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Biomedical subjects

T Xie

Publications and source records attributed to T Xie.

At least 19 recordsLinked to original sources
PubMed2000

Effect of temperature on dopamine transporter function and intracellular accumulation of methamphetamine: implications for methamphetamine-induced dopaminergic neurotoxicity.

Hyperthermia exacerbates and hypothermia attenuates methamphetamine (METH)-induced dopamine (DA) neurotoxicity. The mechanisms underlying these temperature effects are unknown. Given the essential role of the DA transporter (DAT) in the expression of METH-induced DA neurotoxicity, we hypothesized that the effect of temperature on METH-induced DA neurotoxicity is mediated, at least in part, at the level of the DAT. To test this hypothesis, the effects of small, physiologically relevant temperature changes on DAT function were evaluated in two types of cultured neuronal cells: (1) a neuroblastoma cell line stably transfected with human DAT cDNA and (2) rat embryonic mesencephalic primary cells that naturally express the DAT. Temperatures for studies of DAT function were selected based on core temperature measurements in animals exposed to METH under usual ambient (22 degrees C) and hypothermic (6 degrees C) temperature conditions, where METH neurotoxicity was fully expressed and blocked, respectively. DAT function, determined by measuring accumulation of radiolabeled DA and 1-methyl-4-phenylpyridinium (MPP(+)), was found to directly correlate with temperature, with higher levels of substrate uptake at 40 degrees C, intermediate levels at 37 degrees C, and lower levels at 34 degrees C. DAT-mediated accumulation of METH also directly correlated with temperature, with greater accumulation at higher temperatures. These findings indicate that relatively small, physiologically relevant changes in temperature significantly alter DAT function and intracellular METH accumulation, and suggest that the effect of temperature on METH-induced DA neurotoxicity is mediated, at least in part, at the level of the DAT.

1-Methyl-4-phenylpyridinium↗
PubMed2000

A niche maintaining germ line stem cells in the Drosophila ovary.

Stromal cells are thought to generate specific regulatory microenviroments or "niches" that control stem cell behavior. Characterizing stem cell niches in vivo remains an important goal that has been difficult to achieve. The individual ovarioles of the Drosophila ovary each contain about two germ line stem cells that maintain oocyte production. Here we show that anterior ovariolar somatic cells comprising three cell types act as a germ line stem cell niche. Germ line stem cells lost by normal or induced differentiation are efficiently replaced, and the ability to repopulate the niche increases the functional lifetime of ovarioles in vivo. Our studies implicate one of the somatic cell types, the cap cells, as a key niche component.

Animals↗
PubMed2000

Disulfide bonds are generated by quinone reduction.

The chemistry of disulfide exchange in biological systems is well studied. However, very little information is available concerning the actual origin of disulfide bonds. Here we show that DsbB, a protein required for disulfide bond formation in vivo, uses the oxidizing power of quinones to generate disulfides de novo. This is a novel catalytic activity, which to our knowledge has not yet been described. This catalytic activity is apparently the major source of disulfides in vivo. We developed a new assay to characterize further this previously undescribed enzymatic activity, and we show that quinones get reduced during the course of the reaction. DsbB contains a single high affinity quinone-binding site. We reconstitute oxidative folding in vitro in the presence of the following components that are necessary in vivo: DsbA, DsbB, and quinone. We show that the oxidative refolding of ribonuclease A is catalyzed by this system in a quinone-dependent manner. The disulfide isomerase DsbC is required to regain ribonuclease activity suggesting that the DsbA-DsbB system introduces at least some non-native disulfide bonds. We show that the oxidative and isomerase systems are kinetically isolated in vitro. This helps explain how the cell avoids oxidative inactivation of the disulfide isomerization pathway.

Bacterial Proteins↗
PubMed2000

Enhancement of immunogenicity of tumor cells by cotransfection with genes encoding antisense insulin-like growth factor-1 and B7.1 molecules.

Insulin-like growth factor-1 (IGF-1) is expressed in many tumor cell lines and has a role in both normal cell proliferation and in the growth of cancers. Tumor cells transfected with a vector encoding an IGF-1 antisense cDNA transcriptional cassette driven by the mouse metallothionein-1 promoter become immunogenic and lose their tumorigenicity in syngeneic animals. The enhanced immunogenicity is associated with an up-regulation in the expression of major histocompatibility complex class I molecule on cell surfaces. Blockade of the expression of IGF-1 in tumor cells by the IGF-1 antisense RNA approach is not uniformly effective in the induction of antitumoral protective immunity in low and nonimmunogenic tumor model systems. Here, we report that the immunogenicity of hepa 1-6 hepatoma and SMCC-1 colon carcinoma cells, which are poorly immunogenic and unresponsive to antisense IGF-1 gene transfer, can be induced by cotransfection with genes encoding antisense IGF-1 and mouse B7.1 molecules. The tumor cells modified in this manner become strongly immunogenic and can be used as a cellular vaccine to induce a protective immune response in vivo. Immunization with the transfected tumor cells also results in regression of the established hepa 1-6 hepatoma and SMCC-1 colon cancer. The immunity is tumor-specific and is mediated by CD3+ CD8+ T cells. Cytotoxic T lymphocytes generated in vitro by priming naive spleen cells and in vivo by immunizing mice with the double-transfected tumor cells specifically lysed autologous tumors cells and were effective in adoptive immunotherapy. The data suggest that modification of tumor cells in vitro by cotransfection with genes encoding antisense IGF-1 and B7.1 molecules may open a new avenue for cancer immunogene therapy.

Adjuvants, Immunologic↗
PubMed2000

Body size and prostate cancer: a population-based case-control study in China.

We conducted a population-based case-control study in China to investigate whether body size plays a role in prostate cancer etiology and whether it can explain the rapid increase in prostate cancer incidence rates in China. A total of 238 cases newly diagnosed with primary prostate cancer in Shanghai, China, during 1993-1995 were included in the study. Four hundred and seventy-one healthy control subjects were randomly selected from among residents of Shanghai and frequency-matched to cases on the basis of age. In-person interviews were conducted to elicit information on height, weight history, and other lifestyle factors. Waist and hip circumferences were measured at interview. Odds ratios (ORs) were used to measure the association between prostate cancer and anthropometric variables including height, weight, body mass index (BMI), waist, hip, and right upper arm circumferences, and waist-to-hip ratio (WHR; an indicator of abdominal adiposity). High levels of WHR were related to an excess risk, with men in the highest quartile (WHR > 0.92) having an almost 3-fold risk (OR, 2.71; 95% CI = 1.66-4.41; Ptrend = 0.0001) compared with men in the lowest quartile (WHR < 0.86). In contrast, men in the highest quartile of hip circumference (>97.4 cm) had a reduced risk (OR, 0.46; 95% CI = 0.29-0.74; Ptrend = 0.0002) relative to men in the lowest quartile (<86 cm). No association was found for height, usual adult weight, or preadult and usual adult BMI. Our results suggest that even in a very lean population (average BMI = 21.9), abdominal adiposity may be associated with an increased risk of clinical prostate cancer, pointing to a role of hormones in prostate cancer etiology. Additional research is needed to confirm these findings in prospective studies, especially in Western populations where abdominal obesity is much more common, and to clarify the underlying hormonal mechanisms involved.

Abdomen↗
PubMed1999

Characterization and implications of estrogenic down-regulation of human catechol-O-methyltransferase gene transcription.

Catechol-O-methyltransferase (COMT, EC 2.1.1.6) is a ubiquitous enzyme that is crucial to the metabolism of carcinogenic catechols and catecholamines. Regulation of human COMT gene expression may be important in the pathophysiology of various human disorders including estrogen-induced cancers, Parkinson's disease, depression, and hypertension. The gender difference in human COMT activity and variations in rat COMT activity during the estrous cycle led us to explore whether estrogen can regulate human COMT gene transcription. Our Northern analyses showed that physiological concentrations of 17-beta-estradiol (10(-9)-10(-7) M) could decrease human 1. 3-kilobase COMT mRNA levels in MCF-7 cells in a time- and dose-dependent manner through an estrogen receptor-dependent mechanism. Two DNA fragments immediately 5' to the published human COMT gene proximal and distal promoters were cloned. Sequence analyses revealed several half-palindromic estrogen response elements and CCAAT/enhancer binding protein sites. By cotransfecting COMT promoter-chloramphenicol acetyltransferase reporter genes with human estrogen receptor cDNA and pSV-beta-galactosidase plasmids into COS-7 cells, we showed that 17-beta-estradiol could down-regulate chloramphenicol acetyltransferase activities, and COMT promoter activities dose-dependently. Functional deletion analyses of COMT promoters also showed that this estrogenic effect was mediated by a 280 base pair fragment with two putative half-palindromic estrogen response elements in the proximal promoter and a 323-base pair fragment with two putative CCAAT/enhancer binding protein sites in the distal promoter. Our findings provide the first evidence and molecular mechanism for estrogen to inhibit COMT gene transcription, which may shed new insight into the role of estrogen in the pathophysiology of different human disorders.

Animals↗
PubMed1999

Lis1, the Drosophila homolog of a human lissencephaly disease gene, is required for germline cell division and oocyte differentiation.

Lissencephaly is a severe congenital brain malformation resulting from incomplete neuronal migration. One causal gene, LIS1, is homologous to nudF, a gene required for nuclear migration in A. nidulans. We have characterized the Drosophila homolog of LIS1 (Lis1) and show that Lis1 is essential for fly development. Analysis of ovarian Lis1 mutant clones demonstrates that Lis1 is required in the germline for synchronized germline cell division, fusome integrity and oocyte differentiation. Abnormal packaging of the cysts was observed in Lis1 mutant clones. Our results indicate that LIS1 is important for cell division and differentiation and the function of the membrane cytoskeleton. They support the notion that LIS1 functions with the dynein complex to regulate nuclear migration or cell migration.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1998

Analysis of CAG/CTG repeat size in Chinese subjects with schizophrenia and bipolar affective disorder using the repeat expansion detection method.

BACKGROUND: Family studies of schizophrenia and bipolar affective disorder provide evidence for genetic anticipation, which (in common with a number of mendelian disorders), may be caused by triplet repeat expansion. This hypothesis is strengthened by evidence from repeat expansion detection (RED) analysis revealing association between the psychoses and long CAG/CTG trinucleotide repeats. METHODS: We performed RED on Han Chinese subjects with schizophrenia (82), bipolar affective disorder (43), and normal controls (61), using a CTG10 oligonucleotide. RESULTS: Comparison between cases and controls revealed no significant association between long repeats and affected status. We also found no detectable association with age at onset and repeat length in either bipolar affective disorder or schizophrenia. Overall, the size distribution of CAG/CTG repeats in Chinese subjects was not significantly different from those reported previously for Caucasian subjects. CONCLUSIONS: These findings indicate that CAG/CTG repeat expansion is not likely to be a major etiological factor for psychosis in Chinese populations.

Adolescent↗
PubMed1998

The relationship between synonymous codon usage and protein structure.

The hypothesis that synonymous codon usage is related to protein three-dimensional structure is examined by investigating the correlation between synonymous codon usage and protein secondary structure. All except two codons in E. coli show the same secondary structural preference for alpha-helix, beta-strand or coil as that of amino acids to be encoded by the respective codons, while 17 codons show secondary structural bias in mammalian proteins. The results indicate that there is no significant correlation between synonymous codon usage and protein secondary structure in E. coli, but there is a correlation in mammals. It could be deduced that synonymous codons carry much less structural information in prokaryotes than in eukaryotes due to their divergent evolutionary mechanism.

Animals↗
PubMed1998

decapentaplegic is essential for the maintenance and division of germline stem cells in the Drosophila ovary.

Stem cells are thought to occupy special local environments, or niches, established by neighboring cells that give them the capability for self-renewal. Each ovariole in the Drosophila ovary contains two germline stem cells surrounded by a group of differentiated somatic cells that express hedgehog and wingless. Here we show that the BMP2/4 homolog decapentaplegic (dpp) is specifically required to maintain female germline stem cells and promote their division. Overexpression of dpp blocks germline stem cell differentiation. Conversely, mutations in dpp or its receptor (saxophone) accelerate stem cell loss and retard stem cell division. We constructed mutant germline stem cell clones to show that the dpp signal is directly received by germline stem cells. Thus, dpp signaling helps define a niche that controls germline stem cell proliferation.

Activin Receptors↗
PubMed1998

Brompheniramine, loratadine, and placebo in allergic rhinitis: a placebo-controlled comparative clinical trial.

A double-blind, randomized, placebo-controlled, parallel-group, multicenter study was conducted to compare the effectiveness of an extended-release formulation of a classical antihistamine, brompheniramine, and a second-generation compound, loratadine, in the treatment of allergic rhinitis. Subjects with symptoms of allergic rhinitis received brompheniramine 12 mg twice daily (n = 112), loratadine 10 mg once daily (n = 112), or placebo twice daily (n = 114) for 7 days. Study medications were blinded using a double-dummy technique. Subjects completed an overall evaluation of symptom relief on a daily basis and returned on treatment days 3 and 7, at which times the investigator assessed symptom severity. The investigator and subject each completed a global efficacy evaluation, and subjects were interviewed regarding adverse experiences. The primary efficacy variable was the physicians' global efficacy evaluation on day 3. Symptoms also were analyzed as summed severity scores for all symptoms and for the nasal symptom cluster of rhinorrhea, sneezing, and nasal blockage. At all post-baseline evaluations (days 3, 7, and averaged over the two days), brompheniramine was significantly better than loratadine and placebo for both sets of summed symptom scores and all three global assessments. Loratadine was significantly better than placebo for physician ratings of total symptom severity averaged over the two days and for the physician and subject ratings of the nasal cluster on day 3. Central nervous system-related symptoms were the most frequently reported adverse experiences; somnolence was reported most frequently by patients taking brompheniramine, and its occurrence was less frequent as treatment continued. A nonprescription, extended-release formulation of brompheniramine 12 mg twice daily provided significantly better relief of symptomatic allergic rhinitis than loratadine 10 mg once daily.

Adolescent↗
PubMed1998

Treatment of hepatocellular carcinoma with the cellular tumor vaccines generated by in vitro modification of tumor cells with non gene transfer approaches.

Anti-tumor immune responses are mediated primarily by T cells. Down regulation of major histocompatibility complex (MHC) and the molecules that costimulate the immune responses is associated with defective signaling of tumor cells for T cell activation. In vitro fusion of autologous tumor cells with antigen presenting cells (APCs) or treatment of tumor cells with a combination of cytokines significantly increased the expression of MHC class I and adhesion molecules on tumor cell surfaces that costimulate host immune responses. The hybrid cells generated by fusion of tumor cells with APCs and the tumor cells treated in vitro with a combination of cytokines and pre-incubated with a bispecific monoclonal antibody (bi-Mab) cross-linking antigen on tumor cells to CD28 on T cells, become immunogenic and able to stimulate naive T cells with generation of tumor specific cytotoxic T cells both in vitro and in vivo. Immunization with the modified tumor cells elicits an immune response mediated by both CD4+ and CD8+ T cells. This response protected against a parental tumor cell challenge and cured established tumors. The approach was effective in both low immunogenic and non-immunogenic tumor systems. Modification of tumor cells with tumor:APC fusion or the two-step procedure may provide a strategy for development of tumor vaccines that is effective for cancer immunotherapy.

Animals↗
PubMed1998

Investigation into the effects of haematocrit and temperature on the resistivity of mammalian blood using a four-electrode probe.

Haematocrit and temperature effects on resistivity are investigated using the electrical impedance method. Measurements are made extensively for pig's blood. The experimental set-up basically involves four ring electrodes being placed around a wooden probe that is subsequently immersed into a syringe containing pig's blood. The syringe is then submerged in water maintained at a constant temperature while measurements are taken. The resistivity of blood is found to increase linearly by approximately 2.9% as the haematocrit level increases from 18% to 49% at a fixed temperature of 37 degrees C. Furthermore, the resistivity is found to decrease linearly by approximately 22% with temperature increasing from 33 degrees C to 42 degrees C for all practical levels of haematocrit.

Animals↗
PubMed1998

Dexamethasone plus retinoids decrease IL-6/IL-6 receptor and induce apoptosis in myeloma cells.

Interleukin 6 (IL-6) is the most important known growth factor for multiple myeloma, and IL-6 signalling pathways are potential targets for therapy. We hypothesized that interfering with the IL-6 signalling pathway at more than one level would be more effective than a single block in inhibiting proliferation of myeloma cells. Accumulating data support the concept that glucocorticoids down-regulate IL-6, whereas retinoic acid derivatives (RA) down-regulate IL-6R in myeloma. We found that all-trans RA (ATRA), 13-cis-RA and 9-cis-RA each similarly inhibited growth of RPMI 8226 myeloma cells and that addition of dexamethasone (DEX) added to RA growth inhibition. The major effects of retinoids were to reduce the proliferative fraction and induce apoptosis whereas DEX increased the apoptotic fraction. When combined, apoptosis was enhanced. Effects of RA + DEX were also least able to be overcome by exogenous IL-6. RA decreased IL-6R levels and addition of DEX to RA delayed recovery of IL-6R levels compared with RA alone. Since RPMI 8226 cells have undetectable IL-6, we investigated U266B1 cells and found that RA and DEX decreased both IL-6 secretion and IL-6 RNA levels. Mechanistically, IL-6R down-regulation by RA was enhanced by DEX, whereas IL-6 protein and RNA levels were reduced by DEX and by RA. In summary, combinations of RA + DEX were not only more effective in inhibiting myeloma cells growth by the dual mechanisms of decreasing proliferative fraction and increasing apoptotic fraction, but were also less able to be overcome by IL-6.

Antineoplastic Agents↗
PubMed1998

[Mutation of p53 gene in human fetal gastric mucosal cells by sterigmatocystin in vitro].

Cell culture, flow cytometry and silver-staining PCR-SSCP methods were used to explore the effects of sterigmatocystin(ST) (1 mg/L and 3 mg/L) on carcinogenesis and mutation of tumor suppressor gene p53 in human fetal gastric mucosal cells in vitro. Four weeks after treated with ST, the cells showed vigorous growth and malignant transformation foci. Twenty-four weeks after ST treatment, the cells could form cellular colonies in soft agar(the mean colony number was 15 and 17 perdish for ST 1 mg/L and 3 mg/L groups respectively). Flow cytometric analysis showed that both proliferation indexes (PI) and the cellular DNA contents of ST treated cells were much higher than those of normal control. The DNA contents of ST treated cells were in DNA aneuploid range. Mutant p53 protein expression was also significantly higher in ST treated cells. Silver-staining PCR-SSCP analysis showed that abnormal electrophoretic migration bands could be seen at exon 8 of p53 gene in ST-treated groups 22 weeks after ST treatment, while no abnormal bands were found in control group. Thus, the results further confirmed the carcinogenic effects of ST on human fetal gastricmucosal cells.

Aneuploidy↗
PubMed1998

[DNA typing for HLA-A, B antigens by polymerase chain reaction with sequence-specific primers and clinical application].

OBJECTIVE: To establish DNA typing for HLA-A, B antigens in Chinese by polymerase chain reaction with sequence-specific primers (PCR-SSP). METHODS: DNA samples were obtained from 178 unrelated donors and 167 kidney recipients. An additional panel of 62 standard DNAs that were typed by UCLA tissue typing lab in USA. A rapid genotyping for HLA-I class (A, B antigens) by PCR-SSP was set up by designed and synthesized 81 specific primers and 1 pair of internal control primer, combining in 61 one-step reactions (20 PCR reactions for A alleles, 41 PCR reactions for B alleles). RESULTS: HLA-A, B alleles were successfully typed in 345 clinical samples and 62 standard DNAs by PCR-SSP technique. No false positive or false negative typing results were obtained. Reproducibility was 100% in 40 samples. The overall time of DNA typing was 5 hours. The typing results were consistent with those of UCLA tissue typing lab. Nineteen alleles of HLA-A and 41 HLA-B alleles were accurately distinguished. Thirteen HLA-A alleles and thirty-two HLA-B alleles in Chinese were practically typed. CONCLUSION: DNA typing for HLA-I class (A, B antigens) by PCR-SSP has proved to be a technique of high-resolution, high-specificity, well-reproducibility, and more suitable for clinical application than serology.

Adolescent↗