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Biomedical subjects

K Cheng

Publications and source records attributed to K Cheng.

At least 37 records · Page 2Linked to original sources
PubMed2000

Adenosine: A partial agonist of the growth hormone secretagogue receptor.

The growth hormone secretagogue receptor (GHS-R) is involved in the regulation of pulsatile GH release. However, until recently, natural endogenous ligands for the receptor were unknown. We fractionated porcine hypothalamic extracts and assayed fractions for activity on HEK293 cells expressing GHS-R and aequorin. A partial agonist was isolated and identified using microspray tandem mass spectrometry as adenosine. GHS-R activation by adenosine and synthetic adenosine agonists is inhibited by the GHS-R selective antagonists L-765,867, D-Lys(3)-GHRP-6, and by theophylline and XAC. Cross desensitization of the GHS-R occurs with both MK-0677 and adenosine. Ligand binding and site directed mutagenesis studies show that adenosine binds to a binding site that is distinct from the previously characterized MK-0677 and GHRP-6 binding pocket. We propose, that adenosine is a physiologically important endogenous GHS-R ligand and speculate that GHS-R ligands modulate dopamine release from hypothalamic neurons.

Adenosine↗
PubMed2000

Mitochondrial translocation of protein kinase C delta in phorbol ester-induced cytochrome c release and apoptosis.

Apoptosis is induced by the release of cytochrome c from mitochondria to the cytoplasm. The present studies demonstrate that the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) induces translocation of protein kinase C (PKC) delta from the cytoplasm to mitochondria. The results also show that translocation of PKCdelta results in release of cytochrome c. The functional significance of this event is further supported by the demonstration that PKCdelta translocation is required for TPA-induced apoptosis. These findings demonstrate that translocation of PKCdelta to mitochondria is responsible, at least in part, for inducing cytochrome c release and apoptosis.

Apoptosis↗
PubMed2000

Isolation and analysis of two cellulase cDNAs from Orpinomyces joyonii.

Two cellulase cDNAs, celB29 and celB2, were isolated from a cDNA library derived from mRNA extracted from the anaerobic fungus, Orpinomyces joyonii strain SG4. The nucleotide sequences of celB2 and celB29 and the primary structures of the proteins encoded by these cDNAs were determined. The larger celB29 cDNA was 1966bp long and encoded a 477 amino acid polypeptide with a molecular weight of 54kDa. Analysis of the 1451bp celB2 cDNA revealed an 1164bp open reading frame coding for a 44kDa protein consisting of 388 amino acids. Both deduced proteins had a high sequence similarity in central regions containing putative catalytic domains. Primary structure analysis revealed that CelB29 contained a Thr/Pro-rich sequence that separated the N-terminal catalytic domain from a C-terminal reiterated region of unknown function. Homology analysis showed that both enzymes belong to glycosyl hydrolase family 5 and were most closely related to endoglucanases from the anaerobic fungi Neocallimastic patriciarum, Neocallimastix frontalis and Orpinomyces sp. The classification of CelB29 and CelB2 as endoglucanases was supported by enzyme assays. The cloned enzymes had high activities towards barley beta-glucan, lichenan and carboxymethylcellulose (CMC), but not Avicel, laminarin, pachyman, xylan and pullulan. In addition, CelB29 and CelB2 showed activity against p-nitrophenyl-beta-D-cellobioside (pNP-G(2)) to p-nitrophenyl-beta-D-cellopentaoside (pNP-G(5)) but not p-nitrophenyl-beta-D-glucopyranoside (pNP-G(1)) with preferential activity against p-nitrophenyl-beta-D-cellotrioside (pNP-G(3)). Based on these results, we proposed that CelB29 and CelB2 are endoglucanases with broad substrate specificities for short- and long-chain beta-1,4-glucans.

Amino Acid Sequence↗
PubMed2000

Potent antagonists of gonadotropin releasing hormone receptors derived from quinolone-6-carboxamides.

SAR studies which focused upon the C-6 position of a recently described series of quinolone gonadotropin releasing hormone antagonists are reported. Synthetic access to diverse quinolone-6-carboxamides was achieved via the palladium-catalyzed amino-carbonylation reactions of iodide 4 with various amines. Amides related to 9y were especially potent, functional antagonists of rat and human GnRH receptors.

Amides↗
PubMed2000

Translocation of SAPK/JNK to mitochondria and interaction with Bcl-x(L) in response to DNA damage.

Activation of the stress-activated protein kinase (SAPK/JNK) by genotoxic agents is necessary for induction of apoptosis. We report here that ionizing radiation ionizing radiation exposure induces translocation of SAPK to mitochondria and association of SAPK with the anti-apoptotic Bcl-x(L) protein. SAPK phosphorylates Bcl-x(L) on threonine 47 (Thr-47) and threonine 115 (Thr-115) in vitro and in vivo. In contrast to wild-type Bcl-x(L), a mutant Bcl-x(L) with the two threonines substituted by alanines (Ala-47, Ala-115) is a more potent inhibitor of ionizing radiation-induced apoptosis. These findings indicate that translocation of SAPK to mitochondria is functionally important for interactions with Bcl-x(L) in the apoptotic response to genotoxic stress.

Apoptosis↗
PubMed2000

Randomized controlled trials in cystic fibrosis (1966-1997) categorized by time, design, and intervention.

The improved prognosis of cystic fibrosis (CF) over the last three decades has been associated with an increased use of a range of treatments, but it is important that the use of an individual treatment is based on evidence. Well-designed randomized controlled trials (RCTs) are a robust method for evaluating the effectiveness of such treatments. We have developed a register of RCTs in CF and have studied when they were performed, their design, and what interventions were investigated. We identified 506 RCTs; 37.5% were identified solely as abstract reports in conference proceedings. There has been about a 30-fold increase in the number of RCTs in CF since 1966. A high proportion of the RCTs (72.7%) had a sample size of 30 or less, and only 8.7% were multicenter trials. Reporting of study design was poor: in 51.4% the report did not state whether there was any blinding in the trial design; 53.6% of studies were of crossover design. The most common interventions studied were antibiotic treatments and physiotherapy, but a number of commonly used therapies had been evaluated only in a small number of patients. Although the number of RCTs of interventions in CF patients has increased over the last 25 years, the sample sizes of these trials are generally too small to indicate whether the intervention was effective, and very few were multicenter. Future RCTs in CF are more likely to provide clinically useful answers if higher numbers of patients are recruited into large, well-designed multicenter trials. This should be a priority of the organization of future research in CF.

Cystic Fibrosis↗
PubMed2000

Ursodeoxycholic acid for cystic fibrosis-related liver disease.

BACKGROUND: Cystic fibrosis-related liver disease peaks in adolescence with up to 20% of patients developing chronic liver disease. Early changes in the liver may ultimately result in end stage liver disease with patients needing transplantation. One therapeutic option currently used is ursodeoxycholic acid. OBJECTIVES: To assess the effectiveness of ursodeoxycholic acid in cystic fibrosis liver disease. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group trials register, and contacted drug companies. Date of the most recent search of the Group's specialised register: June 1999. SELECTION CRITERIA: Randomised and quasi-randomised trials of use of ursodeoxycholic acid for at least three months compared with placebo or no additional treatment in people with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial eligibility and quality. MAIN RESULTS: Three trials involving 118 patients were included. The complex study design used in two trials meant that data could only be analysed for subsets of patients. There was no difference in weight change (weighted mean difference -0.496, 95% confidence interval -1.545 to +0.553) based on 30 patients from two trials. Improvement in biliary excretion was reported in only one study and no significant change after treatment was shown. Long term outcomes such as death or need for liver transplantation were not reported. REVIEWER'S CONCLUSIONS: There are few trials assessing the effectiveness of ursodeoxycholic acid. There is insufficient evidence to justify is its routine use in cystic fibrosis.

Cholagogues and Choleretics↗
PubMed2000

Oral steroids for cystic fibrosis.

BACKGROUND: In cystic fibrosis, airway obstruction and recurrent respiratory infection leads to inflammation and eventually long term lung damage, (bronchiectasis), respiratory failure and death. Inflammation occurs early in the disease process, hence the rationale for the use of anti-inflammatory agents such as oral steroids. OBJECTIVES: To assess the effectiveness of oral steroids in management of respiratory complications cystic fibrosis with particular regard to lung function and occurrence of adverse events. We aimed to to examine short term use for a respiratory exacerbation separately (up to 30 days) from long term anti-inflammatory use (greater than 30 days). SEARCH STRATEGY: We searched The Cochrane Cystic Fibrosis and Genetic Disorders Group specialist trials register. Date of the most recent search of the Group's specialised register: November 1999. SELECTION CRITERIA: All randomised or pseudorandomised trials comparing oral corticosteroids given for a period of five to 30 days for treatment of an exacerbation or for more than 30 days used long term, with placebo or no additional therapy in patients with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial eligibility and quality. MAIN RESULTS: Three trials were identified studying a total of 354 patients. Two of these were long term trials with four year follow up whilst one had follow up to 12 weeks only. There was a lack of data on our predefined outcomes with common outcomes examined at different time-points and also variations in the presentation of common outcomes. A meta-analysis was not possible. Oral corticosteroids at a prednisolone equivalent dose of 1 mg/kg alternate days appear to slow the progression of lung disease in cystic fibrosis. At 24 months from commencement, 70.4% patients treated with 1mg/kg prednisolone on alternate days had an increase in per cent predicted forced vital capacity (FVC) compared to 41.6% patients treated with placebo. The mean absolute change in per cent predicted forced expiratory volume at one second (FEV1) 48 months from commencement was -2% in the 1 mg/kg alternate days prednisolone group but -6% in the placebo group. In the long term, this benefit needs to be weighed against the occurrence of adverse events. Linear growth retardation was observed as early as six months from start of treatment in the 2 mg/kg alternate days prednisolone group and from 24 months of treatment in the 1 mg/kg alternate days prednisolone group. Occurrence of adverse events, particularly glucose abnormalities, cataracts and growth retardation resulted in early termination of one of the four year studies ( approximately approximately Eigen 1995 approximately approximately ), with the group taking 2 mg/kg prednisolone on alternate days being stopped first but followed by the 1 mg/kg alternate days. REVIEWER'S CONCLUSIONS: Oral corticosteroids at a prednisolone equivalent dose of 1-2 mg/kg alternate days appear to slow the progression of lung disease in CF but this benefit needs to be weighed against the occurrence of adverse events, in particular, development of cataracts and effect on linear growth. A risk/benefit analysis of low-dose alternate days corticosteroids would be important and the role of short term use of oral steroids should be more fully evaluated.

Anti-Inflammatory Agents↗
PubMed2000

Autoantibodies to Abl and Bcr proteins.

Formation of an aberrant, chimeric Bcr-Abl protein is the hallmark of Philadelphia (Ph) chromosome-positive leukemias. The Bcr-Abl protein, as well as its normal cellular counterparts--Abl and Bcr--are intracellular molecules with postulated roles in a variety of critical biologic functions. In this study, we demonstrate the existence of autoantibodies against these proteins. Plasma from 18 of 31 individuals (58%), including 14 of 20 Ph-positive CML patients (70%), two of four normal volunteers (50%), and two of seven patients with Ph-negative leukemia (29%) recognized p210Bcr-Abl when used in immunoprecipitation followed by immunoblotting experiments. In all 18 patients, plasma was able to recognize baculovirus-expressed Abl protein; in four patients, recognition of baculovirus-expressed Bcr protein was also demonstrated. These observations suggest that a humoral immune response to p210Bcr-Abl is discernible in both Ph-positive and -negative leukemias and in healthy individuals, and is most likely due to autoantibodies which recognize normal Abl and, to a lesser extent, normal Bcr proteins.

Adult↗
PubMed2000

Detection of bilateral symmetry in complex biological images.

The recognition of bilateral symmetry in simple dot patterns is reliably influenced by orientation. Performance is best when the axis of symmetry is vertical. We conducted two experiments to determine whether stimulus orientation also affects detection of the low levels of naturally occurring asymmetry in complex biological images. University students judged whether colour images displayed on a computer monitor possessed perfect bilateral symmetry. Stimuli were generated from high-resolution plan-view images of crabs and insects. In experiment 1, the asymmetric stimuli were the original animals, displayed on a standard black background. Symmetrical versions of each natural image were generated by sectioning the shape at the midline, copying and reflecting one side and then fusing the two halves together. To facilitate comparison of results with those obtained in earlier studies, we also presented dot patterns based upon both the slightly asymmetric and perfectly symmetrical natural images. Experiment 2 was designed to assess whether symmetry detection was dependent upon the markings and patterns on the body and appendages of the animals. The natural images were converted to silhouettes and tested against matched dot patterns. In both studies, images were presented in a random sequence with the axis of symmetry vertical, horizontal, oblique left, and oblique right. Performance with the biological images was consistently better than with the dot patterns. Abolishing fine detail did not appreciably reduce this effect. A pronounced vertical advantage was apparent with all stimuli, demonstrating that this phenomenon is robust despite considerable variation in image complexity. The implications of orientation effects for perception of natural structures are discussed.

Anatomy↗
PubMed2000

Shepard's universal law supported by honeybees in spatial generalization.

An animal that is rewarded for a response in one situation (the S+) is likely to respond to similar but recognizably different stimuli, the ubiquitous phenomenon of stimulus generalization. On the basis of functional analyses of the probabilistic structure of the world, Shepard formulated a universal law of generalization, claiming that generalization gradients, as a function of the appropriately scaled distance of a stimulus from S+, should be exponential in shape. This law was tested in spatial generalization in honeybees. Based on theoretically derived scales, generalization along both the dimensions of the distance from a landmark and the direction to a landmark followed Shepard's law. Support in an invertebrate animal increases the scope of the law, and suggests that the ecological structure of the world may have driven the evolution of cognitive structures in diverse animals.

Adaptation, Physiological↗
PubMed2000

Relative contributions of bacteria, protozoa, and fungi to in vitro degradation of orchard grass cell walls and their interactions.

To assess the relative contributions of microbial groups (bacteria, protozoa, and fungi) in rumen fluids to the overall process of plant cell wall digestion in the rumen, representatives of these groups were selected by physical and chemical treatments of whole rumen fluid and used to construct an artificial rumen ecosystem. Physical treatments involved homogenization, centrifugation, filtration, and heat sterilization. Chemical treatments involved the addition of antibiotics and various chemicals to rumen fluid. To evaluate the potential activity and relative contribution to degradation of cell walls by specific microbial groups, the following fractions were prepared: a positive system (whole ruminal fluid), a bacterial (B) system, a protozoal (P) system, a fungal (F) system, and a negative system (cell-free rumen fluid). To assess the interactions between specific microbial fractions, mixed cultures (B+P, B+F, and P+F systems) were also assigned. Patterns of degradation due to the various treatments resulted in three distinct groups of data based on the degradation rate of cell wall material and on cell wall-degrading enzyme activities. The order of degradation was as follows: positive and F systems > B system > negative and P systems. Therefore, fungal activity was responsible for most of the cell wall degradation. Cell wall degradation by the anaerobic bacterial fraction was significantly less than by the fungal fraction, and the protozoal fraction failed to grow under the conditions used. In general, in the mixed culture systems the coculture systems demonstrated a decrease in cellulolysis compared with that of the monoculture systems. When one microbial fraction was associated with another microbial fraction, two types of results were obtained. The protozoal fraction inhibited cellulolysis of cell wall material by both the bacterial and the fungal fractions, while in the coculture between the bacterial fraction and the fungal fraction a synergistic interaction was detected.

Animals↗
PubMed2000

Identification of Phe313 of the gonadotropin-releasing hormone (GnRH) receptor as a site critical for the binding of nonpeptide GnRH antagonists.

The dog GnRH receptor was cloned to facilitate the identification and characterization of selective nonpeptide GnRH antagonists. The dog receptor is 92% identical to the human GnRH receptor. Despite such high conservation, the quinolone-based nonpeptide GnRH antagonists were clearly differentiated by each receptor species. By contrast, peptide antagonist binding and functional activity were not differentiated by the two receptors. The basis of the differences was investigated by preparing chimeric receptors followed by site-directed mutagenesis. Remarkably, a single substitution of Phe313 to Leu313 in the dog receptor explained the major differences in binding affinities and functional activities. The single amino acid replacement of Phe313 of the human receptor with Leu313 resulted in a 160-fold decrease of binding affinity of the nonpeptide antagonist compound 1. Conversely, the replacement of Leu313 of the dog receptor with Phe313 resulted in a 360-fold increase of affinity for this compound. These results show that Phe313 of the GnRH receptor is critical for the binding of this structural class of GnRH antagonists and that the dog receptor can be "humanized" by substituting Leu for Phe. This study provides the first identification of a critical residue in the binding pocket occupied by nonpeptide GnRH antagonists and reinforces cautious extrapolation of ligand activity across highly conserved receptors.

Amino Acid Sequence↗
PubMed2000

[Functional reconstruction of the hand after electrical injury with a composite flap of the vessel nerve and fascia].

OBJECTIVE: In the case of electrical injury of the wrist, it may be necessary to transplant a long tendon, nerve and vessel for functional reconstruction. But the fibrosis of the recipient bed often makes the survival and functioning of the grafts difficult. This clinical study was to solve the problem. METHODS: A composite flap was designed consisting of the small saphenous vein, the sural nerve and the fascia of the lower-leg. The small saphenous vein and the nerve were transplanted to repair the defects of the radial or ulnar artery and the media nerve. The fascia was used to reconstruct the recipient bed for tendon grafting. RESULTS: Six cases were treated with this method with success in 5 cases. 5 to 18 months' follow-up revealed restoration of sensation and finger flexion in the 5 cases. CONCLUSION: This method is effective in alleviating tendon adhesion, accelerating functional restoration of the injured hand.

Adolescent↗
PubMed2000

[Urethra fistula repair without using a urethral stent].

OBJECTIVE: To report the experience in fistula repair without a urethral stent. METHOD: During the operation, the wound after approximating the epithelium was made twice the diameter of the fistula. Then an adjacent flap was turned over to cover and close the fistula. 50 fistulae in 37 patients were repaired without using a urethral stent after the operation. RESULT: There has been no recurrence in the past 7 years. CONCLUSION: This method is one of the best ways for fistula repair and has a bright prospect in application.

Humans↗
PubMed2000

[Further investigation on Second Volume of Essay on Simple Recipe and Pulsology (SESR) and Wang's Simple Recipes (WSR)].

There are 2 extant editions of SESR, written in Chunyou Jiachen (1244) reign. In the facsimile copy of Song manuscript recorded in Kojima's Records of Investigating Ancient Classics which was brought by Yang Shoujing and is now collected in the Library of Palace Museum in Taipei. There is also a facsimile copy of Song dynasty postscribed by Taki Genkan now collected in Library of Relics and Naturalist Academy of National Imperial Secretariat in Japan. The book is written in one volume, dealing first with four diagnostic methods, followed by drug and therapy and compounding of recipes and "processing" of drugs, thus forming a complete system. The WSR included in Classified Collection of Recipes is not the Essay on Pulsology, neither WANG Shou's Simple Recipes, but Yi jian gui yi (Unity of Simplicity and Easiness) by XU Ruoxu of Yuzhang, Jiangxi of Yuan dynasty, being an epitomized work of all physicians of Yongjia medical schools with only 3 pieces of incomplete papers remained.

China↗