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Biomedical subjects

T Li

Publications and source records attributed to T Li.

At least 343 records · Page 19Linked to original sources

Association analysis of the dopamine D4 gene exon III VNTR and heroin abuse in Chinese subjects.

Although social and cultural influences are clearly important, family, twin and adoption studies indicate that genes contribute significantly to substance abuse. Substance abuse is associated with novelty seeking, a heritable human personality trait which may be influenced by alleles of the dopamine D4 (DRD4) gene exon III VNTR. Consequently Kotler et al analysed the DRD4 VNTR in opiate-dependent subjects from Israel, and found a significant excess of the 7-repeat allele. We have attempted to replicate this finding using a Han Chinese case-control sample of 121 heroin-dependent subjects and 154 normal controls. We found two 7-repeat alleles which occurred exclusively in the patient group, and overall there was an excess of longer alleles, which did not reach significance (chi 2 = 7.04; P = 0.07). When the D4 VNTR was divided into 'long' (5-7 repeats) and 'short' (2-4 repeats), a significant excess of long alleles was observed in the patient group (P = 0.023, one-tailed), with an odds ratio of 2.30 (95% CI 1.07-4.93). We conclude that our findings support the hypothesis that alleles of the DRD4 exon III VNTR are susceptibility factors for heroin abuse.

Adolescent↗

Evaluation of recombinant adeno-associated virus as a gene transfer vector for the retina.

PURPOSE: To evaluate recombinant adeno-associated virus (AAV) as an in vivo gene transfer vector for the retina. METHODS: A recombinant AAV, vCMVp-lacZ, in which the bacterial beta-galactosidase reporter gene (lacZ) was placed under the control of a cytomegalovirus (CMV) early promoter, was injected into the vitreous body or the subretinal space of mouse eyes. The reporter gene expression was followed by histochemical analyses from 10 to 100 days post-injection. The effect of several variables on the extent of AAV-mediated gene transfer was examined, including routes of delivery, presence of an underlying mutation that caused retinal degeneration, and prior treatment with hydroxyurea. RESULTS: As measured by reporter gene expression, the AAV vector mediated gene transfer to three major cell types in the retina: the retinal pigment epithelium (RPE), ganglion cells and photoreceptor cells. Following a single injection, more than half of the total retinal areas were typically positive for gene transfer. Reporter gene expression was stable for at least 3 months, the farthest time point examined. Gene transfer to photoreceptor cells was observed only following subretinal delivery, and was greatly enhanced in mice undergoing early retinal degeneration. Cells in the inner nuclear layer were rarely transduced. Systemic administration of a genotoxic drug, hydroxyurea, 2 days prior to AAV delivery did not affect the patterns and extent of reporter gene expression. There was minimal histopathology associated with AAV transduction in the retinas of recipient mice, as determined by light microscopy. CONCLUSION: Recombinant AAV mediates efficient gene transfer to RPE and ganglion cells, and to photoreceptor cells under certain conditions. Persistence of transgene expression is of long duration and without apparent histopathology. The greater stability, lower cytopathicity, and the ability to transduce retinal ganglion cells are three distinct features of the AAV vector compared to current adenovirus-based vectors.

Animals↗

Adriamycin cardiomyopathy: pathophysiology and prevention.

Current knowledge about adriamycin cardiomyopathy indicates that the major cause of this condition is increased oxidative stress although the drug's antitumor action in patients may involve other mechanisms. Controversies about the different antioxidants in preventing cardiomyopathy likely stem from the fact that antioxidants must be effective in both the lipid and water phases, and the dose must be optimal, in order to be protective. Probucol, an antioxidant and promoter of endogenous antioxidants, is one such agent. Conducting clinical trials with an optimal dose of probucol is the next step and should make this great anticancer drug safer and more efficient in the fight against the cancer.

Animals↗

Efficacy and cost-effectiveness of multihole fine-needle aspiration of head and neck masses.

To determine whether the specimen from fine-needle aspiration (FNA) biopsy of head and neck masses has greater diagnostic accuracy when using multihole needles than when using conventional, single-hole needles, we did a prospective, randomized, single-blinded study comparing diagnoses obtained using both types of needles in FNA biopsies of head and neck masses. Eighty-eight patients served as their own controls and had 91 FNA biopsies with both multihole and single-hole, 22-gauge needles. Order of biopsy was randomized and was unknown to the cytopathologist. No statistically significant differences were noted in quantity of specimen material obtained, quality of fixation, or diagnostic value between the multihole and conventional needle. We found no advantage in using the more costly multihole needle in FNA biopsy of head and neck masses.

Biopsy, Needle↗

Catechol-O-methyltransferase Val158Met polymorphism: frequency analysis in Han Chinese subjects and allelic association of the low activity allele with bipolar affective disorder.

Catechol-O-methyltransferase catalyses the O-methylation of biologically active or toxic catechols and is a major component of the metabolism of drugs and neurotransmitters such as L-dopa, noradrenaline, adrenaline, and dopamine. Human catechol-O-methyltransferase activity is an autosomal partially dominant trait and is strongly associated with a valine to methionine substitution at codon 158 of the protein. About 25% of Caucasians have low activity, 50% intermediate activity and 25% high activity as determined by either phenotypic or genotypic measurement. In black populations, the low activity allele (Met158; COMTL) is less frequent with about 7% being homozygous. Using a PCR based genotyping assay, we report that the Met158 allele is also less frequent in normal Han Chinese subjects with about 3% of the population being homozygous. Because of its role in catecholamine metabolism and several lines of evidence pointing to a locus for psychosis near the COMT gene on chromosome 22q11, we have analysed the COMT Val158Met polymorphism as a candidate susceptibility factor for bipolar affective disorder. We report an association between bipolar affective disorder and the Met158 allele (p = 0.004) and genotype (p = 0.01) in 93 affected Chinese subjects and 98 controls. We hypothesize that either the low activity allele of catechol-O-methyltransferase is a risk factor for bipolar affective disorder in Chinese populations or is in linkage disequilibrium with a nearby susceptibility gene or polymorphism.

Bipolar Disorder↗

Catechol-O-methyltransferase polymorphisms and schizophrenia: a transmission disequilibrium study in multiply affected families.

Catechol-O-methyltransferase (COMT) metabolizes catecholamines such as dopamines, noradrenaline and adrenaline. It exists as common high and low activity alleles in the population (determined by a valine 158 methionine polymorphisms), and high red blood cell activity of COMT has previously been associated with schizophrenia. To examine the relationship between COMT and schizophrenia genetically, the transmission disequilibrium test was performed on 22 multiply affected Caucasian and Japanese families genotyped for val158met and a second, silent, polymorphism (C256G), using PCR based assays. The high activity val158 allele was transmitted from parents to the affected individuals more frequently than the low activity met158 allele, although this was not statistically significant. Combining this data with a previous study using Chinese family trios with schizophrenia (Li et al., 1996) gave a highly significant result (p = 0.0015). The G256 allele was also transmitted preferentially to the affected offspring, and this was statistically significant when schizophrenia, schizoaffective disorder and unspecified functional psychosis were included in the definition of the affected phenotype (p = 0.03). Overall, these findings may indicate an effect of COMT alleles on susceptibility to schizophrenia, or reflect linkage disequilibrium with a different causative polymorphism in the vicinity. Other reported associations of COMT with obsessive compulsive and rapid cycling bipolar disorder indicate that the COMT gene may have complex and pleiotropic effects on susceptibility and symptomatology of neuropsychiatric disorders.

Amino Acid Substitution↗

Sex determination in dioecious Silene latifolia. Effects of the Y chromosome and the parasitic smut fungus (Ustilago violacea) on gene expression during flower development.

We have embarked on a molecular cloning approach to the investigation of sex determination in Silene latifolia Poiret, a dioecious plant species with morphologically distinguishable sex chromosomes. One of our key objectives was to define a range of genes that are up-regulated in male plants in response to Y chromosome sex-determination genes. Here we present the characterization of eight male-specific cDNA sequences and classify these according to their expression dynamics to provide a range of molecular markers for dioecious male flower development. Genetically female S. latifolia plants undergo a partial sex reversal in response to infection by the parasitic smut fungus Ustilago violacea. This phenomenon has been exploited in these studies; male-specific cDNAs have been further categorized as inducible or noninducible in female plants by smut fungus infection. Analysis of the organ-specific expression of male-specific probes in male and female flowers has also identified a gene that is regulated in a sex-specific manner in nonreproductive floral tissues common to both male and female plants. This observation provides, to our knowledge, the first molecular marker for dominant effect of the Y chromosome in nonreproductive floral organs.

Amino Acid Sequence↗

Comparison of solution properties of human and rat ciliary neurotrophic factor.

The solution structure and stability of rat and human ciliary neurotrophic factor (CNTF) were examined by circular dichroism (CD), Fourier transform infrared (FTIR) and fluorescence spectroscopy and sedimentation equilibrium analyses. The secondary structure of both proteins, as assessed by CD and FTIR, consists primarily of alpha-helix, consistent with CNTF being a member of the four-helical bundle family of cytokines and neurokines, with rat CNTF containing slightly less helix (about 10% less) and slightly more disordered structure. The environment of the tyrosine and tryptophan residues, assessed by intrinsic fluorescence emission spectroscopy, appears to be the same in both proteins. Binding of anilinonaphthalene sulfonate is identical for both proteins, indicating that these two proteins have similar surface hydrophobicities in the native state. The thermal stability of the human CNTF is significantly less than that of the rat CNTF, yet their stabilities to guanidine HCl-induced denaturation are equivalent. This apparent discrepancy in stability between the two proteins may be explained by solubility differences upon thermal unfolding. Although the human protein precipitates as it is denatured by heat, the rat protein does not. It thus appears that the unfolded state of human CNTF is less soluble and more prone to aggregation than that of the rat protein upon heating, although their conformational stability is similar. Both proteins remain largely folded at pH 3.0. Sedimentation equilibrium analysis demonstrates that both rat and human CNTF exist primarily as monomers; however, significant dimer formation occurs as the protein concentrations are increased to greater than 3 mg/mL, particularly in the presence of ammonium sulfate.

Anilino Naphthalenesulfonates↗

Granulocyte-colony stimulating factor maintains a thermally stable, compact, partially folded structure at pH2.

At acidic pH many proteins exist in a partially unfolded form, called the "A" state. This is defined as a flexible, expanded structure with well-defined, usually native-like secondary structure, but no unique tertiary structure, and showing no cooperativity during thermal-induced denaturation. Granulocyte-colony stimulating factor (G-CSF), a four-helix bundle cytokine, maintains both thermal stability and tertiary structure at pH 2.0. We therefore examined the conformation and thermal unfolding of G-CSF at pH 2.0, 4.0 and 7.0 using circular dichroism (CD) and Fourier transform infrared spectroscopy (FTIR). The secondary structure of the molecule remains highly helical as the pH is lowered from 7.0 to 2.0. The tertiary structure of the protein is slightly different at each pH value, but even at pH 2.0 G-CSF maintains a regular three-dimensional structure. The structure is hydrodynamically compact at these different pH values, with no increase in Stoke's radius even at pH 2.0. The thermal-induced denaturation of G-CSF was determined by monitoring changes in the CD or FTIR spectra. At pH 2.0 the temperature at which thermal-induced denaturation begins is higher than it is at pH 4.0 or 7.0, the thermal unfolding transition remains cooperative and some alpha-helical structure persists even at 86 degrees C. At pH 4.0 and 7.0, secondary and tertiary structures disappear simultaneously during thermal denaturation, whereas at pH 2.0 small changes in the far-UV CD region begin to occur first, followed by the simultaneous cooperative loss of tertiary structure and much of the remaining secondary structure. The structure of G-CSF at pH 2.0 is thus revealed as compact, with a unique, three-dimensional structure, highly helical secondary structure, and most importantly, a cooperative thermal unfolding transition. G-CSF at acid pH thus does not adopt the "A" state.

Circular Dichroism↗

Purification, characterization, and properties of an aryl aldehyde oxidoreductase from Nocardia sp. strain NRRL 5646.

An aryl aldehyde oxidoreductase from Nocardia sp. strain NRRL 5646 was purified 196-fold by a combination of Mono-Q, Reactive Green 19 agarose affinity, and hydroxyapatite chromatographies. The purified enzyme runs as a single band of 140 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The molecular mass was estimated to be 163 +/- 3.8 kDa by gel filtration, indicating that this enzyme is a monomeric protein. The binding of the enzyme to Reactive Green 19 agarose was Mg2+ dependent. The binding capacity was estimated to be about 0.2 mg of Reactive Green agarose per ml in the presence of 10 mM MgCl2. This enzyme can catalyze the reduction of a wide range of aryl carboxylic acids, including substituted benzoic acids, phenyl-substituted aliphatic acids, heterocyclic carboxylic acids, and polyaromatic ring carboxylic acids, to produce the corresponding aldehydes. The Km values for benzoate, ATP, and NADPH were determined to be 645 +/- 75, 29.3 +/- 3.1, and 57.3 +/- 12.5 microM, respectively. The Vmax was determined to be 0.902 +/- 0.04 micromol/min/mg of protein. Km values for (S)-(+)-alpha-methyl-4-(2-methylpropyl)-benzeneacetic acid (ibuprofen) and its (R)-(-) isomer were determined to be 155 +/- 18 and 34.5 +/- 2.5 microM, respectively. The Vmax for the (S)-(+) and (R)-(-) isomers were 1.33 and 0.15 micromol/min/mg of protein, respectively. Anthranilic acid is a competitive inhibitor with benzoic acid as a substrate, with a Ki of 261 +/- 30 microM. The N-terminal and internal amino acid sequences of a 76-kDa peptide from limited alpha-chymotrypsin digestion were determined.

Aldehyde Oxidoreductases↗

Phosphorylation within the amino-terminal acidic domain I of the phosphoprotein of vesicular stomatitis virus is required for transcription but not for replication.

Phosphorylation by casein kinase II at three specific residues (S-60, T-62, and S-64) within the acidic domain I of the P protein of Indiana serotype vesicular stomatitis virus has been shown to be critical for in vitro transcription activity of the viral RNA polymerase (P-L) complex. To examine the role of phosphorylation of P protein in transcription as well as replication in vivo, we used a panel of mutant P proteins in which the phosphate acceptor sites in domain I were substituted with alanines or other amino acids. Analyses of the alanine-substituted mutant P proteins for the ability to support defective interfering RNA replication in vivo suggest that phosphorylation of these residues does not play a significant role in the replicative function of the P protein since these mutant P proteins supported replication at levels > or = 70% of the wild-type P-protein level. However, the transcription function of most of the mutant proteins in vivo was severely impaired (2 to 10% of the wild-type P-protein level). The level of transcription supported by the mutant P protein (P(60/62/64)) in which all phosphate acceptor sites have been mutated to alanines was at best 2 to 3% of that of the wild-type P protein. Increasing the amount of P(60/62/64) expression in transfected cells did not rescue significant levels of transcription. Substitution with other amino acids at these sites had various effects on replication and transcription. While substitution with threonine residues (P(TTT)) had no apparent effect on transcription (113% of the wild-type level) or replication (81% of the wild-type level), substitution with phenylalanine (P(FFF)) rendered the protein much less active in transcription (< 5%). Substitution with arginine residues led to significantly reduced activity in replication (6%), whereas glutamic acid substituted P protein (P(EEE)) supported replication (42%) and transcription (86%) well. In addition, the mutant P proteins that were defective in replication (P(RRR)) or transcription (P(60/62/64)) did not behave as transdominant repressors of replication or transcription when coexpressed with wild-type P protein. From these results, we conclude that phosphorylation of domain I residues plays a major role in in vivo transcription activity of the P protein, whereas in vivo replicative function of the protein does not require phosphorylation. These findings support the contention that different phosphorylated states of the P protein regulate the transcriptase and replicase functions of the polymerase protein, L.

Amino Acid Substitution↗

Immunocytochemical expression of growth factors by odontogenic jaw cysts.

AIM: To determine the immunocytochemical pattern of expression of transforming growth factor (TGF) alpha, epidermal growth factor (EGF), and TGF beta in the three most common types of odontogenic jaw cyst. METHODS: Growth factor expression was detected in paraffin wax sections of odontogenic cysts (27 odontogenic keratocysts, 10 dentigerous cysts, and 10 radicular cysts) using a streptavidin-biotin peroxidase technique with monoclonal antibodies directed against TGF alpha (clone 213-4.4) and TGF beta (clone TB21) and a polyclonal antibody directed against EGF (Z-12). RESULTS: The epithelial linings of all cysts showed reactivity for TGF alpha which was mainly localised to basal and suprabasal layers. Odontogenic keratocyst linings expressed higher levels of TGF alpha than those of dentigerous and radicular cysts, with 89% (24/27) of odontogenic keratocysts exhibiting a strong positive reaction compared with 50% (five of 10) of dentigerous and radicular cysts, respectively. EGF reactivity was similar in all cyst groups, weaker than that for TGF alpha and predominantly suprabasal. TGF alpha and EGF were also detected in endothelial cells, fibroblasts and inflammatory cells within the cyst walls. The most intense TGF beta staining in odontogenic cysts was extracellular within the fibrous tissue capsules, irrespective of cyst type. CONCLUSIONS: These results, together with previous studies of EGF receptor, indicate differential expression of TGF alpha, EGF and their common receptor between the different types of odontogenic cyst, suggesting that these growth factors (via autocrine or paracrine, or both, pathways) may be involved in their pathogenesis.

Dentigerous Cyst↗

[Surgical handling of primary hepatic carcinoma with severe cirrhosis and portal hypertension].

Four hundred and ninety eight cases of primary hepatic carcinoma (PHC) were discovered complicating with cirrhosis in 608 PHC cases during 1974-1994. 63 cases of them were with severe cirrhosis and portal hypertension (10.4%). Laparotomy indication was evaluated according to Child's grade and image data such as BUS and CT etc. Operative extension should be limited as segment or wedge hepatectomy or semi-hepatic artery chemo-embolization. Splenic artery ligation plus venous ligalion of cardiac region of stomach were applied to portal hypertension and hypersplenism. Frusemide, antacid and insulin were used in the perioperation period. Three-year survival rate was 57%. It is considered that splenic artery ligation instead of splenectomy is the first choice for preventing and treating hypersplenism and digestive tract bleeding in PHC with severe cirrhosis.

Adult↗

[Effects of radix Salviae miltiorrhizae on hemodynamics of portal hypertension: clinical and experimental study].

By measuring portal pressure of hepatocirrhotic dogs of bile duct ligation directly, and detecting portal system flow in patients with hepatic cirrhosis by ultrasound doppler, we studied the portal hemodynamic effects of Radix Salviae Miltiorrhizae (RSM). After intravenous administration of RSM in hepatocirrhotic dogs, the portal venous pressure (PPV), wedge hepatic venous pressure (WHVP), and hepatic venous pressure gradient (HVPG) were significantly decreased (P < 0.05-0.01), but the mean arterial pressure (MAP), and heart rate (HR) unchanged (P > 0.05). After long-term administration of RSM (10-12 weeks), the diameter of portal vein (DPV) and splenic vein (DSV), the flow of portal vein (QPV), and splenic vein (QSV) in patients with hepatic cirrhosis were significantly decreased respectively (P < 0.05-0.001). Hypodynamia, abdominal distension, anorexia and liver function (ALT) were improved partially after administration of RSM in patients with hepatic cirrhosis. Side-effects of RSM were not found. The results demonstrated that RSM is an effective drug of depressing portal pressure with few side-effects.

Aged↗

[Chemical constituents of Strychnos nitida G. Don].

Six compounds were isolated from the root and stem of Strychnos nitida for the first time. On the basis of chemical properties and spectral data, the compounds were identified as beta-sitosterol, strychnine, brucine, cantieyine, lignoceric acid and palmitic acid.

Alkaloids↗

[Determination of soluble interleukin-2 receptor levels in patients with allergic rhinitis].

To explore the regulatory mechanism of the soluble interleukin-2 receptor (SIL-2R) in patient allergic rhinitis, SIL-2R levels in serum and nasal secretion were detected in 39 patients with allergic rhinitis, 19 patients with chronic rhinitis and 15 normal controls, The determination of SIL-2R was done by a sandwich ELISA method. The results showed that the SIL-2R concentrations in patients with allergic rhinitis were significantly higher than those of the controls (P < 0.001). These results suggest that SIL-2R may play an important role in allergic rhinitis.

Adolescent↗

[Mechanism and treatment of cancer cachexia in tumor-bearing mice].

OBJECTIVE: To evaluate the role of TNF-alpha in the development of cancer cachexia, and the effects of TNF-alpha antibody and high agglutinated staphylococcin (BM828) in the treatment of experimental cancer cachexia. METHODS: T739 mice bearing LA795 tumor were used as murine tumor cachexia model and also the T739 receiving TNF-alpha. The level of serum TNF-alpha was assayed by TNF-alpha RIA in each group. Comparisons were made in the food intake and body weight of all the five groups including BM828 and TNF-alpha AB groups. RESULTS: Two weeks after being inoculated with LA795, the tumor-bearing mice developed significant anorexia and weight loss. The level of serum TNF-alpha in tumor-bearing mice was significantly higher than that in the non-tumor bearing mice (P < 0.01). TNF-alpha administration to mice resulted also in marked anorexia and weight loss as in cancer cachexia. CONCLUSION: The results suggested that the mechanism of cachexia be correlated with TNF-alpha. BM828 and TNF-alpha AB have the potentiality of attenuating the development of cachexia in murine models.

Adenocarcinoma↗