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Biomedical subjects

M McGinley

Publications and source records attributed to M McGinley.

18 recordsLinked to original sources

Identification of stathmin as a novel substrate for p38 delta.

p38 mitogen-activated protein kinases (MAPK) are a family of kinases that are activated by cellular stresses and inflammatory cytokines. Although there are many similarities shared by the isoforms of p38 (alpha, beta, gamma, and delta), p38 delta differs from the others in some respects such as inhibitor sensitivity and substrate specificity. Utilizing in a solution kinase assay, we identified a novel p38 delta substrate as stathmin. Stathmin is a cytoplasmic protein that was previously reported to be a substrate of several intracellular signaling kinases and has recently been linked to regulation of microtubule dynamics. p38 delta has significantly higher in vitro phosphorylating activity against stathmin than other p38 isoforms or related MAPKs. In transient expression studies, we found that in addition to different stimuli osmotic stress activates p38 delta to phosphorylate stathmin. The sites of phosphorylation were mapped to Ser-25 and Ser-38, both in vitro and in cells.

Base Sequence↗

Satisfaction with midwife-managed care in different time periods: a randomised controlled trial of 1299 women.

OBJECTIVE: To compare women's satisfaction with midwife-managed care with 'shared care' over three different time periods. DESIGN: Randomised controlled trial. SETTING: Glasgow Royal Maternity Hospital, Glasgow, UK. PARTICIPANTS: 1299 women experiencing normal pregnancy (consent rate: 82%). Six hundred and forty-eight women were randomised to midwife-managed care and 651 to 'shared care'. METHODS: Three self-report questionnaires were sent to women's homes. The questionnaires examined: satisfaction with antenatal care at 34-35 weeks' gestation, and satisfaction with intrapartum, hospital- and home-based postnatal care at seven weeks postnatally. The third questionnaire reviewed satisfaction with intrapartum care seven months after delivery. FINDINGS: Women in both groups were satisfied. However, women in the midwife-managed group were more highly satisfied in relation to the dimensions examined: relationships with staff, information transfer, choices and decisions, and social support. The differences between the two groups were evident for all time periods (i.e. antenatal, intrapartum and postnatal periods) and were sustained at seven-month follow-up. This is illustrated in the mean scores for relationships with staff, as measured at 34-35 weeks' gestation (possible range -2; very negative attitudes to 2; very positive attitudes). Women in the midwife-managed group scored a mean of 1.22 compared to 0.74 for the 'shared care' group (mean diff: 0.48; 95% CI: 0.42 to 0.55). While women in both groups were more likely to make positive rather than negative comments in open-ended questions, the midwife-managed group were more likely to make positive comments whereas the 'shared care' group were more likely to make negative comments. CONCLUSION: Midwife-managed care for healthy pregnant women which is integrated into existing services improves satisfaction with antenatal, intrapartum and postnatal care.

Adult↗

Use of monetary reinforcement to reduce the cigarette smoking of persons with schizophrenia: a feasibility study.

The feasibility of using monetary reinforcement to promote abstinence from substance use in adult individuals with schizophrenia was addressed. Cigarette smoking was studied as an exemplar of drug use in 11 individuals with schizophrenia by use of a within-subject experimental design. The study duration was 3 weeks, with weeks 1 and 3 serving as baseline conditions and week 2 serving as the intervention condition; in the latter, patients could earn money by abstaining from cigarette smoking. Abstinence was significantly greater during the intervention condition than during the baseline conditions. These results illustrate the potential sensitivity of drug use in this population to reinforcement contingencies, suggesting that contingency-management interventions are a feasible option for treating the substance abuse of individuals with schizophrenia.

Adult↗

A randomized trial of three iron dextran infusion methods for anemia in EPO-treated dialysis patients.

Forty-three hemodialysis patients receiving recombinant erythropoietin (rHuEPO, epoietin alpha) were randomized to receive intravenous iron dextran as a total-dose infusion, 500-mg infusion to total dose, or 100-mg bolus to total dose, in each case during the dialysis procedure. The dose of iron dextran was calculated from the patient's existing hemoglobin to achieve a desired hemoglobin. Patients were eligible to receive intravenous iron dextran if they had a serum ferritin of < or = 100 ng/mL or a serum ferritin of 100 to 200 ng/mL, along with a transferrin saturation of < or = 19%. Patients were excluded if they had prior therapy with iron dextran, aluminum intoxication, or transfusion during the study. The time to the maximum hemoglobin, acute adverse reactions, and delayed adverse reactions were analyzed statistically, and no differences were seen in any of the three groups. Total-dose intravenous iron dextran infusion is safe, convenient, less expensive, and as efficacious as divided-dose infusions.

Anemia↗

Kinase suppressor of Ras is ceramide-activated protein kinase.

A proline-directed serine/threonine ceramide-activated protein (CAP) kinase mediates transmembrane signaling through the sphingomyelin pathway. CAP kinase reportedly initiates proinflammatory TNF alpha action by phosphorylating and activating Raf-1. The present studies delineate kinase suppressor of Ras (KSR), identified genetically in Caenorhabditis elegans and Drosophila, as CAP kinase. Mouse KSR, like CAP kinase, renatures and autophosphorylates as a 100-kDa membrane-bound polypeptide. KSR overexpression constitutively activates Raf-1. TNF alpha or ceramide analogs markedly enhance KSR autophosphorylation and its ability to complex with, phosphorylate, and activate Raf-1. In vitro, low nanomolar concentrations of natural ceramide stimulate KSR to autophosphorylate, and transactivate Raf-1. Other lipid second messengers were ineffective. Moreover, Thr269 the Raf-1 site phosphorylated by CAP kinase, is also recognized by KSR. Thus, by previously established criteria, KSR appears to be CAP kinase.

Amino Acid Sequence↗

Randomised, controlled trial of efficacy of midwife-managed care.

BACKGROUND: Midwife-managed programmes of care are being widely implemented although there has been little investigation of their efficacy. We have compared midwife-managed care with shared care (ie, care divided among midwives, hospital doctors, and general practitioners) in terms of clinical efficacy and women's satisfaction. METHODS: We carried out a randomised controlled trial of 1299 pregnant women who had no adverse characteristics at booking (consent rate 81.9%). 648 women were assigned midwife-managed care and 651 shared care. The research hypothesis was that compared with shared care, midwife-managed care would produce fewer interventions, similar (or more favourable) outcomes, similar complications, and greater satisfaction with care. Data were collected by retrospective review of case records and self-report questionnaires. Analysis was by intention to treat. FINDINGS: Interventions were similar in the two groups or lower with midwife-managed care. For example, women in the midwife-managed group were less likely than women in shared care to have induction of labour (146 [23.9%] vs 199 [33.3%]; 95% CI for difference 4.4-14.5). Women in the midwife-managed group were more likely to have an intact perineum and less likely to have had an episiotomy (p = 0.02), with no significant difference in perineal tears. Complication rates were similar. Overall, 32.8% of women were permanently transferred from midwife-managed care (28.7% for clinical reasons, 3.7% for non-clinical reasons). Women in both groups reported satisfaction with their care but the midwife-managed group were significantly more satisfied with their antenatal (difference in mean scores 0.48 [95% CI 0.41-0.55]), intrapartum (0.28 [0.18-0.37]), hospital-based postnatal care (0.57 [0.45-0.70]), and home-based postnatal care (0.33 [0.25-0.42]). INTERPRETATION: We conclude that midwife-managed care for healthy women, integrated within existing services, is clinically effective and enhances women's satisfaction with maternity care.

Adult↗

Changes in midwives' attitudes to their professional role following the implementation of the midwifery development unit.

OBJECTIVE: to examine changes in midwives' attitudes to their professional role following the implementation of the midwifery development unit (MDU). DESIGN: prospective cohort study. SETTING: the MDU is based at a major teaching hospital in Glasgow, UK. The MDU midwives provide care via a new self-rostering system which is intended to improve continuity of care. Midwives aim to provide total care for each woman from the antenatal period through delivery and the postnatal period. PARTICIPANTS: 21 midwives who joined the MDU were compared with a group of 64 midwives at the hospital who were also eligible and who continued in their usual pattern of work (non-MDU midwives). MEASUREMENTS: an audit questionnaire was distributed to MDU and non-MDU midwives prior to the implementation of the unit and about 15 months afterwards. In addition, the MDU midwives were sent the questionnaire every three months. Extra questions were added at each time period in order to identify specific problems. This information was then fed back to the midwifery management team to aid in the planning and implementation of the care programme. FINDINGS: the MDU midwives experienced a significant positive change in attitudes; no significant change was evident for the non-MDU group. There was no evidence of increased stress in the MDU midwives. In general, both groups of midwives had positive attitudes towards the unit and felt that MDU-style care had a role to play in the future provision of maternity care. A number of areas of concern were also highlighted, such as the system of liaison with colleagues. CONCLUSIONS: innovative models of midwifery care such as an MDU can have a positive impact on midwives' attitudes towards their professional role. IMPLICATIONS FOR PRACTICE: if change is managed in a systematic manner which involves the midwives, it may be possible to increase midwives' professional satisfaction, while at the same time minimising any negative effects such as increased stress.

Adult↗

Comparison of various methods for the enumeration of blood cells in urine.

This study compared the use of conventional urine microscopy, the KOVA system, Neubauer hemacytometry, and the Yellow IRIS for the determination of white blood cell (WBC) and red blood cell (RBC) counts in urine samples. Both KOVA WBC and RBC counts correlated better with the IRIS counts than with conventional microscopy. KOVA WBC counts correlated with Neubauer hemacytometry to the same degree as they did with IRIS WBC counts. The RBC count correlation was fairly similar between KOVA, hemacytometry, and the conventional method. It was concluded that the KOVA system is a suitable replacement for conventional urine microscopy.

Blood Cell Count↗

Effect of amino-terminal processing by Staphylococcus aureus V-8 protease on activity and structure of recombinant human interferon-gamma.

Treatment of recombinant human interferon-gamma (rHuIFN-gamma) with Staphylococcus aureus V-8 protease generated a transiently stable species that lacks 10 amino-terminal residues. This protein showed distinct secondary and higher-order structures with an alpha-helical content of 31%, suggesting that the secondary and tertiary structure largely remain upon removal of 10 amino-terminal residues. The antiviral activity was abolished, or greatly reduced, for this species relative to the intact protein. These results suggest an important role for the amino-terminal portion in the activity of human interferon-gamma. Since the digested protein is difficult to refold from the acid-denatured state, it was concluded that, although not essential for maintaining the core structure of the protein, the amino-terminal portion is critical for refolding the protein from acid.

Amino Acid Sequence↗

Alteration in folding efficiency and conformation of recombinant human tumor necrosis factor-alpha by replacing cysteines 69 and 101 with aspartic acid 69 and arginine 101.

An analog of human tumor necrosis factor-alpha (TNF-alpha) was created involving the replacement of Cys69 with Asp and Cys101 with Arg. The solution structure and behavior of this analog were compared with the native protein. The analog exhibited a greatly decreased folding efficiency following dilution from urea, but essentially identical circular dichroic spectra in both the folded and unfolded states. The Stokes radius of the native and analog TNF-alpha in the folded state were identical, with the analog exhibiting a slight broadening of the eluting peak. The fluorescence emission spectrum of the native protein exhibits a plateau from 320 to 328 nm, while the spectrum of the analog consisted of a single peak with a maximum at 335 nm. The analog also had a 1.4-fold increase in the fluorescence intensity. Limited proteolysis of the analog resulted in only one of the two peptides seen following digestion of the native protein, and this product was less stable than the equivalent native protein fragment. The analog exhibited a 10-fold lower cytolytic activity than the native protein. These results demonstrated that the disulfide bond is not necessary for folding and activity, but are consistent with the analog having a looser, more flexible structure in solution than the native TNF-alpha.

Amino Acid Sequence↗

Colostral transfer of Clostridium perfringens type C beta antitoxin in swine.

Nine bred gilts were vaccinated with 2 doses of a Clostridium perfringens type C toxoid at a 5-week interval. Time of vaccination during gestation differed among the gilts. Clostridium perfringens beta antitoxin in colostral samples and in serum samples was titrated in mice. Blood was collected from 2 to 5 neonatal pigs from each dam (total = 32 pigs) when the pigs were 36 to 48 hours old. Antitoxin titers in colostrum were 123 to 4.5 IU/ml, indicating considerable variation in individual responses of the gilts to toxoid. Serum titers of neonatal pigs reflected colostrum titers of their dams. This colostrum-to-serum titer correlation was essentially a straight-line fit by least-squares linear regression analysis, establishing a direct proportional relationship between colostrum titers and serum titers of neonatal pigs. In the dams, a correlation was not found between colostral titers and serum titers of blood samples collected 2 weeks after collection of colostrum.

Animals↗