antigen, as endothelial cell markers, in their cytoplasm. This cell line synthesized prostacyclin, tissue-type plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1) as well as produced the proform of matrix metalloproteinase 1, which was activated by cultivating the cells with plasminogen. These findings reveal that this immortalized endothelial cell line retains characteristics of human coronary endothelial cells, indicating that this cell line is useful for studying atherogenesis of the coronary artery.

Aged↗

PubMed1994

Histamine as an activator of cell growth and extracellular matrix reconstruction for human vascular smooth muscle cells.

Atherosclerosis is characterised by unusual growth of vascular smooth muscle cells (VSMCs) in the intima. We examined the effects of histamine on human VSMCs and the VSMC-derived cell line, ISS10. Histamine enhanced phosphoinositide hydrolysis, increased cytoplasmic Ca2+ level and stimulated the transcription of c-fos protooncogene, which resulted in DNA synthesis and the enhancement of proMMP-1 expression. These results indicate that histamine may play some roles in the pathological process of atherosclerosis and raise the possibility that mast cells migrating into the atherosclerotic foci are involved in the process of atherosclerogenesis.

Arteriosclerosis↗

PubMed1994

Ambient pressure stimulates immortalized human aortic endothelial cells to increase DNA synthesis and matrix metalloproteinase 1 (tissue collagenase) production.

In the present study, we investigated the effect of ambient pressure on [3H]-thymidine incorporation and on the production of matrix metalloproteinase 1 (tissue collagenase/proMMP-1) using human aortic endothelial cells immortalized with simian virus 40 (SE-1). Incubation of cells at ambient pressures of 50 and 100 mmHg for 24 h slightly increased [3H]-thymidine incorporation when directly compared with normal culture conditions. The amount of [3H]-thymidine incorporated in SE-1 reached a maximum at 150 mmHg, while a further increase in pressure to 200 mmHg decreased incorporation. The same ambient pressure slightly stimulated human aortic intimal smooth muscle cells (SMC) to increase [3H]-thymidine incorporation but not medial SMC. Immunoblot analysis also showed that ambient pressure, ranging from 50 to 200 mmHg, like 12-O-tetradecanoyl-phorbol-13-acetate stimulated SE-1 to produce proMMP-1, an effect not seen with either intimal or medial SMC. The amount of proMMP-1 produced also reached a maximum level at 150 mmHg. We postulate that human endothelial cells are ambient pressure sensitive and that relatively lower ambient pressures play an important role in the growth of endothelial cells, while higher pressures injure endothelial cells, resulting in the initiation of atherosclerosis. This cell line may prove useful in the investigation of both the physiological and pathological roles of blood pressure on endothelial cell function.

Aorta↗

PubMed1994

Cytopathological changes induced by cadmium-exposure in canine proximal tubular cells: a cytochemical and ultrastructural study.

A highly sensitive cytochemical method for demonstrating intracellular Cd using 8-hydroxyquinoline was developed and applied in the cytopathological study of primary-cultured renal tubular cells from beagle kidneys. The Cd-8-hydroxyquinoline emitted a yellowish-green fluorescence which first appeared in the cytoplasm within 30 min and in the nucleus about 60-90 min after exposure to 100 mM CdCl2. It was noteworthy that intranuclear Cd was stained in the nucleolar regions. The sensitivity of the cytochemical method for Cd was estimated to be about 1.0 pg Cd/cell. Ultrastructural features of the dead cells were consistent with those of apoptosis. We conclude that Cd absorbed by proximal tubular cells rapidly reaches to the nuclei and affects nuclear as well as cytoplasmic metabolism.

Animals↗

PubMed1994

Stimulation of the biosynthesis of interleukin 8 by interleukin 1 and tumor necrosis factor alpha in cultured human chorionic cells.

Human chorion, but not amnion, tissue explants produced substantial quantities of neutrophil chemoattractant in response to interleukin 1 (IL-1) and tumor necrosis factor alpha (TNF alpha). This suggested that chorion is one of the chemoattractant producing tissues. Therefore, the biochemical properties and the regulation of a chemoattractant in human chorionic cells were examined. IL-1 alpha and TNF alpha stimulated human chorionic cells to produce neutrophil chemotactic factor in both a dose- and time-dependent manner. This chemotactic factor was a heat-stable and trypsin-sensitive protein with an apparent molecular weight of 10000, and it was also immunologically identified as a chemotactic cytokine of the human IL-8 family. Immunohistochemical observations with IL-1 alpha- and TNF alpha-treated chorion explants indicated that trophoblasts and stromal cells, including fibroblast-like and macrophage-like cells, but not endothelial cells, were characterized as IL-8-producing cells. From these observations, it is very likely that both IL-1 and TNF alpha may participate in the production of chemotactic factor/IL-8 in pre-term parturition, accompanied by an intraamniotic infection, along with their known promotive effect on the production of matrix metalloproteinases, which is connected with the destruction of matrix components of fetal membranes.

Amnion↗

PubMed1994

Expression of the c-kit mRNA in human aortic endothelial cells.

We investigated the expression of the c-kit gene in human aortic endothelial cells. RT-PCR and Northern blot analyses showed that a human aortic endothelial cell line expressed mRNA specific for the c-kit gene. Furthermore, the addition of stem cell factor stimulated the cells to increase the amount of c-kit mRNA transcribed in response to its ligand. In situ hybridization also revealed that endothelial cells in vivo express the c-kit gene.

Aorta↗

PubMed1994

[Kawasaki vasculitis].

Kawasaki disease is an acute febrile illness recognized most often in children under 4 years of age. It is characterized by mucosal inflammation, indurative edema of the hands and feet, skin rash and cervical lymphadenopathy. This is an acute systemic vasculitis syndrome of unknown etiology which has been recognized not only in Japan but all over the world. This article reports on the clinical spectrum of Kawasaki disease, analysis of coronary artery and other lesions, and long-term cardiovascular problems including premature atherosclerosis. The etiology and pathogenesis of this disease are still unknown. Current hypotheses and leading studies on the etiology and the pathogenesis of Kawasaki disease are also reviewed.

Coronary Angiography↗

PubMed1994

Immunohistochemical approach for the investigation of nerve distribution in the shoulder joint capsule.

Twenty six shoulder joint capsules obtained from 13 autopsy cases were studied to evaluate the nerve distribution using immunohistochemical techniques. Immunohistochemical staining of polyclonal S-100 protein or protein gene product 9.5 was more sensitive, specific, and reproducible compared with conventional gold chloride methods. A small number of clustered nerve fibers were found in the superficial layer, and many nerve fibers with large diameters were found in anteroinferior portions of the deep layer. Nerve fibers of various sizes were more numerous in posterosuperior and anterosuperior portions of the boundary zone between labrum and capsule. A Pacinian corpuscle was clearly recognized in a capsule. In the central portion of the long head of some biceps brachii tendons, relatively large nerve fibers continued from capsules. The results suggest that the capsule and long head of the biceps brachii tendon may play a partial role in the stability of the shoulder joint through afferent feedback.

Aged↗

PubMed1994

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↗

PubMed1993

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↗

PubMed1993

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↗