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21.
The effects of glycine on the phasic changes in locomotor activity in the rat, caused by a persistent infusion of dopamine (DA) into the nucleus accumbens (ACB) were investigated. Dopamine (25 μg/24 hr), infused into the nucleus accumbens for 13 days, caused hyperactivity, with two peaks occurring on days 3–4 and 9–11. Glycine (12.5 or 25 μg/24 hr) infused into the nucleus accumbens on its own did not alter the locomotor activity, yet when infused at the same time as DA (25 μg/24 hr), glycine (12.5 or 25 μg/24 hr) inhibited the development of the first peak of hyperactivity induced by DA, with no effect on the second peak. A larger dose of glycine (50 μg/24 hr), infused alone, significantly increased locomotor activity, and a combination of this dose with DA (25 μg/24 hr), led to a temporal shift in the response to DA such that the first peak of hyperactivity was delayed to “fuse” with the second peak. The locomotor response to a threshold dose of DA (6.25 μg/24 hr) plus glycine (50 μg/24 hr) was no greater than could be accounted for by the hyperactivity response to glycine alone (50 μg/24 hr). Strychnine (10 μg/24 hr), infused into the nucleus accumbens, produced no alteration in locomotor activity. Similarly, when infused together with DA (25 μg/24 hr), strychnine (10 μg/24 hr) caused no significant alteration in the phasic hyperactivity induced by DA. However, strychnine (10 μg/24 hr), infused together with DA and glycine (25 and 12.5 μg/24 hr respectively), prevented the inhibition by glycine of the first peak of hyperactivity induced by DA. The results indicate that while glycine may not normally exert a tonic modulatory influence on those mechanisms in the nucleus accumbens which regulate locomotor activity, when applied exogenously glycine can partially moderate the locomotor response to DA, through an action on strychnine-sensitive receptors. 相似文献
22.
Coexisting rheumatoid arthritis and ankylosing spondylitis 总被引:2,自引:0,他引:2
G H Fallet C G Barnes H Berry A G Mowat H Roux J Villiaumey 《The Journal of rheumatology》1987,14(6):1135-1138
Since the second publication by some of the present authors in which 10 patients with coexisting rheumatoid arthritis (RA) and ankylosing spondylitis (AS) were described, 7 new cases have been found. For accuracy, all cases of the original study still available were reexamined. Of the total of 17 cases, 13 were male and 4 female. All had positive tests for rheumatoid factor and 6 had subcutaneous nodules. The male predominance and the frequency of nodules are consistent with other publications. In addition, our study demonstrates the strong association of each of these 2 diseases with its genetic marker: the antigen HLA-DR4 was present in 8 of 12 cases tested and the antigen HLA-B27 was present in 16 of the 17 cases. The coexistence of these 2 classical rheumatological entities in the same patient appears to occur by chance and is probably often overlooked. 相似文献
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Sanjeev Kakar Thomas A Einhorn Siddharth Vora Lincoln J Miara Gregory Hon Nathan A Wigner Daniel Toben Kimberly A Jacobsen Maisa O Al-Sebaei Michael Song Philip C Trackman Elise F Morgan Louis C Gerstenfeld George L Barnes 《Journal of bone and mineral research》2007,22(12):1903-1912
Studies have shown that systemic PTH treatment enhanced the rate of bone repair in rodent models. However, the mechanisms through which PTH affects bone repair have not been elucidated. In these studies we show that PTH primarily enhanced the earliest stages of endochondral bone repair by increasing chondrocyte recruitment and rate of differentiation. In coordination with these cellular events, we observed an increased level of canonical Wnt-signaling in PTH-treated bones at multiple time-points across the time-course of fracture repair, supporting the conclusion that PTH responses are at least in part mediated through Wnt signaling. INTRODUCTION: Since FDA approval of PTH [PTH(1-34); Forteo] as a treatment for osteoporosis, there has been interest in its use in other musculoskeletal conditions. Fracture repair is one area in which PTH may have a significant clinical impact. Multiple animal studies have shown that systemic PTH treatment of healing fractures increased both callus volume and return of mechanical competence in models of fracture healing. Whereas the potential for PTH has been established, the mechanism(s) by which PTH produces these effects remain elusive. MATERIALS AND METHODS: Closed femoral fractures were generated in 8-wk-old male C57Bl/6 mice followed by daily systemic injections of either saline (control) or 30 microg/kg PTH(1-34) for 14 days after fracture. Bones were harvested at days 2, 3, 5, 7, 10, 14, 21, and 28 after fracture and analyzed at the tissue level by radiography and histomorphometry and at the molecular and biochemical levels level by RNase protection assay (RPA), real-time PCR, and Western blot analysis. RESULTS: Quantitative muCT analysis showed that PTH treatment induced a larger callus cross-sectional area, length, and total volume compared with controls. Molecular analysis of the expression of extracellular matrix genes associated with chondrogenesis and osteogenesis showed that PTH treated fractures displayed a 3-fold greater increase in chondrogenesis relative to osteogenesis over the course of the repair process. In addition, chondrocyte hypertrophy occurred earlier in the PTH-treated callus tissues. Analysis of the expression of potential mediators of PTH actions showed that PTH treatment significantly induced the expression of Wnts 4, 5a, 5b, and 10b and increased levels of unphosphorylated, nuclear localized beta-catenin protein, a central feature of canonical Wnt signaling. CONCLUSIONS: These results showed that the PTH-mediated enhancement of fracture repair is primarily associated with an amplification of chondrocyte recruitment and maturation in the early fracture callus. Associated with these cellular effects, we observed an increase in canonical Wnt signaling supporting the conclusion that PTH effects on bone repair are mediated at least in part through the activation of Wnt-signaling pathways. 相似文献
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D A Curson S R Hirsch S D Platt R W Bamber T R Barnes 《British medical journal (Clinical research ed.)》1986,293(6549):726-728
A randomised double blind placebo controlled trial is the most reliable method of assessing putative new developments in medical treatment. In schizophrenia, however, some clinicians believe that relapse contributes to long term deterioration and therefore that patients exposed to either placebo or an inactive new treatment may be put at a disadvantage in the long run if the trial leads to an additional relapse. A seven year follow up of patients included in a randomised placebo controlled trial of fluphenazine decanoate, in which 66% of the group given placebo relapsed compared with 8% of those who received the active drug, permitted examination of any long term adverse consequences in those patients who had received placebo. Seventy six (94%) of the 81 patients in the original trial were followed up. At the end of the follow up period there were no consistent or important differences in any measure of clinical or social outcome between the patients who had received placebo and those who had received the active drug. This negative finding has implications for the debate on the risk of placebo controlled trials of maintenance treatment in chronic schizophrenia. 相似文献
27.
A P Milstone L M Brumble J Barnes W Estes J E Loyd R N Pierson S Dummer 《The European respiratory journal》2006,28(1):131-137
The frequency and complications of respiratory viral infections (RVI) were studied in 50 ambulatory lung transplant patients during a single winter season, using viral antigens, viral cultures and PCR of nasal washes or bronchoalveolar lavages. Patients' survival, episodes of acute rejection and occurrence of bronchiolitis obliterans (BO) or BO syndrome (BOS) were monitored for 1 yr after the study. Overall, 32 (64%) patients had 49 symptomatic episodes. Documented infections included eight due to respiratory syncytial virus (RSV), one due to parainfluenza virus (PIV) and 10 due to influenza (FLU). Four of the FLU infections were serological rises without symptoms. Overall, 17 (34%) patients had documented viral infection; four patients had lower respiratory involvement and two (one RSV, one PIV) were hospitalised for aerosolised ribavirin treatment. After 1 yr there were three (6%) deaths unrelated to RVI. BO or BOS had occurred in one (6%) out of 17 patients with and three (12%) out of 33 without RVI. Respiratory viruses infected one-third of ambulatory lung transplant recipients in a single season. In conclusion, respiratory viral infection was not associated with subsequent graft dysfunction. Larger prospective studies are required to better define the acute and long-term morbidity of these infections. 相似文献
28.
Serum interleukin 5 concentrations in atopic and non-atopic patients with glucocorticoid-dependent chronic severe asthma. 总被引:7,自引:1,他引:6 下载免费PDF全文
BACKGROUND--Interleukin (IL)-5 is thought to play a part in asthmatic bronchial mucosal inflammation and is a potential therapeutic target. Detectable serum IL-5 concentrations have been found previously in a proportion of patients with acute severe asthma, but not in the same patients following oral glucocorticoid therapy or in normal controls. A study was undertaken to investigate whether or not IL-5 is detectable in the serum of patients with glucocorticoid-dependent chronic severe asthma. METHODS--Serum concentrations of IL-5 were measured in 29 patients with stable oral glucocorticoid-dependent chronic severe asthma (mean PEFR 59.7% predicted) and seven normal controls using a specific enzyme-linked immunoassay calibrated with recombinant human IL-5 standards (lower limit of sensitivity 40 pg/ml). RESULTS--Interleukin 5 was detectable in the serum of 15 of the 29 patients at a median concentration of 150 pg/ml (range 40-690), but was undetectable in the serum of all the control subjects. The patients with detectable serum IL-5 concentrations did not differ from those with undetectable concentrations in terms of atopic status, disease severity (percentage predicted PEFR or FEV1), prednisolone dosage, serum IgE concentrations, or peripheral eosinophil count. CONCLUSIONS--Interleukin 5 is detectable in the serum of a proportion of both atopic and non-atopic patients with chronic severe asthma, and concentrations in these patients were higher than in normal controls. These observations are compatible with the hypothesis that IL-5 release occurs in these patients during a period of stable asthma despite systemic glucocorticoid therapy. 相似文献
29.
Emmanuel Ellie Anne Vital Andreas Steck Jean-Michel Boiron Claude Vital Jean Julien 《Journal of neurology》1996,243(1):34-43
We studied 33 patients presenting with a peripheral neuropathy associated with non-malignant anti-myelin-associated glycoprotein (MAG) IgM monoclonal gammopathy (MG) in an attempt to delineate their clinical, immunological, electrophysiological and pathological characteristics; we also reviewed our experience concerning long-term follow-up and therapy. Peripheral neuropathy associated with non-malignant anti-MAG IgM MG was observed mostly in males (sex ratio 7.2), and mean age at onset was 67 years (range 46–81). A predominantly sensory pattern was noted in more than 80% of cases, although some patients were affected by a predominantly motor peripheral neuropathy. Although disease progression was slow in most cases, 45% of patients suffered severe disability, and in 2 cases, the patient's death appeared to stem directly from the neuropathy. The electrophysiological findings were indicative of a demyelinating process in 90% of cases, and electron microscopic examination of nerve biopsy specimens demonstrated widening of the myelin lamellae in more than 95% of cases. Most of our patients showed a disappointing response to steroids and chemotherapy or plasma exchanges. Intravenous immune globulin, evaluated in 17 patients, had a transient, mostly subjective effect in 35% and led to a clear-cut improvement in 24% of cases. We did not observe any correlation between the severity of the clinical picture and the anti-sulphoglucuronyl paragloboside antibody titre; in individual cases, clinical improvement occurred without lowering of IgM levels. Although the severity and the rate of progression may greatly vary from patient to patient, the combination of clinical, electrophysiological and pathological features delineates a characteristic pattern in peripheral neuropathy associated with non-malignant anti-MAG IgM MG. 相似文献
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