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81.
Francine Noel Sapna Mehta Yuwei Zhu Patricia De Matteis Rouzier Abdias Marcelin Jian R. Shi Claudine Nolte Linda Severe Marie Marcelle Deschamps Daniel W. Fitzgerald Warren D. Johnson Peter F. Wright Jean W. Pape 《PloS one》2008,3(11)
Background
Since 1999 GHESKIO, a large voluntary counseling and HIV testing center in Port-au-Prince, Haiti, has had an ongoing collaboration with the Haitian Ministry of Health to reduce the rate of mother to child HIV transmission. There are limited data on the ability to administer complex regimens for reducing mother to child transmission and on risk factors for continued transmission and infant mortality within programmatic settings in developing countries.Methods and Findings
We analyzed data from 551 infants born to HIV-infected mothers seen at GHESKIO, between 1999 and 2005. HIV-infected mothers and their infants were given “short-course” monotherapy with antiretrovirals for prophylaxis; and, since 2003, highly active antiretroviral therapy (HAART) when clinical or laboratory indications were met. Infected women seen in the pre-treatment era had 27% transmission rates, falling to 10% in this cohort of 551 infants, and to only 1.9% in infants of women on HAART. Mortality rate after HAART introduction (0.12 per year of follow-up [0.08–0.16]) was significantly lower than the period before the availability of such therapy (0.23 [0.16–0.30], P<0.0001). The effects of maternal health, infant feeding, completeness of prophylaxis, and birth weight on mortality and transmission were determined using univariate and multivariate analysis. Infant HIV-1 infection and low birth weight were associated with infant mortality in less than 15 month olds in multivariate analysis.Conclusions
Our findings demonstrate success in prevention of mother-to-child HIV transmission and mortality in a highly resource constrained setting. Elements contributing to programmatic success include provision of HAART in the context of a comprehensive program with pre and postnatal care for both mother and infant. 相似文献82.
A new technique for resolving N-alkylprotoporphyrins into each structural isomer is described. The technique has been used to investigate the rate of formation and loss of N-alkylporphyrins during reaction of the parent porphyrin with alkyl iodides and to establish the conditions required for optimal yields of the various isomers. Preferential loss of the isomers bearing the N-alkyl group on one of the vinyl-substituted pyrrole rings is observed on prolonged incubation and HI generated during the reaction has been shown to be responsible. A method for detection and partial resolution by HPLC of N-alkylprotoporphyrins produced by liver microsomes in vitro is also described. Microsomes from rats induced with 3-methylcholanthrene produce significantly more N-ethylprotoporphyrin from either 4-ethyl-3,5-diethoxycarbonyl-1,4-dihydro- 2,6-dimethyl-pyridine or ethylhydrazine than do microsomes from control animals, but the isomeric composition of the isolated N-alkylporphyrin differs from that reported in vivo. Evidence that authentic N-alkylporphyrins are lost during incubation with microsomes has been obtained, and here again, the isomers bearing the N-alkyl group on vinyl-substituted pyrrole rings are preferentially lost. Experiments with 14C-labeled N-methylprotoporphyrin show that approximately 40% of the lost porphyrin could be recovered bound covalently to the microsomal pellet. 相似文献
83.
Gabriele Valentini Antonella Marcoccia Giovanna Cuomo Serena Vettori Michele Iudici Francesco Bondanini Carlo Santoriello Aldo Ciani Domenico Cozzolino Giovanni Maria De Matteis Salvatore Cappabianca Filiberto Vitelli Alberto Spanò 《Arthritis research & therapy》2013,15(3):R63
Introduction
Early systemic sclerosis (SSc) is characterized by Raynaud''s phenomenon together with scleroderma marker autoantibodies and/or a scleroderma pattern at capillaroscopy and no other distinctive feature of SSc. Patients presenting with marker autoantibodies plus a capillaroscopic scleroderma pattern seem to evolve into definite SSc more frequently than patients with either feature. Whether early SSc patients with only marker autoantibodies or capillaroscopic positivity differ in any aspect at presentation is unclear.Methods
Seventy-one consecutive early SSc patients were investigated for preclinical cardiopulmonary alterations. Out of these, 44 patients and 25 controls affected by osteoarthritis or primary fibromyalgia syndrome were also investigated for serum markers of fibroblast (carboxyterminal propeptide of collagen I), endothelial (soluble E-selectin) and T-cell (soluble IL-2 receptor alpha) activation.Results
Thirty-two of the 71 patients (45.1%) had both a marker autoantibody and a capillaroscopic scleroderma pattern (subset 1), 16 patients (22.5%) had only a marker autoantibody (subset 2), and 23 patients (32.4%) had only a capillaroscopic scleroderma pattern (subset 3). Patients with marker autoantibodies (n = 48, 67.6%) had a higher prevalence of impaired diffusing lung capacity for carbon monoxide (P = 0.0217) and increased serum levels of carboxyterminal propeptide of collagen I (P = 0.0037), regardless of capillaroscopic alterations. Patients with a capillaroscopic scleroderma pattern (n = 55, 77.5%) had a higher prevalence of puffy fingers (P = 0.0001) and increased serum levels of soluble E-selectin (P = 0.0003) regardless of marker autoantibodies.Conclusion
These results suggest that the autoantibody and microvascular patterns in early SSc may each be related to different clinical-preclinical features and circulating activation markers at presentation. Longitudinal studies are warranted to investigate whether these subsets undergo a different disease course over time. 相似文献84.
85.
Increased oxidation of uroporphyrinogen by an inducible liver microsomal system. Possible relevance to drug-induced uroporphyria. 下载免费PDF全文
Sickle-cell-anaemia erythrocytes (SS cells) are known to have a high Ca2+ content (particularly the dense cell fraction) and to take up Ca2+ on deoxygenation. It has been reported that this high Ca2+ was responsible for the activation of the Ca2+-dependent K+ loss, and of the Ca2+-sensitive polyphosphoinositide phospholipase C (PIC) in dense SS cells. We found that, either in the total population of SS cells or in the light or dense fractions, the content of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] was not changed, whereas that of phosphatidylinositol 4-phosphate was increased and that of phosphatidic acid (PtdOH) was decreased compared with normal (AA) erythrocytes. Deoxygenation-induced Ca2+ entry into SS cells did not change the concentration or, in 32P-prelabelled cells, the radioactivity of polyphosphoinositides and PtdOH. It also failed to induce the formation of inositol 1,4,5-trisphosphate, the product of PtdIns(4,5)P2 hydrolysis by PIC, which was measured by an original method using ion-pair reverse-phase h.p.l.c. Thus there was no evidence of an endogenous Ca2+ effect on the PIC activity in SS cells, in agreement with the demonstration that the excess Ca2+ in SS cells is compartmentalized into internal vesicles and unavailable as free Ca2+. The 32P incorporation in polyphosphoinositides and PtdOH was markedly higher in SS than in AA cells, but this increase was the same in both dense and light SS cells. The increase in the turnover of these phospholipids in SS cells is consistent either with an activation of the lipid kinases and phosphatases or with perturbation in the metabolic compartmentation of these lipids. 相似文献
86.
The vascular endothelium of the adipose tissue gives rise to both white and brown fat cells 总被引:1,自引:0,他引:1
Tran KV Gealekman O Frontini A Zingaretti MC Morroni M Giordano A Smorlesi A Perugini J De Matteis R Sbarbati A Corvera S Cinti S 《Cell metabolism》2012,15(2):222-229
Adipose tissue expansion involves the enlargement of existing adipocytes, the formation of new cells from committed preadipocytes, and the coordinated development of the tissue vascular network. Here we find that murine endothelial cells (ECs) of classic white and brown fat depots share ultrastructural characteristics with pericytes, which are pluripotent and can potentially give rise to preadipocytes. Lineage tracing experiments using the VE-cadherin promoter reveal localization of reporter genes in ECs and also in preadipocytes and adipocytes of white and brown fat depots. Furthermore, capillary sprouts from human adipose tissue, which have predominantly EC characteristics, are found to express Zfp423, a recently identified marker of preadipocyte determination. In response to PPARγ activation, endothelial characteristics of sprouting cells are progressively lost, and cells form structurally and biochemically defined adipocytes. Together these data support an endothelial origin of murine and human adipocytes, suggesting a model for how adipogenesis and angiogenesis are coordinated during adipose tissue expansion. 相似文献
87.
Giovanni D'Angelo Libera Prencipe Luisa Iodice Galina Beznoussenko Marco Savarese PierFrancesco Marra Giuseppe Di Tullio Gianluca Martire Maria Antonietta De Matteis Stefano Bonatti 《The Journal of biological chemistry》2009,284(50):34849-34860
The Golgi matrix proteins GRASP65 and GRASP55 have recognized roles in maintaining the architecture of the Golgi complex, in mitotic progression and in unconventional protein secretion whereas, surprisingly, they have been shown to be dispensable for the transport of commonly used reporter cargo proteins along the secretory pathway. However, it is becoming increasingly clear that many trafficking machineries operate in a cargo-specific manner, thus we have investigated whether GRASPs may control the trafficking of selected classes of cargo. We have taken into consideration the C-terminal valine-bearing receptors CD8α and Frizzled4 that we show bind directly to the PSD95-DlgA-zo-1 (PDZ) domains of GRASP65 and GRASP55. We demonstrate that both GRASPs are needed sequentially for the efficient transport to and through the Golgi complex of these receptors, thus highlighting a novel role for the GRASPs in membrane trafficking. Our results open new perspectives for our understanding of the regulation of surface expression of a class of membrane proteins, and suggests the causal mechanisms of a dominant form of autosomal human familial exudative vitreoretinopathy that arises from the Frizzled4 mutation involving its C-terminal valine. 相似文献
88.
Lise Madsen Lone M. Pedersen Haldis Haukaas Lillefosse Even Fj?re Ingeborg Bronstad Qin Hao Rasmus K. Petersen Philip Hallenborg Tao Ma Rita De Matteis Pedro Araujo Josep Mercader M. Luisa Bonet Jacob B. Hansen Barbara Cannon Jan Nedergaard Jun Wang Saverio Cinti Peter Voshol Stein Ove D?skeland Karsten Kristiansen 《PloS one》2010,5(6)
Background
The uncoupling protein 1 (UCP1) is a hallmark of brown adipocytes and pivotal for cold- and diet-induced thermogenesis.Methodology/Principal Findings
Here we report that cyclooxygenase (COX) activity and prostaglandin E2 (PGE2) are crucially involved in induction of UCP1 expression in inguinal white adipocytes, but not in classic interscapular brown adipocytes. Cold-induced expression of UCP1 in inguinal white adipocytes was repressed in COX2 knockout (KO) mice and by administration of the COX inhibitor indomethacin in wild-type mice. Indomethacin repressed β-adrenergic induction of UCP1 expression in primary inguinal adipocytes. The use of PGE2 receptor antagonists implicated EP4 as a main PGE2 receptor, and injection of the stable PGE2 analog (EP3/4 agonist) 16,16 dm PGE2 induced UCP1 expression in inguinal white adipose tissue. Inhibition of COX activity attenuated diet-induced UCP1 expression and increased energy efficiency and adipose tissue mass in obesity-resistant mice kept at thermoneutrality.Conclusions/Significance
Our findings provide evidence that induction of UCP1 expression in white adipose tissue, but not in classic interscapular brown adipose tissue is dependent on cyclooxygenase activity. Our results indicate that cyclooxygenase-dependent induction of UCP1 expression in white adipose tissues is important for diet-induced thermogenesis providing support for a surprising role of COX activity in the control of energy balance and obesity development. 相似文献89.
Daniele T Di Tullio G Santoro M Turacchio G De Matteis MA 《Traffic (Copenhagen, Denmark)》2008,9(12):2221-2235
The activation state of the EGF receptor (EGF-R) is tightly controlled in the cell so as to prevent excessive signalling, with the dangerous consequences that this would have on cell growth and proliferation. This control occurs at different levels, with a key level being the trafficking and degradation of the EGF-R itself. Multiple guanosine triphosphatases belonging to the Arf, Rab and Rho families and their accessory proteins have key roles in these processes. In this study, we have identified ARAP1, a multidomain protein with both Arf GTPase-activating protein (GAP) and Rho GAP activities, as a novel component of the machinery that controls the trafficking and signalling of the EGF-R. We show that ARAP1 localizes to multiple cell compartments, including the Golgi complex, as previously reported, and endosomal compartments, where it is enriched in the internal membranes of multivesicular bodies. ARAP1 distribution is controlled by its phosphorylation and by its interactions with the 3- and 4-phosphorylated phosphoinositides through its five PH domains. We provide evidence that ARAP1 controls the late steps of the endocytic trafficking of the EGF-R, with ARAP1 knockdown leading to EGF-R accumulation in a sorting/late endosomal compartment and to the inhibition of EGF-R degradation that is accompanied by prolonged signalling. 相似文献
90.
Marra P Salvatore L Mironov A Di Campli A Di Tullio G Trucco A Beznoussenko G Mironov A De Matteis MA 《Molecular biology of the cell》2007,18(5):1595-1608
The Golgi complex in mammalian cells forms a continuous ribbon of interconnected stacks of flat cisternae. We show here that this distinctive architecture reflects and requires the continuous input of membranes from the endoplasmic reticulum (ER), in the form of pleiomorphic ER-to-Golgi carriers (EGCs). An important step in the biogenesis of the Golgi ribbon is the complete incorporation of the EGCs into the stacks. This requires the Golgi-matrix protein GM130, which continuously cycles between the cis-Golgi compartments and the EGCs. On acquiring GM130, the EGCs undergo homotypic tethering and fusion, maturing into larger and more homogeneous membrane units that appear primed for incorporation into the Golgi stacks. In the absence of GM130, this process is impaired and the EGCs remain as distinct entities. This induces the accumulation of tubulovesicular membranes, the shortening of the cisternae, and the breakdown of the Golgi ribbon. Under these conditions, however, secretory cargo can still be delivered to the Golgi complex, although this occurs less efficiently, and apparently through transient and/or limited continuities between the EGCs and the Golgi cisternae. 相似文献