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1.
Julie Despres Yasmina Ramdani Marine di Giovanni Magalie Bnard Abderrakib Zahid Mait Montero‐Hadjadje Florent Yvergnaux Thibaut Saguet Azeddine Driouich Marie‐Laure Follet‐Gueye 《Experimental dermatology》2019,28(8):922-932
It is well recognized that the world population is ageing rapidly. Therefore, it is important to understand ageing processes at the cellular and molecular levels to predict the onset of age‐related diseases and prevent them. Recent research has focused on the identification of ageing biomarkers, including those associated with the properties of the Golgi apparatus. In this context, Golgi‐mediated glycosylation of proteins has been well characterized. Additionally, other studies show that the secretion of many compounds, including pro‐inflammatory cytokines and extracellular matrix–degrading enzymes, is modified during ageing, resulting in physical and functional skin degradation. Since the Golgi apparatus is a central organelle of the secretory pathway, we investigated its structural organization in senescent primary human dermal fibroblasts using confocal and electron microscopy. In addition, we monitored the expression of Golgi‐related genes in the same cells. Our data showed a marked alteration in the Golgi morphology during replicative senescence. In contrast to its small and compact structure in non‐senescent cells, the Golgi apparatus exhibited a large and expanded morphology in senescent fibroblasts. Our data also demonstrated that the expression of many genes related to Golgi structural integrity and function was significantly modified in senescent cells, suggesting a relationship between Golgi apparatus function and ageing. 相似文献
2.
Erika Cecon Anna Ivanova Marine Luka Florence Gbahou Anne Friederich Jean‐Luc Guillaume Patrick Keller Klaus Knoch Raise Ahmad Philippe Delagrange Michele Solimena Ralf Jockers 《Journal of pineal research》2019,66(2)
Melatonin receptors play important roles in the regulation of circadian and seasonal rhythms, sleep, retinal functions, the immune system, depression, and type 2 diabetes development. Melatonin receptors are approved drug targets for insomnia, non‐24‐hour sleep‐wake disorders, and major depressive disorders. In mammals, two melatonin receptors (MTRs) exist, MT1 and MT2, belonging to the G protein‐coupled receptor (GPCR) superfamily. Similar to most other GPCRs, reliable antibodies recognizing melatonin receptors proved to be difficult to obtain. Here, we describe the development of the first monoclonal antibodies (mABs) for mouse MT1 and MT2. Purified antibodies were extensively characterized for specific reactivity with mouse, rat, and human MT1 and MT2 by Western blot, immunoprecipitation, immunofluorescence, and proximity ligation assay. Several mABs were specific for either mouse MT1 or MT2. None of the mABs cross‐reacted with rat MTRs, and some were able to react with human MTRs. The specificity of the selected mABs was validated by immunofluorescence microscopy in three established locations (retina, suprachiasmatic nuclei, pituitary gland) for MTR expression in mice using MTR‐KO mice as control. MT2 expression was not detected in mouse insulinoma MIN6 cells or pancreatic beta‐cells. Collectively, we report the first monoclonal antibodies recognizing recombinant and native mouse melatonin receptors that will be valuable tools for future studies. 相似文献
3.
Sissa Brito dos Santos Aurélia Bertholet-Thomas Marine Butin Laurence Dubourg Alain Fouilhoux Justine Bacchetta 《Archives de pédiatrie》2021,28(4):338-341
The main clinical features of tyrosinemia type 1 usually appear in the first months of life, including fever, diarrhea, vomiting, liver involvement, growth failure, and renal proximal tubulopathy with subsequent hypophosphatemic rickets. An early diagnosis is crucial in order to provide specific management and to prevent complications. Here, we report on two cases referred primarily to pediatric nephrologists for the diagnosis of “neonatal tubulopathy” and management of “X-linked hypophosphatemia (XLH),” respectively. Our aim is to emphasize that (1) even a mixed tubulopathy can reveal tyrosinemia, and (2) tyrosinemia is a classic differential diagnosis of XLH that should not be forgotten, especially in the era of the anti-FGF23 burosumab. 相似文献
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Establishment and characterization of a chronic infectious mononucleosislike syndrome in common marmosets 总被引:1,自引:0,他引:1
E A Emini J Luka M E Armstrong F S Banker P J Provost G R Pearson 《Journal of medical virology》1986,18(4):369-379
Epstein-Barr virus (EBV) was inoculated into two species of marmosets. Successful infection was established in the majority of the animals of one species, Callithrix jacchus, as evidenced by the development of high, persistent levels of antibody against virus-specific capsid and early nonstructural proteins. Antibodies also were produced against the major membrane antigen and, in some animals, against EBV nuclear antigen (EBNA) 2 but not against EBNA 1. This is the antibody profile normally noted in individuals with chronic infectious mononucleosis (IM). EBV-induced lymphoproliferation was not seen, and EBV-specific proteins were not detected in the peripheral blood lymphocytes of infected animals. Hence, EBV infection in C. jacchus apparently does not generally include extensive B-cell involvement. However, the marmosets clearly are useful as a model for EBV primary infection and also possibly for chronic IM. 相似文献
7.
Danny R. Welch Douglas P. Evans Stephen P. Tomasovic Luka Milas Garth L. Nicolson 《Clinical & experimental metastasis》1984,2(4):357-371
We have shown that, with in vitro passage, subclones derived from clonal cell populations of 13762NF mammary adenocarcinoma undergo phenotypic drift and diversification in their cellular properties. Here we examine whether phenotypic divergence of 13762NF cell clones extends to therapeutic treatments used in eliminating mammary tumors and whether the apparent rates of phenotypic divergence vary for different treatments. Six subclones isolated from low passage clone MTF7 (T11 l; tissue culture passage 11) cells were compared to a similar number of subclones isolated from high passage clone MTF7 (T35; tissue culture passage 35) cells. Subclones derived from clone MTF7 (TI l) were relatively homogeneous (not significantly different) in their inherent sensitivities to ionizing radiation, extrapolation coefficients and quasithreshold dose values (Do = 1·61–1·99 Gy; n=0·89–3·42; Dq = 0–2·34). When the MTF7 (Tll) subclones were examined for their sensitivities to 45°C hyperthermic treatment, the inherent sensitivities and dose-response curve parameters (Do = 5·24–10·05 min; n = 1·08–10·47; Dq = 0·78–12·31) were heterogeneous (significantly different). In addition, the MTF7 (T1 l) subclones were heterogeneous (significantly different) in their sensitivities and dose-response curve parameters to 5-fluoro-2-deoxyuridine (FUdR) treatment (slope= –0·70 to –1·59; y-intercept = 1·31 × 102 to 47·80 × 102). The LD50 values for FUdR ranged from 14–150 nm for the MTF7 (T11) subclones. At high passage MTF7 (T35) subclones were heterogeneous in their dose-response parameters to ionizing radiation (Do = 1·17–2·05 Gy; n = 0·80–41·18; Dq = 1·79-\24·94), hyperthermia (Do = 3·57–6·32 min; n = 2·08–13·54; Dq = 3·68–9·30) and FUdR (slope= –0·77 to –0·93; y-intercept = 4·64 × 102 to 8·83 × 102; LD50 = 50–160nm). The results indicate that clonal cells diverge for distinct phenotypic properties at differing rates to form heterogeneous cell populations with unique sensitivities to various therapeutic treatments. 相似文献
8.
Gabriel Lopez-Berestein Luka Milas Nancy Hunter Kapil Mehta Evan M. Hersh Carol G. Kurahara Marjorie Vanderpas Deborah A. Eppstein 《Clinical & experimental metastasis》1984,2(2):127-137
A new lipophilic muramyl dipeptide analog, 6-O-stearoyl-N-acetylmuramyl-L--aminobutyryl-D-isoglutamine, when incorporated in liposomes, was effective in both the prevention and eradication of experimental pulmonary metastases in mice. Multilamellar vesicles composed of synthetic phospholipids (phosphatidylglycerol and phosphatidylcholine) containing saturated myristoyl or unsaturated dioleoyl acyl chains were found to potentiate the antimetastatic activity of this glycopeptide. Prophylactic and therapeutic efficacy was observed against the three murine tumors tested: FSa, an immunogenic fibrosarcoma; NFSa, a nonimmunogenic fibrosarcoma; and B16 melanoma. Neither the administration of empty liposomes or free glycopeptide, nor their coadministration, had a significant antimetastatic effect. This approach is promising for the therapy of cancer metastases in humans, particularly in the prevention of metastatic seeding and in the treatment of micrometastases.This is contribution No. 180 from the Institute of Bio-Organic Chemistry, Syntex Research. 相似文献
9.
Descamps D Flandre P Joly V Meiffrédy V Peytavin G Izopet J Tamalet C Zeng AF Harel M Lastère S Aboulker JP Yéni P Brun-Vézinet F;NOVAVIR 《Journal of acquired immune deficiency syndromes (1999)》2002,31(5):464-471
The authors studied the effect of zidovudine (ZDV) resistance mutation on virologic response to treatment with ZDV or stavudine (d4T) each in combination with lamivudine and indinavir. Viral genotyping was performed on plasma HIV-1 RNA at study entry and concerned 155 patients previously treated with ZDV, didanosine, or zalcitabine and enrolled in the NOVAVIR (Agence National de Recherche sur le SIDA [ANRS] 073) trial. Three virologic responses were investigated: early response (<50 copies/mL at week 24), late response (<500 copies/mL at week 80), and virologic failure (two HIV-1 RNA >5000 copies/mL). Patients were classified as resistant or susceptible to ZDV according to the ANRS algorithm. Plasma viral RNA from 123 of 155 patients had two or more ZDV resistance mutations. The number of ZDV resistance mutations was positively correlated with the duration of prior antiviral therapy (p <.001). At week 24, 74% and 77% of patients with virus classified as resistant were responders in the d4T and ZDV arm, respectively. Similar results were found at week 80. Virologic failure was reached in 7 of 24 patients with virus classified as susceptible and in 26 of 131 patients with resistant virus (p =.29). In the ZDV arm, patients classified as resistant had longer times to virologic failure than those classified as susceptible (p =.003). In conclusion, sustained virologic response despite presence of ZDV resistance mutations implies that these mutations do not preclude an early and durable response to treatment with a potent three-drug regimen in these patients. Patients susceptible to ZDV had lower median mean corpuscular volumes and lower random indinavir levels, suggesting that adherence was the main reason for failure. 相似文献
10.
J Roger Guard Ralph F Brueggemann Robert F Highsmith Stephen A Marine Josette R Riep Leslie C Schick 《Academic medicine》2005,80(11):1032-1038
The academic health center information environment is saturated with information of varying quality and overwhelming quantity. The most significant challenge is transforming data and information into knowledge. The University of Cincinnati Medical Center's (UCMC) focus is to develop an information architecture comprising data structures, Web services, and user interfaces that enable individuals to manage the information overload so that they can create new knowledge. UCMC has accomplished much of what is reported in this article with the help of a four-year Integrated Advanced Information Management Systems (IAIMS) operation grant awarded by the National Library of Medicine in 2003. In the UCMC vision for knowledge management, individuals have reliable, secure access to information that is filtered, organized, and highly relevant for specific tasks and personal needs. Current applications and tool sets will evolve to become the next generation knowledge management applications or smart digital services. When smart digital services are implemented, silo applications will disappear. A major focus of UCMC's IAIMS grant is research administration. Testing and building out existing and new research administration applications and digital services is underway. The authors review UCMC's progress and results in developing a software architecture, tools, and services for research administration. Included are sections on the evolution to full integration, the impact of the work at UCMC to date, lessons learned during this research and development process, and future plans and needs. 相似文献