Biomedical subjects

Kun Yang

Publications and source records attributed to Kun Yang.

83 records · Page 5Linked to original sources

PubMed2002

Origins of GABA(B) receptor-like immunoreactive terminals in the rat spinal dorsal horn.

By means of immunohistochemistry for gamma-aminobutyric acid receptor B subtype (GABA(B)R), the origins of GABA(B)R-like immunoreactive (GABA(B)R-LI) terminals in the rat spinal dorsal horn were investigated. After dorsal root rhizotomy and/or spinal cord hemisection, the densities of GABA(B)R-LI terminals were remarkably depleted in the ipsilateral superficial dorsal horn of relevant segments, whereas GABA(B)R-LI neurons and sparsely distributed GABA(B)R-LI terminals remained. After injection of Fluoro-Gold (FG) into the left side of superficial lumbar dorsal horn, FG retrograde-labeled neurons were mainly observed in the ipsilateral rostral ventromedial medulla (RVM) and brainstem raphe nuclei. Some of the FG-labeled neurons, especially in the RVM, exhibited GABA(B)R-like immunoreactivity. Additionally, immunofluorescence histochemical double-staining revealed that the majority of GABA(B)R-LI neurons in the periaqueductal gray (PAG), RVM and brainstem raphe nuclei showed 5-hydroxytryptamine (5-HT)-like immunoreactivity. The present study morphologically proves that GABA(B)R-LI terminals in the spinal dorsal horn originate from peripheral afferents, intrinsic neurons and supraspinal structures; GABA(B)R and 5-HT co-exist in many neurons in the PAG, RVM and brainstem raphe nuclei. Considering that PAG, RVM, brainstem raphe nuclei and spinal dorsal horn are important structures involved in the pain modulation, we suggest that the descending pain modulation system might be mediated, at least in part, by GABA(B)R.

Afferent Pathways↗

PubMed2002

Norepinephrine depresses the capsaicin-evoked miniature excitatory postsynaptic currents in substantia gelatinosa of the rat spinal cord.

Capsaicin selectively excites nociceptive primary afferent fibers and increases the frequency of glutaminergic miniature excitatory postsynaptic currents (mEPSCs) in the substantia gelatinosa of the spinal dorsal horn. The whole-cell voltage-clamp recording technique was used to examine the effect of norepinephrine (NE) on the capsaicin-induced increase in the frequency of mEPSCs. In the presence of tetrodotoxin, bath application of capsaicin (1 microM) remarkably enhanced the frequency of mEPSCs (295+/-52% of control). Following pretreatment with NE (10 microM), the capsaicin-induced frequency facilitation of mEPSCs was significantly depressed to 151+/-17% of the control. NE-induced depression in capsaicin action was blocked by yohimbine, a selective alpha(2)-adrenergic receptor antagonist, indicating that NE exerts depression by activating the alpha(2)-adrenergic receptor. As the postsynaptic action of NE has been precluded in the present study, the results suggest that NE inhibits nociceptive input at a presynaptic site, the primary afferent terminal, during the nociceptive transmission in the spinal dorsal horn.

Adrenergic alpha-Agonists↗

PubMed2002

Reconstruction of fractional quantum Hall edges.

We study the interplay of electron-electron interaction, confining potential and effects of finite temperature at the edge of a quantum Hall liquid. Our exact diagonalization calculation indicates that edge reconstruction occurs in the fractional quantum Hall regime for a variety of confining potential, including ones that correspond to a "sharp" edge. Our finite temperature Hartree-Fock calculation for integer quantum Hall edges indicates that reconstruction is suppressed above a certain temperature. We discuss the implication of our results on recent edge tunneling and microwave absorption experiments.

Journal Article↗

PubMed2002

The second National Epidemiological Survey on illicit drug use at six high-prevalence areas in China: prevalence rates and use patterns.

AIMS: This is the first part of the Second National Epidemiological Survey on Illicit Drug Use in six high-prevalence areas in China in 1996. The scale of illicit drug abuse and patterns of use in the survey areas were assessed. DESIGN, SETTING AND PARTICIPANTS: 67 319 registered permanent residents in the community and those who were at institutions at the point of the survey (15 years old and over, males 34 755, 51.6%; females 32 564, 48.4%) in selected areas in China were screened and interviewed by trained psychiatrists. MEASUREMENTS: Demographics and drug-related data were assessed using the Epidemiological Inventory for Illicit Drug Use developed by the authors. Illicit drugs in this study were defined as a group of psychoactive substances controlled by international and national laws, used for non-medical purposes, including opiate, cocaine, amphetamine-type stimulants (ATS), cannabis, hallucinogens, etc. FINDINGS: The lifetime prevalence of illicit drug use was 1.60% (male, 2.58%, female 0.57%), and 1-year prevalence was 1.17% (male 1.80%, female 0.48%). There were 67 cases who used a drug initially before 1952; no new cases of illicit drug use could then be found during the period of 1952-86. However, the number of new drug users in each year has been rising steadily since 1986. The majority of drugs used were opiates in which heroin dominated, although there was some variability among the six sites. The main routes of administration were inhalation and intravenous injection. More than half the users (59.1%) took drugs on seven occasions or less per week, and 15.8% users used drugs on 21 occasions or more per week. CONCLUSION: Compared with the data from the 1993 survey, illicit drug use has continued to escalate across the areas, calling for priority concern in various sections of the country.

Adolescent↗

PubMed2002

Impairment of polymorphonuclear neutrophil functions precedes nosocomial infections in critically ill patients.

OBJECTIVE: A postinjury immunodepression involving neutrophil functions has been described in critically ill patients. The aim of this prospective study was to search for a relationship between an impairment of neutrophil functions and the subsequent development of nosocomial infection. DESIGN: Twenty-one severely ill (simplified acute physiology score II >20 on admission), nonimmunosuppressed patients who were receiving no antibiotics active against methicillin-resistant Staphylococcus aureus and highly resistant Pseudomonas aeruginosa were included. Twelve healthy subjects constituted a control group. MEASUREMENTS: Neutrophil functions (phagocytosis and bactericidal activity toward S. aureus and P. aeruginosa in homologous plasma, reactive oxygen species secretion) were studied at day 4 +/- 1 after admission, and occurrence of nosocomial infection was prospectively recorded over the following 5 days. Interleukin-10 concentration was assessed by enzyme-linked immunosorbent assay. Results are expressed as median (25th-75th percentiles). MAIN RESULTS: Six out of the 21 patients acquired a nosocomial infection during the 5 days after blood sampling (infected group). Compared with the patients who did not acquire nosocomial infection (noninfected group, n = 15), the neutrophils of the infected group demonstrated a higher percentage of intracellular bacterial survival (17% [2% to 67%] vs. infected: 62% [22% to 100%], p <.05), leading to an impairment of S. aureus killing in homologous plasma (killed bacteria: 4.93 log(10) colony forming units/mL [4.24-5.29] vs. infected: 3.62 log(10) colony forming units/mL [0.00-4.58], p <.05). Interleukin-10 plasma concentration was higher in infected patients (78 pg/mL [60-83]) compared with noninfected patients (22 pg/mL [14-58], p <.05). By contrast, P. aeruginosa killing was similar in patients whether or not they acquired a nosocomial infection. CONCLUSION: A decrease in S. aureus killing capabilities of neutrophils can be evidenced within the days before occurrence of a nosocomial infection.

Adult↗

PubMed2002

Granulocyte colony-stimulating factor enhances host defenses against bacterial pneumonia following peritonitis in nonneutropenic rats.

OBJECTIVE: Polymorphonuclear cell functions frequently are impaired in critically ill patients, and restoration of normal functions could help to prevent nosocomial infections. The aim of this study was to evaluate the effects of pretreatment with granulocyte colony-stimulating factor (G-CSF) on bacterial pneumonia induced 48 hrs after peritonitis (cecal ligation and puncture [CLP]) in rats. DESIGN: Controlled animal study. SETTING: Research laboratory of an academic institution. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: First, the CLP model was characterized. Second, alveolar endotoxin instillation allowed us to evaluate the ability of neutrophils to migrate to airspaces after CLP was assessed. In the last set of experiments, CLP was followed by G-CSF treatment as a preventive therapy for subsequent bacterial superinfection induced by alveolar instillation. MEASUREMENTS AND MAIN RESULTS: CLP induced a brief increase in proinflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta) at the 6th hr followed by a longer-lived anti-inflammatory response (interleukin-10 increase from days 1 to 3) in plasma, compared with healthy rats. Impaired neutrophil migration to alveolar spaces denoting immunoparalysis was evidenced after endotracheal endotoxin instillation following CLP, compared with non-CLP rats challenged with endotoxin. No such impairment was found when G-CSF (100 microg/kg: glycosylated recombinant human G-CSF, Lenograstim) was given before endotoxin. G-CSF (100 microg/kg 24 and 48 hrs after CLP) given before endotracheal instillation increased bacterial clearance, as shown by counts in both bronchoalveolar lavage (8.9 x 10 +/- 2.8 x 10 colony-forming units/mL vs. 3.3 x 10 +/- 1.5 x 10 colony-forming units/mL with saline) and lung tissue (4.2 x 10 +/- 1.0 x 10 colony-forming units/g vs. 1.5 x 10 +/- 0.6 x 10 colony-forming units/g with saline). Furthermore, G-CSF pretreatment kept clearance in CLP rats similar to that in non-CLP rats challenged with. CONCLUSION: These results suggest that G-CSF (Lenograstim) may enhance host defenses in rats with peritonitis and immunoparalysis.

Animals↗

PubMed2002

Exacerbation by granulocyte colony-stimulating factor of prior acute lung injury: implication of neutrophils.

OBJECTIVE: Granulocyte colony-stimulating factor is widely prescribed to hasten recovery from cancer chemotherapy-induced neutropenia and has been reported to induce pulmonary toxicity. However, circumstances and mechanisms of this toxicity remain poorly known. DESIGN: To reproduce a routine situation in cancer patients receiving chemotherapy, we investigated the mechanisms underlying granulocyte colony-stimulating factor-induced exacerbation of alpha-naphthylthiourea-related pulmonary edema. SETTING: Laboratory research unit. SUBJECTS: Male specific-pathogen-free Sprague-Dawley rats. INTERVENTIONS: The effects of granulocyte colony-stimulating factor given alone or after alpha-naphthylthiourea used to induce acute lung injury were investigated. MEASUREMENTS AND MAIN RESULTS: Lung injury was assessed based on neutrophil sequestration (myeloperoxidase activity in lung tissue) and influx into alveolar spaces (bronchoalveolar lavage fluid cell quantification) and on edema formation (wet/dry lung weight ratio) and alveolar protein concentration into bronchoalveolar lavage fluid. Tumor necrosis factor-alpha and interleukin-1beta were measured in serum, lung homogenates, and isolated alveolar macrophage supernatants. In control rats, granulocyte colony-stimulating factor (25 microg/kg) significantly elevated circulating neutrophil counts without producing alveolar recruitment or pulmonary edema. alpha-Naphthylthiourea significantly increased the wet/dry lung weight ratio (4.68 +/- 0.04 vs. 4.38 +/- 0.07 in controls, p=.04) and induced alveolar protein leakage. Adding granulocyte colony-stimulating factor to alpha-naphthylthiourea exacerbated pulmonary edema, causing neutrophil sequestration in pulmonary vessels, significantly increasing lung myeloperoxidase activity (12.7 +/- 2.0 mOD/min/g vs. 1.1 +/- 0.4 mOD/min/g with alpha-naphthylthiourea alone; p<.0001), and increasing proinflammatory cytokine secretion. alpha-Naphthylthiourea-related pulmonary edema was not exacerbated by granulocyte colony-stimulating factor during cyclophosphamide-induced neutropenia or after lidocaine, which antagonizes neutrophil adhesion to endothelial cells. Tumor necrosis factor-alpha and interleukin-1beta concentrations in alveolar macrophage supernatants and lung homogenates were significantly higher with alpha-naphthylthiourea + granulocyte colony-stimulating factor than with either agent alone, and anti-tumor necrosis factor-alpha antibodies abolished granulocyte colony-stimulating factor-related exacerbation of alpha-naphthylthiourea-induced pulmonary edema. In rats with cyclophosphamide-induced neutropenia, tumor necrosis factor-alpha concentrations in alveolar macrophage supernatants and lung homogenates were significantly decreased compared with rats without neutropenia. CONCLUSION: Granulocyte colony-stimulating factor-related pulmonary toxicity may involve migration of neutrophils to vascular spaces, adhesion of neutrophils to previously injured endothelial cells, and potentiation of proinflammatory cytokine expression.

Animals↗

PubMed2002

Identification of CD226 ligand on colo205 cell surface.

AIM: To confirm the existence of CD226 ligand and its distribution, which is a novel molecule cloned in 1996. METHODS: The mRNA was extracted from TPA activated Jurkat cells and used as a template for reverse-transcription. After PCR amplification, the fragment including CD226 extracellular region and the splice donor sequence "ACTTACCTGT" was obtained and cloned into fusion expression vector pIG. The recombinant vector pCD226/Ig was transfected in COS-7 cells by DEAE-Dextran method, the secreting fusion protein was identified by Sandwich ELISA, and was purified by anti-CD226 affinity chromatography. This fusion protein was used as a probe in the investigation of CD226 ligand by immunohistochemistry. Existence of CD226 ligand was further identified by adhesion experiment. RESULTS: Expression of a secreting fusion protein was identified by sandwich ELISA,indicating that both CD226 extracellular domain and IgGFc domain could be recognized respectively by anti-CD226 and anti-hIgFc mAb. About 130g CD226/Ig fusion protein could be obtained from 100mL COS-7 culture supernatants by anti-CD226 affinity chromatography purification. SDS-PAGE showed that this fusion protein has a molecular mass of 83ku. It was confirmed by immunohistochemistry that CD226 ligand expressed on the Colo205 cells, but not on Jurkat cell, U937 cell and mixed lymphocyte culture cells. In adhesive assay, resting Jurkat cells did not have significant adhesion to Colo205 cells. In contrast, activated Jurkat cells could bind to colon carcinoma Colo205 cells and this adhesive reaction could be blocked by CD226/Ig fusion protein or anti-CD226 mAb. Immunochemical experiment showed that Colo205 cells could be specifically stained by CD226/Ig, indicating that CD226 ligand exists on the surface of Colo205 cells. CONCLUSION: Existence of CD226 ligand on the surface of Colo205 cells was identified by immunohistochemistry and adhesion blocking experiment. In addition, the secreting CD226/Ig fusion protein prepared in this study will be a potential tool for further investigation of CD226 ligand.

Animals↗

PubMedDate not supplied

Virtual screening of novel noncovalent inhibitors for SARS-CoV 3C-like proteinase.

The SARS coronavirus 3C-like proteinase is considered as a potential drug design target for the treatment of severe acute respiratory syndrome (SARS). Owing to the lack of available drugs for the treatment of SARS, the discovery of inhibitors for SARS coronavirus 3C-like proteinase that can potentially be optimized as drugs appears to be highly desirable. We have built a "flexible" three-dimensional model for SARS 3C-like proteinase by homology modeling and multicanonical molecular dynamics method and used the model for virtual screening of chemical databases. After Dock procedures, strategies including pharmocophore model, consensus scoring, and "drug-like" filters were applied in order to accelerate the process and improve the success rate of virtual docking screening hit lists. Forty compounds were purchased and tested by HPLC and colorimetric assay against SARS 3C-like proteinase. Three of them including calmidazolium, a well-known antagonist of calmodulin, were found to inhibit the enzyme with an apparent K(i) from 61 to 178 microM. These active compounds and their binding modes provide useful information for understanding the binding sites and for further selective drug design against SARS and other coronavirus.

Binding Sites↗

PubMedDate not supplied

Prevalence and evolution of drug resistance HIV-1 variants in Henan, China.

To understand the prevalence and evolution of drug resistant HIV strains in Henan China after the implementation of free antiretroviral therapy for AIDS patients. 45 drug naïve AIDS patients, 118 AIDS patients who received three months antiretroviral therapy and 124 AIDS patients who received six months antiretroviral treatment were recruited in the southern part of Henan province. Information on general condition, antiretroviral medicines, adherence and clinical syndromes were collected by face to face interview. Meanwhile, 14 ml EDTA anticoagulant blood was drawn. CD4/CD8 T cell count, viral load and genotypic drug resistance were tested. The rates of clinical improvement were 55.1% and 50.8% respectively three months and six months after antiretroviral therapy. The mean CD4 cell count after antiretroviral therapy was significantly higher than in drug naïve patients. The prevalence rate of drug resistant HIV strains were 13.9%, 45.4% and 62.7% in drug naïve patients, three month treatment patients and six month treatment patients, respectively. The number of resistance mutation codons and the frequency of mutations increased significantly with continued antiretroviral therapy. The mutation sites were primarily at the 103, 106 and 215 codons in the three-month treatment group and they increased to 15 codon mutations in the six-month treatment group. From this result, the evolution of drug resistant strains was inferred to begin with the high level NNRTI resistant strain, and then develop low level resistant strains to NRTIs. The HIV strains with high level resistance to NVP and low level resistance to AZT and DDI were highly prevalent because of the AZT+DDI+NVP combination therapy. These HIV strains were also cross resistant to DLV, EFV, DDC and D4T. Poor adherence to therapy was believed to be the main reason for the emergence and prevalence of drug resistant HIV strains. The prevalence of drug resistant HIV strains was increased with the continuation of antiretroviral therapy in the southern part of Henan province. Measures, that could promote high level adherence, provide new drugs and change ART regimens in failing patients, should be implemented as soon as possible.

CD4-Positive T-Lymphocytes↗

PubMedDate not supplied

Activation of capsaicin receptors on the sciatic nerve induces FOS expression in the spinal dorsal horn of adult rats.

By using immunohistochemical staining for FOS protein in the spinal cord, the role of capsaicin receptors on the sciatic nerve was investigated. After topical application of capsaicin (1%) to the sciatic nerve, FOS-like immunoreactive (FOS-LI) neurons were observed, chiefly in the superficial laminae of the lumbar dorsal horn. Topical application of capsazepine (5%) or lidocaine (2%) to the sciatic nerve for 15 min before the application of capsaicin reduced the number of FOS-LI neurons in the superficial dorsal horn (by 83.2 +/- 1.7 and 32.4 +/- 1.2%, respectively). One week after pretreatment of the sciatic nerve with colchicine, the number of FOS-LI neurons induced by capsaicin was greatly decreased (by 74.6 +/- 1.7%). Given that FOS protein expression after peripheral noxious stimulation is found in a location similar to that in the present study, our results indicate that the capsaicin receptor on the sciatic nerve is involved in the transmission of noxious information.

Anesthetics, Local↗