Biomedical subjects

Q Hao

Publications and source records attributed to Q Hao.

At least 55 records · Page 3Linked to original sources

PubMed1998

Novel catheterization technique for the in vivo measurement of pulmonary vascular responses in rats.

A novel cardiac catheterization technique was devised to investigate the pulmonary arterial pressure-blood flow relationship in intact spontaneously breathing rats (ISBR) under physiological conditions with constant left atrial pressure and controlled blood flow within the normal range. Observations using this new technique in vivo were contrasted with data derived with isolated perfused rat lungs in vitro. Unlike results in in vitro isolated perfused rat lungs, the pressure-flow curves in vivo were curvilinear, with pulmonary artery pressure increasing more rapidly at low pulmonary blood flows of 4-8 ml/min and less rapidly at higher flow rates. Pressure-flow curves were reproducible and were not altered by 1-1.5 h of arrested perfusion, cyclooxygenase blockade, or perfusion with aortic or mixed venous blood. In contrast to results in in vitro isolated perfused rat lungs, NG-nitro-L-arginine methyl ester (L-NAME) increased pulmonary arterial pressure at all but the lowest flow rates with a slight effect on the curvilinear pressure-flow relationship. L-NAME reversed pulmonary vasodilator responses to acetylcholine and bradykinin and enhanced the pulmonary vasodilator response to nitroglycerin. The present data suggest that actively induced pulmonary hypertension is under greater control by endothelium-derived relaxing factor (EDRF). Unlike previous results in in vitro perfused rat lungs, results in ISBR demonstrate that the pulmonary vasodilator response to adrenomedullin-(13-52) is not mediated by calcitonin gene-related peptide receptors, which are not coupled to the release of EDRF. These results indicate that this novel technique may provide a useful model for the study of the pulmonary circulation in the intact chest rat.

Acetylcholine↗

PubMed1998

Analysis of responses to adrenomedullin-(13-52) in the pulmonary vascular bed of rats.

The effects of human adrenomedullin-(13-52) [hADM-(13-52)] were investigated in the rat pulmonary vascular bed and in isolated rings from the rat pulmonary artery (PA). Under conditions of controlled blood flow and constant left atrial pressure when tone was increased with U-46619, injection of hADM-(13-52) produced dose-related decreases in lobar arterial pressure. Pulmonary vasodilator responses in the intact rat and vasorelaxant responses to hADM-(13-52) in rat PA rings were inhibited by NG-nitro-L-arginine methyl ester (L-NAME) and L-N5-(1-iminoethyl)-ornithine hydrochloride (L-NIO). Vasorelaxant responses to hADM-(13-52) were also inhibited by methylene blue, endothelium removal, hADM-(26-52), and iberiotoxin, whereas meclofenamate, calcitonin gene-related peptide-(8-37) [CGRP-(8-37)], glibenclamide, and apamin were without effect. Because vasorelaxant responses to NS-1619, a large-conductance Ca(2+)-activated K+ channel agonist, were not altered by L-NAME and vasorelaxant responses to acetylcholine and CGRP were not altered by hADM-(26-52), the present data suggest that ADM-(13-52) acts on a receptor in the pulmonary vascular bed that is coupled to endothelial nitric oxide release. These data suggest that this nitric oxide release may lead to guanosine 3',5'-cyclic monophosphate-dependent K+ channel activation, which produces a pulmonary vasorelaxant response through hyperpolarization of vascular smooth muscle cells. The present data suggest that ADM-(13-52) modulates receptor-mediated, but not voltage-dependent, pulmonary vascular contraction by influencing Ca2+ influx. These results suggest that the ADM fragment, hADM-(13-52), acts as an endothelium-dependent vasodilator agent in the pulmonary vascular bed of the rat.

Adrenomedullin↗

PubMed1997

Use of single isomorphous replacement data of proteins - resolving the phase ambiguity and a new procedure for phase extension.

A procedure combining direct methods and solvent flattening to break the phase ambiguity intrinsic to the single isomorphous replacement (SIR) technique has been tested with the experimental SIR data of the known protein RNase Sa at 2.5 A resolution. The use of direct methods provided better initial phases for the solvent-flattening procedure, while the solvent-flattening procedure greatly improved direct-method phases leading to a traceable Fourier map. A small subset of known phases at low resolution makes direct phasing of SIR data much easier. Accordingly a method for extending low-resolution phases to high-resolution ones is proposed making use of additional SIR information. This reduces the problem of finding a value in the range of 0-2pi for each unknown phase to that of just making a choice between two possible values. Tests with the known protein RNase Sa showed that the method is able to extend phases from a resolution of 6 to 2.5 A leading to an easily traceable Fourier map. The solvent-flattening technique and the combination of which with direct methods were used for the phase extension. Either procedure yielded reasonably good results, but on the whole, the result from the combination of direct methods with solvent flattening is better. Results of the latter procedure were further compared with that from direct phasing of the 2.5 A SIR data and with that from phase extension by solvent flattening without SIR information. An improvement gained by the use of SIR information is evident.

Journal Article↗

PubMed1997

Nociceptin: an endogenous agonist for central opioid like1 (ORL1) receptors possesses systemic vasorelaxant properties.

The purpose of the present study was to investigate the effects of nociceptin on peripheral arterial rings from the cat. When feline renal, mesenteric, carotid and femoral rings with intact endothelium were precontracted with phenylephrine (100 nanomolar), nociceptin (3 x 10(-11)-3 x 10(-6) M) decreased tension in a concentration-dependent manner. The present data suggest nociceptin possesses biologic activity outside the CNS and may contribute to the regulation of systemic blood pressure and regional blood flow.

Animals↗

PubMed1997

Fusion of phospholipid vesicles induced by the ribosome inactivating protein saporin.

The single chain ribosome-inactivating protein Saporin-S6 (SO-6) induces the fusion of acid phospholipid vesicles. The extent of fusion was measured by resonance energy transfer assay between the N-(7-nitro-2-1,3-benzoxadiazol-4-yl)-dimyristoylphosphatidyl lithanolamine (NBD-PE)(donor) and N-(lissamine rhodamine B sulphonyl)-diacylphoshaidylethanolamine (Rh-PE) (acceptor) incorporated in the vesicle. The saturated lipid/protein molar ratio is approx. 100:1. The time course of fusion of vesicles induced by the protein showed that the process was completed within 10 minutes, and the size of the particles in the medium was enlarged which conforms the occurrence of the fusion occurring. The fusion is temperature dependent and the liquid-crystalline state lipid is more apt to fuse than the gel phase lipid. The effect of SO-6 is also dependent on ionic strength and pH, high salt concentration and basic pH may abolish fusion, which suggests that both electrostatic and hydrophobic components may be involved in the process.

Hydrogen-Ion Concentration↗

PubMed1997

Campylobacter jejuni isolates from Japanese patients with Guillain-Barré syndrome.

Serologic evidence of recent Campylobacter jejuni infection was found in 92 (45%) of 205 Japanese patients with Guillain-Barré syndrome (GBS), and 49% of those 92 patients also had antibodies to GM1. Sixteen independent clinical isolates from GBS patients were serotyped: 12 belonged to Penner's heat-stable (HS) O serotype HS-19, 3 to HS-2, and 1 to HS-4. Of the patients whose C. jejuni isolates belonged to HS-19, 80% had elevated anti-GM1 antibodies. Although the correlation was significant between C. jejuni and GM1 antibody, anti-GM1 also was detected in 25% of patients without C. jejuni infection. Polymerase chain reaction-based restriction fragment length polymorphism analysis of an flaA gene showed that all HS-19 isolates, regardless of a GBS association, had an identical and distinguishable pattern, Cj-1, suggesting that HS-19:Cj-1 isolates are distinctive among C. jejuni isolates. Lectin typing showed that all GBS-associated HS-19 isolates contained terminal beta-N-acetylglucosamine residues on their cell surface, but HS-19 isolates from patients with enteritis did not.

Adolescent↗

PubMed1997

A novel model to study the effects of burn lymph on pulmonary vascular hemodynamic variables.

OBJECTIVE: To determine the effects of burn lymph on pulmonary hemodynamic variables. METHODS: A balloon-tipped catheter was fluoroscopically passed from a jugular vein into the right lower lobe (RLL) pulmonary artery of rats, its distal lumen used to measure pulmonary artery pressure. Inflation allowed measurement of RLL wedge pressure, which represents pulmonary venous pressure. After inflation, the RLL underwent constant flow pump-perfusion with carotid artery blood. Preburn (n = 5) or post-burn (n = 6) dog lymph was infused into the RLL for 50 minutes. MEASUREMENTS: Because perfusion flow rate was constant throughout the experiment, RLL changes in pulmonary artery pressure reflect changes in pulmonary vascular resistance. RESULTS: Animals given preburn lymph had no alterations in RLL pulmonary hemodynamics. The immediate, significant (p < 0.005, analysis of variance) increases in RLL pulmonary artery pressure (16.2 +/- 2.3 mm Hg at baseline vs. 35.4 +/- 2.1 mm Hg at 30 minutes) and pulmonary vascular resistance (0.0 at baseline vs 1.37 +/- 0.24 at 30 minutes) after burn lymph injection persisted beyond infusion interruption. CONCLUSION: The persistent pulmonary hypertensive response to postburn lymph warrants further investigation.

Animals↗

PubMed1997

[The influence of KCl on SERS of fuchsin basic in silver colloids].

Surface enhanced Raman scattering (SERS) spectra of fuchsin basic (FB) in silver colloids were measured. The influence of KCl on the SERS of FB was studied systematically with different excitation wavelengths (476.5, 488.0, 514.5, 632.8nm). The dependence of the relative SERS intensity of the 1366cm(-1) and 242cm(-1) bands of FB on KCl mole value at different excitation wavelengths were given. The SERS spectra of FB at 514.5nm and 632.8nm wavelength excitations were very different, and the relative intensity of 242cm(-1) to 1366cm(-1) SERS spectra was changed.

English Abstract↗

PubMed1996

Direct-method structure determination of the native azurin II protein using one-wavelength anomalous scattering data.

The one-wavelength anomalous scattering (OAS) X-ray diffraction data of azurin II, a copper-containing protein from Alcaligenes xylosoxidans were collected at the Photon Factory, Japan at a 'routine' wavelength of 0.97 A. The structure had been originally solved by the molecular-replacement method [Dodd, Hasnain, Abraham, Eady & Smith (1995). Acta Cryst. D51, 1052-1064]. As a technique of ab initio structure determination, the direct method [Fan, Hao, Gu, Qian, Zheng & Ke (1990). Acta Cryst. A46, 935-939] was attempted to break the phase ambiguity intrinsic to OAS data. The phases were then improved using the solvent-flattening method. The final electron-density map clearly shows most Calpha positions and many side chains and it is traceable without prior knowledge of the structure. It is concluded that the direct method is capable of phasing anomalous scattering data collected at one wavelength from moderate-sized native proteins (M(w) approximately 20 kDa) which contain copper or atoms with a similar scattering power.

Journal Article↗

PubMed1996

Structure Solution of Azurin II from Alcaligenes xylosoxidans using the Laue Method: Possibility of Studying In Situ Redox Changes using X-rays.

We have recently demonstrated that X-rays can be used for changing the redox states of the metal centre in metalloproteins [Murphy et al. (1995). J. Synchrotron Rad. 2, 64-69]. The possibility of using the Laue method for studying the structural changes associated with such X-ray-induced reactions is explored by applying the method to the structure determination of a new azurin (hereafter referred to as azurin II) from the denitrifying bacterium Alcaligenes xylosoxidans. Laue X-ray diffraction data of azurin II were collected at station 9.7 of the SRS Daresbury. Three diffraction patterns were recorded on film packs at three different crystal orientations. The data were processed using the Daresbury Laue Software Suite to give 2224 independent single reflections (R(merge) = 0.136) in the wavelength range 0.36-1.40 A. The data completeness was 44% at 2.55 A resolution. Phase determination for the data was undertaken using the molecular-replacement method; the top peak was chosen in both the rotation function and the subsequent translation function. This solution agreed well with the molecular-replacement solution achieved independently using monochromatic data. The electron-density map showed reasonably good agreement with the model and the copper site was readily recognizable as it had the highest density. To see if the electron-density map could be improved, ;the doublets in the diffraction data were then deconvoluted. This added 26% data in the region infinity-2d(min) resulting in an improvement in the data completeness to 50% and thus in improved continuity of the electron-density map. The quality of these maps is discussed from the point of view of the suitability of this approach for studying redox-induced structural changes.

Journal Article↗

PubMed1996

Adrenotensin: an adrenomedullin gene product contracts pulmonary blood vessels.

The purpose of the present study was to determine the effects of adrenotensin, a newly described product of the ADM gene, on cat pulmonary arterial (PA) rings. Under resting conditions, adrenotensin increased tension of PA rings in a concentration-dependent manner. Although addition of diphenhydramine, ONO-3708, phentolamine, methysergide, atropine, and meclofenamate did not alter the contractile response to adrenotensin, removal of the endothelial cell layer significantly reduced this response. Moreover, precontraction of PA rings with adrenotensin selectively attenuated the pulmonary vasorelaxant response to ADM but not to other vasodilator substances, including isoproterenol, pinacidil, nifedipine, and adenosine. The present data suggest that adrenotensin acts in an endothelium-dependent manner to contract PA rings. Moreover, the present data suggest that adrenotensin may act in a modulatory manner to influence vasorelaxation in response to ADM, a sister proADM product.

Adrenomedullin↗

PubMed1996

Aggregation of phospholipid vesicles induced by the ribosome inactivating protein saporin.

Saporin-S6(SO-6) is a single chain ribosome inactivating protein, which can inhibit protein synthesis by inactivating eukaryotic ribosomes. The interaction of SO-6 with phospholipid model systems was described. SO-6 can specifically interact with negatively-charged phospholipid vesicles and it induces the aggregation of the lipid vesicles. The kinetics of the vesicle aggregation induced by SO-6 was studied. The saturating protein/lipid molar ratio was determined to be 1:100 based on titration experiments. The aggregation is dependent on the temperature in a range that was many times higher than the phase transition temperature of the phospholipid. The effect of pH on the aggregation of the vesicles can not be explained by simple deprotonation of side chain amino groups of the protein, and may be related to conformational changes of the protein. The maintenance of physiological ionic strength was required for the aggregation of SO-6 with vesicles. Finally, the interaction was prompted by Ca2+ ions, and was totally inhibited by EDTA, which suggests that SO-6 may interact with phospholipid vesicles in a Ca(2+)-dependent manner.

Calcium↗

PubMed1995

Evaluation of Reflection Intensities for the Components of Multiple Laue Diffraction Spots. III. Using a Real-Space Density Modification Method.

In the Laue diffraction pattern, 10--20% of the spots result from the exact superposition of two or more reflections that are ;harmonics', e.g. hkl; 2h 2k 2l, ...; a high proportion of these are low-resolution reflections. For the solution of large or difficult structure problems, the intensities of the remaining 80-90% of the reflections, measurable as singles, may not be sufficient and thus the evaluation of the intensities of the components of the multiple spots is important. A new procedure, DECONV, for this deconvolution using real-space density modifications on the Patterson map is given. This development is based on a procedure in reciprocal space related to direct methods [Hao, Campbell, Harding & Helliwell (1993). Acta Cryst. A49, 528-531]. A Patterson map is calculated using single reflections and modified by removing negative densities and squaring with an appropriate adjustment at the origin peak. The procedure can be repeated until convergence is reached. It has been tested with Laue diffraction data from 4Zn insulin and cytochrome c peroxidase (CCP). 304 and 1134 reflection intensities were evaluated from multiple spots of insulin and CCP, respectively; the mean fractional differences (on F), showing the agreement with high-quality monochromatic data, were 0.27 and 0.21, respectively.

Journal Article↗

PubMed1995

Agmatine: a novel endogenous vasodilator substance.

The purpose of the study was to investigate the effects of agmatine, an endogenous clonidine-displacing substance (CDS), on systemic hemodynamics in the anesthetized rat. Bolus intravenous (i.v.) injections of agmatine decreased systemic arterial pressure (SAP) and systemic vascular resistance in a dose-dependent manner. The development of acute tachyphylaxis to the systemic vasodepressor response to agmatine did not induce cross-tachyphylaxis to the systemic vasodepressor responses to bradykinin, isoproterenol and nitroglycerin. The present data demonstrate agmatine, as a CDS and agonist for imidazoline (I) receptors, possesses marked systemic vasodilator activity in the rat. The present data suggest that activation of I receptors may represent a novel mechanism of vasodilation in vivo.

Agmatine↗

PubMed1995

Role of G proteins in the vasodilator response to endothelin isopeptides in vivo.

The purpose of the present study was to determine the influence of pertussis toxin (PTX) on the pulmonary and systemic vasodilator responses to endothelin (ET) isopeptides in the intact cat under conditions of constant pulmonary blood flow and left atrial pressure. When pulmonary vasomotor tone was actively increased by an intralobar arterial infusion of U-46619, intralobar arterial bolus injections of ET-1, ET-2, and ET-3 decreased lobar arterial pressure and systemic vascular resistance in a dose-related manner. The vasodilator responses to ET-1 and ET-2 in the cat lung were abolished by PTX pretreatment, whereas PTX pretreatment did not alter the pulmonary vasodilator response to ET-3 and cromakalim, a specific ATP-sensitive potassium (KATP) channel activator, and the systemic vasodilator responses to all ET isopeptides studied. Glipizide, an inhibitor of KATP channels, inhibited the pulmonary vasodilator responses to ET-1, ET-2, and ET-3, whereas the systemic vasodilator responses to these isopeptides were not changed. The present data are the first to provide a functional correlate in vivo suggesting the existence of different signal transduction mechanisms for two pulmonary vascular ET receptor subtypes, ETA-like that is PTX sensitive and has greater sensitivity to ET-1 and ET-2 (than to ET-3) and ETc-like that is PTX insensitive and has sensitivity to ET-3 (than to ET-1 and ET-2). However, both ET-receptor subtypes promote vasodilation in the adult pulmonary vascular bed by activating KATP channels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Angiotensin induction of PAI-1 expression in endothelial cells is mediated by the hexapeptide angiotensin IV.

Recent studies from this laboratory have demonstrated that angiotensin II (Ang II) stimulates the expression of plasminogen activator inhibitor 1 (PAI-1) in cultured endothelial cells. This response does not appear to be mediated via an interaction with either the AT1 or the AT2 receptor subtype. Since a novel angiotensin receptor has been identified in a variety of tissues that specifically binds the hexapeptide Ang IV (Ang II, [3-8]), we therefore examined the effects of Ang IV on the expression of PAI-1 mRNA in bovine aortic endothelial cells. Ang IV stimulated dose- and time-dependent increases in the expression of PAI-1 mRNA. The effect of Ang IV (10 nM) was not inhibited by Dup 753 (1.0 microM), a highly specific antagonist of the AT1 receptor, or by PD123177 (1.0 microM), a highly specific antagonist of the AT2 receptor. In contrast, the AT4 receptor antagonist, WSU1291 (1.0 microM), effectively prevented PAI-1 expression. Although larger forms of angiotensin (i.e., Ang I, Ang II, and Ang III) are capable of inducing PAI-1 expression, this property is lost in the presence of converting enzyme or aminopeptidase inhibitors. These results indicate that the hexapeptide Ang IV is the form of angiotensin that stimulates endothelial expression of PAI-1. This effect appears to be mediated via the stimulation of an endothelial receptor that is specific for Ang IV.

Angiotensin II↗

PubMed1995

No association of the 11778 mitochondrial DNA mutation and multiple sclerosis in Japan.

Leber's hereditary optic neuropathy (LHON), a maternally inherited disease causing severe bilateral visual loss in young men, is linked to 12 point mutations in mitochondrial DNA, the most common of which is at the nucleotide position 11778. The 11778 point mutation has also been detected in several patients with possible multiple sclerosis (MS), especially women with severe visual loss in both eyes. Because frequent and severe optic neuropathy is a feature of MS in Japan, we screened 80 Japanese MS patients for the presence of the 11778 mutation by mutation-specific polymerase chain reaction. Eighteen women with MS had bilateral optic neuropathy, but none had the mutation at 11778. There is no association between Japanese MS and the 11778 mitochondrial DNA mutation.

Base Sequence↗

PubMed1995

Fluorescence spectroscopic study of the interaction of adenine and nucleotide with trichosanthin.

Trichosanthin (TCS) is an N-glycosidase that can attack the 28s rRNA of the ribosome at a highly conserved adenine residue. The interactions of adenine and its derivative nucleotides with TCS are reported. The fluorescence of Trp 192 of TCS is sensitive to the proximity of adenine, and produces a marked red shift indicative of trytophan in a more hydrophilic environment. By contrast AMP and ATP quench the maximal emission at 328nm. The binding of the adenine and ATP with TCS result in lower tryptophan accessibility to the quencher acrylamide, but higher tryptophan accessibility to the quencher iodide, while AMP caused higher tryptophan accessibility to acrylamide, and lower tryptophan accessibility to iodide. Also, the binding of nucleotides induces tryptophan heterogeneity in the protein. These findings lead us to propose that binding of nucleotides and adenine base cause different microenvironmental changes of the tryptophan residue, and Trp 192 may be involved in the active site of TCS.

Adenine↗