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31.
X-linked chronic granulomatous disease: correction of NADPH oxidase defect by retrovirus-mediated expression of gp91-phox 总被引:3,自引:0,他引:3
Chronic granulomatous disease (CGD) is an inherited immunodeficiency resulting from the inability of an individual's phagocytes to produce superoxide anions because of defective NADPH oxidase. The disease may be treated by bone marrow transplantation and as such is a candidate for somatic gene therapy. Two thirds of patients have defects in an X- linked gene (X-CGD) encoding gp91-phox, the large subunit of the membrane cytochrome b-245 component of NADPH oxidase. Epstein-Barr virus-transformed B-cell lines from patients with CGD provide a model system for the disease. We have used retrovirus-mediated expression of gp91-phox to reconstitute functionally NADPH oxidase activity in B-cell lines from three unrelated patients with X-CGD. The protein is glycosylated and membrane associated, and the reconstituted oxidase is appropriately activated via protein kinase C. The kinetics of superoxide production by such reconstituted cells is similar to that of normal B-cell lines. These data show the potential of gene therapy for this disease. 相似文献
32.
Eelke M Bos Harry van Goor Jaap A Joles Matthew Whiteman Henri G D Leuvenink 《British journal of pharmacology》2015,172(6):1479-1493
Hydrogen sulfide (H2S) has become a molecule of high interest in recent years, and it is now recognized as the third gasotransmitter in addition to nitric oxide and carbon monoxide. In this review, we discuss the recent literature on the physiology of endogenous and exogenous H2S, focusing upon the protective effects of hydrogen sulfide in models of hypoxia and ischaemia.
Linked Articles
This article is part of a themed section on Pharmacology of the Gasotransmitters. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-6 相似文献33.
Andreas Papapetropoulos Matthew Whiteman Giuseppe Cirino 《British journal of pharmacology》2015,172(6):1633-1637
The purpose of this brief review is to help researchers in their initial approach to the H2S field and to provide answers for the most frequently posed questions by newcomers to the topic related to H2S donors and inhibitors of H2S synthesis, as well as methods to measure H2S production. Here the reader will find a practical guide that provides fast and to the point information on how to (i) deliver H2S to cells; (ii) modulate its endogenous production; and (iii) measure its levels in fluids, cells and tissues in order to gain an understanding of its role in health and disease.
Linked Articles
This article is part of a themed section on Pharmacology of the Gasotransmitters. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-6 相似文献34.
Cancers in Australia attributable to exposure to solar ultraviolet radiation and prevented by regular sunscreen use
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Catherine M. Olsen Louise F. Wilson Adele C. Green Christopher J. Bain Lin Fritschi Rachel E. Neale David C. Whiteman 《Australian and New Zealand journal of public health》2015,39(5):471-476
Objectives: To estimate the proportion and numbers of cancers occurring in Australia attributable to solar ultraviolet radiation (UVR) and the proportion and numbers prevented by regular sun protection factor (SPF) 15+ sunscreen use. Methods: We estimated the population attributable fraction (PAF) and numbers of melanomas and keratinocyte cancers (i.e. basal cell carcinomas and squamous cell carcinomas) due to exposure to ambient UVR resulting from residing in Australia versus residing in the UK (for melanoma) or Scandinavia (for keratinocyte cancers). We also estimated the prevented fraction (PF): the proportion of cancers that would have occurred but were likely prevented by regular sunscreen use. Results: An estimated 7,220 melanomas (PAF 63%) and essentially all keratinocyte cancers occurring in Australia were attributable to high ambient UVR levels in Australia. We estimated that regular sunscreen use prevented around 14,190 (PF 9.3%) and 1,730 (PF 14%) people from developing SCC and melanoma, respectively. Conclusions: Although our approach was conservative, a high proportion of skin cancers in Australia are attributable to high ambient levels of UVR. Prevailing levels of sunscreen use probably reduced skin cancer incidence by 10–15%. Implications: Most skin cancers are preventable. Sunscreen should be a component of a comprehensive sun protection strategy. 相似文献
35.
Cancers in Australia in 2010 attributable to total breastfeeding durations of 12 months or less by parous women
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Susan J. Jordan Louise F. Wilson Christina M. Nagle Adele C. Green Catherine M. Olsen Christopher J. Bain Nirmala Pandeya David C. Whiteman Penelope M. Webb 《Australian and New Zealand journal of public health》2015,39(5):418-421
Objectives: To estimate the proportion and number of cancers occurring in Australia in 2010 attributable to parous women having breastfed for total durations of ≤12 months. Methods: We estimated the population attributable fraction (PAF) of breast cancers (the only cancer site with convincing evidence of causal association) associated with women breastfeeding for ≤12 months in total, using standard formulae incorporating breastfeeding prevalence data, relative risks associated with breastfeeding and cancer incidence. We also estimated the proportion change in disease incidence (potential impact fraction [PIF]) that might have occurred under two hypothetical scenarios of women breastfeeding for longer durations. Results: An estimated 235 (1.7%) breast cancer cases that occurred in Australian in 2010 could be attributed to women breastfeeding for total durations of ≤12 months. Assuming a hypothetical increase in breastfeeding, we estimated that the number of breast cancers prevented would range from 36 to 51 (prevented fraction = 0.3% to 0.4%). Conclusions: More than 200 breast cancers were attributable to women breastfeeding for total durations of ≤12 months. Implications: Policies to increase breastfeeding duration may help prevent breast cancers in the future. 相似文献
36.
Bradley J. Kendall Louise F. Wilson Catherine M. Olsen Penelope M. Webb Rachel E. Neale Christopher J. Bain David C. Whiteman 《Australian and New Zealand journal of public health》2015,39(5):452-457
Objectives: To estimate the proportion and number of cancers occurring in Australia in 2010 attributable to overweight/obesity. Methods: We estimated the population attributable fraction (PAF) and number of cancers causally associated with overweight/obesity. We used standard formulae incorporating Australian prevalence data for body mass index (BMI), relative risks associated with BMI and cancer. We also estimated the proportion change in cancer incidence (potential impact fraction [PIF]) that may have occurred assuming that the prevalence of overweight/obesity had remained at 1990 levels. Results: An estimated 3,917 cancer cases (3.4% of all cancers) diagnosed in 2010 were attributable to overweight/obesity, including 1,101 colon cancers, 971 female post‐menopausal breast cancers and 595 endometrial cancers (PAFs of 10%, 8% and 26%, respectively). Highest PAFs were observed for oesophageal adenocarcinoma (31%), endometrial cancer (26%) and kidney cancer (19%). If the prevalence of overweight/obesity in Australia had remained at levels prevailing in 1990, we estimate there would have been 820 fewer cancers diagnosed in 2010 (PIF 2%). Conclusions: Overweight/obesity causes a substantial number of cancers in Australia. Implications: Public health strategies to reduce the prevalence of overweight and obesity will reduce the incidence of cancer, particularly of the colon, breast and endometrium. 相似文献
37.
Rebecca A. Ellwood Jennifer E. Hewitt Roberta Torregrossa Ashleigh M. Philp Justin P. Hardee Samantha Hughes David van de Klashorst Nima Gharahdaghi Taslim Anupom Luke Slade Colleen S. Deane Michael Cooke Timothy Etheridge Mathew Piasecki Adam Antebi Gordon S. Lynch Andrew Philp Siva A. Vanapalli Matthew Whiteman Nathaniel J. Szewczyk 《Proceedings of the National Academy of Sciences of the United States of America》2021,118(9)
38.
J. L. Salemi V. E. Whiteman E. M. August K. Chandler A. K. Mbah H. M. Salihu 《Journal of viral hepatitis》2014,21(11):e144-e153
To examine the associations between maternal hepatitis B (HBV) and hepatitis C (HCV) infection status and selected infant neurological outcomes diagnosed at birth, we conducted a population‐based, retrospective cohort study on singleton live births in Florida from 1998 to 2009. Primary exposures included maternal HBV and HCV monoinfection. The neurological outcomes included brachial plexus injury, cephalhematoma, foetal distress, feeding difficulties, intraventricular h aemorrhage and neonatal seizures. Multivariable logistic regression models were used to generate odds ratios (OR) and 95% confidence intervals (CI) that were adjusted for socio‐demographic characteristics, risky behaviours, pregnancy complications and pre‐existing medical conditions, and timing of delivery. The risk of an adverse neurological outcome was higher in infants born to mothers with hepatitis viral infection (7.2% for HCV, 5.0% for HBV), compared with infants of hepatitis virus‐free mothers (4.2%). After adjusting for potential confounders, women with HBV were twice as likely to have infants who suffered from brachial plexus injury (OR = 2.04, 95% CI = 1.15–3.60), while those with HCV had an elevated odds of having an infant with feeding difficulties (OR: 1.32, 95% CI = 1.06–1.64) and a borderline increased likelihood for neonatal seizures (OR = 1.74, 95% CI = 0.98–3.10). Additionally, HCV+ mothers had a 22% increased odds of having an infant with some type of adverse neurological outcome (OR: 1.22, 95% CI = 1.03–1.44). Our findings add to current understanding of the association between maternal HBV/HCV infections and infant neurological outcomes. Further research evaluating the role of maternal HBV and HCV infections (including viraemia, treatment) on pregnancy outcomes is warranted. 相似文献
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