PubMed HealthSearch

Biomedical subjects

J Mulholland

Publications and source records attributed to J Mulholland.

At least 19 recordsLinked to original sources

The transcriptional program of sporulation in budding yeast.

Diploid cells of budding yeast produce haploid cells through the developmental program of sporulation, which consists of meiosis and spore morphogenesis. DNA microarrays containing nearly every yeast gene were used to assay changes in gene expression during sporulation. At least seven distinct temporal patterns of induction were observed. The transcription factor Ndt80 appeared to be important for induction of a large group of genes at the end of meiotic prophase. Consensus sequences known or proposed to be responsible for temporal regulation could be identified solely from analysis of sequences of coordinately expressed genes. The temporal expression pattern provided clues to potential functions of hundreds of previously uncharacterized genes, some of which have vertebrate homologs that may function during gametogenesis.

Animals

A complaints management system: strengths and weaknesses.

AIMS: To describe the complaints management process in a base hospital and to outline its guiding principles. METHOD: A review and analysis of the complaints lodged during 1996 with the Complaints Management System of the hospital. RESULTS: There were 146 complaints lodged after 132,400 patient contacts. Overall resolution time was 14 days, but 24 appeals were lodged against the initial opinion and were all subsequently resolved satisfactorily. CONCLUSION: The complaints process should be user friendly, result in a quick response and be seen as a quality rather than a disciplinary tool.

Female

Mediators of estradiol-stimulated mitosis in the rat uterine luminal epithelium.

The effects of estradiol treatment, which stimulates cell division in rat uterine epithelial cells, on the in vivo expression of heparin-binding epidermal growth factor (HB-EGF), cyclin D1, and cyclin B1 messenger RNA (mRNA) in these cells have been examined using ribonuclease protection assays. Estradiol gave rise to significant increases in steady state levels of HB-EGF 2 and 24 h after treatment. Cyclin D1 mRNA levels were elevated 8 and 10 h after estradiol administration, corresponding to the G1 phase of the mitotic cycle, and cyclin B1 mRNA was only expressed 16-24 h after estradiol treatment, which corresponds to the G2 and M phases of the rat uterine epithelial cell cycle. Estradiol-stimulated increases in HB-EGF mRNA were not affected by treatment with cycloheximide, but were inhibited by the estrogen antagonist compound, ICI 164,384, demonstrating that the estrogen-stimulated increase in HB-EGF mRNA is a primary, estrogen receptor-mediated response of rat uterine epithelium to estradiol. Progesterone treatment, which blocks epithelial cells in G1 of the cycle, suppressed levels of HB-EGF mRNA below those observed in ovariectomized rats. These results indicate that HB-EGF mediates the regulatory effects of both estradiol and progesterone on rat uterine epithelial cell proliferation through an effect on the production of G1 phase molecules such as cyclin D1.

Animals

Can we make it better?

The range and nature of patient complaints that resulted from the services provided in Southland base hospital over a 1-year period were studied. The data were assessed in the hope that they would provide new and important information to further develop quality assurance in the hospital service. There were 146 complaints, 15 of which were significant. Ten of these involved clinical care standards. There were 132,400 patient contacts during this time. The most common complaints related to the attitudes of health professionals, as perceived by the patient, and about information and other aspects that pertained to their individual care. These patient complaints did not provide unique information but would be useful if combined with other methods to determine patient dissatisfaction with the service provided.

Hospitals

Two new Ypt GTPases are required for exit from the yeast trans-Golgi compartment.

Small GTPases of the Ypt/rab family are involved in the regulation of vesicular transport. These GTPases apparently function during the targeting of vesicles to the acceptor compartment. Two members of the Ypt/rab family, Ypt1p and Sec4p, have been shown to regulate early and late steps of the yeast exocytic pathway, respectively. Here we tested the role of two newly identified GTPases, Ypt31p and Ypt32p. These two proteins share 81% identity and 90% similarity, and belong to the same protein subfamily as Ypt1p and Sec4p. Yeast cells can tolerate deletion of either the YPT31 or the YPT32 gene, but not both. These observations suggest that Ypt31p and Ypt32p perform identical or overlapping functions. Cells deleted for the YPT31 gene and carrying a conditional ypt32 mutation exhibit protein transport defects in the late exocytic pathway, but not in vacuolar protein sorting. The ypt31/ 32 mutant secretory defect is clearly downstream from that displayed by a ypt1 mutant and is similar to that of sec4 mutant cells. However, electron microscopy revealed that while sec4 mutant cells accumulate secretory vesicles, ypt31/32 mutant cells accumulate aberrant Golgi structures. The ypt31/32 phenotype is epistatic to that of a sec1 mutant, which accumulates secretory vesicles. Together, these results indicate that the Ypt31/32p GTPases are required for a step that occurs in the trans-Golgi compartment, between the reactions regulated by Ypt1p and Sec4p. This step might involve budding of vesicles from the trans-Golgi. Alternatively, Ypt31/32p might promote secretion indirectly, by allowing fusion of recycling vesicles with the trans-Golgi compartment.

Cell Compartmentation

Assimilating sociology: critical reflections on the 'sociology in nursing' debate.

We are witnessing the emergence of a 'new nursing'. In part, this has been associated with the adoption of a 'holistic' model of health and a commitment to a holistic curriculum within nurse education. The role of sociology within the nursing enterprise has been the subject of much debate. This paper seeks to further this debate by arguing that sociology is invaluable to nursing for many reasons but that its value may be undermined as a consequence of being overly constrained within the nursing arena, at the mutual expense of both sociology and the long term interests of nursing itself. This paper will suggest that central to an understanding of how this 'surplus constraint' of sociology occurs in an understanding of the manner in which the holistic model has been adopted in much of nursing and nurse education. The 'indeterminacy' of the holistic model is such that is has empowered a questionable eclecticism, marginalized philosophical controversies within nursing theory, disguised difficult epistemological and ontological conflicts associated with competing claims to truth and facilitated the operation of a form of power whereby sociology has been excluded, at the very moment of its apparent inclusion. This paper goes on to argue that the value of sociology to nursing is dependent upon: firstly, a more systematic and rigorous discussion of its relationship to, and role within, nursing and secondly, a movement away from an implicit 'assimilation' model regarding the incorporation of sociology into nursing towards a more 'multi-cultural' approach. Only under such circumstances may sociology's value to nursing be realized but in a manner that places an importance on maintaining the ontological and epistomological integrity of the sociological tradition.

Education, Nursing

Communication between nurses and nurse managers: a case study from an NHS Trust.

The role of effective communication in promoting organizational efficiency and effectiveness is being increasingly recognized. This paper proposes a communication audit methodology as a useful means of examining the quality of communication between nurses and their managers. Utilizing a case study methodology, results from an exploratory study are presented and discussed. These data suggest that significant problems in this field currently exist. The general applicability of the findings throughout the NHS are considered, and proposals on how relationships and communication could be improved are examined.

Adult

An essential role of the yeast pheromone-induced Ca2+ signal is to activate calcineurin.

Previous studies showed that, in wild-type (MATa) cells, alpha-factor causes an essential rise in cytosolic Ca2+. We show that calcineurin, the Ca2+/calmodulin-dependent protein phosphatase, is one target of this Ca2+ signal. Calcineurin mutants lose viability when incubated with mating pheromone, and overproduction of constitutively active (Ca(2+)-independent) calcineurin improves the viability of wild-type cells exposed to pheromone in Ca(2+)-deficient medium. Thus, one essential consequence of the pheromone-induced rise in cytosolic Ca2+ is activation of calcineurin. Although calcineurin inhibits intracellular Ca2+ sequestration in yeast cells, neither increased extracellular Ca2+ nor defects in vacuolar Ca2+ transport bypasses the requirement for calcineurin during the pheromone response. These observations suggest that the essential function of calcineurin in the pheromone response may be distinct from its modulation of intracellular Ca2+ levels. Mutants that do not undergo pheromone-induced cell cycle arrest (fus3, far1) show decreased dependence on calcineurin during treatment with pheromone. Thus, calcineurin is essential in yeast cells during prolonged exposure to pheromone and especially under conditions of pheromone-induced growth arrest. Ultrastructural examination of pheromone-treated cells indicates that vacuolar morphology is abnormal in calcineurin-deficient cells, suggesting that calcineurin may be required for maintenance of proper vacuolar structure or function during the pheromone response.

Biological Transport

Yeast actin cytoskeleton mutants accumulate a new class of Golgi-derived secretary vesicle.

Many yeast actin cytoskeleton mutants accumulate large secretory vesicles and exhibit phenotypes consistent with defects in polarized growth. This, together with actin's polarized organization, has suggested a role for the actin cytoskeleton in the vectorial transport of late secretory vesicles to the plasma membrane. By using ultrastructural and biochemical analysis, we have characterized defects manifested by mutations in the SLA2 gene (also known as the END4 gene), previously found to affect both the organization of the actin cytoskeleton and endocytosis in yeast. Defects in cell wall morphology, accumulated vesicles, and protein secretion kinetics were found in sla2 mutants similar to defects found in act1 mutants. Vesicles that accumulate in the sla2 and act1 mutants are immunoreactive with antibodies directed against the small GTPase Ypt1p but not with antibodies directed against the homologous Sec4p found on classical "late" secretory vesicles. In contrast, the late-acting secretory mutants sec1-1 and sec6-4 are shown to accumulate anti-Sec4p-positive secretory vesicles as well as vesicles that are immunoreactive with antibodies directed against Ypt1p. The late sec mutant sec4-8 is also shown to accumulate Ypt1p-containing vesicles and to exhibit defects in actin cytoskeleton organization. These results indicate the existence of at least two classes of morphologically similar, late secretory vesicles (associated with Ypt1p+ and Sec4p+, respectively), one of which appears to accumulate when the actin cytoskeleton is disorganized.

Antibody Specificity

Protocols and guidelines for managing wounds.

The management of a chronic wound is aimed at symptom control and maintaining the individual's quality of life. Wound-care guidelines will promote a co-ordinated and systematic approach to wound management. The administration of wound-care products according to protocol can enhance the care of patients with complex chronic wounds.

Clinical Protocols

Effects of tamoxifen and ICI 164384 on protein synthesis and vectorial secretion in polarized rat uterine epithelial cells.

A polarized, primary cell, bicameral culture system was utilized to test the effects of two types of antiestrogens, tamoxifen (class I) and ICI 164384 (class II) on post-mitotic, uterine epithelial cells. The results demonstrate that in addition to blocking estrogen action in a dose-dependent manner, each of these compounds has independent effects on protein synthesis and secretion in these cells. The effects of both tamoxifen and ICI 164384 on vectorial protein secretion were completely opposite to those of estradiol. Both antiestrogens given alone repressed apical secretion and stimulated basal secretion, whereas estradiol stimulated apical and repressed basal secretion. Furthermore, specific protein bands in both the apical and basal secretory compartments responded differently according to dose to each compound. These experiments using polarized uterine epithelial cell cultures have identified apical and basal protein secretion as two cellular response with increased sensitivity to steroids and antisteroids.

Animals

Analysis of Tub4p, a yeast gamma-tubulin-like protein: implications for microtubule-organizing center function.

gamma-Tubulin is a conserved component of microtubule-organizing centers and is thought to be involved in microtubule nucleation. A recently discovered Saccharomyces cerevisiae gene (TUB4) encodes a tubulin that is related to, but divergent from, gamma-tubulins. TUB4 is essential for cell viability, and epitope-tagged Tub4 protein (Tub4p) is localized to the spindle pole body (Sobel, S.G., and M. Snyder. 1995.J. Cell Biol. 131:1775-1788). We have characterized the expression of TUB4, the association of Tub4p with the spindle pole body, and its role in microtubule organization. Tub4p is a minor protein in the cell, and expression of TUB4 is regulated in a cell cycle-dependent manner. Wild-type Tub4p is localized to the spindle pole body, and a Tub4p-green fluorescent protein fusion is able to associate with a preexisting spindle pole body, suggesting that there is dynamic exchange between cytoplasmic and spindle pole body forms of Tub4p. Perturbation of Tub4p function, either by conditional mutation or by depletion of the protein, results in spindle as well as spindle pole body defects, but does not eliminate the ability of microtubules to regrow from, or remain attached to, the spindle pole body. The spindle pole bodies in tub4 mutant cells duplicate but do not separate, resulting in a monopolar spindle. EM revealed that one spindle pole body of the duplicated pair appears to be defective for the nucleation of microtubules. These results offer insight into the role of gamma-tubulin in microtubule-organizing center function.

Animals

Nursing, humanism and transcultural theory: the 'bracketing-out' of reality.

This paper addresses the emergence of a humanist discourse within nursing and questions the extent to which it represents the panacea implied within much of the humanist nursing literature. Particular attention will be given to whether it represents an ontological and epistemological framework capable of understanding the social, economic and political dynamics formative in the structuring of nurse-client relations. It will be argued that the humanist analyses extant within much nursing literature are vague, idealistic, inconsistent and inadequate in the sense that they offer little by way of a meaningful analysis of power. A critique will also be made of the methodological individualism implicit within much humanist analyses. The paper will go on to identify the influence of humanist approaches on transcultural theory, and the manner in which the epistemological foundations of the latter have shared the limitations of the humanistic nursing approach generally. As such, the transcultural nursing literature is often vague, inconsistent in its use of terminology, lacking in any rigorous analysis of power, and suspect in its conceptualizations of culture. Its capacity for enabling nurses to examine critically the socio-economic and political dynamics of nurse-client relations and develop strategies for addressing racisms, considered by many to be endemic within nursing and health care system generally, is seriously undermined.

Cultural Diversity

Morphological and immunohistochemical differentiation patterns of rabbit uterine epithelium in vitro.

We describe morphological and immunohistochemical changes of uterine epithelium from immature rabbits in vitro in response to hormonal treatments, using a matrix-coated semipermeable filter. These investigations were compared to in vivo studies of uterine epithelium from immature rabbits treated with estrogen and/or progesterone. In vitro, polarization of the epithelium seems to be best developed under progesterone dominance, and the pattern of cell organelles is similar to those seen in vivo. Two types of apical protrusions could be observed in cultures treated with progesterone, some shaped like domes, containing cell organelles, and some irregular in shape with small lucent vesicles. Both types of apical differentiation are typical for the in vivo situation. In vitro, estrogen leads to a more pseudostratified growth pattern of the cells. They develop apical protrusions with big vesicles probably containing mucin, as in vivo. Treatment with both steroid hormones leads to a heterogeneous response of the uterine epithelial cells in culture, some cells responding more to the estrogen, others to the progesterone whereas in vivo the progesterone-dominant features are obvious. Immunohistochemistry of uteroglobin in monensin-treated cultures gives evidence for uteroglobin secretion in all cultures, but to a lesser extent in the untreated, and this is strongly increased in cultures treated with estrogen and progesterone. These results correspond to observations made in vivo. This in vitro cell culture method seems therefore to provide a useful model for investigating the regulatory mechanisms of sexual steroid hormones and the cell biology of uterine receptivity.

Animals

Ultrastructure of the yeast actin cytoskeleton and its association with the plasma membrane.

We characterized the yeast actin cytoskeleton at the ultrastructural level using immunoelectron microscopy. Anti-actin antibodies primarily labeled dense, patchlike cortical structures and cytoplasmic cables. This localization recapitulates results obtained with immunofluorescence light microscopy, but at much higher resolution. Immuno-EM double-labeling experiments were conducted with antibodies to actin together with antibodies to the actin binding proteins Abp1p and cofilin. As expected from immunofluorescence experiments, Abp1p, cofilin, and actin colocalized in immuno-EM to the dense patchlike structures but not to the cables. In this way, we can unambiguously identify the patches as the cortical actin cytoskeleton. The cortical actin patches were observed to be associated with the cell surface via an invagination of plasma membrane. This novel cortical cytoskeleton-plasma membrane interface appears to consist of a fingerlike invagination of plasma membrane around which actin filaments and actin binding proteins are organized. We propose a possible role for this unique cortical structure in wall growth and osmotic regulation.

Actins

Regulation of connexin26 and connexin43 expression in rat endometrium by ovarian steroid hormones.

A distinct spatial and temporal pattern of connexin26 and connexin43 (cx26 and cx43) expression was observed in the rat endometrium in response to embryo implantation; however, connexin expression was suppressed during the preimplantation period. Pseudopregnant rats did not show connexin mRNA, while artificial decidualization induced by a scratch led to a strong expression of cx26 and cx43 in the endometrium of these animals. In order to examine the regulatory effects of ovarian steroid hormones on connexin expression, ovariectomized rats were treated with progesterone (P) and/or estradiol-17 beta (E2). Untreated, ovariectomized animals expressed mRNA for cx43, but not for cx26. Endometrial expression of mRNA for both connexins was strongly enhanced by E2 treatment; immunolabeling revealed protein for cx26 in the uterine luminal epithelial cells and for cx43 in the uterine stromal cells. P treatment, either alone or in combination with E2, suppressed expression of connexin mRNA. P suppression in the presence of E2 was reversible when P was withdrawn. When administered on Days 0-2 of pregnancy, the antiprogestin onapristone inhibited the effect of P and gave rise to strong expression of both connexin transcripts. These results demonstrate that expression of cx26 and cx43 in the rat uterine endometrium is differentially regulated by E2 and P during early pregnancy.

Animals

Competency-based learning applied to nursing management.

The ability to manage change has become an essential skill for all managers, particularly those employed within the Health and Social Services. It is recognized that managers may have received an introduction to management concepts and skills within their professional education but require more specific management development. The government approach to adult education with an increased emphasis on vocational training as opposed to professional education (Hyland 1991) has had an important impact upon the theory and practice of nurse management. Nurses are now required to demonstrate, not only the appropriate knowledge and theory of management, but also the competencies necessary to fulfil their role. This is becoming an important dimension of management development programmes. This paper discusses aspects of competency based learning and considers how these concepts are applied to a higher education nurse management programme on 'Managing Change'. The difficulties experienced in applying vocational standards to professional education within the culture of a higher education will be explored, difficulties identified and some alternatives offered.

Competency-Based Education