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31.
32.
Granulocyte-macrophage colony-stimulating factor mRNA stabilization enhances transgenic expression in normal cells and tissues 总被引:3,自引:1,他引:2
To increase transgenic production of granulocyte-macrophage colony- stimulating factor (GM-CSF), we mutated the mRNA's 3'-untranslated region, AUUUA instability elements. Expression vectors containing human or murine GM-CSF cDNAs coding for wild-type (GM-AUUUA) or mutant versions with reiterated AUGUA repeats (GM-AUGUA) were transfected into cells in culture or animals using particle-mediated gene-transfer technology. Normal peripheral blood mononuclear cells accumulated 20- fold greater levels of GM-CSF mRNA and secreted comparably greater amounts of cytokine after transfection with hGM-AUGUA expression vectors versus hGM-AUUUA. hGM-AUGUA mRNA was fivefold more stable (t 1/2 = 95 minutes) than hGM-AUUUA mRNA (t 1/2 = 20 minutes), accounting for elevated steady-state levels. Transfection site extracts and serum samples obtained 24 hours after gene transfer of hGM-AUGUA cDNA into mouse skin contained greater than 32 ng/mL and 650 pg/mL of GM-CSF protein, respectively, compared with 0.33 ng/mL and less than 8 pg/mL for hGM-AUUUA cDNA. GM-CSF produced from mGM-AUGUA cDNA transfected into rat abdominal epidermis induced a profound neutrophil infiltrate. These data suggest a novel strategy for enhanced production of biologically active cytokines by normal cells after in vivo gene transfer. 相似文献
33.
Musculoskeletal modelling in determining the effect of botulinum toxin on the hamstrings of patients with crouch gait 总被引:2,自引:0,他引:2
NS Thompson FRCS RJ Baker PhD AP Cosgrove MD FRCS IS Corry MD FRCS HK Graham MD FRCS FRACS 《Developmental medicine and child neurology》1998,40(9):622-625
This study aimed to determine the effect of hamstring botulinum toxin A (Btx-A) injection in 10 children with crouch gait in terms of changes in muscle length and lower-limb kinematics. Before Btx-A injection limb kinematics were recorded. Maximum hamstring lengths and excursions were calculated by computer modelling of the lower limb. Data were compared with the averaged hamstring lengths of 10 control children. Hamstrings were denned as short if their length was shorter than the average maximum length minus one standard deviation. Gait analysis was repeated 2 weeks after isolated hamstring Btx-A injection. Pre- and postinjection kinematic data and muscle lengths were then compared. Four of 18 injected limbs in three subjects had short medial hamstring before injection, none of the subjects had short lateral hamstrings. Muscle excursion was significantly reduced in the short and adequate maximum muscle length groups. A significant increase in the semimembranosus and semitendinosus length in all of the injected limbs was noted. Only in the short muscle group was a significant increase in muscle excursion observed. Knee extension improved by 13° in the adequate muscle length group and by 15.6° in the short muscle length group. Pelvic tilt and hip flexion increased in both groups non-significantly. Average walking speed postinjection increased from 0.60 ms-1 to 0.71 ms-1 . Short hamstrings are over-diagnosed in crouch gait. Hamstring Btx-A injection in patients with crouch gait produces significant, repeatable muscle lengthening and improved ambulatory function. 相似文献
34.
Acetylcarbocholine and acetylsilicocholine: Directly or indirectly acting cholinergic spasmogens? 总被引:1,自引:0,他引:1
P. TH. HENDERSON E. J. ARIËNS B. W. J. ELLENBROEK A. M. SIMONIS 《The Journal of pharmacy and pharmacology》1968,20(1):26-35
The cholinergic and anticholinergic actions of nitrogen-free isosteres of acetylcholine and benzilylcholine are described. Esters of two kinds of choline analogues, carbocholine and silicocholine, were used. The spasmogenic activity of acetylcarbocholine and acetylsilicocholine on the guinea-pig ileum was identified as an indirect cholinergic action, in contrast to the direct cholinergic action of furtrethonium and the mainly non-cholinergic action of barium ions. In addition to this indirect cholinergic action, both esters show a weak anticholinergic and a weak noncompetitive “papaverine-like” spasmolytic activity. The corresponding benzilyl esters, although without an onium group, are relatively potent anticholinergic compounds. 相似文献
35.
The combination of even parts lidocaine and prilocaine in crème substance was used for surface anesthesia in 73 children, aged 1,5-16 years. Such surgical interventions as molluscum contagiosum eradication, laser wart resection and prepuce synechia dissection were performed. The described anesthetic was highly effective in all areas, but the nasolabial triangle. Resection of warts larger then 0,5 sm required either additional infiltrative anesthesia or step-wise resection. Local allergic reaction was registered in one case, no systemic reactions were noticed. Generally, the used method of surface anesthesia proved to be highly appropriate in pediatric practice. 相似文献
36.
S Sinha S Gupta S Malhotra NS Krishna AV Meru V Babu V Bansal M Garg N Kumar A Chugh A Ray 《British journal of pharmacology》2010,160(5):1119-1127
Background and purpose:
AE9C90CB (N- [(1R, 5S, 6R)-3-azabicyclo [3.1.0] hex-6-ylmethyl]-2-hydroxy-N-methyl-2, 2-diphenylacetamide), a novel muscarinic receptor antagonist, was synthesized for the treatment of overactive bladder. Here we describe the in vitro and in vivo profiles of AE9C90CB for action in bladder over salivary gland and compare it with four agents already in clinical use (tolterodine, oxybutynin, solifenacin and darifenacin).Experimental approach:
Radioligand binding assay and isolated tissue-based functional assay were used to evaluate affinity, potency, and receptor subtype selectivity of compounds. Inhibition of carbachol-induced increase in intravesicular pressure and salivary secretion were measured in anaesthetized rabbits to assess the functional selectivity.Key results:
In vitro radioligand binding study using human recombinant muscarinic receptors showed that AE9C90CB had greater affinity for M3 muscarinic receptors with pKi of 9.90 ± 0.11 and was 20-fold more selective for M3 than for M2 muscarinic receptors. AE9C90CB exhibited an unsurmountable antagonism on rat bladder strips (pKB, 9.13 ± 0.12). In anaesthetized rabbits after intravenous administration, AE9C90CB dose dependently inhibited carbachol-induced increase in intravesicular pressure and salivary secretion, and exhibited functional selectivity for urinary bladder over salivary gland which was ninefold better than that of oxybutynin.Conclusions and implications:
We have identified AE9C90CB, a compound exhibiting moderate selectivity for M3 over M2 receptors but greater selectivity for urinary bladder over salivary gland than oxybutynin, tolterodine, solifenacin and darifenacin. Therefore, AE9C90CB may be a promising compound for the treatment of overactive bladder with reduced potential to cause dry mouth than currently available antimuscarinic drugs. 相似文献37.
38.
39.
p53 and MDM2 expression in odontogenic cysts and tumours 总被引:1,自引:0,他引:1
OBJECTIVE: The aim of this report was to assess p53 and MDM2 expression in odontogenic cysts and tumours, as they are known to play important roles in cell proliferation and tumorigenesis. MATERIALS AND METHODS: The expression of p53 and MDM2 proteins was determined immunohistochemically in 51 formalin-fixed, paraffin embedded specimens of odontogenic cysts and tumours.RESULTS: No positivity to p53 was found in the cases studied. MDM2 expression in ameloblastoma was higher than in radicular cysts, but lower than that observed in odontogenic keratocysts. No difference was observed between MDM2 expression in radicular cyst and adenomatoid odontogenic tumour. The clear-cell odontogenic ameloblastoma presented strong immunoreaction to this antigen.CONCLUSIONS: The results suggest that MDM2 overexpression may be involved in the pathogenesis of some odontogenic lesions. 相似文献
40.
Gluckman PD, Sizonenko SV, Bassett NS. The transition from fetus to neonate - an endocrine perspective. Acta Pædiatr 1999; Suppl 428: 7–11. Stockholm. ISSN 0803–5326
The transition from fetus to neonate involves three phases: late gestation, parturition and the processes needed to establish independent homoeostatic regulation after separation from the placenta. These phases are regulated by a series of fetal and placental endocrine events. Glucocorticoids have an important role in the preparation for birth, including involvement in lung and cardiac development, and the maturation of enzymes in a variety of pathways. Fetal Cortisol production is, in turn, also under hormonal control. Parturition is a complex process, which is still poorly understood in humans. The final steps are largely dependent on the effect of prostaglandin F2α on the myometrium associated with increased oxytocin activity. The transition to birth is accompanied by changes in respiration, circulation, glucose homoeostasis, and the onset of independent oral feeding and thermoregulation. Several examples of endocrine components of the transition from fetal to neonatal life are reviewed here: the role of prostanoids, the onset of thermogenesis, and changes in the thyroid hormone and growth hormone axes. The effects of hormone levels on prematurity and growth retardation are also discussed. □ Birth transition, fetus, gestation, hormonal control, neonate, parturition 相似文献
The transition from fetus to neonate involves three phases: late gestation, parturition and the processes needed to establish independent homoeostatic regulation after separation from the placenta. These phases are regulated by a series of fetal and placental endocrine events. Glucocorticoids have an important role in the preparation for birth, including involvement in lung and cardiac development, and the maturation of enzymes in a variety of pathways. Fetal Cortisol production is, in turn, also under hormonal control. Parturition is a complex process, which is still poorly understood in humans. The final steps are largely dependent on the effect of prostaglandin F