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Biomedical subjects

T Furuya

Publications and source records attributed to T Furuya.

At least 37 records · Page 2Linked to original sources

TcSCA complements yeast mutants defective in Ca2+ pumps and encodes a Ca2+-ATPase that localizes to the endoplasmic reticulum of Trypanosoma cruzi.

Intracellular Ca(2+) in Trypanosoma cruzi is mainly located in an acidic compartment named the acidocalcisome, which among other pumps and exchangers possesses a plasma membrane-type Ca(2+)-ATPase. Evidence for an endoplasmic reticulum-located Ca(2+) uptake has been more elusive and based on indirect results. Here we report the cloning and sequencing of a gene encoding a sarcoplasmic-endoplasmic reticulum-type Ca(2+)-ATPase from T. cruzi. The protein (TcSCA) predicted from the nucleotide sequence of the gene has 1006 amino acids and a molecular mass of 109.7 kDa. Several sequence motifs found in sarcoplasmic-endoplasmic reticulum-type Ca(2+)-ATPases were present in TcSCA. Expression of TcSCA in yeast mutants deficient in the Golgi and vacuolar Ca(2+) pumps (pmr1 pmc1 cnb 1) restored growth on EGTA. Membranes were isolated from the pmr1 pmc1 cnb1 mutant transformed with TcSCA, and it was found that the TcSCA polypeptide formed a Ca(2+)-dependent and hydroxylamine-sensitive (32)P-labeled phosphoprotein of 110 kDa in the presence of [gamma-(32)P]ATP. Cyclopiazonic acid, but not thapsigargin, blocked this phosphoprotein formation. Transgenic parasites expressing constructs of TcSCA with green fluorescent protein exhibited co-localization of TcSCA with the endoplasmic reticulum proteins BiP and calreticulin. An endoplasmic reticulum location was also found in amastigotes and trypomastigotes using a polyclonal antibody against a COOH-terminal region of the protein. The ability of TcSCA to restore growth of mutant pmr1 pmc1 cnb 1 on medium containing Mn(2+) suggests that TcSCA may also regulate Mn(2+) homeostasis by pumping Mn(2+) into the endoplasmic reticulum of T. cruzi.

Amino Acid Sequence↗

Low expression of p27(Kip1), a cyclin-dependent kinase inhibitor, is a marker of poor prognosis in synovial sarcoma.

BACKGROUND: Low expression of p27(kip1), a dominant cyclin-dependent kinase inhibitor involved in G1-S transition of the cell cycle, recently has been reported to be associated with aggressive tumor growth. It has been shown that active cell proliferation alludes to poor prognosis in patients with synovial sarcoma. However, to the authors' knowledge, little is known about the clinicopathologic significance of p27(kip1) in synovial sarcoma. METHODS: p27(kip1) expression was examined immunohistochemically in 55 cases of primary synovial sarcoma, and the relations between p27(kip1) expression and several cell proliferation markers, i.e., mitotic index (MI), Ki-67 labeling index (Ki-67 LI), and clinicopathologic parameters related to poor prognosis, were determined. Univariate and multivariate survival analyses were performed to evaluate the prognostic significance of p27(kip1) expression in synovial sarcomas. RESULTS: p27(kip1) labeling index (p27(kip1) LI) correlated inversely with MI (r = -0.44, P = 0.0007) and Ki-67 LI (r = -0.63, P < 0.0001). Of the clinicopathologic parameters examined, tumor necrosis (P = 0.019) and American Joint Committee on Cancer (AJCC) stage (P = 0.021) correlated significantly with p27(kip1) LI. Survival analysis showed that p27(kip1) LI was an independent prognostic factor for overall survival in patients with synovial sarcoma (P = 0.0031). CONCLUSIONS: The study results suggested that low expression of p27(kip1) may be useful as a marker of poor-prognosis synovial sarcoma.

Adolescent↗

Activated human T cells directly induce osteoclastogenesis from human monocytes: possible role of T cells in bone destruction in rheumatoid arthritis patients.

OBJECTIVE: To elucidate the direct role of human T cells in the induction of osteoclastogenesis in rheumatoid arthritis (RA), by studying human monocytes and the pathogenetic roles of receptor activator of nuclear factor kappaB ligand (RANKL), RANK, and osteoprotegerin (OPG). METHODS: Synovial tissue obtained at total knee replacement was stained immunohistologically using anti-RANKL, CD3, and CD4 antibodies. Synovial fluid was obtained from patients with RA, osteoarthritis (OA), gout, or trauma. Concentrations of the soluble form of RANKL (sRANKL) and OPG in the synovial fluid were measured by enzyme-linked immunosorbent assay. Activated T cells from peripheral blood mononuclear cells (PBMC) of healthy volunteers were cultured with human monocytes from PBMC. RESULTS: Immunostaining of the synovial tissue of RA patients demonstrated that RANKL-positive cells were detected in a subset of fibroblast-like synoviocytes and infiltrating mononuclear cells. Double immunostaining revealed that RANKL-positive cells were detected in a subset of CD3+ cells and CD4+ cells. An increased concentration of sRANKL and a decreased concentration of OPG were detected in synovial fluid from RA patients. The ratio of the concentration of sRANKL to that of OPG was significantly higher in synovial fluid of RA patients than in synovial fluid of patients with OA or gout. The activated T cells expressing RANKL induced osteoclastogenesis from autologous peripheral monocytes. The role of RANKL in this osteoclastogenetic process was confirmed by dose-dependent inhibition by OPG. CONCLUSION: The present study is the first to demonstrate osteoclastogenesis using human-derived T cells and monocytes. In addition, the present findings suggest that excess production of RANKL by activated T cells increases the level of sRANKL in synovial fluid and may contribute to osteoclastic bone resorption in RA patients.

Antibodies↗

Evaluation of an Estimation of Physiologic Ability and Surgical Stress (E-PASS) scoring system to predict postoperative risk: a multicenter prospective study.

We previously reported generating a scoring system termed E-PASS that predicted postsurgical risk. This study was undertaken to evaluate the usefulness of this system. A consecutive series of 902 patients who underwent elective gastrointestinal operations in six national hospitals in Japan were prospectively assessed for a comprehensive risk score (CRS) of the E-PASS, which was compared with their postoperative course. The postoperative morbidity rates linearly increased as the CRS increased. The postoperative mortality rate was only 0.13%, when the CRS was below 0.5; however, it increased to 9.7% when the CRS ranged from 0.5 to <1.0, and to 26.9% when the CRS was > or =1.0. The CRS correlated significantly with the severity of postoperative complications (rs = 0.527, P < 0.0001) and the costs of hospital stay (rs = 0.810, P < 0.0001). When the CRS-adjusted mortality rate at the CRS of > or =0.5 was compared among the hospitals, it was related to the hospital volume of operations, being 44.2% at the volume of <100 cases per year, 20.6% at the range of 100-199 cases, and 8.6% at the volume of > or =200 cases. These results suggest that E-PASS may be useful for predicting postsurgical risk, estimating medical expense, and comparing surgical quality.

Adolescent↗

Amplification of 3q26 approximately qter correlates with tumor progression in head and neck squamous cell carcinomas.

Biological characteristics of malignant tumors including head and neck squamous cell carcinoma (HNSCC) are greatly affected by genetic alterations. However, the relationship between chromosomal aberrations and pathologic tumor stage in HNSCC has not been elucidated. In 32 patients, DNA sequence copy number aberrations (DSCNA) were surveyed by comparative genomic hybridization (CGH) combined with a microdissection method. The average number of DSCNA was 15.3 per tumor and increased with tumor stage (P<.05). DNA copy number gain was detected at 3q26 approximately qter in 29 tumors (91%), and 13 of these tumors displayed marked DNA amplification. Tumor stage was linked with this amplification (P<.05). The increase in DSCNA and amplification of 3q26 approximately qter are likely to be useful markers for estimating tumor progression in HNSCC.

Adult↗

Biogenesis and function of peroxisomes and glycosomes.

Peroxisomes of higher eukaryotes, glycosomes of kinetoplastids, and glyoxysomes of plants are related microbody organelles that perform differing metabolic functions tailored to their cellular environments. The close evolutionary relationship of these organelles is most clearly evidenced by the conservation of proteins involved in matrix protein import and biogenesis. The glycosome can be viewed as an offshoot of the peroxisomal lineage with additional metabolic functions, specifically glycolysis and purine salvage. Within the parasitic protozoa, only kinetoplastids have been conclusively demonstrated to possess glycosomes or indeed any peroxisome-like organelle. The importance of glycosomal pathways and their compartmentation emphasizes the potential of the glycosome and glycosomal proteins as drug targets.

Animals↗

Polymorphisms of the tumor necrosis factor alpha locus among autoimmune disease susceptible and resistant inbred rat strains.

Inbred rat strains manifest remarkable differences in susceptibility/severity to autoimmune disease. MHC alleles strongly influence the pathogenesis of autoimmune disease in rats, but the precise mechanism(s) remain inadequately defined. The TNFalpha gene is located in the class III region of the MHC. Polymorphisms, influencing either the structure or expression of the TNF protein, might contribute to differences in autoimmune disease susceptibility/severity. We therefore sequenced the Tnf locus using genomic DNA from ACI, BB(DR), BN, DA, F344, and LEW rats that vary in susceptibility/severity to autoimmune diseases. We found 42 polymorphisms among these six strains. Although none of these polymorphisms are predicted to change the amino acid sequence of the TNF protein, several reside in potential non-coding regulatory regions and may influence expression levels. These polymorphisms may serve as good candidates for analysis of TNF expression to elucidate the mechanism(s) by which the MHC regulates susceptibility and/or severity of autoimmune diseases.

Animals↗

Expression of p53 protein as a prognostic indicator of reduced survival time in diffuse-type gastric carcinoma.

To determine whether p53 expression is different in intestinal and diffuse types of gastric carcinoma, we investigated p53 immunohistochemical expression in 178 primary gastric carcinomas. Overexpression of p53 was observed in 50 out of 100 intestinal-type tumors (50.0%) and in 27 out of 78 diffuse-type tumors (34.6%). A significant difference was found in the timing of p53 overexpression between the two types of carcinomas. Overexpression of p53 occurred often in the early stage of intestinal-type tumors, and there was no significant difference in expression between early and advanced cancers. In contrast, p53 overexpression did not occur often in the early stage of diffuse-type tumors, but it increased progressively as the tumor advanced. Analysis of patient survival revealed that p53 overexpression correlates significantly with a poor prognosis in diffuse-type gastric carcinoma (P = 0.003) but not in intestinal-type. Multivariate analysis showed that only pathological stage was an independent prognostic indicator. Our results suggest that p53 overexpression plays a different role in tumor carcinogenesis and progression of these two types of gastric cancers.

Adenocarcinoma↗

Successful management of tracheo-innominate artery fistula with endovascular stent graft repair.

Tracheo-innominate artery fistula is a highly lethal complication after tracheostomy. A 37-year-old man who had undergone a tracheostomy 14 years earlier because of dysphagia after brain surgery had a tracheo-innominate artery fistula with exsanguinating hemorrhage from his tracheostomy site. After temporary control of the bleeding, a stent graft was implanted in the innominate artery through the brachial artery. The patient recovered uneventfully and remained well 14 months after the procedure, with no sign of infection. Endovascular stent grafting may be the treatment of choice for patients with tracheo-innominate artery fistula.

Adult↗

DNA sequence copy number aberrations associated with histological subtypes and DNA ploidy in gastric carcinoma.

We have analyzed DNA sequence copy number aberrations (DSCNAs) and DNA ploidy by using comparative genomic hybridization and laser scanning cytometer in gastric carcinomas (GCs) to elucidate the genomic aberrations in relation to clinicopathological parameters. Thirty-two out of 33 cases showed one or more DSCNAs with a mean number of 11.7 per tumor. High-level gains were detected at 2p, 3q, 6p, 7p, 7q, 8q, 12p, 13q, 19q, and 20q. Frequency of gross genomic abnormalities and chromosome regions that have genomic aberrations were similar in both intestinal- and diffuse-type GCs, except aberrations at 8p, 9p, 12q, and 20q. The overall number of DSCNAs was significantly greater in DNA aneuploid tumors than that in DNA diploid tumors. We detected genomic aberrations characterized by histological subtype, tumor location, and DNA ploidy status: gain of 20q and losses of 8p and 9p in intestinal-type GCs, gains of 8p and 12q in diffuse-type GCs, gain of 20q in the lower third GCs, and loss of 5q, 9p, 10q, 16q, and 18q in DNA aneuploid GCs. Furthermore, 5q loss is associated with DNA aneuploidy (P = 0.0001) or the total number of losses (P = 0.001), gain + losses (P = 0.004), and high-level gains (P = 0.001) in GCs. Among these loci, chromosome 8p was unique. Gain of 8p was more common in diffuse-type GC, whereas loss of 8p was more frequently detected in intestinal-type GC. In conclusion, we describe chromosomal regions of 5q, 8p, and 20q, which are of interest for further investigation of GCs.

Adenocarcinoma↗

Conflict and integration of spatial attention between disconnected hemispheres.

OBJECTIVES: To clarify how the disconnected hemispheres perceive a line and bisect it with successful or unsuccessful integration of spatial attention. METHODS: Eye movements were recorded when a patient with an extensive callosa infarction bisected horizontal lines. The lesion extended into the left cingulate gyrus. RESULTS: When the patient bisected lines with the right hand, the gaze was initially directed rightward and shifted further to the right side with the execution of manual response, which resulted in rightward errors. Shortly after bisection, rapid ocular searches occurred to the left side, whereas the rightward errors did not decrease throughout the trials. When using the left hand, there was no deviation of the gaze before presentation of lines. In the first few trials, the patient bisected the line with a leftward error and then searched rapidly to the right side. The subsequent bisections were almost accurate, as the subjective midpoint was placed near the point of the initial fixation that fell around the true centre. Ocular searching was mostly absent during and after line bisection. CONCLUSIONS: In callosa disconnection, left unilateral spatial neglect may appear when use of the right hand induces a rightward bias in the attentional control of the left hemisphere and damage to its cingulate gyrus inhibits interhemispheric integration of attention. Resultant rightward errors of line bisection often cause interhemispheric conflict of attention, as the right hemisphere perceives the longer extent on the left side. By contrast, the disconnected but intact right hemisphere may bisect a line accurately by integrating attention to the extents perceived in the left and right visual fields.

Attention↗

A comparison of DNA copy number changes detected by comparative genomic hybridization in malignancies of the liver, biliary tract and pancreas.

Tumors arising from the liver, biliary tract and pancreas, which originate in the foregut and are in close anatomical proximity to each other, sometimes show similar histological features. No studies have focused on genetic similarities and differences between tumors of these organs. To elucidate the similarities and differences in DNA copy number alterations between tumors of these organs, we applied comparative genomic hybridization (CGH) to cancers of the liver (31 cases), biliary tract (42 cases) and pancreas (27 cases). Some alterations were common to tumors of all three organs, and some were preferential in certain types of tumor. Gains of 1q and 8q and losses of 8p and 17p were common to all tumors. In contrast, 13q14 and 16q losses were detected exclusively in hepatocellular carcinomas (HCCs; p < 0.01). The incidence of 17q21 gain and 5q loss was higher in biliary tract cancers than in the other two types (p < 0.05). Pancreatic cancers exhibited higher incidence of 5q14-q23 gain and 19p loss than tumors of other organs (p < 0.01). Gains of 7p, 7q, 12p and 20q and losses of 3p, 6q, 9p and 18q were frequent in both biliary tract and pancreatic cancers but rare in HCCs (p < 0.05). The present results suggest that although genes located at 1q, 8p, 8q and 17p are frequently involved in HCC, biliary tract and pancreatic cancer, at least some of the genes implicated in carcinogenesis are different between these three types. It is also suggested that CGH analysis is useful as a potential adjunct for the diagnosis and management of these tumors of organs that are anatomically close to one another.

Aged↗

Biodesulfurization of dibenzothiophene and its derivatives through the selective cleavage of carbon-sulfur bonds by a moderately thermophilic bacterium Bacillus subtilis WU-S2B.

Heterocyclic organosulfur compounds such as dibenzothiophene (DBT) in petroleum cannot be completely removed by hydrodesulfurization using chemical catalysts. A moderately thermophilic bacterium Bacillus subtilis WU-S2B, which could desulfurize DBT at 50 degrees C through the selective cleavage of carbon-sulfur (CS) bonds, was newly isolated. At 50 degrees C, growing cells of WU-S2B could degrade 0.54 mM DBT within 120 h to produce 2-hydroxybiphenyl, and the resting cells could also degrade 0.81 mM DBT within 12 h. The DBT-desulfurizing ability of WU-S2B is high over a wide temperature range from 30 to 50 degrees C, and highest at 50 degrees C for both the growing and resting cells, and this is an extremely advantageous property for the practical biodesulfurization. In addition, WU-S2B could also desulfurize DBT derivatives such as 2,8-dimethylDBT, 4,6-dimethylDBT and 3,4-benzoDBT. Therefore, B. subtilis WU-S2B is considered to have more beneficial properties than other desulfurizing bacteria such as Rhodococcus strains previously reported, particularly from the viewpoint of its capacity for thermophilic desulfurization through the CS bond cleavage.

Journal Article↗

[Clinical features of myelitis in patients with atopic symptoms].

It is rare to see atopic symptoms in patients with multiple sclerosis(MS). However, it has been reported that in atopic patients, particularly in patients with atopic dermatitis, a benign myelitis occasionally occurs. In the present report, three atopic patients with myelitis were studied clinically and neuroradiologically. All the patients were adult men(Case 1, 2, and 3 were 41-year-old, 31-year-old, and 34-year-old, respectively), and all of them had bronchial asthma without histories of atopic dermatitis. Their manifestations were not severe and were only numbness of upper and/or lower extremities. There was no motor weakness, ataxia, or urinary incontinence. MRI studies revealed a T2-high intensity lesion in the high cervical spinal cord in the two patients(Case 2 and 3) and a T2-high intensity lesion in the lumber spinal cord in the remaining patient(Case 1). Their clinical courses were essentially all benign and well responsive to steroid therapy. Although myelitis of these patients may be a first attack of MS, their findings appear to support a recently emerging concept of the atopic myelitis.

Adult↗