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Search Results: 1 - 10 of 128 matches for " Ophira Ginsburg "
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Breastfeeding and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers
Joanne Kotsopoulos, Jan Lubinski, Leonardo Salmena, Henry T Lynch, Charmaine Kim-Sing, William D Foulkes, Parviz Ghadirian, Susan L Neuhausen, Rochelle Demsky, Nadine Tung, Peter Ainsworth, Leigha Senter, Andrea Eisen, Charis Eng, Christian Singer, Ophira Ginsburg, Joanne Blum, Tomasz Huzarski, Aletta Poll, Ping Sun, Steven A Narod, the Hereditary Breast Cancer Clinical Study Group
Breast Cancer Research , 2012, DOI: 10.1186/bcr3138
Abstract: We conducted a case-control study of 1,665 pairs of women with a deleterious mutation in either BRCA1 (n = 1,243 pairs) or BRCA2 (n = 422 pairs). Breast cancer cases and unaffected controls were matched on year of birth, mutation status, country of residence and parity. Information about reproductive factors, including breastfeeding for each live birth, was collected from a routinely administered questionnaire. Conditional logistic regression was used to estimate the association between ever having breastfed, as well as total duration of breastfeeding, and the risk of breast cancer.Among BRCA1 mutation carriers, breastfeeding for at least one year was associated with a 32% reduction in risk (OR = 0.68; 95% CI 0.52 to 0.91; P = 0.008); breastfeeding for two or more years conferred a greater reduction in risk (OR = 0.51; 95% CI 0.35 to 0.74). Among BRCA2 mutation carriers, there was no significant association between breastfeeding for at least one year and breast cancer risk (OR = 0.83; 95% CI 0.53 to 1.31; P = 0.43).These data extend our previous findings that breastfeeding protects against BRCA1-, but not BRCA2-associated breast cancer. BRCA mutation carriers should be advised of the benefit of breastfeeding in terms of reducing breast cancer risk.In the general population, reproductive factors, including late age at menarche, parity and breastfeeding, have been shown to protect against the development of breast cancer [1-3]. Various proposed mechanisms include reducing lifetime exposure to ovarian hormones, reducing the cumulative number of ovulatory cycles and differentiation of the breast lobules [4,5]. We and others have evaluated the impact of reproductive factors in the etiology of BRCA-associated breast cancer, although the results are conflicting and vary by BRCA1 or BRCA2 mutation [6-8]. With respect to breastfeeding and breast cancer risk in BRCA1 mutation carriers, two previous studies reported no relationship [9,10] and three studies reported a protectiv
Transport pathways in the malaria-infected erythrocyte: characterization and their use as potential targets for chemotherapy
Ginsburg, Hagai;
Memórias do Instituto Oswaldo Cruz , 1994, DOI: 10.1590/S0074-02761994000600022
Abstract: the intraerythrocytic malarial parasite is involved in an extremely intensive anabolic activity while it resides in its metabolically quiescent host cell. the necessary fast uptake of nutrients and the discharge of waste product, are guaranteed by parasite-induced alterations of the constitutive transporters of the host cell and the production of new parallel pathways. the membrane of the host cell thus becomes permeable to phospholipids, purine bases and nucleosides, small non-electrolytes, anions and cations. when the new pathways are quantitatively unimportant, classical inhibitors of native transporters can be used to inhibit parasite growth. several compounds were found to effectively inhibit the new pathways and consequently, parasite growth. the pathways have also been used to introduce cytotoxic agents. the parasitophorous membrane consists of channels which are highly permeable to small solutes and display no ion selectivity. transport of some cations and anions across the parasite membrane is rapid and insensitive to classical inhibitors, and in some cases it is mediated by specific antiporters which respond to their respective inhibitors. macromolecules have been shown to reach the parasitophorous space through a duct contiguous with the host cell membrane, and subsequently to be endocytosed at the parasite membrane. the simultaneous presence of the parasitophorous membrane channels and the duct, however, is incompatible with experimental evidences. no specific inhibitors were found as yet that would efficiently inhibit transport through the channels or the duct.
Tibolone and the endometrium - Tibolone and bleeding
Ginsburg J
Journal für Menopause , 1999,
The Early Burdigalian (MN3; Miocene) large mammals from Estrepouy (Aquitaine basin, France): an updated faunal list
Ginsburg, L.
Estudios Geologicos , 2011, DOI: 10.3989/egeol.40714.197
Abstract: The purpose of the present work is to describe the mammals from the Early Miocene locality of Estrepouy, Gers, France. We have identified 17 species belonging to 3 orders; Carnivora; Amphicyon lanthanicus, Cynelos helbingi, Plithocyon bruneti, Hemicyon gargan, Palaeogale hyaenoides, Semigenetta elegans y Pseudaelurus turnauensis. Perissodactyla; Anchitherium aurelianense, Protaceratherium minutum y Diaceratherium cf. aurelianense. Arctiodactyla; Aureliachoerus aurelianensis, Xenohyus venitor, Caenotherium aff. lintillae, Andegameryx andegaviensis, Oriomeryx willii, Procervulus praelucidus, Lagomeryx parvulus y Procervulus praelucidus. The Estrepouy mammal assemblage seems older than that represented in Wintershof-West (Alemania), MN 3 reference locality. [fr] Des grands mammifères sont determines pour le Miocène inférieur (MN3) de Etrepouy, Gers, France. 17 taxons appartenant à trois déterminés ont été identifies: Carnivora; Amphicyon lanthanicus, Cynelos helbingi, Plithocyon bruneti, Hemicyon gargan, Palaeogale hyaenoides, Semigenetta elegans et Pseudaelurus turnauensis. Perissodactyla; Anchitherium aurelianense, Protaceratherium minutum et Diaceratherium cf. aurelianense. Arctiodactyla; Aureliachoerus aurelianensis, Xenohyus venitor, Caenotherium aff. lintillae, Andegameryx andegaviensis, Oriomeryx willii, Procervulus praelucidus, Lagomeryx parvulus et Procervulus praelucidus. L’association des mammifères Estrepouy regarde un peu plus agé que celui représenté à la localité de référence du MN3 á Wintershof-Ouest (Allemagne).
Antioxidant defense in Plasmodium falciparum – data mining of the transcriptome
Zbynek Bozdech, Hagai Ginsburg
Malaria Journal , 2004, DOI: 10.1186/1475-2875-3-23
Abstract: The Plasmodium-infected erythrocyte is under constant oxidative stress. This is caused by exogenous reactive oxidant species (ROS) and reactive nitrogen species (RNS) produced by the immune system of the host, and by endogenous production of ROS generated during the digestion of host cell haemoglobin and concomitant biochemical reactions. Small amounts of ROS can also be produced by the mitochondrial electron transport and by various metabolic processes. The biochemistry and molecular biology of antioxidant defense-related enzymes and intermediates, shown schematically in Fig. 1, have been extensively discussed in recent reviews [1-5]. The entire battery of antioxidant enzymes and their substrates must be functionally present when the parasite starts the digestion of host cell haemoglobin and when the immune system starts to be challenged by parasite antigens. These events start to happen at the late ring-early trophozoite stage when the parasite engages in intensive digestion of the host cell haemoglobin and the surface of the erythrocyte is sufficiently altered to be recognized by the reticuloendothelial system as 'non-self'. Some ROS may escape the antioxidant defense of the parasite and reach the host erythrocyte where they are handled by catalase and glutathione peroxidase. However, even this defense system is not fully effective since the fingerprints of oxidative stress are discernable in the membrane of the infected red blood cells (RBC) such as clustering of band 3 [6] and increased levels of lipid peroxides [7]. It is not intended to review in depth the redox metabolism of the plasmodium-infected red blood cell (IRBC), as several recent reviews are available. Rather, the stage-dependent transcription of genes that code for enzymes and proteins that are involved in the antioxidant defense of the IRBC will be analysed in a functional context.The expression data used in this study was obtained from the DeRisi transcriptome database http://malaria.ucsf.edu/ we
Data mining of the transcriptome of Plasmodium falciparum: the pentose phosphate pathway and ancillary processes
Zbynek Bozdech, Hagai Ginsburg
Malaria Journal , 2005, DOI: 10.1186/1475-2875-4-17
Abstract: The analysis of the transcriptome of Plasmodium falciparum has revealed that during the intraerythrocytic development of the parasite, genes coding for enzymes and proteins that are involved in complex cellular functions such as transcription, replication or energy metabolism, each involving many gene products, are transcribed in a coordinated fashion, supporting the notion that all components must be present at the right time to allow for optimal function [1-3]. While this may be true in general, it has already been found that scrutinizing the details of specific metabolic functions reveal some significant departures from this paradigm [4]. Such scrutiny has also provided some intriguing peculiarities that through detailed biochemical studies may reveal some parasite-specific functions that may enlighten our understanding of parasitism or even provide for novel targets for chemotherapeutic intervention. The present analysis explores of the transcriptome to fathom additional metabolic pathways.During the erythrocytic stage the malaria parasite is engaged in intensive synthesis of nucleotides and is subjected to endogenously produced oxidative radicals that must be detoxified. Like other cells, in order to perform its anabolism, the parasite needs not only energy (ATP): it also needs reducing power, under the form of NADPH. Enzymes that function primarily in the reductive direction utilize NADP+/NADPH pair as co-factors as opposed to oxidative enzymes that utilize the NAD+/NADH cofactor pair. The conversion of ribonucleotides to deoxyribonucleotides (through the action of ribonucleotide reductase) requires NADPH as the electron source. Thus, any cell that proliferates rapidly requires large quantities of NADPH. NADPH can be produced during glucose-6-phosphate oxidation through the pentose-phosphate pathway (PPP; Figure 1). This pathway also produces ribose-5-phosphate (R5P), the sugar component of nucleic acids.The reactions of the PPP operate exclusively in the cyto
Analysis of additivity and synergism in the anti-plasmodial effect of purified compounds from plant extracts
Deharo Eric,Ginsburg Hagai
Malaria Journal , 2011, DOI: 10.1186/1475-2875-10-s1-s5
Abstract: In the search for antimalarials from ethnobotanical origin, plant extracts are chemically fractionated and biological tests guide the isolation of pure active compounds. To establish the responsibility of isolated active compound(s) to the whole antiplasmodial activity of a crude extract, the literature in this field was scanned and results were analysed quantitatively to find the contribution of the pure compound to the activity of the whole extract. It was found that, generally, the activity of isolated molecules could not account on their own for the activity of the crude extract. It is suggested that future research should take into account the “drugs beside the drug”, looking for those products (otherwise discarded along the fractionation process) able to boost the activity of isolated active compounds.
A call for using natural compounds in the development of new antimalarial treatments – an introduction
Ginsburg Hagai,Deharo Eric
Malaria Journal , 2011, DOI: 10.1186/1475-2875-10-s1-s1
Abstract: Natural compounds, mostly from plants, have been the mainstay of traditional medicine for thousands of years. They have also been the source of lead compounds for modern medicine, but the extent of mining of natural compounds for such leads decreased during the second half of the 20th century. The advantage of natural compounds for the development of drugs derives from their innate affinity for biological receptors. Natural compounds have provided the best anti-malarials known to date. Recent surveys have identified many extracts of various organisms (mostly plants) as having antiplasmodial activity. Huge libraries of fractionated natural compounds have been screened with impressive hit rates. Importantly, many cases are known where the crude biological extract is more efficient pharmacologically than the most active purified compound from this extract. This could be due to synergism with other compounds present in the extract, that as such have no pharmacological activity. Indeed, such compounds are best screened by cell-based assay where all potential targets in the cell are probed and possible synergies identified. Traditional medicine uses crude extracts. These have often been shown to provide many concoctions that deal better with the overall disease condition than with the causative agent itself. Traditional medicines are used by ~80 % of Africans as a first response to ailment. Many of the traditional medicines have demonstrable anti-plasmodial activities. It is suggested that rigorous evaluation of traditional medicines involving controlled clinical trials in parallel with agronomical development for more reproducible levels of active compounds could improve the availability of drugs at an acceptable cost and a source of income in malaria endemic countries.
George Steiner, Natalia Ginsburg
Desde el Jardín de Freud , 2006,
Le genre Sivanasua (Lophocyoninae, Hyaenodontidae, Creodonta, Mammalia)
Ginsburg, L.,Morales, J.
Estudios Geologicos , 1999, DOI: 10.3989/egeol.99553-4173
Abstract: Two upper teeth from the lower Miocene of Le Chêne de Navere (Gers, France) are interpreted as MI and M2 of Sivanasua viverroides. The genus is known in Europe by two species. The origin of the Lophocyoninae is re-evaluated. We consider the group as rooted in some African Hyaenodontoid Creodonta. Dos dientes del yacimiento mioceno (MN4b) de Chêne de Navere (Gers, Francia) se interpretan como MI y M2 de Sivanasua viverroides. El género Sivanasua está representado en Europa por dos especies. El origen de los Lophocyoninae se reconsidera, primero atribuidos a los Ailuridae y después relacionados con los Viverridae, aquí son considerados como emparentados a los Creodontos Hyaenodontidae africanos.
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