An Interview with Stephanie Meakin of the Faculty of Health Sciences regarding developing leadership skills in students.

Mp3 format

Attitude in students of Health Sciences toward scientific knowledge

Educating health professionals implies the challenge of creating and developing an inquiring mind, ready to be in a state of permanent questioning. For this purpose, it is fundamental to generate a positive attitude toward the generation of knowledge and science. Objective: to determine the attitude toward science and the scientific method in undergraduate students of health sciences. Materials and methods: a cross-sectional study was made by applying a self-administered survey, excluding those who were transferred from other universities and repeated. The attitude toward science and the scientific method were valued using the scale validated and published by Hren, which contains three domains: value of scientific knowledge, value of scientific methodology, and value of science for health professions. Results: 362 students were included, 86,6% of them graded the attitude toward scientific knowledge above 135 points, neutral scale value. Similar scores were registered in the domains value of scientific knowlede for the human dimension of the students and value of science for health professions. 91,4% of the students graded the value of scientific methodology below 48 points. Conclusions: the favorable attitude of the students can be explained by the contact that they have with the scientific method since the beginning of their studies and its concordance with the evolution of science. The domain value of scientific methodology obtained the lowest grade on the part of the students, which could be related to the lack of knowledge about scientific methodology.

Human biology and health studies.

Proporciona a los estudiantes los temas requeridos para el primer año del curso GCSE, especialidad biología. Es una edición revisada para el nuevo AQA GCSE en Fisiología humana y estudios de la salud.

Master of Population Health Sciences Graphic

http://digitalcommons.wustl.edu/becker_graphics/1004/thumbnail.jpg

Teaching research and epidemiology to undergraduate students in the health sciences

Objective: To identify and address particular challenges in the teaching of epidemiological concepts to undergraduate students in non-clinical health disciplines. Methods and Results: Relevant pedagogical literature was reviewed to identify a range of evidence-based teaching approaches. The authors also drew on their experience in curriculum development and teaching in this field to provide guidelines for teaching epidemiology in a way that is engaging to students and likely to promote deep, rather than surface, learning. Discussion of a range of practical strategies is included along with applied examples of teaching epidemiological content. Conclusions and Implications: Increasingly, there is a greater emphasis on improved learning outcomes in higher education. Graduates from non-clinical health courses are required to have a core understanding of epidemiology and teachers of epidemiology need to be able to access resources that are relevant and useful for these students. A theoretically grounded framework for effective teaching of epidemiological principles to non-clinical undergraduates is provided, together with a range of useful teaching resources (both paper and web-based). Implementation of the strategies discussed will help ensure graduates are able to appropriately apply epidemiological skills in their professional practice.

Friends of the library groups in health sciences libraries.

The Houston Academy of Medicine--Texas Medical Center (HAM--TMC) Library collected data on friends of the library groups from 103 health sciences libraries, using a mail questionnaire. Sixteen of the responding libraries had independent friends groups; seven had friends groups that were subordinate to a university group. The sixteen independent groups gave as their major purposes (1) to raise money for their associated library and (2) to develop support for their library. These groups contributed an average of $4,870 a year to their libraries, the money being used primarily to purchase rare books and working-collection books and to sponsor social events. The subordinate groups contributed relatively little money to the health sciences libraries responding to the survey.

Master of Education in Teaching Program with an Emphasis in the Health Sciences

Introduction: Concerns about the quality of physician education have changed current medical education practices. Learners must demonstrate competency in core areas, rather than solely participating in educational activities. Academic medical institutions are challenged with identifying leaders to direct curricular and evaluation reforms. An innovative partnership between the University of Houston College of Education and Baylor College of Medicine, the University of Texas Medical School at Houston, and the University of Texas Dental Branch at Houston offers a Masters of Education in Teaching degree with an emphasis in Health Sciences. Courses encompass fundamental areas including curriculum, instruction, technology, measurement, research design and statistics. [See PDF for complete abstract]

Molecular events associated with trisomy of chromosome 7 in mouse skin chemical carcinogenesis

The primary objective of this study has been to investigate the effects at the molecular level of trisomy of mouse chromosome 7 in chemically induced skin tumors. It was previously proposed that the initiation event in the mouse skin carcinogenesis model is a heterozygous mutation of the Ha-ras-1 gene, mapped to chromosome 7. Previous studies in this laboratory identified trisomy 7 as one of the primary nonrandom cytogenetic abnormalities found in the majority of severely dysplastic papillomas and squamous cell carcinomas induced in SENCAR mice by an initiation-promotion protocol. Therefore, the first hypothesis tested was that trisomy 7 occurs by specific duplication of the chromosome carrying a mutated Ha-ras-1 allele. Results of a quantitative analysis of normal/mutated allelic ratios of the Ha-ras-1 gene confirmed this hypothesis, showing that most of the tumors exhibited overrepresentation of the mutated allele in the form of 1/2, 0/3, and 0/2 (normal/mutated) ratios. In addition, histopathological analysis of the tumors showed an apparent association between the degree of malignancy and the dosage of the mutated Ha-ras-1 allele. To determine the mechanism for loss of the normal Ha-ras-1 allele, found in 30% of the tumors, a comparison of constitutional and tumor genotypes was performed at different informative loci of chromosome 7. By combining Southern blot and polymerase chain reaction fragment length polymorphism analyses of DNAs extracted from squamous cell carcinomas, complete loss of heterozygosity was detected in 15 of 20 tumors at the Hbb locus, and in 5 of 5 tumors at the int-2 locus, both distal to Ha-ras-1. In addition, polymerase chain reaction analysis of DNA extracted from papillomas indicated that loss of heterozygosity occurs in late-stage lesions exhibiting a high degree of dysplasia and areas of microinvasion, suggesting that this event may be associated to the acquisition of the malignant phenotype. Allelic dosage analysis of tumors that had become homozygous at Hbb but retained heterozygosis at Ha-ras-1, indicated that loss of heterozygosity on mouse chromosome 7 occurs by a mitotic recombination mechanism. Overall, these findings suggest the presence of a putative tumor suppressor locus on the 7F1-ter region of mouse chromosome 7. Thus, loss of function by homozygosis at this putative suppressor locus may complement activation of the Ha-ras-1 gene during tumor progression, and might be associated with the malignant conversion stage of mouse skin carcinogenesis. ^

Nuclear proteins interacting with an AP-1/CRE-like promoter sequence in the human TNF$\alpha$ gene

Monocyte developmental heterogeneity is reflected at the cellular level by differential activation competence, at the molecular level by differential regulation of gene expression. LPS activates monocytes to produce tumor necrosis factor-$\alpha$ (TNF). Events occurring at the molecular level necessary for TNF regulation have not been elucidated, but depend both on activation signals and the maturation state of the cell: Peripheral blood monocytes produce TNF upon LPS stimulation, but only within the first 72 hours of culture. Expression of c-fos is associated with monocytic differentiation and activation; the fos-associated protein, c-jun, is also expressed during monocyte activation. Increased cAMP levels are associated with down regulation of macrophage function, including LPS-induced TNF transcription. Due to these associations, we studied a region of the TNF promoter which resembles the binding sites for both AP-1(fos/jun) and CRE-binding protein (or ATF) in order to identify potential molecular markers defining activation competent populations of monocytic cells.^ Nuclear protein binding studies using extracts from THP-1 monocytic cells stimulated with LPS, which stimulates, or dexamethasone (Dex) or pentoxyfilline (PTX), which inhibit TNF production, respectively, suggest that a low mobility doublet complex may be involved in regulation through this promoter region. PTX or Dex increase binding of these complexes equivalently over untreated cells; approximately two hours after LPS induction, the upper complex is undetectable. The upper complex is composed of ATF2 (CRE-BP1); the lower is a heterodimer of jun/ATF2. LPS induces c-jun and thus may enhance formation of jun-ATF2 complexes. The simultaneous presence of both complexes may reduce the amount of TNF transcription through competitive binding, while a loss of the upper (ATF2) and/or gain of the lower (jun-ATF2) allow increased transcription. AP-1 elements generally transduce signals involving PKC; the CRE mediates a cAMP response, involving PKA. Thus, this element has the potential of receiving signals through divergent signalling pathways. Our findings also suggest that cAMP-induced inhibition of macrophage functions may occur via down regulation of activation-associated genes through competitive binding of particular cAMP-responsive nuclear protein complexes. ^

Immune responses against major histocompatibility complex and interleukin-2 gene transfected K1735 murine melanoma: Potential vaccines for the immunotherapy of cancer

Tumor specific immunity is mediated by cytotoxic T lymphocytes (CTL) that recognize peptide antigen (Ag) in the context of major histocompatibility complex (MHC) class I molecules and by helper T (Th) lymphocytes that recognize peptide Ag in the context of MHC class II molecules. The purpose of this study is (1) to induce or augment the immunogenicity of nonimmunogenic or weakly immunogenic tumors by genetic modification of tumor cells, and (2) to use these genetically altered cells in cancer immunotherapy. To study this, I transfected a highly tumorigenic murine melanoma cell line (K1735) that did not express constitutively either MHC class I or II molecules with syngeneic cloned MHC class I and/or class II genes, and then determined the tumorigenicity of transfected cells in normal C3H mice. K1735 transfectants expressing either $\rm K\sp{k}$ or $\rm A\sp{k}$ molecules alone produced tumors in normal C3H mice, whereas most transfectants that expressed both molecules were rejected in normal C3H mice but produced tumors in nude mice. The rejection of K1735 transfectants expressing $\rm K\sp{k}$ and $\rm A\sp{k}$ Ag in normal C3H mice required both $\rm CD4\sp+$ and $\rm CD8\sp+$ T cells. Interestingly, the $\rm A\sp{k}$ requirement can be substituted by IL-2 because transfection of $\rm K\sp{k}$-positive/A$\sp{\rm k}$-negative K1735 cells with the IL-2 gene also resulted in abrogation of tumorigenicity in normal C3H mice but not in nude mice. In addition, 1735 $(\rm I\sp+II\sp+)$ transfected cells can function as antigen presenting cells (APC) since they could process and present native hen egg lysozyme (HEL) to HEL specific T cell hybridomas. Furthermore, the transplantation immunity induced by K1735 transfectants expressing both $\rm K\sp{k}$ and $\rm A\sp{k}$ molecules completely cross-protected mice against challenge with $\rm K\sp{k}$-positive transfectants but weakly protected them against challenge with parental K1735 cells or $\rm A\sp{k}$-positive transfectants. Finally, I demonstrated that MHC $(\rm I\sp+II\sp+)$ or $\rm K\sp{k}$-positive/IL-2-positive cells can function as anti-cancer vaccines since they can abrogate the growth of established tumors and metastasis.^ In summary, my results indicate that expression of either MHC class I or II molecule alone is insufficient to cause the rejection of K1735 melanoma in syngeneic hosts and that both molecules are necessary. In addition, my data suggest that the failure of $\rm K\sp{k}$-positive K1735 cells to induce a primary tumor-rejection response in normal C3H mice may be due to their inability to induce the helper arm of the anti-tumor immune response. Finally, the ability of MHC $(\rm I\sp+II\sp+)$ or $\rm K\sp{k}$-positive/IL-2-positive cells to prevent growth of established tumors or metastasis suggests that these cell lines can serve as potential vaccines for the immunotherapy of cancer. (Abstract shortened by UMI.) ^

Multisite phosphorylation of ornithine decarboxylase in transformed macrophages

Ornithine decarboxylase (ODC), the initial inducible enzyme in the polyamine biosynthetic pathway, exists in the transformed macrophage RAW264 cell line as a phosphoprotein following cell stimulation. The hypothesis that ODC is phosphorylated at multiple sites in stimulated RAW264 cells was investigated. ODC isolated from tetradecanoyl-phorbol-13-acetate (TPA)-stimulated cells metabolically radiolabeled in the presence of $\sp{32}$P$\sb{\rm i}$ was subjected to cyanogen bromide (CNBr) cleavage followed by phosphopeptide mapping and two dimensional phosphoamino acid analysis. These phosphorylation studies demonstrated six in situ phosphorylated CNBr-generated fragments having apparent molecular weights of 17, 14.3, 8, 6.5, 4, and 2.7 kDa and also revealed that ODC is phosphorylated in RAW264 cells on at least 5 serine and 2 threonine residues.^ In addition, the in vivo specific activity and phosphorylation pattern of ODC in response to various kinase cascade stimulants was studied. A differential response in ODC specific activity and a variation in the relative distribution of $\sp{32}$P-labeling of serine and threonine residues on the ODC molecule was noted in response to fetal bovine serum, cAMP and isobutylmethylxanthine, lipopolysaccharide, or TPA.^ Based on information derived from consensus sequence motifs, three protein kinases responsible for the phosphorylation of ODC in vitro were identified. Purified ODC was phosphorylated in vitro by casein kinase II (CK II), extracellular signal-regulated kinase 1 (ERK1), and its activator, extracellular signal-regulated kinase kinase (MEK). CK II phosphorylated ODC on serine residues contained on three CNBr-generated peptides with apparent molecular weights of 14.3, 6.5, and 2.7 kDa. Both ERK1 and MEK phosphorylated ODC on serine and threonine residues on a CNBr-generated peptide fragment with an apparent molecular weight of 6.5 kDa. The in vitro radiolabeled peptides corresponded in molecular mass with some of the CNBr fragments of ODC phosphorylated in situ in stimulated RAW264 cells.^ This study concludes that ODC is phosphorylated in the transformed macrophage RAW264 cell line at multiple sites in response to various kinase cascade stimulants. These stimulants also led to a differential response in specific activity and phosphorylation pattern of ODC in RAW264 cells. Three protein kinases have been identified which phosphorylate ODC in vitro on peptides and amino acid residues which correspond with those phosphorylated in situ. ^

The processing of human pro-tumor necrosis factor

Human pro-TNF-$\alpha$ is a 26 kd type II transmembrane protein, and it is the precursor of 17 kd mature TNF. Pro-TNF release mature from its extracellular domain by proteolytic cleavage between resideu Ava ($-$1) and Val (+1). Both forms of TNF are biologically active and the native form of mature TNF is a bell-shaped trimer. The structure of pro-TNF was studied both in intact cell system and in an in vitro translation system by chemical crosslinking. We found that human pro-TNF protein exist as a trimer in intact cells (LPS-induced THP-1 cells and TNF cDNA transfected COS-3 cells) and this trimeric structure is assembled intracellularly, possibly in the ER. By analysis several deletion mutants, we observed a correlation between expression of pro-TNF cytotoxicity in a juxtacrine fashion and detection of the trimer, suggesting the trimeric structure is very important for its biologic activity. With a series of deletion mutants in the linking domain, we found that the small deletion did not block the cleavage and large deletion did regardless of the presence or absence of the native cleavage site, suggesting that the length of the residues between the plasma membrane and the base of the trimer determines the rate of the cleavage, possibly by blocking the accessibility of the cleavage enzyme to its action site. Our data also suggest that the native cleavage site is not sufficient for the release of mature TNF and alternative cleavage site(s) exists. ^

Studies on the role of BCR in Philadelphia chromosome-positive leukemias

It is well established that the chimeric Bcr-Abl oncoprotein resulting from fusing 3$\sp\prime$ ABL sequences on chromosome 9 to 5$\sp\prime$ BCR sequences on chromosome 22 is the primary cause of Philadelphia chromosome-positive (Ph$\sp1$) leukemias. Although it is clear that the cis-Bcr sequence present within Bcr-Abl is able to activate the tyrosine kinase activity and F-actin binding capacity of Bcr-Abl which is critical for the transforming ability of BCR-ABL, the biological role of normal BCR gene product (P160 BCR) remains largely unknown. The previous finding by our lab that P160 BCR forms stable complexes with Bcr-Abl oncoprotein in Ph$\sp1$-positive leukemic cells implicated P160 BCR in the pathogenesis of Ph$\sp1$-positive leukemias. Here, we demonstrated that P160 BCR physically interacts with P210 BCR-ABL and become tyrosine phosphorylated when co-expressed with P210 BCR-ABL in COS1 cells while no tyrosine phosphorylation of P160 BCR can be detected when it is expressed alone. The results suggest that P160 BCR is a target for the Bcr-Abl tyrosine kinase. Although we were unable to detect stable physical interaction between P160 BCR and P145 c-ABL (Ib) in COS1 cells overexpressing both proteins, P160 BCR was phosphorylated on tyrosine residues when co-expressed with activated tyrosine kinase of P145 c-ABL (Ib). In addition, studies of tyrosine phosphorylation of BCR deletion mutants and 2-dimensional tryptic mapping of in vitro phosphorylated wild type and mutant (tyrosine to phenylalanine) Bcr-Abl indicated that tyrosine 177, 283 and 360 of Bcr represent some of the phosphorylation sites. Even though the significance of tyrosine phosphorylation of residues 283 and 360 of Bcr has not been determined, tyrosine phosphorylation of residue 177 within Bcr-Abl has been reported to be critical for its interaction with Grb2 molecule and subsequent activation of Ras signaling pathway. Here, we further demonstrated that tyrosine 177 phosphorylated P160 BCR is also able to bind to Grb2 molecule suggesting the role of P160 BCR in the Ras signaling pathway.^ Surprisingly, using 3$\sp\prime$ BCR antisense oligonucleotide to reduce the expression of P160 BCR without interfering with the expression of BCR-ABL resulted in increased growth or survival of B15 cells and M3.16 cells expressing either P185 BCR-ABL or P210 BCR-ABL respectively. The results provided strong arguments that P160 BCR may function as a negative regulator for cell growth.^ Considering all these results, we hypothesize that P160 BCR negatively regulate cell growth and tyrosine phosphorylation of P160 BCR turns off its growth suppressor function and turns on its growth stimulatory function. We further speculate that Bcr-Abl oncoprotein in leukemia cells stably interacts with and constitutively phosphorylates portions of P160 BCR converting it into a growth stimulatory state. In normal cells, the growth suppressor effects of P160 BCR could only be transiently and conditionally switched to growth stimulatory action by a strictly regulated cellular tyrosine kinase such as c-ABL. The model will be further discussed in the text. ^