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Biomedical subjects

M Kyogoku

Publications and source records attributed to M Kyogoku.

At least 37 records · Page 2Linked to original sources
PubMed1993

A macrophage differentiating factor derived from human T cell line HUT102 acting on a mouse myeloid cell line M1.

Human T cell leukemia virus type I-transformed T cell line HUT102 constitutively secreted soluble factors which induced differentiation of a murine myeloid leukemic cell line, M1, to increase the immune complex-binding and/or phagocytizing capacity. This macrophage differentiating factor(s) (MDF) was purified from the culture supernatants of HUT102 cells by using several steps of column chromatography and novel immune-adherence and/or immune-phagocytic assays. The finally purified MDF activity was detected in the fraction that consisted of 40,000- and 45,000- molecular weight molecules. Antibodies specific for human interleukin-6 or for human granulocyte-colony stimulating factor, both of which have differentiation-inducing activity on M1 cells when used as a single factor, could not neutralize the MDF activity. These findings suggest that the 40,000- and/or 45,000- molecular weight molecules in the HUT102 cell products may be possible novel differentiation-inducing factors acting on a murine macrophage lineage across the species barrier.

Animals↗
PubMed1993

Induction of different types of glomerulonephritis by monoclonal antibodies derived from an MRL/lpr lupus mouse.

MRL/Mp-lpr/lpr(MRL/lpr) lupus mice develop glomerulonephritis in which the histopathological manifestations of the disease are characterized by diffuse cell-proliferative, crescentic, and/or wire loop-like lesions, resembling those of human lupus nephritis. Although these lesions are thought to be mediated by antibodies, little data is available to explain these regular variations in glomerular lesions induced by antibodies at the monoclonal level. We studied glomerular lesions of normal or severe combined immunodeficient mice injected with nephritogenic immunoglobulin G3-producing hybridoma clones (2B11.3 and 7B6.8), which we previously established from an unmanipulated MRL/lpr mouse. Both clones caused increased serum levels of immunoglobulin G3 with identical patterns over time and both induced glomerular deposits of immunoglobulin G3 and C3. However, 2B11.3 and 7B6.8 induced glomerular lesions that differed in their histopathological manifestations. The 2B11.3 clone generated cell-proliferative lesions associated with marked Mac-2-positive macrophage infiltrates, but the 7B6.8 clone induced lesions characterized by subendothelial hyaline deposits resembling wire loops. The latter was not associated with significant inflammatory cell infiltrates at any point throughout the progression of the lesion. Thus, our findings suggest that the histopathological variation in glomerulonephritis seen in MRL/lpr mice results from clonally expanded B cell clones that produce nephritogenic antibodies with different pathogenic potencies.

Animals↗
PubMed1992

Attempts to induce immune-mediated cerebral arterial injury for an experimental model of moyamoya disease.

To examine the possible role of immune complex-mediated reactions in moyamoya disease, a novel experimental system using a serum sickness vasculitis model combined with intracisternal administration of antibodies or antigens was developed. Twenty-eight male Japanese white rabbits were divided into four experimental groups. Group I was treated twice with intravenous injections of heterologous serum. In group II, intracisternal administration of antibodies or antigens was combined with the second injection of serum. Group III received a single intravenous injection of antigens simultaneously with intracisternal administration of antibodies. Group IV was a technical control group. Cerebral arteritis, although likely in the initial process, was induced only in groups II and III. This study suggests that the cerebral arteries rarely develop arteritis in a serum sickness model alone. The cerebral arteries may require additional intracisternal administration of antibodies or antigens to induce in situ deposition of immune complexes around them.

Animals↗
PubMed1992

Spontaneous development of pancreatitis in the MRL/Mp strain of mice in autoimmune mechanism.

MRL/Mp mice are known to have autoimmune disease-prone genetic background, which contributes to the development of a lethal autoimmune disease at an early age in association with the lymphoproliferative gene, lpr. In this study, we found that MRL/Mp mice, not bearing lpr (MRL/Mp-(+)/+), spontaneously developed pancreatitis at a late stage of life, which was histopathologically characterized by destruction of pancreatic acinar cells with mononuclear cell infiltration. In female 34-38-weeks-old mice the incidence of pancreatitis reached 74%, whereas the male mice developed the disease with a reduced incidence, at a later stage of life and with a reduced severity. Cell infiltrates in the affected lesions were composed predominantly of CD4+ cells and to lesser extent Mac-2+ macrophages. Adoptive transfer of the spleen cells obtained from pancreatitis-bearing female mice generated pancreatitis in female normal mice, but not in the male mice. Transfer of the serum of pancreatitis-bearing mice failed to induce any pancreatic lesions. These findings indicate that pancreatitis in MRL/Mp-(+)/+ mice may be mediated by cellular autoimmune mechanism. This may present a useful concept for analysis of the developmental mechanisms of human chronic pancreatitis in an aspect of autoimmunity.

Animals↗
PubMed1992

An autopsy case of Kawasaki disease with reference to occurrence of acute coronary thrombosis in the convalescent stage.

A one-year, four month-old boy who had suffered from Kawasaki disease died suddenly during convalescence despite intensive gamma-globulin treatment. Autopsy revealed a) sausage-like aneurysms of the left and right coronary arteries and fresh thrombosis in the right coronary aneurysm, b) fresh transmural myocardial necrosis in the whole wall of the left ventricle and the anterior part of the wall of the right ventricle, and c) swelling of the cervical lymph nodes and thymus (60 g). Histologically, fibrocellular thickening of the intima and destruction of the media and internal elastic lamina were conspicuous in the area of the aneurysm, but those of the intima and media in the areas adjacent to the aneurysm were mild. Abrupt narrowing of the lumen at the border between the aneurysm and periphery of the right coronary artery was detected, and this may have been responsible for formation of the thrombus in the right coronary aneurysm. In the systemic arteries, perivascular fibrosis was very noticeable despite less severe injury to the intima and media. These findings suggest that severe inflammation of the periarterial regions was present in the acute phase. The lymph system still showed inflammation, supporting the infectious or toxic nature of Kawasaki disease.

Acute Disease↗
PubMed1992

MRL/MP-lpr/lpr mouse as a model of immune-induced sensorineural hearing loss.

Hearing acuity and inner ear disorders of MRL/lpr mice, bred for the study of autoimmune disease, were examined in comparison to those of BALB/c mice. The auditory brain stem response threshold of 20-week-old MRL/lpr mice was significantly higher than that of BALB/c mice of the same age (p < .01). The pathologic changes of 20-week-old MRL/lpr mice were characterized by the degeneration of intermediate cells, widened intercellular spaces, and immunoglobulin G deposition on the basement membrane of strial blood vessels as well as in the basal infolding of strial marginal cells, which were absent in BALB/c mice. That there were no other evident pathologic findings in the cochlea or middle ear suggests that these changes in the stria vascularis seemed to be responsible for the sensorineural hearing loss of this mouse. The MRL/lpr mouse was thought to be a good experimental model to study the spontaneous sensorineural hearing loss caused by an immune reaction.

Animals↗
PubMed1992

Application of two-color immunofluorescence staining to demonstration of T-cells and HLA-DR-bearing cells in rheumatoid synovitis.

We studied the localization of T-cells and HLA-DR antigen-bearing (DR+) cells in rheumatoid synovitis by employing an improved two-color immunofluorescent staining (TCIF) technique. With this technique we have successfully identified DR+ activated T-cells in the inflammatory synovium. T-cells expressed HLA-DR antigen when they were in contact with DR+ antigen-presenting cells (APC). In addition, activated T-cells showed characteristic distribution within the synovium: they were found around high endothelial venules, within lymphoid follicles, and in hyperplastic synovial lining, suggesting their involvement in the development of rheumatoid synovial lesions via interaction with synovial DR+ APC lineage cells. These findings may contribute to better understanding of the role of activated T-cells in the histogenesis of rheumatoid synovitis, a typical chronic inflammatory lesion.

Arthritis, Rheumatoid↗
PubMed1992

[Histopathological characteristics of rheumatoid arthritis--as a clue to elucidate its pathogenesis].

A correct histopathological diagnosis of Rheumatoid Arthritis (RA) is quite important for the decision of early phase treatment to cure it fundamentally. But, generally speaking, usual hospital pathologist is not so much experienced about RA. The purpose of this article is originally to let such pathologist familiar in RA pathology, but for the RA specialist to offer any clue to elucidate the still-unknown etio-pathogenesis of RA or to cure RA fundamentally. The "Tetralogy of RA Arthritis for pathologist" must be as follows: (1) Enormous proliferation of well-permeable granulation-tissue-type neo-vascularization, some of which became high column-endothelial and the center of primary as well as secondary follicle-like lymphoid cell cluster. (2) Lymphoid cluster in RA synovium is also pathological in function. It consisted of preferentially CD4T and B cells to produce IgG rheumatoid factor endlessly. (3) Synovial lining A and B cells proliferate as far as five layers of each, but later, the sublining D (M) and D (F) cells proliferate more and more and finally replace the lining cells. D (M) cells express macrophage marker and full of lysosome, on the contrary, D (F) cells express mesenchymal marker and contains much metalloproteinase. Both express strong Class II antigens but neither has complement activation inhibitor DAF. (4) Proliferation of these D cells with full of mesenchymal tissue destroying and inflammation accelerating activity must be playing a major role in the joint destruction of RA, some in shape of pannus and more in shape of granulation tissue in and around the bone.

Arthritis, Rheumatoid↗
PubMed1991

IgG3 production in MRL/lpr mice is responsible for development of lupus nephritis.

MRL/Mp-lpr/lpr (MRL/lpr) mice spontaneously develop lethal glomerulonephritis (GN) similar to human lupus nephritis, associated with the expression of lymphoproliferation gene lpr. To examine whether a particular IgG subclass is responsible for development of GN in these mice, first quantitative analysis of IgG subclasses in serum and in kidney eluates was performed. Although IgG2a was the dominant subclass in serum throughout the lifespan of mice, the IgG3 level in kidney eluates was three times higher than that of IgG2a at the 16 wk of age, which is the time of onset of development of severe GN. In sera of the 12-wk-old mice, half of the IgG3 was in immune complex form, whereas IgG2a in this form was only 17% of the total amount. Second, cyclosporin A, which ameliorates GN in MRL/lpr mice despite autoantibody production, was found to reduce serum IgG3 and mRNA levels, associated with the revision of cationic shift of the serum IgG3 spectrotype seen in isoelectric focusing. Third, among the hybrid mice with non-autoimmune-prone C3H/HeJ-lpr/lpr (C3H/lpr) mice, MRL/lpr x (MRL/lpr x C3H/lpr) F1, in which the genetic background for GN is likely segregated, the mRNA level for IgG3 correlated well with the degree of glomerular lesion. These findings indicate that production of IgG3 in MRL/lpr mice is one of the major factors responsible for development of GN in these mice, and that this is due to the genetic background of the MRL strain.

Animals↗
PubMed1991

Expression of decay-accelerating factor is reduced on hyperplastic synovial lining cells in rheumatoid synovitis.

Decay-accelerating factor (DAF), a membrane inhibitor of homologous complement activation, is present in synovial cells lining joint space and detected in synovial fluid. DAF is considered to protect synovial membrane from complement-mediated injury associated with articular inflammation. We studied the immunohistopathological features of DAF molecules in synovial membrane of rheumatoid synovitis using a DAF-specific monoclonal antibody, 1C6. Reacting molecules with the 1C6 antibodies in synovial tissue extracts formed a 70-kD band in Western blot analysis. DAF was strongly detected on the flat synovial lining cells, but weakly on the hyperplastic and multi-layered lining cells in rheumatoid synovitis. The latter cells reacted with anti-Leu-M3 antibodies specific for a cell surface marker of activated macrophages, sometimes accompanied by C3 and IgM deposition on the superficial synovial membrane. These results suggest that active rheumatoid synovitis characteristically with hyperplastic synovial lining cells is out of control by DAF, thereby permitting further complement-mediated injury.

Antibodies, Monoclonal↗
PubMed1991

Pathogenic significance of serum components in the development of autoimmune polyarthritis in MRL/Mp mice bearing the lymphoproliferation gene.

MRL/Mp mice bearing the lymphoproliferation gene (lpr) (MRL/Mp-lpr/lpr) spontaneously develop polyarthritis, associated with autoimmune traits, including rheumatoid factor production, which resembles rheumatoid arthritis. To investigate possible arthritogenic activity of serum of these mice, intraarticular injections of the serum components to knee joints of nonarthritic MRL/Mp mice not bearing the lpr gene (MRL/Mp(-)+/+) were performed. Two fractions from the serum were obtained by a gel chromatography. The void fraction (VF), but not the nonvoid fraction (NVF), induced acute inflammatory lesions in the joints by single injection, and destructive arthritis by repeated injections. VF had immune complex activity, and contained a large amount of cryoglobulin, which in itself was found arthritogenic. These findings indicate that the serum components of MRL/Mp-lpr/lpr mice have a potency to cause destructive arthritis. These results are direct evidence in a syngeneic animal model system, which suggests the pathogenic significance of serum components in rheumatoid arthritis.

Animals↗
PubMed1990

Recombinant Fc of human IgG1 prepared in an Escherichia coli system escapes recognition by macrophages.

The Fc portion of IgG is recognized by macrophages via Fc receptors on their cell surface. The recognition of human IgG1-Fc by macrophages was compared for the native and recombinant proteins by a novel assay method using competitive inhibition of the aggregated IgG-mediated chemiluminescence reaction of human macrophage cell line THP-1. Recombinant Fc proteins, prepared in an Escherichia coli system, which lack oligosaccharides and retain normal staphylococcal protein A reactivity and, to a lesser extent, C1q binding capacity, showed inhibitory ability greater than 500 times lower than that of native Fc fragments obtained by proteolytic digestion of myeloma proteins. This suggests that the oligosaccharide chains on IgG1-Fc molecules may be critical for recognition by Fc receptors on macrophages.

Amino Acid Sequence↗
PubMed1990

Competence growth factors evoke the phenotypic transition of arterial smooth muscle cells.

Vascular smooth muscle cells (V-SMC) alter their functions from contraction to production of extracellular matrices during the response to injury of the arterial wall. Accumulation of these matrices characterize the chronic structural change of arteriosclerosis. In this paper, we reported as follows. (1) V-SMC freshly isolated from human aortic media had strong reactivity with anti-smooth muscle specific alpha-actin (alpha-SM actin) antibody but not with anti-prolyl 4-hydroxylase (ProHy) antibody. (2) The exponentially growing cells in serum-containing culture media reduced alpha-SM actin and induced ProHy distinctly. (3) Growth-arrested cells with serum starvation rearranged numerous alpha-SM actin fibers in their cytoplasm. And the rearrangement of contractile filaments inhibited by the addition of single competence growth factor, such as platelet derived growth factor (PDGF) or basic fibroblast growth factor (bFGF). These results suggest that V-SMC change their phenotype in a competence-factor-dependent manner.

Actins↗
PubMed1990

Stromelysin synthesizing cells in the synovial tissues of rheumatoid arthritis demonstrated by in situ hybridization and immunohistochemical methods.

We identified the cells synthesizing stromelysin to be synovial cells in the synovial tissue from four biopsy cases with rheumatoid arthritis (RA) by in situ hybridization and immunohistochemical studies. In the cases which showed severe inflammation of synovia such as well developed lymphoid follicle and diffuse inflammatory infiltration, synovial cells located only in the superficial layer of synovial tissues showed abundant mRNA and enzymic protein of stromelysin.

Arthritis, Rheumatoid↗
PubMed1990

Tissue distribution of HRF20, a novel factor preventing the membrane attack of homologous complement, and its predominant expression on endothelial cells in vivo.

A 20,000 molecular weight (MW) homologous restriction factor (HRF20), detected by 1F5 monoclonal antibody (mAb), is present on blood cell surfaces and inhibits the terminal stage of the formation of membrane attack complexes by homologous complement activation. The tissue distribution of HRF20 was studied by immunohistochemical analysis using 1F5. HRF20 was predominantly expressed on endothelial cells of systemic arteries, veins and capillaries, as well as on the surface of cultured human umbilical vein endothelial cells. HRF20 was also detected, to a lesser extent, on the Schwann sheath of peripheral nerve fibres, ependymal cells and certain epithelial cells such as acinar cells of the salivary gland, bronchial epithelium, renal tubules and squamous epithelium. The distribution pattern of HRF20 differed somewhat from that of decay-accelerating factor (DAF), which is another membrane inhibitor of homologous complement activation.

Antibodies, Monoclonal↗