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Biomedical subjects

B Cheng

Publications and source records attributed to B Cheng.

At least 127 records · Page 7Linked to original sources
PubMed1992

A new approach for the determination of ventilatory and lactate thresholds.

In order to determine the ventilatory threshold (VT) and the lactate threshold (LT) in a reliable way, a new method is proposed and compared with conventional methods. The new method consists of calculating the point that yields the maximal distance from a curve representing ventilatory and metabolic variables as a function of oxygen uptake (VO2) to the line formed by the two end points of the curve (Dmax method). Male cyclists (n = 8) performed two incremental exercise tests a week apart. Ventilatory/metabolic variables were measured and blood was sampled for later lactate measurement during each workload and immediately after exercise. No statistical differences were observed in the threshold values (expressed as absolute oxygen uptake; VO2) determined by the Dmax method and the conventional linear regression method (according to O2 equivalent; EqO2) and venous blood at the onset of blood lactate (OBLA), while VT assessed with the conventional linear method (according to the slope of CO2 output; Vslope) yielded significantly lower threshold values. Similar results were obtained from the reproducibility test. Thus, the Dmax method appears to be an objective and reliable method for threshold determination, which can be applied to various ventilatory or metabolic variables yet yield similar results. The results also showed that breathing frequency can be used to determine VT.

Adolescent↗
PubMed1992

pH regulation in adult rat carotid body glomus cells. Importance of extracellular pH, sodium, and potassium.

The course of intracellular pH (pHi) was followed in superfused (36 degrees C) single glomus (type I) cells of the freshly dissociated adult rat carotid body. The cells had been loaded with the pH-sensitive fluorescent dye 2',7'-(2-carboxyethyl)-5 (and -6)-carboxyfluorescein. The high K(+)-nigericin method was used for calibration. The pHi of the glomus cell at pHo 7.40, without CO2, was 7.23 +/- 0.02 (n = 70); in 5% CO2/25 mM HCO3-, pHi was 7.18 +/- 0.08 (n = 9). The pHi was very sensitive to changes in pHo. Without CO2, delta pHi/delta pHo was 0.85 (pHo 6.20-8.00; 32 cells), while in CO2/HCO3- this ratio was 0.82 irrespective of whether pHo (6.80-7.40; 14 cells) was changed at constant PCO2 or at constant [HCO3-]o. The great pHi sensitivity of the glomus cell to pHo is matched only by that of the human red cell. An active Na+/H+ exchanger (apparent Km = 58 +/- 6 mM) is present in glomus cells: Na+ removal or addition of the amiloride derivative 5-(N,N-hexamethylene)-amiloride induced pHi to fall by as much as 0.9. The membrane of these cells also contains a K+/H+ exchanger. Raising [K+]o from 4.7 to 25, 50, or 140 mM reversibly raised pHi by 0.2, 0.3, and 0.6, respectively. Rb+ had no effect, but in corresponding concentrations of Tl+ alkalinization was much faster than in K+. Reducing [K+]o to 1.5 mM lowered pHi by 0.1. These pHi changes were shown not to be due to changes in membrane voltage, and were even more striking in the absence of Na+. Intrinsic buffering power (amount of strong base required to produce, in the nominal absence of CO2, a small pHi rise) increased from 3 to approximately 21 mM as pHi was lowered, but remained nearly unchanged below pHi 6.60. The fitted expression assumed the presence of one "equivalent" intracellular buffer (pK 6.41, 41 mM). The exceptional pHi sensitivity to pHo suggests that the pHi of the glomus cell is a link in the chemoreceptor's response to external acidity.

Acid-Base Equilibrium↗
PubMed1992

IGF-I and IGF-II protect cultured hippocampal and septal neurons against calcium-mediated hypoglycemic damage.

Insulin and insulin-like growth factors I and II (IGF-I and IGF-II) have recently been shown to have biological activity in central neurons, but their normal functions and mechanisms of action in the brain are unknown. Since central neurons are particularly vulnerable to hypoglycemia that results from ischemia or other insults, we tested the hypothesis that growth factors can protect central neurons against hypoglycemic damage in vitro. IGF-I and IGF-II (3-100 ng/ml) each prevented glucose deprivation-induced neuronal damage in a dose-dependent manner in rat hippocampal and septal cell cultures. High concentrations of insulin (greater than 1 microgram/ml) also protected neurons against hypoglycemic damage. Epidermal growth factor did not protect against hypoglycemic damage. Both IGFs and insulin were effective when administered 24 hr before or immediately following the onset of glucose deprivation. Direct measurements of intraneuronal calcium levels and manipulations of calcium influx demonstrated that calcium influx and sustained elevations in intraneuronal calcium levels mediated the hypoglycemic damage. IGF-I and IGF-II each prevented the hypoglycemia-induced elevations of intraneuronal free calcium. Studies with excitatory amino acid receptor antagonists and calcium channel blockers indicated that NMDA receptors did, and L-type calcium channels did not, play a major role in hypoglycemic damage. Taken together, these findings indicate that IGFs can stabilize neuronal calcium homeostasis and thereby protect against hypoglycemic damage.

Animals↗
PubMed1992

beta-Amyloid peptides destabilize calcium homeostasis and render human cortical neurons vulnerable to excitotoxicity.

In Alzheimer's disease (AD), abnormal accumulations of beta-amyloid are present in the brain and degenerating neurons exhibit cytoskeletal aberrations (neurofibrillary tangles). Roles for beta-amyloid in the neuronal degeneration of AD have been suggested based on recent data obtained in rodent studies demonstrating neurotoxic actions of beta-amyloid. However, the cellular mechanism of action of beta-amyloid is unknown, and there is no direct information concerning the biological activity of beta-amyloid in human neurons. We now report on experiments in human cerebral cortical cell cultures that tested the hypothesis that beta-amyloid can destabilize neuronal calcium regulation and render neurons more vulnerable to environmental stimuli that elevate intracellular calcium levels. Synthetic beta-amyloid peptides (beta APs) corresponding to amino acids 1-38 or 25-35 of the beta-amyloid protein enhanced glutamate neurotoxicity in cortical cultures, while a peptide with a scrambled sequence was without effect. beta APs alone had no effect on neuronal survival during a 4 d exposure period. beta APs enhanced both kainate and NMDA neurotoxicity, indicating that the effect was not specific for a particular subtype of glutamate receptor. The effects of beta APs on excitatory amino acid (EAA)-induced neuronal degeneration were concentration dependent and required prolonged (days) exposures. The beta APs also rendered neurons more vulnerable to calcium ionophore neurotoxicity, indicating that beta APs compromised the ability of the neurons to reduce intracellular calcium levels to normal limits. Direct measurements of intracellular calcium levels demonstrated that beta APs elevated rest levels of calcium and enhanced calcium responses to EAAs and calcium ionophore. The neurotoxicity caused by EAAs and potentiated by beta APs was dependent upon calcium influx since it did not occur in calcium-deficient culture medium. Finally, the beta APs made neurons more vulnerable to neurofibrillary tangle-like antigenic changes induced by EAAs or calcium ionophore (i.e., increased staining with tau and ubiquitin antibodies). Taken together, these data suggest that beta-amyloid destabilizes neuronal calcium homeostasis and thereby renders neurons more vulnerable to environmental insults.

Amino Acid Sequence↗
PubMed1991

Inactivation of gamma-glutamylcysteine synthetase by SAPH-3 disulfide: role of the histaminyl moiety.

Certain disulfide analogues of cystamine were prepared and evaluated for the ability to inhibit gamma-glutamylcysteine synthetase (GCS), the rate-limiting enzyme in glutathione synthesis. The compound SAPH-3 disulfide (2a) was found to be the most effective inactivator of GCS reported to date. Studies of structural analogues of 2a indicate that the histamine moiety plays a significant role in enzyme inactivation. Substitution of methyl groups on the carbon atoms adjacent to both sulfur atoms of the disulfide drastically decreases inhibitory action, probably due to a steric repulsion near the sulfur atom at the enzyme active site.

Animals↗
PubMed1991

NGF and bFGF protect rat hippocampal and human cortical neurons against hypoglycemic damage by stabilizing calcium homeostasis.

NGF and bFGF have recently been shown to have biological activity in central neurons, but their normal functions and mechanisms of action are unknown. Since central neurons are particularly vulnerable to hypoglycemia that occurs with ischemia or insulin overdose, we tested the hypothesis that growth factors can protect neurons against hypoglycemic damage. NGF and bFGF each prevented glucose deprivation-induced neuronal damage in human cerebral cortical and rat hippocampal cell cultures (EGF was ineffective). Protection was afforded when the growth factors were administered before (NGF and bFGF) or up to 12 hr following (NGF) the onset of hypoglycemia. Direct measurements of intracellular calcium levels and manipulations of calcium influx demonstrated that sustained elevations in intracellular calcium levels mediated the hypoglycemic damage. NGF and bFGF each prevented the hypoglycemia-induced elevations of intracellular calcium. These findings indicate that growth factors can stabilize neuronal calcium homeostasis in central neurons and thereby protect them against environmental insults.

Calcium↗
PubMed1991

[Presynaptic regulation of co-release of neuropeptide Y and noradrenaline induced by electrical stimulation of the sympathetic nerve in guinea pig heart].

In the present study, co-release of noradrenaline and neuropeptide y (NPY) evoked by electrical stimulation of the left stellate ganglion, was investigated in the in situ perfused guinea pig heart with intact sympathetic innervation, a model modified from Legendorff technique. Endogenous noradrenaline was measured by HPLC and endogenous NPY was determined by RIA. Electrical stimulation of the left stellate ganglion (4, 8, 12 and 50 Hz) evoked a calcium-dependent and frequency-related overflow of noradrenaline and NPY. The release of both transmitters was positively correlated (r = 0.83, p less than 0.001). When two subsequent stimulations were performed in the same heart, adding exogenous noradrenaline before the second stimulation reduced NPY overflow on the contrary, and NPY decreased the overflow of noradrenaline. The stimulated release of noradrenaline and NPY was increased by the alpha 2-adrenergic receptor antagonist yohimbine, and attenuated by the alpha 2-adrenergic receptor agonist B-HT 920, respectively. The adenosine analogue cyclohexyladenosine significantly reduced co-release of noradrenaline and NPY. Blocking the uptake of NA with despramine or Nisoxetine significantly increased noradrenaline overflow, however, NPY release was markedly reduced. We concluded that electrical stimulation can induce calcium-dependent co-release of noradrenaline and NPY, and this co-release of both transmitters is modulated by presynaptic alpha 2-adrenoceptors.

Animals↗
PubMed1990

Diminished adrenal steroidogenic activity in aging rats: new evidence from adrenal cells cultured from young and aged normal and hypoxic animals.

Adrenal cells from 2-6-month-old young rats (Y cells) and from 19-25-month-old aged male rats (O cells) were adapted to primary monolayer culture. The cultures of Y and O cells appeared to be primarily epithelial and rounded up in response to stimulation with adrenocorticotropic hormone (ACTH). The general morphology of O cells was comparable to that observed in Y cells except for the presence of lipofuscin-like granules, a cellular marker of aging, in O cells, but not in Y cells. ACTH-stimulated steroid production by O cells was 52% lower than that by Y cells. Exposure of intact young rats to hypoxia (0.5 atmosphere) for 21 days prior to sacrifice and culture resulted in a 122% increase of ACTH-stimulated adrenal steroidogenic activity in the cultured cells, but this effect was not observed in adrenal cells cultured from hypoxic aged rats. The results suggest that there is an age-related diminution in rat adrenal steroidogenic capacity in response to ACTH stimulation in culture derived from Y and O animals; hypoxic stress magnifies this difference.

Adrenal Cortex↗
PubMed1990

Further characterization of the inhibitory effect of monensin on adrenal steroidogenesis.

We have previously reported that treatment of cultured mouse adrenal tumor cells with 0.6-1.2 microM monensin, a monovalent carboxylic ionophore, results in disruption of the organized structure of the Golgi complex. This is associated with an inhibition of adrenocorticotropic hormone (ACTH) or dibutyryl cAMP-stimulated steroidogenesis and impairment of mitochondrial cholesterol side-chain cleavage activity. The present report describes further investigations regarding possible mechanisms for the inhibition. Monensin inhibits both synthesis of fluorogenic steroids and incorporation of [14C]acetate into the end-product steroid 11 beta,20 alpha-dihydroxy-4-pregnen-3-one. Supplementation of monensin-treated cells with 25-hydroxycholesterol, a readily available substrate for steroidogenesis, does not reverse the inhibitory effect on the reaction. The incorporation of L-[35S]methionine into trichloroacetic acid precipitable proteins in the isolated mitochondria of monensin-treated cells is inhibited approximately by 40%, whereas the inhibitory effect on the proteins in the cell homogenate is marginal. These findings suggest that a deficiency of newly synthesized proteins in mitochondria, rather than the availability of the substrate cholesterol, may be the primary factor causing impairment of steroidogenesis.

Acetates↗
PubMed1990

Structural studies on the inactivation of gamma-glutamylcysteine synthetase by the disulphide analogues of radioprotective cysteamine derivatives. Effects of aminoalkyl and hydroxyalkyl chain length and beta beta-bis-dimethylation.

Disulphide compounds have been shown to inactivate gamma-glutamylcysteine synthetase, the rate-limiting enzyme for GSH synthesis. Such compounds bind to a cysteine residue at or near the glutamate-binding site of the enzyme. This phenomenon is thought to be responsible for the synergistic toxicity of the thiophosphate radio- and chemo-protective agent WR2721 and the oxygen-radical generator 6-hydroxydopamine (2,4,6-trihydroxyphenethylamine). 6-Hydroxy-dopamine enhances conversion of WR2721 into its disulphide metabolite NN'-bis-(3-aminopropyl)cystamine, which, in turn, paralyses the synthetase. In an effort to identify radio- and chemo-protective thiols and thiol derivatives that do not have this toxicity, we have begun to define the structure-activity relationship that governs inactivation of the enzyme by analogues of WR2721 disulphide. NN'-Bis(aminoalkyl)cystamines and bis(hydroxyalkyl)cystamines with an alkyl chain length of C5 or greater are not inactivators of the synthetase. That this is not due solely to the size of these compounds is shown by the potent inactivation of the enzyme by SAPH3 disulphide, an extremely bulky cystamine analogue. beta beta-Bis-dimethylation of the cystamine portion of the molecule also obviates inactivation. This is almost certainly due to steric interference with disulphide interchange. These findings may facilitate the safe adjunctive use of the thiol counterparts of such compounds with oxygen-radical-generating chemotherapeutic agents, and may shed light on the structure of the region of the synthetase adjacent to the glutamate-binding site.

Animals↗
PubMed1990

Growth of Plasmodium falciparum in human erythrocytes containing abnormal membrane proteins.

To evaluate the role of erythrocyte (RBC) membrane proteins in the invasion and maturation of Plasmodium falciparum, we have studied, in culture, abnormal RBCs containing quantitative or qualitative membrane protein defects. These defects included hereditary spherocytosis (HS) due to decreases in the content of spectrin [HS(Sp+)], hereditary elliptocytosis (HE) due to protein 4.1 deficiency [HE(4.1(0))], HE due to a spectrin alpha I domain structural variant that results in increased content of spectrin dimers [HE(Sp alpha I/65)], and band 3 structural variants. Parasite invasion, measured by the initial uptake of [3H]hypoxanthine 18 hr after inoculation with merozoites, was normal in all of the pathologic RBCs. In contrast, RBCs from six HS(Sp+) subjects showed marked growth inhibition that became apparent after the first or second growth cycle. Preincubation of HS(Sp+) RBCs in culture for 3 days did not alter these results. Normal parasite growth was observed in RBCs from one HS subject with normal membrane spectrin content. The extent of decreased parasite growth in HS(Sp+) RBCs closely correlated with the extent of RBC spectrin deficiency (r = 0.90). Homogeneous subpopulations of dense HS RBCs exhibited decreased parasite growth to the same extent as did HS whole blood. RBCs from four HE subjects showed marked parasite growth inhibition, the extent of which correlated with the content of spectrin dimers (r = 0.94). RBCs from two unrelated subjects with structural variants of band 3 sustained normal parasite growth. Decreased growth in the pathologic RBCs was not the result of decreased ATP or glutathione levels or of increased RBC hemolysis. We conclude that abnormal parasite growth in these RBCs is not the consequence of metabolic or secondary defects. Instead, we suggest that a functionally and structurally normal host membrane is indispensable for parasite growth and development.

Animals↗
PubMed1989

Interaction between the release of adenosine and noradrenaline during sympathetic stimulation: a feed-back mechanism in rat heart.

Interactions between the release of adenosine and noradrenaline were studied during sympathetic stimulation in rat heart perfused in situ. Cardiac sympathetic nerves were activated by electrical stimulation of the left cervicothoracic ganglion, and endogenous noradrenaline and adenosine were measured in the effluent from the heart. Following the onset of a continuous stimulation (6 min) a rise of heart rate was observed which was accompanied by the release of noradrenaline and adenosine. Specific blockade of adenosine receptors by 8-phenyltheophylline enhanced the stimulation induced release of noradrenaline suggesting an effective suppression of the noradrenaline release by endogenous adenosine. Heart rate and the release of adenosine were reduced by the beta 1-adrenergic antagonist bisoprolol, while noradrenaline overflow increased. These results are compatible with the concept of a negative feed-back regulation of noradrenaline release by endogenous adenosine from the stimulated cardiomyocytes. In order to characterize the subtype of the presynaptic adenosine receptors involved, the inhibitory potency on stimulus induced noradrenaline release of metabolically stable adenosine agonists was tested. The order of potency (Cyclohexyladenosine greater than or equal to R-phenylisopropyl-adenosine greater than N-ethylcarboxamidoadenosine greater than S-phenylisopropyl-adenosine) suggests an adenosine A1-receptor mediated presynaptic inhibition of noradrenaline release.

Adenosine↗