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Biomedical subjects

A Tanaka

Publications and source records attributed to A Tanaka.

At least 73 records · Page 4Linked to original sources
PubMed2003

Role of COX inhibition in pathogenesis of NSAID-induced small intestinal damage.

Nonsteroidal antiinflammatory drugs (NSAIDs) such as indomethacin decrease mucosal PGE(2) production by inhibiting cyclooxygenase (COX) activity and produce damage in the small intestine. The development of intestinal lesions as induced by indomethacin was accompanied by increases in intestinal motility, enterobacterial invasion, and myeloperoxidase (MPO) as well as inducible nitric oxide synthase (iNOS) activity, together with the up-regulation of COX-2 and iNOS mRNA expression. Neither the selective COX-1 inhibitor, SC-560, nor the selective COX-2 inhibitor, rofecoxib, alone caused intestinal damage, but their combined administration produced lesions. SC-560, but not rofecoxib, caused intestinal hypermotility, bacterial invasion and the expression of COX-2 as well as iNOS mRNAs, yet the iNOS and MPO activity was increased only when rofecoxib was administered together with SC-560. Although SC-560 inhibited the PG production, the level of PGE(2) was recovered, in a rofecoxib-dependent manner. The intestinal hypermotility response to indomethacin was prevented by both 16,16-dimethyl PGE(2) and atropine but not ampicillin, yet all these agents inhibited not only the bacterial invasion but also the expression of COX-2 as well as the iNOS activity in the intestinal mucosa following indomethacin treatment, resulting in preventing the intestinal lesions. These results suggest that inhibition of COX-1, despite causing intestinal hypermotility, bacterial invasion and iNOS expression, up-regulates the expression of COX-2, and the PGE(2) derived from COX-2 counteracts deleterious events caused by COX-1 inhibition and maintains the mucosal integrity. These sequences of events explain why intestinal damage occurs when both COX-1 and COX-2 are inhibited.

Animals↗
PubMed2002

Long anchor using Flo1 protein enhances reactivity of cell surface-displayed glucoamylase to polymer substrates.

We investigated the influence of anchor length on the reactivity to polymer substrate of enzyme displayed on yeast cell surfaces. Using various lengths [42, 102, 146, 318, 428, and 1,326 amino acids (aa)] of the C-terminal region of the Saccharomyces cerevisiae Flo1 protein (Flo1p), which plays a major role in yeast flocculation, six display systems with various anchor lengths were constructed. In these systems, the target protein was displayed on the yeast cell surface under the control of the 5'-upstream region of the isocitrate lyase gene of Candida tropicalis ( UPR-ICL). Cell-surface display of Rhizopus oryzae glucoamylase by these systems was induced and confirmed in all systems by immunofluorescence microscopy and immunoblotting. Flow-cytometer measurement of the fluorescence intensity of immunofluorescence-labeled yeast cells displaying glucoamylase indicated that glucoamylase displayed with longer anchors, especially those of 428 and 1,326 aa in length, had higher reactivity to antibodies. The reactivity of starch to displayed glucoamylase, which was evaluated by plate assay, increased with anchor length, as did the cell growth-rate in starch-containing medium. These results indicate that cell-surface display systems using 428- and 1,326-aa length anchors of Flo1p are effective for the display of enzymes on the outer surface of yeast cells.

Cloning, Molecular↗
PubMed2002

An arming yeast with the ability to entrap fluorescent 17beta-estradiol on the cell surface.

We constructed a novel surface-engineered yeast displaying the ligand-binding domain of the rat estrogen receptor (ERLBD). ERLBD, display of which on the yeast cell surface was confirmed by immunofluorescence, possessed strong binding activity to fluorescent 17beta-estradiol - an analogue of the natural ligand of the estrogen receptor - that was comparable to the activity of the native receptor. Environmental homeostasis has recently been disturbed by endocrine disruptors, which cause confusion in the hormone secretion system. It is therefore very important to identify chemical compounds with hormone-like activity and remove them from the environment. The present results demonstrate that the new arming yeast displaying ERLBD on its cell surface will be capable of screening, entrapping, and removing estradiol-like compounds from the environment.

Animals↗
PubMed2002

Cell surface-engineered yeast with ability to bind, and self-aggregate in response to, copper ion.

In order to construct a cell surface-engineered yeast Saccharomyces cerevisiae that facilitates adsorption and recovery of heavy metal ions, we endowed it with the ability to self-aggregate in response to binding and accumulation of copper ion. A fusion gene for the expression of GTS1, which encodes a putative zinc-finger transcription factor related to occurrence of cell-aggregation, was constructed under the control of the copper ion-inducible CUP1 promoter from the yeast metallothionein gene. The multicopy plasmid carrying the fusion gene was introduced into a cell surface-engineered yeast displaying histidine hexa-peptide, which can chelate copper ion. This transformant strain aggregated in medium only in the presence of copper ion, with aggregation induced by as little as 1 mM copper ion. The copper ion-induced aggregation did not interfere with the copper ion-adsorbing function of the cell surface-engineered yeast, indicating that this transformant strain has the twin features of enhanced cell surface adsorption of copper ion and self-aggregation in response to environmental copper ion.

Adsorption↗
PubMed2002

Screening of a molecule endowing Saccharomyces cerevisiae with n-nonane-tolerance from a combinatorial random protein library.

A combinatorial random protein library was constructed from random DNA fragments generated by "DNA random priming", an improved method of "random-priming recombination" using random-sequence primers and template cDNA from the yeast Saccharomyces cerevisiae. In order to express this library on the yeast cell surface, a yeast multicopy cassette vector was constructed, in which the random-protein-encoding DNA fragments were fused to a gene encoding the C-terminal 320 amino acids of alpha-agglutinin. Fluorescent labeling of the immuno-reaction of RGS(His)(6) epitope confirmed the surface display of random proteins. The surface display of heterologous random proteins on yeast cells will have a wide application. As an example, an n-nonane-tolerant yeast strain that could grow very well in nonane-overlaid culture medium was screened out from transformants displaying this combinatorial library. n-Nonane tolerance was dependent on the transformed plasmid, and the related protein was confirmed to localize on the cell surface by papain treatment and immunofluorescent labeling. Analysis of this displayed protein was also carried out. This strain is the first one to have been endowed artificially with organic solvent tolerance. This is a good example of creating cells exhibiting new phenotypes using a combinatorial protein library.

Adaptation, Physiological↗
PubMed2002

A quantity control mechanism regulating levels of the HapE subunit of the Hap complex in Aspergillus nidulans: no accumulation of HapE in hapC deletion mutants.

The Aspergillus nidulans CCAAT-binding complex (Hap complex) consists of at least three subunits, HapB, HapC and HapE. To investigate the quantity control mechanisms of the subunits during assembly of the Hap complex, reconstitution studies with the recombinant subunits and extracts prepared from the respective hap subunit deletion mutants were carried out. Furthermore, Western blot analysis of the Hap subunits and Northern blot analysis of the hap genes with the respective deletion mutants were also performed. From all the results together, it was suggested that the number of the HapC molecule could adjust that of the HapE molecule by forming stable heterodimers prior to assembly of the Hap complex.

Aspergillus nidulans↗
PubMed2002

High-level ethanol production from starch by a flocculent Saccharomyces cerevisiae strain displaying cell-surface glucoamylase.

A Strain of host yeast YF207, which is a tryptophan auxotroph and shows strong flocculation ability, was obtained from SaccharomYces diastaticus ATCC60712 and S. cerevisiae W303-1B by tetrad analysis. The plasmid pGA11, which is a multicopy plasmid for cell-surface expression of the Rhyzopus oryzae glucoamylase/alpha-agglutinin fusion protein, was then introduced into this flocculent yeast strain (YF207/pGA11). Yeast YF207/pGA11 grew rapidly under aerobic condition (dissolved oxygen 2.0 ppm), using soluble starch. The harvested cells were used for batch fermentation of soluble starch to ethanol under anaerobic condition and showed high ethanol production rates (0.71 g h(-1) l(-1)) without a time lag, because glucoamylase was immobilized on the yeast cell surface. During repeated utilization of cells for fermentation, YF207/pGA11 maintained high ethanol production rates over 300 h. Moreover, in fed-batch fermentation with YF207/pGA11 for approximately 120 h, the ethanol concentration reached up to 50 g l(-1). In conclusion, flocculent yeast cells displaying cell-surface glucoamylase are considered to be very effective for the direct fermentation of soluble starch to ethanol.

Aerobiosis↗
PubMed2002

A comparison of trace element concentrations in cultured and wild carp (Cyprinus carpio) of Lake Kasumigaura, Japan.

The concentrations of 13 elements were determined in the muscle, liver, intestine, kidney, and gonads of cultured and wild carp caught at two sites in Lake Kasumigaura, Japan, between September 1994 and September 1995. Despite having a reputation for being heavily polluted, the carp were not heavily burdened with metals. Our results suggest that despite their dietary differences, the wild and cultured fish were accumulating and distributing metals in the same manner and that aquaculture practices are not increasing metal concentrations in these fish. Metal concentrations were lowest in muscle, and did not exceed established quality standards for fish. The differences in metal concentrations between cultivated and wild carp are negligible and should pose no health problems for consumers of either type of fish.

Animal Feed↗
PubMed2002

Western blotting analysis of the beta-hexosaminidase alpha- and beta-subunits in cultured fibroblasts from cases of various forms of GM2 gangliosidosis.

OBJECTIVES: The GM2 gangliosidoses are a group of genetic disorders caused by the accumulation of ganglioside GM2 in neuronal cells. We examined the alpha- and beta-subunits of beta-hexosaminidases by a non-radioisotopes detecting system to evaluate whether it was a useful method for understanding of the pathophysiologies of GM2 gangliosidoses. MATERIALS AND METHODS: We investigated the alpha- and beta-subunits of beta-hexosaminidases in cultured fibroblasts from cases of various forms of GM2 gangliosidosis by means of Western blotting and a chemiluminescence detection system. RESULTS: In a patient with infantile Tay-Sachs disease [HEXA genotype, Int5-SA(g-1-->t)/Int5-SA(g-1-->t)], the mature alpha-subunit was undetectable. In a patient with infantile Sandhoff disease (HEXB genotype, C534Y/C534Y), the mature beta-subunit was deficient. However, a small amount of the mature beta-subunit was detected in a patient with adult Sandhoff disease (HEXB genotype, R505Q(+I207V)/R505Q(+I207V)), which may have resulted in the residual enzyme activity and mild clinical course. Normal amounts of alpha- and beta-subunits were detected in a patient with GM2 activator deficiency. CONCLUSION: This method is easy and sensitive for detecting target proteins, and is useful for clarification of the pathophysiologies of GM2 gangliosidoses.

Adult↗
PubMed2002

Up-regulation of COX-2 by inhibition of COX-1 in the rat: a key to NSAID-induced gastric injury.

BACKGROUND: A recent study demonstrated that inhibition of both cyclooxygenase (COX)-1 and COX-2 is required for the development of nonsteroidal anti-inflammatory drug (NSAID)-induced gastric lesions. However, the role of COX-1 or COX-2 inhibition in the pathogenisis of these lesions remains unclear. AIM: To examine the gastric ulcerogenic properties of selective COX-1 and COX-2 inhibitors in rats and to investigate further the relationship of COX inhibition to various events involved in the process of NSAID-induced gastric lesions. METHODS: Animals were given various COX inhibitors p.o., either alone or in combination, and killed 8 h later. Under the treatment, gastric damage, prostaglandin (PG) E2 content, mucosal permeability, myeloperoxidase (MPO) activity as well as gastric motility were examined. RESULTS: The nonselective COX inhibitor indomethacin inhibited PGE2 production, enhanced gastric motility, and provoked severe lesions in the stomach, with an increase in mucosal permeability and MPO activity. In contrast, the selective COX-2 inhibitor rofecoxib did not induce any damage in the stomach and had no effect on mucosal PGE2 content. Similarly, the selective COX-1 inhibitor SC-560 also caused no gastric damage, despite inhibiting PGE2 production. The combined administration of SC-560 and rofecoxib, however, provoked gross damage in the gastric mucosa, in a dose-dependent manner for each drug. SC-560, but not rofecoxib, caused marked gastric hypermotility and an increase in mucosal permeability, although an increase in MPO activity was observed only when rofecoxib was coadministered. The normal gastric mucosa expressed COX-1 mRNA and not COX-2 mRNA, but COX-2 mRNA was expressed in the stomach after administration of SC-560 as well as indomethacin but not rofecoxib. CONCLUSION: These results suggest that the gastric ulcerogenic properties of NSAIDs are not accounted for solely by COX-1 inhibition, but require the inhibition of both COX-1 and COX-2. The inhibition of COX-1 up- regulates COX-2 expression, and COX-2/PGs may, in turn, counteract the deleterious affects of gastric hypermotility due to COX-1 inhibition.

Amino Acid Sequence↗
PubMed2002

Suplatast tosilate inhibits thymus- and activation-regulated chemokine production by antigen-specific human Th2 cells.

BACKGROUND: Suplatast tosilate is an anti-allergic agent that suppresses cytokine production by human Th2 cells. OBJECTIVE: We investigated the effects of suplatast tosilate on the production of thymus- and activation-regulated chemokine (TARC) by T cells from allergic patients with asthma. METHODS: Purified protein derivative (PPD)-specific Th1 cell lines and Dermatophagoides farinae (Der f)-specific Th2 cell lines were established from nine patients with house dust mite-allergic asthma. The effects of suplatast tosilate on mRNA expression of TARC and protein production of TARC from antigen-specific Th1 or Th2 cell lines were investigated after stimulation with relevant antigens or phytohemagglutinin (PHA). In addition, the effects of IL-4, IL-10, and IFN-gamma on TARC production by Der f-specific Th2 cell lines in the presence or absence of suplatast tosilate were studied. RESULTS: Although PPD-specific Th1 cell lines did not produce TARC after stimulation with PPD antigen or PHA, stimulation of Der f-specific Th2 cell lines with Der f antigen or PHA increased production of TARC. Suplatast tosilate significantly and dose-dependently inhibited production of TARC by Der f-specific Th2 cell lines stimulated with either Der f antigen (76.5% inhibition at 100 microg/mL, P < 0.01) or PHA (81.9% inhibition at 100 microg/mL, P < 0.01). TARC production by Der f-specific Th2 cell lines was significantly increased only by activation with IL-4 but not with IL-10 or IFN-gamma; this increase in TARC production was significantly inhibited by suplatast tosilate (97.5% inhibition at 100 microg/mL, P < 0.01). CONCLUSION: Suplatast tosilate inhibits TARC production by human Th2 cells. Therefore, this agent inhibits both Th2 cytokine and Th2 chemokine and may be a useful anti-allergic agent.

Adult↗
PubMed2002

Use of facial artery musculomucosal flap for closure of soft tissue defects of the mandibular vestibule.

We present the use of the inferiorly based facial artery musculomucous (FAMM) flap to repair a defect of the mandibular vestibule, and discuss the advantages and disadvantages of this procedure. The FAMM flap an effectively cover defects of the mandibular vestibule and other regions of the oral cavity, and its softness, toughness, and minimal shrinkage allow for the use of dental prostheses.

Arteries↗
PubMed2002

Arsenic contamination in Bangladesh groundwater: a major environmental and social disaster.

In attempting to eliminate disease caused by drinking polluted surface water, millions of shallow surface wells were drilled into the Ganges delta alluvium in Bangladesh. The latest statistics indicate that 80% of Bangladesh and an estimated 40 million people are at risk of arsenic poisoning-related diseases because the ground water in these wells is contaminated with arsenic. The clinical manifestations of arsenic poisoning are myriad, and the correct diagnosis depends largely on awareness of the problem. Patients with melanosis, leuco-melanosis, keratosis, hyperkeratosis, dorsum, non-petting edema, gangrene and skin cancer have been identified. The present article reviews the current arsenic contamination of ground water, hydrological systems, groundwater potential and utilization and environmental pollution in Bangladesh. This paper concludes by clarifying the main actions required to ensure the sustainable development of water resources in Bangladesh.

Arsenic↗
PubMed2002

[Therapeutic strategy for a patient suffering from a peripheral pulmonary tumor in the right upper lobe and an endotracheal tumor in the carina].

A 64-year-old male, who had received successful radiotherapy for the previous laryngeal cancer, was admitted to our department for the treatment of a peripheral pulmonary tumor in the right upper lobe and an endotracheal tumor in the carina. The endotracheal biopsy of the carinal tumor demonstrated squamous cell carcinoma, though preoperative examination of the intrapulmonary tumor was unable to clarify it's pathological type. The intrapulmonary tumor required right upper lobectomy and R2 lymph node dissection as a measure against the possibility of primary lung cancer. Since the endotracheal cancer was diagnosed as an intra mucosal tumor by the preoperative computed tomography (CT) scans and the bronchoscopic examination, laser abrasion therapy to the endotracheal tumor was performed 4 days before the lobectomy of the intrapulmonary tumor. After the pulmonary operation, the intrapulmonary tumor was diagnosed as squamous cell carcinoma without lymph node metastasis, and it was suggested to be a metastatic tumor of the previous laryngeal cancer. Both radiotherapy to the carina and general chemotherapy with docetaxel hydrate and carboplatin were used as adjuvant therapies 36 days after the lobectomy. One year after the pulmonary surgery, there is no recurrence of the tumor in the lung or carina. Laser abrasion therapy to the endotracheal tumor is very useful and safe for the patient, who should then receive pulmonary resection soon after the therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

[Clinical study of eight thymic carcinomas].

Eight patients with thymic carcinoma were surgically treated at Sapporo City General Hospital from September 1990 to January 2002. The histological subtypes of thymic carcinoma were squamous cell in 5, undifferentiated in 2, and small cell in one. After median sternotomy, 5 patients had total resection of the tumor, and 3 had incomplete resection due to extensive mediastinal invasion involving the main pulmonary artery in the A-P window. Of 3 cases with intra pericardial malignant effusion, one patient survived 7 years without recurrence of the tumor after the exploratory operation followed by mediastinal irradiation without chemotherapy. In this patient, existence of the malignant cells in the pericardial effusion was not associated with poor outcome.

Adult↗
PubMed2001

Design and synthesis of non-peptidic inhibitors for the Syk C-terminal SH2 domain based on structure-based in-silico screening.

Structure-based in-silico screening was carried out for the Syk C-terminal SH2 domain. Fragments that could interact with the pY or pY+1 pockets were selected by our in-silico screening. After tethering two fragments bound to these pockets, we have designed and synthesized new compounds that show favorable interaction with the pY+3 pocket. One such compound, having a cyclohexylmalonic acid moiety identified as a novel potent phosphotyrosyl mimetic, exhibited an affinity comparable to that of the monophosphorylated ligand peptide.

Binding, Competitive↗