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Biomedical subjects

M Cobb

Publications and source records attributed to M Cobb.

At least 19 recordsLinked to original sources
PubMed2004

A new quality assurance package for hospital palliative care teams: the Trent Hospice Audit Group model.

Cancer patients in hospitals are increasingly cared for jointly by palliative care teams, as well as oncologists and surgeons. There has been a considerable growth in the number and range of hospital palliative care teams (HPCTs) in the United Kingdom. HPCTs can include specialist doctors and nurses, social workers, chaplains, allied health professionals and pharmacists. Some teams work closely with existing cancer multidisciplinary teams (MDTs) while others are less well integrated. Quality assurance and clinical governance requirements have an impact on the monitoring of such teams, but so far there is no standardised way of measuring the amount and quality of HPCTs' workload. Trent Hospice Audit Group (THAG) is a multiprofessional research group, which has been developing standards and audit tools for palliative care since the 1990s. These follow a format of structure-process-outcome for standards and measures. We describe a collaborative programme of work with HPCTs that has led to a new set of standards and audit tools. Nine HPCTs participated in three rounds of consultation, piloting and modification of standard statements and tools. The final pack of HPCT quality assurance tools covers: policies and documentation; medical notes review; questionnaires for ward-based staff. The tools measure the HPCT workload and casemix; the views of ward-based staff on the supportive role of the HPCT and the effectiveness of HPCT education programmes, particularly in changing practice. The THAG HPCT quality assurance pack is now available for use in cancer peer review.

Hospice Care↗
PubMed2002

Timeline: exorcizing the animal spirits: Jan Swammerdam on nerve function.

For more than 1,500 years, nerves were thought to function through the action of 'animal spirits'. In the seventeenth century, René Descartes conceived of these 'spirits' as liquids or gases, and used the idea to explain reflex action. But he was rapidly proven wrong by a young Dutchman, Jan Swammerdam. Swammerdam's elegant experiments pioneered the frog nerve muscle preparation and laid the foundation of our modern understanding of nerve function.

Animals↗
PubMed2002

HIV/AIDS and care provider attributions: who's to blame?

The discovery of HIV/AIDS prompted a profusion of research focusing on the disease and its causes. Though the bulk of this research emphasizes behavioural risk factors, treatment and disease progression, researcher efforts are beginning to examine the public's attitude toward individuals who are HIV-positive or have developed AIDS. Utilizing Weiner's Attribution Theory, the current study examines the beliefs of social service providers who work directly with individuals affected by HIV/AIDS. Forty-six (28 female and 18 male) HIV/AIDS social service providers from three community-based organizations were asked to read a hypothetical scenario depicting an individual at-risk for HIV/AIDS because of multiple high-risk behaviours. The gender of the target was manipulated and at the conclusion of the scenario participants completed a questionnaire designed to assess attributions. Results of the study show that social service providers who perceive individuals as more responsible for their illness report increased anger, attribute more blame and express less willingness to help those at-risk for HIV/AIDS. This research suggests that despite growing numbers of media campaigns and national distribution of information regarding the disease and its transmission, in general, people continue to stigmatize and place blame on those at-risk.

Adult↗
PubMed2001

Wondrous order.

Explore the source record for details and available documents.

Animals↗
PubMed2001

Activated MEK5 induces serial assembly of sarcomeres and eccentric cardiac hypertrophy.

Mitogen-activated protein kinase (MAPK) pathways couple intrinsic and extrinsic signals to hypertrophic growth of cardiomyocytes. The MAPK kinase MEK5 activates the MAPK ERK5. To investigate the potential involvement of MEK5-ERK5 in cardiac hypertrophy, we expressed constitutively active and dominant-negative forms of MEK5 in cardiomyocytes in vitro. MEK5 induced a form of hypertrophy in which cardiomyocytes acquired an elongated morphology and sarcomeres were assembled in a serial manner. The cytokine leukemia inhibitory factor (LIF), which stimulates MEK5 activity, evoked a similar response. Moreover, a dominant-negative MEK5 mutant specifically blocked LIF-induced elongation of cardiomyocytes and reduced expression of fetal cardiac genes without blocking other aspects of LIF-induced hypertrophy. Consistent with the ability of MEK5 to induce serial assembly of sarcomeres in vitro, cardiac-specific expression of activated MEK5 in transgenic mice resulted in eccentric cardiac hypertrophy that progressed to dilated cardiomyopathy and sudden death. These findings reveal a specific role for MEK5-ERK5 in the induction of eccentric cardiac hypertrophy and in transduction of cytokine signals that regulate serial sarcomere assembly.

Animals↗
PubMed2001

Isolation and characterization of pmk-(1-3): three p38 homologs in Caenorhabditis elegans.

p38, a member of the mitogen-activated protein kinase (MAPK) superfamily, is activated in response to a variety of cellular stresses and ligands. Since the genome of the nematode C. elegans has been sequenced, we sought to identify and characterize the nematode homolog of mammalian p38. By sequence analysis and RT-PCR, we isolated cDNAs encoding three kinases, PMK-1, PMK-2, and PMK-3, which we call p38 map kinases due to their high sequence identity with p38. The three genes are contiguous on chromosome IV and comprise an operon. By use of a GFP reporter, we found that the promoter of the pmks is active throughout the intestine. An active form of MAPK/ERK kinase 6 (MEK6) phosphorylated and activated recombinant PMK-1 and PMK-2 in vitro. PMK-1 and PMK-2 phosphorylated activating transcription factor-2 (ATF-2), indicating an activity similar to mammalian p38. When transfected into mammalian cells, these kinases, like p38, are stimulated by osmotic stresses.

Activating Transcription Factor 2↗
PubMed2001

Sex, age and ovarian activity affect cuticular hydrocarbons in Diacamma ceylonense, a queenless ant.

In the queenless ant, Diacamma ceylonense, the cuticular hydrocarbons (C25-C35) of nestmate workers vary in their proportions according to age and fertility. Newly eclosed adults ('callows') initially have the same cuticular profile, but with time this changes to that typical of foragers. In contrast, workers that begin to produce eggs develop a different cuticular profile. Several substances (n-C29 and some methyl C25 and C27) discriminate these different social categories (callows, foragers and egg-layers). In Diacamma ceylonense, inter-colony variation of the cuticular hydrocarbons was much lower than intra-colony variation. We also found qualitative differences between the sexes, with males having a clearly different profile with much more alkanes. We discuss these results in the context of physiological models of the relation between ovarian activity and the synthesis of cuticular hydrocarbons. Variations in cuticular profile are a reliable reflection of ovarian activity, and could be used by ants as a fertility signal.

Journal Article↗
PubMed2000

Olfactory coding in a simple system: adaptation in Drosophila larvae.

Drosophila melanogaster larvae were pre-stimulated with high concentrations of six homologous alcohols (C4-C9) and then tested for adaptation and cross-adaptation using these same alcohols, four aliphatic n-acetates and three acids. Pre-stimulation with hexanol effectively reduced to zero (abolished) test responses to all six alcohols, whereas test responses to hexanol were only affected by pre-stimulation with hexanol. This substance appears to play a fundamental role in the organization of the larval olfactory system. Test responses to butanol and pentanol, and the effect of pre-stimulation with butanol and pentanol, were not significantly different, indicating that they are sensory equivalents. Heptanol, octanol and nonanol induce a complex set of responses among one another. Cross-adaptation between functional groups was observed, in particular following pre-stimulation with hexanol, but there was also evidence that functional groups are coded separately. A model of olfactory processing in the fruitfly maggot is presented that explains the data and provides predictions for future anatomical, genetic and electrophysiological studies.

Acetates↗
PubMed2000

Substrate recognition domains within extracellular signal-regulated kinase mediate binding and catalytic activation of mitogen-activated protein kinase phosphatase-3.

Mitogen-activated protein (MAP) kinase phosphatase-3 (MKP-3) is a dual specificity phosphatase that inactivates extracellular signal-regulated kinase (ERK) MAP kinases. This reflects tight and specific binding between ERK and the MKP-3 amino terminus with consequent phosphatase activation and dephosphorylation of the bound MAP kinase. We have used a series of p38/ERK chimeric molecules to identify domains within ERK necessary for binding and catalytic activation of MKP-3. These studies demonstrate that ERK kinase subdomains V-XI are necessary and sufficient for binding and catalytic activation of MKP-3. These domains constitute the major COOH-terminal structural lobe of ERK. p38/ERK chimeras possessing these regions display increased sensitivity to inactivation by MKP-3. These data also reveal an overlap between ERK domains interacting with MKP-3 and those known to confer substrate specificity on the ERK MAP kinase. Consistent with this, we show that peptides representing docking sites within the target substrates Elk-1 and p90(rsk) inhibit ERK-dependent activation of MKP-3. In addition, abolition of ERK-dependent phosphatase activation following mutation of a putative kinase interaction motif (KIM) within the MKP-3 NH(2) terminus suggests that key sites of contact for the ERK COOH-terminal structural lobe include residues localized between the Cdc25 homology domains (CH2) found conserved between members of the DSP gene family.

Amino Acid Sequence↗
PubMed2000

Open field is more sensitive than automated activity monitor in documenting ouabain-induced hyperlocomotion in the development of an animal model for bipolar illness.

1. Intracerebroventricular (i.c.v.) administration of ouabain to rats induces motor hyper- and hypoactivity that have been hypothesized to model the mania and depression of bipolar illness, respectively. 2. The extent of ouabain-induced change in activity may vary according to the test environment. 3. To determine the degree of differential response to i.c.v. ouabain in the open field and automated activity monitors, the authors examined a large number of animals (n=40) in both environments. 4. I.c.v. ouabain produced a four-fold increase in open field activity versus i.c.v. artificial cerebrospinal fluid (aCSF) (mean +/- SD: 258.7 +/- 316.61 vs. 84.8 +/- 86.16 squares traversed) (t = 2.648, P = 0.011), but did not alter horizontal activity in automated activity monitors (8193.5 +/- 4902.52 vs. 7088.47 +/- 3046.85 beam interruptions) (t = 0.847, P = 0.4). This increase in activity persisted for at least one week (161.0 +/- 186.35 for i.c.v. ouabain vs. 46.1 +/- 47.46 for i.c.v. aCSF, P = 0.065). 5. Open field is superior to automated activity monitors in capturing ouabain-induced hyperlocomotion response.

Animals↗
PubMed2000

Fragmented forests, evolving flies: molecular variation in African populations of Drosophila teissieri.

Microsatellite variation from eight loci was studied in five populations of Drosophila teissieri, a fruit-fly found only in the rain forests of sub-Saharan Africa. Five noncontiguous rain forest sites (from Tanzania, Gabon and Ivory Coast) were sampled to measure the effects of historical forest fragmentation on population structure in an obligatory forest-dwelling species. The Ivory Coast and Gabon populations showed a wider range of alleles, different modal alleles and had a higher genetic diversity than the three East African populations. As could be expected, genetic differentiation (FST) was significantly correlated with physical distance, but the westernmost population (Ivory Coast) showed values that were intermediate between the central (Gabon) and Eastern (Tanzania) populations. A migration-drift equilibrium in a stable continuum of populations did not appear adequate to describe the observed distribution. It seems probable that the species has undergone abrupt changes involving isolation, merging and migration of populations, as a consequence of repeated waves of forest fragmentation and coalescence.

Africa↗
PubMed1999

Genetic elimination of known pheromones reveals the fundamental chemical bases of mating and isolation in Drosophila.

Overexpression of the UAS-tra transgene in Drosophila melanogaster females led to the complete elimination of their cuticular pheromones. According to current models of Drosophila behavior, these flies should induce no courtship. In fact, they are still attractive to conspecific males. Three classes of stimuli are shown to induce courtship, with different effects on male behavior: (i) known pheromones produced by control females, (ii) stimuli produced by living control and transgenic flies, and (iii) as-yet-undetermined pheromones present on both control and transgenic flies. Only the latter class of pheromones are required for mating. They appear to represent a layer of ancestral attractive substances present in D. melanogaster and its sibling species; known cuticular pheromones modulate this attractivity positively or negatively. The absence of inhibitory pheromones leads to high levels of interspecific mating, suggesting an important role for these cuticular hydrocarbons in isolation between species.

Animals↗
PubMed1999

Chronic pulmonary disease in West Highland white terriers.

This paper describes the clinical features, and diagnostic findings of a chronic respiratory condition in 29 West Highland white terriers. Typically, the dogs were coughing chronically, had dyspnoea and tachypnoea of varying severity, and had deteriorated progressively over months to years. The mean (sem) survival time in months from the clinical signs being first noted by the owners was 17.9 (2.3). Most cases had a combination of respiratory signs, but coughing was the predominant sign in 18 cases. Inspiratory crackles were audible on chest auscultation in 28 cases, 10 of which were also wheezing. Rhonchi were the predominant sound in the remaining case. The main radiographic changes were mild to severe increased Interstitial markings in all cases, with additional bronchial markings in 14 of the dogs. Right-sided cardiomegaly (cor pulmonale) was recorded in 15. Bronchoscopic findings in 17 of the dogs were either normal or involved a mild airway mucoid reaction in eight. Chronic mucosal changes were observed in eight, but in two this finding was equivocal. Dynamic changes to the lumen of the airway were present in seven cases. No significant haematological or biochemical changes could be detected in 20 cases, but four cases were hypercholestrolaemic. A histopathological assessment of four cases revealed alveolar septal fibrosis to be the predominant change. Prednisolone, with or without bronchodilators, was the most commonly used therapy, and the response was variable. The condition appears to be associated with significant pulmonary interstitial fibrosis of unknown aetiology and has clinical similarities to idiopathic pulmonary fibrosis (cryptogenic fibrosing alveolitis) in human beings.

Animals↗
PubMed1999

Midlatency auditory-evoked potentials in the rat: effects of interventions that modulate arousal.

The vertex-recorded P13 midlatency auditory-evoked potential in the rat shows the same characteristics as the P1 potential in the human, namely, sleep-state dependence, rapid habituation and blockade by the cholinergic antagonist scopolamine. The P13 potential appears to be generated, at least in part, by projections of the pedunculopontine nucleus, the cholinergic arm of the reticular activating system. On the other hand, the auditory cortex-recorded P7 potential appears to be of primary cortical origin. Simultaneous recordings from the vertex and the auditory cortex showed that (1) the P13 potential was suppressed by administration of the anesthetics ketamine, pentobarbital or halothane in a dose-dependent manner, but the P7 potential was not; (2) the P13 potential was suppressed by intragastric injections of ethanol in a dose-dependent manner, but the P7 potential was not; (3) the amplitude of the P13 potential was negatively correlated with blood ethanol levels; (4) both the P13 and P7 potentials were still present following injections of the neuromuscular blocker pancuronium bromide; and (5) both the P13 and P7 potentials were decreased by diffuse brain injury induced by a weight-drop device in a weight-dependent manner. These findings suggest that the P13 potential is more sensitive than the P7 potential to changes in arousal and that the P13 and P7 potentials are not of myogenic but of neural origin.

Anesthetics↗
PubMed1998

Cutaneous epithelioid schwannomas: a rare variant of a benign peripheral nerve sheath tumor.

Although benign epithelioid peripheral nerve sheath tumors have been described, they are rare, and benign epithelioid schwannomas have not yet been established as a specific histologic variant. We present four cases of tumors which we believe would meet criteria to be classified as benign epithelioid schwannomas. Biopsy specimens obtained from four different patients were examined with routine and immunohistochemical staining. All the tumors were well-circumscribed lesions that were surrounded by a capsule containing EMA-positive cells. The cellular component was composed of epithelioid cells, in which there was a lack of mitotic activity. Immunohistochemical studies showed the tumor cells were S-100 protein and Leu 7 positive and HMB-45 negative. In addition, type IV collagen encircled individual cells within the tumor, indicating a continuous basal lamina. We report a group of cutaneous epithelioid schwannomas. Although the presence of such tumors is not unexpected, this diagnosis may not be initially considered because of this rare cytologic feature.

Adult↗
PubMed1997

NIK is a new Ste20-related kinase that binds NCK and MEKK1 and activates the SAPK/JNK cascade via a conserved regulatory domain.

Nck, an adaptor protein composed of one SH2 and three SH3 domains, is a common target for a variety of cell surface receptors. We have identified a novel mammalian serine/threonine kinase that interacts with the SH3 domains of Nck, termed Nck Interacting Kinase (NIK). This kinase is most homologous to the Sterile 20 (Ste20) family of protein kinases. Of the members of this family, GCK and MSST1 are most similar to NIK in that they bind neither Cdc42 nor Rac and contain an N-terminal kinase domain with a putative C-terminal regulatory domain. Transient overexpression of NIK specifically activates the stress-activated protein kinase (SAPK) pathway. Both the kinase domain and C-terminal regulatory region of NIK are required for full activation of SAPK. NIK likely functions upstream of MEKK1 to activate this pathway; a dominant-negative MEK kinase 1 (MEKK1) blocks activation of SAPK by NIK. MEKK1 and NIK also associate in cells and this interaction is mediated by regulatory domains on both proteins. Two other members of this kinase family, GCK and HPK1, contain C-terminal regulatory domains with homology to that of NIK. These findings indicate that the C-terminal domain of these proteins encodes a new protein domain family and suggests that this domain couples these kinases to the SAPK pathway, possibly by interacting with MEKK1 or related kinases.

Adaptor Proteins, Signal Transducing↗
PubMed1997

The meaning of spirituality: a literature review.

This paper presents a literature review in relation to the meaning of spirituality. It is proposed that meeting the spiritual needs of patients is a fundamental part of providing holistic nursing care, but that the assessment and meeting of those needs is impeded by inadequate definitions and conceptual frameworks. It should not be assumed that spirituality is either synonymous, or coterminous, with religion, and it is suggested that to adopt this restrictive view is unhelpful in the provision of individualized care. Reflection on the literature reveals that the self, others and 'God' provide the key elements within a definition of spirituality, and that other emerging themes namely meaning, hope, relatedness/connectedness, beliefs/belief systems and expressions of spirituality, can be articulated in the context of those three key elements. In particular, it is proposed that the nature of 'God' may take many forms and, essentially, is whatever an individual takes to be of highest value in his/her life. It is suggested that the themes emerging from the literature can be utilized as a framework to give practitioners and researchers a direction for future exploration of the concept of spirituality.

Holistic Nursing↗