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Biomedical subjects

M Murphy

Publications and source records attributed to M Murphy.

At least 343 records · Page 19Linked to original sources

Personality disorders in patients with somatisation disorder. A controlled study.

Twenty-five women with somatisation disorder (SD) were compared with matched patient controls for the presence of personality disorders. Personality was assessed with the Personality Assessment Schedule (PAS). Interviewers were unaware of the patients' diagnoses. All controls had DSM-III-R axis I diagnoses of depressive or anxiety disorders. The prevalence of personality disorders among patients with somatisation disorder was 72% compared with 36% among controls. Certain personality disorders, including passive-dependent, histrionic, and sensitive-aggressive, occurred significantly more often in the SD patients than controls.

Adult↗

Involvement of leukemia inhibitory factor and nerve growth factor in the development of dorsal root ganglion neurons.

Leukemia inhibitory factor (LIF) was recently shown to stimulate the generation of sensory neurons from the murine neural crest in vitro. Here, we examine the respective activities of LIF and nerve growth factor (NGF) throughout the embryonic development of sensory neurons in dorsal root ganglia (DRG) and neural crest. In cultures of embryonic day 12 (E12) DRG, which contain sensory neuron precursor cells, a combination of both LIF and NGF are required for the differentiation of mature sensory neurons from their neurofilament negative (NF-) precursors. The primary differentiation step from NF- cell to NF+ immature neuron is promoted by LIF, whereas the survival and further maturation of the newly differentiated neurons depends on NGF. In cultures of sensory neurons isolated at the time of target innervation (E14 and E15 DRG), the survival of the majority of the neurons is dependent on NGF. However, LIF acts as a survival agent for a discrete population of NGF non-responsive neurons. From E16, the number of neurons maintained by LIF increases to > 90% by birth. Consistent with the in vitro observations, LIF mRNA could be detected at early developmental stages (E12-E13), within the spinal column and DRG as well as the limbs and, later (after E15), in areas of sensory innervation (skin, limbs, feet and gut). This supports the idea that LIF, as well as NGF, may regulate sensory development in vivo.

Animals↗

Education and training: mission through total quality management.

Planning for 1994 to 1996 is underway with a focus on innovative, system-wide approaches to clinical and nonclinical quality improvement needs for FHSC's customers. TQM is a pivotal point in the system's future as a health care provider. As part of the TQM process, gaining knowledge and imparting it to employees is, in itself, a continuing journey.

Catholicism↗

Constructing period parity progression ratios from household survey data.

"An own-child analysis is applied to the household composition data of two rounds of the U.K. Labour Force Survey, each of which has a sample size of about 200 thousand people. Period parity progression ratios and the corresponding total fertility measure (TFPPR) are derived for up to twenty years before the survey date. The biases that arise when using such a source are discussed and assessed by replication using surveys in different years. Methods for correcting bias are developed. Analysis of the standard errors of the measures suggests that such sources provide the most precise, routine and timely indicators of period fertility in many situations...."

Bias↗

Time-series approaches to the analysis of fertility change.

"A variety of time-series approaches to the analysis of fertility are considered. Attention is concentrated on published official data [for the United Kingdom], although alternative approaches such as more sophisticated period measures and cohort indicators are also discussed. The advantages of a period perspective are emphasized. A proximate determinants approach to the analysis of fertility is advocated."

Birth Rate↗

Identification and characterization of genes differentially expressed in meningiomas.

Meningiomas are common tumours derived from the thin membrane that surrounds the brain and spinal cord. Currently, the molecular mechanisms responsible for the initiation and progression of these tumors are largely unknown. Toward the elucidation of such mechanisms, we have formulated an experimental design utilizing the technique of subtractive hybridization that is aimed at identifying the changes in gene expression between intracranial meningiomas and their normal precursor cells, leptomeningeal cells. We report here the identification and initial characterization of three genes whose expression is altered or aberrant in meningioma cell lines and tumours relative to cultures of normal leptomeningeal cells. Complementary DNA probes from one of these genes detect transcripts of altered size in several meningiomas relative to normal leptomeningeal cells. Another of these genes demonstrates decreased expression in meningiomas and in tumours associated with the disorder neurofibromatosis 2. A third gene isolated by this procedure is differentially expressed in both meningiomas and breast carcinomas. Therefore, the decreased expression of these genes may play roles in growth-regulatory pathways that are abrogated not only in meningiomas, but in other tumor types as well.

Amino Acid Sequence↗

Large-scale synthesis of triple helix forming oligonucleotides using a controlled-pore glass support.

Triple helix forming oligonucleotides that involve purine:purine:pyrimidine interactions are purine-rich oligonucleotides containing 60%-90% G and are usually 25-40 bases long. Synthesis and purification of G-rich oligonucleotides of this length can be difficult even at small scales. Procedures to synthesize these compounds at 200 to 400 mumol scales with high coupling efficiency have been developed using a controlled-pore glass support.

Base Sequence↗

Fatal myocardial infarction and use of psychotropic drugs in young women.

We have observed an unexpected 17-fold increase in risk of fatal [corrected] myocardial infarction (relative risk 16.9, 95% confidence interval 3.9-72.8) associated with current use of psychotropic drugs. This incidental finding, in a case-control study of cardiovascular mortality in women aged 16-39 not designed to test any hypothesis about psychotropic drugs, should be treated cautiously. There is, however, evidence of a relation between psychiatric morbidity and cardiovascular disease and the association recorded here requires further investigation.

Adolescent↗

Tumor necrosis factor-alpha and IFN-gamma expression in human thymus. Localization and overexpression in Down syndrome (trisomy 21).

In vitro studies suggest that TNF-alpha and IFN-gamma regulate thymocyte proliferation, but little evidence exists for the constitutive production of these cytokines in normal human thymus. In paired experiments, we examined frozen sections of postnatal human thymus from four control children and four age-matched children with Down syndrome (DS) (trisomy 21) for TNF-alpha and IFN-gamma mRNA expression using in situ hybridization. We studied thymuses from children with DS because this aneuploid condition is associated with a greatly increased incidence of infection and has abnormal thymic anatomy and patterns of thymocyte maturation. We found cells expressing constitutive levels of TNF-alpha mRNA in the trabeculae, corticomedullary junctions, and medulla of both control and DS thymuses and the number of these cells was an average of 3.9-fold higher in DS thymuses than in age-matched control thymuses. DS thymuses also contained an average of 3 fold higher numbers of cells with mast cell morphology, identified by toluidine blue histologic staining and electron microscopy. In both DS and control thymuses the mast cells colocalized with TNF-alpha mRNA-expressing cells. In addition, TNF-alpha protein- expressing cells, identified by immunohistochemistry, displayed a granular pattern of staining that is characteristic of mast cells. These results suggest that mast cells may be one source of TNF-alpha in human postnatal thymus. Discrete cells expressing IFN-gamma mRNA were distinctly localized to the cortical region of both DS and control thymuses and were 2.4-fold more abundant in DS thymuses than in the controls. Our results demonstrate, for the first time, the constitutive production and location of TNF-alpha and IFN-gamma in postnatal human thymus. The overexpression of both of these cytokines in DS thymuses suggests a dysregulation in cytokine production in DS and may provide an explanation for the abnormal thymic anatomy and thymocyte maturation associated with this syndrome.

Down Syndrome↗

Fatal stroke and use of oral contraceptives: findings from a case-control study.

A case-control study of women less than 40 years of age in England and Wales was performed to evaluate the risk of fatal stroke associated with the use of the newer, low-dose oral contraceptives. Included were 296 cases with subarachnoid hemorrhage, 105 cases with other hemorrhagic stroke, and 21 cases with occlusive stroke, all of which occurred during 1986-1988. Two living controls per case, matched for age and marital status, were chosen from the general practice lists. The power of the study was such that the minimum significant increased relative risk of subarachnoid hemorrhage associated with ever having used oral contraceptives that could have been detected with 90% certainty was 1.6; the equivalent value for occlusive stroke was 28.4. Relative risk was estimated by conditional logistic regression allowing for matching. The adjusted relative risk of subarachnoid hemorrhage associated with oral contraceptives was estimated to be 1.1 (95% confidence interval (CI) 0.6-1.9) for current use and 1.3 (95% CI 0.9-1.8) for ever use, while the equivalent relative risk of an occlusive stroke associated with ever use was 4.4 (95% CI 0.8-24.4). Oral contraceptive use may be associated with a small increase in the risk of subarachnoid hemorrhage. These data are consistent with a substantial increase in the risk of occlusive stroke associated with oral contraceptive use.

Adolescent↗

Leukemia inhibitory factor promotes the neuronal development of spinal cord precursors from the neural tube.

Recent evidence from our laboratory has shown that leukemia inhibitory factor (LIF) can act early in peripheral nervous system development. We have investigated a potential role of LIF in the developing spinal cord. In explants and dissociated cultures of spinal cord primordium, LIF stimulated a profuse neurite outgrowth. To determine if these effects were related to neuronal differentiation, cells were plated at low cell density and stained for neurofilament. LIF stimulated an increase in the number of newly differentiated neurons, without inducing proliferation of the precursors. Given that LIF has previously reported effects as a cholinergic switching factor for sympathetic neurons, we investigated whether LIF had similar effects in these spinal cord cultures. LIF increased the number of cholinergic neurons in proportion to its overall effect on the stimulation of all neurofilament positive neurons in the culture. These data show that LIF stimulates the generation of spinal cord neurons from their precursors and further implicates a role for LIF in nervous system development.

Animals↗

Steel factor is required for maintenance, but not differentiation, of melanocyte precursors in the neural crest.

Skin melanocytes are derived from neural crest cells that migrate into the dermis during embryogenesis. Two mouse mutants, Steel and White dominant-spotting, which have defects in melanocyte production, have recently been shown to have deletions in the genes that code for a new growth factor, steel factor (SLF), and its receptor, respectively. Here, we have investigated the role that SLF plays in melanogenesis using cultures of mouse neural crest and found that its primary action is the maintenance of melanocyte precursors. It has no effect on the final stage of melanocyte differentiation, the production of melanin, which appears to require an additional factor whose action is mimicked by the phorbol ester TPA (12-O-tetradecanoyl-phorbol-13-acetate).

Animals↗

Down syndrome (DS) peripheral blood contains phenotypically mature CD3+TCR alpha, beta+ cells but abnormal proportions of TCR alpha, beta+, TCR gamma, delta+, and CD4+ CD45RA+ cells: evidence for an inefficient release of mature T cells by the DS thymus.

Down syndrome (DS) thymocytes have a markedly diminished proportion of cells expressing high levels of the alpha, beta T cell receptor (TCR alpha, beta) and the associated CD3 molecule. Thus, we examined the surface expression of TCR alpha, beta and CD3 as well as TCR gamma, delta, CD4, CD8, CD16, and CD45RA on peripheral blood lymphocytes (PBL) from 13 noninstitutionalized subjects with DS and 13 closely age-matched sibling controls using immunofluorescence and flow cytometry. DS PBL expressed high surface levels of TCR alpha, beta and CD3, but, as compared to controls, they had a lower proportion of cells expressing TCR alpha, beta (61% vs. 68%, respectively; P less than or equal to 0.05). Moreover, the absolute number of TCR alpha, beta+ cells was considerably lower for DS subjects than for controls (1634 +/- 229 vs. 2763 +/- 530, respectively; P less than or equal to 0.05). DS subjects had a markedly higher proportion of cells expressing TCR gamma, delta than did the controls (12% vs. 7%, respectively; P less than or equal to 0.02). In addition, DS subjects had a lower proportion of CD4+CD45RA+ cells than controls (22% vs. 35%, respectively; P less than or equal to 0.02), representing naive T cells which have recently emigrated from the thymus. The imbalance in the proportions of T cell subpopulations we have observed in DS PBL may contribute to the increased susceptibility to infection associated with DS and may represent a diminished efficiency in the production of newly differentiated T cells by the DS thymus.

Adolescent↗

Influence of blood handling techniques on lactic acid concentrations.

Despite the popularity of measuring blood lactic acid concentrations, many of the common variations in technique have not been evaluated. The purposes of this study were to: 1) establish the relationship between plasma and blood lactate concentrations, 2) determine the inter-analyzer reliability, and 3) assess the stability of lactate concentration in blood stored for up to one week. Blood was sampled from 26 volunteers before exercise, at 80% of estimated maximum heart rate, and 5 minutes after a treadmill run to exhaustion. Inter-machine reliability was tested between two Yellow Springs Instruments analyzers with buffer treated with a lysing agent and between two without. Blood lactate levels at all three levels could be predicted from plasma with R2 greater than .95. Correlations between duplicates on the same machine were greater than .96 for blood and .97 for plasma. In the worst cases, between duplicate differences and between machine differences were 2%. Lactate in stored blood was in some cases significantly different after 24 hours of storage. Moderate and high lactate concentrations in plasma were not significantly altered after 2 days of storage.

Adult↗