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Biomedical subjects

S Katsuda

Publications and source records attributed to S Katsuda.

At least 55 records · Page 3Linked to original sources
PubMed1996

Matrix metalloproteinase 9 (gelatinase B) is expressed in multinucleated giant cells of human giant cell tumor of bone and is associated with vascular invasion.

Human giant cell tumor (GCT) consists of multinucleated giant cells and mononuclear stromal cells, and is characterized by frequent vascular invasion without distant metastases. To study the role of matrix metalloproteinases (MMPs) in the vascular invasion, we examined production of MMP-1 (tissue collagenase), -2 (gelatinase A), -3 (stromelysin-1), -9 (gelatinase B), and tissue inhibitors of metalloproteinases (TIMP-1 and -2) in GCT. MMP-9 was highly and predominantly expressed in giant cells by both immunohistochemistry and in situ hybridization. Expression of other MMPs was also observed in some cases but was inconstant. Sandwich enzyme immunoassays demonstrated that MMP-9 is the predominant MMP secreted by GCT. There was a definite imbalance between the amounts of MMP-9 and those of TIMPs in the culture media of GCT, leading to detectable gelatinolytic activity in an assay using 14C-gelatin. Gelatin zymography demonstrated the main activity at about 90 kd, which was identified as the zymogen of MMP-9 by immunoblotting. Immunohistochemistry for type IV collagen and laminin, major basement membrane components, showed that disappearance of the proteins is closely associated with MMP-9-positive giant cells. These results indicate the production of MMP-9 by multinucleated giant cells and suggest that the metalloproteinase may contribute to proteolysis associated with vascular invasion and local bone resorption in human GCT.

Adolescent↗
PubMed1995

Pulmonary vasculitis with hypereosinophilia and episodic pulmonary hypertension: report of three siblings.

Three siblings with eosinophilia who developed pulmonary hypertension are reported. They consisted of a 3 year old boy (case 1), a 9 year old boy (case 2) and a 13 year old girl (case 3), all of whom died within an 18 month period of severe episodic attacks of pulmonary hypertension and the resultant low cardiac output. Marked peripheral eosinophilia was found in cases 1 and 2, and mild eosinophilia in case 3. Open lung biopsy of case 1 revealed pulmonary arteritis with massive eosinophilic infiltration and intimal thickening of muscular arteries of 300-1500 microns in diameter. At autopsy, cases 2 and 3 showed almost similar findings, comprising widespread obliteration of the pulmonary arteries by concentric intimal thickening, medial hypertrophy and recanalized thrombi of arterioles. Rarely, there were foci of granulomas in the thickened intima surrounding birefringent foreign bodies. There were small areas of infarction in the lungs and heart due to arterial thrombi. Vascular lesions other than those in the lungs were mild and almost limited to the branches of the coronary arteries. Therefore, the present cases appear to be a single disease of pulmonary hypertension secondary to endothelial injury and the resultant intimal fibrosis probably evoked by toxic substances, although such agents were not confirmed.

Adolescent↗
PubMed1994

Immunohistochemical study on the infection of herpes simplex virus, human cytomegalovirus, and Epstein-Barr virus in secondary diffuse interstitial pneumonia.

We examined the infection of herpes simplex virus (HSV), human cytomegalovirus (HCMV), and Epstein-Barr virus (EBV) in 61 autopsy cases with secondary diffuse interstitial pneumonia (SDIP) by immunohistochemistry and compared our findings with those in 46 individuals without lung complications. There was no significant difference in positivity of HSV infection between SDIP cases (28 of 61; 45.9%) and the controls (24 of 46; 52.2%). However, HSV was more extensively distributed in the lungs of seven SDIP cases than in those of controls and proliferated to form inclusion bodies in host cells of 11 SDIP cases. Twenty-two (36.1%) and 19 (31.1%) SDIP cases were positive for HCMV and EBV, respectively, whereas all the 46 controls were negative for both viruses. Eighteen of 22 HCMV-positive cases contained classical inclusion bodies in host cells. Epstein-Barr virus was detected extensively in the lungs of seven SDIP patients, but no viral inclusion bodies were observed in host cells. These findings indicate that the herpes viruses replicate excessively in a considerable number of SDIP cases, but classical inclusion bodies are not always associated with viral infection in the lungs. Major infected cells of these viruses were alveolar lining pneumocytes and intra-alveolar cells. Herpes simplex virus and EBV were detected in leukocytes as well as in pneumocytes. In addition, compared with HCMV and HSV, EBV frequently multiplied in bronchial or bronchiolar epithelial cells. Preferential host cells for these types of herpes virus were somewhat different from one another.

Antigens, Viral↗
PubMed1994

Detection of human cytomegalovirus, Epstein-Barr virus, and herpes simplex virus in diffuse interstitial pneumonia by polymerase chain reaction and immunohistochemistry.

Using formalin-fixed and paraffin-embedded tissues from autopsy, the authors examined infection by human cytomegalovirus, Epstein-Barr virus, and herpes simplex virus in 54 patients with primary or secondary diffuse interstitial pneumonia (DIP) by polymerase chain reaction and immunohistochemistry and compared it with that in 32 persons without lung complications. Polymerase chain reaction and immunohistochemistry demonstrated that approximately 40% and 30% of DIP were positive for human cytomegalovirus and Epstein-Barr virus, respectively, but none of 32 controls had evidence of infection by human cytomegalovirus and Epstein-Barr virus. The polymerase chain reaction was more sensitive than the immunohistochemical technique for detection of herpes simplex virus. The former technique revealed herpes simplex virus infection in approximately 90% of DIP and controls and the latter in approximately 50% of each group. However, immunohistochemistry had the advantage of demonstrating the morphologic location of infected cells and of allowing their semiquantitative evaluation. Herpes simplex virus was more extensively distributed in the lungs of several DIP cases than in those of controls, suggesting the reactivation of herpes simplex virus. Only DIP patients (31 cases [57.4%]) were infected by two or three kinds of herpesviruses. The combination of polymerase chain reaction and immunohistochemistry revealed that these herpesviruses proliferated in many cases of DIP.

Base Sequence↗
PubMed1994

An autopsy case of hepatic sarcomatoid tumor: immunohistochemical comparison with a sarcomatous component of hepatocellular carcinoma.

A case of primary hepatic tumor exclusively composed of malignant cells with sarcomatous features is described and compared immunohistochemically with two cases of hepatocellular carcinoma (HCC) with a sarcomatous component. More than 30% of HCC cells were positively stained with anti-cytokeratin (CAM5.2), anti-albumin, anti-fibrinogen and anti-alpha 1-antitrypsin antibodies, and some with anti-epithelial membrane antigen. The present sarcomatoid tumor and the sarcomatous component with HCC showed similar immunohistochemistry; many tumor cells were strongly immunoreactive for vimentin and some positive for cytokeratin, albumin, fibrinogen and alpha 1-antitrypsin. Other immunohistochemical markers, indicating specific differentiations to lineage of macrophages, muscle cells, glial cells, endothelial cells and so forth, were not detected in sarcomatous tumor cells of all cases. These findings suggest that the present sarcomatoid tumor would belong to an anaplastic sarcomatous variant of HCC.

Aged↗
PubMed1994

Matrix metalloproteinase-9 (92-kd gelatinase/type IV collagenase equals gelatinase B) can degrade arterial elastin.

Degradation of elastic fibers in the arterial walls is an important step in the development of atherosclerosis. To identify the enzyme(s) responsible for the elastinolysis, we have designed an ex vivo model of aortic explants cultured with or without THP-1 cells (human monocyte/macrophage-like cells). After culturing with THP-1 cells for 5 days elastic fibers of the aortic explants were fragmented and lost. With insoluble [3H] elastin as a substrate, elastin-degrading activity could be detected in the culture medium. Zymography in sodium dodecyl sulfate-polyacrylamide gel electrophoresis containing alpha-elastin showed the presence of elastinolytic activity with 92 kd in the medium from the aortic tissue with THP-1 cell cultures, whereas the medium from the aortic tissue without THP-1 cells contained negligible elastinolytic activity. The activity was inhibited by ethylenediamine tetraacetic acid but not by phenylmethane sulfonyl fluoride, N-ethylmaleimide, or pepstatin A, indicating that the enzyme belongs to a class of metalloproteinases. In addition, destruction of the elastic fibers of the aortic explants cultured with THP-1 cells was completely inhibited only by metalloproteinase inhibitors. Immunoblot analyses demonstrated that the proteinase responsible for the elastinolytic activity is matrix metalloproteinase-9 (92-kd gelatinase/type IV collagenase = gelatinase B). Using immunocytochemistry, the metalloproteinase was localized in the THP-1 cells but not in the medial smooth muscle cells. These results suggest that matrix metalloproteinase-9 produced by THP-1 cells is of importance to degradation of elastic fibers in the aortic explants. The role of macrophages in the atherosclerosis is discussed with reference to elastinolysis of the arterial walls.

Animals↗
PubMed1993

An elastinolytic enzyme detected in the culture medium of human arterial smooth muscle cells.

The culture medium of human arterial smooth muscle cells exhibits an elastinolytic activity with 68 and 64 kDa on elastin substrate gels. The enzymatic activities are inhibited by ethylenediamine tetraacetic acid, a metalloproteinase inhibitor, but not by other inhibitors of serine, cysteine and aspartic proteinases. The proteinase in the culture medium is activatable by 4-aminophenylmercuric acetate and degrades insoluble elastin. Compared to other matrix metalloproteinases (MMP), the activity shows the similar elastinolytic pattern to that by MMP-2 purified from human rheumatoid synovium, while MMP-3 and MMP-9 have different lytic patterns and MMP-1 possesses no elastinolytic activity. An immunoblot analysis demonstrated that the 68-kDa enzyme is MMP-2. An immunofluorescence study illustrates that MMP-2 is localized within the cytoplasm of the smooth muscle cells. These findings suggest that the elastinolytic enzyme secreted by human arterial smooth muscle cells is MMP-2.

Cells, Cultured↗
PubMed1993

Collagen synthesis of human arterial smooth muscle cells: effects of platelet-derived growth factor, transforming growth factor-beta 1 and interleukin-1.

The effects of platelet-derived growth factor (PDGF), transforming growth factor-beta 1 (TGF-beta 1) and interleukin-1 (IL-1) on collagen synthesis of cultured human arterial smooth muscle cells in a confluent state were investigated. Synthetic activity of collagenous protein was determined with [3H]-proline uptake, and subsequent analysis of collagen types by sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by fluorography. Although PDGF (0.5 U/mL and 5.0 U/mL) enhanced total collagen synthesis per dish, it suppressed total collagen synthesis per DNA (DNA content in a dish). TGF-beta 1 (10 pmol/L and 100 pmol/L) enhanced total collagen synthesis both per dish and per DNA. IL-1 (0.1 U/mL and 1.0 U/mL) suppressed total collagen synthesis both per dish and per DNA. A fluorogram revealed that human arterial smooth muscle cells synthesize types I, III, IV and V collagen. Densitometric analysis showed PDGF suppressed the proportion of type IV collagen and increased that of type V collagen. TGF-beta 1 increased the proportions of types IV and V collagen. IL-1 elicited un- remarkable change in the proportion of collagen types. These results suggest that, in the event of human atherosclerosis, TGS-beta 1 is most effective in enhancing collagen synthesis, and PDGF modulates collagen metabolism by stimulating a cell division of smooth muscle cells with a resultant increase of collagenous protein, especially of type V collagen.

Adult↗
PubMed1993

Human atherosclerosis. IV. Immunocytochemical analysis of cell activation and proliferation in lesions of young adults.

The accumulation of smooth muscle cells is a major phenomenon associated with the pathogenesis of lesions of atherosclerosis. Smooth muscle cell proliferation in response to the release of growth factors from neighboring cells, both smooth muscle and macrophages, is one mechanism postulated to account for the increasing numbers of smooth muscle cells as atherosclerotic lesions progress. Indeed, we recently demonstrated the B chain of platelet-derived growth factor (PDGF-B), a potent smooth muscle mitogen, within macrophages in monkey and human lesions of atherosclerosis. To further test the hypothesis that smooth muscle proliferation and/or activation (eg, expression of major histocompatibility complex proteins) plays a role in the early development of these lesions, we applied antibodies to PDGF-B, HLA-DR (a marker of cell activation), and proliferating-associated marker) on a series of early human atherosclerotic lesions from young adults in conjunction with cell-type-specific antibodies. Smooth muscle cells had previously been demonstrated to comprise a major fraction of the cell population in these lesions. In a continuing study of early and intermediate lesions of individuals ranging in age from 15 to 34 years, PDGF-B was detected within macrophages in 2 of 15 lesions. There was no evidence of HLA-DR expression by the smooth muscle cell population in any of the lesions. PCNA-positive cells comprised less than 2% of the cells in the lesions, and the majority of these were blood-borne cells (macrophages and/or lymphocytes), although a small fraction of the PCNA-positive cells were identified as smooth muscle. Concurrent PCNA and 5'-bromodeoxyuridine studies of peripheral blood monocytes demonstrated the presence of significant numbers of cells positive for these proliferation-related markers. It is concluded that the growth factor PDGF-B may have a role in regulating cell proliferation in early human fatty streaks, but the number of proliferating smooth muscle cells is relatively small, and there is no evidence of smooth muscle cell activation, as judged by HLA-DR positivity, in these lesions.

Adolescent↗
PubMed1992

Gastric carcinoma cells with endocrine differentiation show no evidence of proliferation.

The proliferative activity of gastric cancer cells with endocrine features was evaluated in five cases by means of a double-immunostaining procedure. The endocrine cells were recognized by a monoclonal antibody to chromogranin A (CGA) and the proliferative activity by a monoclonal antibody to proliferating cell nuclear antigen (PCNA). With the use of two different chromogens it was easy to determine whether CGA was located in the cytoplasm and whether PCNA was located in the nucleus of the same section. The CGA-positive endocrine cells of the normal gastric antral mucosa could be readily distinguished from the PCNA-positive cells scattered in the mucosal neck zones. Over 1,000 CGA-positive cancer cells were counted per case. A few cells (average, less than 1.0%) exhibited faint nuclear staining with anti-PCNA; in no instance was unequivocal PCNA reactivity demonstrable in the gastric cancer cells with endocrine differentiation. By contrast, the PCNA reaction was positive in one fourth to one third of the other cancer cells. These observations suggest that gastric cancer cells with endocrine features are differentiated and do not participate in the cell cycle.

Cell Division↗
PubMed1992

The modulation of collagen synthesis in cultured arterial smooth muscle cells by platelet-derived growth factor.

Changes on collagen synthetic activity of cultured arterial smooth muscle cells of rabbits induced with purified platelet-derived growth factor (PDGF) were examined. PDGF treatment (final concentration was 5 units/ml) decreased the total collagen synthesis per cell, while the rate of collagen synthesis against total protein synthesis was raised by PDGF. Type analysis of collagen revealed substantial reduction of type IV collagen and relative increase of type V collagen in the PDGF-treated cells. By immunofluorescence study using anti-type IV collagen antibody, the lacework fluorescence was decreased with PDGF supplement. These findings indicate that PDGF induces the decrease of type IV collagen synthesis with the simultaneous diminution of basement membrane formation probably in association with phenotypic modulation of smooth muscle cells.

Animals↗
PubMed1992

Collagens in human atherosclerosis. Immunohistochemical analysis using collagen type-specific antibodies.

This study represents a systematic analysis of the distribution of collagen types in human atherosclerotic lesions. Formalin-fixed, paraffin-embedded aortic tissues of 40 lesions from 16 different individuals ranging in age from 1 month to 84 years were examined immunohistochemically using antibodies to type I, III, IV, V, and VI collagens. Preembedding immunoelectron microscopy was used to simultaneously localize type V and VI collagens within the lesions. Localization of type III collagen was very similar to that of type I, and type VI collagen appeared together with these two types of collagen in the thickened intimas of all stages of the lesion. Type V collagen was not detected in either fatty streaks or the mild intimal thickening of the aortas of children. With advancing age and lesion progression, the immunoreactivity with anti-type V collagen antibody became more intense. Type IV collagen was detected in the basement membrane region of intimal cells. In advanced lesions thick deposits of type IV collagen were found around the elongated smooth muscle cells. Using immunoelectron microscopy, type V collagen was found to be localized to cross-banded collagen fibers, and type VI collagen was found to be localized to beaded filaments present throughout the interstitium of the thickened intima. These findings suggest that collagens preserve the pathophysiological and functional integrity of the vascular wall by providing mechanical support as well as assuring the proper interaction of cells during the formation of atherosclerotic lesions.

Adult↗
PubMed1992

Effects of atherosclerosis on mean and daily variation of arterial pressure in conscious WHHL rabbits.

Effects of atherosclerosis on the mean value and daily variation of arterial pressure were studied in 12 Watanabe-heritable hyperlipidemic (WHHL) rabbits aged 12 to 35 months and 25 normal Japanese white rabbits aged 6 to 30 months. A pressure catheter was inserted through the left subclavian artery under pentobarbital anesthesia. A few days after the catheterization, the mean arterial pressure (MAP) of the rabbits, which were active and in a good state of appetite, was recorded by an analogue-to-digital converter every second for about 6 hrs and stored in a computer. The mean (M) and standard deviation (SD) in the WHHL rabbit, calculated from each successive MAP record, ranged widely from 85.8 to 131.4 mmHg and 5.6 to 12.6 mmHg, respectively. There was no significant correlation between M and SD in the WHHL rabbit. M and variance (V) of MAP in the WHHL rabbit were significantly higher than those in the normal rabbit. M did not show any significant change with increasing ages, whereas SD increased significantly with aging in the WHHL rabbit. Concentrations of serum total cholesterol and triglyceride in the WHHL rabbit were 475 and 328 mg/dl, which were about nine and seven times as high as those in the normal rabbit, respectively. Macroscopic and histopathological examinations of the aorta revealed development and spread of sclerotic lesions with aging in the WHHL rabbit. We can conclude that development of atherosclerosis with aging in the WHHL rabbit causes malfunction of the baroreceptors, which contributes to hypertension and lability of arterial pressure.

Aging↗
PubMed1992

Impaired baroreflex control of arterial pressure in WHHL rabbits.

The present study was designed to investigate baroreflex control capacity of arterial pressure (AP) in the conscious Watanabe heritable hyperlipidemic (WHHL) rabbit. The control capacity of the baroreflex system was assessed with overall open-loop gain (G). Seven WHHL and 14 normal Japanese white rabbits were chronically implanted two catheters in the aortic arch through the left subclavian and common carotid arteries. A small amount of blood (2 ml/kg, body weight) was rapidly extracted into a syringe via the left common carotid artery in the conscious state. Mean arterial pressure (MAP) was monitored with a catheter-transducer system through the left subclavian artery. The MAP responses to the rapid hemorrhage were averaged 8 times by a computer. G was calculated as G = delta API/delta APS-1, where delta API was an immediate MAP fall after the hemorrhage and delta APS was a steady-state error 1-2 min after the hemorrhage. The values of G in the conscious normal and WHHL rabbits were 7.35 +/- 0.24 and 1.91 +/- 0.29 (mean +/- SE, p < 0.01), respectively. To investigate effects of pentobarbital anesthesia on baroreflex system, the hemorrhage experiment was repeated several times under pentobarbital anesthesia (20 mg/kg, i.v.). The values of G in the anesthetized normal and WHHL rabbits were 6.69 +/- 0.23 and 1.68 +/- 0.34 (mean +/- SE, p < 0.01), respectively. G in the normal and WHHL rabbits did not show any significant change in the presence and absence of pentobarbital anesthesia (p > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗
PubMed1992

Human atherosclerosis. III. Immunocytochemical analysis of the cell composition of lesions of young adults.

There have been only limited immunocytochemical studies of the cell composition of the early lesions of human atherosclerosis, and none that incorporate a comprehensive panel of antibodies to various cell types and subsets. The authors thus performed a prospective study of 27 lesions from 16 different individuals ranging in age from 15 to 34 years. These were all lesions that appeared grossly as slightly raised, yellow fatty streaks in the posterior ascending aorta, but on histologic examination had varying degrees of round-cell, spindle-cell, and foam-cell accumulation. Using a panel of antibodies, including monoclonal antibodies specific for smooth muscle cells [HHF35], human macrophages [HAM56], endothelial cells [monoclonal antibodies to F. VIII related antigen], lymphocytes [anti-CD45, anti-CD20, anti-CD45RO, anti-T-cell receptor], it was revealed that the predominant cell type in these early lesions was the smooth muscle cell, including the vast majority of the foam cells, which tended to appear in the deeper regions of the lesions. There were variable numbers of smooth muscle cells and lymphocytes; the latter were exclusively T cells. It is concluded that in atherosclerotic lesions of young adults, which may represent various stages of fatty streak formation and advanced fatty streaks, smooth muscle cell accumulation may be an early event.

Adolescent↗
PubMed1991

Induction of graft versus leukemia effect in bone marrow transplantation: dosage and time schedule dependency of interleukin 2 therapy.

The present work is a continuation of our studies to improve the graft versus leukemia (GVL) effect in autologous bone marrow transplantation. We have recently shown that the GVL effect of bone marrow transplantation (BMT) with interleukin 2 (IL-2)-activated bone marrow (ABM) followed by IL-2 therapy immediately after BMT is superior to the GVL effect of BMT with fresh, syngeneic bone marrow, with or without IL-2 therapy, in mice with acute myeloid leukemia. The present studies show that institution of IL-2 treatment 1, 2, or 3 weeks after BMT with ABM resulted in shortening of survival and fall in cure rate as compared to IL-2 therapy instituted immediately after BMT with ABM. Increasing the dose of IL-2 did not improve results. However, reducing the frequency of IL-2 administration to once a day instead of twice a day affected the results adversely. Commencing IL-2 therapy 1, 2, or 3 weeks after BMT with fresh, syngeneic bone marrow did not improve the GVL effect as compared to IL-2 therapy started immediately after BMT with fresh, syngeneic bone marrow. Cryopreserved bone marrow was effectively activated with IL-2 and used successfully for BMT after thawing. The animals cured of leukemia by BMT with ABM and and IL-2 therapy were not resistant to leukemia and died when reinfused with leukemic cells. Our findings suggest that for optimum GVL effect, activation of bone marrow is necessary and IL-2 therapy should be started immediately after BMT with ABM.

Acute Disease↗
PubMed1991

Microfilamentous type VI collagen in the hyalinized stroma of the hypertrophied ligamentum flavum.

Thickened ligamenta flava obtained from 14 patients with spinal canal stenosis were examined with special reference to type VI collagen. The characteristic histological finding in the thickened area was rupture or normal elastic fibre meshwork with resultant fibrosis which usually appeared hyaline. Using an immunohistological method, collagen types VI, I and III were found to be present in the hyaline matrix. Ultrastructural study revealed many microfilamentous structures of type VI collagen admixed in loosely packed, banded collagen fibres. With differential salt precipitation of pepsin-extracted collagen the existence of type VI collagen was confirmed by SDS-polyacrylamide gel electrophoresis analysis and Western blotting analysis using anti-type VI collagen antibody. Quantification of type VI collagen in pepsin-extracted crude collagen samples by an inhibition enzyme-linked immunosorbent assay showed an increasing amount of type VI collagen in the thickened ligamenta flava compared to the normal ligaments. Thus, increase of type VI collagen is the main contribution to the thickening of the ligamentum flavum. This may represent an adaptational and reparative process associated with disruption of elastic fibres.

Collagen↗