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Biomedical subjects

J Simon

Publications and source records attributed to J Simon.

At least 253 records · Page 14Linked to original sources
PubMed1996

Divergent selection for high or low growth rate modifies the response of muscle cells to serum or insulin-like growth factor-I in vitro.

Genetic differences in growth potential could result from changes in the levels of growth stimulatory factors or in the response of target tissues. The latter possibility was tested in adult myoblasts prepared from chickens selected for high (HG) or low growth rate (LG). Stimulation of [3H]-thymidine incorporation into DNA by serum was of higher amplitude in HG than LG muscle cells irrespective of whether the cell preparations were enriched in myoblasts or fibroblasts. HG myoblasts were also more responsive to insulin-like growth factor-I (IGF-I) in terms of [3H]-thymidine incorporation. IGF analogues with a reduced affinity for IGF binding proteins gave similar results suggesting that activity of binding proteins could not explain the difference between cells from the HG and LG lines. This difference was restricted to the proliferative stage because in myotubes, basal or IGF-I stimulated glucose and amino acid transports, tyrosine incorporation and protein degradation were not different.

Aging↗
PubMed1995

Characterisation of a recombinant P2Y purinoceptor.

We have previously cloned a cDNA encoding a G-protein-coupled P2 purinoceptor from chick brain and designated this as a P2Y1 purinoceptor (Webb, T.E., J. Simon, B.J. Krishek, A.N. Bateson, T.G. Smart, B.J. King, G. Bumstock and E.A. Barnard, 1993, FEBS Lett. 324, 219). Here, we describe the further characterisation of this recombinant receptor expressed in both simian kidney endothelial (COS-7) cells and Xenopus oocytes. In transfected COS-7 cell membranes, the recombinant receptor showed a high level of expression (Bmax = 7.9 +/- 2.2. pmol [35S]dATP alpha S bound/mg protein) and affinity (Kd = 6.6 +/- 0.3 nM). In these COS-7 cells, the activation of the implanted purinoceptor induced a suramin-sensitive formation of inositol 1,4,5-triphosphatic (1,4,5InsP3). Upon expression in Xenopus oocytes, ATP was the only natural nucleoside triphosphate to elicit a Ca(2+)-activated chloride current. The P2 purinoceptor antagonists suramin and Reactive Blue-2 were both able to inhibit this evoked current. Utilizing both expression systems, the binding affinity profile and the functional pharmacological profile of the agonists, the common series found was: 2-methylthioATP (2-MeSATP) > or = ATP > ADP beta S > ADP. These two agonist series and the lack of activity of adenosine, alpha, beta-methyleneATP (alpha, beta-meATP), 3'-O-(4-benzoyl) benzoyl-ATP (Bz-ATP) and UTP, together confirmed that this receptor is a specific subtype of the P2Y purinoceptors.

Adenosine↗
PubMed1995

[Effect of recombinant human erythropoietin on autologous blood donation for heart surgery].

Pharmacological stimulation of erythropoiesis was studied in patients selected for open heart surgery, and undergoing a programme of autologous blood predonation prior to surgery. Sixteen patients (group I: ery) received 4000 I. U. of recombinant human erythropoietin (r-huepo) subcutaneously weekly three times during a 3-week period preoperatively, another group of 21 patients (group II: control) were not given r-huepo. Patients in both groups received orally 2 x 80 mg iron daily. Predonation of five units of blood was planned in each patients, beginning on the 21. preoperative day; no blood was taken from patients if the hematocrit dropped below 0.34, or if any other complications occurred. The average amount of blood taken from patients in the ery group was 4.8 +/- 0.4 Units, and in the control group: 3.7 +/- 1.1 Units. In the ery group the planned 5 Units of blood could be taken from 13/16 patients, while in the controls only from 7/21. The differences are statistically significant. Reticulocyte counts were significantly higher consecutively during the preoperative period in the ery group than in the controls. In the postoperative period erythropoiesis was less pronounced in the ery group than in the controls. It is concluded that 1. r-huepo is an effective drug in preventing (or reducing) the anaemia due to repeated preoperative blood withdrawals, and thus larger amounts of autologous blood will be available for predonation. 2. More pronounced decrease of circulating reticulocytes observed in the postoperative period points to a possible suppression of endogenous erythropoietin production in the ery group.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Loss, Surgical↗
PubMed1995

Biotherapy for xenografted human central nervous system leukemia in mice with severe combined immunodeficiency using B43 (anti-CD19)-pokeweed antiviral protein immunotoxin.

The study of central nervous system (CNS) leukemia has been hampered by the lack of a suitable animal model. We report that severe combined immunodeficiency (SCID) mice invariably develop rapidly progressive fatal CNS leukemia within 3 weeks after intravenous injection of NALM-6 pre-B acute lymphoblastic leukemia (ALL) cells. Colonization of the dura mater and subarachnoid space, usually of the distal spinal cord with occasional extension into the Virchow-Robin spaces of blood vessels subjacent to the meninges, followed involvement of bone marrow in the skull, vertebrae, and, occasionally, the appendicular skeleton. Occult CNS leukemia was detectable by polymerase chain reaction amplification of human DNA as early as 8 days postinoculation of leukemia cells. We used this in vivo model of human CNS leukemia to examine the therapeutic efficacy and toxicity of intrathecally administered B43 (anti-CD19)-pokeweed antiviral protein (PAP), an anti-B-lineage ALL immunotoxin directed against the pan-B-cell antigen CD19/Bp95. Intrathecal therapy with B43 (anti-CD19)-PAP immunotoxin at nontoxic dose levels significantly improved survival of SCID mice and was superior to intrathecal methotrexate therapy.

Animals↗
PubMed1995

Properties of the menaquinol oxidase (Qox) and of qox deletion mutants of Bacillus subtilis.

Menaquinol oxidase isolated from the membrane of Bacillus subtilis W23 was found to consist of four polypeptides (QoxA, B, C, and D) that were predicted by the sequence of the qox operon of B. subtilis 168 (Santana et al. 1992). The preparation contained 7 mol cytochrome aa3 per g protein, which corresponds to 2 mol heme A per mol enzyme of 144 kDa molecular mass. Respiration with dimethylnaphthoquinol catalyzed by the enzyme was ten times faster than that with menadiol. Activities with more electropositive quinols were negligible. The activity of the enzyme was inhibited by equimolar amounts of HQNO, while antimycin, myxothiazol, and stigmatellin were more than tenfold less effective. When cells of both strains of B. subtilis (W23 and 168) were grown with glucose, quinol respiration was an order of magnitude more active than respiration with N,N,N',N'-tetramethyl-1,4-phenylenediamine plus ascorbate. Surprisingly, the same result was obtained with mutant strains lacking qoxB. As cytochromes a and d were virtually absent, a second quinol oxidase, possibly of the cytochrome o-type, was apparently formed by the mutants.

Amino Acid Sequence↗
PubMed1995

MEG based brain laterality: sex differences in normal adults.

Magnetoencephalographic (MEG) auditory evoked fields produced by short tone pips were recorded from 34 normal adults (17 males, 17 females) and the 100 msec latency component (M100) localized in left and right hemispheres. Absolute M100 location in the antero-posterior dimension was calculated for each subject. M100 sources were significantly further anterior in the right hemisphere of males. Magnetic resonance (MR) based anatomy of the superior temporal gyri (STG) in a subset of 17 subjects showed that in the left STG of both males and females M100 sources were located approximately midway on the STG. In the right hemisphere of males, however, M100 sources were significantly further anterior on the STG than was the case for females. The findings are compatible with a sex based difference in right STG functional anatomy, with evidence of greater hemispheric lateralization in males compared to females based upon a predominantly right hemisphere contribution.

Adult↗
PubMed1995

The extra sex combs product contains WD40 repeats and its time of action implies a role distinct from other Polycomb group products.

The extra sex combs (esc) gene product is a transcriptional repressor of homeotic genes. Although it is classified in the Polycomb group (PcG) on the basis of phenotypic criteria, it is distinct from most other PcG repressors in its time of action during development. We describe the temporal profile of esc mRNA expression during embryogenesis and the stage-specific rescue of esc mutants with a heat shock-inducible esc cDNA transformation construct. Both experiments support the idea that esc product plays an early, transient role in repression of homeotic genes. We also present the sequence of a full-length esc cDNA. The predicted esc protein is composed primarily of multiple copies of a repeat motif, termed the WD40 repeat, which are likely used in protein-protein contact. We provide evidence that individual copies of the esc WD40 repeats are needed for function in vivo. We suggest that esc protein is an adaptor that binds to multiple protein partners and assists in the assembly or targeting of other PcG proteins.

Amino Acid Sequence↗
PubMed1995

Effect of glibenclamide on the metabolism of fatty acids in cultures of newborn rat heart cells under normoxic and hypoxic conditions.

Several deleterious biochemical alterations have been observed in myocardial cells during ischemia, including perturbations of transmembrane ion equilibria, production of noxious oxygen-derived radicals and loss of membrane phospholipids. Although the precise relationship between these alterations and the reduction of oxygen and glucose supplies is not fully understood, the decrease of intracellular ATP content appears to be a key event in the cascade. Recent evidence suggests that opening of ATP-sensitive K+ channels may constitute an endogenous protective mechanism during ischemia. We have thus tested the effects of glibenclamide, a channel blocker, and aprikalim, a channel opener, on the metabolism of membrane fatty acids in cultures of newborn rat heart cells under normoxic and hypoxic conditions. We showed that glibenclamide partially blocks the loss of membrane phospholipids induced by oxygen deprivation in contractile myocytes, whereas aprikalim fails to alter this metabolism under either normoxic or ischemic conditions. In cultures of fibroblast-like heart cells neither drug was able to modify fatty acid metabolism.

Adenosine Triphosphate↗
PubMed1995

Locking in stable states of gene expression: transcriptional control during Drosophila development.

Cell fate decisions can be maintained during long periods of developmental time by stable states of gene expression. The Polycomb group and trithorax group proteins of Drosophila are key transcriptional regulators that maintain stable expression states during development. Recent advances in knowledge about individual Polycomb group and trithorax group proteins, their mechanisms of action, and potential homologs in mice and humans are contributing to a greater understanding of their roles in gene expression and development.

Animals↗
PubMed1995

The mechanism of blood pressure variability. Study in patients with fixed ventricular pacemaker rhythm.

BACKGROUND: Several studies have shown that heart rate variability plays an anti-oscillatory role in the regulation of blood pressure variability in humans. We tested whether systolic blood pressure variability in patients with a fixed ventricular pacemaker rhythm differs from that in patients with sinus rhythm. METHODS AND RESULTS: In 18 patients with a fixed ventricular pacemaker rhythm and in ten age-matched patients with sinus rhythm the systolic blood pressure oscillation and the low and high-frequency spectral components of systolic blood pressure were studied in the resting supine position during spontaneous breathing and during forced deep ventilation of 6 cycles.min-1. Patients with a pacemaker had a higher amplitude of systolic blood pressure oscillation than control subjects during spontaneous breathing (13.5 +/- 2.0 mmHg vs 6.4 +/- 1.6 mmHg, P = 0.035), and a slight but not significant difference also persisted during forced deep ventilation 19.0 +/- 2.3 mmHg vs 15.0 +/- 2.3 mmHg, P = 0.18). The increment in systolic blood pressure fluctuation from spontaneous breathing to forced deep ventilation was less marked in the pacemaker group than in the control subjects (40% vs 130%, P = 0.43). Although all the systolic blood pressure spectral components of the pacemaker patients were higher during both spontaneous breathing and forced deep ventilation, the differences between the two groups did not reach statistical significance. CONCLUSIONS: Our observations in patients with a fixed ventricular pacemaker rhythm suggest that the mechanical effects on the intrathoracic vessels and the consecutive stroke volume changes are responsible for respiration-related systolic blood pressure oscillation and reflex systolic blood pressure changes.

Aged↗
PubMed1995

Characterization of a P2Y purinoceptor in the brain.

Little has been known of the abundance in the brain of any of the G protein coupled P2 purinoceptors nor their pharmacology. Here we show that [35S]dATP alpha S is a suitable radioligand for investigating these receptors and hence that they are exceptionally abundant both in one-day-old chick (Bmax: 37 pmol agonist sites/mg protein) and adult rat brain membranes (Bmax: 39 pmol/mg protein). [35S]dATP alpha S (which is selective for P2Y over the P2X types of purinoceptor) binds with high affinity to these sites in the chick (Kd: 13.3 nM) and in the rat brain membranes (Kd: 9.1 nM). The rank order of potency of purinoceptor-active agonists and antagonists displacing [35S]dATP alpha S binding is: dATP alpha S > (3'-deoxyATP, 2-methylthioATP, ATP alpha S, ATP) > 2'-deoxyATP > 2-methylthioADP > ADP >> suramin, Reactive Blue-2 >> UTP, L-beta,gamma-methyleneATP, adenosine; this defines these binding sites as P2Y subtypes of the P2 purinoceptors. This pharmacological profile of purinergic ligands is in excellent agreement with the potency order established for the recombinant P2Y1 purinoceptor from chick brain, identifying the great majority of the brain P2 purinoceptors as identical or very similar to the native P2Y1 receptor.

Animals↗
PubMed1995

Biological activity of immunoreactive insulin-like activity extracted from rat submandibular gland.

Earlier studies indicate the presence of an insulin-like immunoreactivity (ILI) in rat submandibular salivary glands (SSG). Previous observations also showed that streptozotocin (STZ)-induced diabetes was accompanied by an increase in SSG ILI concentrations. In the present work we studied the effect of SSG ILI from normal and STZ diabetic rats (ILI-N and ILI-D, respectively) on insulin receptor binding and function in LMH cell line. ILI-N and ILI-D inhibited 125I-insulin binding to intact cells and wheat germ agglutinin (WGA)-purified insulin receptors with a high affinity. Furthermore, ILI-N and ILI-D activated, although weakly, the beta-subunit autophosphorylation of solubilized and WGA-purified insulin receptors. An ATP hydrolytic activity was present in ILI-N and, to a greater extent, in ILI-D extracts, which can at least in part explain their low potency for activating autophosphorylation and kinase activity of insulin receptors in vitro. However, after ILI treatment of intact cells and immunoprecipitation of insulin receptors, ILI induced a dose-dependent tyrosine phosphorylation of the insulin receptor beta-subunit. Finally, ILI-N and ILI-D stimulated amino acid uptake and lipogenesis in LMH cells. These findings suggest that SSG ILI is biologically active and can participate in metabolic regulations.

Amino Acids↗
PubMed1995

Identification of vasopressin mRNA in rat aorta.

We have reported previously that several blood vessels of the rat and cow contain immunoreactive vasopressin and further suggested that this peptide might be produced locally. To provide additional support for this hypothesis, we conducted the present study to determine whether mRNA for arginine vasopressin is also present in blood vessels. Ribonuclease protection analysis of total RNA isolated from rat hypothalamus and aorta revealed the presence of arginine vasopressin message in both tissues but not in RNA isolated from liver, a tissue devoid of vasopressin. Subsequent comparison of the autoradiographic intensities of the signals in these two tissues indicated that vasopressin message was 100- to 1000-fold lower in aorta. Additional studies showed that RNA isolated from endothelium-denuded vessels contained levels of arginine vasopressin message similar to those in intact vessels, indicating that endothelium was not a major source of this message. These data were substantiated by further studies using a vasopressin radioimmunoassay, which showed that vasopressin peptide levels in intact and endothelium-denuded vessels did not differ. Thus, the present study showed that rat aorta contains arginine vasopressin mRNA as well as the vasopressin peptide and that both the message and the peptide are contained in nonendothelial structures. However, the data do not rule out endothelium as a possible source of vasopressin. These studies add further support to the hypothesis that blood vessels are capable of producing vasopressin.

Animals↗
PubMed1995

Discrete Polycomb-binding sites in each parasegmental domain of the bithorax complex.

The Polycomb protein of Drosophila melanogaster maintains the segmental expression limits of the homeotic genes in the bithorax complex. Polycomb-binding sites within the bithorax complex were mapped by immunostaining of salivary gland polytene chromosomes. Polycomb bound to four DNA fragments, one in each of four successive parasegmental regulatory regions. These fragments correspond exactly to the ones that can maintain segmentally limited expression of a lacZ reporter gene. Thus, Polycomb acts directly on discrete multiple sites in bithorax regulatory DNA. Constructs combining fragments from different regulatory regions demonstrate that Polycomb-dependent maintenance elements can act on multiple pattern initiation elements, and that maintenance elements can work together. The cooperative action of maintenance elements may motivate the linear order of the bithorax complex.

Animals↗