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Biomedical subjects

Z Yang

Publications and source records attributed to Z Yang.

At least 469 records · Page 26Linked to original sources
PubMed1998

Microcirculation of the distal humeral epiphyseal cartilage: implications for post-traumatic growth deformities.

The purpose of this study was to determine if there is an anatomic basis for development of the avascular necrosis infrequently seen after elbow trauma. The microcirculation to the distal humeral epiphyseal cartilage was studied in 38 elbow joints from 19 skeletally immature individuals. The findings of this study were as follows: (1) Vascularity is centripetal within the epiphyseal cartilages of the capitellum, trochlea, and medial and lateral epicondyles. Because of this vascularity pattern, it is not easy for avascular necrosis to develop after trauma within these epiphyses. (2) Vascularity is longitudinal in the epiphyseal cartilage between the capitellum and trochlea. The longitudinal vessels appear susceptible to fractures around the elbow in childhood. (3) A rich vascular network exists in the olecranon fat pad, and a vascular arch forms from the vascular network adjacent to the distal humeral epiphyseal cartilage. The vascular arch sends several large branches into the epiphyseal cartilage in a vertical fashion. Disruption of either the longitudinal intraosseous vasculature (vertical extraosseous blood supply) or the vascular arch in more than 2 places may lead to selective avascular necrosis of the epiphyseal cartilage between the capitellum and trochlea. These findings suggest vascular compromise as a possible explanation for "fish-tail" deformities seen as sequellae of different fracture patterns.

Female↗
PubMed1998

Response of the timeless protein to light correlates with behavioral entrainment and suggests a nonvisual pathway for circadian photoreception.

The period (per) and timeless (tim) genes are required for circadian behavioral rhythms in Drosophila. The current model for how these rhythms entrain to light is based upon the light induced decrease in timeless protein (TIM) levels. We show here that the TIM response to light correlates with the effect of light on the behavioral rhythm. To identify components of the entrainment pathway, we also assayed the TIM response in flies with mutant visual systems. Flies that lacked eyes displayed a normal response in lateral neurons. The TIM response to a light pulse was attenuated in flies that were mutant for the transient receptor potential (trp) and trp-like (trpl) genes, which are required for calcium conductance in the visual transduction cascade. The reduced TIM response was accompanied by a reduced phase shift in the behavioral rhythm, but neither response was completely eliminated, and the trpl;trp flies entrain to light-dark cycles, suggesting that these genes perturb some aspect of circadian entrainment when mutated but are not essential for it. The TIM response was also unaffected in ninaE flies that lack the rhodopsin protein (rh1). These results support the hypothesis that circadian entrainment does not rely on the visual system and likely involves a dedicated pathway for photoreception.

Animals↗
PubMed1998

RNA enzymes with two small-molecule substrates.

BACKGROUND: The 'RNA world' hypothesis posits ancient organisms employing versatile catalysis by RNAs. In particular, such a metabolism would have required RNA catalysts that join small molecules. Such anabolic reactions now occur very widely, for example in phospholipid, terpene, amino acid and nucleotide synthetic pathways in modern organisms. Present RNA systems, however, do not perform such reactions using substrates that do not base pair. Here we ask whether this lack is a methodological artifact due to the practice of selection-amplification, or a fundamental property of active sites reconstructed within RNA structures. RESULTS: Three rationally modified RNA enzymes, Iso6-G, Iso6-2G and Iso63G, catalyze the formation of (5'-->5') polyphosphate-linked oligonucleotides in trans. One of these, Iso6-G RNA, has a specific substrate site for a guanosine triphosphate, GTP, dGTP or ddGTP, and one nonspecific substrate site for a terminal-phosphate-containing small molecule. This ribozyme catalyzes multiple turnovers, proceeding at a constant rate. Guanosine specificity is probably not attributable to Watson-Crick base pairing. CONCLUSIONS: Ribozymes can readily bind multiple small-molecule substrates simultaneously and catalyze reactions that build up larger products, apparently independent of substrate-RNA Watson-Crick base pairing. RNA enzymes therefore parallel proteins, which often overcome the entropic difficulties of positioning multiple small substrates for catalysis of anabolic reactions. These results support the idea of a complex ancestral metabolism based on RNA catalysis.

Algorithms↗
PubMed1998

Signaling tip growth in plants.

Tip growth is an extreme form of polar growth modulated by both intrinsic and extrinsic spatial cues. Pollen tubes and root hairs have been used as model systems to investigate tip growth signaling in higher plants. Recent studies have focused on tip-localized Ca2+ gradients and Rho GTPases in pollen tubes and a series of mutants affecting root hair tip growth. These molecular and genetic markers will serve as stepping stones towards uncovering tip growth pathways in plants.

Calcium↗
PubMed1998

Experimental studies on traumatic facial nerve injury.

PURPOSE: The purpose of this study was to investigate the outcome of different injuries to the facial nerve. MATERIALS AND METHODS: Six patterns of injuries (exposure, compression, crushing, stretching, division and post-division anastomosis) were produced in the buccal branches of the facial nerve in 60 rabbits. Electroneuronography (ENoG) and histology at definite time were used to evaluate the results. RESULTS AND CONCLUSIONS: Exposure and compression injuries produced a neuropraxic injury and rapid recovery. Crushing and stretching injuries resulted in axonotmesis and whilst complete recovery can take place it may be very slow. Division and post-division anastomosis fall into neurotmesis injury and do not completely recover within six months; the former recovers slower and later than the latter.

Animals↗
PubMed1998

Osteoinduction by calcium phosphate biomaterials.

Different materials were implanted in muscles of dogs to study the osteoinduction of calcium phosphate biomaterials. Bone formation was only seen in calcium phosphate biomaterials with micropores, and could be found in hydroxyapatite (HA) ceramic, tricalcium phosphate/hydroxyapatite ceramic (BCP), beta-TCP ceramic and calcium phosphate cement. The osteoinductive potential was different in different materials. The results indicate that osteoinduction can be a property of calcium phosphate biomaterials when they exhibit specific chemical and structural characteristics.

Journal Article↗
PubMed1998

Bone morphogenetic protein and ceramic-induced osteogenesis.

To investigate the relationship between bone morphogenetic proteins (BMP) and calcium phosphate ceramic-induced osteogenesis in soft tissues, in vitro and in vivo experiments were performed. In an in vitro study, the ability of different calcium phosphate ceramics to absorb bovine BMP (bBMP) from a bBMP solution was tested. In vivo studies included immunohistochemical BMP staining before bone formation in the ceramics was detected, and the enhancement of bone formation in calcium phosphate ceramics by bBMP. The results were: (1) calcium phosphate ceramics have a strong ability to absorb bBMP; (2) a high BMP concentration reaches inside the ceramic implants before bone formation in soft tissues of domestic pig occurs; (3) by 56% at 50 d and by 23% at 100 d, bBMP enhances bone formation in calcium phosphate ceramics implanted in soft tissues of dogs. The results indicate the BMP plays an important role in calcium phosphate ceramic-induced osteogenesis and that adsorption of native BMP from the body fluids to ceramic implants may be a key step in osteoinduction by calcium phosphate ceramics.

Journal Article↗
PubMed1998

Immunization for Ebola virus infection.

Infection by Ebola virus causes rapidly progressive, often fatal, symptoms of fever, hemorrhage and hypotension. Previous attempts to elicit protective immunity for this disease have not met with success. We report here that protection against the lethal effects of Ebola virus can be achieved in an animal model by immunizing with plasmids encoding viral proteins. We analyzed immune responses to the viral nucleoprotein (NP) and the secreted or transmembrane forms of the glycoprotein (sGP or GP) and their ability to protect against infection in a guinea pig infection model analogous to the human disease. Protection was achieved and correlated with antibody titer and antigen-specific T-cell responses to sGP or GP. Immunity to Ebola virus can therefore be developed through genetic vaccination and may facilitate efforts to limit the spread of this disease.

Animals↗
PubMed1998

Differential roles of GATA-1 and GATA-2 in growth and differentiation of mast cells.

BACKGROUND: While mast cells have been previously shown to express both GATA-1 and GATA-2 mRNAs, individual functions for these related factors during their course of differentiation within the mast cell lineage have not yet been defined. To address this question, the expression of GATA-1 and GATA-2 mRNAs and proteins were examined in three mouse mast cell progenitor lines as well as in mast cells isolated from both wild-type and GATA-1-deficient mice. RESULTS: Both mast cell progenitor lines, as well as primary mouse bone marrow-derived mast cells (BMMCs) and peritoneal mast cells (PMCs) were examined by RNA blotting and immunological analyses. GATA-2 protein was abundantly expressed in all three mast cell lines and in BMMCs, but only weakly in some of PMCs. In contrast, GATA-1 protein was expressed in PMCs and BMMCs after culture in the presence of IL3 and SCF. We also found the presence of Alcian blue staining-positive but berberine staining-negative mast cells in the skin of mice heterozygous to GATA-1 knock-down allele. CONCLUSION: These results suggest that the expression of GATA factor-dependent genes is regulated by GATA-2 during mast cell development and that GATA-1 is required for the specification of differentiated mast cell phenotypes.

Animals↗
PubMed1998

Allozyme diversity in Leavenworthia populations with different inbreeding levels.

Levels of allozyme diversity were studied in five species of the annual plant genus Leavenworthia. The breeding systems of the populations were also characterized in terms of measures of autogamous seed-set and self-fertility. The populations that appeared more inbreeding by these criteria also tended to have lower within-population gene diversity (Hs) values, but there was nevertheless considerable allozyme variability in two of the four sets of inbred populations studied. Comparing the outcrosser L. stylosa and the related inbreeders L. uniflora and L. torulosa the reduction in diversity associated with inbreeding was very high, as no variants were seen within populations of the inbreeders. In L. crassa and L. alabamica, the reduction was lower, but correcting for the fact that this comparison is over less extreme selfing rate differences, it is estimated that the difference between extreme inbreeding and outcrossing populations of L. crassa considerably exceeds twofold. These results are compared with published studies within closely related taxa with different inbreeding levels. The effect of inbreeding on allozyme diversity is consistently larger than has been estimated from comparisons of unrelated species.

Brassicaceae↗
PubMed1998

A new set of chemotaxis homologues is essential for Myxococcus xanthus social motility.

Myxococcus xanthus cells aggregate and develop into multicellular fruiting bodies in response to starvation. A new M. xanthus locus, designated diffor defective in fruiting, was identified by the characterization of a mutant defective in fruiting body formation. Molecular cloning, DNA sequencing and sequence analysis indicate that the dif locus encodes a new set of chemotaxis homologues of the bacterial chemotaxis proteins MCPs (methyl-accepting chemotaxis proteins), CheW, CheY and CheA. The dif genes are distinct genetically and functionally from the previously identified M. xanthus frz chemotaxis genes, suggesting that multiple chemotaxis-like systems are required for the developmental process of M. xanthus fruiting body formation. Genetic analysis and phenotypical characterization indicate that the M. xanthus dif locus is required for social (S) motility. This is the first report of a M. xanthus chemotaxis-like signal transduction pathway that could regulate or co-ordinate the movement of M. xanthus cells to bring about S motility.

Amino Acid Sequence↗
PubMed1998

On the best evolutionary rate for phylogenetic analysis.

The effect of the evolutionary rate of a gene on the accuracy of phylogeny reconstruction was examined by computer stimulation. The evolutionary rate is measured by the tree length, that is, the expected total number of nucleotide substitutions per site on the phylogeny. DNA sequence data were simulated using both fixed trees with specified branch lengths and random trees with branch lengths generated from a model of cladogenesis. The parsimony and likelihood methods were used for phylogeny reconstruction, and the proportion of correctly recovered branch partitions by each method was estimated. Phylogenetic methods including parsimony appear quite tolerant of multiple substitutions at the same site. The optimum levels of sequence divergence were even higher than upper limits previously suggested for saturation of substitutions, indicating that the problem of saturation may have been exaggerated. Instead, the lack of information at low levels of divergence should be seriously considered in evaluation of a gene's phylogenetic utility, especially when the gene sequence is short. The performance of parsimony, relative to that of likelihood, does not necessarily decrease with the increase of the evolutionary rate.

Biological Evolution↗
PubMed1998

Dissemination of Mycobacterium tuberculosis across the San Francisco Bay Area.

The propensity of Mycobacterium tuberculosis genotypes to spread across geographic boundaries was investigated by comparing the IS6110 and polymorphic GC-rich sequence patterns of M. tuberculosis isolates from San Francisco and the East Bay, two distinct regions separated by San Francisco Bay. Of 724 isolates from incident tuberculosis patients during 1992 and 1993, only 53 (7.3%) had patterns matching > or = 1 isolates from the other region. In the multivariable analysis of patient risk factors, an AIDS diagnosis (odds ratio [OR], 1.89; 95% confidence interval [CI], 1.00-3.57) and non-Asian race (OR, 3.43; 95% CI, 1.59-7.42) were associated with having an isolate with a matching pattern. Of 375 unique IS6110 patterns among San Francisco isolates, only 9 (2.4%) matched patterns of East Bay isolates. These population-based data suggest that in the San Francisco Bay Area, M. tuberculosis does not rapidly spread across geographic boundaries, and tuberculosis control efforts should focus on transmission within defined areas.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Characterization of the KIF3C neural kinesin-like motor from mouse.

Proteins of the kinesin superfamily define a class of microtubule-dependent motors that play crucial roles in cell division and intracellular transport. To study the molecular mechanism of axonal transport, a cDNA encoding a new kinesin-like protein called KIF3C was cloned from a mouse brain cDNA library. Sequence and secondary structure analysis revealed that KIF3C is a member of the KIF3 family. In contrast to KIF3A and KIF3B, Northern and Western analysis indicated that KIF3C expression is highly enriched in neural tissues such as brain, spinal cord, and retina. When anti-KIF3C antibodies were used to stain the cerebellum, the strongest signal came from the cell bodies and dendrites of Purkinje cells. In retina, anti-KIF3C mainly stains the ganglion cells. Immunolocalization showed that the KIF3C motor in spinal cord and sciatic nerve is mainly localized in cytoplasm. In spinal cord, the KIF3C staining was punctate; double labeling with anti-giantin and anti-KIF3C showed a clear concentration of the motor protein in the Golgi complex. Staining of ligated sciatic nerves demonstrated that the KIF3C motor accumulated at the proximal side of the ligated nerve, which suggests that KIF3C is an anterograde motor. Immunoprecipitation experiments revealed that KIF3C and KIF3A, but not KIF3B, were coprecipitated. These data, combined with previous data from other labs, indicate that KIF3C and KIF3B are "variable" subunits that associate with a common KIF3A subunit, but not with each other. Together these results suggest that KIF3 family members combinatorially associate to power anterograde axonal transport.

Amino Acid Sequence↗
PubMed1998

Likelihood models for detecting positively selected amino acid sites and applications to the HIV-1 envelope gene.

Several codon-based models for the evolution of protein-coding DNA sequences are developed that account for varying selection intensity among amino acid sites. The "neutral model" assumes two categories of sites at which amino acid replacements are either neutral or deleterious. The "positive-selection model" assumes an additional category of positively selected sites at which nonsynonymous substitutions occur at a higher rate than synonymous ones. This model is also used to identify target sites for positive selection. The models are applied to a data set of the V3 region of the HIV-1 envelope gene, sequenced at different years after the infection of one patient. The results provide strong support for variable selection intensity among amino acid sites The neutral model is rejected in favor of the positive-selection model, indicating the operation of positive selection in the region. Positively selected sites are found in both the V3 region and the flanking regions.

Amino Acids↗
PubMed1998

Preponderance of slightly deleterious polymorphism in mitochondrial DNA: nonsynonymous/synonymous rate ratio is much higher within species than between species.

We estimated synonymous (dN) and nonsynonymous (dS) substitution rates for protein-coding genes of the mitochondrial genome from two individuals each of the species human, chimpanzee, and gorilla. The genes were analyzed both separately and in a combined data set. Pairwise sequence comparisons suggest that the dN/dS rate ratios are about 5-10 times higher in within-species comparisons than in between-species comparisons. This result is confirmed by a more rigorous likelihood ratio test, which rejected the null hypothesis that the dN/dS rate ratios are identical within and between species. The likelihood models account for the genetic code structure, transition/transversion rate ratio, and codon usage bias and are expected to produce more reliable results than the commonly used contingency test. Separate analyses of different genes show that the dN/dS rate ratios are higher within species than between species for all 13 mitochondrial genes, with the difference being statistically significant for all except three small or slowly evolving genes. Furthermore, in conserved genes, nonsynonymous rates within species tend to be higher than the between-species rates by a greater proportion than in fast-changing genes. Our findings confirm and extend earlier results obtained from smaller data sets and suggest the operation of slightly deleterious mutations throughout the mitochondrial genome in the hominoids. Implications of the results for evolutionary studies and, in particular, for studies of the origin of modern humans, are discussed.

Adenosine Triphosphatases↗
PubMed1998

Models of amino acid substitution and applications to mitochondrial protein evolution.

Models of amino acid substitution were developed and compared using maximum likelihood. Two kinds of models are considered. "Empirical" models do not explicitly consider factors that shape protein evolution, but attempt to summarize the substitution pattern from large quantities of real data. "Mechanistic" models are formulated at the codon level and separate mutational biases at the nucleotide level from selective constraints at the amino acid level. They account for features of sequence evolution, such as transition-transversion bias and base or codon frequency biases, and make use of physicochemical distances between amino acids to specify nonsynonymous substitution rates. A general approach is presented that transforms a Markov model of codon substitution into a model of amino acid replacement. Protein sequences from the entire mitochondrial genomes of 20 mammalian species were analyzed using different models. The mechanistic models were found to fit the data better than empirical models derived from large databases. Both the mutational distance between amino acids (determined by the genetic code and mutational biases such as the transition-transversion bias) and the physicochemical distance are found to have strong effects on amino acid substitution rates. A significant proportion of amino acid substitutions appeared to have involved more than one codon position, indicating that nucleotide substitutions at neighboring sites may be correlated. Rates of amino acid substitution were found to be highly variable among sites.

Amino Acid Substitution↗