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61.
62.
63.
The discovery of an inducible isoform of cyclooxygenase (COX-2) requires a refinement of the theory that inhibition of cyclooxygenase
activity is responsible for both therapeutic and side-effects of nonsteroidal anti-inflammatory drugs (NSAIDs). Pharmacological
results with developmental compounds suggest that COX-2 is the relevant target for the therapeutic (i.e. anti-inflammatory)
effects of NSAIDs, whereas gastric and renal side-effects are related to inhibition of constitutive COX-1. However a role
of COX-1 in inflammation cannot be excluded. Furthermore, more research effort is needed to investigate the functional relevance
of COX-2 in normal tissue. 相似文献
64.
Sinusoids are found not only in the normal liver but also in certain liver tumours, including hepatoblastoma, the most common malignant liver tumour in childhood. In this study, sinusoids in 12 hepatoblastomas, of various subtypes, and in normal liver were investigated with UEA-1 and antibodies against von Willebrand's factor, CD31 and CD34 to detect differences of possible diagnostic significance. In the normal liver, staining of sinusoids was seen with all these markers, but it was focal and confined to a few sinusoids near the portal tracts. In hepatoblastoma, the endothelial markers reacted with the sinusoids to varying extents. UEA-1 and anti-CD34 usually stained the majority of these vessels, anti-CD34 staining greater numbers of sinusoids and with greater intensity. Immunostaining revealed that both number and spatial organization of sinusoids in hepatoblastoma are dependent on the subtype. In addition to staining of endothelium, one of the two small cell hepatoblastomas exhibited strong immunoreactivity of the tumour cells for CD34. These findings show that the marked difference in sinusoidal immunoreactivity for CD34 between normal liver and hepatoblastoma could be useful for discriminating between non-neoplastic liver tissue and highly differentiated fetal hepatoblastoma. Our findings also show that small cell hepatoblastoma, in addition to acute leukaemia, should be considered when immunoreactivity for CD34 is found in small round and blue cell tumours in childhood. 相似文献
65.
Metastatic renal cell carcinoma has occasionally been reported to mimic malignant pleural mesothelioma. Morphologically, histochemically and immunohistochemically, similarities in the two tumours exist making their differentiation difficult, particularly in biopsy specimens. The aim of this study was to make a comparative immunohistochemical analysis of the two tumours by use of a panel of four antibodies (Leu M1; Ber EP4; thrombomodulin and Tamm-Horsfall protein). Their suitability in differentiating between the two tumours was assessed. We examined 20 cases of renal cell carcinoma and 20 cases of malignant pleural mesothelioma. On immunostaining with Leu M1, 14 of 20 renal cell carcinomas were positive, yielding 70% sensitivity and 95% specificity and one of 20 mesotheliomas. In comparison, Ber EP4 antibody stained only seven of 20 of the renal cell carcinomas. In addition, it was noted that four tubulopapillary pattern renal cell carcinomas stained positively with both anti-Leu M1 antibody and Ber EP4 antibody. Thrombomodulin immunostaining was present in 11 of 20 mesotheliomas (55% sensitivity and demonstrated 95% specificity) and one of 20 renal cell carcinomas. For epithelial mesotheliomas only, thromobomodulin staining was identified in 10 of 14 cases. In the differentiation of renal cell carcinoma from epithelial mesothelioma we recommend the use of Leu M1 and thrombomodulin as diagnostically useful markers. None of the antibodies used in this study was effective in distinguishing sarcomatoid renal cell carcinoma from sarcomatous mesothelioma. Tamm-Horsfall protein showed little diagnostic utility in differentiating the two tumours. 相似文献
66.
G. Wu S. F. Fan Z.-H. Lu R. W. Ledeen S. M. Crain 《Journal of neuroscience research》1995,42(4):493-503
Prolongation of the action potential duration of dorsal root ganglion (DRG) neurons by low (nM) concentrations of opioids occurs through activation of excitatory opioid receptors that are positively coupled via Gs regulatory protein to adenylate cyclase. Previous results suggested GM1 ganglioside to have an essential role in regulating this excitatory response, but not the inhibitory (APD-shortening) response to higher (μM) opioid concentrations. Furthermore, it was proposed that synthesis of GM1 is upregulated by prolonged activation of excitatory opioid receptor functions. To explore this possibility we have utilized cultures of hybrid F11 cells to carry out closely correlated electrophysiological and biochemical analyses of the effects of chronic opioid treatment on a homogeneous population of clonal cells which express many functions characteristic of DRG neurons. We show that chronic opioid exposure of F11 cells does, in fact, result in elevated levels of GM1 as well as cyclic adenosine monophosphate (AMP), concomitant with the onset of opioid excitatory supersensitivity as manifested by naloxone-evoked decreases in voltage-dependent membrane K+ currents. Such elevation of GM1 would be expected to enhance the efficacy of excitatory opioid receptor activation of the Gs/adenylate cyclase/cyclic AMP system, thereby providing a positive feedback mechanism that may account for the remarkable supersensitivity of chronic opioid-treated neurons to the excitatory effects of opioid agonists as well as antagonists. These in vitro findings may provide novel insights into the mechanisms underlying naloxone-precipitated withdrawal syndromes and opioid-induced hyperalgesia after chronic opiatf addiction in vivo. © 1995 Wiley-Liss, Inc. 相似文献
67.
M. Vrethem B. Lindvall S. Kihlstrand E. Bckman T. Brismar P. Fredman K.G. Henriksson 《European journal of neurology》1996,3(2):156-159
We report improvement in muscle strength in a patient with multifocal motor neuropathy (MMN) when given high-dose intravenous immunoglobin (i.v.-Ig) treatment. The patient had asymmetrical limb weakness, atrophy and absent or weak reflexes, but no sensory disturbances. Neurography showed multiple conduction blocks in peripheral motor nerves but no sensory nerve abnormalities. Serum and anti-GM1 antibodies were not found, however, the patient had serum antibodies against the glycolipid LK1, an epitope found both in glycolipid and also in some glycoproteins in peripheral nerve myelin. Muscle strength improved 5 days after i.v.-Ig therapy, and lasted about 10 weeks. Repeated courses of treatment resulted in similar improvement. This is, to our knowledge, the first patient reported with MMN found to have antibodies against the glycolipid LK1. 相似文献
68.
硒和/或维生素E预防大鼠内皮细胞损伤的实验研究 总被引:15,自引:1,他引:14
用含硒(Se0.5mg/kg)和/或维生素E(VE0.6g/kg)的高脂饲料喂养成年雄性Wistar大鼠12周。结果:高脂对照组大鼠血浆前列腺素Flα(6-酮-PGF1α)水平下降,而血清脂质过氧化物(LPO)、血浆血栓素(TXB2)及内皮素(ET)水平上升;补Se、VE及Se+VE可明显降低大鼠血清LPO、血浆TXB2、ET及TXB2/6-酮-PGF1α比值。同时,除了明显提高血浆谷胱甘肽过氧化物酶(GSH-Px)活力外,血浆6-酮-PGF1α浓度明显升高。实验提示,Se和/或VE有调节花生四烯酸代谢及保护内皮细胞的作用。 相似文献
69.
Purpose. To determine whether the non-toxic pentameric B subunit of Cholera toxin (CTB) binding to ganglioside GM1 on both the lipid vesicles and epithelial cells may provide a means to target lipid vesicles to mucosal cells expressing surface GM1.
Methods. Sonicated lipid vesicles containing ganglioside GM1 were prepared. Inter-vesicle cross-linking due to pentameric CTB binding to these GM1 vesicles was determined with a sub-micron particle analyzer. Association of CTB to GM1 vesicles was analyzed with continuous sucrose gradient centrifugation. CTB-mediated binding of GM1 vesicles to human mucosal epithelial cells (Caco-2 and HT-29), mucous membranes of mouse trachea, and nasal tissues were detected with fluorescent labeled vesicles.
Results. An increase in lipid particle size due to binding of CTB to lipid vesicles and inter-vesicles cross-linking was detected. At a 30-to-1 mole ratio of membrane-bound GMl-to-CTB, optimum increase in GM1 vesicle aggregation, was detected. Under such conditions, all the added CTB molecules were associated with GM1 vesicles. Time course analysis showed that inter-vesicles cross linking by CTB was detectable within 10 min. and reached a maximum value at 60 min. CTB associated GM1-vesicles bind to mucosal epithelial cells HT-29 and Caco-2 with similar affinity [Kd = 7.8 × 10–4 M lipid (Caco-2) and 7.6 × 10–4 M lipid (HT-29)]. GM1 mediated binding specificity was demonstrated by blocking with anti-GMl antibody and the insignificant degree of CTB-associated GM1 vesicle binding to GM1 deficient C6 cells.
Conclusions. The CTB-mediated GM1 binding to multiple membrane surfaces provides selective localization of GM1 vesicles to GM1 expressing mucosal cells and tissues. The strategy may be useful in localizing drugs and proteins to gut and respiratory tract mucosa. 相似文献
70.
Zusammenfassung
Eine neu aufgetretene Dyspnoesymptomatik und eine symmetrische, apikal betonte retikulonodul?re Zeichnungsvermehrung im R?ntgen-Thorax
bei jungen rauchenden Erwachsenen müssen an das seltene Krankheitsbild der pulmonalen Histiocytosis X denken lassen. Klinischer
Befund, laborchemische- und Lungenfunktionsuntersuchungen zeigen unspezifische Befunde. Neue radiologische Verfahren wie die
hochaufl?sende Computertomographie (HRCT) leisten bei gezielter Indikationsstellung eine entscheidende differentialdiagnostische
Hilfestellung.
Dieser Fall verdeutlicht die M?glichkeit einer Diagnosesicherung durch transbronchiale Biopsien unter Verzicht auf offene
Lungenbiopsien. Eine ambulante Diagnostik war m?glich, das h?here Risiko eines operativen Eingriffes konnte vermieden werden.
Die Indikation zur Therapie ist nicht gesichert und wird daher durch den Grad der subjektiven bzw. funktionellen Einschr?nkung
sowie den Verlauf bestimmt. 相似文献