Search PubMed⌕ Search

Biomedical subjects

M Noble

Publications and source records attributed to M Noble.

At least 37 records · Page 2Linked to original sources
PubMed1999

Orofacial exercises for babies with breastfeeding problems?

Young babies occasionally have aberrant orofacial movements that may appear to be the cause of their breastfeeding difficulties. There has been a trend to treat this by introducing corrective exercises for the affected muscle(s). Such treatments have had their bases in therapeutic measures that were originally designed for severely neurologically impaired babies. In fact, most babies with breastfeeding problems are neurologically intact, with many needing only minimal but specific interventions predominantly involving the gape response, attachment and positioning. If the baby's gape response is poor, a minimal amount of breast tissue is taken into the baby's mouth, and abnormal orofacial movements during breastfeeds are the automatic result. This paper re-examines the use of orofacial exercises--often called "suck training"--for babies with breastfeeding problems. There can be negative results from using specific orofacial exercises in an arbitrary or generalised manner. Precautions and guidelines for appropriate corrective measures are discussed.

Breast Feeding↗
PubMed1998

Quantitative insight into proliferation and differentiation of oligodendrocyte type 2 astrocyte progenitor cells in vitro.

As part of our attempts at understanding fundamental principles that underlie the generation of nondividing terminally differentiated progeny from dividing precursor cells, we have developed approaches to a quantitative analysis of proliferation and differentiation of oligodendrocyte type 2 astrocyte (O-2A) progenitor cells at the clonal level. Owing to extensive previous studies of clonal differentiation in this lineage, O-2A progenitor cells represent an excellent system for such an analysis. Previous studies have resulted in two competing hypotheses; one of them suggests that progenitor cell differentiation is symmetric, the other hypothesis introduces an asymmetric process of differentiation. We propose a general model that incorporates both such extreme hypotheses as special cases. Our analysis of experimental data has shown, however, that neither of these extreme cases completely explains the observed kinetics of O-2A progenitor cell proliferation and oligodendrocyte generation in vitro. Instead, our results indicate that O-2A progenitor cells become competent for differentiation after they complete a certain number of critical mitotic cycles that represent a period of symmetric development. This number varies from clone to clone and may be thought of as a random variable; its probability distribution was estimated from experimental data. Those O-2A cells that have undergone the critical divisions then may differentiate into an oligodendrocyte in each of the subsequent mitotic cycles with a certain probability, thereby exhibiting the asymmetric type of differentiation.

Animals↗
PubMed1998

Protein recovery using gas-liquid dispersions.

Two separation techniques, foam separation and colloidal gas aphrons (CGAs), both of which are based on gas-liquid dispersions, are compared as potential applications for protein recovery in downstream processing. The potential advantages of each method are described and the concentration and selectivity achieved with each method, for a range of proteins is discussed. The physical basis of foam separation is the preferential adsorption of surface active species at a gas-liquid interface, with surface inactive species remaining in bulk solution. When a solution containing surface active species is sparged with gas, a foam is produced at the surface: this foam can be collected, and upon collapse contains surface active species in a concentrated form. CGAs are microbubble dispersions (bubble diameters 10-100 microm) with high gas hold ups (>50%) and relatively high stability, which are formed by stirring a surfactant solution at speeds above a critical value (typically around 5000 rpm). It is expected that when proteins are brought into contact with aphrons, protein adsorbs to the surfactant through electrostatic and/or hydrophobic forces. The aphron phase can be separated easily from the bulk solution due to its buoyancy, thus allowing separation of protein in a concentrated form.

Chemistry Techniques, Analytical↗
PubMed1998

A tripotential glial precursor cell is present in the developing spinal cord.

We have isolated a tripotential glial precursor cell population from spinal cords of E13.5 rats. In vitro, these A2B5+E-NCAM- glial-restricted precursor (GRP) cells can undergo extensive self-renewal, and can differentiate into oligodendrocytes and two distinct astrocyte populations, but do not differentiate into neurons. The differentiation potential of GRP cells is retained through at least three cycles of expansion and recloning. Unlike oligodendrocyte-type 2 astrocyte progenitor cells, freshly isolated GRP cells do not respond to platelet-derived growth factor as a mitogen or survival factor, nor do GRP cells differentiate into oligodendrocytes--or even survive--when plated in mitogen-free chemically defined medium. Exposure to fetal calf serum induces GRP cells to differentiate into A2B5- fibroblast-like astrocytes, whereas growth in the presence of basic fibroblast growth factor and ciliary neurotrophic factor induces the generation of A2B5+ process-bearing astrocytes. The early appearance of GRP cells during spinal cord development suggests that they may represent the earliest GRP cell population.

Animals↗
PubMed1998

A stochastic model of brain cell differentiation in tissue culture.

The timing of cell differentiation can be controlled both by cellintrinsic mechanisms and by cell-extrinsic signals. Oligodendrocyte type-2 astrocyte progenitor cells are known to be the precursor cells that give rise to oligodendrocytes. When stimulated to divide by purified cortical astrocytes or by platelet-derived growth factor, these progenitor cells generate oligodendrocytes in vitro with a timing like that observed in vivo. The most widely accepted model of this process assumes a cell-intrinsic biological clock that resides in the progenitor cell. The intrinsic clock model originally proposed in 1986 remains as the dominant theoretical concept for the analysis of timed differentiation in this cell lineage. However, the results of a recent experimental study (Ibarrola et al., Developmental Biology, vol. 180, 1-21, 1996) are most consistent with the hypothesis that the propensity of a clone of dividing O-2A progenitor cells initially to generate at least one oligodendrocyte may be regulated by cell-intrinsic mechanisms, but that environmental signals regulate the extent of further oligodendrocyte generation. We propose a stochastic model of cell differentiation in culture to accommodate the most recent experimental findings. Our model is an age-dependent branching stochastic process with two types of cells. The model makes it possible to derive analytical expressions for the expected number of progenitor cells and of oligodendrocytes as functions of time. The model parameters were estimated by fitting these functions through data on the average (sample mean) number of both types of cells per colony at different time intervals from start of experiment. Using this method we provide a biologically meaningful interpretation of the observed pattern of oligodendrocyte generation in vitro and its modification in the presence of thyroid hormone.

Animals↗
PubMed1998

Alleletyping of an oligodendrocyte-type-2 astrocyte lineage derive from a human glioblastoma multiforme.

We have conducted alleletyping of two novel cell lines derived from glioblastoma multiforme, which appear to have arisen from different glial lineages, by using 76 fluorescently labeled oligonucleotide primers amplifying microsatellite loci covering the entire human genome. One cell line, Hu-O-2A/Gb1, expresses antigens and metabolic profiles characteristic of the oligodendrocyte-type-2 astrocyte (0-2A) lineage of the rat central nervous system. This cell line generated, in vitro, cells with characteristics of 0-2A progenitor cells, oligodendrocytes and astrocytes. The second cell line, IN1434, is derived from an astrocyte or a precursor cell restricted to astrocytic differentiation. Hu-O-2A/Gbl cells show allelic losses of loci on chromosomes 2, 5, 6, 7, 8, 9, 10, 11, 13, 15, 16, 17, 20 and 21. IN1434 cells are likely to have allelic losses of loci on chromosomes 1, 3, 8 and 10, although no control DNA is available for this cell line. These results, for the first time, provide a detailed information of the molecular genetic defects occurring in Hu-O-2A/Gb1 and IN1434.

Alleles↗
PubMed1998

Potentiation of the contraction following a prolonged depolarization in isolated ferret myocardium.

The contractile force was studied in ferret papillary muscles during voltage clamp depolarizations, using the single sucrose gap method. Prolongation of a test depolarization within a train produced potentiation of the following contraction. The effects of varied duration and membrane potential of the test depolarization upon the potentiated force of the following beat were studied. We assumed that force of a beat was an index of calcium entry on the previous depolarization. The relationship between the peak contractile force of the following potentiated beat and the systolic membrane potential of the test depolarization revealed an equilibrium around -18 mV. This was manifest after 100 ms of no effect. Positive potentials caused potentiation of force of the following beat; negative potentials caused suppression of force of the following beat. Calcium entry, if carried by an electrogenic exchange mechanism, would be revealed as a membrane current developing after 100 ms. Membrane current at these times was always outward. When the duration of the test depolarization was prolonged, outward current prior to repolarisation progressively increased. When the duration of the test depolarization was held constant, outward current was varied by variation in membrane potential. Force of the following beat was proportional to the test clamp membrane potential. The potentiation of the contraction following a prolonged depolarization was abolished by substituting 75% of the sodium in the perfusion medium with lithium. These results are compatible with the hypothesis that potentiation of force following a prolonged depolarization is derived from calcium entry into myocardial cells by reversed sodium-calcium exchange.

Animals↗
PubMed1998

Lipoprotein(a) as a risk predictor for cardiac mortality in patients with acute coronary syndromes.

AIMS: Raised lipoprotein(a) concentrations are considered to be a risk factor for atherothrombotic diseases. We examined whether baseline concentrations were a risk factor for an adverse outcome in patients admitted with acute coronary syndromes. METHODS AND RESULTS: Five hundred and nineteen patients admitted with suspected acute coronary syndromes were studied and followed prospectively for a median of 3 years. The prognostic significance of a baseline lipoprotein(a) concentration of > or = 30 mg x dl(-1) or lower for subsequent cardiac death was assessed in patients with myocardial infarction (266) and unstable angina (197) and compared with other variables in regression models. In patients with myocardial infarction, a baseline lipoprotein(a) concentration of > or =30 mg x dl(-1) was associated with a 62% increase in subsequent cardiac death compared to the lower concentration group (29.8% vs 18.6%, Log rank P=0.04). In a multivariate regression model a baseline lipoprotein(a) concentration of > or = 30 mg x dl(-1) retained its significance as an independent predictor of cardiac death (P=0.037). In patients with unstable angina, baseline concentrations of > or = 7.9 mg x dl(-1) were found to be significant predictors of cardiac death in univariate (P=0.021) and multivariate (P=0.035) regression models. CONCLUSION: Baseline lipoprotein(a) concentrations in patients admitted with acute coronary syndromes are associated with an increased risk of cardiac death. For patients with myocardial infarction a concentration of > or = 30 mg x dl(-1) appears appropriate as a risk discriminator; for patients admitted with unstable angina, however, much lower concentrations of lipoprotein(a) appear to be prognostically important.

Acute Disease↗
PubMed1997

Growth factors, glia and gliomas.

The abilities of growth factors to cause normal cells to express the properties associated with transformed cells is discussed in specific reference to the oligodendrocyte-type-2 astrocyte (O-2A) progenitor cell. In the O-2A lineage, it has been possible to use growth factors and other defined molecules to induce or promote in normal cells all of the main properties of tumor cells, these being continued cell division in the absence of differentiation, more subtle modulations of self-renewal probabilities, promotion of cell migration and inhibition of programmed cell death. In addition to our studies on primary cells, our application to the growth of human tumor specimens of techniques utilized to study primary glial progenitor cells has allowed us to isolate a human glioblastoma multiforme (GBM)-derived population that expresses many properties otherwise uniquely expressed by oligodendrocyte-type-2 astrocyte (O-2A) progenitor cells. Hu-O-2A/Gb1 (for Human O-2A lineage Glioblastoma number 1) cells responded to similar mitogens and differentiation modulators as rodent O-2A progenitors, and generated cells with features of precursor cells, oligodendrocytes and astrocytes. Moreover, 1H-NMR analysis of amino acid composition demonstrated a striking conservation of types and quantities of free amino acids between the human tumour cells and the rodent primary cells. Hu-O-2A/Gb1 cells represent the first human glioma-derived population for which unambiguous lineage assignment has been possible. Our results thus demonstrate that the human O-2A lineage can contribute to one of the most malignant of glial tumours. Our analyses further indicate that at least two distinct glial lineages can generate glioblastomas. In addition, the highly diagnostic 1H-NMR spectrum expressed by Hu-O-2A/Gb1 cells raises the possibility of eventual non-invasive identification of tumors of this lineage.

Animals↗
PubMed1997

Metabolic studies of human primitive neuroectodermal tumour cells by proton nuclear magnetic resonance spectroscopy.

Well-characterized cell lines established from primitive neuroectodermal tumours (PNETs) were examined by proton nuclear magnetic resonance (1H-NMR) spectroscopy and chromatographic analysis of perchloric acid extracts, following amplification in cell culture. A characteristic 1H-NMR spectroscopic metabolite pattern was found for medulloblastoma cell lines, which clearly discriminates these cells from PNETs of other locations in the central nervous system (CNS), on the basis of their N-acetyl aspartate (NAA) and aspartate expression. Medulloblastoma cell lines were heterogeneous in respect of their metabolite expression, possibly owing to the heterogeneity in their differentiation along lineages of the CNS. All PNET spectra displayed similar features, including decreased NAA and creatine peaks and increased signals from choline compounds (Cho) compared with normal cerebellum. The expression of NAA by the medulloblastoma lines was in the opposite order to the extent of neuronal differentiation, which may indicate their origin from a progenitor cell with the phenotype of an oligodendrocyte-type-2 astrocyte cell.

Aspartic Acid↗
PubMed1997

A prospective study of the role of lipoprotein(a) in the pathogenesis of unstable angina.

AIM: Lipoprotein(a) is considered to be a risk factor for atherothrombotic diseases. The aim of the study was to examine the potential role of lipoprotein(a) concentrations in patients admitted with unstable angina with particular reference to their cardiac Troponin T concentrations, which identifies a subgroup at high risk of subsequent cardiac events. METHODS AND RESULTS: Consecutive patients admitted with chest pain to a single coronary care unit were studied. One hundred and sixty-seven patients had a final diagnosis of unstable angina, of whom 56 were cardiac Troponin T-positive. Admission lipoprotein(a) concentrations were significantly higher in the cardiac Troponin T-positive unstable angina group as compared to the cardiac Troponin T-negative unstable angina group: median and interquartile ranges 22.25 mg.dl-1 (6.25, 32.0) vs 6.0 mg.dl-1 (2.22, 14.8) respectively) P = 0.0004. A highly significant correlation was also found between the level of cardiac Troponin T at diagnosis and the lipoprotein(a) concentration: rs = 0.2798, P = 0.0001. CONCLUSION: This study provides the first evidence in man of a significant role for lipoprotein(a) in unstable angina. The correlation between lipoprotein(a) concentration and cardiac Troponin T concentration suggests that lipoprotein(a) may be significantly involved in the early failure of plaque rupture stabilization.

Adult↗
PubMed1996

Evidence for the existence of at least two timing mechanisms that contribute to oligodendrocyte generation in vitro.

We have been studying oligodendrocyte generation in vitro to obtain insights into how the timely generation of these cells might be regulated. Our studies suggest the existence of timing mechanisms quite different from those of existing models, wherein it is proposed that timely oligodendrocyte generation is associated with synchronous and symmetric differentiation controlled by cell-intrinsic biological clocks. Our results are most consistent with the hypothesis that the propensity of a clone of dividing oligodendrocyte type-2 astrocyte (O-2A) progenitors initially to generate at least one oligodendrocyte may be regulated by cell-intrinsic mechanisms, but that cell-extrinsic signals regulate the extent of further oligodendrocyte generation. In cultures of embryonic rat cortex grown in the presence of platelet-derived growth factor (PDGF), oligodendrocytes appeared in a timely manner in the absence of clonal differentiation. In contrast with previous suggestions, the presence or absence of thyroid hormone (T3) did not alter the probability of individual clones of O-2A progenitors generating at least one oligodendrocyte in vitro at a time equal to the rat's day of birth. Instead, T3 increased the proportion of oligodendrocytes generated within clones. For postnatally derived progenitor cells, the initial appearance of oligodendrocytes also was followed by further asymmetric generation of these cells, with the ratio of progenitors to oligodendrocytes within clones being regulated by environmental signals. T3 and ciliary neurotrophic factor increased oligodendrocyte generation, while neurotrophin-3 (NT-3) suppressed oligodendrocyte generation. Also in contrast to previous reports, NT-3 was not required for the promotion of extensive division of O-2A progenitor cells by PDGF.

Animals↗
PubMed1996

Prognostic significance of admission troponin T concentrations in patients with myocardial infarction.

BACKGROUND: New, highly specific cardiac structural proteins can now be measured. The early presence of one of these proteins, troponin T, has been found to have important prognostic significance in patients with unstable angina pectoris. The prognostic significance of its presence on admission was assessed in patients with myocardial infarction. METHODS AND RESULTS: Two hundred forty patients admitted with myocardial infarction were studied and followed prospectively for a median of 3 years. The prognostic significance of an admission troponin T concentration > or = 0.2 ng/mL for subsequent cardiac death and/or reinfarction was assessed and compared with other variables in a regression model. Any detectable troponin T on admission was associated with a worse prognosis on follow-up. An admission concentration of > or = 0.2 ng/mL was associated with a higher risk of subsequent cardiac death (chi 2, 13.3; P = .0002) and death or nonfatal reinfarction (chi 2, 16; P = .00006). The excess risk was seen primarily in patients with admission ECG ST-segment elevation (cardiac death chi 2, 9.7; P = .001; death or nonfatal reinfarction chi 2, 10.3; P = .001). In a stepwise regression model for cardiac death or nonfatal reinfarction, troponin T was superior to most of the other variables entered in both myocardial infarction subgroups. CONCLUSIONS: The presence of admission troponin T in patients with myocardial infarction defines a subgroup, particularly those with ST-segment elevation, at increased risk of subsequent cardiac events and identifies a group that may benefit from alternative early management strategies.

Biomarkers↗
PubMed1996

Prospective study of the role of cardiac troponin T in patients admitted with unstable angina.

OBJECTIVE: To examine the prognostic significance and role in risk stratification of the biochemical marker troponin T in patients admitted with unstable angina. DESIGN: Single centre, blinded, prospective study of patients admitted with chest pain. SETTING: Coronary care unit of a district general hospital. SUBJECTS: 460 patients admitted with chest pain and followed up for a median of three years. 183 patients had a final diagnosis of unstable angina. MAIN OUTCOME MEASURES: Cardiac death, need for coronary revascularisation, or readmission with non-fatal myocardial infarction as first events. RESULTS: 62 (34%) unstable angina patients were troponin T positive. This group had significantly increased incidence rates of subsequent cardiac death (12 cases (19%) v 14 (12%)), coronary revascularisation (22 (35%) v 26 (21%)), death or revascularisation (33 (53%) v 40 (33%)), and death or non-fatal myocardial infarction (18 (29%) v 21 (17%)) compared with the troponin T negative group. In multiple logistic regression troponin T status was a highly significant predictor for the end points coronary revascularisation and cardiac death or revascularisation as first events. CONCLUSION: Troponin T in the serum of patients with unstable angina identifies a subgroup at higher risk of subsequent cardiac events and its measurement aids in risk factor stratification. The increased risk extends to two years after admission. Prospective randomised trials are required to identify optimum therapeutic strategies for this subgroup.

Angina, Unstable↗
PubMed1996

LIM-kinase1 hemizygosity implicated in impaired visuospatial constructive cognition.

To identify genes important for human cognitive development, we studied Williams syndrome (WS), a developmental disorder that includes poor visuospatial constructive cognition. Here we describe two families with a partial WS phenotype; affected members have the specific WS cognitive profile and vascular disease, but lack other WS features. Submicroscopic chromosome 7q11.23 deletions cosegregate with this phenotype in both families. DNA sequence analyses of the region affected by the smallest deletion (83.6 kb) revealed two genes, elastin (ELN) and LIM-kinase1 (LIMK1). The latter encodes a novel protein kinase with LIM domains and is strongly expressed in the brain. Because ELN mutations cause vascular disease but not cognitive abnormalities, these data implicate LIMK1 hemizygosity in imparied visuospatial constructive cognition.

Base Sequence↗