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Biomedical subjects

Lei Jin

Publications and source records attributed to Lei Jin.

62 records · Page 4Linked to original sources
PubMed2003

[Distribution of the HIV/AIDS associated CCR5Delta32,CCR2b-64I,SDF1-3'A allelesin Chinese Dai and Chingpaw populations from Dehong autonomous prefecture of Yunnan Province].

The purpose of the work is to investigate the frequencies and polymorphisms of HIV-1 resistant CCR5delta32,CCR2b-64I,SDF1-3'A alleles in Chinese Dai and Chingpaw populations. Whole blood samples from 101 Dai subjects and 113 Chingpaw were collected randomly and their genomic DNA were extracted with QIAgen Blood Kits. Allelic frequencies were identified by PCR-RFLP analysis. Allelic polymorphisms in Dai population or Chingpaw population and both sexes in the samples were analyzed by chi(2) test. The frequencies of CCR5delta32,CCR2b-64I,SDF1-3'A alleles in Dai population were 0.0000,0.2130,0.2030, respectively. The frequencies of CCR5delta32,CCR2b-64I,SDF1-3'A alleles in Chingpaw population were 0.000, 0.1637, 0.1770, respectively. Distributions of the CCR2b-64I,SDF1-3'A alleles among the both populations were in accordance with Hardy-Weinberg equilibrium. No statistical difference was found in the allelic frequencies of both CCR2b-64I and SDF1-3'A between male and female individuals. The frequencies of CCR5delta32,CCR2b-64I alleles in Chinese Dai and Chingpaw populations are similar to that in Chinese Han population, while the frequency of SDF1-3'A allele in Chinese Dai and Chingpaw populations are lower in contrast to that in Chinese Han population. The genotyping and polymorphism of CCR5delta32,CCR2b-64I,SDF1-3'A alleles in Chinese Dai and Chingpaw populations of Yunnan Province are the first time studied in China. The significance of the three mutant alleles conferring genetic resistance to HIV-1 and AIDS progression remains to be clarified.

English Abstract↗
PubMed2002

Effects of physician experience on costs and outcomes on an academic general medicine service: results of a trial of hospitalists.

BACKGROUND: Hospitalists may decrease costs and improve outcomes in hospitalized patients, but existing evidence is limited and has not identified mechanisms for such effects. OBJECTIVE: To study the costs and outcomes for patients on an academic general medicine service assigned to teams led by hospitalists and nonhospitalists. DESIGN: Cohort study. SETTING: Academic general medicine service. PATIENTS: 6511 patients admitted to the hospital from July 1997 through June 1999. INTERVENTION: All patients admitted every fourth day were assigned to 1 of 2 hospitalists caring for inpatients 6 months each year or 1 of 58 nonhospitalists caring for inpatients 1 to 2 months each year. MEASUREMENTS: Length of stay; inpatient costs; and 30-, 60-, and 365-day mortality. RESULTS: Patients assigned to hospitalists (24.8%) and nonhospitalists (75.2%) did not differ in age, race, sex, diagnosis mix, or Charlson index score. In year 1, average adjusted length of stay was 0.29 day shorter for patients cared for by hospitalists than by nonhospitalists (95% CI, -0.66 to 0.06 day; P = 0.06); in year 2, average adjusted length of stay was 0.49 day shorter for patients cared for by hospitalists (CI, -0.79 to -0.15 day; P = 0.01). Average adjusted costs were not significantly reduced for hospitalists compared with nonhospitalists in year 1 but were reduced by $782 in year 2 (CI, -$1313 to -$187; P = 0.01). When years 1 and 2 were combined or when year 1 was analyzed alone, 30-day mortality was not significantly different for hospitalists and nonhospitalists; however, 30-day mortality was 4.2% for hospitalists compared with 6.0% for nonhospitalists in year 2 (CI for difference, 1.8 percentage points [-3.6 to -0.1 percentage points]; P = 0.04) and the adjusted relative risk was 0.65 (CI, 0.44 to 0.96; P = 0.03). In multivariate analyses, resource use decreased with the physician's cumulative experience in caring for a patient's primary diagnosis. Mortality showed a similar pattern. CONCLUSIONS: Hospitalist care was associated with lower costs and short-term mortality in the second but not the first year of hospitalists' experience. Disease-specific physician experience may reduce resource use and improve patient outcomes; in addition, it may be an important determinant of the effectiveness of hospitalists.

Chicago↗
PubMed2002

[Identification of new mutant sites and 894C deletion variant genotyping of HIV-1 coreceptor CCR5 in indigenous Chinese populations].

OBJECTIVE: To investigate the new single nucleotide polymorphism (SNP) sites of HIV-1 coreceptor CCR5 gene and conduct genotyping of CCR5-894C deletion allele in Chinese populations. METHODS: The full length fragment of CCR5 gene coding region was amplified by PCR amplification and sequenced in 45 healthy subjects from Han ethnic group. The sequencing data was analyzed by using DNAstar software for identification of new SNP sites. Furthermore, the genotyping of CCR5-894C deletion variant was performed by PCR-RFLP assay in 627 indigenous Chinese individuals including HIV-1 carriers, HIV-1 high risk population of STDs or IDUs as well as normal contrast. RESULTS: Totally six SNPs and one cytosine base deletion at the 894 nucleotide of CCR5 gene coding region were found in forty five Chinese Han subjects. Four SNPs, i.e. 184A-->G, 503G-->T, 668G-->A, 999G-->T, cause alteration of corresponding amino acids in CCR5 protein and two SNPs are nonsense mutations. The 894C deletion mutation results in a frame shift mutation of CCR5 gene. Among the six SNPs identified, the three sites 184A-->G, 503G-->T, 999G-->T were firstly reported only in Chinese people. The allelic frequencies of mutant 184G, 503T and 999T alleles were 1.1%, 21.1% and 10.0% in Han healthy subjects, respectively. PCR-RFLP assay showed the frequencies of CCR5-894C deletion alleles are 1.11%, 0.53% and 0% for Chinese Han, Tibetan and Mongolian healthy individuals, respectively. There was not significant different of the frequencies of CCR5-894C deletion allele among HIV-1 high risk populations, HIV-1 carries and healthy subjects. CONCLUSION: The subjects from Chinese Han group has its own distinctive SNP sites in the HIV-1 coreceptor CCR5 gene, three new SNPs (184A-->G, 503G-->T, 999G-->T) were firstly identified. Taking together, the significance and implication of these distinctive SNP sites and the 894C deletion mutation in the pathogenesis of HIV/AIDS disease need to be further studied.

Amino Acid Sequence↗
PubMed2002

Crystal structure of human calcineurin complexed with cyclosporin A and human cyclophilin.

Calcineurin (Cn), a Ca(2+)/calmodulin-dependent Ser/Thr protein phosphatase, is an important participant in signaling pathways that activate T cells. It is the target of the immunosuppressive drugs cyclosporin A (CsA) and FK506. These drugs bind proteins known as cyclophilin (Cyp) and FK506-binding protein, respectively, and the drug-protein complexes in turn inhibit Cn. We report the crystal structure of a Cyp/CsA/Cn ternary complex, determined to a resolution of 3.1 A. Residues 3-9 of CsA, particularly N-methyl leucines 4 and 6, and Trp-121 of Cyp form a composite surface for interaction with Cn. The hydrophobic interface buries two hydrogen bonds. The structure accounts clearly for the effects of mutations in Cn on CsA-resistance and for the way modifications of CsA alter immunosuppressive activity.

Binding Sites↗
PubMed2002

Sialic acid binding domains of CD22 are required for negative regulation of B cell receptor signaling.

CD22, a negative regulator of B cell antigen receptor signaling, binds glycoconjugates terminating in alpha2, 6 sialic acid. The physiological ligand(s) for CD22 remain unknown. We asked whether the sialic acid binding domains are necessary for CD22 to function as a negative regulator. We generated two mutants that lack sialic acid binding activity and expressed them in a novel CD22(-/-) murine B cell line. Anti-IgM activated B cells expressing either CD22 mutant had greater Ca(2+) responses than cells expressing wild-type CD22. Each variant also had reduced CD22 tyrosine phosphorylation and Src homology 2 domain-containing protein tyrosine phosphatase-1 association. These data suggest that the alpha2, 6 sialic acid ligand binding activity of CD22 is critical for its negative regulatory functions.

Animals↗
PubMed2002

Two novel mutations of the retinitis pigmentosa GTPase regulator gene in two Chinese families with X-linked retinitis pigmentosa.

OBJECTIVE: To detect mutations of the retinitis pigmentosa GTPase regulator (RPGR) gene in two Chinese X-linked retinitis pigmentosa families. METHODS: Fragments of exons 1-19 of the RPGR gene were amplified with intronic primers, using genomic DNA as template. The polymerase chain reaction (PCR) products were analysed by single-strand conformation polymorphism (SSCP) and direct sequencing. Mutations were identified by comparing DNA sequences of the patients with those of the normal controls. RESULTS: Two novel mutations, c1536delC and E332X, were identified in exons 12 and 9 of the RPGR gene in both families. Each mutation was the first mutation found in their respective exons. Both mutations were predicted to cause premature termination, which resulted in truncated proteins without normal functions of the RPGR products. CONCLUSIONS: Both mutations are the genetic basis of the pathogenesis in the respective families. Our data might be helpful in analysing the function of the RPGR protein.

Carrier Proteins↗
PubMed2002

[Adenovirus-mediated transfer of anti-MDR1 ribozyme in the treatment of multidrug-resistant human lymphoma in SCID mice].

OBJECTIVE: To evaluate the effect of adenovirus-mediated transfer of anti-MDR1 ribozyme on restoring drug sensitivity of multidrug-resistant human lymphoma both in vitro and in SCID mice. METHODS: A recombinant adenovirus expressing ribozyme against codon 196 of MDR1 mRNA (Ad-196MDR1-Rz) was developed through cotransfection of shuttle vector pCA14 containing 196MDR1-Rz and rescue vector pJM17 into human embryonic kidney cell line 293. In vitro Daudi/MDR20, a MDR1-mediated drug-resistant human lymphoma cell line, was transduced by Ad-196MDR1-Rz at MOI of 400 pfu/cell. RT-PCR and FACS analyses were used to evaluate the MDR1 expression in both transcriptional and translational levels. MTT assay was used for analysis of drug resistance. In vivo, SCID mice were inoculated subcutaneously by 5 x 10(6) Daudi/MDR20 or parental Daudi/wt cells. Adenovirus was injected locally. Vincristine (VCR) was given intraperitoneally. RESULTS: In vitro transduction of Ad-196MDR1-Rz to Daudi/MDR20 cells was able to interrupt MDR1 transcription, inhibit P-gp expression and restore drug sensitivity to VCR. Of SCID mice bearing Daudi/MDR20 cells, tumor free rate and long term survival were 66.7% (6/9) and > 120 days in the therapeutic group of Ad-196MDR1 + VCR vs 12.5% (7/8) and none survived > 120 days in the control groups of Ad-Mock + VCR or VCR alone. The difference was very statistically significant. CONCLUSION: Ad-mediated transfer of 196MDR1-Rz can revert drug resistance of MDR tumor cells both in vitro and in vivo. Ad-196MDR1-Rz may be helpful as an adjuvant in the chemotherapy of P-gp mediated MDR human tumor.

ATP Binding Cassette Transporter, Subfamily B, Mem↗