Search PubMed⌕ Search

Biomedical subjects

S Eto

Publications and source records attributed to S Eto.

At least 19 recordsLinked to original sources
PubMed2000

Constitutive activation of LIL-Stat in adult T-cell leukemia cells.

The activation status of a recently identified STAT (signal transducers and activators of transcription) factor, LIL-Stat (lipopolysaccharide [LPS]/IL-1-inducible Stat) in adult T-cell leukemia (ATL) cells was investigated by electrophoretic mobility shift assays using nuclear extracts of leukemic cells from 7 patients with ATL and a GAS (gamma interferon activation site)-like element termed LILRE (LPS/IL-1-responsive element), which is found in the human prointerleukin 1beta (IL1B) gene. Spontaneous DNA binding of LIL-Stat was observed in all ATL cells examined. However, in normal human peripheral lymphocytes, DNA binding of LIL-Stat was detected only after stimulation with IL-1. These results demonstrated that LIL-Stat is constitutively activated in ATL cells. Furthermore, our transient transfection studies using LILRE chloramphenicol acetyltransferase (CAT) reporters argue that LIL-Stat in ATL cells functions as a transcriptional activator through binding to the LILRE in the IL1B gene. (Blood. 2000;95:2715-2718)

Acute Disease↗
PubMed2000

Suppressive effects of swainsonine and N-butyldeoxynojirimycin on human bone marrow neutrophil maturation.

The effects of the N-linked oligosaccharide inhibitors swainsonine and N-butyldeoxynojirimycin (NB-DNJ) on granulopoiesis was investigated using human bone marrow cells in in vitro liquid and agar cultures. The addition of the inhibitors into cultures containing granulocyte colony-stimulating factor (G-CSF) suppressed maturation from myelocytes into mature neutrophils. Swainsonine did not induce apoptosis, but NB-DNJ induced considerable apoptosis, especially in the presence of G-CSF. This result indicated that the decrease of mature neutrophils by swainsonine was not because of cell degeneration. In the case of NB-DNJ, it was thought to be because of both maturation suppression and apoptosis. In a colony-forming unit-granuloid (CFU-G) colony assay, the number of colonies was increased in the presence of the inhibitors, but the morphology of colonies was predominantly compact, or immature. The inhibitors also suppressed the expressions of mRNAs of CCAAT/enhancer binding protein epsilon (C/EBPepsilon) and G-CSF receptor as markers of terminal neutrophil maturation. These findings suggested that the incompleteness of N-linked oligosaccharide leads to the suppression of terminal neutrophil maturation.

1-Deoxynojirimycin↗
PubMed2000

Environmental stress modifies glycemic control and diabetes onset in type 2 diabetes prone Otsuka Long Evans Tokushima Fatty (OLETF) rats.

This study was designed to investigate the effects of environmental stress on metabolic derangements and the expression of diabetes phenotype in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of human type 2 diabetes (NIDDM). Acute environmental stress, i.e., exposure to water with immobilization for 1 h, caused a transient increase in blood glucose with decreased insulin secretion, and the stress-induced hyperglycemia augmented with age. The increased glycemia was associated with increased plasma levels of catecholamines and corticosterone. Short-term stress, the same stress of 1 h/day for 10 days, caused a significant decrease of food intake, which led to weight reduction in OLETF rats, aged 50 weeks. Blood glucose and insulin responses in OGTT showed no change before or after the short-term stress, despite the weight reduction. In chronic stress experiments, i.e., exposure to the same kind of stress for 6 days/week from 8 to 75 weeks of age, stressed rats did not gain weight, compared to control rats. Blood HbA1c levels and the index of insulin resistance after a 4-h unfed period were significantly lower in stressed rats than in controls from 35 and 45 weeks of age on, respectively. The occurrence of diabetes, diagnosed by OGTT, was also significantly lower in the rats subjected to chronic stress than in controls. These results suggest that chronic stress from 8 weeks of age inhibited weight gain, probably due to changes in eating behavior, preventing the deterioration of insulin resistance in OLETF rats. Plasma leptin levels were not modulated by stress, and correlated with body weight in the rats under chronic stress and in controls. These results suggest that in type 2 diabetes, blood glucose derangement due to stress is presumably associated not only with changes in counterregulatory hormones involved in glucose metabolism, but also with stress-induced changes in eating behavior.

Animals↗
PubMed2000

Skeletal changes in rats bearing mammosomatotrophic pituitary tumors: a model of acromegaly with gonadal dysfunction.

Growth hormone (GH) exerts potent effects on bone metabolism, resulting in an increased bone formation in animals and humans. Acromegaly has been associated with increased bone turnover, whereas the net effect of the increased bone metabolism has been obscured because patients with acromegaly are often associated with hypogonadism. We investigated changes in cortical and cancellous bone in adult rats implanted mammosomatotrophic pituitary tumor cells (GH3) as a model of acromegaly with gonadal dysfunction. Acromegaly model rats were prepared by implanting GH3 cells into female Wistar-Furth rats at 17 weeks of age. At 28 weeks of age, GH3-bearing rats (GH rats) showed very high serum GH levels and a moderate increase in serum prolactin levels, resulting in low circulating estradiol levels. The GH rats showed significant increases in body weight and in length and volume of both the femur and vertebral body. Bone mineral content values of either the midfemur or the whole lumbar body were significantly greater in the GH rats compared with littermate controls, while the areal bone mineral density values of the respective bones were not different between the two groups. The parameters of mechanical strength of the femur were significantly larger in the GH rats than in controls, whereas those of the lumbar vertebral body cylinder specimen were not different between the two groups. Respective normalized mechanical parameters of the femur and the vertebral body were the same in the GH rats as in controls. In the midfemur, the GH rats showed a significant increase in the total cross-sectional area without influencing the bone marrow area, resulting in an increase in the cortical bone area and the moment of inertia compared with controls. The indices of periosteal bone formation in the midfemur were greater in the GH rats compared with controls, but the endocortical bone formation and resorption were not different between the two groups. In the vertebral body cancellous bone, the GH rats had an increase in bone turnover rate, whereas the structural parameters were not different between the two groups. These results from GH3-bearing rats demonstrate that an excess of GH increases cortical bone mass in rats accompanied with estrogen deficiency, while no large effect on vertebral body cancellous bone mass is seen.

Acromegaly↗
PubMed2000

Ultrasonographic evaluation of lansoprazole-induced improvement of submucosal injury in patients with gastroesophageal reflux.

OBJECTIVE: Endoscopic ultrasonographic (EUS) changes in gastroesophageal reflux disease (GERD) after treatment with proton pump inhibitor have been poorly evaluated. We conducted a randomized, double-blind 12-wk clinical trial to compare the EUS effects of lansoprazole to histamine H2-receptor antagonist therapy in GERD. METHODS: Seventeen patients with reflux-related symptoms received 40 mg of famotidine for 6 wk or 30 mg of lansoprazole for 6 wk followed by 40 mg of famotidine or 30 mg of lansoprazole for another 6 wk, respectively. Patients underwent EUS before and at 6 and 12 wk after treatment. RESULTS: Before treatment, a variable degree of wall thickening was noted on EUS in the lower esophagus, compared with 20 normal subjects. After 6 wk of therapy, esophageal wall was significantly thicker in the famotidine group compared with the lansoprazole group (p<0.01). Surprisingly, thickening of esophageal wall and abnormal architecture were also detected in endoscopically negative reflux disease. Lansoprazole was superior to famotidine in reducing the thickness of esophageal wall. CONCLUSIONS: EUS was very useful for evaluation of submucosal injury in patients with GERD. EUS showed that a 6-wk course of lansoprazole therapy reduced thickening of esophageal wall, which was resistant to histamine H2-receptor antagonist therapy. Our results also suggest that inflammatory damage to the submucosal and muscle layers of the lower esophagus is the underlying mechanism of heartburn and associated symptoms in patients with endoscopically negative reflux disease.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2000

Thyrocyte proliferation by cellular adhesion to infiltrating lymphocytes through the intercellular adhesion molecule-1/lymphocyte function-associated antigen-1 pathway in Graves' disease.

Graves' disease (GD) is an autoimmune thyroid disease characterized by infiltration of lymphocytes into the thyroid, and intrathyroid lymphocytes are known to play an important role in the pathogenesis of GD. However, it remains to be understood how lymphocytes adhere to thyrocytes and regulate the thyrocyte function through cellular adhesion. We studied the mechanisms of T cell adhesion to thyrocytes using intrathyroid mononuclear cells (ITMC) and thyrocytes purified from the thyroids of patients with GD. The following novel features of cellular adhesion of ITMC to thyrocytes in the regulation of the thyrocyte function in GD were observed: 1) GD-ITMC expressed lymphocyte function-associated antigen (LFA)-1, which became an active adhesive configuration much higher than peripheral blood mononuclear cells (PBMC) from normal volunteers and GD patients; 2) GD-thyrocytes expressed a high quantity of intercellular adhesion molecule (ICAM)-1; 3) GD-ITMC adhered to GD-thyrocytes, whereas normal PBMC required activation stimuli by phorbol myriacetate, a pharmacological integrin-trigger, to adhere to GD- thyrocytes; 4) monoclonal antibody-blocking studies showed that the adhesion of the activated PBMC and ITMC to thyrocytes was mainly mediated by the LFA-1/ICAM-1 pathway; 5) the adhesion of GD-thyrocytes to the activated-PBMC or ITMC induced the proliferation of the thyrocytes, which was blocked by the addition of ICAM-1 and/or LFA-1 monoclonal antibodies; and 6) in GD thyrocytes of early cultures, ICAM-1 expression on GD-thyrocytes and its adhesion to LFA-1 on phorbol myriacetate-activated PBMC or ITMC were not modulated by the addition of interleukin-1beta or interferon-gamma, and proliferation of thyrocytes by the cellular adhesion via the ICAM-1/LFA-1 pathway was independent of the proliferative response of these cytokines. Taken together, these results suggest that lymphocytes infiltrating GD thyroid induce proliferation of GD-thyrocyte by the cellular adhesion to thyrocytes via ICAM-1/LFA-1, which may lead to the development of a goiter.

Cell Adhesion↗
PubMed2000

[A patient with life-threatening giant hematoma caused by acquired inhibitor to factor VIII].

A 66-year-old non-hemophiliac man developed widely spreaded hematoma in soft tissues around neck. On the day of admission, he was nearly choked by the giant hematoma which markedly compressed trachea. Initially, to keep air way, an intratracheal intubation using a fiber scope was carried out. Coagulation studies revealed a marked prolongation of activated partial thromboplastin time (129 seconds, control: 24.9-33.2), a diminished activity of factor VIII (less than 1%) and a significant increase of factor VIII inhibitor titer (60 Bethesda unit/ml). We thereby diagnosed coagulopathy related to acquired inhibitor against factor VIII. The general combination therapy of intravenous infusion of both prothrombin complex concentrates and activated prothrombin complex concentrates, prednisolone and plasma exchange successfully stopped expansion of the giant hematoma. However, because the titer of factor VIII inhibitor remained increased and the activity of factor VIII was continued to reduced, cyclosporin was additionally administrated. As a result, the titer of factor VIII inhibitor was markedly improved, but the reduced activity of factor VIII was continued and re-bleeding around neck was observed. We thereby administered steroid pulse therapy, which resulted in complete remission of the disease activity and recovery of factor VIII activity.

Aged↗
PubMed1999

H-Ras signals to cytoskeletal machinery in induction of integrin-mediated adhesion of T cells.

The adhesive function of integrins is regulated through cytoplasmic signaling. The present study was performed to investigate the relevance of cytoplasmic signaling and cytoskeletal assembly to integrin-mediated adhesion induced by chemokines. Adhesion of T cells induced by chemokines macrophage inflammatory protein (MIP)-1alpha and MIP-1beta was inhibited by pertussis toxin, wortmannin, and cytochalasin B, suggesting that both G protein-sensitive phosphatidylinositol (PI) 3-kinase activation and cytoskeletal assemblies are involved. The chemokine-induced T cell adhesion could be mimicked by expression of small G proteins, fully activated H-RasV12, or H-RasV12Y40C mutant, which selectively binds to PI 3-kinase, in T cells, inducing activated form of LFA-1alpha and LFA-1-dependent adhesion to ICAM-1. H-Ras expression also induced F-actin polymerization which colocalized with profilin in T cells. Adult T cell leukemia (ATL) cells spontaneously adhered to ICAM-1, which depended on endogenous MIP-1alpha and MIP-1beta through activation of G protein-sensitive PI 3-kinase. H-Ras signal pathway, leading to PI 3-kinase activation, also induced active configuration of LFA-1 and LFA-1-mediated adhesion of ATL cells, whereas expression of a dominant-negative H-Ras mutant failed to do. Profilin-dependent spontaneous polymerization of F-actin in ATL cells was reduced by PI 3-kinase inhibitors. In this paper we propose that H-Ras-mediated activation of PI 3-kinase can be involved in induction of LFA-1-dependent adhesion of T cells, which is relevant to chemokine-mediated signaling, and that profilin may form an important link between chemokine- and/or H-Ras-mediated signals and F-actin polymerization, which results in triggering of LFA-1 on T cells or leukemic T cells.

Actins↗
PubMed1999

CD44 stimulation induces integrin-mediated adhesion of colon cancer cell lines to endothelial cells by up-regulation of integrins and c-Met and activation of integrins.

For cancer metastasis, tumor cells present in the circulation must first adhere to the endothelium. Integrins lymphocyte function-associated antigen (LFA) 1 and very late antigen 4 play a central role in leukocyte adhesion to the endothelium and subsequent migration into tissues. The majority of tumor cells derived from solid cancers including colorectal cancer do not express suitable adhesion receptors, LFA-1 and very late antigen 4. We investigated the mechanisms of adhesion and transendothelial migration of cancer cells using colorectal carcinoma cell lines. Our results showed the following novel features of CD44 on the cells: (a) colon cancer cells express high levels of CD44; (b) stimulation of cancer cells by CD44 cross-linking or fragmented hyaluronan markedly induces the expression of LFA-1s, some of which reveal an activation epitope on the cells; (c) CD44 cross-linking induces F-actin polymerization in the cell cortex; (d) fragmented hyaluronan induces up-regulation of the activation epitope of LFA-1, which is mediated through protein kinase C; (e) stimulation of CD44 augments the LFA-1-mediated adhesion of cancer cells to endothelial cells and intercellular adhesion molecule 1-transfected cells and facilitates transendothelial migration; (f) stimulation of CD44 also induces expression of the hepatocyte growth factor (HGF) receptor c-Met on cancer cells; and (g) HGF further amplifies the LFA-1-mediated adhesion of cells prestimulated by CD44-derived signaling. Our results indicated that stimulation by CD44 induces "outside-in signaling," which consists of a direct pathway via CD44 and an alternate pathway through the induction of c-Met expression via HGF. Such stimuli augment the expression and trigger the function of integrins via "inside-out signaling" in colon cancer cells, which leads to amplification of integrin-mediated adhesion to the vessel wall and subsequent transendothelial migration.

Actins↗
PubMed1999

Cross-linking of CD44 on rheumatoid synovial cells up-regulates VCAM-1.

CD44 is a ubiquitous molecule also known as hyaluronic acid or homing receptor. However, the cellular functions and its role in inflammation, for example, rheumatoid synovitis, are currently unknown. In this study, we propose a novel function for CD44. Using synovial cells from rheumatoid arthritis (RA) patients, we demonstrated that CD44 cross-linking and binding to hyaluronan augmented VCAM-1 expression and subsequently VCAM-1-mediated cell adhesion. Briefly, we found that 1) rheumatoid synovial cells highly expressed CD44; 2) cross-linking of CD44 markedly but transiently augmented VCAM-1 expression and its mRNA transcription much more than did IL-1beta and TNF-alpha; 3) hyaluronan, especially when fragmented, also up-regulated VCAM-1; 4) CD44 activated the transcription factor AP-1; and 5) the integrin-dependent adhesive function of RA synovial cells to T cells was also amplified by CD44 cross-linking. These results indicate that the adhesion of RA synovial cells to matrices such as hyaluronic acid through CD44 could up-regulate VCAM-1 expression and VCAM-1-mediated adhesion to T cells, which might in turn cause activation of T cells and synovial cells in RA synovitis. We therefore propose that such cross-talking among distinct adhesion molecules may be involved in the pathogenesis of inflammation, including RA synovitis.

Adjuvants, Immunologic↗
PubMed1999

Renal hemodynamics in Otsuka Long-Evans Tokushima fatty rat, a model rat of spontaneous non-insulin-dependent diabetes mellitus with obesity.

Renal hemodynamic features in obese non-insulin-dependent diabetic rats remain unknown. We investigated renal hemodynamic and morphologic changes in Otsuka Long-Evans Tokushima Fatty (OLETF) rats at the age of 5 and 10 months compared with age-matched lean nondiabetic control rats (LETO). OLETF rats showed obesity compared with age-matched LETO rats. Hyperglycemia was mild in 5-month-old OLETF rats and moderate in 10-month-old OLETF rats. The absolute value for glomerular filtration rate (GFR) was significantly higher in OLETF rats than in age-matched LETO rats at the age of 5 and 10 months. Ten-month-old OLETF rats had significantly higher absolute values for renal plasma flow (RPF) than age-matched LETO rats but not 5-month-old OLETF rats. Stepwise multiple regression analysis revealed that body weight was a powerful determinant of GFR and RPF. When factored for body weight, no difference in GFR was demonstrated between 5-month-old OLETF and LETO rats, whereas 10-month-old OLETF rats still had significantly higher GFR and RPF than age-matched LETO rats. Renal hypertrophy was demonstrated in both 5- and 10-month-old OLETF rats even when factored for body weight. Glomerular volume was significantly increased in 10-month-old OLETF rats, but the ratio of glomerular volume to body weight was not different among the groups. Both absolute value for glomerular capillary length free from mesangial area and the value factored for glomerular area were significantly longer in OLETF rats than in age-matched LETO rats. Mesangial matrix expansion was remarkable in 10-month-old OLETF rats, and the glomerular sclerosis index was significantly higher in 10-month-old OLETF rats than in age-matched LETO rats. Stepwise multiple regression analysis revealed that body weight, hemoglobin A1c, and hypertriglyceridemia were powerful determinants for kidney weight and glomerular volume. These data suggest that renal hyperfiltration and hypertrophy observed in 10-month-old OLETF rats are related to diabetic metabolic disorders and that obesity-related conditions may be involved in the renal hemodynamic and morphologic features in OLETF rats.

Animals↗
PubMed1999

Comparison of recombinant human thyrotropin receptors versus porcine thyrotropin receptors in the thyrotropin binding inhibition assay for thyrotropin receptor autoantibodies.

Thyrotropin receptor autoantibodies (TRAb) are most commonly measured in a thyrotropin-binding inhibition (TBI) assay using solubilized porcine thyrotropin receptors (pTSHR). Recently, we reported modifications in recombinant human thyrotropin receptor (hTSHR) production and extraction that made substitution of this antigen for the pTSHR practical. We now report the first comparison of the behavior in a TBI assay of the recombinant, solubilized hTSHR with the pTSHR in a large series of clinically characterized patients with autoimmune thyroid disease. We studied 227 patients with Graves' disease (32 untreated patients, 156 patients receiving antithyroid medications, 24 patients in remission, 9 patients with recurrence of disease, and 6 thyroidectomized patients), as well as 32 patients with Hashimoto's thyroiditis and 28 normal individuals. In patients with untreated Graves' disease, 29 of 32 (90.6%) were TBI positive with either antigen, although two sera gave discrepant data in the two assay. Of the patients receiving antithyroid drugs, 94 of 156 (60.3%) were positive with the pTSHR and 106 of 156 (67.9%) were positive with the hTSHR TBI assay (p < 0.05%). In all other respects, however, there was no difference between the two TBI assays. Neither assay performed well in providing clinical guidance in the remission or relapse of disease. Of the 24 Graves' patients in remission, 75.0% and 79.2% were TBI negative with the hTSHR and pTSHR assays, respectively. The TBI assay at the time of relapse was even less informative; 6 of 9 (66.7%) being TBI negative in the pTSHR assay and 3/9 (33.3%) being negative in the hTSHR assay. In TBI assays with both species of TSHR, 3 of 32 hypothyroid patients with Hashimoto's thyroiditis were TBI positive. In summary, production of the recombinant hTSHR is now a practical reality and this antigen can clearly substitute at least as well for the pTSHR in the imperfect, although most commonly used, TBI assay. It is, therefore, likely that the hTSHR will supplant the pTSHR in this important assay. However, the use of the hTSHR rather than pTSHR does not appear to provide a major advantage, at least in terms of TBI assay sensitivity, specificity and predictive value.

Animals↗
PubMed1999

Effect of long-term ethanol consumption on ability to produce cytokine-induced neutrophil chemoattractant-1 in the rat liver and its gender difference.

Gut-derived lipopolysaccharide (LPS) may contribute to hepatocellular necrosis in alcoholic hepatitis through neutrophil sequestration in hepatic sinusoids. It is well known that the female has a greater susceptibility to alcoholic liver injury than the male. The aim of the present study was to investigate the effect of long-term ethanol consumption on ability of the liver to produce cytokine-induced neutrophil chemoattractant-1 (CINC-1), the most potent neutrophil-chemokine in rats, after LPS administration. Furthermore, we aimed to evaluate the gender difference in this ability. Male and female rats were pair-fed a liquid diet containing 36% of the total calories as ethanol or dextrose for 6 to 8 weeks. They were given LPS intravenously, and chemokine mRNA expression in the liver was evaluated after 2 and 6 hr. To study the organ or chemokine specificity, CINC-1 mRNA expression in the spleen and monocyte chemoattractant protein (MCP)-1 mRNA level were also determined. Serum ALT activity started to increase between 2 and 6 hr. Female rats fed an ethanol diet showed significantly higher ALT activity 6 hr after LPS injection than the male rats. CINC-1 mRNA expressions in the liver after 2 and 6 hr were significantly higher in the ethanol-fed group, compared with the pair-fed control. Female rats fed an ethanol diet showed a significantly higher level of CINC-1 mRNA in the liver than the male rats 2 hr after LPS injection. CINC-1 levels in the liver homogenates paralleled closely its mRNA expression, whereas its concentrations in sera did not correlate with those in the liver. Neither CINC-1 mRNA expression in the spleen nor MCP-1 mRNA expression in the liver was affected by ethanol feeding or gender. An additional experiment using the gonadectomized rats fed an ethanol diet showed that gonadectomy totally abolished the gender difference in CINC-1 mRNA of the liver. We conclude that CINC-1 induction in the liver may be responsible for LPS-induced hepatitis in the ethanol-fed rats, and that the difference in ability to produce CINC-1 between males and females is one important factor that may partly account for the gender difference of alcoholic liver disease.

Alcoholism↗
PubMed1999

Centrally administered murine leptin stimulates plasma arginine-vasopressin secretion and increases the level of mRNA expression in the supraoptic nucleus of conscious rats.

The product of the ob gene protein, leptin, has been suggested to function as an endogenous mediator of the cardiovascular system via sympathetic nerve activity. Moreover, extensive distribution of leptin receptor-like immunoreactivity has been demonstrated in the choroid plexus, cerebral cortex, hippocampus, thalamus and hypothalamus, especially in the paraventricular nucleus (PVN) and supraoptic nucleus (SON). In this study, we have investigated the in vivo effects of leptin on plasma arginine-vasopressin (AVP) secretion and the level of AVP messenger ribonucleotic acid (AVP mRNA) in the SON of conscious rats. Intracerebroventricularly administered leptin increased plasma AVP concentration in a dose-dependent manner (0-400 pmol/rat). The maximal effect was obtained at 15 min after the administration of leptin. Furthermore, in Northern blot analyses, the levels of AVP mRNa in the SON increased approximately 2-fold from the basal level after the administration of leptin. AVP mRNA expression in the PVN was also increased by leptin. However, leptin had no effects on plasma oxytocin (OXT) secretion and OXT gene expression in the SON. In conclusion, leptin is involved in AVP secretion via the central nervous system, however, its physiological role is unknown.

Animals↗
PubMed1999

Interleukin-1alpha regulates G1 cell cycle progression and arrest in thyroid carcinoma cell lines NIM1 and NPA.

This study provides the first report that the same cytokine (interleukin-1 (IL-1)) can induce opposite effects on cyclin-dependent kinases (Cdks) and Cdk inhibitors (Cdkis) in the G1 phase even in the same type of cancer cells (papillary thyroid carcinoma cells). Cell cycle analysis revealed an increase in NIM1 cells and a decrease in NPA cells in the S and G2+M phases after treatment with IL-1alpha. The addition of IL-1alpha to NIM1 cells reduced the expression of p16 and p21 protein and induced the expression of Cdk2 and Cdk4 protein, which leads to the phosphorylation of retinoblastoma protein. The addition of IL-1alpha to NPA cells induced the expression of p27 protein and reduced the expression of Cdk2 protein, which leads to induction of p107 protein expression. It is of interest that p21 protein expression was not observed in NPA cells. These results suggest that several Cdks and Cdkis play a regulatory role in the G1 cell cycle progression and arrest induced by IL-1alpha in thyroid carcinoma cell lines.

Blotting, Western↗
PubMed1999

[A case of mixed connective tissue disease with microscopic polyarteritis nodosa associated with perinuclear-antineutrophil cytoplasmic antibody and anti-glomerular basement membrane].

A 46-year-old female was admitted to our hospital due to general fatigue, systemic edema and dyspnea with history of systemic sclerosis (SSc). The patient was diagnosed as mixed connective tissue disease (MCTD) based on Raynaud phenomenon, a high anti-RNP antibody level and clinical symptoms and laboratory findings suggesting SSc, dermatomyositis (DM) and systemic lupus erythematosus (SLE). After the admission, both alveolar hemorrhage and a rapidly progressive glomerulonephritis (RPGN) also developed and laboratory findings showed a positive remark of myeloperoxydase-antineutrophil cytoplasmic antibody (MPO-ANCA) and anti-glomerular basement membrane (GBM) antibody. She was therefore re-diagnosed as microscopic polyarteritis nodosa (microscopic PAN) combined with MCTD and treatment with high dose prednisolone and steroid pulse therapy dramatically improved general conditions and lung symptoms, but maintenance dialysis was persistent because of irreversible renal failure. However, 3 months after the admission, she died of acute exacerbation of interstitial pneumonitis that was unresponsive to steroid pulse therapy. Autopsy revealed interstitial pneumonitis with alveolar hemorrhage and crescentic glomerulonephritis (CrGN), in which immunofluorescent microscopy showed no deposition in agreement with pauciimmune type. The histological findings supported the diagnosis; primary microscopic PAN combined with MCTD, which is a quite rare case, to our knowledge. Furthermore, co-existence of MPO ANCA and anti-GBM antibody, clinical and histological findings of the case also lead us to reconsider the relevance of these antibodies to pathogenesis and/or categories of microscopic PAN and Goodpasture's syndrome.

Antibodies, Antineutrophil Cytoplasmic↗