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O Tachiwaki

Publications and source records attributed to O Tachiwaki.

10 recordsLinked to original sources

Immune complex-degradation ability of macrophages in MRL/Mp-lpr/lpr lupus mice and its regulation by cytokines.

Impaired clearance of circulating and/or deposited immune complexes (IC) by the mononuclear phagocytic system is one of the major factors in the pathogenesis of IC diseases. MRL/Mp-lpr/lpr (MRL/lpr) lupus mice spontaneously develop a lethal glomerulonephritis associated with IC deposition. The ability of macrophages to degrade phagocytozed IC and regulation of this degradation in MRL/lpr mice were examined. In 4-month-old MRL/lpr mice, macrophages accumulated in the affected glomeruli and these macrophages contained many phagosomes containing electron-dense bodies. When culture supernatant of human T cell line HUT102 was administered intraperitoneally into disease-bearing MRL/lpr mice, degradation of these electron-dense bodies in the macrophages in glomeruli was noted. We developed a quantitative in vitro assay for IC degradation activity of MRL/lpr resident peritoneal macrophages (RPM) using peroxidase-labelled IC derived from MRL/lpr mouse sera. The ability of the RPM to degrade IC was remarkably enhanced by the pretreatment with HUT102 cell products and the related human recombinant cytokines, lymphotoxin and IL-1 alpha. Moreover, pretreatment of RPM from non-diseased MRL/Mp-+/+ mice with the culture supernatant of spleen cells from diseased MRL/lpr mice reduced their IC degradation activity. These results suggested that the ability of macrophages to degrade IC in MRL/Mp strains of mice is under the regulation of cytokines, and the impaired ability in the disease-bearing mice may be the result of abnormalities in the cytokine system in these mice.

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Histologic changes in tissue components of the hyperplastic thyroid gland during its involution in the rat.

Male Fischer rats were fed a low-iodine diet containing thiouracil for 21 days to produce hyperplastic thyroid glands, and then fed a high-iodine diet for various time intervals, from 5 hr to 180 days, in order to study the morphological changes that occur during involution. Thyroids were fixed by perfusion fixation and embedded in Epon. Sections were examined by light microscopy. Initially at 0 days of involution (at the time of the change to the high-iodine diet), follicular lumens were very narrow and capillary lumens were very wide. The capsule was thick and infiltrated with mononuclear leukocytes. No obvious changes occurred for 1 day after the change in diet, but shortly thereafter capillary lumens began to narrow. By 4 days, most capillary lumens were close to normal size; capillaries formed a more or less normal bed except that many were embedded in a relatively thick or wide interfollicular matrix. This matrix was largely gone by 21 days. Between 1 and 21 days, follicular lumens dilated progressively as colloid accumulated. The density of staining of the accumulated colloid varied from follicle to follicle, and this variation was also observed in older controls. Inflammatory cells gradually disappeared from the capsule and most were gone by 15 days. Starting at approximately 15 days and continuing to 180 days, one or more disintegrating cells were found in some lumen profiles. Colloid goiters were not observed in these rats even after several months of involution. Some lumens were rather large, however, and small fractions of the follicles, both small and large, were bounded by flat cells and resembled "cold" follicles morphologically.

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Ultrastructural changes in thyroid epithelium during involution of the hyperplastic thyroid gland.

The ultrastructure of the thyroid epithelial cell was examined at various time intervals after induction of involution of the hyperplastic thyroid gland. Thyroids were made hyperplastic by the feeding of thiouracil in a Remington low-iodine diet to male Fischer rats for 3 weeks. Involution was induced by replacing the thiouracil-containing diet with Purina Laboratory Chow, a high-iodine diet. During involution, organelles that play a role in the synthesis and secretion of thyroglobulin, such as the rough endoplasmic reticulum, Golgi apparatus, and apical vesicles, were well preserved and prominent features of the epithelial cell. The apical plasma membrane of many cells was highly irregular for approximately 2 weeks with signs suggesting rapid discharge of apical-vesical contents into the lumen of the follicle. Pseudopods and colloid droplets were present but were not very prominent features of the cell. No signs of extensive autophagy or obvious increased incidence of lysosomes were present, although there was an elevation in the incidence of small dense bodies starting about day 8, and prominent by 15 days. Some of these may be phagosomes formed from luminal debris. The observations indicate that involution of the hyperplastic thyroid in which there is maintenance of the protein synthetic apparatus and little sign of autophagy or death of the epithelial cells is remarkably different from phenomena occurring during involution of prostate or mammary glands.

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Comparison of a special class of epithelial cells in hyperplastic thyroids undergoing involution and in thyroids in hypophysectomized rats.

In male Fischer rats, a class of follicles with flat epithelium is present as a minor component of thyroid glands in which most of the follicles have cuboidal epithelium. These follicles occur in thyroids that have been made hyperplastic by feeding the rats thiouracil for 21 days and then allowing involution for 21 days or more. They also occur in older control rats. The follicles resemble in morphology, at the light-microscope level, the so-called "cold" follicles that occur in aged mice. We have examined the ultrastructure of the flat cells in these follicles and compared it with that of the flat cells occurring in the thyroid follicles of hypophysectomized rats. The cells in involution have abundant rough endoplasmic reticulum (RER) and few lysosomes and, in these respects, differ markedly from cells in hypophysectomized rats. The follicles with flat cells are surrounded by a normal incidence of blood capillaries, so that the cells do not appear to be deprived of access to an adequate supply of materials necessary to satisfy their metabolic requirements. Their abundant RER suggests that they have thyroid-stimulating hormone (TSH) receptors, so that the flat cell may be the result of some process occurring at a step distal to receptor coupling with TSH. Their occurrence in young rats after the induction of hyperplasia may be a consequence of cell multiplication producing a clone of neighboring abnormal cells that have an abnormally small cell height.

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Pancreatic islet cell surface glycoproteins containing Gal beta 1-4GlcNAc-R identified by a cytotoxic monoclonal autoantibody.

To investigate the autoimmune pathogenesis of spontaneously occurring diabetes mellitus in BB rats, spleen cells of newly diagnosed diabetic BB rats were fused with mouse myeloma cells. Hybridoma supernatants were screened for antibodies by indirect immunofluorescence and by 51Cr-release assays using the RINm5F rat insulinoma cell line. One clone, E5C2, produced an IgM kappa antibody that was cytotoxic for RINm5F cells, but not for other rat cell lines nor for primary rat islet cells. However, treatment of primary rat islet cells with neuraminidase exposed surface antigens and rendered the cells susceptible to complement-mediated lysis by antibody E5C2. Using immunostaining of glycolipids separated by thin-layer chromatography, hapten inhibition assays with defined carbohydrates, and Western blots, the antigens recognized by E5C2 on RINm5F cells were identified as glycoproteins with molecular weights of 60,000 and 68,000. The antibody recognizes a carbohydrate antigen containing the sequence Gal beta 1-4GlcNAc-R, which on RINm5F cells is predominantly hidden by covalently bound sialic acid. These studies raise the possibility that hidden antigenic determinants on islet cells exposed by a variety of means may be the target of autoimmune attack.

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Immunopathology of murine lupus-overview, SL/Ni and MRL/Mp-lpr/lpr-.

Murine lupus is a useful animal model for the study of disease based on some defect in the immune system including the so-called collagen diseases. Seven strains are available in Japan; NZB, NZB/WF1, MRL/Mp-lpr/lpr, BxSB, SL/Ni, NC and C3H/HeJ-gld/gld. Characteristics of these strains of mice are outlined. Care should be taken about applying the knowledge or information obtained from animal models to the analysis of related human disease because there are various genetic or species barriers which cannot be overcome. Therefore, it is rather dangerous to conclude that the pathogenesis of some human disease is similar to that of an animal model from a study of the latter. Therefore, one should divide the data obtained from animal experiments into "factors" and insert each factor in the "formula" of a human disease in order to better understand it. Recent studies by the authors on two strains of lupus mouse; SL/Ni and MRL/Mp-lpr/lpr from such a standpoint are presented and discussed in detail.

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Honeycomb structure of the apical surface of thyroid epithelium during involution of the hyperplastic thyroid gland.

A heretofore undescribed feature consisting of closely packed pits 0.5-1 micron in diameter was observed on the apical surface of thyroid epithelial cells. The walls of the pits were generally smooth, except at the base where there was a high incidence of irregularities looking like sites of recent fusion of apical vesicles with the pits. The matrix of the partition between pits was similar to the matrix of pseudopods in these cells in being free of membrane-bounded organelles and containing a low concentration of ribosomes. The pits were observed early in the involution of the hyperplastic gland, most prominently between 14 h and 8 days of involution. This is a time when thyroglobulin is accumulating in follicular lumens and the apical end of the epithelial cells usually contains a high concentration of apical vesicles ordinarily considered to be exocytic in character. It is important to recognize the existence of this feature to avoid confusing profiles of it with structures involved in macropinocytosis.

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Shedding of dense cell fragments into the follicular lumen early in involution of the hyperplastic thyroid gland.

Membrane-bounded fragments of thyroid epithelial cells are found in the lumen of the thyroid follicle at early stages of involution of the hyperplastic gland. To demonstrate this, thyroid glands were made hyperplastic by feeding rats a low iodine diet containing thiouracil for 3 weeks. Involution was induced by the feeding of a high iodine diet. Three types of dense cell fragments were observed in the lumen at its periphery within 5 hours after the change of diet: (1) single, relatively large fragments that contained vesicles occasionally, (2) a cluster of rounded fragments of relatively small size. Some of these had a narrow tail, and (3) elongated narrow fragments in a row parallel to the apical surface of one or more epithelial cells. The fragments are probably derived from the thyroid epithelial cells since no other cell types were generally present. By 14 hours the fragments were distributed randomly throughout the lumen. Fragments were no longer present by 12 days of involution in most follicles. Fragment formation may be a mechanism for disposal of excess plasma membrane deposited by exocytic vesicles during rapid secretion of thyroglobulin into the follicular lumen early in involution.

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