Functional imaging in PNH caused by a new FilaminA mutation.
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Biomedical subjects
Publications and source records attributed to M Schröder.
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GermOnline provides information and microarray expression data for genes involved in mitosis and meiosis, gamete formation and germ line development across species. The database has been developed, and is being curated and updated, by life scientists in cooperation with bioinformaticists. Information is contributed through an online form using free text, images and the controlled vocabulary developed by the GeneOntology Consortium. Authors provide up to three references in support of their contribution. The database is governed by an international board of scientists to ensure a standardized data format and the highest quality of GermOnline's information content. Release 2.0 provides exclusive access to microarray expression data from Saccharomyces cerevisiae and Rattus norvegicus, as well as curated information on approximately 700 genes from various organisms. The locus report pages include links to external databases that contain relevant annotation, microarray expression and proteome data. Conversely, the Saccharomyces Genome Database (SGD), S.cerevisiae GeneDB and Swiss-Prot link to the budding yeast section of GermOnline from their respective locus pages. GermOnline, a fully operational prototype subject-oriented knowledgebase designed for community annotation and array data visualization, is accessible at http://www.germonline.org. The target audience includes researchers who work on mitotic cell division, meiosis, gametogenesis, germ line development, human reproductive health and comparative genomics.
INTRODUCTION: Regarding the promising results of international trials we conducted the first German prospective multicentre phase II trial for organ preservation with primary simultaneous chemoradiation in advanced laryngeal and hypopharyngeal cancer. PATIENTS AND METHODS: 28 of 30 recruited patients suffering from stage II and III (UICC) laryngeal and hypopharyngeal cancer were treated with primary simultaneous chemoradiation within an organ preservation program and monitored in follow-up of one year. Exclusion criteria included tumor infiltration of the laryngeal cartilage, bilateral neck nodes (N2c) and need for flap reconstruction in case of laryngectomy. The protocol included an accelerated concomitant boost chemoradiation (66 Gy) with Carboplatinum (70 mg/m2 1st and 5th week) and a restaging procedure one month after therapy. In case of residual disease, salvage laryngectomy and/or neck dissection were performed. RESULTS: After follow-up of one year 20 of 28 patients (71%) were presented with stable complete remission and functionally preserved larynx. Of these 20 patients 3 developed pulmonary metastases, 1 secondary primary carcinoma of the lung and 3 neck metastases which needed neck dissections. The other patients showed in 4 cases relapsing tumor which was indicated for laryngectomy. One patient needed tracheotomy because of persisting edema and 2 patients died due to tumor progress. One patient died after complications due to salvage surgery. CONCLUSION: The organ preservation protocol was feasible with well tolerated early toxicity. Problems of screening for recurrent disease, salvage surgery and late toxicity should be noted and pronounced in patient information. Further studies should focus on the improvement of patient selection which could be realized by induction Chemotherapy (using new components like taxan) and/or use of prediction factors such as tumor volume and hemoglobin levels.
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4,4'-Bipyridine N,N'-dioxide (L) acts as a hydrogen-bond acceptor in the compounds ([M(NO3)2(H2O)4].L2) (M = Co, Ni) to form doubly-interpenetrated framework materials with sixfold topological connectivity.
PURPOSE: Iliac artery occlusions that are more than a few centimeters in length are normally treated with surgical bypass grafting. The aim of this study was to evaluate the results of primary stent implantation after Excimer laser-assisted recanalization of iliac artery occlusions. SUBJECTS AND METHODS: We studied 212 consecutive patients with chronic unilateral iliac artery occlusions (mean [+/- SD] length 8.9 +/- 3.9 cm) who were treated with Excimer laser-assisted recanalization and stent implantation. Based on the criteria of the Society of Cardiovascular and Interventional Radiology, lesions were graded as class III occlusions (<5 cm) in 46 patients and as class IV (> or =5 cm) in 166 patients. A total of 527 stents (Palmaz stent, 346; Wallstent, 94; Strecker stent, 38; covered stents, 49) were implanted. RESULTS: Technical success was achieved in 190 (90%) patients. There was a clinical improvement of three grades in 112 (53%) patients and of two grades in 67 (32%) patients. The rate of major complications was 1.4%, which included arterial rupture (1) and embolic events (2). Primary patency rates were 84% at 1 year, 81% at 2 years, 78% at 3 years, and 76% at 4 years. Secondary patency rates were 88% at 1 year, 88% at 2 years, 86% at 3 years, and 85% at 4 years. CONCLUSION: Stent-supported angioplasty is an effective treatment for iliac artery occlusions, with less morbidity and mortality than is associated with surgery. However, reported long-term patency rates after bypass surgery are greater than those we observed with interventional treatment. The value of primary stenting as compared with angioplasty alone should be evaluated in a randomized trial.
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Hypertension contributes to cardiac and cerebrovascular complications in HD patients. Endogenous inhibitors of nitric oxide synthase accumulate in renal failure and may interfere with the regulation of vascular tone. We investigated the elimination of asymmetric dimethylarginine (ADMA) by using biocompatible Polyamide Strade mark membranes in low-flux (Polyflux 6L) or high-flux (Polyflux 14S) hemodialysis or hemodiafiltration (HDF) compared with hemodialysis with cellulosic membranes. Removal rates for ADMA, symmetric dimethylarginine (SDMA), and beta2-microglobulin significantly increased in HDF. The plasma total amino acid concentration and the arginine/ADMA ratio increased, and the mean 24-hour blood pressure decreased during the study. In a second study, we investigated whether plasma amino acids and interdialytic blood pressure are influenced by the use of a biocompatible membrane and HDF. Seventeen end-stage renal disease patients were treated for six weeks with hemodialysis using cellulosic membranes, six weeks with low-flux hemodialysis using Polyflux 6L, and six weeks with HDF using Polyflux 14S. Only in the diabetic patients were the hemoglobin concentration (from 10.6 +/- 1.5 to 11.9 +/- 0.6 mg/dL) and hematocrit (from 33.6 +/- 1.9 to 36.2 +/- 1.5%) increased significantly, whereas the mean 24-hour systolic blood pressure decreased (from 154 +/- 22 to 129 +/- 18 mm Hg). No significant changes were observed in nondiabetic patients. We conclude that primarily diabetic patients seem to benefit from the use of biocompatible membranes--most in HDF--after a period of six weeks. The regulation of nitric oxide pathways by ADMA removal and changed ADMA/arginine ratio might be contributing factors. Further prospective studies are required to show whether the long-term application of HDF or other changes of dialysis treatment modalities may help to improve well-being, morbidity, and mortality in hemodialysis patients.
PURPOSE: The use of biodegradable implants for arthroscopic repair of meniscal lesions is becoming increasingly popular. The aim of this study was to test the biomechanical stability and the mode of failure of these implants. TYPE OF STUDY: Biomechanical testing study. METHODS: Biomechanical investigations were performed on human menisci using 6 commonly used biodegradable implants for meniscal repair to compare them with horizontal mattress suture using 2/0 Ethibond (Ethicon, Norderstedt, Germany). Included in this study were the Meniscus Arrow (Bionx, Tampere, Finland), Dart (Arthrex, Naples, FL), Stinger (Linvatec, Largo, FL), Meniscal Screw (Innovasive, Marlborough, MA), T-Fix (Acufex, Mansfield, MA), and the Fastener (Mitek, Westwood, MA). The tests were carried out using a material testing machine at a loading rate of 10 N/second. The ultimate tension load (UTL), elongation, and stiffness were evaluated for each implant technique. RESULTS: The highest UTL was shown by Ethibond (62 +/- 7.91 N) and the T-Fix (51.35 +/- 16.31 N), followed by the Fastener (32.67 +/- 2.97 N). All other implants had a significantly lower UTL (P =.001). Less elongation under a load of 5 N was noted for Ethibond (0.64 +/- 0.25 mm) and for T-Fix (0.43 +/- 0.32 mm) compared with the other implants. The greatest elongation was found for the Fastener (2.239 +/- 0.581 mm). The stiffness of the fixation was similar in all implants, except for the Dart and Fastener, which were significantly inferior (P <.05). CONCLUSIONS: All of the biodegradable implants had lower UTL than the suture techniques. Therefore, when using the implants, they should be inserted close together to provide sufficient stability. In cases of an extended lesion, there might even be an option to combine the implant and suturing techniques.
In the title complex, [CuCl2(C12H24S6)]n, the CuCl2 unit and the ligand lie on and about inversion centres, respectively. The coordination geometry at CuII is a tetragonally elongated octahedron with the equatorial positions occupied by two chlorides, Cu-Cl 2.2786 (12) A, and two S donors, Cu-S 2.3710 (13) A. The apical positions of the octahedron are defined by two S donors at distances of 2.8261 (14) A from the metal. The macrocyclic ligand adopts a very puckered and distorted conformation. Eight of the 18 torsion angles are less than 90 degrees and all S-donors are oriented exo to the ring.
PURPOSE: To examine the safety and efficacy of excimer laser-assisted angioplasty (ELA) for recanalization of superficial femoral artery (SFA) occlusions. METHODS: Data were analyzed from 318 consecutive patients (207 men; mean age 64.2 +/- 10.7 years, range 33-91) who underwent ELA of 411 SFAs with chronic occlusions averaging 19.4 +/- 6.0 cm in length. More than 75% of patients had severe claudication (category 3). Critical lower limb ischemia with rest pain or minor tissue loss was present in 6 and 15 patients, respectively. The mean ankle brachial index (ABI) before and after exercise was 0.62 +/- 0.15 and 0.40 +/- 0.18, respectively. RESULTS: The initial attempt (crossover approach 89.7%, antegrade 6.6%, transpopliteal 3.6%) to cross the occlusion with an excimer laser catheter was successful in 342 (83.2%) of 411 limbs. A secondary attempt performed in 44 of 69 failed cases was successful in 30 limbs, increasing the technical success rate to 90.5% (372/411). Complications included acute reocclusion (4, 1.0%), perforation (9, 2.2%), and distal thrombosis/embolization (16, 3.9%). Postprocedurally, 219 (68.8%) patients were asymptomatic; mild (category 1) or moderate (category 2) claudication remained in 53 (16.6%) and 26 (8.2%) patients, respectively. The primary patency at 1 year was 33.6%. In the majority of patients, reocclusion was treatable on an outpatient basis. The 1-year assisted primary and secondary patency rates were 65.1% and 75.9%, respectively. CONCLUSIONS: Long SFA occlusions can be recanalized safely and successfully by ELA. However, to maintain patency and quality of life, intensive surveillance using objective testing followed by prompt repeat intervention are mandatory.
PURPOSE: To present a patient who developed an asymptomatic large iliac pseudoaneurysm complicating stent-supported iliac artery recanalization. CASE REPORT: The pseudoaneurysm was detected in an asymptomatic 69-year-old man during routine angiography 6 months after an uncomplicated procedure to implant 3 overlapping Palmaz stents in an occluded external iliac artery. There was no evidence of stent infection. During a second intervention, the pseudoaneurysm was successfully treated by percutaneous implantation of an EndoPro System I stent-graft. Contrast-enhanced spiral computed tomography at 6 and 12 months confirmed the durability of aneurysm exclusion and the patency of the endoprosthesis. CONCLUSIONS: Angioplasty-induced pseudoaneurysm is rare and usually asymptomatic, but elective percutaneous stent-graft repair should be considered as the first treatment option.
Diploid budding yeast exhibits two developmental programs in response to nitrogen starvation, pseudohyphal growth, and sporulation. Here we show that both programs are repressed by activation of the unfolded protein response (UPR), a stress-signal transduction pathway responsible for induction of endoplasmic reticulum (ER)-resident chaperones when protein folding in the ER is impaired. Pseudohyphal growth was derepressed in ire1Delta/ire1Delta and hac1Delta/hac1Delta strains. Activation of the UPR or overexpression of the transcription factor Hac1(i)p, the product of an unconventional splicing reaction regulated by the UPR, was sufficient for repression of pseudohyphal growth and meiosis. HAC1 splicing occurred in a nitrogen-rich environment but ceased rapidly on nitrogen starvation. Further, addition of ammonium salts to nitrogen-starved cells was sufficient to rapidly reactivate HAC1 splicing. We propose that high translation rates in a nitrogen-rich environment are coupled to limited protein unfolding in the ER, thereby activating the UPR. An activated UPR then represses pseudohyphal growth and meiosis. Nitrogen starvation slows translation rates, allowing for more efficient folding of nascent polypeptide chains, down-regulation of the UPR, and subsequent derepression of pseudohyphal growth and meiosis. These findings significantly broaden the range of physiological functions of the UPR and define a role for the UPR in nitrogen sensing.
Reactions of 1,4-dimethyl-1,4,7-triazacyclononane (L1a) and 1,4-diisopropyl-1,4,7-triazacyclononane (L1b) to form 1-aminopropyl-4,7-di-R-1,4,7-triazacyclononane [R = Me (H2L3a) or Pri (H2L3b)] and 1-(2-aminobenzyl)-4,7-di-R-1,4,7-triazacyclononane [R = Me (H2L5a) or Pri (H2L5b)] are reported. Reaction of H2L3a and H2L5a with [Ti(NMe2)2Cl2] gives the ansa-linked macrocycle-imido complexes [Ti(kappa 4-L3a)Cl2] (5a) and [Ti(kappa 4-L5a)Cl2] (6a), respectively, and NHMe2. Reaction of H2L3a with [Ti(NBut)Cl2(py)3] gives [Ti(NBut)(kappa 3-H2L3a)Cl2] (7), which possesses a pendant alkylamine group that does not undergo amine/tert-butylimido group exchange to give 5a and ButNH2. However, reaction of H2L3b and H2L5b with [Ti(NBut)Cl2(py)3] does give amine/tert-butylimido group exchange to form [Ti(kappa 4-L3b)Cl2] (5b), [Ti(kappa 4-L5b)Cl2] (8b), and ButNH2. The compounds 5a,b and 6a,b are isolobal analogues of group 4 ansa-metallocene complexes and relatives of titanium cyclopentadienyl-amido constrained geometry olefin polymerization catalysts. Reaction of 5b with AgOTf affords [Ti(kappa 4-L3b)(OTf)Cl] (8) as the major product, the crystal structure of which has been determined. Alkylation of 6b by RLi gives the dialkyl derivatives [Ti(kappa 4-L5b)(R)2] [R = Me (9) or CH2SiMe3 (10)]. The ethylene polymerization capability of the compounds 5a,b, 6a,b, and 10 in the presence of methylaluminoxane has been determined and compared to that of [Ti(NBut)(kappa 3-L1a,b)Cl2] (11a,b); in all instances, low yields of high-molecular-weight polymer are obtained.
BACKGROUND: Iliac artery aneurysms have traditionally been treated by direct surgical reconstruction. Endovascular stent grafts have been developed to provide an effective but less invasive treatment option for patients with peripheral arterial aneurysms. METHODS AND RESULTS: In 48 patients, a total of 53 endoprostheses (mean length 7. 3 cm, mean diameter 8.1 mm) were implanted into the iliac arteries (common iliac artery n=29, external iliac artery n=19) for percutaneous exclusion of aneurysmal lesions. The technical success of complete exclusion of the aneurysm was achieved in 47 of 48 cases (97.9%). In 1 case, persistent perfusion through a collateral branch was detected; however, this aneurysm thrombosed spontaneously within 2 weeks. In all patients, graft patency was monitored by clinical examination, which included the standardized treadmill test with calculation of the ankle-brachial Doppler index and color-coded duplex ultrasound. Forty-two of the 48 patients (87.5%) underwent follow-up angiography. According to Kaplan-Meier life-table calculations, primary patency rates were 100% after 1 year, 97.9% after 2 years, 94.9% after 3 years, and 87.6% after 4 years. Serial contrast-enhanced spiral CT scans were performed to rule out late procedural failures and to assess growth progression of the lesions. No secondary leaks were observed. Furthermore, the aneurysm diameter had reduced from 24.8+/-8.0 mm to 23.1+/-6.6 mm at the last follow-up (P:=NS). CONCLUSIONS: Stent grafts are a safe and effective treatment option for iliac artery aneurysms and provide good long-term patency of the graft.
IRE1 and PERK are type I transmembrane serine/threonine protein kinases that are activated by unfolded proteins in the endoplasmic reticulum (ER) to signal adaptive responses. IRE1 is present in all eukaryotic cells and signals the unfolded protein response through its kinase and endoribonuclease activities. PERK signals phosphorylation of a translation initiation factor to inhibit protein synthesis in higher eukaryotic cells but is absent in the Saccharomyces cerevisiae genome. The amino acid sequences of the amino-terminal ER luminal domains (NLDs) from IRE1 and PERK display limited homology and have diverged among species. In this study, we have demonstrated that the NLD of yeast Ire1p is required for signaling. However, the NLDs from human IRE1alpha and murine IRE1beta and the Caenorhabditis elegans IRE1 and PERK function as replacements for the S. cerevisiae Ire1p-NLD to signal the unfolded protein response. Replacement of the Ire1p-NLD with a functional leucine zipper dimerization motif yielded a constitutively active kinase that surprisingly was further activated by ER stress. These results demonstrate that ER stress-induced dimerization of the NLD is sufficient for IRE1 and PERK activation and is conserved through evolution. We propose that ligand-independent activation of IRE1 and PERK permits homodimerization upon accumulation of unfolded proteins in the lumen of the ER.
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