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Karger Kompass
   Full-text available via subscription Subscription journal
     ISSN (Print) 2296-0368 - ISSN (Online) 2296-0317
     Published by Karger Homepage  [104 journals]
  • Chimerism and Tolerance Induction in Kidney Transplantation
    • Abstract: Chimerism is a state in which bone marrow hematopoietic stem cells from two genetically different animals coexist. To date, the approach has been used successfully to induce the state of immunologic tolerance in the animal models and is now being evaluated in clinical trials of both HLA-identical and HLA-mismatched living-donor kidney transplant recipients in some transplant centers with varying degrees of success. Although the results are promising, the current conditioning regimens are not optimal and longer-term follow up and multicenter studies are needed to ensure the efficacy and safety of the procedures.
  • RANK Ligand Blockade with Denosumab in Combination with Sorafenib in
           Chemorefractory Osteosarcoma: A Possible Step Forward'
    • Abstract: Background: There is no established systemic treatment option for unresectable osteosarcoma progressing after standard chemotherapy. A recently published clinical trial has demonstrated some activity of sorafenib in this situation. Preclinical research suggests a role for the inhibition of the receptor activator of nuclear factor-ĸB ligand (RANKL), but no clinical data have been reported so far. Case Report: A 37-year-old man was diagnosed with unresectable osteoblastic, osteoblastoma-like osteosarcoma in the C7/Th1 vertebra. The tumour progressed locally despite two lines of chemotherapy and stereotactic radiotherapy. On treatment with sorafenib and denosumab, a complete metabolic remission was achieved and is ongoing for over 18 months. Immunohistochemistry revealed an overexpression of RANK and RANKL in the patient's primary tumour. Discussion: This is the first report of activity achieved by the combination of the tyrosine kinase inhibitor sorafenib and the RANKL inhibitor denosumab in a patient with osteosarcoma. It confirms preclinical data on RANK/RANKL inhibition in osteosarcoma and could serve as a hypothesis-generating approach for clinical trials in this patient population.
      Oncology 2015;88:257-260
  • Phenotypic Characteristics of Nasal Mast Cells in a Mouse Model of
           Allergic Rhinitis
    • Abstract: Background: Mast cells (MCs) in the nasal respiratory mucosa (NRM) play a triggering role in the pathogenesis of allergic rhinitis (AR). Recent research evidence in mouse models of AR suggests an underlying MC-related allergic response in mouse nasal olfactory mucosa (NOM). Objective: We sought to investigate the phenotypic characteristics of nasal MCs in a mouse model of AR. Methods: By MC-specific staining and immunohistochemistry, we analyzed the subset, protease and IgE-binding phenotypes of nasal MCs in ovalbumin (OVA)-sensitized unchallenged and challenged mice. Results: In OVA-sensitized challenged mice, increased serum OVA-specific IgE levels (p < 0.001) and eosinophil infiltration confirmed AR induction. In addition to constitutive connective tissue MCs, mucosal MCs were induced in NRM and NOM of OVA-sensitized challenged mice. Connective tissue MCs and mucosal MCs in mouse NRM and NOM were positive for mouse MC protease-1, -4, -5, -6, -7 and carboxypeptidase-A3. In line with MCs in NRM, there were increased numbers (p = 0.019) and proportions (p = 0.027) of MCs with surface-bound IgE in NOM of OVA-sensitized challenged mice. Conclusion: In the setting of AR, MCs in mouse NOM exhibit the same subset, protease and IgE-binding phenotypes as MCs in mouse NRM.
      ORL 2014;76:303-313
  • Symptomatic Thoracic Arachnoid Cyst with Coexisting Tick Paralysis: Case
           Report and Review of the Literature
    • Abstract: Tick paralysis is an uncommon phenomenon resulting from the release of a neurotoxin from the salivary glands of an engorged, gravid female tick about 5-7 days after attachment. The neurotoxin produces ascending weakness, mimicking other ascending paralytic processes. We present a case of a child presenting with weakness of the lower extremities and frequent falls who was found to have a compressive thoracic arachnoid cyst and a large distal syrinx. After surgical decompression, the patient made significant improvement in her leg strength, but quickly developed an ascending quadriparesis, followed by respiratory depression. Subsequent imaging and physical examination revealed an engorged tick embedded in her scalp. The tick was removed, and the patient made a rapid and complete clinical recovery. We present a unique case of concomitant tick paralysis and a symptomatic spinal intradural arachnoid cyst, and review the literature on tick paralysis.
      Pediatr Neurosurg
  • Effects of MCP-1 Inhibition by Bindarit Therapy in a Rat Model of
           Polycystic Kidney Disease
    • Abstract: Background/Aims: Experimental and clinical evidence suggested that monocyte chemoattractant protein-1 (MCP-1/CCL2) has a role in the development of interstitial inflammation and renal failure in polycystic kidney disease (PKD). We investigated whether bindarit, an inhibitor of MCP-1/CCL2 synthesis, could influence the evolution of PKD in PCK rats. Methods: PCK rats were treated from 5 to 15 weeks of age with vehicle or bindarit. Sprague-Dawley rats served as control. For in vitro studies, murine podocytes were exposed to albumin with or without bindarit. Results: MCP-1 mRNA was upregulated in the kidney of PCK rats and reduced by bindarit. Treatment limited overexpression of MCP-1 protein by epithelial cells of dilated tubules and cysts, and interstitial inflammatory cells. Excessive renal accumulation of monocytes/macrophages was lowered by bindarit by 41%. Serum creatinine slightly increased in PCK rats on vehicle and was similar to controls after bindarit. Kidney and liver cysts were not affected by treatment. Bindarit significantly reduced progressive proteinuria of PCK rats. The antiproteinuric effect was associated with the restoration of the defective nephrin expression in podocytes of PCK rats. Bindarit limited podocyte foot process effacement and ameliorated slit diaphragm frequency. In cultured podocytes, bindarit reduced MCP-1 production in response to albumin and inhibited albumin-induced cytoskeletal remodeling and cell migration. Conclusion: This study showed that although bindarit did not prevent renal cyst growth, it limited interstitial inflammation and renal dysfunction and reduced proteinuria in PKD. Thus, bindarit could be considered a therapeutic intervention complementary to therapies specifically acting to block renal cyst growth.
  • Interactions between Traumatic Brain Injury and Frontotemporal
    • Abstract: Background/Aims: Prior work in smaller cohorts suggests that traumatic brain injury (TBI) may be a risk factor for frontotemporal degeneration (FTD). We sought to confirm and extend these results using the National Alzheimer's Coordinating Center Uniform Data Set. Methods: We compared the TBI prevalence between FTD subjects and matched normal controls. Indices of cognitive, behavioral, functional, and global dementia severity were compared between FTD subjects with and without prior TBI. Results: Remote TBI with extended loss of consciousness (TBI-ext) was more common in individuals with FTD than in controls (OR: 1.67; 95% CI: 1.004-2.778). With TBI-ext, less functional and global impairment was seen in the behavioral variant of FTD, but more behavioral pathology was seen in the semantic variant. Conclusion: TBI may increase the FTD risk and influence clinical symptomatology and severity in FTD subtypes.
      Dement Geriatr Cogn Disord 2015;39:143-153
  • Cytological Findings for the Diagnosis of Primary Thyroid
           Mucosa-Associated Lymphoid Tissue Lymphoma by Fine Needle Aspiration
    • Abstract: Objective: We examined cytological findings for the diagnosis of primary thyroid mucosa-associated lymphoid tissue (MALT) lymphoma by fine needle aspiration. Study Design: During the study period of 4 years, a total of 101 cases including 51 MALT lymphomas, 20 Hashimoto's thyroiditis (HT), and 30 diffuse large-cell B-cell lymphomas were cytologically examined. MALT lymphomas were divided into 44 common MALT and 7 MALT lymphomas with extreme plasmacytic differentiation (MALT-EPCD). Results: (1) Small- to medium-sized cells displaying irregularly shaped nuclei with prominent nucleoli (ISN-PN) were neoplastic cells. (2) In the case of a frequency of plasma cells (PC) below 15%, the accuracy rate for distinguishing common MALT from HT was 97% for ISN-PN cell frequencies above 20% in combination with the presence of lymphoepithelial lesion clusters (LELC) and mountain range-like clusters (MRLC). The frequency of large-sized cells was below 15% in common MALT. (3) In the case of a frequency of PC above 15%, cases with a sum of PC and ISN-PN cells above 30% were MALT-EPCD. (4) MRLC were cell clusters derived from regions of follicular colonization, and LELC were cell clusters from lymphoepithelial lesions of MALT lymphomas. Conclusion: Useful cytological criteria for the diagnosis of thyroid primary MALT lymphoma, such as neoplastic cells and cell clusters, were defined.
      Acta Cytologica
  • Stimulation of Cyclooxygenase 2 Expression in Rat Peritoneal Mesothelial
    • Abstract: Objective: Since peritoneal dialysis causes peritoneal fibrosis, we examined how glucose (osmotic factor), mannitol (osmotic control), and angiotensin II (AngII) regulate proinflammatory cyclooxygenase 2 (COX-2) in primary rat peritoneal mesothelial cells. Materials and Methods: For this study, we used the following material (n = 4-8 cell lines): cells, passages 1-2; 125I-AngII receptor surface binding (AT1R antagonist losartan, AT2R antagonist PD123319; both 10 µM); intracellular calcium probe calcium-5; COX-2 immunoblotting (β-actin normalized); real-time PCR of COX-2 gene PTGS2, and NF-κB inhibitor Ro-1069920 (5 µM). Results: AngII surface receptors were predominantly AT1R (minimally AT2R). AngII and glucose increased COX-2 protein expression concentration dependently; mannitol also increased COX-2 expression. Maximal COX-2 protein expression was observed after 6 h (AngII) and 24 h (glucose, mannitol). The time course of increases in PTGS2 mRNA levels reflected that of COX-2 protein expression. At optimal exposure conditions (time/concentration), glucose was 5-fold more efficacious in stimulating COX-2 protein expression than AngII or mannitol. Losartan fully inhibited COX-2 protein responses to AngII and mannitol, but minimally inhibited responses to glucose. Ro-1069920 fully inhibited COX-2 protein responses to each effector. Conclusion: AngII, glucose, and osmotic stress (mannitol) activate COX-2; NF-κB may be an ideal site for COX-2 blockade, and COX-2 activation by osmotic stress requires AT1R, but activation by glucose is more robust and mechanistically complex.
      Nephron Exp Nephrol
  • Effect of Intravitreal Bevacizumab Injection before Ahmed Glaucoma Valve
           Implantation in Neovascular Glaucoma
    • Abstract: Ophthalmologica 2013;229:94–100
  • Long-Term Outcome of Polymyositis Treated with High Single-Dose
           Alternate-Day Prednisolone Therapy
    • Abstract: Eur Neurol 2012;68:117–121
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