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1.
Familial risk and heritability of intellectual disability: a population-based cohort study in Sweden
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Erika Cecon Anna Ivanova Marine Luka Florence Gbahou Anne Friederich Jean‐Luc Guillaume Patrick Keller Klaus Knoch Raise Ahmad Philippe Delagrange Michele Solimena Ralf Jockers 《Journal of pineal research》2019,66(2)
Melatonin receptors play important roles in the regulation of circadian and seasonal rhythms, sleep, retinal functions, the immune system, depression, and type 2 diabetes development. Melatonin receptors are approved drug targets for insomnia, non‐24‐hour sleep‐wake disorders, and major depressive disorders. In mammals, two melatonin receptors (MTRs) exist, MT1 and MT2, belonging to the G protein‐coupled receptor (GPCR) superfamily. Similar to most other GPCRs, reliable antibodies recognizing melatonin receptors proved to be difficult to obtain. Here, we describe the development of the first monoclonal antibodies (mABs) for mouse MT1 and MT2. Purified antibodies were extensively characterized for specific reactivity with mouse, rat, and human MT1 and MT2 by Western blot, immunoprecipitation, immunofluorescence, and proximity ligation assay. Several mABs were specific for either mouse MT1 or MT2. None of the mABs cross‐reacted with rat MTRs, and some were able to react with human MTRs. The specificity of the selected mABs was validated by immunofluorescence microscopy in three established locations (retina, suprachiasmatic nuclei, pituitary gland) for MTR expression in mice using MTR‐KO mice as control. MT2 expression was not detected in mouse insulinoma MIN6 cells or pancreatic beta‐cells. Collectively, we report the first monoclonal antibodies recognizing recombinant and native mouse melatonin receptors that will be valuable tools for future studies. 相似文献
3.
Both vascular surgery and endovascular interventions traumatise the arterial wall, especially the endothelium. The vessel responds with neointimal hyperplasia and/or constrictive remodelling, and this is still the limiting factor in curative interventions. Stent placement prevents constrictive remodelling but is the main trigger for in-stent restenosis. Hyperproliferation of neointimal tissue is the main response to arterial thrombosis, local inflammation or medio-intimal injury such as occurs, for example, after balloon dilatation in the region of arterial anastomoses or of a thrombectomy (Fogarty-manoeuvre). At present, research on prevention of restenosis is focused on inhibiting neointimal hyperproliferation by using drug-eluting stents, and especially sirolimus- or paclitaxel-eluting stents. In addition, further experimental research work is in progress, with the aim of esablishing new treatment regimens and solving the problem of neointimal formation, thrombosis and constrictive remodelling. These include both local and systemic pharmacological therapy, brachy- and laser therapy, and many genetic treatment options, some of which are currently the subjects of experimental studies and early-stage clinical trials. Gene therapy seems like a promising way of preventing restenosis, but has not yet been tested in clinical trials. In the near future, selective, simultaneous, and perhaps even polyphasic regulation for gene silencing of two or more genes involved in the development of restenosis could improve the long-term patency rate. 相似文献
4.
Hendrik Seeliger Alois Fürst Carl Zülke Karl-Walter Jauch 《Langenbeck's archives of surgery / Deutsche Gesellschaft fur Chirurgie》2002,387(7-8):286-293
BACKGROUND: Biliary tract lesions pose a dreaded complication of laparoscopic cholecystectomy. In a retrospective study we analyzed the clinical presentation, diagnostic and therapeutic management and outcome of 28 patients presenting with iatrogenic bile duct injuries. PATIENTS AND METHODS: Between 1994 and 2001 we treated 28 patients with bile duct lesions following laparoscopic cholecystectomy at our center. Operation notes and charts of all patients were reviewed systematically. A follow-up examination of each patient was performed after a median of 12 months (range 1-90). RESULTS: Twenty-two patients presented with major circumferential bile duct defect lesions. Less severe injuries (n=6) were two minor bile leaks, one bile duct stricture and three tangential lesions. Twenty-six patients were referred to our institution within 16 days (range 0-226 days). Six patients were treated by nonsurgical procedures: endoscopic stenting in four and percutaneous intervention in two. In one of the remaining patients a cystic duct leak was closed via laparotomy, and in 21 a hepaticojejunostomy was performed. Reconstruction of a hepaticojenunostomy was performed in two of these patients. Patients were dismissed from the hospital after a median of 13 days (range 4-156). Four patients presenting with generalized biliary peritonitis required prolonged intensive care. One or more episodes of cholangitis were seen in five patients during follow-up examinations. CONCLUSIONS: Major iatrogenic bile duct injuries are associated with high morbidity and prolonged hospitalization. Interdisciplinary cooperation and early referral to an experienced center is crucial in the management of patients suffering from this affliction. Cholangitis is a marked problem in the follow-up. 相似文献
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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
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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
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