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Biomedical subjects

K Eguchi

Publications and source records attributed to K Eguchi.

At least 217 records · Page 12Linked to original sources
PubMed1998

CD4+ T-cell-mediated cytotoxicity against staphylococcal enterotoxin B-pulsed synovial cells.

Apoptosis of synovial cells in rheumatoid arthritis (RA) synovium determined in vivo is suggested to counteract the overgrowth of synovium. Immunohistological examination has revealed the infiltration of activated CD4+ T cells, which express Fas ligand (FasL), in RA synovium. The presence of a putative antigen (Ag) of autoimmune disorders in a target organ may induce the activation of specific T cells in the inflammatory region such as RA synovium. We examined the possible role of CD4+ T cells activated by synovial cells in a staphylococcal enterotoxin B (SEB)-dependent manner, inducing synovial cell apoptosis. Synovial cells were cultured with or without interferon-gamma (IFN-gamma) and further incubated with CD4+ T cells in the presence of SEB. After the cocultivation, both the cytotoxicity and FasL expression of CD4+ T cells were investigated. Constitutive Fas expression was detected on both unstimulated and IFN-gamma-stimulated synovial cells. CD4+ T cells did not kill SEB-pulsed unstimulated synovial cells efficiently. In contrast, when CD4+ T cells were incubated with IFN-gamma-stimulated synovial cells with SEB whose human leucocyte antigen (HLA)-DR and -DQ expression was markedly induced, significant cytotoxicity by these cells against synovial cells was detected. The addition of anti-HLA-DR and -DQ monoclonal antibodies (mAbs) or human Fas chimeric protein (hFas-Fc) reduced this cytotoxicity. FasL expression of CD4+ T cells cocultured with IFN-gamma-stimulated synovial cells with SEB was significantly induced. Furthermore, the addition of mAbs against CD54, CD58 and CD106 inhibited both the cytotoxicity and FasL expression of CD4+ T cells induced by IFN-gamma-stimulated synovial cells in the presence of SEB, indicating the importance of costimulatory molecules on synovial cells in activating CD4+ T cells. Our results suggest that CD4+ T cells are activated by synovial cells by an SEB-dependent manner and express FasL, inducing Fas-mediated apoptosis of the latter cells. These phenomena may regulate the overgrowth of synovial cells in RA synovium.

Antibodies, Monoclonal↗
PubMed1998

Low copy numbers of human T-cell lymphotropic virus type I (HTLV-I) tax-like DNA detected in the salivary gland of seronegative patients with Sjögren's syndrome in an HTLV-I endemic area.

To evaluate the hypothesis, proposed in previous reports from HTLV-I non-endemic areas, that HTLV-I is involved in a significant proportion, about a quarter, of Sjögren's syndrome patients who lack serum antibodies to the virus, we examined for the presence or absence of HTLV-I in DNA samples isolated from salivary gland tissues of 17 seronegative as well as 7 seropositive patients with Sjögren's syndrome in Nagasaki, Japan, where the virus is highly endemic. The nested two-step polymerase chain reaction (PCR), with a sensitivity capable of detecting a single DNA molecule, failed to amplify the HTLV-I tax sequence from DNA of 14 of the 17 seronegative patients. The tax was only amplifiable from the tissue DNA of the remaining three seronegative patients. The detection rate, 3/17 (18%), was, unexpectedly, less than those previously reported from the HTLV-I non-endemic areas. Moreover, in contrast to high viral loads (10(-1) to 10(-3) per cell) in the salivary gland of the seropositive patients, a semiquantitative PCR revealed that the copy number of the HTLV-I tax in the gland tissue of these seronegative patients was very low, 10(-5) per cell. This level is unlikely to be sufficient to promote an inflammatory reaction in the tissue. Our findings might argue against the involvement of "prototype" HTLV-I in the pathogenesis of Sjögren's syndrome in seronegative patients.

Adult↗
PubMed1998

Removal of low-density lipoprotein from plasma by adsorption increases bradykinin and plasma nitric oxide levels in patients with peripheral atherosclerosis.

Low-density lipoprotein (LDL) adsorption using a dextran sulfate cellulose column is brought about by electrostatic binding between the positive charges of apolipoprotein B in LDL and the negative charges of dextran sulfate cellulose. There is general agreement that the initial contact phase in the coagulation pathway may be activated by a negatively charged surface such as dextran sulfate cellulose, resulting in the generation of bradykinin. We investigated whether the increase in the generation of bradykinin during LDL adsorption is accompanied by the activation of endogenous production of nitric oxide (NO) in patients with peripheral atherosclerosis. LDL adsorption therapy was repeated ten times over a period of 3 months in ten peripheral atherosclerosis patients. Treatment significantly reduced serum total cholesterol and LDL cholesterol levels. This was associated with a significant improvement in Fontaine's classification and ankle pressure index. We also measured the kinin-kallikrein system and plasma levels of NO in the same patients. The results showed that coagulation factors of the intrinsic pathway including high-molecular-weight kininogen and prekallikrein decreased markedly after initial adsorption compared with the levels before treatment. There was a marked increase in bradykinin and NO concentrations after the initial adsorption, compared with their levels before adsorption. Our results suggest that the generation of bradykinin and increased plasma levels of NO may contribute to the improvement in peripheral circulation after LDL adsorption in peripheral atherosclerosis patients.

Adsorption↗
PubMed1998

Dexamethasone modulates the expression of endothelin-1 and -A receptors in A7r5 vascular smooth muscle cells.

Endothelin-1 (ET-1) is synthesized and released by vascular smooth-muscle cells (VSMCs). Glucocorticoids induce the release of ET-1 from VSMCs into the medium. We investigated whether glucocorticoids modulate ET-1 action by an autocrine production of ET-1 in A7r5 VSMCs. Dexamethasone (100 nM) stimulated the release of ET-1 into the medium. Treatment with 100 nM dexamethasone for 24 h reduced the peak increase of intracellular free Ca2+ induced by ET-1 (100 nM) by 50%, an effect that was dose-dependently inhibited by the specific ET(A)-receptor antagonist FR139317. Scatchard plots of [125I]-ET-1 binding revealed that dexamethasone reduced the number of maximal ET-1 binding sites without altering their binding affinity. FR139317 reversed the decrease in ET-1 binding capacity induced by dexamethasone. Northern blot analysis revealed that dexamethasone increased the level of prepro-ET-1 messenger RNA (mRNA) and decreased the level of ET(A)-receptor mRNA. FR139317 prevented the decrease in the level of ET(A)-receptor mRNA induced by dexamethasone. Results indicate that dexamethasone downregulates ET(A) receptors in A7r5 VSMCs at the mRNA level, in part by the autocrine production of ET-1.

Animals↗
PubMed1998

Corticosteroid irrigation of parotid gland for treatment of xerostomia in patients with Sjögren's syndrome.

OBJECTIVE: To determine the efficacy of corticosteroid irrigation of the parotid gland in relieving salivary flow deficiency in patients with Sjögren's syndrome. METHODS: The parotid glands of 31 patients with primary (24) or secondary (seven) Sjögren's syndrome were irrigated either with saline solution followed by corticosteroid solution, or with saline solution alone. Salivary function was assessed by Saxon test. RESULTS: Corticosteroid irrigation significantly increased the salivary flow rate in patients with Sjögren's syndrome (p < 0.0001), with clinical improvement detectable 3.7 (2.4) weeks (mean (SD)) after initial corticosteroid irrigation. The extent of improvement in salivary function was reciprocal to the clinical severity of the disease, with patients at the early stages obtaining 1.20 (0.57) g net increase in salivary flow rate, and patients at the most advanced stages obtaining 0.20 (0.47) g net increase. Repeated corticosteroid irrigations did not evoke corticosteroid refractoriness of the salivary gland; similar levels of net increase in salivary flow rate were observed after the second to fourth challenge of the corticosteroid in these patients. The sustained period was 8.4 (3.5) months (mean (SD)). CONCLUSION: These findings suggest the clinical usefulness of corticosteroid irrigation therapy in relieving xerostomia in patients with Sjögren's syndrome.

Adult↗
PubMed1998

Relationship between extreme dippers and orthostatic hypertension in elderly hypertensive patients.

Among elderly hypertensive subjects, extreme dippers with marked nocturnal fall in blood pressure (BP) as well as nondippers with absent nocturnal fall in BP are more prone to cerebrovascular disease when compared with those with appropriate nocturnal BP fall. However, the relationship between these abnormal diurnal BP variation patterns and postural BP variation has not been investigated. We investigated the diurnal BP variation by ambulatory BP monitoring and postural BP variation during 70 degrees head-up tilt in 110 asymptomatic hypertensive elderly subjects, who consisted of 29 subjects with white-coat hypertension and 81 with sustained hypertension with various patterns of nocturnal fall in BP (14 extreme dippers, with asleep systolic BP decrease by > or =20% of awake systolic BP; 56 dippers, with decrease by > or =0% to <20%; 11 nondippers, with decrease by <0%). During tilt, the mean (SD) systolic BP increased 10 (19) mm Hg in the extreme dippers (P<.02), and it decreased by 7.5 (13) mm Hg in the nondippers (P<.05), whereas it did not change in the dippers and white-coat hypertensive subjects. The heart rate increased in all four groups to similar degrees during tilt. Orthostatic hypertension defined as systolic BP rise of 10 mm Hg or more during tilt was found in 10 (72%) of the 14 extreme dippers, 6 (11%) of the 56 dippers, and 1 (9%) of the 11 nondippers, while orthostatic hypotension defined as systolic BP decrease of 20 mm Hg or more was found in 3 (27%), 5 (9%), and 1 (7%) of the nondippers, dippers, and extreme dippers, respectively (chi2=29.3, P<.0001). In conclusion, the abnormal diurnal BP variation is closely related to the abnormal postural BP variation in elderly hypertensive patients, with extreme dippers showing orthostatic hypertension and nondippers showing orthostatic hypotension. The upright position during the daytime, which increases the BP in the extreme dippers and decreases it in the nondippers, may in part produce abnormal diurnal BP variation.

Aged↗
PubMed1998

Inhibitory effect of glucocorticoid for osteoblast apoptosis induced by activated peripheral blood mononuclear cells.

Recent studies suggest a protective effect of glucocorticoid against progression of bone erosion and periarticular osteoporosis in patients with rheumatoid arthritis (RA), although this steroid hormone itself is believed to increase bone loss. To understand the antagonistic effect of glucocorticoid for osteopenic process in RA patients, we examined the effect of dexamethasone on Fas-mediated apoptosis of cultured human osteoblasts induced by either anti-Fas IgM or activated peripheral blood mononuclear cells (PBMC). Human osteoblastic cell line MG63 and primary osteoblast-like cells obtained from biopsy specimens were used in this study. PBMC isolated from healthy donors were cultured with or without recombinant interleukin-2 (rIL-2) followed by 12-O-tetradecanoyl-phorbol 13-acetate (PMA) with ionomycin in the presence or absence of dexamethasone. Fas was functionally expressed on MG63 and primary osteoblast-like cells, and treatment of these cells with dexamethasone affected neither Fas expression nor anti-Fas IgM-induced apoptosis. Activated PBMC expressing membrane-type Fas ligand (mFasL) efficiently killed both MG63 and primary osteoblasts-like cells, and the addition of human Fas chimeric protein (hFas-Fc) significantly diminished the cytotoxicity, indicating that interactions between mFasL of activated PBMC and Fas on human osteoblasts induce apoptosis of the latter. Although dexamethasone did not affect apoptosis of MG63 and primary osteoblast-like cells induced by anti-Fas IgM, treatment of activated PBMC with dexamethasone markedly inhibited both mFasL expression and cytotoxicity of these cells against human osteoblasts, suggesting that dexamethasone preferentially acts not on osteoblasts but PBMC. Cultured supernatants from activated PBMC induced apoptosis of human osteoblasts and the addition of hFas-Fc also inhibited the cytotoxicity of the supernatants. In addition, soluble form FasL (sFasL) was detected in the supernatants of activated PBMC. Furthermore, both the cytotoxicity and sFasL concentration of cultured supernatants of activated PBMC incubated with dexamethasone was significantly lower than that in the absence of dexamethasone. Our data suggest that glucocorticoid suppresses the apoptotic process of osteoblasts by inhibiting the expression of both mFasL and sFasL derived from activated PBMC, mediating a protective effect against periarticular bone loss and bone erosion in inflammatory arthritis such as RA.

Apoptosis↗
PubMed1998

Role of apoptosis of thyrocytes in a rat model of goiter. A possible involvement of Fas system.

Apoptosis, a physiological process of cell death, may modulate the mass of the thyroid gland. We investigated the role of apoptosis and the possible involvement of Fas/Fas ligand (FasL) system in apoptosis during goiter formation and involution in a rat model of goiter. Rats were fed a low iodine diet and a goitrogen, 6-propyl-2-thiouracil, to induce goiter. Rats with goiter were then fed a high iodine diet to study the phase of involution. We examined the presence of apoptosis by electron microscopy (EM) and terminal deoxy-UTP nick end labeling (TUNEL). We also investigated the association between Fas and FasL expression and thyrocyte apoptosis using immunohistochemistry and Western blotting. To evaluate the proliferation of thyrocytes, proliferating cell nuclear antigen was examined immunohistochemically. The number of apoptotic cells increased during goiter formation and the early stage of involution, which were also associated with increased number of Fas-positive thyrocytes, and some of these cells contained TUNEL-positive nuclei. However, the expression of FasL was almost constant throughout the experiment. Proliferating cell nuclear antigen/TUNEL ratio markedly increased during goiter formation but decreased particularly during the late stage of goiter involution. Our results indicate that apoptosis of thyrocytes is a main factor of cell loss during goiter formation and involution and suggest that the Fas/FasL system is involved in the induction of apoptosis of these cells. Moreover, the delicate balance between apoptosis and cell proliferation may play an important role in the control of thyroid gland mass.

Animals↗
PubMed1998

Effects of successful adenomectomy on body composition in acromegaly.

The purpose of the present study was to investigate postsurgical change in body composition in patients who have undergone surgery for acromegaly. Eight patients with acromegaly had determination of serum GH, insulin-like growth factor-I (IGF-I), height, body weight, and bioelectric impedance before surgery and at 2 weeks, 1 month, 3 months, and 6 months after surgery. Body composition was analyzed by bioelectric impedance analysis (BIA). We analyzed body fat (BF), body lean mass (BLM), body cell mass (BCM), total body water (TBW), intracellular water (ICW) and extracellular water (ECW). The serum GH concentration and IGF-I had decreased significantly 2 weeks after surgery. Body weight had decreased significantly 1 month after surgery and recovered 3 months after surgery. BIA showed that TBW and BCM had decreased significantly 2 weeks after surgery. BF gradually increased up to 1 month after surgery and was increased significantly at 3 months after surgery. The percent ratio of TBW/body weight decreased and the percent ratio of BF/body weight increased during the 6 months after surgery. The percent ratio of ECW/TBW did not change during the 6 months following surgery. In conclusion, the rapid body weight loss which occurred within 2 weeks after surgery was caused by decreases in TBW and BCM. The recovery of body weight, which was seen later than 1 month after surgery, was caused by an increase in BF. The postoperative change in body composition in acromegaly ceased 3 months after surgery.

Acromegaly↗
PubMed1998

Thyrotropin secreting pituitary adenoma effectively treated with octreotide.

We report a 65-year-old woman with thyrotropin (TSH) secreting pituitary adenoma, who was diagnosed based on the lack of inhibition of serum TSH despite an increased serum free thyroxine (T4), a low response of serum TSH to thyrotropin releasing hormone, and a pituitary tumor as revealed by magnetic resonance imaging. The pituitary adenoma was, however, inoperable due to chronic respiratory failure. The treatment with octreotide in a dose of 100 microg b.i.d. resulted in inhibition of serum TSH and free T4 to euthyroid levels and considerable shrinkage of the pituitary tumor. These effects were continued over 8 months after the start of octreotide therapy without any adverse effects. These findings add further evidence that octreotide is useful for treating inoperable TSH secreting pituitary adenoma.

Adenoma↗
PubMed1998

[An autopsy case of rheumatoid arthritis accompanied with acute exacerbation of interstitial pneumonia].

An autopsy case of rheumatoid arthritis (RA) with acute exacerbation of interstitial pneumonia is reported. A 57-year-old woman with longstanding RA was admitted to our hospital because of progressive dyspnea. On chest roentogenogram, diffuse interstitial shadow was confirmed in both lungs. Chest computed tomography (CT) showed diffuse lesion of elevated density of CT level in both lung. She was diagnosed as an acute exacerbation of interstitial pneumonia, and treated by methylpredonisolone pulse therapy (1,000 mg/day). Although cyclosporin A (2 mg/kg/day) was combined to steroid therapy, she was died of progressive respiratory failure. The histological findings of the lung showed extensive fibrosis with alveolar damage associated with hyaline membranes, edema and hemorrhage in alveolar space.

Acute Disease↗
PubMed1998

MR features of the lacrimal gland in Sjögren's syndrome.

OBJECTIVE: Our purpose was to investigate the MR features of the lacrimal glands in patients with Sjögren's syndrome. SUBJECTS AND METHODS: Using MR imaging, we examined 58 lacrimal glands in 29 women with Sjögren's syndrome and 150 lacrimal glands in 75 female control subjects. The patients ranged in age from 21 to 76 years, and the control subjects ranged in age from 0 to 78 years. We analyzed the thicknesses and internal signal intensity patterns of the lacrimal glands and compared the results with lacrimal flow rates using Schirmer's test. RESULTS: On the basis of the profile of normal age-related decreases in lacrimal gland thickness that we obtained from our control subjects, we categorized the lacrimal glands in the patients with Sjögren's syndrome as hypertrophic (7.8 +/- 0.8 mm), normal-sized (4.8 +/- 1.2 mm), or atrophic (2.4 +/- 0.5 mm). The patients had slower lacrimal flow rates than did the control subjects. Atrophic lacrimal glands had slower lacrimal flow rates (1.8 +/- 1.2 mm/5 min) than did normal-sized (5.2 +/- 2.8 mm/5 min) and hypertrophic (4.3 +/- 2.6 mm/5 min) glands. Normal-sized lacrimal glands with homogeneous MR features had faster lacrimal flow rates (7.6 +/- 2.2 mm/5 min) than did normal-sized glands with heterogeneous MR features (4.0 +/- 2.4 mm/5 min). Fat suppression studies showed that fat deposition was accelerated in the lacrimal glands of patients with Sjögren's syndrome. CONCLUSION: These results suggest that change in size associated with accelerated fat deposition may be the characteristic MR feature of lacrimal glands affected by Sjögren's syndrome. Thus, MR imaging could be a useful tool for assessment of the extent of lacrimal gland involvement in patients with Sjögren's syndrome.

Adolescent↗
PubMed1998

Retrovirus-mediated gene therapy for human hepatocellular carcinoma transplanted in athymic mice.

Gene therapy using a retrovirus vector carrying herpes simplex virus thymidine kinase gene under the control of the 0.3-kb human alpha-fetoprotein (AFP) gene promoter (LNAF0.3TK virus) in combination with ganciclovir (GCV) treatment was performed in athymic mice harboring AFP-producing HuH-7 human hepatoma cells. GCV treatment resulted in pronounced growth inhibition of the virus-infected HuH-7 xenograft in mice, but did not affect growth of the parental xenograft. These results indicate that the AFP gene promoter sequence allows enough therapeutic gene expression to induce the GCV-mediated cytotoxicity in vivo in AFP-producing human hepatoma cells.

Animals↗
PubMed1998

[The levels of FDP, FDP-E and D-dimer in patients with rheumatoid arthritis].

We studied the relationship of FDP and D-dimer levels of rheumatoid arthritis (RA) patients with their activities of RA. We evaluated FDP/D-dimer levels of thirty-six RA patients. And we also evaluated FDP/D-dimer levels of 14 patients with systemic lupus erythematosus (SLE) and 12 patients with other rheumatic diseases as control. RA patients were divided into two groups according to their activities. Nineteen patients, who fulfilled at least three of four activities criteria, were classified as active group [RA (A) group], and other 17 patients were classified as not-active group [RA (B) group]. FDP and D-dimer levels of RA patients were higher than those of SLE or other patients group significantly (P < 0.01). Furthermore, in RA patients, high levels of FDP and D-dimer were observed in RA (A) group compared to RA (B) group. In some RA patients, decrease of FDP and D-dimer levels were observed according to their RA activities. FDP and D-dimer levels were not correlated with the level of rheumatoid factor (RF). These results show that the FDP and D-dimer levels were elevated according to RA activity in RA patients.

Adult↗
PubMed1998

Serum amyloid A protein induces production of matrix metalloproteinases by human synovial fibroblasts.

Serum amyloid A (SAA) is a precursor protein for amyloid A, which is a constituent for amyloid fibrils in secondary amyloidosis. To determine the role of SAA in the articular destruction in patients with rheumatoid arthritis (RA), we investigated the effects of SAA on the production of matrix metalloproteinases (MMPs) by rheumatoid synovial fibroblasts. SAA stimulated rheumatoid synovial fibroblasts to produce MMP-2 and MMP-3 in a dose-dependent manner. Pretreatment of synovial fibroblasts with cycloheximide prevented SAA-mediated MMP-2 and MMP-3 secretion. When SAA-containing media were immunodepleted by anti-SAA-specific antibody, SAA-mediated MMP secretion was also abrogated. The level of MMP-3 mRNA was increased in SAA-stimulated synovial fibroblasts compared with that of control cells. Our data indicate that SAA is a potent inducer of MMPs in the RA synovium and may play a critical role in the degradation of extracellular matrix in the rheumatoid joint.

Arthritis, Rheumatoid↗
PubMed1998

[Bone changes in thyrotoxicosis].

Thyroid hormone (T3) is essential for normal bone growth and bone metabolism. T3 stimulates bone formation directly through T3 receptors in osteoblasts. T3 also stimulates bone resorption by osteoclasts probably secondary through osteoblasts. In thyrotoxicosis accelerated bone formation and resorption resulted in high turn-over bone loss. Bone metabolic markers elevate reflecting thyrotoxic state. Normalizing thyroid hormone level at least partially restore bone mineral content. In patients under thyroid hormone replacement therapy or TSH suppression therapy TSH and free thyroid hormones should be monitored to prevent unnecessary bone loss. Especially in postmenopausal women with thyrotoxicosis or thyroid hormone therapy the assessment of bone mineral content is required.

Bone Resorption↗