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Biomedical subjects

C Yang

Publications and source records attributed to C Yang.

At least 91 records · Page 5Linked to original sources

[Sequential intensified immunosuppressive therapy combining with hematopoietic growth factors in the treatment of severe aplastic anemia].

OBJECTIVE: To explore more effective regimen for reducing early mortality of severe aplastic anemia (SAA) and improving therapeutic effectiveness. METHODS: Antilymphocyte globulin/antithymocyte globulin (ALG/ATG) and cyclosporine A (CsA) (sequential intensified immunosuppressive therapy, SIIST), with or without hematopoietic growth factors (HGFs) were administered to 73 SAA patients in a prospective randomized clinical trial to test the effectiveness of the addition of HGFs for the patients. RESULTS: The response rate of SIIST with HGFs group was significantly higher than that of SIIST alone group (89.2% vs 63.9%), with lower rates of early infection (24.3% vs 55.3%) and mortality (4.0% vs 16.7%), shorter duration of cytopenia and blood transfusion dependence and faster recovery of bone marrow hematopoiesis. The addition of HGFs to SIIST was tolerated well in all patients. There was no difference in the treatment outcome of the two groups with GM-CSF plus Epo or G-CSF plus Epo. CONCLUSION: The use of HGFs in combination with SIIST could reduce early infection and mortality rates and, therefore, improve the response rates in SAA patients.

Adolescent↗

[The mutation of anti-CD3 antibody (HIT3a) gene and its expression].

OBJECTIVE: To improve the expression of anti-CD(3) single chain Fv (scFv) by site mutation and identify its biological activity. METHODS: Anti-CD(3) scFv gene was mutated by PCR, the target clones were screened by both the fingerprints of DNA restriction endonuclease digestion and Western blot, the antigen-binding activity of scFv was examined by FACS, competitive inhibition was performed with (125)I-labeled HIT3a and the cytotoxic effect mediated by the anti-CD(3) scFv-activated T lymphocytes was analyzed by (51)Cr-released assays. RESULTS: The DNA sequencing showed that the 6th amino acid of the anti-CD(3) antibody (HIT3a) heavy chain gene was mutated from E (GAG) to Q (CAG). The expression of mutated anti-CD(3) scFv (m2) was increased by 100 times higher than that of the parent scFv, and there was no difference in the Jurkat cell (CD(3)(+))-binding activity between the (m2) and parent scFv. The preliminary results of competitive assays showed that m2 could partially block the sites of CD(3)(+) Jurkat cells where the parent antibody bound to. Cytotoxicity assays demonstrated that CD(3)AK cells induced by IL-2 and m2 showed stronger cytotoxic effect than that of LAK cells induced by IL-2 alone in vitro. CONCLUSION: By site mutation, a high expression fragment m2 of anti-CD(3) scFv antibody was obtained. The results of some experiments indicated that m2 could bind to CD(3)(+) Jurkat cells, furthermore, by co-stimulated with IL-2, it could activate peripheral T lymphocytes and induce CD(3)AK cytotoxic effect.

CD3 Complex↗

[Study on the transformation from myelodysplastic syndromes into acute leukemias].

OBJECTIVE: To study the patterns of transformation from myelodysplastic syndromes (MDS) into acute leukemias (AL). METHODS: Leukemic transformation of MDS patients was dynamically followed up and the clinical manifestations, peripheral blood and bone marrow pictures, karyotypes, immunophenotypes, response to treatment and prognosis of post MDS acute leukemia (postMDS-AL) were observed. RESULTS: During the past eight year and seven months, 21 (13.91%) of 151 MDS patients progressed to overt leukemia with a median interval of 5 (1 - 21) months. There were no significant differences among the rates of leukemia from RA, RAEB and RAEB-t groups. The transformation was developed either gradually or rapidly. There were five parameters related to the leukemic transformation: under 40 years of age, pancytopenia, more than 0.15 blasts in bone marrow, at least two types of abnormal karyotype and combined chemotherapy. All of the 21 post MDS-AL were acute myeloid leukemia (AML); and most of them were M(2), M(4) and M(5). Two (9.52%) post MDS-AML developed extramedullary infiltration. Leukopenia was found in 47.62% of patients. Two third of the patients, whose bone marrows were generally hypercellular, showed neutropenias. After evolving into AML, 8 (47.06%) patients developed abnormal karyotypes. High expression of immature myeloid antigens, including CD(33) (49.83 +/- 24.50)%, CD(13) (36.38 +/- 33.84)%, monocytic antigen CD(14) (38.50 +/- 24.60)%, and stem cell marker CD(34) (34.67 +/- 30.59)% were found on bone marrow mononuclear cells of post MDS-AML cases. In some cases, lymphoid antigens, such as CD(5), CD(7), CD(9) and CD(19) were coexisted with myeloid antigens. A low complete remission rate (31.25%) and short survival duration with median survival of 6 (1 - 28) months were found in patients with post MDS-AML treated by induction therapy. CONCLUSION: MDS was at high risk of evolving into AML, either gradually or rapidly. Patients with post MDS-AML had specific biologic features and worse prognoses.

Acute Disease↗

[Study of specific targeting cytotoxicity mediated by anti-CD(3)/anti-CD(20) Diabody].

OBJECTIVE: To study the specific targeting cytotoxicity mediated by an anti-CD(3)/anti-CD(20) diabody. METHODS: The diabody was purified by affinity chromatography and identified by Western blot assay, size exclusion chromatography, FACS and rosetting assay; the effect of the anti-CD(3)/anti-CD(20) diabody mediated lysis of CD(20)-expressing tumor cells was assayed by (51)Cr release assay in vitro and by human B cell tumor nude mice xenograft model in vivo. RESULTS: The anti-CD(3)/anti-CD(20) diabody could bind both Jurkat cells (CD(3)(+)) and Daudi cells (CD(20)(+)) and appeared to be potent in targeting activated peripheral blood mononuclear cell (PBMC) to lyse Daudi cells in vitro. Furthermore, it inhibited tumor growth and prolonged the survival of mice bearing xenografted Raji cells. CONCLUSION: The diabody proved to be a potent agent for targeting peripheral blood lymphocytes to lyse CD(20) antigen expressing tumor cells in vitro and in vivo.

Animals↗

[Effects of different processing products of Cortex Phellodendri on scavenging oxygen free radicals and anti-lipid peroxidation].

OBJECTIVE: To investigate the effects of different processing products of Cortex Phellodendri on scavenging oxygen free radicals and anti-lipid peroxidation. METHOD: The oxygen free radicals generation system and mouse liver homogenate lipid peroxidation in vitro were used. RESULT: The aqueous and 80% alcohol extracts of raw, stir-fried, stir-fried with salt, stir-fried with yellow alcohol products of Cortex Phellodendri could scavenge superoxide radical(O2-.) generated through hypoxanthine-oxidase system and(.OH) generated through Fenton action, and inhibit lipid peroxidation induced by hydroxyl radical generation system, respectively. But the carbonized product has no effect. There are differences among these processed products. CONCLUSION: 80% alcohol extract of stir-fried with yellow alcohol products of Cortex Phellodendri was more intense.

Animals↗

[Effects of processing on antioxidation of Radix et Rhizoma Rhei and Rhizoma Polygoni Cuspidati].

OBJECTIVE: To investigate the effects of Processing on antioxidation of Radix et Rhizoma Rhei and Rhizoma Polygoni Cuspidati. METHOD: The oxygen free radicals generation system and mouse liver homogenate lipid peroxidation in vitro were used. RESULT: The processed products of Radix et Rhizoma Rhei and Rhizoma Polygoni Cuspidati could scavenge superoxide radical (O2-.) generated through hypoxanthine-oxidase system and (.OH) generated through Fenton action, and inhibit lipid peroxidation induced by hydroxyl radical generation system, respectively. There existed significant differences among the different processed products. CONCLUSION: After Radix et Rhizoma Rhei and Rhizoma Polygoni Cuspidati were processed, their effects became weaker.

Animals↗

[Uvulopalatopharyngoplasty for the treatment of obstructive sleep apnea syndrome in 70 cases].

OBJECTIVE: To elevate the effect of uvulopalatopharyngoplasty (UPPP) and minimize the postoperative complications. METHOD: The data of 70 patients with obstructive sleep apnea syndrome diagnosed with polysomnography were analyzed. RESULT: 15 cases (21%) reported unchanged snoring and apnea and hyponea index. 55 cases improved after UPPP for at least 6 months. The complications included hypertensive crisis (2 cases), respiratory embarrassment (4 cases) in period of paretic UPPP. After UPPP, The complications included local hemorrhage (1 case), wound dehiscence (2 cases), temporal velopalatal insufficiency (9 cases), one had suffocation after extraction of endotracheal tube. CONCLUSION: Our results indicate that the strategies of improving the effect and avoiding the complications include: Excision of the lateral pharyngeal wall in retropalatal region and fat tissue in soft palate. Protection of palatosalpingeus and palatostaphylinus. Part preservation of uvula. Confirmation of the obstructive region. Choice of the anesthesia and preventive tracheotomy. Modified tracheotomy were safe and convenient when exchanging trachea canula.

Adult↗

[The correlation of multidrug resistance phenotype with clinical response to chemotherapy in laryngeal cancer].

OBJECTIVE: The correlation of multidrug resistance(MDR) phenotype with clinical response to chemotherapy was investigated in patients with laryngeal cancer. METHOD: Tumor specimens prior to neoadjuvant chemotherapy from 36 cases of laryngeal cancer were collected for detection of P-glycoprotein (P-gp) with anti-Pgp monoclonal antibodies (JSB-I). Immunohistochemical assays were used for P-gp detection on 5 microns thick frozen section. Anti-Pgp monoclonal antibodies(JSB-I) as primary antibodies and goat anti-mouse IgG monoclonal antibodies as second antibodies were applied. All patients received preoperative induction chemotherapy with a regimen of cisplatin, 5-fluorouracil and pingyangmycin. Evaluation for tumor response was scored as follows: Response to chemotherapy was graded as good for complete response or partial response; as poor for stable disease or progressive disease. RESULT: Of the 36 pretreatment specimens, 12(33.3%) were P-gp positive and 24 (66.7%) were P-gp negative. Among the 12 patients with P-gp positive, 3(25%) had a good response and 9(75%) had a poor response. Of the 24 patients with P-gp negative, 21(87.5%) had a good response and 3(12.5%) had a poor response (P < 0.05). CONCLUSION: These preliminary data suggest that a significant correlation between MDR phenotype, Pgp-mediated and chemotherapy resistance existed.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

The roles of bcl-2 gene family in the pulmonary artery remodeling of hypoxia pulmonary hypertension in rats.

OBJECTIVE: To investigate the roles of apoptosis in the pulmonary artery remodeling of pulmonary hypertension secondary to hypoxia and illustrate the relative genes expression. METHODS: Thirty rats were divided into hypoxia group (10% O2, 8 h/d) and normal control group. On the 15th day of hypoxia, pulmonary artery pressure and right ventricular hypertrophy index were measured and pulmonary artery vessels were studied by light microscope. Then terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) technique was used to detect nucleosomal DNA fragmentation of apoptotic cells. In situ hybridization and RT-PCR were used to detect the expression level of bcl-2 and bax. RESULTS: The pulmonary artery pressure and right ventricular hypertrophy index of hypoxia group were increased significantly, the pulmonary artery wall of hypoxic group become incrassate than control group. Apoptotic cells can be found in lung with hypoxia or without hypoxia. Compared with control group, apoptotic index of hypoxic group decreased significantly. Through the methods of in situ hybridization and RT-PCR, we found the expression of bcl-2 increased whereas bax decreased significantly in the hypoxic group. CONCLUSION: The alternation in bcl-2 and bax expression induced by hypoxia play an important role in the pulmonary artery remodeling which is the main pathologic change of pulmonary hypertension secondary to hypoxia.

Animals↗

Macrophages deficient in CTP:Phosphocholine cytidylyltransferase-alpha are viable under normal culture conditions but are highly susceptible to free cholesterol-induced death. Molecular genetic evidence that the induction of phosphatidylcholine biosynthesis in free cholesterol-loaded macrophages is an adaptive response.

Macrophages in atherosclerotic lesions accumulate excess free cholesterol (FC) and phospholipid. Because excess FC is toxic to macrophages, these observations may have relevance to macrophage death and necrosis in atheromata. Previous work by us showed that at early stages of FC loading, when macrophages are still healthy, there is activation of the phosphatidylcholine (PC) biosynthetic enzyme, CTP:phosphocholine cytidylyltransferase (CT), and accumulation of PC mass. We hypothesized that this is an adaptive response, albeit transient, that prevents the FC:PC ratio from reaching a toxic level. To test this hypothesis directly, we created mice with macrophage-targeted disruption of the major CT gene, CTalpha, using the Cre-lox system. Surprisingly, the number of peritoneal macrophages harvested from CTalpha-deficient mice and their overall health under normal culture conditions appeared normal. Moreover, CT activity and PC biosynthesis and in vitro CT activity were decreased by 70-90% but were not absent. As a likely explanation of this residual activity, we showed that CTbeta2, a form of CT that arises from another gene, is induced in CTalpha-deficient macrophages. To test our hypothesis that increased PC biosynthesis is an adaptive response to FC loading, the viability of wild-type versus CTalpha-deficient macrophages under control and FC-loading conditions was compared. After 5 h of FC loading, death increased from 0.7% to only 2.0% in wild-type macrophages but from 0. 9% to 29.5% in CTalpha-deficient macrophages. These data offer the first molecular genetic evidence that activation of CTalpha and induction of PC biosynthesis in FC-loaded macrophages is an adaptive response. Furthermore, the data reveal that CTbeta2 in macrophages is induced in the absence of CTalpha and that a low level of residual CT activity, presumably due to CTbeta2, is enough to keep the cells viable in the peritoneum in vivo and under normal culture conditions.

Animals↗

Munc18c regulates insulin-stimulated glut4 translocation to the transverse tubules in skeletal muscle.

To examine the intracellular trafficking and translocation of GLUT4 in skeletal muscle, we have generated transgenic mouse lines that specifically express a GLUT4-EGFP (enhanced green fluorescent protein) fusion protein under the control of the human skeletal muscle actin promoter. These transgenic mice displayed EGFP fluorescence restricted to skeletal muscle and increased glucose tolerance characteristic of enhanced insulin sensitivity. The GLUT4-EGFP protein localized to the same intracellular compartment as the endogenous GLUT4 protein and underwent insulin- and exercise-stimulated translocation to both the sarcolemma and transverse-tubule membranes. Consistent with previous studies in adipocytes, overexpression of the syntaxin 4-binding Munc18c isoform, but not the related Munc18b isoform, in vivo specifically inhibited insulin-stimulated GLUT4-EGFP translocation. Surprisingly, however, Munc18c inhibited GLUT4 translocation to the transverse-tubule membrane without affecting translocation to the sarcolemma membrane. The ability of Munc18c to block GLUT4-EGFP translocation to the transverse-tubule membrane but not the sarcolemma membrane was consistent with substantially reduced levels of syntaxin 4 in the transverse-tubule membrane. Together, these data demonstrate that Munc18c specifically functions in the compartmentalized translocation of GLUT4 to the transverse-tubules in skeletal muscle. In addition, these results underscore the utility of this transgenic model to directly visualize GLUT4 translocation in skeletal muscle.

Animals↗

Stress-level cortisol treatment impairs inhibitory control of behavior in monkeys.

Most studies of cortisol-induced cognitive impairments have focused on hippocampal-dependent memory. This study investigates a different aspect of cognition in a randomized placebo-controlled experiment with monkeys that were treated with cortisol according to a protocol that simulates a prolonged stress response. Young adult and older adult monkeys were assigned randomly to placebo or chronic treatment with cortisol in a 2 x 2 factorial design (n = 8 monkeys per condition). Inhibitory control of behavior was assessed with a test shown previously in primates to reflect prefrontal cortical dysfunction. Failure to inhibit a specific goal-directed response was evident more often in older adults. Treatment with cortisol increased this propensity in both older and young adult monkeys. Age-related differences in response inhibition were consistent across blocks of repeated test trials, but the treatment effects were clearly expressed only after prolonged exposure to cortisol. Aspects of performance that did not require inhibition were not altered by age or treatment with cortisol, which concurs with effects on response inhibition rather than nonspecific changes in behavior. These findings lend support to related reports that cortisol-induced disruptions in prefrontal dopamine neurotransmission may contribute to deficits in response inhibition and play a role in cognitive impairments associated with endogenous hypercortisolism in humans.

Adrenocortical Hyperfunction↗

BAC contig from a 3-cM region of mouse chromosome 11 surrounding Brca1.

Even with the completion of a draft version of the human genome sequence only a fraction of the genes identified from this sequence have known functions. Chromosomal engineering in mouse cells, in concert with gene replacement assays to prove the functional significance of a given genomic region or gene, represents a rapid and productive means for understanding the role of a given set of genes. Both techniques rely heavily on detailed maps of chromosomal regions, initially to understand the scope of the regions being modified and finally to provide the cloned resources necessary to allow both finished sequencing and large insert complementation. This report describes the creation of a BAC clone contig on mouse chromosome 11 in a region showing conservation of synteny with sequences on human chromosome 17. We have created a detailed map of an approximately 3-cM region containing at least 33 genes through the use of multiple BAC mapping strategies, including chromosome walking and multiplex oligonucleotide hybridization and gap filling. The region described is one of the targets of a large effort to create a series of mice with regional deletions on mouse chromosome 11 (33-80 cM) that can subsequently be subjected to further mutagenesis.

Animals↗

Role of gender and personality on quality-of-life impairment in intermittent atrial fibrillation.

Patients with atrial fibrillation (AF) report impaired health-related quality of life (QOL). Differences between men and women with AF have not been described and personality attributes such as somatization (tendency to amplify benign bodily sensations) may mediate potential gender differences in QOL. Patients with AF (n = 264, 59% men) who participated in the Canadian Trial of Atrial Fibrillation (n = 403) completed validated QOL questionnaires at baseline, 3 months, and 12 months after antiarrhythmic drug treatment. Women were significantly older than men and a greater proportion had hypertension, but other cardiac variables did not differ between women and men. At baseline, after controlling for significant clinical and demographic factors, women reported worse physical health (p = 0.002) and functional capacity (p < 0.001), but not mental health or general well-being. Women also had more frequent and severe cardiac symptoms than men (both p < 0.001). Physical health improved significantly from baseline to 3 months for women (p = 0.002), but not for men (p = 0.066). Conversely, mental health improved for men (p = 0.007), but not for women. Cardiac symptom frequency and severity improved over time for women and men (all p < 0.001). Tendency to somatize predicted poor QOL, and women had higher scores than men (p = 0.023). However, after controlling for somatization, women still had worse physical function, functional capacity, and symptom burden than men. Independent of cardiac disease severity and age, women with AF had significantly more impaired QOL than men, specifically on domains related to physical rather than emotional functioning. Personality attributes may have a role in influencing QOL outcomes.

Age Factors↗

Energetics and carbon metabolism during growth of microalgal cells under photoautotrophic, mixotrophic and cyclic light-autotrophic/dark-heterotrophic conditions.

Chlorella pyrenoidosa was cultivated under photoautotrophic, mixotrophic and cyclic light-autotrophic/dark-heterotrophic conditions. The influence of light on the carbon and energy metabolism of microalgae was investigated by the use of metabolic flux analysis. The respiratory activity of microalgae in the light was assessed from the autotrophic flux distribution. Results showed that the glycolytic pathway, tricarboxylic acid cycle and mitochondrial oxidative phosphorylation maintained high activities during illumination, indicating little effect of light on these pathways, while the flux through the pentose phosphate pathway during illumination was very small due to the light-mediated regulation. The theoretical yields of biomass on ATP decreased in the following order: heterotrophic culture>mixotrophic culture>autotrophic culture, and a significant amount of the available ATP was required for maintenance processes in microalgal cells. The energy conversion efficiency between the supplied energy to culture, the absorbed energy by cells and the free energy conserved in ATP were analyzed for the different cultures. Analysis showed that the heterotrophic culture generated more ATP from the supplied energy than the autotrophic and mixotrophic cultures. The maximum thermodynamic efficiency of ATP production from the absorbed energy, which was calculated from the metabolic fluxes at zero growth rate, was the highest in the heterotrophic culture and as low as 16% in the autotrophic culture. By evaluating the energy economy through the energy utilization efficiency, it was found that the biomass yield on the supplied energy was the lowest in the autotrophic cultivation, and the cyclic culture gave the most efficient utilization of energy for biomass production.

Journal Article↗

Profilin enhances Cdc42-induced nucleation of actin polymerization.

We find that profilin contributes in several ways to Cdc42-induced nucleation of actin filaments in high speed supernatant of lysed neutrophils. Depletion of profilin inhibited Cdc42-induced nucleation; re-addition of profilin restored much of the activity. Mutant profilins with a decreased affinity for either actin or poly-l-proline were less effective at restoring activity. Whereas Cdc42 must activate Wiskott-Aldrich Syndrome protein (WASP) to stimulate nucleation by the Arp2/3 complex, VCA (verpolin homology, cofilin, and acidic domain contained in the COOH-terminal fragment of N-WASP) constitutively activates the Arp2/3 complex. Nucleation by VCA was not inhibited by profilin depletion. With purified N-WASP and Arp2/3 complex, Cdc42-induced nucleation did not require profilin but was enhanced by profilin, wild-type profilin being more effective than mutant profilin with reduced affinity for poly-l-proline. Nucleation by the Arp2/3 complex is a function of the free G-actin concentration. Thus, when profilin addition decreased the free G-actin concentration, it inhibited Cdc42- and VCA-induced nucleation. However, when profilin was added with G-actin in a ratio that maintained the initial free G-actin concentration, it increased the rate of both Cdc42- and VCA-induced nucleation. This enhancement, also seen with purified proteins, was greatest when the free G-actin concentration was low. These data suggest that under conditions present in intact cells, profilin enhances nucleation by activated Arp2/3 complex.

Actins↗

[Approach to application of laser scanning confocal microscope in bone morphometry].

The laser scanning confocal microscope(LSCM) is the new high distinguishing microscope, which can be used in observation on fluorescence, since 1990. The bone morphometry is an important way to study metabolic bone diseases. Our study on research combination of LSCM with bone morphometry in observing microarchitecture of bone found that LSCM could make the photo of bone trabecula distinctly and its location accurately. Because of its technical advantages, LSCM could link histochemical or immunohistochemical method for the bone morphometry and bone cells at the same time and obserrate the thick-slide. It is a new method and way to study and diagnose metabolic bone diseases.

Animals↗