12 results on '"Zobel L"'
Search Results
2. Laparoscopic Sleeve Gastrectomy with Staple-Line Oversewing in a Patient with Factor XI Deficiency: A Case Report.
- Author
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Beomonte Zobel L, Dhimolea S, Billeci F, Sbraccia P, and Sica GS
- Subjects
- Humans, Female, Middle Aged, Surgical Stapling, Gastrectomy methods, Laparoscopy, Factor XI Deficiency complications, Obesity, Morbid surgery
- Abstract
BACKGROUND Bariatric surgery (BS) has a lower percentage of complications than other abdominal surgeries. Hemorrhage in one of the most common complications and can be life-threatening. Hereditary factor XI (FXI) deficiency is a coagulation disorder that can result in excessive bleeding requiring intervention to restore hemostasis. Risks over benefits in patients with morbid obesity with BS indication, as well as those with FXI deficiency, should be carefully evaluated. This article reports the case of an obese woman with FXI deficiency -undergoing SG. CASE REPORT A 49-year-old woman with a BMI of 51 kg/m² was diagnosed as having severe FXI deficiency during preoperative exams prior to bariatric surgery. Virus-inactivated homo-group plasma 10 ml/kg infusion was administrated 1 h before surgery, during the entire procedure, and continuing until postoperative day (POD) 4. A very low-calorie ketogenic diet (VLCKD) was proposed to the patient 4 weeks before surgery. Laparoscopic sleeve gastrectomy was performed with staple-line reinforcement by oversewing the seromuscular layer using continuous suture. Subcutaneous enoxaparin 4000 U.I. was administered from POD 1 until POD 25 to prevent any thromboembolic event. The patient was discharged on POD 5 in good clinical condition. CONCLUSIONS Risks of bleeding andor thromboembolic events before or after BS are increased in patient with FXI deficiency. Bariatric surgery in these patients is safe in experienced BS centers, and the risks associated with the obesity seem to exceed those of the coagulopathy and surgery. Careful preoperative counseling, extensive hematological checks, and meticulous surgery are essential to reduce BS risks. Sleeve gastrectomy oversewing the stapler line seems a reasonable choice.
- Published
- 2024
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3. Development of a translatable gene augmentation therapy for CNGB1-retinitis pigmentosa.
- Author
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Occelli LM, Zobel L, Stoddard J, Wagner J, Pasmanter N, Querubin J, Renner LM, Reynaga R, Winkler PA, Sun K, Marinho LFLP, O'Riordan CR, Frederick A, Lauer A, Tsang SH, Hauswirth WW, McGill TJ, Neuringer M, Michalakis S, and Petersen-Jones SM
- Subjects
- Humans, Animals, Dogs, Mice, Cyclic Nucleotide-Gated Cation Channels genetics, Cyclic Nucleotide-Gated Cation Channels metabolism, Retina metabolism, Electroretinography, Rhodopsin metabolism, Retinitis Pigmentosa genetics, Retinitis Pigmentosa therapy, Retinitis Pigmentosa metabolism, Parvovirinae
- Abstract
In this study, we investigate a gene augmentation therapy candidate for the treatment of retinitis pigmentosa (RP) due to cyclic nucleotide-gated channel beta 1 (CNGB1) mutations. We use an adeno-associated virus serotype 5 with transgene under control of a novel short human rhodopsin promoter. The promoter/capsid combination drives efficient expression of a reporter gene (AAV5-RHO-eGFP) exclusively in rod photoreceptors in primate, dog, and mouse following subretinal delivery. The therapeutic vector (AAV5-RHO-CNGB1) delivered to the subretinal space of CNGB1 mutant dogs restores rod-mediated retinal function (electroretinographic responses and vision) for at least 12 months post treatment. Immunohistochemistry shows human CNGB1 is expressed in rod photoreceptors in the treated regions as well as restoration of expression and trafficking of the endogenous alpha subunit of the rod CNG channel required for normal channel formation. The treatment reverses abnormal accumulation of the second messenger, cyclic guanosine monophosphate, which occurs in rod photoreceptors of CNGB1 mutant dogs, confirming formation of a functional CNG channel. In vivo imaging shows long-term preservation of retinal structure. In conclusion, this study establishes the long-term efficacy of subretinal delivery of AAV5-RHO-CNGB1 to rescue the disease phenotype in a canine model of CNGB1-RP, confirming its suitability for future clinical development., Competing Interests: Declaration of interests C.R.O. and A.F. are employees of Sanofi. S.M. is listed as inventor on the patent application WO2018172961A1 ‘‘Gene therapy for the treatment of cngb1-linked retinitis pigmentosa’’ and is co-founder of the gene therapy company ViGeneron GmbH., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
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4. Cross border adjustment mechanism: Initial data for the assessment of hydrogen-based steel production.
- Author
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Rübbelke D, Vögele S, Grajewski M, and Zobel L
- Abstract
Ambitious climate targets affect the competitiveness of industries in the international market. To prevent such industries from moving to other countries in the wake of increased climate protection efforts, cost adjustments may become necessary. Their design requires knowledge of country-specific production costs. Here, we present country-specific cost figures for different production routes of steel, paying particular attention to transportation costs. The data can be used in floor price models aiming to assess the competitiveness of different steel production routes in different countries [1]., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)
- Published
- 2023
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5. Mutations within the cGMP-binding domain of CNGA1 causing autosomal recessive retinitis pigmentosa in human and animal model.
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Kandaswamy S, Zobel L, John B, Santhiya ST, Bogedein J, Przemeck GKH, Gailus-Durner V, Fuchs H, Biel M, de Angelis MH, Graw J, Michalakis S, and Amarie OV
- Abstract
Retinitis pigmentosa is a group of progressive inherited retinal dystrophies that may present clinically as part of a syndromic entity or as an isolated (nonsyndromic) manifestation. In an Indian family suffering from retinitis pigmentosa, we identified a missense variation in CNGA1 affecting the cyclic nucleotide binding domain (CNBD) and characterized a mouse model developed with mutated CNBD. A gene panel analysis comprising 105 known RP genes was used to analyze a family with autosomal-recessive retinitis pigmentosa (arRP) and revealed that CNGA1 was affected. From sperm samples of ENU mutagenesis derived F
1 mice, we re-derived a mutant with a Cnga1 mutation. Homozygous mutant mice, developing retinal degeneration, were examined for morphological and functional consequences of the mutation. In the family, we identified a rare CNGA1 variant (NM_001379270.1) c.1525 G > A; (p.Gly509Arg), which co-segregated among the affected family members. Homozygous Cnga1 mice harboring a (ENSMUST00000087213.12) c.1526 A > G (p.Tyr509Cys) mutation showed progressive degeneration in the retinal photoreceptors from 8 weeks on. This study supports a role for CNGA1 as a disease gene for arRP and provides new insights on the pathobiology of cGMP-binding domain mutations in CNGA1-RP., (© 2022. The Author(s).)- Published
- 2022
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6. Deletion of Abi3/Gngt2 influences age-progressive amyloid β and tau pathologies in distinctive ways.
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Ibanez KR, McFarland KN, Phillips J, Allen M, Lessard CB, Zobel L, De La Cruz EG, Shah S, Vo Q, Wang X, Quicksall Z, Ryu D, Funk C, Ertekin-Taner N, Prokop S, Golde TE, and Chakrabarty P
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- Animals, Humans, Mice, Amyloid beta-Peptides metabolism, Amyloid beta-Protein Precursor genetics, Brain metabolism, Disease Models, Animal, Gliosis metabolism, Membrane Glycoproteins metabolism, Mice, Transgenic, Plaque, Amyloid pathology, Receptors, Immunologic metabolism, tau Proteins genetics, tau Proteins metabolism, Adaptor Proteins, Signal Transducing genetics, Alzheimer Disease pathology, Amyloidosis genetics, GTP-Binding Protein gamma Subunits genetics
- Abstract
Background: The S209F variant of Abelson Interactor Protein 3 (ABI3) increases risk for Alzheimer's disease (AD), but little is known about its function in relation to AD pathogenesis., Methods: Here, we use a mouse model that is deficient in Abi3 locus to study how the loss of function of Abi3 impacts two cardinal neuropathological hallmarks of AD-amyloid β plaques and tau pathology. Our study employs extensive neuropathological and transcriptomic characterization using transgenic mouse models and adeno-associated virus-mediated gene targeting strategies., Results: Analysis of bulk RNAseq data confirmed age-progressive increase in Abi3 levels in rodent models of AD-type amyloidosis and upregulation in AD patients relative to healthy controls. Using RNAscope in situ hybridization, we localized the cellular distribution of Abi3 in mouse and human brains, finding that Abi3 is expressed in both microglial and non-microglial cells. Next, we evaluated Abi3
-/- mice and document that both Abi3 and its overlapping gene, Gngt2, are disrupted in these mice. Using multiple transcriptomic datasets, we show that expression of Abi3 and Gngt2 are tightly correlated in rodent models of AD and human brains, suggesting a tight co-expression relationship. RNAseq of the Abi3-Gngt2-/- mice revealed upregulation of Trem2, Plcg2, and Tyrobp, concomitant with induction of an AD-associated neurodegenerative signature, even in the absence of AD-typical neuropathology. In APP mice, loss of Abi3-Gngt2 resulted in a gene dose- and age-dependent reduction in Aβ deposition. Additionally, in Abi3-Gngt2-/- mice, expression of a pro-aggregant form of human tau exacerbated tauopathy and astrocytosis. Further, using in vitro culture assays, we show that the AD-associated S209F mutation alters the extent of ABI3 phosphorylation., Conclusions: These data provide an important experimental framework for understanding the role of Abi3-Gngt2 function and early inflammatory gliosis in AD. Our studies also demonstrate that inflammatory gliosis could have opposing effects on amyloid and tau pathology, highlighting the unpredictability of targeting immune pathways in AD., (© 2022. The Author(s).)- Published
- 2022
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7. Internal herniation of small bowel through the minimizer ring after banded one anastomosis gastric bypass: Case report with diagnosis and management of a rare complication.
- Author
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Sensi B, Beomonte Zobel L, Forte V, Alicata F, Procaccini C, Pavoncello D, Arcudi C, Bianciardi E, and Gentileschi P
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- Abdomen, Female, Humans, Middle Aged, Retrospective Studies, Bariatric Surgery, Gastric Bypass adverse effects, Laparoscopy adverse effects, Obesity, Morbid complications, Obesity, Morbid surgery
- Abstract
Introduction: One Anastomosis Gastric Bypass has been increasingly performed in the setting of bariatric surgery. The addition of gastric pouch banding (BOAGB) may reduce weight regain in the long term. BOAGB may rarely be complicated by MiniMizer ring-related affections. This article reports for the first time a case of bowel obstruction due to internal hernia (IH) through the ring itself, occurring 15 months after BOAGB., Case Report: A 55 years-old woman presented with unspecific symptoms of sub-acute bowel obstruction 15 months after BOAGB. Work-up revealed IH through the MiniMizer ring and its erosion into the liver. Successful management included laparoscopic ring removal and adhesion-lysis. Postoperative course was uneventful., Discussion and Conclusion: IH through MiniMizer ring is a rare complication of BOAGB and awareness of this possibility may help diagnosis and prevention. Diagnosis requires high index of suspicion and per-oral contrast CT. Successful management entails laparoscopic device removal. Prevention includes non re-absorbable suture fixation and adequate gastric pouch encirclement., Competing Interests: Conflict of Interest The authors declare no conflict of interest., (Copyright © 2022 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2022
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8. Combinatorial model of amyloid β and tau reveals synergy between amyloid deposits and tangle formation.
- Author
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Koller EJ, Ibanez KR, Vo Q, McFarland KN, Gonzalez De La Cruz E, Zobel L, Williams T, Xu G, Ryu D, Patel P, Giasson BI, Prokop S, and Chakrabarty P
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- Alzheimer Disease metabolism, Animals, Brain metabolism, Mice, Mice, Transgenic, Neurofibrillary Tangles metabolism, Neurons metabolism, Neurons pathology, Plaque, Amyloid metabolism, Alzheimer Disease pathology, Amyloid beta-Peptides metabolism, Brain pathology, Disease Models, Animal, Neurofibrillary Tangles pathology, Plaque, Amyloid pathology, tau Proteins metabolism
- Abstract
Aims: To illuminate the pathological synergy between Aβ and tau leading to emergence of neurofibrillary tangles (NFT) in Alzheimer's disease (AD), here, we have performed a comparative neuropathological study utilising three distinctive variants of human tau (WT tau, P301L mutant tau and S320F mutant tau). Previously, in non-transgenic mice, we showed that WT tau or P301L tau does not form NFT while S320F tau can spontaneously aggregate into NFT, allowing us to test the selective vulnerability of these different tau conformations to the presence of Aβ plaques., Methods: We injected recombinant AAV-tau constructs into neonatal APP transgenic TgCRND8 mice or into 3-month-old TgCRND8 mice; both cohorts were aged 3 months post injection. This allowed us to test how different tau variants synergise with soluble forms of Aβ (pre-deposit cohort) or with frank Aβ deposits (post-deposit cohort)., Results: Expression of WT tau did not produce NFT or altered Aβ in either cohort. In the pre-deposit cohort, S320F tau induced Aβ plaque deposition, neuroinflammation and synaptic abnormalities, suggesting that early tau tangles affect the amyloid cascade. In the post-deposit cohort, contemporaneous expression of S320F tau did not exacerbate amyloid pathology, showing a dichotomy in Aβ-tau synergy based on the nature of Aβ. P301L tau produced NFT-type inclusions in the post-deposit cohort, but not in the pre-deposit cohort, indicating pathological synergy with pre-existing Aβ deposits., Conclusions: Our data show that different tau mutations representing specific folding variants of tau synergise with Aβ to different extents, depending on the presence of cerebral deposits., (© 2021 British Neuropathological Society.)
- Published
- 2022
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9. In Vivo Potency Testing of Subretinal rAAV5.hCNGB1 Gene Therapy in the Cngb1 Knockout Mouse Model of Retinitis Pigmentosa.
- Author
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Wagner JE, Zobel L, Gerhardt MJ, O'Riordan CR, Frederick A, Petersen-Jones SM, Biel M, and Michalakis S
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- Animals, Cyclic Nucleotide-Gated Cation Channels, Dependovirus genetics, Dependovirus metabolism, Genetic Therapy, Mice, Mice, Knockout, Nerve Tissue Proteins genetics, Nerve Tissue Proteins metabolism, Retina metabolism, Rhodopsin genetics, Retinitis Pigmentosa genetics, Retinitis Pigmentosa therapy
- Abstract
Retinitis pigmentosa type 45 (RP45) is an autosomal-recessively inherited blinding disease caused by mutations in the cyclic nucleotide-gated channel subunit beta 1 ( CNGB1 ) gene. In this study, we developed and tested a novel gene supplementation therapy suitable for clinical translation. To this end, we designed a recombinant adeno-associated virus (rAAV) vector carrying a genome that features a novel human rhodopsin promoter (hRHO194) driving rod-specific expression of full-length human CNGB1 (rAAV5.hCNGB1). rAAV5.hCNGB1 was evaluated for efficacy in the Cngb1 knockout ( Cngb1
-/- ) mouse model of RP45. In particular, increasing doses of rAAV5.hCNGB1 were delivered through single subretinal injection in 4-week-old Cngb1-/- mice and the treatment effect was assessed over a follow-up period of 9 months at the level of (1) retinal morphology, (2) retinal function, (3) vision-guided behavior, and (4) transgene expression. We found that subretinal treatment with rAAV5.hCNGB1 resulted in efficient expression of the human CNGB1 protein in mouse rods and was able to normalize the expression of the endogenous mouse CNGA1 subunit, which together with CNGB1 forms the native heterotetrameric cyclic guanosine monophosphate-gated cation channel in rod photoreceptors. The treatment led to a dose-dependent recovery of rod photoreceptor-driven function and preservation of retinal morphology in Cngb1-/- mice. In summary, these results demonstrate the efficacy of hCNGB1 gene supplementation therapy in the Cngb1-/- mouse model of RP45 and support the translation of this approach toward future clinical application.- Published
- 2021
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10. Metabolic implication of tigecycline as an efficacious second-line treatment for sorafenib-resistant hepatocellular carcinoma.
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Meßner M, Schmitt S, Ardelt MA, Fröhlich T, Müller M, Pein H, Huber-Cantonati P, Ortler C, Koenig LM, Zobel L, Koeberle A, Arnold GJ, Rothenfußer S, Kiemer AK, Gerbes AL, Zischka H, Vollmar AM, and Pachmayr J
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- Animals, Apoptosis drug effects, Apoptosis genetics, Carcinoma, Hepatocellular genetics, Carcinoma, Hepatocellular metabolism, Cell Line, Tumor, Cell Proliferation drug effects, Cell Proliferation genetics, Female, Humans, Liver Neoplasms genetics, Liver Neoplasms metabolism, Mice, SCID, Mitochondria drug effects, Mitochondria metabolism, Neoplasm Recurrence, Local prevention & control, Protein Synthesis Inhibitors pharmacology, Carcinoma, Hepatocellular drug therapy, Drug Resistance, Neoplasm drug effects, Liver Neoplasms drug therapy, Sorafenib pharmacology, Tigecycline pharmacology, Xenograft Model Antitumor Assays methods
- Abstract
Sorafenib represents the current standard of care for patients with advanced-stage hepatocellular carcinoma (HCC). However, acquired drug resistance occurs frequently during therapy and is accompanied by rapid tumor regrowth after sorafenib therapy termination. To identify the mechanism of this therapy-limiting growth resumption, we established robust sorafenib resistance HCC cell models that exhibited mitochondrial dysfunction and chemotherapeutic crossresistance. We found a rapid relapse of tumor cell proliferation after sorafenib withdrawal, which was caused by renewal of mitochondrial structures alongside a metabolic switch toward high electron transport system (ETS) activity. The translation-inhibiting antibiotic tigecycline impaired the biogenesis of mitochondrial DNA-encoded ETS subunits and limited the electron acceptor turnover required for glutamine oxidation. Thereby, tigecycline prevented the tumor relapse in vitro and in murine xenografts in vivo. These results offer a promising second-line therapeutic approach for advanced-stage HCC patients with progressive disease undergoing sorafenib therapy or treatment interruption due to severe adverse events., (© 2020 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)
- Published
- 2020
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11. Serum perfluorooctane sulfonate and hepatic and lipid clinical chemistry tests in fluorochemical production employees.
- Author
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Olsen GW, Burris JM, Mandel JH, and Zobel LR
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- Adult, Alabama, Belgium, Bilirubin blood, Cholesterol blood, Cross-Sectional Studies, Dose-Response Relationship, Drug, Humans, Lipoproteins blood, Liver enzymology, Male, Middle Aged, Regression Analysis, Alkanesulfonic Acids, Fluorocarbons, Lipids blood, Liver drug effects, Occupational Exposure adverse effects
- Abstract
The 3M Company manufactures fluorochemicals, which have as a precursor perfluorooctane sulfonyl fluoride (C8F17SO2F). These compounds may be expected to transform metabolically, to an undetermined degree, to perfluorooctane sulfonate (PFOS, C8F17SO3-) as an end-stage metabolite. Subchronic studies in rats and primates indicate a potential for cumulative toxicity with PFOS with the primary effect related to metabolic wasting with hypolipidemia as a consistent finding. Biennial medical surveillance has been offered to the company's fluorochemical production workers located in Decatur, Alabama, and Antwerp, Belgium. In 1995, the mean serum PFOS level, as measured by high-performance liquid chromatography mass spectrometry, for 178 male employees was 2.19 parts per million (ppm; range, 0.00 to 12.83 ppm), and in 1997, for 149 male employees, it was 1.75 ppm (0.10 to 9.93 ppm). Our analyses suggest that among these production employees, there were no substantial changes in serum hepatic enzymes, cholesterol, or lipoproteins associated with PFOS levels less than 6 ppm. It was not possible to derive inferences from the few employees who had serum PFOS levels > or = 6 ppm. These results may be due to the lower levels of serum PFOS measured among these production employees, compared to those suspected to cause effects in laboratory animals.
- Published
- 1999
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12. Pressure pulse contour analysis in determining the effect of vasodilator drugs on vascular hemodynamic impedance characteristics in dogs.
- Author
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Zobel LR, Finkelstein SM, Carlyle PF, and Cohn JN
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- Animals, Cardiac Output drug effects, Cardiography, Impedance, Dogs, Heart Rate drug effects, Hydralazine pharmacology, Nitroglycerin pharmacology, Nitroprusside pharmacology, Pressure, Propranolol pharmacology, Pulse drug effects, Time Factors, Hemodynamics drug effects, Vasodilator Agents pharmacology
- Published
- 1980
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- View/download PDF
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