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11.
Olney JW Ishimaru MJ Bittigau P Ikonomidou C 《Apoptosis : an international journal on programmed cell death》2000,5(6):515-521
It has been known for three decades that ethanol, the most widely abused drug in the world, has deleterious effects on the developing human brain, but progress has been slow in developing animal models for studying this problem, and the underlying mechanisms have remained elusive. Recently, we have shown that during the synaptogenesis period, also known as the brain growth spurt period, ethanol has the potential to trigger massive neuronal suicide in the in vivo mammalian brain. The brain growth spurt period in humans spans the last trimester of pregnancy and first several years after birth. The NMDA antagonist and GABAmimetic properties of ethanol may be responsible for its apoptogenic action, in that other drugs with either NMDA antagonist or GABAmimetic actions also trigger apoptotic neurodegeneration in the developing brain. Our findings provide a likely explanation for the reduced brain mass and neurobehavioral disturbances associated with the human fetal alcohol syndrome. Furthermore, since NMDA antagonist and GABAmimetic drugs are sometimes abused by pregnant women and also are used as anticonvulsants, sedatives or anesthetics in pediatric medicine, our findings raise several complex drug safety issues. In addition, the observation that ethanol and several other drugs trigger massive neuronal apoptosis in the developing brain provides an unprecedented opportunity to study both neuropathological aspects and molecular mechanisms of apoptotic neurodegeneration in the in vivo mammalian brain. 相似文献
12.
Aires-de-Sousa M Parente CE Vieira-da-Motta O Bonna IC Silva DA de Lencastre H 《Applied and environmental microbiology》2007,73(12):3845-3849
Eighty-four staphylococcal isolates were obtained from milk samples from cows, sheep, goats, and buffalo with subclinical mastitis and from colonization samples from ostriches. The animals were hosted in 18 small dairy herds and an ostrich breeding located in 10 municipalities of the state of Rio de Janeiro, Brazil. Thirty isolates were identified as Staphylococcus aureus by biochemical and molecular techniques and were comparatively characterized by phenotypic and genotypic methods. The molecular characterization by pulsed-field gel electrophoresis (PFGE), spa typing, and multilocus sequence typing (MLST) revealed five clonal types (PFGE A, spa type t359, sequence type 747 [ST747]; PFGE B, spa type t1180, ST750; PFGE C, spa type t605, ST126; PFGE D, spa type t127, ST751; and PFGE F, spa type t002, ST5). None of the isolates harbored the Panton-Valentine leukocidin or exfoliative toxin D gene. The detection of major clone A (in 63% of the isolates) in different herds, among all animal species studied, and in infection and colonization samples evidenced its geographical spread among Rio de Janeiro State and no host preference among the animal species. Comparison with S. aureus from a human origin suggested that all but one clone found in the present study might be animal specific. 相似文献
13.
Characterization of Staphylococcus aureus Isolates from Buffalo, Bovine, Ovine, and Caprine Milk Samples Collected in Rio de Janeiro State, Brazil
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Marta Aires-de-Sousa Carlos E. S. R. Parente Olney Vieira-da-Motta Isabel C. F. Bonna Denise A. Silva Hermínia de Lencastre 《Applied microbiology》2007,73(12):3845-3849
Eighty-four staphylococcal isolates were obtained from milk samples from cows, sheep, goats, and buffalo with subclinical mastitis and from colonization samples from ostriches. The animals were hosted in 18 small dairy herds and an ostrich breeding located in 10 municipalities of the state of Rio de Janeiro, Brazil. Thirty isolates were identified as Staphylococcus aureus by biochemical and molecular techniques and were comparatively characterized by phenotypic and genotypic methods. The molecular characterization by pulsed-field gel electrophoresis (PFGE), spa typing, and multilocus sequence typing (MLST) revealed five clonal types (PFGE A, spa type t359, sequence type 747 [ST747]; PFGE B, spa type t1180, ST750; PFGE C, spa type t605, ST126; PFGE D, spa type t127, ST751; and PFGE F, spa type t002, ST5). None of the isolates harbored the Panton-Valentine leukocidin or exfoliative toxin D gene. The detection of major clone A (in 63% of the isolates) in different herds, among all animal species studied, and in infection and colonization samples evidenced its geographical spread among Rio de Janeiro State and no host preference among the animal species. Comparison with S. aureus from a human origin suggested that all but one clone found in the present study might be animal specific. 相似文献
14.
Kan Chen Wanlu Cao Juan Li Dave Sprengers Pratika Y Hernanda Xiangdong Kong Luc JW van der Laan Kwan Man Jaap Kwekkeboom Herold J Metselaar Maikel P Peppelenbosch Qiuwei Pan 《Molecular medicine (Cambridge, Mass.)》2015,21(1):792-802
As uncontrolled cell proliferation requires nucleotide biosynthesis, inhibiting enzymes that mediate nucleotide biosynthesis constitutes a rational approach to the management of oncological diseases. In practice, however, results of this strategy are mixed and thus elucidation of the mechanisms by which cancer cells evade the effect of nucleotide biosynthesis restriction is urgently needed. Here we explored the notion that intrinsic differences in cancer cell cycle velocity are important in the resistance toward inhibition of inosine monophosphate dehydrogenase (IMPDH) by mycophenolic acid (MPA). In short-term experiments, MPA treatment of fast-growing cancer cells effectively elicited G0/G1 arrest and provoked apoptosis, thus inhibiting cell proliferation and colony formation. Forced expression of a mutated IMPDH2, lacking a binding site for MPA but retaining enzymatic activity, resulted in complete resistance of cancer cells to MPA. In nude mice subcutaneously engrafted with HeLa cells, MPA moderately delayed tumor formation by inhibiting cell proliferation and inducing apoptosis. Importantly, we developed a lentiviral vector–based Tet-on label-retaining system that enables to identify, isolate and functionally characterize slow-cycling or so-called label-retaining cells (LRCs) in vitro and in vivo. We surprisingly found the presence of LRCs in fast-growing tumors. LRCs were superior in colony formation, tumor initiation and resistance to MPA as compared with fast-cycling cells. Thus, the slow-cycling compartment of cancer seems predominantly responsible for resistance to MPA. 相似文献
15.
Fife MS Gutierrez A Ogilvie EM Stock CJ Samuel JM Thomson W Mack LF Lewis CM Woo P 《Arthritis research & therapy》2006,8(5):R148-5
Juvenile idiopathic arthritis (JIA) is the most common cause of chronic childhood disability and encompasses a number of disease
subgroups. In this study we have focused on systemic JIA (sJIA), which accounts for approximately 11% of UK JIA cases. This
study reports the investigation of three members of the IL10 gene family as candidate susceptibility loci in children with
sJIA. DNA from 473 unaffected controls and 172 patients with sJIA was genotyped for a single nucleotide polymorphism (SNP)
in IL19 and IL20 and two SNPs in IL10. We examined evidence for association of the four SNPs by single marker and haplotype
analysis. Significant differences in allele frequency were observed between cases and controls, for both IL10-1082 (p = 0.031)
and IL20-468 (p = 0.028). Furthermore, examination of the haplotypes of IL10-1082 and IL20-468 revealed greater evidence for
association (global p = 0.0006). This study demonstrates a significant increased prevalence of the low expressing IL10-1082
genotype in patients with sJIA. In addition, we show a separate association with an IL20 polymorphism, and the IL10-1082A/IL20-468T
haplotype. The two marker 'A-T' haplotype confers an odds ratio of 2.24 for sJIA. This positive association suggests an important
role for these cytokines in sJIA pathogenesis. 相似文献
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—Monosodium l -glutamate was injected subcutaneously into 4-day-old mice at a dose of 2 mg/g body wt. The infants were killed at sequential intervals after injection, the brains were frozen, and samples of the arcuate nucleus (NA), ventromedial hypothalamus (VMH) and lateral thalamus (LT) were micro-dissected from lyophilized sections for glutamate assay. Blood glutamate levels were also determined for comparison with brain levels of glutamate at corresponding post-injection intervals. Glutamate levels in the NA steadily increased to reach a peak value of 110.9 mmol/kg dry wt. at 3 h following injection, whereas the highest levels reached in the VMH or LT were about 41.7 mmol/kg dry wt. Return to control values of about 25 mmol/kg dry wt. occurred gradually over a period of 12–15 h in all three brain regions. Blood glutamate concentrations peaked rapidly, reaching a maximum of 40 mm within 15 min but returned precipitously to near-baseline values (below 1 mm ) in the 1–3 h interval after injection. We discuss possible mechanisms to account for the transient marked accumulation of subcutaneously administered glutamate in the NA and how this might relate to the selective destruction of arcuate neurons which occurs simultaneously. 相似文献
19.
David J Lee Lewis EH Bingle Karin Heurlier Mark J Pallen Charles W Penn Stephen JW Busby Jon L Hobman 《BMC microbiology》2009,9(1):252
Background
Homologous recombination mediated by the λ-Red genes is a common method for making chromosomal modifications in Escherichia coli. Several protocols have been developed that differ in the mechanisms by which DNA, carrying regions homologous to the chromosome, are delivered into the cell. A common technique is to electroporate linear DNA fragments into cells. Alternatively, DNA fragments are generated in vivo by digestion of a donor plasmid with a nuclease that does not cleave the host genome. In both cases the λ-Red gene products recombine homologous regions carried on the linear DNA fragments with the chromosome. We have successfully used both techniques to generate chromosomal mutations in E. coli K-12 strains. However, we have had limited success with these λ-Red based recombination techniques in pathogenic E. coli strains, which has led us to develop an enhanced protocol for recombineering in such strains. 相似文献20.