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Biomedical subjects

H Cheng

Publications and source records attributed to H Cheng.

At least 73 records · Page 4Linked to original sources
PubMed2001

Ca2+ signalling between single L-type Ca2+ channels and ryanodine receptors in heart cells.

Ca2+-induced Ca2+ release is a general mechanism that most cells use to amplify Ca2+ signals. In heart cells, this mechanism is operated between voltage-gated L-type Ca2+ channels (LCCs) in the plasma membrane and Ca2+ release channels, commonly known as ryanodine receptors, in the sarcoplasmic reticulum. The Ca2+ influx through LCCs traverses a cleft of roughly 12 nm formed by the cell surface and the sarcoplasmic reticulum membrane, and activates adjacent ryanodine receptors to release Ca2+ in the form of Ca2+ sparks. Here we determine the kinetics, fidelity and stoichiometry of coupling between LCCs and ryanodine receptors. We show that the local Ca2+ signal produced by a single opening of an LCC, named a 'Ca2+ sparklet', can trigger about 4-6 ryanodine receptors to generate a Ca2+ spark. The coupling between LCCs and ryanodine receptors is stochastic, as judged by the exponential distribution of the coupling latency. The fraction of sparklets that successfully triggers a spark is less than unity and declines in a use-dependent manner. This optical analysis of single-channel communication affords a powerful means for elucidating Ca2+-signalling mechanisms at the molecular level.

Animals↗
PubMed2001

Expression of neural cell adhesion molecule in spinal cords following a complete transection.

Neural cell adhesion molecule (NCAM) regulates tissue organization during development and in the adult. NCAM upregulation occurs after an injury to brains and sciatic nerves. However, little is known about NCAM expression after spinal cord injury (SCI). By using a complete spinal cord transection with a 5 mm tissue removal, an increase in the NCAM level is detected in spinal cord stumps proximal and distal to the transection site at 1 d and 3 d post injury, while its expression at 8 d is declined to a lower level than that observed in sham-operated spinal cords. The strong NCAM expression is present in motor neurons at 3 d post transection whereas the intensive NCAM immunostaining is localized in dorsal sensory and corticospinal fiber tracts at 8 d following injury. Collectively, NCAM level is elevated and strongly expressed in dorsal fiber tracts after SCI, implying that the endogenous process for spinal cord regeneration may take place after SCI.

Animals↗
PubMed2001

Proteomic analysis of apoptosis initiation induced by all-trans retinoic acid in human acute promyelocytic leukemia cells.

The irreversible destiny of apoptosis in its early stage might play a critical role in the apoptosis of human acute promyelocytic leukemia (APL) cell line induced by all-trans retinoic acid (ATRA). To characterize protein alterations during the apoptosis-initiation phase and to understand the metabolic status at that time, we investigated the protein profiles in the apoptosis-initiation phase of APL cell line HL-60 by proteomic analysis. ATRA-withdrawal was conducted to demonstrate that there was committed initiation phase of apoptosis triggered by 10(-6) M ATRA at day 3. Only after that time point, ATRA-treated cells irreversibly went to apoptosis. Also at that time point, the positive regulators of apoptosis such as STAT3 increased at protein level, whereas negative regulators (Bcl-2 and p-STAT3) decreased. In addition, caspase-3 also increased after that time. Furthermore, comparative proteomic analysis was utilized to examine the protein expression profiles during the initiation stage of apoptosis. Our results showed 12 upregulated and 7 downregulated proteins experiencing twofold alteration, including key regulators of signal transduction such as G-proteins and nucleic receptors, proteins related with metabolism, oxidation and reduction, proteins associated with the nucleus and cytoskeleton-related proteins. Some of them could be positive modulators to trigger apoptosis, whereas others could contribute to intracellular defense against apoptosis induced by exogenous triggers. The results above suggest that there is a subtle balance between apoptosis and the intracellular defense against apoptosis. Once the balance is disturbed, cells would irreversibly initiate to undergo the execution of apoptosis.

Amino Acids↗
PubMed2001

High-precision U-series dating of Locality 1 at Zhoukoudian, China.

Thermal ionization mass spectrometric(230)Th/(234)U dating has been carried out on intercalated speleothem samples from the limestone cave occupied by Homo erectus at Zhoukoudian, China. The samples were recently collected in proper stratigraphic context after detailed field examinations. The results show that the age of the No. 5 Skull from Layer 3 is >400 ka, possibly in the range of about 400-500 ka, and that the hominid fossils from the lower strata are at least 600 ka and possibly >800 ka, much older than previously thought. The near-equilibrium(230)Th/(234)U ratios and internal consistency of the dates and stratigraphy lend credence to the results and allow us to comment on their important implications for human evolution.

Animals↗
PubMed2001

A review of the DNA standard reference materials developed by the National Institute of Standards and Technology.

The Standard Reference Materials Program at the US National Institute of Standards and Technology (NIST) has three human DNA standard reference materials (SRM 2390, SRM 2391a, and SRM 2392) currently available [1, 2]. Both the DNA profiling SRM 2390 and the polymerase chain reaction (PCR)-based DNA profiling SRM 2391a are intended for use in forensic and paternity identifications, for instructional law enforcement, or for non-clinical research purposes and are not intended for clinical diagnostics. The mitochondrial DNA (mtDNA) SRM 2392 is to provide standardization and quality control when performing PCR and sequencing any segment or the entire 16,569 base pairs that comprise human mitochondrial DNA. SRM 2392 is designed for use by the forensic, medical, and toxicological communities for human identification, disease diagnosis or mutation detection.

DNA↗
PubMed2001

A preferred amplitude of calcium sparks in skeletal muscle.

In skeletal and cardiac muscle, calcium release from the sarcoplasmic reticulum, leading to contraction, often results in calcium sparks. Because sparks are recorded by confocal microscopy in line-scanning mode, their measured amplitude depends on their true amplitude and the position of the spark relative to the scanned line. We present a method to derive from measured amplitude histograms the actual distribution of spark amplitudes. The method worked well when tested on simulated distributions of experimental sparks. Applied to massive numbers of sparks imaged in frog skeletal muscle under voltage clamp in reference conditions, the method yielded either a decaying amplitude distribution (6 cells) or one with a central mode (5 cells). Caffeine at 0.5 or 1 mM reversibly enhanced this mode (5 cells) or induced its appearance (4 cells). The occurrence of a mode in the amplitude distribution was highly correlated with the presence of a mode in the distribution of spark rise times or in the joint distribution of rise times and spatial widths. If sparks were produced by individual Markovian release channels evolving reversibly, they should not have a preferred rise time or amplitude. Channel groups, instead, could cooperate allosterically or through their calcium sensitivity, and give rise to a stereotyped amplitude in their collective spark.

Algorithms↗
PubMed2001

Differential expression of decorin and biglycan genes during mouse tooth development.

Small leucine-rich proteoglycans (SLRPs) have a number of biological functions and some of them are thought to regulate collagen mineralizaton in bone and tooth. We have previously identified and immunolocalized two members of the SLRPs family, decorin and biglycan, in bovine tooth/periodontium. To investigate their potential roles in tooth development, we examined the mRNA expression patterns of decorin, biglycan and type I collagen in newborn (day 19) mice tooth germs by in situ hybridization. At this developmental stage, the first maxillary and mandibular molars include stages before and after secretion of the predentin matrix, respectively. The expression of decorin mRNA coincided with that of type I collagen mRNA and was mostly observed in secretory odontoblasts, while the biglycan mRNA was expressed throughout the tooth germ, including pre-secretory odontoblasts/ameloblasts, dental papilla and stellate reticulum. However, its signal in secretory odontoblasts was not as evident as that of decorin. In mandibular incisors, where a significant amount of predentin matrix and a small amount of enamel matrix were already secreted, a similar differential expression pattern was observed. In secretory ameloblasts the biglycan mRNA expression was apparent, while that of decorin was not. These differential expression patterns suggest the distinct roles of biglycan and decorin in the process of tooth development.

Animals↗
PubMed2001

Structural and kinetic characterization of early folding events in beta-lactoglobulin.

We have defined the structural and dynamic properties of an early folding intermediate of beta-lactoglobulin known to contain non-native alpha-helical structure. The folding of beta-lactoglobulin was monitored over the 100 micros--10 s time range using ultrarapid mixing techniques in conjunction with fluorescence detection and hydrogen exchange labeling probed by heteronuclear NMR. An initial increase in Trp fluorescence with a time constant of 140 micros is attributed to formation of a partially helical compact state. Within 2 ms of refolding, well protected amide protons indicative of stable hydrogen bonded structure were found only in a domain comprising beta-strands F, G and H, and the main alpha-helix, which was thus identified as the folding core of beta-lactoglobulin. At the same time, weak protection (up to approximately 10-fold) of amide protons in a segment spanning residues 12--21 is consistent with formation of marginally stable non-native alpha-helices near the N-terminus. Our results indicate that efficient folding, despite some local non-native structural preferences, is insured by the rapid formation of a native-like alpha/beta core domain.

Animals↗
PubMed2001

Neurourologic findings in patients with traumatic thoracolumbar vertebra junction lesions.

OBJECTIVE: To investigate neurourologic involvement in injuries to the thoracolumbar vertebra junction with magnetic resonance imaging (MRI) and electrophysiologic and urodynamic measurements and to characterize the neurogenic mechanisms of voiding dysfunctions. DESIGN: Baseline comparisons among 3 anatomic groups before neural repair. SETTING: Tertiary care center. PATIENTS: Thirty-five T11 to L2 spinal cord injury patients consecutively admitted to a rehabilitation unit. Eight patients (Group 1) had above-conus lesions without denervation and polyphasic waves revealed in the anal sphincter electromyography; 13 patients (Group 2) had conal and/or above-conus lesions and anal sphincter electromyographic abnormalities; and 14 patients (Group 3) had below-conus lesions and anal sphincter electromyographic abnormalities. MAIN OUTCOME MEASURES: Comparison of features identified on pudendal nerve terminal motor latency, urethral pressure profiles, and multichannel voiding pressure-flow study. RESULTS: The pudendal nerve terminal motor latency in Group 3, showing a significantly higher abnormal ratio (100%; p =.011, Fisher's exact test), indicated that cauda equina lesions might be the cause. Urodynamic data from Group 3 showed a significant decrease in maximal urethral closure pressure (48 +/- 17cm H2O, p =.0022, analysis of variance [ANOVA], repeated measure) and an increase in bladder capacity (429 +/- 194mL, p =.037, ANOVA, repeated measure). There were no significant changes in the other groups. CONCLUSION: Neurourologic abnormalities are less predictable with injuries to thoracolumbar junction, except in patients with cauda equina lesions.

Adult↗
PubMed2001

Quantitative and morphological characteristics of the human corneal endothelium in relation to age, gender, and ethnicity in cataract populations of South Asia.

PURPOSE: To describe the differences of corneal endothelial cell densities, cell size variability and cell hexagonality in cataract populations of south Asia between sexes and ethnic groups. METHODS: 1,235 eyes of 1,235 male and female patients 40-75 years of age with senile cataract were examined with non contact specular microscopy with semi-automated analysis technique. The cell data of the study population was analyzed in relation to age, sex, and ethnic groups. Mean arithmetic differences and the coefficient of variation of repeated observations were calculated to estimate precision of the technique utilized. The main outcome measures were corneal endothelial cell density, cell size variability and cell hexagonality. RESULTS: The mean corneal endothelial cell density was 2,720 cells/mm2, mean cell size variability was 37.8% and percent cell hexagonality 40%. We found statistical significant difference between the three ethnic populations in all the corneal endothelial cell measurements (p<0.0001). Females had a 2.9% greater cell density than males (p = 0.0001). There was no significant difference in mean cell density according to age. Variability of cell size, however, increased with age (p<0.001). These findings were consistent across the three ethnic groups. CONCLUSIONS: In a total sample of 1,235 eyes distributed evenly in three cataract patient populations of south Asia, we found statistically significant differences of corneal endothelial cell densities of cell size variability and cell hexagonality between sexes and ethnic groups.

Adult↗
PubMed2001

Relative accuracy of nucleic acid amplification tests and culture in detecting Chlamydia in asymptomatic men.

Published estimates of the sensitivity and specificity of PCR and ligase chain reaction (LCR) for detecting Chlamydia trachomatis are potentially biased because of study design limitations (confirmation of test results was limited to subjects who were PCR or LCR positive but culture negative). Relative measures of test accuracy are less prone to bias in incomplete study designs. We estimated the relative sensitivity (RSN) and relative false-positive rate (RFP) for PCR and LCR versus cell culture among 1,138 asymptomatic men and evaluated the potential bias of RSN and RFP estimates. PCR and LCR testing in urine were compared to culture of urethral specimens. Discordant results (PCR or LCR positive, but culture negative) were confirmed by using a sequence including the other DNA amplification test, direct fluorescent antibody testing, and a DNA amplification test to detect chlamydial major outer membrane protein. The RSN estimates for PCR and LCR were 1.45 (95% confidence interval [CI] = 1.3 to 1.7) and 1.49 (95% CI = 1.3 to 1.7), respectively, indicating that both methods are more sensitive than culture. Very few false-positive results were found, indicating that the specificity levels of PCR, LCR, and culture are high. The potential bias in RSN and RFP estimates were <5 and <20%, respectively. The estimation of bias is based on the most likely and probably conservative parameter settings. If the sensitivity of culture is between 60 and 65%, then the true sensitivity of PCR and LCR is between 90 and 97%. Our findings indicate that PCR and LCR are significantly more sensitive than culture, while the three tests have similar specificities.

Bias↗
PubMed2001

Molecular cloning and characterization of a novel human gene (HSPBAP1) from human fetal brain.

Rat PASS1 is a novel protein binding specifically to hsp27 and thus plays a role in regulating stress response in the living cell. Here we report on a human homologue of PASS1, encoded by the gene HSPBAP1. The gene was cloned and identified during a large-scale sequencing analysis of a human fetal brain cDNA library. The human protein shared 80% amino acid identity with rat PASS1. According to bioinformatics analysis, the HSPBAP1 gene is located on chromosome 3q21. RT-PCR analysis indicated that HSPBAP1 was abundant in thymus and pancreas but had a ubiquitously low expression pattern in other human adult tissues except for brain where it was absent.

Amino Acid Sequence↗
PubMed2001

Adenoviral vector-mediated gene transfer for human gene therapy.

Human gene therapy promises to change the practice of medicine by treating the causes of disease rather than the symptoms. Since the first clinical trial made its debut ten years ago, there are over 400 approved protocols in the United States alone, most of which have failed to show convincing data of clinical efficacy. This setback is largely due to the lack of efficient and adequate gene transfer vehicles. With the recent progress in elucidating the molecular mechanisms of human diseases and the imminent arrival of the post genomic era, there are increasing numbers of therapeutic genes or targets that are available for gene therapy. Therefore, the urgency and need for efficacious gene therapies are greater than ever. Clearly, the current fundamental obstacle is to develop delivery vectors that exhibit high efficacy and specificity of gene transfer. Recombinant adenoviruses have provided a versatile system for gene expression studies and therapeutic applications. Of late, there has been a remarkable increase in adenoviral vector-based clinical trials. Recent endeavors in the development of recombinant adenoviral vectors have focused on modification of virus tropism, accommodation of larger genes, increase in stability and control of transgene expression, and down-modulation of host immune responses. These modifications and continued improvements in adenoviral vectors will provide a great opportunity for human gene therapy to live up to its enormous potential in the second decade.

Adenoviridae↗
PubMed2001

Electroacupuncture-induced neural activation detected by use of manganese-enhanced functional magnetic resonance imaging in rabbits.

OBJECTIVE: To investigate the effects of acupuncture on neural activity detected by use of manganese-enhanced functional magnetic resonance imaging (fMRI) and elucidate the relationship between somatic acupoint stimulation and brain activation. ANIMALS: 40 New Zealand White rabbits. PROCEDURE: Manganese-enhanced fMRI was performed in anesthetized rabbits manipulated with electroacupuncture (EA) on Zusanli (ST-36) and Yanglingquan (GB-34) acupoints. Image acquisition was performed on a 1.5T superconductive clinical scanner with a circular polarized extremity coil. T1-weighted images were acquired sequentially as follows: baseline, after mannitol injection, after manganese infusion, and 5 and 20 minutes after initiation of EA. RESULTS: Changes in focal neural activity were detected by use of manganese-enhanced fMRI. Stimulation on Zusanli (ST-36) for 5 minutes resulted in activation of the hippocampus, whereas stimulation on Yanglingquan (GB-34) resulted in activation of the hypothalamus, insula, and motor cortex. Activation became less specific after 20 minutes of EA. Furthermore, stimulation on ipsilateral acupoints led to bilateral brain activation. CONCLUSIONS AND CLINICAL RELEVANCE: Each acupoint has a corresponding cerebral linkage, and stimulation on these points resulted in time-dependent neural activation. Understanding the linkage between peripheral acupoint stimulation and central neural pathways may provide a useful guide for clinical applications of acupuncture.

Animals↗
PubMed2001

A metastatic pituitary carcinoid tumor successfully treated with gamma knife radiosurgery.

Intracranial metastasis occurs in a certain number of patients with carcinoid tumor. However, carcinoid tumor with metastasis to the pituitary gland is extremely rare. Up to the present, no effective treatment for either a metastatic intracranial carcinoid tumor or a metastatic pituitary lesion of any origin has been documented. We have treated a case of metastatic carcinoid tumor of the pituitary gland with transsphenoidal tumor resection followed by gamma knife radiosurgery. A 59-year-old man presented with headache and left oculomotor palsy. He was treated at the same hospital for bronchial atypical carcinoid tumor one and a half years ago. Magnetic resonance image of the brain showed a pituitary tumor. There were no signs of recurrent or metastatic lesion elsewhere despite thorough investigation. Transsphenoidal approach for removal of tumor was done and the pathology turned out to be a metastatic carcinoid tumor. Subsequent gamma knife radiosurgery was given for residual tumor. The oculomotor palsy improved after radiosurgery. No neurological deficit occurred. Follow-up CT scan of the brain showed complete resolution of the tumor. We concluded that gamma knife radiosurgery could be used to treat a metastatic intracranial carcinoid tumor. It can also be used to treat a metastatic lesion of the pituitary gland without causing neurological deficit.

Carcinoid Tumor↗
PubMed2001

[cDNA cloning and sequence analysis of human lactoferrin].

Human lactoferrin (hLF) cDNA was amplified by RT-PCR from normal human mammary tissue obtained from Daxing County of Beijing City of China, and then subcloned into pGEM-T vector. hLF cDNA sequence was determined, which consists of 2136 bp. Comparison with five other hLF cDNA sequences registered in GenBank shows 99% homology in DNA sequence. However, there are two base substitutions (nucleotide 1740 G-->C, nucleotide 1756 T-->C), one of which subsequently leads to an amino acid change (residue 580 Glu-->Asp).

Base Sequence↗