Abstract：
:Conventional therapies for low back pain (LBP) are purely symptomatic and do not target the cause of LBP, which in approximately 40% of cases is caused by degeneration of the intervertebral disc (DIVD). Targeting therapies to inhibit the process of degeneration would be a potentially valuable treatment for LBP. There is increasing evidence for a role for IL-1 in DIVD. A natural inhibitor of IL-1 exists, IL-1Ra, which would be an ideal molecular target for inhibiting IL-1-mediated effects involved in DIVD and LBP. In this study, the feasibility of ex vivo gene transfer of IL-1Ra to the IVD was investigated. Monolayer and alginate cultures of normal and degenerate human intervertebral disc (IVD) cells were infected with an adenoviral vector carrying the IL-1Ra gene (Ad-IL-1Ra) and protein production measured using an enzyme-linked immunosorbent assay. The ability of these infected cells to inhibit the effects of IL-1 was also investigated. In addition, normal and degenerate IVD cells infected with Ad-IL-1Ra were injected into degenerate disc tissue explants and IL-1Ra production in these discs was assessed. This demonstrated that both nucleus pulposus and annulus fibrosus cells infected with Ad-IL-1Ra produced elevated levels of IL-1Ra for prolonged time periods, and these infected cells were resistant to IL-1. When the infected cells were injected into disc explants, IL-1Ra protein expression was increased which was maintained for 2 weeks of investigation. This in vitro study has shown that the use of ex vivo gene transfer to degenerate disc tissue is a feasible therapy for the inhibition of IL-1-mediated events during disc degeneration.
journal_name
Int J Exp Patholjournal_title
International journal of experimental pathologyauthors
Le Maitre CL,Freemont AJ,Hoyland JAdoi
10.1111/j.0959-9673.2006.00449.xsubject
Has Abstractpub_date
2006-02-01 00:00:00pages
17-28issue
1eissn
0959-9673issn
1365-2613pii
IEP449journal_volume
87pub_type
杂志文章abstract：:We determined the feasibility of producing protoporphyric hepatopathy in unrestrained rats by infusing protoporphyrin into their portal circulation via chronic indwelling catheters. Sprague-Dawley rats, 200-300 g, received single (8.5-27.8 mumol) or multiple (64.1-208.7 mumol) infusions of protoporphyrin over 3-240 h....
journal_title：International journal of experimental pathology
pub_type： 杂志文章
doi：
更新日期：1992-10-01 00:00:00
abstract：:Summary K-ras mutations are found in 40-50% of human colorectal adenomas and carcinomas, but their functional contribution remains incompletely understood. Here, we show that a conditional mutant K-ras mouse model (K-ras(Asp12)/Cre), with transient intestinal Cre activation by beta-Naphthoflavone (beta-NF) treatment, ...
journal_title：International journal of experimental pathology
pub_type： 杂志文章
doi：10.1111/j.1365-2613.2009.00667.x
更新日期：2009-10-01 00:00:00
abstract：:Administration of mercuric chloride (HgCl(2)) to Brown Norway rats causes Th2-dominated autoimmunity with raised immunoglobulin E concentrations and gut vasculitis, both of which are T-cell dependent, peak at 14 days after starting HgCl(2) and then spontaneously resolve. If animals are re-challenged with HgCl(2) 6 wee...
journal_title：International journal of experimental pathology
pub_type： 杂志文章
doi：10.1111/j.0959-9673.2004.00382.x
更新日期：2004-06-01 00:00:00
abstract：:C-cell tumours of the thyroid gland are among the most common spontaneous neoplasms of the laboratory rat. With the exception of calcitonin, little attention has been paid to the secretory peptides of C cells during the development of neoplasia. Of these peptides, somatostatin (SS) is of particular interest because it...
journal_title：International journal of experimental pathology
pub_type： 杂志文章
doi：10.1111/j.0959-9673.2004.00367.x
更新日期：2004-02-01 00:00:00
abstract：:An autoimmune kidney disease morphologically and functionally similar to Heymann nephritis (HN) was induced in mature male Sprague Dawley rats by repeated weekly IP injections of a chemically modified azo sonicated ultracentrifuged (u/c) rat kidney fraction 3 (rKF3) antigen in an aqueous medium. The experiment was ter...
journal_title：International journal of experimental pathology
pub_type： 杂志文章
doi：10.1111/j.0959-9673.2004.00389.x
更新日期：2004-10-01 00:00:00
abstract：:The pathogenesis of dengue haemorrhagic fever (DHF) is incompletely understood but it has been suggested that various cytokines may have a role in the process. In this study the profile of the cytokine Transforming Growth Factor-beta 1 (TGF-beta1) was investigated in the sera of 79 patients with various grades of deng...
journal_title：International journal of experimental pathology
pub_type： 杂志文章
doi：10.1046/j.1365-2613.1999.00107.x
更新日期：1999-06-01 00:00:00
abstract：:Ureteropelvic junction (UPJ) obstruction is the most frequently observed cause of obstructive nephropathy in children. Neonatal and foetal animal models have been developed that mimic closely what is observed in human disease. The purpose of this review is to discuss how obstructive nephropathy alters kidney histology...
journal_title：International journal of experimental pathology
pub_type： 杂志文章,评审
doi：10.1111/j.1365-2613.2010.00727.x
更新日期：2011-06-01 00:00:00
abstract：:The Fell-Muir Award requires the recipient to deliver a lecture and a review manuscript which provides a personal overview of significant scientific developments in the field of matrix biology over the period of the recipient's career. In this context, this review considers the collagen family of structural proteins a...
journal_title：International journal of experimental pathology
pub_type： 杂志文章,评审
doi：10.1111/j.1365-2613.2007.00537.x
更新日期：2007-08-01 00:00:00
abstract：:The original two strains of Mycoplasma genitalium were isolated from the human urogenital tract. No other strains have been isolated from this site since then. We have recently succeeded in propagating a third strain from a urogenital specimen from a patient with urethritis in Vero cell cultures. By electron microscop...
journal_title：International journal of experimental pathology
pub_type： 杂志文章
doi：
更新日期：1994-04-01 00:00:00
abstract：:The acute phase of experimental Chagas' disease in rats is associated with early lesions of the post-ganglionic sympathetic nerve terminals of the heart, the varicosities being the target. In the superior cervical and stellate ganglia the preganglionic fibres showed no signs of lesion in the course of experimental Cha...
journal_title：International journal of experimental pathology
pub_type： 杂志文章
doi：10.1046/j.1365-2613.1996.00971.x
更新日期：1996-06-01 00:00:00
abstract：:Groups of mice were given oestrone acetate or vitamin E subcutaneously to determine how these treatments might modify responses to endotoxic lipopolysaccharide given intraperitoneally. Release of hepatic transaminase and tumour necrosis factor (TNF) into serum and induction of manganous superoxide dismutase in the liv...
journal_title：International journal of experimental pathology
pub_type： 杂志文章
doi：
更新日期：1993-06-01 00:00:00
abstract：:The α2-adrenoceptors regulate the sympathetic nervous system, controlling presynaptic catecholamine release. However, the role of the α2-adrenoceptors in cutaneous wound healing is poorly understood. Mice lacking both the α2A/α2C-adrenoceptors were used to evaluate the participation of the α2-adrenoceptor during cutan...
journal_title：International journal of experimental pathology
pub_type： 杂志文章
doi：10.1111/iep.12093
更新日期：2014-10-01 00:00:00
abstract：:The formation of new blood vessels, angiogenesis, is an important event in inflammation, wound healing and tumour growth. Mediators produced by various cells when exposed to endotoxin include cytokines (tumour necrosis factor, interleukins 1 and 6, and basic fibroblast growth factor) which, it has been suggested, stim...
journal_title：International journal of experimental pathology
pub_type： 杂志文章
doi：
更新日期：1994-06-01 00:00:00
abstract：:A simple method is presented for selective cell culture of human mesangial cells using explantation of mesangial cell hillocks. Glomeruli which had been incubated with collagenase were explanted on plastic tissue culture flasks. Three to 6 weeks after explantation, a rapidly growing multilayer of elongated mesangial c...
journal_title：International journal of experimental pathology
pub_type： 杂志文章
doi：
更新日期：1992-02-01 00:00:00
abstract：:The aim of this study was to estimate the relationship of endothelial dysfunction induced by intracellular S-adenosylhomocysteine (SAH) accumulation and DNA methylation in human umbilical vein endothelial cells (HUVEC). The isolated HUVEC were incubated with 3-deazaadenosine (DZA) to induce experimental intracellular ...
journal_title：International journal of experimental pathology
pub_type： 杂志文章
doi：10.1111/j.1365-2613.2009.00687.x
更新日期：2009-12-01 00:00:00
abstract：:The relationship between donor age and the growth characteristics of normal human smooth muscle cell cultures derived from aorta and stomach was examined in a series of growth studies. A negative correlation was demonstrated between donor age and growth potential of both cell types in primary culture. This decreased g...
journal_title：International journal of experimental pathology
pub_type： 杂志文章
doi：
更新日期：1991-12-01 00:00:00
abstract：:Blister formation and skin damage can be induced by BaP1, a haemorrhagic metalloproteinase from the venom of the snake Bothrops asper. Pathological changes in the skin were investigated after intramuscular injections of Bothrops asper haemorrhagic metalloproteinase BaP1. Blisters developed within the first hour, with ...
journal_title：International journal of experimental pathology
pub_type： 杂志文章
doi：
更新日期：1998-08-01 00:00:00
abstract：:A recent global gene expression profiling study unexpectedly showed that activated oncogenic NRAS may recruit neural precursor cell expressed, developmentally downregulated 4L (Nedd4L; a human homologue of Nedd4-2) in cultured melanoma cells. However, whether Nedd4L was expressed in melanoma tissues or participated in...
journal_title：International journal of experimental pathology
pub_type： 杂志文章
doi：10.1111/iep.12051
更新日期：2014-02-01 00:00:00
abstract：:Nonalcoholic steatohepatitis (NASH) is one of the life-threatening hepatic diseases; however, its pathogenesis is still unknown. To evaluate the causative role of hyperlipidaemia and high-fat diet, we compared C57BL/6 mice with inherited hyperlipidaemic model mice (LDLR(-/-)mice and ApoE(-/-) mice) fed a normal or a h...
journal_title：International journal of experimental pathology
pub_type： 杂志文章
doi：10.1111/j.0959-9673.2004.00401.x
更新日期：2004-12-01 00:00:00
abstract：:The interradicular region of primary molars is permeated by many foramina, channels and accessories that connect the pulp cavity with the periapical tissues anatomically. Thus, pulp decomposition products or drugs used in endodontic treatment can trigger inflammatory reactions. The aim of this study was to evaluate th...
journal_title：International journal of experimental pathology
pub_type： 杂志文章
doi：10.1111/iep.12292
更新日期：2018-10-01 00:00:00
abstract：:Tumour growth is angiogenesis dependent. Thrombosis and thromboembolism are very common in cancer patients. These patients are often treated with heparin as an anti-coagulant. Many tumour angiogens, including VEGF165, and endogenous anti-angiogenesis factors bind heparin tightly. Using the non-surgical mesenteric-wind...
journal_title：International journal of experimental pathology
pub_type： 杂志文章
doi：10.1046/j.1365-2613.2000.00150.x
更新日期：2000-06-01 00:00:00
abstract：:Over the past 40 years there have been giant steps forward in our understanding of cellular and molecular biology that have given us the framework by which to understand tissue organization and tissue function on a range of scales. However, although the progress has been great, the more we have discovered, the more we...
journal_title：International journal of experimental pathology
pub_type：
doi：10.1111/j.1365-2613.2010.00719.x
更新日期：2010-06-01 00:00:00
abstract：:Reovirus type 2-induced diabetes-like syndrome in suckling mice is considered to be an animal model for human insulin-dependent diabetes mellitus. We have previously demonstrated that immunopathologic pancreatic islet cell damage might be relevant to reovirus type 2 infection. In this study the involvement of adhesion...
journal_title：International journal of experimental pathology
pub_type： 杂志文章
doi：
更新日期：1995-12-01 00:00:00
abstract：:Several methods have been described for investigating chondrocyte metabolism in vitro. In this study, in-situ hybridization (ISH) using an oligonucleotide probe (i.e. a poly-d(T) probe) to detect total messenger RNA (mRNA) in cartilage explants has been compared with radiosulphate and radioleucine uptake studies in an...
journal_title：International journal of experimental pathology
pub_type： 杂志文章
doi：
更新日期：1991-04-01 00:00:00
abstract：:Heparan sulphate (HS) sits at the interface of the cell and the extracellular matrix. It is a member of the glycosaminoglycan family of anionic polysaccharides with unique structural features designed for protein interaction and regulation. Its client proteins include soluble effectors (e.g. growth factors, morphogens...
journal_title：International journal of experimental pathology
pub_type： 杂志文章
doi：10.1111/iep.12135
更新日期：2015-08-01 00:00:00
abstract：:Diets enriched with fat, especially unsaturated fat, promote experimental pancreatic carcinogenesis, but little is known of the effects of individual fatty acids. The effect of stearic and oleic acid on pancreatic fatty acids and atypical acinar cell nodules (preneoplastic lesions) was studied in 14-day-old weanling m...
journal_title：International journal of experimental pathology
pub_type： 杂志文章
doi：
更新日期：1991-10-01 00:00:00
abstract：:Most patients with epithelial ovarian cancer (EOC) are diagnosed at an advanced stage, and therapeutic options for these patients are limited. The identification of suitable biomarkers could be helpful for patients with EOC, who might benefit from targeted therapies even in advanced stages of the disease. Trophoblast ...
journal_title：International journal of experimental pathology
pub_type： 杂志文章
doi：10.1111/iep.12174
更新日期：2016-04-01 00:00:00
abstract：:Interstitial fibrosis, associated with extensive accumulation of extracellular matrix constituents in the cortical interstitium, is directly correlated to progression of renal disease. The earliest histological marker of this progression is the accumulation in the interstitium of fibroblasts with the phenotypic appear...
journal_title：International journal of experimental pathology
pub_type： 杂志文章,评审
doi：10.1111/j.1365-2613.2011.00764.x
更新日期：2011-06-01 00:00:00
abstract：:A reversible impairment in the ability of the liver to secrete cholephilic compounds has been reported to exist in infant rats born from mothers with surgically induced complete cholestasis during the last third of the pregnancy. Canalicular plasma membranes (CPM) were purified from livers obtained from 4 and 8 week-o...
journal_title：International journal of experimental pathology
pub_type： 杂志文章
doi：10.1046/j.1365-2613.1997.360372.x
更新日期：1997-12-01 00:00:00
abstract：:Regression of submandibular acinar cell hyperplasia after withdrawal of the mitogenic stimulus induced by isoprenaline was studied in male Wistar rats. Intraperitoneal administration of 39 mg of isoprenaline, in divided doses over a 9-day period, resulted in a marked increase in gland size and weight. The proportional...
journal_title：International journal of experimental pathology
pub_type： 杂志文章
doi：
更新日期：1995-08-01 00:00:00
