Specific, Reversible Cytostatic Protection of Normal Cells Against Negative Effects of Chemotherapy

Chemotherapy is a common and effective method to treat many forms of cancer. However, treatment of cancer with chemotherapy has severe side effects which often limit the doses of therapy administered. Because some cancer chemotherapeutics target proliferating cells and tissues, all dividing cells, whether normal or tumor, are affected. Cell culture studies have demonstrated that UCN-01 is able to reversibly and selectively arrest normal dividing cells; tumor cells lines do not undergo this temporary arrest. Following UCN-01 treatment, normal cells displayed a 50-fold increase in IC50 for camptothecin; tumor cells showed no such increased tolerance. We have examined the response of the proliferating tissues of the mouse to UCN- 01 treatment, using the small bowel epithelium as a model system. Our results indicate that UCN-01 treatment can cause a cell cycle arrest in the gut epithelium, beginning 24 hours following UCN-01 administration, with cell proliferation remaining suppressed for one week. Two weeks post-UCN-01 treatment the rate of proliferation returns to normal levels. 5-FU administered during this period demonstrates that UCN-01 is able to provide protection to normal cells of the mouse within a narrow window of efficacy, from three to five days post-UCN-01. UCN-01 pretreated mice displayed improved survival, weight status and blood markers following 5-FU compared to control mice, indicating that UCN-01 can protect normal dividing tissues. The mechanism by which UCN-01 arrests normal cells in vivo was also examined. We have demonstrated that UCN-01 treatment in mice causes an increase in the G1 phase cell cycle proteins cdk4 and cyclin D, as well as the inhibitor p27. Phosphorylated Rb was also elevated in the arrested cells. These results are a departure from cell culture studies, in which inhibition of G1 phase cyclin dependent kinases led to hyposphosphorylation of Rb. Future investigation will be required to understand the mechanism of UCN-01 action. This is important information, especially for identification of alternate compounds which could provide the protection afforded by UCN-01.

Laser-induced transient grating analysis of dynamics of interaction between sensory rhodopsin II D75N and the HtrII transducer.

The interaction between sensory rhodopsin II (SRII) and its transducer HtrII was studied by the time-resolved laser-induced transient grating method using the D75N mutant of SRII, which exhibits minimal visible light absorption changes during its photocycle, but mediates normal phototaxis responses. Flash-induced transient absorption spectra of transducer-free D75N and D75N joined to 120 amino-acid residues of the N-terminal part of the SRII transducer protein HtrII (DeltaHtrII) showed only one spectrally distinct K-like intermediate in their photocycles, but the transient grating method resolved four intermediates (K(1)-K(4)) distinct in their volumes. D75N bound to HtrII exhibited one additional slower kinetic species, which persists after complete recovery of the initial state as assessed by absorption changes in the UV-visible region. The kinetics indicate a conformationally changed form of the transducer portion (designated Tr*), which persists after the photoreceptor returns to the unphotolyzed state. The largest conformational change in the DeltaHtrII portion was found to cause a DeltaHtrII-dependent increase in volume rising in 8 micros in the K(4) state and a drastic decrease in the diffusion coefficient (D) of K(4) relatively to those of the unphotolyzed state and Tr*. The magnitude of the decrease in D indicates a large structural change, presumably in the solvent-exposed HAMP domain of DeltaHtrII, where rearrangement of interacting molecules in the solvent would substantially change friction between the protein and the solvent.

ANALYSIS OF THE CORYNEBACTERIUM PARVUM-INDUCED DECLINE OF MURINE NATURAL KILLER CELL-MEDIATED CYTOTOXICITY

Treatment of mice with the immunomodulating agent, Corynebacterium parvum (C. parvum), was shown to result in a severe and long-lasting depression of splenic natural killer (NK) cell-mediated cytotoxicity 5-21 days post-inoculation. Because NK cells have been implicated in immunosurveillance against malignancy (due to their spontaneous occurrence and rapid reactivity to a variety of histological types of tumors), as well as in resistance to established tumors, this decreased activity was of particular concern, since this effect is contrary to that which would be considered therapeutically desirable in cancer treatment (i.e. a potentiation of antitumor effector functions, including NK cell activity, would be expected to lead to a more effective destruction of malignant cells). Therefore, an analysis of the mechanism of this decline of splenic NK cell activity in C.parvum treated mice was undertaken.^ From in vitro co-culturing experiments, it was found that low NK-responsive C. parvum splenocytes were capable of reducing the normally high-reactivity of cells from untreated syngeneic mice to YAC-1 lymphoma, suggesting the presence of NK-directed suppressor cells in C. parvum treated animals. This was further supported by the demonstration of normal levels of cytotoxicity in C. parvum splenocyte preparations following Ficoll-Hypaque separation, which coincided with removal of the NK-suppressive capabilities of these cells. The T cell nature of these regulatory cells was indicated by (1) the failure of C. parvum to cause a reduction of NK cell activity, or the generation of NK-directed suppressor cells in T cell-deficient athymic mice, (2) the removal of C. parvum-induced suppression by T cell-depleting fractionation procedures or treatments, and (3) demonstration of suppression of NK cell activity by T cell-enriched C. parvum splenocytes. These studies suggest, therefore, that the eventual reduction of suppression by T cell elimination and/or inhibition, may result in a promotion of the antitumor effectiveness of C. parvum due to the contribution of "freed" NK effector cell activity.^ However, the temporary suppression of NK cell activity induced by C. parvum (reactivity of treated mice returns to normal levels within 28 days after C. parvum injection), may in fact be favorable in some situations, e.g. in bone marrow transplantation cases, since NK cells have been suggested to play a role also in the process of bone marrow graft rejection.^ Therefore, the discriminate use of agents such as C. parvum may allow for the controlled regulation of NK cell activity suggested to be necessary for the optimalization of therapeutic regimens. ^

Nonparametric Measures of Capacity Utilization: A Dual Approach

This paper develops a nonparametric method of obtaining the minimum of the long run average cost curve of a firm to define its capacity output. This provides a benchmark for measuring of capacity utilization at the observed output level of the firm. In the case of long run constant returns to scale, the minimum of the short run average cost curve is determined to measure short run capacity utilization. An empirical application measures yearly rates of capacity utilization in U.S. manufacturing over the period 1968-1998. Nonparametric determination of the short run average cost curve under variable returns to scale using an iterative search procedure is described in an appendix to this paper.

Are Some Indian Bank Too Large? A Examination of Size Efficiency in Indian Banking

In this paper we use data from the years 1997 through 2003 to evaluate the size efficiency of Indian banks. Following Maindiratta (1990) we consider a bank to be too large if breaking it up into a number of smaller units would result in a larger output bundle than what could be produced from the same input by a single bank. When this is the case, the bank is not size efficient. Our analysis shows that many of the banks are, in deed, too large in various years. We also find that often a bank is operating in the region of diminishing returns to scale but is not a candidate for break up.

Correlation between dental care utilization and oral cavity cancer in a large sample of community-based United States residents

Cancer of the oral cavity and pharynx remains one of the ten leading causes of cancer death in the United States (US). Besides smoking and alcohol consumption, there are no well established risk factors. While poor dental care had been implicated, it is unknown if the lack of dental care, implying poor dental hygiene predisposes to oral cavity cancer. This study aimed to assess the relationship between dental care utilization during the past twelve months and the prevalence of oral cavity cancer. A cross-sectional design of the National Health Interview Survey of adult, non-institutionalized US residents (n=30,475) was used to assess the association between dental care utilization and self reported diagnosis of oral cavity cancer. Chi square statistic was used to examine the crude association between the predictor variable, dental care utilization and other covariates, while unconditional logistic regression was used to assess the relationship between oral cavity cancer and dental care utilization. There were statistically significant differences between those who utilized dental care during the past twelve months and those who did not with respect to education, income, age, marital status, and gender (p < 0.05), but not health insurance coverage (p = 0.53). Also, those who utilized dental care relative to those who did not were 65% less likely to present with oral cavity cancer, prevalence odds ratio (POR), 0.35, 95% Confidence Interval (CI), 0.12–0.98. Further, higher income advanced age, people of African heritage, and unmarried status were statistically significantly associated with oral cavity cancer, (p < 0.05), but health insurance coverage, alcohol use and smoking were not, p > 0.05. However, after simultaneously controlling for the relevant covariates, the association between dental care and oral cavity cancer did not attenuate nor persist. Thus, compared with those who did not use dental care, those who did wee 62% less likely to present with oral cavity cancer adjusted POR, 0.38, 95% CI, 0.13-1.10. Among US adults residing in community settings, use of dental care during the past twelve months did not significantly reduce the predisposition to oral cavity cancer. However, due to the nature of the data used in this study, which restricts temporal sequence, a large sample prospective study that may identify modifiable factors associated with oral cancer development namely poor dental care, is needed. ^

Comparison of health behaviors of Mexican American and non -Hispanic White females: Implications for health promotion programs

Hispanics form the second-largest minority group in the United States totaling 22 million people. Health data on this population are sparse and inconsistent. This study seeks to determine use of preventative services and risk factor behaviors of Mexican American and non-Hispanic White females residing in South Texas.^ Baseline data from female respondents in household surveys in six South Texas counties (Ramirez and McAlister, 1988; McAlister et al., 1992) were analyzed to test the following hypotheses: (1) Mexican American and Non-Hispanic White females exhibit different patterns of health behaviors; (2) Mexican American females will exhibit different health behaviors regardless of age; and (3) the differences between Mexican American women and non-Hispanic White females are due to education and acculturation factors.^ Over the past decade, the traditional behaviors of Mexican American females have begun to change due to education, acculturation, and their participation in the labor force. The results from this study identify some of the changes that will require immediate attention from health care providers. Results revealed that regardless of ethnicity, age, education, and language preference, non-Hispanic White females were significantly more likely to participate in preventive screening practices than were Mexican American females. Risk factor analysis revealed a different pattern with Mexican American females significantly more likely to be non-smokers, non-alcoholic drinkers, and to have good fat avoidance practices compared to non-Hispanic White females. However, compared to those who are less-educated or Spanish-speaking, Mexican American females with higher levels of education and preference for speaking English only showed positive and negative health behaviors that were more similar to the non-Hispanic White females. The positive health behaviors that come with acculturation, e.g., more participation in preventive care and more physical activity, are welcome changes. But this study has implications for global health development and reinforces a need for "primordial" prevention strategies to deter the unwanted concomitants of economic development and acculturation. Smoking and drinking behaviors among Mexican American females need to be kept at low levels to prevent increased morbidity and premature deaths in this population. ^

El espacio de lo provincial en el siglo XIX : memoria descriptiva sobre el Tucumán, de Juan Bautista Alberdi

Hacia el año 1834, Juan Bautista Alberdi regresa a su Tucumán natal, luego de una larga ausencia. En ese momento, instigado por el entonces gobernador, general Alejandro Heredia, redactó su Memoria descriptiva sobre el Tucumán, considerada el primer exponente de la literatura provincial en la Argentina. En este breve texto, de menos de treinta páginas, el escritor aúna a su perspectiva de extra-ambientado, de viajero, la del romántico y la del patriota, las cuales determinan las isotopías que lo estructuran. Este trabajo intenta rescatar del olvido tan valioso texto. Para ello se analizan la estructura, procedimientos y recursos que, estando al servicio de una intención precisamente manifestada por el autor, configuran una visión idealizada del terruño natal. El procedimiento descriptivo es el principal canal de textualización. A través de él, el autor ofrece una visión subjetiva, idealizadora y humanizada del paisaje para detenerse luego en la presentación del hombre tucumano, cuyo temperamento aparece determinado por la geografía de su entorno. Finalmente, Alberdi centra su mirada en los monumentos históricos; en este caso, su discurso materializa la confrontación entre lo que ve y lo que recuerda e identifica la vida de la patria con su propia vida.

¿Incluir las diferencias o a los diferentes? Una cuestión mal planteada en una realidad desoladora

Este texto se plantea una relectura ética acerca del derecho a la educación de las personas con discapacidades, con un énfasis prioritario de la situación en América Latina. A partir de considerar los sistemas jurídicos, los modos de financiamiento políticos, los porcentajes de inclusión y los programas de seguimiento de la población con discapacidad en edad escolar, se deriva toda una serie de discusiones sobre la idea de formación educativa, el estar junto a otros y las responsabilidades éticas en la tarea de educar.

Derechos de autor y acceso al conocimiento : la educación pública en el medio

El presente proyecto se propone investigar la legislación de derechos de autor en relación con la universidad pública, su historia en el contexto nacional y educativo. Indagamos en torno de la normativa vigente, los aspectos facilitadores u obstaculizadores en la educación y las excepciones a las leyes con material de uso educativo en universidades públicas y las modalidades de implementación en el acceso al conocimiento libre. Asimismo, nos interesa conocer la diferencia entre bienes materiales e inmateriales, el estatuto del conocimiento humano como bien inmaterial y los impactos en el tratamiento de los bienes culturales y el conocimiento como bienes económicos susceptibles de apropiación privada.

Análisis situacional de la educación y la formación para el trabajo de las personas con discapacidad según el informe OEA-CIDI 2008 : revisión crítica

Este artículo consiste en una revisión crítica del análisis de la situación en la República Argentina, de la Educación y Formación para el trabajo según el informe publicado por la Organización de los Estados Americanos y el CIDI (México 2008); dicho informe es una presentación conjunta con otros países latinoamericanos que encuadran sus servicios en la normativa que rige para la educación inclusiva. Concretamente este artículo propone un cuestionamiento a lo expresado por el informe desde su relación con la escuela, su nexo con la sociedad y el derecho a una educación de buena calidad para todos.

La dignidad en la diversidad : educación especial — terapia ocupacional

Es la intención de este trabajo aportar reflexiones y poner en perspectiva la complejidad de avanzar en una Educación para la Diversidad que haga posible la inclusión y con ello el derecho universal a la Educación como bien social. En este momento histórico las diversidades han tomado voz y forma, al cuestionar nuestro modo de pensar la vida social. Las culturas, los sujetos, los géneros, los lenguajes, los imaginarios y las formas de habitar un mundo diverso, encuen tran eco en la sociedad de la información, en apariencia un mundo sin fronteras. Frente a las transformaciones tecnológicas y económicas del siglo XXI cabe preguntarse cuál es nuestra sensibilidad ante la diferencia, cuanto hemos avanzado en la capacidad para reconocer a “los Otros", que sabemos de sus sueños y frustraciones, como nos estamos preparando para convivir “ Nosotros y los Otros", en un mundo polifónico. Frente a estas problemáticas el aporte interdisciplinario permitirá buscar modelos alternativos que rompan este círculo a través de dispositivos de inclusión social reduciendo los temores y mitos que han impulsado en otras ocasiones a marginar a las personas. El contenido interdisciplinar de la Educación Especial ha permitido y requiere la convergencia de disciplinas, entre ellas la Terapia Ocupacional.

Reflexiones en torno a propuestas de educación para mujeres privadas de libertad en unidades penitenciarias de Mendoza

En este ensayo se reflexiona sobre algunas propuestas educativas de Nivel Superior para mujeres privadas de libertad en unidades penitenciarias de Mendoza. Algunos de los condicionantes que estas mujeres deben enfrentar, si bien fueron observados en torno a experiencias de educación universitaria, permiten entrever, limitaciones que aparecen, en general, cuando se trata del ejercicio del derecho a la educación por parte de mujeres. Cada logro va acompañado, a la vez, de relegaciones, o al menos de postergaciones, ya que se trata de avances que se obtienen una vez que han sido conseguidos para los hombre que están privados de libertad.

La espacialidad en Eero Tarasti : aportes a un modelo de análisis semiótico

El trabajo retoma el análisis semiótico de Eero Tarasti y en particular el concepto de espacialidad desarrollado en su Sémiotique musicale (1996), y basado en los estudios del estructuralista A. J. Greimas. A partir de un nuevo estudio de caso, se proponen modificaciones que permitirán complementar el análisis armónico tradicional, y suplir algunas falencias que toda traducción a un nuevo código implica. El aparato metodológico es concebido como herramienta para el conocimiento profundo de las estructuras narrativas y como apoyo para la interpretación.

El desierto y su semilla : política e ironía

El presente artículo estudia la relación entre el arte y lo político en la novela El desierto y su semilla, de Jorge Baron Biza (2013), caracterizada por una intencionalidad irónica, porque hace uso de técnicas propias de esta figura del discurso que le permiten decir lo político difiriendo del enunciado literal. Se dejan de lado las lecturas biográficas y acudimos a los aportes de Jacques Rancière acerca de la estética elusiva, que hace al arte político y sus advertencias sobre las diversas formas en que el arte es repolitizado. Por otra parte, se tendrá en cuenta el estudio propuesto por Ana María Amar Sánchez sobre el discurso de los perdedores, para así poder complementar el estudio sobre la novela y la reflexión en torno a lo político. Por último, la intencionalidad irónica del autor se expresa en el uso de la alusión que le permite hablar de lo político, alterando así, en términos de Rancière, el dispositivo estético que vuelve a la obra subversiva.