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Biomedical subjects

R Hardy

Publications and source records attributed to R Hardy.

At least 73 records · Page 4Linked to original sources
PubMed1997

Development of a scale to measure symptoms of anxiety and depression in the general UK population: the psychiatric symptom frequency scale.

OBJECTIVES: The psychiatric symptom frequency (PSF) scale was developed to assess symptoms of anxiety and depression (i.e. affective symptoms) experienced over the past year in the general population. This study aimed to examine the distribution of PSF scores, internal consistency, and factor structure and to investigate relationships between total scores for this scale and other indicators of poor mental health. PARTICIPANTS: The Medical Research Council national survey of health and development, a class stratified cohort study of men and women followed up from birth in 1946, with the most recent interview at age 43 when the PSF scale was administered. MAIN RESULTS: The PSF scale showed high internal consistency between the 18 items (Cronbach's alpha = 0.88). Ratings on items of the scale reflected one predominant factor, incorporating both depression and anxiety, and two additional factors of less statistical importance, one reflecting sleep problems and the other panic and situational anxiety. Total scores were calculated by adding 18 items of the scale, and high total scores were found to be strongly associated with reports of contact with a doctor or other health professional and use of prescribed medication for "nervous or emotional trouble or depression," and with suicidal ideas. CONCLUSIONS: The PSF is a useful and valid scale for evaluating affective symptoms in the general population. It is appropriate for administration by lay interviewers with minimal training, is relatively brief, and generates few missing data. The total score is a flexible measure which can be used in continuous or binary form to suit the purposes of individual investigations, and provides discrimination at lower as well as upper levels of symptom severity.

Adult↗
PubMed1997

Discontinuation rates of SSRIs and tricyclic antidepressants: a meta-analysis and investigation of heterogeneity.

BACKGROUND: Previous meta-analyses suggest that individuals treated with serotonin-specific reuptake inhibitors (SSRIs) in randomised controlled trials (RCTs) are less likely to discontinue treatment than those on tricyclic antidepressants. This metaanalysis investigates whether this is due to the frequent use in RCTs of older reference tricyclics (imipramine and amitriptyline), which may have worse side-effects than more recent compounds. METHODS: A meta-analysis of RCTs comparing tricyclic and heterocyclic antidepressants with SSRIs in the treatment of depression. RESULTS: The overall odds ratio of discontinuation on tricyclic/heterocyclic antidepressants compared with SSRIs was 0.86 (95% CI 0.78-0.94). The odds ratio for reference tricyclics was 0.82 95% CI 0.72-0.23), newer tricyclics 0.89 (95% CI 0.74-1.06), and heterocyclics 1.02 (95% CI 0.78-1.35). The pooled advantage of SSRIs over tricyclics was maintained whether the population studied consisted of younger adults or only the elderly. No differences in discontinuation rates were detected between the SSRIs. CONCLUSIONS: The lower rate of discontinuation in patients on SSRIs may be due to the use of old tricyclics (which have worse side-effects) as reference compounds. The SSRIs do not show a statistically significant difference in discontinuation rates when compared with newer tricyclics or heterocyclics.

Antidepressive Agents, Tricyclic↗
PubMed1996

GGF/neuregulin is a neuronal signal that promotes the proliferation and survival and inhibits the differentiation of oligodendrocyte progenitors.

We show that GGF/neuregulin is a mitogen for prooligodendrocytes (O4+/O1- cells), oligodendrocytes (O4+/O1+ cells), and type-2 astrocytes. Heregulin beta 1, another neuregulin isoform, is also mitogenic. The proliferative effect of glial growth factor (GGF) does not require, but is greatly potentiated by, serum factors. GGF also promotes the survival of pro-oligodendrocytes under serum-free conditions. High levels of GGF reversibly inhibit the differentiation and lineage commitment of oligodendrocyte progenitors and, in differentiated cultures, result in loss of O1 and myelin basic protein expression. All three erbB receptors are expressed by progenitors and are activated by GGF; the relative abundance of these receptors changes during differentiation. Finally, cortical neurons release a soluble mitogen for pro-oligodendrocytes that is specifically blocked by antibodies to GGF. These results implicate the neuregulins in the neuronal regulation of oligodendrocyte progenitor proliferation, survival, and differentiation.

Animals↗
PubMed1996

[Living conditions of prostitutes: consequences for the prevention of HIV infection].

Since 1990, several community-based interventions have been set up for populations of prostitutes in France with the principal objective of preventing HIV infection in prostitutes and their sexual partners. Field workers have suggested that extremely precarious living conditions are a major obstacle for the diffusion of prevention messages. A multidisciplinary working group thus set up a study in order to determine which living conditions could affect the adoption of behaviour at low risk for HIV infection. In May 1995, six of the seven teams conducting prevention actions among prostitutes in France used a short standardised questionnaire to collect information including type of housing, health insurance cover, physical aggressions, drug use. It was planned to collect data from all persons attending the drop-in centres. A total of 355 questionnaires were completed (sampling was exhaustive for 3 of the 6 teams). The population comprised women, men and transvestites. The median age was 28 years. Only 39% (135/348) of the subjects had access to health insurance. Approximately 50% (160/324) of the persons lived in precarious accommodation (hotel or no fixed address) and 33% (119/355) had been victims of physical aggressions during the 5 months preceding the study. Transvestites and young people had the most precarious living conditions. Despite the limits of this study due to the difficulty in carrying out a survey in this very marginalised population, the unique information collected may enable community health action strategies to be suitably adapted. In particular, it is important to improve partnership between field workers and existing social and health services, to improve access to better accommodation, health care and physical security while disseminating prevention messages and distributing condoms.

Adolescent↗
PubMed1995

Gq alpha protein function in vivo: genetic dissection of its role in photoreceptor cell physiology.

Heterotrimeric G proteins mediate a variety of signaling processes by coupling seven-transmembrane receptors to intracellular effector molecules. The Drosophila phototransduction cascade is a G protein-coupled signaling cascade that utilizes a phospholipase C (PLC beta) effector. PLC beta has been shown to be activated by Gq alpha in reconstituted systems. To determine whether a Gq-like protein couples rhodopsin to PLC, and to study its function, we isolated a mutant defective in a photoreceptor-specific Gq protein, DGq. We now demonstrate that Gq is essential for the activation of the phototransduction cascade in vivo. We also generated transgenic flies expressing DGq under an inducible promoter and show that it is possible to manipulate the sensitivity of a photoreceptor cell by controlled expression of DGq. Characterization of quantum bumps in mutants expressing less that 1% of the levels of DGq revealed that the rhodopsin-G protein interaction does not determine the gain of the single photon responses. Together, these results provide significant insight into the role of Gq in regulating the output of a photoreceptor cell.

Amino Acid Sequence↗
PubMed1994

Variability in the pharmacokinetics of cyclophosphamide, methotrexate and 5-fluorouracil in women receiving adjuvant treatment for breast cancer.

A total of 23 women with stage II breast cancer receiving adjuvant cyclophosphamide, methotrexate and 5-fluorouracil had detailed pharmacokinetic monitoring performed on the first and third courses of therapy. The area under the concentration time curve (AUC) of each of these three drugs varied by a factor of 3-4 among patients. No systematic change in pharmacokinetics between the first and third courses was seen for cyclophosphamide, methotrexate or 5-fluorouracil, and the mean AUC for each of the three drugs did not change. However, significant intrapatient variability in drug pharmacokinetics was observed for all three drugs such that the AUC, clearance and half-life in an individual on the third course could not be reliably predicted from data generated on the first course. On the basis of these results, cyclophosphamide, methotrexate, and 5-fluorouracil pharmacokinetic data from one treatment would not be useful information from which the doses of subsequent courses could be determined.

Adult↗
PubMed1994

Upregulation of bcl-2 by the Epstein-Barr virus latent membrane protein LMP1: a B-cell-specific response that is delayed relative to NF-kappa B activation and to induction of cell surface markers.

An ability of the Epstein-Barr virus latent membrane protein LMP1 to enhance the survival of infected B cells through upregulation of the bcl-2 oncogene was first suggested by experiments involving gene transfection and the selection of stable LMP1+ clones (S. Henderson, M. Rowe, C. Gregory, F. Wang, E. Kieff, and A. Rickinson, Cell 65:1107-1115, 1991). However, it was not possible to ascertain whether Bcl-2 upregulation was a specific consequence of LMP1 expression or an artifact of the selection procedure whereby rare Bcl-2+ cells already present in the starting population might best be able to tolerate the potentially toxic effects of LMP1. We therefore reexamined this issue by using two different experimental approaches that allowed LMP1-induced effects to be monitored immediately following expression of the viral protein and in the absence of selective pressures; activation of the NF-kappa B transcription factor and upregulation of the cell adhesion molecule ICAM-1 were used as early indices of LMP1 function. In the first approach, stable clones of two B-cell lines carrying an LMP1 gene under the control of an inducible metallothionein promoter were induced to express LMP1 in all cells. Activation of NK-kappa B and upregulation of ICAM-1 occurred within 24 h and were followed at 48 to 72 h by upregulation of Bcl-2. In the second approach, we tested the generality of this phenomenon by transiently expressing LMP1 from a strong constitutively active promoter in a range of different cell types. All six B-cell lines tested showed NF-kappa B activation in response to LMP1 expression, and this was followed in five of six lines by expression of ICAM-1 and Bcl-2. In the same experiments, all three non-B-cell lines showed NF-kappa B activation and ICAM-1 upregulation but never any effect upon Bcl-2. We therefore conclude that Bcl-2 upregulation is part of the panoply of cellular changes induced by LMP1 but that the effect is cell type specific. Our data also suggest that whilst NF-kappa B may be an essential component of LMP1 signal transduction, other cell-specific factors may be required to effect some functions of the viral protein.

Antigens, CD↗
PubMed1993

Neuron-oligodendroglial interactions during central nervous system development.

It is well established that a variety of growth factors influence the differentiation of oligodendroglial lineage cells in culture, although little information is available concerning the role and source of these factors in vivo. Developing oligodendroglia are almost constantly in a neuronal environment and would be expected to respond to a variety of signals from neurons that affect their survival, migration, division, maturation and myelin production. However, very little is known about the specific interactions that occur between these two cell types. Here we review the experimental evidence for the influence of neurons on oligodendroglial differentiation, including studies on the effects of both soluble factors and contact dependent events. We also propose a scheme for the control of myelinogenesis via both internal and external signals.

Animals↗
PubMed1993

Rat cerebral cortical neurons in primary culture release a mitogen specific for early (GD3+/04-) oligodendroglial progenitors.

The development of cells of the oligodendroglial lineage, from immature progenitor to myelinating cells, occurs largely in a neuronal environment, yet little is known about specific interactions between these 2 cell types. We have tested the effects of medium conditioned by cultures of rat cerebral cortical neurons (CCM), cerebellar granule interneurons (GCM), and a dorsal root ganglion derived cell line (NDCM) on cells of the oligodendroglial lineage in culture. Different stages of the lineage were defined using the cell surface antigens GD3, 04, and GalC. CCM and NDCM were mitogenic for the early GD3+/04- oligodendroglial progenitor, whereas GCM was mitogenic for the later GD3+/04+ stage. Neutralising antibodies to PDGF and bFGF were able to eliminate the mitogenic activity of NDCM and GCM, respectively, but did not abolish the mitogenic effect of CCM. We have demonstrated that neurons in primary culture from distinct CNS regions exert different influences on cells of the oligodendroglial lineage, and specifically that cortical neurons release an unknown mitogen for GD3+/04- oligodendroglial progenitors.

Animals↗
PubMed1993

Principles for forging a national health plan.

One point which has emerged with a resounding voice during this conference is the need to clearly assemble and carefully communicate data and information as a means of empowerment. We hope that the recommendations from this conference will contribute to this end. We urge all to become actively involved in seeking change, and ensuring that the future health of Americans and of our nation will not reflect our inequitable, costly present.

Cost Control↗
PubMed1991

Down-regulation of GAP-43 During Oligodendrocyte Development and Lack of Expression by Astrocytes In Vivo: Implications for Macroglial Differentiation.

The discovery of molecular markers which are selectively expressed during the development of specific classes of rat central nervous system macroglia has greatly advanced our understanding of how these cells are related. In particular, it has been shown in tissue culture that oligodendrocytes and some astrocytes (type-2) may be derived from a common progenitor cell (O-2A progenitor). However, the existence of type-2 astrocytes in vivo has yet to be unequivocally established. Recently, it has been reported that the neural-specific growth-associated protein-43 (GAP-43, otherwise known as B-50, F1, pp46 and neuromodulin) may be expressed by cells of the O-2A lineage in vitro. We set out to examine the cellular specificity of GAP-43 in O-2A progenitors and their descendants in vitro and in vivo. Using a polyclonal antiserum against a GAP-43 fusion protein we have shown the presence of immunoreactive GAP-43 in the membranes of bipotential O-2A glial progenitor cells and type-2 astrocytes by Western blotting and immunocytochemistry of cells in culture. In contrast to previous studies, double labelling with mature oligodendrocyte markers showed that GAP-43 is down-regulated during oligodendrocyte differentiation in vitro. Immunohistochemical staining of sections of developing rat brain demonstrated the same developmental regulation of GAP-43, suggesting that oligodendrocytes only express GAP-43 at immature stages. In addition, normal and reactive astrocytes in tissue sections were not labelled with GAP-43.

Journal Article↗
PubMed1991

Proliferation and differentiation potential of rat forebrain oligodendroglial progenitors both in vitro and in vivo.

We have followed the development of the O-2A progenitor cell from the neonatal rat forebrain, both in dissociated cell culture and in cryostat sections, using immunocytochemical techniques employing a panel of antibodies that recognise the cells at different stages of their development. This included the monoclonal antibody LB1, which binds to the surface ganglioside GD3 expressed on O-2A progenitor cells. In secondary cultures enriched for O-2A progenitors maintained in a serum-free chemically defined medium, a large proportion of the cells are primed to differentiate into oligodendroglia and go on to express the oligodendroglial specific surface glycolipid galactocerebroside (GC) and then the myelin proteins CNP and MBP. However, a significant proportion of immature bipolar GD3+ cells remained after 6 days in secondary culture. It appears that not all the O-2A progenitors in our cultures differentiate immediately and some cells remain in an undifferentiated state and divide to replenish progenitor numbers. We have also identified in our cultures a small apolar GD3- cell, which when isolated differentiated into a GD3+ bipolar O-2A progenitor cell. We have termed this cell type a preprogenitor. The differentiation of this cell type into O-2A progenitors may be the source of the immature GD3+ cells present at the later stages of our secondary cultures. The proliferative profile of the cultures was studied using 5'bromo-2-deoxyuridine (BrdU) incorporation as an index of mitosis. Only the immature, bipolar O-2A progenitors were seen to divide at any time in serum-free culture. Neither the more mature multipolar O-2A cells nor the oligodendroglia were seen to divide. The developmental profile of the O-2A cells in the rat forebrain in vivo showed a largely similar progression to that in culture, with a time lag of at least 6 days between GD3 expression and the onset of myelination. BrdU incorporation studies in vivo also showed that the GD3+ progenitor cell is mitotic whereas the GC(+)-expressing oligodendroglia is not. We have shown that there are several significant alterations in the timing of antigen expression in both O-2A progenitors and oligodendroglia in vitro compared to that seen in vivo.

Animals↗
PubMed1991

Molecular biologic studies in the clinical evaluation of non-Hodgkin's lymphoma.

Recent advances in DNA technology have revealed new information about the biology of the non-Hodgkin's lymphomas that is both provocative and exciting. Because these technologies are just beginning to be applied to the clinical evaluation of the non-Hodgkin's lymphomas, the results of clinical studies must be regarded as preliminary. At this time we can only speculate on how they might lead to improved clinical management or provide the basis for new therapies.

Gene Rearrangement↗