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Biomedical subjects

K Cheng

Publications and source records attributed to K Cheng.

At least 19 recordsLinked to original sources
PubMed2006

Quantum size effect on surface photovoltage spectra: alpha-Fe(2)O(3) nanocrystals on the surface of monodispersed silica microsphere.

A new method for the preparation of Fe(2)O(3) nanoparticle/SiO(2) microsphere composites is described, in which fine alpha-Fe(2)O(3) nanocrystals were prepared by forced hydrolysis of FeCl(3) aqueous solution. The structure and optical spectra of these alpha-Fe(2)O(3) nanocrystals have been studied. Their visible optical absorption can be enhanced by their adsorptions on the surface of SiO(2) microspheres and thereafter simple packing of these microspheres to the aggregated structures. The size-dependent photogenerated surface photovoltage spectra (SPS) of these composites were studied, and quantum confinement effects of the SPS properties were observed. The transport of photoinduced charges between nanocrystals with intrinsic electronic nature of confined states accounts for this phenomenon. These results are helpful in understanding the relationship among d-d transition and charge-transfer transition in transition metal oxides and find applications in photovoltaic devices.

Journal Article↗
PubMed2004

Adenovirus-based vascular endothelial growth factor gene delivery to human pancreatic islets.

Islet transplantation is limited by islet graft failure due to poor revascularization, host immune rejection and nonspecific inflammatory response. Delivery of human vascular endothelial growth factor (hVEGF) gene to the islets is likely to promote islet revascularization and survival. We used a bicistronic adenoviral vector encoding hVEGF and CpG-free allele of green fluorescent protein (Adv-GFP-hVEGF) and introduced into human pancreatic islets by transfection. We found that transfection efficiency and apoptosis were dependent on the multiplicity of infection (MOI). Compared to Adv-GFP transfected and nontransfected islets, the levels of hVEGF secreted from Adv-GFP-hVEGF transfected islets were higher and exhibit a linear relationship between hVEGF expression and MOI (10-5000). Persistent, but low level expression of hVEGF from nontransfected islets was also observed. This may be due to expression of the endogenous hVEGF gene under hypoxic conditions. The levels of DNA fragmentation determined by ELISA of islet lysates were dependent on the MOI of Adv-GFP-hVEGF. On glucose challenge, insulin release from transfected islets was comparable to nontransfected islets. Immunohistochemical staining for hVEGF was very high in Adv-GFP-hVEGF transfected islets. Weak staining was also observed for hCD31 in both transfected and nontransfected islets. These findings suggest that Adv-GFP-hVEGF is a potential candidate for promoting islet revascularization.

Adenoviridae↗
PubMed2003

Discrepancies between population-based data and adverse reaction reports in assessing drugs as causes of acute pancreatitis.

BACKGROUND: Many drugs are believed, clinically, to cause acute pancreatitis. We used information held on the UK General Practitioner Research Database to compare risks for drugs for which reports of pancreatitis were common or uncommon. METHODS: Drug prescriptions were examined in 3673 patients with acute pancreatitis and in matched controls. Odds ratios were calculated for recent (1-90 days before the episode), past (91-360 days before the episode) or continuing (prescription in both periods) use. RESULTS: Odds ratios were markedly increased for recent antisecretory use in non-ulcer patients only [all H2-antagonists, 12.4 (9.5-16.4); all proton pump antagonists, 9.3 (6.6-13.0)], with smaller increases for past [3.1 (2.5-3.7) and 3.5 (2.6-4.6), respectively] and continuing [2.6 (2.2-3.1) and 3.7 (2.9-4.7), respectively] use in patients without ulcer. Recent users of mesalazine showed a markedly increased risk [9.0 (1.8-44.6)], with smaller increases in past and continuing users [4.5 (1.3-16.0) and 2.5 (1.2-5.0), respectively]. Odds ratios for other drugs, suspect or not, were modestly increased, irrespective of whether the use was recent, past or continuing. The presence of gall-stones was not associated with a modified risk. CONCLUSIONS: Mesalazine, azathioprine and antisecretory drugs in non-ulcer subjects may increase the risk of pancreatitis, but warnings of drug-induced pancreatitis are generally not accompanied by increased population risks.

Acute Disease↗
PubMed2003

Consistent and precise localization of brain activity in human primary visual cortex by MEG and fMRI.

The tomographic localization of activity within human primary visual cortex (striate cortex or V1) was examined using whole-head magnetoencephalography (MEG) and 4-T functional magnetic resonance imaging (fMRI) in four subjects. Circular checkerboard pattern stimuli with radii from 1.8 to 5.2 degrees were presented at eccentricity of 8 degrees and angular position of 45 degrees in the lower quadrant of the visual field to excite the dorsal part of V1 which is distant from the V1/V2 border and from the fundus of the calcarine sulcus. Both fMRI and MEG identified spatially well-overlapped activity within the targeted area in each subject. For MEG, in three subjects a very precise activation in V1 was identified at 42 ms for at least one of the two larger stimulus sizes (radii 4.5 and 5.2 degrees ). When this V1 activity was present, it marked the beginning of a weak wave of excitations in striate and extrastriate areas which ended at 50 ms (M50). The beginning of the next wave of activations (M70) was also marked by a brief V1 activation, mainly between 50 and 60 ms. The mean separation between V1 activation centers identified by fMRI and the earliest MEG activation was 3-5 mm.

Adult↗
PubMed2001

Human ocular dominance columns as revealed by high-field functional magnetic resonance imaging.

We mapped ocular dominance columns (ODCs) in normal human subjects using high-field (4 T) functional magnetic resonance imaging (fMRI) with a segmented echo planar imaging technique and an in-plane resolution of 0.47 x 0.47 mm(2). The differential responses to left or right eye stimulation could be reliably resolved in anatomically well-defined sections of V1. The orientation and width ( approximately 1 mm) of mapped ODC stripes conformed to those previously revealed in postmortem brains stained with cytochrome oxidase. In addition, we showed that mapped ODC patterns could be largely reproduced in different experiments conducted within the same experimental session or over different sessions. Our results demonstrate that high-field fMRI can be used for studying the functions of human brains at columnar spatial resolution.

Adult↗
PubMed2001

Orally bioavailable, indole-based nonpeptide GnRH receptor antagonists with high potency and functional activity.

Stereospecific introduction of a methyl group to the indole-3-side chain enhanced activity in our tryptamine-derived series of GnRH receptor antagonists. Further improvements were achieved by variation of the bicyclic amino moiety of the tertiary amide and by adjustment of the tether length to a pyridine or pyridone terminus. These modifications culminated in analogue 24, which had oral activity in a rat model and acceptable oral bioavailability and half-life in dogs and monkeys.

Administration, Oral↗
PubMed2001

Substituted indole-5-carboxamides and -acetamides as potent nonpeptide GnRH receptor antagonists.

The 2-aryltryptamine class of GnRH receptor antagonists has been modified to incorporate carboxamide and acetamide substituents at the indole 5-position. With either a phenol or methanesulfonamide terminus on the N-aralkyl side chain, potent binding affinity to the GnRH receptor was achieved. A functional assay for GnRH antagonism was even more sensitive to structural modification and revealed a strong preference for branched tertiary amides.

Amides↗
PubMed2001

Potent nonpeptide GnRH receptor antagonists derived from substituted indole-5-carboxamides and -acetamides bearing a pyridine side-chain terminus.

A pyridine side-chain terminus has been incorporated into the indole-5-carboxamide and indole-5-acetamide series of GnRH antagonists. Potent activity was observed in binding and functional assays. Certain branched or cyclic tertiary amides were identified as preferred in each series. Alkylation of the side-chain secondary amine had generally unfavorable effects. Variations of the gem-dialkyl substituents in the indole-5-acetamide series were also investigated.

Amides↗
PubMed2001

Heterocyclic derivatives of 2-(3,5-dimethylphenyl)tryptamine as GnRH receptor antagonists.

A series of heterocyclic 2-(3,5-dimethylphenyl)tryptamine derivatives was prepared and evaluated on a rat gonadotropin releasing hormone receptor assay. The carbon tether length and heterocyclic ring attached to the amino group of 2-(3,5-dimethylphenyl)tryptamine were varied. Several of these derivatives were potent GnRH antagonists with the most potent compound having an IC50 of 16 nM.

Animals↗
PubMed2001

2-(3,5-Dimethylphenyl)tryptamine derivatives that bind to the GnRH receptor.

A series of 2-(3,5-dimethylphenyl)tryptamine derivatives was prepared and evaluated on a rat gonadotropin releasing hormone receptor assay. Some para-substituents on the 4-phenylbutyl side chain attached to the tryptamine nitrogen led to compounds with potent GnRH receptor binding. The study has helped define structural requirements for GnRH receptor binding for the 2-aryltryptamine GnRH antagonists.

Animals↗
PubMed2001

A potent, nonpeptidyl 1H-quinolone antagonist for the gonadotropin-releasing hormone receptor.

Extensive development of the structure-activity relationships of a screening lead determined three important pharmacophores for gonadotropin-releasing hormone (GnRH) receptor antagonist activity. Incorporation of the 3,4,5-trimethylphenyl group at the 3-position, 2-(2(S)-azetidinyl)ethoxy group at the 4-position, and N-4-pyrimidinylcarboxamide at the 6-position of the quinolone core resulted in the identification of 4-(2-(azetidin-2(S)-yl)ethoxy)-7-chloro-2-oxo-3-(3,4,5-trimethylphenyl)-1,2-dihydroquinoline-6-carboxylic acid pyrimidin-4-ylamide (1) as a potent antagonist of the GnRH receptor. A 10(4)-fold increase in in vitro binding affinity is observed for the GnRH receptor as compared to the initial screening lead. Compound 1 exhibits nanomolar binding activity and functional antagonism at the human receptor and is 7-fold less active at the rhesus receptor. Intravenous administration of compound 1 to rhesus monkeys results in a significant decrease of the serum levels of downstream hormones, luteinizing hormone (79% decrease in area under the curve) and testosterone (92% decrease in area under the curve), at a dose of 3 mg/kg. Quinolone 1 is a potent nonpeptidyl antagonist for the human GnRH receptor that is efficacious for the suppression of luteinizing hormone and testosterone in primates.

Animals↗
PubMed2001

Immune enhancing effect of a growth hormone secretagogue.

Growth hormone (GH) has been known to enhance immune responses, whether directly or through the insulin like growth factor-1, induced by GH. Recently a nonpeptidyl small m.w. compound, a GH secretagogue (GHS), was found to induce the production of GH by the pituitary gland. In this study, we examined the effect of GHS in immunological functions of 5- to 6-wk-old and 16- to 24-month-old mice. In young mice, we observed a significant increase in PBLs, but T and B cell-proliferative responses were not consistently enhanced. The old mice, treated with GHS for 3 wk, did not show increases in peripheral lymphocytes, but they exhibited a statistically significant increase in thymic cellularity and differentiation. When inoculated with a transplantable lymphoma cell line, EL4, the treated old mice showed statistically significant resistance to the initiation of tumors and the subsequent metastases. Generation of CTL to EL4 cells was also enhanced in the treated mice, suggesting that GHS has a considerable immune enhancing effect, particularly in the old mice. We have also found that GHS promoted better thymic engraftment in bone marrow transplant of SCID mice. We found more cycling cells in the spleens of treated mice, suggesting that GHS may exert its immune enhancing effect by promoting cell division in lymphoid cells. These observations ascribe to GHS a novel therapy possible for aging, AIDS, and transplant individuals, whose immune functions are compromised.

Adjuvants, Immunologic↗
PubMed2001

Initial structure-activity relationship of a novel class of nonpeptidyl GnRH receptor antagonists: 2-arylindoles.

A nonpeptidyl GnRH receptor antagonist (1), with a unique 2-arylindole core, was identified through the Merck in-house screening for binding affinity on the rat GnRH receptor. SAR studies directed toward the alkoxy-ethanolamine and 2-aryl groups resulted in a simpler lead structure with improved activity. This compound 50 exhibits a 60-fold improvement in binding activity over our initial lead 1.

Animals↗
PubMed2001

Way-finding and landmarks: the multiple-bearings hypothesis.

Clark's nutcrackers (Nucifraga columbiana) are capable of very precise searching using the metric relationships between a goal and multiple landmarks to relocate the goal location. They can judge the direction more accurately than the distance to a landmark when the landmark is distant from the goal. On the basis of these findings, we propose that nutcrackers use a set of bearings, each a measure of the direction from the goal to a different landmark, when searching for that goal. The results of a simulation demonstrate that increasing the number of landmarks used results in increasingly precise searching. This multiple-bearings hypothesis makes a series of detailed predictions about how the distribution of searches will vary as a function of the geometry of the locations of the relevant landmarks and the goal. It also suggests an explanation for inconsistencies in the literature on the effects of clock-shifts on searching and on homing.

Animals↗