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Biomedical subjects

A Clarke

Publications and source records attributed to A Clarke.

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

Comparative health systems: international collaborative education using the internet.

Between January and June 1998, postgraduate and undergraduate students from seven centres participated in a discussion of suicide from a public health perspective, using a listserver on the Internet. Most contributions were in English but a few were in Spanish with subsequent translation. Eighteen out of 32 students responding to evaluation, found the module worthwhile and their learning objectives were met. After making a few modifications to procedures resulting from the evaluation, further rounds of discussion were started in October 1998. International discussion groups using listservers on the Internet provide a new and apparently effective method of education.

Education, Medical, Continuing↗
PubMed2000

NO way back: nitric oxide and programmed cell death in Arabidopsis thaliana suspension cultures.

Recent research has implicated nitric oxide (NO) in the induction of the hypersensitive response (HR) during plant-pathogen interactions. Here we demonstrate that Arabidopsis suspension cultures generate elevated levels of NO in response to challenge by avirulent bacteria, and, using NO donors, show that these elevated levels of NO are sufficient to induce cell death in Arabidopsis cells independently of reactive oxygen species (ROS). We also provide evidence that NO-induced cell death is a form of programmed cell death (PCD), requiring gene expression, and has a number of characteristics of PCD of mammalian cells: NO induced chromatin condensation and caspase-like activity in Arabidopsis cells, while the caspase-1 inhibitor, Ac-YVAD-CMK, blocked NO-induced cell death. A well-established second messenger mediating NO responses in mammalian cells is cGMP, produced by the enzyme guanylate cyclase. A specific inhibitor of guanylate cyclase blocked NO-induced cell death in Arabidopsis cells, and this inhibition was reversed by the cell-permeable cGMP analogue, 8Br-cGMP, although 8Br-cGMP alone did not induce cell death or potentiate NO-induced cell death. This suggests that cGMP synthesis is required but not sufficient for NO-induced cell death in Arabidopsis. In-gel protein kinase assays showed that NO activates a potential mitogen-activated protein kinase (MAPK), although a specific inhibitor of mammalian MAPK activation, PD98059, which blocked H2O2-induced cell death, did not inhibit the effects of NO.

Amino Acid Chloromethyl Ketones↗
PubMed2000

A model protocol evaluating the introduction of genetic assessment for women with a family history of breast cancer.

Randomised controlled trials allow comparisons to be made between different models of service delivery, but have not been used in the field of clinical genetics. With the advent of clinical governance, the evidence provided by such trials will be increasingly important in informing and shaping clinical genetics practice. The TRACE project (Trial of genetic assessment in breast cancer) is a randomised controlled trial of genetic assessment for women who are at increased risk of breast cancer because of their family history. The absence of cancer genetics service provision in Wales before this study gave a window of opportunity in which this important trial could be conducted. The present paper describes how TRACE will provide crucial evidence regarding the psychosocial as well as resource implications of adding individualised genetic assessment, genetic counselling, and (where appropriate) gene testing to typical advice and surveillance from a hospital breast clinic. In addition, it is anticipated that TRACE will represent a model for future trials of service delivery in the increasing number of complex genetic disorders where evidence on the economic implications of screening and management is currently limited.

Adult↗
PubMed2000

Why do women attend familial breast cancer clinics?

The increasing demand for genetic assessment for familial breast cancer has necessitated the development of cancer genetics services. However, little is known about the factors motivating the client population likely to approach these services. A cross sectional questionnaire survey of 1000 women with a family history of breast cancer was conducted to identify self-reported reasons for attending a familial breast cancer clinic and possible differences in the characteristics of women who were attending for diverse reasons. Before attendance at clinic, 833 women completed a baseline questionnaire (83% response rate). Women who gave personal risk (n=188), awareness of a family history (n=120), risk to family members (n=84), reassurance (n=69), genetic testing (n=65), breast screening (n=46), or prevention (n=39) as their main reason for attending were compared on demographic and medical variables, and on psychological variables including general anxiety, cancer worry, perceived risk, and attitudes towards prophylactic surgery and genetic testing. Important differences in the psychological characteristics of these groups were found, which were unrelated to reported family history. In particular, women who primarily wanted genetic testing felt extremely vulnerable to developing breast cancer, were more likely to be considering prophylactic surgery, and perceived fewer limitations of testing. Those who primarily wanted reassurance were highly anxious about the disease. We recommend that cancer genetics services take into consideration the informational and psychological needs and concerns of their client group.

Ambulatory Care Facilities↗
PubMed1999

NuA4, an essential transcription adaptor/histone H4 acetyltransferase complex containing Esa1p and the ATM-related cofactor Tra1p.

Post-translational acetylation of histone H4 N-terminal tail in chromatin has been associated with several nuclear processes including transcription. We report the purification and characterization of a native multisubunit complex (NuA4) from yeast that acetylates nucleosomal histone H4. NuA4 has an apparent molecular mass of 1.3 MDa. All four conserved lysines of histone H4 can be acetylated by NuA4. We have identified the catalytic subunit of the complex as the product of ESA1, an essential gene required for cell cycle progression in yeast. Antibodies against Esa1p specifically immunoprecipitate NuA4 activity whereas the complex purified from a temperature-sensitive esa1 mutant loses its acetyltransferase activity at the restrictive temperature. Additionally, we have identified another subunit of the complex as the product of TRA1, an ATM-related essential gene homologous to human TRRAP, an essential cofactor for c-Myc- and E2F-mediated oncogenic transformation. Finally, the ability of NuA4 to stimulate GAL4-VP16-driven transcription from chromatin templates in vitro is also lost in the temperature-sensitive esa1 mutant. The function of the essential Esa1 protein as the HAT subunit of NuA4 and the presence of Tra1p, a putative transcription activator-interacting subunit, supports an essential link between nuclear H4 acetylation, transcriptional regulation and cell cycle control.

Acetylation↗
PubMed1999

Magma flow instability and cyclic activity at soufriere hills volcano, montserrat, british west indies

Dome growth at the Soufriere Hills volcano (1996 to 1998) was frequently accompanied by repetitive cycles of earthquakes, ground deformation, degassing, and explosive eruptions. The cycles reflected unsteady conduit flow of volatile-charged magma resulting from gas exsolution, rheological stiffening, and pressurization. The cycles, over hours to days, initiated when degassed stiff magma retarded flow in the upper conduit. Conduit pressure built with gas exsolution, causing shallow seismicity and edifice inflation. Magma and gas were then expelled and the edifice deflated. The repeat time-scale is controlled by magma ascent rates, degassing, and microlite crystallization kinetics. Cyclic behavior allows short-term forecasting of timing, and of eruption style related to explosivity potential.

Journal Article↗
PubMed1999

Harpin induces mitogen-activated protein kinase activity during defence responses in Arabidopsis thaliana suspension cultures.

Elicitation of Arabidopsis thaliana (L.) Heynh. suspension cultures with the bacterial protein harpin (from Pseudomonas syringae pv. syringae) induced the activation of two kinases of 39 and 44 kDa, as demonstrated by in-gel kinase assays using myelin basic protein (MBP) as a substrate. Both these kinases appeared to be tyrosine-phosphorylated upon activation, as demonstrated by treatment with tyrosine phosphatase and immunoprecipitation using an anti-phosphotyrosine monoclonal antibody. An inhibitor of mammalian mitogen-activated protein kinase (MAPK) activation, PD98059, inhibited harpin-induced MBPK activation, but did not inhibit the activity of these kinases. PD98059 also inhibited harpin-induced programmed cell death and defence gene expression, suggesting the involvement of harpin-induced MAPKs in defence responses in Arabidopsis thaliana.

Apoptosis↗
PubMed1999

Micrometastases in esophagogastric cancer: high detection rate in resected rib segments.

BACKGROUND & AIMS: Micrometastases within bone marrow indicate a poor prognosis. We prospectively examined micrometastases in patients undergoing resection of esophagogastric cancers for (1) prevalence in rib marrow; (2) comparative detection rates in rib and iliac crest marrow; (3) responsiveness to neoadjuvant therapy; and (4) viability and tumorigenicity. METHODS: In 50 consecutive patients, marrow was obtained before manipulation of the primary tumor. Micrometastatic cells were detected by staining contaminant cytokeratin-18-positive cells. Viability and tumorigenicity were determined by culture and xenograft. RESULTS: Micrometastases were detected in rib marrow from 88% of patients (44 of 50). When bilateral iliac crest marrow was also obtained, micrometastases were found in 15% (4 of 27) compared with 89% (24 of 27) for ribs (P < 0.001). Detection rates were independent of histological type or nodal status and were similar in patients with and without neoadjuvant therapy. Metastatic cells were cultured from rib marrow of 5 of 7 patients and were tumorigenic in nude mice. CONCLUSIONS: Most patients undergoing resection of esophagogastric malignancies have micrometastases in rib marrow. Detection rates based on iliac crest marrow are underestimates. Hematogenous spread of metastatic cells is independent of histological type or nodal status. The metastatic cells are viable, tumorigenic, and resistant to neoadjuvant therapy.

Adenocarcinoma↗
PubMed1999

Characterization of 34 novel and six known MTM1 gene mutations in 47 unrelated X-linked myotubular myopathy patients.

X-linked myotubular myopathy (XLMTM) is a congenital muscle disorder mainly affecting newborn males. Neonatal muscle weakness and hypotonia usually leads to a rapid demise. The responsible gene, MTM1, was isolated in 1996, and mutational data derived from 90 patients have been published. We report on our findings in a further 53 patients, using genomic DNA and mRNA screening protocols. Thirty-four novel mutations were identified in 37 cases, and six known mutations found in 10 other patients. The 34 new mutations include five large deletions, eight nonsense, six frameshift, five missense, and eight splice-site mutations, whereas two intronic variants causing partial exon skipping represent the first report on such a mechanism in MTM1. Two deletions, one involving exon 1, and the second exon 15, are the first defects to be identified in these exons. The heterogeneity of the mutations, their mutational origins, and the varied ethnic backgrounds of the patients, indicate that the majority of XLMTM families are affected by unique MTM1 mutations.

Adult↗
PubMed1999

Respite care for frail older people and their family carers: concept analysis and user focus group findings of a pan-European nursing research project.

This paper provides a concept analysis of respite care for frail older people and their family carers. The authors re-examine the broader conceptualization of respite care delineated by Nolan & Grant, namely, users' needs for information, education and support about respite care, based on a review of recent literature and on a user focus group study. This work was undertaken by the Sheffield arm of the ACTION Project research team. ACTION is a 36-month project (1997-1999), involving Northern Ireland, The Republic of Ireland, Portugal, Sweden and England and is the largest nurse-led project to have received funding from the European Union TIDE sector (DGXIII Telematics Applications Programme, Disabled and Elderly). The authors discuss the key elements of respite and, more specifically, how they can be successfully used so that the potential of respite may be realized fully by family carers. Recommendations within the context of the ACTION research project are put forward to enable family carers and the persons they care for to make informed choices about respite care.

Adaptation, Psychological↗
PubMed1999

A multimedia intervention to support family caregivers.

The lack of choice and predominance of crisis-oriented care in relation to respite and long-term care for family carers and frail older people provided the authors with the rationale for the development, within the European-funded Assisting Carers using Telematic Interventions to meet Older person's Needs (ACTION) project, of two innovative multimedia programs. The key aim of the programs is to provide education, information, and support about respite care and planning for the future for family carers and frail older people in their homes. In this way, it is intended that family carers and frail older people will be able to make informed choices concerning their health and social care needs. The authors describe the conceptual basis of the multimedia programs, the research and development process, the content of the multimedia programs, and the evaluation of the developed product.

Aged↗
PubMed1999

End-stage renal failure in adults with the tuberous sclerosis complex.

BACKGROUND: Tuberous sclerosis (TSC) is a multisystem disorder encompassing a wide spectrum of pathological renal lesions. Renal involvement is commonly asymptomatic but can result in significant morbidity, and renal failure has been reported. The risk of renal failure in patients with TSC in the UK has not been defined. METHODS: A survey of the 170 members of the European Dialysis and Transplant Association was carried out to identify and collect clinical information on patients with TSC in their renal replacement programme. RESULTS: Ten patients were identified as having end-stage renal failure (ESRF) and TSC, giving an incidence of 1% in patients with TSC and normal intellect. There was a wide spectrum of underlying pathology and clinical presentation within this group. CONCLUSION: ESRF is rare in TSC but does contribute to significant morbidity and mortality in this group.

Acute Kidney Injury↗
PubMed1999

Comparison of isolation media for recovery of Burkholderia cepacia complex from respiratory secretions of patients with cystic fibrosis.

Burkholderia cepacia selective agar (BCSA) has previously been devised for isolation of B. cepacia from respiratory secretions of patients with cystic fibrosis and tested under research laboratory conditions. Here we describe a study in which BCSA, oxidation-fermentation polymyxin bacitracin lactose agar (OFPBL), and Pseudomonas cepacia agar (PCA) were compared in routine culture procedures for the ability to grow B. cepacia and inhibit other organisms. Three hundred twenty-eight specimens from 209 patients at two pediatric centers and 328 specimens from 109 adults were tested. Plates were inoculated, incubated, and read for quality and quantity of growth at 24, 48, and 72 h. Five (1.5%) specimens from 4 (1.9%) children and 75 (22.9%) specimens from 16 (14.7%) adults grew B. cepacia complex. At 24, 48, and 72 h, BCSA achieved 43, 93, and 100% detection, respectively; OFPBL achieved 26, 84, and 96%, respectively; and PCA achieved 33, 74, and 84% detection, respectively. Quality was assessed as pinpoint or good growth. At 24 h, most cultures growing B. cepacia complex had pinpoint colonies. By 48 and 72 h, 48 and 69% of B. cepacia complex cultures, respectively, had good growth on BCSA, while on OFPBL 19 and 30%, respectively, had good growth and on PCA 11 and 18%, respectively, had good growth. BCSA was superior to OFPBL and PCA in suppressing organisms other than B. cepacia complex; 40 non-B. cepacia complex organisms were isolated from BCSA, 263 were isolated from OFPBL, and 116 were isolated from PCA. We conclude that BCSA is superior to OFPBL and PCA in its ability to support the growth of B. cepacia complex and to suppress other respiratory organisms.

Adult↗