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1.
T J Molloy Y Wang A Horner T M Skerry G A C Murrell 《Journal of orthopaedic research》2006,24(4):842-855
Tendon healing is a complex process consisting of a large number of intricate pathways roughly divided into the phases of inflammation, proliferation, and remodeling. Although these processes have been extensively studied at a variety of levels in recent years, there is still much that remains unknown. This study used microarray analyses to investigate the process at a genetic level in healing rat Achilles tendon at 1, 7, and 21 days postinjury, roughly representing the inflammation, proliferation, and remodeling phases. An interesting temporal expression profile was demonstrated, identifying both known and novel genes and pathways involved in the progression of tendon healing. Both inflammatory response and pro-proliferative genes were shown to be significantly upregulated from 24 h postinjury through to 21 days. Day 7 showed the largest increase in genetic activity, particularly with the expression of collagens and other extracellular matrix genes. Interestingly, there was also evidence of central nervous system-like glutamate-based signaling machinery present in tendon cells, as has recently been shown in bone. This type of signaling mechanism has not previously been shown to exist in tendon. Another novel finding from these analyses is that there appears to be several genes upregulated during healing which have exclusively or primarily been characterized as key modulators of proliferation and patterning during embryonic development. This may suggest that similar pathways are employed in wound healing as in the tightly regulated progression of growth and development in the embryo. These results could be of use in designing novel gene-based therapies to increase the efficacy and efficiency of tendon healing. 相似文献
2.
The century-old effort to rid Trichinella spiralis from the food supply has had variable success, and in some regions trichinellosis remains a serious public health concern. However, the research advanced during the past 5 years points toward greater success in developing practical and efficient control strategies. The application of monoclonal antibody and recombinant DNA technologies has permitted great improvement in diagnosis and production of diagnostic reagents. Further, the epidemiology of the disease has undergone considerable revision because of the power of DNA analytical technics which are unravelling the complex genetics of Trichinella spiralis. This improved understanding of the parasite's epidemiology is critical to the design of improved control strategies. 相似文献
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Summary The effect of vitamin A deficiency was studied in chickens infected with 500 Ascaridia galli eggs and controls. Diet 1 (deficient, 500 IU vitamin A or 172 μg retinol acetate per kg diet), Diet 2 (deficient, 1000 IU
vitamin A or 344 μg retinol acetate per kg diet) and Diet 3 (sufficient, 1500 IU vitamin A or 516 μg retinol acetate per kg
diet) were assigned to 46 chickens each. Clinical signs, weight gains, livers’ weights, vitamin A levels, worm burdens and
parasite eggs’ excretions were recorded.
Infected chickens had lower weight gains than the controls fed alike. Chickens given Diet 1 stored lesser vitamin A in liver
than those fed Diet 3. Although worm counts in the 3 groups did not differ significantly, chickens fed Diet 1 excreted more
A. galli eggs than those fed the 2 other diets. Female worms harboured by chickens fed Diet 1 had higher fecundity at week 5 pi than
those of chickens fed Diet 2. Results indicated that Vitamin A is important for poultry in the moderation of the infection
with A. galli. 相似文献
5.
T.G.C. Murrell 《Medical hypotheses》1991,36(4):389-396
Damage to the breast epithelium by chemical carcinogens as products of oxygen free radical release can lead to fibroblast proliferation, hyperplasia of epithelium, cellular atypia and breast cancer. Chemical carcinogens may accumulate in breast fluid in the non-lactating breast consequent to superoxide free radical production which occurs via the adenosine triphosphate (ATP) hypoxanthine pathway. This pathway is initiated by hypoxia of local tissue. Under hypoxic conditions ATP is broken down to form hypoxanthine. Hypoxanthine itself is broken down to produce xanthine and then uric acid. This results in the production of superoxide free radicals, the products of which are carcinogenic. The development of localized hypoxia, which is central to this hypothesis, is caused by acinal gland distention from fluid secreted by raised prolactin levels in the absence of oxytocin. Stimulation of the nipple in a non-lactating breast may raise plasma oxytocin and lower plasma prolactin levels. Contraction of the myoepithelial cells of the breast under the influence of oxytocin would relieve distention of the acinal glands and thus reduce hypoxia and the generation of lipid peroxidoses as products of free radical damage. The epidemiology of breast fibrosis and cancer support the notion that lack of nipple stimulation over time may be a significant variable. A review of this literature linked with current biochemical work on fibrosis and carcinogenesis suggest that draining the breasts of the products of superoxide free-radical release by the encouragement of regular nipple erections may prevent such breast disease. 相似文献
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7.
An association between variants in the IGF2 gene and Beckwith-Wiedemann syndrome: interaction between genotype and epigenotype 总被引:5,自引:0,他引:5
Murrell A Heeson S Cooper WN Douglas E Apostolidou S Moore GE Maher ER Reik W 《Human molecular genetics》2004,13(2):247-255
Beckwith-Wiedemann syndrome (BWS) is a fetal overgrowth disorder involving the deregulation of a number of genes, including IGF2 and CDKN1C, in the imprinted gene cluster on chromosome 11p15.5. In sporadic BWS cases the majority of patients have epimutations in this region. Loss of imprinting of the IGF2 gene is frequently observed in BWS, as is reduced CDKN1C expression related to loss of maternal allele-specific methylation (LOM) of the differentially methylated region KvDMR1. The causes of epimutations are unknown, although recently an association with assisted reproductive technologies has been described. To date the only genetic mutations described in BWS are in the CDKN1C gene. In order to screen for other genetic predispositions to BWS, the conserved sequences between human and mouse differentially methylated regions (DMRs) of the IGF2 gene were analyzed for variants. Four single nucleotide polymorphisms (SNPs) were found in DMR0 (T123C, G358A, T382G and A402G) which occurred in three out of 16 possible haplotypes: TGTA, CATG and CAGA. DNA samples from a cohort of sporadic BWS patients and healthy controls were genotyped for the DMR0 SNPs. There was a significant increase in the frequency of the CAGA haplotype and a significant decrease in the frequency of the CATG haplotype in the patient cohort compared to controls. These associations were still significant in a BWS subgroup with KvDMR1 LOM, suggesting that the G allele at T382G SNP (CAGA haplotype) is associated with LOM at KvDMR1. This indicates either a genetic predisposition to LOM or interactions between genotype and epigenotype that impinge on the disease phenotype. 相似文献
8.
C. M. O. Kapel P. Webster P. Lind E. Pozio S.-A. Henriksen K. D. Murrell P. Nansen 《Parasitology research》1998,84(4):264-271
The infectivity of Trichinella spiralis, T. nativa, and T. britovi was experimentally compared in pigs. Blood sampling was performed weekly, and muscle juices were obtained at slaughter 10
weeks after inoculation. Muscle larvae were found in all of four pigs inoculated with T. spiralis [mean 190 larvae per gram (lpg)] and in three of four pigs inoculated with T. britovi (mean 7 lpg). No larvae were found in pigs inoculated with T. nativa. For T. spiralis and T. britovi, the neck muscle (m. splenius) appears to be a predilection site in addition to the tongue, the diaphragm, and the jaw. High antibody responses were found
in all experimental groups, independent of the antigen used, and even in pigs in which no muscle larvae were recovered. The
strong and consistent antibody response found with meat juice indicates the usefulness of this material where a blood sample
is not obtainable, e.g. meat samples from wild animals. Immunoblotting (Western blots) on slaughter sera revealed no species
specificity when comparing homologous versus heterologous staining.
Received: 30 July 1997 / Accepted: 25 September 1997 相似文献
9.
10.
This study investigates the accuracy and reliability of a novel handheld indentation system designed to ascertain the dynamic biomechanical properties of articular cartilage. A series of standard elastomers were assessed with both the handheld indentation system and a bench-top dynamic indentation system to assess the accuracy of the instrument. Interoperator and intraoperator experiments were undertaken to investigate the reliability of the system when used by an individual operator and by five different operators. Intraclass coefficients (Rho) were derived using a random effects model. The system was then used to ascertain the topographical variation in the shear moduli and phase lag of articular cartilage across normal ovine tibial plateaux. The system was shown to be highly accurate (R2 = 0.97), and had excellent reliability when measuring the dynamic shear modulus of articular cartilage (interoperator Rho = 0.75, intraoperator Rho = 0.79). Measurement of static shear modulus was less reliable (interoperator Rho = 0.15, intraoperator Rho = 0.52), but may be improved by monitoring the load applied to the instrument by the operator. The instrument was used to differentiate between different regions of cartilage and generated a topographical map of an ovine tibial plateau. The cartilage located beneath the menisci was 200-500% stiffer than the cartilage that was not covered by the menisci, while the phase lag was almost constant (10+/-2 SD) over the entire tibial plateau. The system was shown to be an accurate and reliable tool for rapidly assessing the dynamic biomechanical properties of articular cartilage, while being small enough to be used arthroscopically. 相似文献