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Biomedical subjects

B Sun

Publications and source records attributed to B Sun.

At least 127 records · Page 7Linked to original sources
PubMed1999

Combined effects of high-frequency ventilation and surfactant treatment in experimental meconium aspiration syndrome.

BACKGROUND: Deterioration of lung function in meconium aspiration syndrome may in part be due to inactivation of endogenous surfactant. We evaluated the efficacy of high-frequency ventilation (HFV) and the combination of HFV and surfactant therapy in the management of respiratory failure induced by experimental meconium aspiration in adult rats. METHODS: Animals were anesthetized and tracheotomized, and received via the tracheal cannula a suspension of human meconium (25 mg/ml, dose 4 or 5 ml/kg). After 30 min of conventional ventilation (CV) with 100% oxygen, animals were in respiratory failure as indicated by a decrease in lung-thorax compliance of > or = 30% and PaO2 < 10 kPa. They were then ventilated for an additional 3 h with either CV (frequency 40/min, inspiration time 50%) or HFV (frequency 15 Hz, inspiration time 50%) using comparable mean airway pressures (about 20 cmH2O) and variable FiO2. Subgroups of animals were treated with Curosurf (80 mg/ml, dose 200 mg/kg) 30 min after meconium aspiration; no additional material was instilled in controls. RESULTS: From 30 min onwards, values for PaO2/FiO2 were significantly higher in animals ventilated with HFV without receiving surfactant than in control animals subjected to CV alone (at 120 min; 18 +/- 7.3 vs. 7.4 +/- 0.8 kPa, P < 0.05). Additional improvement in oxygenation was seen in HFV-treated animals receiving Curosurf (at 120 min: 39 +/- 16 kPa: P vs. HFV alone < 0.01). Relative lung volumes at a deflation pressure of 10 cmH2O, expressed as percent of maximum volume, were larger in animals ventilated with HFV than in those undergoing CV (41 +/- 12 vs. 33 +/- 10%; P < 0.05), and were further increased in the groups of animals treated with surfactant and ventilated with HFV (55 +/- 9.9%; P vs. animals ventilated with HFV not receiving surfactant < 0.01) or CV (49 +/- 9.6%; P vs. animals ventilated with CV without receiving surfactant < 0.05). Hyaline membranes, granulocytes in cytospin preparations from lung lavage fluid, and vascular-to-alveolar leak of albumin were less prominent in the HFV than in the CV group, particularly in animals treated with surfactant. CONCLUSION: Our data indicate that HFV, especially in combination with surfactant therapy, may be superior to CV for treatment of respiratory failure in this animal model of meconium aspiration syndrome.

Air Pressure↗
PubMed1999

Hepatitis B virus transgenic mouse model of chronic liver disease.

A model for hepatitis B virus-associated chronic liver disease has been made using cloned hepatitis B virus DNA as a transgene in a severe combined immunodeficient host. These mice consistently support virus gene expression and replication. After adoptive transfer of unprimed, syngeneic splenocytes, these mice cleared virus from liver and serum, and developed chronic liver disease. This model will permit identification of the host and virus contributions to chronic liver disease in the absence of tolerance.

Adoptive Transfer↗
PubMed1999

Determination of ancestral alleles for human single-nucleotide polymorphisms using high-density oligonucleotide arrays.

Here we report the application of high-density oligonucleotide array (DNA chip)-based analysis to determine the distant history of single nucleotide polymorphisms (SNPs) in current human populations. We analysed orthologues for 397 human SNP sites (identified in CEPH pedigrees from Amish, Venezuelan and Utah populations) from 23 common chimpanzee, 19 pygmy chimpanzee and 11 gorilla genomic DNA samples. From this data we determined 214 proposed ancestral alleles (the sequence found in the last common ancestor of humans and chimpanzees). In a diverse human population set, we found that SNP alleles with higher frequencies were more likely to be ancestral than less frequently occurring alleles. There were, however, exceptions. We also found three shared human/pygmy chimpanzee polymorphisms, all involving CpG dinucleotides, and two shared human/gorilla polymorphisms, one involving a CpG dinucleotide. We demonstrate that microarray-based assays allow rapid comparative sequence analysis of intra- and interspecies genetic variation.

Alleles↗
PubMed1999

Targeted cytotoxic analogue of bombesin/gastrin-releasing peptide inhibits the growth of H-69 human small-cell lung carcinoma in nude mice.

Recently, we developed a powerful cytotoxic analogue of bombesin AN-215, in which the bombesin-like carrier peptide Gln-Trp-Ala-Val-Gly-His-Leu-psi(CH2-NH)-Leu-NH2 (RC-3094) is conjugated to a potent derivative of doxorubicin, 2-pyrrolinodoxorubicin (AN-201). Small-cell lung carcinomas (SCLCs) are known to express high levels of bombesin receptors. We evaluated whether these receptors could be used for targeting cytotoxic bombesin analogue to H-69 SCLC cells. H-69 cells were xenografted into male nude mice, which then received an intravenous injection of AN-215, cytotoxic radical AN-201, the carrier peptide RC-3094 alone or unconjugated mixture of RC-3094 and AN-201. The levels of mRNA for bombesin receptor subtypes were evaluated by reverse transcription-polymerase chain reaction. In vitro, both the analogue AN-215 and the radical AN-201 showed strong antiproliferative effects on H-69 cells, AN-215 requiring more time to exert its action at 10(-8) M concentration than AN-201. In vivo, the growth of H-69 SCLC tumours was significantly inhibited by the treatment with 200 nmol kg(-1) of AN-215, while equimolar doses of the cytotoxic radical AN-201 or the mixture of AN-201 and the carrier peptide were toxic and produced only a minor tumour inhibition as compared with control groups. mRNA for bombesin receptor subtypes 2 (BRS-2) and 3 (BRS-3) was detected in H-69 tumours. The mRNA levels for BRS-3, but not for BRS-2, were lower in the AN-215-treated tumours as compared with controls. Our results demonstrate that the cytotoxic bombesin analogue AN-215 could be considered for targeted therapy of tumours, such as SCLC, that express bombesin receptors.

Animals↗
PubMed1999

PSMA mimotope isolated from phage displayed peptide library can induce PSMA specific immune response.

Prostate-specific membrane antigen (PSMA) is a cell surface glycoprotein expressed predominantly in prostate secretory acinar epithelium and prostate cancer cells as well as in several extraprostatic tissues. Mouse monoclonal antibody 4G5 specific to the extracellular domain of PSMA was used to screen two phage displayed peptide libraries (9aa linear and 9aa cys library). Three 4G5-reactive phagotopes were identified. Sequence analysis of isolated clones demonstrated that the interaction motif "VDPA/SK" has high homology to 719-725aa on PSMA. Immunohistochemical staining of the prostate cancer sample with the PSMA-mimic phagotope (mimotope) immunized serum antibodies demonstrate that the mimotope isolated from the phage displayed peptide libraries can induce PSMA specific immune response in vivo.

Animals↗
PubMed1999

Autoimmunity to a pathogenic retinal antigen begins as a balanced cytokine response that polarizes towards type 1 in a disease-susceptible and towards type 2 in a disease-resistant genotype.

Susceptible, but not resistant, strains of rodents immunized for induction of experimental autoimmune uveitis (EAU) with the uveitogenic protein interphotoreceptor retinoid-binding protein (IRBP) exhibit a type 1 response at the time of disease expression. Here we investigate the evolution of this response using the prototypic EAU-susceptible and EAU-resistant mouse strains, B10.A and BALB/c. Disease severity and IRBP-specific responses (proliferation, cytokines and antibody isotypes) were evaluated 7, 14 and 21 days after uveitogenic immunization. B10.A mice initially exhibited an IgG1-dominated antibody response, and their lymph node cells produced IL-4 and IL-5 in addition to IFN-gamma. On day 14 and 21, however, the IgG2a isotype became predominant, and the primed lymph node cells produced mainly IFN-gamma and IL-12. B10.A mice developed EAU before day 14. BALB/c mice initially produced IL-12 and IFN-gamma in addition to IL-5, IL-4 and IL-10. At later time points IL-12 and IFN-gamma production diminished, and IL-4, IL-5 and IL-10 increased. An IgG1-dominated antibody response was maintained throughout. BALB/c mice failed to develop EAU even at day 21. Thus, both susceptible and resistant genotypes initially mount a balanced, type 0-like cytokine response to a uveitogenic challenge, that subsequently polarizes towards type 1 in the susceptible strain and towards type 2 in the resistant strain.

Animals↗
PubMed1999

Comparison of the effects of cilostazol and milrinone on intracellular cAMP levels and cellular function in platelets and cardiac cells.

Cilostazol is a potent cyclic nucleotide phosphodiesterase (PDE) type 3 (PDE3) inhibitor that was recently approved by the Food and Drug Administration (FDA) for the treatment of intermittent claudication. Its efficacy is presumed to be due to its vasodilatory and platelet activation inhibitory activities. Compared with those treated with placebo, patients treated with cilostazol showed a minimal increase in cardiac adverse events. Because of its PDE3 inhibitory activity, however, the possibility that cilostazol exerts positive cardiac inotropic effects is a safety concern. Therefore we compared the effects of cilostazol with those of milrinone, a selective PDE3 inhibitor, on intracellular cyclic adenosine monophosphate (cAMP) levels in platelets, cardiac ventricular myocytes, and coronary smooth muscle cells. We also compared the corresponding functional changes in these cells. Cilostazol and milrinone both caused a concentration-dependent increase in the cAMP level in rabbit and human platelets with similar potency. Furthermore, cilostazol and milrinone were equally effective in inhibiting human platelet aggregation with a median inhibitory concentration (IC50) of 0.9 and 2 microM, respectively. In rabbit ventricular myocytes, however, cilostazol elevated cAMP levels to a significantly lesser extent (p < 0.05 vs. milrinone). By using isolated rabbit hearts with a Langendorff preparation, we showed that milrinone is a very potent cardiotonic agent; it concentration-dependently increased left ventricular developed pressure (LVDP) and contractility. Cilostazol was less effective in increasing LVDP and contractility (p < 0.05 vs. milrinone), which is consistent with the cardiac cAMP levels. The cardiac effect of OPC-13015, a metabolite of cilostazol with about sevenfold higher PDE3 inhibition, was similar to cilostazol. Whereas milrinone concentration-dependently increased cAMP in rabbit coronary smooth muscle cells, cilostazol did not have such an effect. However, both compounds increased coronary flow equally in rabbit hearts. Our results show that although cilostazol and milrinone both inhibit PDE3, cilostazol preferentially acts on vascular elements (platelets and flow). This unique profile of cilostazol is consistent with its beneficial and safe clinical outcomes in patients with intermittent claudication.

Animals↗
PubMed1999

Human T-cell leukemia virus type 1 can infect a wide variety of cells in mice.

Analysis of human T-cell leukemia virus type 1 (HTLV-1)-infected cell types and the interplay of these infected cells in vivo should provide valuable information to elucidate the pathogenesis of HTLV-1-associated diseases in humans and in animal models. In this study, HTLV-1-infected cell types were identified in HTLV-1-infected C3H/HeJ mice. Pan T, CD4+, CD8+, granulocyte and pan B cell fractions in the splenocytes of MT-2 cell-inoculated mice were sorted by use of their cell surface high-density expression of CD3e, CD4, CD8, Gr-1 and B220 antigens, respectively, with a fluorescence-activated cell sorter. The pX sequence of HTLV-1 provirus in the lysate of each fraction was amplified by polymerase chain reaction and detected by Southern hybridization. Interestingly, in addition to the CD4+ cell fraction, the pX sequence was also found in CD8+ cell, B cell and granulocyte fractions. The broad cell spectrum of HTLV-1 infection in mice is consistent with the situation in humans. Our finding indicate that HTLV-1 receptor or coreceptor is widely distributed among different cell types in mice.

Animals↗
PubMed1999

Two distinct HCO(-)(3)-dependent H(+) efflux pathways in human vascular endothelial cells.

Intracellular pH (pH(i)) regulation in human umbilical vein endothelial cells (HUVEC) was investigated. The pH(i) was recorded using seminaphthorhodafluor-1 (SNARF-1). Cells were intracellularly acid loaded with NH(4)Cl prepulse. In HEPES-buffered Tyrode (nominally HCO(-)(3) free), pH(i) recovery from acid load was inhibited by 1.5 mM amiloride or Na(+)-free solution. Additionally, in HCO(-)(3)-buffered Tyrode, a HCO(-)(3)-dependent pH(i) recovery from acidosis was evident in the presence of 1.5 mM amiloride, which mediated complete recovery of pH(i) (7.26). In Na(+)-free solution, the HCO(-)(3)-dependent acid extruder mediated pH(i) recovery after an acid load but only back to 7.09. These results suggest that there are two HCO(-)(3)-dependent acid extruders in the HUVEC. One is Na(+) dependent, and the other is Na(+) independent. The former was further shown to be completely inhibited by 0.5 mM DIDS, whereas the latter was only inhibited by 24.6%. In Cl(-)-free solution, both of the HCO(-)(3)-dependent pathways were inhibited. In conclusion, one HCO(-)(3)-dependent acid extruder in the HUVEC resembles the Na(+)-dependent Cl(-)/HCO(-)(3) exchange found in other tissues, and the other is Cl(-) dependent but Na(+) independent.

Bicarbonates↗
PubMed1999

Effects of inhaled nitric oxide and high-frequency ventilation in rabbits with meconium aspiration.

AIM: To evaluate effects of inhaled nitric oxide (iNO) in experimental meconium aspiration treated with high-frequency (HFV) or conventional mechanical ventilation (CMV). Ventilated adult rabbits had meconium instilled intratracheally resulting in respiratory failure as evidenced by more than 50% reduction of dynamic lung compliance (Cdyn) and increase in mean oxygenation index (OI) from 1 to 16. The animals were then allocated to 2 groups treated without (control) or with iNO at 20 ppm (NO). In each group the animals were initially ventilated with CMV or HFV mode for 3 h and then in a crossover fashion with HFV or CMV for another 3 h (CMV-->HFV, HFV-->CMV), respectively. In the first 3 h of treatment, the animals subjected to HFV-CMV in the control, and those with both HFV-CMV and CMV-HFV in the NO group had significantly reduced OI. In the subsequent 3 h, the animals in the control group with CMV-HFV did not improve in OI and those with HFV-CMV had deteriorated. In the NO group with both CMV-HFV and HFV-CMV moderate improvement of OI was observed. Platelet aggregation capability and counts were significantly decreased and bleeding time prolonged in animals receiving iNO treatment. These results suggest that both HFV alone and a combined treatment of iNO with either CMV or HFV are more effective in improving blood oxygenation than that of CMV in this animal model. The influence of iNO on platelet aggregation should be considered.

Administration, Inhalation↗
PubMed1999

Mesoderm induction in Xenopus is a zygotic event regulated by maternal VegT via TGFbeta growth factors.

The maternal transcription factor VegT is important for establishing the primary germ layers in Xenopus. In previous work, we showed that the vegetal masses of embryos lacking maternal VegT do not produce mesoderm-inducing signals and that mesoderm formation in these embryos occurred ectopically, from the vegetal area rather than the equatorial zone of the blastula. Here we have increased the efficiency of the depletion of maternal VegT mRNA and have studied the effects on mesoderm formation. We find that maternal VegT is required for the formation of 90% of mesodermal tissue, as measured by the expression of mesodermal markers MyoD, cardiac actin, Xbra, Xwnt8 and alphaT4 globin. Furthermore, the transcription of FGFs and TGFbetas, Xnr1, Xnr2, Xnr4 and derrière does not occur in VegT-depleted embryos. We test whether these growth factors may be endogenous factors in mesoderm induction, by studying their ability to rescue the phenotype of VegT-depleted embryos, when their expression is restricted to the vegetal mass. We find that Xnr1, Xnr2, Xnr4 and derrière mRNA all rescue mesoderm formation, as well as the formation of blastopores and the wild-type body axis. Derrière rescues trunk and tail while nr1, nr2 and nr4 rescue head, trunk and tail. We conclude that mesoderm induction in Xenopus depends on a maternal transcription factor regulating these zygotic growth factors.

Animals↗
PubMed1999

Cytokines and apoptotic molecules in experimental melanin-protein induced uveitis (EMIU) and experimental autoimmune uveoretinitis (EAU).

The cytokine profile and occurrence of apoptosis during experimental melanin-protein induced uveitis (EMIU) were investigated and compared with that of experimental autoimmune uveoretinitis (EAU). EMIU or EAU was induced in Lewis rats. Eyes were collected at different time points after immunization. Cytokine mRNA expression was identified in the inflammatory cells in the uvea of EMIU rats; IL-2, IFN-gamma and IL-12 increased at the peak of the inflammation, and then tapered off as inflammation subsided. IL-4 and IL-10 increased at the peak of ocular inflammation, and persisted with inflammation resolved. Fas and FasL were expressed consistently in ocular resident cells of EMIU, but were elevated in EAU. In EAU, Bcl-2 expression showed a sharp peak in inflammatory cells but not in the resident cells. In EMIU, high levels of Bcl-2 were present and persisted in both ocular resident and inflammatory cells. Expression of Bax was relatively stable in both EAU and EMIU. Cellular DNA fragmentation was detected in the retinal glial cells of EAU and some inflammatory cells of EMIU. In EMIU, the dynamics of Th1 cytokines were consistent with the ocular inflammation, whereas persistent expression of Th2 cytokines was consistent with their known regulatory role. The continuous high expression of Bcl-2 and the high ratio of Bcl-2 to Bax in the eyes of EMIU may possibly contribute to prevention of ocular tissue damage, and of inflammatory cells from undergoing apoptosis, thus resulting in chronic recurrent inflammation.

Animals↗
PubMed1999

Comparison of effects of surfactant and inhaled nitric oxide in rabbits with surfactant-depleted respiratory failure.

AIM: To compare effects of pulmonary surfactant and inhaled nitric oxide (iNO) in improvement of survival and blood oxygenation in ventilated rabbits with acute hypoxic respiratory failure induced by repeated bronchoalveolar lavage (BAL). METHODS: After BAL all the rabbits had more than 50% reduction of dynamic lung compliance (Cdya), 50% increment of resistance of respiratory system (Rrs), and an increase of mean oxygenation index (OI) from 1 to 22. The rabbits were then randomly allocated to groups receiving (1) mechanical ventilation only (Control), (2) iNO 0.8 mumol.L-1 (20 ppm) (NO), (3) intratracheal bolus surfactant phospholipids at 100 mg.kg-1 (Surf), and (4) combined surfactant at 100 mg.kg-1 with inhaled NO at 0.8 mumol.L-1 (Surf + NO). All the rabbits were ventilated with standardized tidal volume (8-10 mL.kg-1) for another 8 h or until early death. RESULTS: The rabbits in both control and NO groups had the lowest survival rate, deterioration of lung mechanics and OI, whereas those in the Surf and Surf + NO groups had modestly improved Cdyn, Rrs, and OI. Only rabbits in the Surf + NO group had significantly improved survival rate and alveolar expansion. CONCLUSION: Surfactant with or without iNO is more effective compared to the control and iNO groups in rabbit, suggesting that iNO is not effective unless a method to recruit alveoli is applied.

Airway Resistance↗
PubMed1999

[The significance of inflammatory markers in sputum of asthmatic and chronic obstructive pulmonary diseases patients before and after glucocorticoid treatment].

OBJECTIVE: To study the change of cytokines and eosinophil cationic protein (ECP) level in the sputum before and after glucocorticoid (GC) inhalation treatment so as to comprehend their effect on asthmatic and chronic obstructive pulmonary diseases (COPD) patients. METHODS: A method to induce sputum with inhaled hypertonic saline was used. The level of interleukin (IL)-5, IL-8 and ECP was measured with enzyme-linked immunosorbent assay method. RESULTS: The concentration of ECP decreased from (500.3 +/- 49.6) microg/L to (59.8 +/- 10.9) microg/L, the percentage of eosinophils (Eos) dropped from (11.6 +/- 1.7) x 10(-2) to (4.1 +/- 0.7) x 10(-2) and there is significant difference in the concentration of IL-5 in the group of asthmatic patients after GC treatment. However, the concentration of IL-5 in the COPD patients did not show significant change after the same therapy. CONCLUSION: Respiratory tract inflammation in asthma is related to Eos activation and increase in ECP and IL-5 excretion, while respiratory tract inflammation in COPD is related to neutrophil increase. These changes can be considered as the indicator of airway inflammation in asthma or COPD. Through regulating the quantity and function of the inflammatory cells and inhibiting the formation of cytokines to control the asthmatic airway inflammation, GC inhalation treatment will have better effect in treating asthmatic patients than COPD patients.

Administration, Inhalation↗
PubMed1999

[A study on proliferation and differentiation of limbal stem cells].

OBJECTIVE: To study the proliferation and differentiation of limbal stem cells (LCs) in vitro and examine the effects of epithelial growth factor (EGF) on cell proliferation. METHODS: The cells were cultured in DMEM/F12 medium. The proliferation and differentiation of cultured cells were studied by colony-forming efficiency (CFE), immunohistochemistry staining and Western blot examination. RESULTS: LCs could be passaged 5 times in this culture condition. The CFE of stem cells was (5.07 +/- 2.35)%, while that of the central epithelial cells (CCs) was (1.12 +/- 0.86)%. The rates of freezing and recovery were (0.43 +/- 0.22)% in LCs and (0.16 +/- 0.07)% in CCs. Limbal stem cells could be stimulated to proliferate better by EGF at the concentration of 5 and 20 ng/ml. The staining of keratin 3 (K3) to stem cells in the primary culture was negative, but positive in the second and third passages. However, the expression of K3 by Western blot examination was positive in the primary and second passages but negative in the fourth one. CONCLUSION: It is better for limbal stem cells to be used for transplantation and drug screening in the primary culture.

Animals↗
PubMed1999

[Use of visual aids for vision of disabled children].

OBJECTIVE: To discuss the effect of using distance and near optical low vision devices for children in low vision clinic. METHOD: 139 subjects from age 6 to 14 years were provided with 2.5 X telescopes and + 8.00D to + 40.00D glasses for improving far and near sight respectively. RESULT: 22.3% subjects' distance visual acuity was >or= 0.5 and 53.2% subjects' near visual acuity was >or= 0.5 after using distance and near low vision aids. CONCLUSIONS: Low vision aid is essential and effective in low vision clinic. It not only improves the visual acuity of visual disabled children, but also helps the development of special education through visual rehabilitation.

Adolescent↗
PubMed1999

[Antihypertensive study of xingnao qingxuan recipe].

OBJECTIVE: To observe the effect of decreasing blood pressure of Xingnao Qingxuan Casuples. METHOD: The blood pressure in normal and anesthetised cats was examined with direct method, the blood pressure in the conscious SHR was obtained by indirect method. RESULTS: Duodenuos administration(id) of XQC of 2.8 g/kg produced a decrease of blood pressure in normal cats; XQC of 1.4, 2.8 and 5.6 g/kg once a day for 14 days produced a dose-dependent reduction of blood pressure in SHR, 3-4 days after administration the blood pressure returned to the level before but the change was not significant. With gastric administration of XQC of 2.8 and 5.6 g/kg for 3 times, the incubation period of eyeball tremor induced by chloroform by dropping into the ear was prolonged by 14.4% and 13.0%, and the keeping time shortened by about 33.3% and 23.3% respectively. Brain basic arterial spasm induced by KCl or 5-HT in dog was relaxed obviously by XQC in vitro experiment. CONCLUSION: XQC has the effect of reducing blood pressure resisting dizziness, which is related to the diastole of brain blood vessel.

Animals↗