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Biomedical subjects

J Teng

Publications and source records attributed to J Teng.

14 recordsLinked to original sources
PubMed2000

Defects in axonal elongation and neuronal migration in mice with disrupted tau and map1b genes.

Tau and MAP1B are the main members of neuronal microtubule-associated proteins (MAPs), the functions of which have remained obscure because of a putative functional redundancy (Harada, A., K. Oguchi, S. Okabe, J. Kuno, S. Terada, T. Ohshima, R. Sato-Yoshitake, Y. Takei, T. Noda, and N. Hirokawa. 1994. Nature. 369:488-491; Takei, Y., S. Kondo, A. Harada, S. Inomata, T. Noda, and N. Hirokawa. 1997. J. Cell Biol. 137:1615-1626). To unmask the role of these proteins, we generated double-knockout mice with disrupted tau and map1b genes and compared their phenotypes with those of single-knockout mice. In the analysis of mice with a genetic background of predominantly C57Bl/6J, a hypoplastic commissural axon tract and disorganized neuronal layering were observed in the brains of the tau+/+map1b-/- mice. These phenotypes are markedly more severe in tau-/-map1b-/- double mutants, indicating that tau and MAP1B act in a synergistic fashion. Primary cultures of hippocampal neurons from tau-/-map1b-/- mice showed inhibited axonal elongation. In these cells, a generation of new axons via bundling of microtubules at the neck of the growth cones appeared to be disturbed. Cultured cerebellar neurons from tau-/-map1b-/- mice showed delayed neuronal migration concomitant with suppressed neurite elongation. These findings indicate the cooperative functions of tau and MAP1B in vivo in axonal elongation and neuronal migration as regulators of microtubule organization.

Aging↗
PubMed2000

DNA-RNA chimeric hammerhead ribozyme to transforming growth factor-beta(1) mRNA inhibits the exaggerated growth of vascular smooth muscle cells from spontaneously hypertensive rats.

OBJECTIVE: The purpose of this study was to develop DNA-RNA chimeric hammerhead ribozyme against transforming growth factor-beta(1) (TGF-beta(1)) mRNA as a gene therapy agent for arterial proliferative diseases. METHODS: A 38-base hammerhead ribozyme against rat TGF-beta(1) mRNA, to produce cleavage at the GUC sequence at nucleotide 825 according to the secondary structure of rat TGF-beta(1) mRNA was designed. To enhance its stability, we synthesized a DNA-RNA chimeric ribozyme with two phosphorothioate linkages at the 3'-terminal. We also synthesized a mismatch ribozyme with single base change in the catalytic loop region as a control. These ribozymes were delivered into rat vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats by lipofectin-mediated transfection, and their biological effects were investigated. RESULTS: According to in vitro cleavage studies, the synthetic ribozyme can cleave the synthetic substrate RNA into two RNA fragments. Chimeric ribozyme significantly inhibited DNA synthesis in VSMC from SHR but not in cells from WKY rats. Mismatch ribozyme showed only a little effect on growth of VSMC from SHR. Chimeric ribozyme significantly inhibited proliferation of VSMC from SHR; in contrast, the proliferation of VSMC from WKY rats was significantly increased by this chimeric ribozyme. Mismatch ribozyme did not affect proliferation of VSMC from either rat strain. Chimeric hammerhead ribozyme to rat TGF-beta(1) dose-dependently inhibited TGF-beta(1) mRNA expression detected by reverse transcription and polymerase chain reaction analysis in VSMC from both rat strains. Chimeric hammerhead ribozyme to rat TGF-beta(1) also dose-dependently inhibited TGF-beta(1) protein production detected by Western blot analysis. CONCLUSIONS: The present results demonstrated that our designed DNA-RNA chimeric hammerhead ribozyme to TGF-beta(1) mRNA might be a useful gene therapy agent for hypertensive vascular diseases.

Analysis of Variance↗
PubMed2000

Angiotensin II regulates the cell cycle of vascular smooth muscle cells from SHR.

We have demonstrated that spontaneously hypertensive rats (SHR)-derived vascular smooth muscle cells (VSMC) show the exaggerated growth and produce angiotensin II (Ang II). In the current study, we investigated the role of endogenous Ang II in the regulation of the cell cycle in VSMC from SHR. Levels of Ang II in conditioned medium from SHR-derived VSMC cultured without serum were significantly higher than levels in conditioned medium from Wistar-Kyoto (WKY) rat-derived VSMC. Basal DNA synthesis was higher in quiescent VSMC from SHR than that in cells from WKY rats. An Ang II type 1 receptor antagonist, CV11974, significantly inhibited the elevation in DNA synthesis in quiescent VSMC from SHR but did not affect it in cells from WKY rats. Cellular DNA content analysis by flow cytometry revealed that the proportion of cells in S phase was higher, whereas the proportion of cells in G1+G0 phase was lower in VSMC from SHR than those in cells from WKY rats. CV11974 significantly decreased the proportion of cells in S phase and correspondingly increased the proportion of cells in G1+G0 phase in VSMC from SHR, but it did not affect the proportion in cells from WKY rats. Cyclin-dependent kinase 2 (CDK2) activity, which is known to induce the progression from G1 to S phase, was higher in VSMC from SHR than in cells from WKY rats. Expression of CDK2 inhibitor p27(kip1) mRNA was markedly higher in VSMC from SHR than in cells from WKY rats. CV11974 decreased expression of p27(kip1) mRNA in VSMC from SHR, whereas CV11974 increased it in cells from WKY rats. These findings indicate that enhanced production of endogenous Ang II regulates the cell cycle especially in the progression from G1 to S phase, and increases CDK2 activity, which is independent of p27(kip1) in VSMC from SHR.

Angiotensin II↗
PubMed1999

The relative power of family-based and case-control designs for linkage disequilibrium studies of complex human diseases. II. Individual genotyping.

In this paper we consider test statistics based on individual genotyping. For sibships without parents, but with unaffected as well as affected sibs, we introduce a new test statistic (referred to as TDS), which contrasts the allele frequency in affected sibs versus that estimated for the parents from the entire sibship. For sibships without parents, this test is analogous to the TDT and is completely robust to nonrandom mating patterns. The efficiency of the TDS test is comparable to that of the THS test (which compares affected vs. unaffected sibs and was based on DNA pooling), for sibships with one affected child. However, as the number of affected sibs in the sibship grows, the relative efficiency of the TDS test versus the THS test also increases. For example, for sibships with three affected, one-third fewer families are required; for families with four affected, nearly half as many are required. Thus, when sibships contain multiple affected individuals, the TDS test provides both an increase in power and robustness to nonrandom mating.

Case-Control Studies↗
PubMed1998

The relative power of family-based and case-control designs for linkage disequilibrium studies of complex human diseases I. DNA pooling.

We consider statistics for analyzing a variety of family-based and nonfamily-based designs for detecting linkage disequilibrium of a marker with a disease susceptibility locus. These designs include sibships with parents, sibships without parents, and use of unrelated controls. We also provide formulas for and evaluate the relative power of different study designs using these statistics. In this first paper in the series, we derive statistical tests based on data derived from DNA pooling experiments and describe their characteristics. Although designs based on affected and unaffected sibs without parents are usually robust to population stratification, they suffer a loss of power compared with designs using parents or unrelateds as controls. Although increasing the number of unaffected sibs improves power, the increase is generally not substantial. Designs including sibships with multiple affected sibs are typically the most powerful, with any of these control groups, when the disease allele frequency is low. When the allele frequency is high, however, designs with unaffected sibs as controls do not retain this advantage. In designs with parents, having an affected parent has little impact on the power, except for rare dominant alleles, where the power is increased compared with families with no affected parents. Finally, we also demonstrate that for sibships with parents, only the parents require individual genotyping to derive the TDT statistic, whereas all the offspring can be pooled. This can potentially lead to considerable savings in genotyping, especially for multiplex sibships. The formulas and tables we derive should provide some guidance to investigators designing nuclear family-based linkage disequilibrium studies for complex diseases.

Case-Control Studies↗
PubMed1998

Studying the reaction between clozapine and glutathione with element-selective detection.

The target of these investigations was a study of covalent binding the antipsychotic drug clozapine and the tripeptide glutathione. Other workers, primarily using radioisotopes, have found many adducts of clozapine and glutathione. We wanted to see how well the chlorine atom in clozapine could serve as an alternate to the use of a radiolabel using the Chemical Reaction Interface/Mass Spectrometer technique with HPLC introduction (HPLC/CRIMS). Here, we examine the capabilities of two such schemes that were previously used with GC introduction: Cl detection with SO2 as the reactant gas; and Cl and S detection using NF3 as the reactant gas. Detecting chlorine as HCl with SO2 was accomplished giving linearity over an 80-fold range of sample size. Incubations of the drug and glutathione with a peroxidase/peroxide system system yielded several metabolites characterized as novel conjugates of clozapine by electrospray mass spectrometry. This tentative identification of two conjugates was confirmed by examining the incubation mixture with NF3 as the CRIMS reactant gas. The simultaneous appearance of both Cl and S is consistent with covalent binding of clozapine to glutathione. A nearly doubled ratio of S to Cl in one peak confirmed the presence of a di-glutathione conjugate. These experiments support our proposition that element selective detection of HPLC effluents with CRIMS can supply additional information, not previously available using radioisotopic methods.

Chromatography, High Pressure Liquid↗
PubMed1998

Multipoint linkage analysis using affected relative pairs and partially informative markers.

Linkage analysis is a method of identifying regions of the human genome harboring genes affecting the risk for a particular disease. It works by finding chromosomal segments inherited by affected relatives from a common ancestor (i.e., identical by descent or IBD) in excess of that expected by chance. Two complicating factors are that only a relatively small number of genomic locations (marker loci) are examined and the number of distinct realizations (alleles) at each marker is not large. Hence, unambiguous determination of IBD is impossible for any genomic location without additional information. Assuming data from a set of mapped, partially informative markers, we evaluate the effectiveness of a method that analyzes the array of markers on each chromosome jointly (multipoint methods) as a function of the informativeness and density of the markers. For the special case of pairs of half siblings whose parents are also typed, a combination of analysis and simulation is used to obtain insight into the problem of setting thresholds to control the false-positive error rate. Approximations are given for the power, and guidelines are developed to help describe the trade-offs between marker density and informativeness.

Biometry↗
PubMed1997

Combining information within and between pedigrees for mapping complex traits.

This paper is concerned with efficient strategies for gene mapping using pedigrees containing small numbers of affecteds and identity-by-descent data from closely spaced markers throughout the genome. Particular attention is paid to additive traits involving phenocopies and/or locus heterogeneity. For a sample of pedigrees containing a particular configuration of affecteds, e.g., pairs of siblings together with a first cousin, we use a likelihood analysis to find 1-df statistics that are very efficient over a broad range of penetrances and allele frequencies. We identify configurations of affecteds that are particularly powerful for detecting linkage, and we show how pedigrees containing different numbers and configurations of affecteds can be efficiently combined in an overall test statistic.

Chromosome Mapping↗
PubMed1997

[Morphogenesis of AcMNPV nucleocapsid].

In this paper we reported that the nucleocapsid morphogenetic process of AcMNPV in which polyhedrin gene was deleted in the nuclei of sf9 cells. First, the capsid proteins entered the nuclei and assembled many 34nm diameter long fascicularly arranged hollow-tube structures. Then viral DNA entered these tubes that turned into solid structure with high electronic density. The solid structure separated at a certain distance to form 34 x 26 nm fascicular bacilliform structure known as nucleocapsid. Finally, fascicular nucleocapsids were wrapped by envelope and became complete multicapsid morphotype viron.

Animals↗
PubMed1994

Experimental study on effect of traditional bone-knitting drugs on traumatic gu bi (bone-rheumatoid lesions).

Traditional bone-knitting drugs (TBKD) are used frequently in the treatment of bone fractures. An animal model of Gu Bi (bone-related rheumatoid lesions) with defects of articular cartilage as the main lesion was developed by surgical trauma under the stereomicroscope in Wistar rats and treated with TBKD. The results showed that TBKD could promote proliferation of cartilage cells around the traumatic site and improve the osteogenetic function in the traumatic state, suggesting that TBKD can be used in combination with other Chinese drugs to treat Gu Bi, including bony lesions of the late-stage rheumatoid arthritis and bony arthritis. But the experimental results also suggested that TBKD might have an effect of promoting development of inflammation, and therefore, should be used with care in the acute phase of inflammation.

Animals↗
PubMed1993

Regulation of myeloblastin messenger RNA expression in myeloid leukemia cells treated with all-trans retinoic acid.

Retinoic acid is known to induce differentiation of human myeloid leukemia cells in vitro. Recently, all-trans retinoic acid has been used to induce remissions in patients with acute promyelocytic leukemia, probably through differentiation of the leukemia cells. Myeloblastin (mbn) is a protease that has been identified in the human leukemia cell line HL-60. Downregulation of this protease can inhibit proliferation and induce differentiation of HL-60-derived leukemia cells. Here we have investigated the regulation of mbn messenger RNA (mRNA) expression in two human leukemia cell lines, HL-60 and NB4, treated with all-trans retinoic acid. Under this treatment, downregulation of mbn mRNA was observed in both cell lines, but was considerably delayed in NB4 cells that carry the t(15;17) translocation characteristic of acute promyelocytic leukemia. We have found that multiple mechanisms were involved in the control of mbn mRNA expression. These mechanisms were different in HL-60 and NB4 cells. Our results show that in HL-60 cells, all-trans retinoic acid rapidly decreased transcription of mbn. In contrast, in the t(15;17)-positive NB4 cells treated with all-trans retinoic acid, upregulation of mbn mRNA expression was followed by a late downregulation, both achieved via posttranscriptional mechanisms.

Cell Cycle↗
PubMed1993

The cardiac troponin T alternative exon contains a novel purine-rich positive splicing element.

We have characterized a novel positive-acting splicing element within the developmentally regulated alternative exon (exon 5) of the cardiac troponin T (cTNT) gene. The exon splicing element (ESE) is internal to the exon portions of the splice sites and is required for splicing to the 3' splice site but not the 5' splice site flanking the exon. Sequence comparisons between cTNT exon 5 and other exons that contain regions required for splicing reveal a common purine-rich motif. Sequence within cTNT exon 5 or a synthetic purine-rich motif facilitates splicing of heterologous alternative and constitutive splice sites in vivo. Interestingly, the ESE is not required for the preferential inclusion of cTNT exon 5 observed in primary skeletal muscle cultures. Our results strongly suggest that the purine-rich ESE serves as a general splicing element that is recognized by the constitutive splicing machinery.

Alternative Splicing↗
PubMed1990

Intestinal helminthiasis in ex-patriates returning to Britain from the tropics. A controlled study.

A retrospective study was performed of clinical features in expatriates attending the Hospital for Tropical Diseases, London, with a sole diagnosis of ascariasis (100), trichuriasis (100), hookworm (75), and strongyloidiasis (36). Results were compared with a control group of 100 ex-patriates attending the same hospital in whom no diagnosis was made and in whom stool microscopy and peripheral blood eosinophil counts were normal. Almost one half of all patients with intestinal helminthiasis were asymptomatic. Of those with symptoms specific clinical features were no different from controls with the exception of a transient itch or rash in patients with strongyloidiasis. The presence of eosinophilia was not a reliable indicator of infection. This study suggests that it may be worth while performing stool microscopy in ex-patriates returning from the tropics even if they are asymptomatic.

Adult↗