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Biomedical subjects

K Cheng

Publications and source records attributed to K Cheng.

At least 55 records · Page 3Linked to original sources
PubMed1997

Organization of corticostriatal and corticoamygdalar projections arising from the anterior inferotemporal area TE of the macaque monkey: a Phaseolus vulgaris leucoagglutinin study.

Corticostriatal and corticoamygdalar projections arising from area TE of the macaque monkey were studied by focal injections of the anterograde tracer Phaseolus vulgaris leucoagglutinin into the dorsolateral and ventromedial subdivisions of the anterior TE (TEad and TEav, respectively). This approach yielded several new results. First, the global distributions of labeled terminals revealed that both TEad and TEav projected to the ventrocaudal striatum, including the tail of the caudate nucleus and the adjacent ventral putamen, and the dorsolateral aspect of the deep amygdaloid nuclei. TEav also projected to the medial basal nucleus of the amygdala and the ventral striatum. Second, the reconstructed single axons (n = 18) demonstrated that some axons originating from TEav or TEad projected simultaneously to the ventrocaudal striatum and the dorsolateral aspect of the deep amygdaloid nuclei by giving off collaterals. TEav axons projected to the medial basal nucleus of the amygdala also had collaterals projecting to the perirhinal cortex or area TG. And third, it was revealed that the axons originating from a focal TEav or TEad projected to a restricted territory (3.4-3.6 mm rostrocaudally) in the ventrocaudal striatum with four to six dispersed, rostrocaudally elongated, rod-like modules. Individual axons with multiple arbors innervated many of these modules. These findings add the evidence that the anterior part of TE is anatomically heterogeneous and suggest that the deep amygdaloid nuclei may be functionally dissociated, with the dorsolateral aspect more closely related to the ventrocaudal striatum and the medial basal nucleus more closely related to the perirhinal cortex.

Amygdala↗
PubMed1997

Changes in Acidity of Fe-Pillared/Delaminated Smectites on Heat Treatment

Hydroxy-iron smectites were prepared using solutions with a OH/Fe content of about 1.2 and 2.5. To study thermal stability, the samples were heated in air at temperatures between 473 and 873 K. Changes in surface chemistry imposed by heat treatment were evaluated using potentiometric titration. The pKa distributions revealed peaks characteristic for iron complexes (FeIII) deposited on the surface of smectite. Heat treatment resulted in significant changes in the chemistry of the material and creation new species; however, the sorbents textural properties did not alter significantly. Data obtained from X-ray diffraction and sorption of nitrogen demonstrate that iron species are adsorbed mainly on the external surface of smectite and that the properties of the final products depend upon the OH/Fe ratio of hydroxy-iron solutions used in their preparation.

Journal Article↗
PubMed1997

Biochemical characterization of the protein tyrosine kinase homology domain of the ErbB3 (HER3) receptor protein.

The putative protein tyrosine kinase domain (TKD) of the ErbB3 (HER3) receptor protein was generated as a histidine-tagged recombinant protein (hisTKD-B3) and characterized enzymologically. CD spectroscopy indicated that the hisTKD-B3 protein assumed a native conformation with a secondary structure similar to that of the epidermal growth factor (EGF) receptor TKD. However, when compared with the EGF receptor-derived protein, hisTKD-B3 exhibited negligible intrinsic protein tyrosine kinase activity. Immune complex kinase assays of full-length ErbB3 proteins also yielded no evidence of catalytic activity. A fluorescence assay previously used to characterize the nucleotide-binding properties of the EGF receptor indicated that the ErbB3 protein was unable to bind nucleotide. The hisTKD-B3 protein was subsequently found to be an excellent substrate for the EGF receptor protein tyrosine kinase, which suggested that in vivo phosphorylation of ErbB3 in response to EGF could be attributed to a direct cross-phosphorylation by the EGF receptor protein tyrosine kinase.

Animals↗
PubMed1997

Growth hormone releasing peptides: a comparison of the growth hormone releasing activities of GHRP-2 and GHRP-6 in rat primary pituitary cells.

In the present study, the effect of GHRP-2 on GH release was evaluated in rat primary pituitary cells, and the results were compared with those elicited by GHRP-6. In the rat system, GHRP-2, like GHRP-6, acts synergistically with GRF to release GH. Co-administration of GHRP-2 and GHRP-6 at maximal concentrations had no further effect on GH release than either one alone. The GHRP's were able to desensitize cells to each other, but not to GRF. The effect of GHRP-2 was inhibited by Peptide Antagonist, but was not affected by a GRF antagonist. In conclusion, GHRP-2 was found to stimulate GH release from rat pituitary cells via the same receptor and mechanism as GHRP-6, despite the structural difference between the peptides.

Animals↗
PubMed1997

Identification of an oligodeoxynucleotide sequence motif that specifically inhibits phosphorylation by protein tyrosine kinases.

Protein tyrosine kinases (PTKs) have central roles in cellular signal transduction. We have identified a sequence motif (CGT[C]GA) in phosphorothioate-modified oligodeoxynucleotides (ODNs) that specifically inhibits the enzymatic activity of recombinant or immunoprecipitated PTK in vitro. Hexamer ODNs containing this motif block both substrate and autophosphorylation of at least four different PTKs but have no apparent effect on the enzymatic activity of a serine/threonine protein kinase. These data suggest possible new applications for ODNs and have implications for the design and interpretation of experiments using antisense or triplex ODNs.

Cell Line↗
PubMed1997

Randomised controlled trial of acetate in preterm neonates receiving parenteral nutrition.

AIMS: To determine whether by partly replacing chloride with acetate in parenteral nutrition, hyperchloraemia, metabolic acidosis, and the subsequent use of interventions such as colloid infusion, alkali treatment, increased assisted ventilation, would be reduced. METHODS: Fifty eight neonates of less than 32 weeks gestation, receiving parenteral nutrition from days 3 to 10, were given either standard parenteral nutrition or a novel formulation with replacement of any chloride dose > 3 mmol/kg/day as acetate. RESULTS: Acetate (0 to 14.2 mmol/kg/day) reduced the incidence of hyperchloraemia from 77% to 25%, and caused an increase in base excess from day 5 onwards (mean intergroup difference 3.6 to 9.9 mmol/l), an increased pH (day 8, 7.34 vs 7.26), with an increased pCO2 (1 kPa). The acetate group received less bicarbonate (median 0 mmol vs 4.8 mmol) and less colloid (41 ml/kg vs 204 ml/kg). There was no difference in any parameter of assisted ventilation. CONCLUSION: Acetate in neonatal parenteral nutrition reduces metabolic acidosis and hyperchloraemia.

Acidosis↗
PubMed1997

cAMP induces heme oxygenase-1 gene expression and carbon monoxide production in vascular smooth muscle.

Recent studies indicate that vascular smooth muscle cells generate carbon monoxide (CO) via the action of heme oxygenase (HO). Because adenosine 3',5'-cyclic monophosphate (cAMP) is an important intracellular signaling molecule in the regulation of vascular cell function, we examined whether this second messenger modulates the expression of HO and the production of CO by rat aortic smooth muscle cells. Treatment of smooth muscle cells with the membrane-permeable cAMP derivative dibutyryl cAMP or with compounds that increase intracellular cAMP levels (isoproterenol and forskolin) resulted in a concentration- and time-dependent increase in the levels of HO-1 mRNA and protein, whereas the expression of HO-2 remained unchanged. Both actinomycin D and cycloheximide blocked the basal expression of HO-1 mRNA and protein and prevented the cAMP-mediated induction of HO-1. Incubation of platelets with cAMP-treated smooth muscle cells resulted in a significant increase in platelet cGMP concentration that was partially reversed by treatment of smooth muscle cells with the nitric oxide synthase inhibitor NG-monomethyl-L-arginine or the HO blocker zinc protoporphyrin-IX. However, the combined addition of these two inhibitors to cAMP-treated smooth muscle cells or the addition of the CO and NO scavenger hemoglobin to platelets completely blocked the stimulatory effect on platelet cGMP levels. These results demonstrate that cAMP induces the expression of the HO-1 gene and stimulates the formation of CO and NO in vascular smooth muscle cells. The capacity of cAMP to induce the synthesis of guanylate cyclase-stimulatory CO from smooth muscle cells may represent a novel mechanism by which this nucleotide regulates vascular tone.

Animals↗
PubMed1997

Inhibition of L-692,429-stimulated rat growth hormone release by a weak substance P antagonist: L-756,867.

H2N,D-Arg,Pro,Lys,Pro,D-Phe,Gln,D-Trp,Phe,D-Trp,Leu, Leu,NH2 (L-756,867), a weak substance P antagonist, inhibited L-692,429-stimulated GH release from rat primary pituitary cells in a dose-dependent manner. At a concentration of 50 nM, L-756,867 shifted the dose-response curve of L-692,429-induced GH release to the right by about tenfold. It also impaired the ability of L-692,429 to potentiate the effect of growth hormone-releasing factor (GRF) on GH release. Substance P (1 microM) had no effect on basal or L-692,429-stimulated GH release. When tested in anesthetized rats, L-756,867 inhibited L-692,429- and growth hormone-releasing hexapeptide- (GHRP-6)-stimulated GH secretion in a dose-dependent manner. Complete inhibition was observed at an i.v. dose of 100 micrograms/kg of L-756,867. However, at the same concentration, it had no effect on GRF-induced GH secretion D-Lys3-GHRP-6, a GHRP-6 antagonist, had no effect on GHRP-6 or L-692,429-induced GH secretion even at an i.v. dose of 2 mg/kg. These results indicate that L-692,429 and GHRP-6 stimulate GH release both in vitro and in vivo via a common receptor and signaling pathway which is different from that of substance P in spite of the fact that their effects are inhibited by a weak substance P antagonist.

Animals↗
PubMed1996

Spread of beta-lactam-resistant Pseudomonas aeruginosa in a cystic fibrosis clinic.

BACKGROUND: Pseudomonas aeruginosa colonisation of the airways of patients with cystic fibrosis (CF) is associated with considerable respiratory morbidity. Although segregation of colonised patients from non-colonised patients to prevent cross-infection has been recommended, there is little evidence that such cross-infection is widespread. We observed that a high proportion of children attending our CF clinic were colonised with P aeruginosa that was resistant to ceftazidime and other beta-lactam antibiotics. We used two genomic fingerprinting techniques to see whether this may have arisen from epidemic spread of a single strain. METHODS: The prevalence of P aeruginosa colonisation and the antibiotic susceptibility of the organisms was determined from review of laboratory reports in the case-notes of 120 children with CF. Isolates were cultured from the sputum of 65 children colonised with ceftazidime-resistant P aeruginosa. Polymorphisms in total bacterial DNA from 92 isolates were analysed with two molecular fingerprinting techniques--pulsed-field gel electrophoresis after restriction enzyme digestion and assessment of flagellin gene polymorphisms by amplification of the whole gene and restriction enzyme digestion. RESULTS: 92 (76.7%) of 120 children were colonised with P aeruginosa, and 65 of the 92 harboured isolates that were resistant to ceftazidime. Only three of the 92 children had never been treated with ceftazidime. The results of the two molecular-fingerprinting techniques were concordant and showed that 55 of 65 children harboured the same epidemic strain. This strain was resistant to ceftazidime, azlocillin, and imipenem, and sensitive to tobramycin and ciprofloxacin. INTERPRETATION: This study provides the first molecular evidence of a long-term outbreak of P aeruginosa in a CF centre. We suggest that careful surveillance of the prevalence of antibiotic resistance in CF centres should be instituted with measures to prevent cross-infection. We believe that antipseudomonal monotherapy should be considered with caution.

Adolescent↗
PubMed1996

The role of ceramides 1 and 2 in the stratum corneum lipid organisation.

A mixture of ceramide 1 and ceramide 2 (CER(1 + 2)) was isolated from pig stratum corneum and mixed in various molar ratios with cholesterol (CHOL) or with CHOL and palmitic acid (PA). The mixtures were hydrated in a buffer solution of pH 5.0 and their phase behaviour was studied by wide- and small-angle X-ray diffraction. The small-angle diffraction curve of the CHOL/CER(1 + 2) mixture at a molar ratio of 0.4 revealed the presence of only one peak at a spacing of 6.7 nm. Increasing the amount of CHOL to a molar ratio of 0.6 was accompanied by a shift of this peak to a smaller spacing (5.7 nm) and the appearance of two weak peaks at 11.8 and 4.1 nm spacings. Increasing the CHOL content to an equimolar ratio resulted in the appearance of two lamellar phases with periodicities of 5.5 and 12 nm, respectively. In a CHOL/CER(1 + 2) mixture at a molar ratio of 2 the periodicities of the two phases were 5.6 and 12 nm, respectively. From these observations it was concluded that the CHOL/CER(1 + 2) mixtures exerted similar phase behaviour, as reported earlier for intact SC (Bouwstra et al. (1995) J. Lipid Res. 36, 496-504) and for mixtures (Bouwstra et al. (1996) J. Lipid Res., in press) prepared from CHOL and total ceramide fraction (CER) isolated from pig stratum corneum. However, in the CHOL/CER mixtures a lower relative amount of CHOL was required to acquire these lamellar phases, indicating that at low CHOL contents, CER 3, 4, 5 and 6 play a crucial role in the formation of the lamellar phases. Furthermore, the solubility of CHOL in the mixtures increased in the presence of CER 1, suggesting its important role for the barrier function of the skin. When palmitic acid (PA) was included, the phase behaviour of the CHOL/CER(1 + 2)/PA mixture was more complex. Next to two lamellar phases, an additional phase with a spacing of 3.77 nm was observed, never seen in intact stratum corneum. In the absence of CHOL, the wide-angle diffraction pattern of the CER(1 + 2) revealed one sharp reflection at 0.456 nm and two diffuse reflections at 0.430, 0.417 nm and 0.395 nm, indicating the presence of a crystalline sublattice. In an equimolar mixture of CHOL/CER(1 + 2) no sharp 0.456 nm reflection was observed indicating a more disordered packing. Furthermore, phase separation of CHOL occurred, this conclusion is based on the presence of reflections corresponding to polycrystalline cholesterol monohydrate. These findings indicate that the lateral packing of mixtures of CHOL/CER(1 + 2) is more complex than that of the CHOL/CER mixtures that reveals a hexagonal lateral packing.

Animals↗
PubMed1996

Platelet-derived growth factor regulates vascular smooth muscle cell proliferation by inducing cationic amino acid transporter gene expression.

Since recent studies demonstrated that platelet-derived growth factor (PDGF) induces vascular smooth muscle cell (SMC) proliferation by stimulating polyamine synthesis, we examined whether the transcellular transport of L-ornithine, the cationic amino acid precursor of polyamines, could regulate the mitogenic response of PDGF. Treatment of SMC with PDGF stimulated DNA and putrescine synthesis, and this was enhanced further by increasing the extracellular concentration of L-ornithine. The potentiating effect of L-ornithine was reversed by the competitive inhibitor of cationic amino acid transport, methyl-L-arginine, or by preventing putrescine formation with alpha-difluoromethylornithine. Cationic amino acid uptake by SMC was Na+-independent and was mediated by both a high and low affinity carrier system. Treatment of SMC with PDGF initially (0-2 h) decreased basic amino acid transport, while longer exposures (6-24 h) progressively increased uptake. Kinetic studies indicated that PDGF-induced inhibition was associated with a decrease in affinity for cationic amino acids, while the stimulation was mediated by an increase in transport capacity. Endogenous PDGF released by collagen-activated platelets likewise up-regulated cationic amino acid transport in SMC. Reverse transcriptase-polymerase chain reaction detected the presence of mRNA encoding two distinct cationic amino acid transporter (CAT) proteins, CAT-1 and CAT-2B. Treatment of SMC with PDGF strongly induced the expression CAT-2B mRNA and modestly elevated the level of CAT-1 mRNA. These results demonstrate that PDGF-induced polyamine synthesis and SMC mitogenesis are dependent on the transcellular transport of L-ornithine. The capacity of PDGF to up-regulate the transport of L-ornithine by inducing the expression of the genes for CAT-1 and CAT-2B may modulate its mitogenic effect by providing SMC with the necessary intracellular precursor for polyamine biosynthesis.

Amino Acid Sequence↗
PubMed1996

Nucleotide binding by the epidermal growth factor receptor protein-tyrosine kinase. Trinitrophenyl-ATP as a spectroscopic probe.

The nucleotide binding properties of the epidermal growth factor (EGF) receptor protein-tyrosine kinase were investigated with the fluorescent nucleotide analog 2'(3')-O-(2,4,6-trinitrophenyl)adenosine 5'-triphosphate (TNP-ATP). TNP-ATP was found to be an active substrate for the autophosphorylation reaction of the recombinant EGF receptor protein-tyrosine kinase domain (TKD). Whereas the Vmax for the TNP-ATP-dependent autophosphorylation reaction was approximately 200-fold lower than that of ATP, the Km for this reaction was similar to that observed with ATP. The nucleotide analog was also shown to be an inhibitor of the ATP-dependent autophosphorylation and substrate phosphorylation reactions of the TKD. Spectroscopic studies demonstrated both a high affinity binding of TNP-ATP to the recombinant TKD and a markedly enhanced fluorescence of the bound nucleotide analog. The fluorescence of enzyme-bound TNP-ATP was attenuated in the presence of ATP, which enabled determination of the dissociation constants for both ATP and the Mn2+ complex of ATP. A truncated form of the EGF receptor TKD lacking the C-terminal autophosphorylation domain exhibited an enhanced affinity for TNP-ATP, which indicated that the autophosphorylation domain occupied the peptide substrate binding site of the TKD and modulated the binding of the nucleotide substrates.

Adenosine Triphosphate↗
PubMed1996

In vivo 3-D distributions of electric fields in pig skin with rectangular pulse electrical current stimulation (RPECS).

We developed stimulating and detecting electrodes. We experimentally examined three dimensional (3-D) distributions of electric fields in living pig skin under and around the stimulating electrodes with the detecting electrodes and rectangular pulsed electrical current stimulation (RPECS). We verified our previous physical assumption, E approximately I/(A sigma dz), in the skin under the electrode, where E, I, A and sigma dz respectively represent the electric field, the externally imposed peak current, the cross sectional area of the stimulating electrode and the perpendicular conductivity of the skin. Pulses were 30 mA, 140 microseconds and 128 pulses per second (pps). These parameters were previously used in our laboratory to enhance cutaneous regeneration, in vivo, with RPECS.

Animals↗
PubMed1996

Conductivities of pig dermis and subcutaneous fat measured with rectangular pulse electrical current.

We examined experimentally the relationship between perpendicular and tangential electrical conductivities, sigma, and peak current density J, in pig skin dermis and subcutaneous fat specimens by using a four-electrode measuring system with rectangular pulse electrical current (RPEC). We also investigated the relationship of the conductivity, sigma, vs. pulse rate, f. The rates were selected at 8, 32, 64, and 128 pulses per second (pps), and the pulse width was fixed at 140 microseconds. These values are often used in vivo to enhance cutaneous regeneration with RPEC stimulation. It was found that the conductivities may be approximated to be [equation: see text] for the skin dermis and [equation: see text] for the subcutaneous fat in the conditions of this experiment. These findings implies that the conductivities of pig skin dermis and subcutaneous fat are anisotropic, i.e., sigma x = sigma y not equal to sigma z. It was also found that the conductivities are independent of current density and pulse rate in the current range from 20 microA/cm2 to 120 mA/cm2.

Adipose Tissue↗
PubMed1996

Averaging temporal duration and spatial position.

Pigeons and humans performed on a task in which spatial position and elapsed time redundantly signaled the availability of reward. On each training trial, a landmark moved steadily across a monitor screen. After a fixed amount of time and movement, reward was available for a response. On occasional unrewarded tests, the landmark moved at 0.50, 0.75, 1.00, 1.50, or 2.00 times the training speed. In both pigeons and humans, the central tendency in the response distribution on tests differed across speeds, when measured in terms of both elapsed time and landmark position. Pigeons and humans seem to average a duration of time and a spatial position to find a single criterion time-place corresponding to the expected time-place of reward.

Animals↗
PubMed1996

Learning the configuration of a landmark array: I. Touch-screen studies with pigeons and humans.

Pigeons and humans searched on a touch-screen monitor for an unmarked goal located relative to an array of landmarks presented in varied screen locations. After training with the goal centered in various square arrays of 4 landmarks, humans, but not pigeons, transferred accurately to arrays with novel elements. Humans searched in the middle of expanded arrays, whereas pigeons preserved the distance and direction to a single landmark. When trained with the goal centered below 2 identical horizontally aligned landmarks, humans responded to horizontal expansions or contractions of the array by shifting their search vertically, preserving angles from landmarks to goal. Pigeons did not adjust their search vertically. Humans trained with a single landmark adjusted search distance when landmark size was changed. Both pigeons and humans use the configuration of a landmark array, but the underlying processes seem to differ.

Adult↗