Biomedical subjects

Y Qin

Publications and source records attributed to Y Qin.

At least 37 records · Page 2Linked to original sources

PubMed2001

Phosphoinositide 3-kinase-dependent membrane recruitment of p62(dok) is essential for its negative effect on mitogen-activated protein (MAP) kinase activation.

A major pathway by which growth factors, such as platelet-derived growth factor (PDGF), regulate cell proliferation is via the receptor tyrosine kinase/Ras/mitogen-activated protein kinase (MAPK) signaling cascade. The output of this pathway is subjected to tight regulation of both positive and negative regulators. One such regulator is p62(dok), the prototype of a newly identified family of adaptor proteins. We recently provided evidence, through the use of p62(dok)-deficient cells, that p62(dok) acts as a negative regulator of growth factor-induced cell proliferation and the Ras/MAPK pathway. We show here that reintroduction of p62(dok) into p62(dok)-(/)- cells can suppress the increased cell proliferation and prolonged MAPK activity seen in these cells, and that plasma membrane recruitment of p62(dok) is essential for its function. We also show that the PDGF-triggered plasma membrane translocation of p62(dok) requires activation of phosphoinositide 3-kinase (PI3-kinase) and binding of its pleckstrin homology (PH) domain to 3'-phosphorylated phosphoinositides. Furthermore, we demonstrate that p62(dok) can exert its negative effect on the PDGFR/MAPK pathway independently of its ability to associate with RasGAP and Nck. We conclude that p62(dok) functions as a negative regulator of the PDGFR/Ras/MAPK signaling pathway through a mechanism involving PI3-kinase-dependent recruitment of p62(dok) to the plasma membrane.

Adaptor Proteins, Signal Transducing↗

PubMed2001

Lewis rat pancreas, but not cardiac xenografts, are resistant to anti-gal antibody mediated hyperacute rejection.

BACKGROUND: The objective of this study was to evaluate the role of anti-Gal Abs and non-anti-Gal Abs in hyperacute rejection (HAR) of concordant pancreas xenografts compared with heart xenografts. In addition, we tested whether rejection of Lewis rat pancreas grafts was T-cell dependent and could be prevented by anti-T-cell treatment. METHODS: To determine the role of anti-Gal Abs in the induction of HAR, Lewis rat pancreas and heart xenografts were transplanted into alpha1,3Galactosyltransferase knockout (GT-Ko) mice treated with normal human serum (NHS) or hyperimmune serum, or into presensitized GT-Ko mice. To investigate whether rejection of pancreas xenograft was mediated by a T-cell dependent response, Lewis rat pancreas grafts were transplanted into streptozotocin (STZ)-induced diabetic GT-Ko mice treated with FK506, anti-CD4 mAbs (GK1.5), and thymectomy. Antidonor-specific IgM and IgG and anti-Gal Abs were analyzed by flow cytometry. Rejected and long-term surviving pancreas xenografts were assessed by functional (blood glucose) and histopathological examination. RESULTS: HAR of Lewis rat pancreas xenografts could not be induced by NHS (0.4 ml), whereas NHS (0.2 ml) resulted in HAR of Lewis heart xenografts. Infusion of Lewis rat-specific hyperimmune serum (0.2 ml) resulted in HAR of Lewis rat pancreas xenografts. In addition, second Lewis rat pancreas grafts were hyperacutely rejected by presensitized GT-Ko mice. Immunohistochemical staining showed a low expression of Galalpha1,3Gal antigen in the endocrine tissue compared with that in the cardiac grafts. The levels of anti-Gal Abs in pancreas xenograft transplantation did not increase in GT-Ko mice after pancreas xenograft transplantation that was significantly increased after heart transplantation. FK506 treatment induced long-term survival of Lewis pancreas xenografts (mean survival time (MST) >90 days). Anti-CD4 treatment delayed rejection of Lewis rat pancreas xenografts with MST of 34.3 days, whereas anti-CD4, in combination with thymectomy, synergistically prolonged survival of pancreas xenograft (MST=70.4 days). CONCLUSION: Pancreas xenograft is resistant to anti-Gal Abs-induced HAR but is susceptible to anti-donor specific Abs. Rejection of Lewis pancreas xenograft in STZ-induced, diabetic, GT-Ko mice is T-cell dependent.

Acute Disease↗

PubMed2001

[Placental leptin correlates with intrauterine fetal growth and development].

OBJECTIVE: To study the role of placental leptin in intrauterine cord leptin production and its relationship with neonatal anthropometry. METHODS: Forty women and their babies were enrolled and approved by Xinhua Hospital (Shanghai, China) and Jiangbei Hospital (Nanjing, China) in this study. Placental tissue was assayed for leptin mRNA by reverse transcription/polymerase chain reaction (RT/PCR), and assayed for ob gene protein, leptin, by Western-Blot and immunohistochemistry. Blood was taken from the umbilical cord of the babies at delivery. Serum leptin was measured by radio-immunoassay. Neonatal anthropometric measurements were recorded within 48 hours after delivery. Linear regression analysis was used to explore the relationship between placental leptin, cord leptin and neonatal anthropometric measures. RESULTS: Ob gene was expressed in placental tissue at comparable or greater levels than that in adipose tissue. Comparison of the relative levels of leptin to beta-actin mRNA by multiplex RT/PCR revealed that the placenta of the small for gestational age (SGA) neonates expressed leptin mRNA at significantly lower levels 0.61 +/- 0.15 than that of the appropriate for gestational age (AGA) neonates 0.83 +/- 0.20 (P = 0.0034), while the placenta of the large for gestational age (LGA) neonates expressed leptin mRNA at significantly higher levels 1.00 +/- 0.23 than that of the AGA neonates (P = 0.043). Immunohistochemical techniques showed the immunostaining pattern in the cytoplasm of trophoblastic cells. Western-blot showed that the placenta of the SGA neonates expressed leptin at significantly lower levels 0.26 +/- 0.05 ng/mg than that of the AGA neonates 0.34 +/- 0.09 ng/mg (P = 0.007 6), while the placenta of the LGA neonates expressed leptin at significantly higher levels 0.43 +/- 0.10 ng/mg than that of the AGA neonates (P = 0.021). Linear regression analysis showed placental ob gene transcription and leptin translation correlated significantly with cord leptin (r = 0.39 and 0.43), and neonatal Ponderal Index (r = 0.66 and 0.69). CONCLUSIONS: Placenta provides a source of leptin for the growing fetus, and this placental leptin might be a growth factor in intrauterine fetal development.

Blotting, Western↗

PubMed2001

Long-term survival of cardiac xenografts in fully xenogeneic (mouse --> rat) bone marrow chimeras.

BACKGROUND: The shortage of human hearts remains a major barrier to the efficacy of heart transplantation for the treatment of end-stage heart disease. One potential solution to the supply problem would be the use of hearts from nonhuman donors (xenografts). We have established a model of mouse to rat xenogeneic bone marrow chimerism, and in this study we have hypothesized that such chimeric rats will accept both donor and recipient specific heart grafts while rejecting third-party mouse and rat grafts. We also investigated humoral responses in naive and chimeric rats with and without donor murine cardiac grafts. METHODS: Recipient Lewis rats (n = 22) were given 1100 cGy lethal total body irradiation and the same day received 300 x 10(6) donor B10.BR mouse bone marrow cells intravenously. Peripheral blood of surviving rats (n = 18) was typed at 4 weeks and then monthly thereafter. Donor and recipient specific and third-party heterotopic heart transplantations were performed at 6 to 8 weeks after reconstitution with bone marrow. RESULTS: Multilineage bone marrow chimerism was produced in all experimental animals with complete replacement of recipient marrow by donor cells. Murine donor and rat recipient strain hearts transplanted in chimeric rats survived indefinitely. Third-party rat and mouse hearts were rejected, though at a slower rate than bone marrow matched naive controls. High levels of antimouse antibodies were detected in rats with rejected hearts. These antibodies were absent in chimeric animals with long-term surviving heart grafts. CONCLUSIONS: Long-term multilineage bone marrow chimerism can be produced in a mouse --> rat bone marrow transplant model. Long-term survival of donor specific and recipient specific vascularized cardiac grafts can be produced in these chimeric animals. These animals are clinically normal but show signs of subclinical immunosuppression regimen as they reject third-party hearts later than naive animals. Our results suggest that antibodies also play a significant role in concordant xenograft rejection, and induction of bone marrow chimerism can overcome this barrier.

Animals↗

PubMed2001

Signal transduction of flumazenil-induced preconditioning in myocytes.

The objective of this study was to examine the role of oxygen radicals, protein kinase C (PKC), and ATP-sensitive K(+) (K(ATP)) channels in mediating flumazenil-produced preconditioning. Chick cardiomyocyte death was quantified using propidium iodide, and oxygen radical generation was assessed using 2',7'-dichlorofluorescin oxidation. Preconditioning was initiated with 10 min of ischemia followed by 10 min of reoxygenation. Alternatively, flumazenil was infused for 10 min and removed 10 min before ischemia. Flumazenil (10 microM) and preconditioning increased oxygen radicals [1,693 +/- 101 (n = 3) and 1,567 +/- 98 (n = 3), respectively, vs. 345 +/- 53 (n = 3) in control] and reduced cell death similarly [22 +/- 3% (n = 5) and 18 +/- 2% (n = 6), respectively, vs. controls 49 +/- 5% (n = 8)]. Protection and increased oxygen radicals by flumazenil were abolished by pretreatment with the antioxidant thiol reductant 2-mercaptopropionyl glycine (800 microM; 52 +/- 10%, n = 6). Specific PKC inhibitors Go-6976 (0.1 microM) and chelerythrine (2 microM), given during ischemia and reoxygenation, blocked flumazenil-produced protection (47 +/- 5%, n = 6). The PKC activator phorbol 12-myristate 13-acetate (0.2 microM), given during ischemia and reoxygenation, reduced cell death similarly to that with flumazenil [17 +/- 4% (n = 6) and 22 +/- 3% (n = 5)]. Finally, 5-hydroxydecanoate (1 mM), a selective mitochondrial K(ATP) channel antagonist given during ischemia and reoxygenation, abolished the protection of flumazenil and phorbol 12-myristate 13-acetate. Thus flumazenil mimics preconditioning to reduce cell death in cardiomyocytes. Oxygen radicals activate mitochondrial K(ATP) channels via PKC during the process.

Animals↗

PubMed2001

Production of delayed death and neoplastic transformation in CGL1 cells by radiation-induced bystander effects.

Other investigators have demonstrated by transfer of medium from irradiated cells and by irradiation with low-fluence alpha particles or microbeams that cells do not have to be directly exposed to ionizing radiation to be detrimentally affected, i.e. bystander effects. In this study, we demonstrate by transfer of medium from X-irradiated human CGL1 hybrid cells that the killing of bystander cells reduces the plating efficiency of the nonirradiated CGL1 cells by 33 +/- 6%. In addition, we show that the amount of cell death induced by bystander effects is not dependent on X-ray dose, and that the induction of apoptosis does not appear to be responsible for the cell death. Furthermore, we found that the reduction in plating efficiency in bystander cells is evident for over 18 days, or 22 cell population doublings, after medium transfer, despite repeated refeeding of the cell cultures. Finally, we report the novel observation that bystander effects induced by the transfer of medium from irradiated cells can induce neoplastic transformation. Exposing unirradiated CGL1 cells to medium from cells irradiated with 5 or 7 Gy increased the frequency of neoplastic transformation significantly from 6.3 x 10(-6) in unirradiated controls to 2.3 x 10(-5) (a factor of nearly four). We conclude that the bystander effect induces persistent, long-term, transmissible changes in the progeny of CGL1 cells that result in delayed death and neoplastic transformation. The data suggest that neoplastic transformation in bystander cells may play a significant role in radiation-induced neoplastic transformation at lower doses of X rays.

Apoptosis↗

PubMed2001

All-trans retinoic acid in pulmonary vascular structural remodeling in rats with pulmonary hypertension induced by monocrotaline.

OBJECTIVE: To determine whether all-trans retinoic acid (atRA) exerts an inhibitory effect on rats with pulmonary hypertension induced by monocrotaline. METHODS: All rats were given a single subcutaneous injection of either monocrotaline (60 mg/kg) or saline. Monocrotaline-injected rats received either atRA (30 mg.kg-1.day-1) or saline through oral-gastro intubation. On Days 7, 14, 21, and 28 respectively after monocrotaline injection, cardiovascular catheters were inserted to examine the mean pulmonary artery pressure of rats in each group. Meanwhile, the matrix metalloproteinase-1 (MMP-1) mRNA expression and hydroxyproline content in the main pulmonary artery were determined by RT-PCR and chromometry, respectively. RESULTS: The mean pulmonary artery pressure of rats in the model group increased significantly on day 21 and reached a peak on Day 28 compared with the control group (25.7 +/- 4.3 mm Hg vs 15.1 +/- 1.5 mm Hg and 38.5 +/- 6.4 mm Hg vs 16.4 +/- 2.0 mm Hg, P < 0.01). MMP-1 mRNA overexpression was present on Day 14 (0.72 +/- 0.15 vs 0.39 +/- 0.08, P < 0.01) and was rapidly down-regulated on Day 21 and 28 compared with Day 14, but was still higher than that in the control. The hydroxyoroline content of the main pulmonary artery dropped significantly on Day 14 (4.01 +/- 1.13 micrograms/mg vs 5.10 +/- 0.91 micrograms/mg, P < 0.05) and increased significantly on Days 21 and 28 compared with the control. atRA inhibited the MMP-1 mRNA overexpression from Day 14 to Day 28 and reduced the hydroxyproline content (5.59 +/- 0.70 micrograms/mg vs 7.96 +/- 1.13 micrograms/mg and 7.77 +/- 0.96 micrograms/mg vs 9.93 +/- 1.27 micrograms/mg, P < 0.01) and the mean pulmonary artery pressure compared with the model group (19.6 +/- 3.2 mm Hg vs 25.7 +/- 4.3 mm Hg and 26.3 +/- 4.6 mm Hg vs 38.5 +/- 6.4 mm Hg, P < 0.01). CONCLUSION: atRA inhibits MMP-1 overexpression and the accumulation of collagen, which might elicit favorable geometric remodeling in rat pulmonary hypertension induced by monocrotaline.

Animals↗

PubMed2001

Placental leptin correlates with intrauterine fetal growth and development.

OBJECTIVE: To study the role of placental leptin in intrauterine cord leptin production and its relationship with neonatal anthropometry. METHODS: Forty women and their babies (40) were enrolled in this study. Placental tissues were assayed for leptin mRNA by reverse transcription/polymerase chain reaction (RT/PCR), and assayed for the obese gene protein leptin by Western-blot and immunohistochemistry. Blood was taken from the umbilical cord of the babies at delivery. Serum leptin was measured by radio-immunoassay. Neonatal anthropometric measurements were recorded within 48 hours after delivery. Linear regression analysis was used to explore the relationship between placental leptin, cord leptin and neonatal anthropometric measures. RESULTS: The obese gene was expressed in placental tissue at comparable or greater levels than that in adipose tissue. The placentas of the small for gestational age (SGA) neonates expressed leptin mRNA and protein at significantly lower levels than those of the appropriate for gestational age (AGA) neonates (P = 0.0034 and 0.0076), while the placentas of the large for gestational age (LGA) neonates expressed leptin mRNA and protein at significantly higher levels than those of the AGA neonates (P = 0.043 and 0.021). Linear regression analysis showed placental ob gene transcription and leptin translation correlated significantly with cord leptin (r = 0.39 and 0.43), and neonatal Ponderal Index (r = 0.66 and 0.69). CONCLUSION: The placenta provides a source of leptin for the growing fetus, and this placental leptin might be a growth factor in intrauterine fetal development.

Blotting, Western↗

PubMed2001

[Locating the impairment of human cognitive function during hypoxia].

Objective. To find the location where the human brain cognitive function impairs under hypoxia. Method. 14 healthy males, aged 18-20 years, performed auditory Oddball test of two different intensities (55 dB, 80 dB) during exposure to 5000 m by breathing low oxygen mixture. EEG and Reaction Time (RT) were recorded. P3, the component of ERP, was extracted from EEG. P3 latency and RT were used as indices of the experiment. Additive Factors Method was used to analyse the result of the experiment. Result. Interaction between hypoxia and stimulus intensity was found for P3 latency and RT. Conclusion. Acute hypoxia influences the preprocessing stage of information processing.

Acoustic Stimulation↗

PubMed2001

[Study of deletion and mutation of p16 gene in primary hepatocellular carcinoma].

OBJECTIVE: To investigate the role the deletion and mutation of p16 gene plays in the pathogenesis of human primary hepatocarcinoma. METHODS: Thirty-one cases of human hepatocarcinoma, 31 cases of adjacent noncancerous liver cirrhosis and the leukocytes of 8 normal human subjects were analyzed for deletion and mutation in p16 gene exons 1, 2 and introns 1, 2 with comparative multiple PCR and PCR-SSCP. RESULTS: Deletion of p16 gene exon 1 and partial intron 1 was found in 4 of 31 cases (13/%). No deletion of exon 2 or intron 2 was found. Three patterns of p16 gene intron 1 and 18 bp-flanking sequence in exon 2 at SSCP analysis were observed in hepatocellular carcinoma and corresponding adjacent noncancerous cirrhosis, and two patterns were found in human normal leukocyte DNA. No aberrant single strand at SSCP in p16 gene exon 1 or most part of exon 2 or intron 2 was detected. CONCLUSION: Low frequency of deletion and rare mutation of p16 suppressor gene occurred in hepatocellular carcinoma.

Carcinoma, Hepatocellular↗

PubMed2001

[Determination of roxithromycin in serum by high-performance liquid chromatography with ultraviolet detection].

OBJECTIVE: To make better the RP-HPLC method for the determination of roxithromycin(RM) in human serum. METHODS: RM and clarithromycin (internal standard) were extracted from alkalinized serum sample (500 microliters) with methylene chloride. After evaporation of the organic layer, the residue was dissolved in 100 microliters of acetonitrile-ammonium phosphate (1:1, pH 6.0) and washed with n-hexane, then 20 microliters was injected onto a column (5 microns, 15 cm x 4.6 mm) of Penomenex luna C18. The mobile phase was acetonitrile-0.05 mol/L phosphoric acid (39:19:42, adjusted to pH 7.2 with ammonia water) pumped at 1.2 ml/min through the column. The variable wavelength UV detector operated at 0.01 aufs and the wavelength was set at 210 nm. RESULTS: The retention times for RM and clarithromycin were 4.4 min and 5.0 min, respectively. Standard curve was linear in the concentration range of 0.25 to 32 mg/L. The detection limit in serum was 0.06 mg/L; the average method recovery 97.4%; the inter-day RSD less than 3.0%. CONCLUSION: This method was found to be simple, rapid, sensitive and accurate for determination of RM in human serum.

Chromatography, High Pressure Liquid↗

PubMed2001

[Effect of conventionally prepared rabbit serum on human umbilical vein endothelial cell-304].

OBJECTIVE: To study the effect of conventionally prepared rabbit serum, usually used in the field of serum pharmacology of TCM, in various concentration on cultured system of human umbilical vein endothelial cell (VEC)-304 cell line. METHODS: Prepared conventionally from healthy rabbit, the effect of uncontaminated and nonhemolytic serum of six concentrations (5%, 10%, 20%, 40%, 60% and 80%) on VEC-304 cells was observed using parameters such as cell morphologic examination, trypan blue exclusion test, methyl thiazolyl tetrazolium (MTT) test, lactate dehydrogenase (LDH) and angiotensin-converting release test. RESULTS: Serum of 5% and 10% concentration showed no effect in all the above-mentioned tests. Serum of 20% concentration also showed no effect in the tests except for LDH releasing (P < 0.01). But when the concentration of serum reached up to 40% or above, distinct cytotoxicity and serious injury appeared in a dose-dependent manner. CONCLUSION: High concentration of conventionally prepared rabbit serum could injure the incubated cell. Therefore, in order to lower the background effect of serum as far as possible in TCM serum pharmacological study, the cytotoxicity of rabbit serum should be tested first of all.

Animals↗

PubMed2001

[Determination of warfarin in plasma by HPLC and an investigation of monitoring patients after cardiac valve replacement].

OBJECTIVE: A simple HPLC method was established for the determination of warfarin in plasma to investigate the relationship between warfarin concentration and anticoagulant effect. METHODS: The mixture of dichloromethane and hexane (1:9) was used as extracting solvent for the plasma samples. The chromatographic separation was on C18 column with a mobile phase consisting of methanol and 50 mmol/L ammonium acetate buffer (pH2.5, 70:30). RESULTS: The calibration curve was linear within 50-2000 ng/ml. The extraction recoveries of warfarin were 78.0%-81.6%. The recoveries of methodology were 103.1%-106.5%. Inter-day and intra-day RSD were 2.33%-5.46% and 5.29%-7.73%, respectively. This method was used for determining warfarin in 70 patients after cardiac valve replacement. The results showed that 44 cases had their INR within the safety range (1.31-2.35) recommended to Chinese, and of them 37(84.1%) cases had a warfarin level at 616.2 +/- 154.8 ng/ml. CONCLUSION: This method is useful in monitoring warfarin concentration during anticoagulant therapy.

Anticoagulants↗

PubMed2001

[Hydroxyapatite for experimental laryngotracheal reconstruction].

OBJECTIVE: The porous hydroxyapatite (HA) tubiform prosthesis was employed for reconstruction of large circumferential defect of the larynx and cervical trachea. The biocompatibility, bioactivity and biofunctionality of the HA prosthesis were evaluated, and the feasibility for laryngotracheal reconstruction was discussed. METHODS: Twelve healthy canines were used to establish the experimental models, a large portion of cricoid cartilage and upper ten-ring segment of cervical trachea were resected and substituted with a corresponding 5 cm HA prosthesis by end-to-end anastomosis. Six months later, the eight survival canines were sacrificed and the HA prostheses with surrounding tissues were removed. They were observed in decalcified sections by optical microscopy and scanning electron microscopy. RESULTS: Two canines died in the immediate postoperative period with unknown reason and another two deaths were attributed to obstruction caused by the complete dislocation of the HA prostheses owing to rupture of the sutures within three weeks after operation. Eight canines survived up to six months. The implanted HA prostheses were tolerated in all cases without any rejection and dislocation or shift. An excellent airway was obtained and no signs of dyspnea and suffocation were found though there were hypergranulation and scar formation occurred at the site of anastomosis. Morphologic examination revealed that collagen fibers, new vessels and plenty of cells penetrated deeply into the pores of HA, and occupying the outer two third of HA wall. HA prostheses were surrounded by connective tissues and anchored firmly to the neighboring tissues, including the ends of the cricoid and tracheal cartilage by ingrowths of cartilaginous tissue into the macropores of the HA. However, the luminal surface of HA prosthesis was not covered at all section levels by respiratory mucosa. CONCLUSIONS: The implantation of the porous HA tubiform prosthesis can maintain the normal respiratory function of the experimental canines, but the proliferating granulation and scar formation at the anastomotic site are questions still remained to be solved. To cover the inner surface of HA with the epithelial mucosa and then reduce the morbidity caused by scar and hypergranulation, some forms of allografts such as pedicled flaps and jejunal autografts will be deserved.

Animals↗

PubMed2000

Polymorphisms of the DNA repair gene XRCC1 and risk of gastric cancer in a Chinese population.

Gastric cancer remains the leading cause of cancer death in China and other countries in eastern Asia. Studies of gastric cancer have revealed that it is a disease of complex etiology involving dietary, infectious, environmental, occupational and genetic factors. DNA repair capacity has been suggested as a genetic factor contributing to variation in susceptibility to cancer. In the present study, we described an association between 2 polymorphisms of the DNA repair gene XRCC1 and risk of gastric cancer in a Chinese population. We used a polymerase chain reaction-based assay to detect Pvu II and Nci I restriction fragment length polymorphisms (XRCC1 26304 C-->T and XRCC1 28152 G-->A, respectively) in 188 patients with gastric cancer and 166 healthy controls. The XRCC1 26304 T allele (194Trp) frequency (34.6%) was higher and the XRCC1 28152 A allele (399Gln) frequency (25.6%) was lower in healthy Chinese controls than previously reported healthy U.S. Caucasian controls (7.2% and 34.1%, respectively). Multivariate logistic regression analysis revealed that the putative high-risk genotypes XRCC1 26304 CC and XRCC1 28152 GA/AA were associated with a non-significant increased risk for gastric cancer (adjusted odds ratio [OR]=1.45, 95% confidence interval [CI]= 0.93-2.25 and OR=1.53, 95% CI= 0.98-2.39, respectively) compared with other genotypes. However, the XRCC1 26304 CC genotype was associated with a significantly increased risk for gastric cardia cancer (adjusted OR=1.86, 95% CI=1.09-3.20). Individuals with both putative high-risk genotypes (CC and GA/AA) had a significantly higher risk (adjusted OR=1.73, 95% CI=1.12-2.69), particularly for gastric cardia cancer (adjusted OR=2.18, 95% CI=1.21-3.94) than individuals with other genotypes. These findings support the hypothesis that these 2 XRCC1 variants may contribute to the risk of developing gastric cancer, particularly gastric cardia cancer.

Adult↗

PubMed2000

Quorum-sensing signal binding results in dimerization of TraR and its release from membranes into the cytoplasm.

Promoter binding by TraR and LuxR, the activators of two bacterial quorum-sensing systems, requires their cognate acyl-homoserine lactone (acyl-HSL) signals, but the role the signal plays in activating these transcription factors is not known. Soluble active TraR, when purified from cells grown with the acyl-HSL, contained bound signal and was solely in dimer form. However, genetic and cross-linking studies showed that TraR is almost exclusively in monomer form in cells grown without signal. Adding signal resulted in dimerization of the protein in a concentration-dependent manner. In the absence of signal, monomer TraR localized to the inner membrane while growth with the acyl-HSL resulted in the appearance of dimer TraR in the cytoplasmic compartment. Affinity chromatography indicated that the N-terminus of TraR from cells grown without signal is hidden. Analysis of heterodimers formed between TraR and its deletion mutants localized the dimerization domain to a region between residues 49 and 156. We conclude that binding signal drives dimerization of TraR and its release from membranes into the cytoplasm.

4-Butyrolactone↗

PubMed2000

Relationship among discharges of neighboring neurons in the rat prefrontal cortex during spatial working memory tasks.

The relationship among discharges of neurons that were recorded simultaneously with tetrodes in the rat medial prefrontal cortex was analyzed. Spatial working memory tasks were divided into several distinct stages based on the behavioral correlates of individual neurons, and interneuronal correlation of signal (mean discharge rate at each stage) and noise (trial-to-trial deviation from the signal) was calculated. Behavioral correlates of neighboring neurons were quite heterogeneous and, accordingly, average signal correlation was relatively low ( approximately 0.16). Noise correlation was even lower ( approximately 0.06), but neuronal noise was more correlated among the neurons with similar signals. Spikes underlying the signal and noise correlation among the prefrontal cortical neurons were loosely synchronized over a few hundred milliseconds. These results suggest that neighboring prefrontal cortical neurons process largely independent information and have weakly correlated noise and that precisely synchronized spikes play a relatively minor role in producing the correlated signal and noise among these neurons.

Action Potentials↗

PubMed2000

Characterization of T cell lines derived from glatiramer-acetate-treated multiple sclerosis patients.

We analyzed the effects of glatiramer acetate (GA) therapy on in vitro proliferative responses and cytokine production by lymphocytes derived from multiple sclerosis patients receiving this therapy. We confirmed that lymphocytes derived from GA naïve patients show a high frequency of response when initially exposed to GA in vitro; this frequency decreased following GA therapy. The frequency of lymphocytes responding to whole MBP stimulation did not change with GA therapy. GA- and MBP-specific T cell lines generated from these patients by repeated cycles of in vitro stimulation did not cross react. Some (23%) whole MBP-reactive T cell lines did cross react with MBP peptide 83-99. The mean levels of interferon (IFN) gamma secretion and the mean ratio of IFN-gamma/IL-5 were lower for GA-reactive cell lines, derived from patients both prior to and during GA therapy, compared to MBP-reactive T cell lines. The proportion of IFN-gamma(+) cells in unfractionated lymphocyte preparations derived from the GA-treated patients did not differ from that found for healthy controls. Our findings indicate that GA-reactive T cell lines derived from GA-treated MS patients continue to show a relative Th2 cytokine bias consistent with a bystander suppressor function. GA treatment is not associated with a cytokine phenotype shift in the total T cell or MBP-reactive T cell populations.

Adult↗