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Biomedical subjects

A Ogata

Publications and source records attributed to A Ogata.

At least 109 records · Page 6Linked to original sources
PubMed1995

Oncostatin M induces association of Grb2 with Janus kinase JAK2 in multiple myeloma cells.

Oncostatin M (OSM) is a 28-kD glycoprotein recently identified as a growth factor for human multiple myeloma cells. It belongs to a family of distantly related cytokines that includes interleukin 6, ciliary neurotrophic factor, leukemia-inhibitory factor, and interleukin 11. These cytokines initiate signaling by inducing either homodimerization of gp130 or heterodimerization of gp130 with leukemia-inhibitory factor receptor beta components. Such dimerization in turn activates receptor-associated tyrosine kinases. In the present study using U266B1 human multiple myeloma cells, we show that OSM induces tyrosine phosphorylation and activation of JAK2, but not JAK1 or Tyk2, kinases. The results also demonstrate that OSM induces direct interaction of JAK2 kinase with Grb2, an SH2/SH3 domain containing adaptor protein. The SH2 domain of Grb2 is directly associated with tyrosine-phosphorylated JAK2. Furthermore, the presence of Sos in the JAK2-Grb2 complex suggests a role for Ras in OSM-transduced signaling.

Adaptor Proteins, Signal Transducing↗
PubMed1995

Suppression of experimental antigen-induced arthritis in transgenic mice producing human alpha-fetoprotein.

Experimental arthritis was induced in the knee joint of transgenic mice expressing human alpha-fetoprotein by immunization with methylated bovine serum albumin in Freund's complete adjuvant. In the control experiment with normal C57BL/6 mice, definite arthritis was observed in 55.6% (5/9) of the mice, but in only 21.1% (4/19) of the transgenic mice. This result suggested that human alpha-fetoprotein functioned as an immunosuppressant to ameliorate the development of the immune disease.

Animals↗
PubMed1995

Hypoxic stress induces cardiac myocyte-derived interleukin-6.

BACKGROUND: Hypoxic and ischemic stresses cause a series of well-documented changes in myocardial cells and tissues, including loss of contractility, changes in lipid and fatty acid metabolism, and irreversible membrane damage leading to eventual cellular death. Activated neutrophils are considered to be involved in this myocardial cellular injury. By stimulation of the neutrophils with chemotactic factors, canine neutrophils can be induced to adhere to isolated cardiac myocytes only if the myocytes have been previously exposed to cytokines such as tumor necrosis factor-alpha, interleukin (IL)-1, and IL-6. METHODS AND RESULTS: To examine the possible involvement of IL-6 in ischemia-reperfusion injury, we used cultured rat neonatal cardiac myocytes to study the effects of hypoxic stress on the production of IL-6 by cardiac myocytes. Unstimulated cardiac myocytes (3 x 10(5) cells per dish) produced 320 pg IL-6 over 4 hours in vitro (ie, biological activity equal to 320 pg recombinant IL-6, as detected by bioassay using the MH-60.BSF2 cell line). The incubation of cardiac myocytes under hypoxic conditions for 4 hours induced significantly increased production of IL-6 compared with normoxic conditions (2.82 +/- 0.49 versus 1.64 +/- 0.18 U/mL, P < .05). Furthermore, reoxygenation for 2 hours after 2 hours of hypoxic stress significantly augmented the production of IL-6 by cardiac myocytes (4.34 +/- 0.52 U/mL, P < .05). These responses to hypoxia and reoxygenation were not observed in fibroblasts isolated from the same tissue. Although unstimulated cardiac myocytes lacked IL-6 mRNA expression detectable by Northern blot analysis, hypoxic stress induced the expression of IL-6 mRNA in the cardiac myocytes. Several pathophysiologically relevant factors also augmented IL-6 release from cultured cardiac myocytes, including IL-1 beta, ionomycin, and epinephrine. CONCLUSIONS: Cardiac myocytes respond to hypoxic stress to augment the production of IL-6, and the IL-6 derived from cardiac myocytes may play an important role in the progression of myocardial dysfunction observed in cardiac ischemia-reperfusion injury.

Animals↗
PubMed1995

Myeloma cells express Fas antigen/APO-1 (CD95) but only some are sensitive to anti-Fas antibody resulting in apoptosis.

To find out which cytokines are involved in the pathogenesis of multiple myeloma, we investigated cytokine receptor expression on myeloma cells using a panel of monoclonal antibodies (MoAbs). Flow cytometric analysis of five myeloma cell lines (RPMI8226, ARH77, KMM-1, U266, and Hs) and myeloma cells freshly isolated from eight patients showed that interleukin-1 receptor (IL-1R) type I and type II, IL-2R alpha and beta chains, IL-4R, IL-6R, IL-7R, IL-8R, granulocyte macrophage colony-stimulating factor receptor (GM-CSFR), c-kit (stem cell factor receptor [SCFR]), membrane bound stem cell factor (MBSCF), and tumor necrosis factor (TNF) receptors type I and type II were not always detected on the myeloma cells. However, interferon-gamma receptor, gp130, and Fas antigen were constitutively expressed, except one sample. To determine the role of Fas antigen on myeloma cells, these cells were cultured with anti-Fas MoAb. Apoptotic changes characterized by loss of cell volume, membrane blebbing, fragmentation of nuclei, and condensed chromatin were observed in three of five myeloma cell lines. When bcl-2 expression was examined, it was seen in all the cell lines regardless of the sensitivity to anti-Fas MoAb. Furthermore, anti-Fas MoAb not only induced apoptosis of freshly isolated myeloma cells but also inhibited the DNA synthesis, although such effects varied from patient to patient. The data indicate that only some myeloma cells undergo apoptosis in response to the signal mediated by the Fas antigen.

Adult↗
PubMed1995

Serum interleukin 6 as a predicator of the therapeutic effect and adverse reactions after transcatheter arterial embolization.

To evaluate the value of serum interleukin 6 (sIL-6) for the prediction of therapeutic effect and adverse reaction after transcatheter arterial embolization (TAE), sIL-6 was measured before and after angiography or TAE in 18 patients (three after angiography and 15 after TAE for hepatocellular carcinoma). The three patients with only angiography showed no elevation of sIL-6, while a significant increase was observed after TAE in the 15 hepatocellular carcinoma patients. The sIL-6 levels of patients with a partial response to TAE were higher at 48-72 hours after the procedure than those of patients with no response (P = 0.045), and the sIL-6 levels of patients who showed adverse reactions were higher at 6-24 h than those of patients without adverse reactions (P = 0.019). sIL-6 level at 48-72 h after TAE reflects the efficacy of TAE, whereas the level at 6-24 h after TAE is related to the severity of adverse reactions. Therefore, sIL-6 may be a useful indicator for prediction of the therapeutic effect of TAE as well as adverse reactions.

Aged↗
PubMed1995

Significance of aminopyrine breath test as a parameter of hepatic functional reserve in 40% partial hepatectomy of rats with CCl4-induced liver injury.

Rats with CCl4-induced liver injury underwent partial (40%) hepatectomy. The [14C]aminopyrine breath test (ABT) values in rats with CCl4-induced liver injury were reduced by 34% compared with those in rats with normal liver. Preoperative ABT values clearly discriminated between survivors and those that died following 40% partial hepatectomy in rats CCl4-induced liver injury (P < 0.05). Hepatic protein synthesis was remarkably enhanced in CCl4-induced liver injury compared with normal liver (P < 0.001), and this was inversely correlated with ABT values (P < 0.001). These data show that the enhanced hepatic protein synthesis could induce a decrease of hepatic functional reserve. ABT seems to be a useful preoperative test for predicting surgical mortality following hepatectomy.

Alanine Transaminase↗
PubMed1995

[Bone mineral density of the lumbar spine and its relation to biological and lifestyle factors in middle-aged and aged Japanese women (Part 3). Relationships of physical fitness and lifestyle factors to bone mineral density in premenopausal and postmenopausal women].

We recruited community-dwelling women for participation in a study to investigate the effects of risk factors in lifestyle on bone mineral density (BMD). The subjects were 177 women aged 35 years and over living in a rural area in Fukui Prefecture. Their BMD of the lumbar spine (L2-L4) was determined by dual energy X-ray absorptiometry (DXA). In addition to measurements of height, body weight and grip strength, the lifestyles of the women, including physical load in work, sporting activities, smoking habits, calcium intake, and history of bone fracture were interviewed in detail. Adjusted for age, the BMD significantly correlated to body weight (r = 0.337, p < 0.05 for premenopausal women and r = 0.289, p < 0.01 for postmenopausal women) and body mass index (kg/m2) (r = 0.291, p < 0.05 for premenopausal women and r = 0.190, p < 0.05 for postmenopausal women). These results indicated the lower body weight to be a risk factor for the osteoporotic process in middle-aged and aged women. With respect to the grip strength as a physical fitness indicator, a significant correlation coefficient (r = 0.267, p < 0.01) with BMD was obtained for postmenopausal women independent of age and body weight. In univariate analysis, BMD showed no significant correlations with sporting activities, smoking habits, lower back pain and history of bone fracture for either premenopausal women or postmenopausal women.(ABSTRACT TRUNCATED AT 250 WORDS)

Asian People↗
PubMed1994

Inhibitory effect of all-trans retinoic acid on the growth of freshly isolated myeloma cells via interference with interleukin-6 signal transduction.

We showed the dose-dependent growth inhibition by alltrans retinoic acid (ATRA) of myeloma cells freshly isolated from patients. ATRA downregulated the cell surface expression of interleukin-6 receptor (IL-6R) and/or glycoprotein (gp) 130. The growth-inhibitory activity of ATRA was well correlated with that of anti-gp 130 antibody in every sample. Furthermore, ATRA inhibited the production of IL-6 from both myeloma cells and marrow stromal cells, and recombinant IL-6 (rIL-6) could partially recover the myeloma cell growth that had been inhibited by ATRA. These data suggest that ATRA may inhibit the proliferation of myeloma cells both by the downregulation of IL-6R and gp130 expression on myeloma cells and by the inhibition of IL-6 production from myeloma and stromal cells. Prednisolone (PSL) and interferon-gamma (IFN-gamma) also inhibited the myeloma growth, while their effects were different from those of ATRA on IL-6 R and gp130 expression, IL-6 production, and morphological change. The inhibitory effect of ATRA on myeloma cell proliferation was observed in 10 of 14 samples obtained from eight patients, which suggests that ATRA may be a potent new therapeutic agent for some myeloma patients.

Antigens, CD↗
PubMed1994

Oncostatin M, leukemia inhibitory factor, and interleukin 6 induce the proliferation of human plasmacytoma cells via the common signal transducer, gp130.

We analyzed the stimulatory effect of oncostatin M (OSM), leukemia inhibitory factor (LIF), interleukin 6 (IL-6), IL-11, and the inhibitory effect of anti-IL-6 antibody (Ab), anti-IL-6 receptor monoclonal antibody (mAb), and anti-gp130 mAb on the growth of human plasmacytoma cells freshly isolated from a patient with multiple myeloma. The purified cells showed a plasmacytoid morphology and expressed CD38, CD54, and CD56 antigens but no CD3, CD5, CD10, CD19, CD20, or very late antigen 5. IL-6 receptor (IL-6R) and its signal transducer, gp130, were expressed on their cell surface at a low level. Dose-dependent proliferation of the cells in response to OSM, LIF, and IL-6, but not to IL-11, was observed using [3H]TdR incorporation in vitro. Both anti-IL-6 Ab and anti-IL-6R mAb inhibited the growth of the cells in the presence or absence of exogenous IL-6. These cells release IL-6 but not OSM or LIF into the culture supernatant during short-term culture. Therefore, an autocrine growth mechanism mediated by IL-6, but not by OSM or LIF, was confirmed. Furthermore, anti-gp130 mAb completely inhibited the proliferation of the cells induced by OSM, LIF, as well as IL-6. These data indicate that OSM, LIF, and IL-6 can act as growth factors of human plasmacytoma cells through a common signal transducer, gp130, on their cell surface, and also suggest the potential therapeutic application of anti-gp130 mAb, as well as anti-IL-6R mAb against myeloma/plasmacytomas.

Antibodies, Monoclonal↗
PubMed1994

[Bone mineral density of the lumbar spine and its relation to biological and lifestyle factors in middle-aged and aged Japanese women (Part 1). Relationship of age and menopause to bone mineral density of the lumbar spine measured by dual-energy X-ray absorptiometry].

Bone mineral density (BMD) of the lumbar spine in 198 community-dwelling Japanese women aged 35 years and over was measured by dual-energy X-ray absorptiometry to investigate the effects of aging and menopause on BMD. A highly significant negative correlation between age and BMD was observed in postmenopausal women as widely accepted. We found a weak but statistically significant negative correlation between age and BMD in even premenopausal women, suggesting that their bone loss had commenced before menopause. Marked decrement in BMD was seen during the first ten years after menopause. Menopause clearly accelerated bone loss in the lumbar spine. Two-way analysis of variance of BMD on age and menopausal status showed that these explanatory variables had a significantly decreasing effect on BMD independently of each other. Menopausal status had a greater sum of squares than age, which suggested that menopause played a greater role in bone loss than did aging. Early menopause has been implied as one of the risk factors for bone loss. The women aged 50 to 59 having encountered menopause before 49 years old exhibited significantly lower BMD than those of similar age who experienced menopause at age 49 and older. This difference in BMD was not observed in the women aged 60 and over. Early menopause was no more likely to be a risk factor for bone loss in the elderly women. We conclude that bone loss in the lumbar spine begins before menopause and is accelerated markedly by menopause for about ten years, and that menopause has a greater decreasing effect on the bone mass than does chronological age while each of them has an independent effect on the bone mass decrement.

Absorptiometry, Photon↗
PubMed1994

Age-related changes in evoked otoacoustic emission in normal-hearing ears.

The evoked otoacoustic emissions (e-OAEs) elicited by both tone-bursts and clicks were investigated in normal-hearing ears of three age groups: young age group (approximately 30 years), middle age group (31-50 years) and old age group (51 years approximately). The pseudothreshold of tone-burst e-OAE at stimulus frequencies between 500 Hz and 2 kHz was significantly elevated in the middle and old age groups compared with that in the young age group. When the relationship between averaged emission cochleograms drawn from the mean pseudothresholds of tone-burst e-OAEs at 6 stimulus frequencies between 500 Hz and 4 kHz and averaged pure-tone audiograms was analyzed, a clear difference was found among the three age groups in a frequency range between 500 Hz and 2 kHz. Total echo power, reproducibility, highest peak power and frequency area peak power up to 4 kHz in click e-OAE significantly decreased in the middle and old age groups compared with those in the young age group. These results indicate the possibility that the function of cochlear micromechanics deteriorates in all cochlear partitions with increasing age, even in normal-hearing ears.

Acoustic Stimulation↗
PubMed1994

Pathophysiology of hearing impairment in acoustic neuroma with profound deafness: analysis by evoked otoacoustic emission and promontory stimulation test.

Evoked otoacoustic emissions (e-OAEs) were examined and promontory stimulus test (PST) done prior to tumor removal in 15 cases of surgically proven unilateral acoustic neuroma (AN) with more than 80 dB in pure-tone hearing level. The e-OAEs were elicited by tone-bursts at 1 kHz and 2 kHz, and an interaural difference in pseudothreshold of more than 10 dB was defined as a significant impairment of the cochlear function. In PST, electrical stimulation was applied by a burst mode at 6 stimulus frequencies between 50 Hz and 1600 Hz. The number of stimulus frequencies with a positive response was defined as the PST score. The results obtained were as follows; i) Mean interaural difference in e-OAE pseudothreshold was 16.0 dB at 1 kHz and 8.0 dB at 2 kHz, ii) Positive PST was found in only 40% of the subjects and the mean PST score was 0.93, iii). When the pathophysiology of hearing impairment was inferred from the combination of the findings in e-OAEs and PST, it was found that 33.3% of the subjects had pure cochlear impairment, 13.3% pure retrocochlear impairment and 46.7% cochlear-retrocochlear impairment. It is concluded that analysis of both e-OAEs and PST could clarify the pathophysiology of hearing impairment in AN with profound deafness, which cannot be determined by conventional psychoacoustic tests.

Acoustic Stimulation↗
PubMed1994

[Interleukin-6].

Interleukin-6 (IL-6) was found to be a pleiotropic cytokine which plays important roles not only in immune response but also in inflammation and hematopoiesis since the cDNA for IL-6 was originally cloned as a B cell differentiation factor (BCDF). IL-11, leukemia inhibitory factor, oncostatin M, and ciliary neurotrophic factor have similar effects with IL-6. This functional redundancy was well explained by the common signal transducer gp 130. Furthermore, recent studies have revealed the mechanisms to regulate the gene expression of IL-6 and to transduce the signal through IL-6 receptor system. On the basis of these results, elucidation of pathogenic significances of IL-6 and new therapeutic approaches in various diseases are now expected.

Animals↗
PubMed1993

Systemic production of interleukin-6 following acute inflammation.

The present study was designed to evaluate whether IL-6 is produced locally or systemically following acute inflammation. Full-thickness scale burns were made on rats. Serum IL-6 levels (SIL-6) showed a constant time-dependent change with a single peak 6 hours after the burn. SIL-6 elevation was correlated with the ratio of burn area to total body surface area. The liver, spleen, lymph node and skin harvested after the burn secreted significantly higher amounts of IL-6 after tissue culture when compared with those taken from sham rats. The venous serum drainage from the burn site induced significantly higher IL-6 production of splenocytes than the arterial and control venous sera. In conclusion, IL-6 production is rapidly and systemically triggered by a humoral factor following acute inflammation in vivo, resulting in constant kinetics for SIL-6.

Animals↗