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T Li

Publications and source records attributed to T Li.

At least 487 records · Page 27Linked to original sources
PubMed1993

No association between schizophrenia and homozygosity at the D3 dopamine receptor gene.

The D3 dopamine receptor gene is an important candidate gene for schizophrenia, since (because of its almost exclusive expression in the limbic system) it combines the dopamine receptor hypothesis with the limbic system hypothesis of schizophrenia. A BalI restriction fragment length polymorphism of the D3 dopamine receptor gene has been typed in 107 schizophrenic patients and 98 normal controls from Sichuan (China). With regard to alleles or genotypes, no significant differences were obtained between controls from Europe and China, between patients and controls, and between patient subgroups and controls. These results indicate a lack of association between schizophrenia and the D3 dopamine receptor gene in our sample. Our findings are at variance with reports of a significant excess of homozygosity at the D3 dopamine receptor gene in schizophrenic patients from Wales (United Kingdom) and Alsace (France). In conclusion, further studies will be needed with larger samples of patients from Wales and Alsace as well as with samples of different racial groups to prove or disprove the initial positive association between schizophrenia and genotypes of the D3 dopamine receptor gene.

Adolescent↗
PubMed1993

Structure determination of antiviral compound SCH 38057 complexed with human rhinovirus 14.

SCH 38057 (1-[6-(2-chloro-4-methoxyphenoxy)-hexyl]imidazole hydrochloride) is a new, water-soluble antiviral compound that has inhibitory activities against a number of picornavirus infections. The structure of the human rhinovirus 14 (HRV14) complex with SCH 38057 was determined at 3.0 A resolution by single-crystal diffraction techniques using synchrotron X-radiation. SCH 38057 was found to bind at the innermost end of the hydrophobic pocket within the capsid protein VP1, a locus of binding of other antipicornaviral agents; however, the complex differs from previously reported complexes in two important aspects. It leaves a considerable volume near the entrance to the binding pocket unoccupied. In addition, the alterations in the conformation of the VP1 polypeptide are similar to, but more extensive than those observed in HRV14 complexes with other antiviral agents. Although only 9 amino acids of VP1 have close contacts with the SCH 38057 molecule (within 3.6 A), at least 36 amino acids from both VP1 and VP3 have significantly altered conformations (C alpha movement > 0.5 A versus native). The structures of complexes of HRV14 with SCH 38057 and WIN 51711 are compared. Aromatic ring interactions between picornavirus capsid residues and antiviral inhibitors are proposed to be among the major determinants for positioning of these compounds.

Antiviral Agents↗
PubMed1993

Ligand diffusion in the distal heme pocket of myoglobin. A primary determinant of geminate rebinding.

There are at least two picosecond kinetic components in the rebinding of NO to native sperm whale myoglobin. Petrich et al. (Petrich, J. W., Lambry, J.-C., Kuczera, K., Karplus, M., Poyart, C., and Martin, J.-L. (1991) Biochemistry 30, 3975-3987) attribute the slowing of the reaction to a movement of the iron atom out of the plane of the heme following ligand dissociation. In contrast, Gibson et al. (Gibson, Q. H., Regan, R., Elber, R., Olson, J. S., and Carver, T. E. (1992) J. Biol. Chem. 267, 22022-22034) have explained multiphasic geminate reactions by diffusion of NO into the distal heme pocket as determined by its detailed structure. O2 and NO rebinding to iron and cobalt derivatives of native, V68F, and V68I sperm whale myoglobin has been examined. Each iron protein shows a biphasic time course of NO rebinding reactions with widely different rates and amplitudes. Although cobalt does not move out of the plane of the porphyrin on ligand removal, the reactions of the iron and cobalt derivatives of each protein were closely similar. The time course of O2 rebinding to cobalt was also similar to that of NO rebinding to iron. These results are consistent with a primary role for the structure of the distal pocket in determining diffusion of ligands away from the metal atom and as a result the time course of picosecond ligand rebinding.

Animals↗
PubMed1993

Localization of a retroviral element within the rd gene coding for the beta subunit of cGMP phosphodiesterase.

Retinal degeneration in the rd mouse is inherited as an autosomal recessive trait and is caused by a defect in the gene encoding the beta subunit of cGMP phosphodiesterase. Recently, a close genetic association of the rd gene with an endogenous xenotropic murine leukemia virus (Xmv-28) was established by linkage analysis using recombinant inbred strains of mice. In this study, genomic DNA mapping and sequence analyses clarify the position of the proviral sequences in relation to the rd gene. We find that the Xmv-28 provirus is integrated into intron I of the rd gene 1511 bp downstream of the exon-intron boundary. The transcriptional orientation of the provirus is opposite to that of the gene for the beta subunit of cGMP phosphodiesterase. Reverse transcription-PCR demonstrates that the integrated Xmv-28 sequences are transcribed in the retina. The provirus is present in every strain of rd mouse tested.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1993

Structural studies of the enveloped dsRNA bacteriophage phi 6 of Pseudomonas syringae by Raman spectroscopy. I. The virion and its membrane envelope.

We report and interpret the first Raman spectrum of a double-stranded RNA virus containing a membrane envelope. Spectra of the native bacteriophage phi 6 and of its isolated host-attachment (spike) protein and phospholipid-free core assembly were collected from aqueous solutions over a wide range of temperature. Comparison of the vibrational spectra by digital difference methods permits the following structural conclusions regarding molecular constituents of the fully assembled virion. (1) The double-stranded RNA, phospholipid and protein components of the phage exhibit Raman amplitudes in accordance with their biochemically determined compositions in the native virion (10, 20 and 70%, respectively). (2) alpha-Helix and irregular conformations are the dominant secondary structures in proteins of both the viral membrane and nucleocapsid. This represents a departure from previously examined icosahedral phage and plant viruses, which are dominated by beta-sheet structures. (3) The phospholipids of the viral membrane are liquid crystalline throughout the determined range of virus thermostability (0 to 40 degrees C). (4) The P3 spike protein of phi 6, which is anchored to, but not sequestered within the viral membrane, is largely alpha-helical (approximately 35%) and highly thermolabile. Denaturation of P3 at temperatures above 30 degrees C leads to appreciable loss (approximately 20%) of alpha-helix in favor of beta-strand structure, and alters significantly the environments of many aromatic side-chains. (5) The secondary structures of integral membrane proteins of phi 6 are overwhelmingly alpha-helical (approximately 70 to 80%) and also thermolabile. In contrast to P3, which exhibits aspartate and glutamate carboxyls in the ionized form (CO2-), the integral membrane proteins exhibit only protonated carboxyl groups (COOH). Treatment of phi 6 with butylated hydroxytoluene (BHT), which has been shown to remove the P3 spike protein, does not significantly perturb phospholipids and associated integral proteins of the viral membrane or structural proteins and packaged double-stranded RNA of the nucleocapsid. However, P3 subunits, which are recovered after BHT treatment, exhibit radically altered secondary and tertiary structures, including the loss of most subunit alpha-helices. Among the P3 side-chains affected by BHT treatment, we note a general trend toward greater hydrophilicity and greater solvent exposure of the aromatic residues Trp and Tyr. On the other hand, the cysteine sulfhydryl groups of the BHT-isolated P3 monomer are not solvent exposed and function as strong hydrogen-bond donors in the protein core.(ABSTRACT TRUNCATED AT 400 WORDS)

Bacteriophage phi 6↗
PubMed1993

Structural studies of the enveloped dsRNA bacteriophage phi 6 of Pseudomonas syringae by Raman spectroscopy. II. Nucleocapsid structure and thermostability of the virion, nucleocapsid and polymerase complex.

Structures and thermostabilities of the double-stranded (ds) RNA bacteriophage phi 6 and of its isolated nucleocapsid-polymerase complex (nucleocapsid core) and dsRNA components have been investigated by Raman spectroscopy. The spectra show that proteins of the phi 6 virion are collectively deficient in beta-sheet secondary structure. In particular, the major protein (P8) of the outer spherical shell of the phi 6 nucleocapsid exhibits a secondary structure dominated largely by alpha-helix and irregular conformations. The absence of appreciable beta-structure in the P8 subunit suggests a tertiary conformation lacking the beta-barrel motif common to subunits of most other spherical viral capsids. In addition, the Raman spectra show that subunits of the dodecahedral nucleocapsid core are also predominantly alpha-helical. The results thus indicate a largely alpha-helical secondary structure for the major subunit (P1) of the phi 6 nucleocapsid core, as well as for the P8 subunit of the outer spherical shell. Using Raman difference spectroscopy, we demonstrate that proteins of the nucleocapsid core (P1, P2, P4 and P7) interact extensively with the packaged phi 6 RNA genome, and further, that conformational stability of the packaged RNA is reduced upon removal from the core. Also, we find that proteins of the phi 6 nucleocapsid are significantly more thermostable than proteins of the viral membrane envelope, which are reported in the accompanying paper (Li et al., 1993). The present results suggest that both the architectural principles and modes of protein-RNA interaction in the phi 6 virion differ fundamentally from those of icosahedral single-stranded RNA viruses. Both Raman and circular dichroism spectra indicate that the dsRNA genome of phi 6 is an A-form structure. The Raman marker bands signify the presence only of C3'-endo/anti nucleoside conformers. The Raman signature of dsRNA, revealed in the spectrum of the phi 6 genome, is discussed here as a model for assessing base-pairing and base-stacking interactions in other ribonucleoprotein assemblies.

Bacteriophage phi 6↗
PubMed1993

Recurrent anterior uveitis induced by multiple systemic injections of muramyl dipeptide.

The development of new therapeutic modalities in the treatment of uveitis has been greatly aided by the availability of suitable animal models. The endotoxin model excellently mimics many features of acute anterior uveitis. A new model that exhibits many features of recurrent anterior uveitis is described here. Muramyl dipeptide, MDP, is a synthetic monomer of Gram positive and Gram negative bacterial cell walls. The molecule is highly inflammatory, but unlike endotoxin does not elicit an antibody response. After a single injection (4 hr post-injection), acute anterior segment changes include massive engorgement of peri-limbal blood vessels, anterior chamber flare, fibrin deposits and heterophil (neutrophil) infiltration which subside within 24-48 hr. There is also break-down of the blood-aqueous barrier. With multiple injections the exacerbations and remissions continue to be observed after each injection but the disease progresses to a recurrent form including the development of synechiae and a mononuclear infiltrate into the anterior segment. The ocular changes are paralleled by changes in the bloodstream with recurrent heterophilia. Thus MDP does not elicit ocular or systemic tolerance. This new model of anterior uveitis should allow study of many of the events that occur in recurrent uveitis in man.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1993

Raman dynamic probe of hydrogen exchange in bean pod mottle virus: base-specific retardation of exchange in packaged ssRNA.

We describe a novel approach to investigating exchange kinetics in biological assemblies. The method makes use of a Raman multichannel analyzer coupled with a dialysis flow cell. We employ this methodology to determine exchange rates of labile hydrogens in both the packaged RNA genome and protein subunits of bean pod mottle virus (BPMV). In the BPMV assembly, which is similar to human picornaviruses, the x-ray structure indicates that about 20% of the ssRNA chain is ordered at the threefold vertices of the icosahedral capsid, although the nucleotide bases in the ordered segments are not known (Chen et al., 1989). Here, we compare exchange profiles of the native virus with those of the empty capsid, model nucleic acids and aqueous solvent to reveal the following exchange characteristics of BPMV RNA and protein: (i) Base-specific retardation of exchange is observed in the packaged RNA. (ii) Retardation is greatest for uracil residues, for which the first-order exchange rate constant (kU = 0.18 +/- 0.02 min-1) is 40% lower than that of either the H2O solvent or adenine or cytosine groups of RNA (ksolv approximately kA approximately kC = 0.30 +/- 0.02 min-1). (iii) Retardation of exchange is also observed for the guanine residues of packaged RNA. (iv) No appreciable exchange of amide NH groups of capsid subunits occurs within the time of complete exchange (t approximately 10 min) of packaged RNA or bulk solvent. Thus, the present results identify sites in both the protein subunits (amide NH) and RNA nucleotides (amino NH2 and imino NH) which are resistant to solvent-catalyzed hydrogen exchange. We propose that retardation of exchange of labile sites of the RNA nucleotides is a consequence of the organization of the RNA chromosome within the virion. Our findings support a model for BPMV in which surface and buried domains of capsid subunits are extensively and rigidly hydrogen-bonded, and in which uracil and guanine exocyclic donor groups of packaged RNA are the principal targets for subunit interaction at the threefold vertices of the capsid.

Biophysical Phenomena↗
PubMed1993

Clinical trials for removal of bilirubin by high-capacity nonionic adsorbent.

To remove bilirubin from patients with hyperbilirubinemia, nonionic macroporous adsorbent NK-110 was tailor-made from styrene and divinyl benzene at Nankai University. Five patients were perfused through shunts filled with 500 ml of the above adsorbent. After 2 h of hemoperfusion, total bilirubin decreased within the range of 22-51%. During the treatment, no noticeable changes in electrolytes, urea nitrogen, serum glutamicpyruvic transaminase (SGPT), TTT, and amino acid concentrations were observed. Platelet depletion was satisfactory. Hemoglobin, white cell count, globulin, and albumin showed no remarkable changes. The nonionic adsorbent shows a high efficacy for bilirubin removal and has a great potential for future clinical applications.

Adsorption↗
PubMed1993

Comparison of the in vitro and in vivo cardiovascular effects of two structurally distinct Ca++ channel activators, BAY K 8644 and FPL 64176.

We compared the cardiovascular effects of two structurally distinct L-type Ca++ channel activators, the 1,4-dihydropyridine Bay K 8644 and the benzoylpyrrole FPL 64176. Both compounds prolonged action potential duration and enhanced contractility in guinea pig papillary muscle with these responses being greater in the presence of FPL 64176 compared to (S)-Bay K 8644. (S)-Bay K 8644 (300 nM) and FPL 64176 (300 nM) increased whole-cell Ca++ channel current amplitude in neonatal rat ventricular cells by 249 +/- 14 and 484 +/- 100%, respectively. (S)-Bay K 8644 had little effect on Ca++ channel activation but significantly enhanced the rate of Ca++ channel current inactivation. FPL 64176 significantly slowed Ca++ channel current activation and inactivation. Tail current decay at -50 mV was monoexponential in the presence of (S)-Bay K 8644 and had a time constant of 4.59 +/- 0.16 msec. FPL 64176 produced biexponential tail current decays at -50 mV with fast and slow time constants of 4.30 +/- 0.30 and 44.52 +/- 4.56 msec, respectively. Intravenous administration (1-100 micrograms/kg) of Bay K 8644 and FPL 64176 produced large increases in cardiac contractile force and diastolic blood pressure in anesthetized dogs. Pretreatment with nifedipine attenuated the blood pressure response to FPL 64176 but not the effects on cardiac contractility. This study demonstrates that the benzoylpyrrole FPL 64176 defines a new and potent class of Ca++ channel agonist molecule and that this compound has pharmacological activity that differs, at least in some respects, from the 1,4-dihydropyridine group of agonists.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1993

[Determination of gelsemium alkaloids by RP-HPLC].

Gelsemium elegans Benth is a kind of traditional Chinese medicine, eight alkaloids have been isolated from this herb. In recent years, an HPLC method for the separation and determination of five of these alkaloids, ie. gelsemium A (G), koumine (F), kumantenidine (D), kumantenine (B) and kumantenmine (A) is described, dichroine being used as the internal standard. In this report a RP column of C18 and the mobile phase methanol--water--n-butylamine (78:22:0.1 V/V) were employed. The flow rate was 1.0 ml/min, the column temperature was 25 degrees C and the detection wavelength was 256 nm. The calibration curves showed good linearity over the range of 0.02-0.12 microgram, r = 0.9835-0.9977 and the recoveries were 95.01-99.70% for the five alkaloids. The method is simple, sensitive and reproducible and can be used for the quality control of Gelsemium preparations for clinical evaluation.

Alkaloids↗
PubMed1993

Insect tolerance of transgenic Populus nigra plants transformed with Bacillus thuringiensis toxin gene.

Leaves and stem segments of Populus nigra were transformed with A. tumefaciens LBA4404 harboring a binary vector containing chimeric genes of NPT and 35S-omega-B.t. toxin-Nos. Nineteen regenerated kanamycin resistant plants were analyzed by DNA hybridization, out of which 10 were shown to be the candidates of transgenic plants. Insect tolerance tests showed that the transgenic plants were toxic to two lepidopteran pests, Lymantria dispar L. and Apocheimia cinerarius Erschoff. Based on the results of Southern blot of PCR products and the cluster analysis of their growth and insect resistance, three independent transgenic plants were selected, which were then propagated in the nursery field. This field test is currently in progress.

Agrobacterium tumefaciens↗