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1.
Familial risk and heritability of intellectual disability: a population-based cohort study in Sweden
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Kerstin Schmidt Johannes Hoffend Annette Altmann Ludwig G Strauss Antonia Dimitrakopoulou-Strauss Britta Engelhardt Dirk Koczan J?rg Peter Thomas J Dengler Walter Mier Michael Eisenhut Uwe Haberkorn Ralf Kinscherf 《Journal of nuclear medicine》2006,47(3):543-551
Growth of malignant tumors is dependent on sufficient blood supply. Thus, inhibition of tumor angiogenesis is emerging as a promising target in the treatment of malignancies. Human angiostatin (hANG) is one of the most potent inhibitors of endothelial cell proliferation, angiogenesis, and tumor growth in vivo. However, its mechanisms operating in vivo are not well understood. METHODS: To obtain more information about functional changes in the angiogenic process, we established Morris hepatoma (MH3924A) cell lines expressing hANG (hANG-MH3924A). The effects of hANG expression on proliferation and apoptosis of human umbilical vein endothelial cells (HUVECs) were measured in coculture experiments in vitro. To evaluate changes in tumor perfusion and blood volume, H2 15O and 68Ga-DOTA-albumin (DOTA is 1,4,7,10-tetraazacyclododecane-N,N',N',N'-tetraacetic acid) were used for PET studies in vivo. Additionally, immunohistologic quantification of vascularization, apoptosis, and proliferation as well as gene array analyses were performed. RESULTS: Our in vitro experiments demonstrate reduced proliferation and increased apoptosis in HUVECs when being cocultured with hANG-MH3924A. In support, tumor growth of hANG-MH3924A is diminished by 95% in vivo. However, tumor perfusion and blood volume are increased in hANG-MH3924A corresponding to an increased microvessel density. Furthermore, hANG-transfected tumors show changes in expression of genes related to apoptosis, stress, signal transduction, and metabolism. CONCLUSION: hANG expression leads to inhibition of tumor growth, increased apoptosis, and changes in the expression of multiple genes involved in stress reactions, signal transduction, and apoptosis, which indicates a multifactorial reaction of tumors. An enhanced microvessel density is seen as part of these reactions and is associated with increased perfusion as measured by PET. 相似文献
4.
J P Dutcher C E Riggs J J Strauman B Link P H Wiernik 《Clinical pharmacology and therapeutics》1989,45(4):424-428
In a phase I-II study, 21 patients with relapsed or refractory acute leukemia were treated with 4'-deoxydoxorubicin (esorubicin), the 4'-deoxy derivative of doxorubicin. Four of 14 evaluable patients with acute nonlymphocytic leukemia (ANLL) in relapse or refractory to other anthracyclines achieved partial response (28.5%). Pharmacokinetics were similar to those of the parent compound, doxorubicin. Esorubicin has activity in ANLL and has pharmacologic properties comparable to those of other anthracyclines. Dose-limiting toxicity occurs in the form of mucositis, which may limit its use in combination with other antileukemic drugs. 相似文献
5.
Christian J. Sauder Cheryl X. Zhang Malen A. Link W. Paul Duprex Kathryn M. Carbone Steven A. Rubin 《Vaccine》2009
The recent global resurgence of mumps has drawn attention to the continued need for robust mumps immunization programs. Unfortunately, some vaccines derived from inadequately attenuated vaccine strains of mumps virus have caused meningitis in vaccinees, leading to withdrawal of certain vaccine strains from the market, public resistance to vaccination, or in some cases, cessation of national mumps vaccination programs. The most widely implicated mumps vaccine in cases of postvaccination meningitis is derived from the Urabe AM9 strain, which remains in use in some countries. The Urabe AM9 vaccine virus has been shown to exhibit a considerable degree of nucleotide and amino acid heterogeneity. Some studies have specifically implicated variants containing a lysine residue at amino acid position 335 in the hemagglutinin-neuraminidase (HN) protein with neurotoxicity, whereas a glutamic acid residue at this position was associated with attenuation. To test this hypothesis we generated two modified Urabe AM9 cDNA clones coding either for a lysine or a glutamic acid at position 335 in the HN gene. The two viruses were rescued by reverse genetics and characterized in vitro and in vivo. Both viruses exhibited similar growth kinetics in neuronal and non-neuronal cell lines and were of similar neurotoxicity when tested in rats, suggesting that amino acid 335 is not a crucial determinant of Urabe AM9 growth or neurovirulence. 相似文献
6.
Die therapieinduzierte Neutropenie kann mit den Kolonie stimulierenden Faktoren (CSF) der Granulopoese (G-CSF und GM-CSF)
vermieden,abgemildert oder in ihrer Zeitdauer verkürzt werden. Die CSF erm?glichen die Mobilisation h?matopoetischer Stammzellen
in das Blut und deren Sammlung für die Transplantation nach Hochdosistherapie.Diese Faktoren sind daher essenziell in der
Supportivtherapie maligner Erkranklungen. Der Arbeitskreis Supportivma?nahmen in der Onkologie (ASO) der Deutschen Krebsgesellschaft
hat Richtlinien zur Therapie mit den Kolonie stimulierenden Faktoren entwickelt, die unterschiedlichen klinischen Situationen
angepasst sind. Der vollst?ndige Text wurde 12/2001 in “Der Onkologe” publiziert [23], er ist auch auf der Homepage des ASO
unter http://www.onkosupport.de zu finden [24].
Prof.Dr. H. Link H?matologie, Internistische Onkologie, Endokrinologie, Medizinische Klinik I, Westpfalz-Klinikum Kaiserslautern, Akademisches
Lehrkrankenhaus der Johannes-Gutenberg-Universit?t Mainz, 67653 Kaiserslautern, E-Mail: hlink@westpfalz-klinikum.de 相似文献
7.
Holger F. Boehm Felix Eckstein Caecilia Wunderer Volker Kuhn Eva-Maria Lochmueller Karin Schreiber Dirk Mueller Ernst J. Rummeny Thomas M. Link 《Journal of clinical densitometry》2005,8(4):488-494
We tested the hypothesis that bone mineral density (BMD) and bone mineral content (BMC) in proximal human femur specimens in the upper neck region of interest (ROI) and femoral neck axis length (FNAL) provide a significantly better prediction of femoral bone strength than standard ROIs in vitro. BMD and BMC were measured in 110 proximal femur specimens using a standard dual-energy X-ray absorptiometry (DXA) scanner. The analysis included a new ROI in the upper neck as well as the standard ROIs. FNAL was obtained from the scan images. The specimens' failure-load was measured in a mechanical loading device, simulating a fall on the greater trochanter. For the standard ROIs, correlations between failure-load and BMD ranged from R2 = 0.64 (shaft ROI) to R2 = 0.70, p < 0.001 (femoral neck). Prediction of strength by BMD did not significantly differ from those of BMC (R2 ranging from 0.65 to 0.75, p < 0.001). In the upper neck ROI, for both BMD and BMC correlations with failure-load were higher (R2 = 0.76 and 0.81, respectively; p < 0.001). A lower, yet still significant, correlation was found between FNAL and bone strength (R2 = 0.23, p < 0.001). Normalization of failure-load with respect to FNAL did not significantly increase the correlations with densitometric measures. This study provides in vitro evidence indicating that among the ROIs of the proximal femur the newly defined upper neck ROI provides the best prediction of bone strength. Only a weak association was observed between failure load and FNAL. 相似文献
8.
I. Kaare Tesdal Werner Jaschke Mathias Bühler Ralf Adamus Thomas Filser Eggert Holm Max Georgi 《Cardiovascular and interventional radiology》1997,20(1):29-37
Purpose To evaluate prospectively our experience with transjugular intrahepatic portosystemic shunt (TIPS) using four different metallic
stents.
Methods Between November 1991 and April 1995, 57 patients (41 men and 16 women; age 35–72 years, mean 54 years) underwent the TIPS
procedure. Techniques for portal vein localization before and during TIPS were fluoroscopy, computed tomography (CT) studies,
wedged hepatic venography, arterial portography, and ultrasound. After predilation we deployed balloon-expandable (n=48) and self-expanding (n=45) metallic stents. Fifteen patients underwent variceal embolization. Initial follow-up angiograms (mean 6.9 months, range
3–24 months) were obtained in 39 of these patients.
Results Fifty-three patients (93%) had successful TIPS placement. The mean decrease in portal pressure was 42.7%. Besides fluoroscopy,
the most helpful techniques for portal vein localization were venography and CT. Residual stenosis (n=1) and late shortening (n=4) of Wallstents resulted in shunt dysfunction. The technical problems encountered with the Palmaz stent resulted from its
lack of flexibility. We combined balloon-expandable and self-expanding stents in 12 patients. The 30-day and late follow-up
(mean 11.9 months) percutaneous reintervention rates were 11.3% and 64.2%, respectively. There were no clinically significant
complications related to the TIPS insertions.
Conclusion An ideal stent does not exist for TIPS, and the authors recommend combining a Palmaz stent with a flexible self-expanding
stent. 相似文献
9.
10.
Stefan Beckers Michael Fries Johannes Bickenbach Matthias Derwall Ralf Kuhlen Rolf Rossaint 《Critical care (London, England)》2004,9(2):R110