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  • 1
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    Online Resource
    Evaluation of the methoxy-X04 derivative BSC4090 for diagnosis of prodromal and early Alzheimer’s disease from bioptic olfactory mucosa
    Springer Science and Business Media LLC ; 2019
    In:  European Archives of Psychiatry and Clinical Neuroscience Vol. 269, No. 8 ( 2019-12), p. 973-984
    Details
    In: European Archives of Psychiatry and Clinical Neuroscience, Springer Science and Business Media LLC, Vol. 269, No. 8 ( 2019-12), p. 973-984
    Type of Medium: Online Resource
    ISSN: 0940-1334 , 1433-8491
    URL: Article
    DOI: 10.1007/s00406-018-0955-6
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2019
    detail.hit.zdb_id: 2793981-9
    detail.hit.zdb_id: 1459045-1
    SSG: 2,1
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  • 2
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    Erythropoietin Prevents Diabetes-Induced Podocyte Damage
    S. Karger AG ; 2008
    In:  Kidney and Blood Pressure Research Vol. 31, No. 6 ( 2008), p. 411-415
    Details
    In: Kidney and Blood Pressure Research, S. Karger AG, Vol. 31, No. 6 ( 2008), p. 411-415
    Abstract: 〈 i 〉 Objective: 〈 /i 〉 Erythropoietin (EPO) has cytoprotective effects apart from its hematopoietic effects. We studied the effects of different EPO molecules on podocyte signaling in vitro and on podocyte survival in an experimental model of diabetic kidney injury (db/db mouse). 〈 i 〉 Methods: 〈 /i 〉 We elucidated intracellular signaling by epoetin-β, darbepoetin-α, and the continuous erythropoietin receptor activator (CERA) in immortalized murine podocyte cultures. Moreover, we treated db/db micewith placebo or with CERA in a chronic (14-week) randomized controlled study. We also studied non-diabetic db/m mice as controls. 〈 i 〉 Results: 〈 /i 〉 We could clearly demonstrate phosphorylation of the JAK/PI3K pathway and Akt signaling in podocytes by epoetin-β, darbepoetin-α and CERA. In the long-term animal study we found significantly reduced podocyte numbers in placebo-treated db/db mice compared to db/m control mice (7.4 ± 0.2 vs. 10.2 ± 0.9 per glomerular field; p 〈 0.05). Chronic CERA treatment ameliorated podocyte loss in kidneys of diabetic animals (8.5 ± 0.5 per glomerular field; p 〈 0.05 vs. placebo-treated db/db mice). 〈 i 〉 Conclusion: 〈 /i 〉 EPO activates pro-survival intracellular pathways in podocytes in vitro, and ameliorates diabetes-induced podocyte loss in vivo. Chronic EPO administration may be a feasible way to protect podocyte from diabetic injury.
    Type of Medium: Online Resource
    ISSN: 1420-4096 , 1423-0143
    URL: Article
    DOI: 10.1159/000186368
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2008
    detail.hit.zdb_id: 1482922-8
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  • 3
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    Inter‐observer agreement for the histological diagnosis of invasive lobular breast carcinoma
    Wiley ; 2022
    In:  The Journal of Pathology: Clinical Research Vol. 8, No. 2 ( 2022-03), p. 191-205
    Details
    In: The Journal of Pathology: Clinical Research, Wiley, Vol. 8, No. 2 ( 2022-03), p. 191-205
    Abstract: Invasive lobular breast carcinoma (ILC) is the second most common breast carcinoma (BC) subtype and is mainly driven by loss of E‐cadherin expression. Correct classification of BC as ILC is important for patient treatment. This study assessed the degree of agreement among pathologists for the diagnosis of ILC. Two sets of hormone receptor (HR)‐positive/HER2‐negative BCs were independently reviewed by participating pathologists. In set A (61 cases), participants were provided with hematoxylin/eosin (HE)‐stained sections. In set B (62 cases), participants were provided with HE‐stained sections and E‐cadherin immunohistochemistry (IHC). Tumor characteristics were balanced. Participants classified specimens as non‐lobular BC versus mixed BC versus ILC. Pairwise inter‐observer agreement and agreement with a pre‐defined reference diagnosis were determined with Cohen's kappa statistics. Subtype calls were correlated with molecular features, including CDH1 /E‐cadherin mutation status. Thirty‐five pathologists completed both sets, providing 4,305 subtype calls. Pairwise inter‐observer agreement was moderate in set A (median κ  = 0.58, interquartile range [IQR]: 0.48–0.66) and substantial in set B (median κ  = 0.75, IQR: 0.56–0.86, p   〈  0.001). Agreement with the reference diagnosis was substantial in set A (median κ  = 0.67, IQR: 0.57–0.75) and almost perfect in set B (median κ  = 0.86, IQR: 0.73–0.93, p   〈  0.001). The median frequency of CDH1 /E‐cadherin mutations in specimens classified as ILC was 65% in set A (IQR: 56–72%) and 73% in set B (IQR: 65–75%, p   〈  0.001). Cases with variable subtype calls included E‐cadherin‐positive ILCs harboring CDH1 missense mutations, and E‐cadherin‐negative ILCs with tubular elements and focal P‐cadherin expression. ILCs with trabecular growth pattern were often misclassified as non‐lobular BC in set A but not in set B. In conclusion, subtyping of BC as ILC achieves almost perfect agreement with a pre‐defined reference standard, if assessment is supported by E‐cadherin IHC. CDH1 missense mutations associated with preserved E‐cadherin protein expression, E‐ to P‐cadherin switching in ILC with tubular elements, and trabecular ILC were identified as potential sources of discordant classification.
    Type of Medium: Online Resource
    ISSN: 2056-4538 , 2056-4538
    URL: Issue
    URL: Article
    DOI: 10.1002/cjp2.v8.2
    DOI: 10.1002/cjp2.253
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2814357-7
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  • 4
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    Reproductive capacity and recurrence of disease after surgery for moderate and severe endometriosis – a retrospective single center analysis
    Springer Science and Business Media LLC ; 2020
    In:  BMC Women's Health Vol. 20, No. 1 ( 2020-12)
    Details
    In: BMC Women's Health, Springer Science and Business Media LLC, Vol. 20, No. 1 ( 2020-12)
    Abstract: Endometriosis can be associated with considerable pain and sterility. After surgical excision of moderate or severe endometriosis lesions, the rate of recurrence reaches up to 67%. The objective of this retrospective study was to establish the recurrence and pregnancy rates following surgical resection of stage III/IV endometriosis lesions. Indications for operation were endometriosis symptoms, sonographic findings and/or infertility. Methods A total of 456 patients who underwent stage III/IV endometriosis surgery between 2004 and 2014 were sent a questionnaire relating to their postoperative medical treatment, pregnancies, relief of symptoms and recurrence. Responses of 206 patients (45.2%) and their clinical data were analysed for this study. Results A total of 66.5% ( N  = 137) of patients had stage III disease, and 33.5% ( N  = 69) had stage IV disease. The average age was 37 years (17–59). A total of 63.1% ( N  = 130) of surgeries were performed by laparoscopy, 21.8% ( N  = 45) were performed by laparotomy and 15% ( N  = 31) were performed by conversion. Complete resection of endometriosis lesions was achieved in 90.8% of patients ( N  = 187). After surgery, 48.5% ( N  = 100) of the women did not receive hormonal treatment; the main reason was the desire for children in 53%. Complete or partial relief in complaints was achieved in 93.2% ( N  = 192). The rate of recurrence was 21.8% ( N  = 45). The statistically significant factors that was associated with a higher risk to develop recurrence was an age  〈  35 ( p   〈  0.005). After surgery, 65.8% (79/120) of patients who wished to have children became pregnant. There was a statistically significant association among a higher postoperative pregnancy rate and age  〈  35 ( p   〈  0.003) in multivariate logistic regression analysis and laparoscopic surgical access in univariate logistic regression analysis ( p   〈  0.01). Conclusion We assessed the high percentage of complete or partial relief of symptoms of 93.2%, the high postoperative pregnancy rate of 65.8% and the low rate of recurrence of 21.8% compared to international literature to be very encouraging for women suffering from moderate and severe endometriosis. Though laparoscopy is considered the ‘gold standard’of endometriosis surgery, laparotomy still may be indicated in patients with extensive endometriosis especially to preserve reproductive function.
    Type of Medium: Online Resource
    ISSN: 1472-6874
    URL: Article
    DOI: 10.1186/s12905-020-01016-3
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2050444-5
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  • 5
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    A preliminary assessment of net box traps to catch gray wolves in Lower Saxony, Germany
    Wiley ; 2022
    In:  Wildlife Society Bulletin Vol. 46, No. 5 ( 2022-12)
    Details
    In: Wildlife Society Bulletin, Wiley, Vol. 46, No. 5 ( 2022-12)
    Abstract: The number of gray wolves ( Canis lupus ) in Lower Saxony, Germany, has increased since they recolonized the region in 2007, and developing appropriate management strategies requires accurate information on wolf habitat use. As research on space use and foraging ecology necessitates capture, tagging, and tracking of wolves, we evaluated the feasibility of using cage traps to catch animals unharmed. Due to legal restrictions in Germany, especially concerning body‐grasping traps (e.g., foothold traps and foot snares), we developed an alternative trapping system. From July 2018 to December 2020, we installed net box traps at different locations in Lower Saxony. However, our study was disrupted and traps were removed prematurely because of human activities and sabotage. Although we did not capture any wolves, we photographically documented wolf pups entering our net box traps on seven occasions and suggest that young wolves can potentially be captured in our net box traps. We believe our work opens the possibility for further trapping options to improve future research on European gray wolves.
    Type of Medium: Online Resource
    ISSN: 2328-5540 , 2328-5540
    URL: Issue
    URL: Article
    DOI: 10.1002/wsb.v46.5
    DOI: 10.1002/wsb.1382
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2067355-3
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  • 6
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    Dual Inhibition of Classical Protein Kinase C-α and Protein Kinase C-β Isoforms Protects Against Experimental Murine Diabetic Nephropathy
    American Diabetes Association ; 2013
    In:  Diabetes Vol. 62, No. 4 ( 2013-04-01), p. 1167-1174
    Details
    In: Diabetes, American Diabetes Association, Vol. 62, No. 4 ( 2013-04-01), p. 1167-1174
    Abstract: Activation of protein kinase C (PKC) has been implicated in the pathogenesis of diabetic nephropathy with proteinuria and peritubular extracellular matrix production. We have previously shown that the PKC isoforms α and β mediate different cellular effects. PKC-β contributes to hyperglycemia-induced renal matrix production, whereby PKC-α is involved in the development of albuminuria. We further tested this hypothesis by deletion of both isoforms and used a PKC inhibitor. We analyzed the phenotype of nondiabetic and streptozotocin (STZ)-induced diabetic homozygous PKC-α/β double-knockout mice (PKC-α/β−/−). After 8 weeks of diabetes mellitus, the high-glucose–induced renal and glomerular hypertrophy as well as transforming growth factor-β1) and extracellular matrix production were diminished in the PKC-α/β−/− mice compared with wild-type controls. Urinary albumin/creatinine ratio also was significantly reduced, however, it was not completely abolished in diabetic PKC-α/β−/− mice. Treatment with CGP41252, which inhibits PKC-α and PKC-β, is able to prevent the development of albuminuria and to reduce existing albuminuria in type 1 (STZ model) or type 2 (db/db model) diabetic mice. These results support our hypothesis that PKC-α and PKC-β contribute to the pathogenesis of diabetic nephropathy, and that dual inhibition of the classical PKC isoforms is a suitable therapeutic strategy in the prevention and treatment of diabetic nephropathy.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db12-0534
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2013
    detail.hit.zdb_id: 1501252-9
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  • 7
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    Evaluation of the routine use of E‐cadherin immunohistochemistry in the typing of breast carcinomas: results of a randomized diagnostic study
    Wiley ; 2023
    In:  Histopathology Vol. 83, No. 5 ( 2023-11), p. 810-821
    Details
    In: Histopathology, Wiley, Vol. 83, No. 5 ( 2023-11), p. 810-821
    Abstract: Invasive lobular carcinoma (ILC) has distinct morphology and association with loss of E‐cadherin function. It has special clinical and imaging features, and its proper recognition is important. Following a recent proposal, we tested the value of the routine use of E‐cadherin immunohistochemistry (IHC) in recognizing ILC. Methods and results Five pathologists with experience in breast pathology from four Hungarian institutions histotyped 1001 breast cancers from diagnostic core biopsies or excision specimens randomly assigned to haematoxylin and eosin (HE) diagnosis first, followed by E‐cadherin IHC; or to immediate HE and E‐cadherin‐based diagnosis. Of 524 cases with HE diagnosis, 73(14%) were deemed uncertain. E‐cadherin made the initial histological type change in 14/524 cases (2.7%), including three with confident HE‐based type allocation. Use of E‐cadherin immunostaining was considered useful in 88/477 cases (18%) with immediate dual assessment, and typing uncertainty went down to 5% (25/477 cases), but was not zero. Collective assessment of 171 uncertain, difficult, nonclassical cases resulted in consensus diagnosis in most cases, but 15 cases were still doubtful as concerns their proper histological type. CDH1 gene sequencing was attempted and successful in 13; pathogenic genetic alterations were identified in seven cases. Conclusions The routine use of E‐cadherin IHC decreases the uncertainty in typing and improves the typing accuracy at the cost of potentially redundant additional immunostains. Furthermore, this procedure does not exclude uncertainty due to E‐cadherin‐positive ILCs, which are occasionally difficult to confidently label as ILC, especially when the growth pattern is not classic.
    Type of Medium: Online Resource
    ISSN: 0309-0167 , 1365-2559
    URL: Issue
    URL: Article
    DOI: 10.1111/his.v83.5
    DOI: 10.1111/his.15026
    RVK:
    XA 10000
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2006447-0
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  • 8
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    Evaluation of Integrated HPV DNA as Individualized Biomarkers for the Detection of Recurrent CIN2/3 during Post-Treatment Surveillance
    MDPI AG ; 2021
    In:  Cancers Vol. 13, No. 13 ( 2021-07-01), p. 3309-
    Details
    In: Cancers, MDPI AG, Vol. 13, No. 13 ( 2021-07-01), p. 3309-
    Abstract: Purpose: Post-treatment follow-up in women with cervical pre-cancers (CIN3) is mandatory due to relapse in up to 10% of patients. Standard follow-up based on hrHPV-DNA/cytology co-testing has high sensitivity but limited specificity. The aim of our prospective, multicenter, observational study was to test the hypothesis that an individualized viral-cellular-junction test (vcj-PCR) combined with cytology has a lower false positive rate for the prediction of recurrence compared to standard co-testing. Methods: Pre-surgical cervical swabs served for the identification of HPV16/18 DNA integration sites by next-generation-sequencing (NGS). Samples taken at 6, 12 and 24 months post-surgery were evaluated by cytology, hrHPV-DNA and the patients’ individual HPV-integration sites (vcj-PCR on the basis of NGS). Results: Integration sites were detected in 48 of 445 patients (10.8%), 39 of them had valid follow-up data. The false positive rate was 18.2% (95% CI 8.6–34.4%) for standard hrHPV/cytology at six months compared to 12.1% (95% CI 4.8–27.3%) for vcj-PCR/cytology, respectively (McNemar p = 0.50). Six patients developed recurrences (1 CIN2, 5 CIN3) during follow-up. Standard co-testing detected all, whereas vcj-PCR/cytology detected only five patients with recurrences. Data of 269 patients without evidence of HPV16/18 integration were subject to post-hoc analyses. Standard co-testing revealed a false positive rate of 15.7% (95% CI 11.7–20.7%) and predicted ten of fourteen recurrences at six months. Conclusions: Although highly specific on its own vcj-PCR could not detect all recurrent CIN2/3. Possible reasons for this unexpected result may be multifocal lesions, intratumoral heterogeneity with respect to HPV integration and/or incident CIN.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers13133309
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527080-1
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  • 9
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    Gadolinium contrast medium administration does not adversely affect T2*‐weighted gradient recalled echo magnetic resonance imaging of the canine brain at 1.5 Tesla
    Wiley ; 2019
    In:  Veterinary Radiology & Ultrasound Vol. 60, No. 2 ( 2019-03), p. 184-191
    Details
    In: Veterinary Radiology & Ultrasound, Wiley, Vol. 60, No. 2 ( 2019-03), p. 184-191
    Abstract: As gadolinium‐based contrast agents are paramagnetic and have T2 shortening effects, they have the potential to adversely affect gradient recalled echo sequences. The aim of this prospective, cross‐sectional study was to evaluate the effects of gadolinium administration on T2*‐weighted sequence diagnostic quality and signal intensity when imaging the canine brain. A total of 100 dogs underwent brain magnetic resonance imaging (MRI) including pre‐ and postcontrast T2*‐weighted sequences acquired with a delay (Group A) or immediately (Group B) following gadolinium administration. Pre‐ and postcontrast images were subjectively compared. In dogs with intracranial enhancing masses, regions of interest were drawn on corresponding images and signal intensity ratios were calculated. The effect of degree and pattern of contrast enhancement, susceptibility artifacts, and time between contrast injection and T2*‐weighted sequence acquisition on signal intensity ratio was evaluated. Overall 31 dogs had contrast enhancing intracranial masses. Subjectively, there was no difference in image quality of T2*‐weighted sequences obtained before and after contrast medium administration. No significant signal intensity differences of intracranial contrast enhancing masses were found (Group A P  = 0.9999; Group B P  = 0.9992). Susceptibility artifacts did not differ in appearance, and there was no effect on calculated signal intensity ratio ( P  = 0.8142). Similarly, there was no effect of degree of enhancement or contrast heterogeneity on signal intensity ratio ( P  = 0.4413). No correlation was found between signal intensity ratio and the time to acquisition ( P  = 0.199). Administration of gadolinium‐based MRI contrast agents does not adversely affect T2*‐weighted imaging of the brain in dogs at 1.5 T even in the presence of contrast enhancing lesions.
    Type of Medium: Online Resource
    ISSN: 1058-8183 , 1740-8261
    URL: Issue
    URL: Article
    DOI: 10.1111/vru.2019.60.issue-2
    DOI: 10.1111/vru.12682
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 2142058-0
    SSG: 22
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  • 10
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    Formation of Glyco-Functionalized Platinum Complexes by Cross-Metathesis and Evaluation of Their Efficacy in Inhibition of Lung Tumor Cell Lines
    Informa UK Limited ; 2012
    In:  Journal of Carbohydrate Chemistry Vol. 31, No. 9 ( 2012-11), p. 702-710
    Details
    In: Journal of Carbohydrate Chemistry, Informa UK Limited, Vol. 31, No. 9 ( 2012-11), p. 702-710
    Type of Medium: Online Resource
    ISSN: 0732-8303 , 1532-2327
    URL: Article
    DOI: 10.1080/07328303.2012.739231
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2012
    detail.hit.zdb_id: 2098238-0
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