177,801 research outputs found

    Cisplatin-based chemotherapy of testicular cancer - Two decades after a major breakthrough

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    Two decades ago the introduction of cisplatin-based combination chemotherapy has dramatically improved the prognosis of patients with metastatic testicular cancer, At present 3 cycles of cisplatin, etoposide and bleomycin are considered as standard treatment for good-risk metastatic disease. Outside of clinical trials patients in the intermediate and poor prognosis categories should receive 4 cycles of this standard regimen, Clinical trials currently evaluate the role of high-dose chemotherapy in first-line treatment of high-risk patients and in the salvage setting, Post-chemotherapy resection of tumor residuals remains an important part of therapy. Attention should be focused on long-term toxicity of therapy and the occurrence of late relapse

    Cytochemical differentiation of the Golgi apparatus from GERL.

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    GERL exhibits a number of structural properties, such as its location at the trans face of the Golgi apparatus, thick limiting membranes with occasional coated regions, and close relationship to the ER, which are similar in all cells wehre it has been identified. Acid hydrolase activity and the formation of lysosomes, also considered characteristic of GERL, have been shown to be less consistent properties of GERL in some cells. Finally, GERL and the Golgi saccules of certain cells undergo significant changes in their cytochemical and structural properties in response to specific alterations in cellular activity. These variations are important for at least two reasons: first, they indicate the care required in differentiating GERL from the Golgi saccules based on limited cytochemical observations; second, and most important, they may yield information regarding the biogenetic and functional relationships between the ER, Golgi saccules, and GERL, such as the origin of GERL in various cells and the role of each organelle in the processing of lysosomal and secretory proteins. </jats:p

    Effects of secretory stimulation on the Golgi apparatus and GERL of rat parotid acinar cells.

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    The structure and cytochemistry of the Golgi apparatus and GERL of rat parotid acinar cells was studied after in vivo secretory stimulation with isoproterenol. Discharge of mature secretory granules was complete within 1 hr after isoproterenol injection, but immature granules in the Golgi region or near the lumen were not released. At early times (1-5 hr) after isoproterenol, acid phosphatase (AcPase) activity was markedly increased in GERL and immature secretory granules compared to uninjected controls. GERL appeared increased in extent and numerous continuities with immature granules were observed. Reaccumulation of mature secretory granules was first evident at 5 hr, and was almost complete by 16 hr after isoproterenol. Thiamine pyrophosphatase (TPPase) activity, normally restricted to the trans Golgi saccules, was frequently present in immature granules during this time. Narrow cisternae resembling GERL, occasionally in continuity with immature granules, also contained TPPase reaction product. By 16-24 hr after stimulation, the activity and distribution of AcPase and TPPase were similar to control cells. These results demonstrate the dynamic nature of the Golgi apparatus and GERL in parotid acinar cells, and emphasize the close structural and functional relationship between these two structures. </jats:p

    The Golgi apparatus and GERL during postnatal differentiation of rat parotid acinar cells: an electron microscopic cytochemical study.

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    Morphological and cytochemical changes in the Golgi apparatus and GERL of differentiating parotid acinar cells were examined in Sprague-Dawley rats from 5 days to young adult. At day 5, the Golgi apparatus consisted of 3-6 narrow saccules, with short segments of GERL lying adjacent to the trans Golgi saccule. As the glands matured, the Golgi apparatus increased in size and the saccules became broadened and fenestrated reaching a maximum from days 15-20. The saccules subsequently narrowed slightly and by day 25 resembled those seen in young adults. Numerous cisternae of GERL could be seen at the trans face during this period. While the glands were maturing, marked changes occurred in the distribution of thiamine pyrophosphatase (TPPase) activity in the Golgi saccules. In the immature cells, TPPase activity was restricted to 1 or 2 trans Golgi saccules. However, by day 10 TPPase could also be localized in immature secretory granules and in GERL-like cisternae. Unreactive segments of GERL were also present. This pattern of localization persisted until day 20, after which the TPPase activity in the GERL-like cisternae diminished gradually until by day 40 TPPase again was localized in 1-2 trans Golgi saccules and an occasional immature secretory granule. Acid phosphatase (AcPase) activity was localized primarily in lysosomes in the very young animals and increased in GERL with age up to day 15. From days 15 to 20 there was a decrease in the amount of activity seen in GERL, but from day 20 on, the AcPase activity increased until it reached that seen in young adult animals. These results indicate that the presence of TPPase activity in GERL-like cisternae and immature secretory granules may be dependent upon the developmental as well as the physiologic state of the acinar cells and lend further support to the suggestion that GERL is derived from the trans Golgi saccules. </jats:p

    Enzyme modulation of the Golgi apparatus and GERL: a cytochemical study of parotid acinar cells.

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    The distribution of thiamine pyrophosphatase (TPPase) and acid phosphatase (AcPase) has been examined in resting parotid acinar cells as well as during decreased and increased secretory granule production. In resting acinar cells, TPPase activity was restricted to the trans Golgi saccules and AcPase activity was localized in GERL and immature secretory granules. Although secretory granule production is diminished during ethionine intoxication, no significant alteration in the distribution of either TPPase or AcPase was noted. However, marked changes in enzyme localization, especially of TPPase, occurred during accelerated secretory granule production. The alterations were essentially the same for all of the conditions studied (recovery from ethionine treatment, recovery from a protein depletion diet, secretory stimulation with isoproterenol, and postnatal maturation of the parotid gland). During maximal secretory granule production, TPPase activity was localized not only in the trans Golgi saccules, but also in GERL-like cisternae and immature secretory granules. The immature secretory granules were often in continuity with the GERL-like cisternae. At the same time that the TPPase activity was increased, the AcPase activity was frequently diminished. These modulations in enzyme activity provide evidence that GERL is derived from the trans Golgi saccule. </jats:p

    The relationships between the Golgi apparatus, GERL, and lysosomes of fetal rat liver Kupffer cells examined by ultrastructural phosphatase cytochemistry.

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    Kupffer cells are the sinusoidal macrophages of the liver. Using ultrastructural phosphatase cytochemical methods, we examined the relationship between the Golgi apparatus, GERL, and lysosomes of Kupffer cells in fetal rat livers identified, in part, by their ability to phagocytize intravenously injected latex spheres. Thiamine pyrophosphatase (TPPase) activity was localized to the inner Golgi saccules and some vesicles in the Golgi region but not to GERL. A TPPase-like activity, demonstrable in lysosomes, was abolished by sodium fluoride but not suppressed by the alkaline phosphatase inhibitors L-cysteine and L-p-bromotetramisole. Acid phosphatase (AcPase) was localized by GERL, some coated vesicles, and in lysosomes, but not to the Golgi stacks. Continuities between GERL and lysosomes were observed. Phagosomes containing internalized latex spheres received TPPase and AcPase sequentially. TPPase was localized in phagosomes immediately after latex administration. AcPase activity was not found here until at least 10 minutes following the injection of the particulates. Our findings indicate that Kupffer cell lysosomes are derived from GERL, but also suggest that phagosomes may receive material packaged by the Golgi apparatus as well as GERL. </jats:p

    Crítica a la ideología desde la cristología. Sobre el diagnóstico de Guardini acerca de su tiempo en El Señor

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    H.-B. Gerl-Falkovitz muestra en este artículo cómo R. Guardini, en su obra El Señor, no solo habla del Mesías en sentido religioso. Según esta lectura, las afirmaciones de Guardini sobre el carácter mesiánico de Jesucristo implican un diagnóstico sobre el modo en que los regímenes totalitarios emplean símbolos y significados pseudorreligiosos para dirigir la acción de los hombres hacia un único poder. Sin embargo, Cristo se presenta como el único Señor, en comparación con otros líderes políticos y religiosos, por cuanto que establece un nuevo comienzo, un principio de la acción, no desde el temor al poder o a lo divino, propio de la política totalitaria o de la actitud religiosa natural. Al cristiano le caracteriza la actitud neumática, la que también hace posible la presencia directa de Jesús, aquella que mueve al creyente de manera escatológica. Un Cristo sinóptico y al mismo tiempo joánico, un Cristo no solo histórico, sino también escatológico y que, por ello, permite también un juicio sobre cada uno de los tiempos, también sobre el de Guardini, un juicio desde el señorío de Cristo descrito en el Apocalipsis. Siguiendo este enfoque escatológico, el artículo de H.-B. Gerl-Falkovitz muestra cómo Guardini realiza un diagnóstico sobre su tiempo al mismo tiempo que describe las características del señorío de Cristo.Gerl-Falkovitz presents in this article how R. Guardini, in his work The Lord, not only speaks of the Messiah in a religious sense. According to this reading, Guardini’s statements about the messianic character of Jesus Christ imply a diagnosis of how totalitarian regimes use symbols and pseudo-religious meanings to direct men’s action towards a single power. However, Christ is introduced as the only Lord, compared to other political and religious leaders, because He establishes a new beginning, the principle of action not from the fear of power or the divine, the own of totalitarian politics or of the natural religious attitude. The Christian is characterized by the pneumatic attitude, which also makes possible the direct presence of Jesus, the one that moves the believer in an eschatological way. A synoptic Christ and, at the same time, joanic one, a Christ not only historical, but also eschatological, and that, therefore, can also make a judgment over the time, also on the time of Guardini, a judgment from the Christ Lordship on, the one described by the apocalypse. Following this eschatological approach, the article by H.-B. Gerl-Falkovitz shows, how Guardini makes a diagnosis about his time while describing the characteristics of the Lordship of Christ

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    "Closing the R&D Gap, Evaluating the Sources of R&D Spending"

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    Both spending and tax policies have been implemented in the United States with the goal of stimulating private sector research and development (R&D). Karier questions whether current R&D policy, especially the research and experimentation tax credit, can contribute to closing the gap between nondefense expenditures on R&D in the United States and such expenditures in other countries, such as Japan and Germany. He also explores possible changes to our current R&D policy to make it more effective.

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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