A Interview with Professor Carl May, Head of Research, Faculty of Health Sciences

13 minute interview in which Professor May discusses his thoughts on the purpose of clinical research.

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

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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]

The biology and mechanism of chemoresistance of brain metastases

Primary brain neoplasms and metastases to the brain are generally resistant to systemic chemotherapy. The purpose of theses studies was to determine the mechanism(s) for this resistance. We have developed a model to study the biology of brain metastasis by injecting metastatic K1735 melanoma cells into the carotid artery of syngeneic C3H/HeN or nude mice. The resulting brain lesions are produced in the parenchyma of the brain. Mice with subcutaneous or brain melanoma lesions were treated intravenously with doxorubicin (DXR) (7 mg/kg). The s.c. lesions regressed in most of the mice whereas no therapeutic benefits were produced in mice with brain metastases. The intravenous injection of sodium fluorescine revealed that the blood-brain barrier (BBB) is intact in and around brain metastases smaller than 0.2 mm$\sp2$ but not in larger lesions, implying that the BBB is not a major obstacle for chemotherapy of brain metastases.^ Western blot and FACS analyses revealed that K1735 melanoma brain metastases expressed high levels of P-glycoprotein (P-gp) as compared to s.c. tumors or in vitro cultures. Similarly, K1735 cells from brain metastases expressed higher levels of mdrl mRNA. This increased expression of mdrl was due to adaptation to the local brain environment. We base this conclusion on the results of two studies. First, K1735 cells from brain metastases cultured for 7 days lost the high mdrl expression. Second, in crossover experiments K1735 cells from s.c. tumors (low mdrl expression) implanted into the brain exhibited high levels of mdrl expression whereas cells from brain metastases implanted s.c. lost the high level mdrl expression.^ To investigate the mechanism by which the brain environment upregulates mdrl expression of the K1735 cells we first studied the regulation of P-gp in brain endothelial cells. Since astrocytes are closely linked with the BBB we cocultured brain endothelial cells for 3 days with astrocytes. These endothelial cells expressed high levels of mdrl mRNA and protein whereas endothelial cells cocultured with endothelial cells or fibroblasts did not. We next cocultured K1735 melanoma cells with astrocytes. Here again, astrocytes (but not fibroblasts or tumor cells) uprelated the mdrl expression in K1735 tumor cells. This upregulation inversely correlated with intracellular drug accumulation and sensitivity to DXR.^ The data conclude that the resistance of melanoma brain metastases to chemotherapy is not due to an intact BBB but to the upregulation of the mdrl gene by the organ microenvironment, i.e., the astrocytes. This epigenetic mediated resistance to chemotherapy has wide implications for the therapy of brain metastases. ^

Ovarian cancer angiogenesis, biology and therapy

The progressive growth of epithelial ovarian cancer tumor is regulated by proangiogenic molecules and growth factors released by tumor cells and the microenvironment. Previous studies showed that the expression of interleukin-8 (IL-8) directly correlates with the progression of human ovarian carcinomas implanted into the peritoneal cavity of nude mice. We examined the expression level of IL-8 in archival specimens of primary human ovarian carcinoma from patients undergoing curative surgery by in situ mRNA hybridization technique. The expression of IL-8 was significantly higher in patients with stage III disease than in patients with stage I disease. To investigate the role of IL-8 in the progressive growth of ovarian cancer, we isolated high- and low-IL-8 producing clones from parental Hey-A8 human ovarian cancer cells, and compared their proliferative activity and tumorigenicity in nude mice. The effect of exogenous IL-8 and IL-8 neutralizing antibody on ovarian cancer cell proliferation was investigated. Finally, we studied the modulation of IL-8 expression in ovarian cancer cells by sense and antisense IL-8 expression vector transfection and its effect on proliferation and tumorigenicity. We concluded that IL-8 has a direct growth potentiating activity in human ovarian cancer cells. ^ The expression level of IL-8 directly correlates with disease progression of human ovarian cancer, but the mechanism of induction is unknown. Since hypoxia and acidic pH are common features in solid tumors, we determined whether hypoxic and acidic conditions could regulate the expression of IL-8. Culturing the human ovarian cancer cells in hypoxic or acidic medium led to a significant increase in IL-8 mRNA and protein. Hypoxic- and acidosis-mediated transient increase in IL-8 expression involved both transcriptional activation of the IL-8 gene and enhanced stability of the IL-8 mRNA. Furthermore, we showed that IL-8 transcription activation by hypoxia or acidosis required the cooperation of NF-κB and AP-1 binding sites. ^ Finally, we studied novel therapies against human ovarian cancer. First, we determined whether inhibition of the catalytic tyrosine kinase activity of the receptors for vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) inhibits the formation of malignant ascites and the progressive growth of human ovarian carcinoma cells implanted into the peritoneal cavity of nude mice. Our results suggest that blockade of the VEGF/VPF receptor may be an efficient strategy to inhibit formation of malignant ascites and growth of VEGF/VPF-dependent human ovarian carcinomas. Secondly, we determined whether local sustained production of murine interferon-β could inhibit the growth of human ovarian cancer cells in the peritoneal cavity of nude mice. Our results showed that local production of IFN-β could inhibit the in vivo growth of human ovarian cancer cells by upregulating the expression of the inducible nitric oxide synthase (NOS) in host macrophages. ^

Modeling a health promotion campaign process

In this work we will present a model that describes how the number of healthy and unhealthy subjects that belong to a cohort, changes through time when there are occurrences of health promotion campaigns aiming to change the undesirable behavior. This model also includes immigration and emigration components for each group and a component taking into account when a subject that used to perform a healthy behavior changes to perform the unhealthy behavior. We will express the model in terms of a bivariate probability generating function and in addition we will simulate the model. ^ An illustrative example on how to apply the model to the promotion of condom use among adolescents will be created and we will use it to compare the results obtained from the simulations and the results obtained by the probability generating function. ^

Insights into the biology of lymphatic metastasis

Recent data suggest that the generation of new lymphatic vessels (i.e. lymphangiogenesis) may be a rate-limiting step in the dissemination of tumor cells to regional lymph nodes. However, efforts to study the cellular and molecular interactions that take place between tumor cells and lymphatic endothelial cells have been limited due to a lack of lymphatic endothelial cell lines available for study. ^ I have used a microsurgical approach to establish conditionally immortalized lymphatic endothelial cell lines from the afferent mesenteric lymphatic vessels of mice. Characterization of lymphatic endothelial cells, and tumor-associated lymphatic vessels revealed high expression levels of VCAM-1, which is known to facilitate adhesion of some tumor cells to vascular endothelial cells. Further investigation revealed that murine melanoma cells selected for high expression of α4, a counter-receptor for VCAM-1, demonstrated enhanced adhesion to lymphatic endothelial cells in vitro, and increased tumorigenicity and lymphatic metastasis in vivo, despite similar lymphatic vessel numbers. ^ Next, I examined the effects of growth factors that regulate lymphangiogenesis, and report that several growth factors are capable of activating survival and proliferation pathways of lymphatic endothelial cells. The dual protein tyrosine kinase inhibitor AEE788 (EGFR and VEGFR-2) inhibited the activation of Akt and MAPK in lymphatic endothelial cells responding to multiple growth factors. Moreover, oral treatment of mice with AEE788 decreased lymphatic vessel density and production of lymphatic metastasis by human colon cancer cells growing in the cecum of nude mice. ^ In the last set of experiments, I investigated the surgical management of lymphatic metastasis using a novel model of sentinel lymphadenectomy in live mice bearing subcutaneous B16-BL6 melanoma. The data demonstrate that this procedure when combined with wide excision of the primary melanoma, significantly enhanced survival of syngeneic C57BL/6 mice. ^ Collectively, these results indicate that the production of lymphatic metastasis depends on lymphangiogenesis, tumor cell adhesion to lymphatic endothelial cells, and proliferation of tumor cells in lymph nodes. Thus, lymphatic metastasis is a multi-step, complex, and active process that depends upon multiple interactions between tumor cells and tumor associated lymphatic endothelial cells. ^