Biomedical subjects

B Ge

Publications and source records attributed to B Ge.

At least 19 recordsLinked to original sources

PubMed2006

BCL3 is induced by IL-6 via Stat3 binding to intronic enhancer HS4 and represses its own transcription.

BCL3 is a proto-oncogene affected by chromosomal translocations in some patients with chronic lymphocytic leukemia. It is an IkappaB family protein that is involved in transcriptional regulation of a number of NF-kappaB target genes. In this study, interleukin (IL)-6-induced BCL3 expression and its effect on survival of multiple myeloma (MM) cells were examined. We demonstrate the upregulation of BCL3 by IL-6 in INA-6 and other MM cell lines. Sequence analysis of the BCL3 gene locus revealed four potential signal transducer and activator of transcription (Stat) binding sites within two conserved intronic enhancers regions: one located within enhancer HS3 and three within HS4. Chromatin immunoprecipitation experiments showed increased Stat3 binding to both enhancers upon IL-6 stimulation. Silencing Stat3 expression by small interfering RNA (siRNA) abrogated BCL3 expression by IL-6. Using reporter gene assays, we demonstrate that BCL3 transcription depends on HS4. Mutation of the Stat motifs within HS4 abolished IL-6-dependent BCL3 induction. Furthermore, BCL3 transcription was inhibited by its own gene product. This repressive feedback is mediated by NF-kappaB sites within the promoter and HS3. Finally, we show that overexpression of BCL3 increases apoptosis, whereas BCL3-specific siRNA does not affect the viability of INA-6 cells suggesting that BCL3 is not essential for the survival of these cells.

B-Cell Lymphoma 3 Protein↗

PubMed2006

Genotyping of Campylobacter spp. from retail meats by pulsed-field gel electrophoresis and ribotyping.

AIMS: To determine the genetic relatedness of Campylobacter spp. from retail meat products, and compare the discriminatory power of pulsed-field gel electrophoresis (PFGE) and automatic ribotyping. METHODS AND RESULTS: A total of 378 Campylobacter isolates recovered from 159 raw meats (130 chicken, 25 turkey, three pork and one beef) sampled from 50 retail grocery stores of four supermarket chains in the Maryland suburban area from August 1999 to July 2000 were analysed by PFGE with SmaI, 120 isolates of which were also characterized by ribotyping with PstI using RiboPrinter system. A total of 148 unique PFGE patterns were identified, 91 of which were present in multiple Campylobacter isolates and 24 in multiple meat samples. Nineteen Campylobacter clones with identical PFGE patterns recurred frequently (up to nine times) throughout the sampling period. Comparing ribotyping with PFGE, we identified 44 PFGE patterns and 22 RiboGroups among the 120 isolates tested. Multiple PFGE patterns within one RiboGroup were commonly observed, as well as multiple RiboGroups within one PFGE pattern. CONCLUSIONS: Although Campylobacter present in retail meats were genetically diverse, certain clones persisted in poultry meats. PFGE had a greater discriminatory power than ribotyping, and the two methods were complementary in genotyping Campylobacter. SIGNIFICANCE AND IMPACT OF THE STUDY: Genomic DNA fingerprinting of Campylobacter confirmed diverse and recurrent Campylobacter clones in the retail meats, which provides additional data for a better understanding of the epidemiological aspect of Campylobacter infection.

Animals↗

PubMed2005

Effect of nebulized albuterol on blood glucose in patients with diabetes mellitus with and without cystic fibrosis.

Over 90% of cystic fibrosis (CF) patients are treated with bronchodilators, and 6% have diabetes. Some with asthma also have diabetes, and most are treated with bronchodilators. Systemic administration of adrenergic agents can cause increases in blood glucose, but the effect of inhaled agents is unclear. A double-blind study was performed on 10 patients with type 1 diabetes mellitus (DM) without CF (3 male, 7 female, mean age 25.5 years) and 9 patients with insulin-dependent CF-related diabetes (CFRD) (8 male, 1 female, mean age 21.9 years). On 2 separate days before 9 AM fasting and the morning dose of insulin, 2.5 mg of albuterol or nebulized placebo were given. Blood glucose was measured by finger stick with a glucose reflectance meter before and 15, 30, 45, and 60 min after treatment. No significant changes from baseline or differences between placebo and albuterol occurred in either group. The mean maximum increase from baseline in DM was 20 mg/dl on placebo, and 38 mg/dl on albuterol; in the CFRD, the respective changes were 7 and 7 mg/dl. Two DM patients had a > 50 mg/dl increase on albuterol vs. placebo; no CFRD patients had differences of such magnitude. DM patients had greater increases from baseline than CFRD patients on placebo and albuterol. Differences reached statistical significance at 30 and 45 min on placebo, and 45 min on albuterol. Albuterol 2.5 mg by nebulizer causes no clinically significant increases in blood glucose in DM or CFRD patients. Diabetes patients without CF have a significantly greater increase of glucose with time (placebo or albuterol) than CFRD patients.

Administration, Inhalation↗

PubMed2003

Electrochemistry of immobilized CuZnSOD and FeSOD and their interaction with superoxide radicals.

Copper, zinc superoxide dismutase (CuZnSOD) from bovine erythrocytes and iron superoxide dismutase from Escherichia coli (FeSOD) were immobilized on 3-mercaptopropionic acid (MPA)-modified gold electrodes, respectively. The characterization of the SOD electrodes showed a quasi-reversible, electrochemical redox behavior with a formal potential of 47+/-4 mV and -154+/-5 mV (vs. Ag/AgCl, 1 M KCl) for surface adsorbed CuZnSOD and FeSOD, respectively. The heterogeneous electron transfer rate constants were determined to be about 65 and 35/s, respectively. Covalent fixation of both SODs was also feasible with only slight changes in the formal potential. The interaction of superoxide radicals (O(2)(-)) with the SOD electrode was investigated. No catalytic current could be observed. However, due to the fast cyclic redox reaction of SOD with superoxide, the communication of the protein with the electrode was strongly influenced. The amperometric detection of superoxide radicals is discussed.

Adsorption↗

PubMed2002

Identification of Escherichia coli O157:H7 and other enterohemorrhagic serotypes by EHEC- hlyA targeting, strand displacement amplification, and fluorescence polarization.

Human disease caused by enterohemorrhagic E. coli O157:H7 and other serotypes (EHEC) has been associated with bovine fecal contamination of food and the environment. The range of serotypes, low infectious dose, and numerous transmission vehicles for EHEC render development of detection methods for this pathogen complex. In this study, the hemolysin gene (EHEC- hly A) was targeted with oligonucleotides, and probe-target hybrids were amplified using strand displacement amplification (SDA). Amplicons were resolved in the complete reaction mix through changes in the fluorescence polarization (FP) of a fluorescein-labeled detector probe hybridized to the amplicons during amplification. Results combining EHEC- hly A, SDA, and FP were obtained within 35 min of reaction initiation. The test specificity was determined on EHEC strains representing 13 serotypes (49 isolates); and control uropathogenic, commensal, and other organisms (10 isolates). Statistical analysis of results indicated a sensitivity in the reaction vessel to 4.3 bacteria (95% confidence interval), and a specificity for EHEC (n=59) at 100% (P=5.11E-17; i.e. P<<0.05). Detection based on combining EHEC- hly A, SDA, and FP was compatible with water sources directly associated with human infection (drinking and recreational supplies), and bovine drinking trough water representing an environmental matrix linked to the maintenance of an EHEC animal reservoir.

Animals↗

PubMed2002

Amperometric biosensor based on a functionalized gold electrode for the detection of antioxidants.

A method for the electrochemical detection of antioxidants has been developed, which is based on a radical measurement with a cytochrome c modified electrode. A controlled enzymatic production system for superoxide radicals based on xanthine oxidase was used. The addition of antioxidants facilitated the decomposition of the radical in addition to the spontaneous dismutation. The steady-state of superoxide generation and decomposition was thus shifted to a new situation due to the higher decomposition rate after antioxidant addition. This resulted in a decreased current level at the electrode. Antioxidant activity could be quantified from the response of the sensor electrode by the percentage of the signal decrease. The 50% inhibition value (IC(50)) for different antioxidants was calculated and the antioxidant activity of numerous substances was compared. Thus, a hierarchy of superoxide radical scavenging abilities of flavonoids was established: flavanols>flavonols>flavones>flavonones>isoflavonones.

Antioxidants↗

PubMed2001

Manganese superoxide dismutase induction by iron is impaired in Friedreich ataxia cells.

Iron-mediated oxidative stress has been implicated in the pathology of the neurodegenerative disease Friedreich ataxia (FRDA). Here, we show that normal upregulation of the stress defense protein manganese superoxide dismutase (MnSOD) fails to occur in FRDA fibroblasts exposed to iron. This impaired induction was observed at iron levels in which increased activation of the redox-sensitive factor NF-kappaB was absent. Furthermore, MnSOD induction could only be partially suppressed by antioxidants. We conclude that an NF-kappaB-independent pathway that may not require free radical signaling is responsible for the reduction of MnSOD induction. This impairment could constitute both a novel defense mechanism against iron-mediated oxidative stress in cells with mitochondrial iron overload and conversely, an alternative source of free radicals that could contribute to the disease pathology.

Antioxidants↗

PubMed2001

[The expression and clinical significance of pRB and E(2)F(1) in human neuroendocrine lung tumor].

OBJECTIVE: To investigate the role pRB and E(2)F(1) play in the cell cycle and the oncogenesis of human nemoendocrine lung fumor and the correlation between their expression and the invasiveness and prognosis of human neuroendocrine lung tumor. METHODS: Immunohistochemistry and in situ hybridization were used to detect the expression of pRB and E(2)F(1) mRNA in the paraffin embedded tissues of 78 cases of human neuroendocrine lung tumor. Statistics was used to analyze the data. RESULTS: The positive expression rate of pRB in both typical and atypical carcinoid was 87.5% (14/16). However, pRB was not expressed in large cell neuroendocrine carcinoma and small cell lung cancer (P < 0.001). The positive rate of E(2)F(1) mRNA expression in human neuroendocrine lung tumor was 87.2% (68/78). The strength of expression of pRB and E(2)F(1) was obviously correlated with the tumor stage, lymph node metastasis and prognosis (P < 0.05). CONCLUSION: The loss of pRB and E(2)F(1) overexpression may play a key role in the development of human neuroendocrine lung tumors.

Adult↗

PubMed2001

SB203580 promotes EGF-stimulated early morphological differentiation in PC12 cell through activating ERK pathway.

MAP kinases have important role in PC12 cell differentiation, since the activities of both extracellular regulated protein kinase (ERK) and p38 have been indicated as necessary signal for PC12 cell differentiation. Epidermal growth factor (EGF) and NGF both activate ERK and p38 in PC12 cells, but only NGF trigger differentiation. It has been proposed that the duration of ERK activation determines the switch from proliferation to differentiation, since EGF causes more transient activation of ERK than NGF in PC12 cells. Here we report that treatment of PC12 cells with EGF in the presence of SB203580, a widely used p38 inhibitor, caused differentiation. The pro-differentiation effect of SB203580 in EGF-treated PC12 cells was found to be independent of its function of p38 inhibition but was through an effect on the ERK pathway that has been recently reported (Kalmes et al. [1999] FEBS Lett. 444: 71-74; Hall-Jackson et al. [1999] Onc. 18: 2047-2054). We found that SB203580 by itself did not affect the activity of ERK1/2 but significantly extended EGF-induced ERK activation in PC12 cells, which resulted in early morphological differentiation. Our data indicated that although both ERK and p38 are required for PC12 cell differentiation, activation of p38 is not required when ERK is superactivated. Our data provided further evidence for the threshold theory that differentiation is determined by the duration of ERK activation.

Adenoviridae↗

PubMed2001

Prevalence of Campylobacter spp., Escherichia coli, and Salmonella serovars in retail chicken, turkey, pork, and beef from the Greater Washington, D.C., area.

A total of 825 samples of retail raw meats (chicken, turkey, pork, and beef) were examined for the presence of Escherichia coli and Salmonella serovars, and 719 of these samples were also tested for Campylobacter spp. The samples were randomly obtained from 59 stores of four supermarket chains during 107 sampling visits in the Greater Washington, D.C., area from June 1999 to July 2000. The majority (70.7%) of chicken samples (n = 184) were contaminated with Campylobacter, and a large percentage of the stores visited (91%) had Campylobacter-contaminated chickens. Approximately 14% of the 172 turkey samples yielded Campylobacter, whereas fewer pork (1.7%) and beef (0.5%) samples were positive for this pathogen. A total of 722 Campylobacter isolates were obtained from 159 meat samples; 53.6% of these isolates were Campylobacter jejuni, 41.3% were Campylobacter coli, and 5.1% were other species. Of the 212 chicken samples, 82 (38.7%) yielded E. coli, while 19.0% of the beef samples, 16.3% of the pork samples, and 11.9% of the turkey samples were positive for E. coli. However, only 25 (3.0%) of the retail meat samples tested were positive for Salmonella. Significant differences in the bacterial contamination rates were observed for the four supermarket chains. This study revealed that retail raw meats are often contaminated with food-borne pathogens; however, there are marked differences in the prevalence of such pathogens in different meats. Raw retail meats are potential vehicles for transmitting food-borne diseases, and our findings stress the need for increased implementation of hazard analysis of critical control point (HACCP) and consumer food safety education efforts.

Animals↗

PubMed2001

Identification and characterization of integron-mediated antibiotic resistance among Shiga toxin-producing Escherichia coli isolates.

A total of 50 isolates of Shiga toxin-producing Escherichia coli (STEC), including 29 O157:H7 and 21 non-O157 STEC strains, were analyzed for antimicrobial susceptibilities and the presence of class 1 integrons. Seventy-eight (n = 39) percent of the isolates exhibited resistance to two or more antimicrobial classes. Multiple resistance to streptomycin, sulfamethoxazole, and tetracycline was most often observed. Class 1 integrons were identified among nine STEC isolates, including serotypes O157:H7, O111:H11, O111:H8, O111:NM, O103:H2, O45:H2, O26:H11, and O5:NM. The majority of the amplified integron fragments were 1 kb in size with the exception of one E. coli O111:H8 isolate which possessed a 2-kb amplicon. DNA sequence analysis revealed that the integrons identified within the O111:H11, O111:NM, O45:H2, and O26:H11 isolates contained the aadA gene encoding resistance to streptomycin and spectinomycin. Integrons identified among the O157:H7 and O103:H2 isolates also possessed a similar aadA gene. However, DNA sequencing revealed only 86 and 88% homology, respectively. The 2-kb integron of the E. coli O111:H8 isolate contained three genes, dfrXII, aadA2, and a gene of unknown function, orfF, which were 86, 100, and 100% homologous, respectively, to previously reported gene cassettes identified in integrons found in Citrobacter freundii and Klebsiella pneumoniae. Furthermore, integrons identified among the O157:H7 and O111:NM strains were transferable via conjugation to another strain of E. coli O157:H7 and to several strains of Hafnia alvei. To our knowledge, this is the first report of integrons and antibiotic resistance gene cassettes in STEC, in particular E. coli O157:H7.

Animals↗

PubMed2001

Novel promoter polymorphism in insulin-like growth factor-binding protein-3: correlation with serum levels and interaction with known regulators.

Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) is a major determinant of circulating levels of the IGFs and is clinically useful for the evaluation of GH deficiency and for predicting the response to GH treatment. Recent studies provide evidence that the circulating level of IGFBP-3 is inversely related to the risk of several common cancers, and that antiproliferative agents such as antiestrogens and retinoids act in part by up-regulating IGFBP-3 gene (IGFBP3) expression. Although approximately 50% of the substantial interindividual variability in circulating IGFBP-3 levels is known to have a genetic basis, the specific loci involved are unknown. Direct sequencing of genomic DNA specimens from a multiethnic population identified several single nucleotide polymorphisms in the promoter region of IGFBP3. For the most common single nucleotide polymorphism (nucleotide -202) found to be in Hardy-Weinberg equilibrium, genotype was highly correlated to circulating level of IGFBP-3 in 478 men from the Physicians' Health Study. In vitro, we documented significantly higher promoter activity of the A allele at the -202 locus compared with the C allele, consistent with the relationship observed between genotype and circulating IGFBP-3 (AA > AC > CC). A positive correlation was observed between circulating retinol levels and circulating IGFBP-3 levels; subset analysis by genotype showed that this relationship was only present among individuals carrying an A allele at -202 (AA > AC > CC). Tall individuals or individuals with a body mass index of 27 or greater had levels of circulating IGFBP-3 that were significantly higher when they possessed at least one A allele (AA > AC > CC). The IGFBP3 promoter region deserves investigation as a locus where polymorphic variation occurs frequently and may influence GH responsiveness, somatic growth, and possibly cancer risk.

Aging↗

PubMed2001

Liposome-C-erbB2 antisense oligodoxynucleotides in human ovarian cancer cells.

OBJECTIVE: To explore the effects of liposome-C-erbB2 antisense phosphorothioate oligodeoxynucleotides (S-ODNs) on C-erbB2 proto-oncogene expression and cell proliferation in human ovarian cancer cells. METHODS: The effects of liposome-C-erbB2 S-ODNs on C-erbB2 protein expression, cell cycle and cell proliferation in human ovarian cancer cells were studied by means of flow cytometry and 3H-thymidine incorporation. RESULTS: Liposome-C-erbB2 S-ODNs can specifically reduce C-erbB2 protein expression in human ovarian cancer cells, accompanied by a 30% inhibition of cell proliferation. The effectiveness of liposome-C-erbB2 S-ODNs on the expression of C-erbB2 was about 40 times higher than that of C-erbB2 S-ODNs. CONCLUSIONS: The data suggest that antisense therapy might be a useful method of gene therapy in ovarian cancer. The effectiveness of C-erbB2 S-ODNs could be greatly increased by adsorption of S-ODNs by liposomes.

Cell Cycle↗

PubMed2000

Tracing human oligodendroglial development in vitro.

Human neural precursor cell cultures (neurospheres) were established from fetal brain tissues of 15-20 gestation weeks and propagated for over a year in the presence of epidermal growth factor, basic fibroblast growth factor and leukemia inhibitory factor. Neurospheres were differentiated without the presence of above growth factors to follow the development of oligodendroglia. Oligodendroglial progenitors, identified by their bipolar morphology and expression of platelet-derived growth factor receptor-alpha (PDGFRalpha), emerged from spheres as early as 1 DIV; O4+ cells with bipolar to multipolar processes were observed at 3 DIV whereas O1+ multiprocess-bearing oligodendroglia did not appear until 5-7 DIV. They further differentiated to myelin basic protein-expressing oligodendrocytes after 2-3 weeks in culture. Thus, human oligodendroglial maturation in vitro follows the same pathway as rat cells but takes twice as long as their rodent counterparts. Bromodeoxyuridine incorporation indicated that PDGFRalpha-expressing cells but not O4+ oligodendroglia proliferated. More oligodendroglial progenitors incorporated BrdU and more O4+ cells survived when they were in contact with neurons and astrocytes than when they developed beyond the astrocyte layer. In addition, oligodendroglia on astrocytes had a complex process branching whereas those growing beyond astrocyte layer often formed membrane sheaths. Thus the survival, proliferation and maturation of oligodendroglia are influenced by other cell types.

Brain↗

PubMed2000

ARSACS, a spastic ataxia common in northeastern Québec, is caused by mutations in a new gene encoding an 11.5-kb ORF.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS or SACS) is an early onset neurodegenerative disease with high prevalence (carrier frequency 1/22) in the Charlevoix-Saguenay-Lac-Saint-Jean (CSLSJ) region of Quebec. We previously mapped the gene responsible for ARSACS to chromosome 13q11 and identified two ancestral haplotypes. Here we report the cloning of this gene, SACS, which encodes the protein sacsin. The ORF of SACS is 11,487 bp and is encoded by a single gigantic exon spanning 12,794 bp. This exon is the largest to be identified in any vertebrate organism. The ORF is conserved in human and mouse. The putative protein contains three large segments with sequence similarity to each other and to the predicted protein of an Arabidopsis thaliana ORF. The presence of heat-shock domains suggests a function for sacsin in chaperone-mediated protein folding. SACS is expressed in a variety of tissues, including the central nervous system. We identified two SACSmutations in ARSACS families that lead to protein truncation, consistent with haplotype analysis.

Amino Acid Sequence↗

PubMed2000

Enhanced proliferation and directed migration of oligodendroglial progenitors co-grafted with growth factor-secreting cells.

Transplantation repair of demyelinating lesions is restricted because relatively few cells can be introduced at only a limited number of sites. Repair could be enhanced by stimulating division of transplanted cells and by directing migration to multiple or distant lesions. This article demonstrates that transplanted oligodendroglial progenitors proliferate more when co-grafted with growth factor-secreting cells, yet retain the capacity to form myelin. Transplanted glial cells also migrate preferentially toward the growth factor-secreting cells when the two are implanted at separate sites. This opens avenues to examine growth factor actions on glia in vivo and improves the prospects for human remyelination therapies.

Animals↗

PubMed2000

[Repair of soft tissue defect of the hand with a fascia lata flap by microvascular anastomosis].

OBJECTIVE: This is to report the clinical experience in repair of the soft tissue defects of the hand using a free fascia lata flap and skin graft. METHODS: Eight cases of soft tissue defects of the hand were repaired with a fascia lata flap by means of microvascular anastomosis. The size of the fascia lata flap ranged from 2.5 cm x 7 cm to 6 cm x 16 cm. RESULTS: All the fascia lata flaps survived completely with satisfactory results. CONCLUSION: The flap is nourished by the descending branch of the lateral femoral circumflex artery and seems to have a constant vascular supply and a long pedicle. The dissection of the flap is easy. The flap is thin and very suitable for repair of soft tissue defects of the hand.

Adolescent↗

PubMed1999

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS): high-resolution physical and transcript map of the candidate region in chromosome region 13q11.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS or SACS) is a neurodegenerative disease frequent in northeastern Québec. In a previous study, we localized the disease gene to chromosome region 13q11 by identifying excess sharing of a marker allele in patients followed by linkage analysis and haplotyping. To create a detailed physical map of this region, we screened CEPH mega-YACs with 41 chromosome 13 sequence-tagged-sites (STSs) known to map to 13q11-q12. The YAC contig, composed of 27 clones, extends on the genetic map from D13S175 to D13S221, an estimated distance of at least 19.3 cM. A high-resolution BAC and PAC map that includes the ARSACS critical region flanked by D13S1275 and D13S292 was constructed. These YAC and BAC/PAC maps allowed the accurate placement of 29 genes and ESTs previously mapped to the proximal region of chromosome 13q. We confirmed the position of two candidate genes within the critical region and mapped the other 27 genes and ESTs to nearby intervals. Six BAC/PAC clones form a contig between D13S232 and D13S787 for sequencing within the ARSACS critical region.

Bacteriophage P1↗