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Biomedical subjects

W Wang

Publications and source records attributed to W Wang.

At least 667 records · Page 37Linked to original sources
PubMed1999

Development of chemosensitivity of rat medullary raphe neurons.

In many neonatal mammals, including humans and rats, there is a developmental increase in the ventilatory response to elevated pCO2. This maturation of central respiratory chemoreception may result from maturation of intrinsic chemosensitivity of brainstem neurons. We have examined age-related changes in chemosensitivity of neurons from the rat medullary raphe, a putative site for central chemoreception, using perforated patch-clamp recordings in vitro. In brain slices from rats younger than 12 days old, firing rate increased in 3% of neurons and decreased in 17% of neurons in response to respiratory acidosis (n = 36). In contrast, in slices from rats 12 days and older, firing rate increased in 18% of neurons and decreased in 15% of neurons in response to the same stimulus (n = 40). A tissue culture preparation of medullary raphe neurons was used to examine changes in chemosensitivity with age from three to 74 days in vitro. In cultured neurons younger than 12 days in vitro, firing rate increased in 4% of neurons and decreased in 44% of neurons in response to respiratory acidosis (n = 54). In contrast, in neurons 12 days in vitro and older, firing rate increased in 30% of neurons and decreased in 24% of neurons in response to respiratory acidosis (n = 105). In both types of chemosensitive neuron ("stimulated" and "inhibited"), the magnitudes of the changes in firing rate were greater in older neurons than in young neurons. These results indicate that the incidence and the degree of chemosensitivity of medullary raphe neurons increase with age in brain slices and in culture. This age-related increase in cellular chemosensitivity may underlie the development of respiratory chemoreception in vivo. Delays in this maturation process may contribute to developmental abnormalities of breathing, such as sudden infant death syndrome.

Aging↗
PubMed1999

Pimobendan inhibits the production of proinflammatory cytokines and gene expression of inducible nitric oxide synthase in a murine model of viral myocarditis.

OBJECTIVES: This study was designed to examine the effects of pimobendan in a murine model of viral myocarditis in relation to proinflammatory cytokine production and nitric oxide (NO) synthesis by inducible NO synthase (iNOS) in the heart. BACKGROUND: Pimobendan has been recently confirmed to improve both acute and chronic heart failure. Since the modulation of myocardial necrosis and contractile dysfunction by various proinflammatory cytokines may be partially mediated by the production of nitric oxide, the effects of pimobendan on the production ofproinflammatory cytokines and NO were investigated in an animal model of viral myocarditis involving heart failure. METHODS: DBA/2 mice were inoculated with the encephalomyocarditis virus. To observe its effect on survival up to 14 days, pimobendan (0.1 mg/kg or 1 mg/kg) or vehicles were given from the day of virus inoculation (day 0) orally once daily. The effects of pimobendan on histological changes, cytokine production, NO production and iNOS gene expression in the heart were studied in mice treated either with pimobendan, 1 mg/kg or with vehicles only, and sacrificed seven days after virus inoculation. RESULTS: The survival of mice improved in a dose-dependent fashion such that a significant difference (p < 0.02) was found between the higher-dose pimobendan group (20 of 30 [66.7%]) and the control group (11 of 30 [36.7%]). Histological scores for cellular infiltration (1.1+/-0.1 vs. 2.0+/-0.0, p < 0.001), intracardiac tumor necrosis factor (TNF)-alpha (18.2+/-1.8 vs. 35.8+/-4.2 pg/mg heart, p < 0.001) and interleukin (IL)-1beta (9.3 +/-1.2 vs. 26.6+/-7.1 pg/mg heart, p < 0.01) were significantly lower in the mice given pimobendan versus those of the control mice. Interleukin-6 levels (7.1+/-0.8 vs. 9.2+/-1.9 pg/mg heart) were also lower in the mice treated with pimobendan. Furthermore, intracardiac NO production was significantly (p < 0.001) less in the pimobendan group (0.165+/-0.004 nmol/mg heart) than in the control group (0.291+/-0.051 nmol/mg heart), and intracardiac iNOS gene expression in the mice given pimobendan was 74% lower than it was in the control animals (p < 0.01). CONCLUSIONS: These findings suggest that the beneficial effects of pimobendan in viral myocarditis are partially mediated by the inhibition of both proinflammatory cytokine production and NO synthesis by iNOS.

Animals↗
PubMed1999

Mevalonate prevents lovastatin-induced apoptosis in medulloblastoma cell lines.

BACKGROUND: 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) is a key rate-limiting enzyme in the mevalonate pathway, which generates precursors for cholesterol biosynthesis and the production of non-steroidal mevalonate derivatives that are involved in a number of growth-regulatory processes. We have reported that lovastatin, a competitive inhibitor of HMG-CoA reductase, not only inhibits medulloblastoma proliferation in vitro, but also induces near-complete cell death via apoptosis. The present study explores some of the pathways which may be involved in lovastatin-induced apoptosis. METHODS: Medulloblastoma cell lines were exposed in vitro to lovastatin with or without mevalonate, and document the effects using morphology, flow cytometry. DNA electrophoresis and Northern analysis. RESULTS: 1) Mevalonate prevents apoptosis when co-incubated with lovastatin, or when administered to lovastatin-pretreated cells. 2) Mevalonate restores the lovastatin-arrested cell cycle, allowing S phase entry. 3) Mevalonate does not prevent lovastatin-induced apoptosis after a critical duration of lovastatin pretreatment. For cell lines Daoy and UW228 this was 24 hours, and for D283 Med and D341 Med it was 48 hours. 4) Increases in HMG-CoA reductase mRNA levels induced by lovastatin are abrogated by co-incubation with lovastatin and mevalonate. CONCLUSIONS: These results confirm that lovastatin inhibition of this enzyme results in blockage of the mevalonate pathway, and that such a block is a critical step in the mechanism of lovastatin-induced apoptosis.

Antineoplastic Agents↗
PubMed1999

RNA binding by the novel helical domain of the influenza virus NS1 protein requires its dimer structure and a small number of specific basic amino acids.

The RNA-binding/dimerization domain of the NS1 protein of influenza A virus (73 amino acids in length) exhibits a novel dimeric six-helical fold. It is not known how this domain binds to its specific RNA targets, one of which is double-stranded RNA. To elucidate the mode of RNA binding, we introduced single alanine replacements into the NS1 RNA-binding domain at specific positions in the three-dimensional structure. Our results indicate that the dimer structure is essential for RNA binding, because any alanine replacement that causes disruption of the dimer also leads to the loss of RNA-binding activity. Surprisingly, the arginine side chain at position 38, which is in the second helix of each monomer, is the only amino-acid side chain that is absolutely required only for RNA binding and not for dimerization, indicating that this side chain probably interacts directly with the RNA target. This interaction is primarily electrostatic, because replacement of this arginine with lysine had no effect on RNA binding. A second basic amino acid, the lysine at position 41, which is also in helix 2, makes a strong contribution to the affinity of binding. We conclude that helix 2 and helix 2', which are antiparallel and next to each other in the dimer conformation, constitute the interaction face between the NS1 RNA-binding domain and its RNA targets, and that the arginine side chain at position 38 and possibly the lysine side chain at position 41 in each of these antiparallel helices contact the phosphate backbone of the RNA target.

Amino Acid Sequence↗
PubMed1999

Lovastatin-induced apoptosis of human medulloblastoma cell lines in vitro.

Medulloblastoma is a malignant paediatric central nervous system tumor with a poor prognosis, stimulating the evaluation of improved treatment strategies. Lovastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, is currently used to treat patients with hypercholesterolemia. This compound also inhibits the production of non-steroidal mevalonate derivatives that are implicated in the control of cellular proliferation, and can induce cell-cycle arrest in vitro. We recently showed that lovastatin inhibited growth and promoted apoptosis of neuroblastoma, the peripheral nervous system 'cousin' of medulloblastoma. Therefore the potential of lovastatin as a possible anticancer drug against medulloblastoma was evaluated in vitro. Four medulloblastoma cell lines, Daoy, UW228, D341 Med and D283 Med, were treated with 1-40 microM of lovastatin in vitro. Analysis of cell morphologic changes, cell viability, DNA fragmentation and flow cytometry in all four cell lines showed growth inhibition and induction of apoptosis with lovastatin treatment. As little as 10 microM of lovastatin was sufficient to cause a marked reduction in cell numbers, and more than 20 microM of lovastatin induced >90% cells to undergo apoptosis, after intervals ranging between 36 and 96 h, depending on the cell line. Lovastatin induced apoptosis in these cell lines was concomitant with cell cycle arrest in G1. The attached cell lines UW228 and Daoy were more sensitive to lovastatin than D283 Med and D341 Med. Daoy cells which survived several cycles of lovastatin treatment could still be induced to undergo apoptosis after longer treatment times. The efficient induction of apoptosis by lovastatin favours this drug as a potential new avenue of therapeutic intervention for medulloablastoma.

Apoptosis↗
PubMed1999

Coumarinic acid-based cyclic prodrugs of opioid peptides that exhibit metabolic stability to peptidases and excellent cellular permeability.

UNLABELLED: To evaluate the cellular permeation characteristics and the chemical and enzymatic stability of coumarinic acid-based cyclic prodrugs 1 and 2 of the opioid peptides [Leu5]-enkephalin (H-Tyr-Gly-Gly-Phe-Leu-OH) and DADLE (H-Tyr-D-Ala-Gly-Phe-D-Leu-OH), respectively. METHODS: The rates of conversion of the cyclic prodrugs 1 and 2 to [Leu5]-enkephalin and DADLE, respectively, in HBSS, pH 7.4 (Caco-2 cell transport buffer) and in various biological media having measurable esterase activity were determined by HPLC. The cell permeation characteristics of [Leu5]-enkephalin, DADLE and cyclic prodrugs 1 and 2 were measured using Caco-2 cell monolayers grown onto microporus membranes and monitored by HPLC. RESULTS: In HBSS, pH 7.4, cyclic prodrugs 1 and 2 degraded chemically to intermediates that further degraded to [Leu5]-enkephalin and DADLE, respectively, in stoichiometric amounts. In 90% human plasma and rat liver homogenate, the disappearance of cyclic prodrugs 1 and 2 was significantly faster than in HBSS, pH 7.4. The half-lives in 90% human plasma and in rat liver homogenate were substantially longer after pretreatment with paraoxon, a known inhibitor of serine-dependent esterases. When applied to the AP side of a Caco-2 cell monolayer, cyclic prodrug 1 exhibited significantly greater stability against peptidase metabolism than did [Leu5]-enkephalin. Cyclic prodrug 2 and DADLE exhibited similar stability when applied to the AP side of the Caco-2 cell monolayer. Prodrug 1 was 665-fold more able to permeate the Caco-2 cell monolayers than was [Leu5]-enkephalin, in part because of its increased enzymatic stability. Prodrug 2 was shown to be approximately 31 fold more able to permeate a Caco-2 cell monolayer than was DADLE. CONCLUSIONS: Cyclic prodrugs 1 and 2, prepared with the coumarinic acid promoiety, were substantially more able to permeate Caco-2 cell monolayers than were the corresponding opioid peptides. Prodrug 1 exhibited increased stability to peptidase metabolism compared to [Leu5]-enkephalin. In various biological media, the opioid peptides were released from the prodrugs by an esterase-catalyzed reaction, which is sensitive to paraoxon inhibition.

Animals↗
PubMed1999

Drosophila choline acetyltransferase temperature-sensitive mutants.

We used the reverse transcription-polymerase chain reaction (RT-PCR) to amplify choline acetyltransferase (ChAT) mRNA fragments from two temperature-sensitive alleles of Drosophila melanogaster, Cha(ts1) and Cha(ts2). Single base substitutions in the mutants (T1614A in Cha(ts1) and G1596A in Cha(ts2)) would result in amino acid changes for ChAT protein (Met403Lys in Ch(ts1) and Arg397His in Cha(ts2)). These base substitutions were confirmed in mRNA extracted from homozygous mutants using a Single Nucleotide Primer Extension assay (SNuPE) and are sufficient to produce thermolabile enzyme. Our results indicate that these temperature-sensitive mutants are point mutations in the structural gene for ChAT. Using a quantitative SNuPE assay we also show that similar levels of Cha(ts) and wild type transcripts are present in heterozygous flies (Cha(ts1)/+ and Cha(Ts2)/+) at both restrictive and permissive temperatures. This contrasts with RNase protection assays of ChAT mRNA in homozygous mutant animals where the levels of mutant mRNA decrease at restrictive temperature.

Alleles↗
PubMed1999

Synthesis and evaluation of the physicochemical properties of esterase-sensitive cyclic prodrugs of opioid peptides using coumarinic acid and phenylpropionic acid linkers.

In an attempt to improve the membrane permeabilities of opioid peptides, we have synthesized cyclic prodrugs of [Leu5]-enkephalin and DADLE using a coumarinic acid or a phenylpropionic acid linker. The synthesis of the coumarinic acid- and phenylpropionic acid-based cyclic prodrugs followed similar strategies. Key intermediates were the compounds with the C-terminal amino acids of opioid peptides (L-Leu, [Leu5]-enkephalin; D-Leu, DADLE) attached to the phenol hydroxyl group and the remaining amino acids of the peptide linked via the N-terminal amino acid (L-Tyr) attached to the carboxylic acid groups of the prodrug moieties (coumarinic acid or propionic acid). Cyclization of these linear precursors gave the cyclic prodrugs in 30-50% yields. These cyclic prodrugs exhibited excellent transcellular permeation characteristics across Caco-2 cell monolayers, an in vitro model of the intestinal mucosa. To correlate the cellular permeabilities of these cyclic prodrugs with their physicochemical properties, we calculated their Stokes-Einstein molecular radii from their diffusion coefficients which were determined by NMR and we determined their membrane interaction potentials using immobilized artificial membrane (IAM) column chromatography. The cyclic prodrugs exhibited molecular radii similar to those of the parent compounds, [Leu5]-enkephalin and DADLE. However, these cyclic prodrugs were shown to have much higher membrane interaction potentials than their corresponding opioid peptides. Therefore, the enhanced cellular permeation of the cyclic prodrugs is apparently due to the alteration of their lipophilicity and hydrogen bonding potential, but not their molecular sizes.

Amino Acid Sequence↗
PubMed1999

A computational approach to simplifying the protein folding alphabet.

What is the minimal number of residue types required to form a structured protein? This question is important for understanding protein modeling and design. Recently, an experimental finding by Baker and coworkers suggested a five-residue solution to this problem. We were motivated by their results and by the arguments of Wolynes to study reductions of protein representation based on the concept of mismatch between a reduced interaction matrix and the Miyazawa and Jernigan (MJ) matrix. We find several possible simplified schemes from the relationship of minimized mismatch versus the number of residue types (N = approximately 2-20). As a specific case, an optimal reduction with five types of residues has the same form as the simplified palette of Baker and coworkers. Statistical and kinetic features of a number of sequences are tested. Comparison of results from sequences with 20 residue types and their reduced representations indicates that the reduction by mismatch minimization is successful. For example, sequences with five types of residues have good folding ability and kinetic accessibility in model studies.

Algorithms↗
PubMed1999

Epstein-Barr virus expression in Hodgkin's disease in relation to patient characteristics, serum factors and blood lymphocyte function.

Epstein-Barr virus (EBV) expression was investigated by immunohistochemistry (latent membrane protein 1 [LMP-1]) and in situ hybridization (EBV encoded RNA [EBER]) in biopsies from 95 patients with untreated Hodgkin's disease (HD). Tumour EBV status was related to EBV antibody titres, spontaneous and concanavalin A induced blood lymphocyte DNA synthesis, serum levels of soluble (s) CD4, sCD8, sCD25, sCD30, sCD54, beta2-microglobulin, thymidine-kinase, routine chemistry, patient characteristics, complete remission and survival. The median follow-up time was 145 months (range 60-257). Tumour EBV-positive (n = 30; 33%) and negative (n = 62; 67%) patients did not differ with regard to sex, age, stage, presence of bulky disease or B-symptoms, remission rate or survival. The proportion of EBV+ cases was significantly higher among patients with mixed cellularity histopathology (58%) as compared to the nodular sclerosis subtype (18%; P < 0.001). The total white blood cell (WBC) counts were significantly lower in EBV+ patients (P < 0.01), who also had significantly higher levels of sCD54 (P < 0.02) and a tendency towards lower levels of sCD30 (P = 0.056). Patients in the tumour EBV+ group had significantly higher IgG antibody titres to restricted early antigen (EA-R) (P < 0.02). Hence, clinical features and outcome were not related to tumour EBV status. However, HD patients with EBV+ tumours had elevated sCD54 levels, higher antibody titres to EA-R and decreased total WBC counts. A potential causal relationship between EBV tumour status and these findings needs to be further explored.

Adult↗
PubMed1999

Evidence for involvement of polymorphic CYP2C19 and 2C9 in the N-demethylation of sertraline in human liver microsomes.

AIMS: The present study was designed to define the kinetic behaviour of sertraline N-demethylation in human liver microsomes and to identify the isoforms of cytochrome P450 involved in this metabolic pathway. METHODS: The kinetics of the formation of N-demethylsertraline were determined in human liver microsomes from six genotyped CYP2C19 extensive (EM) and three poor metabolisers (PM). Selective inhibitors of and specific monoclonal antibodies to various cytochrome P450 isoforms were also employed. RESULTS: The kinetics of N-demethylsertraline formation in all EM liver microsomes were fitted by a two-enzyme Michaelis-Menten equation, whereas the kinetics in all PM liver microsomes were best described by a single-enzyme Michaelis-Menten equation similar to the low-affinity component found in EM microsomes. Mean apparent Km values for the high-and low-affinity components were 1.9 and 88 microm and V max values were 33 and 554 pmol min-1 mg-1 protein, respectively, in the EM liver microsomes. Omeprazole (a CYP2C19 substrate) at high concentrations and sulphaphenazole (a selective inhibitor of CYP2C9) substantially inhibited N-demethylsertraline formation. Of five monoclonal antibodies to various cytochrome P450 forms tested, only anti-CYP2C8/9/19 had any inhibitory effect on this reaction. The inhibition of sertraline N-demethylation by anti-CYP2C8/9/19 was greater in EM livers than in PM livers at both low and high substrate concentrations. However, anti-CYP2C8/9/19 did not abolish the formation of N-demethylsertraline in the microsomes from any of the livers. CONCLUSIONS: The polymorphic enzyme CYP2C19 catalyses the high-affinity N-demethylation of sertraline, while CYP2C9 is one of the low-affinity components of this metabolic pathway.

Antibodies, Monoclonal↗
PubMed1999

Parathyroid hormone is not a key hormone in the rapid minute-to-minute regulation of plasma Ca2+ homeostasis in rats.

BACKGROUND: The role of parathyroid hormone (PTH) in the rapid minute-to-minute regulation of plasma Ca2+ (p-Ca2+) was studied in vivo in rats. MATERIALS AND METHODS: The rapid calcaemic response to exogenous rat PTH1-34 (16 microg) was examined in normal rats, and the long-term calcaemic response was examined in parathyroidectomized (PTX) rats receiving PTH1-34 for 24 h at 0.2, 0. 4 and 0.8 microg h-1. Acute hypocalcaemia was induced by EGTA for 30 min, and then the rapid recovery of p-Ca2+ was studied for 130 min in normal rats, 24 h after PTX and in PTX rats infused with exogenous rat PTH1-34. The dynamics of the rapid recovery of p-Ca2+ was studied at two additional doses of EGTA. RESULTS: No rapid calcaemic response was observed in the first 60 min after administration of PTH and no hypocalcaemia was seen for 2 h after acute PTX. This slow effect of PTH suggests that PTH might not be responsible for maintaining the stable p-Ca2+ on a rapid minute-to-minute basis. EGTA induced acute hypocalcaemia in both normal and PTX rats (P < 0.01). In both groups a rapid and similar increase in p-Ca2+ took place 10 min after discontinuing EGTA (P < 0. 05). Within 60 min, p-Ca2+ increased further, independently of the presence of PTH. Infusion of PTH to PTX rats did not affect the rapid recovery of p-Ca2+ (P < 0.05) from EGTA induced hypocalcaemia. CONCLUSION: PTH is not a key hormone in the rapid recovery of p-Ca2+ after induction of hypocalcaemia, but might, however, set the long-term levels of p-Ca2+ maintained by mammalian organisms. The involvement of an as yet unknown factor in the rapid regulation of p-Ca2+ is suggested.

Animals↗
PubMed1999

The effect of Glu75 of staphylococcal nuclease on enzyme activity, protein stability and protein unfolding.

Staphylococcal nuclease mutants, E57G and E75G, were generated. A comparison of the kinetic parameters both for mutants and wild-type protein shows that the Michaelis constants (Km) were almost identical for the wild-type protein and E57G mutant. An approximately 30-fold decrease in Km compared with the wild-type protein was observed for the E75G mutant. The turnover numbers for the enzyme (kcat) were higher with both the wild-type protein and the E57G mutant (3.88 +/- 0.21 x 103 s-1 and 3.71 +/- 0.28 x 103 s-1) than with the E75G mutant (3.04 +/- 0.02 x 102 s-1). The results of thermal denaturation with differential scanning microcalorimetry indicate that the excess calorimetric enthalpy of denaturations, DeltaHcal, was almost identical for the wild-type protein and E57G mutant (84.1 +/- 6.2 kcal.mol-1 and 79.3 +/- 7.1 kcal.mol-1, respectively). An approximately twofold decrease in DeltaHcal compared with the wild-type protein was observed for the E75G mutant (42.7 +/- 5.5 kcal.mol-1). These outcomes imply that Glu at position 75 plays a significant role in maintaining enzyme activity and protein stability. Further study of the unfolding of the wild-type protein and E75G mutant was conducted by using time-resolved fluorescence with a picosecond laser pulse. Two fluorescent lifetimes were found in the subnanosecond time range. The faster lifetime (tau2) did not generally vary with either pH or the concentration of guanidinium hydrochloride (GdmHCl) in the wild-type protein and the E75G mutant. The slow lifetime (tau1), however, did vary with these parameters and was faster as the protein is unfolded by either pH or GdmHCl denaturation. The midpoints of the transition for tau1 are pH 3.5 and 5.8 for the wild-type protein and E75G mutant, respectively, and the GdmHCl concentrations are 1.1 m and 0.6 m for the wild-type protein and E75G mutant, respectively. Parallel steady-state fluorescence measurements have also been carried out and the results are in general agreement with the time-resolved fluorescence experiments, indicating that Glu at position 75 plays an important role in protein unfolding.

Calorimetry, Differential Scanning↗
PubMed1999

Personality and response to repeated visual stimulation in migraine and tension-type headaches.

Migraine sufferers potentiate their visual evoked potentials (VEPs) from a short period of 2 min to a longer period of 15 min. As a lack of habituation is linked to higher level arousal, we thus hypothesized that short-term VEP potentiation might be correlated with an arousal-related personality trait. We therefore carried out short-term VEPs, Plutchik-van Praag's Depression Inventory, Zuckerman's Sensation-Seeking Scales (Form V), and Zuckerman-Kuhlman's Personality Questionnaire in 26 healthy subjects, 22 patients suffering from migraine without aura between attacks, 13 episodic and 20 chronic tension-type headaches. The chronic tension-type headache sufferers showed increased depression compared with other groups, which might be a consequence of the headache itself. Migraines, however, showed steeper habituation slopes of N1-P1 and P1-N2, decreased thrill and adventure-seeking, and general sensation-seeking than healthy controls; in addition, the habituation slope of P1-N2 was positively correlated with experience-seeking in migraine. The short-term VEP potentiation and the decreased thrill and adventure-seeking and general sensation-seeking in migraine might be related to a high level of cortical arousal and a low 5HT neurotransmission. In compliance with the long-term VEP study, the positive correlation between the P1-N2 habituation slope and experience-seeking in migraine suggests a continuous metabolic overload for the brain interictally, which can trigger the activation of a migraine attack.

Adult↗
PubMed1999

Modulation of Ca2+ channel-gated Ca2+ release by W-7 in cardiac myocytes.

Cardiac muscle excitation-contraction coupling is controlled by the Ca(2+)-induced Ca2+ release mechanism. The present study examines the effects of a calmodulin antagonist W-7 on Ca2+ current (ICa)-induced Ca2+ release in whole cell-clamped rat ventricular myocytes. Exposure of cells to W-7 suppressed ICa, but the intracellular Ca(2+)-transients showed a lesser degree of reduction, suggesting possible enhancement of Ca(2+)-induced Ca2+ release. The effects of W-7 on the efficacy of Ca2+ release were most prominent at negative potentials. At test potentials of -30 mV, 20 microM W-7 almost completely blocked ICa, but significant Ca(2+)-transients remained, thus causing a four to six-fold increase in the efficacy of Ca(2+)-induced Ca2+ release. The depolarization-dependent Ca(2+)-transients were eliminated in absence of extracellular Ca2+, blocked by Cd2+, and were absent when the sarcoplasmic reticulum was depleted of Ca2+, implicating dependency on Ca(2+)-signaling between the L-type channel and the ryanodine receptor. W-7 mediated increase in the efficacy of Ca(2+)-induced Ca2+ release was eliminated when myocytes were dialyzed with the internal solution containing gluathione (5 mM), suggesting the possible role of cellular redox state in the regulation of Ca2+ release by the calmodulin antagonist.

Animals↗
PubMed1999

Porous balloon delivery of S-dC28 does not prevent restenosis in the porcine coronary artery model of balloon injury.

Phosphorothioate (PS) oligodeoxynucleotides (ODN) inhibit vascular smooth muscle cell proliferation through antisense and G-quartet aptameric mechanisms. PS-ODN such as the cytidine homopolymers, have been demonstrated to have non-G-quartet, nonsequence-specific inhibitory effects in a rat carotid balloon injury model of neointimal proliferation. We sought to test the efficacy of S-dC28, a cytidine homopolymer lacking G-quartets, on neointimal proliferation in the porcine coronary artery model of balloon injury. A total of 23 animals (11 controls, 12 treated) were subjected to balloon injury in a coronary artery, followed by infusion of control solution or S-dC28 via porous balloon, the Scimed Dispatch Coronary Infusion Catheter. After a mean interval of 49 days, the animals were killed, and the target coronary segments were examined histologically. S-dC28 did not significantly inhibit neointimal formation. Fluorescein isothiocyanate (FITC)-labeled S-dC28 was present in the intima and media immediately after administration but was present mainly within the adventitia 3 hours after administration. S-dC28, when delivered by a Scimed Dispatch Coronary Infusion Catheter (Maple Grove, MN), did not significantly affect neointimal proliferation after balloon injury in a porcine coronary artery model.

Angioplasty, Balloon, Coronary↗
PubMed1999

Hydration of fat-free body mass: review and critique of a classic body-composition constant.

The assumed "constancy" of fat-free body mass hydration is a cornerstone in the body-composition research field. Hydration, the observed ratio of total body water to fat-free body mass, is stable at approximately 0.73 in mammals and this constancy provides a means of estimating total body fat in vivo. This review examines both in vitro and in vivo data that support the hydration constancy hypothesis and provides a critique of applied methodology. Biological topics of interest are then examined and critical areas in need of future research are identified. These are important issues because water dilution is the only method currently available for estimating body fat in all mammals, which range in body mass by a factor of 10(4).

Absorptiometry, Photon↗