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M Murphy

Publications and source records attributed to M Murphy.

At least 37 records · Page 2Linked to original sources
PubMed1992

Binding and retrograde transport of leukemia inhibitory factor by the sensory nervous system.

Leukemia inhibitory factor (LIF), a peptide growth factor with multiple activities, has recently been shown to support the generation and survival of sensory neurons in cultures of mouse neural crest and dorsal root ganglia (DRG). We have conducted binding experiments with 125I-LIF on cultures of DRG to determine the receptor distribution for LIF on these cells and found that at least 60% of the sensory neurons in the cultures bound 125I-LIF, all of which could be eliminated by the addition of unlabeled LIF. The other cells in the culture, which morphologically appeared to be Schwann cells, did not bind appreciable quantities of 125I-LIF. In order to investigate whether LIF is retrogradely transported to sensory neurons in vivo, 125I-LIF was injected into the footpads and gastrocnemius muscles of newborn and adult mice, following sciatic nerve ligation. Radioactivity accumulated in the distal portion of the sciatic nerve, indicating retrograde transport of LIF. Subsequent experiments on mice with unligated sciatic nerves showed that 125I-LIF is specifically transported into the sensory neurons of the DRG. There was no apparent transport of 125I-LIF into motor neurons in the spinal cord. These experiments demonstrate that LIF can specifically bind to and be transported by sensory neurons and further support the idea that LIF acts as a target-derived neurotrophic factor, analogous to NGF.

Animals↗
PubMed1991

How accurate is antenatal sonographic identification of discordant birthweight in twins?

The association between discordant birth weight in twins and poor perinatal outcome is well recognised. Antenatal identification of discordant fetal growth in twins using ultrasound has been previously reported. In this study we have assessed the accuracy of interpair percentage estimated fetal weight difference determination (interpair EFW%) in identifying an interpair percentage birth weight difference (interpair BW%) of greater than or equal to 20% and greater than or equal to 25% in 85 twin pregnancies. The maximum sensitivity, specificity, positive and negative predictive values we noted were 54.5, 98.5, 75 and 94.4%, respectively. These results suggest that interpair EFW% results should be interpreted with caution when used in the antenatal assessment of birth weight in twin pregnancies.

Abdomen↗
PubMed1991

Generation of sensory neurons is stimulated by leukemia inhibitory factor.

The processes that regulate the development of peripheral neurons from their precursors in the embryonic neural crest are essentially unknown. In this report, we show that leukemia inhibitory factor stimulates the generation of neurons in cultures of mouse neural crest. These neurons have the morphology of sensory neurons and contain neuropeptides found in mammalian sensory neurons. Consistent with these neurons being of the sensory lineage is the finding that they arise from nondividing precursors within the neural crest. In addition, we show that leukemia inhibitory factor supports the generation and/or maturation of sensory neurons in cultures of cells obtained from embryonic dorsal root ganglia. In cultures of postnatal dorsal root ganglia, which contain mature sensory neurons, leukemia inhibitory factor acts directly as a survival molecule on the majority of neurons.

Animals↗
PubMed1991

Fibroblast growth factor-mediated proliferation of central nervous system precursors depends on endogenous production of insulin-like growth factor I.

Fibroblast growth factor stimulates proliferation and subsequent differentiation of precursor cells isolated from the neuroepithelium of embryonic day 10 mice in vitro. Here we show that fibroblast growth factor-induced proliferation is dependent on the presence of insulin-like growth factors (IGFs) and that IGF-I is endogenously produced by the neuroepithelial cells. Blocking of endogenous IGF-I activity with anti-IGF-I antibodies results in complete inhibition of fibroblast growth factor-mediated proliferation and in cell death. IGF-I alone acts as a survival agent. These observations correlate with the detection of transcripts for IGF-I and basic fibroblast growth factor in freshly isolated neuroepithelium and are consistent with an autocrine action of these factors in early brain development in vivo.

Animals↗
PubMed1991

Establishment and characterization of a human leptomeningeal cell line.

Human leptomeningeal cells grown in culture were immortalized via transfection with an SV40 large T antigen gene construct under the control of the Rous sarcoma virus promoter. This cell line, designated LTAg2B, maintained the polygonal morphology characteristic of primary cultures, and stained positively in early passage for cytokeratin, a specific marker for arachnoid cells of the leptomeninges. Additional immunofluorescent staining revealed that these cells express vimentin and desmoplakin as well; these antigens have been found together only in normal arachnoid tissue and in meningiomas, which are the neoplastic derivatives of leptomeningeal cells. Significantly, LTAg2B cells demonstrate a greatly increased life span and growth rate relative to primary cultures. The establishment of this cell line should thus facilitate studies on the cellular and molecular biology of leptomeningeal cells, as well as elucidate their roles in certain pathological situations involving the leptomeninges, such as meningitis and meningioma tumor formation.

Antigens, Polyomavirus Transforming↗
PubMed1991

Cell lines derived from mouse neural crest are representative of cells at various stages of differentiation.

In order to study mammalian neural crest differentiation in vitro, a series of clonal neural crest (NC) cell lines have been generated by infection of migrating mouse neural crest cells with two recombinant retroviruses containing either the c-myc or N-myc proto-oncogenes. Many cell lines were generated which could be subdivided into three groups based on their appearance in culture. Eleven of these cell lines representative of each of the morphological groups were characterized for the expression of six antigenic markers expressed by neural cells. In addition, mRNA was prepared from these cell lines and analyzed for the expression of a number of neural specific genes. These analyses show that the cell lines are representative of the following cell types: (1) neural crest-like cell lines that do not differentiate in 10% serum; (2) progenitor cell lines, some of which can partially differentiate in culture; and (3) mature neuronal cell lines or bipotential cell lines. Southern blot analysis of DNA from these lines indicated that they have multiple integration sites for the provirus and suggest that phenotypically different cell types have arisen from a single cell. None of the cell lines showed any proliferative or morphological response to nerve growth factor (NGF), whereas over two-thirds of the lines showed both marked proliferative and morphological responses to fibroblast growth factor (FGF). These data indicate that we have generated a range of cell lines representative of a spectrum of mouse neural crest derivatives.

Animals↗
PubMed1991

Basic fibroblast growth factor upregulates steady-state levels of laminin B1 and B2 chain mRNA in cultured neuroepithelial cells.

The growth of purified populations of murine neuroepithelial cells isolated from 10 day embryonic (E10) telencephalon and mesencephalon can be specifically enhanced by supplementing growth culture media with basic fibroblast growth factor (bFGF). One effect of bFGF on cultured neuroepithelial cells was to enhance the amount of laminin expressed at the protein level as detected by immunofluorescence. This was correlated with significant upregulation of steady-state levels of laminin B1 and B2 chain expression as analyzed at the mRNA level. When E12 neuroepithelial cells were split into precursor neuronal or glial subpopulations on the basis of differential expression of major histocompatibility class-1 antigens, only the glial progenitor fraction was found to be capable of detectable laminin synthesis. It is thus possible that a primary action of FGF is to increase the synthesis and release of extracellular matrix molecules from neural cells which act back in a paracrine manner to stimulate differentiation.

Animals↗
PubMed1991

Expression of the outer capsid protein VP5 of two bluetongue viruses, and synthesis of chimeric double-shelled virus-like particles using combinations of recombinant baculoviruses.

We have previously reported the assembly of virus-like particles (VLPs), consisting of the four major structural proteins of bluetongue virus (BTV), in Spodoptera frugiperda cells coinfected with recombinant baculoviruses (French et al. (1990). J. Virol. 64, 5695-5700). In this paper we report further studies using this system to assemble heterologous VLPs containing the outer capsid proteins (VP2 and VP5) of a range of different BTV serotypes. S. frugiperda cells were coinfected with three recombinant baculoviruses; a dual recombinant expressing VP3 and VP7 (of BTV-17 and -10, respectively) in combination with a single recombinant expressing VP2 of BTV-1, -2, -10, -11, 13, or -17 and an additional single recombinant expressing VP5 of BTV-2, BTV-10, or BTV-13. The resultant VLPs were purified and analyzed by electronmicroscopy, Western immunoblotting, and hemagglutination assays to determine whether double-shelled VLPs had been assembled. In the course of these experiments the VP2 proteins of all six available serotypes were successfully incorporated into VLPs. Particles from two different combinations of chimeric VLPs (having VP2 derived from BTV-1 or that of BTV-17) were used to raise antisera in guinea pigs. Both of these sera showed high neutralizing antibody titers against live BTV, indicating that heterologous VLPs may have potential for use in anti-BTV vaccines.

Animals↗
PubMed1991

A method for the isolation of purified murine neuroepithelial cells from the developing mouse brain.

The adult mammalian central nervous system develops from the pseudostratified neuroepithelium of the neural tube. In order to study, in vitro, the differentiation of the neuroepithelial cells in detail and to identify factors that may influence this process, an uncontaminated, viable population of neuroepithelial cells, that still retains full developmental potential, is required. In this paper we describe a highly efficient method, involving differential trypsinization and micro-dissection, to cleanly separate the neuroepithelium from surrounding mesenchyme and ectoderm. The purity of isolated neuroepithelium has been assessed by monitoring for the presence of endothelial cells using an anti-endothelial antibody, MTS-12, and found to contain no significant level of contamination. Neuroepithelial cells prepared by this method have been demonstrated to divide and differentiate in tissue culture, to act as target cells for immortalization by proto-oncogenes and to differentiate into neurons in neural transplantation studies.

Animals↗
PubMed1991

Attitudes, knowledge, and training of medical residents regarding adolescent health issues.

This study examined attitudes, knowledge, and training relating to adolescent health issues, of medical residents in six different specialties who provide care to adolescents, at a southern, rural medical school without an organized curriculum in adolescent medicine. An original 18-item questionnaire was developed which examined four broad health care categories: general medicine, sexuality, high-risk behaviors, and development. Of 118 residents 91 (77%) responded. For any health care area, residents reported managing fewer than 10 adolescent patients and often fewer than 3 patients. However, they reported comfort and confidence and little desire for additional training in most of these areas. There were few differences between specialties or year of training. Almost one-half (42%) believed that pediatric care should end by age 16 years; 32% thought it should end at age 18 years. However, there was little support for pediatricians providing prenatal care to pregnant teens. These findings are useful for planning curriculum in ambulatory adolescent health and developing strategies for encouraging residents to understand and embrace the challenge of adolescent health care.

Adolescent↗
PubMed1991

Progressive platelet activation with storage: evidence for shortened survival of activated platelets after transfusion.

Platelets are known to become activated during storage, but it is unclear whether such activation affects recovery or survival after platelet concentrate (PC) transfusion. With the use of flow cytometry to determine the percentage of platelets expressing the alpha-granule membrane protein 140 (GMP-140), a known adhesive ligand appearing on the platelet surface after activation, several studies were conducted. These investigations evaluated 1) the occurrence of significant platelet activation over time in PCs (n = 46) stored under standard blood bank conditions; 2) the correlation between platelet activation and platelet recovery in normal subjects after PC storage (n = 12), as assessed by the recovery of Indium-labeled platelets; and 3) the recovery of activated and unactivated platelets in thrombocytopenic cancer patients transfused with standard PCs (n = 11). It was determined 1) that an increasing duration of storage of PC was associated with increasing platelet activation as measured by the percentage of platelets expressing GMP-140, progressing from a mean of 4 +/- 2 percent (SD) on the day of collection to a mean of 25 +/- 8 percent by 5 days of storage: 2) that, in normal subjects, posttransfusion recovery of autologous platelets stored for 2 to 4 days and then labeled with In111 was inversely correlated with the percentage of activated platelets in the transfused PC (r = -0.55, p = 0.05); and 3) that, when thrombocytopenic patients were transfused with standard PCs, the recovery of the activated platelets in the transfused PCs averaged only 38 +/- 15 percent of the number predicted by the absolute platelet increment.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1991

A prospective analysis of injury severity among helmeted and nonhelmeted bicyclists involved in collisions with motor vehicles.

To evaluate the impact of helmet use on injury severity, patient information was prospectively obtained for all bicyclists involved in collisions with motor vehicles seen at a level-I trauma center from January 1986 to January 1989. Two hundred ninety-eight patients were evaluated; in 284 (95.3%, study group) cases there was documentation of helmet use or nonuse. One hundred sixteen patients (40.9%) wore helmets and 168 (59.1%) did not. One hundred ninety-nine patients (70.1%) had an ISS less than 15, while 85 (29.9%) were severely injured (ISS greater than 15). Only 5.2% of helmet users (6/116) had an ISS greater than 15 compared with 47.0% (79/168) of nonusers (p less than 0.0001). The mean ISS for helmet users was 3.8 compared with 18.0 for nonusers (p less than 0.0001). Mortality was higher for nonusers (10/168, 6.0%) than for helmet users (1/116, 0.9%; p less than 0.025). A striking finding was noted when the group of patients without major head injuries (246) was analyzed separately. Helmet users in this group still had a much lower mean ISS (3.6 vs. 12.9, p less than 0.001) and were much less likely to have an ISS greater than 15 (4.4% vs. 32.1%, p less than 0.0001) than were nonusers. In this group, 42 of 47 patients with an ISS greater than 15 (89.4%) were not wearing helmets. We conclude that helmet nonuse is strongly associated with severe injuries in this study population. This is true even when the patients without major head injuries are analyzed as a group; a finding to our knowledge not previously described.(ABSTRACT TRUNCATED AT 250 WORDS)

Accidents, Traffic↗
PubMed1991

Does flexibility at mealtimes disturb blood glucose control on a multiple insulin injection regimen?

Randomized crossover studies of a half-sized lunch with reduced insulin dose in 21 patients, and a delayed (by 2 h) evening meal in 22 patients, compared with normal meals, were performed in Type 1 diabetic patients. The aim was to examine whether the size and timing of meals can be varied in patients on multiple injection regimens without disturbance of blood glucose control. All patients had previously had their control optimized on multiple injection therapy using a pen-injector. The studies were carried out at home on 6 days (3 changed meals, 3 control) over 2 months, and as 8- and 7-h metabolic profiles (1 study day, 1 control) in an investigation unit. A halved calorie lunch with half the usual insulin dose resulted in equivalent blood glucose control on the study day (area under curve: changed meal 40.0 +/- 3.4 vs control meal 40.3 +/- 3.5 mmol l-1 h for the 5-h period after the meal). Ketone body levels were also unchanged. The late evening meal shifted the post-prandial blood glucose concentration accordingly, but the excursion was not different in extent from the control day (24.8 +/- 1.9 vs 21.0 +/- 1.7 mmol l-1 h). A small excursion of 3-hydroxybutyrate levels before the delayed meal (to 187 +/- 48 mumol l-1) was quickly corrected on eating. Hypoglycaemia was not different in frequency on the changed meal days. Thus no problems of clinical significance were observed when some flexibility in meal size and timing was allowed.

Adult↗
PubMed1991

Is oral contraceptive use still associated with an increased risk of fatal myocardial infarction? Report of a case-control study.

OBJECTIVE: To investigate the association between fatal myocardial infarction and use of modern low-dose oral contraceptives. DESIGN: A case-control study. SETTING: General practices throughout England and Wales. SUBJECTS: 161 women aged under 40 dying from myocardial infarction during 1986-1988. Living controls (2 per case), matched for age and marital status, were chosen from general practice lists. Information was collected during structured interviews with general practitioners, and from postal questionnaires sent to surviving partners of the cases and to control women. MAIN OUTCOME MEASURES: Mortality from myocardial infarction in relation to many risk factors, notably oral contraception, as measured by relative risk. RESULTS: After allowing for the confounding effects of medical risk factors and for surgical sterilization, the overall relative risk associated with both current and past use of oral contraceptives was estimated to be 1.9 (95% CI 0.7 to 4.9, and 1.0 to 3.5 respectively). The relative risk associated with current use of preparations containing 50 micrograms of oestrogen, however, was estimated to be 4.2 (0.5 to 39.2). At least some of the relative risk associated with oral contraceptive use is likely to be attributable to the confounding effect of cigarette smoking, but it is impossible to estimate how much from the available data. CONCLUSIONS: If there was an increased risk of fatal myocardial infarction associated with oral contraceptive use in 1986-1988 it is likely to have been less than two-fold; in this study risks were slightly, but not significantly, elevated with both current and previous use. It may be that any increase in risk is associated solely with the older combined preparations containing 50 micrograms of oestrogen.

Adult↗
PubMed1991

Potential clinical use of an adrenergic/cholinergic agent (HP 128) in the treatment of Alzheimer's disease.

A novel compound designated HP 128, which manifests adrenergic and cholinergic properties, was administered for 10 days to patients with Alzheimer's disease in a double-blind, placebo-controlled trial. All patients who entered the trial had previously failed to respond to a structurally related cholinesterase inhibitor without adrenergic properties (HP 029). The primary purpose of the study was to assess the safety and tolerance of HP 128. Efficacy measures were obtained to generate hypotheses for possible future studies. In the dosage range examined, HP 128 was safe and well tolerated. Effects on clinical measures of dementia severity were equivocal.

Aged↗
PubMed1991

Cholinesterase inhibition in the scopolamine model of dementia.

Scopolamine produces a satisfactory model of the attentional and secondary memory deficits seen in Alzheimer's disease (AD) that can be used to screen compounds for potential therapeutic usefulness. Physostigmine, which is known to enhance memory in AD, produced marked and widespread antagonism of the scopolamine-induced impairments, indicating the sensitivity of the model and establishing its relevance for the clinical situation. HP 029, a novel anticholinesterase, also exhibited widespread potency in the model, and in an international trial with patients with AD, it subsequently showed improvement on similar measures, demonstrating the predictive use of the scopolamine model.

Alzheimer Disease↗