Biomedical subjects

K Hirota

Publications and source records attributed to K Hirota.

At least 73 records · Page 4Linked to original sources

PubMed2001

[Pulmonary hypertension associated with refractory hyperthyroidism: a case report].

A 25-year-old woman was admitted to our hospital with goiter. The diagnosis was Grave's disease. Diagnostic transthoracic echocardiography revealed a hyperdynamic stage of the heart with right ventricular dilation. Doppler echocardiography showed mild to moderate tricuspid regurgitation and elevated systolic right ventricular pressure. Right heart catheterization revealed high cardiac output (9.49 l/min) and pulmonary hypertension (57 mmHg) with increased pulmonary vascular resistance and total pulmonary resistance. No intracardiac shunts were detected. Since neither thiomazole nor propylthiouracil was effective and both caused side effects, she underwent subtotal thyroidectomy. After the surgery, pulmonary hypertension improved and cardiac output normalized, but without normalization of pulmonary vascular resistance and total pulmonary resistance. Reversible pulmonary hypertension may occur in patients with hyperthyroidism. Increased pulmonary blood flow and sustained high pulmonary artery resistance were suspected as the causes of pulmonary hypertension. In addition, pulmonary endothelial dysfunction as a result of sustained increased pulmonary blood flow could be another cause of pulmonary hypertension.

Adult↗

PubMed2001

Detection of anti-ovalbumin IgG in serum by immune complex transfer enzyme immunoassay.

An immune complex transfer enzyme immunoassay for anti-ovalbumin IgG in serum is described. Serum-specific antibody was reacted simultaneously with 2,4-dinitrophenyl-bovine serum albumin-ovalbumin conjugate and ovalbumin-peroxidase conjugate. The complex formed by the three components was trapped onto polystyrene balls coated with anti-2,4-dinitrophenyl group IgG, eluted with epsilonN-2,4-dinitrophenyl-L-lysine and transferred to polystyrene balls coated with anti-human IgG-gamma-chain. Bound peroxidase activity was determined by fluorometry. This enzyme immunoassay was 300- to 1,000-fold more sensitive and more reliable than the enzyme-linked immunosorbent assay (ELISA). Anti-ovalbumin IgG was detected in 100% of healthy subjects using this method while only 14% were detected by ELISA.

2,4-Dinitrophenol↗

PubMed2001

[Establishment of tolerable upper intake levels of calcium in Japan and U.S].

Dietary reference intake for Japanese was revised for use from 2000 to 2004. It was included not only the recommended dietary allowances but also new tolerable upper intake levels (UL) . The UL of calcium is 2,500 mg/day and the level has been decided by a model of the risk assessment by lowest observed adverse effect level with uncertain factors such as the sensitivity for individuals. The way how to decide Japanese UL levels has mostly referred to those by American National Academy of Science. Enough calcium intake is necessary for accumulating optimal peak bone mass in the young and also for suppressing the decrease in bone density in the old, however, too much high intake of calcium will have adverse effect on balance of other minerals.

English Abstract↗

PubMed2001

[Not Available].

Explore the source record for details and available documents.

Journal Article↗

PubMed2000

Thioredoxin nuclear translocation and interaction with redox factor-1 activates the activator protein-1 transcription factor in response to ionizing radiation.

Thioredoxin (TRX) is a cytoplasmic, redox-sensitive signaling factor believed to participate in the regulation of nuclear transcription factors mediating cellular responses to environmental stress. Activation of the activator protein (AP)-1 transcription factor is thought to be mediated in part by redox-sensitive interactions between the nuclear signaling protein redox factor-1 (Ref-1) and TRX. In this study, the role of TRX and Ref-1 in the activation of the AP-1 complex was examined in HeLa and Jurkat cell lines exposed to ionizing radiation (IR). After exposure to IR, nuclear levels of immunoreactive TRX increased, accompanied by an increase in AP-1 DNA binding activity. It was shown that a physical interaction between Ref-1 and TRX occurs within the nucleus and is enhanced after exposure to IR. Furthermore, TRX immunoprecipitated from irradiated cells was capable of activating AP-1 DNA binding activity in nonirradiated nuclear extracts. In addition, immunodepletion of Ref-1 from nuclear extracts demonstrated that the increase in AP-1 DNA binding activity after IR was also dependent upon the presence of Ref-1 from irradiated cells. Finally, the ability of both TRX and Ref-1 from irradiated cells to stimulate AP-1 DNA binding in nonirradiated nuclear extracts was abolished by chemical oxidation and restored by chemical reduction. These results indicate that, in response to IR, TRX and Ref-1 undergo changes in redox state that contribute to the activation of AP-1 DNA binding activity. These experiments suggest that a redox-sensitive signaling pathway leading from TRX to Ref-1 to the AP-1 complex participates in the up-regulation of DNA binding activity in response to ionizing radiation.

Animals↗

PubMed2000

Synthesis and applications of [1-(15)N]-labeled 4,6-dimethyl-4H-[1,2,5]oxadiazolo[3,4-d]pyrimidine-5,7-dione 1-oxide as a useful tool for mechanistic investigations.

[1-(15)N]-Labeled 4,6-dimethyl-4H-[1,2,5]oxadiazolo[3,4-d]pyrimidine-5,7-dione 1-oxide (1-(15)N1) was easily prepared by nitration of commercially available 6-amino-1,3-dimethyl-1H-pyrimidine-2,4-dione using 15N-enriched nitric acid followed by an intramolecular oxidative cyclization with iodosylbenzene diacetate under mild conditions. On the basis of the experimental results using 1-(15)N1, the formation of 8-phenyltheophylline (3), the 1,3-dimethylalloxazines (4: n = 0, 1), and 1,3,7,9-tetramethyl-1H,9H-pyrimido[5,4-g]pteridine-2,4,6,8-tetraone++ + (5) in the thermal reaction of the N-oxide 1 with benzylamine, aniline, or piperidine, and the generation of NO or NO-related species in the reaction with N-acetylcysteamine were reasonably explained by considering the initial attack of the employed nucleophiles on the 3a-position of 1.

Aniline Compounds↗

PubMed2000

Barbiturates inhibit K(+)-evoked noradrenaline and dopamine release from rat striatal slices--involvement of voltage sensitive Ca(2+) channels.

The cellular target site(s) for anaesthetic action remain unclear. In rat striatal slices we have previously demonstrated that K(+)-evoked noradrenaline (NA) and dopamine (DA) release is mediated predominantly via P/Q-type voltage sensitive Ca(2+) channels (VSCC). Using this model of Ca(2+) dependent transmitter release we have evaluated the effects of anaesthetic and non-anaesthetic barbiturates. Rat brain striatal slices were incubated in the absence and presence of barbiturate for 10 min at 37 degrees C. The slices were then incubated for 6 min with 40 mM KCl. All anaesthetic barbiturates produced a concentration-dependent inhibition of K(+)-evoked NA and DA release. Non-anaesthetic barbiturate, barbituric acid was ineffective. The pIC(50) for NA and DA release (thiopental: 4.90+/-0.13 and 5.00+/-0.10, pentobarbital: 4.39+/-0.07 and 4.43+/-0.14, phenobarbital: 3.85+/-0.08 and 3.59+/-0.10, respectively) correlated with lipid solubility (NA: r(2)=0.999, DA: r(2)=0.987). We therefore suggest that barbiturates inhibit catecholamine release via an interaction with P/Q VSCC further implicating this channel in anaesthetic action.

Anesthetics↗

PubMed2000

Geranylgeranylacetone enhances expression of thioredoxin and suppresses ethanol-induced cytotoxicity in cultured hepatocytes.

Geranylgeranylacetone (GGA) has been introduced into the clinical field as an anti-ulcer drug. In addition to protective effects on gastric mucosal cells, GGA also has anti-apoptotic effects against ischemia and reperfusion injury in hepatocytes and intestinal cells. However, the molecular mechanisms of the cytoprotective or anti-apoptotic effect of GGA are largely unknown. To explore the molecular mechanism of GGA action, we focused on thioredoxin (TRX), an endogenous-redox-acting molecule. We have demonstrated that GGA induces the messenger RNA and protein of TRX and affects the activation of transcription factors, AP-1 and NF-kappaB, and that GGA blunted ethanol-induced cytotoxicity of cultured hepatocytes. These results provide evidence suggesting that a possible novel molecular mechanism of GGA is to protect cells via the induction of TRX and the activation of transcription factors such as NF-kappaB and AP-1.

Animals↗

PubMed2000

Nucleoredoxin, glutaredoxin, and thioredoxin differentially regulate NF-kappaB, AP-1, and CREB activation in HEK293 cells.

Well-established mechanisms for regulation of protein activity include thiol-mediated oxidoreduction in addition to protein-protein interactions and phosphorylation. Nucleoredoxin (NRX), glutaredoxin (GRX), and thioredoxin (TRX) have been shown to act as a potent thiol reductase and reactive oxygen species regulator. They constitute a oxidoreductase superfamily and have been suggested as a candidate operating in the redox regulation of gene expression. We demonstrated here that intracellular localization of these redox molecules differ from each other and that the redox molecules differentially regulate NF-kappaB, AP-1, and CREB activation induced by TNFalpha, PMA, and forskolin and by expression of signaling intermediate kinases, NIK, MEKK, and PKA in HEK293 cells. This is a first report that describes involvement of NRX and GRX and differences from TRX in transcriptional regulation of NF-kappaB, AP-1, and CREB in living cells.

3T3 Cells↗

PubMed2000

Highly chemoselective hydrogenation with retention of the epoxide function using a heterogeneous Pd/C-ethylenediamine catalyst and THF

In general, palladium-carbon (Pd/C) catalyzed hydrogenation of epoxides affords the corresponding primary and secondary alcohols as a mixture. It has been found that the catalytic activity of a Pd/C -ethylenediamine complex catalyst [Pd/C(en)] in the hydrogenolysis of epoxide functions is drastically reduced. Herein we describe a mild and chemoselective method for the hydrogenation of olefin, nitro, and azide functions with retention of the epoxide function. The chemoselectivity was accomplished by using a combination of 5% Pd/C(en) and THF as solvent. A significant drop in the chemoselectivity of the hydrogenation is observed with 5% Pd/C(en) in MeOH. These results reinforce the utility of epoxides as important precursors of alcohols in synthetic chemistry.

Journal Article↗

PubMed2000

The effects of n-alcohols on evoked synaptic potentials in rat hippocampal slices: Hill coefficients account for the cut-off phenomenon.

The anesthetic potencies of n-alcohols increase progressively with lengthening of the carbon chain and then disappear at a cut-off point of a longer-chain n-alcohol. In order to assess the mechanisms for cut-off in mammalian central nervous system, the effects of a series of n-alcohols (C(2)-C(11)) were examined on the evoked synaptic potentials of the rat hippocampal preparation in vitro. The n-alcohols (C(2)-C(10)) reduced the slope of the excitatory post-synaptic potential in a concentration-dependent manner, and the inhibitory potencies enhanced as a function of carbon chain length. The effect disappeared at n-undecanol (C(11)). The Hill coefficients of the concentration-response curves of the n-alcohols negatively correlated with the number of carbon atoms. The decrease in the Hill coefficient could account for the cut-off phenomenon, indicating that the results can support the anesthetic pocket hypothesis.

Alcohols↗

PubMed2000

Inhibition of the human intermediate conductance Ca(2+)-activated K(+) channel, hIK1, by volatile anesthetics.

Ca(2+)-activated K(+) channels (K(Ca)) regulate a wide variety of cellular functions by coupling intracellular Ca(2+) concentration to membrane potential. There are three major groups of K(Ca) classified by their unit conductances: large (BK), intermediate (IK), and small (SK) conductance of channels. BK channel is gated by combined influences of Ca(2+) and voltage, while IK and SK channels are gated solely by Ca(2+). Volatile anesthetics inhibit BK channel activity by interfering with the Ca(2+) gating mechanism. However, the effects of anesthetics on IK and SK channels are unknown. Using cloned IK and SK channels, hIK1 and hSK1-3, respectively, we found that the currents of hIK1 were inhibited rapidly and reversibly by volatile anesthetics, whereas those of SK channels were not affected. The IC(50) values of the volatile anesthetics, halothane, sevoflurane, enflurane, and isoflurane for hIK1 inhibition were 0.69, 0.42, 1.01 and 1.03 mM, respectively, and were in the clinically used concentration range. In contrast to BK channel, halothane inhibition of hIK1 currents was independent of Ca(2+) concentration, suggesting that Ca(2+) gating mechanism is not involved. These results demonstrate that volatile anesthetics, such as halothane, enflurane, isoflurane, and sevoflurane, affect BK, IK, and SK channels in distinct ways.

Anesthetics, Inhalation↗

PubMed2000

Direct observation of antiferroquadrupolar ordering: resonant X-Ray scattering study of DyB2C2

Antiferroquadrupolar (AFQ) ordering has been conjectured in several rare-earth compounds to explain their anomalous magnetic properties. No direct evidence for AFQ ordering, however, has been reported. Using the resonant x-ray scattering technique near the Dy L(III) absorption edge, we have succeeded in observing the AFQ order parameter in DyB2C2 and analyzing the energy and polarization dependence. The much weaker coupling between the orbital degrees of freedom and the lattice in 4f electron systems than in 3d compounds makes them an ideal platform to study orbital interactions originating from electronic mechanisms.

Journal Article↗

PubMed2000

Effects of 6-formylpterin, a xanthine oxidase inhibitor and a superoxide scavenger, on production of nitric oxide in RAW 264.7 macrophages.

As well as superoxide generated from neutrophils, nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) in macrophages plays an important role in inflammation. We previously showed that 6-formylpterin, a xanthine oxidase inhibitor, has a superoxide scavenging activity. In the present study, to elucidate other pharmacological activities of 6-formylpterin, we investigated the effects of 6-formylpterin on production of nitric oxide (NO) in the murine macrophage cell line RAW 264.7 stimulated by lipopolysaccharide (LPS) and interferon-gamma (INF-gamma). 6-Formylpterin suppressed the expression of iNOS, and it also inhibited the catalytic activity of iNOS, which collectively resulted in the inhibition of NO production in the stimulated macrophages. However, 6-formylpterin did not scavenge the released NO from an NO donor, S-nitroso-N-acetylpenicillamine (SNAP). These results indicate that 6-formylpterin inhibits pathological NO generation from macrophages during inflammation, but that it does not disturb the physiological action of NO released from other sources.

Animals↗

PubMed2000

Renin-dependent cardiovascular functions and renin-independent blood-brain barrier functions revealed by renin-deficient mice.

Renin plays a key role in controlling blood pressure through its specific cleavage of angiotensinogen to generate angiotensin I (AI). Although possible existence of the other angiotensin forming enzymes has been discussed to date, its in vivo function remains to be elucidated. To address the contribution of renin, we generated renin knockout mice. Homozygous mutant mice show neither detectable levels of plasma renin activity nor plasma AI, lowered blood pressure 20-30 mm Hg less than normal, increased urine and drinking volume, and altered renal morphology as those observed in angiotensinogen-deficient mice. We recently found the decreased density in granular layer cells of hippocampus and the impaired blood-brain barrier function in angiotensinogen-deficient mice. Surprisingly, however, such brain phenotypes were not observed in renin-deficient mice. Our results demonstrate an indispensable role for renin in the circulating angiotensin generation and in the maintenance of blood pressure, but suggest a dispensable role for renin in the blood-brain barrier function.

Angiotensin I↗

PubMed2000

Lidocaine added to a tracheostomy tube cuff reduces tube discomfort.

PURPOSE: To examine whether lidocaine diffusion across an endotracheal tube cuff affects tracheostomy tube discomfort. METHODS: Two tracheostomy tube cuffs were inflated with 5 ml lidocaine 4% solution and air at 20 cmH2O, and then placed in 20 ml distilled water at 37 degrees C. After vigorous stirring, 100 microl of this water was then sampled immediately then 1, 2, 4, 8, 24 hr later to measure lidocaine concentration by high-performance liquid chromatography. Sixteen patients undergoing tracheostomy following oral cancer resection were randomly assigned to two groups: lidocaine (n=8) and placebo (n=8). A tracheostomy tube cuff was inflated with 5 ml lidocaine 4% or saline 0.9% and air to a cuff pressure of 20 cmH2O, in the lidocaine and placebo groups respectively. Tube discomfort was evaluated using a visual analogue scale at 0, 0.5, 1, 2 and 4 hr after lidocaine or saline administration. Neither analgesics nor sedatives was given during the evaluation period. RESULTS: Lidocaine time-dependently diffused across the tracheostomy tube cuff. Thirty and 60 min after cuff inflation lidocaine concentrations in the water bath reached approximately 8 and 17 microg x ml(-1) representing 160 and 340 microg in 20 ml of water, respectively. The VAS decreased from 53.5 +/- 10.6 to 25.1 +/- 9.8 mm (P < 0.01) 0.5 hr following lidocaine administration which continued until the end of evaluation period. In the placebo group, VAS did not change. CONCLUSION: Lidocaine diffusion across the tracheostomy tube cuff reduces tube discomfort.

Adult↗

PubMed2000

Effects of intravenous and local anesthetic agents on omega-conotoxin MVII(A) binding to rat cerebrocortex.

PURPOSE: The cellular target site(s) for anesthetic action remain controversial. In this study we have examined any interaction of i.v. anesthetics (thiopental, pentobarbital, ketamine, etomidate, propofol, alphaxalone), local anesthetics (lidocaine, prilocaine, procaine and tetracaine), and the non anesthetic barbiturate, barbituric acid with the omega-conotoxin MVII(A) binding site on N-type voltage sensitive Ca2+ channels in rat cerebrocortical membranes. METHODS: [125I] omega-conotoxin MVII(A) binding assays were performed in 0.5 ml volumes of Tris.HCl buffer containing BSA 0.1% for 30 min at 20 degrees C using fresh cerebrocortical membranes (5 microg of protein). Non-specific binding was defined in the presence of excess (10(-8) M) omega-conotoxin MVII(A). The interaction of i.v. (alphaxolone, etomidate, propofol, pentobarbitone, ketamine and thiopentone), local (lidocaine, prilocaine, procaine and tetracaine) anesthetics and barbituric acid was determined by displacement of [125I] omega-conotoxin MVII(A) (approximately 1 pM). RESULTS: The binding of [125I] omega-conotoxin was concentration-dependent and saturable with Bmax and Kd of 223 +/- 15 fmol/mg protein and 2.13 +/- 0.14 pM, respectively. Unlabelled omega-conotoxin MVII(A) displaced [125I] omega-conotoxin MVII(A) yielding a pKd of 11.04 +/- 0.04 (9.2 pM). All i.v. and local anesthetics at clinically relevant concentrations did not show any interaction with the omega-conotoxin MVII(A) binding site. CONCLUSION: The present study suggests that omega-conotoxin MVII(A) binding site on N-type voltage sensitive Ca2+ channels may not be a target for i.v. and local anesthetic agents.

Anesthetics, Intravenous↗

PubMed2000

Prognostic value of Doppler transmittal flow patterns and cardiac natriuretic peptides in patients with chronic congestive heart failure admitted for episodes of acute decompensation.

This study was designed to determine whether the restrictive filling transmitral flow velocity pattern is associated with increased plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). It was also designed to evaluate the prognostic value of these parameters from patients with chronic congestive heart failure (CHF) admitted for episodes of acute decompensation. We performed Doppler echocardiography, measured plasma levels of ANP and BNP in 33 patients at the time of admission, and assessed the subsequent cardiac mortality for 3 months. Eleven patients (33%) had a restrictive filling pattern of deceleration time (DcT) < 120ms. Plasma ANP and BNP levels were markedly increased in all patients to 189 +/- 145 pg/ml and 865 +/- 559 pg/ml, respectively. Seventeen patients (52%) showed more than 700 pg/ml of plasma levels of BNP. There was a significant correlation of DcT with the plasma ANP level (r = -0.41, P = 0.017), and a better correlation of DcT with the plasma BNP level (r =-0.50, P = 0.003). The combined index of both shorter DcT (< 120 ms) and higher plasma BNP levels (>700 pg/ml) was the best predictor of cardiac mortality by Cox univariate analysis (chi2 = 5.87, P = 0.015). Furthermore, the sensitivity and specificity of this index for the detection of cardiac mortality were 80% and 86%, respectively. In conclusion, the combined analysis of the Doppler transmitral flow velocity pattern and measurement of the plasma BNP level is noteworthy since it is noninvasive and convenient. Moreover, it is extremely useful in predicting the prognosis for patients with chronic CHF admitted for episodes of acute decompensation.

Acute Disease↗