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Biomedical subjects

Y Luo

Publications and source records attributed to Y Luo.

At least 127 records · Page 7Linked to original sources

[Combination of mycophenolate mofetil with cyclosporine A and methotrexate as acute GVHD prophylaxis after unrelated donor allogeneic bone marrow transplantation].

OBJECTIVE: To evaluate the efficacy and safety of mycophenolate mofetil (MMF) in combination with cyclosporine A (CsA) and methotrexate (MTX) for prevention of acute graft versus host disease (GVHD) after unrelated donor allogeneic bone marrow transplantation (allo-BMT). METHOD: Twelve cases of unrelated donor allo-BMT were evaluated in a single center trial. The acute GVHD was prevented with 1 g MMF daily in addition to CsA 3 mg x kg(-1) x (-1) and MTX 10 - 15 mg at post BMT day1, day3, day6 and day11. RESULTS: Acute GVHD was found in one case (Grade IV) at the seventh day and two cases (Grade II) at the tenth day and seventeenth day after BMT. These patients were treated with a combination of MMF, methyprednisolone and CsA. The common adverse hematologic events of MMF was leukopenia. CONCLUSION: The preliminary study showed that MMF could be used effectively and safely for prevention of acute GVHD in unrelated donor allo-BMT.

Acute Disease↗

[The effect of leukotriene antagonist on the parameters of dose-response curve obtained after methacholine challenge test].

OBJECTIVE: To investigate the effect of leukotriene antagonist (zafirlucast) on the parameters of dose-response curve (DRC) obtained after methacholine challenge test. METHODS: A therapy trial was conducted with the use of zafirlucast in 20 cases of cough variant asthma (CVA) and 20 cases of asthma. Placebo was used in 4 cases of CVA and 10 cases of asthma for comparison with the two therapy groups respectively. Before and after the zafirlucast treatment a series of parameters of DRC were obtained after the methacholine challenge test and were calculated. These included the response threshold (PC35sGaw), the dose-response slope (DRS), the ratio of the area under the curve to the logarithm of the maximal concentration (AUC/1 g[Cmax]), and the maximal response. RESULTS: Zafirlucast significantly increased the PC35sGaw in the CVA and asthma groups. It conspicuously decreased all the parameters of DRS and AUC/1 g[Cmax] except for maximal response in the cases of CVA, and it had no significant effects on all the parameters of DRS and AUC/1 g[Cmax] except for PC35sGaw in the cases of asthma. CONCLUSION: Short-term use of Zafirlucast in asthmatic patients could improve the parameters of dose-response curve obtained after the methacholine challenge test.

Adult↗

[A comparison between the effects of albuterol and isoproterenol in bronchodilation test].

OBJECTIVE: To compare albuterol with isoproterenol as a bronchodilator in pulmonary function test and their value in the diagnosis and differential diagnosis of asthma. METHODS: Two groups (59 patients with asthma and 37 patients with COPD) were included in this study, and the patients of each group were randomly divided into 2 subgroups. The patients in the 2 subgroups inspired the two drugs in a cross-over by odd or even days. The pulmonary functions were evaluated. RESULTS: The changing rates of pulmonary functions induced by the two drugs in the two groups were positively correlated (P < 0.005), The changing rates of FEV1, MMEF, Raw, sGaw induced by albuterol were higher than the ones induced by isoproterenol in patients with asthma(P < 0.02), however the changing rates of FVC and PEF in asthma cases and all the above parameters in COPD cases were not significantly different between the two drugs(P > 0.10). The comparison of positive case number between asthma and COPD cases induced by both drugs showed significant difference(P < 0.005); especially, when the positive rate of sGaw induced by albuterol in asthma cases reached 98%, the positive rates in COPD cases was generally much lower. CONCLUSION: Bronchodilation test is a valuable diagnostic method for asthma. In this study, albuterol was superior to isoproterenol. The most sensitive index in bronchodilation test was sGaw, then in order, FEV1(92%), MMEF and Raw; the FVC and PEF were relatively insensitive.

Adult↗

[Measurement of central respiratory drive and inspiratory muscles strength in patients with uremia].

OBJECTIVE: To investigate the changes of central respiratory drive and inspiratory muscles function in patients with uremia. METHODS: We performed the measurement of forced vital capacity (FVC), maximal voluntary ventilation (MBC), forced expiratory volume in one second (FEV1), peak expiratory flow (PEF), maximal midexpiratory flow (MMEF), expiratory flow of 25 per cent of FVC (V25), lung carbon monoxide diffusing capacity (DLco), maximal inspiratory mouth pressure (MIP) and airway occlusion pressure (P0.1) in 25 patients with uremia and 20 normal subjects. RESULTS: In patients with uremia, the FVC, MBC, FEV1, PEF, MMEF and V25 which reflect the lung ventilatory function and the DLco which reflects the lung diffusing function were significantly lower than those in normal subjects. The patients' MIP which reflects inspiratory muscles strength was significantly lower and their P0.1 which reflects the central respiratory drive was significantly higher, compared with the normal subjects'. CONCLUSION: Our findings suggest that on the basis of the disorder of ventilation and diffusing function of the lungs, the inspiratory muscles function of the patients with uremia is significantly decreased and the central respiratory drive of the patients is increased.

Aged↗

[Measurement of the parameters of dose-response curve obtained after the methacholine challenge test].

OBJECTIVE: To investigate the clinical value in the measurement of parameters of the dose-response curve (DRC) obtained after the methacholine challenge test. METHODS: Twenty-seven cases of cough variant asthma (CVA), 29 of mild asthma, 19 of moderate asthma, and 15 healthy volunteers underwent the methacholine challenge test. The dose-response curves were constructed. The following parameters were calculated: position (PC35sGaw), dose-response curve (DRS), ratio of the area under the curve to the logarithm of the maximal concentration (AUC/lg[Cmax]) and maximal response. RESULTS: A plateau appeared in 11 cases among the healthy subjects, while a plateau appeared only in 2 cases of CVA and 2 of asthma. There were no significant differences among the asthmatic groups in the measurements of PC35sGaw and AUC/lg[Cmax] (geometric mean PC35sGaw: mild asthmatics = 0.369, moderate asthmatics = 0.251, cough variant asthmatics = 0.547), AUC/lg[Cmax] was significantly greater in the asthmatic groups than in the normal group [AUC/lg [Cmax](mean +/- s): mild asthmatics = 24.7 +/- 4.7, moderate asthmatics = 26.6 +/- 4.3, cough variant asthmatics = 25.6 +/- 3.7, normal subjects = 15.5 +/- 4.3, P < 0.01]. DRS of moderate asthmatics was significantly greater as compared with cough variant asthmatics (geometric mean DRS: mild asthmatics = 30.761, moderate asthma-tics = 59.020, cough variant asthmatics = 19.231, P < 0.05), but there was no difference between the other groups. PC35sGaw was negatively correlated with DRS (r = 0.866, P < 0.001) and with AUC/lg[Cmax] (r = 0.502, P < 0.001). CONCLUSION: Four parameters of DRC obtained after the methacholine challenge represent airway sensitivity and reactivity respectively. The parameters of DRC of asthmatic patients are different from those of normal subjects. The sensitivity is related to the reactivity, but they are not completely parallel with each other.

Adult↗

[Surgical treatment and reconstruction for the patients with advanced-stage tonsillar cancer].

OBJECTIVE: To investigate the operative approach and reconstruction for the patients with advanced-stage tonsillar cancer. METHOD: 7 cases with advanced-stage tonsillar cancer were operated from Dec. 1994 to May 1999. Among them, 5 cases were operated through combined neck-mandible-oral cavity approach (CNMOCA) and with immediate reconstruction. Forearm free skin (FFS) flaps were applied in 3 cases. Pectoralis major myocutaneous (PMM) flaps were applied in 2 cases. 2 other cases were operated separately through approach of oral cavity or lateral pharynx. 6 cases were operated with radical neck dissection. RESULT: 5 cases who were operated through CNMOCA or with reconstruction were followed up from 1 year to 5 years and 3 months. They had not recurrence of tumor and complication. All had function recovery of speech. Swallowing or appearance is satisfactory in the 3 cases with FFS flaps. 2 Other cases died as recurrence of tumor in 1 year and 2 years and 10 months post-operation. CONCLUSION: CNMOCA is able to provide a good exposure method to remove the extensive tumors completely for the patients with advanced stage tonsillar cancer. It is necessary to reconstruct immediately for the patients.

Adult↗

[A multi-centered clinical study an domestic intravenous Turbutalin sulfate in the treatment of asthma and chronic asthmatic bronchitis].

OBJECTIVE: This multi-centered clinical trial was designed to assess the efficacy and safety of domestic intravenous Turbutalin Sulfate in the treatment of asthma and chronic asthmatic bronchitis. METHODS: Bricanyl was used as control. A total of 120 patients were included in this randomized controlled study. The two medications, both at a dose of 0.25 mg intravenous drip, were given three times a day for 3-5 days. RESULTS: The two drugs' clinical excellent rates were 66.7% and 73.3%; overall efficacy rates were 98.3% and 100.0%, respectively. Their pulmonary functional excellent rates were 78.4% and 76.6%; overall effect rates were 88.3% and 90.0%, respectively. Composite curative evaluation showed that the two drug's composite excellent rates were 61.6% both; their overall efficacy rates were 88.3% and 90.0%, respectively. All of these showed no significant difference (P > 0.05). The incidence rates of adverse side effects of the two groups were 13.5% and 15.0%, respectively; most of them were mild and tolerable. CONCLUSION: Domestic intravenous Terbutalin Sulfate is effective and safe in treating asthma and chronic asthmatic bronchitis.

Adolescent↗

[An epidemiological study of spongiform leucoencephalopathy among heorin abusers].

OBJECTIVE: To understand the distribution and related risk factors of heroin spongiform leucoencephalopathy among drug users in coastland of Guangdong Province. METHODS: A cross-sectional study was conducted in four thousand four hundred and twenty eight drug users from eighteen detoxification organizations in six cities on coastland of Guangdong, using clustered random sampling methods. The six cities are Chaoyang (714), Heyuan (462), Shantou (572), Huidong (1286), Guangzhou (871) and Zhanjiang (523) and heroin abuse was considered serious in these cities. Questionnaire was used to collect the data on sex (man 3632, 82 percent; woman 795, 18 percent), age (minimum 15y, maximum 54y), duration of using heroin (minimum 1 month, maximum 150 months), daily dosage (minimum 0.02 g, maximum 6.0 g) and manner of using heroin. In addition, the neurological examination was taken in all of them and cerebral MRI was carried out in those with signs of cerebellar ataxia. RESULTS: Results showed that the total incidence of heroin spongiform leucoencephalopathy in six cities is 3.16 per thousand. Poisson regression analysis showed that the incidence was related to residential areas. In comparison with other cities, there are higher incidences in Chaoyang and Heyuan. Our investigation also showed that all the patients with this disease used heroin by inhaling the pyrolysate. The incidence of heroin spongiform leucoencephalopathy was unrelated to the daily inhaling amount of heroin and the duration of inhaling heroin. No differences could be observed between the groups of different age and sex. CONCLUSIONS: Spongiform leucoencephalopathy after inhalation of heroin is a rare complication and has never been reported in mainland of China before. The lesions are symmetrical and spongiform, but not necrotic and the cerebellum is invariably involved--a feature consistent with the clinical presentation that begins with ataxia. Cerebral CT showed symmetrical non-enhancing hypodense areas in both cerebellar hemispheres. Cerebral MRI showed the corresponding areas with decreased signal intensity on T1 weighted images and increased signal intensity on T2 weighted images. There was no contrast enhancement. When it occurs, several cases are affected as a small epidemic. It is suggested that the aetiology is related to the heroin batch and could perhaps be a toxic effect of a substance which came from heroin pyrolysis.

Administration, Inhalation↗

Hypobaric hypoxia induces fos and neuronal nitric oxide synthase expression in the paraventricular and supraoptic nucleus in rats.

This study examined the effects of high altitude exposure on neurons in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus in adult and neonatal rats. In adult control rats, occasional Fos-like immunoreactive neurons were localized in both the hypothalamic nuclei. A marked increase in Fos positive cells was induced at 1-4 h following altitude exposure but it was reduced to levels comparable to the controls at 24 h. The expression of neuronal nitric oxide synthase (nNOS) immunoreactivity in the PVN and SON followed a similar temporal pattern. The nNOS immunoreactivity, which was constitutively expressed in the hypothalamic neurons in the control rats, was noticeably augmented at 1-4 h, but it was comparable to the controls at 24 h following altitude exposure. In postnatal rats, Fos expression was not detected in the hypothalamic neurons of the controls. Induction of Fos expression was observed in some neurons at 1-4 h following altitude exposure but it was diminished at 24 h. There was no noticeable change in nNOS expression in both the control and altitude exposed postnatal rats; in both instances, it was barely detectable. It is concluded that both the PVN and SON of the adult rats are activated at high altitude exposure and that they may be involved in the regulation of neuroendocrine, cardiovascular and respiratory functions in hypobaric hypoxia. This study has also shown the differential response of the hypothalamus neurons between the two age groups to the hypoxic insult. Our results suggest that the adult neurons are probably more sensitive to the reduced oxygen levels in hypobaric hypoxia, as reflected by the upregulated NOS expression in this age group but not in the postnatal rats.

Altitude Sickness↗

Proximity relationships between residue 6 of troponin I and residues in troponin C: further evidence for extended conformation of troponin C in the troponin complex.

Skeletal muscle troponin C (TnC) adopts an extended conformation when crystallized alone and a compact one when crystallized with an N-terminal troponin I (TnI) peptide, TnI(1-47) [Vassylyev et al. (1998) Proc. Natl. Acad. Sci. U.S.A. 95, 4847-4852]. The N-terminal region of TnI (residues 1-40) was suggested to play a functional role of facilitating the movement of TnI's inhibitory region between TnC and actin [Tripet et al. (1997) J. Mol. Biol. 271, 728-750]. To test this hypothesis and to investigate the conformation of TnC in the intact troponin complex and in solution, we attached fluorescence and photo-cross-linking probes to a mutant TnI with a single cysteine at residue 6. Distances from this residue to residues of TnC were measured by the fluorescence resonance energy transfer technique, and the sites of photo-cross-linking in TnC were determined by microsequencing and mass spectrometry following enzymatic digestions. Our results show that in the troponin complex neither the distance between TnI residue 6 and TnC residue 89 nor the photo-cross-linking site in TnC, Ser133, changes with Ca(2+), in support of the notion that this region plays mainly a structural rather than a regulatory role. The distances to residues 12 and 41 in TnC's N-domain are both considerably longer than those predicted by the crystal structure of TnC.TnI(1-47), supporting an extended rather than a compact conformation of TnC. In the binary TnC.TnI complex and the presence of Ca(2+), Met43 in TnC's N-domain was identified as the photo-cross-linking site, and multiple distances between TnI residue 6 and TnC residue 41 were detected. This was taken to indicate increased flexibility in TnC's central helix and that TnC dynamically changes between a compact and an extended conformation when troponin T (TnT) is absent. Our results further emphasize the difference between the binary TnC.TnI and the ternary troponin complexes and the importance of using intact proteins in the study of structure-function relationships of troponin.

Animals↗

Astrocytes express functional chemokine receptors.

Multiple lines of evidence are presented characterizing the functional expression of chemokine receptors CXCR4, CCR1, CCR5, and CX3CR1 on astrocytes. Most of these receptors are expressed at low levels and may only be detectable on a subset of cells during disease or following cytokine induction. The expression of CXCR2, CCR2, CCR3, CCR10, CCR11, and several orphan receptors associated with HIV-1 infection has also been proposed. The appearance of several chemokine receptors implies a wider role for chemokines in the regulation of central nervous system functions. Available evidence indicates that selected chemokines induce further chemokine synthesis in astrocytes providing a mechanism to amplify inflammatory responses in the central nervous system.

Animals↗

Angiogenesis is induced in a rabbit model of hindlimb ischemia by naked DNA encoding an HIF-1alpha/VP16 hybrid transcription factor.

BACKGROUND: Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric transcription factor that regulates expression of genes involved in O(2) homeostasis, including vascular endothelial growth factor (VEGF), a potent stimulator of angiogenesis. We sought to exploit this native adaptive response to hypoxia as a treatment for chronic ischemia. METHODS AND RESULTS: A hybrid protein consisting of DNA-binding and dimerization domains from the HIF-1alpha subunit and the transactivation domain from herpes simplex virus VP16 protein was constructed to create a strong, constitutive transcriptional activator. After transfection into HeLa, C6, and Hep3B cells, this chimeric transcription factor was shown to activate expression of the endogenous VEGF gene, as well as several other HIF-1 target genes in vitro. The bioactivity of HIF-1alpha/VP16 hybrid gene transfer in vivo was examined in a rabbit model of hindlimb ischemia. Administration of HIF-1alpha/VP16 was associated with significant improvements in calf blood pressure ratio, angiographic score, resting and maximal regional blood flow, and capillary density (all P:<0.01). CONCLUSIONS: The HIF-1alpha/VP16 hybrid transcription factor is able to promote significant improvement in perfusion of an ischemic limb. These results confirm the feasibility of a novel approach for therapeutic angiogenesis in which neovascularization may be achieved indirectly by use of a transcriptional regulatory strategy.

Angiography↗

The nonsense-mediated decay pathway and mutually exclusive expression of alternatively spliced FGFR2IIIb and -IIIc mRNAs.

Exons IIIb and IIIc of the FGFR2 gene are alternatively spliced in a mutually exclusive manner in different cell types. A switch from expression of FGFR2IIIb to FGFR2IIIc accompanies the transition of nonmalignant rat prostate tumor epithelial cells (DTE) to cells comprising malignant AT3 tumors. Here we used transfection of minigenes with and without alterations in reading frame and with and without introns to examine how translation affects observed FGFR2 splice products. We observed that nonsense mutations in other than the last exon led to a dramatic reduction in mRNA that is abrogated by removal of downstream introns in both DTE and AT3 cells. The mRNA, devoid of both IIIb and IIIc exons (C1-C2), is a major splice product from minigenes lacking an intron downstream of the second common exon C2. From these observations, we suggest that repression of exon IIIc and activation of exon IIIb inclusion in DTE cells lead to the generation of both C1-IIIb-C2 and C1-C2 products. However, the C1-C2 product from the native gene is degraded due to a frameshift and a premature termination codon caused by splicing C1 and C2 together. Derepression of exon IIIc and repression of exon IIIb lead to the generation of both C1-IIIc-C2 and C1-C2 products in AT3 cells, but the C1-C2 product is degraded. The C1-IIIb-IIIc-C2 mRNA containing a premature termination codon in exon IIIc was present, but at apparently trace levels in both cell types. The nonsense-mediated mRNA decay pathway and cell type-dependent rates of inclusion of exons IIIb and IIIc result in the mutually exclusive expression of FGFR2IIIb and IIIc.

Alternative Splicing↗

Cross-linked hyaluronic acid hydrogel films: new biomaterials for drug delivery.

A new hyaluronic acid (HA)-based hydrogel film was prepared and evaluated for use in drug delivery. This biocompatible material crosslinks and gels in minutes, and the dried film swells and rehydrates to a flexible hydrogel in seconds. HA was first converted to the adipic dihydrazide derivative and then crosslinked with the macromolecular homobifunctional reagent poly(ethylene glycol)-propiondialdehyde to give a polymer network. After gelation, a solvent casting method was used to obtain a HA hydrogel film. The dried film swelled sevenfold in volume in buffer, reaching equilibrium in less than 100 s. Scanning electron microscopy (SEM) of the hydrogel films showed a condensed and featureless structure before swelling, but a porous microstructure when hydrated. The thermal behavior of the hydrogel films was characterized by differential scanning calorimetry. The enzymatic degradation of the HA hydrogel films by hyaluronidase was studied using both SEM and a spectrophotometric assay. Drug release from the hydrogel film was evaluated in vitro using selected anti-bacterial and anti-inflammatory drugs. This novel biomaterial can be employed for controlled release of therapeutic agents at wound sites.

Anti-Infective Agents↗

Modulation of experimental autoimmune encephalomyelitis: effect of altered peptide ligand on chemokine and chemokine receptor expression.

Experimental autoimmune encephalomyelitis (EAE) is a T helper 1 (Th1) cell mediated demyelinating disease and the principal animal model for multiple sclerosis. Spinal cords from SJL mice primed with proteolipid protein peptide 139-151 (pPLP) expressed the chemokines RANTES, MCP-1, MIP-2, KC, MIP-1alpha, MIP-1beta, Mig, and fractalkine. We also identified IP-10 in these samples and described a sequence polymorphism in this transcript. Chemokine expression was specific for tissues of the central nervous system. MCP-1, IP-10, and MIP-2 RNA expression significantly correlated with clinical score. Chemokine receptor expression generally correlated with ligand expression. pPLP-primed mice expressed the Th1-associated markers CCR5 and CXCR3 on mononuclear cells. In addition, cells expressing CCR1, CCR2, CCR3, CCR4, CCR8, and CXCR2 were detected. Here we demonstrate that altered peptide ligand (APL)-induced protection from EAE was accompanied by modulation of chemokine and chemokine receptor expression. Spinal cord tissue sections from APL-protected mice showed greatly reduced levels of all chemokines and of CCR1, CCR5, CCR8, CXCR2 and CXCR3. The Th2-associated chemokine receptors CCR3 and CCR4 were found in protected mice, supporting the hypothesis that Th1 but not Th2 cells are down-regulated by APL treatment. This report concludes that chemokines and chemokine receptors can be useful tools to follow modulation of autoimmune disease.

Animals↗

Macrophage inflammatory protein-2 and KC induce chemokine production by mouse astrocytes.

Astrocytes are specialized cells of the CNS that are implicated in the pathogenesis of multiple sclerosis and experimental allergic encephalomyelitis. In acute and relapsing-remitting experimental allergic encephalomyelitis, the neutrophil chemoattractant CXC chemokines macrophage-inflammatory protein (MIP)-2 and KC are associated with reactive astrocytes in the parenchyma. In vitro treatment of primary astrocyte cultures with nanomolar concentrations of MIP-2 or KC markedly up-regulated expression of the monocyte/T cell chemoattractants monocyte chemoattractant protein-1, inflammatory protein-10, and RANTES by a mechanism that includes stabilization of mRNA. Production of TNF-alpha and IL-6 transcripts were also noted, as was autocrine induction of MIP-2 and KC message. In addition, low levels of MIP-1alpha and MIP-1beta were induced following treatment with MIP-2 or KC. These effects are specific to astrocytes as MIP-2 treatment of microglial cells failed to elicit chemokine production. The astrocyte chemokine receptor for MIP-2 has 2.5 nM affinity for ligand. Astrocytes from CXCR2-deficient mice still respond to KC and MIP-2, indicating the presence of an alternative or novel high affinity receptor for these ligands. We propose that this KC/MIP-2 chemokine cascade may contribute to the persistence of mononuclear cell infiltration in demyelinating autoimmune diseases.

Acute Disease↗

Sterol-dependent transactivation of the ABC1 promoter by the liver X receptor/retinoid X receptor.

Tangier disease, a condition characterized by low levels of high density lipoprotein and cholesterol accumulation in macrophages, is caused by mutations in the ATP-binding cassette transporter ABC1. In cultured macrophages, ABC1 mRNA was induced in an additive fashion by 22(R)-hydroxycholesterol and 9-cis-retinoic acid (9CRA), suggesting induction by nuclear hormone receptors of the liver X receptor (LXR) and retinoid X receptor (RXR) family. We cloned the 5'-end of the human ABC1 transcript from cholesterol-loaded THP1 macrophages. When transfected into RAW macrophages, the upstream promoter was induced 7-fold by 22(R)-hydroxycholesterol, 8-fold by 9CRA, and 37-fold by 9CRA and 22(R)-hydroxycholesterol. Furthermore, promoter activity was increased in a sterol-responsive fashion when cotransfected with LXRalpha/RXR or LXRbeta/RXR. Further experiments identified a direct repeat spaced by four nucleotides (from -70 to -55 base pairs) as a binding site for LXRalpha/RXR or LXRbeta/RXR. Mutations in this element abolished the sterol-mediated activation of the promoter. The results show sterol-dependent transactivation of the ABC1 promoter by LXR/RXR and suggest that small molecule agonists of LXR could be useful drugs to reverse foam cell formation and atherogenesis.

ATP Binding Cassette Transporter 1↗