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21.
A model of corrective gene transfer in X-linked ichthyosis 总被引:5,自引:0,他引:5
Freiberg RA; Choate KA; Deng H; Alperin ES; Shapiro LJ; Khavari PA 《Human molecular genetics》1997,6(6):927-933
Single gene recessive genetic skin disorders offer attractive prototypes
for the development of therapeutic cutaneous gene delivery. We have
utilized X-linked ichthyosis (XLI), characterized by loss of function of
the steroid sulfatase arylsulfatase C (STS), to develop a model of
corrective gene delivery to human skin in vivo. A new retroviral expression
vector was produced and utilized to effect STS gene transfer to primary
keratinocytes from XLI patients. Transduction was associated with
restoration of full-length STS protein expression as well as steroid
sulfatase enzymatic activity in proportion to the number of proviral
integrations in XLI cells. Transduced and uncorrected XLI keratinocytes,
along with normal controls, were then grafted onto immunodeficient mice to
regenerate full thickness human epidermis. Unmodified XLI keratinocytes
regenerated a hyperkeratotic epidermis lacking STS expression with
defective skin barrier function, effectively recapitulating the human
disease in vivo. Transduced XLI keratinocytes from the same patients,
however, regenerated epidermis histologically indistinguishable from that
formed by keratinocytes from patients with normal skin. Transduced XLI
epidermis demonstrated STS expression in vivo by immunostaining as well as
a normalization of histologic appearance at 5 weeks post-grafting. In
addition, transduced XLI epidermis demonstrated a return of barrier
function parameters to normal. These findings demonstrate corrective gene
delivery in human XLI patient skin tissue at both molecular and functional
levels and provide a model of human cutaneous gene therapy.
相似文献
22.
Zeynep H. Coban‐Akdemir Wu‐Lin Charng Mahshid Azamian Ingrid S. Paine Jaya Punetha Christopher M. Grochowski Tomasz Gambin Santiago O. Valdes Bryan Cannon Gladys Zapata Patricia P. Hernandez Shalini Jhangiani Harsha Doddapaneni Jianhong Hu Fatima Boricha Donna M. Muzny Eric Boerwinkle Yaping Yang Richard A. Gibbs Jennifer E. Posey Xander H. T. Wehrens John W. Belmont Jeffrey J. Kim Christina Y. Miyake James R. Lupski Seema R. Lalani 《American journal of medical genetics. Part A》2020,182(6):1387-1399
23.
24.
Frederick H Koh Jason MW Chua Joselyn LJ Tan Fung-Joon Foo Winson J Tan Sharmini S Sivarajah Leonard Ming Li Ho Bin-Tean Teh Min-Hoe Chew 《World journal of gastrointestinal surgery》2021,13(8):734-755
A growing body of evidence has demonstrated the prognostic significance of sarcopenia in surgical patients as an independent predictor of postoperative complications and outcomes. These included an increased risk of total complications, major complications, re-admissions, infections, severe infections, 30 d mortality, longer hospital stay and increased hospitalization expenditures. A program to enhance recovery after surgery was meant to address these complications; however, compliance to the program since its introduction has been less than ideal. Over the last decade, the concept of prehabilitation, or “pre-surgery rehabilitation”, has been discussed. The presurgical period represents a window of opportunity to boost and optimize the health of an individual, providing a compensatory “buffer” for the imminent reduction in physiological reserve post-surgery. Initial results have been promising. We review the literature to critically review the utility of prehabilitation, not just in the clinical realm, but also in the scientific realm, with a resource management point-of-view. 相似文献
25.
14th International HLA and Immunogenetics Workshop: Report on the HLA component of type 1 diabetes 总被引:1,自引:0,他引:1
26.
1 病例报告 男 ,71岁 ,因排尿困难于 1999- 0 9- 0 4入院 .B超确诊前列腺增生 5 a,既往无高血压、心脏病及心率失常史 .查体 :Bp17/ 10 k Pa,心界不大 ,心率 6 2次· min- 1 ,心律齐 .下腹部可触及涨大的膀胱 ,约耻骨上 4指 .入院时 ECG正常 .肝肾功能无异常 ,确诊前列腺增生伴急性尿潴留 .首先予导尿 ,导出尿液约 90 0 m L,之后 im乙稀雌酚 1mg,2 h后患者突发心慌、胸闷、气短、心前区疼痛 .发现患者大汗BP12 /6 k Pa,P110次· min- 1 ,R2 8次· min- 1 ,心率绝对不齐 ,脉搏明显短促 ,两肺底可闻及湿性罗音及哮鸣音 ,ECG示房颤 ,心… 相似文献
27.
Internet网上细胞凋亡研究的信息资源及其利用 总被引:1,自引:0,他引:1
0 引言 Internet网上含有丰富的信息资源 ,科研人员可以通过 Internet网了解其所研究领域的最新发展动态 ,获取全面和系统的科研信息 ,有利于进行学术交流[1 ] .然而网上信息浩如烟海 ,当检索某一专门领域的资料时 ,有时无从下手 .我们在科研实践中对 Internet网上主要的细胞凋亡研究信息资源及其查找方法进行了归纳 .1 细胞凋亡专业网站1. 1 The Cell death society (http:/ / www.celldeath-apoptosis.org) 为美国细胞死亡学会主办 ,概括了细胞凋亡和程序性细胞死亡研究的各个领域 ,包括与细胞凋亡有关的各种疾病 .可以免费注册… 相似文献
28.
Hypospadias trends in two US surveillance systems 总被引:6,自引:0,他引:6
OBJECTIVE: Hypospadias is a common congenital anomaly, the cause of which is unknown. Unexplained increases in the rates of hypospadias occurred in five European countries in the 1970s and 1980s. We examined data from two birth defects surveillance systems in the United States for evidence of similar trends. METHODOLOGY: The Metropolitan Atlanta Congenital Defects Program (MACDP) provided birth prevalence rates from 1968 to 1993. The nationwide Birth Defects Monitoring Program (BDMP) provided rates from 1970 to 1993. MACDP data are population-based and could be categorized by the severity of the hypospadias. BDMP data allowed analysis of rate trends for the four census regions of the United States. RESULTS: Data from both surveillance systems showed an approximate doubling of hypospadias rates in the 1970s and 1980s. MACDP data showed that the rate of severe cases increased while the ratio of mild to severe cases decreased. BDMP data showed that hypospadias rates increased markedly in all four regions of the United States. CONCLUSIONS: The observed increases are unlikely to be attributable to increased sensitivity of the surveillance systems or the identification of more mild cases by physicians over time, because either trend would have increased rather than decreased the ratio of mild to severe cases. If real, these trends represent the largest number of cases and the first report of an increase in hypospadias rates outside of Europe. Additional investigation of a possible increase in hypospadias rates is warranted. 相似文献
29.
Black tea and mammary gland carcinogenesis by 7,12- dimethylbenz[a]anthracene in rats fed control or high fat diets 总被引:3,自引:1,他引:3
Epidemiological studies suggest that tea may reduce cancer risk, and in
laboratory rodents, chemopreventive effects of tea or purified extracts of
tea have been demonstrated in lung, gastrointestinal tract and skin. There
is some evidence of chemoprevention by tea in the mammary gland, but the
data are not conclusive. In order to evaluate more fully the possible
influence of black tea on 7,12-dimethylbenz[a]anthracene (DMBA)-induced
mammary gland tumors in the female S-D (Sprague-Dawley) rat, three large
studies were performed: experiment 1, tumorigenesis in rats fed AIN-76A
diet and given 25 mg/kg DMBA and 1.25 or 2.5% whole tea extract or water to
drink; experiment 2, tumorigenesis in rats given 15 mg/kg DMBA and the same
diet and fluids as in experiment 1; experiment 3, tumorigenesis in rats fed
control or HF (high fat, corn oil) diet and given 15 mg/kg DMBA and 2% tea
or water to drink. Tea was given throughout the experiment; DMBA was given
by gastric gavage at 8 weeks of age. There was no consistent effect of tea
on tumorigenesis in rats fed AIN-76A diet; there was, however, evidence in
experiment 3 of a reduction of tumorigenesis by tea in rats fed the HF
diet. In experiment 3, rats fed the HF diet and given water showed the
expected increase in tumor burden (number and weight) compared with rats
fed control diet. However, rats fed the HF diet and given 2% tea showed no
increase in tumor burden; their tumor burden was significantly lower than
in rats fed the HF diet and given water (P < 0.01) and was not different
from rats fed control diet and given water or tea. In addition, in
experiment 3, the number of malignant tumors per tumor- bearing rat was
increased by the HF diet in water-drinking rats (P < 0.01) but not in
tea-drinking rats. Therefore, it appears that tea partially blocked the
promotion of DMBA-induced mammary tumorigenesis by the HF diet.
相似文献
30.
Determination of malondialdehyde-induced DNA damage in human tissues using an immunoslot blot assay 总被引:3,自引:4,他引:3
Leuratti C; Singh R; Lagneau C; Farmer PB; Plastaras JP; Marnett LJ; Shuker DE 《Carcinogenesis》1998,19(11):1919-1924
Malondialdehyde (MDA) is a product of lipid peroxidation and prostaglandin
biosynthesis. It is mutagenic and carcinogenic and the major adduct formed
by reaction with DNA, a highly fluorescent pyrimidopurinone (M1-dG), has
been detected in healthy human liver and leukocyte DNA. Analytical methods
used so far for the detection of M1- dG have not been applied to a large
number of individuals or variety of samples. Often, only a few microg of
DNA from human tissues are available for analysis and a very sensitive
assay is needed in order to detect background levels of M1-dG in very small
amounts of DNA. In this paper, the development of an immunoslot blot (ISB)
assay for the measurement of MI-dG in 1 microg of DNA is described. The
limit of detection of the assay is 2.5 adducts per 10(8) bases. A series of
human samples were analysed and levels of 5.6-9.5 (n = 8) and 3.1-64.3 (n =
42) of M1-dG per 10(8) normal bases were detected in white blood cell and
gastric biopsy DNA, respectively. Results on four human samples were
compared with those obtained using an HPLC/32P-post- labelling (HPLC/PPL)
method previously developed and indicated a high correlation between M1-dG
levels measured by the two assays. The advantages of ISB over other assays
including HPLC/PPL, such as the possibility of analysing 1 microg
DNA/sample and the fact that it is less time-consuming and laborious, means
that it can be more easily used for routine analysis of a large number of
samples in biomonitoring studies.
相似文献