14 results on '"Hanzelka K"'
Search Results
2. Mimitin Überexpression schützt insulinproduzierende Zellen vor zytokin-induziertem ER Stress
- Author
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Hanzelka, K, primary, Lenzen, S, additional, and Gurgul-Convey, E, additional
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- 2011
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3. Mimitin Überexpression schützt gegenüber Zytokin-induzierter Apoptose durch Unterdrückung der MAP1S Wirkung
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Hanzelka, K, primary, Lenzen, S, additional, and Gurgul-Convey, E, additional
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- 2010
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4. Zytoprotektion und Erhalt der Insulinsekretion durch PGIS Überexpression in insulinproduzierenden Zellen
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Gurgul-Convey, E, primary, Hanzelka, K, additional, and Lenzen, S, additional
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- 2010
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5. Die Rolle von Mimitin in insulin-produzierende Zellen
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Hanzelka, K, primary, Gurgul-Convey, E, additional, Jura, J, additional, and Lenzen, S, additional
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- 2009
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6. Die Rolle Stickstoffmonoxids für Zytokin-vermittelten Mimitin Genexpression in insulinproduzierenden Zellen
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Gurgul-Convey, E, primary, Hanzelka, K, additional, Kacheva, S, additional, Jura, J, additional, and Lenzen, S, additional
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- 2009
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7. Thrombosis risk prediction in lymphoma patients: A multi-institutional, retrospective model development and validation study.
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Ma S, La J, Swinnerton KN, Guffey D, Bandyo R, De Las Pozas G, Hanzelka K, Xiao X, Rojas-Hernandez CM, Amos CI, Chitalia V, Ravid K, Merriman KW, Flowers CR, Fillmore N, and Li A
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- Humans, Retrospective Studies, Middle Aged, Female, Male, Aged, Risk Assessment, Adult, Pulmonary Embolism etiology, Pulmonary Embolism epidemiology, Venous Thrombosis etiology, Venous Thrombosis epidemiology, Risk Factors, Incidence, Aged, 80 and over, Lymphoma complications, Lymphoma epidemiology, Venous Thromboembolism etiology, Venous Thromboembolism epidemiology
- Abstract
Venous thromboembolism (VTE) poses a significant risk to cancer patients receiving systemic therapy. The generalizability of pan-cancer models to lymphomas is limited. Currently, there are no reliable risk prediction models for thrombosis in patients with lymphoma. Our objective was to create a risk assessment model (RAM) specifically for lymphomas. We performed a retrospective cohort study to develop Fine and Gray sub-distribution hazard model for VTE and pulmonary embolism (PE)/ lower extremity deep vein thrombosis (LE-DVT) respectively in adult lymphoma patients from the Veterans Affairs national healthcare system (VA). External validations were performed at the Harris Health System (HHS) and the MD Anderson Cancer Center (MDACC). Time-dependent c-statistic and calibration curves were used to assess discrimination and fit. There were 10,313 (VA), 854 (HHS), and 1858 (MDACC) patients in the derivation and validation cohorts with diverse baseline. At 6 months, the VTE incidence was 5.8% (VA), 8.2% (HHS), and 8.8% (MDACC), respectively. The corresponding estimates for PE/LE-DVT were 3.9% (VA), 4.5% (HHS), and 3.7% (MDACC), respectively. The variables in the final RAM included lymphoma histology, body mass index, therapy type, recent hospitalization, history of VTE, history of paralysis/immobilization, and time to treatment initiation. The RAM had c-statistics of 0.68 in the derivation and 0.69 and 0.72 in the two external validation cohorts. The two models achieved a clear differentiation in risk stratification in each cohort. Our findings suggest that easy-to-implement, clinical-based model could be used to predict personalized VTE risk for lymphoma patients., (© 2024 Wiley Periodicals LLC.)
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- 2024
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8. Inhibition of SCD1 impairs palmitate-derived autophagy at the step of autophagosome-lysosome fusion in pancreatic β-cells.
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Janikiewicz J, Hanzelka K, Dziewulska A, Kozinski K, Dobrzyn P, Bernas T, and Dobrzyn A
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- Animals, Apoptosis drug effects, Cell Line, Tumor, Insulin pharmacology, Insulin-Secreting Cells cytology, Insulin-Secreting Cells enzymology, Insulin-Secreting Cells metabolism, Insulinoma, Lysosomes metabolism, Membrane Fusion drug effects, Palmitic Acid pharmacology, Phospholipids metabolism, Rats, Stearoyl-CoA Desaturase genetics, Stearoyl-CoA Desaturase metabolism, Autophagy drug effects, Enzyme Inhibitors pharmacology, Insulin-Secreting Cells drug effects, Palmitates pharmacology, Stearoyl-CoA Desaturase antagonists & inhibitors
- Abstract
Autophagy is indispensable for the proper architecture and flawless functioning of pancreatic β-cells. A growing body of evidence indicates reciprocal communication between autophagic pathways, apoptosis, and intracellular lipids. The way in which elevated levels of free saturated or unsaturated FAs contribute to progressive β-cell failure remains incompletely understood. Stearoyl-CoA desaturase (SCD)1, a key regulatory enzyme in biosynthesis of MUFAs, was shown to play an important role in regulation of β-cell function. Here, we investigated whether SCD1 activity is engaged in palmitate-induced pancreatic β-cell autophagy. We found augmented apoptosis and diminished autophagy upon cotreatment of INS-1E cells with palmitate and an SCD1 inhibitor. Furthermore, we found that additional treatment of the cells with monensin, an inhibitor of autophagy at the step of fusion, exacerbates palmitate-induced apoptosis. Accordingly, diminished SCD1 activity affected the accumulation, composition, and saturation status of cellular membrane phospholipids and neutral lipids. Such an effect was accompanied by aberrant endoplasmic reticulum stress, mitochondrial injury, and decreases in insulin secretion and cell proliferation. Our data reveal a novel mechanism by which the inhibition of SCD1 activity affects autophagosome-lysosome fusion because of perturbations in cellular membrane integrity, thus leading to an aberrant stress response and β-cell failure., (Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.)
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- 2015
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9. Islet β-cell failure in type 2 diabetes--Within the network of toxic lipids.
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Janikiewicz J, Hanzelka K, Kozinski K, Kolczynska K, and Dobrzyn A
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- Autophagy, Ceramides metabolism, Endoplasmic Reticulum metabolism, Endoplasmic Reticulum physiology, Humans, Mitochondria physiology, Diabetes Mellitus, Type 2 physiopathology, Islets of Langerhans physiopathology
- Abstract
Obesity-related type 2 diabetes develops in individuals with the onset of β-cell dysfunction. Pancreatic islet lipotoxicity is now recognized as a primary reason for the onset and progression of the disease. Such dysfunction is reflected by the aberrant secretory capacity and detrimental loss of β-cell mass and survival. Elevated circulating serum fatty acid levels and disordered lipid metabolism management are particularly interesting in the search for biologically relevant triggers of β-cell demise. Herein, we review various types of toxic lipid metabolites that may play a significant role in pancreatic islet failure. The lipotoxic effect on β-cells depends on the type of lipid mediator (e.g., long-chain fatty acids, diacylglycerols, ceramides, phospholipids), cellular location of its action (e.g., endoplasmic reticulum, mitochondria), and associated-organelle conditions (e.g., membranes, vesicles). We also discuss various aspects of lipid action in β-cells, including effects on metabolic pathways, stress responses (e.g., oxidative stress, endoplasmic reticulum stress, and autophagy), and gene expression., (Copyright © 2015 Elsevier Inc. All rights reserved.)
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- 2015
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10. Is there a role for neuronal nitric oxide synthase (nNOS) in cytokine toxicity to pancreatic beta cells?
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Gurgul-Convey E, Hanzelka K, and Lenzen S
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- Animals, Base Sequence, Cytokines metabolism, Glucose metabolism, Insulin metabolism, Insulin Secretion, Interleukin-1beta genetics, Interleukin-1beta metabolism, Islets of Langerhans metabolism, Male, Molecular Sequence Data, Nitric Oxide Synthase Type I genetics, Nitric Oxide Synthase Type II genetics, Nitric Oxide Synthase Type II metabolism, Nitric Oxide Synthase Type III genetics, Nitric Oxide Synthase Type III metabolism, Rats, Rats, Inbred Lew, Real-Time Polymerase Chain Reaction, Tumor Necrosis Factor-alpha genetics, Tumor Necrosis Factor-alpha metabolism, Cytokines toxicity, Insulin-Secreting Cells metabolism, Nitric Oxide Synthase Type I metabolism
- Abstract
Nitric oxide (NO), produced by the action of the inducible NO synthase, plays a crucial role in cytokine toxicity to pancreatic beta cells during type 1 diabetes development. It was the aim of this study to analyze the role of the neuronal NOS (nNOS) in proinflammatory cytokine-mediated beta cell toxicity. Expression of different isoforms of nitric oxide synthase in insulin-secreting INS1E cells and rat islets was analyzed by quantitative real-time PCR and Western blotting. The expression of nNOS in insulin-secreting INS1E cells was similar to that found in rat brain, while two other isoforms, namely the endothelial eNOS and inducible iNOS were not expressed in untreated cells. IL-1β alone or in combination with TNF-α and/or IFNγ induced iNOS but not eNOS expression. In contrast, nNOS expression was strongly decreased by the mixture of the three proinflammatory cytokines (IL-1β, TNF-α and IFNγ) both on the gene and protein level in INS1E cells and rat islet cells. The effects of cytokines on glucose-induced insulin-secretion followed the pattern of nNOS expression reduction and, on the other hand, of the iNOS induction. The data indicate that a low level of nitric oxide originating from the constitutive expression of nNOS in pancreatic beta cells is not deleterious. In particular since proinflammatory cytokines reduce this expression. This nNOS suppression can compensate for NO generation by low concentrations of IL-1β through iNOS induction. Thus, this basal nNOS expression level in pancreatic beta cells represents a protective element against cytokine toxicity., (2012 Elsevier Inc. All rights reserved)
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- 2012
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11. Effects of the novel mitochondrial protein mimitin in insulin-secreting cells.
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Hanzelka K, Skalniak L, Jura J, Lenzen S, and Gurgul-Convey E
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- Adenosine Triphosphate metabolism, Animals, Base Sequence, Caspases metabolism, Cell Line, Cell Proliferation, Cell Survival, Cytokines pharmacology, DNA Primers genetics, Electron Transport Complex I antagonists & inhibitors, Electron Transport Complex I genetics, Gene Expression, Gene Knockdown Techniques, Humans, In Vitro Techniques, Insulin genetics, Insulin metabolism, Insulin Resistance physiology, Insulin Secretion, Insulin-Secreting Cells cytology, Insulin-Secreting Cells drug effects, Insulin-Secreting Cells metabolism, Male, Mice, Mice, Obese, Mitochondrial Proteins antagonists & inhibitors, Mitochondrial Proteins genetics, Molecular Chaperones antagonists & inhibitors, Molecular Chaperones genetics, Obesity physiopathology, Rats, Rats, Inbred Lew, Electron Transport Complex I metabolism, Insulin-Secreting Cells physiology, Mitochondrial Proteins metabolism, Molecular Chaperones metabolism
- Abstract
Mimitin, a novel mitochondrial protein, has been shown to act as a molecular chaperone for the mitochondrial complex I and to regulate ATP synthesis. During Type 1 diabetes development, pro-inflammatory cytokines induce mitochondrial damage in pancreatic β-cells, inhibit ATP synthesis and reduce glucose-induced insulin secretion. Mimitin was expressed in rat pancreatic islets including β-cells and decreased by cytokines. In the ob/ob mouse, a model of insulin resistance and obesity, mimitin expression was down-regulated in liver and brain, up-regulated in heart and kidney, but not affected in islets. To further analyse the impact of mimitin on β-cell function, two β-cell lines, one with a low (INS1E) and another with a higher (MIN6) mimitin expression were studied. Mimitin overexpression protected INS1E cells against cytokine-induced caspase 3 activation, mitochondrial membrane potential reduction and ATP production inhibition, independently from the NF-κB (nuclear factor κB)-iNOS (inducible NO synthase) pathway. Mimitin overexpression increased basal and glucose-induced insulin secretion and prevented cytokine-mediated suppression of insulin secretion. Mimitin knockdown in MIN6 cells had opposite effects to those observed after overexpression. Thus mimitin has the capacity to modulate pancreatic islet function and to reduce cytokine toxicity.
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- 2012
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12. Mechanism of prostacyclin-induced potentiation of glucose-induced insulin secretion.
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Gurgul-Convey E, Hanzelka K, and Lenzen S
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- Animals, Blotting, Western, Cells, Cultured, Cyclic AMP metabolism, Cytochrome P-450 Enzyme System genetics, Cytochrome P-450 Enzyme System metabolism, Drug Synergism, Guanine Nucleotide Exchange Factors genetics, Guanine Nucleotide Exchange Factors metabolism, Insulin genetics, Insulin Secretion, Insulin-Secreting Cells metabolism, Intramolecular Oxidoreductases genetics, Intramolecular Oxidoreductases metabolism, Islets of Langerhans metabolism, Male, RNA Interference, Rats, Rats, Inbred Lew, Reverse Transcriptase Polymerase Chain Reaction, Epoprostenol pharmacology, Glucose pharmacology, Insulin metabolism, Insulin-Secreting Cells drug effects, Islets of Langerhans drug effects
- Abstract
Arachidonic acid metabolites are crucial mediators of inflammation in diabetes. Although eicosanoids are established modulators of pancreatic β-cell function, the role of prostacyclin (prostaglandin I2) is unknown. Therefore, this study aimed to analyze the role of prostacyclin in β-cell function. Prostacyclin synthase (PGIS) was weakly expressed in rat islet cells but nevertheless significantly increased by incubation with 30 mM glucose, especially in non-β-cells. PGIS was overexpressed in INS1E cells, and the regulation of insulin secretion was analyzed. PGIS overexpression strongly potentiated glucose-induced insulin secretion along with increased insulin content and ATP production. Importantly, overexpression of PGIS potentiated only nutrient-induced insulin secretion. The effect of PGIS overexpression was mediated by prostacyclin released from insulin-secreting cells and dependent on prostacyclin receptor (IP receptor) activation, with concomitant cAMP production. The cAMP-mediated potentiation of glucose-induced insulin secretion by prostacyclin was independent of the protein kinase A pathway but strongly attenuated by the knockdown of the exchange protein directly activated by cAMP 2 (Epac2), pointing to a crucial role for Epac2 in this process. Thus, prostacyclin is a powerful potentiator of glucose-induced insulin secretion. It improves the secretory capacity by inducing insulin biosynthesis and probably by stimulating exocytosis. Our findings open a new therapeutical perspective for an improved treatment of type 2 diabetes.
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- 2012
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13. Saddle pulmonary embolism in a cancer patient with thrombocytopenia: a treatment dilemma.
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Zalpour A, Hanzelka K, Patlan JT, Rozner MA, and Yusuf SW
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The association between cancer and venous thromboembolism (VTE) is well established. Saddle pulmonary embolism is not uncommon in hospitalized cancer patients and confers a higher mortality. We report a case of saddle pulmonary embolism in a cancer patient with thrombocytopenia, discuss the bleeding risks, complexity of managing such patients and review current guidelines.
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- 2010
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14. Prospective, double-blind, randomized, placebo-controlled comparison of acetazolamide versus ibuprofen for prophylaxis against high altitude headache: the Headache Evaluation at Altitude Trial (HEAT).
- Author
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Gertsch JH, Lipman GS, Holck PS, Merritt A, Mulcahy A, Fisher RS, Basnyat B, Allison E, Hanzelka K, Hazan A, Meyers Z, Odegaard J, Pook B, Thompson M, Slomovic B, Wahlberg H, Wilshaw V, Weiss EA, and Zafren K
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- Adolescent, Adult, Aged, Double-Blind Method, Female, Headache epidemiology, Humans, Logistic Models, Male, Middle Aged, Mountaineering, Pain Measurement, Placebos, Young Adult, Acetazolamide administration & dosage, Altitude Sickness complications, Altitude Sickness prevention & control, Anti-Inflammatory Agents, Non-Steroidal administration & dosage, Headache etiology, Headache prevention & control, Ibuprofen administration & dosage
- Abstract
Objective: High altitude headache (HAH) is the most common neurological complaint at altitude and the defining component of acute mountain sickness (AMS). However, there is a paucity of literature concerning its prevention. Toward this end, we initiated a prospective, double-blind, randomized, placebo-controlled trial in the Nepal Himalaya designed to compare the effectiveness of ibuprofen and acetazolamide for the prevention of HAH., Methods: Three hundred forty-three healthy western trekkers were recruited at altitudes of 4280 m and 4358 m and assigned to receive ibuprofen 600 mg, acetazolamide 85 mg, or placebo 3 times daily before continued ascent to 4928 m. Outcome measures included headache incidence and severity, AMS incidence and severity on the Lake Louise AMS Questionnaire (LLQ), and visual analog scale (VAS)., Results: Two hundred sixty-five of 343 subjects completed the trial. HAH incidence was similar when treated with acetazolamide (27.1%) or ibuprofen (27.5%; P = .95), and both agents were significantly more effective than placebo (45.3%; P = .01). AMS incidence was similar when treated with acetazolamide (18.8%) or ibuprofen (13.7%; P = .34), and both agents were significantly more effective than placebo (28.6%; P = .03). In fully compliant participants, moderate or severe headache incidence was similar when treated with acetazolamide (3.8%) or ibuprofen (4.7%; P = .79), and both agents were significantly more effective than placebo (13.5%; P = .03)., Conclusions: Ibuprofen and acetazolamide were similarly effective in preventing HAH. Ibuprofen was similar to acetazolamide in preventing symptoms of AMS, an interesting finding that implies a potentially new approach to prevention of cerebral forms of acute altitude illness., (Copyright 2010 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.)
- Published
- 2010
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