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Biomedical subjects

M Davies

Publications and source records attributed to M Davies.

At least 109 records · Page 6Linked to original sources
PubMed2000

Xylocaine heavy.

Explore the source record for details and available documents.

Anesthesia, Spinal↗
PubMed1999

Validation of the human T-lymphocyte cloning assay--ring test report from the EU concerted action on HPRT mutation (EUCAHM).

The T-cell cloning assay, which enables the enumeration and molecular analysis of 6-thioguanine resistant (HPRT-negative) mutant T-cells, has been extensively used for studying human somatic gene mutation in vivo. However, large inter-laboratory variations in the HPRT mutant frequency (MF) call for further investigation of inter-laboratory differences in the experimental methodology, and development of an optimal but easy uniform cloning protocol. As part of the EU Concerted Action on HPRT Mutation (EUCAHM), we have carried out two Ring tests for the T-cell cloning assay. For each test, duplicate and coded samples from three buffy coats were distributed to five laboratories for determination of MF using six different protocols. The results indicated a good agreement between split samples within each laboratory. However, both the cloning efficiencies (CEs) and MFs measured for the same blood donors showed substantial inter-laboratory variations. Also, different medium compositions used in one and the same laboratory resulted in a remarkable difference in the level of MF. A uniform operating protocol (UOP) was proposed and compared with the traditional protocols in the second Ring test. The UOP (preincubation) increased the CE in laboratories traditionally using preincubation, but decreased the CE in laboratories traditionally using priming. Adjusted for donor, use of different protocols contributed significantly to the overall variation in lnCE (P = 0.0004) and lnMF (P = 0.03), but there was no significant laboratory effect on the lnCE (P = 0.38) or lnMF (P = 0.14) produced by the UOP alone. Finally, a simplified version of the UOP using the serum-free medium X-Vivo 10 and PMA was tested in one laboratory, and found to produce a considerable increase in CE. This modified UOP needs to be further evaluated in order to be used for future databases on HPRT MFs in various populations.

Clone Cells↗
PubMed1999

Altered expression of bcl-2 family member proteins in nonmelanoma skin cancer.

BACKGROUND: Differentiation, proliferation, and cell death are coordinated tightly within the epidermis. Alterations within keratinocytes that disrupt these processes are believed to contribute to the development of nonmelanoma skin cancers (NMSC). In the current study the authors examined the expression of selected members of the bcl-2 gene family in the skin and in case-matched samples of NMSC. METHODS: Immunohistochemistry was performed on tissue sections using antibodies against bcl-2, bcl-x, bax, and bak. Case-matched frozen nonneoplastic skin samples and tumor tissues were used for Western blot analysis. RESULTS: In normal epidermis, bcl-2 oncoprotein is expressed in keratinocytes of the basal layer but is down-regulated in suprabasal layers. The proapoptotic bax protein is expressed at low levels in basal keratinocytes and is up-regulated in suprabasal layers. The bcl-x and bak proteins both are expressed in the basal and spinous strata but are down-regulated in the granular cell layer. Both bcl-2 and bax were diffusely cytosolic whereas bcl-x and bak exhibited a distinct perinuclear distribution. Squamous cell carcinomas (SCC) were negative for bcl-2 whereas bcl-2 increased 5.5-fold in basal cell carcinomas (BCC). The distribution of bcl-x and bax proteins within BCC and SCC overlapped and were associated with squamous differentiation. Bax protein was increased twofold to threefold in NMSC. An increase in bak protein also was observed in SCC. However, bak was diffusely cytosolic within BCC in contrast to the perinuclear distribution in nonneoplastic keratinocytes. CONCLUSIONS: These findings suggest that altered expression of bcl-2 family members may play a role in the pathogenesis of NMSC.

Apoptosis↗
PubMed1999

Expression of laminin alpha1, alpha2, alpha4, and alpha5 chains, fibronectin, and tenascin-C in skeletal muscle of dystrophic 129ReJ dy/dy mice.

The dy/dy mouse is an animal model for human merosin-negative congenital muscular dystrophy (CMD), which has been reported to have reduced or no expression of the basement membrane protein laminin alpha2. We here investigate various myogenic and nonmyogenic tissues of mature dy/dy and control 129ReJ mice histologically and for laminin alpha2 expression. In addition, expression patterns of laminin alpha1, alpha2, alpha4, and alpha5 chains, the interstitial proteins fibronectin and tenascin-C, and the adhesion molecules VCAM-1, ICAM-1, and alpha4 integrin were characterized in skeletal muscle of 1- and 7-day and mature (>6 weeks old) dy/dy and control 129ReJ mice. The laminin alpha2 chain remained detectable in myogenic tissues of dy/dy mice by immunofluorescence using two different monoclonal antibodies and by Northern blot analysis. However, laminin alpha2 expression was significantly reduced or not detectable in nonmyogenic tissues of dy/dy mice, including skin, lung, kidney, brain, thymus, and eye. Focal lesions were observed in mature skeletal muscle only, characterized by necrotic tissue, isolated VCAM-1- and ICAM-1-positive cells indicative of inflammatory processes, and regenerating muscle fibers surrounded by intense tenascin-C and fibronectin expression. In contrast to studies on human CMD muscle, laminin alpha1 was not detectable in either dy/dy or control skeletal muscle using immunofluorescence or Northern blot analysis. Immunofluorescence localized laminin alpha4 to basement membranes of blood vessels, the endoneurium of the intramuscular nerves, and the neuromuscular junction in skeletal muscle of 1- and 7-day-old dy/dy and control mice. In mature muscle, laminin alpha4 expression shifted to the perineurium of intramuscular nerves in both dy/dy and control mice. Furthermore, strong upregulation of laminin alpha4 in the basement membranes of blood vessels, the perineurium of intramuscular nerves, and of isolated regenerating muscle fibers in the dy/dy mice was apparent. Investigation of 1-day-old animals revealed expression of laminin alpha5 in skeletal muscle fiber basement membranes of dy/dy but not control animals. This difference between dy/dy and control animals was no longer apparent at 7 days after birth, indicating a temporary shift in expression pattern of laminin alpha5 in dy/dy animals. Analysis of the extracellular matrix components of 1- and 7-day-old dy/dy and control skeletal muscle revealed an early onset of the dystrophy, even before histopathological features of the disease were evident. Our data confirm the absence of laminin alpha1 chain in myogenic tissues of both dy/dy and control mice and suggest compensation for reduced laminin alpha2 in dy/dy skeletal muscle by laminin alpha4 and, in early development, also laminin alpha5. These results have significant ramifications in the diagnosis of human merosin-negative CMD.

Age of Onset↗
PubMed1999

Familial tumoral calcinosis: association with cerebral and peripheral aneurysm formation.

Two siblings with histologically and radiologically proven tumoral calcinosis presented with cerebral and peripheral aneurysms. The brother died of a ruptured subclavian artery aneurysm after surgical repair of brachial, iliofemoral and coeliac axis aneurysms. Magnetic resonance and catheter angiography in the sister demonstrated marked carotid dysplasia and a left ophthalmic segment aneurysm, not amenable to treatment. We believe this is the first reported case of familial aneurysms in association with tumoral calcinosis.

Aneurysm↗
PubMed1999

Informant-based determinants of symptom attenuation in structured child psychiatric interviews.

Informant-related determinants of item attenuation, that is, the drop-off in symptom endorsement rates at retest, were examined in an enriched community subsample of 245 parent-child pairs drawn from the National Institute of Mental Health Methods for Epidemiology of Child and Adolescent Mental Disorders Study. Youngsters and their parents were interviewed with the Diagnostic Interview Schedule for Children (Version 2.3; DISC-2.3) on two occasions with a mean test-retest interval of 12 days. Item attenuation rates were high for both informants, with adults failing to confirm 42% and children 58% of baseline responses at retest. Stepwise regressions revealed that item attenuation at DISC-P retest was higher for adult informants who were younger, and who reported on older and less impaired children. On the DISC-C, attenuation was higher for children who were less impaired, rated as doing worse in school, and who had a longer test-retest interval. These results are broadly consistent with past studies examining the determinants of attenuation and test-retest reliability and have implications for the design and use of structured diagnostic instruments.

Adolescent↗
PubMed1999

Training, skills and caseloads of community mental health support workers involved in case management: evaluation from the initial UK demonstration sites.

This paper describes phase one of a three phase, Department of Health funded project, led by the Mental Health Programme of the Royal College of Nursing Institute in collaboration with the Research Unit of the Royal College of Psychiatrists and the School of Social Work at the University of East Anglia. Its project aims were to establish whether the work of demonstration sites in mental health case management had developed beyond their original structure, to compare their current profile with the general literature on case management and assertive outreach and to use this data to reach consensus about issues affecting the work of those healthcare workers who currently see themselves working as case managers. Central to these aims were the experiences and narratives of the demonstration site case managers themselves. In 1995 data were collected from six fieldwork sites in England using semistructured interviews. Similarities and differences between the literature and the fieldwork data were used to inform a consensus conference. The main areas of investigation were organizational considerations, the nature of innovative projects and user involvement. The paper concludes that there are serious problems with the perceived role of case managers, their support and training and further difficulties attributed to interagency working. Finally, it is clear that the exact nature of the client group most suited to UK case management typology has not yet been resolved.

Case Management↗
PubMed1999

Liquid ventilation.

Research on using liquid ventilation to provide artificial respiration in mammals has been ongoing since the 1960s. The development of inert perfluorocarbon (PFC) liquids with high oxygen and carbon dioxide solubility has made gas exchange with liquid ventilation possible. In 1991 the technique of partial liquid ventilation was introduced where PFC are instilled into the lungs whilst continuing with conventional mechanical ventilation. Partial liquid ventilation has been shown to improve gas exchange and lung function with decreased secondary lung injury, in animal models of acute lung injury and surfactant deficiency. It has been used in uncontrolled trials in preterm neonates, and preliminary results are available from a randomized controlled trial of partial liquid ventilation in paediatric acute respiratory distress syndrome. Perfluorocarbons can also be used to deliver drugs to the lungs, to lavage inflammatory exudate and debris from the lungs, and as an intrapulmonary X-ray contrast medium. Many questions about partial liquid ventilation remain unanswered particularly with regard to the dose of PFC required, its ideal method of administration and the long-term effects. Partial liquid ventilation promises to be an exciting new therapy for infants and children with a variety of respiratory problems. The technique requires ongoing research and experimentation.

Acute Disease↗
PubMed1999

The antioxidant profiles of patients with recurrent acute and chronic pancreatitis.

OBJECTIVE: It has been suggested that patients with chronic pancreatitis have antioxidant deficiencies. It is unclear whether these antioxidant deficiencies also occur in patients with recurrent acute pancreatitis and whether this condition represents an intermediate state between normality and chronic pancreatitis. The aim of this study was to determine the antioxidant profiles of patients with pancreatitis (recurrent acute and chronic) and to compare their profiles with a control population. METHODS: The antioxidant profiles of patients with chronic pancreatitis (n = 27) and recurrent acute pancreatitis (n = 11) were determined and compared with the antioxidant profiles of control subjects (n = 19). The following parameters were measured in blood: trace elements (selenium, copper, zinc), vitamins A and E, and carotenoids (alpha-carotene, beta-carotene, xanthine, beta-cryptoxanthine, lycopene). RESULTS: Patients with chronic pancreatitis had significantly lower plasma concentrations of selenium, vitamin A, vitamin E, beta-carotene, xanthine, beta-cryptoxanthine, and lycopene compared with both control subjects and patients with recurrent acute pancreatitis (p < 0.05). There were no significant differences between the antioxidant profiles of patients with chronic pancreatitis due to alcohol excess and patients with idiopathic chronic pancreatitis, or between the antioxidant profiles of patients with recurrent acute pancreatitis and control subjects. CONCLUSIONS: Patients with chronic pancreatitis had evidence of multiple antioxidant deficiencies. The antioxidant profiles of patients with recurrent acute pancreatitis did not differ from those of control subjects, discounting the hypothesis that recurrent acute pancreatitis represents an intermediate state between normality and chronic pancreatitis.

Acute Disease↗
PubMed1999

Loss of differentiation of 4NQO-induced rat malignant oral keratinocytes correlates with metastatic dissemination and is associated with a reduced cellular response to TGF-beta1 and an altered receptor profile.

This study examined the metastatic capacity of clonal populations of 4NQO-induced rat malignant oral keratinocytes following orthotopic transplantation to athymic mice. Polygonal and spindle cells formed well-differentiated squamous cell carcinomas (keratin positive and vimentin negative) and undifferentiated spindle cell tumours (keratin negative and vimentin positive), respectively, in almost 100% of animals at the site of inoculation (floor of mouth). Transplantation of 5x 10(6) cells of either cell type at high cell density resulted in approximately 50% of animals forming pulmonary metastases. By contrast, inoculation of 2x 10(6) differentiated polygonal cells resulted in the formation of significantly fewer pulmonary metastases than the undifferentiated spindle cells. A single well-differentiated clone of polygonal cells and 3 of 4 of the undifferentiated spindle cell lines produced comparable levels of TGF-beta1. One undifferentiated spindle cell line expressed significantly more TGF-beta1 and, following transplantation orthotopically, fewer animals formed pulmonary metastases despite the formation of primary tumours in almost all grafted animals, suggesting that TGF-beta1 can act as a tumour suppressor in this cell type. All cell lines produced comparable amounts of TGF-beta2. The clones of polygonal cells were markedly inhibited and the spindle cells were only partially inhibited by exogenous TGF-beta1. Both cell types expressed high-affinity TGF-beta cell surface receptors; the ratio of type I to type II TGF-beta receptors was 1.0:<3.0 in the spindle cells and 1.0:17.9 in the polygonal clone. The results suggest that differentiated rat malignant oral keratinocytes are less aggressive and have a decreased potential to metastasise than their undifferentiated spindle cell counterparts. This may be attributable, in part, to a change in TGF-beta receptor profile leading to the partial loss of response to exogenous TGF-beta1.

4-Nitroquinoline-1-oxide↗