ABSTRACT
<p><b>OBJECTIVE</b>To explore the myelo-protection effect of mdr1 transfected cord blood cells (CBMNCs) graft against high-dose homoharringtonine leukemia-bearing severe combined immunodeficient (SCID) mice model.</p><p><b>METHODS</b>Multidrug resistant (mdr1)gene was transferred into CBMNCs by a retrovirus vector, containing full-length cDNA of human mdr1 gene. CBMNCs and high-titer retrovirus supernatant were cocultured with cytokine combinations for 5 - 6 days. The SCID mouse models bearing human HL-60 cell leukemia were divided into three groups. Group A received tail vein injection of 2 x 10(6) mdr1 gene transduced CBMNCs at day 1 and 3, groups B and C 2 x 10(6) un-transduced CBMNCs and same volume of normal saline, respectively. The 3 groups of the mouse model were treated with weekly escalated doses of homoharringtonine. The peripheral white blood cell (WBC) counts, the human leukemia cells percentage in peripheral blood, the histological findings of main organs were assayed. The CD33 positive HL-60 cells in bone marrow were determined by flow cytometry. The function and expression of mdr1 gene were examined by PCR, immunochemistry (IC) and DNR extrusion test in vivo.</p><p><b>RESULTS</b>(1) mdr1 gene was transferred into CBMNCs successfully and the transfection frequency was 30%. (2) Leukemia SCID mice were xenotransplanted with mdr1-transfected BMMNCs by a programmed procedure and could be used as a valuable model for in vivo evaluating myelo-protection effects. (3) The transfected mice could tolerate homoharringtonine 5 approximately 6 folds higher than conventional dose and kept peripheral WBC count at a mean of 3 x 10(9)/L, with the peripheral human myeloid leukemia cells percentage decreasing to less than 5%. Histological examination showed that there was no leukemia infiltration in the main organs, the CD33 positive HL-60 cells in bone marrow were less than 5%. (4) The repopulation frequency of the transfected CBMNs in marrow were 9.13%. DNR extrusion test confirmed that the P-gp product maintained its biological function in the marrow.</p><p><b>CONCLUSION</b>mdr1 transferred-human CBMNC can xenotransplanted and repopulated in leukemia-bearing SCID mouse and are protected from chemotherapy-induced myelosuppression.</p>
Subject(s)
Animals , Female , Humans , Male , Mice , ATP Binding Cassette Transporter, Subfamily B, Member 1 , Genetics , Metabolism , Antineoplastic Agents, Phytogenic , Therapeutic Uses , Cord Blood Stem Cell Transplantation , Methods , Fetal Blood , Cell Biology , Genetic Vectors , HL-60 Cells , Harringtonines , Therapeutic Uses , Leukemia, Promyelocytic, Acute , Drug Therapy , Pathology , General Surgery , Leukocytes, Mononuclear , Cell Biology , Metabolism , Transplantation , Mice, SCID , Random Allocation , Retroviridae , Genetics , Transfection , Treatment Outcome , Xenograft Model Antitumor AssaysABSTRACT
Objective To investigate whether the monthly distribution of birth was associated with congenital heart disease(CHD).Methods The monthly distribution of birth of 5 070 patients with CHD who accepted examination or treatment from Jan.2003 to Dec.2006 was investigated and compared with that of 6 627 healthy newborn children born in 2001-2006.The statistic analysis was accomplished with SPSS 12.0 software for ?2 test.Results Four hundred and forty-four of the 5 070 patients with CHD were born in January(8.8%),432 cases in February(8.5%),384 cases in March(7.6%),339 cases in April(6.7%),390 cases in May(7.7%),393 cases in June(7.8%),414 cases in July(8.2%),489 cases in August(9.6%),498 cases in September(9.8%),492 cases in October(9.7%),396 cases in November(7.8%),and 399 cases in December(7.8%).The structural ratio of the number of CHD patients were the highest for those who were born in August,September,October,and the lowest among those who were born of February and March,April.The number of CHD patients who were born in the autumnal months of August,September and October was 1 479(29.1%),much higher than those who were born in February,March and April(1 155 cases,22.8%)(P
ABSTRACT
Objective To discuss the methods of selecting different shapes occluder and to evaluate the feasibility,safety and efficacy of them in transcatheter closures of congenital ventricular septal defect (VSD) in children.Methods Transcatheter closures were performed in 226 children with congenital VSD,age ranging from 2 to 14 years(mean 5.62 years) under the guidance of transthoracic echocardiography(TTE) and fluoroscopy.There were 14 patients with intracristal VSD,209 patients with perimembranous VSD and 3 patients with muscular VSD.Left ventriculography and transthoracic echocardiography were performed repeatedly after the procedure to assess the effect of occlusion.The echocardiography and electrocardiography were scheduled before discharge,1,6 and 12 months for the follow-up.Results The occluders were deployed successfully in 211 patients.The successful rate was 93.4%.Thin waist shape occluders,were deployed in 7 patients;equal side shape occluders,were deployed in 191 patients;eccentric shape occluders were deployed in 12 patients,and muscular defect occluders were deployed in 1 patient.There were no complications encountered during or after closure.Conclusions It is very important in transcatheter closure of congenital in children to select different shape occluder according to pathologic characteristics.In general,equal side shape occluder is suita-ble for a large number of defect and it is easy for deployment.In some conditions,the other shape occluder may be necessary.