OBJECTIVETo provide a quantitative summary in estimating the association between polymorphisms of 3 loci in NRAMP1 gene and susceptibility to tuberculosis in East-Asia population by means of meta-analysis.

METHODSWe searched databases (MEDLINE, OVID and CBM disc) from January 1995 to May 2005 using "NRAMP1" or "SLC11A1", in combination with "tuberculosis", also performed a manual search of citations from relevant original studies and literature. For each study involved, information was collected concerning the characteristics of the subjects, such as mean age of cases and the size of study. These characteristics were used to evaluate the sources of variation. Summary ORs and corresponding 95% CI were estimated by fixed effects (Mantel-Haenszel) or random effects (DerSimonian and Laird) model. To check for publication bias,a funnel plot, using Egger's linear regression method, was constructed. Cumulative meta-analysis was performed to evaluate whether the summary OR for studies with the polymorphisms of the 3 loci in the NRAMP1 gene was changing along with the accumulation of more data. Chi-square goodness of fit was used to test deviation from Hardy-Weinberg equilibrium.

RESULTSEight publications, with the number of cases and controls of 1067 and 1084 respectively, were identified and all genotype frequencies were consistent with Hardy-Weinberg equilibrium. The summary ORs for studies with polymorphisms of 3' UTR, D543N and INT4 loci of the NRAMPI gene among the East-Asia population were 1.68(95% CI: 1.31-2.16, P< 0.001), 1.78(95% CI: 1.38-2.30, P< 0.001), 1.56 (95% CI: 0.72- 3.35, P = 0.26), respectively when compared with their corresponding common homozygotes. Publication bias was not found in the studies with the three loci, except for INT4 locus, by Egger linear regression method. The cumulative summary effects ORs were 1.85 (P = 0.02) in 2000, 1.35 (P = 0.12) in 2002,1.64 (P= 0.001) in 2003, and 1.68 (P<0.001) in 2004 for 3'UTR locus, 1.88 (P = 0.001) in 2000,1.65(P = 0.001) in 2002,1.70(P<0.001) in 2003,1.76(P<0.001) in 2004, and 1.78(P<0.001) in 2005 for D543N locus, and 0.88(P = 0:70) in 2002, 2.50(P = 0.41) in 2003, 1.52(P = 0.42) in 2004 and 1.56(P = 0.26) in 2005 for INT4 loucs.

CONCLUSIONPolymorphisms at 3' UTR and D543N loci had statistically significant association between the NRAMP1 variants and susceptibility to tuberculosis in the East-Asia descendants, and variant in the INT4 locus failed to show statistically significant association in the East-Asia population.

Asian Continental Ancestry Group ; genetics ; Cation Transport Proteins ; genetics ; Far East ; Genetic Predisposition to Disease ; Humans ; Odds Ratio ; Polymorphism, Genetic ; Tuberculosis ; genetics

Objective To investigate the effect of hypertonic saline on cerebral water content, tumor necrosis factor-α (TNF-α) level and neuronal apoptosis following focal cerebral ischemia-reperfusion (IR) injury in rats and explore the mechanisms involved. Methods Ninety-six rats were randomized equally into 4 groups, namely the shame-operated group, untreated IR injury group, and 4.2% and 7.5% hypertonic saline groups (HS-A and HS-B groups, respectively). In the latter 3 groups, cerebral ischcmia was induced by middle cerebral artery occlusion for 2 h followed by administration of the corresponding treatments. Serum sodium concentration was measured at 5 min before and at 30, 60 and 90 min after the reperfilsion. At 22 h of rcperfusion, the rats were sacrificed after neurological deficit evaluation, and brain edema was assessed by measuring the wet-to-dry weight ratio of the brain tissue. TNF-α expression in the ischemic brain tissue was measured by enzyme-linked immunosorbent assay (ELISA), and the neuronal apoptosis was analyzed using TUNEL assay. Results In the saline-treated rats, serum sodium level increased significantly after saline administration, lasting for 60 min before recovering the normal levels in HS-A group and for over 90 min in HS-B group. Compared with that in the sham-operated group, the brain water content in rats of the IR group increased in both of the hemispheres, but more obviously in the ischemic hemisphere. In the two saline-treated groups, the water content decreased significantly in the bilateral hemispheres, which was especially obvious in the ischemic hemisphere;administration of 7.5% saline resulted in greater water content reduction in the ischemic hemisphere than 4.2% saline. Compared with the IR group, the two saline-treated groups showed significant reduction in TNF-α levels and apoptotic cells in the brain along with decreased neurological deficits. Conclusion Hypertonic saline can ameliorate cerebral focal IR injury by decreasing the cerebral water content, TNF-α level and neuronal apoptosis following the injury.

Objective To investigate the effects of acute normovolemic hemodilution(ANH)on intraoperative intracranial pressure(ICP),jugular venous oxygen saturation(SvO_2),and venous blood lactate(VBL)of patients with intracranial tumor, Methods Forty-two patients,elected to perform supratentorial intracranial tumor resection on some certain days,were randomly divided into ANH(n=21)and control (n=21)groups.Bloodletting was performed in the radial artery after anesthesia induction and the same amount of hydroxyethyl starch was injected into the internal jugular vein at the same time so as to induce the haematocrit reaching to 30% in the ANH group.ANH was not performed in the control group.Acetated Ringer's solution was used during the operation in both groups.The level of arterial partial pressure of oxygen(PaO_2),arterial oxygen saturation(SaO_2),venous oxygen partial pressure (PvO_2),mixed venous O_2 saturation(SvO_2)and VBL was measured before hemodilution(T_0),30 min after the hemodilution(T_1),1 h after the hemodilution(T_2),and at the time the operation was finished(T_3)in both groups.And the changes of ICP before hemodilution(T_0),immediate after hemodilution(T_1),30 min after the hemodilution(T_Ⅱ),and before the endocranium was cut open(T_Ⅲ)in both groups. Results The ICP value in the two groups was not significantly different at different time points;The level of SvO_2 in the control group was significantly lower than that in the ANH group at T_2 and T_3(P<0.05);Significantly decreased level of SvO_2 and increased level of VBL was found in the control group at T2 and T_3 as compared with those in the control group at T_0 and T_Ⅱ(P<0.05). Conclusion Maintaining ICP in patients with intracranial tunlor during the operation through performing ANH with Hct reaching 30%,can significantly improve the oxygen supply and consumption in the brain tissue.

OBJECTIVETo diagnose achondroplasia prenatally by FGFR3 gene detection.

METHODSSeventy-eight fetuses affected by short-limb dysplasias were recruited. Umbilical blood sampling was employed to obtain fetal blood for karyotyping and FGFR3 gene detection. Genomic DNA was extracted, and the exon 10 of the FGFR3 gene was amplified. PCR amplicons were analyzed by DNA sequencing and restriction fragment length polymorphism with Bfm I. The FGFR3 exon 10 from the parents of the positive fetuses was screened by the same method.

RESULTSIn 78 fetuses affected with short-limb dysplasias, 8 cases had G1138A heterozygotic mutation and normal karyotype, and were diagnosed as achondroplasia. The other 70 fetuses had normal nucleotide at nucleotide 1138 in exon 10 of FGFR3, therefore were excluded from achondroplasia. Only one father in parents of the 8 achondroplasia fetuses also had the G1138A mutation.

CONCLUSIONAchondroplasia could be diagnosed prenatally in the fetuses affected with short-limb dysplasias by using PCR-RFLP and DNA sequencing of the exon 10 of the FGFR3 gene.

Achondroplasia ; diagnosis ; genetics ; DNA Mutational Analysis ; Female ; Humans ; Male ; Polymorphism, Restriction Fragment Length ; Pregnancy ; Prenatal Diagnosis ; methods ; Receptor, Fibroblast Growth Factor, Type 3 ; genetics

OBJECTIVETo evaluate the correlation of 64-multidetector-row CT (64MDCT) perfusion imaging with microvessel density(MVD) and vascular endothelial growth factor(VEGF) in colorectal carcinoma.

METHODS64MDCT perfusion imaging was performed in 33 patients with pathologically verified colorectal carcinoma. Time-density curves (TDC) were created from the region of interest (ROI) drawn over the tumor, target artery and vein by 64MDCT with perfusion functional software. The individual perfusion maps generated were for blood flow (BF), blood volume (BV), mean transit time (MTT) and permeability-surface area product (PS). MVD and VEGF expression of surgical specimens were examined by immunohistochemical staining with anti-CD34, anti-VEGF monoclonal antibody. MVD and VEGF were compared among the different types of TDC in colorectal carcinoma. The correlation of CT perfusion parameters with MVD and VEGF was also examined.

RESULTSTDC of colorectal carcinoma was divided into five types according to their shapes. MVD in the colorectal carcinoma was 22.61+/-9.01. VEGF staining was found in 25 of 29 tumors (86.2%). The score of VEGF expression was 4.15+/-1.09. No significant differences of MVD and VEGF expression among TDC types were found (F=2.59, 1.11, P>0.05). There were also no correlations of MVD and VEGF expression with any dynamic CT parameters (P>0.05).

CONCLUSION64MDCT perfusion imaging, MVD and VEGF may reflect angiogenic activity, but no significant correlations are found among them.

Adult ; Aged ; Colorectal Neoplasms ; blood supply ; diagnostic imaging ; Female ; Humans ; Male ; Microvessels ; Middle Aged ; Neovascularization, Pathologic ; Tomography, Spiral Computed ; methods ; Vascular Endothelial Growth Factor A ; metabolism ; Young Adult

OBJECTIVETo study the pathological features of liver tissues from patients clinically diagnosed with mild chronic hepatitis B based on current guideline and emphasize the important significance of liver puncture and biopsy for these patients.

METHODSTotally 156 patients clinically diagnosed with mild chronic hepatitis B based on current guideline received liver puncture under the real-time Doppler ultrasonographic guiding. Pathological diagnosis was made after microscopic examinations of the liver tissue specimens stained with hematoxylin-eosin (HE) and reticular fiber staining. The differences between clinical and pathological diagnosis for these patients were analyzed.

RESULTSFinally, 105 (67.3%) patients were pathologically diagnosed with mild chronic hepatitis B; 28 (18.0%), 3 (1.9%) and 20 (12.8%) patients were pathologically diagnosed as moderate, severe chronic hepatitis B and cirrhosis, respectively. Forty-eight (30.8%) and 39 (25.0%) patients of non-mild chronic hepatitis B were found to have G3-4 inflammation and S3-4 fibrosis, respectively. Differences in serum alanine aminotransferase, aspartate aminotransferase, total bilirubin or albumin between mild and non-mild chronic hepatitis B based on pathological diagnosis were not statistically significant (t-test, P > 0.05).

CONCLUSIONSAccurate pathological diagnosis is helpful to guiding an antiviral therapy.

Adolescent ; Adult ; Aged ; Female ; Hepatitis B, Chronic ; diagnosis ; pathology ; Humans ; Liver ; pathology ; Male ; Middle Aged ; Young Adult

OBJECTIVEThe aim of this study was to investigate the relationship between liver function test, serum HBeAg, HBV DNA level and liver pathological changes in patients with chronic hepatitis B.

METHODS233 patients with chronic hepatitis B accept liver puncture biopsy, liver function test, HBeAg detection and HBV DNA fluorescent quantitation PCR detection. Comparisons of liver function test, HBeAg and HBV DNA level were conducted among different liver pathological changes including inflammation grading and fibrosis staging.

RESULTSIn different inflammation grading groups, ALT was highest in group G3 and lowest in group G(0-1)(P = 0.016); TBil was highest in group G4 and lowest in group G(0-1) (P = 0.000); HBV DNA level was highest in group G4 and lowest in group G(0-1), but not statistically significant among groups (P = 0.463). In different fibrosis staging groups, ALT was highest in group S3 and lowest in group S(0-1), but not statistically significant among groups (P = 0.562); TBil was highest in group S4 and lowest in group S2 (P = 0.039); HBV DNA level was highest in group S3 and lowest in group S(0-1), but not statistically significant among groups (P = 0.395). In HBeAg positive group,the proportion of G(3-4) in inflammation grading or S(3-4) in fibrosis staging was lower than that in HBeAg negative group (46% vs. 52%, P = 0.438; 38% vs. 53%, P = 0.025; respectively).

CONCLUSIONHBV DNA level can not indicate the severity of liver inflammation or fibrosis in chronic HBV infection. Patients with HBeAg negative often are complicated with more severity of liver fibrosis. In routine liver function test, TBil level correlates with liver inflammation grading or fibrosis staging; ALT level also correlates with liver inflammation grading but not with fibrosis staging.

Adult ; Clinical Laboratory Techniques ; DNA, Viral ; analysis ; Female ; Hepatitis B Surface Antigens ; immunology ; Hepatitis B e Antigens ; metabolism ; Hepatitis B virus ; isolation & purification ; Hepatitis B, Chronic ; immunology ; pathology ; physiopathology ; Humans ; Inflammation ; etiology ; Liver Cirrhosis ; etiology ; immunology ; Liver Function Tests ; statistics & numerical data ; Male ; Viral Load

OBJECTIVETo evaluate the dose-limiting toxicity (DLT), efficacy and maximum tolerated dose (MTD) of capecitabine with concurrent radiotherapy in patients with node-positive stage II nasopharyngeal cancer.

METHODSFrom August 2002 to June 2003, 30 patients with node-positive stage II T(2)N(1)M(0) nasopharyngeal cancer were retrospectively reviewed. Median age 43 years (range 32 - 63 years), ECOG performance status

RESULTSTwenty-eight patients were evaluable for toxicity and efficacy: CR 12 (42.9%), PR 13 (46.4%), SD 3 (10.7%), the overall response rate (CR + PR) was 89.3%. The CR response rate of the node-positive area and of the nasopharynx were 50.0% (14/28) and 46.4% (13/28). No DLT was observed at the dosage group of 500 mg/m(2) and 750 mg/m(2). Three of 9 patients experienced DLT at 1000 mg/m(2) with grade III stomatitis; 4 of 6 at 1250 mg/m(2) with grade III stomatitis (4/6), grade III diarrhea with grade IV febrile neutropenia (1/6) and grade III thrombocytopenia (1/6). The toxicity of grade I and II was hand-foot syndrome (4/28), fatigue (14/28), nausea and vomiting (19/28), diarrhea (5/27), and weight loss (21/28).

CONCLUSIONA dose of 750 mg/m(2) of capecitabine might be recommended for combination with radiotherapy. This regimen is tolerable and valid for nasopharyngeal carcinoma. A randomised phase III comparison with 5-Fu is justified.

Adult ; Antimetabolites, Antineoplastic ; adverse effects ; therapeutic use ; Capecitabine ; Combined Modality Therapy ; Deoxycytidine ; adverse effects ; analogs & derivatives ; therapeutic use ; Dose-Response Relationship, Drug ; Female ; Fluorouracil ; analogs & derivatives ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; drug therapy ; pathology ; radiotherapy ; Neoplasm Staging ; Stomatitis ; chemically induced ; Thrombocytopenia ; chemically induced

OBJECTIVETo assess the accuracy and reliability of the nest-PCR-sequence specific primer(SSP) method in HLA-A site genotyping of single blastomeres retrieved from human pre-implantation embryos.

METHODSBy nest PCR on HLA-A exon 2, the success rate of first-round amplification was estimated for single blastomeres. Based on the first-round amplification, the HLA-A genotype of every single blastomeres was analyzed by commercially available PCR-SSP kits.

RESULTSThe amplification of HLA-A exon 2 were performed to 120 blasotmeres retrieved from in vitro fertilization(IVF) surplus embryos donated by 10 couples. The average success rate of family 1-5 and 6-10 was 78.2%(43/55) and 93.8%(61/65), respectively. And 86.7%(104/120) in total. Eighty blastomeres were further tested by nest-PCR-SSP, among which 11 blastomeres failed to HLA-A exon 2 amplification and then failed to genotyping while the other 69 blastomeres succeed in HLA-A exon 2 amplification and succeed in genotyping. Except for 6 blastomeres that were uncertain for allele lost because of parents' homozygosity, the left 63 blastomeres had accurate HLA genotyping. Among these 63 blastomeres, 59 blastomeres had genotypes confirmed from their parents(93.6%), 3 blastomeres lost one of parents' alleles(4.8%), and only one blastomere had two more than parents' alleles(1.6%).

CONCLUSIONThe above research results indicated that based on the successful first round amplification of single blastomeres, nest-PCR-SSP strategy offers a convenient and reliable option for HLA genotyping on single blastomeres, which is a key process in pre-selecting HLA-identical sibling for allogeneic cord blood cell transplantation.

Base Sequence ; Blastomeres ; metabolism ; DNA ; analysis ; DNA Fingerprinting ; methods ; DNA Mutational Analysis ; Female ; HLA Antigens ; analysis ; HLA-A Antigens ; analysis ; genetics ; Histocompatibility Antigens Class I ; analysis ; genetics ; Humans ; Male ; Polymerase Chain Reaction ; methods ; Single Person

OBJECTIVETo investigate whether dendritic cells fused with tumor cells could elicit in vitro antitumor responses against renal cell carcinoma (RCC) cells.

METHODSRenal carcinoma cells were purified from tumor tissue excised from patients with metastatic RCC through tumor cell purifying technique and cultured in RPMI-1640 medium containing 10% FCS. Monocyte-derived DCs generated from peripheral blood mononuclear cell of RCC patients were cultured in the presence of human recombinant granulocyte-macrophage colony stimulating factor and interleukin-4. Tumor cells and DCs were cocultured in the presence of polyethylene glycol (PEG) to generate cell fusion. The phenotype of tumor cells, DCs and fusion cells were detected by flow cytometry. MTT was used to measure the ability of fusion cells to stimulate T cell proliferation. T cell-mediated antitumor responses were measured by lactate dehydrogenase release (LDH) assay for lysis of autologous tumor cells.

RESULTSThe DCs expressed MHC class I, MHC class II and costimulatary molecules (CD80 and CD86), while the renal carcinoma cells expressed a high molecular glycoprotein MUC-1. The DC/tumor fusion cells coexpressed MUC-1 and the phenotype of DCs, and could stimulate T cell proliferation effectively. CTLs stimulated by the fusion vaccine showed distinct lytie activity in vitro to autologous tumor cells.

CONCLUSIONDendritic cells fused with tumor cells can elicit distinct antitumor responses in vitro against tumor cells from patients with metastatic RCC, providing a basis for further research on the clinical application of fusion vaccine in treatment for renal cancers.

B7-2 Antigen ; metabolism ; Cancer Vaccines ; immunology ; Carcinoma, Renal Cell ; immunology ; metabolism ; pathology ; Cell Fusion ; Cell Proliferation ; Coculture Techniques ; Cytotoxicity, Immunologic ; immunology ; Dendritic Cells ; cytology ; immunology ; metabolism ; Humans ; Hybrid Cells ; cytology ; immunology ; metabolism ; Kidney Neoplasms ; immunology ; metabolism ; pathology ; Mucin-1 ; metabolism ; T-Lymphocytes ; immunology ; T-Lymphocytes, Cytotoxic ; immunology ; Tumor Cells, Cultured