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Retinoids have long been known to influence skeletal development and bone remodeling. Cells of the osteoblastic lineage play a key role in these processes. In this study we have used the differential display PCR technique to identify retinoic acid (RA)-induced mRNAs in human osteoblast-like cells. We report the cloning and sequencing of one such mRNA, AT-RA 6, which was specifically induced by all-trans RA both in normal human osteoblast-like cells and in MG-63 osteosarcoma cells. Maximal expression was found after 60 min, suggesting that this may be an early response gene. Expression was found in all tissues examined. No homology to known mRNA sequences was detected.  相似文献   
115.
Metabolic side-effects of antihypertensive drugs may increase the risk of coronary heart disease despite an adequate blood pressure reduction. Since combinations of different antihypertensive drugs are often necessary and frequently used, we performed a randomized study comparing the effects of a fixed combination of hydrochlorothiazide and sotalol (group A), or hydrochlorothiazide and captopril (group B) on blood pressure and on lipid and glucose metabolism in 40 men with essential hypertension over 1 year. Significant blood pressure reductions (p < 0.001) were achieved in both treatment groups: from 160/105 to 128/88 mmHg in group A (mean doses: hydrochlorothiazide 33 and sotalol 197 mg) and from 162/106 to 135/89 mmHg in group B (hydrochlorothiazide 33 and captopril 64 mg) after 12 months, respectively. No significant changes in body weight were observed in either treatment group. Triglycerides increased (p < 0.05) in both treatment groups (from 183 to 262 mg/dl in A, and from 160 to 196 mg/dl in B) and HDL cholesterol decreased (p < 0.001 and < 0.05) in both groups (from 45.1 to 35.7 mg/dl in A, and from 49.3 to 46.3 mg/dl in B), whereas LDL cholesterol increased significantly (p < 0.05) only in group A from 153 to 164 mg/dl. No significant changes were observed in total cholesterol nor in lipoprotein(a) concentrations in either treatment group. Fasting plasma glucose and hemoglobin A1 increased significantly (p < 0.05) only in group A after 1 year of treatment (from 91.6 to 98.0 mg/dl, and from 6.3 to 6.9%, respectively). Serum levels of creatinine and potassium decreased, and uric acid increased significantly under either combination. Our data show that the diuretic/beta-blocker combination has adverse effects on lipid and glucose metabolism after long-term therapy. The effects of the diuretic/ACE inhibitor combination on lipid metabolism are less pronounced and there are no adverse effects on glucose metabolism. However, the ACE inhibitor component could not completely counteract the metabolic effects of the diuretic. Both combinations have no effects on Lp(a). We conclude that the combination of hydrochlorothiazide with an ACE inhibitor has a better metabolic profile for the treatment of essential hypertension than the combination with a beta-blocker.  相似文献   
116.
Gerhard Mathé 《NTM》1994,2(1):13-26
This paper on the occasion of the 500th birthday of the great Saxon humanistic scholar Georgius Agricola deals with his contributions to geology in the narrow sense. These, contrary to his voluminous works on mining, metallurgy and mineralogy (De re metallica and De natura fossilium, resp.) are parts of the booksDe ortu et causis subterraneorum andDe natura eorum, quae effluunt ex terra. In those we find statements on the causes of earthquakes, on volcanos and the subterranean fire as well as the effects of the running water in mountain-building. Agricola's ideas on geological time and his statements on dynamics of the Earth's crust are remarkable.  相似文献   
117.
Discusses the theoretical and clinical applications of the postmodern paradigm of social constructionism as a basis for counseling culturally different clients. Such applications avoid the trap of perpetuating the status-quo when working with minority and marginalized clientele. The main points of multiculturalism and social constructionism are summarized, and issues of mutual concern to both perspectives are examined. Applications to psychotherapy are explored, and the challenges of applying the social constructionist approach to culturally competent counseling are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   
118.
The galanin-receptor ligand M40 [galanin-(1-12)-Pro3-(Ala-Leu)2-Ala amide] binds with high affinity to [mono[125I]iodo-Tyr26]galanin-binding sites in hippocampal, hypothalamic, and spinal cord membranes and in membranes from Rin m5F rat insulinoma cells (IC50 = 3-15 nM). Receptor autoradiographic studies show that M40 (1 microM) displaces [mono[125I]iodo-Tyr26]galanin from binding sites in the hippocampus, hypothalamus, and spinal cord. In the brain, M40 acts as a potent galanin-receptor antagonist: M40, in doses comparable to that of galanin, antagonizes the stimulatory effects of galanin on feeding, and it blocks the galaninergic inhibition of the scopolamine-induced acetylcholine release in the ventral hippocampus in vivo. In contrast, M40 completely fails to antagonize both the galanin-mediated inhibition of the glucose-induced insulin release in isolated mouse pancreatic islets and the inhibitory effects of galanin on the forskolin-stimulated accumulation of 3',5'-cAMP in Rin m5F cells; instead M40 is a weak agonist at the galanin receptors in these two systems. M40 acts as a weak antagonist of galanin in the spinal flexor reflex model. These results suggest that at least two subtypes of the galanin receptor may exist. Hypothalamic and hippocampal galanin receptors represent a putative central galanin-receptor subtype (GL-1-receptor) that is blocked by M40. The pancreatic galanin receptor may represent another subtype (GL-2-receptor) that recognizes M40, but as a weak agonist. The galanin receptors in the spinal cord occupy an intermediate position between these two putative subtypes.  相似文献   
119.
Using ion exchange chromatography and an ATP-dependent actin precipitation step, we have isolated three myosin-I isozymes that, together, account for most of the K+EDTA-ATPase activity recovered from extracts of Dictyostelium. The two major myosin-I isozymes, present in approximately equal amounts, had apparent molecular masses of 125 kDa on SDS gels and have been identified by amino acid sequence analysis as the products of the Dictyostelium myosin-IB (DMIB) and myosin-ID (DMID) genes. DMIB, with a specific K+EDTA-ATPase activity 10-fold higher than DMID, was responsible for most of the activity in cell extracts. The third isozyme, present in low amounts, had an apparent molecular mass of 137 kDa on SDS gels and is too large to be the product of any of the known myosin-I genes. DMIB eluted from DE53 cellulose columns as two distinct peaks (II and III). Addition of the phosphatase inhibitor okadaic acid to the extraction buffer increased the fraction of DMIB recovered from growth phase cells in peak III from 35 to 70%. DMIB isolated from peak III, but not from peak II, displayed a significant level of actin-activated MgATPase activity. These results indicate that peak III represents a phosphorylated, actin-activatable form of DMIB.  相似文献   
120.
Rat brain cortex slices and synaptosomes preincubated with [3H]noradrenaline were used to investigate whether the NMDA-evoked noradrenaline release is modulated by agonists or antagonists at presynaptic alpha 2-adrenoceptors. In experiments on slices, noradrenaline and the preferential alpha-adrenoceptor agonists talipexole (former B-HT 920) and clonidine inhibited the NMDA-evoked tritium overflow whereas the selective alpha 1-adrenoceptor agonists cirazoline and methoxamine were ineffective. The alpha 2-adrenoceptor antagonists rauwolscine and idazoxan facilitated the NMDA-evoked tritium overflow whereas the preferential alpha 1-adrenoceptor antagonist prazosin was ineffective. The concentration-response curve of talipexole for its inhibitory effect on NMDA-evoked overflow was shifted to the right by idazoxan (apparent pA2 = 7.5). The EC50 of NMDA (97 mumol/l) for its stimulating effect on tritium overflow was not substantially changed by blockade of alpha 2-autoreceptors with 1 mumol/l rauwolscine (EC50 of NMDA in the presence of the alpha 2-adrenoceptor antagonist, 155 mumol/l), but the maximal overflow of tritium was increased 2.5 fold by this rauwolscine concentration. In experiments on synaptosomes, talipexole and noradrenaline inhibited the NMDA-evoked tritium overflow. The inhibitory effect of talipexole was abolished by idazoxan which, given alone, was ineffective, as was prazosin. Talipexole did also not produce an inhibition when tritium overflow was evoked by NMDA in the presence of omega-conotoxin GVIA 0.1 mumol/l; the latter, by itself, decreased the response to NMDA by about 55%.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   
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