Biomedical subjects

E Ma

Publications and source records attributed to E Ma.

At least 19 recordsLinked to original sources

PubMed2002

Homogeneity of a supersaturated solid solution.

Extended x-ray absorption fine structures, small-angle x-ray scattering, and atomistic model calculations have been employed to probe the homogeneity of the fcc solution created in Ag-Cu, a classical system demonstrating the extension of solubility across the entire miscibility gap through rapid quenching. Our results reveal that in many cases the supersaturated solutions formed have decomposition features on the scale of 1 nm. Conventional diffraction methods are inadequate in determining the level of supersaturation or the uniformity of such solid solution alloys.

Journal Article↗

PubMed2002

Evaluation of paediatric osteosarcomas by classic cytogenetic and CGH analyses.

Classic cytogenetic and comparative genomic hybridisation (CGH) data on osteosarcomas have been reported extensively in the literature. However, the number of paediatric osteosarcoma cases studied below the age of 14 years remains relatively small. This study reports four new cases of paediatric osteosarcoma in patients aged 3 to 13 years, evaluated by classic cytogenetics and CGH analyses. Clonal chromosomal alterations were detected in all the cases and included structural rearrangements at 1p11-13, 1q11, 4q27-33, 6p23-25, 6q16-25, 7p13-22, 7q11-36, 11p10-15, 11q23, 17p11.2-13, 21p11, and 21q11-22. The CGH analysis revealed recurrent gains at 1p, 4q, 17p, and 21q and losses at 3q and 16p. Five amplification sites were observed at 1q11-23, 6p21, 8q13, 8q21.3-24.2, and 17p. The data are discussed and compared with other cytogenetic reports in the literature.

Adolescent↗

PubMed2001

Melting mechanisms at the limit of superheating.

The atomic-scale details during melting of a surface-free Lennard-Jones crystal were monitored using molecular dynamics simulations. Melting occurs when the superheated crystal spontaneously generates a sufficiently large number of spatially correlated destabilized particles that simultaneously satisfy the Lindemann and Born instability criteria. The accumulation and coalescence of these internal local lattice instabilities constitute the primary mechanism for homogeneous melt nucleation inside the crystal, in lieu of surface nucleation for equilibrium melting. The vibrational and elastic lattice instability criteria as well as the homogeneous nucleation theory all coincide in determining the superheating limit.

Journal Article↗

PubMed2001

Neutrino mass, muon anomalous magnetic moment, and lepton flavor nonconservation.

If the generating mechanism for neutrino mass is to account for both the newly observed muon anomalous magnetic moment as well as the present experimental bounds on lepton flavor nonconservation, then the neutrino mass matrix should be almost degenerate and the underlying physics should be observable at future colliders. We illustrate this assertion with two specific examples, and show that gamma(mu;-->egamma)/m5(mu), gamma(tau-->egamma)/m5tau, and gamma(tau-->(mu)gamma)/m5tau are in the ratio ((Delta)m2)2sol/2, ((Delta)m2)2sol/2, and ((Delta)m2)2atm, respectively, where the (Delta)m2 parameters are those of solar and atmospheric neutrino oscillations and bimaximal mixing has been assumed.

Journal Article↗

PubMed2001

Co-existence of alternative forms of 8q gain in cytogenetic clones of three patients with acute myeloid leukemia, pointing to 8q22 approximately 8qter as a region of biologic significance.

Clonal trisomy 8 chromosome abnormalities can be detected in 15% of patients with acute myeloid leukemia (AML). The most common form of change is complete gain of the whole chromosome 8, followed by partial gains in unbalanced forms. The biologic consequences of trisomy 8 remain unclear, but a gene dosage effect is suspected. We report on three patients with AML who had alternative forms of chromosome 8 gain in their bone marrow cells. The partial gains resulted from a breakpoint in the chromosome band 8q22. This indicates that the region 8q22 to 8qter may be of particular pathogenetic importance.

Acute Disease↗

PubMed2001

Amorphous structures in the immiscible Ag-Ni system.

Vapor quenching in the phase-separating Ag-Ni system creates alloys that appear homogeneously amorphous under conventional probes. However, an atomic-level structural analysis based on extended x-ray absorption fine structures in combination with reverse Monte Carlo and molecular dynamics simulations demonstrates that these new phases are characterized by nonuniform, spinodal-like structures on an extremely fine scale. This heterogeneous nature of the structure is directly responsible for the unexpectedly low heat (and temperature) of crystallization observed in calorimetric measurements.

Journal Article↗

PubMed2001

Naturally small seesaw neutrino mass with no new physics beyond the TeV scale.

If there is no new physics beyond the TeV energy scale, such as in a theory of large extra dimensions, the smallness of the seesaw neutrino mass, i.e., m(nu) = m(2)(D)/m(N), cannot be explained by a very large m(N). In contrast to previous attempts to find an alternative mechanism for a small m(nu), I show how a solution may be obtained in a simple extension of the standard model, without using any ingredient supplied by the large extra dimensions. It is also experimentally testable at future accelerators.

Journal Article↗

PubMed2001

Familial deletion of (8)(q24.13q24.22) associated with a normal phenotype.

We report a familial deletion of (8q) detected in amniocytes of a fetus with a normal ultrasound and in the phenotypically normal mother, who has now had three pregnancy losses. Chromosome analysis of amniocytes and maternal peripheral blood cells showed an interstitial deletion of (8)(q24.13q24.22), which is distal to the region associated with Langer-Giedion syndrome (LGS) or trichorhinophalangeal (TRP) syndrome. This deletion was confirmed by fluorescence in situ hybridization with a c-myc cosmid clone and chromosome 8 painting library.

Adult↗

PubMed2001

Mutation in pre-mRNA adenosine deaminase markedly attenuates neuronal tolerance to O2 deprivation in Drosophila melanogaster.

O2 deprivation can produce many devastating clinical conditions such as myocardial infarct and stroke. The molecular mechanisms underlying the inherent tissue susceptibility or tolerance to O2 lack are, however, not well defined. Since the fruit fly, Drosophila melanogaster, is extraordinarily tolerant to O2 deprivation, we have performed a genetic screen in the Drosophila to search for loss-of-function mutants that are sensitive to low O2. Here we report on the genetic and molecular characterization of one of the genes identified from this screen, named hypnos-2. This gene encodes a Drosophila pre-mRNA adenosine deaminase (dADAR) and is expressed almost exclusively in the adult central nervous system. Disruption of the dADAR gene results in totally unedited sodium (Para), calcium (Dmca1A), and chloride (DrosGluCl-alpha) channels, a very prolonged recovery from anoxic stupor, a vulnerability to heat shock and increased O2 demands, and neuronal degeneration in aged flies. These data clearly demonstrate that, through the editing of ion channels as targets, dADAR, for which there are mammalian homologues, is essential for adaptation to altered environmental stresses such as O2 deprivation and for the prevention of premature neuronal degeneration.

Adenosine Deaminase↗

PubMed2001

Neuronal tolerance to O2 deprivation in drosophila: novel approaches using genetic models.

In spite of many advances in monitoring oxygenation and preventing cerebro-vascular accidents, there is still considerable morbidity and mortality from conditions with cerebral blood flow impairment and O2 deprivation leading to hypoxic/ischemic brain injury. Part of this failure is related to the complexity of the cascade of events that ensue after hypoxia or ischemia, but also part of it may be related to the fact that most research in the previous few decades has focused, justifiably, on cerebral vessel disease. However, an important aspect of the cascade is dependent on many factors that are inherent to the nature and response of the tissue itself. Hence, there is more need now for a two-pronged approach to hypoxic/ischemic brain injury, one focusing on vessel disease, its prevention, and treatment, and the other centering on the brain tissue itself and the factors that render neurons and glia more susceptible or more tolerant to a lack of oxygenation. In the past several years, a number of methods, techniques, and animal models have been used to address the response of neurons and glia to lack of oxygen. In this review, we highlight some novel ideas and some results that we and others have obtained, mostly pertaining to the genetic endowment and responses of the central nervous system to O2 deprivation. The role and importance of genetic models, such as the Drosophila melanogaster, are discussed, and an example illustrating how to harness the power of Drosophila genetics is detailed.

Adaptation, Physiological↗

PubMed2000

Verifiable model of neutrino masses from large extra dimensions

We propose a new scenario of neutrino masses with a Higgs triplet (xi(++),xi(+),xi(0)) in a theory of large extra dimensions. Lepton number violation in a distant brane acts as the source of a very small trilinear coupling of xi to the standard Higgs doublet in our brane. Small realistic Majorana neutrino masses are naturally obtained with the fundamental scale M(*) approximately O(1) TeV, foretelling the possible discovery of xi (m(xi) less, similarM(*)) at future colliders. Decays of xi(++) into same-sign dileptons are fixed by the neutrino mass matrix. Observation of &mgr;-e conversion in nuclei is predicted.

Journal Article↗

PubMed2000

[Effect of serum and wound exudates on PMN apoptosis in burned patients].

OBJECTIVE: To study in vitro the effect of burn serum and wound exudates on PMN apoptosis in burned patients. METHODS: The burn serum was obtained from patients within 3 days postburn. The blister fluid was collected from intact blisters in burn wound within 24 hours postburn, and subeschar tissue fluid underneath III degree burn wound during escharectomy. PMNs were isolated from healthy human donors and cultured for 24 hours at 37 degreeC and 5% CO(2) with normal serum (NS), burn serum (BS), burn blister fluid (BBF) and subeschar tissue fluid (STF), respectively. Morphological assessment and quantification of PMN apoptosis were performed with AO + EB stain and flow cytometric analysis. RESULTS: The number of apoptotic PMN and DNA fragmentation of PMN significantly decreased (P < 0.05) when PMN were cultured with BS, BBF, and STF when compared with that with NS. In addition, the specific DNA "ladder" pattern for apoptotic cells couldn't be found on the agarose gel electrophoresis in this case. However, BBF exhibited weaker inhibiting effect than BS and STF on PMN apoptosis. CONCLUSION: PMN apoptosis could be inhibited in vitro by BS, STF and BBF from burned patients.

Apoptosis↗

PubMed1999

Isolation and characterization of the hypoxia-inducible factor 1beta in Drosophila melanogaster.

The hypoxia-inducible factor 1 (HIF-1), a heterodimer composed of alpha and beta subunits, plays an important role in the cellular response to O(2) deprivation. In this paper, Drosophila HIF-1beta (dHIF-1beta) homolog is cloned and characterized. Further, Northern analyses showed that dHIF-1alpha and dHIF-1beta expressed their highest level at an embryonic stage. From the pupal stage on, their expression was sharply reduced and maintained at a steady level. Anoxia treatment up-regulated the expression of the both alpha and beta subunits. Over-expression of dHIF-1alpha in transgenic embryos resulted in embryonic lethality, while over-expression of dHIF-1beta significantly prolonged fly recovery time from a 5-min anoxic stupor. The cloning and characterization dHIF-1beta reported in this paper provide a framework for further genetic dissection of the HIF-1 complex in its role in the cellular or tissue response to O(2) deprivation.

Amino Acid Sequence↗

PubMed1999

A Drosophila CDK5alpha-like molecule and its possible role in response to O(2) deprivation.

Cyclin-dependent kinase 5 activator (Cdk5alpha) is an activator of Cdk5 kinase activity and its expression is restricted to neurons. The complex of Ckd5/Cdk5alpha is essential for neurite outgrowth during neuronal differentiation and possibly also for neuronal degeneration. Here we report the isolation and characterization of a Drosophila Cdk5alpha-like molecule (dCdk5alpha). The gene encoding this molecule is localized in the Drosophila chromosome region of 31D1-31D2. The expression of this gene is differentially regulated with a very low level at earlier developmental stages and reaches the highest level in the adult. The C-terminal of this molecule shares high homology with the mammalian Cdk5alpha molecule. Constitutive over-expression of dCdk5alpha in transgenic flies significantly prolongs their recovery time from 5 min to O(2) deprivation or anoxia in older flies (15 days) but not in young ones (4 days). In addition, anoxia up-regulated the expression of this gene. Taken together, the results in this report and others provide a framework for genetically dissecting the functions of Cdk5alpha/Cdk5 complex in the CNS.

Amino Acid Sequence↗

PubMed1999

Gene regulation by O2 deprivation: an anoxia-regulated novel gene in Drosophila melanogaster.

Organisms, across the animal kingdom, vary in their tolerance or susceptibility to cell injury from O2 deprivation. In this study we have taken advantage of the genetically well studied fruit fly to dissect basic mechanisms underlying their ability to tolerate lack of O2. Using differential display and molecular techniques, we cloned and characterized a novel gene, named fau, which is up-regulated considerably following anoxia in Drosophila melanogaster. Northern blot analysis revealed that the transcript of this gene is approximately 0.9 kb in length with an open reading frame encoding a small hydrophilic protein ( approximately 14.4 kDa). This protein has no homology to previously described gene products but has many potential phosphorylation sites. In situ hybridization showed that this gene is located in region 7C-D on the Drosophila X-chromosome and its transcript concentrated in the lamina and cortical neurons of the Drosophila central nervous system (CNS). Transgenic flies showed that over-expression of fau significantly reduced the recovery time of the flies from anoxia. We conclude that (1) this study provided a framework on which the mechanisms underlying anoxia tolerance can be dissected in the fruit fly and (2) fau gene plays an important role in the regulation of tissue responsiveness to O2 deprivation.

Amino Acid Sequence↗

PubMed1999

Maturation of medial efferent system function in humans.

Otoacoustic emissions are typically reduced in amplitude when broadband noise is presented to the contralateral ear. This contralateral suppression is attributed to activation of the medial olivocochlear system, which has an inhibitory effect on outer hair-cell activity. By studying the effects of contralateral noise on cochlear output at different stages of auditory maturation in human neonates, it is possible to describe the timecourse for development of medial efferent system function in humans. The present study recorded 2 f1-f2 distortion product otoacoustic emissions (DPOAE) in human adults, term and premature neonates at three f2 frequencies: 1500, 3000, and 6000 Hz, using fixed primary tone frequency ratio (f2/f1 = 1.2) and level separation (10 dB, L1 > L2). Average DPOAE growth functions were recorded with and without contralateral broadband noise. Results indicate that contralateral suppression of DPOAEs is absent at 6000 Hz, but present at 1500 and 3000 Hz for all ages. However, DPOAE amplitude from premature neonates was not altered by noise in an adult-like manner; in this age group, DPOAE amplitude was equally likely to by suppressed or enhanced by noise presented contralaterally. Contralateral enhancement may reflect a temporary stage of immaturity in outer hair cell-medial efferent fiber synapses just prior to term birth.

Adult↗

PubMed1999

Developmental changes in leg coordination of the chick at embryonic days 9, 11, and 13: uncoupling of ankle movements.

To understand changes in motor behavior during development, kinematic measurements were made of the right leg during embryonic motility in chicks on embryonic (E) days 9, 11, and 13. This is an interesting developmental period during which the embryo first becomes large enough to be physically constrained by the shell. Additionally, sensory systems are incorporated at that time into the spinal motor circuitry. Previous electromyographic (EMG) recordings have shown that the basic pattern of muscle activity seen at E9, composed of half-center-type alternation of extensor and flexor activation, breaks down by E13. This breakdown in organization could be because of disruption of motor patterns by the immature sensory system and/or new spatial constraints on the embryo. The current article describes several changes in leg movement patterns during this period. Episodes of motility increase in duration and the intervals of time between episodes of motility decrease in length. The range of motion of the leg increases, but the overall posture of the leg becomes more flexed. It was found that in-phase coordination of movement among the hip, knee, and ankle decreased between E9 and E13 in agreement with the previous EMG recordings. However, it was also found that the decrease of in-phase coordination among the three joints was accompanied by an increase in the time any two joints were moving in the same manner. Furthermore, examination of in-phase coordination within pairs of joints showed that all three pairs were well coordinated at E9, but that at E13 the in-phase coordination of the ankle with the other two joints decreased, whereas the knee and hip coordination was maintained. This suggests that the hip-knee synergy was closely coupled and that coupling of the ankle with other joints was more labile. The authors conclude that embryos respond to the reduction of free space in the egg during this period not by decreasing the amplitude or coordination of leg movements in general, but instead by differentially controlling the movements of the ankle from those of the hip and knee. Additionally, the changes in movement patterns do not represent a decrease in organization, but rather an alteration of motor coordination possibly as the result of information from the newly acquired sensory systems. These data also support theories that limb central pattern generators (CPGs) are composed of unit CPGs for each joint that can be modulated individually and that this organization is already established early in embryogenesis.

Analysis of Variance↗

PubMed1999

Intracellular pH regulation of CA1 neurons in Na(+)/H(+) isoform 1 mutant mice.

To understand the role of Na(+)/H(+) exchanger 1 (NHE1) in intracellular pH (pH(i)) regulation and neuronal function, we took advantage of natural knockout mice lacking NHE1, the most ubiquitously and densely expressed NHE isoform in the central nervous system (CNS). CA1 neurons from both wild-type (WT) and NHE1 mutant mice were studied by continuous monitoring of pH(i), using the fluorescent indicator carboxy-seminaphthorhodafluor-1 (SNARF-1) and confocal microscopy. In the nominal absence of CO(2)/HCO(3)(-), steady-state pH(i) was higher in WT neurons than in mutant neurons. Using the NH(4)Cl prepulse technique, we also show that H(+) flux in WT neurons was much greater than in mutant neurons. The recovery from acid load was blocked in WT neurons, but not in mutant neurons, by removal of Na(+) from the extracellular solution or by using 100 microM 3-(methylsulfonyl-4-piperidino-benzoyl)-guanidine methanesulfonate (HOE 694) in HEPES buffer. Surprisingly, in the presence of CO(2)/HCO(3)(-), the difference in H(+) flux between WT and mutant mice was even more exaggerated, with a difference of more than 250 microM/s between them at pH 6.6. H(+) flux in CO(2)/HCO(3)(-) was responsive to diisothiocyanato-stilbene-2, 2'-disulfonate (DIDS) in the WT but not in the mutant. We conclude that (a) the absence of NHE1 in the mutant neurons tended to cause lower steady-state pH(i) and, perhaps more importantly, markedly reduced the rate of recovery from an acid load; and (b) this difference in the rate of recovery between mutant and WT neurons was surprisingly larger in the presence, rather than in the absence, of HCO(3)(-), indicating that the presence of NHE1 is essential for the regulation and/or functional expression of both HCO(3)(-)-dependent and -independent transporters in neurons.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗