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Biomedical subjects

S Dowd

Publications and source records attributed to S Dowd.

At least 19 recordsLinked to original sources

Social stress increases fecal shedding of Salmonella typhimurium by early weaned piglets.

"Segregated early weaning" (SEW) of pigs reduces exposure to pathogenic bacteria, but upon arrival at grower facilities pigs may be co-mingled regardless of farm of origin. The present study was designed to examine the effect of mixing (social) stress on populations of Salmonella enterica Typhimurium in SEW pigs. Piglets (7 days old; n = 28 in each of 2 replicates) were separated into 2 treatments (control and mixed groups) of 2 pens per treatment (7 piglets/pen). One (n = 1) "seeder" pig/pen was inoculated with 10(9) CFU of S. Typhimurium. Each seeder was placed with non-inoculated "contact" piglets (n = 6). A"contact" piglet was swapped each day between the "mixed" pens for 5 days; pigs in control pens were not exchanged. On day 5, the incidence of fecal Salmonella shedding was higher in the mixed contact pigs (P < 0.05). Rectal Salmonella and cecal coliform populations in mixed pigs were significantly (P < 0.05) greater than in control pigs but cecal Salmonella populations were not different. Mixed pigs were more susceptible to tissue invasiveness (i.e., Salmonella-positive tonsils and lymph nodes) than control pigs. These results indicate that social stress of weaned pigs may increase susceptibility to and/or fecal shedding of Salmonella. Food-borne Salmonella infections in the United States are estimated to cost the economy dollar 2.4 billion annually (ERS/USDA, 2001). Approximately 6-9% of human salmonellosis is associated with the consumption of pork products (Frenzen et al., 1999). Salmonella is relatively common on swine farms and has been isolated from all stages of the pork production chain (Davies et al., 1999; Fedorka-Cray et al., 1997b; Rostagno et al., 2003). Salmonella is a threat to the pork industry not only from a food-safety perspective as a public health concern, but some Salmonella serotypes can cause clinical illnesses in swine, negatively impacting production efficiency and profitability (Schwartz, 1991).

Animals↗

Cryptococcomas distinguished from gliomas with MR spectroscopy: an experimental rat and cell culture study.

PURPOSE: To use magnetic resonance (MR) spectroscopy to characterize clinical isolates of Cryptococcus neoformans and a glioma cell line in culture and in experimental rats. MATERIALS AND METHODS: One- and two-dimensional hydrogen 1 MR spectra were acquired from fungi cultured in vitro (16 isolates of C neoformans, three of Candida albicans, three of Aspergillus fumigatus, three of Saccharomyces cerevisiae) and a C6 glioma cell line. Cerebral biopsy specimens were obtained from healthy rats and animals with experimental infections or gliomas (19 healthy brains, 20 cryptococcomas, and 19 gliomas). Unequivocal signal assignment was performed for cell suspensions and tissue samples by using homo- and heteronuclear two-dimensional correlation spectra. RESULTS: MR spectra of C neoformans and cerebral cryptococcomas--but not of other fungi, healthy brains, or gliomas--were dominated by resonances from the cytosolic disaccharide alpha,alpha-trehalose. This spectral pattern was different from that of gliomas, which was dominated by lipids and an increased choline-creatine ratio, and that of healthy brain. CONCLUSION: A remarkably high concentration of alpha,alpha-trehalose in relation to other metabolites that are visible with MR spectroscopy is diagnostic of C neoformans. Cerebral cryptococcomas are an uncommon but serious manifestation of cryptococcosis in humans. Application of these results to the noninvasive diagnosis of cerebral cryptococcomas would help reduce the risk and expense of unnecessary surgery or biopsy and expedite patient treatment.

Animals↗

"How to get along with doctors and other health professionals".

All nurses will from time to time find themselves in negative interactions with doctors and other healthcare professionals. By using positive communication techniques the nurse can promote healthy interpersonal interactions and a positive atmosphere. By selecting responses rather than responding spontaneously difficult situations can be managed and a professional environment maintained.

Anger↗

Nuclear translocation of p42/p44 mitogen-activated protein kinase is required for growth factor-induced gene expression and cell cycle entry.

Mitogen-activated protein kinase (MAPK) modules, composed of three protein kinases activated by successive phosphorylation, are involved in the signal transduction of a wide range of extracellular agents. In mammalian cells, mitogenic stimulation triggers the translocation of p42/p44MAPK from the cytoplasm to the nucleus, whereas the other protein kinases of the module remain cytosolic. Since MAPK has been shown to phosphorylate and activate nuclear targets, such as the transcription factor Elk1, it has been proposed, but not yet demonstrated, that MAPK nuclear translocation could represent a critical step in signal transduction. In this study, we sequestered p42/p44MAPK in the cytoplasm by the expression of a catalytically inactive form of cytoplasmic MAP kinase phosphatase (MKP-3/Pyst-1). Sequestering MAPK in the cytoplasm did not alter its activation or its ability to phosphorylate cytoplasmic substrates of MAPK (p90RSK1 or an engineered cytoplasmic form of Elk1). In contrast, prevention of MAPK nuclear translocation strongly inhibited Elk1-dependent gene transcription and the ability of cells to reinitiate DNA replication in response to growth factors. Thus the relocalization of MAPK to the nucleus appears to be an important regulatory step for mitogen-induced gene expression and cell cycle re-entry.

Animals↗

Crystal structure of the MAPK phosphatase Pyst1 catalytic domain and implications for regulated activation.

The crystal structure of the catalytic domain from the MAPK phosphatase Pyst1 (Pyst1-CD) has been determined at 2.35 A. The structure adopts a protein tyrosine phosphatase (PTPase) fold with a shallow active site that displays a distorted geometry in the absence of its substrate with some similarity to the dual-specificity phosphatase cdc25. Functional characterization of Pyst1-CD indicates it is sufficient to dephosphorylate activated ERK2 in vitro. Kinetic analysis of Pyst1 and Pyst1-CD using the substrate p-nitrophenyl phosphate (pNPP) reveals that both molecules undergo catalytic activation in the presence of recombinant inactive ERK2, switching from a low- to high-activity form. Mutation of Asp 262, located 5.5 A distal to the active site, demonstrates it is essential for catalysis in the high-activity ERK2-dependent conformation of Pyst1 but not for the low-activity ERK2-independent form, suggesting that ERK2 induces closure of the Asp 262 loop over the active site, thereby enhancing Pyst1 catalytic efficiency.

Amino Acid Sequence↗

Will you fit if you move to a job in another culture?

In today's health care environment, many health care managers choose to move to a new setting. Because environments vary from setting to setting, a manager who plans to move needs to evaluate potential "fit" in the new locality. An evaluation of "fit" includes an assessment of both the job culture and persons in the environment. The Giger-Davidhizar transcultural assessment model provides a model for evaluating a new job culture.

Acculturation↗

Moving from Illness to wellness: an important goal of home care.

For many clients in home care with chronic illness the real work of getting well involves learning to adjust to chronic illness and to disability. Learning to adjust to disability by maximizing the abilities and qualities that are present can mean overcoming otherwise very significant problems while still maintaining a high quality of life. Home care providers play an important role in helping clients and their families optimize functioning to do the real work of getting "well."

Adaptation, Psychological↗

Managing diversity in the health care workplace.

Cultural diversity is increasing in the United States as increasing numbers of minorities enter the United States from abroad, and cultural diversity is especially prevalent in the health care workplace. In fact, the health care professions are particularly interested in the presence of minorities among caregivers because this often enhances the cultural competence of care delivery. Nevertheless, subtle discrimination can still be found, and managers must be alert that such behavior is not tolerated. Use of the Giger-Davidhizar Cultural Assessment Model can provide managers with information needed to respond to diversity among staff appropriately.

Communication↗

Keeping the care in patient care in the laboratory.

Keeping the care in patient care is an important behavior for technologists in the laboratory. This paper has considered the construct of caring and has outlined strategies for communicating caring to the patient who is interacting with the laboratory technologist. Problems with overinvolvement have also been identified. A laboratory technologist needs to balance caring with appropriate feelings of detachment.

Humans↗

Characterization of the lipid-carrier involved in the synthesis of enterobacterial common antigen (ECA) and identification of a novel phosphoglyceride in a mutant of Salmonella typhimurium defective in ECA synthesis.

The polysaccharide chains of enterobacterial common antigen (ECA) consist of linear trisaccharide repeat units with the structure -->3)-alpha-d-Fuc4NAc-(1-->4)-beta-d-ManNAcA-(1--> 4)-alpha-d-GlcNAc-(1-->, where Fuc4NAc is 4-acetamido-4, 6-dideoxy-d-galactose, ManNAcA is N -acetyl-d- mannosaminuronic acid, and GlcNAc is N -acetyl-d-glucosamine. The major form of ECA (ECAPG) consists of polysaccharide chains that are believed to be covalently linked to diacylglycerol through phosphodiester linkage; the phospholipid moiety functions to anchor molecules in the outer membrane. The ECA trisaccharide repeat unit is assembled as a polyisoprenyl-linked intermediate which has been tentatively identified as Fuc4NAc-ManNAcA-GlcNAc-pyrophosphorylundecaprenol (lipid III). Subsequent chain-elongation presumably occurs by a block-polymerization mechanism. However, the identity of the polyisoprenoid carrier-lipid has not been established. Accordingly, the current studies were conducted in an effort to structurally characterize the polyisoprenyl lipid-carrier involved in ECA synthesis. Isolation and characterization of the lipid carrier was facilitated by the accumulation of a ManNAcA-GlcNAc-pyrophosphorylpolyisoprenyl lipid (lipid II) in mutants of Salmonella typhimurium defective in the synthesis of TDP-Fuc4NAc, the donor of Fuc4NAc residues for ECA synthesis. Analyses of lipid II preparations by fast atom bombardment tandem mass spectroscopy (FAB-MS/MS) resulted in the identification of the lipid-carrier as the 55-carbon polyisoprenyl alcohol, undecaprenol. These analyses also resulted in the identification of a novel glycolipid which copurified with lipid II. FAB-MS/MS analyses of this glycolipid revealed its structure to be 1,2-diacyl- sn -glycero-3-pryophosphoryl-GlcNAc-ManNAcA (DGP-disaccharide). An examination of purified ECAPGby phosphorus-31 nuclear magnetic resonance spectroscopy confirmed that the polysaccharide chains are linked to diacylglycerol through phosphodiester linkage. Thus, DGP-disaccharide does not appear to be an intermediate in ECAPGsynthesis. Nevertheless, although the available evidence clearly indicate that lipid II is a precursor of DGP-disaccharide, the function of this novel glycolipid is not yet known, and it may be an intermediate in the biosynthesis of a molecule other than ECAPG.

Antigens, Bacterial↗

Sexual harassment. Where to draw the line.

Research reveals a widespread and frequently mismanaged problem--sexual harassment. Federal and state rulings, workplace guidelines and the Equal Opportunity Commission's definition of sexual harassment can help determine where to draw the line.

Female↗

Writing scholarly papers as a team.

Use of a team approach is a technique that can facilitate writing for professional publication. There is an art to writing with a team, which includes carefully selecting a writing partner who will complement personal skills and expertise and being able to work in a collaborative way through the writing process. There are benefits in the team approach that are of particular significance in mentoring novice writing in the publication process. However, there are also obstacles that should be anticipated and planned for.

Authorship↗

Recognizing abuse in culturally diverse clients.

Abuse is a major problem in American society. The problem of abuse among ethnically diverse persons is an area about which most health care professionals know little. This article describes the Giger-Davidhizar Model of Transcultural Assessment as a tool of assessment of the client who is abused. Use of a framework for assessment can enable more culturally competent care to be delivered.

Adolescent↗

Isolation of the human genes encoding the pyst1 and Pyst2 phosphatases: characterisation of Pyst2 as a cytosolic dual-specificity MAP kinase phosphatase and its catalytic activation by both MAP and SAP kinases.

We have isolated the human genes encoding the Pyst1 (MKP-3) and Pyst2 (MKP-X) MAP kinase phosphatases. Both genes consist of three exons interrupted by two introns and lack an intron which is conserved in all the other members of this gene family characterised to date. This reinforces the conclusion that Pyst1 and Pyst2 are members of a distinct and structurally homologous subfamily of dual-specificity (Thr/Tyr) MAP kinase phosphatases. We find that Pyst2 mRNA is constitutively expressed in a wide variety of human cell lines including those derived from ovarian, bladder and breast cancers. While there is no evidence for inducible expression of Pyst2 mRNA in human skin fibroblasts in response to cellular stress, Pyst2 mRNA levels are moderately increased in response to serum stimulation. Pyst2 protein is predominantly cytosolic when expressed in COS-1 cells. In common with Pyst1, Pyst2 shows substrate selectivity for the classical p42 (ERK2) isoform of MAP kinase both in vitro and in vivo, displaying much reduced activity towards stress activated MAP kinase isoforms such as JNK-1 and p38/RK. Pyst2 binds p42 MAP kinase in vivo and both MAP kinase binding and substrate selectivity correlate with the ability of different recombinant MAP and SAP kinases to cause catalytic activation of the Pyst2 phosphatase in vitro.

Animals↗

The older patient in the laboratory department.

The elderly patient in the laboratory department often brings special needs. The accelerated rate of social change, as well as technological changes in the world in general, have subjected the elderly to an unprecedented need to adapt. The ability of elderly persons to make effective adaptations is impeded by a society that places less value on age, resulting in psychological and psychosocial stresses that do not affect younger individuals. In addition to the pressures of society, the elderly patient often comes to the laboratory with special needs. When staff are alert to these special needs and respond therapeutically, the experience of the elderly patient in the laboratory can be enhanced and positive.

Aged↗

Role of the yeast phosphatidylinositol/phosphatidylcholine transfer protein (Sec14p) in phosphatidylcholine turnover and INO1 regulation.

In yeast, mutations in the CDP-choline pathway for phosphatidylcholine biosynthesis permit the cell to grow even when the SEC14 gene is completely deleted (Cleves, A., McGee, T., Whitters, E., Champion, K., Aitken, J., Dowhan, W., Goebl, M., and Bankaitis, V. (1991) Cell 64, 789-800). We report that strains carrying mutations in the CDP-choline pathway, such as cki1, exhibit a choline excretion phenotype due to production of choline during normal turnover of phosphatidylcholine. Cells carrying cki1 in combination with sec14(ts), a temperature-sensitive allele in the gene encoding the phosphatidylinositol/phosphatidylcholine transporter, have a dramatically increased choline excretion phenotype when grown at the sec14(ts)-restrictive temperature. We show that the increased choline excretion in sec14(ts) cki1 cells is due to increased turnover of phosphatidylcholine via a mechanism consistent with phospholipase D-mediated turnover. We propose that the elevated rate of phosphatidylcholine turnover in sec14(ts) cki1 cells provides the metabolic condition that permits the secretory pathway to function when Sec14p is inactivated. As phosphatidylcholine turnover increases in sec14(ts) cki1 cells shifted to the restrictive temperature, the INO1 gene (encoding inositol-1-phosphate synthase) is also derepressed, leading to an inositol excretion phenotype (Opi-). Misregulation of the INO1 gene has been observed in many strains with altered phospholipid metabolism, and the relationship between phosphatidylcholine turnover and regulation of INO1 and other co-regulated genes of phospholipid biosynthesis is discussed.

Carrier Proteins↗

A two-phase, double-blind randomized study of three haloperidol plasma levels for acute psychosis with reassignment of initial non-responders.

To clarify the plasma level/therapeutic response relationship of haloperidol (HPDL) we used a prospective double-blind design in 95 acutely psychotic patients. After drug washout, patients were randomly assigned to a low, middle or high plasma level range for 2 weeks (phase A), and then 50% of the initial non-responders were randomly reassigned into the putative therapeutic range for an additional 2 weeks (phase B). There were no significant differences in clinical outcome between the three plasma level ranges in phase A. However, in phase B initial non-responders displayed greater improvement in the middle range than in the low or the high ranges. No further benefit was observed when plasma levels were raised to or maintained in the high range.

Acute Disease↗