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Biomedical subjects

H Luo

Publications and source records attributed to H Luo.

At least 37 records · Page 2Linked to original sources
PubMed2001

A proteasome inhibitor effectively prevents mouse heart allograft rejection.

BACKGROUND: We have previously demonstrated in vitro that proteasome inhibitors could suppress proliferation and induce apoptosis of activated T cells. This finding suggests that such inhibitors could be used as a novel category of immunosuppressants in blocking allograft rejection. METHODS: The proteasome inhibitor dipeptide boronic acid (DPBA) was tested in vitro for its inhibitory effect on mouse T-cell proliferation and lymphokine secretion. DPBA was also used in vivo to treat mouse heterotopic heart allograft rejection. Possible side effects of this compound were examined according to blood chemistry of mice treated with DPBA. RESULTS: DPBA suppressed the T-cell proliferation and potently inhibited interleukin (IL)-2, IL-6, IL-10, IL-13, and IFN-gamma produced by anti-CD3-activated T cells. Given i.p. starting 1 day after transplantation at 0.66 mg/kg per day for 16 days, or at 1 mg/kg per day for 4 days followed by 0.5 mg/kg per day for 12 days, DPBA could prolong heart allograft survival to 35.5 days (mean survival time, MST) and to 36.2 days, respectively. The control group had MST of 7.3 days. When administrated 72 hr post operation at 1 mg/kg per day for 4 days, DPBA could prolong the graft survival to 19.8 days. During the course of these effective dosages, DPBA had no apparent toxicity in the liver, kidney, pancreas, or heart, according to analysis of blood chemistry. CONCLUSIONS: The proteasome inhibitor could repress allograft rejection in mice without apparent side-effects at the effective dosages. This finding has opened a new dimension in development of novel immunosuppressants for organ transplantation.

Animals↗
PubMed2001

[Effects of noninvasive positive pressure ventilation on gas exchange and patients' transformation in chronic obstructive pulmonary disease and respiratory failure].

OBJECTIVE: This paper was to observe the effects of noninvasive positive pressure ventilation (NPPV) on gas exchange and patients' transformation and to evaluate their clinical value. METHODS: Patients were randomly treated by either NPPV, or conventional medicine. The arterial blood gas readings, heart rates (HR), and respiratory rates (HR) were obtained at admission after the treatment. It was necessary to intubate when the clinical deterioation was marked by PaCO2 > 70 mmHg, PaCO2 gradually increasing 5-10 mmHg, pH decreasing 0.05-0.1 or mental obstacle, or PaO2 < 45 mmHg. RESULTS: NPPV significantly decreased the PaCO2 level, HR, and RR, significantly increased the PaO2 level, and also decreased the opportunity of intubation. CONCLUSION: The results suggest that NPPV can improve the gas exchange and reduce the need of intubation in COPD patients with acute respiratory failure.

Aged↗
PubMed2001

Multi-residue analysis of avermectins in swine liver by immunoaffinity extraction and liquid chromatography-mass spectrometry.

A multi-residue LC-MS method was developed to determine avermectin residues in swine liver. Abamectin and ivermectin (22,23-dihydroabamectin) were extracted, and cleaned up by immunoaffinty columns with immobilized anti-avermectin polyclonal antibodies. The cleaned samples were separated by high-performance liquid chromatography (HPLC) with a C8 column and determined by negative-ion atmospheric pressure chemical ionization (APCI) mass spectrometry (MS) using selective ion monitoring (SIM) of [M-H]-. Recoveries of abamectin and ivermectin from fortified samples at 5-100 microg kg(-1) levels ranged from 74 to 94% and from 65 to 87%, respectively. The limits of detection were 5 microg of abamectin or ivermectin in 1 kg sample.

Animals↗
PubMed2001

Proteasome activity is required for T lymphocyte aggregation after mitogen activation.

The proteasome is a multicatalytic complex of proteases involved in T lymphocyte proliferation and activation through multiple mechanisms. In this study, we investigated its role in lymphocyte aggregation. We found that blocking proteasome activity by a proteasome-specific inhibitor lactacystin (LAC) prevented clustering of T lymphocytes after stimulation with various mitogens. Expression of adhesion molecules ICAM-1 and LFA-1 at cell surfaces of activated T cells was decreased after treatment with LAC. Mechanisms by which the proteasome intervenes in the expression of these adhesion molecules were different. LAC inhibited ICAM-1 expression at the mRNA level, whereas LFA-1 inhibition was probably at a post-translational level. Downregulation of these molecules after proteasome inhibition likely contributes to the observed repression of T cell aggregation. Our results show that the proteasome plays an important role in cell-cell interaction during T cell activation.

Acetylcysteine↗
PubMed2001

Investigation of the electrochemical and electrocatalytic behavior of single-wall carbon nanotube film on a glassy carbon electrode.

The electrochemical behavior of a film of single-wall carbon nanotubes (SWNTs) functionalized with carboxylic acid groups was studied extensively on a glassy carbon (GC) electrode. One stable couple corresponding to the redox of the carboxylic acid group, which was supported by XPS and IR experiments, was observed. The electrode process involved four electrons, while the rate-determining step was a one-electron reduction. The SWNT film-modified electrode showed favorable electrocatalytic behavior toward the oxidation of biomolecules such as dopamine, epinephrine, and ascorbic acid.

Ascorbic Acid↗
PubMed2001

Proteasomes modulate balance among proapoptotic and antiapoptotic Bcl-2 family members and compromise functioning of the electron transport chain in leukemic cells.

The mechanism underlying apoptosis induced by proteasome inhibition in leukemic Jurkat and Namalwa cells was investigated in this study. The proteasome inhibitor lactacystin differentially regulated the protein levels of proapoptotic Bcl-2 family members and Bik was accumulated at the mitochondria. Bik overexpression sufficed to induce apoptosis in these cells. Detailed examination along the respiration chain showed that lactacystin compromised a step after complex III, and exogenous cytochrome c could overcome this compromise. Probably as a result, the succinate-stimulated generation of mitochondrial membrane potential was significantly diminished. Bcl-x(L) interacted with Bik in the cells, and Bcl-x(L) overexpression prevented cytochrome c leakage out of the mitochondria, corrected the mitochondrial membrane potential defect, and protected the cells from apoptosis. These results show that proteasomes can modulate apoptosis of lymphocytes by affecting the half-life of Bcl-2 family members, Bik being one of them.

Acetylcysteine↗
PubMed2001

Coronary remodeling of proximal and distal stenotic atherosclerotic plaques within the same artery by intravascular ultrasound study.

The aim of this intravascular ultrasound study was to compare the type and the degree of vessel remodeling in proximal and distal de novo lesions within the same coronary artery in patients with stable angina pectoris. Seventy-six de novo coronary artery lesions in 38 coronary arteries of 38 patients were imaged by intravascular ultrasound. The vessel area (VA) within the external elastic lamina and the lumen area (LA) were measured, and the wall area (VA-LA) was calculated at the lesion site, and the proximal and distal reference sites. The VA ratio was defined as (lesion VA/average of the proximal and distal reference VAs) to represent the degree of vessel remodeling. The proximal coronary segments showed compensatory enlargement more often (68% vs 29%, p < 0.01) than the distal segments, and the VA ratio at the lesion site was significantly larger (1.1 +/- 0.3 vs 1.0 +/- 0.2, p <0 .01) in proximal segments than in distal segments. The type of coronary remodeling was discordant in 61% and concordant in only 39% of coronary arteries between the proximal and distal segments. The type of coronary remodeling of proximal and distal coronary lesions was inhomogeneous, even within the same vessel. Proximal coronary segments showed more prominent compensatory enlargement than distal segments, which have a similar degree of luminal narrowings.

Adult↗
PubMed2001

Syntheses and characterizations of metal complexes derived from cis,cis-1,3,5-triaminocyclohexane-N,N',N"-triacetic acid.

A convenient six-step procedure is developed to routinely prepare the hexadentate ligand cis,cis-1,3,5-triaminocyclohexane-N,N',N"-triacetic acid (H3tachta) as an HCl salt. Complexes of gallium(III) and indium(III), [Ga(tachta)] and [In(tachta)], are synthesized from the reactions of the ligand and the corresponding metal precursors. Copper(II), palladium(II), and cobalt(II) complexes, [Cu(Htachta)], [Pd(Htachta)], and [Co(Htachta)], are obtained from the reactions of H3tachta with the corresponding metal chlorides. The structures of H3tachta.3HCl.2H2O (C12H28Cl3N3O8) and [Ga(tachta)] (C12H18GaN3O6) are characterized. The crystal of H3tachta.3HCl.2H2O is monoclinic, of the space group P2(1)/c, with a = 15.1688(4) A, b = 8.4708(2) A, c = 15.9408(2) A, beta = 108.058(1) degrees, and Z = 4; that of [Ga(tachta)] is cubic, of space group Pa3, with a = 14.0762(1) A and Z = 8. The gallium atom of [Ga(tachta)] is six-coordinated in the solid state, and the complex assumes a pseudooctahedronal geometry with the completely deprotonated hexadentate ligand encapsulating the metal ion.

Crystallography, X-Ray↗
PubMed2001

Molecular cloning of mouse ERK5/BMK1 splice variants and characterization of ERK5 functional domains.

The mitogen-activated protein kinases (MAPKs) play important roles in regulation of cell growth and survival. Human MAPK 5 (ERK5) or Big MAP kinase 1 (BMK1) is a recently cloned member of the MAPK family. To identify ERK5-related kinases, we searched the GenBanktrade mark expressed sequence tag (EST) data base for mouse cDNAs with homology to human ERK5. A full-length mouse cDNA that was highly homologous to the human ERK5 was identified. Further analysis of ERK5 polymerase chain reaction products generated from mouse embryo cDNA yielded three mouse ERK5 cDNAs (mERK5a, mERK5b, and mERK5c). Sequence analysis showed that these cDNAs are alternative splice products of the mouse ERK5 gene. Interestingly, expressed mERK5b and mERK5c act as dominant negative inhibitors based on inhibition of mERK5a kinase activity and mERK5a-mediated MEF2C transactivation. However, the physiological significance of mERK5b and mERK5c is not fully understood. Further investigation using these mouse ERK5 splice variants and other constructed mutants identified functional roles of several regions of mERK5, which appear to be important for protein-protein interaction and intracellular localization. Specifically, we found that the long C-terminal tail, which contains a putative nuclear localization signal, is not required for activation and kinase activity but is responsible for the activation of nuclear transcription factor MEF2C due to nuclear targeting. In addition, the N-terminal domain spanning amino acids (aa) 1-77 is important for cytoplasmic targeting; the domain from aa 78 to 139 is required for association with the upstream kinase MEK5; and the domain from aa 140-406 is necessary for oligomerization. Taken together, these observations indicate that ERK5 is regulated by distinct mechanisms determined by its unique structure and presumably the presence of multiple splice variants.

Alternative Splicing↗
PubMed2001

The JAK/STAT pathway and Drosophila development.

The JAK/STAT signal transduction pathway plays a critical role in mammalian cells, particularly in hematopoiesis and immune responses. Several components of this pathway have been identified and characterized in Drosophila. Mutational analyses of these components have revealed a number of interesting developmental roles, and provide a mechanism to identify other interacting molecules and pathways. Hence, the JAK/STAT pathway in Drosophila serves as an attractive model for in vivo functional analyses of JAK/STAT signaling.

Animals↗
PubMed2001

The experimental study on the effect calcitonin gene-related peptide on bone resorption mediated by interleukin-1.

To investigate the effect of calcitonin gene-related peptide (CGRP) on bone resorption mediated by interleukin-1 beta(IL-1 beta) in vitro, the osteoclasts isolated from the long bones of newborn SD rats were co-cultured with osteoblasts on ivory slices placed in 24-well plates. 24 h later, conditioned media containing CGRP and/or IL-1 beta were added to the wells respectively, and continued culturing for 48 h. After the cells were stripped off by ultrasonication, the ivory slices were stained in toludine blue. The number and the total area of resorption lacunae on each slice were measured by computer imaging analysis system. Our results showed that IL-1 beta significantly stimulated bone resorption, but CGRP inhibited the effect mediated by IL-1 beta in a dose-dependent manner. It is suggested that CGRP may inhibit osteoclastic bone resorption through two ways: One is that CGRP functions directly on osteoclasts to block their activation; the other is that CGRP regulates the release of cytokines by osteoblasts and indirectly affects the function of osteoclasts.

Animals↗
PubMed2001

Detection and genotyping of GBV-C/HGV variants in China.

We detected GBV-C/HGV sequences in the sera from 64 out of a total of 324 subjects in the south of China. In agreement with findings of others, we noted an especially high rate of infection among intravenous drug addicts and patients with chronic hepatitis C virus infection. The detection was achieved by nested PCR to amplify the 5' noncoding region (5'NCR) of the viral genome. Sequence analysis of the resulting 234 bp product revealed a total of 26 different sequences of which 25 were found to belong to the genotype G3, which is the most prevalent genotypes among Asian isolates, and one belonged to genotype G1, common among African isolates. The sequence divergence between the genotypes was largely clustered in a short variable region (V2) within the 5'NCR, and we showed that genotyping may be achieved equally well by analysis of this variable region as by the more detail analysis of the entire 5'NCR or of the entire viral genome.

5' Untranslated Regions↗
PubMed2001

Association of mitral annulus calcification, aortic valve sclerosis and aortic root calcification with abnormal myocardial perfusion single photon emission tomography in subjects age < or =65 years old.

OBJECTIVES: We examined the hypothesis that mitral annulus calcification (MAC), aortic valve sclerosis (AVS) and aortic root calcification (ARC) are associated with coronary artery disease (CAD) in subjects age < or =65 years. BACKGROUND: Mitral annulus calcification, AVS and ARC frequently coexist and are associated with coronary risk factors and CAD in the elderly. METHODS: We studied 338 subjects age < or =65 years who underwent evaluation of chest pain with myocardial perfusion single photon emission computed tomography (SPECT) and a two-dimensional transthoracic echocardiogram for other indications. The association of MAC, AVS and ARC with abnormal SPECT was evaluated by using chi-square analyses and logistic regression analyses. RESULTS: Compared with no or one calcium deposit and no or one coronary risk factor other than diabetes, multiple (> or =2) calcium (or sclerosis) deposits with diabetes or multiple (> or =2) coronary risk factors were significantly associated with abnormal SPECT in women age < or =55 years old (odds ratio [OR], 20.00), in women age >55 years old (OR, 10.00) and in men age < or =55 years old (OR, 5.55). Multivariate analyses identified multiple calcium deposits as a significant predictor for an abnormal SPECT in women (p < 0.001), younger subjects age < or =55 years (p < 0.05) and the total group of subjects (p < 0.01). CONCLUSIONS: When coronary risk factors are also taken into consideration, the presence of multiple calcium deposits in the mitral annulus, aortic valve or aortic root appears to be a marker of CAD in men < or =55 years old and women.

Aged↗
PubMed2001

Stereoselective synthesis, in vitro, and initial in vivo evaluation of 1-methylpiperidin-4-yl alpha-hydroxy-alpha-(1-iodo-1-propen-3-yl)-alpha-phenylacetate (IPIP): a novel radioiodinated molecular probe with high affinity for the muscarinic receptor.

1-Methylpiperidin-4-yl alpha-hydroxy-alpha-(1-iodo-1-propen-3-yl)-alpha-phenylacetate (IPIP, Fig. 1) was investigated as a potential radioiodinated molecular probe targeted to the muscarinic receptor complex. The IPIP stereoisomers were synthesized via a chiral intermediate in >95% enantiomeric excess. The R-isomers demonstrated a M(1) to M(2) subtype selectivity of approximately 3 to 1 and the S-isomers demonstrated non-subtype selective binding in vitro. IPIP was radiolabeled with iodide-125 with an average radiochemical yield of 74.4% (+/-14.8, n = 5), specific activities >800 mCi/micromol, and radiochemical purities >97%. In vivo the Z-isomers demonstrated high uniform cerebral uptake suggesting non-subtype selective binding. In contrast, E-R-IPIP, after allowing a low uptake in M(2) rich areas to clear, demonstrated a retention of activity in M(1) and M(4) rich cerebral regions. In addition, the cerebral uptake of E-R-IPIP and Z-S-IPIP were inhibited by 70-90% via pretreatment with R-QNB, an established muscarinic antagonist. An ex vivo metabolism study demonstrated Z-S-IPIP was stable at the receptor site with an absence of radiolabeled metabolites.

Animals↗
PubMed2001

Augmentation of in-vitro clot dissolution by low frequency high-intensity ultrasound combined with antiplatelet and antithrombotic drugs.

BACKGROUND: Glycoprotein IIb/IIIa antagonists and heparin are increasingly used for treatment of acute coronary syndromes. There is no data on the effect of these drugs on clot dissolution when combined with low frequency high-intensity ultrasonic energy. We examined a possible additive effect of low frequency high-intensity ultrasound with an antithrombotic, an antiplatelet and a fibrinolytic agent alone or in combinations for in vitro blood clot dissolution. METHODS: Human blood clots were incubated for 10', 15' and 30' in normal saline containing commonly used concentrations of heparin, tirofiban, t-PA and Optison (echocardiographic contrast agent) alone and in combinations. Clots were then randomly exposed to low frequency high-intensity ultrasound (27[emsp3 ]kHz) for 5 minutes. The percent difference in clot weight and the incremental effect of ultrasound energy were calculated. RESULTS: The most significant additive effect of ultrasound energy was detected with the combination of tirofiban and heparin (39+/-2% augmentation after 10' of incubation, p<0.0001). The greatest magnitude of percent clot weight reduction was observed with ultrasound energy combined with either t-PA alone (72+/-1% after 30' incubation, p=0.0016) or with the combination of t-PA, tirofiban, heparin and Optison (68+/-4% after 30' incubation, p=0.015). CONCLUSIONS: Application of low frequency high-intensity ultrasound has an additive effect to antiplatelet, antithrombotic and fibrinolytic drugs, specifically with the combination of tirofiban and heparin or with t-PA; this effect is observed after a short incubation period.

Blood Coagulation↗
PubMed2001

Noninvasive transthoracic low frequency ultrasound augments thrombolysis in a canine model of acute myocardial infarction--evaluation of the extent of ST-segment resolution.

BACKGROUND: Recently it has been demonstrated that transcutaneous delivery of ultrasound combined with tissue plasminogen activator (tPA) is more effective than tPA alone in recanalizing acutely thrombosed canine coronary arteries. In the present study, we investigated the incidence of partial (> or =50%) and complete (> or =70%) ST-segment elevation resolution in the precordial leads of dogs with experimental acute myocardial infarction that were treated with tissue plasminogen activator (tPA) alone or in combination with noninvasive transcutaneous delivery of high-intensity low frequency (27[emsp3 ]kHz) ultrasound. METHODS: Thrombotic coronary occlusions were induced in the midportion of left anterior descending (LAD) coronary artery by electrical injury in 24 dogs. All dogs were given intravenous heparin and tPA. Dogs were randomized to tPA alone (n=12) or combined tPA and adjunctive transcutaneous ultrasound (US) delivery (n=12). Electrocardiograms were recorded at 1) baseline, 2) after coronary occlusion just before initiation of therapy, 3) when coronary angiography showed recanalization of the coronary artery (or at 90 minutes after initiation of therapy if reperfusion did not occur before then) and 4) 90 minutes later. ST amplitude was measured in all 6 precordial leads. RESULTS: ST-segment amplitude at baseline was comparable between the tPA and the US group. Before initiation of therapy, sum of ST-segment elevation tended to be higher in the US group. At reperfusion and 90 minutes thereafter, sum of ST-segment amplitude tended to be smaller for the US group than in the tPA group (p<0.001 for the time effect; p=0.118 for the time x group interaction). Up to 90 minutes after initiation of therapy >/=50% resolution of the sum of precordial ST elevation was detected in 7 out of 11 dogs (63.6%) in the tPA group versus 10 out of 11 dogs (90.9%) in the US group. Ninety minutes thereafter, 3 out of 7 dogs in the tPA group (42.9%) versus 9 of 11 dogs in the US group (81.8%) had >/=50% resolution of the sum of precordial ST elevation. CONCLUSIONS: The combination of tPA with noninvasive transcutaneous delivery of low frequency high-intensity ultrasound resulted in greater resolution of ST-segment elevation when reperfusion occurs and 90 minutes thereafter, as well as a higher rate of epicardial coronary artery reperfusion.

Animals↗
PubMed2001

Influence of ejection fraction and valvular regurgitation on the accuracy of aortic valve area determination.

OBJECTIVE: To examine the influence of left ventricular dysfunction, aortic regurgitation, and mitral regurgitation on commonly used methods for aortic valve area (AVA) determination. BACKGROUND: Each method for AVA determination has its inherent limitations. METHODS: AVA determinations by transesophageal echocardiography (TEE) using planimetry, transthoracic echocardiography (TTE) with application of the continuity equation, and cardiac catheterization applying the Gorlin formula were performed in 74 patients with aortic stenosis. The severity of the aortic stenosis was defined by consensus of at least two methods. Over- or underestimation of AVA associated with ejection fraction, aortic regurgitation, mitral regurgitation, or severity of the aortic stenosis for each method in relation to the other two methods was assessed. RESULTS: Mean AVAs were 1.05 +/- 0.51 by TEE, 1.06 +/- 0.51 by TTE, and 1.08 +/- 0.53 by cardiac catheterization. An overestimation of the severity of the aortic stenosis by the Gorlin formula in patients with moderate-to-severe aortic regurgitation as compared to TEE-derived data was found (P = 0.014). A similar trend of overestimation by catheterization in comparison with the TTE data was found. In the context of moderate-to-severe mitral regurgitation, AVA determination by TTE overestimated the degree of aortic stenosis as compared to TEE (P = 0.011) and cardiac catheterization (P = 0.023). CONCLUSIONS: Overall mean AVA did not differ between methods, suggesting that these three methods are equally accurate in a nonselected clinical patient group. However, in the presence of significant aortic regurgitation, the two echocardiographic methods appear more accurate. Our observation of an overestimation of the severity of aortic stenosis by TTE in the presence of moderate-to-severe mitral regurgitation indicates that this possibility should be accounted for in clinical decisions based on TTE determinations of AVA.

Adult↗