Biomedical subjects

T Mizuno

Publications and source records attributed to T Mizuno.

At least 37 records · Page 2Linked to original sources

PubMed2003

Fas-induced apoptosis in B cells.

Engagement of the cell surface receptor Fas/APO-1 (CD95) initiates a sequence of intracellular events that leads to apoptotic cell death, and this outcome occurs in B cells as it does in other cell types. Fas signaling for B cell death is of particular interest because the expression and function of Fas is altered by engagement of additional cell surface receptors, leading to marked receptor-specific variation in susceptibility to Fas-induced apoptosis. Evidence suggests that the sensitivity of B cells to Fas-mediated apoptosis is intimately connected to homeostasis in the serological arm of the immune system and plays a role in the dysregulation that occurs in certain autoimmune and malignant dyscrasias.

Animals↗

PubMed2003

Molecular cloning of feline tumour necrosis factor receptor type I (TNFR I) and expression of TNFR I and TNFR II in lymphoid cells in cats.

Tumour necrosis factor (TNF)-alpha is a pro-inflammatory cytokine produced by many types of cells. It has been shown that two distinct TNF receptors (TNFRs), TNFR type I (TNFR I) and TNFR type II (TNFR II), have different functions in signal transduction, which is possibly associated with the development of a variety of diseases. In this study, we isolated a feline TNFR I cDNA clone and analysed the expression of TNFR I and TNFR II mRNA in feline lymphoid cells. The deduced amino acid sequence of feline TNFRI cDNA showed 75.8, 62.5 60.9 and 72.1% similarity with those of its human, mouse, rat, and pig counterparts, respectively. The feline TNFR I cDNA was shown to encode extracellular, transmembrane and intracellular domains fundamentally conserved in the homologues of other species. Expression of TNFR I and TNFR II mRNAs was shown to be up-regulated in feline peripheral blood mononuclear cells (PBMC) by stimulation with concanavalin A. Five of six feline lymphoma cell lines were shown to express both TNFR I and TNFR II mRNAs. The expression of TNFR I in PBMC was up-regulated in cats infected with feline immunodeficiency virus (FIV), whereas the expression of TNFR II in PBMC was not different between FIV-infected cats and uninfected cats. The present study indicate that expression of TNFR I and TNFR II may be associated with disease progression, especially in retrovirus infections in cats.

Amino Acid Sequence↗

PubMed2002

Effect of increased dosage of the ML-236B (compactin) biosynthetic gene cluster on ML-236B production in Penicillium citrinum.

The gene cluster responsible for ML-236B (compactin) biosynthesis has recently been characterized from P. citrinum No. 41520. Here, we describe how the ML-236B-producing strain was improved using a cosmid-mediated recombination technique. The introduction of the cosmid pML48, which contains seven of the nine ML-236B biosynthetic genes, into P. citrinum No. 41520 resulted in transformants which produced increased amounts of ML-236B. Southern analysis showed that pML48 had been incorporated by a homologous recombination event, and all high producers possessed two copies of each of the seven genes, mlcA- mlcF and mlcR, suggesting that increased dosage of the biosynthetic gene cluster was responsible for the enhanced production of ML-236B. On the other hand, various kinds of mutants with decreased titers of ML-236B were also obtained. Characterization of one such mutant, designated as T48.28, which was more sensitive to ML-236B than the parental strain, suggested that one of the ML-236B biosynthetic genes, mlcD, which encodes a putative HMG-CoA reductase, was involved in conferring resistance to ML-236B.

Base Sequence↗

PubMed2002

CADASIL and genetics of cerebral ischaemia.

Recent advances suggest the existence of several autosomal dominantly inherited forms of cerebrovascular disorders. Mutations in diverse genes may induce direct pathological changes in intracranial vessels to cause cerebral ischaemic or haemorrhagic strokes leading to cognitive impairment and dementia. Similar pathology may also be caused by systemic vascular disease resulting from mutations and polymorphisms in genes that regulate cardiovascular physiology, blood coagulation and metabolic functions. The most common form of familial stroke appears to be CADASIL or cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. CADASIL is an arterial disease that has been linked to nucleotide substitutions and deletions in the Notch 3 gene. The pathogenesis of the disorder or how the mutations lead to cerebral infarcts and dementia is not known. However, elucidation of the microvascular pathology associated with such genetic disorders not associated with physiological risk factors for cardiovascular disease or stroke can bear much light on primary vascular mechanisms that lead to ischaemic blood flow and neuronal vulnerability.

Animals↗

PubMed2002

Measurement of ulnar flow is helpful in predicting ischemia after radial artery harvest.

BACKGROUND: Despite a negative Allen test, some patients develop hand ischemia after radial artery harvesting. The presence of large interosseous collaterals may reduce the sensitivity of Allen test. To evaluate the combination of ulnar flow measurements and the Allen test as an effective screening technique, we performed Doppler ultrasonography during Allen's maneuver. METHODS: The Allen test was used to select candidates for harvesting radial artery from 80 patients undergoing coronary bypass surgery. RESULTS: Of 71 patients with a negative Allen test, one patient developed hand ischemia. This patient was one of six (7.5 %) possessing low ulnar flow levels (less than 40 ml/min/m(2) during compression of the radial artery). This low-flow group had a higher risk for ischemia of the 71 patients with a negative Allen test. The post-operative flow differed greatly from the pre-operative flow in eight patients (11.3 %), which was likely due to large sacrificed interosseous collaterals. CONCLUSION: Combined use of ulnar flow measurement with the Allen test appears to increase the sensitivity of the Allen test. Neither test, however, is sufficient for a group of patients with large interosseous collaterals.

Coronary Artery Bypass↗

PubMed2002

Acetazolamide vasoreactivity in vascular dementia and persistent vegetative state evaluated by transcranial harmonic perfusion imaging and Doppler sonography.

To clarify the pathophysiological differences of the cerebrovascular reserve capacity in relation to cerebral cognitive impairments between vascular dementia (VaD) and persistent vegetative state (PVS), we evaluated acetazolamide (ACZ) vasoreactivity testing by transcranial harmonic perfusion imaging (HPI) and Doppler sonography (TCD). Sixteen patients (age: 29-85 years; mean: 62) were divided into three groups: 7 VaD, 4 PVS, and 5 nondementia patients. Mean velocity (Vm) in the middle and posterior cerebral artery (MCA, PCA) was measured, and time-intensity curves of the HPI were evaluated at three regions of interest-the bilateral temporal lobe (TL), basal ganglia (BG), and thalamus (Th). TCD and HPI were evaluated before (resting state) and after ACZ administration, and vasoreactivity was compared among the three groups in terms of resting values and relative changes (%Delta) of Vm, peak intensity (PI), area under curve (AUC), and mean transit time (MTT). Results of the resting state: Decreased Vm, PI, and AUC of the VaD and PVS groups were more obvious in the right side. Results of vasoreactivity: In the PVS group, %DeltaVm decreased in the left PCA and MCA; %DeltaPI and %DeltaAUC decreased in the left TL and bilateral BG. In the VaD group, %DeltaPI and %DeltaAUC decreased in the right TL; %DeltaMTT tended to increase in the left side. ACZ vasoreactivity tests by transcranial HPI and TCD allowed bedside, noninvasive quantitative evaluation of the pathophysiology of cognitive function impairment in relation to cerebrovascular reserve capacity in VaD and PVS.

Acetazolamide↗

PubMed2002

2-Nicotinamidoethyl nitrale (2-NN) protects myocardium in ischemia and reperfusion via the protein kinase C pathway.

BACKGROUND: Several recent studies have suggested an ATP-sensitive potassium channel opener (2-nicotinamidoethyl nitrate: 2-NN) may exert a protective effect against the myocardial ischemic/reperfusion injury. This study examines the effects of 2-NN on intracellular signaling by measuring intracellular cyclic AMP, cyclic GMP accumulation and protein kinase C (PKC) activity after 2-NN perfusion. METHODS: Ischemia/reperfused hearts were made by LAD occlusion for 30 min followed by 30 min of reperfusion in isolated rat hearts. Hearts were pre-perfused with 0.1 mM 2-NN, 100 nM Calphostin C, or 2-NN plus Calphostin C for 10 min prior to ischemia. The left ventricular function, cyclic AMP, cyclic GMP and LDH were examined to determine the effects of 2-NN on ischemic/reperfusion injury. Four separate groups of hearts were stained with a bisindolylmaleimide PKC inhibitor conjugated to fluorescein (fim, Teflabs) and PKC activity was measured. RESULTS: 2-NN reduced ischemia/reperfusion injury as evidenced by the enhanced myocardial functional recovery, decreased LDH release after reperfusion, and decreased reperfusion arrhythmias. The PKC inhibitor attenuated myocardial functional recovery but not reperfusion arrhythmias. Cyclic AMP levels decreased after 10 min of 2-NN perfusion, compared to controls. We observed an increase in PKC activity after 2-NN treatment. CONCLUSIONS: These results suggest that PKC plays a significant role in the cardioprotective effect of 2-NN on ischemic and reperfused myocardium. The anti-arrhythmic effect of 2-NN in the reperfusion phase may be linked its action on the ATP-sensitive potassium channel itself rather than its effect on PKC activity.

Animals↗

PubMed2001

TNF-alpha-induced cell death in feline immunodeficiency virus-infected cells is mediated by the caspase cascade.

TNF-alpha induced apoptosis in a feline fibroblastic cell line (CRFK) infected with FIV but not in its uninfected control. In this study, to understand the molecular basis of the different susceptibilities to TNF-alpha between FIV-infected and uninfected cells, we examined the expression of TNF receptors and the activation of the caspase and NF-kappaB pathways. Expression levels of TNFR I and TNFR II mRNAs were similar between uninfected and FIV-infected CRFK cells. To understand the role of caspases in TNF-alpha-induced apoptosis, we examined the effect of three different classes of caspase inhibitors, Z-VAD-FMK, Ac-YVAD-CMK, and Z-DEVD-FMK, on the TNF-alpha-induced apoptosis in FIV-infected cells. Pretreatment with each of these caspase inhibitors protected FIV-infected CRFK cells from TNF-alpha-induced cell death. Moreover, one of the caspase substrates, poly(ADP-ribose) polymerase, was shown to be cleaved after TNF-alpha treatment in FIV-infected CRFK cells but not in uninfected CRFK cells. Electrophoretic mobility shift assay using an NF-kappaB motif oligonucleotide and promoter assay using an NF-kappaB luciferase reporter construct indicated that TNF-alpha treatment had induced activation of NF-kappaB in both FIV-infected and uninfected CRFK cells. The present study indicates that TNF-alpha-induced apoptosis in FIV-infected CRFK cells is mediated by the activation of the caspase cascade, but not by either upregulation of TNF receptor or inhibition of NF-kappaB.

Amino Acid Chloromethyl Ketones↗

PubMed2001

Possible association of beta2- and beta3-adrenergic receptor gene polymorphisms with susceptibility to breast cancer.

BACKGROUND: The involvement of beta2-adrenergic receptor (ADRB2) and beta3-adrenergic receptor (ADRB3) in both adipocyte lipolysis and thermogenic activity suggests that polymorphisms in the encoding genes might be linked with interindividual variation in obesity, an important risk factor for postmenopausal breast cancer. In order to examine the hypothesis that genetic variations in ADRB2 and ADRB3 represent interindividual susceptibility factors for obesity and breast cancer, we conducted a hospital-based, case-control study in the Aichi Cancer Center, Japan. METHODS: A self-administered questionnaire was given to 200 breast cancer patients and 182 control individuals, and pertinent information on lifestyle, family history and reproduction was collected. ADRB2 and ADRB3 genotypes were determined by polymerase chain reaction (PCR) restriction fragment length polymorphism assessment. RESULTS: Twenty-five (12.4%) breast cancer patients and 32 (17.6%) control individuals were found to bear a glutamic acid (Glu) allele for the ADRB2 gene (odds ratio [OR] 0.67, 95% confidence interval [CI] 0.38-1.18), and 60 (30.0%) breast cancer patients and 61 (33.5%) control individuals were found to bear an Arg allele for the ADRB3 gene (OR 0.85, 95% CI 0.55-1.31). A significantly lower risk was observed in those who carried the Glu ADRB2 allele and who reported first childbirth when they were younger than 25 years (OR 0.35; 95% CI 0.13-0.99). CONCLUSION: A potential association may exist between risk of breast cancer and polymorphisms in the ADRB2 and ADRB3 genes; further studies in larger samples and/or in different ethnic groups are warranted to investigate this potential association.

Adult↗

PubMed2001

LeuO expression in response to starvation for branched-chain amino acids.

The recently identified role of LeuO in the regulation of transcription has prompted us to search for the specific function(s) of LeuO in bacterial physiology. The cryptic nature of expression of leuO has previously limited such analysis. A conditional leuO expression was found when bacteria enter stationary phase and was shown to be guanosine 3',5'-bispyrophosphate-dependent. Multiple physiological events, including the stringent response, are induced upon the increase of the bacterial stress signal, guanosine 3',5'-bispyrophosphate. In this study, we tested whether LeuO was directly involved in the bacterial stringent response. LeuO was shown to be indispensable for growth resumption following a 2-h growth arrest caused by starvation for branched-chain amino acids in an E. coli K-12 relA1 strain. This result supports a functional role for LeuO in the bacterial stringent response.

Amino Acids, Branched-Chain↗

PubMed2001

Solution structure and dynamic character of the histidine-containing phosphotransfer domain of anaerobic sensor kinase ArcB from Escherichia coli.

An Escherichia coli sensor kinase, ArcB, transfers a phosphoryl group to a partner response regulator in response to anaerobic conditions. Multidimensional NMR techniques were applied to determine the solution structure of the histidine-containing phosphotransfer signaling domain of ArcB (HPt(ArcB)), which has a phosphorylation site, His717. The backbone dynamics were also investigated by analyses of the (15)N relaxation data and amide hydrogen exchange rates. Furthermore, the protonation states of the histidine imidazole rings were characterized by means of (1)H and (15)N chemical shifts at various pHs. The determined solution structure of HPt(ArcB) contains five helices and forms a four-helix bundle motif like other HPt domains. The obtained order parameters, S (2), [(1)H]-(15)N heteronuclear NOE values, and chemical exchange parameters, R(ex), showed that the alpha-helical regions of HPt(ArcB) are rigid on both picosecond to nanosecond and microsecond to millisecond time scales. On the other hand, helix D, which contains His717, exhibited low protection factors of less than 4000, indicating the presence of fluctuations on a slower time scale in helix D. These results suggest that HPt(ArcB) may undergo a small conformational change in helix D upon phosphorylation. It was also shown that the imidazole ring of His717 has a pK(a) value of 6.76, which is similar to that of a solvent-exposed histidine imidazole ring, and that a pair of deprotonated neutral tautomers are rapidly exchanged with each other. This is consistent with the solution structure of HPt(ArcB), in which the imidazole ring of His717 is exposed to the solvent.

Amides↗

PubMed2001

Molecular diversity in zebrafish NCAM family: three members with different VASE usage and distinct localization.

NCAM in vertebrates and its related molecules, apCAM in Aplysia, fasciclin II in Drosophila, and OCAM in mammals, play key roles in various aspects of brain development and functions. In this study, we have identified and characterized three members of the NCAM gene family in zebrafish, designated as zNCAM, zOCAM, and zPCAM. Three molecules exhibit similar domain organization: an amino-terminal signal peptide, five immunoglobulin-like domains, two fibronectin type III-like domains, a transmembrane segment, and a carboxy-terminal cytoplasmic region. A novel molecule zPCAM is most closely related to zNCAM with 66% amino acid identity. Diversity in the extracellular region of zPCAM is generated by insertion of two different types of variable alternatively spliced exons. In situ hybridization analysis revealed that three molecules were specifically expressed by the central and peripheral nervous systems from early developmental stages in region-specific and cell-type-specific manners. For example, zPCAM showed a neuromere-specific segmental expression pattern, while zOCAM first appeared in specific clusters of secondary neurons in the forebrain. These results suggest that each member of the NCAM gene family plays distinct roles in the formation and maintenance of functional neuronal networks in the zebrafish nervous system.

Age Factors↗

PubMed2001

Double patch technique for repairing postinfarction ventricular septal defect.

We report 2 cases in which the double patch technique was used to repair an anterior postinfarction ventricular septal defect. To do this, we modified infarct exclusion as follows: In addition to a conventional patch excluding the infarcted muscle, another small patch is used to directly close the septal defect. Gelatin-resorcin-formal glue is applied between the double patches, which prevent the glue from being washed away and enhance it to polymerize stably, thereby rapidly stabilizing the infarcted myocardium with the endocardial patch. Echocardiography immediately after operation showed the infarcted septum had completely adhered to the endocardial patch. Both patients demonstrated satisfactory postoperative hemodynamics. Although 1 patient did well, the other died 6 months postoperatively due to complications of pneumonia and gastrointestinal bleeding secondary to colon carcinoma. This double patch technique appears useful, although further experience is needed to verify its safety and efficacy.

Aged↗

PubMed2001

Transvenous embolization for vertebral arteriovenous fistula: report of two cases and technical notes.

BACKGROUND: Vertebral arteriovenous fistulas are relatively rare. Although the common treatment is transarterial embolization, it may be impossible to pass through the fistula (e.g. a microfistula created by a needle puncture). We report two patients with vertebral arteriovenous fistulas due to penetrating trauma who were successfully treated by transvenous embolization. METHOD: We present 2 patients with vertebral arteriovenous fistulas. One patient is presented to demonstrate complications following attempted internal jugular cannulation and the other is presented to demonstrate complications after surgery for a jugular foramen neurinoma. Both patients manifested the sign of a severe bruit. FINDINGS: To identify the fistula point, simultaneous transarterial and transvenous angiography was performed. Using the transvenous approach, microcoils were applied to the fistula and the bruit completely disappeared. Interpretation. Transvenous embolization is a useful technique and a first-choice strategy to treat patients with the vertebral arteriovenous fistula due to penetrating trauma.

Adult↗

PubMed2001

Use of some natural and waste materials for waste water treatment.

A fundamental study was conducted to assess removal and filtration capacity of waste and natural indigenous materials as treatment mediums e.g., shell, limestone, waste paper mixed with refuse concrete, refuse cement, also processed nitrolite, charcoal-bio and charcoal. Under room temperature condition removal of phosphoric, nitric and ammonium-ions, filtration of suspended substance (SS) together with removal of COD in waste water was investigated. Influence of particle size effect for all treatment mediums except for waste paper was pursued. Significant improvement of waste water quality with respect to SS, phosphoric ions and decrease in COD is possible by treating with these filtration mediums. With specific reference to some treatment mediums NO3-N and NH4-N showed reasonable improvement in quality, although generally removal effect was not very significant. Efficacy of treatment was dependent on the particle size of treatment mediums in general, however, nitrolite for NH4--N, charcoal-A for SS and COD, refuse cement mixed with waste paper for PO4 ion removal showed insignificant variability on the particle size effect. Results of this fundamental study demonstrate effectiveness and feasibility for applied application of these proposed waste and naturally available treatment ingredients at lower cost.

Charcoal↗

PubMed2001

Calcium phosphate invert glass-ceramic coatings joined by self-development of compositionally gradient layers on a titanium alloy.

A glass-ceramic layer containing beta-Ca3(PO4)2 crystals could be joined easily with a new type of titanium alloy (Ti-29Nb-13Ta-4.6Zr) consisting of a beta-titanium phase by heating the metal, on which glass powders with a composition of 60CaO x 30P2O5 7Na2O x 3TiO2 were placed, at 800 degrees C in air. Measurement of tensile bonding strength revealed that the joining between the coating layer and the substrate is very strong. Even after the large deformation (e.g., approximately 90 degrees in bending angle) of the titanium alloy, the coating layer was not peeled off from the substrate. A compositionally gradient layer in the TiO2-P2O5-Na2O-CaO system is developed automatically on the titanium alloy during the heating, resulting in the formation of the strong joining. By soaking in simulated body fluid at 37 degrees C, hydroxyapatite phase was formed newly on the surface of the coating layer.

Alloys↗

PubMed2001

Differential induction of LTP and LTD is not determined solely by instantaneous calcium concentration: an essential involvement of a temporal factor.

Two opposite types of synaptic plasticity in the CA1 hippocampus, long-term potentiation (LTP) and long-term depression (LTD), require postsynaptic Ca2+ elevation. To explain these apparently contradictory phenomena, the current view assumes that a moderate postsynaptic increase in Ca2+ leads to LTD, whereas a large increase leads to LTP. No detailed study has so far been attempted to investigate whether the instantaneous Ca2+ elevation level differentially induces LTP or LTD. We therefore used low-frequency (1 Hz) stimulation of Schaffer collateral/commissural fibers in rat hippocampal slices, during a Mg2+-free period, as the conditioning stimulus to investigate this. This allowed low-frequency afferent stimulation to cause a postsynaptic Ca2+ influx because the voltage-dependent block of N-methyl-D-aspartate (NMDA) receptor-channels by Mg2+ was removed. When delivered during the Mg2+-free period, a single pulse, as well as 2-600 pulses, induced LTP that was occluded with tetanus-induced LTP. To decrease the Ca2+ influx, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors were completely blocked by the addition of 10 microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) to the conditioning medium, in which 1 Hz afferent stimuli (1-600 pulses) induced less LTP and never induced LTD. To further reduce the Ca2+ influx, NMDA receptors were partially blocked with D-(-)-2-amino-5-phosphonopentanoic acid (D-AP5). A small number of 1 Hz stimuli, however, never induced LTD. Only when the conditioning stimuli exceeded 200 pulses was LTD induced. The present findings provide definitive evidence that protracted conditioning is a prerequisite for the induction of LTD. Thus, not only the amplitude but also the duration of postsynaptic Ca2+ elevation could be essential factors for differentially inducing LTP or LTD.

2-Amino-5-phosphonovalerate↗

PubMed2001

A novel feature of the multistep phosphorelay in Escherichia coli: a revised model of the RcsC --> YojN --> RcsB signalling pathway implicated in capsular synthesis and swarming behaviour.

In this study, we re-investigated the previously characterized RcsC (sensor His-kinase) --> RcsB (response regulator) phosphorelay system that is involved in the regulation of capsular polysaccharide synthesis in Escherichia coli. The previously proposed model hypothesized the occurrence of a direct phosphotransfer from RcsC to RcsB in response to an unknown external stimulus. As judged from the current general view as to the His --> Asp phosphorelay, this RcsC --> RcsB framework is somewhat puzzling, because RcsC appears to contain both a His-kinase domain and a receiver domain, but not a histidine (His)-containing phosphotransmitter domain (e.g. HPt domain). We thus suspected that an as yet unknown mechanism might be underlying in this particular His --> Asp phosphorelay system. Here, we provide several lines of in vivo and in vitro evidence that a novel and unique His-containing phosphotransmitter (named YojN) is essential for this signalling system. A revised model is proposed in which the multistep RcsC --> YojN --> RcsB phosphorelay is implicated. It was also demonstrated that this complex signalling system is somehow involved in the modulation of a characteristic behaviour of E. coli cells during colony formation on the surface of agar plates, namely swarming.

Amino Acid Sequence↗