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Biomedical subjects

B Li

Publications and source records attributed to B Li.

At least 127 records · Page 7Linked to original sources
PubMed2001

P15INK4B gene methylation and expression in normal, myelodysplastic, and acute myelogenous leukemia cells and in the marrow cells of cured lymphoma patients.

P15INK4B methylation and expression was studied in bone marrow cells obtained from normal individuals, from patients who had been cured of lymphoma, and from patients with either MDS or AML. The level of p15 methylation was very low in normal BM cells and in CD34+ and CD34- subpopulations (0-6.5%; med, = 2.5%). P15INK4B transcripts were present in each of these cell populations. In contrast, methylation was the usual situation in MDS and AML marrows. The presence of methylation of the p15INK4B gene did not always indicate an absence of expression nor was expression always present if methylation was absent. P15INK4B methylation was studied in the marrows of nine patients (one studied twice) who had been cured of lymphoma and in whom hemopoiesis was believed to be normal. Increased methylaton was present in all 10 marrows. These data indicate that p15INK4B methylation is likely to be a very early event in the development of the secondary hematologic disorders.

Adult↗
PubMed2001

Pattern and component motion selectivity in cortical area PMLS of the cat.

Visual motion perception is one of the most prominent functions performed by the mammalian cerebral cortex. The moving images are commonly considered to be processed in two stages. The first-stage neurons are sensitive to the motion of one-dimensional orientated components, and their outputs are combined at the second stage to perceive the global motion of the whole pattern. Alternatively, the pattern motion may be signalled by monitoring a distinctive feature of the image, such as a line-end or a corner. In the present study, a series of 'random-line' patterns were used to measure the direction-tuning responses of 138 neurons in the posteromedial lateral suprasylvian area of the cat. The novel stimuli comprised identical thin line segments, with a length : width ratio no less than 10 : 1, which were moved perpendicularly or obliquely to their common orientation during the recordings. When the component lines were much shorter than the size of receptive field, the majority of cells were selective to the direction of pattern motion while only a small subset was sensitive to the direction of component motion. However, the response profiles of most cells became more component-motion selective with the increment of orientation element in stimulus by elongating the component lines in the patterns. These findings imply that the two-stage theory might be incomplete for modelling the visual motion analysis. Even at relatively low levels of the visual system, some kind of nonorientation-based processing may coexist with the orientation-sensitive processing in a dynamic competition, where one rises as the other falls depending upon the strength of the orientation element in the stimulus, so that under some circumstances it becomes possible to signal the veridical direction of pattern motion.

Action Potentials↗
PubMed2001

Assessment of the ratio of pollen to seed flow in a cline for genetic variation in a quantitative trait.

A dispersal-selection cline model is analysed to evaluate the role of the ratio of pollen to seed flow (r) in spatial genetic variation, with a focus on clines in additive and dominant variances of major genes affecting a quantitative trait, assuming one locus with two alleles, no genetic drift and no mutation. It is shown that under weak selection, steady-state departures from the value at Hardy-Weinberg equilibrium (HWE) for genotype frequency (D) and additive variance (DeltaVa) generally display a small value on one side of the selection boundary point, a high value around the point, and a moderate value on the other side of the boundary point. A large value of r can enhance formation of this pattern. However, this is not the case for clines in the average effect of a gene substitution (Deltaalpha) or in dominance variance (DeltaVd), where large values of r can eradicate the clines. Direct use of their values at HWE to approximate the real case is acceptable. There is an expected turning point that divides clines of either additive variance or dominance variance into two subclines, each with a shorter width than that of allele frequency. Integration of these properties can help to indicate the existence of major genes affecting a quantitative trait.

Gene Frequency↗
PubMed2001

Ceramide inhibits the outward potassium current in rat pinealocytes.

In the present study, we investigated the effect of ceramide on the outward K(+) current in rat pinealocytes using whole cell and single channel recordings. Three components of the whole cell outward K(+) current were separated, an iberiotoxin (IBTX)-sensitive K(+) current (I(KCa)), a transient A current (I(A)) and a delayed rectifier current (I(K)). C6-ceramide reduced all three components of the outward K(+) current. C6-ceramide (30 microM) caused a 53% inhibition of I(KCa) [a component that is generated by the IBTX-sensitive K(+) channel (BK channel)], a 27% inhibition of I(A) and a 17% inhibition of I(K). Additional studies showed that the BK channel was not inhibited by dihydroC6-ceramide, the inactive analog of C6-ceramide, but mimicked by sphingomyelinase which increased intracellular ceramide. The ceramide inhibition of the BK channel was only partly dependent on its inhibition of the L-type Ca(2+) channel. Studies using specific kinase inhibitors showed that calphostin C (a protein kinase C inhibitor) and to a lesser degree lavendustin A (a tyrosine kinase inhibitor) were effective in reducing the ceramide inhibition of I(KCa). Taken together, our results show that, in rat pinealocytes, ceramide reduces the outward K(+) current predominantly by inhibiting I(KCa). Moreover, protein kinase C appears to be the main kinase involved in the ceramide inhibition of I(KCa).

Animals↗
PubMed2001

Quantitation of interferon regulatory factor transcripts in patients with acute myeloid leukemia.

Interferon regulatory factors IRF-1 and IRF-2, the two mutually antagonistic factors, fluctuate during the cell cycle and play an important role in normal and neoplastic growth processes. The relative levels of these two transcripts were analyzed in 5 normal and 43 acute myeloid leukemia (AML) bone marrow (BM) specimens by a semiquantitative RT-PCR method. IRF-1 and IRF-2 cDNA sequences were coamplified using primers that were designed to span regions of high homology between the genes. Each primer can anneal equally to both IRF-1 and IRF-2 sequences. Hence, the relative amount of amplified products from each cDNA species provides an estimation of proportional concentration of the RNA transcripts in the test sample. Results indicate expression of both the transcripts on all the leukemia and lymphoma cell lines tested, normal and AML BM. Significantly higher IRF-1:IRF-2 ratio was observed in normal as compared to AML BM (p = 0.007). There was no correlation with clinical factors such as FAB subtype. A single dose of amifostine or three daily doses of recombinant IL-4 were administered to 5 and 8 AML patients, respectively. The changes in the expression of these transcripts were studied prior to administration of the agent (d0) and after 3 days (d3). IL-4 treatment showed significant increase in the IRF-1:IRF-2 ratio in 4 of 8 patients (p = 0.05); amifostine treatment did not show any appreciable change.

Acute Disease↗
PubMed2001

QSAR modeling of bioconcentration factors in fish based on fragment constants and structural correction factors.

The quantitative structure-activity relationship between the BCF and fragment constant of organic chemicals was studied using a database containing 337 experimental BCF values. The database covered a large variety of chemicals ranging from the very hydrophobic to the very hydrophilic with logKow values between 0.39 and 8.60. The structural features affecting the BCFs were identified and evaluated during a preliminary modeling. A final linear multivariate regression model was derived that was able to account for as much as 98.0% of the variation in the experimental BCF values. The mean absolute error for the final model was 0.315 log-units. In addition, the predictability and robustness of the model was also evaluated.

Animals↗
PubMed2001

APC2 Cullin protein and APC11 RING protein comprise the minimal ubiquitin ligase module of the anaphase-promoting complex.

In mitosis, the anaphase-promoting complex (APC) regulates the onset of sister-chromatid separation and exit from mitosis by mediating the ubiquitination and degradation of the securin protein and mitotic cyclins. With the use of a baculoviral expression system, we have reconstituted the ubiquitin ligase activity of human APC. In combination with Ubc4 or UbcH10, a heterodimeric complex of APC2 and APC11 is sufficient to catalyze the ubiquitination of human securin and cyclin B1. However, the minimal APC2/11 ubiquitin ligase module does not possess substrate specificity, because it also ubiquitinates the destruction box deletion mutants of securin and cyclin B1. Both APC11 and UbcH10 bind to the C-terminal cullin homology domain of APC2, whereas Ubc4 interacts with APC11 directly. Zn(2+)-binding and mutagenesis experiments indicate that APC11 binds Zn(2+) at a 1:3 M ratio. Unlike the two Zn(2+) ions of the canonical RING-finger motif, the third Zn(2+) ion of APC11 is not essential for its ligase activity. Surprisingly, with Ubc4 as the E2 enzyme, Zn(2+) ions alone are sufficient to catalyze the ubiquitination of cyclin B1. Therefore, the Zn(2+) ions of the RING finger family of ubiquitin ligases may be directly involved in catalysis.

Amino Acid Sequence↗
PubMed2001

Functional and morphologic comparison of two methods to produce transient retinal ischemia in the rat.

OBJECTIVES: Much of our knowledge of the pathophysiology of retinal ischemic injury is from a multitude of studies that use in vitro or in vivo animal models of retinal ischemia followed by reperfusion. The objective of this study was to compare histopathologic and electrophysiologic (electroretinography) parameters using two different models of transient retinal ischemia: high intraocular pressure (HIOP) and suture ligation of the optic nerve (SL). METHODS: Transient retinal ischemia was induced using the HIOP model or the SL model in the Sprague-Dawley rat for either 30 or 60 minutes. Histopathologic outcome was determined at 1 and 7 days after ischemia. In addition, electroretinography (ERG) was performed at 2 hours, I day, 3 days, and 7 days after ischemia. RESULTS: At 1 and 7 days after 30 minutes of ischemia, there were no significant histopathologic abnormalities in the retina with either model, except for a slight decrease of the cell count in the ganglion cell layer (GCL) with the SL method. After 60 minutes of ischemia, there was significant thinning of the inner retina. There was a significant early dropout of cells at 1 day in the inner nuclear layer (INL) in the HIOP method compared to the SL method where the dropout was delayed and gradually progressive. Dropout of cells in the GCL was early (I day) and gradually progressive in both models but more severe in HIOP than SL. There was a significant decrease in the ERG b-wave amplitudes as early as 2 hours after both 30 and 60 minutes of ischemia compared to preischemic baselines. CONCLUSIONS: The degree of retinal injury after transient retinal ischemia was more severe at 1 day after reperfusion in the HIOP method compared to the SL method but was similar at 7 days in both models. Furthermore, our data suggests that functional assessment of ischemic damage by electroretinography may be a more sensitive parameter than conventional histopathologic quantification. The timing of either measurement relative to the ischemic stimulus is critical because histologic measurements performed too early after ischemia may underestimate the degree of injury.

Animals↗
PubMed2001

Computer-aided virtual surgery for congenital aural atresia.

HYPOTHESIS: Computer-enhanced three-dimensional (3D) computed tomography (CT) provides accurate spatial representation of the complex surgical anatomy of congenitally atretic ears, and is superior to conventional CT for surgical planning. BACKGROUND: The surgical repair of congenital aural atresia is challenging. Conventional CT, routinely used for surgical planning, is limited in its ability to represent spatial relationships between important structures. Because of the lack of density differences between bony structures in the ear, 3D CT has thus far been useful for representing surface contour but not internal anatomy. METHODS: A two-level segmentation scheme was developed to distinguish structures in the temporal bone. 3D CT reconstructions of congenital ears were produced with a high-resolution helical scanner. An interactive tool was used to mark the ossicles and facial nerve. The segmentation scheme was used to color-enhance the ossicles and otic capsule, and render the surrounding bone translucent. "Virtual surgery" was then performed by subtracting a cylindrical volume of bone lateral to the atresia plate. The enhanced 3D CT reconstructions were correlated with intraoperative video recordings. RESULTS: In four congenital ears, computer-enhanced 3D CT was highly predictive of the actual anatomy. Surgery was avoided in two anatomically unfavorable cases. CONCLUSION: Computer-enhanced 3D CT is a major advance over conventional CT for demonstrating the complex spatial relationships in congenitally atretic ears.

Adolescent↗
PubMed2001

A maximum likelihood-based method for mining major genes affecting a quantitative character.

In this article, we present a maximum likelihood-based analytical approach for detecting a major gene of large effect on a quantitative trait in a progeny population derived from a mating design. Our analysis is based on a mixed genetic model specifying both major gene and background polygenic inheritance. The likelihood of the data is formulated by combining the information about population behaviors of the major gene during hybridization and its phenotypic distribution densities. The EM algorithm is implemented to obtain maximum likelihood estimates for population and quantitative genetic parameters of the major locus. This approach is applied to detect an overdominant gene governing stem volume growth in a factorial mating design of aspen trees. It is suggested that further molecular genetic research toward mapping single genes affecting aspen growth and production based on the same experimental data has a high probability of success.

Algorithms↗
PubMed2001

Agonist-mediated down-regulation of rat beta1-adrenergic receptor transcripts: role of potential post-transcriptional degradation factors.

The human beta1-adrenergic receptor (AR) and hamster beta2-AR transcripts can be post-transcriptionally regulated at the level of mRNA stability and undergo accelerated agonist-mediated degradation via interaction of their 3' untranslated regions (UTR) with RNA binding proteins. Using RNase protection assays, we have determined that chronic isoproterenol exposure of rat C6 glioma cells results in the accelerated reduction of beta1-AR mRNAs. To determine the role of cellular environment on the agonist-independent and agonist-mediated degradation of beta1-AR mRNAs, we transfected rat beta1-AR expression recombinants into both hamster DDT1MF2 cells and rat L6 cells. The rat beta1-AR mRNAs in the two transfectant cell pools retain longer agonist-independent half-lives than in the C6 environment and undergo accelerated degradation upon chronic agonist exposure. Using UV-cross-linking/immunoblot and immunoprecipitation analyses, we have determined that the rat beta1-AR 3' UTR recognizes a predominant M(r) 39,000 component, identified as the mammalian elav-like protein HuR, and several other minor components, including the heteronuclear protein hnRNP A1. HuR levels are more highly expressed in C6 cells than in DDT1MF2 and L6 cells and are induced after chronic isoproterenol treatment. Furthermore, C6 transfectants containing an HuR expression recombinant exhibit reduced beta1-AR mRNA half-lives that were statistically comparable with half-lives identified in isoproterenol-treated C6 cells. These results imply that HuR plays a potential role in the agonist-independent and agonist-mediated down-regulation of beta1-AR mRNAs.

3' Untranslated Regions↗
PubMed2001

New pulp biobleaching system involving manganese peroxidase immobilized in a silica support with controlled pore sizes.

Attempts have been made to use manganese peroxidase (MnP) for chlorine-free pulp biobleaching, but they have not been commercially viable because of the enzyme's low stability. We developed a new pulp biobleaching method involving mesoporous material-immobilized manganese peroxidase from Phanerochaete chrysosporium. MnP immobilized in FSM-16, a folded-sheet mesoporous material whose pore size is nearly the same as the diameter of the enzyme, had the highest thermal stability and tolerance to H(2)O(2). MnP immobilized in FSM-16 retained more than 80% of its initial activity even after 10 days of continuous reaction. We constructed a thermally discontinuous two-stage reactor system, in which the enzyme (39 degrees C) and pulp-bleaching (70 degrees C) reactions were performed separately. When the treatment of pulp with MnP by means of the two-stage reactor system and alkaline extraction was repeated seven times, the brightness of the pulp increased to about 88% within 7 h after completion of the last treatment.

Enzyme Stability↗
PubMed2001

Internal transcribed spacer regions of rRNA genes of Pneumocystis carinii from monkeys.

Analysis of sequence variations among isolates of Pneumocystis carinii f. sp. macacae from 14 Indian rhesus monkeys (Macaca mulatta) at the internal transcribed spacer (ITS) regions of the nuclear rRNA gene was undertaken. Like those from P. carinii f. sp. hominis, the ITS sequences from various P. carinii f. sp. macacae isolates were not identical. Two major types of sequences were found. One type of sequence was shared by 13 isolates. These 13 sequences were homologous but not identical. Variations were found at 13 of the 180 positions in the ITS1 region and 28 of the 221 positions in the ITS2 region. These sequence variations were not random but exhibited definite patterns when the sequences were aligned. According to this sequence variation, ITS1 sequences were classified into three types and ITS2 sequences were classified into five types. The remaining specimen had ITS1 and ITS2 sequences substantially different from the others. Although some specimens had the same ITS1 or ITS2 sequence, all 14 samples exhibited a unique whole ITS sequence (ITS1 plus ITS2). The 5.8S rRNA gene sequences were also analyzed, and only two types of sequences that differ by only one base were found. Unlike P. carinii f. sp. hominis infections in humans, none of the monkey lung specimens examined in this study were found to be infected by more than one type of P. carinii f. sp. macacae. These results offer insights into the genetic differences between P. carinii organisms which infect distinct species.

Animals↗
PubMed2001

Phylogenetic evidence for horizontal transfer of mutS alleles among naturally occurring Escherichia coli strains.

mutS mutators accelerate the bacterial mutation rate 100- to 1,000-fold and relax the barriers that normally restrict homeologous recombination. These mutators thus afford the opportunity for horizontal exchange of DNA between disparate strains. While much is known regarding the mutS phenotype, the evolutionary structure of the mutS(+) gene in Escherichia coli remains unclear. The physical proximity of mutS to an adjacent polymorphic region of the chromosome suggests that this gene itself may be subject to horizontal transfer and recombination events. To test this notion, a phylogenetic approach was employed that compared gene phylogeny to strain phylogeny, making it possible to identify E. coli strains in which mutS alleles have recombined. Comparison of mutS phylogeny against predicted E. coli "whole-chromosome" phylogenies (derived from multilocus enzyme electrophoresis and mdh sequences) revealed striking levels of phylogenetic discordance among mutS alleles and their respective strains. We interpret these incongruences as signatures of horizontal exchange among mutS alleles. Examination of additional sites surrounding mutS also revealed incongruous distributions compared to E. coli strain phylogeny. This suggests that other regional sequences are equally subject to horizontal transfer, supporting the hypothesis that the 61.5-min mutS-rpoS region is a recombinational hot spot within the E. coli chromosome. Furthermore, these data are consistent with a mechanism for stabilizing adaptive changes promoted by mutS mutators through rescue of defective mutS alleles with wild-type sequences.

Adenosine Triphosphatases↗
PubMed2001

Role of polypyrimidine tract binding protein in the function of the hepatitis B virus posttranscriptional regulatory element.

The hepatitis B virus posttranscriptional regulatory element (PRE) is an RNA element that increases the expression of unspliced mRNAs, apparently by facilitating their export from the nucleus. We have identified a cellular protein that binds to the PRE as the polypyrimidine tract binding protein (PTB), which shuttles rapidly between the nucleus and the cytoplasm. Mutants of the PRE with mutations in PTB binding sites show markedly decreased activity, while cells that stably overexpress PTB show increased PRE-dependent gene expression. Export of PTB from the nucleus, like PRE function, is blocked by a mutant form of Ran binding protein 1 but not by leptomycin B. Therefore, PTB is important for PRE activity and appears to function as an export factor for PRE-containing mRNAs.

Base Sequence↗
PubMed2001

Intracranial pressure accommodation is impaired by blocking pathways leading to extracranial lymphatics.

Tracer studies indicate that cerebrospinal fluid (CSF) transport can occur through the cribriform plate into the nasal submucosa, where it is absorbed by cervical lymphatics. We tested the hypothesis that sealing the cribriform plate extracranially would impair the ability of the CSF pressure-regulating systems to compensate for volume infusions. Sheep were challenged with constant flow or constant pressure infusions of artificial CSF into the CSF compartment before and after the nasal mucosal side of the cribriform plate was sealed. With both infusion protocols, the intracranial pressure (ICP) vs. flow rate relationships were shifted significantly to the left when the cribriform plate was blocked. This indicated that obstruction of the cribriform plate reduced CSF clearance. Sham surgical procedures had no significant effects. Estimates of the proportional flow through cribriform and noncribriform routes suggested that cranial CSF absorption occurred primarily through the cribriform plate at low ICPs. Additional drainage sites (arachnoid villi or other lymphatic pathways) appeared to be recruited only when intracranial pressures were elevated. These data challenge the conventional view that CSF is absorbed principally via arachnoid villi and provide further support for the existence of several anatomically distinct cranial CSF transport pathways.

Animals↗
PubMed2001

Endothelin is a potent inhibitor of matrix metalloproteinase-2 secretion and activation in rat mesangial cells.

We examined the effects of endothelin (ET) on the activity of matrix metalloproteinase-2 (MMP-2) in cultured MCs. Addition of the ET(A) receptor antagonists or neutralizing anti-endothelin antibody into MC cultures markedly augmented the secretion and activation of MMP-2. On the contrary, addition of the exogenous ET-1 into MC culture significantly inhibited the synthesis of MMP-2 in both basal and cytokines (tumor necrosis factor-alpha and interferon-gamma) plus lipopolysaccharide-stimulated conditions. Furthermore, pretreatment of cells with exogenous ET-1 obviously prevented cytochalasin D-elicited activation of MMP-2, an effect that was completely abolished by ET(A) receptor antagonist, FR139317. In addition, ET-1 was found to be able to suppress the expression of membrane type-1 MMP (MT1-MMP) and promote the conversion of tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) from cell associated form to secreted form. The addition of recombinant TIMP-2 into the culture abrogated dose-dependently the cytochalasin D-elicited activation of MMP-2. These results suggest that ET is a potent inhibitor of MMP-2 secretion and activation in MCs. These novel findings may help us understand the subtle regulation of the synthesis and activation of MMP-2 in MCs. It also provides us with further insight into the pathophysiological mechanisms involving ET in the regulation of matrix turnover in glomerulus.

Animals↗