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Biomedical subjects

E Chang

Publications and source records attributed to E Chang.

At least 109 records · Page 6Linked to original sources
PubMed1994

Biochemical characteristics of a calmodulin-phosphodiesterase activator increased in spontaneously hypertensive mice and rats.

The biochemical characteristics of calmodulin-phosphodiesterase (CaM-PDE) are described. It is a cytosolic, hydrophobic, and heat-, acid-, and base-stable compound sensitive to proteases. It is optimally extracted from neutral supernatants by CHCl3/MeOH (2:1 or 1:1). It partitions into the organic fraction of CHCl3/MeOH extracts, whereas the aqueous fraction contains a component that potentiates the activator's capacity to stimulate CaM-PDE. The activator interacts with PDE by increasing its apparent affinity for CaM. Size partition chromatography of CHCl3/MeOH extracts from spontaneously hypertensive rats produces two activity peaks, one eluting at void volume with the second eluting at a position corresponding to a 4-kDa peptide. The compound at void volume can be converted to the 4-kDa entity by sonication. The CaM-PDE activator behaves as a lipopeptide that shares several characteristics with parathyroid hypertensive factor.

Acid-Base Equilibrium↗
PubMed1994

The T alpha 1 alpha-tubulin promoter specifies gene expression as a function of neuronal growth and regeneration in transgenic mice.

We have previously demonstrated that one member of the alpha-tubulin multigene family, termed T alpha 1 in rats, is regulated as a function of neuronal growth and regeneration. To elucidate the molecular mechanisms responsible for coupling gene expression to morphological differentiation, we have isolated the T alpha 1 gene, have fused 1.1 kb of the 5' flanking region to a nuclear lacZ reporter gene, and have generated transgenic mice. Analysis of these transgenic mice demonstrated that marker gene expression was specific to the CNS and PNS, with expression in vivo at embryonic day 13.5 being similar to expression of the endogenous gene. Moreover, the induction of transgene expression was correlated temporally with neuronal commitment in developing neural crest-derived peripheral neurons and in the developing retina. Immunocytochemical analysis of mixed primary embryonic brain cultures confirmed that transgene expression was specific to neurons, with the majority of neurons, but not astrocytes or oligodendrocytes, expressing beta-galactosidase. Transgene expression in vivo was maintained in developing neurons until early in postnatal life, subsequent to which its expression decreased coincident with neuronal maturation. The transgene was then reinduced in regenerating facial motoneurons following unilateral axotomy of the facial nerve. Thus, 1.1 kb of 5' flanking sequence from the T alpha 1 gene contains the sequence elements responsible for specifying gene expression to embryonic neurons and for subsequently regulating gene expression in both developing and mature neurons as a function of morphological growth.

Animals↗
PubMed1993

The shear strength and the failure mode of plasma-sprayed hydroxyapatite coating to bone: the effect of coating thickness.

Plasma-sprayed hydroxyapatite coated (HAC) 50 and 200 microns thick on Ti-6Al-4V cylinders was transcortically implanted in the femora of canines to evaluate in detail the effect of coating thickness on the pushout shear strength and failure mode examined under scanning electron microscope after the periods of 4, 6, 8, and 12 weeks. The HAC coating exhibited higher shear strength at 50 microns than at 200 microns. Its failure mode was conclusively at or near the HAC-bone interface, and the slight attack of body fluid had not degraded the implant to the extent that failure occurred at the HAC-Ti alloy interface after 12 weeks of observation. For 200 microns-HAC, failure was found at the HAC-bond interface, inside the HAC lamellar splat layer and at the HAC-Ti alloy substrate interface, depending on the period of implantation. It was also deduced that the variation of failure mode of 200 microns-HAC with time could not be accounted for by the attack of body fluid alone; the degradation must be a synergetic adverse result of residual stress in the HAC and the attack of body fluid.

Analysis of Variance↗
PubMed1993

Generation of a human chromosome 18-specific YAC clone collection and mapping of 55 unique YACs by FISH and fingerprinting.

A yeast artificial chromosome (YAC) library was constructed from a somatic cell hybrid line in which the human chromosome content had been reduced by repeated subcloning to one or two copies of chromosome 18. Screening of 4700 primary yeast transformants generated 74 clones containing a YAC with a human DNA insert averaging 190 kb in size. The human YACs were localized to subregions of chromosome 18 by in situ hybridization of biotin-labeled Alu-PCR products obtained using total yeast DNA as a template. Comparisons of interspersed repetitive sequence-PCR and restriction fragment fingerprint patterns identified five sets of identical and three sets of overlapping YACs. Dual-label fluorescence in situ hybridization interphase mapping was used to determine the order of some nonoverlapping YACs. STS (sequence-tagged site) content mapping was carried out with PCR primers for 56 chromosome 18-specific markers. The identification of YACs containing four known genes--encoding the pituitary adenylate cyclase activating polypeptide (PA-CAP), the myelin basic protein (MBP), ferrochelatase (FECH), and SSAV1, an endogenous retroviral element related to the SSAV virus--provides a precise cytological map position for the respective loci. Our final collection of 55 randomly isolated, unique, and regionally localized YACs (D18S107-D18S161) is distributed over the entire chromosome and collectively covers approximately 12 Mb, i.e., 16% of the estimated 77 Mb of DNA in euchromatin of chromosome 18. These YACs provide reagents for the isolation of genes in these regions and represent nucleation points for the generation of STS to increase coverage of the chromosome by YAC contigs.

Adenylyl Cyclases↗
PubMed1993

Anxiety and depression over the first year of spinal cord injury: a longitudinal study.

The literature concerning the psychological consequences following spinal cord injury (SCI) indicates a discordance between clinical impressions and empirical research. Although many studies report that psychological morbidity is not an inevitable consequence of SCI, much of this research is characterised by methodological inadequacies and the conclusions are therefore tenuous. The present study assessed 41 persons with SCI for depression and anxiety using objective psychological measures on three occasions over the first year of SCI and compared them with 41 able bodied controls matched for age, sex, education and, as far as possible, occupation. Results demonstrated significant differences between the two groups, with the SCI group being more anxious and depressed. However, psychological morbidity was not an inevitable consequence of SCI, with group means reflecting mild levels of depression and anxiety. No significant differences were found across time and no interactions between groups and time were detected. Implications for the treatment of SCI are discussed.

Adolescent↗
PubMed1993

A conserved alternative splice in the von Recklinghausen neurofibromatosis (NF1) gene produces two neurofibromin isoforms, both of which have GTPase-activating protein activity.

Sequence analysis has shown significant homology between the catalytic regions of the mammalian ras GTPase-activating protein (GAP), yeast Ira1p and Ira2p (inhibitory regulators of the RAS-cyclic AMP pathway), and neurofibromin, the protein encoded by the NF1 gene. Yeast expression experiments have confirmed that a 381-amino-acid segment of neurofibromin, dubbed the GAP-related domain (GRD), can function as a GAP. Using the RNA polymerase chain reaction with primers flanking the NF1-GRD, we have identified evidence for alternative splicing in this region of the NF1 gene. In addition to the already published sequence (type I), an alternative RNA carrying a 63-nucleotide insertion (type II) is present in all tissues examined, although the relative amounts of types I and II vary. The insertion is conserved across species but is not present in GAP, IRA1, or IRA2. GenBank searches have failed to identify significant similarity between the inserted sequence and known DNA or protein sequences, although the basic amino acid composition of the insertion shares features with nuclear targeting sequences. Expression studies in yeasts show that despite the partial disruption of the neurofibromin-IRA-GAP homology by this insertion, both forms of the NF1-GRD can complement loss of IRA function. In vivo assays designed to compare the GAP activity of the two alternatively spliced forms of the NF1-GRD show that both can increase the conversion of GTP-bound ras to its GDP-bound form, although the insertion of the 21 amino acids weakens this effect. The strong conservation of this alternative splicing suggests that both type I and II isoforms mediate important biological functions of neurofibromin.

Amino Acid Sequence↗
PubMed1993

The influence of spinal cord injury on coping styles and self-perceptions: a controlled study.

Well-controlled research investigating psychological responses following Spinal Cord Injury (SCI) is lacking. In addition, much of the literature is based on depression following SCI and is dominated by data from the USA. The effects of SCI on perceptions of control, self-esteem and coping styles over the first year of SCI were investigated. Forty-one acute spinal injured patients and 41 able-bodied controls matched for age, sex and education completed a variety of standardised questionnaires on three occasions over one year. The instruments included the Locus of Control of Behaviour Scale, Rosenberg's Self-Esteem Scale, and an adapted Mental Adjustment to Cancer (MAC) Scale which measures coping styles, including fighting spirit, helplessness/hopelessness and fatalism. The SCI group were found to be more external in their perceptions of control, lower in self-esteem, and more helpless/hopeless and fatalistic in attitude than the controls. The majority of the SCI group had scores reflecting adaptive coping styles and intact levels of self-esteem but there were still a substantial proportion who displayed maladaptive coping styles (e.g. external locus of control, fatalism, helplessness). No differences in scores across time were found for either group. Implications for psychological rehabilitation are discussed.

Adaptation, Psychological↗
PubMed1992

Oncogenic ras triggers the activation of 42-kDa mitogen-activated protein kinase in extracts of quiescent Xenopus oocytes.

Quiescent, full-grown Xenopus oocytes, which are arrested at the G2/M border of meiosis, contain an inactive 42-kDa mitogen-activated protein kinase (p42MAPK) that is activated when oocytes are stimulated to resume the meiotic cell cycle. We have made extracts from these oocytes that respond to four cell cycle activators: oncogenic [Val12]Ras protein, clam cyclins A delta 60 and B delta 97, and the phosphatase inhibitor okadaic acid. All four induce the tyrosine phosphorylation and activation of p42MAPK. Both cyclins and okadaic acid, but not [Val12]Ras, also lead to activation of the endogenous cyclin B/cdc2 kinase complexes in extracts of quiescent oocytes. Using extracts prepared from cycloheximide-arrested interphase cells, we show that although p42MAPK activation can occur in response to cyclin-activated cdc2, the Ras-induced activation of p42MAPK occurs without intervening cdc2 activation. Neither the nononcogenic [Gly12]Ras nor [Val12,Arg186]Ras, a mutant that lacks the C-terminal consensus sequence directing prenylation and subsequent membrane association, is an effective activator of p42MAPK in vitro.

Animals↗
PubMed1992

Phosphatidate phosphohydrolases in liver, heart and adipose tissue of the JCR:LA corpulent rat and the lean genotypes: implications for glycerolipid synthesis and signal transduction.

The activities of two distinct phosphatidate phosphohydrolases (PAP) were measured in livers, hearts and adipose tissues of the JCR:LA corpulent rat which is hyperphagic, hypertriglyceridaemic and insulin resistant. The specific activity of PAP-1, which requires Mg2+, was similar in the livers of lean and corpulent female rats and in male corpulent rats, but these activities were about 1.6-fold higher than in lean males. There was a correlation between the specific activity of PAP-1 and the concentrations of hepatic and serum triacylglycerols in the males, but not in the females. Chronic treatment of the corpulent rats with ethanol did not significantly alter the hepatic activity of PAP-1, or the concentrations of hepatic or serum triacylglycerols. Specific activities of PAP-1 in the heart were higher in the lean compared to the corpulent males. There was no significant difference for the females. Specific activities of PAP-1 were over 5-fold higher in the subcutaneous adipose tissue of the corpulent males and females compared to the lean genotypes. The differences were smaller (1.6-1.9-fold) in the gonadal adipose tissue of both sexes and in the peri-renal depot for the males. PAP-1 activity in the peri-renal depots of corpulent females was 23% lower than in lean females. PAP-2 activity was insensitive to N-ethylmaleimide and did not require Mg2+ for activity. Its activity was 1.5-2.0-fold higher in the livers and hearts of the lean male and female rats than in the corpulent genotypes. Chronic treatment with ethanol increased the activity of PAP-2 in the hearts of the corpulent males, but had no effect in the corpulent females. The specific activity of PAP-2 was higher in subcutaneous, gonadal and peri-renal adipose depots in the females and in the peri-renal depot of the corpulent males compared with the lean genotypes. Lean males had higher specific activities in all three depots compared to lean females. The tissue specificity and the sex differences in the specific activities of PAP-1 and PAP-2 are discussed in terms of their proposed functions in glycerolipid biosynthesis and signal transduction. It is proposed that a decreased activity of PAP-2 could be involved in the insulin insensitivity in the corpulent rats.

Adipose Tissue↗
PubMed1991

Cyclic nucleotides and calmodulin-phosphodiesterase activator: potential biochemical markers of salt sensitivity.

Salt sensitivity affects a fraction of hypertensive and normotensive subjects, but biochemical markers that target salt-sensitive individuals are not available at present. The aim of these studies was to establish if calmodulin-phosphodiesterase (CaM-PDE) activator (J Clin Invest 82: 276, 1988) and platelet cyclic nucleotides could serve as potential markers of salt sensitivity. The results demonstrated that CaM-PDE activator was increased in the heart of Dahl salt-sensitive rats (DS/JR) compared to Dahl salt-resistant (DR/JR) animals fed a 1% sodium diet. Normotensive male Wistar rats given a low (0.15%) or high (3.5%) sodium diet from age 7 weeks to 11 weeks presented significant increases (p less than 0.01) of three parameters: blood pressure (from 106 +/- 4 to 128 +/- 8 mmHg); platelet aggregation in response to ADP and thrombin; and CaM-PDE activator levels (from 1.57 +/- 0.14 to 2.8 +/- 0.18). Basal as well as stimulated cyclic nucleotide levels were significantly reduced in rats fed the high sodium diet. Since the degree of stimulation by the agonists was unaltered, the results are compatible with augmented PDE activity. These preliminary data suggest that CaM-PDE activator should be explored as a potential marker of salt sensitivity.

Animals↗
PubMed1990

Procaine isothiocyanate: an irreversible inhibitor of the specific binding of [3H]batrachotoxinin-A benzoate to sodium channels.

[3H]Batrachotoxinin-A benzoate ([3H]BTX-B) binds with high affinity to sites on voltage sensitive sodium channels in synaptoneurosomes from guinea pig cerebral cortex. Local anesthetics competitively antagonize the binding of [3H]BTX-B. An irreversible local anesthetic, procaine isothiocyanate (PRIT) and a tritiated derivative [( 3H]PRIT) have been prepared. PRIT inhibits the binding of [3H]BTX-B in a noncompetitive, irreversible manner (apparent Ki = 13 microM) whereas the parent compound, procaine, inhibits in a competitive, reversible manner (Ki = 40 microM). The dissociation rate of [3H]BTX-B from sites on the sodium channel is greatly accelerated in a concentration dependent manner in the presence of PRIT. A 50% increase in the dissociation rate of [3H]BTX-B is achieved in the presence of 0.98 microM PRIT. [3H]PRIT binds irreversibly to three proteins in synaptoneurosomes with apparent molecular weights of 20, 42, and 68 kDa. Protection studies with procaine and other local anesthetics suggest that only the 68 kDa species was related to local anesthetic binding.

Anesthetics, Local↗
PubMed1990

Cisplatin-resistant cells express increased levels of a factor that recognizes damaged DNA.

Cancer treatment with the drug cisplatin is often thwarted by the emergence of drug-resistant cells. To study this phenomenon, we identified two independent cellular factors that recognize cisplatin-damaged DNA. One of the two factors, designated XPE binding factor, is deficient in complementation group E of xeroderma pigmentosum, an inherited disease characterized by defective repair of DNA damaged by ultraviolet radiation, cisplatin, and other agents. Human tumor cell lines selected for resistance to cisplatin showed more efficient DNA repair and increased expression of XPE binding factor. These results suggest that XPE binding factor may be responsible, at least in part, for the development of cisplatin resistance in human tumors and that the mechanism may be increased DNA repair.

Cell Line↗
PubMed1990

Increase of calmodulin activator in hypertension. Modulation by dietary sodium and calcium.

The aim of this study was to investigate the effects of dietary calcium and sodium on blood pressure (BP) in normotensive rats (Wistar, WKY), spontaneously hypertensive rats (SHR) and Dahl rats and on calmodulin (CaM) activator, a newly-discovered hydrophobic compound that increases CaM activity in SHR and spontaneously hypertensive mice (SHM) tissues (J Clin Invest 82:276, 1988). The CaM activator was assessed by its capacity to stimulate a CaM-dependent phosphodiesterase (CaM-PDE). In Wistar rats, which were fed a high sodium diet (3.5%), BP significantly increased (P less than .01) from 106 +/- 4 to 128 +/- 8 mm Hg in parallel to an elevation of the CaM activator from 1.57 +/- 0.14 to 2.80 +/- 0.18 U. WKY, SHR, and Dahl salt-sensitive (DS/JR) and salt-resistant (DR/JR) rats were given low (0.15%) or high (2.5%) Ca diets, both with 1% sodium. In rats receiving high dietary Ca the progression of hypertension diminished and BP was lower in SHR (156 +/- 4 mm Hg) and young DS/JR rats (125 +/- 3 mm Hg) than in those receiving low dietary Ca (192 +/- 10 and 183 +/- 2 mm Hg). There was a concomitant decrease of CaM activator in these animals to levels indistinguishable from those of WKY or DR/JR rats. The activator was also found in the heart, kidneys and erythrocytes from SHM. In the presence of exogenously added CaM, lipidic extracts from the SHM heart showed augmented CaM-PDE activity relative to normotensive preparations. This difference was eliminated by trifluoperazine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Psychological consequences of spinal injury: a review of the literature.

The traumatic nature of spinal cord injury necessitates adjustments for the individual physically, socially, vocationally and sexually, as well as placing great strain on the family. Although one would suspect a high prevalence of psychological disruption following spinal cord injury, there is still much debate concerning the extent of the psychological reaction to such a trauma. This situation can partly be attributed to the lack of systematic research characteristic of most studies in this area. This paper reviews more recent literature which has investigated psychological morbidity in persons with spinal cord injury. The inadequacies of this research are discussed and suggestions for future research and psychological treatment for the spinal injured are provided.

Adaptation, Psychological↗
PubMed1990

How cells recognize damaged DNA: clues from xeroderma pigmentosum and yeast.

Xeroderma pigmentosum (XP) is characterized by the defective excision repair of DNA damaged by many agents, including ultraviolet radiation (UV) and cisplatin. We have identified a factor in human cells that recognizes multiple forms of DNA damage and is absent in XP complementation group E. Denoted XPE binding factor, it is expressed at five-fold higher levels in tumor cell lines resistant to the antitumor drug cisplatin. Finally, although it does not have photoreactivating activity, XPE binding factor shares multiple binding characteristics with yeast photolyase, suggesting that it is the human homolog of photolyase.

Cells, Cultured↗