Biomedical subjects

Y Cheng

Publications and source records attributed to Y Cheng.

At least 37 records · Page 2Linked to original sources

PubMed1998

Virtual electrode effects in transvenous defibrillation-modulation by structure and interface: evidence from bidomain simulations and optical mapping.

INTRODUCTION: Our goal in this combined modeling and experimental study was to gain insight into the transmembrane potential changes in defibrillation conditions, namely, when shocks are delivered by an implantable cardioverter defibrillator (ICD). Two hypotheses concerning the presence and characteristics of virtual electrode effects (VEE) during an ICD shock were tested numerically and experimentally: (H1) anisotropy-dependent VEE are induced over a considerable portion of the "bulk" myocardium; and (H2) surface (epicardial and endocardial) VEE are generated under special tissue bath conditions and are not fully anisotropy determined. METHODS AND RESULTS: Optical mapping was performed on Langendorff-perfused rabbit hearts (n = 4) stained with di-4-ANEPPS. Monophasic shocks were applied during the plateau phase of an action potential through a 9-mm long distal electrode in the right or left ventricle and a 6-cm proximal electrode positioned 3 cm posteriorly to the heart. We modeled the experiment using an ellipsoidal bidomain heart with transmural fiber rotation, placed in a perfusing bath, and subjected to defibrillation shocks delivered by an electrode configuration as described. Our numerical simulations demonstrated VEE occupying a significant portion of the myocardium in the conditions of unequal anisotropy ratios for the intra- and extracellular domains. Statistically significant differences in epicardial polarization patterns were predicted numerically and confirmed experimentally when the interface conditions varied. CONCLUSION: The present study concludes that VEE are present in transvenous defibrillation. They are shaped by the combined effect of cardiac tissue characteristics and interface conditions. Because of their size, VEE might contribute significantly to defibrillation outcome.

Animals↗

PubMed1998

Two alternatively spliced transcripts from the Drosophila period gene rescue rhythms having different molecular and behavioral characteristics.

The period (per) and timeless (tim) genes encode key components of the circadian oscillator in Drosophila melanogaster. The per gene is thought to encode three transcripts via differential splicing (types A, B, and C) that give rise to three proteins. Since the three per mRNA types were based on the analysis of cDNA clones, we tested whether these mRNA types were present in vivo by RNase protection assays and reverse transcriptase-mediated PCR. The results show that per generates two transcript types that differ only by the presence (type A) or absence (type B') of an alternative intron in the 3' untranslated region. Transgenic flies containing transgenes that produce only type B' transcripts (perB'), type A transcripts (perA), or both transcripts (perG) rescue locomotor activity rhythms with average periods of 24.7, 25.4, and 24.4 h, respectively. Although no appreciable differences in type A and type B' mRNA cycling were observed, a slower accumulation of PER in flies making only type A transcripts suggests that the intron affects the translation of per mRNA.

Alternative Splicing↗

PubMed1997

Control of mouse U1 snRNA gene expression during in vitro differentiation of mouse embryonic stem cells.

Early in mouse development, two classes of U1 RNAs, mU1a and mU1b, are synthesized, but as development proceeds, transcription of the embryo-specific mU1b genes is selectively down-regulated to a barely detectable level. We show here that during in vitro differentiation of mouse embryonic stem (ES) cells, both exogenously introduced and endogenous U1b genes are subject to normal developmental regulation. Thus, ES cells represent a convenient isogenic system for studying the control of expression of developmentally regulated snRNA genes. Using this system, we have identified a region in the proximal 5'flanking region, located outside the PSE element, that is responsible for differential transcription of the mU1a and mU1b genes in both developing cells and transiently transfected NIH 3T3 cells.

3T3 Cells↗

PubMed1997

Equilibrium and non-equilibrium conformations of peptides in lipid bilayers.

A synthetic, hydrophobic, 27-amino-acid-residue peptide 'K27', modelled on the trans-membrane domain of the slow voltage-gated potassium channel, IsK, has been incorporated into a lipid bilayer and its conformational properties studied using FT-IR spectroscopy. The conformation following reconstitution is found to be dependent on the nature of the solvent employed. When the reconstitution is conducted by solvent evaporation from a methanol solution, aggregates comprised of beta-strands are stabilised and their concentration is essentially invariant with time. By contrast, when trifluoroethanol is used, the initial conformation of the peptide is alpha-helical. This then relaxes to an equilibrium state between alpha-helices and beta-strands. The alpha-helix-to beta-strand conversion rate is relatively slow, and this allows the kinetics to be studied by FT-IR spectroscopy. The reverse process is much slower but again can be demonstrated by FT-IR. Thus, it appears that a true equilibrium structure can only be achieved by starting with peptide in the alpha-helical conformation. We believe this result should be of general validity for hydrophobic peptide reconstitution. The implications for conformational changes in membrane proteins are discussed.

Amino Acid Sequence↗

PubMed1997

The Drosophila protein Wunen repels migrating germ cells.

In Drosophila, germ cells migrate in embryonic development from the lumen of the developing gut towards the overlying mesoderm, where they enter the gonads. The gene wunen is responsible for guiding the germ cells early in this process. Here we report that the protein Wunen has two properties that allow it to use repulsion to guide the germ cells. Wunen can transform a permissive cellular environment into a repulsive one, and is expressed in the gut in a pattern that guides germ cells towards the mesoderm. Wunen shows strong similarity to the enzyme type 2 phosphatidic acid phophatase (PAP2)4, suggesting that it is involved in lipid metabolism.

Amino Acid Sequence↗

PubMed1997

Marked age-dependent neuroprotection by brain-derived neurotrophic factor against neonatal hypoxic-ischemic brain injury.

Hypoxic-ischemic brain injury in survivors of perinatal asphyxia is a frequently encountered clinical problem for which there is currently no effective therapy. Neurotrophins, such as brain-derived neurotrophic factor (BDNF), can protect responsive neurons against cell death in some injury paradigms. While the role of BDNF in hypoxic-ischemic brain injury is not clear, evidence suggests that BDNF may have different effects in the developing, as opposed to the adult, brain. We found that a single intracerebroventricular (ICV) injection of BDNF resulted in rapid and robust phosphorylation of trk receptors in multiple brain regions in the postnatal day (PD) 7 rat brain. BDNF also markedly protected against hypoxic-ischemic brain injury at PD7. It protected against 90% of tissue loss due to hypoxic-ischemia when given just prior to the insult and against 50% of tissue loss when give after the insult. In contrast, ICV injection of BDNF in PD21 and adult rats resulted in little trk phosphorylation and less dramatic protection against unilateral hypoxic-ischemic injury at PD21. Because of its potent neuroprotective actions in the developing brain, BDNF may be a potential treatment for asphyxia and other forms of acute injury in the perinatal period.

Age Factors↗

PubMed1997

The use of electron tomography for structural analysis of disordered protein arrays.

A method based on Fourier transforms is described for obtaining a 3-D reconstruction from a paracrystalline object with static disorder. The method is derived from the standard methods used in 3-D reconstruction of 2-D crystals except that all of the Fourier coefficients are used and not just the sampled data from the periodic lattice. Thus, not only is the spatially ordered part of the structure visualized in 3-D, but also the spatially disordered part. Application of the method to 3-D reconstructions Application of the method to 3-D reconstructions of insect flight muscle is described as well as prospects for extension of the method to radiation-sensitive specimens.

Algorithms↗

PubMed1997

Contraceptive practices of women requesting termination of pregnancy: a study from China.

In order to develop a program for prevention of unwanted pregnancies, we conducted a survey of contraceptive practices and reasons for contraceptive failures of 1520 women seeking abortion at eight large hospitals in Zheng Zhou City, Henan Province, P.R. China, during the period from March 1996 to May 1996. The most frequent cause of the unplanned pregnancy was contraceptive failure (71.9%) 61.7% (938) of these current pregnancies were potentially predictable by virtue of nonuse of contraception (427) or by recognition of contraceptive failures (511). Among the contraceptive failures, the proportion of condom mishaps was the highest (29.7%), next was IUD failures (23.5%), then rhythm miscalculation (15.9%). Most of abortion seekers (77.1%) used some contraceptive methods previously. But only 19.7% of them used a contraceptive method at the first sexual intercourse. Among 1520 abortion seekers. 57.6% had used condoms previously; 50.9% of the condom users had at least one instance of condom mishap. The rhythm method had been used by 31.7% of abortion seekers previously; 59.1% of the rhythm users had at least one instance of rhythm failure. Of the 16.8% of abortion seekers who had used pills, 58.0% of them had pill failures Among condom and pill failures, most of them (46.4% condom users and 56.0%, pill users) belonged to the users failure category (poor compliance). Of those seeking abortion 56.4% had experienced at least one instance of previous abortion; 5.3% had experienced previous abortions at least two times. Emergency contraception had been utilized by only 10 subjects prior to this current pregnancy.

Abortion, Induced↗

PubMed1997

Alzheimer-type of pathological changes in Chinese.

There has been no previous description of the pathological features of Alzheimer's disease and little description of Alzheimer-type changes in Chinese brains. In this study, we examined the brains of 17 cases of Alzheimer's disease and concurrently 95 consecutive autopsy cases of non-demented patients aged above 60. Six standard regions of the brains were stained for beta-amyloid immunostaining, Bielschowsky and Bodian. Neuritic plaques, neurofibrillary tangles and diffuse plaques were quantified as per mm2. The Alzheimer's disease brains exhibited a marked increase of neurodegenerative changes over the non-demented brains. Plaque counts were similar to those proposed by Khachaturian (1985; Arch. Neurol. 42: 1097-1105) and CERAD, although the distribution of tangles was more variable with some regions of the neocortex containing few or no tangles. For the non-demented brains, overall neuritic plaques were seen in 31% and neurofibrillary tangles were seen in 42% of cases, with the overall plaque score being 1.8 per mm2 and tangle score being 0.7 per mm2. No age-dependent variation of plaque count and tangle count could be demonstrated in this group of elderly brains. Comparison with similar studies of Caucasians suggests that neuritic plaques and neurofibrillary tangles were less frequently encountered in aging Chinese brains than among the western populations.

Aged↗

PubMed1997

Ethanol-induced cell death by lipid peroxidation in PC12 cells.

Free radical generation is hypothesized to be the cause of alcohol-induced tissue injury. Using fluorescent cis-parinaric acid and TBARS, lipid peroxidation was shown to be increased in the presence of trace amounts of free ferrous ion in PC12 cells. This increase in lipid peroxidation was enhanced by ethanol in a dose dependent manner and also correlated with loss of cell viability, as measured by increased release of lactate dehydrogenase (LDH). Resveratrol, a potent antioxidant, had a protective effect against lipid peroxidation and cell death. These findings strongly suggest that ethanol-induced tissue injury and cell death is a free radical mediated process, and may be important in alcohol-related premature aging and other degenerative diseases.

Animals↗

PubMed1997

Clinical findings for patients with Lyme borreliosis caused by Borrelia burgdorferi sensu lato with genotypic and phenotypic similarities to strain 25015.

In the course of performing culture isolation of Borrelia burgdorferi sensu lato for the diagnosis of Lyme borreliosis in Slovenia, we encountered nine patients who were infected with atypical strains. Molecular analyses of these strains suggested that they were more closely related to the North American tick isolate, strain 25015 (which belongs to the DN127 genomic group of B. burgdorferi sensu lato), than they were to the three species (B. burgdorferi sensu stricto, Borrelia garinii, and Borrelia afzelii) hitherto found to be associated with European Lyme borreliosis. Review of the case histories of these patients revealed some atypical clinical features and variability in clinical presentation. In this study, we present the clinical findings for these patients and discuss their significance for the diagnosis of Lyme borreliosis. The DN127 genomic group shares with B. burgdorferi sensu stricto the distinction of being present in both the Old and New Worlds.

Adult↗

PubMed1997

Molecular subtyping of Borrelia burgdorferi sensu lato isolates from five patients with solitary lymphocytoma.

Solitary lymphocytoma is a rare cutaneous manifestation of Lyme borreliosis that has been reported almost exclusively from Europe. This suggests that its etiologic agent may be absent or extremely rare on the North American continent. All three species of B. burgdorferi sensu lato known to be associated with human Lyme borreliosis (B. burgdorferi sensu stricto, B. garinii, and B. afzelii have been isolated in Europe, whereas only B. burgdorferi sensu stricto has been found in North America. This suggests that either B. garinii or B. afzelii might be the etiologic agent of borrelial lymphocytoma. To investigate this hypothesis we characterized five strains of B. burgdorferi sensu lato isolated from lymphocytoma lesions of patients residing in Slovenia. The methods used included: large restriction fragment pattern analysis of restriction enzyme MluI-digested genomic DNA, plasmid profiling, protein profiling, ribotyping using 5S, 16S, and 23S rDNA probes, and polymerase chain reaction amplification of the rrf (5S)-rrl (23S) intergenic spacer region. Molecular subtyping showed that four of the five isolates belonged to the species B. afzelii; however, this species is the predominant patient isolate in Slovenia and, therefore, may not represent a preferential association with lymphocytoma. The fifth isolate appeared to be most closely related to the DN127 genomic group of organisms. Further characterization of the isolate revealed that it possessed a unique molecular "fingerprint." The results not only show that borrelial lymphocytoma can be caused by B. afzelii but also demonstrate an association with another genomic group of B. burgdorferi sensu lato that is present in North America as well.

Adult↗

PubMed1997

High-resolution fluorescent imaging does not reveal a distinct atrioventricular nodal anterior input channel (fast pathway) in the rabbit heart during sinus rhythm.

INTRODUCTION: We sought to determine the precise pathways of engagement of the AV node during sinus rhythm. METHODS AND RESULTS: Langendorff-perfused rabbit hearts were stained with 20 microM of the voltage-sensitive dye di-4-ANEPPS. Preparations containing the right atrium, sinoatrial (SA) and AV nodes, and interatrial septum were subsequently dissected and mapped in vitro using a 16 X 16 photodiode array with an adjustable resolution of 150 to 750 microns per diode. Motion artifacts were eliminated by using 15 mM 2,3-butanedione monoxime (BDM). Activation time-points were defined as (-dF/dt)max' where F = fluorescence. Isochronal maps of activation were plotted using the triangulation method. In all preparations, spontaneous activation began at the SA node, rapidly spread along the crista terminalis (CrT), entered the AV nodal region via the posterior "slow" pathway, and retrogradely spread to the septal region with a smaller conduction velocity compared to that along the CrT. Collision of anterograde and retrograde wavefronts was frequently observed in the mid-septum. Notably, there was no evidence for the presence of a distinct anterior entrance into the AV node. CONCLUSIONS: Fast pathway conduction during sinus rhythm results from a broad posterior wavefront that envelops the AV node with subsequent retrograde atrial septal activation.

Action Potentials↗

PubMed1997

Effects of 2,3-butanedione monoxime on atrial-atrioventricular nodal conduction in isolated rabbit heart.

INTRODUCTION: 2,3-Butanedione monoxime (BDM) has been found to reversibly block cardiac contraction, without blocking electrical conduction. This study characterizes the dose-dependent effects of BDM on the conduction through the atrioventricular node (AVN) of rabbit heart. METHODS AND RESULTS: Thirteen isolated atrial-AVN preparations were used in control, during and after exposure to 5, 10, and 20 mM BDM. Anterograde and retrograde pacing protocols were used to obtain the Wenckebach cycle length, effective and functional refractory periods of the AVN, index of AVN conduction delay (the area under the AVN conduction curve), as well as index of intra-atrial conduction delay between the AVN inputs. Compared to control, 5 and 10 mM BDM produced either shortening or no effect on all of the above parameters except a slight (6% and 14%, respectively) increase in the intra-atrial delay. At 20 mM, BDM produced a further increase in the intra-atrial delay (up to 50%) as well as in the retrograde AVN conduction delay (up to 16%), while the characteristics of the anterograde conduction were still improved. The effects of perfusion with BDM on these parameters were reversible after washout. CONCLUSIONS: Aside from its known effect as an electromechanical uncoupler, BDM reversibly altered some of the electrical responses of the AVN. Most of these alterations, however, did not impede but rather improved AVN conduction. Since a dose of 10 mM is sufficient to fully eliminate undesirable motion, BDM should be considered a safe and valuable tool in AVN studies in vitro requiring a mechanically quiescent preparation.

Action Potentials↗

PubMed1997

Puumala hantavirus genome in patients with nephropathia epidemica: correlation of PCR positivity with HLA haplotype and link to viral sequences in local rodents.

Reverse transcription-PCR was used to analyze specimens from 20 Finnish nephropathia epidemica (NE) patients hospitalized during the period from October 1994 to January 1995. Blood and/or urine sediment specimens from seven patients were found to be positive for the genome sequences of Puumala hantavirus (PUU). PCR positivity of the specimens from the patients correlated well with the HLA-DRB1*0301 and HLA B8 alleles, which previously were shown to associate with severe courses of NE. Genetic analysis of the partial M-and/or S-segment sequences obtained from three severely ill NE patients revealed three PUU strains related to but distinct from previously reported strains from Finland. The M-segment sequence of PUU from bank voles trapped near the probable site of infection for one of the patients showed 98.2% identity to that of the PUU strain obtained from the patient, suggesting a link between wild-type PUU from the natural focus and the NE case. The S-segment sequences from the patient and the bank voles, however, showed substantially lower identity (95.8%). As this difference in diversity for M and S genes (1.8 and 4.2%) is atypical for PUU genetic drift, one possibility is that the strain acquired at the putative place of infection is a reassortant one.

Adult↗

PubMed1997

Cell culture adaptation of Puumala hantavirus changes the infectivity for its natural reservoir, Clethrionomys glareolus, and leads to accumulation of mutants with altered genomic RNA S segment.

This paper reports the establishment of a model for hantavirus host adaptation. Wild-type (wt) (bank vole-passaged) and Vero E6 cell-cultured variants of Puumala virus strain Kazan were analyzed for their virologic and genetic properties. The wt variant was well adapted for reproduction in bank voles but not in cell culture, while the Vero E6 strains replicated to much higher efficiency in cell culture but did not reproducibly infect bank voles. Comparison of the consensus sequences of the respective viral genomes revealed no differences in the coding region of the S gene. However, the noncoding regions of the S gene were found to be different at positions 26 and 1577. In one additional and independent adaptation experiment, all analyzed cDNA clones from the Vero E6-adapted variant were found to carry substitutions at position 1580 of the S segment, just 3 nucleotides downstream of the mutation observed in the first adaptation. No differences were found in the consensus sequences of the entire M segments from the wt and the Vero E6-adapted variants. The results indicated different impacts of the S and the M genomic segments for the adaptation process and selective advantages for the variants that carried altered noncoding sequences of the S segment. We conclude that the isolation in cell culture resulted in a phenotypically and genotypically altered hantavirus.

Adaptation, Physiological↗

PubMed1997

A two year prospective study to compare culture and polymerase chain reaction amplification for the detection and diagnosis of Lyme borreliosis.

AIM: To compare polymerase chain reaction (PCR) amplification of borrelial DNA and culture isolation of spirochaetes for the diagnosis of Lyme borreliosis by direct detection of Borrelia burgdorferi sensu lato in patients with erythema migrans and acrodermatitis chronica atrophicans lesions. METHODS: Skin biopsy specimens from erythema migrans and acrodermatitis chronica atrophicans lesions were subdivided and tested by PCR amplification assay and culture using two artificial growth media, Barbour-Stoenner-Kelly II (BSK II) and modified Kelly-Pettenkofer (MKP). Five classes of lesions were studied: typical erythema migrans, spontaneously resolved erythema migrans, atypical/partially treated erythema migrans, typical acrodermatitis chronica atrophicans, and atypical/partially treated acrodermatitis chronica atrophicans. RESULTS: For both erythema migrans and acrodermatitis chronica atrophicans lesions, the most sensitive detection method was MKP culture. PCR was less sensitive than MKP culture, but more sensitive than BSK II culture. Results for 758 typical erythema migrans specimens showed positivity rates of 36% for MKP, 25% for PCR, and 24% for BSK II. Differences were statistically significant. The overall positivity rate for all three methods combined was 54%, but few specimens (6%) were positive by all three methods. Examination of multiple erythema migrans lesions from the same patient increased the diagnostic yield. These findings, and similar results for acrodermatitis chronica atrophicans lesions, suggest that the distribution of spirochaetes in skin biopsies is not homogeneous. CONCLUSIONS: Although possessing the potential to provide a rapid diagnosis, PCR is not more sensitive than culture for the direct detection of borrelia. Spirochaetes appear to be unevenly distributed throughout biopsy specimens, suggesting that diagnosis of Lyme borreliosis by direct detection of the causative agent in skin lesions in vulnerable to sample bias.

Acrodermatitis↗

PubMed1997

Mechanism of atrioventricular nodal facilitation in the rabbit heart: role of the distal AV node.

We investigated whether atrioventricular (AV) nodal facilitation is the result of distal AV nodal action potential shortening. Atrial and bundle of His (H) electrograms and microelectrode recordings from proximal and distal AV nodal cells were analyzed in eight superfused rabbit AV node preparations in response to two pacing protocols. In the facilitation protocol, an atrial extrastimulus (A3) was preceded by an atrial impulse (A2) introduced 300, 200, 150, or 125 ms after 30 basic beats (A1). The preexcitation protocol differed from the facilitation protocol by the addition of a premature His depolarization (h2) such that the H1-h2 interval was shorter than the H1-H2 interval. Conduction curves (A3-H3 vs. H2-A3, h2-A3, and A2-A3 intervals) were constructed. Facilitation was demonstrated in all preparations when H2-A3 was used (P = 0.02) but not in the A2-A3 format. Compared with facilitation at the same A1-A2 intervals, preexcitation, despite shortening the distal cellular action potential duration, resulted in longer A3-H3 delays (P = 0.002), shorter A2-A3 intervals, and depression of the proximal nodal cellular response. Thus facilitation does not result from altered distal AV nodal characteristics and instead is a manifestation of an uncontrolled pacing protocol-dependent modulation of proximal AV nodal function.

Action Potentials↗