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Biomedical subjects

Y Zhong

Publications and source records attributed to Y Zhong.

At least 109 records · Page 6Linked to original sources

Analysis of allele distribution for six short tandem repeat loci in the French Canadian population of Québec.

Short tandem repeat (STR) loci represent a rich source of highly polymorphic markers in the human genome which are useful for the purposes of forensic identification and determination of biological relatedness of individuals. Here, as a part of an ongoing extensive study, we report the analysis of a multilocus genotype survey of 642 to 870 chromosomes in the French Canadian Caucasian population of Québec at six STR loci. The loci HUMCSF1PO, HUMTPOX, HUMTH01, HUMF13A01, HUMFESFPS, and HUMvWA were typed using two multiplex polymerase chain reactions (PCR). Amplified DNA samples were subsequently analyzed by polyacrylamide gel electrophoresis followed by silver staining. The heterozygote frequencies of the loci range from 0.614 to 0.820 (0.661 to 0.818 expected) and the number of alleles from 7 to 12 per locus. Although statistically significant deviation from Hardy-Weinberg expectations of genotype frequencies was noted at some loci by one or more tests, in general, the genotype frequencies are well estimated from the product of allele frequencies at all loci. The most frequent six-locus genotype is expected to occur in the French Canadian population with a frequency of 3.50 by 10(-5) and together, these six loci have an average probability of discrimination of 0.9999985. The study presented here indicates that these six STR loci are informative genetic markers for identity testing purposes in the French Canadian Caucasian population of Québec.

Adult↗

[A prospective study on respiratory symptoms and functions in new employees exposed to cotton dust].

Sixty new employees in a cotton textile mill were followed up for five years to study their occurrence of byssinosis and its natural history. Results showed that the workers complained more cough, expectoration and other respiratory irritation symptoms at their early exposure to cotton dust, and the frequency of chest tightness in them reached the peak one year after exposure and remained at higher level later. Stratified analysis showed that all the respiratory symptoms did not correlate with their smoking habits, specific body constitution, etc. Forced expiratory volume at one second (FEV1) after shift declined with length of exposure and appeared a tendency to exacerbate gradually, especially in workers with a positive skin test of cotton antigen. Smoking had no influence on it. It suggests that exposure to cotton dust and idiosyncracy of the workers play important roles in damage to lung function.

Adolescent↗

Estimation of mutation rates from parentage exclusion data: applications to STR and VNTR loci.

Nonpaternity is a common source of bias in estimating mutation rates when they are obtained from family data showing discordance of parental and children's genotypes. With the availability of hypervariable DNA markers, this source of bias can be largely eliminated. However, the proportion of cases where parentage exclusion is caused by presumed mutation(s) of parental alleles must be adjusted to obtain a valid mutation rate estimate. The present work derives the basis of this adjustment factor, called the proportional bias. This proportional bias depends upon the allele frequency distribution at the locus. The maximum and minimum bounds of the proportional bias depend on the number of alleles at the locus. Using data from Caucasian populations at tandem repeat loci commonly used for parentage testing and forensic identification purposes, we show that when mutation rates are estimated at these loci, the proportional bias is generally very close to the maximum possible value for the observed number of alleles (or binned fragment sizes) at each locus. The expected proportional bias decreases with increasing mutation rate at a locus. For the short tandem repeat loci, without bias correction, the direct count method can result in an underestimation of up to 60% of their true value. In contrast, for the minisatellite VNTR loci, even with crude measurements on allele sizes, we show that the absolute proportional bias is generally below the coefficient of variation of the direct estimates.

Chromosome Mapping↗

Localization of 7H6 tight junction-associated antigen along the cell border of vascular endothelial cells correlates with paracellular barrier function against ions, large molecules, and cancer cells.

To study the regulation of the endothelial barrier, we examined the relationship between the paracellular barrier function and the expression of 7H6 antigen localized at tight junctions of endothelial cells by using transendothelial electrical resistance (TER), fluxes of albumin and dextran, transmigration of rat mammary cancer (SST-2) cells across rat lung endothelial (RLE) cells, and immunocytochemical expression of 7H6 antigen as parameters. RLE cells cultured at a confluent cell density did not express immunohistochemically demonstrable 7H6 antigen and had low paracellular barrier functions. However, treatment of the endothelial cells with 0.5 mM dibutyryl-cAMP or 10(-6) M all-trans-retinoic acid for 4 days induced 7H6 antigen preferentially at the cell border and simultaneously enhanced the barrier function twofold, in terms of TER and fluxes of albumin and dextran. Furthermore, RA-treated RLE cell monolayers with the enhanced barrier function significantly inhibited the transmigration of SST-2 cells. These results together with those of our previous study indicate that 7H6 antigen has a crucial role in the regulation of paracellular barrier function not only in epithelial cells but also in vascular endothelial cells. The present study also suggests that tight junctions of vascular endothelium in vivo function as a barrier between blood and tissues against metastatic cancer cells.

Animals↗

Pharmacological characterisation of multiple components in the enhancement by pregnanolone and propofol of [3H]flunitrazepam binding to GABAA receptors.

The enhancement by pregnanolone (5 beta-pregnan-3 alpha-ol-20-one) and propofol (2,6-diisopropylphenol) of [3H]flunitrazepam (FNZ) binding to GABAA receptors in rat whole brain homogenate has been investigated. Two components in the concentration-effect relationship for pregnanolone were distinguished by the sensitivity of one component to antagonism by bicuculline and enhancement by muscimol, and the selective but weak antagonism of the bicuculline-insensitive component by 11-ketoprogesterone (4-pregnen-3,11,20-trione). Unlike pregnanolone, the enhancement by propofol of [3H]FNZ binding appeared to comprise a single component which was insensitive to 11-ketoprogesterone and was only slightly antagonised by bicuculline and slightly enhanced by muscimol. These results provide evidence for distinct GABA-dependent and GABA-independent components of the action of pregnanolone in the enhancement of [3H]FNZ binding, with the GABA-independent component being sensitive to 11-ketoprogesterone. The data also support the suggestion of different binding sites for pregnanolone and propofol.

Anesthetics, Intravenous↗

Enhanced paracellular barrier function of rat mesothelial cells partially protects against cancer cell penetration.

To study pathophysiological roles of mesothelial barrier functions in protection against cancer cell invasion, we isolated mesothelial cells from the rat abdominal cavity and then cultured them with 10(-6)M all-trans-retinoic acid (RA) for 10 days. Mesothelial barrier function assessed by measuring transcellular electrical resistance (TER) and the expression of 7H6 tight junction-associated antigen at the cell border were induced by the treatment (10.01 +/- 0.8 vs 6.05 +/- 0.7 omega cm2, without RA; mean +/- s.e.m., n = 10). Then we quantified the attachment and penetration of rat mammary cancer cells (SST-2 cells) into the mesothelial cell monolayer by prelabelling of the cancer cells with fluorescent dye and by observing optical sections at different heights using a laser confocal scanning microscope. When SST-2 cells were overlaid onto the mesothelial cell monolayer treated with RA, the number of cancer cells found at the basal level of the monolayer was significantly reduced. These results showed that enhanced mesothelial barrier function at least partially prevents the penetration of cancer cells into mesothelial cells and suggested that 7H6 antigen serves as a reliable immunocytochemical marker for monitoring mesothelial barrier function.

Animals↗

Cancer incidence among Icelandic pesticide users.

BACKGROUND: This study was done to examine the cancer risk among pesticide users in Iceland. METHODS: We have followed a cohort of 2449 licensed pesticide users, students from a horticultural college, members of a pension fund for market gardeners, horticulturists and vegetable farmers up until the end of 1993 in the Icelandic Cancer Registry of cancer incidence. The observed number of cancers was compared with expected values calculated on the basis of cancer incidence for males and females in Iceland. RESULTS: The standardized incidence ratio (SIR) for all cancer sites was 0.80. Among females the increased incidence for cancer of lymphatic and haematopoietic tissue was significant (SIR = 5.56, 95% confidence interval (CI) 1.12-16.23). The incidence of rectal cancer was three times that expected (SIR = 2.94, 95% CI: 1.07-6.40), and this cancer was even more predominant among the licensed pesticides users (SIR = 4.63, 95% CI: 1.49-10.80). All cancers of the rectum were adenocarcinoma, however, one was adenocarcinoma in villous adenoma and one adenocarcinoma in tubulo-villous adenoma. CONCLUSION: The results provide some support for the suggestion that pesticide exposure may lead to cancer of the lymphatic and haematopoietic tissue in females. We suggest that some of the pesticides to which the licensed pesticide users were exposed may lead to rectal cancer.

Aged↗

Distribution and evolution of CTG repeats at the myotonin protein kinase gene in human populations.

We have analyzed the CTG repeat length and the neighboring Alu insertion/deletion (+/-) polymorphism in DNA samples from 16 ethnically and geographically diverse human populations to understand the evolutionary dynamics of the myotonic dystrophy-associated CTG repeat. Our results show that the CTG repeat length is variable in human populations. Although the (CTG)5 repeat is the most common allele in the majority of populations, this allele is absent among Costa Ricans and New Guinea highlanders. We have detected a (CTG)4 repeat allele, the smallest CTG known allele, in an American Samoan individual. (CTG) > or = 19 alleles are the most frequent in Europeans followed by the populations of Asian origin and are absent or rare in Africans. To understand the evolution of CTG repeats, we have used haplotype data from the CTG repeat and Alu(+/-) locus. Our results are consistent with previous studies, which show that among individuals of Caucasian and Japanese origin, the association of the Alu(+) allele with CTG repeats of 5 and > or = 19 is complete, whereas the Alu(-) allele is associated with (CTG)11-16 repeats. However, these associations are not exclusive in non-Caucasian populations. Most significantly, we have detected the (CTG)5 repeat allele on an Alu(-) background in several populations including Native Africans. As no (CTG)5 repeat allele on an Alu(-) background was observed thus far, it was proposed that the Alu(-) allele arose on a (CTG)11-13 background. Our data now suggest that the most parsimonious evolutionary model is (1) (CTG)5-Alu(+) is the ancestral haplotype; (2) (CTG)5-Alu(-) arose from a (CTG)5-Alu(+) chromosome later in evolution; and (3) expansion of CTG alleles occurred from (CTG)5 alleles on both Alu(+) and Alu(-) backgrounds.

Biological Evolution↗

Artificial neural network to assist psychiatric diagnosis.

BACKGROUND: Artificial Neural Network (ANN), as a potential powerful classifier, was explored to assist psychiatric diagnosis of the Composite International Diagnostic Interview (CIDI). METHOD: Both Back-Propagation (BP) and Kohonen networks were developed to fit psychiatric diagnosis and programmed (using 60 cases) to classify neurosis, schizophrenia and normal people. The programmed networks were cross-tested using another 222 cases. All subjects were randomly selected from two mental hospitals in Beijing. RESULTS: Compared to ICD-10 diagnosis by psychiatrists, the overall kappa of BP network was 0.94 and that of Kohonen was 0.88 (both P < 0.01). In classifying patients who were difficult to diagnose, the kappa of BP was 0.69 (P < 0.01). ANN-assisted CIDI was compared with expert system assisted CIDI (kappa = 0.72-0.76); ANN was more powerful than a traditional expert system. CONCLUSION: ANN might be used to improve psychiatric diagnosis.

Adult↗

[Preparation of galactosyl-cytochrome C and studies on its hepatic targeting property].

This paper reports the preparation of the coupling compound between thiogalactose and cytochrome C(Cyt-C). The binding tests of this compound to asialoglycoprotein receptor have also been carried out in vivo. The results show that the pharmacokinetics of this compound is in accordance with the basic characteristic of receptor induced binding. The highest uptake of liver reaches to 32.9% and at the same time the conjugate remains 78.6% the biological activity of Cyt-C. It is possibly a hepatic targeting drug or a hepatic targeting carrier.

Animals↗

Mediation of PACAP-like neuropeptide transmission by coactivation of Ras/Raf and cAMP signal transduction pathways in Drosophila.

Much work on the signal transduction mechanisms underlying neurotransmission has been directed towards studying the roles of the cyclic AMP and phosphoinositide pathways. Upon ligand binding, the transmitter receptors interact with heterotrimeric G proteins, allowing G alpha and G beta gamma subunits to disengage. The free G alpha then modulates the activity of adenylyl cyclase and phospholipase C. It has been suggested that the G beta gamma complex which is activated through muscarinic or neuropeptide receptors can stimulate mitogen-activated protein kinase (MAPK) via activation of the small guanine-nucleotide-binding protein Ras. Sequential activation of the intermediates in the Ras/Raf serine-threonine protein kinase/MAPK kinase/MAPK/transcription factor pathway has emerged as a central mechanism for controlling cell proliferation and differentiation in yeast, worms, fruitflies and mammals. Here we show, by analysis of Drosophila mutants, that synaptic current and modulation of K+ current, triggered by a pituitary adenylyl cyclase-activating polypeptide-like neuropeptide, are mediated by coactivation of the Ras/Raf and Rutabaga-adenylyl cyclase pathways. Thus the Ras/Raf pathway also appears to be essential for G-protein-coupled neurotransmission.

Adenylyl Cyclases↗

A novel synaptic transmission mediated by a PACAP-like neuropeptide in Drosophila.

Neuropeptide-mediated transmission was analyzed at Drosophila larval body-wall neuromuscular junctions. Focal application of vertebrate pituitary adenylyl cyclase-activating polypeptide (PACAP38) to the neuromuscular junction region triggered two temporally distinct muscle responses: an immediate depolarization followed by a large enhancement of K+ current. This late enhancement occurred many minutes after the early depolarization. High frequency stimulation of motor nerve fibers evoked a postsynaptic response mimicking that induced by PACAP38. This evoked response was desensitized by preincubation of the preparation with PACAP38. PACAP38-like immunoreactivity was also found in the Drosophila CNS and at almost all larval neuromuscular junctions. Moreover, an immunoreactive band that compares well with PACAP38 in size was identified in Western blot. These results demonstrate that a PACAP-like peptide may function in invertebrates and that a neuropeptide can evoke two distinct postsynaptic responses, each separated by up to 15 min. In addition, this initial electrophysiological study provides a basis for genetic analysis of neuropeptide function in Drosophila.

Animals↗

Development of the blood-retinal barrier in vitro: formation of tight junctions as revealed by occludin and ZO-1 correlates with the barrier function of chick retinal pigment epithelial cells.

To elucidate the molecular mechanisms of the blood-retinal barrier (BRB), we examined chick retinal tissues histochemically using antibodies against tight junction proteins such as ZO-1, 7H6 antigen, and occludin. Retinal pigment epithelial (RPE) cells in situ in chickens and late chick embryos expressed all of the tight junctional proteins examined, showing that tight junctions seal the cell borders of chick RPE cells in vivo. On the other hand, RPE cells isolated from late chick embryos and transferred in vitro did not express occludin, ZO-1 and 7H6 antigen. The effects of differentiation-inducing agents, such as retinoic acid, dexamethasone and dimethyl sulfoxide (DMSO) were tested. Only DMSO induced an increase in transepithelial electrical resistance (TER) in a time-dependent manner. Under supplementation with DMSO, immunofluorescently demonstrable occludin and ZO-1 were induced progressively at cell borders in parallel with the increase in TER that occurred with decreases in inulin and dextran permeability. Electron microscopically tight junction-like junctional apparatus were induced in RPE cells. These results indicated that tight junctions of RPE cells play an important role in the formation of the BRB.

Animals↗

A new data model for biological classification.

In the domain of biological classification, classifications are performed hierarchically. There are no standard classifications which are unanimously accepted by the community of each domain; many different interacting views of classification exist about the same data, and the discovery of new data results in changes to the existing classification. Even a single individual may change his or her own classification of a particular group. Since multiple classification views interact, they are semantically related. It is difficult to model this kind of dynamically evolving and semantically interacting classification system using traditional data models, which lack the structural flexibility necessary to support dynamic views of hierarchic classifications, and cannot properly capture the history of these complex interactions. We have developed a new data model which is suitable for supporting semantically interacting dynamic views of hierarchic biological classifications. On the basis of our new data model we have developed a prototype database system called HICLAS (HIerarchical CLAssification System); its domain is plant taxonomy. HICLAS is available through the Internet and an X-window interface has been implemented to support queries to classification data.

Classification↗

Altered nerve terminal arborization and synaptic transmission in Drosophila mutants of cell adhesion molecule fasciclin I.

This work investigates the role of cell adhesion molecules in development of synaptic connections and functions through a genetic approach. Fasciclin I (Fas I) is an insect glycoprotein capable of mediating homophilic cell adhesion. It has been shown that Fas I is expressed in motor nerve axons and terminals that innervate larval body-wall muscles in Drosophila. Immunohistochemical analysis of these motor nerve terminals has revealed that nerve terminal arborization, quantified by the numbers of the nerve terminal branches and varicosities, is enhanced in the null mutant fas ITE. In contrast, the number of branches and varicosities are reduced in larvae that overexpress the Fas I molecule resulting from additional copies of the fas I transgene in P(fas I+) or the chromosome duplication in Dp(fas I) mutants. Although arborization is altered, the overall stereotypical pattern of nerve terminal innervation of the body-wall muscle fibers is preserved in all the Fas I mutants examined. The voltage-clamp analysis of excitatory junctional currents (ejcs) at the neuromuscular junction indicates that the amplitude of ejcs is reduced in fas ITE, but increased in P(fas I+) and Dp(fas I) compared to that in wild-type larvae. Further electrophysiological analysis shows that the quantal content and the evoked frequency-dependent response are affected in these mutants, indicating a defective presynaptic function in addition to the anatomic abnormality. Therefore, the cell adhesion molecule Fas I may not be essential for target recognition and synaptogenesis at the larval neuromuscular junction, but may play a role in fine-turning nerve terminal arborization and possibly in modifying, directly or indirectly, development of presynaptic functions.

Animals↗

[Apolipoprotein (a) phenotypes of patients with myocardial infarction].

We studied apolipoprotein (a) (apo(a)) phenotypes of 69 myocardial infarction survivors and 56 stroke patients, and compared them with those of 190 healthy Chinese. The distribution of apo(a) phenotype frequency in cardio-cerebrovascular disease patients was different from those of controls. The frequency of the phenotypes B, S1 and S2 in patients was remarkably higher than that in controls within the same single-band apo(a) phenotype. Moreover, the Lp(a) serum concentrations in CCVD patients were significantly higher than those in controls within the same single-band apo(a) phenotype.

Aged↗

Characterization of K+ currents and the cAMP-dependent modulation in cultured Drosophila mushroom body neurons identified by lacZ expression.

Electrophysiological analysis of cultured neurons provides a potential approach toward understanding the physiological defects that may contribute to abnormal behavior exhibited by mutants of the fruit fly Drosophila. However, its application has been restricted by an inability to identify a particular functional or anatomical subpopulation of neurons from the CNS. To study neurons composing the CNS mushroom body proposed as a center for insect olfactory learning, we utilized a Drosophila enhancer detector line that expresses a lacZ reporter gene in these neurons and identified them in acutely dissociated larval CNS cultures by vital fluorescent staining. The patch-clamp analysis suggests that whole-cell voltage-activated K+ currents can be classified into two types in identified mushroom body neurons. Type 1 current comprises a TEA-sensitive slowly inactivating current and noninactivating component while type 2 current contains a 4-AP-sensitive transient A-current and a noninactivating component. Application of cAMP analogs induced distinct modulation of type 1 and type 2 currents. Our results demonstrate that the expression of the lacZ gene and the subsequent staining do not significantly alter the different types of K+ currents. This initial characterization provides a basis for further analysis of mutations that impair learning and memory resulting from an abnormal cAMP cascade preferentially expressed in the mushroom body.

Animals↗