27 resultados para Biology, Neuroscience|Biology, Genetics|Health Sciences, Public Health


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During their transitional period from childhood to adulthood, adolescents engage in risk-taking behaviors that become public health concerns. It is important for school health education professionals to design instructional programs that focus on adolescents' developmental needs and foster healthier lifestyles. The goal of health education is to help students acquire health skills that are necessary to succeed in school and in life. This is especially important because the increase in teenagers' risky behaviors can affect their health, well being, and eventually the course of their lives. ^ This study examined the effects of health education on health-related behaviors of public high school students. A multivariate analysis of variance was conducted to determine whether the comprehensive approach based on The Jessors' Problem Behavior Theory (PBT) had a greater impact on adolescents' risk-taking behaviors than the traditional approach. After 18 weeks of health instruction using one of these approaches, the Youth Risk Behavior Survey (YRBS) was administered to measure the level of subjects' self-reported behaviors in six categories of adolescent risky behaviors: the use of tobacco; the use of alcohol and other drugs; engagement in injurious activities; consumption of unhealthy diet; an inadequate level of participation in physical activities; and engagement in risky sexual activities. ^ The results of this study did not support the hypothesis that using the comprehensive health education approach was more influential than the traditional health education approach in improving students' health-risk behaviors. Further research studies based on bio-psychosocial theories are needed to develop and evaluate methods of instruction and delivery of health skills. ^

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In the first part of this study human immunodeficiency virus type 1 (HIV-1) proviral DNA sequences derived from 201 clones of the C2-V3 env region and the first exon of the tat gene were obtained from six MV-1 infected heterosexual couples. These molecular data were used to confirm the epidemiological relationships. The ability of the molecular data to draw such conclusions was also tested with multiple phylogenetic analyses. The tat region was much more useful in establishing epidemiological relationships than the commonly used C2-V3.^ Subsequently, using nucleotide sequences from the first exon of the Tat gene, we tested the hypothesis that a Florida dentist (a common source) infected five of his patients in the course of dental procedures, against the null hypothesis that the dentist and each individual of the dental group independently acquired the virus within the local community. Multiple phylogenetic analyses demonstrated that the sequences of the five patients were significantly more related to each other than to sequences of the controls. Our results using Tat sequences, combined with envelope sequence data, strongly support a common phylogenetic epidemiological relationship among these five patients.^ A third study is presented, which deals with the effects of genomic variations in drug resistance. HIV-1 reverse transcriptase (RT) mutations were detected in DNA from peripheral blood mononuclear cells from 11 of 12 HIV-infected children after 11-20 months of zidovudine monotherapy. The codon 41/215 mutant combination was associated with general decline in health status. Patients developing the codon 70 mutation tended to have a better health status. ^

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Twelve plants used medicinally in Callejon de Huaylas, Department of Ancash, northeastern Peru were selected and screened in vitro for cytotoxic and cytostatic activities. Traditional preparations, aqueous extracts and organic extracts (methanol:dimethyl chloride) were tested against murine leukemia P388 cells using flow cytometry. Seventy-five percent or more of the traditional and aqueous extracts were cytostatic at concentrations of 1mg/ml. For organic extracts, cytostatic activity ranged from 8.3% (at 6.25 μg/ml) to 58.3% (at 100 μg/ml). Quinchamalium procumbens, Ophryosporus chilca and Baccharis genistelloides showed strong activity. Extracts of Brachyotum rostratum, Monnina salicifolia, and Orthrosanthus chimboracensis were particularly interesting, since they were cytostatic but not cytotoxic at concentrations of 0.5 mg/ml. These Andean plants merit further analysis. The high percentage of activity found among the traditional preparations suggests that the traditional medical knowledge of Callejon de Huaylas healers deserves respect and merits further research. ^

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The health status of wild and captive Atlantic Bottlenose dolphins ( Tersiops truncatis) is difficult to ascertain. Mass strandings of these animals have been attributed to pollutants, as well as bacterial infections. Using human Enzyme Linked Immuno-Assays (ELISA) for immunological cytokines, I measured soluble cytokine levels with respect to their health status. In a retrospective analysis of dolphin sera, there was a trend of higher cytokine levels in “sick” animals. I cultured dolphin lymphocytes in the presence of a mitogen (PHA), a super antigen (Staph-A), Lipopolysaccharide (LPS), and a calcium flux inducer (PMA). Levels of messenger RNA, from these cultured cells, were assayed with Polymerase Chain Reaction (PCR) using primers for the human cytokines IL-2, IL-4, IL-6, IL-10, Tumor Necrosis Factor, and Interferon gamma. Only IL-4, IL-6, and IL-10 messages were obtained, inferring similar nucleotide homology to the human primer sequences. The PCR products were sequenced. Sixteen IL-4 sequences, twelve IL-6 sequences and seven IL-10 sequences were obtained and analyzed. Each cytokine exhibited the same nucleotide sequence in all dolphins examined. There was no difference in the cytokine profile in response to the various stimuli. The derived amino acid composition for each of the dolphin cytokines was used for molecular modeling, which showed that dolphin IL-4, IL-6, and IL-10 were structurally similar to the corresponding proteins of Perissodactyla. ^

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The immune system is composed of innate and adaptive mechanisms. Innate immune responses are significantly modulated by immunomodulatory factors that act through the induction of specific patterns of cytokine production in responding cells. Human leukocytes have been shown to respond to substance(s) present in acid extracts of commercial shark cartilage (SC). Shark cartilage is a food supplement taken by consumers as a prophylaxis and for the treatment of conditions ranging from arthritis to cancer. No reliable scientific evidence in the literature supports the alleged usefulness of shark cartilage supplements, but their use remains popular. Cartilage extracts exhibit immunomodulatory properties by inducing various inflammatory, Th1-type cytokines and potent chemokines in human peripheral blood leukocytes (HPBL) in vitro. The objectives of the study were to (1) to determine the nature of the active component(s), (2) to define the scope of cellular response to SC extract, and (3) to elucidate the molecular mechanisms underlying bioactivity. Results showed that there are at least two cytokine-inducing components which are acid stable. One anionic component has been identified as a small (14-21 kDa) glycoprotein with at least 40% carbohydrate content. Shark cartilage stimulated HPBL to produce cytokines resembling an inflammatory, Th1 polarized response. Leukocyte-specific responses consist of both initial cytokine responses to SC directly (i.e., TNF-α) and secondary responses such as the IFN-γ response by lymphocytes following initial SC stimulation. Response of RAW cells, a murine macrophage cell line, indicated that TNF-á could be induced in macrophages of another mammalian species in the absence of other cell types. The results suggest that the human monocyte/macrophage is most likely to be the initial responding cell to SC stimulation. Stimulation of cells appears to engage at least one ligand-receptor interaction with TLR 4, although the role of TLR 2 cannot be ruled out. Initial activation is likely followed by the activation of the JNK and p38 MAPK signal transduction pathways resulting in activation, release, and translocation of transcription factor nuclear factor κB (Nf-κB). This dissertation research study represents the first in-depth study into characterizing the bioactive component(s) of commercial shark cartilage responsible for its immunomodulating properties and defining cellular responses at the molecular level.

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Infectious diarrhea results in 2 to 5 million deaths worldwide per year, and treatments that are safe, effective, and readily available are under investigation. The field of medicinal ethnobotany focuses on plants that are used by different cultural groups for treating various diseases and evaluates these plants for efficacy and cytotoxicity. In the present study, ethnobotanical research was conducted with Central Anatolian villagers in Turkey. Folk concepts and etiologies surrounding diarrhea were analyzed, as were salient plant-based remedies for diarrhea. Reviewing the literature, 91 plant species were described as anti-diarrheal in all of Turkey. In Central Anatolia, villagers described 35 species. For continued research via bactericidal and bacteriostatic bioassays, 15 plants were selected. Methanolic and aqueous extracts of medicinally used plant parts were evaluated for inhibitory properties against 10 diarrhea-causing bacteria in the first bioassay, and later 21 bacteria in a second assay utilizing spectrophotometry. The cytotoxic properties were also evaluated in an Alamar Blue Assay using HepG-2, PC-3, and SkMEL-5 human cell lines. While several extracts showed bactericidal and bacteriostatic properties, the methanolic extract of R. canina galls inhibited the most bacteria at the lowest concentrations. They were not cytotoxic. Thus, R. canina methanolic gall extracts were selected for bio-assay guided fractionation. Antibacterial activity was maintained in the third fraction which was composed of almost pure ellagic acid. The bioassay was repeated with standard ellagic acid, and the polyphenol retained potency in inhibiting multiple bacterial strains. Several other extracts showed promise for safe, effective anti-bacterial remedies for diarrhea.

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The etiology of central nervous system tumors (CNSTs) is mainly unknown. Aside from extremely rare genetic conditions, such as neurofibromatosis and tuberous sclerosis, the only unequivocally identified risk factor is exposure to ionizing radiation, and this explains only a very small fraction of cases. Using meta-analysis, gene networking and bioinformatics methods, this dissertation explored the hypothesis that environmental exposures produce genetic and epigenetic alterations that may be involved in the etiology of CNSTs. A meta-analysis of epidemiological studies of pesticides and pediatric brain tumors revealed a significantly increased risk of brain tumors among children whose mothers had farm-related exposures during pregnancy. A dose response was recognized when this risk estimate was compared to those for risk of brain tumors from maternal exposure to non-agricultural pesticides during pregnancy, and risk of brain tumors among children exposed to agricultural activities. Through meta-analysis of several microarray studies which compared normal tissue to astrocytomas, we were able to identify a list of 554 genes which were differentially expressed in the majority of astrocytomas. Many of these genes have in fact been implicated in development of astrocytoma, including EGFR, HIF-1α, c-Myc, WNT5A, and IDH3A. Reverse engineering of these 554 genes using Bayesian network analysis produced a gene network for each grade of astrocytoma (Grade I-IV), and ‘key genes’ within each grade were identified. Genes found to be most influential to development of the highest grade of astrocytoma, Glioblastoma multiforme (GBM) were: COL4A1, EGFR, BTF3, MPP2, RAB31, CDK4, CD99, ANXA2, TOP2A, and SERBP1. Lastly, bioinformatics analysis of environmental databases and curated published results on GBM was able to identify numerous potential pathways and geneenvironment interactions that may play key roles in astrocytoma development. Findings from this research have strong potential to advance our understanding of the etiology and susceptibility to CNSTs. Validation of our ‘key genes’ and pathways could potentially lead to useful tools for early detection and novel therapeutic options for these tumors.

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Coral diseases were unknown in the scientific community fifty years ago. Since the discovery of a coral disease in 1965, there has been an exponential increase in the number of known coral diseases, as the abundance, prevalence, distribution, and number of host species affected has also significantly increased. Coral diseases are recognized as contributing significantly to the dramatic losses of coral cover on a global basis, particularly in the Caribbean. The apparent sudden emergence of coral diseases suggests that they may be a symptom of an overall trend associated with changing environmental conditions. However, not much evidence has been gathered to address this question. The following studies were designed to build a comprehensive argument to support this hypothesis for one important coral disease—black band disease (BBD). A meta-analysis of clone libraries identifying the microbial communities associated with BBD reveal important information including that a single cyanobacterial operational taxonomic unit (OTU) was by far the most prevalent OTU in diseased samples, and that the alphaproteobacteria, which include some of the most common bacteria in marine waters, were the most diversely represented. The analysis also showed that samples exhibited regional similarities. An fine and ultrastructural characterization of the disease revealed that the cyanobacteria are prolific borers through the coral skeleton, and that the cyanobacteria penetrate coral tissue, leading to their presence ahead of the main migrating disease band. It was further found that apparently healthy corals exposed to toxins found in BBD, exhibited similar tissue degradation to those infected with BBD. Comparing the disease progression to biofilm formation, it was determined that scouting cyanobacteria may contribute to the migration of the disease through progressive biofilm development over intact coral tissue. Together, these studies provide significant evidence for the hypothesis that BBD is an opportunistic disease, caused by common environmental bacteria, facilitated by the changing environmental conditions associated with climate change.

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In the 1980s, government agencies sought to utilize research on drug use prevention to design media campaigns. Enlisting the assistance of the national media, several campaigns were designed and initiated to bring anti-drug use messages to adolescents in the form of public service advertising. This research explores the sources of information selected by adolescents in grades 7 through 12 and how the selection of media and other sources of information relate to drug use behavior and attitudes and perceptions related to risk/harm and disapproval of friends' drug-using activities.^ Data collected from 1989 to 1992 in the Miami Coalition School Survey provided a random selection of secondary school studies. The responses of these students were analyzed using multivariate statistical techniques.^ Although many of the students selected media as the source for most of their information on the effects of drugs on the people who use them, the selection of media was found to be positively related to alcohol use and negatively related to marijuana use. The selection of friends, brothers, or sisters was a statistically significant source for adolescents who smoke cigarettes, use alcohol or marijuana.^ The results indicate that the anti-drug use messages received by students may be canceled out by media messages perceived to advocate substance use and that a more persuasive source of information for adolescents may be friends and siblings. As federal reports suggest that the economic costs of drug abuse will reach an estimated $150 billion by 1997 if current trends continue, prevention policy that addresses the glamorization of substance use remains a national priority. Additionally, programs that advocate prevention within the peer cluster must be supported, as peers are an influential source for both inspiring and possibly preventing drug use behavior. ^

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The eggs of the dengue fever vector Aedes aegypti possess the ability to undergo an extended quiescence period hosting a fully developed first instar larvae within its chorion. As a result of this life history stage, pharate larvae can withstand months of dormancy inside the egg where they depend on stored reserves of maternal origin. This adaptation known as pharate first instar quiescence, allows A. aegypti to cope with fluctuations in water availability. An examination of this fundamental adaptation has shown that there are trade-offs associated with it. ^ Aedes aegypti mosquitoes are frequently associated with urban habitats that may contain metal pollution. My research has demonstrated that the duration of this quiescence and the extent of nutritional depletion associated with it affects the physiology and survival of larvae that hatch in a suboptimal habitat; nutrient reserves decrease during pharate first instar quiescence and alter subsequent larval and adult fitness. The duration of quiescence compromises metal tolerance physiology and is coupled to a decrease in metallothionein mRNA levels. My findings also indicate that even low levels of environmentally relevant larval metal stress alter the parameters that determine vector capacity. ^ My research has also demonstrated that extended pharate first instar quiescence can elicit a plastic response resulting in an adult phenotype distinct from adults reared from short quiescence eggs. Extended pharate first instar quiescence affects the performance and reproductive fitness of the adult female mosquito as well as the nutritional status of its progeny via maternal effects in an adaptive manner, i.e., anticipatory phenotypic plasticity results as a consequence of the duration of pharate first instar quiescence and alternative phenotypes may exist for this mosquito with quiescence serving as a cue possibly signaling the environmental conditions that follow a dry period. M findings may explain, in part, A. aegypti's success as a vector and its geographic distribution and have implications for its vector capacity and control.^

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Melanocytes, pigment-producing cells, derive from the neural crest (NC), a population of pluripotent cells that arise from the dorsal aspect of the neural tube during embryogenesis. Many genes required for melanocyte development were identified using mouse pigmentation mutants. The deletion of the transcription factor Ets1 in mice results in hypopigmentation; nevertheless, the function of Ets1 in melanocyte development is unknown. The goal of the present study was to establish the temporal requirement and role of Ets1 in murine melanocyte development. In the mouse, Ets1 is widely expressed in developing organs and tissues, including the NC. In the chick cranial NC, Ets1 is required for the expression of Sox10, a transcription factor critical for the development of melanocytes, enteric ganglia, and other NC derivatives. ^ Using a combination of immunofluorescence and cell survival assays Ets1 was found to be required between embryonic days 10 and 11, when it regulates NC cell and melanocyte precursor (melanoblast) survival. Given the requirement of Ets1 for Sox10 expression in the chick cranial NC, a potential interaction between these genes was investigated. Using genetic crosses, a synergistic genetic interaction between Ets1 and Sox10 in melanocyte development was found. Since Sox10 is essential for enteric ganglia formation, the importance of Ets1 on gut innervation was also examined. In mice, Ets1 deletion led to decreased gut innervation, which was exacerbated by Sox10 heterozygosity. ^ At the molecular level, Ets1 was found to activate a Sox10 enhancer critical for Sox10 expression in melanoblasts. Furthermore, mutating Ets1 at a site I characterized in the spontaneous variable spotting mouse pigmentation mutant, led to a 2-fold decrease in enhancer activation. Overexpression and knockdown of Ets1 did not affect Sox10 expression; nonetheless, Ets1 knockdown led to a 6-fold upregulation of the transcription factor Sox9, a gene required for melanocyte and chondrocyte development, but which impairs melanocyte development when its expression is prolonged. Together, these results suggest that Ets1 is required early during melanocyte development for NC cell and melanoblast survival, possibly acting upstream of Sox10. The transcription factor Ets1 may also act indirectly in melanocyte fate specification by repressing Sox9 expression, and consequently cartilage fate.^

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Memory deficits and executive dysfunction are highly prevalent among HIV-infected adults. These conditions can affect their quality of life, antiretroviral adherence, and HIV risk behaviors. Several factors have been suggested including the role of genetics in relation to HIV disease progression. This dissertation aimed to determine whether genetic differences in HIV-infected individuals were correlated with impaired memory, cognitive flexibility and executive function and whether cognitive decline moderated alcohol use and sexual transmission risk behaviors among HIV-infected alcohol abusers participating in an NIH-funded clinical trial comparing the efficacy of the adapted Holistic Health Recovery Program (HHRP-A) intervention to a Health Promotion Control (HPC) condition in reducing risk behaviors. A total of 267 individuals were genotyped for polymorphisms in the dopamine and serotonin gene systems. Results yielded significant associations for TPH2, GALM, DRD2 and DRD4 genetic variants with impaired executive function, cognitive flexibility and memory. SNPs TPH2 rs4570625 and DRD2 rs6277 showed a risk association with executive function (odds ratio = 2.5, p = .02; 3.6, p = .001). GALM rs6741892 was associated with impaired memory (odds ratio = 1.9, p = .006). At the six-month follow-up, HHRP-A participants were less likely to report trading sex for food, drugs and money (20.0%) and unprotected insertive or receptive oral (11.6%) or vaginal and/or anal sex (3.2%) than HPC participants (49.4%, p