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Biomedical subjects

K Wilson

Publications and source records attributed to K Wilson.

At least 91 records · Page 5Linked to original sources
PubMed2000

Distribution and origin of secretoneurin-immunoreactive nerves in the female rat uterus.

Secretoneurin is a 33-amino acid peptide derived from secretogranin II. Secretoneurin immunoreactivity has been localized in the peripheral nervous system where it exerts potent chemotactic activity for monocytes and may play a role in inflammation. Secretoneurin could play a role in this process, although the presence and distribution of secretoneurin-immunoreactive neurons in the female reproductive system has not been documented. Thus, this study was undertaken to examine secretoneurin immunoreactivity in nerves of the rat uterus and uterine cervix. A moderate plexus of secretoneurin-immunoreactive nerve fibers was present in the myometrium and endometrium of the uterus as well as in the smooth muscle and endocervix of the cervix. Many of these fibers were associated with the vasculature as well as the myometrium. Secretoneurin immunoreactivity was present in small- to medium-sized neurons of dorsal root and nodose ganglia. Retrograde tracing with FluoroGold indicated that some of these sensory neurons project axons to the cervix and uterine horns. Secretoneurin-immunoreactive terminal-like structures were associated with neurons in the sacral parasympathetic nucleus of the lumbosacral spinal cord. In addition, some secretoneurin terminals were apposed to pelvic parasympathetic neurons in the paracervical ganglia that projected axons to the uterus and cervix. Double-immunostaining indicated co-existence of calcitonin gene-related peptide or substance P with secretoneurin in some sensory neurons, in some terminals of the pelvic ganglia, as well as nerve fibers in the uterine horn and cervix. Finally, fibers in the uterus and cervix were depleted of secretoneurin by capsaicin treatment. This study indicates that secretoneurin is present in the uterus in C-afferent nerve fibers whose cell bodies are located in sensory ganglia. Some of these fibers contain both secretoneurin and calcitonin gene-related peptide or substance P. These substances have functions in inflammatory reactions. Further, secretoneurin could influence postganglionic parasympathetic "uterine-related" neurons in the pelvic ganglia and preganglionic parasympathetic neurons in the lumbosacral spinal cord.

Animals↗
PubMed2000

Depression and the dying older patient.

Depression remains a source of considerable suffering among dying older adults. Unfortunately, clinical depression commonly is overlooked in this vulnerable population and often goes untreated. An overview of diagnosing depression in older patients is presented. Various risk factors for depression in the palliative care setting are examined. The somatic therapies that are available for treatment consideration in older, depressed adults nearing death are reviewed.

Aged↗
PubMed2000

Identifying male college students' perceived health needs, barriers to seeking help, and recommendations to help men adopt healthier lifestyles.

Seven focus groups at a university campus were formed to identify college men's health concerns, barriers to seeking help, and recommendations to help college men adopt healthier lifestyles. Content analysis was used to identify and organize primary patterns in the focus-group data. Results of the study revealed that the college men were aware that they had important health needs but took little action to address them. The participants identified both physical and emotional health concerns. Alcohol and substance abuse were rated as the most important issues for men. The greatest barrier to seeking services was the men's socialization to be independent and conceal vulnerability. The most frequently mentioned suggestions for helping men adopt healthier lifestyles were offering health classes, providing health information call-in service, and developing a men's center. Implications of the results are discussed.

Adaptation, Psychological↗
PubMed2000

The complete sequence of the mitochondrial genome of the crustacean Penaeus monodon: are malacostracan crustaceans more closely related to insects than to branchiopods?

The complete sequence of the mitochondrial genome of the giant tiger prawn, Penaeus monodon (Arthropoda, Crustacea, Malacostraca), is presented. The gene content and gene order are identical to those observed in Drosophila yakuba. The overall AT composition is lower than that observed in the known insect mitochondrial genomes, but higher than that observed in the other two crustaceans for which complete mitochondrial sequence is available. Analysis of the effect of nucleotide bias on codon composition across the Arthropoda reveals a trend with the crustaceans represented showing the lowest proportion of AT-rich codons in mitochondrial protein genes. Phylogenetic analysis among arthropods using concatenated protein-coding sequences provides further support for the possibility that Crustacea are paraphyletic. Furthermore, in contrast to data from the nuclear gene EF1alpha, the first complete sequence of a malacostracan mitochondrial genome supports the possibility that Malacostraca are more closely related to Insecta than to Branchiopoda.

Animals↗
PubMed2000

Diagnostic evaluation of patients with blunt abdominal trauma: a decision analysis.

OBJECTIVES: Using decision analysis, to compare the expected utility (EU) of diagnostic peritoneal lavage (DPL), computed tomography (CT), and ultrasonography (US) to determine the optimal modality for the evaluation of blunt abdominal trauma (BAT) in hemodynamically stable adults. METHODS: Data points for the decision analysis were obtained from three sources: 1) prevalence of BAT and the sensitivity and specificity of each diagnostic modality were determined through a criteria-based review of the literature; 2) rate of BAT necessitating immediate intervention, perioperative complication rate, and operative mortality rate were calculated using data from the authors' institution's trauma registry; and 3) outcome utilities were determined by telephone survey of adults in a random sample of households in the region. The decision tree was constructed and evaluated in standard fashion. For each diagnostic modality, the authors calculated the EU using the minimum, mean, and maximum sensitivity and specificity across a range of prevalence. Mean outcome utilities were used for each branch of the tree when calculating the EU. RESULTS: The EU of CT was consistently lower than the EUs of DPL and US at all levels of prevalence. However, the rank order of the EUs of US and DPL varied with the prevalence of BAT. When the prevalence was <30%, the EU of US was higher than that for DPL. When the prevalence was 30-40%, the EUs were similar. When the prevalence was >40%, the EU of US was less than that of DPL. CONCLUSIONS: Among institutions operating under constraints similar to those used in this model, the optimal diagnostic modality for the evaluation of BAT can be determined based on the sensitivity and specificity of the modality at their institution and the prevalence of BAT in their patient population.

Abdominal Injuries↗
PubMed2000

Discovery of novel antifungal (1,3)-beta-D-glucan synthase inhibitors.

The increasing incidence of life-threatening fungal infections has driven the search for new, broad-spectrum fungicidal agents that can be used for treatment and prophylaxis in immunocompromised patients. Natural-product inhibitors of cell wall (1,3)-beta-D-glucan synthase such as lipopeptide pneumocandins and echinocandins as well as the glycolipid papulacandins have been evaluated as potential therapeutics for the last two decades. As a result, MK-0991 (caspofungin acetate; Cancidas), a semisynthetic analogue of pneumocandin B(o), is being developed as a broad-spectrum parenteral agent for the treatment of aspergillosis and candidiasis. This and other lipopeptide antifungal agents have limited oral bioavailability. Thus, we have sought new chemical structures with the mode of action of lipopeptide antifungal agents but with the potential for oral absorption. Results of natural-product screening by a series of newly developed methods has led to the identification of four acidic terpenoid (1,3)-beta-D-glucan synthase inhibitors. Of the four compounds, the in vitro antifungal activity of one, enfumafungin, is comparable to that of L-733560, a close analogue of MK-0991. Like the lipopeptides, enfumafungin specifically inhibits glucan synthesis in whole cells and in (1,3)-beta-D-glucan synthase assays, alters the morphologies of yeasts and molds, and produces a unique response in Saccharomyces cerevisiae strains with point mutations in FKS1, the gene which encodes the large subunit of glucan synthase.

Antifungal Agents↗
PubMed2000

Visualism in community nursing: implications for telephone work with service users.

This article explores the potential effects of visualism (a prejudice in favor of the seen) on the perceived legitimacy of telephone work in community nursing. It discusses data from an exploratory study on telephone work, which used guided interviews with a purposive sample of 14 community nurses. Interviewees expressed both positive and negative ideas about telephone work and had particular concerns about the assessment of people, context, problems, and comprehension by telephone. These issues are discussed with reference to publications on visualism, metaphor, communication, and nursing work. The authors conclude that an awareness of the possible effects of visualism on ideas and practice could lead to improvements in both communication and assessment, whether carried out by telephone or face to face.

Attitude of Health Personnel↗
PubMed2000

Changing demographic characteristics of women veterans: results from a national sample.

Women veterans are a small but growing percentage of the U.S. veteran population. There are some indications that, along with this increase, the characteristics and military experiences of younger women veterans differ considerably from those of older colleagues. Many of these characteristics are not well defined, but they could have implications for women's health care needs and health policy initiatives. Using the first sample drawn from the Department of Veterans Affairs' new National Registry of Women Veterans, we designed and administered a telephone survey to a representative sample of women veterans across several major age groups. Groups approximated primary eras of military and wartime service based on the assumption that different eras might be associated with differing military experiences. We found a number of age-related similarities and differences in women veterans' demographic characteristics, military experiences, physical health symptoms, and functional outcomes. Women veterans in general also differed from female civilian counterparts on exposure to sexual trauma. Trends in the population of women veterans are likely to have implications for the variety of health care systems that treat women veterans.

Adult↗
PubMed2000

Prayer in medicine: a survey of primary care physicians.

Prayer and spirituality have been shown to have a significant impact on several health variables. Additionally, studies have shown that patients think prayer is important to their health. Very little research, however, has been done to determine primary care physicians' opinions regarding prayer and spirituality as it pertains to healthcare. We surveyed primary care physicians in Mississippi to assess their use of prayer in medical practice. Ninety-one percent of respondents considered prayer an important treatment modality, but 50.6% rarely or never discussed prayer with patients. Most who excluded prayer from clinical practice did so to avoid imposing their beliefs upon patients. A majority of primary care physicians in Mississippi recognize prayer as an important psychosocial variable in assessing and treating patients, but many are hesitant to incorporate this variable into the doctor-patient encounter.

Attitude of Health Personnel↗
PubMed1999

A clinical trial of retroviral-mediated transfer of a rev-responsive element decoy gene into CD34(+) cells from the bone marrow of human immunodeficiency virus-1-infected children.

Genetic modification of hematopoietic stem cells with genes that inhibit replication of human immunodeficiency virus-1 (HIV-1) could lead to development of T lymphocytes and monocytic cells resistant to HIV-1 infection after transplantation. We performed a clinical trial to evaluate the safety and feasibility of this procedure, using bone marrow from four HIV-1-infected pediatric subjects (ages 8 to 17 years). We obtained bone marrow, isolated CD34(+) cells, performed in vitro transduction with a retroviral vector carrying a rev-responsive element (RRE) decoy gene, and reinfused the cells into these subjects with no evidence of adverse effects. The levels of gene-containing leukocytes in peripheral blood samples in the 1 year after gene transfer/cell infusion have been extremely low. These observations support the potential of performing gene therapy for HIV-1 using hematopoietic cells, but emphasize the need for improved gene transfer techniques.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Heritable variation in resistance to gastro-intestinal nematodes in an unmanaged mammal population.

The impact of parasites on natural populations has received considerable attention from evolutionary biologists in recent years. Central to a number of theoretical developments during this period is the assumption of additive genetic variation in resistance to parasites. However, very few studies have estimated the heritability of parasite resistance under field conditions, and those that have are mainly restricted to birds and their ectoparasites. In this paper, to our knowledge, we show for the first time in a free-ranging mammal population, Soay sheep (Ovis aries) living on the islands of St Kilda, that there is significant heritable variation in resistance to gastrointestinal nematodes. This result is consistent with earlier studies on this population which have indicated locus-specific associations with parasite resistance. We discuss our results in the context of current studies examining heritable resistance to parasites in domestic sheep and the possible mechanisms of selective maintenance of genetic variation for resistance to gastrointestinal nematodes in the St Kilda Soay sheep population.

Animals↗
PubMed1999

Structure of catalase HPII from Escherichia coli at 1.9 A resolution.

Catalase HPII from Escherichia coli, a homotetramer of subunits with 753 residues, is the largest known catalase. The structure of native HPII has been refined at 1.9 A resolution using X-ray synchrotron data collected from crystals flash-cooled with liquid nitrogen. The crystallographic agreement factors R and R(free) are respectively 16.6% and 21.0%. The asymmetric unit of the crystal contains a whole molecule that shows accurate 222-point group symmetry. The structure of the central part of the HPII subunit gives a root mean square deviation of 1.5 A for 477 equivalencies with beef liver catalase. Most of the additional 276 residues of HPII are located in either an extended N-terminal arm or in a C-terminal domain organized with a flavodoxin-like topology. A small number of mostly hydrophilic interactions stabilize the relative orientation between the C-terminal domain and the core of the enzyme. The heme component of HPII is a cis-hydroxychlorin gamma-spirolactone in an orientation that is flipped 180 degrees with respect to the orientation of the heme found in beef liver catalase. The proximal ligand of the heme is Tyr415 which is joined by a covalent bond between its Cbeta atom and the Ndelta atom of His392. Over 2,700 well-defined solvent molecules have been identified filling a complex network of cavities and channels formed inside the molecule. Two channels lead close to the distal side heme pocket of each subunit suggesting separate inlet and exhaust functions. The longest channel, that begins in an adjacent subunit, is over 50 A in length, and the second channel is about 30 A in length. A third channel reaching the heme proximal side may provide access for the substrate needed to catalyze the heme modification and His-Tyr bond formation. HPII does not bind NADPH and the equivalent region to the NADPH binding pocket of bovine catalase, partially occluded in HPII by residues 585-590, corresponds to the entrance to the second channel. The heme distal pocket contains two solvent molecules, and the one closer to the iron atom appears to exhibit high mobility or low occupancy compatible with weak coordination.

Amino Acid Sequence↗
PubMed1999

Trypanosoma brucei: cis-acting sequences involved in the developmental regulation of PARP expression.

The procyclic acidic repetitive protein (PARP or procyclin) of the parasitic protozoan Trypanosoma brucei is a developmentally regulated protein that shows extreme differences in its level of expression in different stages of the parasite's life cycle. Specifically, it is the major surface protein in the procyclic (insect) stage and, although the PARP gene is being actively transcribed in the mammalian bloodstream stage, there is no detectable PARP mRNA or protein in these cells. The 3'-untranslated region (UTR) of PARP, as well as other trypanosome genes, has the ability to confer the appropriate developmental regulation pattern onto chimeric reporter genes. To understand the mechanism of posttranscriptional regulation, selective replacement mutagenesis of the PARP mRNA 3'UTR was done to identify the cis-acting sequences involved in the down-regulation of this mRNA in bloodstream-form T. brucei. Transient transformation of constructs containing the PARP promoter and 5'UTR, the beta-glucuronidase coding region, and the selectively mutagenized or unaltered PARP 3'UTR were performed in procyclic and bloodstream T. brucei. The results of the reporter gene assays on the transformed cells indicate that there are at least two elements in the PARP 3'UTR which in bloodstream cells are involved in regulation of PARP expression and which appear to function as negative elements. In procyclic cells, there are two regions in which mutagenesis indicates positive cis-regulatory sequences, one of which has been previously defined (A. Hehl et al., 1994, Proc. Natl. Acad. Sci. USA 91, 370-374). These results indicate that multiple cis-acting elements within the PARP 3'UTR are involved in the developmental regulation of PARP expression and that regulation is controlled in a complex manner, presumably involving several cellular trans-acting factors.

Animals↗
PubMed1999

Modelling density-dependent resistance in insect-pathogen interactions.

We consider a mathematical model for a host-pathogen interaction where the host population is split into two categories: those susceptible to disease and those resistant to disease. Since the model was motivated by studies on insect populations, we consider a discrete-time model to reflect the discrete generations which are common among insect species. Whether an individual is born susceptible or resistant to disease depends on the local population levels at the start of each generation. In particular, we are interested in the case where the fraction of resistant individuals in the population increases as the total population increases. This may be seen as a positive feedback mechanism since disease is the only population control imposed upon the system. Moreover, it reflects recent experimental observations from noctuid moth-baculovirus interactions that pathogen resistance may increase with larval density. We find that the inclusion of a resistant class can stabilise unstable host-pathogen interactions but there is greatest regulation when the fraction born resistant is density independent. Nonetheless, inclusion of density dependence can still allow intrinsically unstable host-pathogen dynamics to be stabilised provided that this effect is sufficiently small. Moreover, inclusion of density-dependent resistance to disease allows the system to give rise to bistable dynamics in which the final outcome is dictated by the initial conditions for the model system. This has implications for the management of agricultural pests using biocontrol agents-in particular, it is suggested that the propensity for density-dependent resistance be determined prior to such a biocontrol attempt in order to be sure that this will result in the prevention of pest outbreaks, rather than their facilitation. Finally we consider how the cost of resistance to disease affects model outcomes and discover that when there is no cost to resistance, the model predicts stable periodic outbreaks of the insect population. The results are interpreted ecologically and future avenues for research to address the shortfalls in the present model system are discussed.

Animals↗
PubMed1999

The bisindolylmaleimide protein kinase C inhibitor, Ro 32-2241, reverses multidrug resistance in KB tumour cells.

Ro 32-2241 is a bisindolylmaleimide that selectively inhibits protein kinase C (PKC) as compared with other protein kinases. Experiments were carried out to examine its potential as a multidrug resistance-reversing agent. Ro 32-2241 inhibited efflux, and increased accumulation, of [3H]-daunomycin in multidrug-resistant (MDR) KB-8-5 and KB-8-5-11 cells and had no effect on drug-sensitive KB-3-1 cells. Ro 32-2241 completely reversed the doxorubicin resistance of KB-8-5 and KB-8-5-11 cells, showing no effect on the sensitivity of drug-sensitive KB-3-1 cells. The potency of Ro 32-2241 was comparable with that of cyclosporin A and better than that of verapamil, known modulators of multidrug resistance. Ro 32-2241 also completely reversed the taxol resistance of KB-8-5 cells and partially reversed the resistance of KB-8-5-11 cells. Vinblastine resistance was also partially reversed. Mechanistic experiments were carried out to determine whether Ro 32-2241 interacted with P-glycoprotein (Pgp) directly. Increased efflux of [14C]-Ro 32-2241 was seen with the more resistant KB-8-5-11 cells (although the percentage effluxed was very low as compared with [3H]-daunomycin), suggesting that Ro 32-2241 can act as a substrate for Pgp. Direct interaction of Ro 32-2241 with Pgp was confirmed by demonstration that it inhibited binding of [3H]-azidopine to Pgp in KB-8-5-11 membranes. In conclusion, Ro 32-2241, acting directly on Pgp (rather than, or in addition to, an effect on PKC), is effective in reducing or reversing resistance to doxorubicin, taxol and vinblastine in human tumour cells with a clinically relevant degree of MDR. However, results of in vivo experiments conducted to investigate the effects of Ro 32-2241 on resistance to doxorubicin suggest that it may not be possible to achieve sufficiently high levels of Ro 32-2241 in vivo to modulate MDR.

ATP Binding Cassette Transporter, Subfamily B, Mem↗