328 results on '"Kachel, P"'
Search Results
302. Der Einfluß von Geburtsmodus und präpartaler Lungenreifung auf Fetal Outcome und Surfactantbedarf bei kleinen Frühgeborenen
- Author
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Strittmatter, H., Zieger, W., Kachel, W., Wischnik, A., and Melchert, F.
- Abstract
Ohne Zusammenfassung:
- Published
- 1993
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303. Subunit-Dependent Inhibition of Neuronal Nicotinic Acetylcholine Receptors by Philanthotoxins
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Kachel, Hamid S., Franzyk, Henrik, Strømgaard, Kristian, Tikhonov, Denis B., and Mellor, Ian R.
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- 2014
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304. Breaking new ground.
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KACHEL, CHRIS
- Abstract
The article focuses on the emergence of clay tennis court facilities in Australia. It notes that players tend to use clay courts when developing their game. Scott Draper, National Academy manager at Tennis Australia, states that young players training on clay courts earn development lessons such as point structure, variety and movement. It discusses the work done by the Clay Court Research Centre in Sydney, New South Wales in the monitor and maintenance of various types of clay courts.
- Published
- 2013
305. DAYTONA BIKE WEEK 2012.
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KACHEL, LEE
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MOTORCYCLE racing - Abstract
A letter to the editor is presented commenting on a chance meeting with Chris Maida of "American Iron Magazine" during Daytona Bike Week 2012.
- Published
- 2013
306. REUNITING WITH HARLEYS.
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Kachel, Lee
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LETTERS to the editor ,TRAVEL ,HARLEY-Davidson motorcycle - Abstract
A letter to the editor is presented recalling a reunion trip with a friend and reminiscing about the pleasurable days of riding Harley-Davidson motorcycles.
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- 2012
307. Bestimmung des Diffusionskoeffizienten von Wasser in Polymerfilmen für Teststreifen
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Kachel, S., Zhou, Y., DuVall, S., Scharfer, P., and Schabel, W.
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- 2010
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308. NEVER TOO LATE.
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KACHEL, LEE
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LETTERS to the editor ,HARLEY-Davidson motorcycle - Abstract
A letter to the editor is presented about the first Harley-Davidson motorcycle of an enthusiast which is a 2009 Dyna Super Glide.
- Published
- 2010
309. CHANGE TO A CALCINEURIN-INHIBITOR FREE IMMUNSUPPRESSION - SAFETY AND EFFECTS TO BLOOD PRESSURE PROFILE
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Lison, A-E, Eilts, V, Zantvoort, F A., Wullstein, H -G., Hillebrand, G F., Gossmann, J, Kachel, H-G, Jochum, E, and Hartmann, H-G
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- 2008
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310. Increasing Efficacy of Autologous Haematopoetic Cell Transplantation in Acute Myeloblastic Leukaemia; a Single Centre Experience in 141 Patients.
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Prof, Jerzy Holowiecki, Czerw, Tomasz, Wojnar, Jerzy, Krawczyk-Kulis, Malgorzata, Grosicki, Sebastian, Stella-Holowiecka, Beata, Prof, Slawomira Kyrcz-Krzemien, Sadus-Wojciechowska, Maria, Giebel, Sebastian, Kachel, Lucja, Wozniczka, Krzysztof, and Holowiecka-Goral, Aleksandra
- Abstract
According to the EBMT activity survey in 2005 autologous hematopoietic cell transplantation - AHCT was performed in 24.4% out of 3573 AML patients treated with HCT, and a similar proportion of 20,1% is reported by CIBMTR. However, the role of AHCT in AML remains controversial. The recent trials focused on efficacy of AHCT in comparison to allotransplantation or chemotherapy in general demonstrate advantage of AHCT versus chemotherapy in disease free survival (DFS) and prove the feasibility of AHCT even in patients >60 y. The transplant related mortality - TRM is about 5%. The goal of this study was to evaluate the efficacy of AHCT in adult AML and to see weather the quality of the results improved with time. Among over 1700 patients treated in our department with HCT between 1991 and 2007 there were 335 AML patients; 194 allografted (66 from URD) and 141 treated using auto-transplantation. This analysis concerns AML patients treated with AHCT; age 16–61 y (median 38), M/F =73/68, 125 in CR 1 and 16 in CR >1. In 124 cases the conditioning regimen was BuCy 4+2, in 3 with additional AraC and in 14 the CAV protocol. The median numbers of transplanted cells (cryopreserved, unpurged) were following: NC 2,3 (0,4–20) x10e8/kg; CD34+ 2,1 (0,5–13) x 10e6/kg. Results. The median regeneration time of granulocytes up to >0.5 G/l and of platelets to >50 G/l equaled 20 (10–59) and 53 (11–374) days respectively. In CR1 patients at median observation time of 6.5 y the probability of 10 y OS and DFS equalled 47% and 43% respectively and the 100 day TRM was 6.3%. In the CR>1 group the corresponding values were 10%, 17% and 6%. The results obtained with CAV conditioning were distinctly worse if compared to BuCy. The TRM was related to oral Bu + Cy regimen toxicity and subsequent infections. The analysis of AML patients transplanted before and after 2000 y revealed that the proportion of autologous transplantation’s decreased in these time periods from 61% to 29% in favour of allografts. Patients auto-transplanted after 2000 were older with median age 48 y (16–61) versus 29 y (16–58) <0,000001, and were more frequently transplanted with peripheral blood cells than with bone marrow 83% vs. 23% p<0,00001. The results obtained in 57 patients treated using AHCT after 2000 were in spite of older age better if compared to 84 patients auto-grafted earlier; the TRM decreased from 8.3% to 3.5%, whereas the probability of OS improved from 37% (27–47) to 57% (42–71), p = 0,03 and DFS from 33% (23–43) to 49% (35–63), p=0,09. The multivariate analysis revealed two independent factors influencing OS: CR1 versus CR2 status (HR=2,1, p=0,02) and the transplantation period >2000y (HR=0,6, p=0,04) whereas only CR status influenced the DFS (HR=2,2, p=0,003). Our observation demonstrates that AHCT is an effective and well tolerated option for patients not eligible for allotransplantation because of age, co-morbidity or lack of the donor and the results of this procedure improved in the last decade. Clinical trials evaluating AHCT in subgroups stratified according to the new molecular risk criteria’s, introduction of less toxic conditioning and development of post-transplant treatments preventing from relapses are keys for AHCT to become still more effective treatment.
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- 2007
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311. A PILOT STUDY OF HIGH-FREQUENCY CHEST WALL OSCILLATION (HFCWO) TO REDUCE ACUTE EXACERBATIONS OF COPD (AE-COPD)
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Diette, Gregory B., Rand, Cynthia, Thompson, Katherine, Bilderback, Andrew, Hansel, Nadia N., Kachel, Diane L., Becker, Brian, and Wise, Robert A.
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- 2007
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312. Clinical Outcome in Patients with AML Exhibiting Poor Mobilization of Progenitor Cells.
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Knopinska-Posluszny, Wanda, Taszner, Michal, Zaucha, Jan M., Kachel, Lucja, Czyz, Anna, Gil, Lidia, Holowiecki, Jerzy, Komarnicki, M., and Hellmann, Andrzej
- Abstract
Intensification of post-remission therapy in patients with AML increases the rate of long-term remissions. High-dose chemotherapy and/or radiotherapy followed by autologous stem cell transplantation have therefore been shown to be promising strategy in the management of AML. The aim of this study was to assess the clinical outcome and risk of relapse in patients with low mobilizing capacity. Materials and methods: Patients from 3 Haematology Departments in Poland were treated according to 3+7 or 3+7+Cladribine protocols. Progenitor cell collection was conducted usually following the 2nd consolidation cycle. Mobilization was conducted in 238 patients in CR. PB was a main source of progenitor cells. The potential influence of recognized prognostic factors (age, WBC, cytogenetics), the number of chemotherapy cycles conducted prior to achieving CR, time elapsed from CR to mobilization, duration of aplasia following chemotherapy (<21 days) and the number of CD34+cells in mobilized material (0, <1, 1–2×106/kg CD34+), on the mobilization capacity, the clinical outcome and the risk of a relapse, was assessed. Results: AutoHSCT was conducted in 199 patients. In 39 cases it was not possible to obtain an adequate number of cells for transplantation (<2×106/kg CD34+) (16,4%). Within that group, maintenance therapy was conducted in 17 (43,6%), auto+alloHSCT was conducted in 19 cases (48,7%), alloHSCT was conducted in 3 cases (7,7%). A relapse occurred in 20 patients (51,3%). Initial WBC, age, CD34+ immunophenotype, morphological subtype, number of induction cycles, duration of cytopenia and the treatment method following ineffective mobilization (mainenance therapy vs. autoSCT, vs. alloSCT) have been shown to have no influence on mobilization capacity and the risk of relapse. Cytogenetics was obtained only in 35% of the cases for the reason that the influence of this factor on the mobilization and the risk of relapse had not been assessed. None of the following parameters; ie. number of MNC, CD34+, CFU-GM, BFU-E cells affected the risk of relapse. However it is likely, having compared a group of patients who did not undergo transplantation with a group of patients who underwent transplantation, that the low number of CD34+ cells is a factor that does not negatively affect the duration of CR. Conclusions: AutoHSCT results obtained are comparable to those achieved in other centres (3ys LFS of 50%). We have found a high percentage of “poor mobilizers”. None of the examined prognostic factors proved to be beneficial in the assessment of the risk of ineffective mobilization of progenitor cells. The lack or poor mobilization of progenitor cells has not been shown to be a negative prognostic factor in patients with AML, as regards clinical outcome and risk of relapse. New prognostic factors, that would allow the isolation of a group of patients with AML, for whom autoHSCT would be the therapy of choice, should be investigated.
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- 2006
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313. Autologous Transplantation of Non-Cryopreserved Bone Marrow for the Treatment of High-Risk Adult Acute Lymphoblastic Leukemia in First Complete Remission.
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Holowiecki, Jerzy, Giebel, Sebastian, Krawczyk-Kulis, Malgorzata, Sadus-Wojciechowska, Maria, Kachel, Lucja, Wojnar, Jerzy, Stella-Holowiecka, Beata, and Grosicki, Sebastian
- Abstract
Autologous hematopoietic stem cell transplantation (HSCT) is a recognised option of post-consolidation therapy for adults with high-risk acute lymphoblastic leukemia (ALL) not having a donor. G-CSF-stimulated peripheral blood SCT results in faster recovery compared to cryopreserved bone marrow transplantation (BMT) and is currentlly used by the majority of centres. In the current study we analyze the feasibility of a new technique of autologous BMT, which does not require cryopreservation. 115 adult patients (median age 24.5 (16–53) years) with high-risk ALL in first complete remission (CR) were treated with autologous BMT between 1991–2004 in a single center using uniform standard operating procedures. Immune phenotype was as follows: proB 17%, preB 9%, common 44%, mature B 1%, preT 9%, mature T 19%. Initial WBC was >30 G/l in 30% of patients. 8% of patients were bcr/abl(+), 38% required >1 course of induction to achieve CR. Bone marrow was collected in general anaesthesia and further stored for 72 hours in 4degC without any processing and reinfused 24 hours after completion of myeloablative therapy. Conditioning regimen (CAV) consisted of cytarabine 2x1000 mg/m2 d. −3, −2, −1, etoposide 800 mg/m2 d. −3, −2, cyclophosphamide 60 mg/kg d. −3, −2. Median NC dose was 2.0 (0.9–10.8)x10e8, CD34+cell dose − 1.6 (0.4–15)x10e6/kg. Median recovery of ANC>0.5 G/l equaled 16(11–45) days, PLT>50 G/l – 16(10–53) days (11% patients received cytokines to stimulate NC recovery). Median duration of hospital stay since the date of BMT was 19(13–51) days. The OS rate at 10 years (median follow-up 6.5 years) equaled 57% (+/−5%), LFS rate − 47% (+/−5%). Three patients died within 100 days after ABMT of septic infections (non-relapse mortality rate − 2.6%). None of the analysed factors (age, WBC at diagnosis, immonophenotype, time to achieve CR) was found to influence the long-term outcome. We conclude that autologous transplantation of non-cryopreserved bone marrow after CAV conditioning is feasible for adults with high-risk ALL. The method is characterized by fast recovery, short hospital stay and low non-relapse mortality, and may constitute good alternative to autologous PBSCT.
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- 2005
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314. UTILITY OF A HIGH-FREQUENCY CHEST WALL OSCILLATION (HFCWO) TRIAL PERIOD TO ASSESS TREATMENT SATISFACTION, ADHERENCE AND BENEFIT IN PATIENTS WITH COPD
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Kachel, Diane L., Davey, Cynthia S., Kennedy, Timothy C., Marchione, Victor L., Rolfe, Mark W., and Rumbak, Mark J.
- Published
- 2005
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315. Observations from a Yakutat eddy in the northern Gulf of Alaska
- Author
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Ladd, C., Kachel, N. B., Mordy, C. W., and Stabeno, P. J.
- Abstract
The impingement of deep basin eddies on the shelf in the Gulf of Alaska has been implicated as an important mechanism for cross‐shelf exchange. The influence of eddies on biological processes has been confirmed with data from the Sea‐viewing Wide Field‐of‐view Sensor showing elevated chlorophyll associated with eddies. Altimetry data suggest that an eddy formed in the winter of 2003 near Yakutat, Alaska, and propagated along the shelf break, reaching the head of the gulf by spring. This eddy was sampled during May and September of 2003. The eddy core water was warm, salty, and high in nitrate relative to basin water of the same density but was similar to historical water properties from the shelf near Yakutat. This suggests a shelf origin for the eddy core water.
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- 2005
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316. Identification of Factors Associated with Poor Hematopoetic Cell Mobilization and Collection from Peripheral Blood in Non-Hodgkin’s Lymphoma; Single Center Analysis of 80 Patients.
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Kachel, Lucja and Holowiecki, Jerzy
- Abstract
To identify the factors influencing hematopoetic cell collection we performed an analysis of a group of patients with uniform diagnosis treated in single center. Patients and methods: For this study we selected out of 1205 transplantation procedures performed in our department a group of 80 patients with non-Hodgkin’s lymphoma (NHL): M/F 42/38, median age 38,5, 17–66 y, who underwent peripheral blood progenitor cell (PBPC) harvest and autologous hematopoetic cell transplantation. The histological NHL subtypes were as follows: -follicular (n=13), -mantle cell (n=2), -small lymphocytic (n=9), -diffuse large B-cell (n=23), -lymphoblastic (n=11), -anaplastic (n=11) and other subtypes (n=11). The involvement of bone marrow at diagnosis or in relapse was proved in 27 patients. Most patients were heavily pretreated: the median time from diagnosis to mobilization was 12,5 months (3,7–70,8). The median number of different chemotherapy regimens was 2 (1–7) and the med. no. of chemotherapy cycles equaled to 9 (3–30). 34 patients received in addition radiation therapy. At the time of PBPC mobilization, 30 patients were in 1st remission (CR), 7 were in ≥2nd CR; 41 patients were in PR and 2 in relapse. Mobilization and harvesting procedures. In 27 patients pre-mobilization chemotherapy consisted of a single high dose of cyclophosphamide - 4,g/m2, 40 patients received IVE (Ifosfamide 3g/m2/d 1–3, Etoposide 0,2g/m2/d 1–3, epirubicine 0,05g/m2/d 1) and 10 patients were given other regimens: Cladribine, COP, F-MACHOP, Mtx, DHAP. Five days after the last chemotherapy dose G-CSF was started at 10mg/kg/day sc and continued until the last day of collection. Apheresis was performed using CS 3000 cell separators. The goal of this study was to determine factor associated with poor number of collected CD34+ cells. The following end-points were taken into account: <1.0x106 CD34+ cells/kg collected on the first day of harvest, <1.0x106 CD34+ cells/kg after two days of harvest, <1.0, <2.5, <5.0x106 CD34+ cells/kg after one entire harvesting procedure. Following variables were analyzed for their impact on the harvest efficacy: sex, age, histological subtype, bone marrow involvement, number of different chemotherapy regimens, number of chemotherapy cycles, adjuvant radiation therapy, chemotherapy scoring system (Drake M), scoring system of myelotoxic chemotherapy (Vantelon JM), time from diagnosis to mobilization, disease status at mobilization and mobilization regimen. Results: Univariate analysis selected the factors associated with unsuccessful harvest (p<0.05) as follows: bone marrow involvement at any time prior to mobilization, diagnosis of low grade lymphoma, a high number of chemotherapy regimens and cycles, additional radiation therapy, type of mobilization regimen (others vs IVE). The subsequent multivariate analysis identified following adverse risk factors: low grade NHL (p 0.01–0.004), bone marrow involvement at any time of treatment (p=0.01–0.002), B line NHL (p=0.04–0.009), number of therapy regimens >2 (p=0.03–0.0001), radiation therapy (p=0.01–0.02), scoroing system of myelotoxic chemotherapy (p=0.02–0.03), mobilization other then IVE (p=0.02–0.0007). Like in our earlier study IVE was found the most effective pre-mobilization regimen Conclusions: The factors associated with poor mobilization of peripheral blood progenitors in this study were: low grade lymphoma, bone marrow involvement, heavy pretreatment and mobilization regimen other then IVE.
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- 2004
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317. Lower Relapse Incidence after Non-Cryopreserved Autologous Bone Marrow Transplantation Compared to Peripheral Blood Stem Cell Transplantation for High-Risk Hodgkin’s Lymphoma.
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Holowiecki, Jerzy, Giebel, Sebastian, Krawczyk-Kulis, Malgorzata, Wojnar, Jerzy, Kachel, Lucja, Sadus-Wojciechowska, Maria, Stella-Holowiecka, Beata, Grosicki, Sebastian, and Czerw, Tomasz
- Abstract
In a number of studies on Hodgkin’s lymphoma (HL), autologous transplantation of peripheral blood hematopoietic stem cells (autoPBSCT) was proved to result in faster hematopoietic recovery compared to bone marrow transplantation (autoBMT), however, no difference regarding long-term outcome has been demonstrated so far. In Katowice transplant centre we developed a new method of autoBMT with bone morrow not-cryopreserved but stored for 3 days in 40C and reinfused 24 hours after completion of CBV conditioning. In this study we analyzed outcome of 40 HL patients treated with this method in comparison with 125 patients given autoPBSCT between 1993–2004. In this setting patients were treated with CBV (n=32), BEAM+/− procarbazine (n=63) or other preparative regimens (n=30). In the autoBMT group patients were transplanted in high-risk CR1 (achieved after >1 line of therapy) (25%), CR>=2 (22.5%), PR1 (35%), PR>=2 (5%), and primary or secondary refractoriness (12.5%). The indications for autoPBSCT were comparable. As well, both groups did not differ in terms of age, histological subtype, disease stage at diagnosis, organ involvement or preceding therapy. At six years, the overall- and progression-free survival for autoBMT and autoPBSCT group equaled 88% vs. 72% (p=0.1) and 69% vs. 54% (p=0.08), respectively. The relapse incidence was significantly lower for patients given autoBMT compared with autoPBSCT (23% vs. 41%, p=0.03). In a univariate analysis, among other analyzed factors (age, disease stage at diagnosis and at transplantation, organ involvement, histological subtype, conditioning regimen, preceding therapy), the only factor influencing the risk of relapse was disease status at transplantation (CR or PR vs. NR - 32% vs. 62%, p=0.001). In a multivariate analysis the impact of both disease status (p=0.001) and the source of stem cells (p=0.04) remained statistically significant. The 100 days incidence of non-relapse mortality equaled 2.5% for autoBMT and 1% for autoPBSCT (p=NS). The neutrophil >0.5 G/L recovery was faster in the autoPBSCT group compared with autoBMT (14.7 vs. 17 d., p=0.006) whereas the difference regarding platelet >50 G/L recovery was not significant (17.5 vs. 19 d., p=NS). Both procedures did not differ in terms of severe adverse events as well as the need for blood products substitution, iv antibiotic therapy, cytokine tharapy or the time of hospital stay. CONCLUSION: AutoBMT without cryopreservation results in lower relapse rate in high-risk HL patients compared with autoPBSCT. Although the neutrophil recovery is longer by 2.5 days, the toxicity of both procedures as well as the need for supportive treatment is comparable.
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- 2004
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318. The use of high–sensitivity sapphire cells in high pressure NMR spectroscopy and its application to proteins
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Kremer, W., R. Arnold, M., Kachel, N., and R. Kalbitzer, H.
- Abstract
The application of high pressure in bioscience and biotechnology has become an intriguing field in un/refolding and misfolding processes of proteins. NMR spectroscopy is the only generally applicable method to monitor pressure–induced structural changes at the atomic level in solution. Up to now the application of most of the multidimensional NMR experiments is impossible due to the restricted volume of the high pressure glass cells which causes a poor signal–to–noise ratio. Here we present high strength single crystal sapphire cells which double the signal–to–noise ratio. This increased signal–to–noise ratio is necessary to perform, for example, phophorus NMR spectroscopy under variable pressures. To understand the effect of pressure on proteins, we need to know the pressure dependence of 1H chemical shifts in random coil model tetrapeptides. The results allow distinguishing structural changes from the pressure dependence of the chemical shifts. In addition, the influence of pressure on the buffer system was investigated. Since high pressure was shown to populate intermediate amyloidogenic states of proteins the investigation of pressure effects on proteins involved in protein conformational disorders like Alzheimer's Disease (AD) and Transmissible Spongiform Encephalopathies (TSE) is of keen interest. 1H–15N–TROSY–spectra were acquired to study the effects of pressure and temperature on chemical shifts and signal volumes of the human prion protein. These measurements show identical pressure sensitivity of huPrP(23–230) and huPrP(121–230). First results suggest a folding intermediate for the human prion protein which can be populated by high hydrostatic pressure.
- Published
- 2004
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319. Intravesical Bacillus Calmette-Guerin Therapy in Patients Failing Standard Intravesical Chemotherapy
- Author
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Kachel, Thomas A., Heney, Niall M., Griffin, Pamela P., and Young, Robert H.
- Published
- 1987
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320. Coronary Arterial Disease and Arrhythmias in Chronic Obstructive Pulmonary Disease
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Kachel, Richard G.
- Published
- 1979
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321. 28 RANDOMIZED EUROPEAN MULTICENTER TRIAL OF SURFACTANT REPLACEMENT IN NEONATAL RESPIRATORY DISTRESS SYNDROME RDS
- Author
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Speer, Ch. P., Curstedt, T., Robertson, B., Herin, P., Noack, G., Kok, Joke, Koppe, Janna, van Sonderen, Loekie, Halliday, H., Nocture, G., Reid, N., Tubman, R., Laufkötter, E., Köhler, w., Soenisch, H., ALbrecht, K., Hanssler, L., Haim, Michaela, Oetoao, S. B., Okken, A., Compagnone, D., Harms, K., Herting, E., Altfeld, P. C., Groneck, P., Kachel, W., Relier, J. P., Walti, H., Göttingen, Stockholm, Amsterdam, Selfast, Bochun, Bonn, Braunschweig, Bremen, Essen, Graz, Groningen, Hannover, Köln, and Mannheia
- Published
- 1990
322. Soluble and EV-bound CD27 act as antagonistic biomarkers in patients with solid tumors undergoing immunotherapy.
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Gorgulho J, Loosen SH, Masood R, Giehren F, Pagani F, Buescher G, Kocheise L, Joerg V, Schmidt C, Schulze K, Roderburg C, Kinkel E, Fritzsche B, Wehmeyer S, Schmidt B, Kachel P, Rolling C, Götze J, Busch A, Sinn M, Pereira-Veiga T, Wikman H, Geffken M, Peine S, Matschl U, Altfeld M, Huber S, Lohse AW, Beier F, Brümmendorf TH, Bokemeyer C, Luedde T, and von Felden J
- Subjects
- Humans, Female, Male, Middle Aged, Aged, Adult, Aged, 80 and over, Neoplasms drug therapy, Neoplasms blood, Neoplasms mortality, Biomarkers, Tumor blood, Extracellular Vesicles metabolism, Immunotherapy methods, Tumor Necrosis Factor Receptor Superfamily, Member 7 metabolism, Tumor Necrosis Factor Receptor Superfamily, Member 7 blood
- Abstract
Background: The major breakthrough in cancer therapy with immune checkpoint inhibitors (ICIs) has highlighted the important role of immune checkpoints in antitumoral immunity. However, most patients do not achieve durable responses, making biomarker research in this setting essential. CD27 is a well known costimulatory molecule, however the impact of its soluble form in ICI is poorly investigated. Therefore, we aimed at testing circulating concentrations of soluble CD27 (sCD27) and CD27 bound to extracellular vesicles (EVs) as potential biomarkers to predict response and overall survival (OS) in patients undergoing ICI., Methods: Serum and plasma levels of sCD27 were assessed by immunoassay in three patient cohorts (n = 187) with advanced solid malignancies including longitudinal samples (n = 126): a training (n = 84, 210 specimens, Aachen ICI) and validation cohort (n = 70, 70 specimens, Hamburg ICI), both treated with ICI therapy, and a second independent validation cohort (n = 33, 33 specimens, Hamburg non-ICI) undergoing systemic therapy without any ICI. In a subset (n = 36, 36 baseline and 108 longitudinal specimens), EV-bound CD27 from serum was measured, while EV characterization studies were conducted on a fourth cohort (n = 45)., Results: In the Aachen and Hamburg ICI cohorts, patients with lower circulating sCD27 levels before and during ICI therapy had a significantly longer progression-free survival (PFS) and OS compared to patients with higher levels, a finding that was confirmed by multivariate analysis (MVA) (Aachen ICI: p
PFS = 0.012, pOS = 0.001; Hamburg ICI: pPFS = 0.040, pOS = 0.004) and after randomly splitting both cohorts into training and validation. This phenomenon was not observed in the Hamburg non-ICI cohort, providing a rationale for the predictive biomarker role of sCD27 in immune checkpoint blockade. Remarkably, EV-bound CD27 baseline levels and dynamics during ICI therapy also emerged as potent predictive biomarkers, acting however antagonistically to soluble sCD27, i.e. higher levels were associated with PFS and OS benefit. Combining both molecules ("multi-CD27" score) enhanced the predictive ability (HRPFS : 17.21 with p < 0.001, HROS : 6.47 with p = 0.011)., Conclusion: Soluble and EV-bound CD27 appear to have opposing immunomodulatory functions and may represent easily measurable, non-invasive prognostic markers to predict response and survival in patients undergoing ICI therapy., (© 2024. The Author(s).)- Published
- 2024
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323. Ex vivo drug response heterogeneity reveals personalized therapeutic strategies for patients with multiple myeloma.
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Kropivsek K, Kachel P, Goetze S, Wegmann R, Festl Y, Severin Y, Hale BD, Mena J, van Drogen A, Dietliker N, Tchinda J, Wollscheid B, Manz MG, and Snijder B
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- Humans, Plasma Cells pathology, Proteasome Inhibitors therapeutic use, Bone Marrow pathology, Immunotherapy, Multiple Myeloma drug therapy, Multiple Myeloma genetics, Multiple Myeloma pathology
- Abstract
Multiple myeloma (MM) is a plasma cell malignancy defined by complex genetics and extensive patient heterogeneity. Despite a growing arsenal of approved therapies, MM remains incurable and in need of guidelines to identify effective personalized treatments. Here, we survey the ex vivo drug and immunotherapy sensitivities across 101 bone marrow samples from 70 patients with MM using multiplexed immunofluorescence, automated microscopy and deep-learning-based single-cell phenotyping. Combined with sample-matched genetics, proteotyping and cytokine profiling, we map the molecular regulatory network of drug sensitivity, implicating the DNA repair pathway and EYA3 expression in proteasome inhibitor sensitivity and major histocompatibility complex class II expression in the response to elotuzumab. Globally, ex vivo drug sensitivity associated with bone marrow microenvironmental signatures reflecting treatment stage, clonality and inflammation. Furthermore, ex vivo drug sensitivity significantly stratified clinical treatment responses, including to immunotherapy. Taken together, our study provides molecular and actionable insights into diverse treatment strategies for patients with MM., (© 2023. The Author(s).)
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- 2023
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324. Self-Reported Reactogenicity After Different COVID-19 Vaccination Regimens.
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Pfrommer LR, Schoeps M, Blettner M, Wollschläger D, Herm-Stapelberg N, Mittnacht L, Kachel P, Jahn K, von Loewenich FD, and Gianicolo EAL
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- Male, Female, Humans, Middle Aged, Self Report, 2019-nCoV Vaccine mRNA-1273, Vaccination, COVID-19 Vaccines adverse effects, COVID-19 epidemiology, COVID-19 prevention & control
- Abstract
Background: In Rhineland-Palatinate, most COVID-19 vaccinations are centrally registered by the Rhineland-Palatinate Division of Vaccine Documentation, which includes self-reported vaccination reactions (SRVR) and their level of perceived intensity. We analyzed the occurrence of SRVR reported between 12/2020 and 12/2021 in relation to the different vaccination regimens involving BioNTech/Pfizer (BNT) and Moderna (m1273) mRNA vaccines and AstraZeneca (ChAd) and Johnson & Johnson (Ad26) viral vector vaccines., Methods: Using sex-specific logistic regression models, we analyzed the occurrence of all local and systemic SRVR, as well as the occurrence of local and systemic SRVR that were self-rated as "severe" by the vaccinated persons, in relation to the vaccine of the first vaccination and the vaccination regimen of the second vaccination (BNT/BNT, ChAd/ChAd, m1273/m1273, ChAd/ BNT, ChAd/m1273). Vaccination with BNT or the BNT/BNT regimen formed the reference category for the estimated odds ratios (OR) with respective 95% confidence intervals., Results: Of all those vaccinated, 40.7% provided valid information on SRVR after the first vaccination and 33.8% after the second vaccination. As a result, 887 052 individuals were included in the analyses. Their median age was 60 years, and 58% were women. The most common vaccination regimen was BNT/BNT (67.3%). The most common SRVR were pain at the injection site and fatigue. Self-reported reactogenicity after the first vaccination was lowest for BNT. Self-reported systemic reactogenicity was notably higher after vaccination with a vector vaccine. After the second vaccination, self-reported reactogenicity was lowest after a ChAd/ChAd regimen and highest after an m1273 second vaccination., Conclusion: With overall acceptable tolerability, differences in self-reported reactogenicity were evident depending on the particular COVID-19 vaccines and vaccination regimens in question.
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- 2022
- Full Text
- View/download PDF
325. A novel dual-cytokine-antibody fusion protein for the treatment of CD38-positive malignancies.
- Author
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De Luca R, Kachel P, Kropivsek K, Snijder B, Manz MG, and Neri D
- Subjects
- ADP-ribosyl Cyclase 1 immunology, Cell Line, Tumor, Humans, Immunoconjugates genetics, Immunoconjugates immunology, Immunoconjugates metabolism, Recombinant Fusion Proteins genetics, Recombinant Fusion Proteins immunology, Recombinant Fusion Proteins metabolism, TNF-Related Apoptosis-Inducing Ligand metabolism, ADP-ribosyl Cyclase 1 metabolism, Cytokines metabolism, Immunoconjugates therapeutic use, Multiple Myeloma drug therapy, Multiple Myeloma metabolism, Recombinant Fusion Proteins therapeutic use
- Abstract
A novel dual-cytokine-antibody fusion protein, consisting of an antibody directed against CD38 [a tumor-associated antigen mainly expressed on the surface of multiple myeloma (MM) cells], simultaneously fused to both tumor necrosis factor ligand superfamily member 10 (TRAIL) and interleukin-2 (IL2), was designed, expressed and purified to homogeneity. The novel fusion protein, termed IL2-αCD38-αCD38-scTRAIL, was able to selectively recognize its cognate antigen expressed on the surface of MM and lymphoma cell lines, as evidenced by flow cytometry analysis. Moreover, the targeted version of TRAIL was able to induce cancer cell death in vitro, both with MM cell lines and with fresh isolates from the bone marrow of MM patients. The experiments provide a rationale for possible future applications of IL2-αCD38-αCD38-scTRAIL for the treatment of patients with MM or other CD38-positive malignancies.
- Published
- 2018
- Full Text
- View/download PDF
326. Bone tissue engineering using polyetherketoneketone scaffolds combined with autologous mesenchymal stem cells in a sheep calvarial defect model.
- Author
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Adamzyk C, Kachel P, Hoss M, Gremse F, Modabber A, Hölzle F, Tolba R, Neuss S, and Lethaus B
- Subjects
- Animals, Disease Models, Animal, Humans, Models, Animal, Osseointegration, Sheep, Benzophenones, Bone Regeneration, Mesenchymal Stem Cell Transplantation, Polymers, Skull, Tissue Engineering methods, Tissue Scaffolds
- Abstract
Polyetherketoneketone (PEKK) a high performance thermoplastic polymer that is FDA-approved for cranio- and maxillo-facial as well as spineal surgery. We studied the viability, growth and osteogenic differentiation of bone marrow-derived human and sheep mesenchymal stem cells (MSC) in combination with a 3D scaffold made of PEKK using different cell-based assays. To investigate if autologous MSC, either undifferentiated or osteogenically pre-differentiated, augmented bone formation after implantation, we implanted cell-seeded 3D PEKK scaffolds into calvarial defects in sheep for 12 weeks. The volume and quality of newly formed bone were investigated using micro-computer tomography (micro-CT) and histological stainings. Our results show that the 3D PEKK scaffolds were cyto- and bio-compatible. They allowed for adherence, growth and osteogenic differentiation of human and ovine MSC. However, bone healing seemed unaffected by whether the scaffolds were seeded with MSC. Considerable amounts of newly formed bone were found in all PEKK treated groups, but a fibrous capsule was formed around the implants regardless of cell seeding with MSC., (Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
327. Phosphorylation of pyruvate kinase M2 and lactate dehydrogenase A by fibroblast growth factor receptor 1 in benign and malignant thyroid tissue.
- Author
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Kachel P, Trojanowicz B, Sekulla C, Prenzel H, Dralle H, and Hoang-Vu C
- Subjects
- Biomarkers, Carrier Proteins genetics, Cell Line, Gene Expression, Humans, Isoenzymes genetics, Isoenzymes metabolism, L-Lactate Dehydrogenase genetics, Lactate Dehydrogenase 5, Membrane Proteins genetics, Phosphorylation, RNA, Messenger genetics, RNA, Messenger metabolism, Receptor, Fibroblast Growth Factor, Type 1 genetics, Thyroid Hormones genetics, Thyroid Neoplasms diagnosis, Thyroid Neoplasms genetics, Thyroid Hormone-Binding Proteins, Carrier Proteins metabolism, L-Lactate Dehydrogenase metabolism, Membrane Proteins metabolism, Receptor, Fibroblast Growth Factor, Type 1 metabolism, Thyroid Gland metabolism, Thyroid Gland pathology, Thyroid Hormones metabolism, Thyroid Neoplasms metabolism
- Abstract
Background: Lactate dehydrogenase A (LDHA) and Pyruvate Kinase M2 (PKM2) are important enzymes of glycolysis. Both of them can be phosphorylated and therefore regulated by Fibroblast growth factor receptor 1 (FGFR1). While phosphorylation of LDHA at tyrosine10 leads to tetramerization and activation, phosphorylation of PKM2 at tyrosine105 promotes dimerization and inactivation. Dimeric PKM2 is found in the nucleus and regulates gene transcription. Up-regulation and phosphorylation of LDHA and PKM2 contribute to faster proliferation under hypoxic conditions and promote the Warburg effect., Methods: Using western blot and SYBR Green Real time PCR we investigated 77 thyroid tissues including 19 goiter tissues, 11 follicular adenomas, 16 follicular carcinomas, 15 papillary thyroid carcinomas, and 16 undifferentiated thyroid carcinomas for total expression of PKM2, LDHA and FGFR1. Additionally, phosphorylation status of PKM2 and LDHA was analysed. Inhibition of FGFR was performed on FTC133 cells with SU-5402 and Dovitinib., Results: All examined thyroid cancer subtypes overexpressed PKM2 as compared to goiter. LDHA was overexpressed in follicular and papillary thyroid cancer as compared to goiter. Elevated phosphorylation of LDHA and PKM2 was detectable in all analysed cancer subtypes. The highest relative phosphorylation levels of PKM2 and LDHA compared to overall expression were found in undifferentiated thyroid cancer. Inhibition of FGFR led to significantly decreased phosphorylation levels of PKM2 and LDHA., Conclusions: Our data shows that overexpression and increased phosphorylation of PKM2 and LHDA is a common finding in thyroid malignancies. Phospho-PKM2 and Phospho-LDHA could be valuable tumour markers for thyroglobulin negative thyroid cancer.
- Published
- 2015
- Full Text
- View/download PDF
328. Primary nursing at Concord (R.G.H.):--it really does work.
- Author
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Kachel P
- Subjects
- Hospitals, General, Humans, Interprofessional Relations, Nursing Service, Hospital organization & administration, Primary Nursing
- Published
- 1980
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