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T Taira

Publications and source records attributed to T Taira.

At least 73 records · Page 4Linked to original sources
PubMed1998

Studies on the stereoselective internal acyl migration of ketoprofen glucuronides using 13C labeling and nuclear magnetic resonance spectroscopy.

Internal acyl migration reactions of drug 1beta-O-acyl glucuronides are of interest because of their possible role in covalent binding to serum proteins and consequent allergic reactions as well as their influence on drug disposition. An approach using 13C labeling and nuclear magnetic resonance (NMR) spectroscopy has been used to investigate in situ the kinetics of acyl migration and hydrolysis of 1beta-O-acyl glucuronides of enantiomeric ketoprofens (KPs) in phosphate buffer solutions at 37 degrees C. Apparent first-order degradation of the 1beta-O-acyl glucuronide labeled in the ester carbonyl carbon and the sequential appearance of 2-, 3-, and 4-O-acyl isomers as both alpha- and beta-anomeric forms were observed for each enantiomer. All of the positional isomers and anomers were characterized using two-dimensional NMR spectroscopy (heteronuclear multiple bond correlation, correlated spectroscopy, totally correlated spectroscopy) of the reaction mixtures. The overall degradation rate constants (hr-1) of (R)- and (S)-KP glucuronides were 1.07 +/- 0.154 and 0.55 +/- 0.034, respectively. To evaluate in detail the stereoselective reactivity, a kinetic model describing the rearrangement reactions was constructed, and the kinetics were simulated using a theoretical approach. Only the acyl migration, 1beta-->2beta, was found to have significant stereoselectivity. The rate constants (hr-1) for 1beta-->2beta migration of (R)- and (S)-KP glucuronides were 1.04 +/- 0.158 and 0. 52 +/- 0.029, respectively. The results may suggest that (R)-KP glucuronide could be more susceptible to covalent binding to proteins via acyl migration than the corresponding antipode. This stereoselective reactivity may be responsible for the stereoselective pharmacokinetics of KP. The direct approach using 13C labeling and NMR spectroscopy could also provide insight into the reactivities of other labile drug acyl glucuronides and their isomeric glucuronides.

Acylation↗
PubMed1997

Activation of serum response factor in the liver of Long-Evans Cinnamon (LEC) rat.

We have studied the DNA binding activities of transcription factors in the liver of Long-Evans Cinnamon (LEC) rats, an animal model of Wilson's disease. Owing to a genetic defect, this strain of rats accumulates excessive copper in the liver and develops severe hepatitis and hepatocellular carcinoma. We found that the DNA binding activity of the serum response factor (SRF) was higher in the liver of LEC rats (approximately 2-fold) than in that of Wistar rats. There was a close correlation between the intensity of the activity and the concentrations of copper in the nuclear protein. The DNA binding activity of Sp1, on the other hand, showed similar levels in both LEC and Wistar rats. SRF may play an important role in the development of hepatocellular carcinoma in LEC rats by mediating the proto-oncogene c-fos induction. We suggest that the copper in nuclear protein may be involved in the activation of SRF.

Animals↗
PubMed1997

Long-lasting GABA-mediated depolarization evoked by high-frequency stimulation in pyramidal neurons of rat hippocampal slice is attributable to a network-driven, bicarbonate-dependent K+ transient.

Biphasic GABAA-mediated postsynaptic responses can be readily evoked in CA1 pyramidal neurons of rat hippocampal slices by high-frequency stimulus (HFS) trains in the presence of ionotropic glutamate receptor antagonists. In the present experiments with sharp microelectrodes, whole-cell techniques, and K+-selective microelectrodes, an HFS train (40 pulses at 100 Hz) applied in stratum radiatum close to the recording site evoked a brief hyperpolarizing IPSP (hIPSP), which turned into a prolonged (2-3 sec) depolarization (GABA-mediated depolarizing postsynaptic potential; GDPSP). The I-V relationships of the postsynaptic currents (hIPSC and GDPSC) had distinct characteristics: the hIPSC and the early GDPSC showed outward rectification, whereas the late GDPSC was reduced with positive voltage steps to zero or beyond (inward rectification), but often no clear reversal was seen. That two distinct currents contribute to the generation of the GDPSP was also evident from the finding that a second HFS train at peak or late GDPSP induced a prompt GABAA-mediated hyperpolarization. The GDPSP/C was dependent on the availability of bicarbonate, but not on interstitial or intrapyramidal carbonic anhydrase activity. The HFS train evoked a rapid GABAA-mediated bicarbonate-dependent increase in the extracellular K+ concentration ([K+]o), and the GDPSP followed the K+ transient in a sub-Nernstian manner. The spatial and pharmacological characteristics of the [K+]o shift indicated that it is generated by a local network of GABAergic interneurons. The brief ascending phase of the GDPSP is linked to a K+-dependent accumulation of intracellular Cl-. Thereafter, a nonsynaptic mechanism, a direct depolarizing effect of the [K+]o shift, is responsible for the most conspicuous characteristics of the GDPSP: its large amplitude and prolonged duration.

Animals↗
PubMed1997

A novel G1-specific enhancer identified in the human heat shock protein 70 gene.

Expression of the human heat shock protein 70 gene (hsp70) is induced by various kinds of stress and by oncogenes. In the absence of stress, hsp70 is mainly expressed in the G1and S phases of the cell cycle, but the elements contributing to cell cycle-dependent expression from the hsp70 promoter remain elusive. We have previously reported that two elements, named HSP-MYCA and HSP-MYCB, located approximately 200 bp upstream (-200) from the transcription start site (+1) of human hsp70, are important for initiation of DNA replication at the hsp70 locus. In this report we examine the effect of these two elements on transcriptional activity from the hsp70 promoter, especially in terms of cell cycle-dependent expression. Various segments of the hsp70 promoter region (up to -300) were linked to the luciferase gene and the constructs were transfected into mouse L cells to examine their transcriptional activity. A strong enhancer activity was defined in the HSP-MYCB element, but not in HSP-MYCA. Mutations introduced within HSP-MYCB abolished the transcriptional activation. In synchronized cells, pHB-Luc (a luciferase construct containing approximately 2.4 kb of the hsp70 promoter region) as well as endogenous hsp70 showed two peaks of expression; one in G1 and the other in the S phase. Site-directed mutagenesis of HSP-MYCB in pHB-Luc abolished the expression peak in G1, but not that in the S phase. To test promoter specificity, wild-type and mutant HSP-MYCB elements were then linked to the luciferase gene in combination with the hsp70 , the cyclin A or the PCNA promoter. Both in transient experiments and established cell lines, a strong peak of expression in mid-G1phase was observed with all the constructs containing wild-type HSP-MYCB, but not with the constructs containing the mutant sequence. These results suggest that the HSP-MYCB sequence is a G1-specific enhancer and is responsible for cell cycle-dependent expression of hsp70.

3T3 Cells↗
PubMed1997

DJ-1, a novel oncogene which transforms mouse NIH3T3 cells in cooperation with ras.

We have isolated and characterized the cDNA encoding a novel protein designated DJ-1. DJ-1, sharing no significant homology with the sequences so far reported, did not show transactivation activity in the Gal4 recombinant system, but transformed mouse NIH3T3 cells by itself. Furthermore, DJ-1 showed a cooperative transforming activity with H-Ras, more than 3 times as strong as the activity of ras/myc combination. DJ-1 was ubiquitously expressed in various human tissues, and the expression was induced by growth stimuli. Moreover, DJ-1 translocated from cytoplasm to nuclei in the S phase of the cell cycle. DJ-1 is thus suggested to be a novel mitogen-dependent oncogene product involved in a Ras-related signal transduction pathway.

3T3 Cells↗
PubMed1997

High prevalence of GAD65 (and IA-2) antibodies in Japanese IDDM patients by a new immunoprecipitation assay based on recombinant human GAD65.

Marked differences have been reported in the prevalence of glutamic acid decarboxylase (GAD) antibodies between Caucasian (63-84%) and Japanese (30-50%) or Asian (5-50%) IDDM patients. Using a new immunoprecipitation assay based on 125I-labelled recombinant human GAD65 we have reassessed prevalence of GAD65 antibodies in Japanese patients. We also assessed prevalence of IA-2 antibodies. GAD65 antibodies were detected in 83.3% of sera taken within 1 year of onset, comparable to the prevalence reported in Caucasian patients. Positivity decreased to 66.7% after 2 to 3 years and to 54.3% after 3 years from onset, still higher than previously reported Asian prevalence. Except in one patient, high antibody levels persisted chronically, up to 12 years. There was no difference in the prevalence of GAD65 antibodies between Japanese IDDM patients with and without autoimmune thyroid disease (AITD). IA-2 antibodies were detected in 64.7% of sera taken within 1 year of onset. Prevalence of IA-2 antibodies was lower than that of GAD65 antibodies. The difference in positivity in Asian IDDM patients between present and previous reports arose from the sensitivity of our assay for GAD65 antibodies. Additionally, the patients we studied had classic IDDM with a well-defined onset. We conclude that prevalence of GAD65 antibodies in Japanese IDDM patients is comparable to that in Western studies. There was no relationship of GAD65 antibody positivity to coexistence of AITD. Our results suggest that autoimmunity is the most significant cause of Japanese IDDM.

Adolescent↗
PubMed1997

Direct detection of the internal acyl migration reactions of benzoic acid 1-O-acylglucuronide by 13C-labeling and nuclear magnetic resonance spectroscopy.

1-O-Acyl-beta-D-glucopyranuronates can undergo irreversible binding to proteins mainly through internal acyl migration reactions, which may have toxicological significance. A new method based on the 13C-labeling and nuclear magnetic resonance (NMR) spectroscopy has been developed to study the reactivity of the 1-O-acyl-beta-D-glucopyranuronate of benzoic acid. In phosphate buffer (pH 7.4) solution at 37 degrees C, the glucuronide showed apparent first-order degradation kinetics (T1/2, 125 min), and concurrent and sequential appearance of 2-, 3- and 4-O-acyl isomers as both alpha- and beta-anomers was observed. The isomeric glucuronides were identified by two-dimensional NMR of the reaction mixture. The direct approach using 13C-labeling and NMR could also provide insights into the reactivities of other labile drug acylglucuronides and their isomeric glucuronides.

Benzoates↗
PubMed1997

Split cannula method for accurate placement of an electrode for deep brain stimulation: technical note.

OBJECTIVE: We describe a "split cannula method" for accurate placement of a deep brain stimulation electrode. This method eliminates the risk of displacement of the electrode when withdrawing the outer guide cannula. METHOD: A separate short guide cannula is covered over the distal part of a long cannula for microrecording or macrostimulation. After confirmation of the stimulation point, the short cannula is fixed with an accessory-holding device and the long cannula is pulled out. The electrode for deep brain stimulation is inserted through the short cannula. Because this cannula is much shorter than the electrode, securing the stimulation electrode at any withdrawal stage of the outer guide cannula is always possible. RESULTS AND CONCLUSION: With this simple method, we experienced no displacement of the stimulation point during stereotactic insertion of a deep brain stimulation electrode. This method can be easily adapted to any stereotactic frame.

Brain↗
PubMed1997

Posttetanic excitation mediated by GABA(A) receptors in rat CA1 pyramidal neurons.

The contributions of gamma-aminobutyric acid (GABA) receptors to posttetanic excitation of CA1 pyramidal neurons in rat hippocampal slices were studied using extracellular and intracellular recording techniques. Synaptic responses were evoked on tetanic stimulation (100-200 Hz, 40-100 pulses) applied in stratum radiatum close (300-600 microm) to the recording site. Under control conditions, tetanic stimulation resulted in a triphasic depolarization/hyperpolarization/sustained depolarization sequence in area CA1 pyramidal cells. The late depolarization usually gave rise to a prolonged (< or = 3 s) spike firing. The late depolarization and the associated spike firing were blocked both specifically and completely (within a time window of 3-6 min starting from picrotoxin application) by the GABA(A) receptor antagonist picrotoxin (PiTX, 100 microM). Paradoxically, at this early stage of PiTX application, overall neuronal firing was attenuated to a higher degree than what was achieved by ionotropic glutamate antagonists. Complete block of ionotropic glutamate receptors by the antagonists D-2-amino-5-phosphonopentoate (AP5, 80 microM), 6-nitro-7-sulphamoylbenzo[f]quinoxaline-2,3-dione (NBQX, 10 microM), and ketamine (50 microM) blocked the initial fast depolarization and suppressed the late one. Exposure to a permeable inhibitor of carbonic anhydrase, ethoxyzolamide (EZA, 50 microM) inhibited the late, apparently GABA-mediated depolarization. It is concluded that GABA can provide the main posttetanic excitatory drive in the adult hippocampus. The present results suggest that intense activation of GABAergic interneurons may accentuate the excitation of principal neurons and, hence, play an important facilitatory role in the induction of long-term potentiation (LTP) and epileptogenesis.

2-Amino-5-phosphonovalerate↗
PubMed1997

Volumegraph (overlaid three-dimensional image-guided navigation). Clinical application of augmented reality in neurosurgery.

OBJECTIVE: We have developed an overlaid three-dimensional image (Volumegraph)-guided navigation system that allows navigation during operative procedures. The three-dimensional image is superimposed on the patient's head and body via a semi-transparent mirror. The Volumegraph can display three-dimensional images in the air by a light beam which is based on CT/MRI. METHOD: The system consists of a Volumegraph (thin plate of three-dimensional recorded medium), a Volumegraphscope and an original designed triangular-shaped marker system for registration. The three-dimensional data obtained from CT and MRI before the operation were processed by a computer. Such image data are applied for preoperative investigation to recognize the three-dimensional structure of organs and tumor. These reconstructed three-dimensional images were superimposed and registered at the patient's head according to a fiducial marker (registration). Then the operator can operate with this three-dimensional-image-guided navigation system. RESULTS: Based on clinical application in 7 cases, the system was found to be advantageous because the surgical procedures could be navigated easily by augmented reality in the surgical field. Invisible parts of the surgical field were supplemented with the overlaid three-dimensional images (Volumegraph) as if it were the virtual operative field. At another time, spatial positioning and overlaid visualization by the Volumegraph was useful for identifying anatomical structures and functional location in the image. CONCLUSION: This preliminary study of overlaid three-dimensional-image-guided navigation demonstrated its clinical usefulness. The application of augmented reality in the surgical field makes it possible to do a neurosurgical intervention easily and accurately.

Brain Neoplasms↗
PubMed1997

Induction of apoptosis in HeLa cells by MSSP, c-myc binding proteins.

MSSP (c-myc gene single strand binding proteins) were identified as protein factors binding to a putative replication origin/transcriptional enhancer sequence present upstream from the human c-myc gene, and two cDNAs encoding highly homologous proteins, MSSP-1 and MSSP-2, have been cloned. Scr2, independently cloned as a factor which complements the cdc2 defective mutant of Schizosaccharomyces pombe, has turned out to be identical to MSSP-1. MSSP-1/Scr2 and MSSP-2 similarly stimulated the initiation of SV40 DNA replication, and thus were suggested to be involved in regulation of cell cycle movement, especially from the G1 to S phase. Here, we examined the functions of MSSP in apoptosis. MSSP expression plasmids were transfected to human HeLa cells together with a beta-galactosidase expression vector. After incubation in the presence of 2% calf serum, cells were stained with X-gal and morphologically apoptotic cells among the beta-galactosidase-positive cells were counted. Both MSSP-1 and 2 induced apoptosis in a dose-dependent manner as in the control experiments with c-myc or adenovirus E1A. DNA fragmentation, a hallmark of apoptosis, was also observed in cells transfected with MSSP expression plasmids. The results of experiments using various deletion mutants of MSSP indicated that the region containing one of the two RNP consensus motifs, RNP1-B, is required for induction of apoptosis as well as specific DNA binding activity.

Adenovirus E1A Proteins↗
PubMed1997

[Objective evaluation of selective peripheral denervation for spasmodic torticollis].

The authors evaluated the results of selective peripheral denervation (SPD) of posterior rami of the cervical spinal nerves and/or the accessory nerve for spasmodic torticollis. Five patients underwent seven operations in total and the results were evaluated with the modified Tsui's score which was used in the clinical trial of botulinum toxin (BTX) for torticollis in Japan. The preoperative score was 10.8 +/- 2.2 (mean +/- S.D.) and the postoperative score was 1.4 +/- 1.7. The score changes indicated the effects of the operation as "excellent" in four cases and "good" in one case. These results indicate that SPD is superior to BTX in terms of control of symptoms in spasmodic torticollis. After the initial operation, however, two patients showed the so-called "mole-hitting game phenomenon" in which normal muscles develop abnormal contraction after denervation of abnormal muscles. This forced us to perform the second operations. Although this phenomenon was first described in botulinum toxin treatment, this is probably the first report in surgically denervated cases.

Adult↗
PubMed1996

Activity-induced enhancement of HB-GAM expression in rat hippocampal slices.

Heparin-binding growth-associated molecule (HB-GAM) is a developmentally regulated secretory protein with neurite outgrowth-promoting activity. High-frequency stimulation leading to induction of long-term potentiation (LTP) resulted in increased expression of HB-GAM in rat hippocampal area CA1. When tetanization was given in the presence of antagonists of the N-methyl-D-aspartate (NMDA) receptor and postsynaptic voltage-gated calcium channels, the mRNA level was comparable to control levels. The results indicate that high frequency stimulation inducing LTP results in calcium-dependent enhancement in HB-GAM expression, and imply a role for this extracellular protein in the modulation of synaptic function in the hippocampus.

Animals↗
PubMed1996

Effects of CO2 on excitatory transmission apparently caused by changes in intracellular pH in the rat hippocampal slice.

It is generally known that hyperventilation produces an increase in neuronal excitability. However, the mechanism whereby a change in CO2 partial pressure (PCO2) leads to changes in neural excitability is not known. We have studied this phenomenon in rat hippocampal slices using double-barrelled microelectrodes for simultaneous recording of field excitatory postsynaptic potentials (EPSPs) and extracellular pH in stratum radiatum of area CA1. A drop in PCO2 from the control level, 36 mmHg to 7 mmHg, produced an increase in extracellular pH of 0.4-0.6 pH units and a transient increase in EPSP slope by about 20-30%. Despite the stable extracellular alkalosis, the EPSP reverted back to its original level within 10 min. Switching back to 36 mmHg PCO2 restored the original extracellular pH and caused a transient decrease in the EPSP slope. Pharmacological blockade of NMDA receptor and/or GABAA receptor had no influence on the effects of CO2. An increase in PCO2 to 145 mmHg led to a stable fall in extracellular pH by 0.6 units and to a transient 30-50% decrease in EPSP slope. The above results indicate that the CO2-induced changes in neuronal excitability were not caused by changes in extracellular pH but they might have been mediated by changes in intracellular pH. Indeed, exposing the slices to the permeant weak base, trimethylamine (20 mM), which is known to produce a rise in intracellular pH, increased the EPSP slope by 50-70%. Application of 20 mM propionate (a permeant weak acid) decreased the EPSP slope by 40-60%. We conclude that the transient changes in the EPSP seen in response to changes in PCO2 are mediated by in intracellular pH.

2-Amino-5-phosphonovalerate↗
PubMed1996

Expression of epidermal growth factor and its receptor in rabbits with ischaemic acute renal failure.

Urinary immunoreactive epidermal growth factor (EGF) levels decrease, and renal immunoreactive EGF levels increase in rats with ischaemic acute renal failure (ARF). We investigated the immunohistochemical localization of EGF and EGF receptor in rabbits with ischaemic ARF to clarify the significance of renal EGF. Male New Zealand White rabbits underwent right nephrectomy prior to a 60 min renal artery clamp. At 3, 6, 24, 48, 72 and 96 h after ischaemia, serum urea nitrogen and serum creatinine were determined. Guinea pig anti-rabbit EGF antibody and monoclonal anti-EGF receptor antibody were used for the primary incubation. EGF was immunolocalized to the ascending limb of Henle and the distal convoluted tubule in the normal right kidneys. However, in the post ischaemic left kidneys at 6, 24, 48 and 72 h, immunoreactivity of EGF was associated with proximal tubules. In the normal kidneys, antibody to EGF receptor reacted with distal tubules and collecting ducts. In the ischaemic kidneys, EGF receptor was localized in the basolateral membrane in the proximal tubules. The expression of EGF and EGF receptor in renal tubules may play an important role in repair following ischaemic renal damage.

Acute Kidney Injury↗
PubMed1996

Comparison of the primary structure of waxy proteins (granule-bound starch synthase) between polyploid wheats and related diploid species.

The waxy proteins encoded by the genomes A, B, and D in polyploid wheats and related diploid species were isolated by SDS-PAGE. The N-terminal amino acid sequences of mature proteins and V8 protease-induced fragments were determined. A total of five amino acid substitutions was detected in these sequences, which represent about 10% of the whole sequences of the waxy proteins. A comparison of these sequences in polyploid wheats with those in related diploid species revealed the following: (i) waxy proteins encoded by the A genome of polyploid wheats were identical to that of Triticum monococcum, (ii) the waxy protein encoded by the B genome of T. turgidum was identical to that of T. searsii, but differed from those of T. speltoides and T. longissimum by one amino acid substitution, (iii) the waxy protein encoded by the B genome of T. aestivum differed from that encoded by the B genome of T. turgidum by one amino acid substitution, and (iv) the waxy protein encoded by the D genome of T. aestivum was identical to that of T. tauschii.

Amino Acid Sequence↗
PubMed1996

A noninvasive method for studying quantitatively heat-evoked nocifensive hindlimb withdrawal reflexes in lightly anesthetized rats.

We have developed a noninvasive method for studying quantitatively the magnitude of hindlimb withdrawal reflexes induced by noxious heat in lightly anesthetized rats. The amplitude, latency, and duration of the hindlimb withdrawal was determined by a very small piezoceramic device placed on the hamstring muscle while the glabrous skin of the hindpaw was stimulated using a feedback-controlled contact thermostimulator. An increase in the amplitude and duration of the withdrawal response, concomitant with a decrease in the response latency, was found with increasing stimulus temperature. The sensitivity of the method was verified using morphine, which produced a dose-related (3.5-7.0 mg/kg) attenuation of all these response components. The use of a piezoceramic device for measuring the withdrawal response provides a quantitative, noninvasive method for evaluating the magnitude of various components of the nocifensive withdrawal reflexes induced by noxious stimuli in lightly anesthetized rats.

Animals↗