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21.
Warner EA Deyoung DZ Hoang TX Franchini BT Westerlund U Havton LA 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2005,161(4):527-531
GAP-43 is normally produced by neurons during developmental growth and axonal regeneration, but it is also expressed in specific regions of the normal adult nervous system. We studied the protein expression of GAP-43 within the conus medullaris portion of the spinal cord in adult male rats. Immunohistochemistry for choline acetyltransferase (ChAT) was first performed to identify specific efferent autonomic and motor nuclei in lumbosacral segments of the spinal cord. Adjacent sections were then processed for GAP-43 immunoreactivity (IR). We show GAP-43 IR in the superficial portion of the dorsal horn, the intermediolateral nucleus, and the dorsal commissural tract. We also demonstrate a differential distribution of GAP-43 IR between different motor nuclei of the conus medullaris. Using densitometry, the most prominent GAP-43 IR was detected in the dorsolateral and dorsomedial motor nuclei, which represent the human Onufs nucleus homologue. Confocal microscopy of double immunofluorescent labeling for ChAT and GAP-43 demonstrate GAP-43 IR in the neuropil of the autonomic and motor nuclei, and many of the GAP-43 IR arbors are in close apposition with the efferent cholinergic neurons. We note that the efferent neurons of both the autonomic and somatic nuclei, which are ultimately responsible for the integrated normal control of the lower urinary tract, bowel and sexual functions, are heavily innervated by GAP-43 enriched projections. We speculate that these functionally related neurons retain a physiological GAP-43-associated synaptic plasticity throughout adult life. 相似文献
22.
Naohiro Yano Masayuki Endoh Raita Naka Fumio Takemura Yasuo Nomoto Hideto Sakai 《Journal of clinical immunology》1996,16(1):71-79
Previously we reported disease-specific interaction between interferon- (IFN-) and interleukin-4 (IL-4) in patients with IgA nephropathy (IgAN), suggesting the existence of unusual T cell behavior in this disease. In the present study, we investigated characteristic synthesis of interferon- (IFN-) and expression of IFN- receptor (IFN-R) in the peripheral blood mononuclear cells (PBMC) from patients with IgAN and other chronic proliferative glomerulonephritis (PGN). Heparinized peripheral blood samples were obtained from 38 patients with chronic mesangial proliferative glomerulonephritis (CGN; including 24 with IgA nephropathy) and 20 healthy controls. PBMC were isolated by gradient centrifugation and fragments were cultured in Iscove's modified Dulbecco's medium (IMDM) supplemented with 10% fetal calf serum (FCS) for 72 hr. IFN- concentrations in supernatants were evaluated by the enzyme-linked immunosorbent assay (ELISA). Other parts of PBMC pellets were reacted with anti-human IFN-R monoclonal antibody and FITC-labeled anti-mouse second antibody for analysis of IFN-R expression on these cells by FACScan. The remaining PBMC were fractionated into CD4+ T cells, CD8+ T cells, B cells, NK, cells and macrophages using the MACS cell sorting system. The isolated cells were evaluated for IFN- or IFN-R mRNA expression by the semiquantitative RT-PCR method.In vitro IFN- synthesis was enhanced in patients with CGN, and NK cells were revealed to be responsible for such enhancement. On the other hand, the expression of IFN-R on macrophages was suppressed in CGN patients. These results suggest that impairment of regulation of the IFN- system might be involved in the development of CGN. 相似文献
23.
24.
Szabo Gyongyi Mandrekar Pranoti Verma Bikash Isaac Ann Catalano Donna 《Journal of clinical immunology》1994,14(6):340-352
The hypothesis that acute ethanol uptake plus trauma can synergize to increase immunosuppression was tested. We found that, unlike non-alcohol-exposed patients, patients with acute alcohol use prior to trauma have a transient decrease in monocyte tumor necrosis factor (TNF) production during the very early postinjury (0–3 days) period. However, TNF production by these alcoholexposed patients' monocytes (MØ) became hyperelevated late postinjury (>9 days). Consequently, these massively elevated MØ TNF levels can contribute to posttrauma immunosuppression after acute alcohol use. We also demonstrate that normal monocyte activation with the superantigen,Staphylococcus enterotoxin B (SEB), results in a preferential induction of cellassociated MØ TNF production, described as characteristic of immunosuppressed trauma patients. Acutein vitro ethanol treatment down-regulated the elevated TNF production by trauma patients' MØ after either SEB, muramyl-dipeptide (MDP), interferon- plus MDP, or lipopolysaccharide (LPS) stimulation. Both SEB- and LPS-induced TNF mRNA induction was inhibited by acute alcohol treatment in normal MØ, indicating that ethanol can regulate cytokine gene expression. An additional immunosuppressive effect of acute ethanol's stimulation was suggested by its induction of elevated transforming growth factor production in trauma patients' activated MØ. 相似文献
25.
Lotfi Aarab Sylvie Siaume-Perez Danielle Chabardès 《Pflügers Archiv : European journal of physiology》1993,425(5-6):417-425
Previous studies have demonstrated that prostaglandin E2 (PGE2) inhibits arginine vasopressin-(AVP)dependent adenosine 3,5-cyclic monophosphate (cAMP) accumulation in microdissected rat outer medullary collecting tubules (OMCD), by a mechanism unrelated to the inhibition of cAMP synthesis. The potential role of the activation of protein kinase C (PKC) to explain the negative regulation elicited by PGE2 was investigated in this study. Single OMCD samples were pre-incubated (10 min, 30°C) in the presence or absence of either activators of PKC, phorbol 12-myristate 13-acetate (PMA), 1-oleoyl-2-acetyl-glycerol (OAG), dioctanoylglycerol (DOG) or an inhibitor of PKC, staurosporine (SSP). These compounds were present also with the agonists tested during the incubation period (4 min, 35°C). In contrast to PGE2, activators of PKC did not decrease AVP-dependent cAMP accumulation (mean ±SEM): 1nM AVP=47.1±6.8 fmol · mm–1· 4 min–1; AVP + 0.3 M PGE2=20.1±2.7, P<0.01 versus AVP; AVP + 10 nM PMA=42.0±4.7, NS versus AVP; AVP + 50 g/ml OAG=44.1±4.8. NS versus AVP, N= 5 experiments. However, 10 nM PMA prevented PGE2-induced inhibition: AVP + PGE2= 44.2±3.5% of the response to AVP and 90.3±3.2% without and with PMA respectively, N= 16. Similar results were obtained with either 50 g/ml OAG or 25 g/ ml DOG (AVP + PGE2 + OAG=92.9±6.6% of the response to AVP, N= 8; AVP + PGE2 + DOG=94.1 ±5.3%, N= 7). OAG, DOG, PMA or PMA + PGE2 had no intrinsic agonist activity in the rat OMCD and the addition of an inactive phorbol ester did not prevent PGE2-induced inhibition. SSP, 50 nM or 0.1 M, did not affect the inhibition due to PGE2 but abolished the reversion by PMA of PGE2-induced inhibition. A similar regulation was observed on forskolin-(FK)dependent cAMP accumulation: 5 M FK + 0.3 M PGE2= 37.7±6.2% of the response to FK; FK + PGE2 + 10 nM PMA=89.5±6.7%; FK + PGE2 + PMA + 0.1 M SSP=43.1±7.9%, N= 4. The inhibition induced by an
2-adrenergic agonist, clonidine 1 M, was not blocked by the activation of PKC. In fura-2-loaded OMCD samples, 10nM PMA decreased by 63.3±5.0% and by 57.2±7.1% the peak and plateau phases, respectively, of the increase in intracellular calcium concentration ([Ca2+]i) obtained with PGE2 when compared to control responses in the same tubules (n=12) and did not affect the increase in [Ca2+]i induced by 0.1 mM carbachol. It is concluded that: (1) in the rat OMCD the activation of PKC by PMA or analogues of diacylglycerol did not reproduce PGE2-induced inhibition of AVP- or FK-dependent cAMP accumulation, but prevented specifically this inhibitory action; and (2) this reversion might be the consequence of the effect of PKC activation which impaired the rises in [Ca2+]i induced by PGE2. 相似文献
26.
Robert R. Ruffolo Jr. Karen Messick J. S. Horng 《Naunyn-Schmiedeberg's archives of pharmacology》1985,329(3):244-252
Summary The enantiomers of 3-O-methyldobutamine, a metabolite of dobutamine, were evaluated for their - and -adrenoceptor mediated effects in vitro in a variety of isolated organs and in radioligand binding studies. Neither enantiomer of 3-O-methyldobutamine possessed 1-adrenoceptor agonist activity in isolated guinea pig aorta. However, both enantiomers of 3-O-methyldobutamine were competitive 1-adrenoceptor antagonists, with the (+)-enantiomer being approximately 10-fold more potent than the (-)-enantiomer as assessed either in guinea pig aorta or by displacement of 3H-prazosin binding from 1-adrenoceptors in rat cerebral cortex. The 1-adrenoceptor blocking activity of (+)-3-O-methyldobutamine was relatively potent and corresponded to a pA2 of 7.33 in guinea pig aorta and a-log K
i of 7.72 in radioligand binding studies. Neither enantiomer of 3-O-methyldobutamine possessed 2-adrenoceptor agonist activity in field-stimulated guinea pig ileum. Although (+)-3-O-methyldobutamine weakly inhibited the twitch response in field-stimulated guinea pig ileum, the response was not blocked by the selective 2-adrenoceptor antagonist, yohimbine, and was found to result from weak anticholinergic activity (pA2=5.06). Neither enantiomer of 3-O-methyldobutamine possessed 1-adrenoceptor agonist activity in guinea pig atria, however the (+)-enantiomer was a weak noncompetitive antagonist at 1-adrenoceptors. In contrast, both enantiomers of 3-O-methyldobutamine were weak 2-adrenoceptor agonists in rat uterus, however these weak effects were not highly stereoselective, which was also confirmed in radioligand binding studies. The results of the present study indicate that 3-O-methyldobutamine is a potent and highly selective 1-adrenoceptor antagonist, with minimal activity at 2-, 1- and 2-adrenoceptors. It is hypothesized that the potent 1-adrenoceptor antagonist activity of 3-O-methyldobutamine, which resides predominantly in the (+)-enantiomer, may play a role in the hemodynamic effects of dobutamine, by contributing, in part, to the decrease in total peripheral vascular resistance observed following administration of dobutamine. 相似文献
27.
Rats were trained to press a bar for sucrose reward on a random-interval (RI) schedule and footshock punishment was then introduced for 3-min intrusion periods (signalled by a tone) on an independent RI schedule. Shock intensity was individually adjusted to produce stable intermediate levels of response suppression during the tone for each animal. Groups of animals were then allocated to a number of separate experiments in which they were systemically injected with anxiolytics (chlordiazepoxide HCl or sodium amylobarbitone), GABA antagonists (picrotoxin or bicuculline), the GABAA agonist muscimol, the GABAB agonist baclofen, an antagonist (RO 15-1788) at the benzodiazepine receptor and, an inverse agonist (FG 7142) at this receptor. The results showed that the alleviation of punishment-induced suppression of barpressing produced by chlordiazepoxide was blocked or partially blocked by RO 15-1788, picrotoxin and bicuculline but not by FG 7142; that picrotoxin (but not FG 7142) increased the suppression of responding by punishment; that neither muscimol nor baclofen affected responding on their own, but their combination weakly but reliably released punished responding from suppression; and that the anti-punishment effect of amylobarbitone was unaffected by either picrotoxin or bicuculline, though the barbiturate reversed the punishment-enhancing effect of picrotoxin. These results are discussed in the light of the hypothesis that anxiolytic behavioural effects are due to increased GABAergic inhibition. 相似文献
28.
Two young patients are described who made good recoveries from a locked-in syndrome presumed to be due to ventral pontine ischemia. The first patient recovered completely from quadriplegia and mutism. In the second patient the only permanent sequellae were slight dysarthria and mild spasticity. Since patients may recover nearly completely from a locked-in syndrome, aggressive supportive therapy seems justified during the initial weeks or months. 相似文献
29.
J. Nuutila S. Kaakkola P. T. MÄnnistö 《Journal of neural transmission (Vienna, Austria : 1996)》1987,70(3-4):233-240
Summary The effects of a COMT-inhibitor, U-0521, and a MAO-B-inhibitor, l-deprenyl, on L-dopa-induced circling behaviour were compared in 6-OHDA-lesioned rats. The actions of U-0521 and l-deprenyl on the anticataleptic effect of L-dopa were also studied. Both U-0521 and l-deprenyl were found to potentiate L-dopa-induced circling behaviour and anticataleptic effect of L-dopa. In both test systems the L-dopa potentiation of l-deprenyl was longer-lasting than that caused by U-0521. Thus inhibition of COMT, like inhibition of MAO, is able to enhance the central effects of L-dopa. This principle might be beneficial in the treatment of Parkinson's disease especially if COMT-inhibitors with greater performance can be developed. 相似文献
30.
H. Rommelspacher Sabine Strau E. FÄhndrich H. J. Haug 《Journal of neural transmission (Vienna, Austria : 1996)》1987,69(1-2):85-96
Summary [3H] UK-14,304 was used to investigate
2-adrenoceptors in rat brain and human platelets. Receptor pharmacology revealed that the ligand binds with high affinity to
2-adrenoceptors. Psychoactive substances like neuroleptics, antidepressants, and-carbolines displace [3H] UK-14,304 from its binding sites in the lower micromolar range. A Hill number around 2 for most neuroleptics suggests a positive cooperativity with the
2-adrenoceptors.Comparative studies with [3H] UK-14,304 and [3H] clonidine utilizing platelet membranes from human volunteers demonstrated that the former ligand is more suitable to investigate possible changes of
2-adrenoceptors; [3H] UK-14,304 labels more receptors with a lower standard deviation, whereby the volume of the blood sample amounted to 35 ml instead of 50 ml required for [3H] clonidine as ligand. No sex differences of binding constants were detected, however an inverse correlation of maximum number of binding sites and affinity was found for female subjects with both ligands.No age-dependent changes of Bmax and KD-values were observed in the range of 24 to 59 years. 相似文献