Biomedical subjects

K Cheng

Publications and source records attributed to K Cheng.

At least 73 records · Page 4Linked to original sources

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↗

PubMed1996

Microsurgical replantation of the avulsed scalp: report of 20 cases.

Our 4-year experience with 20 patients who had suffered avulsion of 75 percent or more of the scalp is reviewed. All patients underwent replantation using microsurgical technique with 100 percent survival in 16, partial survival in 3, and failure in only 1 case. The emergency management and indications for replantation are demonstrated. The roles of sufficient preoperative preparation, generous debridement of damaged vessels, interpositional vein grafts, and the shortening of operative time in contributing to this success are emphasized. We developed a new surgical procedure called simultaneous vein grafts on donor and recipient sites in an effort to use less time in the anastomosis of interpositional vein grafts. Furthermore, we anastomosed the extra artery of the scalp to the vein on the recipient head when no suitable vein could be found. Intraoperative repair of the scalp sensory nerve and no postoperative use of any vasodilator or anticoagulant are discussed.

Adolescent↗

PubMed1996

Modulation of pulsatile GH release through a novel receptor in hypothalamus and pituitary gland.

Hormone replacement should provide a serum hormone profile similar to that found in normal physiology. This is generally impractical because hormones are usually released episodically and therefore require frequent administration. However, rather than replacing the hormone directly, in theory, one could administer a mimic or amplifier of the pulse generator that controls pulsatile release of the particular hormone. Using growth hormone (GH) as a paradigm we sought such a mimetic that would provide episodic GH release when administered by the oral route. A GH secretagogue MK0677, is described that has these ideal properties; following oral administration MK0677 amplifies episodic GH release. Mechanistically, it synergizes with growth hormone releasing hormone (GHRH) through a receptor and signal transduction pathway distinct from that of GHRH and is a functional antagonist of somatostatin (SRIF). MK0677 also acts on the arcuate nucleus and appears to stimulate GHRH release. By using 35S-MK0677, a new G-protein coupled receptor for MK0677 was characterized in the plasma membrane fraction of pituitary and hypothalamic tissue. The receptor is present in very low abundance and couples to phospholipase C. Other ligands selective for this receptor also cause synchronization of well-defined pathways leading to GH release. Repeated oral treatment of dogs once daily with MK0677 initiates amplified pulsatile GH release accompanied by increases in IGF-1 that are sustained. The unique biological properties of MK0677 and other synthetic ligands that bind to the same receptor force us to predict that these ligands mimic a naturally occurring hormone that regulates pulsatile GH release. Understanding the regulatory mechanisms involved in this paradigm has broad implications for the control of pulsatile rhythms in the endocrine system.

Amino Acid Sequence↗

PubMed1996

Phase behavior of isolated skin lipids.

Ceramides were isolated from the pig stratum corneum (SC) and mixed in varying molar ratios with either cholesterol or with cholesterol and free fatty acids. The phase behavior of the mixtures was studied by small-(SAXD) and wide-angle (WAXD) X-ray diffraction. Ceramides alone did not exhibit a long range ordering. Upon addition of cholesterol to ceramides, lamellar phases were formed and a hexagonal lateral packing was detected similar to that seen in intact SC. At a cholesterol/ceramide molar ratio of 0.1, only one reflection at 5.9 nm was observed. At a cholesterol/ceramide molar ratio of 0.2, three reflections corresponding to 12.3, 5.56, and 4.26 nm appeared. The reflections were based on two phases. Increasing the cholesterol/ceramide ratio to 0.4, the peak positions were slightly shifted. The diffraction pattern revealed the presence of two lamellar phases with periodicities of 12.2 and 5.2 nm, respectively. The positions of the peaks remained unchanged when the cholesterol/ceramide ratio was increased up to 1.0. At a cholesterol/ceramide molar ratio of 2.0, the intensity of various peaks based on the 12.2 nm phase decreased in intensity. The phase behavior of the cholesterol/ceramide mixtures in a ratio between 0.4 and 1.0 was very similar to that found in intact pig SC in which two lamellar phases with periodicities of 6.0 and 13.2 nm are present. Our data further indicate that the formation of the 5.2 nm lamellar phase requires a higher cholesterol content than the formation of the 12.2 nm lamellar phase. Furthermore, when the relative amount of cholesterol is very high, the 5.2 nm phase is the most pronounced one. Addition of free fatty acids increased the solubility of cholesterol, indicating the role free fatty acids may play for the skin barrier function. The phase behavior of cholesterol/ceramide/fatty acid mixtures was found to be dependent on the chain length of fatty acids used. Namely, addition of short-chain free fatty acids (C14-C18) did not change the periodicity of the 12.2 and 5.2 nm phases, but induced the formation of an additional 4.2 nm phase. In the presence of long-chain free fatty acids (C16-C26), the periodicity of the lamellar phases was slightly increased (to 13.0 and 5.3 nm, respectively) but no additional 4.2 nm phase was formed. These results indicate that the lipid phase behavior of the cholesterol/ceramide/free fatty acid mixtures closely mimics that of the intact stratum corneum only in the presence of long-chain free fatty acids.

Animals↗

PubMed1996

Selective induction of a cationic amino acid transporter by tumor necrosis factor-alpha in vascular endothelium.

Treatment of bovine aortic endothelial cells with tumor necrosis factor-alpha (TNF-alpha) resulted in a concentration-dependent increase in L-arginine transport. The stimulatory effect of TNF-alpha was time-dependent, requiring at least 6 hr of exposure. Both actinomycin D and cycloheximide inhibited the TNF-alpha mediated increase in L-arginine transport, indicating that de novo RNA and protein synthesis were required. Ribonuclease protection analysis revealed the presence of cationic amino acid transporter (CAT)-1 and CAT-2 mRNA. Treatment of bovine aortic endothelial cells with TNF-alpha selectively increased the levels of CAT-2 mRNA, whereas message for CAT-1 remained unchanged. These results demonstrate that TNF-alpha stimulates L-arginine transport in endothelial cells by selectively inducing the expression of CAT-2 mRNA. The capacity of TNF-alpha to stimulate the expression of CAT-2 protein may provide an important mechanism by which increases in substrate are provided to endothelial cells during periods of elevated L-arginine metabolism.

Animals↗

PubMed1996

The patient advocate: a cooperative agent to support patient-centered needs and demands.

Knowledge-based monitoring and therapy planning systems were mainly built for the convenience of health care providers. They neglected the consumers of health care, namely, the patients. Our approach is concentrated on the individual patients' demands and needs. We are designing, building, and demonstrating a cooperative agent to support patients' management of their own health-related behavior on a day-to-day basis at home. Clinical treatment protocols are represented in an intention-based time-oriented representation language to overcome the drawbacks of vague or ill-structured problem definitions (e.g., missing functional dependencies). These representations are used to guide the patients, to provide necessary explanations, and to observe and critique whether the patients obey the instructions of the health-care providers. We will present a prototype which supports women with gestational diabetes mellitus.

Ambulatory Care↗

PubMed1996

Omniplane transesophageal echocardiography imaging planes exploration.

One hundred and twenty-four patients with heart disease were examined by omniplane TEE in order to systematically research every views of omniplane TEE, and further explore anatomy and image feature of each view. The result showed that omniplane TEE transducer can be rotated in probe from 0 degree to 180 degrees, obtain many views at various angles behind the heart and fully demonstrate the structure and pathology of the heart and great vessels. It was useful for clinical diagnosis because of getting more information about the heart and great vessels. As omniplane TEE probe was little rotated in esophagus, it lessened esophagus stimulation. Meanwhile, it was suitable for three-dimensional reconstruction of left ventriculum.

Adolescent↗

PubMed1996

Clinical application of Omniplane transesophageal echocardiography.

One hundred and twenty-four patients with heart disease (75 cases of rheumatic heart disease, 26 cases of congenital heart disease, 13 cases of aortic disease and 10 cases of other disease) were examined by Omniplane transesophageal echocardiography (TEE). The result showed that Omniplane TEE transducer can be rotated from 0 degree to 180 degrees in probe and had the advantages of broader scope, obtaining more information, less stimulation to esophagus and easy to manipulate. It suggests that Omniplane TEE is a efficient technique in clinical diagnosis and can be extensively used in the future.

Adolescent↗

PubMed1995

Design and biological activities of L-163,191 (MK-0677): a potent, orally active growth hormone secretagogue.

A potent, orally active growth hormone (GH) secretagogue L-163,191 belonging to a recently synthesized structural class has been characterized. L-163,191 releases GH from rat pituitary cells in culture with EC50 = 1.3 +/- 0.09 nM and is mechanistically indistinguishable from the GH-releasing peptide GHRP-6 and the prototypical nonpeptide GH secretagogue L-692,429 but clearly distinguishable from the natural GH secretagogue, GH-releasing hormone. L-163,191 elevates GH in dogs after oral doses as low as 0.125 mg/kg and was shown to be specific in its release of GH without significant effect on plasma levels of aldosterone, luteinizing hormone, thyroxine, and prolactin after oral administration of 1 mg/kg. Only modest increases in cortisol were observed. Based on these properties, L-163,191 has been selected for clinical studies.

Administration, Oral↗

PubMed1995

Ethanol potentiates interleukin-1 beta-stimulated inducible nitric oxide synthase expression in cultured vascular smooth muscle cells.

Experiments were performed to examine the effect of ethanol on the production of nitric oxide from interleukin-1 beta (IL-1 beta)-treated cultured rat aortic smooth muscle cells. Incubation of vascular smooth muscle cells with IL-1 beta resulted in the release of nitrite and in the intracellular accumulation of L-citrulline. In parallel with this, IL-1 beta increased inducible nitric oxide synthase (iNOS) mRNA and protein. Ethanol (6.5-650 mM) potentiated the IL-1 beta-mediated stimulation of iNOS mRNA production, the appearance of iNOS protein and the generation of nitrite and L-citrulline from smooth muscle cells in a concentration-dependent manner. In the absence of IL-1 beta, ethanol failed to induce iNOS expression. These results demonstrate that pharmacologically relevant concentrations of ethanol enhance the IL-1 beta-induced expression of the iNOS gene in vascular smooth muscle. The ability of ethanol to augment the release of the platelet inhibitor and vasodilator nitric oxide may, in part, contribute to the beneficial cardiovascular effects associated with moderate alcohol consumption.

Amino Acid Oxidoreductases↗

PubMed1995

Human cortical regions activated by wide-field visual motion: an H2(15)O PET study.

1. Several areas in the monkey dorsal visual pathway, including the dorsal part of the medial superior temporal area, have been found to contain cells responding to movements of a wide visual field and are suggested to be involved in analyzing self-induced motion information. In the present study, positron emission tomography was used to localize human cortical regions responding to wide-field visual motion. Changes in regional cerebral blood flow (rCBF) were measured when subjects maintained fixation and viewed low-contrast (0.15 log units brighter than the background) dots subtending 80 x 80 degrees and moving either coherently or incoherently. Brain foci were localized after activity in a fixation-only paradigm was subtracted from that in the two moving dot paradigms. 2. Both the coherent and incoherent movements significantly activated the primary/secondary visual cortex and surrounding visual areas in the cuneus and superior occipital gyrus. Subtraction of images between the coherent and incoherent movements showed that the activity caused by the two types of movement was comparable in these early visual cortical regions. 3. In the lateral occipitotemporoparietal cortex, the coherent movement specifically activated two separate areas; a posterior focus was located at the border of the right occipitotemporal gyri, and a dorsoanterior focus was located bilaterally in the temporoparietal cortex. The incoherent movement did not activate these regions. 4. A fine anatomic localization using individual magnetic resonance images was performed for the bilateral activation in the temporoparietal cortex, which was found to be located mainly in the depth of the inferior parietal lobule and a small portion of the superior and middle temporal gyri. 5. Both the coherent and incoherent movements activated a part of the superior parietal lobule located within the intraparietal sulcus (Brodmann area 7). The bilateral foci activated by the coherent movement were located more anteriorly than the focus activated by the incoherent movement. Subtraction images between the coherent and incoherent movements, however, did not reveal any significant rCBF increases in the superior parietal lobule. 6. Several other cortical regions known to be involved in visuospatial and visuomotor functions were also activated by the coherent movement, including the frontal eye field (Brodmann area 8) and premotor cortex (Brodmann area 6) in the frontal lobe. 7. The posteriorly located activation at the border of occipito-temporal gyri corresponds to the homologue of the middle temporal area reported in previous activation studies using small to medium-sized motion stimuli. The bilateral activation in the inferior parietal lobule appeared to rely on wide-field motion stimulation.

Adult↗