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Biomedical subjects

Z Yang

Publications and source records attributed to Z Yang.

At least 379 records · Page 21Linked to original sources
PubMed1999

Inhibitors of mitochondrial respiration, iron (II), and hydroxyl radical evoke release and extracellular hydrolysis of glutathione in rat striatum and substantia nigra: potential implications to Parkinson's disease.

In this investigation, microdialysis has been used to study the effects of 1-methyl-4-phenylpyridinium (MPP+), an inhibitor of mitochondrial complex I and alpha-ketoglutarate dehydrogenase and the active metabolite of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), on extracellular concentrations of glutathione (GSH) and cysteine (CySH) in the rat striatum and substantia nigra (SN). During perfusion of a neurotoxic concentration of MPP+ (2.5 mM) into the rat striatum or SN, extracellular concentrations of GSH and CySH remain at basal levels (both approximately 2 microM). However, when the perfusion is discontinued, a massive but transient release of GSH occurs, peaking at 5,000% of basal levels in the striatum and 2,000% of basal levels in the SN. The release of GSH is followed by a slightly delayed and smaller elevation of extracellular concentrations of CySH that can be blocked by the gamma-glutamyl transpeptidase (gamma-GT) inhibitor acivicin. Low-molecular-weight iron and extracellular hydroxyl radical (OH*) have been implicated as participants in the mechanism underlying the dopaminergic neurotoxicity of MPTP/MPP+. During perfusion of Fe2+ (OH*) into the rat striatum and SN, extracellular levels of GSH also remain at basal levels. When perfusions of Fe2+ are discontinued, a massive transient release of GSH occurs followed by a delayed, small, but progressive elevation of extracellular CySH level that again can be blocked by acivicin. Previous investigators have noted that extracellular concentrations of the excitatory/excitotoxic amino acid glutamate increase dramatically when perfusions of neurotoxic concentrations of MPP+ are discontinued. This observation and the fact that MPTP/MPP+ causes the loss of nigrostriatal GSH without corresponding increases of glutathione disulfide (GSSG) and the results of the present investigation suggest that the release and gamma-GT/dipeptidase-mediated hydrolysis of GSH to glutamate, glycine, and CySH may be important factors involved with the degeneration of dopamine neurons. It is interesting that a very early event in the pathogenesis of Parkinson's disease is a massive loss of GSH in the SN pars compacta that is not accompanied by corresponding increases of GSSG levels. Based on the results of this and prior investigations, a new hypothesis is proposed that might contribute to an understanding of the mechanisms that underlie the degeneration of dopamine neurons evoked by MPTP/MPP+, other agents that impair neuronal energy metabolism, and Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1999

Sialyl Lewis X, Lewis X, and N-acetyllactosamine expression on normal and glaucomatous eyes.

PURPOSE: Sialyl Lewis X (sLex), Lewis X (Lex), and N-acetyllactosamine are carbohydrate chains of neolactoglycoconjugates which are expressed by specific cell types and are important in the functioning of cells within an organism. This study attempts to determine the expression of these glycoconjugates on the conjunctiva, cornea, and trabecular meshwork (TM) of both normal and glaucomatous eyes. METHODS: Frozen anterior segment sections of both normal and glaucomatous human cadaver eyes, as well as rabbit eyes, were stained with a panel of monoclonal antibodies (mAbs) to neolactoglycoconjugates using an Avidin Biotin Peroxidase Complex/Alkaline Phosphatase staining method. RESULTS: SLex characteristically stained both human conjunctival and corneal epithelia in normal (n=5) and glaucomatous (n=5) sections. SLex stained corneal and conjunctival epithelia of glaucomatous eyes much more intensely than normal eyes. Rabbit cornea sections stained for sLex, Lex, and N-acetyllactosamine. However, human cornea only consistently stained with sLex. Normal and glaucomatous human TM sections did not stain for sLex, Lex, or N-acetyllactosamine. CONCLUSIONS: The expression of glycoconjugates with sLex side chains appears to be upregulated in the conjunctival and corneal epithelia of glaucomatous eyes. Distinct species specific differences were noted in Lex and N-acetyllactosamine staining patterns in rabbit and human corneal epithelia.

Aged↗
PubMed1999

Enhanced capacity of a widespread strain of Mycobacterium tuberculosis to grow in human macrophages.

To determine whether the extent of spread of Mycobacterium tuberculosis strains in the community correlated with their capacity to replicate in human macrophages, intracellular growth rates of M. tuberculosis patient isolates were measured. Strain 210 caused disease in 43 patients in central Los Angeles, 3 "small-cluster" strains caused disease in 8-23 patients, and 5 "unique" strains each caused disease in only 1 patient who was positive by sputum acid-fast smear and spent substantial amounts of time at homeless shelters that were tuberculosis transmission sites. Strain 210 isolates grew significantly more rapidly than small-cluster and unique strains in macrophages. All strains elicited production of similar amounts of tumor necrosis factor-alpha, interleukin (IL)-6, IL-10, and IL-12 and were equally susceptible to reactive nitrogen intermediates. It was concluded that the extensive spread of an M. tuberculosis strain correlated with its capacity to replicate rapidly in human macrophages, which may be a marker of virulence.

Cells, Cultured↗
PubMed1999

Recombinant fusion protein and DNA vaccines against foot and mouth disease virus infection in guinea pig and swine.

In this study, we provide evidence that a recombinant fusion protein containing beta-galactosidase and a tandem repeat peptide of immunogenic dominant epitope of foot-and-mouth disease virus (FMDV) VP1 protein elicits high levels of neutralizing antibody and protects both guinea pigs and swine against infection. Vaccination with this fusion protein induced a FMDV-specific proliferative T-cell response and a neutralizing antibody response. The immunized guinea pigs and swine were protected against FMD type O virus infection. Two DNA plasmids expressing genes of foot-and-mouth disease were constructed. Both plasmids pBO1 and pCO1 contain a signal sequence of the swine immunoglobulin G (IgG) gene and fusion protein gene of pXZ84. The signal sequence and fusion protein gene were under the control of a metallothionein promoter in the case of the pBO1 plasmid and under the control of a cytomegalovirus immediate early promoter in the case of pCO1 plasmid. When pBO1 and pCO1 were inoculated intramuscularly into guinea pigs, both plasmids elicited a neutralizing antibody response and spleen cell proliferation increased following stimulation with FMDV antigen, but animals were not protected from viral challenge.

Animals↗
PubMed1999

Substitution rate variation among sites in mitochondrial hypervariable region I of humans and chimpanzees.

Mitochondrial D-loop hypervariable region I (HVI) sequences are widely used in human molecular evolutionary studies, and therefore accurate assessment of rate heterogeneity among sites is essential. We used the maximum-likelihood method to estimate the gamma shape parameter alpha for variable substitution rates among sites for HVI from humans and chimpanzees to provide estimates for future studies. The complete data of 839 humans and 224 chimpanzees, as well as many subsets of these data, were analyzed to examine the effect of sequence sampling. The effects of the genealogical tree and the nucleotide substitution model were also examined. The transition/transversion rate ratio (kappa) is estimated to be about 25, although much larger and biased estimates were also obtained from small data sets at low divergences. Estimates of alpha were 0.28-0.39 for human data sets of different sizes and 0.20-0.39 for data sets including different chimpanzee subspecies. The combined data set of both species gave estimates of 0.42-0.45. While all those estimates suggest highly variable substitution rates among sites, smaller samples tend to give smaller estimates of alpha. Possible causes for this pattern were examined, such as biases in the estimation procedure and shifts in the rate distribution along certain lineages. Computer simulations suggest that the estimation procedure is quite reliable for large trees but can be biased for small samples at low divergences. Thus, an alpha of 0.4 appears suitable for both humans and chimpanzees. Estimates of alpha can be affected by the nucleotide sites included in the data, the overall tree length (the amount of sequence divergence), the number of rate classes used for the estimation, and to a lesser extent, the included sequences. The genealogical tree, the substitution model, and demographic processes such as population expansion do not have much effect.

Animals↗
PubMed1999

Colletotrichum trifolii mutants disrupted in the catalytic subunit of cAMP-dependent protein kinase are nonpathogenic.

Colletotrichum trifolii is the fungal pathogen of alfalfa that causes anthracnose disease. For successful plant infection, this fungus must undergo a series of morphological transitions following conidial attachment, including germination and subsequent differentiation, resulting in appressorium formation. Our previous studies with pharmacological effectors of signaling pathways have suggested the involvement of cyclic AMP (cAMP)-dependent protein kinase (PKA) during these processes. To more precisely evaluate the role of PKA in C. trifolii morphogenesis, the gene encoding the catalytic (C) subunit of PKA (Ct-PKAC) was isolated, sequenced, and inactivated by gene replacement. Southern blot analysis with C. trifolii genomic DNA suggested that Ct-PKAC is a single-copy gene. Northern (RNA) blot analysis with total RNA from different fungal growth stages indicated that the expression of this gene was developmentally regulated. When Ct-PKAC was insertionally inactivated by gene replacement, the transformants showed a small reduction in growth relative to the wild type and conidiation patterns were altered. Importantly, PKA-deficient strains were unable to infect intact alfalfa (host) plants, though only a slight delay was observed in the timing for conidial germination and appressorial formation in the Ct-PKAC disruption mutants. Moreover, these mutants were able to colonize host tissues following artificial wounding, resulting in typical anthracnose disease lesions. Coupled with microscopy, these data suggest that the defect in pathogenicity is likely due to a failure in penetration. Our results demonstrate that PKA has an important role in regulating the transition between vegetative growth and conidiation, and is essential for pathogenic development in C. trifolii.

Amino Acid Sequence↗
PubMed1999

The CLAVATA1 receptor-like kinase requires CLAVATA3 for its assembly into a signaling complex that includes KAPP and a Rho-related protein.

The CLAVATA1 (CLV1) and CLAVATA3 (CLV3) genes are required to maintain the balance between cell proliferation and organ formation at the Arabidopsis shoot and flower meristems. CLV1 encodes a receptor-like protein kinase. We have found that CLV1 is present in two protein complexes in vivo. One is approximately 185 kD, and the other is approximately 450 kD. In each complex, CLV1 is part of a disulfide-linked multimer of approximately 185 kD. The 450-kD complex contains the protein phosphatase KAPP, which is a negative regulator of CLV1 signaling, and a Rho GTPase-related protein. In clv1 and clv3 mutants, CLV1 is found primarily in the 185-kD complex. We propose that CLV1 is present as an inactive disulfide-linked heterodimer and that CLV3 functions to promote the assembly of the active 450-kD complex, which then relays signal transduction through a Rho GTPase.

Arabidopsis Proteins↗
PubMed1999

Control of pollen tube tip growth by a Rop GTPase-dependent pathway that leads to tip-localized calcium influx.

We have shown that Rop1At, a pollen-specific Rop GTPase that is a member of the Rho family of small GTP binding proteins, acts as a key molecular switch controlling tip growth in Arabidopsis pollen tubes. Pollen-specific expression of constitutively active rop1at mutants induced isotropic growth of pollen tubes. Overexpression of wild-type Arabidopsis Rop1At led to ectopic accumulation of Rop1At in the plasma membrane at the tip and caused depolarization of pollen tube growth, which was less severe than that induced by the constitutively active rop1at. These results indicate that both Rop1At signaling and polar localization are critical for controlling the site of tip growth. Dominant negative rop1at mutants or antisense rop1at RNA inhibited tube growth at 0.5 mM extracellular Ca(2+), but growth inhibition was reversed by higher extracellular Ca(2+). Injection of anti-Rop antibodies disrupted the tip-focused intracellular Ca(2+) gradient known to be crucial for tip growth. These studies provide strong evidence for a Rop GTPase-dependent tip growth pathway that couples the control of growth sites with the rate of tip growth through the regulation of tip-localized extracellular Ca(2+) influxes and formation of the tip-high intracellular Ca(2+) gradient in pollen tubes.

Arabidopsis↗
PubMed1999

Evidence from molecular fingerprinting of limited spread of drug-resistant tuberculosis in Texas.

To determine the contribution of recent transmission to spread of drug-resistant tuberculosis in Texas, we performed IS6110-based and pTBN12-based restriction fragment length polymorphism (RFLP) analyses on Mycobacterium tuberculosis isolates. Isolates collected from 201 patients in Texas between 1992 and 1994 were studied. The distribution of cases was strikingly focal. All cases were reported from 35 of the 254 counties in Texas, and 74% (148 of 201) were reported from only 9 counties. One hundred sixty-one (80%) of the patients had M. tuberculosis isolates with unique RFLP patterns, and 41 (20%) patients were in 20 clusters, each comprising 2 to 3 patients. The largest number of cases of drug-resistant tuberculosis were reported in counties bordering Mexico, but the percentage of clustered cases was highest in northeast Texas and in counties that included the cities of Dallas, Fort Worth, and Houston. Compared to nonclustered patients, clustered patients were more likely to be African American and to have been born in the United States. Clustered patients were significantly more likely to be from the same geographic area, and clustered patients from the same geographic area were more likely to have isolates with identical drug susceptibility patterns, suggesting that they were linked by recent transmission. In 11 of 20 clusters, clustered patients were from geographically separate regions, and most isolates did not have identical drug susceptibility patterns, suggesting that tuberculosis was contracted from a common source in the remote past. Based on the low percentage of clustered cases and the small cluster size, we conclude that there is no evidence for the extensive transmission of drug-resistant tuberculosis in Texas.

Adolescent↗
PubMed1999

Human CD46 enhances nitric oxide production in mouse macrophages in response to measles virus infection in the presence of gamma interferon: dependence on the CD46 cytoplasmic domains.

CD46 is a transmembrane complement regulatory protein widely expressed on nucleated human cells. Laboratory-adapted strains of measles virus (MV) bind to the extracellular domains of CD46 to enter human cells. The cytoplasmic portion of CD46 consists of a common juxtamembrane region and different distal sequences called Cyt1 and Cyt2. The biological functions of these cytoplasmic sequences are unknown. In this study, we show that expression of human CD46 with the Cyt1 cytoplasmic domain in mouse macrophages enhances production of nitric oxide (NO) in response to MV infection in the presence of gamma interferon (IFN-gamma). Human CD46 does not increase the basal levels of NO production in mouse macrophages and does not augment NO production induced by double-stranded polyribonucleotides. Replacing the cytoplasmic domain of human CD46 with Cyt2 reduces MV and IFN-gamma-induced NO production in mouse macrophages. Deleting the entire cytoplasmic domains of human CD46 does not prevent MV infection but markedly attenuates NO production in response to MV and IFN-gamma. Mouse macrophages expressing a tailless human CD46 mutant are more susceptible to MV infection and produce 2 to 3 orders of magnitude more infectious virus than mouse macrophages expressing human CD46 with intact cytoplasmic domains. These results reveal a novel function of CD46 dependent on the cytoplasmic domains (especially Cyt1), which augments NO production in macrophages. These findings may have significant implications for roles of CD46 in innate immunity and MV pathogenesis.

Animals↗
PubMed1999

Cytomegalovirus IE2 protein stimulates interleukin 1beta gene transcription via tethering to Spi-1/PU.1.

Potent induction of the gene coding for human prointerleukin 1beta (il1b) normally requires a far-upstream inducible enhancer in addition to a minimal promoter located between positions -131 and +12. The transcription factor Spi-1 (also called PU.1) is necessary for expression and binds to the minimal promoter, thus providing an essential transcription activation domain (TAD). In contrast, infection by human cytomegalovirus (HCMV) can strongly activate il1b via the expression of immediate early (IE) viral proteins and eliminates the requirement for the upstream enhancer. Spi-1 has been circumstantially implicated as a host factor in this process. We report here the molecular basis for the direct involvement of Spi-1 in HCMV activation of il1b. Transfection of Spi-1-deficient HeLa cells demonstrated both the requirement of Spi-1 for IE activity and the need for a shorter promoter (-59 to +12) than that required in the absence of IE proteins. Furthermore, in contrast to normal, enhancer-dependent il1b expression, which absolutely requires both the Spi-1 winged helix-turn-helix (wHTH) DNA-binding domain and the majority of the Spi-1 TAD, il1b expression in the presence of IE proteins does not require the Spi-1 TAD, which plays a synergistic role. In addition, we demonstrate that a single IE protein, IE2, is critical for the induction of il1b. Protein-protein interaction experiments revealed that the wing motif within the Spi-1 wHTH domain directly recruits IE2. In turn, IE2 physically associates with the Spi-1 wing and requires the integrity of at least one region of IE2. Functional analysis demonstrates that both this region and a carboxy-terminal acidic TAD are required for IE2 function. Therefore, we propose a protein-tethered transactivation mechanism in which the il1b promoter-bound Spi-1 wHTH tethers IE2, which provides a TAD, resulting in the transactivation of il1b.

Binding Sites↗
PubMed1999

Foci of tuberculosis transmission in central Los Angeles.

To identify sites of tuberculosis transmission and to determine the contribution of HIV-infected patients to tuberculosis morbidity in an urban area, we prospectively evaluated 249 patients with culture-proven tuberculosis in central Los Angeles. Restriction fragment length polymorphism (RFLP) analysis was performed on Mycobacterium tuberculosis isolates to identify patients infected with the same strain. Using RFLP and clinical and epidemiologic data, we identified the most likely source case and site of transmission for 79 patients. Homelessness, birth in the United States and Native American ethnicity were independent predictors of being a source case, but HIV infection was not. Three homeless shelters were sites of tuberculosis transmission for 55 (70%) of the 79 patients. HIV-infected patients constituted 27% (66/249) of the study population, but only 17% (13/79) of patients were infected by an HIV-infected source case. We conclude that transmission of tuberculosis in central Los Angeles was highly focal, and that the major transmission sites were three homeless shelters. HIV- infected tuberculosis patients did not play a major role in spread of tuberculosis. Tuberculosis control measures targeted at specific homeless shelters can reduce tuberculosis morbidity in urban areas where homelessness is common and the incidence of tuberculosis is high.

AIDS-Related Opportunistic Infections↗
PubMed1999

Attitudes toward the mentally ill in a sample of professionals working in a psychiatric hospital in Beijing (China).

The attitudes of psychiatric doctors and nurses toward the mentally ill in a large urban psychiatric hospital in China were compared using the Community Attitudes toward the Mentally Ill (CAMI). Data indicated that the attitude of professionals differed on 11 of the 40 questions of this instrument. Those questions are divided along 4 dimensions: authoritarianism, benevolence, social restrictiveness and rehabilitation in the community. Results showed that psychiatric doctors have a more liberal and positive attitude toward the mentally ill than psychiatric nurses, especially about their rehabilitation in the community. Factor analysis also indicated that nurses were more likely than doctors to attribute negative characteristics to the mentally ill. Some explanations are proposed to explain these differences.

Adult↗
PubMed1999

Green tea and its major components ameliorate immune dysfunction in mice bearing Lewis lung carcinoma and treated with the carcinogen NNK.

The protective effects of tea and/or its components on dysfunction of immune functions during tumor growth and carcinogenesis in mice were studied using two experimental models: C57/BL6J mice transplanted with Lewis lung carcinoma (LLC) and Kunming mice treated with a single dose of 4-(methylnitrosamino-)-1-(3-pyridyl)-1-butanone (NNK). In C57/BL6J mice bearing LLC, the weight of the thymus decreased, the proportion of CD4(+)-positive T lymphocytes and the ratio of CD4+ to CD8+ decreased, luminol-enhanced chemiluminescence of white blood cells in peripheral blood stimulated by zymosan increased, and plaque-forming cells (PFC) decreased. However, in LLC-bearing mice given green tea as drinking water, all immune functions were improved, along with inhibition of tumor growth. In Kunming mice treated with NNK, during the four weeks of observation, their immunologic indicators, such as phagocytosis of macrophages in the abdominal cavity, luminol-enhanced chemiluminescence of white blood cells, plaque-forming cells, and delayed-type hypersensitivity, increased or decreased to various extents compared with normal controls. However, these changes were significantly prevented in the mice given green tea, mixed tea, or tea polyphenol as drinking water. In conclusion, tea and its components ameliorated immune dysfunction in mice bearing LLC or treated with the carcinogen NNK.

Animals↗
PubMed1999

[An investigation of the polymorphism of HLA class II alleles in the Han population in Hubei Province of China].

OBJECTIVE: To investigate the polymorphism of HLA class II alleles in the Han population in Hubei province. METHODS: The alleles of DRB1*(n=168), DQB1*(n=160) and DPB1*(n=93) were typed by using the polymerase chain reaction/sequence specific primer(PCR/SSP) and polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) techniques. RESULTS: 39 HLA-DRB1, 15 DQB1 and 17 DPB1 alleles were found. Alleles with higher frequencies are DRB1*0901 (GF=14%), *1501(GF=11.3%), *0301(GF=7.1%), *0803(GF=4.8%); DQB1*0301(GF=18.8%), *0303(GF=18.4%), *0201(GF=10%), *0302(GF=8.4%); DPB1*0501(GF=31.2%), *0401(GF=15.1%), *0201(GF=14%), *0402(GF=11.8%), respectively. As compared with Caucasians, the Han people in Hubei province have higher gene frequencies of DRB1*0901, *1001, *0803; DQB1*0303, *0502 and DPB1*0501, *0202; and lower gene frequencies of DRB1*0301, *0401, *1301; DQB1*0201, *0603 and DPB1*0401, suggesting that Hubei Hans have their own layout of HLA class II allele frequencies. CONCLUSION: These data may serve as normal reference values for the Han population in south China.

Alleles↗
PubMed1999

What makes the circadian clock tick: genes that keep time?

Intense activity in the field of circadian rhythms has led in recent years to a basic understanding of how an endogenous clock is generated. Oscillating products of the period (per) and timeless (tim) genes, which feed back to regulate their own synthesis, and transcription factors, which activate these genes, combine to generate a molecular loop that apparently drives behavioral and physiological rhythms. The best-characterized component of this system is the per gene, with considerable effort directed towards identifying the mechanisms that regulate cyclic expression of RNA and protein. Since the cycling of PER protein is controlled largely by post-transcriptional mechanisms, the relative importance of RNA versus protein cycling has been addressed in several studies that are discussed in this chapter. However, it now is clear that regulation of per cannot be dissociated from that of tim, since they are co-dependent components. The overt behavioral phenotype likely depends upon the effect that any perturbation has on both components, rather than on either alone. Major features of the feedback loop appear to be conserved, from fruit flies to mammals. One difference between the two systems is the manner in which the "molecular clock" responds to light. In flies, levels of TIM protein are reduced in response to light, while in mammals, per RNA is induced. The pathway that conducts light to the clock is poorly understood but there is increasing evidence in support of a dedicated pathway for circadian photoreception, as opposed to the sole use of the visual transduction system.

Animals↗