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31.
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
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WILLIAM W. O'NEILL M.D. PATRICK SERRUYS M.D. Ph.D. MERRILL KNUDTSON M.D. † GERRIT-ANN VAN ES M.D.‡ GERALD C. TIMMIS M.D. § COEN VAN DER ZWAAN M.D. JAY KLEIMAN M.D. M.P.A. ¶ KERRY BARKER Ph.D. ¶ ROGER DREILING M.D. # RICHARD HUBBARD M.D. ¶ JOHN ALEXANDER M.D. M.P.H. ¶ ROBERT ANDERS PHARM.D. ¶ 《Journal of interventional cardiology》1999,12(2):109-116
Clinical trials have demonstrated the efficacy of glycoprotein (GP) IIb/IIIa antagonists in preventing the thrombotic end points of death, myocardial infarction, and urgent revascularization when they are administered at the time of percutaneous coronary revascularization (PTCR). It has been postulated that prolongation of receptor blockade beyond acute intervention would extend the clinical benefit of these agents. The Evaluation of Oral Xemilofiban in Controlling Thrombotic Events (EXCITE) study was a multicenter, international, randomized placebo-controlled trial of the oral GP IIb/IIIa antagonist Xemilofiban administered prior to and after PTCR. The study was designed to assess the efficacy and safety of continuing oral xemilofiban for 6 months to prevent these primary thrombotic end points. More than 7,200 patients were randomized in 29 countries to receive placebo or one of two doses of xemilofiban. Stenting was performed at the discretion of the operator. All patients received aspirin and periprocedural heparin; all stented patients received continuous xemilofiban, or ticlopidine for 2–4 weeks followed by xemilofiban-placebo. Most patients were also evaluated 1 month after conclusion of the study drug treatment. Clinical data from up to 6 months of drug treatment and 1 month posttreatment were used to evaluate the acute and long-term efficacy and safety of xemilofiban. Secondary end points included the need for any revascularization, repeat hospitalization for unstable angina, and nonhemorrhagic stroke. The cumulative incidence of bleeding events and effects of xemilofiban in stented and nonstented patients were evaluated. The efficacy of continuing xemilofiban and aspirin therapy as the sole antithrombotic medications following stent deployment was assessed against a ticlopidine and aspirin control group. The incremental clinical benefit of long-term receptor blockade over acute receptor antagonism was evaluated. 相似文献
35.
ES Dimitry MRCOG M Phil RK Atalla RCOG 《International journal of clinical practice》1996,50(7):376-380
The recent increase in the incidence of ectopic pregnancies was associated with rapid improvement in the diagnostic and therapeutic techniques. Quantitative serum B-HCG radioimmunoassay and high resolution vaginal ultrasonography have facilitated early diagnosis of ectopic pregnancy allowing a more conservative approach to patient management. Different conservative surgical and medical lines of management recently developed were associated with and increased chance of subsequent intrauterine pregnancy with no increase in the incidence of repeat ectopic pregnancy. Outpatient systemic medical treatment seems to be a preferred alternative to conservative surgery. In selected cases, it is associated with a lower complication rate and promising result for fertility. (Br J Clin Pract 1996; 50(7) : 376-380.) 相似文献
36.
乙肝病毒和人乳头状瘤病毒分别是肝细胞癌和子宫颈癌的风险因素,针对这2种病毒感染的疫苗已在临床上成功用于癌症化学预防。分子靶向药物能够预防乳腺癌(雷洛昔芬与他莫昔芬)、大肠腺瘤(塞来昔布)和前列腺癌(非那雄胺)。然而,化学预防广泛应用于临床还不现实。分子靶标的深入研究将扩展化学预防的范围并使其个性化。 相似文献
37.
Contact allergy in relation to hand eczema and atopic diseases in north Norwegian schoolchildren 总被引:3,自引:0,他引:3
Dotterud LK, Falk ES. Contact allergy in relation to hand eczema and atopic diseases in north Norwegian schoolchildren. Acta Psediatr 1995;84:402–6. Stockholm. ISSN 0803–5253
Patch testing was carried out in 424 schoolchildren (223M, 201F), aged 7–12 years, in northern Norway. In 99 (23.3%) of these children, one or more allergic patch test reactions were demonstrated; 30 children reacted to two and 6 to three or more substances; 53 irritant reactions were recorded in 33 (7.8%) of those tested. From a total of 144 positive tests, the most common allergen was nickel (14.9%), followed by cobalt (5.7%), kathon CG (5.2%), lanolin (1.7%) and neomycin (1.4%). Both allergic and irritant reactions were found twice as frequently in girls as in boys. Positive patch tests were significantly more frequent in atopic (28.8%) than in non–atopic (17.9%) children, being most pronounced in atopic girls (37.4%). Hand eczema was reported to have occurred or to be present in 6.5% of cases. Twenty–nine of 36 children reporting hand eczema participated in the clinical examination. Altogether 15 (3.5%) children had hand eczema at the time of the clinical examination but 12 of these children had no previous history of hand eczema. In 14 of these 15 subjects, the eczema was localized to the back of the hands, with 13 having atopic dermatitis. In 4 of these 15 children, an allergic patch test reaction was found; however, in only 2 of these 4 was the test considered to be clinically relevant for the diagnosis allergic hand eczema. In conclusion, irritant hand eczema may occur in early childhood and is most prevalent in children with atopic dermatitis 相似文献
Patch testing was carried out in 424 schoolchildren (223M, 201F), aged 7–12 years, in northern Norway. In 99 (23.3%) of these children, one or more allergic patch test reactions were demonstrated; 30 children reacted to two and 6 to three or more substances; 53 irritant reactions were recorded in 33 (7.8%) of those tested. From a total of 144 positive tests, the most common allergen was nickel (14.9%), followed by cobalt (5.7%), kathon CG (5.2%), lanolin (1.7%) and neomycin (1.4%). Both allergic and irritant reactions were found twice as frequently in girls as in boys. Positive patch tests were significantly more frequent in atopic (28.8%) than in non–atopic (17.9%) children, being most pronounced in atopic girls (37.4%). Hand eczema was reported to have occurred or to be present in 6.5% of cases. Twenty–nine of 36 children reporting hand eczema participated in the clinical examination. Altogether 15 (3.5%) children had hand eczema at the time of the clinical examination but 12 of these children had no previous history of hand eczema. In 14 of these 15 subjects, the eczema was localized to the back of the hands, with 13 having atopic dermatitis. In 4 of these 15 children, an allergic patch test reaction was found; however, in only 2 of these 4 was the test considered to be clinically relevant for the diagnosis allergic hand eczema. In conclusion, irritant hand eczema may occur in early childhood and is most prevalent in children with atopic dermatitis 相似文献
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Inhibition of 2-nitropropane-induced rat liver DNA and RNA damage by benzyl selenocyanate 总被引:3,自引:2,他引:3
We observed that pretreatment of male F344 rats with benzyl selenocyanate,
a versatile organoselenium chemopreventive agent in several animal model
systems, decreases the levels of DNA and RNA modifications produced in the
liver by the hepatocarcinogen 2- nitropropane. To clarify the mechanisms
involved, we pretreated male F344 rats with either benzyl selenocyanate,
its sulfur analog benzyl thiocyanate, phenobarbital or cobalt
protoporphyrin IX; the latter is a depletor of P450. We then determined (1)
the ability of liver microsomes to denitrify 2-nitropropane, (2) effects on
2-nitropropane- induced liver DNA and RNA modifications and (3) amount of
nitrate excreted in rat urine following administration of the carcinogen.
Pretreatment with benzyl selenocyanate or phenobarbital increased the
denitrification activity of liver microsomes by 217 and 765%, respectively,
increased liver P4502B1 by 31- and 435-fold, respectively, decreased the
levels of 2-nitropropane-induced modifications in liver DNA (29-70% and
17-30%, respectively) and RNA (67-85% and 30-50%, respectively), and
increased the 24-h urinary excretion of nitrate by 157 and 209%,
respectively. Pretreatment with benzyl thiocyanate had no significant
effect on any of these parameters. Pretreatment with cobalt protoporphyrin
IX decreased liver P4502B 1 by 87%, decreased the denitrification activity
of liver microsomes by 76%, decreased the 24 h urinary excretion of nitrate
by 88.5%, but increased the extent of 2-nitropropane-induced liver nucleic
acid modifications by 17-67%. These results indicate that the metabolic
sequence from 2-nitropropane to the reactive species causing DNA and RNA
modifications does not involve the removal of the nitro group. Moreover,
they suggest that benzyl selenocyanate inhibits 2-NP-induced liver nucleic
acid modifications in part by increasing its detoxication through induction
of denitrification, although it is evident that other mechanisms must also
be involved.
相似文献
40.