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Biomedical subjects

L Y Zhang

Publications and source records attributed to L Y Zhang.

At least 37 records · Page 2Linked to original sources

Death the Fas way: regulation and pathophysiology of CD95 and its ligand.

Apoptotic cell death mediated by the members of the tumor necrosis factor receptor family is an essential process involved in the regulation of cellular homeostasis during development, differentiation, and pathophysiological conditions. Among the cell death receptors comprising the tumor necrosis factor receptor superfamily, CD95/APO-1 (Fas) is the best characterized. The specific interaction of Fas with its cognate ligand, Fas ligand (FasL), elicits the activation of a death-inducing caspase (cysteine aspartic acid proteases) cascade, occurring in a transcription-independent manner. Caspase activation executes the apoptosis process by cleaving various intracellular substrates, leading to genomic DNA fragmentation, cell membrane blebbing, and the exposure of phagocytosis signaling molecules on the cell surface. Recent studies have shown that the Fas/FasL pathway plays an important role in regulating the life and death of the immune system through activation-induced cell death. In addition, these molecules have been implicated in aging, human immunodeficiency virus infection, drug abuse, stress, and cancer development. In this review, we will focus on the mechanisms that regulate Fas and FasL expression, and how their deregulation leads to diseases.

Aging↗

Fibrillation potential amplitude to quantitatively assess denervation muscle atrophy.

Denervated muscle fibers exhibit spontaneous, repetitive single muscle fiber discharges and display fibrillation potentials detectable by electromyography. To explore the changing pattern of fibrillation potential amplitude after peripheral nerve injury and its relationship to the degree of muscle atrophy, fibrillation potential amplitudes were recorded on completely denervated biceps brachii of 173 patients with brachial plexus injury. Biceps brachii biopsies were taken at the same sites as the electromyogram recordings in 63 patients. The biopsies were analyzed by ATPase staining and the cross-sectional areas of fast and slow-twitch fibers were calculated. We found that the fibrillation potential amplitude and the cross-sectional areas of denervated muscle decay over time (P < 0.05), and both correlate negatively with denervation time (P < 0.01-0.05) within the first 15 months. The fibrillation potential amplitude correlates positively with both type I and II fiber cross-sectional areas (P < 0.0005-0.01). Our results show that fibrillation potential amplitude is closely correlated with muscle fiber size during the first 15 months after nerve injury, and it may therefore serve as a convenient index to evaluate quantitatively the degree of atrophy of denervated muscles. Electromyographic studies thus may help in designing treatment strategies.

Adolescent↗

Cholesterol homeostasis in rat astrocytoma cells GA-1.

Astrocytes play a key role in cholesterol metabolism in central nervous system. We have shown that fetal rat astrocytes in primary culture secrete cholesterol-rich HDL with the endogenous apolipoprotein (apo) E and generate cholesterol-poor HDL with exogenous apoE and apoA-I [Ito et al. (1999) J. Neurochem. 72, 2362]. In order to study these reactions in relation to the stage of cell differentiation, we examined generation of HDL by rat astrocytoma cells. Lack of apoE secretion was found in three astrocytoma cell lines, human T98G, rat C6, and GA-1 [Kano-Tanaka et al. (1986) Proc. Jpn. Acad. Ser. B 62, 109]. GA-1 produced apoE at very low level and therefore generated much less HDL by itself than the astrocytes in primary culture. In contrast, GA-1 interacted with exogenous apoE and apoA-I to produce cholesterol-rich HDL while the astrocytes produced cholesterol-poor HDL with these apolipoproteins. Cholesterol biosynthesis rate measured from mevalonate was higher and down-regulated more by LDL in the astrocytes than GA-1. On the other hand, the cellular cholesterol level, uptake of LDL, and cyclodextrin-mediated non-specific diffusion of cholesterol from cell surface were same between these two cells. Treatment of GA-1 with acidic fibroblast growth factor influenced neither the production of apoE nor the baseline lipid secretion, but increased the cholesterol synthesis from mevalonate and the magnitude of its down-regulation by LDL, and decreased cholesterol content in the HDL produced by exogenous apoA-I. In conclusion, suppression of apoE biosynthesis in the undifferentiated astrocytes GA-1 resulted in poor secretion of cholesterol-rich HDL and in turn more production of HDL with exogenous apolipoprotein. Cellular cholesterol homeostasis was altered accordingly.

Animals↗

Genetic linkage analysis of susceptibility to particle exposure in mice.

Particle-induced increases in respiratory morbidity and mortality have been observed worldwide in industrialized cities but the toxicologic mechanisms have not been elucidated. It is hypothesized that subpopulations including the elderly and individuals with cardiopulmonary disease are particularly at risk to the effects of exposure. Genetic background is another important host factor that may contribute to interindividual responsivity to particulate exposure. This study was designed to identify susceptibility loci for alveolar macrophage (AM) immune dysfunction induced by inhalation of sulfate-associated carbon particles in susceptible C57BL/6J and resistant C3H/ HeJ inbred mice. AMs were chosen for study because they represent an important component of host defense, and compromised host defense has been hypothesized to be an important factor in particle-induced respiratory morbidity. The quantitative phenotype for these studies was Fc receptor-mediated phagocytic function, an index of AM integrity. Analyses of macrophage dysfunction phenotypes of segregant and nonsegregant populations derived from these two strains indicate that two unlinked genes control susceptibility. A genome-wide linkage analysis of an intercross (F(2)) cohort identified significant and suggestive quantitative trait loci (QTLs) on chromosomes 17 and 11, respectively. Candidate susceptibility genes were identified for mice and humans by comparative mapping. Importantly, both QTLs overlap previously identified QTLs for susceptibility to another common pollutant, ozone. This is the first demonstration that genetic background is an important determinant of responsiveness to particle-induced immune dysfunction, and it has important implications for understanding the epidemiologic associations between particulates and morbidity and mortality.

Air Pollution↗

Genetic susceptibility to ozone-induced lung hyperpermeability: role of toll-like receptor 4.

The pollutant ozone (O(3)) induces lung hyperpermeability and inflammation in humans and animal models. Among inbred strains of mice, there is a 3-fold difference in total protein (a marker of permeability) recovered in bronchoalveolar lavage (BAL) fluid after a 72-h exposure to 0.3 ppm O(3). To determine the chromosomal locations of susceptibility genes, we performed a genome screen using recombinant inbred (RI) strains of mice derived from O(3)-susceptible C57BL/6J (B6) and O(3)-resistant C3H/HeJ (HeJ) progenitors. Each RI strain was phenotyped for O(3)-induced hyperpermeability, and linkage was assessed for 558 markers using Map Manager QTb27. A significant quantitative trait locus (QTL) was identified on chromosome 4. The likelihood ratio chi(2) statistic (16.6) for the peak of the QTL was greater than the significance threshold (16.3) determined empirically by permutation test. This QTL contains a candidate gene, Toll-like receptor 4 (Tlr4 ), that recently has been implicated in innate immunity and endotoxin susceptibility. The amount of the total trait variance explained by the QTL at Tlr4, the gene with the highest likelihood ratio statistic in the QTL, was approximately 70%. To test the role of Tlr4 in O(3)-induced hyperpermeability, BAL protein responses to O(3) were compared in C3H/HeOuJ (OuJ) and HeJ mice that differ only at a polymorphism in the coding region of Tlr4. Significantly greater protein concentrations (430 +/- 35 microg/ml) were found in OuJ mice compared with HeJ mice (258 +/- 18 microg/ml) after exposure to O(3). Furthermore, reverse transcriptase/polymerase chain reaction analysis demonstrated differential expression of Tlr4 message levels between HeJ and OuJ mice after O(3) exposure. Together, results indicate that a QTL on mouse chromosome 4 explains a significant portion of the genetic variance in O(3)-induced hyperpermeability, and support a role for Tlr4 as a strong candidate susceptibility gene.

Air Pollution↗

[Research on improving rice resistance to the pest by B.t. and SBTi genes].

B.t. gene alone or and SBTi gene together were introduced into two elite indica rice varieties grown in South China by bombardment. And 21 independent transgenic lines containing B.t. gene and 4 independent transgenic lines containing B.t. gene and SBTi gene were obtained. Molecular and genetics analysis for R1 plants showed integration of multiple transgenes occurred at one genetic locus. Northern blot result proved B.t. gene expressed in R2 transgenic plants stably. Bioassays using R2 transgenic plants with leaf-folder (Cnaphalocrosis medinalis), indicated that transgenic rice plants are more resistant to the pest than untransformed control plants. And those transgenic plants containing B.t. and SBTi genes showed more resistance compared with those plants containing B.t. gene.

Bacillus thuringiensis Toxins↗

Differential generation of high-density lipoprotein by endogenous and exogenous apolipoproteins in cultured fetal rat astrocytes.

Most peripheral cells generate cholesterol-rich high-density lipoprotein (HDL) with exogenous apolipoprotein as one of the mechanisms for the maintenance of cellular cholesterol homeostasis. Astrocytes isolated from fetal rat brain showed a unique behavior in this reaction. Consistent with previous findings, the astrocytes synthesized apolipoprotein (apo) E and generated cholesterol-rich pre-beta-HDL-like lipoprotein with this apoE, and cellular cholesterol and phospholipids. When exogenous apoA-I and E were added to the medium, they caused generation of additional HDL with cellular phospholipid. It is interesting that this additional part was very poor in cholesterol except for the generation of relatively cholesterol-rich HDL only in the initial few hours of the incubation. The mobilization of intracellular cholesterol for this reaction was also very limited, reflecting the poor cholesterol incorporation into the HDL. Thus, the results demonstrated a unique profile of HDL generation and cholesterol efflux by apolipoproteins in rat astrocytes, with endogenous apoE producing cholesterol-rich HDL and exogenous apolipoproteins producing cholesterol-poor HDL. These lipoproteins may play differential roles in cholesterol transport in the CNS.

Animals↗

Ab initio calculation of electronic coupling in the photosynthetic reaction center.

We have carried out an ab initio electronic structure calculations of electron transfer couplings between chromophores in the bacterial photosynthetic reaction center. The couplings agree remarkably well with parameters obtained from recent quantum dynamical modeling of experimental data assuming an explicit intermediate mechanism. We also have computed couplings on the M-side of the reaction center and have found that the interaction of the primary donor to the M-side intermediate bacteriochlorophyll is quite small because of destructive interference of the two localized coupling matrix elements. This may explain the slow rate of electron transfer down the M-side of the reaction center.

Computer Simulation↗

Detection of Chlamydia trachomatis intrauterine infection using polymerase chain reaction on chorionic villi.

OBJECTIVE: To detect Chlamydia trachomatis intrauterine infection in the early pregnancy by using chorionic villi. METHOD: The C. trachomatis infection in pregnant women was investigated by cervical specimens and Clearview kits. DNA of chorionic villi was extracted and the gene of a major outer membrane protein of C. trachomatis was amplified by polymerase chain reaction (PCR). RESULTS: 120 cervical specimens of the pregnant women were analyzed and 10 cervical specimens were positive for C. trachomatis infection. In this study, the prevalence of C. trachomatis infection was approx. 8.3%. Fifty-nine specimens of chorionic villi and three positive specimens of C. trachomatis infection were analyzed by PCR. The incidence of C. trachomatis intrauterine infection in the early pregnancy was 5.1%. CONCLUSION: The vertical transmission of C. trachomatis infection in the early pregnancy may be a pathway of intrauterine infection. Chorionic villus sampling in early pregnancy and the PCR method could be developed as a technique for prenatal diagnosis of C. trachomatis intrauterine infection.

Cervix Uteri↗

Long-term functional results of contralateral C7 transfer.

From 1986 to 1994, 82 patients with brachial plexus root avulsion were operated on using a contralateral C7 nerve-root transfer. Forty-four patients underwent a one-stage procedure in which the distal end of the ulnar nerve was anastomosed to the contralateral C7 root, and the other 38 underwent a two-stage procedure (first phase: C7 root --> ulnar nerve; second phase: ulnar nerve --> recipient nerve). Twenty postoperative cases were followed-up for 2 years. Of them, the ulnar nerve was transferred to the musculocutaneous nerve in six cases, with recovery of the biceps up to M3 in four and S3 in five cases; the ulnar nerve was transferred to the median nerve in eight cases, with recovery of the wrist and finger flexors up to M3 in five and S3 in six cases; the ulnar nerve was transferred to the radial nerve in four cases, with recovery of the triceps up to M4 in two and S3 in three cases; and the ulnar nerve was transferred to the thoracodorsal nerve in two cases, with recovery of the latissimus dorsi to M4 in one case. The total muscle recovery rate (up to M3) of the series was 60 percent, and the sensory recovery rate (S3) was 78 percent. Outcomes were related to patient age, operative delay, and whether or not the ulnar nerve was used as a bridge for transfer.

Adolescent↗

Femoral nerve transfer for treatment of brachial plexus root avulsion.

Femoral nerve transfer to the muscular branches of the thenar and hypothenar muscles was performed to determine its protective effect on the hand intrinsic muscles. Seven cases of brachial plexus root avulsion treated from May of 1989 to October of 1991 were involved. The femoral nerve transfer to the muscular branches of the thenar and hypothenar muscles was done at the same stage of multiple neurotization. The muscular branches derived from the femoral nerve were isolated and coapted with the thenar muscle branch of the median nerve and the deep branch of the ulnar nerve. A groin flap was harvested simultaneously to form a skin-tube pedicle that covered the nerve bridge. At the second stage, when regeneration of the median and ulnar nerves was found to reach as far as the level of the wrist, the femoral nerve was divided and the muscular branches of the thenar and hypothenar muscles were anastomosed with the regenerated median and ulnar nerves. All the cases were followed up for more than 6 years. Six months after femoral nerve transfer, muscle power of the interosseous muscles and adductor pollicis recovered to MRC3, whereas that of the abductor pollicis brevis recovered to MRC1 to 2. Five cases underwent second-stage transfer. Four to five years of follow-up revealed that the muscle power of the interosseous muscles and adductor pollicis was MRC2 in one case, MRC1 in three cases, and MRC0 in one case. As for the donor area, muscle power of the quadriceps femoris reduced to M3 to 4 within 1 month after femoral nerve transfer and recovered to normal at 3 months. In conclusion, femoral nerve transfer to the muscular branches of the thenar and hypothenar muscles has some protective effect on the hand intrinsic muscles. The outcome of the second stage, however, is not satisfactory.

Adolescent↗

Two-year follow-up of directly-observed intermittent regimens for smear-positive pulmonary tuberculosis in China.

SETTING: The tuberculosis component of the Infectious and Endemic Disease Control Project in the People's Republic of China is the largest single tuberculosis control project in the world using directly-observed therapy and standardized intermittent regimens. OBJECTIVE: To determine the two-year relapse and mortality rates following completion of treatment. DESIGN: A prospective cohort study of 649 cases cured in this project. The 306 new and 343 retreatment cases were treated under field conditions with 2H3R3Z3S3/4H3R3 and 2H3R3Z3E3S3/6H3R3E3, respectively. Following treatment completion, two sputum samples were collected every six months for two years and examined for acid-fast bacilli. Causes of death were identified. RESULTS: The two-year relapse rates for new and retreatment cases were 3.3% and 5.6%, respectively. Retreatment cases with delayed sputum conversion had a greater risk for subsequent relapse. The two-year mortality rate for new and retreatment cases was 3.3% and 8.5%, respectively. The higher mortality rate in retreatment cases was not attributable to relapse of disease, but rather to non-infectious sequelae of tuberculosis. CONCLUSION: The use of directly-observed intermittent regimens is effective in permanently removing infectious tuberculosis cases from the community.

Antitubercular Agents↗

Interleukin 9: a candidate gene for asthma.

Asthma is a complex heritable inflammatory disorder of the airways associated with clinical signs of atopy and bronchial hyperresponsiveness. Recent studies localized a major gene for asthma to chromosome 5q31-q33 in humans. Thus, this segment of the genome represents a candidate region for genes that determine susceptibility to bronchial hyperresponsiveness and atopy in animal models. Homologs of candidate genes on human chromosome 5q31-q33 are found in four regions in the mouse genome, two on chromosome 18, and one each on chromosomes 11 and 13. We assessed bronchial responsiveness as a quantitative trait in mice and found it linked to chromosome 13. Interleukin 9 (IL-9) is located in the linked region and was analyzed as a gene candidate. The expression of IL-9 was markedly reduced in bronchial hyporesponsive mice, and the level of expression was determined by sequences within the qualitative trait locus (QTL). These data suggest a role for IL-9 in the complex pathogenesis of bronchial hyperresponsiveness as a risk factor for asthma.

Animals↗

Prevalence of hepatitis C virus infection in Nanjing, southern China.

There is little information on the prevalence of hepatitis C virus (HCV) infection in China. The prevalence of HCV infection was determined in 998 subjects (398 with liver disease and 600 without) in the city of Nanjing in southern China. Subjects were tested for anti-HCV antibodies by a second generation assay. We also determined serological HCV genotypes and HCV RNA sequences. Among the 600 subjects without liver disease, 3 (0.5%) were seroreactive for anti-HCV. All were less than 12 years of age and had a history of transfusion. Of the 398 liver disease patients, 20 (5.0%) were seroreactive for anti-HCV. Of 16 patients in whom serological HCV genotype was determined, 10 (62.5%) were infected with HCV type 1, 5 (31.3%) with type 2 and 1 (6.3%) undetermined. HCV genomes sequenced from 2 patients belonged to genotype 2 and were closely related to strains in Beijing and Japan by molecular evolutionary analysis. These results suggest that HCV infection is rare and not a major cause of liver disease in southern China.

Adult↗

Linkage analysis of susceptibility to ozone-induced lung inflammation in inbred mice.

Exposures to the common air pollutant ozone (O3) cause decrements in pulmonary function and induce airway inflammation that is characterized by infiltration of polymorphonuclear neutrophils (PMNs; refs 1-4). Because of the impact that O3 may have on public health, it is critical to identify susceptibility factors. Highly reproducible, significant inter-individual variations in human pulmonary function responses to O3 support the hypothesis that genetic background is an important determinant. Initial analysis of PMN responses to O3 exposure in segregant populations derived from inflammation-prone (susceptible) C57BL/6J (B6) and inflammation-resistant C3H/HeJ (C3) inbred mice indicated that susceptibility was controlled by a locus we termed Inf2 (ref. 7). Subsequent analyses with recombinant inbred strains suggested that a more complex interaction of genes is involved. In this report, we identify a quantitative trait locus (QTL) for O3 susceptibility on chromosome 17. Candidate genes for the locus include Tnf, the gene encoding the pro-inflammatory cytokine tumour necrosis factor-alpha (Tnf). Antibody neutralization of the protein product of this putative candidate gene significantly protected against O3 injury in susceptible mice. These results strongly support linkage of O3 susceptibility to a QTL on chromosome 17 and Tnf as a candidate gene.

Animals↗