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Biomedical subjects

M Kyogoku

Publications and source records attributed to M Kyogoku.

At least 19 recordsLinked to original sources
PubMed1995

A human keratinocyte cell line produces two autocrine growth inhibitors, transforming growth factor-beta and insulin-like growth factor binding protein-6, in a calcium- and cell density-dependent manner.

Two growth inhibitors were identified in culture medium conditioned by a human keratinocyte cell line, HaCat. TGF-beta was detected in media conditioned by growing or confluent HaCat cells, as well as in media conditioned at physiological (1 mM) or low (0.03 mM) Ca2+ concentrations. However, a considerable part of transforming growth factor beta (TGF-beta) in media conditioned at a physiological Ca2+ concentration was in active form, whereas most TGF-beta in media conditioned at a low Ca2+ concentration was latent. The other growth-inhibitory activity, which was detected only in media conditioned by confluent cells at a physiological Ca2+ concentration, was purified to homogeneity by a four-step procedure. The N-terminal amino acid sequence of the 33-kDa protein was identical with that of insulin-like growth factor binding protein-6 (IGFBP-6). Purified IGFBP-6 inhibited the growth of HaCat and Balb/MK keratinocyte cell lines, as well as Mv1Lu cells. The growth activity was also demonstrated by human recombinant IGFBP-6. In summary, HaCat cells secrete at least two possible autocrine growth inhibitors: TGF-beta which is secreted constitutively, but activated in a Ca(2+)-dependent manner, and IGFBP-6 which is secreted in a cell density- and Ca(2+)-dependent manner.

Amino Acid Sequence↗
PubMed1995

Sequence analysis of the germ-line VH gene corresponding to a nephritogenic antibody in MRL/lpr lupus mice.

In order to investigate the genetic origin of nephritogenic antibodies in MRL/Mp-lpr/lpr (MRL/lpr) lupus mice, we isolated the germ-line heavy chain variable region (VH) gene corresponding to the nephritogenic antibody, B1, derived from an unmanipulated MRL/lpr mouse. Injection of this antibody into C.B-17/Icr-scid/scid mice resulted in the generation of wire loop-like glomerular lesions resembling those of lupus nephritis. Nucleotide sequences of this germ-line VH gene showed no replacement mutation in the VH region of the B1 antibody. Furthermore, this gene was identical to that found in the C3H/HeJ-lpr/lpr strain of mice. Our results suggest that germ-line VH genes can encode nephritogenic antibodies without somatic mutation, even in a mouse strain not prone to lupus.

Animals↗
PubMed1995

Establishment of a new human cell line, LI90, exhibiting characteristics of hepatic Ito (fat-storing) cells.

BACKGROUND: Thus far, human hepatic Ito (fat-storing) cell lines have not been established. Therefore, functional characteristics of Ito cells have not been fully investigated. EXPERIMENTAL DESIGN: We established a new cell line, LI90, that exhibited characteristics compatible with those of Ito cells from a human hepatic mesenchymal tumor. LI90 cells were examined with phase-contrast microscopy, immunohistochemistry, and cytogenetics, and their vitamin A-storing activity was analyzed. To obtain a marker specific for Ito cells for immunohistochemical analyses, we raised mAb against LI90 cells and clarified the molecular nature of the Ag recognized with the new Ab using an expression cloning approach. RESULTS: LI90 cells showed polygonal shape and had well developed alpha-smooth muscle actin filaments in their cytoplasm. In an overconfluent culture condition, LI90 cells aggregated to form a typical hills-and-valleys structure, LI90 cells produced various connective tissue components, such as collagen types I, III, IV, V, and VI, laminin, and fibronectin. In culture media containing vitamin A, LI90 cells formed many fat droplets in their cytoplasm, and fluorescence characteristic of vitamin A was observed in the droplets. By immunizing mice with LI90 cells, three separate mAb specifically reacting with Ito cells in human liver sections were established, and the Ag recognized with all three Ab were identified as extracellular matrix tenascin. CONCLUSIONS: The above-described morphologic and functional characteristics, including vitamin A-storage and biosynthesis of tenascin, are compatible with those of Ito cells. Therefore, LI90 cells will be useful for in vitro studies of functions of human Ito cells.

Antibodies, Monoclonal↗
PubMed1994

Immunopathological features of palatine tonsil characteristic of IgA nephropathy: IgA1 localization in follicular dendritic cells.

IgA nephropathy (IgAN) is generally thought to be mediated by the glomerular deposition of circulating immune complexes containing IgA as the major antibody component. Upper respiratory infections and tonsillitis often precede IgAN, and in some cases tonsillectomy is effective for the treatment of IgAN. Thus, the tonsil seems to be a unique organ causing initial and/or progressive events to generate nephritogenic immune complexes in IgAN. In this study we focused on the analysis of immunopathological features of the palatine tonsil characteristic of IgAN patients by using an immunohistochemical technique. The IgA1 subclass was demonstrated in follicular dendritic cells (FDC) of the tonsil of IgAN patients, but not in FDC of non-IgAN controls. On the other hand, IgA2, IgG, IgM and C3 did not show any differences in distribution between the two groups. Moreover, the expression of decay-accelerating factor (DAF), an inhibitor of homologous complement activation, and transforming growth factor-beta 1 (TGF-beta 1), an inducer of antibody-producing cells to IgA class switching, in FDC and interdigitating dendritic cells of the tonsil, respectively, which was also clarified in this study for the first time, was found to be identically distributed in the two groups. These findings may support the idea that IgA1, possibly in an immune complex form, is trapped by FDC and plays an important role in the persistent activation of particular B cell repertoires responsible for the onset and/or progression of IgAN.

Adolescent↗
PubMed1994

Nephritogenic antibodies in MRL/lpr lupus mice: molecular characteristics in pathological and genetic aspects.

MRL/lpr mice spontaneously develop a lethal glomerulonephritis (GN). We found that IgG3 production in this strain of mice has a critical role on the development of GN; 1) IgG3 levels were high in kidney-extracted IgG and in circulating IgG immune complexes (IC), 2) serum IgG3 was selectively reduced by cyclosporin A treatment, associated with amelioration of GN, and 3) the mRNA levels of IgG3 correlated well with the severity of GN among the MRL/lpr x (MRL/lpr x C3H/lpr) F1 backcross mice with the rearranged genetic profile. Based on these results, we have successfully established five hybridoma clones which produce nephritogenic IgG3 antibodies from an unmanipulated MRL/lpr mouse. When they were injected to normal mice, four of the five clones generated cell-proliferative GN associated with the marked cellular infiltrates, while the remaining clone induced wire loop-like lesions. This result suggests that particular antibodies generated in MRL/lpr mice have a different pathogenic potency. The V-region sequence study of these nephritogenic antibodies revealed that the two types of the glomerular lesions were mediated by a different B cell precursor. In conclusion, GN in MRL/lpr lupus mice is thought to be generated by the expansion of clonally different B cells producing nephritogenic antibodies with a different pathogenic potency.

Amino Acid Sequence↗
PubMed1994

[Inflammatory abdominal aortic aneurysm].

Inflammatory abdominal aortic aneurysm (IAAA) is a distinct clinicopathological entity, characterized by: (1) clinical presentation, such as back pain, weight loss, and increased ESR, (2) patchy and/or diffuse lymphoplasmacytic infiltration, and (3) marked periaortic fibrosis resulting in thickening of the aneurysmal wall and occasional retroperitoneal fibrosis. Its pathogenesis is unknown, but some authors support the theory that IAAA is a subtype of atherosclerotic abdominal aortic aneurysm because of close relationship between IAAA and atherosclerotic change. In this article, we describe clinical and histological features of IAAA on the basis of the literature and our review of 6 cases of IAAA, emphasizing the similarity and difference between IAAA and atherosclerotic abdominal aortic aneurysm. Our review supports that marked lamellar fibrosis completely replacing the media and adventitia, patchy lymphocytic infiltration (mostly B cells) and endarteritis obliterans are characteristic features of IAAA.

Aorta, Abdominal↗
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↗