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1.
Transpl Immunol ; 82: 101985, 2024 02.
Article in English | MEDLINE | ID: mdl-38184211

ABSTRACT

Currently, approximately 19 million people with a migration background live in Germany. The majority of those descend from regions where the population has a genetically different distribution of HLA antigens when compared to the HLA frequencies usually found in North Western Europe. In case of severe haematological disorders of these individuals, allogeneic stem cell transplantation may be the treatment of choice. However, finding appropriate histocompatible hematopoietic stem cell donors continues to be a major challenge. If no matching sibling donors are available, there are only few suitable donors with a similar genetic background available in international blood stem cell donor registries. The "BluStar.NRW" project aimed to recruit new blood and hematopoietic stem cell donors with a migration background and to noticeably increase the number of suitable donors for patients within this group. Since December 2017, a total number of 9100 blood and stem cell donors with a migration background were recruited and typed for this project. HLA typing for HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 was performed by Next Generation Sequencing. We assessed the proportion of rare alleles according to HLA frequency tables, as defined by a frequency of <1:1000. The rare HLA allele frequencies according to HLA frequency tables of the BluStar.NRW cohort were compared with a matched control donor cohort: Rare HLA-A, -B, -C, -DRB1 and -DQB1 alleles occurred three times more frequent than in the control group, but rare HLA-DPB1 alleles occurred more frequently in the control cohort. This difference was highly significant for all HLA alleles (p < 0.0001 for HLA-A, -B, -C, -DRB1, -DPB1; p = 0.0002 for HLA-DQB1). In addition, the distribution of rare alleles differed between the two groups. To date, 29 work-ups were initiated, 12 PBSC, one BM and three DLI were collected so far out of the BluStar.NRW cohort. The apheresis probability is twofold higher (0.18% vs. 0.07%) compared to the control group which clearly shows a serious medical need. However, 13 work-ups were cancelled in the BluStar.NRW donor cohort which represents an almost twice as higher cancellation rate (45% vs. 25%). This single registry analysis with a large sample cohort clearly indicates that hematopoietic stem cell donors with a migration background represent an adequate donor pool to serve patients of comparable ethnicity.


Subject(s)
Hematopoietic Stem Cell Transplantation , Refugees , Transients and Migrants , Humans , Ethnicity/genetics , Tissue Donors , Histocompatibility Antigens Class I/genetics , Hematopoietic Stem Cells , Gene Frequency , HLA-A Antigens/genetics , Alleles , Histocompatibility Testing , Haplotypes
2.
Pediatr Rheumatol Online J ; 19(1): 41, 2021 Mar 22.
Article in English | MEDLINE | ID: mdl-33752685

ABSTRACT

BACKGROUND: Oligoarticular juvenile idiopathic arthritis (oligoJIA) is the most commonly diagnosed category of chronic arthritis in children. Nevertheless, there are no evidence- based guidelines for its treatment, in particular for the use of methotrexate (MTX). The primary objective of this analysis is to evaluate the outcomes in patients with persistent oligoJIA compared to those with extended oligoJIA and rheumatoid factor (RF) negative polyarthritis treated with methotrexate. METHODS: Patients with persistent or extended oligoJIA or RF negative PA recorded in the Biologics in Pediatric Rheumatology Registry (BiKeR), receiving methotrexate for the first time were included in the analyses. Efficacy was determined using the Juvenile Arthritis Disease Activity Score 10 (JADAS 10). Safety assessment included the documentation of adverse and serious adverse events. RESULTS: From 2005 through 2011, 1056 patients were included: 370 patients with persistent oligoJIA, 221 patients with extended oligoJIA and 467 patients with RF negative PA. Therapeutic efficacy was observed following the start of methotrexate. Over a period of 24 months JADAS-minimal disease activity (JADAS ≤2) was reached in 44% of patients with persistent oligoJIA, 38% with extended oligoJIA, 46% with RF negative PA, JADAS-remission defined as JADAS ≤1 was reached in 33% of patients with persistent oligoJIA, 29% with extended oligoJIA and 35% (RF negative PA). Patients with extended oligoJIA achieved JADAS remission significantly later and received additional biologic disease-modifying drugs significantly more often than patients with persistent oligoJIA or RF negative PA (p < 0.001). Tolerability was comparable. New onset uveitis occurred in 0.3 to 2.2 per 100 patient years. CONCLUSIONS: Patients with persistent oligoJIA taking methotrexate are at least as likely to enter remission as patients with extended oligo JIA or polyarticular JIA. Patients with extended oligoJIA achieved JADAS remission significantly later. Within 2 years, almost half of the patients with persistent oligoJIA achieved JADAS-minimal disease activity.


Subject(s)
Antirheumatic Agents/therapeutic use , Arthritis, Juvenile/drug therapy , Arthritis/drug therapy , Methotrexate/therapeutic use , Child , Child, Preschool , Female , Germany , Humans , Male , Registries , Treatment Outcome
3.
Ann Anat ; 231: 151511, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32304739

ABSTRACT

Mini dental implants (MDI) have proven to be a good alternative of the conventional implants to support lower overdentures in elderly edentulous patients with narrow residual ridge. The aim of the present study was to define drilling protocols for each diameter of the MDI in each bone quality. The number and the diameter of the drilling bur and the drilling depth was investigated. A total of 48 MDIs with a ball head and transgingival collar were used to the drilling protocol in four different bone qualities (Q1-Q4). All available four diameters of the implants were included: 1.8mm, 2.1mm, 2.4mm, and 2.9mm. The length of all implants was 15mm. Three different protocols were prepared for each of the four bone qualities and for each implant diameter. The insertion torques and the primary stability of the implants were measured in their final position. Regardless of implant diameter and bone quality, the insertion torque was significantly higher using drilling protocol 1 than 3 and using drilling protocol 2 than 3 as well. The insertion torque was significantly higher in bone quality Q1 than in Q2-Q4. The unscrewing resulted in considerably increase in the torque, which exceeded the insertion torques by up to two times. This repeatedly led to the bending and fractures of implants.


Subject(s)
Dental Implants/standards , Mandible/surgery , Aged , Dental Implants/classification , Humans , Mandible/physiology , Pilot Projects
4.
Am J Pathol ; 190(2): 484-502, 2020 02.
Article in English | MEDLINE | ID: mdl-31843498

ABSTRACT

Targeted therapeutics are needed for triple-negative breast cancer (TNBC). In this study, we investigated the activation of Src family of cytoplasmic tyrosine kinases (SFKs) and two SFK substrates-CUB-domain containing protein 1 (CDCP1) and protein kinase C δ (PKCδ)-in 56 formalin-fixed, paraffin-embedded (FFPE) TNBCs. Expression of SFK phosphorylated at Y416 (SFK_pY416+) in tumor cells was strongly associated with phosphorylation of CDCP1 and PKCδ (CDCP1_ pY743+ and PKCδ_pY311+), as assessed by immunohistochemistry, indicating increased SFK activity in situ. To enable biochemical analysis, protein extraction from FFPE tissue was optimized. Cleaved CDCP1 isoform (70 kDa) was expressed to a varying degree in all samples but only phosphorylated in TNBC tumor cells that expressed SFK_pY416. Interestingly, active SFK was found to be biphosphorylated (SFK_pY416+/pY527+). Biphosphorylated active SFK was observed more frequently in forkhead box protein A1 (FOXA1)- TNBCs. In addition, in SFK_pY416- samples, FOXA1+ TNBC tended to be SFK_pY527+ (classic inactive SFK), and FOXA1- TNBC tended to be SFK_pY527- (SFK poised for activation). Strong SFK_pY416 staining was also observed in tumor-infiltrating lymphocytes in a subset of TNBCs with high tumor-infiltrating lymphocyte content. This report will facilitate protein biochemical analysis of FFPE tumor samples and justifies the development of therapies targeting the SFK/CDCP1/PKCδ pathway for TNBC treatment.


Subject(s)
Antigens, Neoplasm/metabolism , Biomarkers, Tumor/metabolism , Cell Adhesion Molecules/metabolism , Lymphocytes, Tumor-Infiltrating/immunology , Protein Kinase C-delta/metabolism , Triple Negative Breast Neoplasms/pathology , Tyrosine/metabolism , src-Family Kinases/metabolism , Aged , Cell Adhesion , Cell Movement , Female , Hepatocyte Nuclear Factor 3-alpha/metabolism , Humans , Middle Aged , Phosphorylation , Prognosis , Signal Transduction , Triple Negative Breast Neoplasms/classification , Triple Negative Breast Neoplasms/immunology , Triple Negative Breast Neoplasms/metabolism , Tumor Cells, Cultured , Vimentin/metabolism
5.
BMJ Case Rep ; 12(5)2019 May 13.
Article in English | MEDLINE | ID: mdl-31088817

ABSTRACT

A 62-year-old man presented with concurrent sigmoid colon adenocarcinoma and small bowel mesenteric dedifferentiated liposarcoma. Following surgical resection of the colon cancer, complete excision of the mesenteric sarcoma and adjuvant folinic acid, fluorouracil and oxaliplatin (FOLFOX) chemotherapy, the patient demonstrated no radiological evidence of disease for more than 2 years. The patient then developed synchronous recurrence of both cancers: the colon cancer metastasised to the liver and a pelvic lymph node, and the liposarcoma recurred in the original location. The patient underwent additional chemotherapy with complete response of the metastatic colon cancer and stable disease for the liposarcoma. The recurrent mesenteric tumour was subsequently resected. Although concurrent cancers have been reported, this unique case of synchronous recurrence raises interesting hypotheses regarding host-tumour interaction and immune surveillance.


Subject(s)
Adenocarcinoma/pathology , Liposarcoma/pathology , Peritoneal Neoplasms/pathology , Sigmoid Neoplasms/pathology , Adenocarcinoma/diagnostic imaging , Adenocarcinoma/drug therapy , Humans , Liposarcoma/diagnostic imaging , Male , Mesentery/pathology , Middle Aged , Neoplasm Recurrence, Local , Neoplasms, Multiple Primary , Peritoneal Neoplasms/diagnostic imaging , Positron-Emission Tomography , Sigmoid Neoplasms/diagnostic imaging , Sigmoid Neoplasms/drug therapy
6.
Int J Immunogenet ; 45(3): 95-101, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29575597

ABSTRACT

We reported previously on the widespread occurrence of anti-HLA alloantibodies of the IgA isotype (anti-HLA IgA) in the sera of solid-organ re-transplantation (re-tx) candidates (Arnold et al., ). Specifically focussing on kidney re-tx patients, we now extended our earlier findings by examining the impact of the presence and donor specificity of anti-HLA IgA on graft survival. We observed frequent concurrence of anti-HLA IgA and anti-HLA IgG in 27% of our multicenter collective of 694 kidney re-tx patients. This subgroup displayed significantly reduced graft survival as evidenced by the median time to first dialysis after transplantation (TTD 77 months) compared to patients carrying either anti-HLA IgG or IgA (TTD 102 and 94 months, respectively). In addition, donor specificity of anti-HLA IgA had a significant negative impact on graft survival (TTD 74 months) in our study. Taken together, our data strongly indicate that presence of anti-HLA IgA, in particular in conjunction with anti-HLA-IgG, in sera of kidney re-tx patients is associated with negative transplantation outcome.


Subject(s)
Graft Survival/immunology , HLA Antigens/immunology , Immunoglobulin A/immunology , Isoantibodies/immunology , Organ Transplantation , Transplant Recipients , Adolescent , Adult , Aged , Aged, 80 and over , Alleles , Antibody Specificity/immunology , Child , Child, Preschool , Female , HLA Antigens/genetics , Humans , Immunoglobulin A/blood , Immunoglobulin G/blood , Immunoglobulin G/immunology , Isoantibodies/blood , Kidney Transplantation , Male , Middle Aged , Organ Transplantation/adverse effects , Prognosis , Retreatment , Young Adult
7.
Cytometry B Clin Cytom ; 94(4): 623-630, 2018 07.
Article in English | MEDLINE | ID: mdl-27860206

ABSTRACT

BACKGROUND: Due to its high sensitivity, the flow cytometry cross-match (FCXM) has been described as valuable tool for identifying an optimal donor. We here focused on the impact of ABO incompatibility on FCXM results. METHODS: We analyzed 29 ABO incompatible and 89 ABO compatible donor-recipient pairs (73 and 175 datasets, respectively) prior to living donor kidney transplantation. In all patients, lymphocytotoxic cross-matches for B and T cells were negative. RESULTS: Recipients with blood group O (A to O and B to O) displayed significantly (P < 0.05) higher T-FCXM results than those with blood group A and B (A to B, B to A and AB to A), respectively. Donor-specific T-FCXM responses (ΔMFI values) were significantly higher (P < 0.05) in ABO incompatible vs. compatible pairs (ABO incompatible recipients with blood group O: 32 ± 6; with blood group A: 19 ± 7; with blood group B: 7 ± 4; recipients with ABO compatibility: 3 ± 2, respectively, data represent mean ± SEM). Consistent with the T-FCXM results donor-specific isohemagglutinins (IgG titers) were significantly higher in recipients with blood group O vs. A, both prior to rituximab treatment and plasmapheresis/immune adsorption (P = 0.004) and immediately prior to transplantation, i.e., after rituximab and antibody-depleting therapies (P = 0.04). CONCLUSIONS: ABO incompatibility was associated with higher T-FCXM responses, especially in recipients with blood group O. This finding has major impact on the interpretation of flow cross-match results. Current cut-off values need to be reassessed in the ABO incompatible setting. © 2016 International Clinical Cytometry Society.


Subject(s)
ABO Blood-Group System/immunology , Flow Cytometry/methods , Histocompatibility Testing/methods , Kidney Transplantation/methods , T-Lymphocytes , Adolescent , Adult , Aged , Female , Flow Cytometry/standards , Histocompatibility Testing/standards , Humans , Male , Middle Aged , Transplantation Immunology/immunology , Young Adult
8.
Clin Neurol Neurosurg ; 156: 48-54, 2017 May.
Article in English | MEDLINE | ID: mdl-28324788

ABSTRACT

OBJECTIVES: To compare clinical features and outcome, imaging characteristics, biopsy results and laboratory findings in a cohort of 69 patients with suspected or diagnosed primary central nervous system vasculitis (PCNSV) in adults; to identify risk factors and predictive features for PCNSV. PATIENTS AND METHODS: We performed a case-control-study including 69 patients referred with suspected PCNSV from whom 25 were confirmed by predetermined diagnostic criteria based on biopsy (72%) or angiography (28%). Forty-four patients turned out to have 15 distinct other diagnoses. Clinical and diagnostic data were compared between PCNSV and Non-PCNSV cohorts. RESULTS: Clinical presentation was not able to discriminate between PCNSV and its differential diagnoses. However, a worse clinical outcome was associated with PCNSV (p=0.005). Biopsy (p=0.004), contrast enhancement (p=0.000) or tumour-like mass lesion (p=0.008) in magnetic resonance imaging (MRI), intrathecal IgG increase (p=0.020), normal Duplex findings of cerebral arteries (p=0.022) and conventional angiography (p 0.010) were able to distinguish between the two cohorts. CONCLUSION: In a cohort of 69 patients with suspected PCNSV, a large number (64%) was misdiagnosed and partly received treatment, since mimicking diseases are very difficult to discriminate. Clinical presentation at manifestation does not help to differentiate PCNSV from its mimicking diseases. MRI and cerebrospinal fluid analysis are unlikely to be normal in PCNSV, though unspecific if pathological. Cerebral angiography and biopsy must complement other diagnostics when establishing the diagnosis in order to avoid misdiagnosis and mistreatment. CLINICAL TRIAL REGISTRATION: German clinical trials register: http://drks-neu.uniklinik-freiburg.de/drks_web/, Unique identifier: DRKS00005347.


Subject(s)
Vasculitis, Central Nervous System/therapy , Adult , Biopsy , Case-Control Studies , Cerebral Angiography , Cerebral Arteries/diagnostic imaging , Cohort Studies , Comorbidity , Diagnosis, Differential , Diagnostic Errors/statistics & numerical data , Female , Humans , Immunoglobulin G , Magnetic Resonance Imaging , Male , Middle Aged , Predictive Value of Tests , Prognosis , Retrospective Studies , Risk Factors , Vasculitis, Central Nervous System/complications , Vasculitis, Central Nervous System/diagnosis
9.
Comput Methods Biomech Biomed Engin ; 20(7): 770-782, 2017 May.
Article in English | MEDLINE | ID: mdl-28279083

ABSTRACT

The effect of implants' number on overdenture stability and stress distribution in edentulous mandible, implants and overdenture was numerically investigated for implant-supported overdentures. Three models were constructed. Overdentures were connected to implants by means of ball head abutments and rubber ring. In model 1, the overdenture was retained by two conventional implants; in model 2, by four conventional implants; and in model 3, by five mini implants. The overdenture was subjected to a symmetrical load at an angle of 20 degrees to the overdenture at the canine regions and vertically at the first molars. Four different loading conditions with two total forces (120, 300 N) were considered for the numerical analysis. The overdenture displacement was about 2.2 times higher when five mini implants were used rather than four conventional implants. The lowest stress in bone bed was observed with four conventional implants. Stresses in bone were reduced by 61% in model 2 and by 6% in model 3 in comparison to model 1. The highest stress was observed with five mini implants. Stresses in implants were reduced by 76% in model 2 and 89% increased in model 3 compared to model 1. The highest implant displacement was observed with five mini implants. Implant displacements were reduced by 29% in model 2, and increased by 273% in model 3 compared to model 1. Conventional implants proved better stability for overdenture than mini implants. Regardless the type and number of implants, the stress within the bone and implants are below the critical limits.


Subject(s)
Dental Implants , Dental Prosthesis, Implant-Supported , Denture, Overlay , Finite Element Analysis , Dental Stress Analysis , Humans , Models, Theoretical , Mucous Membrane/pathology , Numerical Analysis, Computer-Assisted , Tooth/pathology , Weight-Bearing
10.
Scand J Immunol ; 85(1): 51-57, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27763680

ABSTRACT

Approximately 70% of kidney transplant recipients are non-responders to conventional hepatitis B virus (HBV) vaccines. We examined whether Fendrix™, an HBV vaccine containing 3-O-desacyl-4'-monophosphoryl lipid A (MPL) as adjuvant, could induce HBV immunity in these patients and compared their vaccination efficacy with healthy controls tested previously by the same assays. We selected 35 kidney transplant recipients who had been vaccinated at least thrice against HBV but had never displayed anti-HBs antibodies. We re-assessed their anti-HBs antibody titres and further determined cellular HBV immunity by proliferation assay and interferon (IFN)-γ ELISpot. Seventeen recipients did neither display humoral nor cellular immunity and could be tested prior to and at month 1 after vaccination. Of note, HLA antigens associated with non-response to HBV vaccination (HLA-DRB1*03 and HLA-DQB1*02) were over-represented in these 17 recipients. At month 1 after a single vaccination with Fendrix™, we observed a significant increase in anti-HBs antibodies (P = 0.02). In seven of 17 recipients, we detected anti-HBs antibodies ≥10 IU/l (10-264), in four HBV-specific lymphocyte proliferation (stimulation index of 2.6-8.7) and in one specific IFN-γ responses (12 spots increment). The vaccination response to Fendrix™ was significantly higher (P = 0.035) than the response to HBVaxPro™ in young healthy controls. In summary, the results show that a single vaccination with Fendrix™ could already induce HBV-specific humoral and/or cellular responses in ten of 17 kidney transplant patients. Thus, Fendrix™ appears as an efficient vaccine in this patient cohort.


Subject(s)
Hepatitis B Vaccines/immunology , Hepatitis B/immunology , Immune Tolerance , Kidney Transplantation , Adult , Aged , Antibodies, Viral/blood , Cell Proliferation , Cells, Cultured , Enzyme-Linked Immunospot Assay , Female , Hepatitis B/prevention & control , Hepatitis B Antibodies/immunology , Humans , Immunity, Cellular , Immunity, Humoral , Interferon-gamma/metabolism , Male , Vaccination , Young Adult
11.
Gesundheitswesen ; 79(3): 195-202, 2017 Mar.
Article in German | MEDLINE | ID: mdl-26630446

ABSTRACT

The aim of the present observational study was to assess the effect of the number and timing of placing fissure sealants (FS) on caries prevalence in elementary school children under real-life conditions. Methods: Oral health data from 7- to 10-year-old elementary school children (n=505) attending 4 consecutive annual checkups between 2004 and 2009 was extracted from the public health service database. The number of intact FS and the number of teeth affected by caries was scored according to WHO standard (1997). Results: 34.9% pupils had at least one, 10% 4 FS. Children without FS had a higher dental caries rate compared to peers with FS (0.2 DT/0.4 DMFT vs. 0.1 DT/0.2 DMFT). Pupils with 4 FS showed the lowest number of teeth with caries (0 DT/0 DMFT). Children with an early application of FS had a lower D-component than children with a later or missing application (0.1 DT vs. 0.2 DT). Pupils with less than 4 FS had a higher risk of developing caries in their permanent dentition compared to peers with 4 FS (OR 4.36). Conclusion: FS is an effective caries preventive measure under real-life conditions. Early application and sealing of all 4 molars can optimize the prevention of caries in the permanent dentition.


Subject(s)
Child Health/statistics & numerical data , Dental Fissures/epidemiology , Dental Fissures/prevention & control , Oral Health/statistics & numerical data , Pit and Fissure Sealants/therapeutic use , Students/statistics & numerical data , Child , Dental Health Surveys , Female , Germany/epidemiology , Humans , Longitudinal Studies , Male , Prevalence , Risk Factors , Treatment Outcome
12.
Ann Anat ; 208: 116-122, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27496252

ABSTRACT

The biting ability of patients improves noticeably after receiving implant-supported overdentures in comparison to conventional complete dentures. However, the change of biting with such treatment concepts has been quantitatively investigated in only a limited number of studies. The aim of the present study has been to measure the biting forces of edentulous patients with complete dentures and after receiving implant-supported overdentures. A total of 26 edentulous patients were included. Ten patients received two to four conventional implants (control group, Ø3.3-3.7mm, L11-13mm) and 16 patients received four to five mini implants (study group, Ø1.8-2.4mm, L13-15mm) inserted in the mandibular interforaminal region. All patients received a lower overdenture with ball/rubber ring attachments and a complete denture for the maxilla. The biting forces were measured using Prescale pressure sheets type low before the insertion of implants and after receiving implant-supported overdenture. The measured sheets were later scanned and analysed using FPD-8010E software. The range of biting forces before the insertion of implants was 80N-122N for the control group and 66-88N for the study group. After the insertion of implants, the range of biting forces increased to 167N-235N for the control group and to 81N-138N for the study group. However, the increase in biting forces after the insertion of implants was not significant for either group. No significant difference was obtained between the two implant systems. The biting forces improved after insertion of implants regardless of which implant system was used. However, the degree of improvement is noticeably related to the original bone quality of the mandible at the insertion regions of implants.


Subject(s)
Bite Force , Dental Implants , Denture, Overlay , Mandible/physiopathology , Mouth, Edentulous/physiopathology , Mouth, Edentulous/therapy , Aged , Combined Modality Therapy/instrumentation , Combined Modality Therapy/methods , Dental Prosthesis Design , Dental Stress Analysis/instrumentation , Dental Stress Analysis/methods , Equipment Failure Analysis , Female , Humans , Male , Mandible/surgery , Mouth, Edentulous/diagnosis , Pilot Projects , Reproducibility of Results , Sensitivity and Specificity , Treatment Outcome
13.
Dalton Trans ; 45(17): 7267-77, 2016 04 25.
Article in English | MEDLINE | ID: mdl-27055252

ABSTRACT

Cage-chiral tetra-tert-butyl-P5-deltacyclene is accessible as a pair of highly enriched enantiomers and . The only secondary phosphorus atom P1 of the cage can be selectively oxidized by reaction with t-BuOOH. The P1-oxo species and , allow the direct determination of their ee values. Oxidation occurs with the complete retention of the optical activity of the compounds. The chiroptical properties of and are strongly dominated by their cage chirality, the oxygen atom does not contribute significantly. Elemental sulfur and selenium oxidize P5 with high preference to yield P5-thio- and P5-seleno-P5-deltacyclenes and of the intact cages again. Longer reaction time and more than stoichiometric amounts of selenium, leads to tri-seleno-P5-tetracycloundecane , a partially opened oxidized rearrangement product. The ligand properties of racemic were determined. Diphosphetane phosphorus atom P2 of is the active donor center to bind a Cr(CO)5 fragment, but a tautomerization of takes place if [(benzene)RuCl2]2 is added. A hydrogen atom migrates from P1 to the oxygen atom to form a phosphinous acid ligand. The lone pair of P1 is regenerated and acts as the active ligand function of the cage in this case. As for , the base n-BuLi induces an efficient cage rearrangement reaction of , where P1 and the neighboring carbon atom C4 containing its t-Bu substituent change places. C4 moves to its new position without breaking the bond with P5, this way forming the novel P1-oxo-P5-norsnoutene cage in a highly diastereoselective process.

14.
Z Rheumatol ; 75(3): 284-91, 2016 Apr.
Article in German | MEDLINE | ID: mdl-27001055

ABSTRACT

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in infancy and childhood. Approximately 20 % of patients with JIA suffer from the polyarticular form of the disease, which causes a substantial disease burden and long-term sequelae. Therapeutic approaches have used steroids and conventional disease modifying antirheumatic drugs (DMARD) but over the last decade new drugs have become available for the treatment of JIA, in particular biologic DMARD. This article summarizes the current therapy options for polyarticular JIA.


Subject(s)
Antibodies, Monoclonal/administration & dosage , Antirheumatic Agents/administration & dosage , Arthritis, Juvenile/drug therapy , Arthritis, Juvenile/prevention & control , Arthritis/drug therapy , Biological Products/administration & dosage , Steroids/administration & dosage , Arthritis/diagnosis , Arthritis/prevention & control , Arthritis, Juvenile/diagnosis , Child , Child, Preschool , Drug Design , Evidence-Based Medicine , Humans , Immunotherapy/trends , Infant , Infant, Newborn , Treatment Outcome
15.
Oncogene ; 35(36): 4762-72, 2016 09 08.
Article in English | MEDLINE | ID: mdl-26876198

ABSTRACT

Triple-negative breast cancer (TNBC) is a highly aggressive and metastatic form of breast cancer that lacks the estrogen, progesterone and HER2 receptors and is resistant to targeted and hormone therapies. TNBCs express high levels of the transmembrane glycoprotein, complement C1r/C1s, Uegf, Bmp1 (CUB)-domain containing protein 1 (CDCP1), which has been correlated with the aggressiveness and poor prognosis of multiple carcinomas. Full-length CDCP1 (flCDCP1) can be proteolytically cleaved, resulting in a cleaved membrane-bound isoform (cCDCP1). CDCP1 is phosphorylated by Src family kinases in its full-length and cleaved states, which is important for its pro-metastatic signaling. We observed that cCDCP1, compared with flCDCP1, induced a dramatic increase in phosphorylation of the migration-associated proteins: PKCδ, ERK1/2 and p38 mitogen-activated protein kinase in HEK 293T. In addition, only cCDCP1 induced migration of HEK 293T cells and rescued migration of the TNBC cell lines expressing short hairpin RNA against CDCP1. Importantly, we found that only cCDCP1 is capable of dimerization, which can be blocked by expression of the extracellular portion of cCDCP1 (ECC), indicating that dimerization occurs through CDCP1's ectodomain. We found that ECC inhibited phosphorylation of PKCδ and migration of TNBC cells in two-dimensional culture. Furthermore, ECC decreased cell invasiveness, inhibited proliferation and stimulated apoptosis of TNBC cells in three-dimensional culture, indicating that the cCDCP1 dimer is an important contributor to TNBC aggressiveness. These studies have important implications for the development of a therapeutic to block CDCP1 activity and TNBC metastasis.


Subject(s)
Antigens, CD/genetics , Cell Adhesion Molecules/genetics , Neoplasm Proteins/genetics , Protein Isoforms/genetics , Triple Negative Breast Neoplasms/genetics , Antigens, CD/chemistry , Antigens, Neoplasm , Apoptosis , Cell Adhesion/genetics , Cell Adhesion Molecules/chemistry , Cell Movement/genetics , Dimerization , HEK293 Cells , Humans , Neoplasm Proteins/biosynthesis , Neoplasm Proteins/chemistry , Phosphorylation , Protein Isoforms/biosynthesis , Signal Transduction/genetics , Triple Negative Breast Neoplasms/pathology , p38 Mitogen-Activated Protein Kinases/genetics
17.
Tissue Antigens ; 86(5): 317-23, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26467895

ABSTRACT

One of the major tasks of histocompatibility and immunogenetics laboratories is the pretransplant determination of unacceptable antigen mismatches (UAM) in kidney transplant recipients. In this procedure, human leucocyte antigen (HLA) specificities are defined against which the patient has circulating alloantibodies that are expected to harm the transplanted organ. Using the information on UAM and the potential donor's complete HLA typing, prediction of the crossmatch result, the so called 'virtual crossmatch', is possible. Currently, the laboratories are using different algorithms for the determination of UAM, and depending on the algorithm, more or fewer organ offers are excluded for patients with a similar antibody profile. In order to bring homogeneity into the allocation of organs to immunized patients in Germany, the German Society for Immunogenetics established, on the basis of current knowledge, recommendations for the determination of UAM. The UAM recommendations, which are thought to serve as a common tool for responsible physicians at different transplant centers, contain technical issues that need to be considered and are individualized for sensitized patients with a high or intermediate risk of antibody-mediated rejection. The present review contains these recommendations and puts them into perspective to current international practice.


Subject(s)
HLA Antigens/genetics , HLA Antigens/immunology , Histocompatibility Testing/methods , Kidney Transplantation/methods , Germany , Humans , Immunogenetics , Practice Guidelines as Topic , Societies, Medical
18.
AJR Am J Roentgenol ; 204(5): 1100-8, 2015 May.
Article in English | MEDLINE | ID: mdl-25905948

ABSTRACT

OBJECTIVE: The purpose of this study was to evaluate the effectiveness of ultrasound-guided cryoablation in treating small invasive ductal carcinoma and to assess the role of contrast-enhanced (CE) MRI in determining the outcome of cryoablation. SUBJECTS AND METHODS: Twenty consecutive participants with invasive ductal carcinomas up to 15 mm, with limited or no ductal carcinoma in situ (DCIS), underwent ultrasound-guided cryoablation. Preablation mammography, ultrasound, and CE-MRI were performed to assess eligibility. Clinical status was evaluated at 1 day, 7-10 days, and 2 weeks after ablation. CE-MRI was performed 25-40 days after ablation, followed by surgical resection within 5 days. RESULTS: Ultrasound-guided cryoablation was uniformly technically successful, and postablation clinical status was good to excellent in all participants. Cryoablation was not clinically successful in 15% (three of 20 patients). Three participants had residual cancer at the periphery of the cryoablation site. Two participants had viable nonmalignant tissue within the central zone of cryoablation-induced necrosis. Postablation CE-MRI had a sensitivity of 0% (0/3) and specificity of 88% (15/17). The predictive value of negative findings on CE-MRI was 83% (15/18). Correlations between cancer characteristics, cryoablation procedural variables, postablation CE-MRI findings, and surgical specimen features were not statistically significant. There were also no significant differences in participants with or without residual cancer. CONCLUSION: In our pilot experience, ultrasound-guided cryoablation of invasive ductal carcinomas up to 15 mm has a clinical failure rate of 15% but is technically feasible and well tolerated by patients. The majority of cryoablation failures are manifest as DCIS outside the cryoablation field. Postablation CE-MRI does not reliably predict cryoablation outcome.


Subject(s)
Breast Neoplasms/surgery , Carcinoma in Situ/surgery , Carcinoma, Ductal, Breast/surgery , Cryosurgery/methods , Magnetic Resonance Imaging , Ultrasonography, Interventional , Aged , Algorithms , Breast Neoplasms/pathology , Carcinoma in Situ/pathology , Carcinoma, Ductal, Breast/pathology , Contrast Media , Female , Humans , Mammography , Middle Aged , Neoplasm Invasiveness , Pilot Projects , Prospective Studies , Sensitivity and Specificity , Treatment Outcome
19.
Strahlenther Onkol ; 189(12): 1032-9, 2013 Dec.
Article in German | MEDLINE | ID: mdl-24196281

ABSTRACT

BACKGROUND AND PURPOSE: After incorporating treatment planning and the organisational model of treatment planning in the operating schedule system (BAS, "Betriebsablaufsystem"), complete document qualities were embedded in the digital environment. The aim of this project was to integrate all documents independent of their source (paper-bound or digital) and to make content from the BAS available in a structured manner. As many workflow steps as possible should be automated, e.g. assigning a document to a patient in the BAS. Additionally it must be guaranteed that at all times it could be traced who, when, how and from which source documents were imported into the departmental system. Furthermore work procedures should be changed that the documentation conducted either directly in the departmental system or from external systems can be incorporated digitally and paper document can be completely avoided (e.g. documents such as treatment certificate, treatment plans or documentation). It was a further aim, if possible, to automate the removal of paper documents from the departmental work flow, or even to make such paper documents superfluous. In this way patient letters for follow-up appointments should automatically generated from the BAS. Similarly patient record extracts in the form of PDF files should be enabled, e.g. for controlling purposes. METHOD: The available document qualities were analysed in detail by a multidisciplinary working group (BAS-AG) and after this examination and assessment of the possibility of modelling in our departmental workflow (BAS) they were transcribed into a flow diagram. The gathered specifications were implemented in a test environment by the clinical and administrative IT group of the department of radiation oncology and subsequent to a detailed analysis introduced into clinical routine. RESULTS: The department has succeeded under the conditions of the aforementioned criteria to embed all relevant documents in the departmental workflow via continuous processes. Since the completion of the concepts and the implementation in our test environment 15,000 documents were introduced into the departmental workflow following routine approval. Furthermore approximately 5000 appointment letters for patient aftercare per year were automatically generated by the BAS. In addition patient record extracts in the form of PDF files for the medical services of the healthcare insurer can be generated.


Subject(s)
Database Management Systems , Documentation/methods , Health Records, Personal , Information Storage and Retrieval/methods , Radiotherapy Planning, Computer-Assisted/methods , Radiotherapy/methods , Software , Workflow
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