Biomedical subjects

Chun Chen

Publications and source records attributed to Chun Chen.

At least 37 records · Page 2Linked to original sources

PubMed2005

[Application of dynamic substrate mapping in ablation of ventricular tachycardias in arrhythmogenic right ventricular cardiomyopathy].

OBJECTIVE: To study the application of abnormal electrophysiological substrate mapping for guiding ablation of ventricular tachycardias in arrhythmogenic right ventricular cardiomyopathy (ARVC-VTs) using a non-contact mapping system. METHODS: Dynamic substrate mapping was performed in three male ARVC patients during sinus rhythm. The sites of the earliest activation, exit point and activation sequence were mapped for each induced VT. RESULTS: Three different patterns of substrates were determined in 3 patients, which located in right ventricular outflow tract, anterior right ventricular wall, and anterolateral right ventricular wall, respectively. Five different clinical VTs [mean CL (348 +/- 65) ms] were induced. Of 5 VTs, three were originated from substrate or boundary of substrate, and two had a remote origin. One VT conducted through the substrate. Linear ablations were created between the sites of the earliest ventricular activation and the VT exit point, or across the critical isthmus. The five clinical VTs were successfully ablated. There were no VT recurrences during 20 months of follow-up. CONCLUSIONS: Defining the abnormal electrophysiologic VT substrates is useful for understanding the mechanisms of ARVC-VTs and determining an ablation strategy. Linear ablation across a critical isthmus or between the earliest activation and the exit point can effectively cure these arrhythmias.

Adult↗

PubMed2005

[Effect of propofol on spinal cord apoptosis associated with aortic cross-clamping in rabbits].

OBJECTIVE: To investigate the effect and mechanism of propofol on the spinal cord apoptosis associated with aortic cross-clamping in rabbits. METHODS: Twenty-four rabbits were randomly divided into sham operation group (A), ischemia/reperfusion group (B) and propofol group (C). In group B and C, the infrarenal aorta was clamped for 40 minutes followed by 7 days reperfusion. Ten minutes before clamping, group C was given propofol 5 mg/kg intravenously and continued at a rate of 20 mg x kg(-1)x h(-1) until unclamping. The aorta was not clamped in group A. The plasma concentrations of malondialdehyde (MDA) and superoxide dismutase (SOD) were determined at 10 minutes before clamping (C-10), before unclamping (C40), at 60 minutes (R60) and on the 7th day (R7 d) unclamping. Apoptotic spinal cord cells and expressions of Bax, Bcl-2 protein were measured by immunohistochemical technique. RESULTS: (1)The concentrations of MDA after ischemia and reperfusion in group B were increased significantly compared with C-10 and those in group A (P<0.05 or P<0.01), which in group C were significantly lower than those in group B (P<0.05), but not in group A. Changes in SOD activity were opposite to those in MDA contents in various groups. (2)The expressions of Bax protein in group B were significantly increased compared with those in group A (P<0.05), while the expression of Bcl-2 protein decreased. In group C, Bax protein expression was markedly lower than those in group B and higher than those in group A (P<0.01 and P<0.05), the expression of Bcl-2 was higher than those in groups B and A (both P<0.01). (3)The number of apoptosis cells in group B was much higher than that in group A, which in group C was much lower than that in group B, but higher than that in group A. (4)The ratio of paralysis in group C was significantly lower than that in group B with a high neurologic score (both P<0.01). CONCLUSION: Propofol can reduce the spinal cord apoptosis associated with aortic cross-clamping in rabbits. The possible mechanism is related to the effect of decreasing Bax expression, increasing Bcl-2 expression, and enhancing antioxidation.

Animals↗

PubMed2005

[Therapy of Duchenne muscular dystrophy with umbilical cord blood stem cell transplantation].

OBJECTIVE: To analyze a Duchenne muscular dystrophy(DMD) patient's muscular regeneration, dystrophin expression and locomotive variation before and after he underwent umbilical cord blood stem cell transplantation in order to assess the therapeutic effect. METHODS: A 12-year-old DMD boy who could not walk for 3 years was confirmed by gene analysis and dystrophin protein immune test on his muscle. He had no other chronic disease. By HLA matching, a piece of umbilical cord blood stem cell with 6 HLA sites matching to the boy was found in Guangdong Umbilical Cord Blood Bank. The number of the nucleated cells of the umbilical cord blood stem cell was 24.08x 10(8). After pretreatment for the DMD boy with busulfan, cyclophosphamide and rabbit anti-human thymocyte globulin, the allergenic cord blood stem cells were transplanted into him by intravenous injection. Cyclosporin A, methylprednisolone, MMF, prostaglandin E1 and ganciclovir were given after the transplantation. At the same time, Gran, the granulocytic cell stimulating factor, and gamma globulin were administered. The biochemistry profile including serum creatine kinase (CK), the reconstruction of blood making, the deletion exon of DMD gene, the regenerating muscles, the dystrophin protein expression, and the locomotive function of the DMD boy were tested regularly. RESULTS: (1) The white blood cells (WBC) of peripheral blood decreased gradually to zero after pretreatment. In a period of 15 days after transplantation, the neutrophil increased to 0.5x 10(9)/L; at 25 days, WBC increased to normal level. Blood platelet was more than 20x 10(9)/L at 22 days. The hemoglobin rose to 85-100 g/L. At 140 days, sternal puncture revealed the rapid growth of neutrophil, blood platelet and hemoglobin. (2)At 140 days, the blood type of the DMD boy transformed from type O to type AB (the donor's blood type being AB). There was no grafe versus host reaction. (3) At 18, 30, 43, 55, 74 and 233 days after transplantation, the PCR-short tandem repeat test of the boy's peripheral blood DNA showed that his genotype was completely the same as the donor's. The results of PCR-short tandem repeat tests of the bone marrow cells DNA by sternal puncture at 140, 183 and 235 days were the same as those of the blood DNA. (4) At 60 days, DMD gene analysis by PCR showed that the defected DMD gene (exon 19 deletion) had been corrected by the umbilical cord stem cells transplantation. (5) At 75 days, the biopsy of calf muscle showed there were myoblast cells and muscular tubes growing. The dystrophin expressions were weak, but a few of them were strong. DNA analysis showed that the donor's gene DNA accounted for 1%-13%. At 126 days, obviously increased dystrophin positive muscular fibers of the boy were found. The donor's fibers rose to 2.5%-25%. (6) The serum CK of the boy declined from 5735 U/L to 274 U/L. (7) At 100 days, physical examination revealed improvement in his arms and legs. CONCLUSION: The therapy of Duchenne muscular dystrophy with allogeneic umbilical cord blood hematopoietic stem cell transplantation may reset up the blood-making function, decrease the serum CK level, restore the dystrophin in muscles, and improve the locomotive function of the DMD boy. These data suggest that the allogeneic umbilical cord blood hematopoietic stem cell transplantation may benefit the DMD boys.

Alprostadil↗

PubMed2005

[Left atrium linear lesion encircling pulmonary veins guided by EnSite-NavX and double-Lasso technique for paroxysmal atrial fibrillation].

OBJECTIVE: To evaluate the efficacy of left atrium linear lesion encircling pulmonary veins (PV) guided by EnSite-NavX and double-Lasso technique for paroxysmal atrial fibrillation (PAF). METHODS: Twenty-two patients (male 19, mean age of 48.5 years +/- 11.4 years) with symptomatic PAF were enrolled. After a geometry of the left atrium was reconstructed by EnSite-NavX system, PV ostia were marked on the map based on venography. Two Lasso catheters were placed within the ipsilateral superior and inferior PVs. Irrigated radiofrequency energy was applied at 0.5-1.0 cm of distance from the PV ostia. Continuous linear lesion was done to obtain the disappearance of pulmonary vein potentials. Patients were on propafenone and perindopril for three months after the procedure. RESULTS: The endpoint for ablation was reached in 21 Patients and 1 patient was not successful because of cardiac tamponade. The mean procedure time was 6.6 h +/- 1.3 h and the mean X-ray exposure time was 56.1 min +/- 18.0 min. After a mean 5.3 months +/- 2.7 months of follow-up, 10 patients were free of symptoms. Two patients had no PAF recurrence after the second procedure. Three patients had clinical recurrence of PAF in the first month. The total success rate in this study was 81% (17/21). Mortality was 0% and the overall complication rate was about 9% (2/22). CONCLUSION: Left atrium circumferential linear ablation surrounding PV ostia guided by EnSite-NavX and double-Lasso technique is effective in PAF, but some patients will need more than one procedure in order to achieve a success.

Adult↗

PubMed2004

Spermidine/spermine N1-acetyltransferase specifically binds to the integrin alpha9 subunit cytoplasmic domain and enhances cell migration.

The integrin alpha9beta1 is expressed on migrating cells, such as leukocytes, and binds to multiple ligands that are present at sites of tissue injury and inflammation. alpha9beta1, like the structurally related integrin alpha4beta1, mediates accelerated cell migration, an effect that depends on the alpha9 cytoplasmic domain. alpha4beta1 enhances migration through reversible binding to the adapter protein, paxillin, but alpha9beta1-dependent migration is paxillin independent. Using yeast two-hybrid screening, we identified the polyamine catabolizing enzyme spermidine/spermine N(1)-acetyltransferase (SSAT) as a specific binding partner of the alpha9 cytoplasmic domain. Overexpression of SSAT increased alpha9beta1-mediated migration, and small interfering RNA knockdown of SSAT inhibited this migration without affecting cell adhesion or migration that was mediated by other integrin cytoplasmic domains. The enzyme activity of SSAT is critical for this effect, because a catalytically inactive version did not enhance migration. We conclude that SSAT directly binds to the alpha9 cytoplasmic domain and mediates alpha9-dependent enhancement of cell migration, presumably by localized effects on acetylation of polyamines or of unidentified substrates.

Acetyltransferases↗

PubMed2004

Sitobion avenae alatae infected by Pandora neoaphidis: their flight ability, post-flight colonization, and mycosis transmission to progeny colonies.

Epizootics caused by the obligate Entomophthorales pathogen Pandora neoaphidis may result from more than one possible means of fungal dissemination among host aphids, but we hypothesize that wide dispersal of the fungus is most likely to be associated with the flight behavior of migratory alates. We tested this hypothesis in a simulation experiment by assessing the flight capability of Sitobion avenae alates infected with P. neoaphidis and the potential of their post-flight survival, colonization, and mycosis transmission to progeny. A total of 281 alates were inoculated with P. neoaphidis, individually flown for up to 5h and 9km in a computer-monitored flight mill system and then reared for 10 days on wheat seedlings. The infected alates were capable of surviving on average for 2.9 days (range 1-7 days) and leaving 4.6 nymphs prior to deaths. Transmission of fungal infection within progeny colonies occurred after the mother alates died from P. neoaphidis mycosis. The level of contagious infection among the nymphs reached up to 16.8% within 7 days but varied with the survival time of the infected mother alates after flight. Based on stepwise polynomial regression analysis, progeny colony size was highly correlated with the interactions of flight time with both post-flight survival time and the number of nymphs left per alate before death (r2 = 0.997). Progeny mortality on day 5 after colonization was inversely correlated with post-flight survival time (r2 = 0.949) whereas infection on day 7 was correlated with flight distance and an interaction of post-flight survival time with fecundity of the infected alates (r2 = 0.970). Progeny mortality observed on day 10 was merely correlated to mortality observed on day 5 (r2 = 0.946). These results indicate a successful transmission of alate-borne P. neoaphidis to progeny colonies and further support our hypothesis on the means of primary dispersal of aphid epizootics by migratory alates in a geographically wide range.

Animals↗

PubMed2004

Dynamic substrate mapping and ablation of ventricular tachycardias in right ventricular dysplasia.

BACKGROUND: Ablation of ventricular tachycardias in arrhythmogenic right ventricular dysplasia (ARVD-VTs) still remains a clinical challenge. We reported the value of abnormal electrophysiological substrate mapping for guiding ablation of ARVD-VTs using a non-contact mapping system. METHODS AND RESULTS: Dynamic substrate mapping was performed in three male ARVD patients during sinus rhythm. The sites of earliest activation, exit point and activation sequence were mapped for each induced VT. Three different patterns of substrates were determined in 3 patients and located in right ventricular outflow tract, anterior right ventricular wall, and anterolateral right ventricular wall, respectively. Five different clinical VTs (mean CL, 348 +/- 65 ms) were induced. Of 5 VTs, three originated from or near the boundary of substrate, and two had a remote origin. One VT conducted through the substrate. Linear ablations were created between the sites of the earliest ventricular activation and the VT exit point, or across the critical isthmus. The five clinical VTs were successfully ablated with a median of 17 radiofrequency applications. One patient was treated with amiodarone for a VT not clinically observed. There were no VT recurrences during 8.6 months of follow-up. CONCLUSIONS: Defining the abnormal anatomical VT substrates is useful for understanding the mechanisms of ARVD-VTs and determining an ablation strategy. Linear ablation across a critical isthmus or between the early activation and the exit point can effectively cure these arrhythmias.

Adult↗

PubMed2004

Umbilical cord blood transplantation in Chinese children with beta-thalassemia.

To evaluate factors affecting outcome of sibling umbilical cord blood transplantation in Chinese children with thalassemia. The authors conducted a retrospective review of all patients undergoing such transplants in a single institution. Nine children with thalassemia major were diagnosed at a median age of 12 months. They received irregular blood transfusions and suboptimal iron chelation therapy before transplant. Sibling cord blood transplant was performed at a median of 5.5 years (range 3.5-10 years). Six donors were HLA-identical; three were one- to three-antigen mismatched. The mean number of nucleated cells infused was 6.6 x 10(7)/kg (range 3.4-12.7); the mean number of CD34+ cells infused was 3.8 x 10(5)kg (range 0.6-11.7). Seven patients had engraftment of donor cells. The median number of days to achieve a neutrophil count of > 0.5 x 10(9)/L was 19 days (range 10-25); the median number of days to achieve a platelet count of > 20 x 10(9)/L was 33 days (range 19-63). Of the six patients who received HLA-identical transplants, one developed grade 2 and two developed grade 1 acute graft-versus-host disease. Two of the three patients receiving mismatched cord blood did not achieve engraftment, and the other one engrafted but developed grade 4 acute graft-versus-host disease. Two patients subsequently developed secondary graft rejection and had autologous marrow regeneration before day 60 posttransplantation. With a median follow-up of 49 months (range 38-64), eight patients survived but only four were transfusion-independent. Umbilical cord blood transplant appears to have a higher chance of nonengraftment and secondary rejection. A more intensive immunosuppressive conditioning regimen may be required.

Adolescent↗

PubMed2004

Wide dispersal of aphid-pathogenic Entomophthorales among aphids relies upon migratory alates.

Entomophthoralean mycoses are of general importance in the natural control of aphids, but mechanisms involved in their dissemination are poorly understood. Despite several possible means of fungal survival, the dispersal of the mycoses in aphids has never been related to the flight of their migratory alates that are able to locate suitable host plants. In this study, aphid-pathogenic fungi proved to be widely disseminated among various aphids by their alates through migratory flight based on the following findings. First, up to 36.6% of the 7139 migratory alates (including nine species of vegetable or cereal aphids) trapped from air > 30 m above the ground in three provinces of China were found bearing eight species of fungal pathogens. Of those, six were aphid-specific Entomophthorales dominated in individual cases by Pandora neoaphidis, which occurs globally but has no resting spores discovered to date. Secondly, infected alates were confirmed to be able to fly for hours, to initiate colonies on plants after flight and to transmit fungal infection to their offspring in a laboratory experiment, in which 238 Sitobion avenae alates were individually flown in a computer-monitoring flight mill system after exposure to a spore shower of P. neoaphidis and then allowed to colonize host plants.

Animal Migration↗

PubMed2004

Killer cell inhibitory receptors involved in graft-versus-host disease and graft-versus-leukemia effect in allogeneic hematopoietic stem cell transplantation - review.

Killer cell inhibitory receptors (KIR) are members of the immunoglobulin superfamily (Ig-SF) and transmembrane molecules type I expressed on human natural killer cells and some T lymphocytes. They are ligands for HLA class I antigens. According to the "missing-self" hypothesis, KIR deliver inhibitory signals that prevent target-cell lysis upon binding to the self MHC class I antigens. KIR regulates NK cell function concerned with the control graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effect after allogeneic hematopoietic stem cell transplantation (HSCT). The KIR repertoire is substantially influenced by the polymorphic and polygeneic nature of the KIR gene family, and there exist the polymorphism of KIR ligands mainly HLA-C molecule. So it is difficult to achieve the beneficial effect of NK cells on the outcome of partly HLA-mismatched hematopoietic cell transplantation. This review aims to provide background and previous observations on the KIRs which are thought to influence the outcome of HSCT.

Animals↗

PubMed2004

[Effects of functional inhibition of p-glycoprotein on radiosensitivity of drug-resistant MCF-7/Adr tumor cells].

OBJECTIVE: To observe the effects of functional inhibition of p-glycoprotein on radiosensitivity of drug-resistant MCF-7/Adr tumor cells. METHODS: Flow cytometry was used to examine the dynamic changes of apoptosis rate and mitochondrial membrane potential (deltapsim) in verapamil-treated and untreated MCF-7/Adr cells after the X-ray exposure. RESULTS: The apoptotic rate of verapamil-treated cells was 25.53%+/-2.85%, 30.43%+/-2.21%, 39.03%+/-2.60% at 6, 12, and 24 h after X-ray exposure, respectively, and was 16.13%+/-1.16%, 21.73%+/-1.31%, and 27.53%+/-2.55% for the untreated cells. The mean fluorescence intensity of verapamil-treated cells was 75.27+/-4.90, 96.47+/-5.59, 57.77+/-2.55, respectively, at the corresponding time points, in comparison with the intensity of 54.17+/-4.05, 62.30+/-5.93, and 39.53+/-2.65 for the untreated cells. The apoptosis rate and deltapsim of the treated cells were significantly higher than those in the untreated cells at each of the specified time point (P<0.01), and in the former cells, the apoptosis rate reached the maximum at 24 h (F=47.870, P=0.000) and the deltapsim at 12 h after X-ray exposure (F=74.485, P=0.000). CONCLUSION: The radiosensitivity of MCF-7/Adr cells is increased after functional inhibition of p-glycoprotein, possibly in relation to the alteration of deltapsim.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2003

The C-terminal kinase domain of the p34cdc2-related PITSLRE protein kinase (p110C) associates with p21-activated kinase 1 and inhibits its activity during anoikis.

The PITSLRE protein kinases are parts of the large family of p34cdc2-related kinases. During apoptosis induced by some stimuli, specific PITSLRE isoforms are cleaved by caspase to produce a protein that contains the C-terminal kinase domain of the PITSLRE proteins (p110C). The p110C induces apoptosis when it is ectopically expressed in Chinese hamster ovary cells. In our study, similar induction of this p110C was observed during anoikis in NIH3T3 cells. To investigate the molecular mechanism of apoptosis mediated by p110C, we used the yeast two-hybrid system to screen a human fetal liver cDNA library and identified p21-activated kinase 1 (PAK1) as an interacting partner of p110C. The association of p110C with PAK1 was further confirmed by in vitro binding assay, in vivo coimmunoprecipitation, and confocal microscope analysis. The interaction of p110C with PAK1 occurred within the residues 210-332 of PAK1. Neither association between p58PITSLRE or p110PITSLRE and PAK1 nor association between p110C and PAK2 or PAK3 was observed. Anoikis was increased and PAK1 activity was inhibited when NIH3T3 cells were transfected with p110C. Furthermore, the binding of p110C with PAK1 and inhibition of PAK1 activity were also observed during anoikis. Taken together, these data suggested that PAK1 might participate in the apoptotic pathway mediated by p110C.

3T3 Cells↗

PubMed2003

Regulation of the expression and activity of beta1,4-galactosyltransferase I by focal adhesion kinase.

beta1,4-Galactosyltransferase I (GalT) participates in both glycoconjugates and cellular interactions. GalT's role in lamellipodia formation and cell migration on laminin is associated with a transient phosphorylation of focal adhesion kinase (FAK) and a consequent reorganization of the actin cytoskeleton and focal adhesions. We transfected wild type FAK and different FAK mutants into NIH3T3 cell line, measured GalT gene expression by Northern blot hybridization, and evaluated its activity. It was found that wtFAK and FAKY576F up-regulated GalT gene expression and its surface activity, while FAKY397F down-regulated them. At the same time, we used ricinus communis agglutinin (RCA)-I lectin staining to demonstrate its binding reactions. We found that wtFAK and FAKY576F bound stronger, while FAKY397F bound weaker than the control. By flow cytometry analysis, it was found that FAK promoted G1/S transition and enhanced the expression of cyclin D1 while FAKY397F inhibited these steps compared with the control NIH3T3 cells. G1/S checkpoint regulation proteins control GalT mRNA transcription. The results indicate that FAK regulated the expression of GalT and its activity in NIH3T3 cells may contribute to the effect of FAK on the cell-cycle.

Animals↗

PubMed2003

Unrelated umbilical cord blood transplant for beta-thalassemia major.

A 5-year-old boy with beta-thalassemia major received an unrelated umbilical cord blood transplantation (URD-UCBT). The URD-UCB was six antigen HLA matched. The infused cell dose was 7.5 x 10(7)/kg nucleated cells. Conditioning included busulfan 20 mg/kg, cyclophosphamide 200 mg/kg, fludarabine 150 mg/kg, thiotepa 6 mg/kg, and antithymocyte globulin 90 mg/kg. The post transplant complications were mild hepatic veno-occlusive disease, acute GVHD grade III, and CMV interstitial pneumonia. The subject has been ex-thalassemic for more than 20 months post transplant. The chronic GVHD was limited and could be controlled by methylprednisolone combined with mycophenolate. This is the first successful report of an unrelated umbilical cord blood transplantation for beta-thalassemia major from China.

Child↗

PubMed2003

[Study of reducing graft-versus-host disease by in vitro blockade of CD40-CD40 ligand co-stimulatory pathway in allogeneic bone marrow transplantation mouse model].

OBJECTIVE: To investigate the effect and its mechanism of reducing graft-versus-host disease (GVHD) by in vitro blockade of CD(40)-CD(40)L pathway in vitro, the donor T lymphocytes cultured in vitro with anti-CD(40)L mAb were transfused in bone marrow transplantation (BMT) GVHD mouse model. METHODS: C57BL/6(H-2b) spleen T cells were isolated as responder cells, and BALB/c(H-2d) spleen cells as stimulator cells. They were cocultured with or without Anti-CD(40)L mAb as anti-CD(40)L mAb group and control group, respectively. At day 5, the mixed lymphocyte response (MLR)-culture cells mixed with bone marrow cells and transfused respectively into the TBI conditioned recipient mice. The mice were divided into two groups: group A, bone marrow cells (2 x 10(6)) and spleen T lymphocytes (2 x 10(6)) from MLR control group; group B, bone marrow cells (2 x 10(6)) and spleen T lymphocytes (2 x 10(6)) from MLR anti-CD(40)L mAb group. The GVHD incidence and hematopoietic reconstitution were observed. Peripheral blood sera and spleen cells of the recipients mice were harvested at scheduled time points for the measurement of cytokines and T cell immunophenotyping with flow cytometry. RESULTS: The incidence of GVHD in group A was 100% (10/10), and in group B was 20% (2/10). The percentage of H-2D(b) positive cells in group B (n = 8) was (93.54 +/- 2.32)% at day 40 after transplantation. The levels of cytokines in serum from group B were significantly lower than those from group A (P < 0.05). The expressions of CD(4)(+), CD(8)(+), CD(4)(+)CD(25)(+), CD(8)(+)CD(25)(+), CD(4)(+)CD(69)(+), CD(8)(+)CD(69)(+) and CD(4)(+)CD(40)L(+) were lower in group B than in group A (P < 0.05). The expressions of CD(8)(+)CD(40)L(+) and CD(4)(+)CD(45)RA(+) were similar in the two groups (P > 0.05). CONCLUSION: Blockade of CD(40)-CD(40)L interaction in vitro could induce immune tolerance in vivo, reduce aGVHD in aGVHD mice model and form chimerism, which was mediated by inhibiting the Th1 and Th2 cytokines production, inducing tolerance of CD(4)(+) and CD(8)(+) cells to alloantigens. The obstruction of T cells activation after tolerance happened mainly at the early and mature phase of T cells activation. These provided the experimental basis for the use of anti-CD(40)L mAb in the clinical transplantation to prevent aGVHD.

Animals↗

PubMed2003

Expression of killer cell inhibitor receptors on immunocompetent cells with relation to graft-versus-host disease after hematopoietic stem cell transplantation.

The study was aimed at the exploration of relationship between T cells expressing killer cell inhibitor receptors (KIR, CD158 and CD94) and graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation. The expression rates of CD158a, CD158b and CD94 on T cells and NK cell were detected by flow cytometry and donor/recipient HLA-Cw was analyzed using PCR after peripheral blood stem cell transplantation (PBSCT) and umbilical cord blood transplantation (UCBT). After both PBSCT and UCBT, the rates of CD3(+)CD158a(+) and CD3(+)CD158b(+) T cells increased, especially the rate of CD8(+)CD158b(+) T cells. In both acute and chronic GVHD groups, the rate of CD3(+)CD158b(+) T cells increased, especially in acute GVHD. The CD94 mainly expressed on CD3(+)CD8(+) T cells. The percentage of the expression of CD94 on CD4(+) and CD8(+) cells after UCBT and PBSCT increased significantly. The expression of KIR in GVHD (early stage of transplantation) increased but the expression of KIR in chronic GVHD (advanced stage of transplantation) decreased. Five patients who HLA-Cw matched had no severe GVHD. In four patients who underwent allo-PBSCT and UCBT from related HLA-matched donors, only 2 patients had no aGVHD. Four patients underwent transplantation from unrelated HLA-matched donors had GVHD. These observations suggested that there is some relationship between GVHD and KIR expression on T cells. CD158b might be an inhibitory molecule of T cell activated at early stage after transplantation. Understanding the mechanism of GVHD with the expression of KIR on T cells, especially those binding the HLA-Cw might shed light on the establishment of the specific immunotolerance for the prevention of GVHD. To pay attention to HLA-Cw typing is very important to reduce GVHD and increase GVL effect in related or unrelated HLA-matched transplantation.

Antigens, CD↗

PubMed2003

[Clinical analysis of 29 children with early infectious complications following hematopoietic stem cells transplantation].

OBJECTIVE: To study the clinical features and the incidence of early infectious complications following children hematopoietic stem cells transplantation (HSCT). METHODS: The clinical data of 29 cases with early infectious complications following HSCT was retrospectively analyzed. RESULTS: The incidence of early infectious complications following HSCT in 31 children (including 22 cord blood transplantation and 9 peripheral blood stem cells transplantation) was 94% (29/31). The first occurrence of the early infectious complications was at a median of 6 (0 - 22) days, the peak time of incidence was at a median of 4 - 7 days post transplantation. The duration of the first early infectious complications was at a median of 9 (3 - 20) days. The occurrence of the second early infectious complications was at a median of 19 (13 - 27) days. For all of the 29 children, when they developed early infectious complications their absolute neutrophil counts (ANC) were all > 0.5 x 10(9)/L. The most common infectious sites were the digestive tract (oral and gastro-intestinal mucositis) and then the respiratory tract. Gram negative blood infections were quite frequent and Pseudomonas aeruginosa was common in the oral-pharynx discharge cultures. Two children had Mycoplasma pneumonia infections and there were 4 incidences with fever but no definite infectious foci. The incidence and duration of early infectious complications following hematopoietic stem cells transplantation were associated with the duration of neutropenia. The source and the MNCs dose of the graft, the difference of conditioning regimen and GVHD prophylaxis method did not have a significant impact on the incidence and duration of early infectious complications. Antibiotic prophylaxis (including Tienam) could delay the occurrence of the early infections significantly. CONCLUSION: The incidence and duration of early infectious complications following hematopoietic stem cells transplantation were directly associated with the duration of neutropenia. Tienam regimen could postpone the early infections incidence and had effect of preventing the early infectious complications.

Adolescent↗

PubMed2002

The two rat alpha 2,6-sialyltransferase (ST6Gal I) isoforms: evaluation of catalytic activity and intra-Golgi localization.

alpha2,6-Sialyltransferase (ST6Gal I) functions in the Golgi to terminally sialylate the N-linked oligosaccharides of glycoproteins. Interestingly, rat ST6Gal I is expressed as two isoforms, STtyr and STcys, that differ by a single amino acid in their catalytic domains. In this article, our goal was to evaluate more carefully possible differences in the catalytic activity and intra-Golgi localization of the two isoforms that had been suggested by earlier work. Using soluble recombinant STtyr and STcys enzymes and three asialoglycoprotein substrates for in vitro analysis, we found that the STcys isoform was somewhat more active than the STtyr isoform. However, we found no differences in isoform substrate choice when these proteins were expressed in Chinese hamster ovary cells, and sialylated substrates were detected by lectin blotting. Immuno-fluorescence and immunoelectron microscopy revealed differences in the relative levels of the isoforms found in the endoplasmic reticulum (ER) and Golgi of transiently expressing cells but similar intra-Golgi localization. STtyr was restricted to the Golgi in most cells, and STcys was found in both the ER and Golgi. The ER localization of STcys was especially pronounced with a C-terminal V5 epitope tag. Ultrastructural and deconvolution studies of immunostained HeLa cells expressing STtyr or STcys showed that within the Golgi both isoforms are found in medial-trans regions. The similar catalytic activities and intra-Golgi localization of the two ST6Gal I isoforms suggest that the particular isoform expressed in specific cells and tissues is not likely to have significant functional consequences.

Animals↗