27 results on '"Menon Y"'
Search Results
2. Reversal of brain dysfunction with UV-A1 irradiation in a patient with systemic lupus
- Author
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Menon, Y, primary, McCarthy, K, additional, and McGrath, H, additional
- Published
- 2003
- Full Text
- View/download PDF
3. Fission yeast Msp1 is a mitochondrial dynamin-related protein
- Author
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Pelloquin, L., primary, Belenguer, P., additional, Menon, Y., additional, Gas, N., additional, and Ducommun, B., additional
- Published
- 1999
- Full Text
- View/download PDF
4. Implementation of a mandatory rheumatology osteoporosis consultation in patients with low-impact hip fracture.
- Author
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Quintos-Macasa A, Quinet R, Spady M, Zakem J, Davis W, Menon Y, Serebro L, and Krousel-Wood MA
- Published
- 2007
- Full Text
- View/download PDF
5. An initial presentation of polyarticular gout with spinal involvement.
- Author
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Fontenot A, Harris P, Macasa A, Menon Y, and Quinet R
- Published
- 2008
- Full Text
- View/download PDF
6. Vaccine Designing Technology against Leishmaniasis: Current Challenges and Implication.
- Author
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Gupta J, Menon Y, Kumar S, and Jain CK
- Abstract
Leishmaniasis, a debilitating disease caused by protozoan parasites of the genus Leishmania and transmitted by the bite of a female sandfly, continues to present significant challenges despite ongoing research and collaboration in vaccine development. The intricate interaction between the parasite's life cycle stages and the host's immunological response, namely the promastigote and amastigote forms, adds complexity to vaccine design. The quest for a potent vaccine against Leishmaniasis demands a comprehensive understanding of the immune mechanisms that confer long-lasting protection, which necessitates extensive research efforts. In this pursuit, innovative approaches such as reverse vaccinology and computer-aided design offer promising avenues for unraveling the intricacies of host-pathogen interactions and identifying effective vaccine candidates. However, numerous obstacles, including limited treatment options, the need for sustained antigenic presence, and the prevalence of co-infections, particularly with HIV, impede progress. Nevertheless, through persistent research endeavours and collaborative initiatives, the goal of developing a highly efficacious vaccine against Leishmaniasis can be achieved, offering hope through the latest Omics data development with immunoinformatics approaches for effective vaccine design for the prevention of this disease., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Published
- 2024
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7. Hemisynthetic alkaloids derived from trilobine are antimalarials with sustained activity in multidrug-resistant Plasmodium falciparum .
- Author
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Nardella F, Dobrescu I, Hassan H, Rodrigues F, Thiberge S, Mancio-Silva L, Tafit A, Jallet C, Cadet-Daniel V, Goussin S, Lorthiois A, Menon Y, Molinier N, Pechalrieu D, Long C, Sautel F, Matondo M, Duchateau M, Médard G, Witkowski B, Scherf A, Halby L, and Arimondo PB
- Abstract
Malaria eradication requires the development of new drugs to combat drug-resistant parasites. We identified bisbenzylisoquinoline alkaloids isolated from Cocculus hirsutus that are active against Plasmodium falciparum blood stages. Synthesis of a library of 94 hemi-synthetic derivatives allowed to identify compound 84 that kills multi-drug resistant clinical isolates in the nanomolar range (median IC
50 ranging from 35 to 88 nM). Chemical optimization led to compound 125 with significantly improved preclinical properties. 125 delays the onset of parasitemia in Plasmodium berghei infected mice and inhibits P. falciparum transmission stages in vitro (culture assays), and in vivo using membrane feeding assay in the Anopheles stephensi vector. Compound 125 also impairs P. falciparum development in sporozoite-infected hepatocytes, in the low micromolar range. Finally, by chemical pull-down strategy, we characterized the parasite interactome with trilobine derivatives, identifying protein partners belonging to metabolic pathways that are not targeted by the actual antimalarial drugs or implicated in drug-resistance mechanisms., Competing Interests: Authors F.N., H.H., L.H., A.S. and P.B.A. declare a patent entitled Trilobine derivatives and use thereof in the treatment of malaria reference WO2021/224491 A1 (11/11/2021)., (© 2023 The Authors.)- Published
- 2023
- Full Text
- View/download PDF
8. Efficacy of Propranolol Between 6 and 12 Months of Age in High-Risk Infantile Hemangioma.
- Author
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Baselga E, Dembowska-Baginska B, Przewratil P, González-Enseñat MA, Wyrzykowski D, Torrelo A, López Gutiérrez JC, Rychłowska-Pruszyńska M, de Lucas-Laguna R, Esteve-Martinez A, Roé E, Zaim M, Menon Y, Gautier S, Lebbé G, Bouroubi A, Delarue A, and Voisard JJ
- Subjects
- Administration, Oral, Drug Administration Schedule, Female, Humans, Infant, Male, Risk Factors, Treatment Outcome, Adrenergic beta-Antagonists administration & dosage, Hemangioma diagnosis, Hemangioma drug therapy, Propranolol administration & dosage
- Abstract
Background and Objectives: There is no consensus on optimal treatment duration for propranolol in infantile hemangioma (IH). We evaluated the efficacy and safety of oral propranolol solution administered for a minimum of 6 months up to a maximum of 12 months of age in high-risk IH., Methods: This single-arm, open-label, phase 3 study was conducted in patients aged 35 to 150 days with high-risk IH in 10 hospitals between 2015 and 2017. The study comprised a 6-month initial treatment period (ITP) plus continuation up to 12 months of age if complete success was not achieved, a follow-up, and a retreatment period. Patients received oral propranolol twice daily (3 mg/kg per day). The primary end point was the success rate at the end of the ITP. Furthermore, the persistence of IH response and efficacy of retreatment was evaluated., Results: The success rate after 6 months of treatment was 47%, increasing to 76% at the end of the ITP. Of the patients who achieved success, 68% sustained success for 3 months without treatment, and 24% required retreatment. Of the 8 patients who were retreated, 7 achieved success. Adverse events, reported by 80% of patients, were mild, which were expected in this population or known propranolol side effects., Conclusions: Oral propranolol administered beyond 6 months and up to 12 months of age meaningfully increases the success rate in high-risk IH. Success was sustained in most patients up to 3 months after stopping treatment. Retreatment was efficacious, and the safety profile satisfactory., Competing Interests: POTENTIAL CONFLICT OF INTEREST: Drs Zaim, Menon, Lebbé, Bouroubi, Delarue, and Voisard and Ms Gautier are current employees of Pierre Fabre; Dr Baselga received research support for this study from Laboratoires Pierre Fabre (and has previously received honoraria and/or reimbursement from Laboratoires Pierre Fabre for the role of consultant, speaker, and/or investigator); Dr Torrelo has been paid for lecturing for Pierre Fabre; and the other authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)
- Published
- 2018
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9. Rational Design of Bisubstrate-Type Analogues as Inhibitors of DNA Methyltransferases in Cancer Cells.
- Author
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Halby L, Menon Y, Rilova E, Pechalrieu D, Masson V, Faux C, Bouhlel MA, David-Cordonnier MH, Novosad N, Aussagues Y, Samson A, Lacroix L, Ausseil F, Fleury L, Guianvarc'h D, Ferroud C, and Arimondo PB
- Subjects
- Cell Line, Tumor, DNA (Cytosine-5-)-Methyltransferase 1, DNA Methylation, DNA Methyltransferase 3A, Genes, Tumor Suppressor, Humans, Neoplasms pathology, Substrate Specificity, DNA (Cytosine-5-)-Methyltransferases antagonists & inhibitors, Drug Design, Enzyme Inhibitors chemistry, Enzyme Inhibitors pharmacology, Neoplasms enzymology
- Abstract
Aberrant DNA hypermethylation of promoter of tumor suppressor genes is commonly observed in cancer, and its inhibition by small molecules is promising for their reactivation. Here we designed bisubstrate analogues-based inhibitors, by mimicking each substrate, the S-adenosyl-l-methionine and the deoxycytidine, and linking them together. This approach resulted in quinazoline-quinoline derivatives as potent inhibitors of DNMT3A and DNMT1, some showing certain isoform selectivity. We highlighted the importance of (i) the nature and rigidity of the linker between the two moieties for inhibition, as (ii) the presence of the nitrogen on the quinoline group, and (iii) of a hydrophobic group on the quinazoline. The most potent inhibitors induced demethylation of CDKN2A promoter in colon carcinoma HCT116 cells and its reactivation after 7 days of treatment. Furthermore, in a leukemia cell model system, we found a correlation between demethylation of the promoter induced by the treatment, chromatin opening at the promoter, and the reactivation of a reporter gene.
- Published
- 2017
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10. Identification and optimization of hydrazone-gallate derivatives as specific inhibitors of DNA methyltransferase 3A.
- Author
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Erdmann A, Menon Y, Gros C, Masson V, Aussagues Y, Ausseil F, Novosad N, Schambel P, Baltas M, and Arimondo PB
- Subjects
- Antineoplastic Agents chemical synthesis, Antineoplastic Agents chemistry, Cell Line, Tumor, Cell Proliferation drug effects, DNA (Cytosine-5-)-Methyltransferases metabolism, DNA Methyltransferase 3A, Dose-Response Relationship, Drug, Drug Screening Assays, Antitumor, Enzyme Inhibitors chemical synthesis, Enzyme Inhibitors chemistry, Gallic Acid chemistry, Humans, Hydrazones chemical synthesis, Hydrazones chemistry, Neoplasms metabolism, Structure-Activity Relationship, Antineoplastic Agents pharmacology, DNA (Cytosine-5-)-Methyltransferases antagonists & inhibitors, Enzyme Inhibitors pharmacology, Gallic Acid pharmacology, Hydrazones pharmacology, Neoplasms drug therapy
- Abstract
DNA methylation is the most studied epigenetic event. Since the methylation profile of the genome is widely modified in cancer cells, DNA methyltransferases are the target of new anticancer therapies. Nucleosidic inhibitors suffer from toxicity and chemical stability, while non-nucleosidic inhibitors lack potency. Here, we found a novel DNMT inhibitor scaffold by enzymatic screening and structure-activity relationship studies. The optimization studies led to an inhibitor containing three fragments: a gallate frame, a hydrazone linker and a benzothiazole moiety. Interestingly, the compound inhibits DNMT3A with micromolar potency (EC50 = 1.6 μM) and does not inhibit DNMT1; this DNMT3A selectivity is supported by a docking study. Finally, the compound reactivates a reporter gene in leukemia KG-1 cells.
- Published
- 2016
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11. Design and synthesis of new non nucleoside inhibitors of DNMT3A.
- Author
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Erdmann A, Menon Y, Gros C, Molinier N, Novosad N, Samson A, Gregoire JM, Long C, Ausseil F, Halby L, and Arimondo PB
- Subjects
- DNA Methyltransferase 3A, Epigenomics, Humans, Molecular Structure, Structure-Activity Relationship, DNA (Cytosine-5-)-Methyltransferases chemical synthesis, DNA (Cytosine-5-)-Methyltransferases chemistry
- Abstract
DNA methylation, an epigenetic modification regulating gene expression, is a promising target in cancer. In an effort to identify new non nucleosidic inhibitors of DNA methyltransferases, the enzymes responsible for DNA methylation, we carried out a high-throughput screening of 66,000 chemical compounds based on an enzymatic assay against catalytic DNMT3A. A family of propiophenone derivatives was identified. After chemical optimization and structure activity relationship studies, a new inhibitor (33) was obtained with an EC50 of 2.1 μM against DNMT3A. The mechanism of inhibition of the compound was investigated as it forms a reactive Michael acceptor group in situ. Thereby, the Michael acceptor 20 was identified. This compound was further characterized for its biological activity in cancer cells., (Copyright © 2015 Elsevier Ltd. All rights reserved.)
- Published
- 2015
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12. Design, synthesis and biological evaluation of 4-amino-N- (4-aminophenyl)benzamide analogues of quinoline-based SGI-1027 as inhibitors of DNA methylation.
- Author
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Rilova E, Erdmann A, Gros C, Masson V, Aussagues Y, Poughon-Cassabois V, Rajavelu A, Jeltsch A, Menon Y, Novosad N, Gregoire JM, Vispé S, Schambel P, Ausseil F, Sautel F, Arimondo PB, and Cantagrel F
- Subjects
- Aminoquinolines chemistry, Cell Line, Tumor, Cell Proliferation drug effects, DNA (Cytosine-5-)-Methyltransferase 1, DNA (Cytosine-5-)-Methyltransferases antagonists & inhibitors, DNA (Cytosine-5-)-Methyltransferases metabolism, DNA Methyltransferase 3A, Dose-Response Relationship, Drug, Drug Screening Assays, Antitumor, Humans, Pyrimidines chemistry, Structure-Activity Relationship, Aminoquinolines chemical synthesis, Aminoquinolines pharmacology, DNA Methylation drug effects, Drug Design, Pyrimidines chemical synthesis, Pyrimidines pharmacology, Quinolines chemistry
- Abstract
Quinoline derivative SGI-1027 (N-(4-(2-amino-6-methylpyrimidin-4-ylamino)phenyl)-4-(quinolin-4-ylamino)benzamide) was first described in 2009 as a potent inhibitor of DNA methyltransferase (DNMT) 1, 3A and 3B. Based on molecular modeling studies, performed using the crystal structure of Haemophilus haemolyticus cytosine-5 DNA methyltransferase (MHhaI C5 DNMT), which suggested that the quinoline and the aminopyridimine moieties of SGI-1027 are important for interaction with the substrates and protein, we designed and synthesized 25 derivatives. Among them, four compounds—namely the derivatives 12, 16, 31 and 32—exhibited activities comparable to that of the parent compound. Further evaluation revealed that these compounds were more potent against human DNMT3A than against human DNMT1 and induced the re-expression of a reporter gene, controlled by a methylated cytomegalovirus (CMV) promoter, in leukemia KG-1 cells. These compounds possessed cytotoxicity against leukemia KG-1 cells in the micromolar range, comparable with the cytotoxicity of the reference compound, SGI-1027. Structure–activity relationships were elucidated from the results. First, the presence of a methylene or carbonyl group to conjugate the quinoline moiety decreased the activity. Second, the size and nature of the aromatic or heterocycle subsitutents effects inhibition activity: tricyclic moieties, such as acridine, were found to decrease activity, while bicyclic substituents, such as quinoline, were well tolerated. The best combination was found to be a bicyclic substituent on one side of the compound, and a one-ring moiety on the other side. Finally, the orientation of the central amide bond was found to have little effect on the biological activity. This study provides new insights in to the structure-activity relationships of SGI-1027 and its derivative.
- Published
- 2014
- Full Text
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13. Development of a universal radioactive DNA methyltransferase inhibition test for high-throughput screening and mechanistic studies.
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Gros C, Chauvigné L, Poulet A, Menon Y, Ausseil F, Dufau I, and Arimondo PB
- Subjects
- Cell Extracts, Cell Line, DNA (Cytosine-5-)-Methyltransferase 1, DNA Methylation drug effects, Dimethyl Sulfoxide, Humans, Solvents, Tritium, DNA (Cytosine-5-)-Methyltransferases antagonists & inhibitors, Enzyme Inhibitors pharmacology, High-Throughput Screening Assays methods
- Abstract
DNA methylation is an important epigenetic mark in eukaryotes, and aberrant pattern of this modification is involved in numerous diseases such as cancers. Interestingly, DNA methylation is reversible and thus is considered a promising therapeutic target. Therefore, there is a need for identifying new small inhibitors of C5 DNA methyltransferases (DNMTs). Despite the development of numerous in vitro DNMT assays, there is a lack of reliable tests suitable for high-throughput screening, which can also give insights into inhibitor mechanisms of action. We developed a new test based on scintillation proximity assay meeting these requirements. After optimizing our assay on human DNMT1 and calibrating it with two known inhibitors, we carried out S-Adenosyl-l-Methionine and DNA competition studies on three inhibitors and were able to determine each mechanism of action. Finally, we showed that our test was applicable to 3 other methyltransferases sources: human DNMT3A, bacterial M.SssI and cellular extracts as well.
- Published
- 2013
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14. Signal recognition antibody-positive myopathy and response to intravenous immunoglobulin G (IVIG).
- Author
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Garcia-Rosell M, Moore S, Pattanaik D, Menon Y, Bertorini T, and Carbone L
- Subjects
- Adult, Creatine Kinase analysis, Humans, Male, Autoantibodies blood, Immunoglobulins, Intravenous therapeutic use, Immunologic Factors therapeutic use, Muscular Diseases immunology, Muscular Diseases therapy, Signal Recognition Particle immunology
- Published
- 2013
- Full Text
- View/download PDF
15. Implementation of a mandatory rheumatology osteoporosis consultation in patients with low-impact hip fracture.
- Author
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Quintos-Macasa AM, Quinet R, Spady M, Zakem J, Davis W, Menon Y, Serebro L, and Krousel-Wood MA
- Subjects
- Aged, Aged, 80 and over, Female, Hip Fractures therapy, Humans, Male, Osteoporosis diagnosis, Retrospective Studies, Rheumatology, Hip Fractures etiology, Osteoporosis complications, Referral and Consultation
- Abstract
Background: Osteoporosis remains an underdiagnosed and undertreated major health problem. The current treatment rate for patients who have experienced at least 1 osteoporotic fracture is 20%-25%. Therefore, the Rheumatology and Internal Medicine Departments of Ochsner Clinic Foundation New Orleans implemented a mandatory rheumatology osteoporosis consult as part of preprinted admission orders for all patients after hip fracture surgery on the Internal Medicine service., Methods: We conducted a retrospective study of 78 patients admitted with a low-impact hip fracture between June 2004 and July 2005. These patients were seen by the rheumatology service in the hospital after hip fracture repair (exposed group). Osteoporosis evaluation was performed based on an interview questionnaire. Seventy-eight age-matched patients previously admitted for low-intensity or low-impact hip fracture in 2002-2003 but not exposed to the mandatory rheumatology consult served as our comparison group. Pearson chi2 test was used for statistical analysis., Results: Mean patient age was 80 years. Of the 78 unexposed patients, 17 (22%) were on treatment (calcium, vitamin D, hormones or antiresorptive agents) before the hip fracture, and 18 (23%) were on treatment after fracture repair. Of the 78 patients exposed to the compulsory rheumatology consultation, 34 (44%) patients were receiving osteoporosis treatment before hip fracture and 75 (96%) patients were receiving treatment after fracture repair. Of the patients not treated before hip fracture repair, there was a significant increase in the percent treated for those patients exposed to the rheumatology consult versus those not exposed (97.6% vs. 2.4%, respectively, P < 0.0001)., Conclusions: In our institution, we were successful in identifying and initiating appropriate therapy for osteoporosis patients through an automatic rheumatology osteoporosis consultation after hip fracture. The implementation of a mandatory osteoporosis consult resulted in a statistically significant increase in treatment of the exposed group compared with the unexposed group.
- Published
- 2007
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16. Transient synovitis of the hip in an adult.
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Quintos-Macasa AM, Serebro L, and Menon Y
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- Acute Disease, Aged, Amitriptyline analogs & derivatives, Amitriptyline therapeutic use, Diagnosis, Differential, Drug Therapy, Combination, Follow-Up Studies, Glucocorticoids therapeutic use, Humans, Magnetic Resonance Imaging, Male, Muscle Relaxants, Central therapeutic use, Prednisone therapeutic use, Range of Motion, Articular, Synovitis drug therapy, Synovitis physiopathology, Hip Joint, Synovitis diagnosis
- Abstract
Transient synovitis of the hip is an acute and self-limited disease commonly seen in children. It is the most common cause of acute hip pain in children ages 3 to 10. It is not considered a disease of adults. It usually only affects one hip. The child may complain of pain that is much worse with walking and may actually walk with a limp. The symptoms usually improve in 4 to 5 days. Over-the-counter pain medicines (acetaminophen, ibuprofen) may help. There is usually no associated residual deficit. Currently, three cases in the literature report the same presentation and symptomatology in adults. We report the fourth case of acute hip pain in an adult that behaved in a way parallel to that seen in the pediatric population.
- Published
- 2006
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17. Frequency of microangiopathic hemolytic anemia in patients with systemic lupus erythematosus exacerbation: Distinction from thrombotic thrombocytopenic purpura, prognosis, and outcome.
- Author
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Dold S, Singh R, Sarwar H, Menon Y, Candia L, and Espinoza LR
- Subjects
- Adolescent, Adult, Aged, Anemia, Hemolytic, Autoimmune etiology, Anemia, Hemolytic, Autoimmune physiopathology, Cohort Studies, Diagnosis, Differential, Female, Health Status, Humans, Lupus Erythematosus, Systemic complications, Lupus Erythematosus, Systemic physiopathology, Male, Middle Aged, Severity of Illness Index, Anemia, Hemolytic, Autoimmune diagnosis, Lupus Erythematosus, Systemic diagnosis, Purpura, Thrombocytopenic diagnosis
- Published
- 2005
- Full Text
- View/download PDF
18. Interferon-alpha-associated sarcoidosis responsive to infliximab therapy.
- Author
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Menon Y, Cucurull E, Reisin E, and Espinoza LR
- Subjects
- Gastrointestinal Agents therapeutic use, Humans, Infliximab, Interferon alpha-2, Male, Middle Aged, Recombinant Proteins, Antibodies, Monoclonal therapeutic use, Hepatitis C, Chronic drug therapy, Interferon-alpha adverse effects, Ribavirin adverse effects, Sarcoidosis chemically induced, Sarcoidosis drug therapy
- Abstract
Sarcoidosis, a multisystem disease characterized by noncaseating granulomas, has been reported to be associated with interferon alpha (IFN-alpha) therapy for hepatitis C infection. INF-alpha is known to stimulate T helper cells with a Th1 profile immune response, which is the key immunologic event of a sarcoid granuloma formation. We report a patient treated with IFN-alpha who developed hypercalcemia and renal insufficiency as presenting clinical manifestation of sarcoidosis. Prednisone therapy was effective in controlling hypercalcemia but had to be discontinued due to an increase in hepatitis C viral RNA count. Infliximab, a chimeric monoclonal antibody directed against tumor necrosis factor alpha was used as therapy in our patient for its known potent anti-inflammatory effects. The patient received three doses of infliximab (5 mg/kg) and achieved a rapid decline in serum calcium to normal levels in 7 days; the serum calcium level has remained normal 3 months after the last infusion.
- Published
- 2004
- Full Text
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19. Decreased nucleotide excision repair activity and alterations of topoisomerase IIalpha are associated with the in vivo resistance of a P388 leukemia subline to F11782, a novel catalytic inhibitor of topoisomerases I and II.
- Author
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Kruczynski A, Barret JM, Van Hille B, Chansard N, Astruc J, Menon Y, Duchier C, Créancier L, and Hill BT
- Subjects
- Animals, Antigens, Neoplasm, Antineoplastic Agents administration & dosage, Antineoplastic Agents therapeutic use, Blotting, Northern, Catalysis drug effects, Cell Line, Tumor, Cisplatin administration & dosage, Cisplatin therapeutic use, DNA Topoisomerases, Type I genetics, DNA Topoisomerases, Type I metabolism, DNA Topoisomerases, Type II genetics, DNA-Binding Proteins, Doxorubicin administration & dosage, Doxorubicin therapeutic use, Drug Resistance, Neoplasm genetics, Etoposide administration & dosage, Etoposide therapeutic use, Leukemia drug therapy, Leukemia enzymology, Leukemia pathology, Mice, Mice, Inbred DBA, Mutation, Missense, Naphthalenes administration & dosage, Neoplasm Transplantation, Neoplasms, Experimental enzymology, Neoplasms, Experimental pathology, Organophosphorus Compounds administration & dosage, Organophosphorus Compounds therapeutic use, Pyrans administration & dosage, RNA, Messenger genetics, RNA, Messenger metabolism, Topoisomerase I Inhibitors, Topoisomerase II Inhibitors, DNA Repair, DNA Topoisomerases, Type II metabolism, Etoposide analogs & derivatives, Naphthalenes therapeutic use, Neoplasms, Experimental drug therapy, Pyrans therapeutic use
- Abstract
Purpose: The purpose of the study was to investigate the mechanisms associated with antitumor activity and resistance to F11782, a novel dual catalytic inhibitor of topoisomerases with DNA repair-inhibitory properties., Experimental Design: For that purpose, an F11782-resistant P388 leukemia subline (P388/F11782) has been developed in vivo and characterized., Results: Weekly subtherapeutic doses of F11782 (10 mg/kg) induced complete resistance to F11782 after 8 weekly passages. This resistant P388/F11782 subline retained some in vivo sensitivity to several DNA-topoisomerase II and/or I complex-stabilizing poisons and showed marked collateral sensitivity to cisplatin, topotecan, colchicine, and Vinca alkaloids, while proving completely cross-resistant only to merbarone and doxorubicin. Therefore, resistance to F11782 did not appear to be associated with a classic multidrug resistance profile, as further reflected by unaltered drug uptake and no overexpression of resistance-related proteins or modification of the glutathione-mediated detoxification process. In vivo resistance to F11782 was, however, associated with a marked reduction in topoisomerase IIalpha protein (87%) and mRNA (50%) levels, as well as a diminution of the catalytic activity of topoisomerase IIalpha. In contrast, only minor reductions in topoisomerases IIbeta and I levels were recorded. However, of major interest, nucleotide excision repair activity was decreased 3-fold in these P388/F11782 cells and was more specifically associated with a decreased (67%) level of XPG (human xeroderma pigmentosum group G complementing protein), an endonuclease involved in this DNA repair system., Conclusions: These findings suggest that both topoisomerase IIalpha and XPG are major targets of F11782 in vivo and further demonstrate the original mechanism of action of this novel compound.
- Published
- 2004
- Full Text
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20. Antiphospholipid Antibody Syndrome.
- Author
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Cucurull E, Gharavi AE, Menon Y, and Wilson WA
- Abstract
Antiphospholipid antibody syndrome (APS) is a recently defined autoimmune disorder characterized by recurrent vascular thromboses or recurrent pregnancy morbidity; these features are linked to the presence in blood of autoantibodies against negatively charged phospholipids or phospholipid-binding proteins. Thrombosis can occur in any tissue, in veins, arteries, or the microvasculature. Pregnancy morbidity in APS includes miscarriages or premature birth. Criteria that define the major clinical and laboratory features of APS were published in 1999. In patients with antiphospholipid antibodies and prior thrombosis or pregnancy morbidity, there is a high risk of recurrence that persists as long as antiphospholipid antibodies occur in blood. This risk for recurrence of thrombosis or pregnancy morbidity is greatly reduced by preventive anticoagulant therapy. Patients presenting with thrombosis in APS are initially managed in much the same way as are patients with vascular thrombosis owing to other causes. However, in patients with APS, high-intensity anticoagulation is usually needed to prevent recurrences of thrombosis. Thrombosis in APS is often multifactorial, as with non-APS thrombosis. Therefore, in all patients with APS, other reversible risk factors for thrombosis should be sought. The pregnancy outcome of women with APS who have had prior miscarriages is greatly improved by treatment during pregnancy with a combination of heparin and low-dose aspirin.
- Published
- 2003
- Full Text
- View/download PDF
21. A six-month randomized, controlled, double-blind, dose-response comparison of intravenous pamidronate (60 mg versus 10 mg) in the treatment of nonsteroidal antiinflammatory drug-refractory ankylosing spondylitis: comment on the article by Maksymowych et al.
- Author
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Singh R, Menon Y, Cuchacovich R, and Espinoza LR
- Subjects
- Adult, Anti-Inflammatory Agents administration & dosage, Anti-Inflammatory Agents, Non-Steroidal therapeutic use, Diphosphonates administration & dosage, Double-Blind Method, Humans, Male, Pamidronate, Randomized Controlled Trials as Topic, Anti-Inflammatory Agents adverse effects, Diphosphonates adverse effects, Hypocalcemia chemically induced, Spondylitis, Ankylosing drug therapy
- Published
- 2003
- Full Text
- View/download PDF
22. Acute abdomen due to spontaneous organ rupture in systemic lupus erythematosus.
- Author
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Singh R, Menon Y, McGrath H, and Espinoza LR
- Subjects
- Adult, Diagnosis, Differential, Female, Hemoperitoneum etiology, Humans, Liver Diseases etiology, Rupture, Spontaneous, Abdomen, Acute etiology, Hemoperitoneum complications, Liver pathology, Liver Diseases complications, Liver Diseases diagnosis, Lupus Erythematosus, Systemic complications
- Published
- 2003
- Full Text
- View/download PDF
23. Shrinking lung syndrome in systemic lupus erythematosus and Sjogren's syndrome.
- Author
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Singh R, Huang W, Menon Y, and Espinoza LR
- Abstract
Shrinking lung syndrome (SLS) is a rare complication of systemic lupus erythematosus (SLE) characterized by unexplained dyspnea, a restrictive pattern on pulmonary function tests, and an elevated hemidiaphragm. A total of 59 cases are reported in literature including the current case. The mean age of these patients is 36.85 years (range, 15-61 years), and the female-to-male ratio is 6:1. This disorder is seen primarily during the later stages of SLE. The most common presenting features include dyspnea and pleuritic chest pain. Myositis has been reported in only 8 of 59 patients (13%). Diagnosis is made with chest x-ray showing an elevated hemidiaphragm and a restrictive pattern on pulmonary function testing without any evidence of interstitial lung disease along with decreased transdiaphragmatic pressure (Pdi). Corticosteroids are the most common method of treatment. Immunosuppressive therapy, beta-agonists, and theophylline are used in those resistant to steroids. The prognosis is generally good. This article reports the case of a 22-year-old man presenting with a 7-month history of dry mouth and dry eyes accompanied by increasing difficulty in breathing, progressing to dyspnea at rest. The patient's history included bilateral parotid gland swelling and nephrotic syndrome diagnosed 4 years earlier. Pertinent physical and laboratory findings included positive Schirmer's test results; bilateral parotid gland enlargement; bibasilar lung crackles; synovitis of the second and third proximal interphalangeal joints; a positive antinuclear antibody (Ro/SSA), Sm, and anticardiolipin antibodies; and elevated right hemidiaphragm on chest x-ray. Pulmonary function tests demonstrated restrictive lung disease with normal high-resolution computerized axial tomography. A dramatic response to oral prednisone (60 mg daily) was observed in all of the patient's complaints in a matter of several days. A diagnosis of SLE with secondary Sjogren's syndrome (SS) and SLS was made. Although SLS has been reported in association with SLE, there has been only one previous report of SLS in SLE/SS overlap syndrome. Early recognition with appropriate treatment can decrease the morbidity associated with this rare syndrome.
- Published
- 2002
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24. Life-threatening complications of systemic sclerosis.
- Author
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Cossio M, Menon Y, Wilson W, and deBoisblanc BP
- Subjects
- Catheterization, Swan-Ganz methods, Clinical Protocols, Humans, Hypertension, Pulmonary etiology, Vasodilator Agents therapeutic use, Ventricular Dysfunction, Right drug therapy, Critical Care methods, Hypertension, Pulmonary diagnosis, Hypertension, Pulmonary therapy, Scleroderma, Systemic complications
- Abstract
Pulmonary arterial hypertension is common in patients with SSc. Fig. 1 shows the diagnostic and therapeutic approach to PAH in SSc. Doppler echocardiography may suggest the diagnosis, but RHC is necessary to confirm PAH and to measure vasoreactivity. Therapy is directed at the underlying connective tissue disease. Vasoreactive patients often benefit from therapy with high-dose calcium-channel [figure: see text] blockers, but most patients are not vasoreactive. Intravenous epoprostenol and oral endothelin-1 receptor antagonists improve hemodynamic measurements and symptoms in SSc-associated PAH. The therapy of right ventricular failure is focused on vasodilators, inotropes, and diuretics with careful attention to avoiding systemic hypotension. The scleroderma pulmonary-renal syndrome and the scleroderma renal crisis are distinct syndromes with different clinical presentations, histopathologic manifestations, treatments, and outcomes. The scleroderma pulmonary renal syndrome is an autoimmune vasculitis of kidney and lung associated with normal blood pressure. Treatment is supportive, and prognosis is dismal. In contrast, scleroderma renal crisis is associated with systemic hypertension, onion skinning of afferent arterioles, and response to ACE inhibition and renal replacement therapy. Pericardial effusions are common but only occasionally lead to tamponade. Esophageal dysmotility is often associated with aspiration, leading to pulmonary fibrosis, pneumonia, or ARDS. Diffuse bowel involvement may result in pseudo-obstruction, bacterial overgrowth, or malabsorption. Prokinetic agents, antibiotics, and parenteral nutrition may be required.
- Published
- 2002
- Full Text
- View/download PDF
25. Pulmonary involvement in hepatitis B-related polyarteritis nodosa.
- Author
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Menon Y, Singh R, Cuchacovich R, and Espinoza LR
- Subjects
- Adrenal Cortex Hormones administration & dosage, Adult, Combined Modality Therapy, Hemorrhage diagnosis, Hemorrhage therapy, Hepatitis B diagnosis, Hepatitis B therapy, Humans, Lamivudine administration & dosage, Lung Diseases diagnosis, Lung Diseases therapy, Male, Plasmapheresis methods, Polyarteritis Nodosa diagnosis, Polyarteritis Nodosa therapy, Prognosis, Risk Assessment, Treatment Outcome, Hemorrhage etiology, Hepatitis B complications, Lung Diseases etiology, Polyarteritis Nodosa complications
- Published
- 2002
- Full Text
- View/download PDF
26. Morbidity not increased in rheumatoid arthritis patient with profound lymphopenia following CD4 monoclonal antibody therapy: comment on the article by Isaacs et al.
- Author
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Menon Y, Singh R, Cuchacovich R, and Espinoza LR
- Subjects
- Aged, Female, Humans, Antibodies, Monoclonal adverse effects, Antilymphocyte Serum adverse effects, Arthritis, Rheumatoid therapy, CD4 Antigens immunology, Lymphopenia etiology
- Published
- 2002
- Full Text
- View/download PDF
27. Identification of a fission yeast dynamin-related protein involved in mitochondrial DNA maintenance.
- Author
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Pelloquin L, Belenguer P, Menon Y, and Ducommun B
- Subjects
- Adenosine Triphosphatases classification, Amino Acid Sequence, Dynamins, Fungal Proteins classification, GTP Phosphohydrolases genetics, Genes, Essential, Genes, Fungal, Molecular Sequence Data, Mutagenesis, Schizosaccharomyces pombe Proteins, Sequence Homology, Amino Acid, Adenosine Triphosphatases genetics, DNA, Mitochondrial metabolism, Fungal Proteins genetics, GTP-Binding Proteins, Mitochondria physiology, Mitochondrial Proteins, Saccharomyces cerevisiae Proteins, Schizosaccharomyces physiology
- Abstract
Members of the dynamin-related proteins family have been identified in a wide range of organisms, however their precise functions remain elusive. We have identified a new member of that GTPase family in the fission yeast Schizosaccharomyces pombe. We show that Msp1+ is an essential nuclear gene encoding a 101 kDa protein whose closest homologue is the S. cerevisiae MGM1 gene product. We also report that msp1 conditional loss of function affects the maintenance of mitochondrial DNA and leads to growth arrest associated with respiratory deficiency., (Copyright 1998 Academic Press.)
- Published
- 1998
- Full Text
- View/download PDF
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