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Biomedical subjects

K Fujiwara

Publications and source records attributed to K Fujiwara.

At least 19 recordsLinked to original sources
PubMed1995

Increase in cystine transport activity and glutathione level in mouse peritoneal macrophages exposed to oxidized low-density lipoprotein.

The transport of cystine has been investigated in mouse peritoneal macrophages incubated with oxidized low-density lipoprotein (oxi-LDL; low-density lipoprotein, LDL). The transport activity for cystine was potently induced by oxi-LDL but not by native or acetylated LDL. The response of the cells to oxi-LDL was dependent on the extent of oxidative modification of LDL. The transport activity for other amino acids was not induced by oxi-LDL. GSH content increased in macrophages incubated with oxi-LDL and this increase was accounted for by the induction of the cystine transport activity because the increase was completely blocked by glutamate or homocysteate which shared the transport system for cystine and thus inhibited the uptake of cystine competitively.

Animals↗
PubMed1995

ICAM-1 expression in hepatocytes following dissociation of cell-to-cell contact in rats.

ICAM-1 was not detected immunohistologically in hepatocytes in normal rats, but detectable in centrilobular degenerative hepatocytes in carbon tetrachloride-intoxicated rats. ICAM-1 expression was observed even in normal hepatocytes following liver perfusion with Hank's balanced salt solution at a flow rate of 4.2 mL/g liver weight/min or with the same solution containing collagenase or EGTA at the physiological flow rate (1.4 mL/g liver weight/min). Such expression was also observed when liver perfusion was performed after pretreatment of rats with cycloheximide. On electron microscopy, ICAM-1 was exclusively stained on hepatocyte plasma membrane that was detached from the plasma membrane of adjacent hepatocytes. ICAM-1 mRNA and ICAM-1 protein were detected in hepatocytes freshly isolated from normal rats. Thus, ICAM-1 expression in degenerative hepatocytes as well as in hepatocytes following liver perfusion can be assumed to result from dissociation of cell-to-cell contact.

Animals↗
PubMed1995

Fluid flow and osmotic stress induce tyrosine phosphorylation of an endothelial cell 128 kDa surface glycoprotein.

To investigate the flow sensing and the early signaling events in vascular endothelial cells (ECs), we surveyed changes in phosphotyrosine levels of glycoproteins using immunoblot analyses. Cultured bovine arterial ECs were exposed to steady laminar flow by using a coneplate type flow apparatus and glycoprotein fractions were partially purified by lectin affinity column chromatography. A 128 kDa protein band in the Ricinus-communis-agglutinin-bound fraction showed a rapid and consistent augmentation of tyrosine phosphorylation by flow. Cell surface domain-restricted biotinylation revealed that the 128 kDa glycoprotein has extracellular domain(s). Tyrosine phosphorylation of the 128 kDa protein was also observed in ECs subjected to hyper- or hypo-osmotic shock but not in ECs stimulated by Ca2+ mobilizing agents.

Animals↗
PubMed1995

Induction of cystine transport activity in mouse peritoneal macrophages by bacterial lipopolysaccharide.

The transport of cystine has been investigated in mouse peritoneal macrophages cultured in vitro. The transport activity for cystine was very low in freshly isolated macrophages but was potently induced during culture in the presence of bacterial lipopolysaccharide (LPS) at concentrations as low as 0.1 ng/ml. The transport activity for cystine was enhanced when the cells were incubated with tumour necrosis factor-alpha (TNF-alpha), but not with interferon-gamma (IFN-gamma) or interleukin-1. IFN-gamma was rather repressive in the induction of the activity by LPS or TNF-alpha. The transport activity for cystine induced by LPS has been characterized. Cystine was transported mainly by Na(+)-independent system and the uptake of cystine was inhibited by extracellular glutamate and homocysteate, but not by aspartate, indicating that the transport of cystine in macrophages treated with LPS is mediated by System xc-. Glutathione content of the macrophages increased when they were exposed to LPS, and this increase was, at least in part, attributable to the induced activity of the cystine transport.

Amino Acids↗
PubMed1995

Natural course of cervical spine lesions in rheumatoid arthritis.

STUDY DESIGN: This study analyzed the natural course of cervical spine involvement in rheumatoid arthritis by serial radiographs. OBJECTIVES: The purpose was to determine the pattern of progression of cervical spine lesions in rheumatoid arthritis and predictors for the extent of progression. SUMMARY OF BACKGROUND DATA: Subluxation frequently occurs as a result of rheumatoid involvement of the cervical spine. It may be severe in patients with mutilans deformities in the hands and feet. The extent of progression in a given patient is still unpredictable. METHODS: Serial cervical radiographs in 49 patients with rheumatoid arthritis were analyzed. The extent of progression was evaluated by rheumatoid arthritis subset defined previously, which reflected the final extent of joint erosion in this systemic disease and could be roughly classified during early stages of the disease. RESULTS: In the upper cervical spine, reducible anterior atlantoaxial subluxation occurred first. Vertical subluxation of the axis appeared next. Irreducible change of preceding anterior atlantoaxial subluxation was a sign of the start of vertical subluxation. In subaxial lesion, subluxation occurred less frequently (22.4%) than upper cervical lesion (77.6%). The extent of progression was different with the rheumatoid arthritis subset. In the upper cervical spine, none of the subset with least erosive disease developed vertical subluxation, whereas 52% of the subset with more erosive disease and 88% of the subset with mutilating disease advanced to vertical subluxation. The extent of progression was well correlated with the number of joints with erosion. Subaxial subluxation was often seen and became irreducible in mutilating disease and more erosive disease, but not in least erosive disease. CONCLUSIONS: A progressive pattern of the upper cervical subluxations was clarified. That is, upper cervical lesions progressed from reducible anterior atlantoaxial subluxation to irreducible anterior atlantoaxial subluxation with vertical subluxation. This extent of progression was different with the rheumatoid arthritis subset, which was also related to the development of subaxial subluxation. The most aggressive arthritis classification, a subset with mutilating disease, had the more severe subluxation in both upper and subaxial cervical spine.

Adolescent↗
PubMed1995

Functional chicken gizzard heavy meromyosin expression in and purification from baculovirus-infected insect cells.

The heavy chain and the essential and the regulatory light chains of chicken gizzard heavy meromyosin (HMM) were coexpressed in Spodoptera frugiperda (fall armyworm) cells infected with a mixture of two recombinant Autographa californica baculoviruses. Soluble HMM consisting of the heavy chain and the two types of light chains was obtained. The recombinant HMM was purified from the virus-infected cells and characterized. The regulatory light chain of the isolated recombinant HMM was phosphorylated by myosin light chain kinase in the presence of calmodulin in a Ca(2+)-dependent manner. The ATPase of the recombinant HMM was activated by rabbit skeletal muscle actin when myosin light chain kinase, calmodulin, and Ca2+ were present in the reaction medium. Chicken gizzard tropomyosin enhanced the actin-activated ATPase activity. The recombinant HMM decorated actin filaments, displaying the characteristic arrowhead pattern along the filaments. This report on a functional recombinant double-headed smooth muscle myosin fragment opens the way to detailed studies on the molecule.

Actins↗
PubMed1995

Focal adhesion proteins associated with apical stress fibers of human fibroblasts.

Human fibroblasts stained with fluorescently labeled phalloidin revealed many stress fibers within the apical cytoplasm in addition to those located along the basal plasma membrane and associated with focal adhesions. The staining patterns of these apical stress fibers with fluorescent phalloidin, anti-alpha-actinin, and antimyosin were identical to those of the basal stress fibers, suggesting the same macromolecular organization for both types of stress fibers. There were two types of apical stress fibers that clearly interacted with the apical plasma membrane, those extending between the basal and the apical plasma membrane and those having both ends on the basal membrane forming arches whose top interacted with the apical plasma membrane. By electron microscopy, we observed that apical stress fibers were associated with the apical plasma membrane via electron-dense plaques reminiscent of the focal adhesion. Since several proteins have been specifically localized to the focal adhesion site, we examined whether they were also present at the apical stress fiber-membrane association site by using immunocytochemical methods and image reconstruction techniques. We found that vinculin, talin, paxillin, a fibronectin receptor protein, several integrin subunits including beta 1, fibronectin, and proteins with phosphorylated tyrosine were also components of the apical plaque. These observations indicate that apical stress fibers are attached to the plasma membrane by using principally the same molecular assembly as the focal adhesion associated with the basal stress fiber. We suggest that the complex molecular organization of the focal adhesion is not demanded by cell adhesion, but rather it is needed for anchoring stress fibers to the plasma membrane. Apical plaques did not stain with the anti-integrin alpha v subunit or anti-focal adhesion associated kinase (FAK), although these antibodies stained focal adhesions. These results suggest that the apical stress fiber-membrane contact has some important functions different from those of the focal adhesion.

Antibody Specificity↗
PubMed1995

Mononuclear cell thyroiditis in rats with graft-versus-host disease.

Rats with graft-versus-host disease (GVHD), induced by injecting spleen cells of parental strain rats (Brown Norway) into non-irradiated (Brown Norway x Lewis) F1 hybrid rats, develop thyroiditis. This is characterized by mononuclear cell infiltration with destruction of the epithelium and a significant reduction in serum thyroid hormone levels. Immunohistochemically, the mononuclear cells consisted mainly of CD8-positive cells and macrophages. These findings provide evidence that the thyroid gland can now be enumerated as one of the target organs during GVHD. The CD8-positive cells may serve as important effector cells in lesion development, either by direct cytotoxicity or by supporting the cytotoxic potential of macrophages.

Animals↗
PubMed1995

Mature cystic teratomas of the ovary with intestinal wall structures harboring intestinal- type epithelial neoplasms.

Mature cystic teratomas of the ovary frequently contain intestinal-type tissues, but these rarely organize into complete intestinal walls, including all layers, and even more rarely develop secondary neoplasms. The present report documents two mature teratomas with formation of complete segments of intestinal wall, one also containing a benign mucinous cystadenoma of the appendiceal type and the other an intestinal-type adenocarcinoma infiltrating into the neoplastic bowel wall but not the surrounding ovarian parenchyma. The latter patient is alive and well 5 years after surgery. These cases expand the repertoire of secondary neoplasms, benign and malignant, developing in mature cystic teratomas.

Adenocarcinoma↗
PubMed1995

Clinical implications of metastases to the ovary.

Predictive factors for ovarian metastases were analyzed in 313 autopsy cases of women dying of malignancy. Genital, hematopoietic, brain tumors, and double primaries were excluded. Ovarian metastases were found in 60 of 313 (19.2%) cases. The primary sites of origin were stomach (18 cases), breast (13), pancreas (7), bile duct (7), large intestine (4), kidney (3), liver (2), lung (1), and other (5). The percentages of ovarian metastasis in each primary site were 50% (3/6) in the kidney, 38.3% (18/47) in the stomach, 30.8% (4/13) in the large intestine, 22.9% (13/57) in the breast, 22.6% (7/31) in the bile duct, 19.4% (7/36) in the pancreas, 5.4% (2/37) in the liver, and 3.4% (1/29) in the lung. Seventy-five percent (75%) of ovaries with metastasis were 5 cm or less in the greatest dimension. Seventy-eight percent (78%) of ovarian metastases were bilateral. Fifty-one percent (51%) of the involved ovaries were cystic. Twenty-four percent (24%) of the metastasis were occult in which microscopic disease was present in normal appearing ovaries. The mean age of death in the cases with ovarian metastasis was 53.8 +/- 16.8 years. This was significantly younger than the mean age without ovarian metastasis that mainly was attributable to the younger ages for breast and bile duct cancer. The number of other extraovarian metastatic sites for positive ovarian cases was significantly greater than for the negative ovarian cases (7.6 +/- 2.4 and 5.8 +/- 2.5, respectively). This difference was dominant in gastric and bile duct cancers. The other metastatic sites that accompanied ovarian metastases were the adrenal gland in gastric cancer, the spleen and small intestine in breast cancer, and the adrenal gland and colon in bile duct cancer. The frequency of peritoneal dissemination was essentially the same between cases with positive and negative ovarian metastasis. Scirrhous adenocarcinoma of the stomach more commonly metastasized to the ovary than any other stomach histological type. These findings suggest that although the impact upon outcome of bilateral salpingo-ophorectomy at the initial operation is unknown, the discovery of ovarian metastases in a large proportion of patients may dramatically alter initial management in patients otherwise thought to have only local disease.

Adolescent↗
PubMed1995

Use of prostaglandin I2 analog in treatment of massive hepatic necrosis associated with endothelial cell injury and diffuse sinusoidal fibrin deposition.

Endothelial cell damage causes massive hepatic necrosis as a result of fibrin deposition in the hepatic sinusoids. When a stable analog of prostaglandin I2, beraprost sodium, was administered to rats given either dimethylnitrosamine, carbon tetrachloride, or endotoxin following Corynebacterium parvum administration, the hepatic necrosis produced in each was attenuated, but to a greater extent in the dimethylnitrosamine and endotoxin/Corynebacterium parvum models, where fibrin deposition in the hepatic sinusoids occurs, as compared to the carbon tetrachloride model, where such fibrin deposition does not occur. Beraprost sodium reduced the expected increase of portal venous pressure in the endotoxin/Corynebacterium parvum model without affecting plasma thrombin-antithrombin III complex levels. Beraprost sodium also significantly reduced cell killing of both isolated rat hepatocytes and hepatic sinusoidal endothelial cells exposed to tert-butyl hydroperoxide when compared to controls. Beraprost sodium could prove to be a therapeutic candidate for the treatment of hepatic necrosis, particularly in cases associated with fibrin deposition in the hepatic sinusoids because of its fibrin clot-clearing action.

Animals↗
PubMed1995

Lipidosis of the dorsal root ganglia in rats treated with an almitrine metabolite.

Toxic effects of a detriazinyl metabolite of almitrine (DTMA) were evaluated in rats and on cultured rat macrophages. In rats daily treated with DTMA for 16 weeks, spastic gaits with heel-lifting appeared, and lamellated and/or crystalloid bodies formed in sensory neurons, satellite cells, Schwann cells, and vascular endothelial cells of the dorsal root ganglia. The lysosomal lamellated bodies, which were not induced by almitrine, were produced also in cultured rat macrophages exposed to over 1 x 10(-5) M DTMA.

Administration, Oral↗
PubMed1995

Regulation of hepatic macrophage function by oral administration of xiao-chai-hu-tang (sho-saiko-to, TJ-9) in rats.

The effect of Xiao-Chai-Hu-Tang (Sho-saiko-to, TJ-9), the extract of a mixture of 7 herbs, on hepatic macrophage function was studied using rats. Hepatic macrophages were activated by injection of Corynebacterium parvum or 70% partial hepatectomy. Oral administration of TJ-9 for 3 weeks did not affect the ability of these macrophages to produce superoxide anions evaluated in situ by liver perfusion with nitro blue tetrazolium (NBT) and phorbol myristate acetate (PMA). However, the similar administration of TJ-9 attenuated the blocking of the activation after partial hepatectomy produced by pretreatment with gum arabic, a polysaccharide of high molecular weight. When gum arabic was added to the medium of rat hepatic macrophages cultured with normal rat sera, their ability to produce superoxide anions was reduced in a dose-related manner. This reduction was attenuated by changing the sera to the sera obtained from rats given oral doses of TJ-9 for 3 weeks. These results suggest that TJ-9 may improve the blocked function of hepatic macrophages in activation.

Administration, Oral↗
PubMed1995

Involvement of pituitary hormone in the sex-related regulation of hepatic epoxide hydrolase activity in mice.

The involvement of the pituitary gland in the expression of sex-related differences in the activities of epoxide hydrolase (EH) in liver was examined in hypophysectomized and neonatally monosodium L-glutamate (MSG)-treated male and female mice. In hypophysectomized mice, the hepatic microsomal EH activity of males and females increased considerably above those of the respective sham-operated controls, and the female activity exceeded that of the sham-operated males. The hypophysectomy caused a decrease in soluble EH activity in males, while the operation led to an elevation of the activity in females. Neonatal treatment with MSG resulted in marked increases of microsomal EH activity in males and females at adulthood and the activity was about 2 times that of the male control mice. Treatment of hypophysectomized males and females with growth hormone (GH) resulted in a significant decrease in microsomal EH activity below those of the corresponding hypophysectomized controls, while the hormone treatment had no effect on the soluble enzyme activities. These results suggest that murine hepatic microsomal EH activity is principally under the suppressive control of the pituitary and GH is a causal hormone involved in the expression of sexual dimorphism in the enzyme activity.

Animals↗
PubMed1995

[Brain deformation caused by hyperplasia molar teeth (macrodonts) in the Japanese field vole (Microtus montebelli)].

Protrusion of hyperplastic upper molar teeth (macrodonts) into the cranial cavity was observed in the Japanese field vole. Protrusions of the upper molars occurred on both sides, but were large on the left than on the right. The teeth invaded the cranial cavity and brain parenchyma. Large concavities on the ventral side of the brain were interposed between the lateral olfactory tract and the optic tract. Invation by one macrodont reached the basal nuclei, hypothalamic and thalamic nuclei. The brain was deformed bilaterally, and nearly the entire olfactory bulb, globus pallidus, internal capsule, and lateral preoptic nucleus, and a portion of the hypothalamus, thalamus and anterior commissure were absent on the left side.

Animals↗
PubMed1995

Cyclosporin A and FK-506 in inhibition of rat Ito cell activation in vitro.

Ito cells are the primary matrix-producing cells in the liver. In hepatic fibrosis in vivo or culture on plastic, these cells undergo activation, a process characterized by cell proliferation, fibrogenesis, and smooth muscle alpha-actin expression. The cytosolic-binding proteins of cyclosporin A (CsA) and FK506 accelerate folding of various proteins including collagen and become inactivated by binding to those agents. CsA is shown to inhibit collagen synthesis in cultured fibroblasts. These findings prompted us to examine the effect of cyclosporin A and FK506 on Ito cell activation. CsA and FK506 reduced DNA synthesis in a dose-related manner, to 26% and 45% of controls at 5 mumol/L, respectively, without affecting total protein synthesis. CsA reduced collagen synthesis in a dose-related manner, to 70% of controls at 5 mumol/L without affecting noncollagenous protein synthesis, whereas FK506 changed neither collagen synthesis nor noncollagenous protein synthesis. Moreover, smooth muscle alpha-actin expression was reduced by 0.5 mumol/L CsA, but not by FK506. CsA merits consideration for the therapy of hepatic fibrosis. FK506 may also be a candidate for such therapy through inhibitory action on Ito cell proliferation.

Actins↗
PubMed1995

Junctional proteins of keratinocytes in Grover's disease, Hailey-Hailey's disease and Darier's disease.

Alterations of junctional structures in non-immune mediated acantholytic diseases (Grover's, Hailey-Hailey's and Darier's diseases) were examined using monoclonal antibodies against desmosomal attachment constituents (desmoplakin I & II and plakoglobin), desmosomal intercellular cement glycoprotein (desmoglein), protein of adherens junction (vinculin), and protein of gap junction (43Kd connexin). Universal cell surface (transmembrane) glycoprotein CD44 was also studied. In acantholytic foci of these diseases, attachment plaque proteins had dissolved and diffused into the acantholytic cells. The normal dotted linear pattern of immunostaining on the cell membrane was totally lost. In contrast, CD44 was well preserved on the cell membranes of acantholytic cells. Adherens junction and gap junction proteins were mostly preserved. Acantholytic cells of pemphigus vulgaris were similarly studied. In these cells, desmosomal attachment plaque proteins were very well preserved, while intercellular cement substance (desmoglein), adherens junctional proteins (vinculin), and gap junction protein (connexin) were totally absent, either on the cell membrane or in the cytoplasm. Electron microscopy confirmed an early dissolution of attachment plaque. Internalized desmosomal structures were seldom found in acantholytic cells of non-immune diseases. It was concluded that the primary event in acantholysis in these three diseases is the dissolution of desmosomal attachment plaque.

Acantholysis↗