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1.
W J Thompson P S Anderson S F Britcher T A Lyle J E Thies C A Magill S L Varga J E Schwering P A Lyle M E Christy 《Journal of medicinal chemistry》1990,33(2):789-808
A series of 73 dibenzo[a,d]cycloalkenimines were synthesized and evaluated for their ability to displace (+)-10,11-dihydro-5-methyl-5H-dibenzo[a,d]cyclohepten-5,10-imine ([3H]-(+)-10) from its specific binding site on rat cortical membranes. A number of the more active compounds (Ki ranging from 0.006 to 0.21 microM) were evaluated for N-methyl-D-aspartate (NMDA) antagonist activity in the rat cortical slice (Kb ranging from 0.08 to 0.9 microM) and anticonvulsant activity in the mouse against NMDA induced convulsions. The ED50 values ranged from 0.22 to 7.76 mg/kg and correlated reasonably well with the Kb determination. In the dibenzo[a,d]cyclohepten-5,10-imine series, the (+)-5S,10R enantiomer displayed consistently higher levels of biological activity. While substitution at the 3-position of (+)-10 with electronegative atoms generally increased in vitro activity, a loss of potency relative to (+)-10 (MK-801) was observed in vivo for all of the compounds tested. 相似文献
2.
Thies H. Jochimsen David G. Norris Toralf Mildner Harald E. Mller 《Magnetic resonance in medicine》2004,52(4):724-732
Functional MRI (fMRI) by means of spin-echo (SE) techniques provides an interesting alternative to gradient-echo methods because the contrast is based primarily on dynamic averaging associated with the blood oxygenation level-dependent (BOLD) effect. In this article the contributions from different brain compartments to BOLD signal changes in SE echo planar imaging (EPI) are investigated. To gain a better understanding of the underlying mechanisms that cause the fMRI contrast, two experiments are presented: First, the intravascular contribution is decomposed into two fractions with different regimes of flow by means of diffusion-weighting gradient schemes which are either flow-compensated, or will maximally dephase moving spins. Second, contributions from the intra- and extravascular space are selectively suppressed by combining flow-weighting with additional refocusing pulses. The results indicate two qualitatively different components of flowing blood which contribute to the BOLD contrast and a nearly equal share in functional signal from the intra- and extravascular compartments at TE approximately 80 ms and 3 T. Combining these results, there is evidence that at least one-half of the functional signal originates from the parenchyma in SE fMRI at 3 T. The authors suggest the use of flow-compensated diffusion weighting for SE fMRI to improve the sensitivity to the parenchyma. 相似文献
3.
Thies RS Chen T Davies MV Tomkinson KN Pearson AA Shakey QA Wolfman NM 《Growth factors (Chur, Switzerland)》2001,18(4):251-259
GDF-8 is a new member of the TGF-beta superfamily which appears to be a negative regulator of skeletal muscle mass. Factors which regulate the biological activity of GDF-8 have not yet been identified. However, the biological activities of TGF-beta superfamily members, TGF-beta1, -beta2 and -beta3, can be inhibited by noncovalent association with TGF-beta1, -beta2 and beta3 propeptides cleaved from the amino-termini of the TGF-beta precursor proteins. In contrast, the propeptides of other TGF-beta superfamily members do not appear to be inhibitory. In this investigation, we demonstrate that purified recombinant GDF-8 propeptide associates with purified recombinant GDF-8 to form a noncovalent complex, as evidenced by size exclusion chromatography and chemical crosslinking analysis. Furthermore, we show that GDF-8 propeptide inhibits the biological activity of GDF-8 assayed on A204 rhabdomyosarcoma cells transfected with a (CAGA)12 reporter construct. Finally, we demonstrate that GDF-8 propeptide inhibits specific GDF-8 binding to L6 myoblast cells. Collectively, these data identify the GDF-8 propeptide as an inhibitor of GDF-8 biological activity. 相似文献
4.
Thies A Schachner M Berger J Moll I Schulze HJ Brunner G Schumacher U 《The Journal of pathology》2004,203(4):933-939
Aberrant glycosylation is a common feature of metastatic sub-clones of malignant tumours and in uveal melanoma in particular, the HNK-1 glycotope has been positively correlated with poor prognosis. So far, no such correlation has been investigated in cutaneous melanoma. In order to do so, HNK-1 expression was evaluated immunohistochemically in 100 primary cutaneous melanomas and correlated with metastasis after up to 10-years' follow-up. Furthermore, HNK-1 expression was analysed in metastatic deposits (19 distant cutaneous metastases and six sentinel lymph node metastases), as well as in benign nevi. Kaplan-Meier analysis revealed a positive association between HNK-1 expression and metastasis (p < 0.005) and multivariate Cox regression analysis adjusted for the standard prognostic markers ulceration and vertical tumour thickness confirmed HNK-1 expression as an independent prognostic marker. HNK-1 expression was preserved in 42% of the distant cutaneous metastases, but metastatic cells in lymph nodes were devoid of HNK-1 immunoreactivity. None of the benign pigmented lesions exhibited HNK-1 immunoreactivity. Expression of the HNK-1 glycotope in cutaneous malignant melanoma is an independent prognostic marker of metastasis. Differential HNK-1 expression at the metastatic sites implies that its expression is modulated by the surrounding environment. As HNK-1 is also transiently expressed during migration of melanocyte precursor cells derived from the neural crest, recapitulation of this transient expression might occur during metastatic spread of cutaneous malignant melanoma. 相似文献
5.
Summary Pupillary test data of 103 normal and 119 diabetic subjects (47 IDDM, 72 NIDDM) were evaluated by factor analysis. From a total of nine pupillary parameters three factors were extracted in the analysis. Factor 1 represents maximal pupillary area, contraction velocity at 1 s, dilation velocity at 6 s and minimal pupillary area — static and simple dynamic parameters; factor 2 amplitude of pupillary unrest, area under the detrended curve of pupillary unrest and period of pupillary unrest — parameters of pupillary unrest; factor 3 fusion frequency of pupillary response following flicker stimuli and latency time of pupillary light reflex — second order dynamic parameters. Factor analysis was then applied to investigate diabetic patients with a high percentage of autonomic neuropathic participants (about 39 % had pupillary and about 35 % had cardio-respiratory function disorders), which revealed the same three factors as those identified in normal subjects. Furthermore, an age-related database of parameters of pupillary unrest is given. It demonstrates that normal subjects and diabetic patients did not differ in the period of pupillary unrest (normal vs diabetic (mean±SEM): 1550±29 vs 1536±27 ms; 2p>0.5). The difference in amplitude (47.8±2.8 vs 41.0±2.6 % percentile; 2p=0.071) and area under the detrended curve of pupillary unrest (47.9±2.8 vs 40.8±2.6 % percentile, 2p=0.062) seems to show a trend but was not significant. In conclusion, factor analysis revealed three different pupillary test factors. From the comparison of normal and diabetic subjects factor 1 which accounts for the highest percentage of variance (43 %) and factor 3(12 %) appear to be useful for investigating the pupillary light reflex. Factor 2 is not useful because of the insignificant differences between the normal and diabetic group. From factor analysis and partial correlation we believe that pupillary autonomic function in diabetic patients can be best assessed by using only two parameters, maximal pupillary area and latency time.Abbreviations IDDM
Insulin-dependent diabetes mellitus
- NIDDM
non-insulin-dependent diabetes mellitus
- lx
lux
- lm
lumen 相似文献
6.
7.
Krüger S Koch KC Kaumanns I Merx MW Schäfer WM Buell U Hanrath P Hoffmann R 《European Journal of Internal Medicine》2005,16(6):429-431
BackgroundFractional flow reserve (FFR) is a valid surrogate for hemodynamic significance in stenotic native coronary arteries. The aim of this study was to examine the value of FFR compared to stress perfusion myocardial scintigraphy (SPMS) in patients with coronary stent restenosis.MethodsWe studied 42 patients, aged 62 ± 10 years, with stent restenosis 5.3 ± 1.6 months after coronary stent implantation. All patients had a single coronary lesion of intermediate severity (diameter stenosis 40–70%). FFR measurement, SPMS, and quantitative angiography of the stent stenosis were performed in all patients.ResultsThe mean percentage in stent diameter stenosis was 53 ± 9%. FFR was 0.77 ± 0.15. In 20 patients FFR was below 0.75. Nineteen patients had reversible perfusion defects in SPMS. FFR showed good diagnostic accuracy for the detection of reversible perfusion defects in SPMS (AUROC 0.86, 95% CI 0.74–0.98). The percentage of agreement of SPMS and FFR was 88%, with the best cutoff value of 0.75 for FFR.ConclusionsA FFR value of 0.75 is not only valid for diagnosing significant native coronary stenosis, but also for stent restenosis. Thus, FFR measurement should be taken into account when making decisions regarding patients with stent restenosis. 相似文献
8.
A cystic entity from the porta hepatis of a 64-year-old female patient was sent in for rapid section diagnostics with a clinical suspicion of pancreatic cancer. The rapid section diagnostics revealed aspects of glandular proliferation with mucous-like material in the lumina which led to the suspicion of infiltration of a highly differentiated mucinous adenocarcinoma. However, conventional paraffin-section histology and the immunohistochemical marker profile could not confirm this suspicion but an adenomatoid tumor was diagnosed. In typical locations in the genital area of both genders, this entity is a current differential diagnosis to infiltrations of an adenocarcinoma. 相似文献
9.
10.
Thies K Gwinnutt C Driscoll P Carneiro A Gomes E Araújo R Cassar MR Davis M 《Resuscitation》2007,74(1):135-141
The Advanced Trauma Life Support (ATLS) course, developed by the American College of Surgeons, has revolutionised in-hospital management of major trauma patients and is now accepted as a standard of care in many countries worldwide. However, within Europe, there are significant differences in both the aetiology of trauma and the specialties involved in its initial management compared to the American model. Over the past 4 years, there have been a number of initiatives aimed at producing a trauma management course that was evidence based, practical and flexible enough to meet regional European needs and team oriented. Initial attempts tried to incorporate both pre- and in-hospital trauma care. This was eventually rationalised to the production of an in-hospital course and the first pilot course was run in Malta in November 2006. This article describes the evolution of the course, its current structure and plans for the future following the feedback received from candidates and instructors who participated in the first course. 相似文献