A new type of half-metallic fully compensated ferrimagnet.

Half-metallic fully compensated ferrimagnets (HM-FCFMs) constitute a special class of half-metals exhibiting zero magnetization at zero temperature. While there have been a number of theoretical studies predicting the existence of such materials over the last 25 years, very few of those have been synthesized and observed that they exhibit expected properties. Herein, we demonstrate that a NiAs-type hexagonal-structured (CrFe)S compound could serve as an HM-FCFM material. It has a half-metallic nature of 100% spin-polarised Fermi surfaces and yet zero magnetisation at the ground state. The magnetisation shows linear behaviour as a function of the magnetic field at temperatures below the compensation temperature (~ 190 K). In addition, it shows a high magnetic coercivity of 3.8 T at 300 K. These magnetic features contribute to a significant development in the application of HM-FCFMs for spintronics devices.

Expression of Tn and sialyl Tn antigens in synovial tissues in rheumatoid arthritis.

OBJECTIVES: The carbohydrate chains represented by mucins (MUCs) are expressed by a variety of normal and malignant secretory epithelial cells and induce a variety of immunoreactions. Tn and sialyl Tn antigens are tumour-associated carbohydrate antigens which are borne on the core proteins of mucins. The purpose of this study is to investigate the existence of tumour-associated carbohydrate antigens in rheumatoid arthritis (RA). METHODS: . We examined the expression of Tn and sialyl Tn antigens in synovial tissues from RA and osteoarthritis (OA) patients by immunohistochemistry. In addition, mucins from synovial fluid (SF) from RA patients are purified by gel filtration and density gradient ultracentrifugation and the existence of these antigens examined by dot and Western blotting. RESULTS: We found that Tn and sialyl Tn antigens were strongly expressed in synovial cells and infiltrating mononuclear cells on the sublining layer and lymphoid follicles in synovial tissues in RA compared with those in osteoarthritis. Tn and sialyl Tn antigens were detected in purified mucins of SF from RA patients. CONCLUSIONS: Tumour-like synovial hyperplasia cells expressed Tn and sialyl Tn antigens. This finding suggests that the mucins exhibiting with abnormal glycosylation may be in part responsible for synovial hyperplasia, leading to the joint destruction in the pathogenesis of RA.

Metabolic syndrome as a risk factor for high-ocular tension.

OBJECTIVE: To investigate the relationship between the metabolic syndrome and intraocular pressure (IOP). METHODS: An observational study was conducted in a medical health checkup program at a general hospital. This study involved 14 003 apparently healthy Japanese men and women, 18-83 years of age, with a mean IOP of 14.8 (3.0) mm Hg. IOP was examined by noncontact tonometer. High-ocular tension was defined as IOP >21 mm Hg without optic-disc abnormalities or history of receiving any anti-glaucoma therapy. Modified criteria of the revised National Cholesterol Education Program Adult Treatment Panel III (rATPIII), the new International Diabetes Federation definition, and the Japan Society for The Study of Obesity definition were used to characterize the metabolic syndrome. Air temperature was assessed from the Gifu Meteorological Observatory, Gifu, Japan. RESULTS: In the male and female subjects, mean IOP and the prevalence of high-ocular tension became high in direct correlation with the increased number of metabolic syndrome components. To analyze by logistic regression, the metabolic syndrome defined by rATPIII was positively and maximum temperature was negatively correlated with high-ocular tension in males (adjusted odds ratio: 2.0 [95% confidence interval, CI, 1.43-2.78] and 0.63 [95% CI, 0.54-0.73], respectively) and in females (adjusted odds ratio: 7.09 [95% CI, 3.74-13.43] and 0.67 [95% CI, 0.53-0.87], respectively). Three of five metabolic syndrome components (fasting plasma glucose, blood pressure, and triglycerides) were related to high-ocular tension. CONCLUSION: The metabolic syndrome is a risk factor for high-ocular tension.

Study of cysteinyl leukotriene-1 receptor in rat renal ischemia-reperfusion injury.

Renal ischemia-reperfusion (I/R) injury is a major cause of renal transplant dysfunction. Recent studies of I/R injury have focused on the function of neutrophils, the mechanisms of action of inflammatory cytokines, and oxygen free radicals, as well as other mediators. However, few reports address the cysteinyl leukotriene-1 receptor (CysLT1R), an important mediator of bronchial asthma in human beings. We examined the expression of CysLT1R in rat renal I/R injury. At laparotomy, the right kidney was harvested and the left renal artery and vein were clamped. The kidney was reperfused after 90 minutes of ischemia, and the rats were killed after 0, 3, 5, 12, or 24 hours. Expression of CysLT1R analyzed at immunohistochemistry was observed only in endothelial cells in nonischemic kidney. At 0 to 3 hours after reperfusion, CysLT1R expression on endothelial cells gradually became stronger, being most intense at 3 hours after reperfusion. Twelve hours after reperfusion, necrosis extended throughout the ischemic kidney; nearly all of the tubular epithelial cells were destroyed. At 3 to 12 hours after reperfusion, CysLT1R expression gradually became weaker on endothelial cells. At 24 hours after reperfusion, CysLT1R expression was almost at the level of that in nonischemic kidney. Expression of CysLT1R was noted in a rat model of renal I/R injury. Several hours after the maximal CysLT1R expression, we observed the maximum renal I/R injury. These results may suggest a relationship between the CysLT1R and renal I/R injury.

ABCB1 C3435T polymorphism influences methotrexate sensitivity in rheumatoid arthritis patients.

OBJECTIVE: Methotrexate (MTX) is most widely used for the treatment of rheumatoid arthritis (RA). However, it has certain drawbacks with regard to individual differences in its therapeutic effects as well as the differences in the patients' response to MTX therapy. We investigated whether multi-drug resistance-1 (ABCB1) C3435T, reduced folate carrier-1 (RFC1) G80A, 5-aminoimidazole-4-carboxamide ribonucleotide transformylase (ATIC) C347G and a 6bp-deletion polymorphism in the 3'-untranslated region of the thymidylase synthase (TYMS) gene are predictive of MTX sensitivity and its adverse effects. METHODS: Patients whose last maintenance dosage of MTX was 6 mg/week or those in whom MTX therapy was changed due to poor response to MTX were regarded as non-responders. The data of 124 RA patients who had received MTX treatment were retrospectively analyzed for polymorphisms in the ABCB1, RFC1, ATIC and TYMS genes, MTX sensitivity and MTX toxicity. RESULTS: There were no significant differences in MTX sensitivity among the genotypes of RFC1, ATIC and TYMS genes. ABCB1 3435TT cases included statistically significantly more non-responders than 3435CC cases according to univariate analysis (crude odds ratio (OR) = 8.91, p = 0.001) and multivariate analysis (adjusted OR = 8.78, p = 0.038). There were no significant differences in MTX toxicity among the genotypes of all the genes. CONCLUSION: These results suggested that the genetic diagnosis of ABCB1 C3435T can be applied to determine MTX sensitivity for the treatment of RA patients. However, further pharmacokinetics studies are required in this regard.

Treatment with edaravone improves the survival rate in renal warm ischemia-reperfusion injury using rat model.

Renal ischemia-reperfusion (I/R) injury during renal transplantation is a significant cause of renal dysfunction. The pathological role of free radicals in this process is a major concern. We investigated the effect of a free radical scavenger, edaravone (MCI-186), in renal I/R injury. Male Lewis rats (270 to 320 g) were used for the model. The right kidney was harvested and left renal artery and vein were clamped as laparotomy. The kidney was reperfused after 90 minutes of ischemia. Edaravone (10 mg/kg) was delivered intravenously before ischemia and after reperfusion to prevent the neutrophil activation. In the nontreatment I/R group, no rat survived beyond 4 days. However, in the edaravone I/R treatment group, one among five rats survived more than 7 days. These results suggested that treatment with edaravone ameliorated renal I/R injury, and that the agent has the potential to ameliorate preservation injury in renal transplantation.

Benefical effect of neutrophil elastase inhibitor on renal warm ischemia-reperfusion injury in the rat.

Renal ischemia-reperfusion (I/R) injury is a significant problem in renal transplantation. Neutrophils play an important role in renal I/R injury. Several reports have demonstrated that neutrophil elastase derived from the activated neutrophils might play an important role in this injury. We investigated the effect of a neutrophil elastase inhibitor in renal I/R injury. Male Lewis rats (270-320 g) were used in the model. The right kidney was harvested and the left renal artery and vein were clamped at laparotomy. The kidney was reperfused after 90 minutes of ischemia. Neutrophil elastase inhibitor (ONO-5046: 30 mg/kg) was delivered intravenously before ischemia and after reperfusion to prevent neutrophil activation. In the nontreatment I/R group, no hosts survived 4 days. However, after treatment with neutrophil elastase inhibitor, 3 of 10 rats in the I/R group, survived more than 7 days. These results demonstrated that treatment with neutrophil elastase inhibitor ameliorated renal I/R injury.

Expression of peroxisome proliferator-activated receptor-gamma in renal ischemia-reperfusion injury.

The pathogenesis of ischemia-reperfusion injury is known to involve cytokines and particularly surface adhesion molecules, the expression of which initiates the attachment of inflammatory cells. Peroxisome proliferator-activated receptor (PPAR)-gamma is considered an important immunomodulatory factor as well as a fatty acid regulator. In this study, we researched the expression of PPAR-gamma in renal ischemia-reperfusion injury of the rat. The right kidney was harvested and left renal artery and vein were clamped under laparotomy. The kidney was reperfused after 90 minutes of ischemia, and rats were sacrificed at 0, 1.5, 3, 5, 12, and 24 hours after reperfusion. PPAR-gamma expression was analyzed by immunohistochemical staining using monoclonal antibody. In normal kidney, PPAR-gamma staining was weak on endothelial cells, including mesangial cells. On the other hand, PPAR-gamma staining was weak on interstitial cells and strong on collecting ducts of medulla. From 1.5 to 5 hours after reperfusion, PPAR-gamma staining was strong on endothelial cells, moderate on interstitial cells, and strong on collecting ducts. Twelve hours after reperfusion, PPAR-gamma staining was weak on endothelial cells, moderate on interstitial cells, and strong on collecting ducts. PPAR-gamma is induced on collecting ducts, interstitial cells, and endothelial cells in a rat model having renal ischemia-reperfusion injury.

Study of cyclooxygenase-2 in renal ischemia-reperfusion injury.

The pathogenesis of ischemia-reperfusion (I/R) injury is known to involve cytokines and particularly surface adhesion molecules, the expression of which initiates the attachment of inflammatory cells. Cyclooxygenase (COX)-1 and COX-2 catalyze the initial key enzymatic steps in the metabolism of arachidonic acid. COX-1 is constitutively expressed in most tissues, whereas COX-2 is induced in response to proinflamamatory cytokines and stress. In this study we examined the expression of COX-1 and COX-2 in the rat after 90 minutes of warm-I/R injury. Rats were sacrificed at 0, 1.5, 3, 5, 12, and 24 hours after reperfusion. COX-2 expressions were analyzed by immunohistochemical staining, which was graded on a scale of 0 to 4. All results are presented as the mean values +/- SD. Data analyses used analysis of variance. COX-2 expression was most intense on endothelial cells at 3 and 5 hours after reperfusion. From 12 to 24 hours after reperfusion COX-2 expression on endothelial cells gradually became weaker. COX-2 expression scores were significantly higher at 1.5, 3, 5, 12, and 24 hours after reperfusion than at 0 hours. However, there were no differences in COX-1 expression after reperfusion. Several hours after the maximum of COX-2 expression the maximum renal I/R injury was observed. These results suggest a relationship between COX-2 expression and renal I/R injury.

The expression of cyclooxygenases and lipoxygenases in renal ischemia-reperfusion injury.

Recent studies of ischemia-reperfusion (I/R) injury have focused on the function of neutrophils as well as the actions of inflammatory cytokines. However, few reports address cyclooxygenases (COXs) and lipoxygenases (LOXs). We researched the expression of COXs (COX-1 and COX-2) and LOXs (5-LOX and 12-LOX) in rat renal I/R injury. The right kidney of male Lewis rats was excised, and the left renal artery and vein clamped for a 90-minute ischemia time. Rats were humanely killed at 0, 1.5, 3, 5, and 12 hours after reperfusion. COX and LOX expressions were studied using immunohistostaining. COX-2 and LOX expressions were observed only on endothelial cells of normal kidney. From 1.5 to 5 hours after reperfusion, COX-2 and LOXs expressions gradually intensified on endothelial cells. COX-2 and LOXs expression were most intense on endothelial cells at 5 hours after reperfusion. Twelve hours after reperfusion, necrosis extended throughout the ischemic kidney and nearly all the tubular epithelial cells were destroyed. Thus, at 12 hours after reperfusion, COX-2 and LOXs expressions on endothelial cells became weaker. However, COX-1 expression was not different at every time after reperfusion. COX-2 and LOXs were expressed in a rat model showing renal I/R injury. Several hours after the maximum of COX-2 and LOXs expressions, the maximal renal I/R injury was observed. These results suggest a relationship between COX-2 and LOXs expressions and renal I/R injury.

Study of peroxisome proliferator-activated receptor (PPAR)-gamma in renal ischemia-reperfusion injury.

Recent studies of ischemia-reperfusion (I/R) injury have focused on the function of neutrophils, the action mechanism of inflammatory cytokines. However, few reports have addressed peroxisome proliferator-activated receptor (PPAR)-gamma. PPAR-gamma is a ligand-activated transcriptional factor belonging to the steroid receptor superfamily. It plays a role in both adipocyte differentiation and tumorigenesis. We researched the expression of PPAR-gamma in renal I/R injury of the rat. Male Lewis rats were used. The right kidney was harvested and the left renal artery and vein were clamped at 90 minutes of ischemic time. Rats were killed at 0, 1.5, 3, 5, and 12 hours after reperfusion. PPAR-gamma expression was studied by immunohistostaining. PPAR-gamma expression was observed only on mesangial and endothelial cells of normal kidney. From 1.5 to 3 hours after reperfusion, PPAR-gamma expression gradually became stronger on mesangial and endothelial cells. PPAR-gamma expression was most intense on mesangial cells and endothelial cells at 3 hours after reperfusion. Twelve hours after reperfusion, necrosis extended throughout the ischemic kidney and nearly all the tubular epithelial cells were destroyed, but 12 hours after reperfusion PPAR-gamma expression gradually became weaker on mesangial and endothelial cells. PPAR-gamma was expressed in the rat model having renal I/R injury. Several hours after maximal of PPAR-gamma expression, maximal renal I/R injury was observed. These results may indicate a relationship between PPAR-gamma expression and renal I/R injury.

Cyclooxygenase-1 and -2 in human testicular tumours.

In this study, we investigated the expression of cyclooxygenase (COX)-1 and -2 in human testicular cancer (TC) and normal testis (NT) tissues, as well as the effects of COX ligands on viability and proliferation. Tumour specimens were obtained from 72 patients with TC and 20 patients with NT. RT-PCR and immunohistochemical methods were used to determine COX expression. While COX expression was not noted in any of the NT tissues, a marked expression was observed in the TC samples. The extent and intensity of immunoreactive COX-1 and -2 polypeptides in the TC tissues was statistically greater than the expression in the NT tissues. The synthetic COX inhibitors inhibited the growth of the TC cells. Both COX-1 and COX-2 are induced in testicular cancer, and these results indicate that both COX-1 and COX-2 are essential for the growth of TC cells.

ACTH expression in synovium of patients with rheumatoid arthritis and Lewis rats with adjuvant arthritis.

Abstract Adrenocorticotropic hormone (ACTH) and another pro-opiomelanocortin-derived neuropeptide, ß-endorphin (ß-End), are stimulated by corticotropin-releasing hormone (CRH) at the anterior pituitary. CRH and ß-End have predominantly proinflammatory effects in peripheral inflammatory sites. We have supposed that inflammatory stimuli develop ACTH as well as ß-End. In this study, we investigated the expression of ACTH in inflamed synovial tissue from patients with rheumatoid arthritis (RA) and osteoarthritis (OA), and at inflammatory joints with adjuvant-induced arthritis (AA) in female Lewis (LEW/N) rats. The expression of ACTH immunostaining was significantly greater in synovium of RA patients than in that of OA patients (P < 0.0001), and correlated with the extent of inflammatory mononuclear cell infiltration. Extensive and intense intracellular ACTH immunostaining, which correlated with the advance in arthritis score, was observed in the synovial lining layer, inflammatory mononuclear cells, and fibroblast-like cells of synovium and chondrocytes in LEW/N rats with AA. In addition, we performed double immunostaining of the same sections from arthritic joints in rats with anti-ACTH and anti-CRH antibodies. ACTH and CRH colocalized in inflammatory mononuclear cells and fibroblast-like cells. ACTH may play a role in the pathogenesis of RA as well as CRH.

Expression of peroxisome proliferator-activated receptor (PPAR)-gamma in human lung cancer.

The peroxisome proliferator-activated receptor (PPAR)-gamma is a member of the steroid nuclear receptors. Recent studies have demonstrated that PPAR-gamma is expressed in several cancer cells. We examined the PPAR-gamma expression in both normal lung and major types of human lung cancer. The expression of PPAR-gamma mRNA was detected in 2 out of 3 normal lung tissues and its protein was detected in 3 out of 5 normal lung tissues. In contrast, a small cell carcinoma cell line and all other types of lung cancer tissues expressed PPAR-gamma mRNA and its protein. Immunoreactive PPAR-gamma is strongly expressed in cancer cells and moderately in mononuclear cells, endothelial cells and fibroblasts of lung cancer tissues. Our results suggest that PPAR-gamma may play an important role in the pathogenesis and/or progression of lung cancer, and may be a novel therapeutical target for therapy of lung cancer.

Urocortin expression in synovium of patients with rheumatoid arthritis and osteoarthritis: relation to inflammatory activity.

Peripherally produced CRH acts as a local auto/paracrine proinflammatory agent. Urocortin is a new member of the CRH family that acts through the family of CRH receptors. In this study, we demonstrated that the expression of urocortin mRNA in synovia of patients with rheumatoid arthritis was greater than that of patients with osteoarthritis. Also, we detected urocortin and CRH receptor immunoreactivity in the synovial lining cell layer, subsynovial stromal cells, blood vessel endothelial cells, and mononuclear inflammatory cells from the joints of rheumatoid arthritis and osteoarthritis patients. The expression of immunoreactive urocortin was significantly greater in rheumatoid arthritis than osteoarthritis (P < 0.0001) and correlated with the extent of inflammatory infiltrate. CRH receptor immunoreactivity was strong in mononuclear inflammatory cells of rheumatoid arthritis synovia. Urocortin stimulated IL-1beta and IL-6 secretion by human peripheral blood mononuclear cells in vitro. These findings suggest that, like CRH, urocortin is present in peripheral inflammatory sites, such as rheumatoid synovium, and acts as an immune-inflammatory mediator.

Expression of peroxisome proliferator-activated receptor gamma in renal cell carcinoma and growth inhibition by its agonists.

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a ligand-activated transcriptional factor belonging to the steroid receptor superfamily. It plays a role in both adipocyte differentiation and tumorgenesis. Up-date, the up-regulation of PPAR-gamma expression is a frequent occurrence in a variety of different malignant tumors. In this study, we investigated the expression of PPAR-gamma in human renal cell carcinoma (RCC) tissues, and the role of PPAR-gamma in cell growth in human RCC-derived cell lines. Immunohistochemistry showed a strong immunoreactive expression of PPAR-gamma in all slides from cancer specimens. RT-PCR and Western blot analysis showed 3 RCC cell lines expressed PPAR-gamma mRNA and its protein. MTT assay in 3 RCC cells showed that the synthetic PPAR-gamma agonists thiazolidinedione compounds (pioglitazone and troglitazone) and the endogeneous PPAR-gamma ligand, 15-deoxy-Delta12,14-prostaglandin J(2) (15dPGJ(2)) inhibited the growth of the RCC cells. These results suggest that PPAR-gamma may become a new target in the treatment of RCC.

Inflammatory pseudotumor of the liver complicated with recurrent gouty arthritis.

Inflammatory pseudotumor (IPT) of the liver is a rare benign lesion of unknown etiology and is often accompanied by fever. Unexplained persistent fever unresponsive to antibiotics developed in a 70-year-old man suffering from intractable recurrent gouty arthritis. 67Ga-scintigraphy disclosed intense focal uptake in the upper abdomen. The lesion in the left lobe of the liver was an ill-defined hypodensity mass on computed tomographic scan and was enhanced on dynamic magnetic resonance imaging. The tumor was surgically removed and a diagnosis of IPT was made. Fever and arthritis resolved completely after surgery. Possible interaction between IPT of the liver and gouty arthritis was suggested.