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Biomedical subjects

T Arao

Publications and source records attributed to T Arao.

At least 19 recordsLinked to original sources

Identification of expressed genes characterizing long-term survival in malignant glioma patients.

Better understanding of the underlying biology of malignant gliomas is critical for the development of early detection strategies and new therapeutics. This study aimed to define genes associated with survival. We investigated whether genes coupled with a class prediction model could be used to define subgroups of high-grade gliomas in a more objective manner than standard pathology. RNAs from 29 malignant gliomas were analysed using Agilent microarrays. We identified 21 genes whose expression was most strongly and consistently related to patient survival based on univariate proportional hazards models. In six out of 10 genes, changes in gene expression were validated by quantitative real-time PCR. After adjusting for clinical covariates based on a multivariate analysis, we finally obtained a statistical significance level for DDR1 (discoidin domain receptor family, member 1), DYRK3 (dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 3) and KSP37 (Ksp37 protein). In independent samples, it was confirmed that DDR1 protein expression was also correlated to the prognosis of glioma patients detected by immunohistochemical staining. Furthermore, we analysed the efficacy of the short interfering RNA (siRNA)-mediated inhibition of DDR1 mRNA synthesis in glioma cell lines. Cell proliferation and invasion were significantly suppressed by siRNA against DDR1. Thus, DDR1 can be a novel molecular target of therapy as well as an important predictive marker for survival in patients with glioma. Our method was effective at classifying high-grade gliomas objectively, and provided a more accurate predictor of prognosis than histological grading.

Adolescent↗

The biological effects of high-pressure gas on the yeast transcriptome.

The aim of the present study was to examine the feasibility of DNA microarray technology in an attempt to construct an evaluation system for determining gas toxicity using high-pressure conditions, as it is well known that pressure increases the concentration of a gas. As a first step, we used yeast (Saccharomyces cerevisiae) as the indicator organism and analyzed the mRNA expression profiles after exposure of yeast cells to nitrogen gas. Nitrogen gas was selected as a negative control since this gas has low toxicity. Yeast DNA microarray analysis revealed induction of genes whose products were localized to the membranes, and of genes that are involved in or contribute to energy production. Furthermore, we found that nitrogen gas significantly affected the transport system in the cells. Interestingly, nitrogen gas also resulted in induction of cold-shock responsive genes. These results suggest the possibility of applying yeast DNA microarray to gas bioassays up to 40 MPa. We therefore think that "bioassays" are ideal for use in environmental control and protection studies.

Feasibility Studies↗

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↗

[A case of very late onset overlap syndrome of systemic sclerosis and systemic lupus erythematosus].

A 88-year-old woman was admitted with appetite loss and dehydration in April 1999. She first noticed finger swelling in May 1996 and systemic sclerosis (SSc) was diagnosed in February 1997 on the basis of a clinical picture of low-grade fever, diffuse skin thickening, Raynaud's phenomenon, and pulmonary fibrosis. Retrospectively pulmonary fibrosis could have been identified on chest X ray film in September 1995. Although her appetite loss and dehydration were improved by hydration, pleural effusion continued. After detailed examinations, anti-topoisomerase 1 (Scl-70) antibody, anti-Sm antibody, and an anti-double-stranded DNA antibody (dsDNA) were found in her serum. However, the other antibodies to anti-SS-A, SS-B, Jo-1, and RNP were not detected. These results suggest that this elderly case was a very late onset overlap syndrome of systemic lupus erythematosus (SLE) and SSc. Thus, the pleural effusion in this case may have been caused by SLE-associated pleuritis. Although the late onset elderly cases with overlap syndrome are very rare, SLE, SSc, and their combination can be found in aged patients over 80 years old. SLE and SSc should be carefully considered for the differential diagnosis of pleural effusion and skin thickening even in elderly patients.

Aged↗

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↗

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↗

A tensile test to facilitate identification of defects in dentine bonded specimens.

OBJECTIVES: To determine the efficacy of a miniaturized dumbbell test procedure designed to more easily identify defect(s) in bonded dentine test specimens. METHODS: Extracted human dentine substrates were pre-conditioned with 10-3 solution for 10, 30 or 60 s prior to dentine bonding with 4-META/MMA-TBB resin. Miniaturized dumbbell-shaped test specimens were prepared from the resin bonded samples. After 24 h storage in 37 degrees C water, the specimens were tensile-loaded to failure. Fractured surfaces and cross-sections were examined and compared under scanning electron microscopy (SEM) and transmission electron microscopy (TEM). RESULTS: Cohesive failure within the bonding resin was observed in specimens pre-conditioned for 10 s. The tensile bond strength of these was excellent. Bond strengths of specimens that were pre-conditioned for 30 and 60 s were significantly lower, and defects in these specimens, formerly difficult or impossible to identify, were readily identified under SEM and TEM microscopy. CONCLUSION: The proposed method of tensile stressing to failure and microscopically examining fractured miniaturized dumbbell-shaped test specimens is a simple and reproducible test procedure. The protocol is capable of clearly elucidating defective resin infiltration of demineralized dentine in bonded interfaces. These defects are difficult to visualize by conventional and/or ISO recommended methods.

Adult↗

Kaikasaponin III and soyasaponin I, major triterpene saponins of Abrus cantoniensis, act on GOT and GPT: influence on transaminase elevation of rat liver cells concomitantly exposed to CCl4 for one hour.

The antihepatotoxic activities of soyasaponin I and kaikasaponin III, triterpenoidal saponins isolated from Abri Herba, the whole plant of Abrus cantoniensis, were studied on liver injury induced by CCl4 in primary cultured rat hepatocytes. The antihepatotoxic activities of these saponins and glycyrrhizin (positive control) were demonstrated by measuring the levels of glutamic pyruvic transaminase (GPT) and glutamic oxaloacetic transaminase (GOT). Soyasaponin I inhibited the elevation of GOT and GPT activities. The activities were comparable to those of glycyrrhizin. On the other hand, kaikasaponin III was more effective than soyasaponin I and glycyrrhizin. Kaikasaponin III showed the antihepatotoxic activity at less than 100 micrograms/ml. Furthermore, the highest activity was observed even in the lower doses (50, 100 micrograms/ml). However, soyasaponin I and kaikasaponin III showed some toxicity at the highest dose (500 micrograms/ml), though glycyrrhizin did not show toxicity at any dose.

Alanine Transaminase↗

Structure-hepatoprotective relationships study of soyasaponins I-IV having soyasapogenol B as aglycone.

As a part of our study on the leguminous plants, we investigated the constituents of the aerial parts of Glycine soya. We isolated and identified four known saponins, soyasaponins I, II, III, and IV which have the same aglycone, soyasapogenol B. As a part of our studies concerning hepatoprotective drugs, we also examined the hepatoprotective actions of these saponins towards immunologically induced liver injury on primary cultured rat hepatocytes. The action of soyasaponin II was almost comparable with that of soyasaponin I, whereas those of soyasaponin III and IV were more effective than soyasaponins I and II. This means that the disaccharide group shows greater action than the trisaccharide group. Furthermore, the saponin having a hexosyl unit shows a slightly greater action than that of the pentosyl unit in each disaccharide group or trisaccharide group. Structure-activity relationships suggest that the sugar moiety linked at C-3 may play an important role in hepatoprotective actions of soybean saponins.

Animals↗

Preventive effects of saponins from the Pueraria lobata root on in vitro immunological liver injury of rat primary hepatocyte cultures.

Preventive effects of nine saponins obtained from Puerariae Radix (the roots of Pueraria lobata) on in vitro immunological liver injury in primary cultured rat hepatocytes were studied. Although all tested saponins showed hepatoprotective action, the levels of activity of individual saponins differed. Structure-activity relationships for the sapogenol moiety suggested that the hydroxy group at C-29 would reduce the hepatoprotective activity while the hydroxy group at C-21 could enhance the hepatoprotective activity. Furthermore, structure-activity relationships for the sugar moiety suggested that the oxygen-bearing group at C-5" would enhance the hepatoprotective activity, though the configuration of the hydroxy group at C-3" could be less important for hepatoprotective activity.

Animals↗

Partial hydrolysis of soyasaponin I and the hepatoprotective effects of the hydrolytic products. Study of the structure-hepatoprotective relationship of soyasapogenol B analogs.

As a part of our studies of hepatoprotective drugs, we prepared some soyasapogenol B analogs from soyasaponin I. We examined the hepatoprotective effects of these analogs, using immunologically-induced liver injury, in primary cultured rat hepatocytes. Soyasaponin III and soyasapogenol B monoglucuronide were more effective than soyasaponin I. Both compounds were significantly effective even at 30 microM. The action of soyasapogenol B was almost equal to that of soyasaponin I, although glucuronic acid did not show any activity even at the highest dose (500 microM). When the two compounds were mixed, the hepatoprotective action did not change, compared with soyasapogenol B. Therefore, we concluded that the linkage between glucuronic acid and soyasapogenol B could enhance the hepato-protective activity.

Animals↗

[Functional fitness and related factors in community-dwelling elderly].

To examine the association of level of functional fitness to demographic, health, and life behavioral or social factors, cross sectional data were obtained for 737 persons aged 60 years or older, and who were independently living in the community. Functional fitness was measured with a functional fitness test containing 4 task items: standing, walking, hand performance, and self-care performance. Among the demographic factors, statistically significant associations with functional fitness were found for age in both male and female and for the presence of spouse in male. Health status, previous or present history of circulatory diseases and musculo-skeletal diseases were significantly associated with lower levels of functional fitness in male, and previous or present history of musculo-skeletal diseases and presence of higher obesity associated with lower fitness level in female. With life behaviors, men who had habitual exercise activities and women who had no habitual nap but habitual exercise activities and frequent out-of-home activities showed significantly higher fitness level than their counterparts. These results suggest that level of functional fitness in independently living aged people in the community was significantly associated with the presence of spouse, history of circulatory and musculo-skeletal diseases, and habitual exercise activities in males; and with the history of musculo-skeletal diseases, obesity, and habitual exercise activities, napping, and frequent out-of-home activities in females.

Activities of Daily Living↗

Preventive effects of saponins from puerariae radix (the root of Pueraria lobata Ohwi) on in vitro immunological injury of rat primary hepatocyte cultures.

The preventive effects of saponins from Puerariae Radix toward in vitro immunological liver injury using an antiserum against the rat liver plasma membranes on primary cultured rat hepatocytes were studied. Crude saponin from Puerariae Radix inhibited the elevation of alanine aminotransferase (ALT) activity at the dose of 90 micrograms/ml. The inhibition was stronger than that of glycyrrhizin, which was a positive control drug. The representative saponins in this drug, soyasaponin I and kudzusaponin SA3, were also more effective than glycyrrhizin, although their effects were weaker than that of crude saponin at the lower doses (90, 200 micrograms/ml). At 500 micrograms/ml, kudzusaponin SA3 showed antihepatotoxic activity equal to that of crude saponin.

Animals↗

Oleanene-type triterpene glycosides from puerariae radix. IV. Six new saponins from Pueraria lobata.

From Puerariae Radix, the root of Pueraria lobata (Leguminosae), six new oleanene-type triterpene glycosides, called kudzusaponins A1 (1), A2 (2), Ar (3), SA4 (5), and SB1 (6) were isolated together with kudzusaponin A3 (7), soyasaponins SA3 (8), and I (9). The structures of 1-6 were determined to be 3-O-alpha-L-rhamnopyranosyl- (1-->2)-beta-D-arabinopyranosyl-(1-->2)beta-D-glucuronopyranosy l kudzusapogenol A 22-O-beta-D-xylopyranoside, 3-O-beta- D-galactopyranosyl-(1-->2)-beta-D-glucuronopyranosyl kudzusapogenol A, 3-O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucuronopyranosyl kudzusapogenol A, 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranosyl-(1-->2)-beta- D-glucoronopyranosyl kudzusapogenol A, 3-O-beta-D-glucuronopyranosyl[(1-->2)-beta-D-glucuronopyranosyl soyasapogenol A22-O-alpha-L-arabinopyranoside,and 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-galactopyranosyl- (1-->2)-beta- D-glucuronopyranosyl (beta-fabatriosyl) soyasapogenol B 22-O-alpha-L-arabinopyranoside, respectively.

Carbohydrate Sequence↗

A case of lymphocutaneous nocardiosis with a review of lymphocutaneous nocardiosis reported in Japan.

An 82-year-old Japanese male developed nodules and ulcers along the lymphatics after a fall in the garden of his house resulting in injuries to the dorsum of his left hand which lasted for 3 months. Nocardia brasiliensis was isolated from a nodule, supporting a diagnosis of the lymphocutaneous type of nocardiosis. He had previously developed generalized bone metastasis from prostatic cancer, and his resulting depressed immunity might have played a part in the nocardiosis genesis. Sixteen cases of the lymphocutaneous type of nocardiosis reported in Japan were reviewed.

Abscess↗

Oleanene-type triterpene glycosides from puerariae radix. III. Three new saponins from Pueraria thomsonii.

From the root of Pueraria thomsonii (Leguminosae), three new oleanane-type triterpene glycosides, named kudzusaponin B1, acetyl-kaikasaponin III and acetyl-soyasaponin I were isolated, together with soyasaponin I (4) and subproside V (5). Their structures were determined to be 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-galactopyranosyl-(1-->2) -beta-D-glucuronopyranosyl kudzusapogenol B (1), 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-galactopyranosyl-(1-->2) -beta-D-glucuronopyranosyl sophoradiol 22-O-acetate (2) and 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-galactopyranosyl-(1-->2) -beta-D-glucuronopyranosyl soyasapogenol B 22-O-acetate (3), respectively.

Chromatography, Thin Layer↗