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Biomedical subjects

D Gregory

Publications and source records attributed to D Gregory.

At least 19 recordsLinked to original sources

Efficient replication by herpes simplex virus type 1 involves activation of the IkappaB kinase-IkappaB-p65 pathway.

Infection by herpes simplex virus type 1 (HSV-1) induces a persistent nuclear translocation of NFkappaB. To identify upstream effectors of NFkappaB and their effect on virus replication, we employed mouse embryo fibroblast (MEF)-derived cell lines with deletions of either IKK1 or IKK2, the catalytic subunits of the IkappaB kinase (IKK) complex. Infected MEFs were assayed for virus yield, loss of IkappaBalpha, nuclear translocation of p65, and NFkappaB DNA-binding activity. Absence of either IKK1 or IKK2 resulted in an 86 to 94% loss of virus yield compared to that of normal MEFs, little or no loss of IkappaBalpha, and greatly reduced NFkappaB nuclear translocation. Consistent with reduced virus yield, accumulation of the late proteins VP16 and gC was severely depressed. Infection of normal MEFs, Hep2, or A549 cells with an adenovirus vector expressing a dominant-negative (DN) IkappaBalpha, followed by superinfection with HSV, resulted in a 98% drop in virus yield. These results indicate that the IKK-IkappaB-p65 pathway activates NFkappaB after virus infection. Analysis of NFkappaB activation and virus replication in control and double-stranded RNA-activated protein kinase-null MEFs indicated that this kinase plays no role in the NFkappaB activation pathway. Finally, in cells where NFkappaB was blocked because of DNIkappaB expression, HSV failed to suppress two markers of apoptosis, cell surface Annexin V staining and PARP cleavage. These results support a model in which activation of NFkappaB promotes efficient replication by HSV, at least in part by suppressing a host innate response to virus infection.

Animals↗

v-Jun stimulates both cdk2 kinase activity and G1/S progression via transcriptional repression of p21 CIP1.

Previous studies have shown that the viral Jun (v-Jun) oncoprotein induces marked alterations in cell cycle control, which are associated with, and may be caused by, increased cdk2 kinase activity. Since p21 CIP1 is an important regulator of cdk2, we investigated whether aberrant expression of this cyclin-dependent kinase inhibitor might contribute to cell cycle deregulation by v-Jun. We find that the basal levels of p21 CIP1 mRNA and protein expression are greatly reduced in chick embryo fibroblasts (CEF) transformed by v-Jun, and that v-Jun blocks the increases in p21 CIP1 expression that normally accompany growth inhibition induced by serum deprivation or confluency in untransformed CEF. Importantly, ectopic expression of p21 CIP1 in v-Jun-transformed CEF inhibits both cdk2 kinase activity and cell cycle progression, indicating that these alterations in p21 CIP1 expression are likely to be functionally significant for growth deregulation. We also investigated the mechanism through which v-Jun disturbs p21 CIP1 expression and the possible involvement of a known p21 CIP1 regulator, p53, as an intermediate in this process. This analysis revealed that repression is mediated primarily at the level of p21 CIP1 gene transcription, however the mechanism is complex; both p53-dependent and -independent mechanisms contribute as judged by analysis of p21 CIP1 promoter mutants and other assays of p53 transcriptional activity.

Amino Acid Sequence↗

Structural studies of biomaterials using double-quantum solid-state NMR spectroscopy.

Proteins directly control the nucleation and growth of biominerals, but the details of molecular recognition at the protein-biomineral interface remain poorly understood. The elucidation of recognition mechanisms at this interface may provide design principles for advanced materials development in medical and ceramic composites technologies. Here, we describe both the theory and practice of double-quantum solid-state NMR (ssNMR) structure-determination techniques, as they are used to determine the secondary structures of surface-adsorbed peptides and proteins. In particular, we have used ssNMR dipolar techniques to provide the first high-resolution structural and dynamic characterization of a hydrated biomineralization protein, salivary statherin, adsorbed to its biologically relevant hydroxyapatite (HAP) surface. Here, we also review NMR data on peptides designed to adsorb from aqueous solutions onto highly porous hydrophobic surfaces with specific helical secondary structures. The adsorption or covalent attachment of biological macromolecules onto polymer materials to improve their biocompatibility has been pursued using a variety of approaches, but key to understanding their efficacy is the verification of the structure and dynamics of the immobilized biomolecules using double-quantum ssNMR spectroscopy.

Amino Acid Sequence↗

Economic impact of beta blockade in heart failure.

We reviewed the literature on clinical trials of beta-adrenergic blockade for treatment of heart failure, seeking evidence of reductions in hospital admissions. To analyze the economic implications of six clinical trials, we developed a stochastic cost model to generate estimates of total medical costs resulting from heart failure and related causes. The model includes inpatient, outpatient, and professional cost estimates based on Medicare claims data, and it is driven by traditional endpoint statistics reported in the clinical trial literature. It provides a common framework for comparing cost effectiveness across clinical trials in the absence of detailed cost information collected in the trial. The incremental expected cost per year of life saved is $3,300 for bisoprolol, $2,500 for metoprolol, and $6,700 for carvedilol. The cost per year of life saved for each compound is well below accepted standards for cost effectiveness. These results are sensitive to the cost of drug therapy and the relative mortality rate for the experimental group. For example, if the relative mortality rate of the experimental group were to increase from the reported 40% to 82%, and if the annual cost of the drug were to decrease from $2,000 to $500, then we estimate that carvedilol would break even and the cost per year of life saved would drop to zero. Whether beta-blocker therapy, as assumed, sustains its differential effectiveness in terms of relative mortality risk beyond the study duration has not been demonstrated.

Adrenergic beta-Antagonists↗

The impact of ferrous ion reduction of chlorite ion on drinking water process performance.

The use of chlorine dioxide (ClO2) as a primary disinfectant and pre-oxidant in drinking water treatment is being explored as an alternative to chlorine for reducing disinfection by-product formation and to assure compliance with United States Environmental Protection Agency's Stage 1 Disinfection/ Disinfection By-Products Rule. However, the ClO2 by-product chlorite ion (ClO2-) is also regulated by the same regulation. Ferrous iron (Fe(II)) has been shown to effectively reduce chlorite ion to chloride ion (Cl-) and this study was conducted to evaluate the impact on overall treatment process performance due to the ferric hydroxide solids that form from the reaction. Ferrous iron application was explored at three different points in a pilot-scale water treatment system: pre-rapid mix. pre-settling and pre-filter. Chlorite ion concentrations were effectively reduced from 2mg/L to less than 0.3mg/L using an Fe(II) dose of approximately 6mg/L for all trials. Fe(II) addition at the rapid mix caused no adverse effects and, in fact, allowed for reduction of the alum dose due to the newly formed ferric hydroxide acting as a supplemental coagulant. An increase of 241 and 247% of total suspended solids influent to the filter process was observed when Fe(II) was applied at the pre-settling and pre-filter locations. Pilot-scale filter runs during these trials were less than 2 h and never obtained true steady state conditions. Jar testing was performed to better understand the nature of the ferric hydroxide solids that are formed when Fe(II) was oxidized to Fe(III) and to explore the effectiveness of Fe(II) addition at intermediate stages in the flocculation process.

Chlorides↗

Patterns of recreational drug use at dance events in Edinburgh, Scotland.

AIMS: To describe the patterns of drug use at dance (rave) events in terms of prevalence, frequency, type of drugs used, patterns of use, access and risk-associated behaviours. DESIGN: Self-selecting participant-completed survey. SETTING: Three dance events in Edinburgh, Scotland, UK. PARTICIPANTS: One hundred and twenty-two drug users (57% males, 43% females), 90% of whom were in employment or education, with an age range of 16-47, 80% between 18 and 23 years. MEASUREMENTS: Participants who answered 'yes' to the question 'Have you used drugs for dance events in the past year' reported (i) the prevalence, types and frequency of drugs used; (ii) prevalence and contents of mixing drugs; (iii) accessing drugs; and (iv) engagement with drug-associated risk behaviours. FINDINGS: Over 80% of the participants had used ecstasy and amphetamine, over 30% cocaine and LSD; over 10% nitrites, psilocybin and ketamine and less than 5% had used crack or tranquillizers. Participants reported regular consumption of ecstasy and amphetamine (e.g. 35% used ecstasy and 25% amphetamine on a weekly basis) often taken in combination, with the occasional use of cocaine, LSD, ketamine and psilocybin. Poly- and mixing-drug behaviours were significantly more likely than monodrug usage. Drugs were accessed through friends than from any other source. Eighty-five per cent reported mixing drugs and/or alcohol, 35% driving on drugs, 36% having a bad experience on drugs; 30% unprotected sex; and 0.9% injecting drugs. Women in the sample reported higher consumption than men. CONCLUSIONS: Dance-drug use has a characteristic pattern that has implications for health promotion and criminal policy.

Adolescent↗

Prescribing patterns for asthma by general practitioners in six European countries.

To assess the level of concordance with international consensus on asthma management, we compared primary care prescribing patterns for asthma in different European countries. A prospective study of prescription items with an associated diagnostic label of asthma in patient consultations with a total of 235 general practitioners (GPs) from Belgium, England, Ireland, Italy, Northern Ireland, Portugal, Scotland and Spain was performed. A total of 101,544 consecutive consultations were recorded in autumns 1994 and 1995 of which 3595 (3.5%) were for patients with asthma and 3243 (3.2%) were for patients receiving a prescription for asthma. Overall, asthma consultations varied from 1.8% in Italy to 5.8% in Ireland (mean 3.4%, SD 1.6). Prescribed inhaled medications for children varied from 72% of the total asthma prescriptions in Ireland and Portugal to 82% in Northern Ireland (mean 79%, SD 8.1) and for adults 55% in Italy to 85% in Spain (mean 70%, SD 10). Inhaled corticosteroid usage for adults varied from 14% in Italy to 31% in Northern Ireland (mean 24%, SD 6.4). For children, beta2-agonist use varied from 24% in Italy to 67% in Spain (mean 45%, SD 13). Despite publication of international guidelines for the management of asthma, inter-country prescribing practices vary considerably and could be improved. The frequency of use of asthma as a diagnostic label also varies markedly.

Administration, Inhalation↗

Test instruments used by Journal of Music Therapy authors from 1984-1997.

Issues of the Journal of Music Therapy from 1984 to 1997 were selected to investigate the application of test instruments in music therapy research. All experimental and descriptive research articles were reviewed to determine if the methodology included test instruments. Other types of measurements-physiological measures, behavioral observations, computerized devices, and self-reports were excluded from the analysis. Test instruments were categorized as either published, unpublished, or researcher-constructed. A test instrument was "published" if, after a search in the "Test Review Locator" of the Buros Mental Measurements Web Site, a reference was found in one or more of the following publications-Mental Measurement Yearbooks, Tests in Print, or Test Critiques. A test was categorized as "unpublished" if the developer was cited in the JMT article but the test was not located in one or more of the above publications. All other test instruments were categorized as researcher-constructed tests designed for the specific study in the article. From 1984-1997, 220 articles were published in JMT. Approximately 83% (n = 183) of the total were experimental or descriptive research studies. Of the 183 articles research studies, 92 (50%) included a test instrument. Reviews of method sections of the 92 articles resulted in a listing of 115 different test instruments. Percentages of researcher-constructed tests, unpublished tests, and published tests were 25%, 35%, and 40% respectively. Lists of tests document the all-encompassing range of client populations and the broad view of human behavior included in the practice of music as therapy. The Journal of Music Therapy, in addition to providing the latest research findings regarding the effectiveness of music as a therapeutic medium, provides an excellent source for updating information about the availability and applicability of test instruments for music therapy clinical practice and training.

Humans↗

A protocol for researcher safety.

Although there is an abundance of literature about how to conduct qualitative research and some consideration of possible threats to researchers' psychological well-being, there is little mention of the personal safety issues that researchers face while in the field. Few researchers have attempted to address the issue of researcher safety as a methodological concern. Consequently, there are minimal guidelines available to researchers to prevent and avoid dangerous incidents in the course of their research. The following is a discussion of the general guidelines for developing a protocol to address the issue of researcher safety in the field. These guidelines have been extrapolated from safety guidelines and policies written for students and clinicians who enter a client's home in their role as health care practitioners, relevant literature in the area of safety for researchers in violent settings, resources such as safety guidelines for employees, and the personal experiences of several researchers.

Accidents, Occupational↗

Exploring the experience of type 2 diabetes in urban aboriginal people.

The experience of diabetes among urban Aboriginal people (status and non-status Indians) was explored through a qualitative study. Because researchers have focused almost exclusively on Aboriginal people living on reserves or in isolated rural communities in Canada, this study conducted face-to-face interviews with participants (n = 20) living in the city of Winnipeg, Manitoba. The data generated 3 themes: diabetes as an omnipresent and uncontrollable disease; beyond high sugar: diabetes revealed in bodily damage; and the good, the bad, and the unhelpful: interactions with health-care providers. Findings from this study and previous research support the existence of a pan-Aboriginal model of diabetes. This contemporary cultural stance appears to transcend geography and has implications for the prevention and treatment approaches used in programs and health services for Aboriginal people living with diabetes.

Adaptation, Psychological↗

Writing poetry: a way of knowing nursing.

Carper's patterns of knowing expose the relevance and importance of different knowledge to the enterprise of nursing. She noted that the aesthetic pattern enables nurses to know unique perceptive experiences. Poetry captures particular perceptive experiences and reconstructs them into universal wholes. The opportunity for nurses to write poetry can illuminate and legitimate their perceptive experiences which often become worn or hidden in the everyday work world and in other ways of knowing. Expressing nursing experiences through writing poetry generally involves three phases: (a) creating an image of experience, (b) fully articulating the image, and (c) sharing a clear, new meaning of the image. A poem, written to express one author's unique nursing experience, is used to explore the knowledge gained through the process of writing poetry. Writing poetry can help nurses connect with and maintain their personal and professional history. Moreover, writing poetry increases our awareness of the sensibilities of nursing practice and the meanings that these sensibilities add to the depth and design of the discipline.

Esthetics↗

Reactions to Ballet with Wheelchairs: Reflections of Attitudes toward People with Disabilities.

Subjects watched 2 videotape excerpts and recorded their reactions along a negative-to-positive continuum on the Continuous Response Digital Interface (CRDI). One excerpt was a classical ballet performance-the final 2 minutes of Stravinsky s Symphony in C by Balanchine. The other excerpt was a 2.5 minute Cable News Network (CNN) newscast about a collaborative performance between the Jeoffrey Ballet and a Chicago-based group of dancers in wheelchairs. Subjects included 32 middle school students, 32 high school students, and 32 undergraduate college music majors. Each age group had equal numbers of male and female subjects. Order of presentation of excerpts was controlled by reversing the sequence for half of the subjects by gender in each age group. A repeated measures ANOVA of mean CRDI ratings by excerpt order, gender, and age revealed a significant difference between newscast ratings and ballet performance ratings. Newscast mean ratings were more positive than ballet performance mean ratings. Order of presentation and gender were not significant factors. Age was the only factor affecting the difference. Newscast mean ratings were highly positive for all 3 groups and minor differences were not significant. Ballet performance mean ratings by college students, however, were significantly more positive compared to the younger groups mean ratings. High school students neutral ratings and middle school students slightly negative ratings were not significantly different. Individual subject s timelines revealed similar levels of discriminating attention with the CRDI across different age groups, different video formats, and different content. Middle and high school students reactions to visual images of dancers in wheelchairs talking about dancing and performing with nondisabled ballet dancers are positive and apparently unrelated to their reactions to classical ballet.

Journal Article↗

The role of intra-operative duplex imaging in arterial reconstructions.

BACKGROUND: This study is a cost-benefit analysis of a less invasive method of intra-operative duplex imaging compared with the use of intra-operative angiogram (including C-arm fluoroscopy) in arterial reconstruction. METHODS: From September 1994 to May 1995, 93 intra-operative duplex imaging studies were performed. Duplex scanning results were recorded for carotid endarterectomy (35), iliac balloon angioplasty and stent placement (12), and infra-inguinal bypass (46). Average cost and time were calculated for each type of study. RESULTS: Thirty-four carotid endarterectomy patients (97%) had normal duplex findings. Three (9%) underwent intra-operative angiogram due to abnormal duplex findings and post-operative neurological deficit. In iliac balloon angioplasty and stent placement cases (12), both intra-operative duplex and C-arm post-stent angiography yielded comparable results in both normal (11) and abnormal (1) studies. In infra-inguinal bypass cases (46), 2 had abnormal duplex findings of the native vessels. Average time and cost required to perform intra-operative duplex studies is significantly less than that required for intra-operative angiogram or C-arm studies. CONCLUSION: Compared with traditional intra-operative angiography, the use of intra-operative duplex imaging is less expensive, less invasive, quicker, and equally accurate when used as an adjunct to access surgical results of arterial reconstructions.

Angioplasty, Balloon↗

Vaccination against tuberculosis by DNA injection.

There are 3 million deaths per annum worldwide due to tuberculosis, and AIDS is compounding the problem. A better vaccine than the live mycobacterium currently in use, bacillus Calmette-Guérin (BCG), is needed. When mice were injected with plasmid DNA encoding a single mycobacterial antigen (65-kDa heat shock protein, hsp65) they made specific cellular and humoral responses to the protein and became immune to subsequent challenge with Mycobacterium tuberculosis. Protection was equivalent to that obtained by vaccinating with live BCG, whereas immunizing with the protein was ineffective. Protection was also obtained with DNA encoding another mycobacterial antigen (36-kDa proline-rich antigen). These results suggest that DNA vaccination might yield improved vaccines to replace BCG.

Animals↗

A struggle for equality: resistance to commissioning of male nurses in the Canadian military, 1952-1967.

Historical research was conducted to explore and describe the forces of resistance that prevented male registered nurses from being employed and conferred officer status in the Nursing Division of the Canadian military. Prior to 1967, only female nurses were permitted to join the Nursing Division. A 25-year struggle by the Registered Nurses Association of Ontario (RNAO), its Male Nurses Committee (MNC), and the Canadian Nurses Association (CNA) was required to change this discriminatory policy. The struggle for equality on behalf of Canadian male nurses was successfully resolved because of the united stand taken by the MNC, the RNAO, and the CNA. The study also demonstrates the need to move beyond matriarchal history perspectives in nursing to more completely understand the evolution of the profession in Canada.

Canada↗

Health and weight control management among wrestlers. A proposed program for high school athletes.

Weight loss is a part of any competitive sport which matches participants of equal weight or sports where participating at lower weights or with a thinner body habitus is considered an advantage. For some wrestlers, weight loss is excessive and often accomplished by methods that lead to loss of lean body mass and total body water. There is convincing evidence that this excessive weight loss is unhealthy for all individuals who follow these practices. Even greater harm is experienced by high school wrestlers who have not yet completed their growth and development. These health consequences include growth retardation, decreased academic performance, altered endocrine or hormonal function and damage to many vital organs. "cycling" of weight results in decrease in strength, power and endurance which would effect adversely a wrestler's likelihood of success. The VHSL has begun an educational program to inform coaches, wrestlers and parents about the hazards inherent in these weight loss practices. History suggests that education alone will not alter the present practices of weight loss. Therefore a weight management program similar to ones initiated in other states is being pursued by the VHSL. The pilot program this year is scheduled to be followed next year by a more wide-spread voluntary program across the Commonwealth.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗