994 resultados para Scientists Against Nuclear Arms
Resumo:
v.7: North Atlantic Region
Resumo:
In articles, already published, we have proved that the strain V. B. of Brazilian virus, goes through the placenta (Macacus rhesus) (1) and the apparently normal gastro-intestinal tube (1934-1937) (Canis familiaris) (2). Today we present the idea that the Brazilian virus can reach the milk of an animal even when the latter has only the unapparent disease. In former articles (**), we have shown that the goat (Capra hircus) can be an excellent reservoir of Brazilian virus, having the strain V. B. in its blood and presenting a Weil Felix reaction high and in group, with the disease unapparent. When the goats are bred in the laboratory, and even in some foci of the disease, they give a negative Weil Felix, being zero for all the nine strains of Proteus. In the interior of Brazil, in many localities, goats substitute cows, in supplying milk for children and adults, and in some districts goats milk is considered superior to cows milk, possessing marvellous qualities for men, women an children. Having proved, now, that goats milk can contain the virus even when the animal presents nothing clinically, and having also shown that this virus goes through the digestive tube apparently sound, it is easy to understand how infants-in-arms, that is, only a few months old, living in strictly domestic surroundings, can contract the disease; we have many such cases on record. Protocol of the experiments: Goat nº 2, white, January 1948. This animal had been inoculated with the V. B. strain of the Brazilian virus in June 1947, via intra-peritoneal, presenting nothing then, not even a feverish reaction. On that occasion it was not possible to isolate the virus of the blood, although the Weil Felix reaction was positive, high and in group. Now January 17, 1948, seven months later, the same animal was reinoculated with a semple of virus V. B. in the same manner (intra-peritoneal) two days after bringing forth two sturdy kids. The virus V. B. was obtained from guinea-pig n. 7170 whose thermic graph was as follows: Temperatura 38,8 39,1 39,5 39,4 39,8 40,4 40,2 40,1 - + Necropsy Typical lesions. The spleen weighed 5 grammes. With 3c.c. of emulsion from the nervous system of this guinea-pig, we inoculated not only the goat, as also two guineapigs, number 14 and number 5. The following is the thermic graph of one: - Guinea-pig n. 14 38,9 39,1 39,2 39.2 40,7 41,0 40,5 40,4 40,1 - + Typical lesions. Guinea-pig n. 2 presented the following thermic graph after the infective inoculation: - 39,5 39,7 39,7 39,7 39,5 39,3 39,5 39,5 39,5 etc. Clinically, this animal presented nothing unusual, feeding well and suckling the kids normally. The Weil Felix reaction was positive, in group high very similar to the reaction obtained in June 1947, with the first infective inoculation. On the third, fourth, fifth, sixth and seventh day after the infective inoculation, we took milk from the goat and inoculated male guinea-pigs via intra-celular and via intra-peritoneal, giving 5 c.c. to each animal. Guinea-pig n. 4663, inoculated with 5 c.c. of milk, via intra-muscular, taken on the third day of the infectaive inoculation, presented the following thermic graph: - 38.8 (*) 39,1 39,0 39,1 40,1 40,1 40,8 (**) 40,8 Killed Typical deisions (***). The virus V. B. of this goat, circulated naturally in the blood up to the third day, having passed into the milk, producing nothing in the kids, on account of the natural resistance of these animals to the disease. The Weil Felix reaction and that of Widal for the Burcellas suis, abortus and militensis were negative for the goat and the kids. It is remarkable that, even with inoculation of the living virus after a period of seven months we cannot get a real and absolute immunity of sensitive animals. We shall return to this subject later. The hart Mazama simplicicornis may be a carrier of the virus in Brasil. The experimental serum against the virus of Exanthematic neotropical typhus has not protected guinea-pigs.
Resumo:
Surgical removal of large amounts of hepatic tissue in male albino rats results in a rapid and conspicuous raise in cellular nuclear volumes. Measurements were made exclusively in resting nuclei. This volume variation is transitory. Nuclear volumes return to the normal value withins 6 days of restoration. The higher value are abserved 48 hours after the hepatic removal, indicating probably that this effect is due to hydration of the nucei, as occurs in the cytoplasm. This hydration could be correlated to the mitotic activity of the renmant tissue since a peak of mitoses parallels the changes in the nuclear volumes.
Resumo:
The localization of the xanthine oxidase (X.O.) and xanthine dehydrogenase (X.D.) activities in rat liver have been studied using separation of cytoplasmic particles into fractions by differential centrifugation. The results clearly demonstrate that practically all the enzymic activity is present in the supernatant fluid corresponding to the cell sap containing the soluble proteins of the cell. No activity could be detected for the nuclear, mitocondrial and microsomal fractions. The enzymatic activity of the mixture of the four factions was 102 per cent of that of the original homogenate. The distribution of the xanthine dehydrogenase in the protein fractions of the rat serum was accomplished in preliminary experiments by means of 50% ammonium sulphate precipitation and subsequent dialysis against water. All enzymatic activity was confined to the globulin fractions of the serum. Paper electrophoresis was performed and the protein and lipoprotein fractions determined. A method for the localization of the X.D. activity in the protein fractions separated by paper electrophoresis was developed. The results obtained suggest that xanthine dehydrogenase is localized in the globulin fractions possessing mobilities of [alpha 1], [beta] and [gamma] globulins and are probably bound to the lipoproteins.
Resumo:
Recently a number of mainstream papers have treated the rise of democracy in 19th century Europe and its instability in Latin America in an eminently Marxist fashion. This paper sets out their implications for Marxist thought. With respect to Europe, Marx's emphasis on political action backed by the threat of violence is vindicated but his justification for socialism is not. With respect to Latin America, the unequal distribution of wealth is the cause of political instability that is, in turn, the root cause of mass poverty. In addition it is possible to explain some of the paradoxical characteristics of neo-liberalism and to make a weak argument for socialism in spite of its rejection in Europe.
Resumo:
Throughout history, nuclear weapons have been considered to be the ultimate weapons. This understanding largely detached them from the portfolio of conventional military means and assigned them a symbolic meaning that influenced the identity and norms creation of nations. In most countries today, the development of nuclear weapons is considered morally prohibitive, incompatible with a country’s identity and international outlook. In some states, however, these negative norms are overridden by a positive set of norms, causing nuclear weapons to become either symbols of invulnerability to perceived threats or the regalia of major power status. Main purpose of this paper is to explore on the conditions that cause most states to develop a moral aversion to nuclear weapons, yet effectively lead to their glorification in others. Many studies on the normative understanding of nuclear weapons consider the existence of a negative normative predisposition, often referred to as ‘nuclear taboo’, as a major factor in preventing their acquisition and use. Other studies acknowledge the existence of a nuclear taboo inhibiting the use of nuclear weapons, but point to the existence of the opposing effect of norms, frequently referred to as the ‘nuclear myth’, when it comes to the acquisition of nuclear weapons. This myth emerges when certain symbolic meanings are attached to nuclear weapons, such as a state’s identity, self-image, and its desired position in the international system. With 180 odd countries in the world abstaining from the acquisition of nuclear weapons and 8 countries in possession of them (with two further countries assumed to have pursued their acquisition), one might consider the dominance of the nuclear taboo over the nuclear myth to be the rule. The core question is thus why and how this relationship reversed in the case of defectors.
Resumo:
El presente proyecto planteaba el paso siguiente a la construcción, por nosotros mismos, de la Colección Nuclear de Cebadas Españolas, que es una representación esquemática de la variabilidad genética de las cebadas ancestralmente cultivadas en nuestro país. Para la explotación completa de estos materiales autóctonos en el Programa Nacional de Mejora de Cebadas, que estamos llevando a cabo los grupos integrantes de este proyecto, se realizó el mismo, que ha comprendido los objetivos siguientes: - Caracterización agronómica, mediante ensayos de campo en ambientes contrastantes y representativos, incluyendo la evaluación de respuestas a factores productores de estreses bióticos y abióticos. - Caracterización fenológica, mediante ensayos en invernadero con protocolos desarrollados por nosotros, para identificar la respuesta de estos genotipos a la vernalización y el fotoperiodo. - Caracterización maltero-cervecera/pienso, mediante análisis de cebada y malta. - Caracterización molecular, mediante el uso de marcadores SSRs y STS.
Resumo:
Studies carried out in Sw outbred mice showed that there is no correlation between the degree of lung granulomatous reaction and the level of acquired resistance against S. mansoni infection induced by BCG.
Resumo:
Ivermectin (0.2 mg/kg body weight) caused a high mortality in nymphs and adults of Rhodnius prolixus following a single meal in mice sub-cutaneously injected with the drug. This effect was more evident in nymphs of 1st-and 2nd-instar than in older nymphs and adults. Third-instar nymphs presented a high mortality when fed on mice treated with ivermectin 24 and 48 hours previously, while mortality was significantly reduced in nymphs fed on mice treated 72 hours before. Surviving 3rd-instar nymphs did not molt. When adult females were fed once on mice treated for 24 hours with ivermectin there was a considerable reduction in egg production. This inhibition was not reversed by a second feeding on normal mice. We concluded that sub-lethal doses of ivermectin caused toxic effects interfering in the neuro-endocrine control of development and reproduction of this bloodsucking insect.
Resumo:
Aberrant blood vessels enable tumor growth, provide a barrier to immune infiltration, and serve as a source of protumorigenic signals. Targeting tumor blood vessels for destruction, or tumor vascular disruption therapy, can therefore provide significant therapeutic benefit. Here, we describe the ability of chimeric antigen receptor (CAR)-bearing T cells to recognize human prostate-specific membrane antigen (hPSMA) on endothelial targets in vitro as well as in vivo. CAR T cells were generated using the anti-PSMA scFv, J591, and the intracellular signaling domains: CD3ζ, CD28, and/or CD137/4-1BB. We found that all anti-hPSMA CAR T cells recognized and eliminated PSMA(+) endothelial targets in vitro, regardless of the signaling domain. T cells bearing the third-generation anti-hPSMA CAR, P28BBζ, were able to recognize and kill primary human endothelial cells isolated from gynecologic cancers. In addition, the P28BBζ CAR T cells mediated regression of hPSMA-expressing vascular neoplasms in mice. Finally, in murine models of ovarian cancers populated by murine vessels expressing hPSMA, the P28BBζ CAR T cells were able to ablate PSMA(+) vessels, cause secondary depletion of tumor cells, and reduce tumor burden. Taken together, these results provide a strong rationale for the use of CAR T cells as agents of tumor vascular disruption, specifically those targeting PSMA. Cancer Immunol Res; 3(1); 68-84. ©2014 AACR.
Resumo:
Transforming growth factor beta (TGF-beta) and platelet-derived growth factor A (PDGFAlpha) play a central role in tissue morphogenesis and repair, but their interplay remain poorly understood. The nuclear factor I C (NFI-C) transcription factor has been implicated in TGF-beta signaling, extracellular matrix deposition, and skin appendage pathologies, but a potential role in skin morphogenesis or healing had not been assessed. To evaluate this possibility, we performed a global gene expression analysis in NFI-C(-/-) and wild-type embryonic primary murine fibroblasts. This indicated that NFI-C acts mostly to repress gene expression in response to TGF-beta1. Misregulated genes were prominently overrepresented by regulators of connective tissue inflammation and repair. In vivo skin healing revealed a faster inflammatory stage and wound closure in NFI-C(-/-) mice. Expression of PDGFA and PDGF-receptor alpha were increased in wounds of NFI-C(-/-) mice, explaining the early recruitment of macrophages and fibroblasts. Differentiation of fibroblasts to contractile myofibroblasts was also elevated, providing a rationale for faster wound closure. Taken together with the role of TGF-beta in myofibroblast differentiation, our results imply a central role of NFI-C in the interplay of the two signaling pathways and in regulation of the progression of tissue regeneration.
Resumo:
Eukaryotic cells generate energy in the form of ATP, through a network of mitochondrial complexes and electron carriers known as the oxidative phosphorylation system. In mammals, mitochondrial complex I (CI) is the largest component of this system, comprising 45 different subunits encoded by mitochondrial and nuclear DNA. Humans diagnosed with mutations in the gene NDUFS4, encoding a nuclear DNA-encoded subunit of CI (NADH dehydrogenase ubiquinone Fe-S protein 4), typically suffer from Leigh syndrome, a neurodegenerative disease with onset in infancy or early childhood. Mitochondria from NDUFS4 patients usually lack detectable NDUFS4 protein and show a CI stability/assembly defect. Here, we describe a recessive mouse phenotype caused by the insertion of a transposable element into Ndufs4, identified by a novel combined linkage and expression analysis. Designated Ndufs4(fky), the mutation leads to aberrant transcript splicing and absence of NDUFS4 protein in all tissues tested of homozygous mice. Physical and behavioral symptoms displayed by Ndufs4(fky/fky) mice include temporary fur loss, growth retardation, unsteady gait, and abnormal body posture when suspended by the tail. Analysis of CI in Ndufs4(fky/fky) mice using blue native PAGE revealed the presence of a faster migrating crippled complex. This crippled CI was shown to lack subunits of the "N assembly module", which contains the NADH binding site, but contained two assembly factors not present in intact CI. Metabolomic analysis of the blood by tandem mass spectrometry showed increased hydroxyacylcarnitine species, implying that the CI defect leads to an imbalanced NADH/NAD(+) ratio that inhibits mitochondrial fatty acid β-oxidation.
Resumo:
BACKGROUND: CD19 is a B cell lineage specific surface receptor whose broad expression, from pro-B cells to early plasma cells, makes it an attractive target for the immunotherapy of B cell malignancies. In this study we present the generation of a novel humanized anti-CD19 monoclonal antibody (mAb), GBR 401, and investigate its therapeutic potential on human B cell malignancies. METHODS: GBR 401 was partially defucosylated in order to enhance its cytotoxic function. We analyzed the in vitro depleting effects of GBR 401 against B cell lines and primary malignant B cells from patients in the presence or in absence of purified NK cells isolated from healthy donors. In vivo, the antibody dependent cellular cytotoxicity (ADCC) efficacy of GBR 401 was assessed in a B cell depletion model consisting of SCID mice injected with healthy human donor PBMC, and a malignant B cell depletion model where SCID mice are xenografted with both primary human B-CLL tumors and heterologous human NK cells. Furthermore, the anti-tumor activity of GBR 401 was also evaluated in a xenochimeric mouse model of human Burkitt lymphoma using mice xenografted intravenously with Raji cells. Pharmacological inhibition tests were used to characterize the mechanism of the cell death induced by GBR 401. RESULTS: GBR 401 exerts a potent in vitro and in vivo cytotoxic activity against primary samples from patients representing various B-cell malignancies. GBR 401 elicits a markedly higher level of ADCC on primary malignant B cells when compared to fucosylated similar mAb and to Rituximab, the current anti-CD20 mAb standard immunotherapeutic treatment for B cell malignancies, showing killing at 500 times lower concentrations. Of interest, GBR 401 also exhibits a potent direct killing effect in different malignant B cell lines that involves homotypic aggregation mediated by actin relocalization. CONCLUSION: These results contribute to consolidate clinical interest in developing GBR 401 for treatment of hematopoietic B cell malignancies, particularly for patients refractory to anti-CD20 mAb therapies.
Resumo:
Three antigens protective against Schistosoma mansoni have been extensively characterized. The schistosomulum surface antigen GP38 possesses an immunodominant carbohydrate epitope of which the structure has been defined. Protection can be achieved via the transfer of monoclonal antibodies recognizing the epitope or by immunization with anti-idiotype monoclonal antibodies. The glycan epitope is shared with the intermediate host, Biomphalaria glabrata as well as being present on other molluscs, including the Keyhole Limpet. A group of molecules at 28 kDa were initially characterized in adult worms and shown to protect rats and mice against a challenge infection. One of these molecules, P28-I, was cloned and expressed in E. coli, yeast and vaccinia virus. The recombinant antigen significantly protected rats, hamsters and baboons against a challenge infection. P28-I is a glutathione-S-transferase and the recombinant antigen produced in yeast exhibits the enzyme activity and has been purified to homogeneity by affinity chromatography. A second P28 antigen, P28-II, has also been cloned, fully sequenced and expressed. This recombinant antigen also protects against S. mansoni infection.