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21.
Spatial Learning Deficits in Mice with a Targeted Glucocorticoid Receptor Gene Disruption 总被引:5,自引:0,他引:5
Melly S. Oitzl E. Ron de Kloet Marian Joëls Wolfgang Schmid Timothy J. Cole 《The European journal of neuroscience》1997,9(11):2284-2296
Previous studies in rats using the Morris water maze suggested that the processing of spatial information is modulated by corticosteroid hormones through mineralocorticoid and glucocorticoid receptors in the hippocampus. Mineralocorticoid receptors appear to be involved in the modulation of explorative behaviour, while additional activation of glucocorticoid receptors facilitates the storage of information. In the present study we used the water maze task to examine spatial learning and memory in mice homozygous and heterozygous for a targeted disruption of the glucocorticoid receptor gene. Compared with wild-type controls, homozygous and heterozygous mice were impaired in the processing of spatial but not visual information. Homozygous mutants performed variably during training, without specific platform-directed search strategies. The spatial learning disability was partly compensated for by increased motor activity. The deficits were indicative of a dysfunction of glucocorticoid receptors as well as of mineralocorticoid receptors. Although the heterozygous mice performed similarly to wild-type mice with respect to latency to find the platform, their strategy was more similar to that of the homozygous mice. Glucocorticoid receptor-related long-term spatial memory was impaired. The increased behavioural reactivity of the heterozygous mice in the open field points to a more prominent mineralocorticoid receptor-mediated function. The findings indicate that (i) the glucocorticoid receptor is of critical importance for the control of spatial behavioural functions, and (ii) mineralocorticoid receptor-mediated effects on this behaviour require interaction with functional glucocorticoid receptors. Until the development of site-specific, inducible glucocorticoid receptor mutants, glucocorticoid receptor-knockout mice present the only animal model for the study of corticosteroid-mediated effects in the complete absence of a functional receptor. 相似文献
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Ambuhl P; Wuthrich R; Korte W; Schmid L; Krapf R 《Nephrology, dialysis, transplantation》1997,12(11):2355-2364
Background: Thrombotic complications are common in
patients with endstage renal disease and contribute substantially to the
morbidity and mortality in this population. The aim of the present study
was to: I) determine the prevalence and the extent of hypercoagulability in
patients undergoing dialysis treatment by measuring parameters that
directly reflect thrombin concentrations, ii) assess changes in coagulation
status during haemodialysis (HD); iii) quantify the relative impact of
heparin, dialysis and their combined effects on coagulation status and iv)
detect factors that modify coagulation haemostasis in dialysis patients.
Method: A total of 39 patients (HD: n=29, CAPD: n=10)
was analysed for procoagulatory and fibrinolytic activity determined by
measurements of partial thromboplastin time, prothrombin fragments F1+2,
thrombin-antithrombin complexes and D-dimer concentrations. HD patients
were investigated prior to and during dialysis. A subgroup of patients was
infused heparin alone without dialysis or was dialysed without heparin
administration. Furthermore, subgroup and correlation analyses were
performed for the type of dialysis (HD vs CAPD), dialyzer and shunt, Kt/V,
underlying disease and treatment with recombinant erythropoietin (rhEPO).
Results: Baseline levels of all
parameters-procoagulatory and fibrinolytic- were substantially elevated in
all patients, but to a higher degree among those on CAPD. Moreover,
haemodialysis treatment increased procoagulatory markers even further,
suggesting stimulated coagulation and/or insufficient anticoagulation
during dialysis. However, after 3 h of dialysis thrombin concentrations,
determined by quantification of prothrombin fragments, were inversely
correlated with Kt/V. Selective heparin infusion diminished procoagulatory
activity only slightly and incompletely, whereas HD without heparin
resulted in excess thrombin accumulation. Finally, subgroup analyses
revealed more pronounced thrombin formation among patients treated with
polysulfon dialyzers, whereas erythropoietin dosage was positively related
with lower procoagulatory activity. Conclusion: A
majority of patients on dialysis are in a hypercoagulable state, which is
further aggravated by the haemodialysis procedure itself and may not be
sufficiently controlled with current anticoagulation regimens. Intensified
heparin treatment and the use of rhEPO are likely to improve coagulation
haemostasis, whereas the type of dialyzer should be considered as a
relevant procoagulatory factor. 相似文献
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In this morphometric study, terminal villi of 22 placentas of maternal diabetes mellitus were compared with the results in terminal villi of 22 normal placentas. The results demonstrate that there is a distinct retardation in maturation, statistically significant with bigger cross sectional surfaces of the terminal villi, particularly, when classified in 3000 mu2-steps, the number of the villous vessels and number of epithelial plates. Only slightly decreased in diabetic placentas is the villous vessels cross sectional surface as well as the degree of vascularization. The correlation between the degree of histometric changes and the severity and duration of the disease was separately investigated (classification was done according to White). It could be shown, that the degree of morphologic changes in the terminal villi does not run strictly parallel to the severity and duration of diabetes. The retardation in maturation of the terminal villi increases from White group A to C. In White group D, which is the most severe stage of diabetes mellitus which we investigated, the values of measured parameters are close to the normal placentas. This observation is interpreted as a compensatory reaction of the fetal organ placenta to the reduction in utero placental blood flow in diabetes caused by the diabetic angiopathy. 相似文献
27.
Hoschek Stefan Hoschek-Risslegger Ursula Fiegl Michael Zabernigg August Pall Georg Auberger Thomas Gunsilius Eberhard Schmid Thomas Jamnig Herbert Hilbe Wolfgang 《Wiener Medizinische Wochenschrift》2007,157(21):562-568
Wiener Medizinische Wochenschrift - Aggressives Tumorwachstum, frühe Metastasierung und hohe Assoziation mit intensivem Nikotinkonsum sind die Charakteristika des kleinzelligen... 相似文献
28.
M Bauer D von Fournier F Kubli H Schmid R Schulz-Wendtland 《Strahlentherapie und Onkologie》1988,164(6):309-318
From January, 1975 through June, 1986, 426 patients with mammary carcinomas were submitted to primary, breast-preserving therapy at the Gynecological Hospital of the University of Heidelberg. 212 women with a minimum observation time of twelve months fulfilled the criteria of a "typical" treatment: tumor size up to 3 cm, segment/quadrant resection and axillary lymphonodectomy with at least eight lymph nodes removed, radiotherapy of the residual breast with greater than or equal to 45 Gy, in case of histological lymph node manifestation adjuvant hormonal and/or chemotherapy. The average observation time was 38 months, the medium age 48 years. Patients with histological lymph node manifestations were compared with a matched control group of women treated treated by modified radical therapy. According to the error estimation of Kaplan and Meier (1958), no differences were found for local recurrence rate, disease-free survival, and overall survival. Patients treated by organ-preserving therapy with adjuvant chemotherapy were opposed to a matched control group of women treated only by surgical/radiological, organ-preserving therapy. In patients with chemotherapy, the incidence of cutaneous erythema (29% versus 24%), telangiectasia (34% versus 24%), hyperpigmentation (41% versus 34%) showed an upward tendency, but was not significantly increased. There was no difference in the incidence of clinically palpable fibroses (37% versus 42%) and fibroses shown by mammography (54% versus 51%). The frequency of pneumonitis/fibrosis of the retromammary lung area (22% versus 10%) after chemotherapy was two times higher than in the matched control group not treated by chemotherapy. 相似文献
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