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Biomedical subjects

W He

Publications and source records attributed to W He.

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

[Observation on efficacy of artemether compound against vivax malaria].

AIM: To observe the efficacy of artemether compound against vivax malaria. METHODS: Each artemether compound tablet contains 120 mg benflumetolum and 20 mg artemether. 132 patients with vivax malaria were divided into 3 groups. Group A, 36 patients received 8 tablets as an initial dose, followed by 4 tablets daily for 2 days; group B, 41 patients received 8 tablets as an initial dose, followed by 3 tablets daily for 4 days; group C, 55 patients receiving chloroguine-primaquine served as control. Two patients of group A were voluntarily to be bitten by Anopheles dirus before and after medication to observe the influence of artemether compound on the sporogony. RESULTS: The average defervescence times for groups A, B and C were 22.3 h, 23.2 h and 25.0 h (P > 0.05), respectively, the average parasite clearance times were 33.5 h, 30.5 h and 44.9 h, respectively, the average parasite clearance times of groups A and B were all significantly shorter than that of group C (P < 0.01). The replase rates of groups A, B and C were 84.9%, 78.8% and 22.9%, respectively, followed-up at nine months, the relapse rates of groups A and B were higher than that of group C(P < 0.01). CONCLUSION: Two regimens of artemether compound have the advantage of high efficacy against vivax malaria.

Adolescent↗
PubMed1999

[Construction of eukaryotic vector for human interleukin-15 cDNA and its expression in lung carcinoma cell lines].

OBJECTIVE: Human interleukin(hIL)-15 expression of lung cancer cell lines transfected by rhIL-15 cDNA in vitro was observed. METHODS: The recombinant plasmid pL-IL-15-SN was established by inserting IL-15 cDNA into vector pLXSN at sites of EcoR I and BamH I. The pL-IL-15-SN was transfected into human lung squmosuse carcinoma (PG) cell line and murine lung adenocarcinoma (LA795) cell line, respectively. Positive clones were obtained by the selection in G418 conditioned culture. Bioactivity on rIL-15 was detected by dependant-proliferation of CTLL-2 cells in vitro. RESULTS: Three positive PG and four positive LA795 cell clones were obtained respectively. The results of the assays for hIL-15 bioactivity showed that the expression levels of rhIL-15 ranged from 142 to 201 or from 138 to 178U/(ml.10(6)) for positive PG cells or LA795 cells, respectively. CONCLUSIONS: Human and murine lung carcinoma cells transfected with IL-15 cDNA can express hIL-15 with bioactivity.

Adenocarcinoma↗
PubMed1999

[Efficient, stable expression of human interleukin-15 cDNA in Chinese hamster oval cells].

OBJECTIVE: To express the human interleukin 15(IL-15) cDNA in Chinese hamster oval (CHO) cells, which would benefit to the further research in the biological activities and the clinical applications of IL-15. METHODS: The entire human interleukin-15(IL-15) coding region, deleted of all the uncoding fragments, was amplified by PCR. The amplified products were subcloned into the EcoR I and Xba I sites of the pcDNA3 plasmid, forming the recombinant eukaryotic expressing vector, pcDNA3-IL-15, which was then identified by the Bg1 II enzymatic digestion, PCR amplification and the sequence analysis. The construct was transfected into CHO cells by means of lipofectamine, followed by a series of determinations to screen the positive cell colonies, such as RT-PCR, SDS-PAGE, ELISA and CTLL-2 proliferation assay. RESULTS: 8 positive cell colonies highly expressed human IL-15 were obtained after G418 selection. The bioassay showed that the mean activities of the supernatants from the CHO-IL-15 cells were (318.54 +/- 32.76) U/(10(6) cells.d) and maintained stable after 6 months culture. CONCLUSIONS: Human IL-15 cDNA was expressed efficiently and persistently in CHO cells.

Animals↗
PubMed1998

Novel cyclic compounds as potent phosphodiesterase 4 inhibitors.

The synthesis and biological activity of a novel series of 2, 2-disubstituted indan-1,3-dione-based PDE4 inhibitors are described. This structurally unique class of PDE4 inhibitors is markedly different from the known PDE4 inhibitors such as RP 73401 (2) and CDP 840 (3). Structure-activity relationship (SAR) studies led to the identification of inhibitors with nanomolar potency and oral activity in a murine endotoxemia model for TNF-alpha inhibition. Unlike other classical PDE4 inhibitors, several analogues were found to be nonemetic in a canine emesis model at intravenous doses of up to 3 mg/kg.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1998

Grb10 interacts differentially with the insulin receptor, insulin-like growth factor I receptor, and epidermal growth factor receptor via the Grb10 Src homology 2 (SH2) domain and a second novel domain located between the pleckstrin homology and SH2 domains.

The Grb10 protein appears to be an adapter protein of unknown function that has been implicated in insulin receptor (IR) signaling. The interaction of this protein with the IR has been shown to be mediated in part by the Src homology 2 (SH2) domain of Grb10. Here we demonstrate the existence of a second novel domain within Grb10 that interacts with the IR and insulin-like growth factor receptor in a kinase-dependent manner. This domain was localized to a region of approximately 50 amino acids, and we term it the BPS domain to denote its location between the PH and SH2 domains. The BPS domain does not bear any obvious resemblance to other known protein interaction domains but is highly conserved among the Grb10-related proteins Grb7 and Grb14. We show that the BPS domain interaction is dependent upon receptor tyrosine kinase activity. Furthermore, interaction of the BPS domain requires the kinase domain of the IR, since mutation of the paired tyrosine residues (Y1150F/Y1151F) within the IR activation loop dramatically reduced the interaction. Last, our data suggest that the presence of two distinct protein interaction domains may help to determine the specificity by which Grb10 interacts with different receptors. Specifically, the IR, which appears to interact most strongly with Grb10, interacts well with both the SH2 and BPS domains. Conversely, the insulin-like growth factor receptor and EGFR, which interact less avidly with Grb10, interact well only with the BPS domain or the SH2 domain, respectively. In summary, our findings demonstrate the existence of a previously unidentified tyrosine kinase activity-dependent binding domain located between the Pleckstrin homology and SH2 domains of Grb10.

Amino Acid Sequence↗
PubMed1998

Gel compression considerations for chromatography scale-up for protein C purification.

This work is to establish theoretical and experimental relationships for the scale-up of Immobilized Metal Affinity Chromatography (IMAC) and Immuno Affinity Chromatography for the low cost production of large quantities of Protein C. The external customer requirements for this project have been established for Protein C deficient people with the goal of providing prophylactic patient treatment. Deep vein thrombosis is the major symptom for protein C deficiency creating the potential problem of embolism transport to important organs, such as, lung and brain. Gel matrices for protein C separation are being analyzed to determine the relationship between the material properties of the gel and the column collapse characteristics. The fluid flow rate and pressure drop is being examined to see how they influence column stability. Gel packing analysis includes two considerations; one is bulk compression due to flow rate, and the second is gel particle deformation due to fluid flow and pressure drop. Based on the assumption of creeping flow, Darcy's law is being applied to characterize the flow through the gel particles. Biot's mathematical description of three-dimensional consolidation in porous media is being used to develop a set of system equations. Finite difference methods are being utilized to obtain the equation solutions. In addition, special programs such as finite element approaches, ABAQUS, will be studied to determine their application to this particular problem. Experimental studies are being performed to determine flow rate and pressure drop correlation for the chromatographic columns with appropriate gels. Void fraction is being measured using pulse testing to allow Reynolds number calculations. Experimental yield stress is being measured to compare with the theoretical calculations. Total Quality Management (TQM) tools have been utilized to optimize this work. For instance, the "Scatter Diagram" has been used to evaluate and select the appropriate gels and operating conditions via Taguchi techniques. Targeting customer requirements under the structure of TQM represents a novel approach to graduate student research in an academic institution which is designed to simulate an industrial environment.

Animals↗
PubMed1998

RGS9, a GTPase accelerator for phototransduction.

The rod outer segment phototransduction GAP (GTPase-accelerating protein) has been identified as RGS9, a member of the RGS family of G alpha GAPs. RGS9 mRNA expression is specific for photoreceptor cells, and RGS9 protein colocalizes with other phototransduction components to photoreceptor outer segment membranes. The RGS domain of RGS9 accelerates GTP hydrolysis by the visual G protein transducin (G alpha(t)), and this acceleration is enhanced by the gamma subunit of the phototransduction effector cGMP phosphodiesterase (PDEgamma). These unique properties of RGS9 match those of the rod outer segment GAP and implicate it as a key element in the recovery phase of visual transduction.

Amino Acid Sequence↗
PubMed1998

Cabin 1, a negative regulator for calcineurin signaling in T lymphocytes.

Calcineurin plays a pivotal role in the T cell receptor (TCR)-mediated signal transduction pathway and serves as a common target for the immunosuppressants FK506 and cyclosporin A. We report the identification of a novel endogenous calcineurin binding protein named Cabin 1 that inhibits calcineurin-mediated signal transduction. The interaction between Cabin 1 and calcineurin is dependent on PKC activation. Overexpression of Cabin 1 or its N-terminal truncation mutants inhibits the transcriptional activation of calcineurin-responsive elements in the interleukin-2 promoter and blocks dephosphorylation of NF-AT upon T cell activation. These results suggest a negative regulatory role for Cabin 1 in calcineurin signaling and provide a possible mechanism of feedback inhibition of TCR signaling through cross-talk between protein kinases and calcineurin.

Adaptor Proteins, Signal Transducing↗
PubMed1998

An antagonist peptide-EPO receptor complex suggests that receptor dimerization is not sufficient for activation.

Dimerization of the erythropoietin (EPO) receptor (EPOR), in the presence of either natural (EPO) or synthetic (EPO-mimetic peptides, EMPs) ligands is the principal extracellular event that leads to receptor activation. The crystal structure of the extracellular domain of EPOR bound to an inactive (antagonist) peptide at 2.7 A resolution has unexpectedly revealed that dimerization still occurs, but the orientation between receptor molecules is altered relative to active (agonist) peptide complexes. Comparison of the biological properties of agonist and antagonist EMPs with EPO suggests that the extracellular domain orientation is tightly coupled to the cytoplasmic signaling events and, hence, provides valuable new insights into the design of synthetic ligands for EPOR and other cytokine receptors.

Amino Acid Sequence↗
PubMed1998

Anti-idiotypic T-cell activation in multiple myeloma induced by M-component fragments presented by dendritic cells.

The monoclonal immunoglobulin (Ig) (M-component) secreted by the tumour plasma cells in multiple myeloma (MM) has specific antigenic determinants (idiotypes; id) that can serve as tumour-specific antigens. The intact Ig molecule is a weak antigen, and small fragments of id protein might be more immunogenic for the induction of id-specific immunity. Dendritic cells (DC) have attracted attention as the most efficient antigen-presenting cells and promising adjuvants for immunotherapy in tumours. In this study the in vitro T-cell response against F(ab')2 and Fab fragments, heavy and light chains of the M-component was examined in five patients with MM clinical stage I. All fragments were able to stimulate T cells but F(ab')2 or Fab fragments and heavy chains induced a stronger response than light chains. DC induced a significantly stronger id-specific immune response than monocytes. Moreover, with DC as antigen-presenting cells, a predominant interferon (IFN)-gamma (type-1 T-cell) response was seen in all patients. Both IFN-gamma and interleukin (IL)-4 (type-1 and type-2 T-cell) responses were noted when monocytes were used. Our study suggests that DC pulsed with idiotypic fragments such as F(ab')2 fragment and heavy chain can be used for the induction of type-1 anti-idiotypic T-cell response for immunotherapy in MM.

Antibodies, Anti-Idiotypic↗
PubMed1998

MK-677, an orally active growth hormone secretagogue, reverses diet-induced catabolism.

The reversal of diet-induced negative nitrogen balance by GH suggests a possible therapeutic role for GH treatment in catabolic patients. A double-blind, randomized, placebo-controlled, two-period cross-over study was designed to investigate whether MK-677, an orally active nonpeptide mimic of GH-releasing peptide, can reverse diet-induced protein catabolism. Eight healthy volunteers (ages 24-39 yr) were calorically restricted (18 kcal/kg.day) for two 14-day periods. During the last 7 days of each diet period, subjects received either oral MK-677 25 mg or placebo once daily. There was a 14- to 21-day washout interval between periods. During the first week of caloric restriction (i.e. diet alone), daily nitrogen losses were similar for both treatment groups (mean +/- SE; MK-677 group -2.67 +/- 0.40 g/day vs. placebo group -2.83 +/- 0.26 g/day). During the second week (diet and study drug), mean daily nitrogen balance was 0.31 +/- 0.21 g/day in the MK-677 treatment group compared with -1.48 +/- 0.21 g/day in the placebo group (P < 0.01). MK-677 improved nitrogen balance integrated over the 7 days of treatment; area under the curve day 8-14 nitrogen balance response was +2.69 +/- 5.0 (SE) for MK-677 and -8.97 +/- 5.26 g.day for placebo (P < 0.001). MK-677 produced a peak GH response of 55.9 +/- 31.7 micrograms/L after single dose (day 1 of treatment) and 22.6 +/- 9.3 micrograms/L after a week of dosing compared with placebo treatment peak GH values of approximately 9 (treatment day 1) and approximately 7 micrograms/L (treatment day 7). Following the initial 7-day caloric restriction, insulin-like growth factor-I (IGF-I) declined from 232 +/- 25 to 186 +/- 19 ng/mL in the MK-677 group and from 236 +/- 19 to 174 +/- 23 ng/mL in the placebo group. Mean IGF-I concentration increased significantly during MK-677 to 264 +/- 31 ng/mL (mean for the last 5 days of treatment) compared with 188 +/- 19 ng/mL with placebo (P < 0.01). No significant difference in IGF binding protein-2 was found between the MK-677 and placebo treatments. However, the mean in IGF binding protein-3 for the last 5 days of MK-677 treatment was also significantly increased to 3273 +/- 330 ng/mL (mean +/- SE) compared with placebo 2604 +/- 253 ng/mL (P < 0.01). Neither the serum cortisol nor the PRL response was significantly greater after 7 days of MK-677 dosing compared with 7 days of placebo. MK-677 (25 mg) was generally well tolerated and without clinically significant adverse experiences. In conclusion, MK-677 reverses diet-induced nitrogen wasting, suggesting that if these short-term anabolic effects are maintained in patients who are catabolic because of certain acute or chronic disease states, it may be useful in treating catabolic conditions.

Adult↗
PubMed1998

[Comparison of secondary ischemia tolerance between free skin flap and island skin flap raised on the buttock of the pig].

OBJECTIVE: This study was to compare skin viability of the free skin flap and the island skin flap in the pig. METHODS: The comparison was made between the 8 cm x 11 cm surgically denervated free skin flap and the pedicle island skin flap raised contralaterally on the buttock of 50 pigs. The free flap and the pedicle flap were subjected to 2 h of primary warm ischemia followed by 12 h of reperfusion and 0, 2, 4, 6, 10 h of secondary warm ischemia (n = 10). Skin viability was assessed 7 days after secondary ischemia. RESULTS: Pedicle skin flaps tolerated up to 10 h secondary ischemia without skin necrosis. However, incidences of flap failure (partial or total) in free flaps subjected to 0, 2, 4, 6, 10 h of secondary ischemia were 0, 10%, 50%, 80%, 100%, respectively. In a separate experiment, skin blood flow was studied in contralateral free skin flaps and pedicle island flaps (n = 20) subjected to 4 h of secondary ischemia. The skin reperfusion was very slow in 8 out of 20 free skin flaps at 1, 5 h after secondary is chemia, and the mean skin blood flow measured by 15 microns microspheres in these 8 free skin flaps was only 8% of their contralateral pedicle skin flaps. The mean skin blood flow in the remaining 12 free skin flaps was 76% of their contralateral pedicle skin flap. CONCLUSION: These observations were interpreted to indicate that buttock free skin flaps in the pig were less tolerant to secondary ischemia compared with their contralateral pedicle skin flaps subjected to the same ischemic protocol, and this reduced ischemic tolerance in free skin flaps was associated with compromised skin blood flow.

Animals↗
PubMed1998

[Effect of inhaled-corticosteroids on the mRNA expressions of endothelin-1 and endothelin converting enzyme in bronchial asthma].

OBJECTIVE: To investigate the expressions of endothelin-1(ET-1) and endothelin converting enzyme (ECE) mRNA in bronchial mucosal biopsis from asthmatics, and the effect of inhaled-corticosteroids on the expressions of ET-1 and ECE genes. METHOD: The expressions of ET-1 and ECEmRNA in bronchial mucosal tissue were evaluated by reverse transcription DNA polymerase chain reaction (RT-PCR); With fibro bronchoscopy, the naked-eye inflammatory severity and inflammatory score of bronchial mucoses were recorded. RESULT: (1) The expression level of ET-1 mRNA was 0.86 +/- 0.06 in non-steroids-treated group and 0.14 +/- 0.06 in control non-asthmatic group. The expression of ECE mRNA in non-steroid group was 0.31 +/- 0.04, and 0.30 +/- 0.05 in control group, P = 0.238. (2) The ET-1 and ECE mRNA expressions were 0.22 +/- 0.01 and 0.16 +/- 0.01 respectively in steroid treated group. (3) The naked-eye bronchial mucosal inflammatory score was 6.0 +/- 1.9 in non-steroids treated group, moreover, the expression of ET-1 mRNA was positively correlated with the score (r = 0.78, P < 0.05). CONCLUSION: There was markedly higher ET-1 mRNA expression in the bronchial mucosa in asthmatics, but the ECE mRNA expression was unchanged significantly; Inhaled corticosteroids obviously inhibited both ET-1 mRNA and ECE mRNA expressions in bronchial mucosa, which may be one of the anti-inflammatory mechanisms of inhaled-corticosteroid in management of bronchial asthma.

Adult↗
PubMed1998

[Effect of heparinoid on the proliferation of rabbit vascular smooth muscle cells in vitro].

Proliferation of vascular smooth muscle cells(VSMCs) represents an important event in vascular lesion formation. In the present study, we investigated whether heparinoid abstracted from porcine duodenum inhibits the proliferation of rabbit aortic VSMCs in vitro, using the method of colorimetric MTT (tetrazolium). Our results showed that heparinoid at 1.6-0.05 mg.ml-1 significantly inhibits VSMCs proliferation induced by fetal calf serum(FCS, 10%), basic fibroblast growth factor(bFGF, 50 ng.ml-1) or interleukin-1(IL-1, 50 u.ml-1). In inducing with bFGF, the inhibitive effect of heparinoid was more potent than that of heparin, while in inducing with FCS or IL-1, the inhibitive effect of heparin was more potent than that of heparinoid. Preincubation with heparinoid at 0.2-0.05 mg.ml-1, the vascular smooth muscle cell proliferation induced by FCS was also inhibited. Our results imply that heparinoid may be useful to protect the atherosclerosis and angioplasty restenosis.

Animals↗
PubMed1998

[A new method for study of the effect of drugs on cancer cells--31PNMR with perfused cell system].

31P NMR was performed for the studies on the metabolic changes of endogenous phosphorus-containing molecules in KB and HCT-8 cells exposed to taxol at a concentration of 10(-6) mol.L-1. Using the perfusion method, the cells can be detected for a longer time by NMR, so as to give continuous spectra of the two cell-lines during the perfusion with and without the drug. The spectra showed that the levels of ATP peaks for both cells enhanced during the perfusion with the drug, but the change of the level is more prominent in KB cells than in HCT-8 cells. This shows that KB cells are more sensitive to taxol than HCT-8 cells. This is in coincident with the result in the cytotoxicity studies. However, the experiment using vincristine at the same concentrations demonstrated that the level of the ATP peak was not changed significantly.

Adenosine Triphosphate↗