首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献,搜索用时 15 毫秒
1.

Introduction

Ligament and meniscal damage can cause joint disease. Arthritic joints contain increased amounts of epidermal growth factor receptor (EGFR) protein, and polymorphisms in EGFR are associated with arthritis risk. The role of endogenous EGFR regulation during joint disease due to ligament and meniscal trauma is unknown. Mitogen-inducible gene 6 (MIG-6) can reduce EGFR phosphorylation and downstream signaling. We examined the effect of EGFR modulation by MIG-6 on joint disease development after ligament and meniscus injury.

Methods

Knee ligament transection and meniscus removal were performed surgically on mice homozygous for a global inactivating mutation in MIG-6 (Mig-6−/−) and in wild-type (WT) animals.

Results

Two weeks after surgery, Mig-6−/−mice had bone erosion as well as greater fibrous tissue area and serum RANKL concentration than WT mice. Four weeks after surgery, Mig-6−/−mice had less cartilage and increased cell proliferation relative to contralateral control and WT knees. Increased apoptotic cells and growth outside the articulating region occurred in Mig-6−/−mice. Tibia trabecular bone mineral density (BMD) and the number of trabeculae were lower in surgically treated knees relative to the respective control knees for both groups. BMD, as well as trabecular thickness and number, were lower in surgically treated knees from Mig-6−/−mice relative to WT surgically treated knees. Phosphorylated EGFR staining in surgically treated knees decreased for WT mice and increased for Mig-6−/−mice. Fewer inflammatory cells were present in the knees of WT mice.

Conclusion

Mig-6−/−mice have rapid and increased joint damage after ligament and meniscal trauma. Mig-6 modification could lessen degenerative disease development after this type of injury.  相似文献   

2.
W. M. Pulliam 《Oecologia》1992,91(1):126-128
Summary Methane emissions were observed from knees of baldcypress (Taxodium distichum) in floodplain swamps of the Ogeechee river, a blackwater river in the lower coastal plain of Georgia, USA Emissions were sampled on 10 dates from March 1988 to September 1989, with small chambers placed over single knees. Methane emission rates from individual knees averaged 0.90 mg/d, corresponding to an average of 0.14 mg m–2 d–1 for the whole floodplain. In the habitat with the highest knee density (0.42 knees/m2), the average rate was 0.55 mg m–2 d–1. Spatial patterns in emissions from knees were similar to those of overall methane emissions from the swamp surface, though because of their low density were a minor contribution (0.42%) to total methane emissions from this system.  相似文献   

3.
In this sheep study, we have tested the hypothesis that an osteogenic response is triggered in the subchondral bone by periosteum implanted in full thickness cartilage defects and can be prevented by replacing the periosteum by a cell-free collagen type I/III membrane. Two 7-mm diameter osteochondral defects were made in the trochlea groove and in the medial femoral condyle of one of the knees in each of 15 adult sheep. The animals were divided into three groups (n=5): a control group with untreated cartilage defects, a group treated with autologous chondrocyte transplantation (ACT) and periosteum, and a group treated with ACT in combination with a collagen I/III membrane cover. Histological examination was performed 1 year later. The optical density of the subchondral bone in the histological sections was measured with digital imaging software. There was a dramatic, statistically significant (P<0.0001; power=1) increase in bone density of 45%–70% under defects that were treated with the periosteal cover, compared with the collagen membrane and control groups, which displayed the same bone density. There was no difference in the cartilaginous reparative tissue in the defects in the three groups. Periosteum thus stimulates the remodelling process in subchondral bone. Stiffening of the subchondral bone can lead to degeneration of the overlying reparative cartilaginous tissue because of an increase in the mechanical stress in the tissue. These findings warrant evaluation of subchondral bone changes in patients treated by ACT and the correlation of these changes with clinical outcome.  相似文献   

4.

Introduction

Detection of (subclinical) synovitis is relevant for both early diagnosis and monitoring of therapy of rheumatoid arthritis (RA). Previously, the potential of imaging (sub)clinical arthritis was demonstrated by targeting the translocator protein in activated macrophages using (R)-[11C]PK11195 and positron emission tomography (PET). Images, however, also showed significant peri-articular background activity. The folate receptor (FR)-β is a potential alternative target for imaging activated macrophages. Therefore, the PET tracer [18F]fluoro-PEG-folate was synthesized and evaluated in both in vitro and ex vivo studies using a methylated BSA induced arthritis model.

Methods

[18F]fluoro-PEG-folate was synthesized in a two-step procedure. Relative binding affinities of non-radioactive fluoro-PEG-folate, folic acid and naturally circulating 5-methyltetrahydrofolate (5-Me-THF) to FR were determined using KB cells with high expression of FR. Both in vivo [18F]fluoro-PEG-folate PET and ex vivo tissue distribution studies were performed in arthritic and normal rats and results were compared with those of the established macrophage tracer (R)-[11C]PK11195.

Results

[18F]fluoro-PEG-folate was synthesized with a purity >97%, a yield of 300 to 1,700 MBq and a specific activity between 40 and 70 GBq/µmol. Relative in vitro binding affinity for FR of F-PEG-folate was 1.8-fold lower than that of folic acid, but 3-fold higher than that of 5-Me-THF. In the rat model, [18F]fluoro-PEG-folate uptake in arthritic knees was increased compared with both contralateral knees and knees of normal rats. Uptake in arthritic knees could be blocked by an excess of glucosamine-folate, consistent with [18F]fluoro-PEG-folate being specifically bound to FR. Arthritic knee-to-bone and arthritic knee-to-blood ratios of [18F]fluoro-PEG-folate were increased compared with those of (R)-[11C]PK11195. Reduction of 5-Me-THF levels in rat plasma to those mimicking human levels increased absolute [18F]fluoro-PEG-folate uptake in arthritic joints, but without improving target-to-background ratios.

Conclusions

The novel PET tracer [18F]fluoro-PEG-folate, designed to target FR on activated macrophages provided improved contrast in a rat model of arthritis compared with the accepted macrophage tracer (R)-[11C]PK11195. These results warrant further exploration of [18F]fluoro-PEG-folate as a putative PET tracer for imaging (sub)clinical arthritis in RA patients.  相似文献   

5.
We present the results of molecular dynamics (MD) computer simulations of rare gas diffusion through breathable nanotubes with pentagon–heptagon pair defects resulting in constrictions and knees. Diffusion involves interrupted high speed “choppy” motion with intermittent reversal in velocity direction. Single atoms exhibit a spiral-like path, in contrast to atoms traveling in groups. Considerable resistance to flow appears to reside in the upstream section of the nanotube where density gradients are small, prior to the constriction. Subsequently, considerable density gradients are present and speeds increase, becoming greatest at the tube exit. For the nanotubes examined, Kr and Xe diffusion was too hindered to provide reliable results. Diffusion of He through the nanotubes with knees occurs in a single-file fashion nearly along the center of the tube and the knee has no detectable effect on the diffusion kinetics. Transport diffusion coefficients are in the order of 10-4–10-2?cm2/s.  相似文献   

6.
Two new field bioassay methods were developed to compare the repellent activity of BioUD® (containing 7.75% 2‐undecanone), 98.1% DEET and 0.5% permethrin against natural populations of nymphal Amblyomma americanum (L.) (Acari: Ixodidae). In a cloth sheet assay, pieces of material measuring 41 × 58 cm, separately treated with one of the test materials or the appropriate solvent carrier, were placed at random on the ground and baited with dry ice for 1 h. Mean numbers of ticks on repellent‐treated sheets were significantly lower than on control sheets. There was no significant difference in the number of ticks collected between sheets treated with BioUD® and those treated with DEET. However, significantly fewer ticks were found on sheets treated with BioUD® or DEET than on permethrin‐treated sheets. In a sock test, over‐the‐calf tube socks were treated with one of the test materials or the appropriate solvent carrier. Human volunteers wore a repellent‐treated and a corresponding carrier‐treated sock on either leg and walked randomly over an area of approximately 4000 m2 for 15 min. Significantly fewer ticks were collected from socks treated with BioUD® or DEET than from socks treated with the carrier and there was no significant difference in repellency between these two agents. No difference in the mean number of ticks collected was found between permethrin‐treated and corresponding carrier‐treated socks. To examine the mechanism of repellency of BioUD®, a four‐choice olfactometer was used to assess spatial repellency against adult A. americanum. As expected in the absence of a repellent, when all choices were represented by water‐treated filter paper, ticks were equally distributed among the choices. When one choice consisted of BioUD®‐treated filter paper and the remaining choices of water‐treated paper, the distribution of ticks on the repellent‐treated paper was significantly lower than might be expected to occur by chance, suggesting that repellency is at least partly achieved by an olfactory mechanism.  相似文献   

7.
Two experiments, one in the winter (January) and the other in the summer (June), were undertaken to treat anestrous buffaloes at a farm. During experiment I, animals were treated with a progesterone releasing intra-vaginal device (PRID)a, whereas during experiment II, animals were allocated to PRID + GnRHb (125 μg) and GnRH-treated (250 μg). In both the experiments, animals were retained as untreated controls. All the treated animals were clinically examined four days post-treatment and inseminated two or three times at 24-hour intervals. The ovulation and fertility rates of PRID, PRID + GnRH and GnRH-treated animals were 25 and 12 %, 43 and 14 %, and 11 and 0 %, respectively. None of the controls exhibited estrus during the course of the study.  相似文献   

8.
Summary Human recombinant DNA interferon gamma (IFN-G), with a specific activity of 2×106 IU/mg protein, was administered s.c. 3 days per week for 2 months to patients with solid tumors. The maximum tolerated dose (MTD) was 10×106 IU/m2 (5.0 mg/m2) per injection, and six patients were treated at the MTD. Two of these ceased treatment because of severe subjective toxity (headache, rigors and pyrexia) and three patients developed WHO grade 3 leucopenia. Subjective toxicity varied considerably between patients and some patients at low dose levels experienced severe constitutional symptoms whilst others treated at the MTD had few side effects. These differences were unrelated to pharmacokinetic parameters. Bioavailability of this IFN-G administered s.c. was very variable from one patient to another at the same dose level. We therefore counsel caution in using this IFN-G preparation s.c. in phase II studies.  相似文献   

9.
Summary The growth promoting capacity of the insecticides/nematicides, Curater (2,3-dihydro-2,2-dimethylbenzofuran-7-yl methylcarbamate), Temik (2-methyl-2-(methylthio) propionaldehyde 0-(methylcarbamoyl) oxim and Mocap (0-ethyl S, S-Dipropyl phosphorodithioate) were compared. For each product, three equimolar doses were applied: 1.3×10−3, 2.6×10−3 and 5.2×10−3 molar per m2. The treatments were applied to a field soil, part of which was untreated, part of which was steamed to test the direct effect of the products on the test plants. In the first experiment wheat, lettuce and mungbeans were sown immediately after broad cast application of the insecticides. In the second experiment three maize cultivars (Suroit, Breda and LG 12) were used as test plants: one half of the soil was treated with the insecticides just before sowing the maize, the other half was originally treated in the previous experiment. Considering the effect on growth (the weight of the two months old wheat and lettuce plants and the length of the mungbeans) in unsteamed and steamed soil increasing amounts of Mocap had a negative effect on the growth of beans and wheat: in contrast the weight of the lettuce was markedly increased. Curater 5G and Temik 10G had no influence on the mungbeans and a slightly positive effect on the growth of lettuce. The growth of wheat was slightly decreased by Temik 10G and slightly increased by Curater 5G. The growth of maize was decreased by increasing amounts of Mocap in both steamed and unsteamed soil. However, in plots treated in the previous experiment the reverse effect was observed, growth being slightly improved.  相似文献   

10.
11.
The effects of slow (apatite, biotite) and fast-release nutrients (P, K, Mg) on C and N mineralization in acid forest soil were studied. These nutrients were applied alone or together with urea or urea and limestone. The production of CO2 in the soil samples taken one and three growing seasons after the application was lower in the soils treated with the fast-release nutrients than in the untreated soils. Similar reduction of microbial activity was not seen after the apatite and apatite+biotite treatments. In the first growing season, urea and urea+limestone enhanced CO2 production, but after three growing seasons, the opposite was true. Apatite and apatite+biotite added together with urea did not compensate for the decreasing effect of urea on the CO2 production. The addition of fast-release salts increased somewhat the concentration of NH inf4 sup+ in the soil and more NH4 + accumulated during laboratory incubation in the soil samples taken one growing season after the application. The urea addition immediately increased the concentrations of NH4 + and of NO3 in the soil, but, three growing seasons after application, urea had only a slight increasing effect on mineral N content of the soil. Slow-release nutrients seem to have a more favourable effect than fast-release salts on nutrient turnover in acid forest soil.  相似文献   

12.
Juvenile (2–23 years old) cynomolgus monkeys are frequently used as recipients in non-human primate islet transplantation studies. The aim of this study was to examine the effects of different doses of streptozotocin (STZ), and find the optimal dose for inducing diabetes in these monkeys. Fifteen juvenile (2–3 years old) cynomolgus monkeys were separated into three groups and administered with different doses of STZ (100, 68 or 60 mg kg−1). Basal and glucose-stimulated blood glucose, insulin, and C-peptide levels, as well as body weights were monitored. Hepatic and renal function tests and pancreatic immunohistochemistry were performed before and after STZ treatment. Monkeys treated with both 100 and 68 mg kg−1 of STZ exhibited continuous hyperglycemia, which coincided with a nearly complete loss of islet β-cells. Two monkeys received 60 mg kg−1 of STZ, but only one became completely diabetic. During the first week following STZ treatment, hepatic and renal function slightly increased in these three groups. However, 24 hours post-STZ, serum total bile acid levels were significantly increased in monkeys treated with 100 mg kg−1 than those treated with 68 mg kg−1 of STZ (P<0.05). These data suggest that 100 mg kg−1 and 68 mg kg−1 of STZ can safely induce diabetes in cynomolgus monkeys aged 2–3 years, but 68 mg kg−1 of STZ, rather than 100 mg kg−1 of STZ, may be more appropriate for inducing diabetes in these monkeys. Furthermore, body surface area, rather than body weight, was a more reliable determinant of dosage, where 700 mg m−2 of STZ should be the lower limit for inducing diabetes in juvenile monkeys.  相似文献   

13.
Roots of Vicia faba were treated with solutions of colchicine or IAA or both. Mitotic indices and the frequencies of the different stages of mitosis were determined immediately after a three hour treatment or following a 24 hour period of recovery. Roots scored after treatment with colchicine for three hours showed several effects, none of which were reversed by simultaneous treatment with IAA. Treatment with IAA for three hours had little detectable effect on mitotic index (MI) on the frequencies of the various stages of mitosis. After a recovery period, following a three hour treatment, of 24 hours, colchicine treated roots showed a significant increase in their MI; this was due largely to an increase in the number of metaphases but it was also due in part to the presence of tetraploid cells in division. IAA treated roots revealed an inhibition of mitotic activity, which was most marked at 3.13–6.26×10–4 M IAA. The results from roots treated with mixtures of colchicine and IAA for three hours and fixed 24 hours later showed: 1) the increase in MI induced by colchicine is reversed by IAA, the intensity of the reversal increasing with increasing concentrations of IAA; 2) reductions in the total numbers of cells in prophase or in metaphase occur after treatment with different concentrations of IAA; 3) IAA leads to a reduction in the number of tetraploid cells seen in division.It appears that colchicine induces a change in the pattern of mitotic activity 24 hours after the end of treatment and its effects are reversed by IAA. At 4.2×10–4 M IAA a balance occurs between the opposing effects of colchicine and IAA and the MI is not significantly different from that of the controls. It is suggested that one result of a treatment with colchicine is a change in the level of growth factors in root meristems. This change, which appears to result in a temporary increase in MI is reversed by the addition of IAA. Thus one of the growth factors, the level of which has been affected, is replaceable by exogenous IAA.  相似文献   

14.
Summary We have investigated the ability of a novel immunopotentiator, 7-thia-8-oxoguanosine (7T8OG) to increase the efficacy of a weakly immunogenic murine L1210 leukemia vaccine. The vaccine was prepared by irradiating L1210 leukemia cells in a cesium source with a total of 6000-R dose. DBA/2 mice were treated with 150 mg/kg 7T8OG and/or with vaccine consisting of 107 irradiated cells. In combination therapy, mice first received the vaccine and then were injected with 75 mg/kg 7T8OG 2 h and 4 h after vaccination. One week after the last treatment all mice were inoculated with 104 live leukemia cells intraperitoneally. Control, untreated mice (n = 66) injected with 104 live leukemia cells had a mean survival time ± standard error of 10.5±0.2 days. Treating mice (n = 66) with one, two or three doses of 7T8OG administered i.p. 1 week apart did not increase survival (mean survival time = 10.7 days). Mice immunized with one, two or three doses of vaccine had 14.5±1.1, 45.4±6.2 and 68.3±10.6 days mean survival, respectively. 7T8OG-stimulated vaccination increased the survival dramatically. The best survival was noted when the mice were treated with 2× (vaccine + 7T8OG). Immunization of mice (n = 30) with this treatment regimen increased the mean survival to 156±10.0 days. Over 90% of mice that were treated this way had a cumulative survival time greater than 160 days. In contrast, only 12% of the mice immunized twice with the leukemia vaccine alone survived over 160 days. These results suggest a rationale for the use of this immuno-potentiator with various vaccines for a more effective immunization.  相似文献   

15.
Evolved resistance to the herbicide glyphosate has been reported in eleven weed species, including Lolium multiflorum. Two glyphosate-resistant L. multiflorum populations were collected, one from Chile (SF) and one from Oregon, USA (OR), and the mechanisms conferring glyphosate resistance were studied. Based on a Petri dish dose–response bioassay, the OR and the SF populations were two and fivefold more resistant to glyphosate when compared to the susceptible (S) population, respectively; however, based on a whole-plant dose–response bioassay, both OR and SF populations were fivefold more resistant to glyphosate than the S population, implying that different resistance mechanisms might be involved. The S population accumulated two and three times more shikimic acid in leaf tissue 96 h after glyphosate application than the resistant OR and SF populations, respectively. There were no differences between the S and the glyphosate-resistant OR and SF populations in 14C-glyphosate leaf uptake; however, the patterns of 14C-glyphosate translocation were significantly different. In the OR population, a greater percentage of 14C-glyphosate absorbed by the plant moved distal to the treated section and accumulated in the tip of the treated leaf. In contrast, in the S and in the SF populations, a greater percentage of 14C-glyphosate moved to non-treated leaves and the stem. cDNA sequence analysis of the EPSP synthase gene indicated that the glyphosate-resistant SF population has a proline 106 to serine amino acid substitution. Here, we report that glyphosate resistance in L. multiflorum is conferred by two different mechanisms, limited translocation (nontarget site-based) and mutation of the EPSP synthase gene (target site-based).  相似文献   

16.
Abscisic acid (ABA) (5 x 10-4M and 5 x 10-5M) and gibberellic acid (1 x 10-4M) was applied to the plumula ofChenopodium plants with partly (one dark period) or completely (three dark periods) fulfilled photoperiodic requirements for flowering. Morphological and cytoogical criteria were used to investigate the time-course of the differentiation of the treated shoot apices. Both substances were ineffective in increasing the mitotic activity of the shoot apex at the suboptimal level of induction. The degree of branching was temporarily stimulated by ABA and GA treatment under these conditions. Moreover, GA caused the elongation of the shoot apex. With the completely induced plants ABA hastened flowering and the rise in branching was observed in all the treatment 48 h following the application of growth substances.  相似文献   

17.
This study tested the hypotheses that in patients with a successful anterior cruciate ligament (ACL) reconstruction, the internal–external rotation, varus–valgus, and knee flexion position of reconstructed knees would be different from uninjured contralateral knees during walking. Twenty-six subjects with unilateral ACL reconstructions (avg 31 years, 1.7 m, 68 kg, 15 female, 24 months past reconstruction) and no other history of serious lower limb injury walked at a self-selected speed in the gait laboratory, with the uninjured contralateral knee as a matched control. Kinematic measurements of tibiofemoral motion were made using a previously-described point-cluster technique. Repeated-measures ANOVA (α=0.017) was used to compare ACL-reconstructed knees to their contralateral knees at four distinct points during the stance phase of walking. An offset towards external tibial rotation in ACL-reconstructed knees was maintained over all time points (95%CI 2.3±1.3°). Twenty-two out of twenty-six individuals experienced an average external tibial rotation offset throughout stance phase. Varus–valgus rotation and knee flexion were not significantly different between reconstructed and contralateral knees. These findings show that differences in tibial rotation during walking exist in ACL reconstructed knees compared to healthy contralateral knees, providing a potential explanation why these patients are at higher risk of knee osteoarthritis in the long-term.  相似文献   

18.
摘要 目的:探讨经脐单孔与常规腹腔镜胆囊切除术(LC)对结石性胆囊炎患者肠胃功能、肝功能及免疫学指标的影响。方法:选取2016年3月~2019年12月间我院收治的157例结石性胆囊炎患者,根据手术方式分为三孔组(n=85,常规三孔LC治疗)和单孔组(n=72,单孔LC治疗),比较两组围术期指标、肠胃功能、肝功能及免疫学指标,并记录两组并发症发生情况。结果:单孔组住院时间短于三孔组,视觉疼痛模拟量表(VAS)评分低于三孔组(P<0.05),单孔组手术时间长于三孔组(P<0.05),两组术中失血量比较无差异(P>0.05)。单孔组肠鸣音恢复时间、肛门排气时间、排便时间、进食时间短于三孔组(P<0.05)。两组术后1 d谷氨酰基转移酶(GGT)、天冬氨酸氨基转移酶(AST)、总胆红素(TBIL)水平均升高,但单孔组低于三孔组(P<0.05)。两组术后1 d免疫球蛋白M(IgM)、免疫球蛋白A(IgA)、CD3+、CD4+/CD8+均降低,但单孔组高于三孔组(P<0.05)。两组术后并发症发生率对比,差异未见统计学意义(P>0.05)。结论:与常规三孔LC相比,经脐单孔LC治疗结石性胆囊炎,可有效减轻对机体肝功能、免疫学的影响,促进肠胃功能改善,减轻术后疼痛感,缩短住院时间。  相似文献   

19.
目的:评估关节镜下膝关节前交叉韧带(ACL)与后交叉韧带(PCL)同时重建的技术和临床效果。方法:自2003年6月~2009年10月,27例病人(28膝)经MRI检查及关节镜检查证实ACL和PCL均断裂,其中9膝伴内侧副韧带损伤(MCL),8膝伴后外侧角损伤(PLC),5膝伴内侧半月板破裂,4膝伴外侧半月板损伤。27例患者于伤后3~10周在关节镜下行膝关节前、后交叉韧带联合重建。结果:本组术后早期均未发生严重并发症。术后随访12~88个月,平均(42.67±3.34)个月,Lysholm膝关节功能评分为78~93分,平均(86.67±5.21)分。国际膝关节文件编制委员会(IKDC)综合评定由术前显著异常(D级)28膝,改进为随访时正常(A级)9膝、接近正常(B级)16膝、异常(C级)3膝。结论:关节镜下膝关节前交叉韧带(ACL)与后交叉韧带(PCL)同时重建创伤小、手术操作精细,术后膝关节功能恢复满意。  相似文献   

20.
Polyphosphate hydrolysis was studied in three surface samples and one subsurface sample of Quebec soil treated with alfalfa residues (44.8 t ha−1) and farmyard manure (FYM; 44.8 t ha−1); and in two acid soil samples treated with CaCO3 (12.5 t ha−1). The polyphosphates used were Na4P2O7. 10H2O (NaPP) and PolyN (a triammonium pyrophosphate-orthophosphate mixture). Each polyphosphate was added at a rate of 1.00g P kg−1 soil. Addition of alfalfa residues promoted polyphosphate hyrolysis of both NaPP and PolyN through reduced polyphosphate sorption and increasing pyrophosphatase activity. Application of FYM increased polyphosphate hydrolysis in Uplands topsoil and retarded hydrolysis in the other soils. Hydrolysis was probably reduced because of orthophosphate (OP) introduced with the FYM. Added CaCO3 accelerated polyphosphate hydrolysis in an acid topsoil sample through reduced sorption, but slowed hydrolysis in the subsoil sample, due to a reduction in enzyme activity.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号