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Biomedical subjects

Y Qiu

Publications and source records attributed to Y Qiu.

At least 181 records · Page 10Linked to original sources
PubMed1996

Nisoldipine attenuates myocardial stunning induced by multiple coronary occlusions in conscious pigs and this effect is independent of changes in hemodynamics or coronary blood flow.

Recent studies suggest that calcium channel blockers attenuate reversible post-ischemic myocardial dysfunction (myocardial "stunning") in vivo. This beneficial effect, however, has been shown either in open-chest preparations, which are subject to the confounding influence of many unphysiological conditions, or in models in which treatment caused significant hemodynamic alterations. Furthermore, all of the studies have been conducted in the dog, and almost all of them have examined the effect of calcium antagonists after a single ischemic episode. The goal of the present investigation was to assess the effect of nisoldipine in a conscious pig model of repetitive ischemia, and to determine whether the drug exerts direct cardioprotection independent of hemodynamic changes. A total of 33 conscious pigs were used. Pigs underwent a sequence of 10 2-min coronary occlusions, each separated by 2 min of reperfusion, and were randomly assigned to a treated group (n = 11), in which nisoldipine was infused at a rate of 0.5 microgram/kg/min from 15 min before the first coronary occlusion till 30 min after the last reperfusion, and a control group (n = 12), which received vehicle. Results showed that there were no significant differences between the two groups with respect to ischemic bed size or hemodynamic variables throughout the experiment. Collateral blood flow to the ischemic regions was virtually nil in both groups. During the sequence of coronary occlusions, systolic thickening fraction in the ischemic region decreased similarly in the two groups. After the 10th reperfusion, however, the recovery of wall thickening was markedly enhanced in treated compared to control pigs, with the differences being statistically significant at 5, 15, and 30 min and 1, 3, 4 and 5 h. The total deficit of wall thickening after the 10th reperfusion (an integrative assessment of post-ischemic dysfunction) was 51% less in the treated compared with the control group (P < 0.001). This study demonstrates that nisoldipine markedly attenuates myocardial stunning after multiple ischemic episodes in conscious pigs, the improvement is evident immediately after the end of the ischemic episodes and is sustained throughout the recovery phase. This beneficial effect is independent of any favourable hemodynamic changes, and therefore indicates a direct cardioprotective action of nisoldipine.

Animals↗
PubMed1996

Lateral dynamics of major histocompatibility complex class II molecules bound with agonist peptide or altered peptide ligands.

We examined the lateral diffusion of I-Ad on A20 cells following the binding of ovalbumin-derived peptides. The peptides were OVA323-339 and OVA325-335 and a related peptide OVA325-335s substituted H331Q. Only OVA323-339 and OVA325-335 were effectively presented by A20 cells to DO-11.10/S4.4 T cells as assessed by IL-2 production. Fluorescence photobleaching recovery (FPR) measurements showed anti-I-Ad to have a lateral diffusion coefficient on untreated A20 cells of 1.8 +/- 1.0 x 10(-10) cm2 s-1 at 25 degrees C with fluorescence recovery after photobleaching greater than 50%. After 24 h incubation of A20 cells with OVA323-339 or OVA325-335, a subpopulation of A20 cells appeared that were approximately half the size of untreated A20 cells. Culture of A20 with OVA325-355s did not stimulate DO-11.10 cells or induce a size change in A20 cells. Class II molecules were laterally immobile on these small cells with fluorescence recoveries after photobleaching of less than 20%. The relative number of small cells in the A20 cell population was correlated with the immunogenicity of the peptides. These results suggest that immobilization of surface I-Ad may be an important event in antigen presentation.

Animals↗
PubMed1996

Chicken ovalbumin upstream promoter-transcription factors and their regulation.

COUP-TFs are orphan members of the steroid/thyroid hormone receptor superfamily. COUP-TF homologues have been cloned in several species, from Drosophila to man. The vertebrate COUP-TFs can be classified into four subgroups according to sequence homology in their ligand-binding domain. COUP-TFs bind to AGGTCA direct repeats or palindromes with various spacings. These include the response elements of several other members of the superfamily, the vitamin D receptor, the thyroid hormone receptor, the retinoic acid receptor, the retinoid X receptor, the peroxisome proliferation activated regulator, and the hepatocyte nuclear factor-4. COUP-TF response elements have been identified in the promoters of many genes and COUP-TFs have been shown to act as negative regulators both in vitro and in vivo. They can compete with the above mentioned receptors for binding to the common response elements. The ratio of COUP-TF and the other positive regulator determines the transcriptional state of the particular gene in any given moment. COUP-TFs are expressed in the developing central nervous system of mouse and zebra-fish. In addition, they are also expressed in many organs during mouse organogenesis. The expression pattern and profile of COUP-TFs favor the hypothesis that they are involved in development and differentiation. The expression of COUP-TFs are also highly regulated. P19 embryonal carcinoma cells have been used as a model system to study COUP-TF regulation. COUP-TFs are up-regulated in retinoic acid (RA) treated P19 cells. Transient transfection assay showed that mouse COUP-TFII promoter directly responded to RA treatment, suggesting that COUP-TF expression is directly regulated by RA signaling pathway.

Animals↗
PubMed1996

Continuous warm versus intermittent cold cardioplegic infusion: a comparison of energy metabolism, sodium-potassium adenosine triphosphatase activity, and postischemic functional recovery in the blood-perfused rat heart.

We used metabolic, enzymatic, and functional end points to compare the protective properties of continuous warm and intermittent cold cardioplegic infusion in isolated, blood-perfused rat hearts. After excision, hearts (n = 12 per group) were preserved for 3 hours by one of the following cardioplegic procedures: (1) continuous infusion of warm (37 degrees C) blood cardioplegic solution prepared by mixing Fremes' solution with rat arterial blood in a ratio of 1:4, (2) continuous infusion of warm (37 degrees C) crystalloid cardioplegic solution prepared by mixing Fremes' solution with bicarbonate buffer solution in a ratio of 1:4, or (3) intermittent infusion of cold (20 degrees C) St. Thomas' Hospital cardioplegic solution number 2 infused for 3 minutes every 30 minutes during a 3-hour period of ischemia. In the continuous-infusion cardioplegic groups, the solution was infused through the aorta at a flow rate of 0.8 ml.min-1.gm-1 heart. At the end of the 3-hour preservation period, myocardial sodium-potassium adenosine triphosphatase activity (an index of ion-exchange activity) was assessed in six hearts in each group. The remaining hearts in each group were then aerobically perfused at 37 degrees C with arterial blood (from a support rat) for a further 50 minutes, during which time they were atrially paced at 320 beats/min. At the end of this period, left ventricular developed and end-diastolic pressures were assessed with an intraventricular balloon; the hearts were then freeze-clamped and taken for the measurement of tissue adenosine triphosphate and creatine phosphate content. Hearts (n = 6) aerobically perfused with blood for 50 minutes (no cardioplegic infusion) served as control preparations. At a balloon volume of 180 microliters, the mean final values for left ventricular developed pressure in the continuous warm blood, continuous warm crystalloid, and intermittent cold cardioplegic groups were 98 +/- 5 mm Hg (p < 0.05), 70 +/- 5 mm Hg, and 78 +/- 5 mm Hg, respectively. This was compared with 122 +/- 5 mm Hg in control hearts (p < 0.05 vs the rest). For left ventricular end-diastolic pressure, the corresponding values were 33 +/- 3 mm Hg, 32 +/- 6 mm Hg, and 14 +/- 4 mm Hg (p < 0.05), respectively. The control value was 16 +/- 3 mm Hg (p < 0.05 vs continuous warm blood and continuous warm crystalloid groups). Tissue content of adenosine triphosphate was similarly reduced to approximately 50% of control values in all groups, and creatine phosphate content fully recovered in all groups. Sodium-potassium adenosine triphosphatase activity was poorly preserved in continuous warm crystalloid-treated hearts (0.012 +/- 0.003 vs 0.030 +/- 0.008 mumol inorganic phosphate-mg-1.min-1.

Adenosine Triphosphate↗
PubMed1996

Immunoregulatory role of neurotransmitters.

The nervous and endocrine systems modulate the immune system functions through releasing neurotransmitters, neuropeptides and endocrine hormones as they regulate the other physiological functions. The immune system in turn communicates with the nervous and endocrine systems through secreting immunocompetent substances. In this report we review our concepts and evidence concerning the immunoregulatory role of acetylcholine (ACh) and monoamine neurotransmitters which include noradrenaline (NA), 5-hydroxytryptamine (5-HT) and dopamine (DA). The immunoregulatory role comprises two aspects, the modulation of immune functions by neurotransmitters and the effect of the immune system on nervous system functions. The inhibition of ACh biosynthesis in the central nervous system (CNS) caused the enhancement of the humoral immune response of rats to sheep red blood cells (SRBC); by contrast, the inhibition of acetyl-cholinesterase (AChE) activity in the CNS resulted in the suppression of the immune response. It seems that ACh in the brain plays an immunoinhibitory role. The role can be blocked by atropine, a muscarinic antagonist, but not by hexamethonium, a nicotinic antagonist. During the humoral immune response (days 3-6 after SRBC injection), activity of AChE in the hypothalamus and hippocampus was strikingly lower. It is suggested that a functional connection is present in the ACh of the brain and the immune system. In vitro, ACh at 10(-9) to 10(-4) mol/l dose range significantly strengthened the spleen cell proliferation induced by concanavalin (Con A). The action of ACh only occurred either before or just after T lymphocytes were activated through muscarinic cholinergic receptors. In vivo, the depletion of monoamine neurotransmitters or only NA in the CNS caused the impairment of the anti-SRBC response of rats. During the phases of days 2-7 post-immunization, the metabolic alterations of NA, 5-HT and DA emerged in the CNS and the lymphoid organs of rats, which mainly exhibited that in the peak periods of the antibody response, the metabolism of the monoamine neurotransmitters in the hypothalamus and hippocampus was markedly increased, but NA content in the spleen and thymus was significantly decreased. These results provide evidence for the bidirectional information exchange network between the monoamine neurotransmitters and the immune system. Exposure to NA (at 10(-8)-10(-5) mol/l concentration range) in vitro was shown to inhibit the Con A-induced proliferation of the rat spleen cells. This effect of NA was related to the early events involved in the initiation of T cell proliferation and was mediated by either alpha- or beta-adrenergic receptors. The evidence that altering 5-HT level in the central or peripheral nervous systems through various ways of administering the drugs to regulate 5-HT biosynthesis led to the variations of the antibody response, and that cyproheptadine, an antagonist of serotoninergic receptors, can block the action of 5-HT show that 5-HT may exert an immunoinhibitory effect, which appears to be mediated via the peripheral mechanism to relate to the 5-HT receptors. However, the antibody response can cause changes in 5-HT metabolism in the CNS. The possible reasons for these results are discussed. Collectively, the antibody response arouses the metabolic variations of ACh, NA, 5-HT and DA in the central and peripheral nervous systems and then, these alterations can in turn influence immune function through neurotransmitter relevant receptors present on the immunocytes. The purpose of this interaction is most likely to maintain the homeostasis of the immune and other physiological functions.

Adjuvants, Immunologic↗
PubMed1996

An efficient synthesis of methyl tetra-O-hexyl gentiooctaoside, an octaosyl analogue of ANP receptor antagonist HS-142-1.

Methyl 0-(3-0-hexyl-beta-D-glucopyranosyl)-(1->6)-[0-(beta-D-glucopyranosyl)-(1 ->6)-0-(3-0-hexyl-beta-D-glucopyranosyl)-(1->6)3-beta-D- glucopyranoside, a 3-0 hexyl analogue of the octaosyl component of fungal lipooligosaccharide HS-142-1, was stereo- and regioselectively synthesized as a potent antagonist for the tetrameric atrial natriuretic peptide (ANP) receptors.

Animals↗
PubMed1996

Time course of late preconditioning against myocardial stunning in conscious pigs.

We have recently found in conscious pigs that a sequence of brief coronary occlusions induces severe myocardial stunning, but when the same sequence is repeated 24 hours later, the severity of stunning is markedly reduced (approximately 50%) ("late preconditioning against stunning"). As an initial step toward elucidating the mechanism and potential clinical significance of this powerful cardioprotective response, the present study was conducted to define the time course of late preconditioning against myocardial stunning. Conscious pigs underwent a sequence of ten 2-minute coronary occlusion/2-minute reperfusion cycles and then a second identical sequence at 6 hours (group I, n = 7), 12 hours (group II, n = 6), 24 hours (group III, n = 10), 3 days (group IV, n = 10), or 6 days (group V, n = 11) after the first. Systolic wall thickening (WTh) in the ischemic/reperfused region remained significantly depressed for at least 3 hours after the 10th reperfusion of the first sequence, indicating myocardial stunning. When the second sequence of coronary occlusions was performed 6 hours after the first (group I), the recovery of WTh was similar to the first. In contrast, when the second sequence was repeated 12 hours after the first (group II), the recovery of WTh was improved, though not consistently, and the total deficit of WTh decreased by 41% (P < .05) compared with the first sequence. When the second sequence was repeated 24 hours (group III) and 3 days (group IV) after the first, the recovery of WTh was substantially enhanced, with 52% and 49% reductions in the total deficit of WTh, respectively (P < .01 versus the first sequence). When the second sequence was repeated 6 days later (group V), the recovery of WTh was indistinguishable from the first sequence. Thus, late preconditioning against myocardial stunning requires > 6 hours to develop, lasts for at least 60 hours after its appearance (with the most effective protection present at 24 hours and 3 days), and disappears within 6 days after the preconditioning ischemia, a time course that is consistent with the synthesis and degradation of cardioprotective proteins. In view of its sustained duration, this endogenous cardioprotective mechanism is of potential clinical importance.

Animals↗
PubMed1996

Decreased receptor-mediated calcium response in prion-infected cells correlates with decreased membrane fluidity and IP3 release.

The most characteristic neuropathologic features of prion diseases are accumulation of PrPSc in the brain and vacuolation of neurons. Neuronal vacuolation suggests plasma membrane dysfunction. In an earlier study, we found that bradykinin (Bk)-stimulated Ca2+ responses in scrapie-infected ScN2a cells were reduced by 30 to 50% compared with uninfected N2a cells. In this study, we investigated the cause. The IP3 second-messenger response to Bk stimulation was reduced 90%, indicating that a defect occurs in the plasma membrane. Receptor-binding assays showed a 3- to 4-fold increase in Bk receptor numbers on ScN2a cells; however, their binding affinity was reduced 5- to 13-fold, which may account for the decreased IP3 and Ca2+ responses. These results argue that scrapie causes a more fundamental change in the properties of the plasma membrane. We verified this by fluorescence recovery after photobleaching (FRAP) analysis with a lipid probe that measures lateral membrane fluidity. A 7-fold reduction of fluidity was found. These results support the hypothesis that the conversion of PrPc to PrPSc or the accumulation of PrPSc in scrapie-infected cells alters the composition of their plasma membranes that secondarily causes the abnormal receptor-mediated function.

Animals↗
PubMed1996

Design and synthesis of gentiohexaosyl derivatives for an ANP receptor antagonist, HS-142-1.

A hexaosyl fragment of the major component of lipooligosaccharide HS-142-1, O-(3-O-caproyl-beta-D-glucopyranosyl)-(1-->6)-[O-(beta-D- glucopyranosyl)-(1-->6)-O-(3-O-caproyl-beta-D-glucopyranosyl)-(1--> 6)]2-D-glucopyranose (1), was efficiently synthesized by block synthesis. More stable analogs, O-(3-O-hexyl-beta-D-glucopyranosyl)-(1-->6)-[O-(beta-D-glucopyranosyl)- (1-->6)-O-(3-O-hexyl-beta-D-glucopyranosyl)-(1-->6)]2-D-glucopyranose (4) and O-(3-O-caproyl-2,4,6-tri-O-methyl-beta-D-glucopyranosyl)-(1-->6)-[O- (2,3,4-tri-O-methyl-beta-D-glucopyranosyl)-(1-->6)-O-(3-O-caproyl-2,4-di -O- methyl-beta-D-glucopyranosyl)-(1-->6)]2-2,3,4-tri-O-methyl-D-glucopyrano se (2), were also designed and synthesized in a similar manner.

Caproates↗
PubMed1996

Synthetic studies on polysaccharide HS-142-1, a novel nonpeptide antagonist for the atrial natriuretic peptide receptor: syntheses of the gentiobiosyl fragments.

Possible disaccharide fragments of the major component of HS-142-1, a novel polysaccharide antagonist for functional atrial natriuretic peptide (ANP) receptors, O-(4-O-caproyl-beta-D-glucopyranosyl)-(1 --> 6)-4-O-caproyl-D-glucopyranose (1) and O-(3-O-caproyl-beta-D-glucopyranosyl)-(1 --> 6)-3-O-caproyl-D-glucopyranose (2), were respectively synthesized in a stereo- and regio-controlled manner. Deprotection of 2,2'-di-O-caproyl derivative 35 gave a complex mixture due to undesired acyl migration. In contrast, 2,4'-di-O-caproyl analog 39 was successfully deprotected to give O-(4-O-caproyl-beta-D-glucopyranosyl)-(1 --> 6)-2-O-caproyl-D-glucopyranose (40).

Carbohydrate Conformation↗
PubMed1996

Abnormal plasma membrane properties and functions in prion-infected cell lines.

A long trail of evidence indicates that the formation of PrPSc or its accumulation causes the neuronal dysfunction and clinical features of prion diseases. The results of our current line of studies argue that the main neuropathological and clinical features of prion diseases are explained by altered ion channel function secondary to decreased plasma membrane fluidity. This kind of mechanism has the potential to functionally disconnect neuronal networks and cause neuronal vacuolation. Our laboratory is currently focusing its investigations on pathogenic mechanisms that have the potential to link the formation of PrPSc with plasma membrane abnormalities in prion diseases. In summary, the first hypothesis suggests that the conversion of PrPC to PrPSc affects plasma membrane fluidity directly, which secondarily alters the properties and functions of its components. In contrast, the second hypothesis argues that PrPSc accumulation alters the ability of chaperones to correctly fold plasma-membrane proteins during their synthesis, which directly affects the properties of nascent proteins and secondarily affects membrane fluidity. Our current investigations are attempting to determine which of these mechanisms are plausible and, then, which is primary.

Animals↗
PubMed1995

Intracellular transport of invariant chain-MHC class II complexes to the peptide-loading compartment.

Th cells recognize peptide fragments of foreign Ags bound to MHC class II molecules. Upon synthesis in the endoplasmic reticulum, the alpha- and beta-chains of the class II molecules rapidly associate with invariant chains (li). The dissociation of li from class II molecules precedes binding of processed Ag and the formation of SDS-stable alpha beta dimers. We previously showed that functional, processed Ag-class II complexes are assembled in a dense lysosome-like compartment that contains stable class II molecules, but no li, referred to in this work as the peptide-loading compartment. We also identified a separate compartment that contains predominantly SDS-unstable li-class II complexes. Because we were unable to identify known organelle markers associated with this compartment, we refer to it as the X compartment. In this work, we provide results that indicate that the X compartment is composed of transport vesicles that move li-class II complexes to the peptide-loading compartment, where all events in the assembly of processed Ag-class II complexes occur.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1995

Isolation, characterization, and chromosomal localization of mouse and human COUP-TF I and II genes.

Chicken ovalbumin upstream promoter transcription factors (COUP-TFs) are orphan members of the steroid/thyroid hormone receptor superfamily. COUP-TF homologues have been cloned in many species, from Drosophila to human. The protein sequences of COUP-TFs are highly homologous across species, suggesting functional conservation. Two COUP-TF genes have been cloned from human, and their genomic organizations have been characterized. To determine whether the genomic organization is conserved between human and mouse, we isolated two mouse COUP-TF genes (I and II) and characterized their genomic structures. Both genes have relatively simple structures that are similar to those of their human counterparts. In addition, we mapped mouse COUP-TF I to the distal region of chromosome 13 and COUP-TF II to the central region of chromosome 7. Furthermore, we mapped human COUP-TF I to 5q14 of chromosome 5 and COUP-TF II to 15q26 of chromosome 15. The results demonstrate that COUP-TF genes are located in chromosomal regions that are syntenic between mouse and human.

Animals↗
PubMed1995

Effect of the hydrophilic alpha-tocopherol analog MDL 74,405 on detection of hydroxyl radicals in stunned myocardium in dogs.

We have previously shown in dogs that the hydrophilic alpha-tocopherol analog, MDL 74,405, attenuates postischemic myocardial dysfunction ("stunning") and generation of free radicals as assessed with the spin trap alpha-phenyl N-tert-butyl nitrone (PBN). However, we could not discern whether this drug acts on primary radicals (such as hydroxyl radical [.OH]) or on secondary radicals. The goal of this study was to directly determine whether the beneficial effects of MDL 74,405 result from actions against .OH. Open-chest dogs undergoing a 15-minute coronary artery occlusion and 3 hours of reperfusion received an intravenous infusion of either saline solution (control group, n = 7) or MDL 74,405 (n = 6) starting 30 minutes before coronary occlusion and ending 60 minutes after reflow at a dose of 0.3 mg/kg/hr. Formation of .OH was estimated by the technique of aromatic hydroxylation of phenylalanine. Phenylalanine was infused intravenously, and the plasma concentrations of the hydroxylated products ortho-, meta-, and para-tyrosines (o-, m-, and p-tyr) in the coronary venous effluent and in the arterial blood were measured with high-performance liquid chromatography. In the control group a dramatic increase in the myocardial release of o-, m-, and p-tyr was observed immediately after reperfusion; the release of tyrosines peaked at 1 minute of reflow and continued up to 10 minutes after reperfusion. MDL 74,405 abolished the release of o-tyr throughout the first 10 minutes of reperfusion but had a less pronounced effect on the production of m- and p-tyr. These results demonstrate that MDL 74,405 is effective in inhibiting .OH-initiated reactions in the postischemic stunned myocardium in the dog, suggesting that the anti-.OH action of MDL 74,405 is an important mechanism of action of this antioxidant.

Animals↗