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21.
Kangaroo Care with a ventilated preterm infant 总被引:4,自引:0,他引:4
22.
The hypoxanthine-guanine phosphoribosyl transferase (hprt) locus in 6-
thioguanine (TG) resistant T-lymphocytes is a useful target for the study
of somatic in vivo mutagenesis, since it provides information about a broad
spectrum of mutation. Mutations in the hprt coding region were studied in
124 TG-resistant T-cell clones from 38 healthy, non- smoking male donors
from a previously studied population of bus maintenance workers,
fine-mechanics and laboratory personnel. Their mean age was 43 years (range
23-64) and their hprt mutant frequency was 9.3 +/- 5.2 x 10(-6) (mean +/-
SD, range 1.4-22.6 x 10(-6)). Sequence analysis of hprt cDNA identified 115
unique mutations; 76% were simple base substitutions, 10% were +/-1 bp
frameshifts, and 10% were small deletions within exons (3-52 bp). In
addition, two tandem base substitutions and one complex mutation were
observed. Simple base substitutions were observed at 55 (20%) of 281 sites
known to be mutable in the hprt coding sequence. The distribution of these
mutations was significantly different than would be expected based upon a
Poisson distribution (P < 0.0001), suggesting the existence of
'hotspots'. All of the 87 simple base substitutions occurred at known
mutable sites, but eight were substitutions of a kind that have not
previously been reported at these sites. The most frequently mutated sites
were cDNA positions 197 and 146, with six and five independent mutations
respectively. Four mutations were observed at position 131, and three each
at positions 143, 208, 508 and 617. Transitions (52%) were slightly more
frequent than tranversions (48%), and mutations at GC base pairs (56%) more
common than mutations at AT base pairs (44%). GC > AT was the most
common type of base pair substitution (37%). The majority of the mutations
at GC base pairs (78%) occurred at sites with G in the non-transcribed
strand. All but one of eight mutations at CpG- sites were of the kind
expected from deamination of methylated cytosine. Deletion of a single base
pair (-1 frameshift) was three times more frequent than insertion of a
single bp (+1 frameshift). Almost half (6/13) of the small (3-52 bp)
deletions within the coding sequence clustered in the 5' end of exon 2.
Short repeats and other sequence motifs that have been associated with
replication error were found in the flanking regions of most of the
frameshifts and small deletions. However, several differences in the local
sequence context between +/-1 frameshift and deletion mutations were also
noticed. The present results identify positions 197, 146 and possibly 131
as hotspots for base substitution mutations, and confirm previously
reported hotspots at positions 197, 508 and 617. In addition, the earlier
notion of a deletion hotspot in the 5'end of exon 2 was confirmed. The
observations of these mutational cluster regions in different human
populations suggest that they are due to endogeneous mechanisms of
mutagenesis, or to ubiquitous environmental influences. The emerging
background spectrum of somatic in vivo mutation in the human hprt gene
provides a useful basis for comparisons with radiation or chemically
induced mutational spectra, as well as with gene mutations in human tumors.
相似文献
23.
Hemoglobin and albumin adducts of benzene oxide among workers exposed to high levels of benzene 总被引:3,自引:0,他引:3
Yeowell-O'Connell K; Rothman N; Smith MT; Hayes RB; Li G; Waidyanatha S; Dosemeci M; Zhang L; Yin S; Titenko-Holland N; Rappaport SM 《Carcinogenesis》1998,19(9):1565-1571
Benzene oxide (BO) reacts with cysteinyl residues in hemoglobin (Hb) and
albumin (Alb) to form protein adducts (BO-Hb and BO-Alb), which are
presumed to be specific biomarkers of exposure to benzene. We analyzed
BO-Hb in 43 exposed workers and 42 unexposed controls, and BO-Alb in a
subsample consisting of 19 workers and 19 controls from Shanghai, China, as
part of a larger cross-sectional study of benzene biomarkers. The adducts
were analyzed by gas chromatography-mass spectrometry following reaction of
the protein with trifluoroacetic anhydride and methanesulfonic acid. When
subjects were divided into controls (n = 42) and workers exposed to < or
=31 (n = 21) and >31 p.p.m. (n = 22) benzene, median BO-Hb levels were
32.0, 46.7 and 129 pmol/g globin, respectively (correlation with exposure:
Spearman r = 0.67, P < 0.0001). To our knowledge, these results
represent the first observation in humans that BO-Hb levels are
significantly correlated with benzene exposure. Median BO-Alb levels in
these 3 groups were 103 (n = 19), 351 (n = 7) and 2010 (n = 12) pmol/g Alb,
respectively, also reflecting a significant correlation with exposure
(Spearman r = 0.90, P < 0.0001). The blood dose of BO predicted from
both Hb and Alb adducts was very similar. These results clearly affirm the
use of both Hb and Alb adducts of BO as biomarkers of exposure to high
levels of benzene. As part of our investigation of the background levels of
BO-Hb and BO-Alb found in unexposed persons, we analyzed recombinant human
Hb and Alb for BO adducts. Significant levels of both BO-Hb (19.7 pmol/g)
and BO-Alb (41.9 pmol/g) were detected, suggesting that portions of the
observed background adducts reflect an artifact of the assay, while other
portions are indicative of either unknown exposures or endogenous
production of adducts.
相似文献
24.
25.
Brian L Sprague Amy Trentham-Dietz Curtis J Hedman Jue Wang Jocelyn DC Hemming John M Hampton Diana SM Buist Erin J Aiello Bowles Gale S Sisney Elizabeth S Burnside 《Breast cancer research : BCR》2013,15(3):R45
Introduction
Humans are widely exposed to estrogenically active phthalates, parabens, and phenols, raising concerns about potential effects on breast tissue and breast cancer risk. We sought to determine the association of circulating serum levels of these chemicals (reflecting recent exposure) with mammographic breast density (a marker of breast cancer risk).Methods
We recruited postmenopausal women aged 55 to 70 years from mammography clinics in Madison, Wisconsin (N = 264). Subjects completed a questionnaire and provided a blood sample that was analyzed for mono-ethyl phthalate, mono-butyl phthalate, mono-benzyl phthalate, butyl paraben, propyl paraben, octylphenol, nonylphenol, and bisphenol A (BPA). Percentage breast density was measured from mammograms by using a computer-assisted thresholding method.Results
Serum BPA was positively associated with mammographic breast density after adjusting for age, body mass index, and other potentially confounding factors. Mean percentage density was 12.6% (95% confidence interval (CI), 11.4 to 14.0) among the 193 women with nondetectable BPA levels, 13.7% (95% CI, 10.7 to 17.1) among the 35 women with detectable levels below the median (<0.55 ng/ml), and 17.6% (95% CI, 14.1 to 21.5) among the 34 women with detectable levels above the median (>0.55 ng/ml; Ptrend = 0.01). Percentage breast density was also elevated (18.2%; 95% CI, 13.4 to 23.7) among the 18 women with serum mono-ethyl phthalate above the median detected level (>3.77 ng/ml) compared with women with nondetectable BPA levels (13.1%; 95% CI, 11.9 to 14.3; Ptrend = 0.07). No other chemicals demonstrated associations with percentage breast density.Conclusions
Postmenopausal women with high serum levels of BPA and mono-ethyl phthalate had elevated breast density. Further investigation of the impact of BPA and mono-ethyl phthalate on breast cancer risk by using repeated serum measurements or other markers of xenoestrogen exposure are needed. 相似文献26.
Paulina M Kowalewska Jacob Fletcher William F Jackson Suzanne E Brett Michelle SM Kim Galina Yu Mironova Nadia Haghbin David M Richter Nathan R Tykocki Mark T Nelson Donald G Welsh 《Journal of cerebral blood flow and metabolism》2022,42(9):1693
Cerebral blood flow is a finely tuned process dependent on coordinated changes in arterial tone. These changes are strongly tied to smooth muscle membrane potential and inwardly rectifying K+ (KIR) channels are thought to be a key determinant. To elucidate the role of KIR2.1 in cerebral arterial tone development, this study examined the electrical and functional properties of cells, vessels and living tissue from tamoxifen-induced smooth muscle cell (SMC)-specific KIR2.1 knockout mice. Patch-clamp electrophysiology revealed a robust Ba2+-sensitive inwardly rectifying K+ current in cerebral arterial myocytes irrespective of KIR2.1 knockout. Immunolabeling clarified that KIR2.1 expression was low in SMCs while KIR2.2 labeling was remarkably abundant at the membrane. In alignment with these observations, pressure myography revealed that the myogenic response and K+-induced dilation were intact in cerebral arteries post knockout. At the whole organ level, this translated to a maintenance of brain perfusion in SMC KIR2.1−/− mice, as assessed with arterial spin-labeling MRI. We confirmed these findings in superior epigastric arteries and implicated KIR2.2 as more functionally relevant in SMCs. Together, these results suggest that subunits other than KIR2.1 play a significant role in setting native current in SMCs and driving arterial tone. 相似文献
27.
28.
Previous studies on the association of ankylosing spondylitis and
abnormalities of the lung parenchyma have been based largely on plain
radiography and pulmonary function testing. This study, although
uncontrolled, is the first to use high-resolution computed tomography to
examine the entire lung parenchyma in ankylosing spondylitis patients, and
to correlate the findings with clinical assessment, plain radiography and
pulmonary function testing. The study population comprised 26 patients
meeting the New York criteria for idiopathic ankylosing spondylitis who
attended the out-patient department at our institution. High-resolution
computed tomography examination revealed abnormalities in 19 patients
(70%): these included interstitial lung disease (n = 4), bronchiectasis (n
= 6), emphysema (n = 4), apical fibrosis (n = 2), mycetoma (n = 1) and
non-specific interstitial lung disease (n = 12). Plain radiography was
abnormal in only four patients and failed to identify any patient with
interstitial lung disease. All patients with interstitial lung disease on
high-resolution computed tomography had respiratory symptoms and three of
the four had evidence of a restrictive process on pulmonary function
testing. This study raises, for the first time, the possible association
between interstitial lung disease and ankylosing spondylitis, and
highlights the use of high-resolution computed tomography in detecting such
disease in ankylosing spondylitis patients.
相似文献
29.
目的:肺癌分期与肿瘤直径的关系已被证实是一个预后指标,因此被纳入1986年肺癌分类的国际系统。近年来由于CT飞速发展,人们可以诊断出更小的肺癌,于是有人提倡对肺癌Ⅰ期进一步分期,即根据肿瘤直径小于还是大于30mm,将无确切远处淋巴结转移的病例(Ⅰ期病例)细分为Ⅰa和Ⅰb期。在诊断无症状(即潜伏)的肺癌时,CT普查的开展使人们考虑肿瘤大小的预后价值。在此我们对CT普查诊断的无症状潜伏型肺癌作了分期与大小关系的报道。 相似文献
30.
BACKGROUND: Cellular blood components are irradiated to prevent graft- versus-host disease in transfusion recipients at risk for this syndrome. Because gamma radiation can result in the production of reactive oxygen species, the role of reactive oxygen species was investigated in radiation-induced red cell damage. STUDY DESIGN AND METHODS: Whole blood from normal donors was exposed to various doses of t-butyl hydroperoxide (0-1 mM) and/or to gamma-radiation (0-50 Gy). Oxidative damage was assessed by the extent of lipid peroxidation (measured by thiobarbituric acid-reactive substances [TBARS]) and hemoglobin oxidation. Fresh blood was divided into three parts-one initially irradiated and stored, another stored with portions irradiated weekly, and a third stored without irradiation. TBARS and hemoglobin oxidation were measured weekly. RESULTS: As expected, t- butyl hydroperoxide induced TBARS formation and hemoglobin oxidation in a dose-dependent fashion. The gamma-radiation not only increased hemoglobin oxidation and TBARS formation, but also enhanced the t-butyl hydroperoxide effect on red cells. Red cell storage increased TBARS generation and hemoglobin oxidation in a time-dependent fashion. When radiation was administered either initially or after weekly storage, TBARS production and hemoglobin oxidation were increased over that measured in unirradiated paired controls. CONCLUSION: Gamma radiation at clinically used doses increases lipid peroxidation and hemoglobin oxidation in human red cells. The effect of gamma-radiation is accentuated by blood storage and induces damage independent of time of storage. 相似文献