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Biomedical subjects

Q L Li

Publications and source records attributed to Q L Li.

At least 37 records · Page 2Linked to original sources

Regulation of the human TRH (hTRH) gene by human thyroid hormone receptor beta 1 (hTR beta 1) mutants.

TRH is negatively regulated by T3 both in the hypothalamic paraventricular nucleus and transient transfection models. Mutations in hTR beta 1 genes are associated with the syndrome of generalized resistance to thyroid hormone. To investigate potential effects of mutant TRs on T3 regulation of the hTRH gene, transient gene expression assays were performed in human neuroblastoma (HTB-11) cells with an hTRH promoter-luciferase construct, wild type (WT) hTR beta 1, and three qualitatively distinct hTR beta 1 mutant forms (ED, OK and PV). In the presence of T3 (10(-9) M), liganded WT-hTR beta 1 inhibited hTRH promoter activity significantly (40%). Cotransfection of each of the two mutants (ED and OK) achieved similar levels of inhibition only at 10 to 100 fold increased T3 concentrations. Of interest, a 10x excess of mutant ED or OK could also exert dominant negative effects upon WT hTR beta 1-T3 mediated inhibitory actions on the hTRH promoter. In contrast, mutant TR-PV exerted neither inhibitory nor dominant negative effects at even higher concentrations of T3. Moreover, all three unliganded mutant forms stimulated TRH promoter activity significantly in the absence of T3, despite their different mutations in the ligand-binding domain (LBD). These data demonstrate that thyroid hormone resistance at the level of TRH gene regulation, due to reduced inhibitory actions of mutant TR-T3 complexes, as well as dominant negative effects upon WT hTR beta 1 mediated inhibition, likely contribute to elevated TSH values observed in the syndrome of thyroid hormone resistance.

Dose-Response Relationship, Drug↗

Status of the eradication of indigenous wild poliomyelitis in the People's Republic of China.

A large nationwide outbreak occurred in 1989-1990 in China, in which nearly 10,000 poliomyelitis cases were reported. After two rounds of oral poliovirus vaccine (OPV) supplemental activity in nearly every province in the 1992-1993 winter season, no wild poliovirus was detected in 1993 in 22 provinces in the middle of China that contained 86% of the population. During the first national immunization days (NIDs) conducted in December 1993 and January 1994, 83 million children 0-47 months of age were immunized. In 1994, wild poliovirus was identified in only 6 of 2397 children with stool specimens tested. After a second NID in December 1994 and January 1995, no wild poliovirus was detected in 1995 despite a very high level of virus surveillance. In summary, double-round mass supplemental OPV immunizations in children 0-3 years old in two consecutive winters eliminated wild poliovirus from 23% of the world's population (1.2 billion people).

Child, Preschool↗

[Studies on the voltammetric behaviour of barbaloin and its application].

In 0.1 mol.L-1 H2SO4 solution, a well-defined reduction wave of barbaloin was obtained by single-sweep osciflopolarography. The peak potential was shown to be -0.75 V (vs SCE). The peak current is proportional to the concentration of barbaloin over the range of 2.0 x 10(-7)-6.0 x 10(-6) mol.L-1. The detection limit is 2.0 x 10(-7) mol.L-1. The voltammetric behaviour of the system was studied by linear sweep and cyclic voltammetry. The adsorption coefficient beta was 1.91 x 10(5). The interaction factor alpha was 1.12. The system is a reversible adsorption wave.

Aloe↗

Reversal of TR-T3 inhibition of the hTRH gene by excess TR ligand-binding domain: evidence for novel accessory protein.

The thyrotropin-releasing hormone (TRH) gene is regulated negatively at the transcriptional level by thyroid hormone (T3). T3 positive regulatory effects on other target genes, such as the growth hormone gene, are mediated through heterodimerization of thyroid hormone receptors (TRs) with RXR or other auxiliary nuclear protein(s). To explore whether an accessory co-suppressor protein(s) may be involved in T3 inhibitory regulation of human TRH gene transcription, transient gene expression studies have been carried out using a hTRH-luciferase (TRH-Luc) chimetric reporter construct, an hTR beta 1 expression construct, and pABgal-hTR beta 1 ligand-binding domain (LBD) fusion constructs, cotransfected into a human neuroblastoma cell line (HTB-11,ATCC). Results herein indicate that T3-dependent inhibitory regulation (48-60% of control) of the hTRH gene promoter by hTR beta 1-T3 complexes could be abrogated completely by cotransfection of a 10 x excess of hTR beta 1-LBD (TR 168-456 aa) in a pABgal94 vector. In striking contrast, cotransfection of a 10 x excess of highly truncated hTR beta 1-LBD (TR 452-456 aa) failed to reverse T3-mediated TRH promoter inhibition. This squelching effect by excessive intact TR-LBD, moreover, could not be reversed by raising T3 concentration 100-fold (from 10(-8) to 10(-6) M), thus excluding a squelching effect of T3 itself by excess LBD. These results suggest that negative regulation of the hTRH gene promoter activity by TR beta 1-T3 complexes involves interactions with an accessory co-suppressor protein, which may bridge DNA-bound TR beta 1-T3 complexes to the transcriptional initiation complex.

Binding Sites↗

Localization of thyrotropin-releasing hormone mRNA expression in the rat heart by in situ hybridization histochemistry.

Our laboratory has recently detected mRNA of thyrotropin-releasing hormone (TRH) in the rat heart. The density of mRNA for TRH is five-fold higher in the atria than in the left and right ventricle. We also found TRH receptor mRNA and 3H-TRH-binding sites in both ventricles. Cardiac contractility was stimulated after intracoronary administration of TRH. This study was performed to investigate the localization of TRH in the heart. We utilized in situ hybridization histochemistry (ISHH) to localize TRH mRNA expression in the rat heart. ISHH was performed on fresh frozen heart tissue sections which were hybridized with a specific 35S-TRH oligo probe and subsequently processed by autoradiography. The autoradiographic signals corresponding to TRH mRNA were analyzed with an image program. For positive controls TRH mRNA was identified in the hypothalamic paraventricular nucleus. This test confirms the specificity of the TRH oligo probe. Cardiac hybridization signals were observed predominantly in the atria and localized preferentially in atrial connective tissues, vascular adventitia and atrial cardiomyocytes. No hybridization signals were found in ventricular cardiomyocytes. These observations suggest that TRH is synthesized in atrial myocytes and atrial vascular structures. Based on studies which show synthesis of the TRH receptors in ventricular cardiomyocytes, we hypothesize that atrial TRH is an endocrine source for the stimulation of ventricular contractility and that endothelial and adventitial TRH may play a role(s) in the regulation of the growth and/or vasomotor tome of the cardiac vascular system.

Animals↗

[Experimental observation on microbicidal activity of a complex glutaraldehyde disinfectant].

The microbicidal activity of a complex glutaraldehyde disinfectant was observed. The result showed that when the temperature of the test was 20 degrees C and 10% calf serum were added to the bacterial suspensions 2% diluted solution of the disinfectant for a two-minute contact could kill 99.99% of Staphylococcus aureus, and 1% diluted solution for two minutes could kill 99.99% of E. coli. The undiluted disinfectant with five-minute contact time could destroy the antigenicity of HBsAg. The undiluted disinfectant with thirty-five minute contact and 50% diluted solution with forty-five minute contact time could completely kill the spores of Bacillus subtilis var. niger under 50 degrees C. It was discovered that the germicidal concentration of the disinfectant was four times as high as the inhibition concentration and the used concentration determinal with capacity test was four times higher than as germicidal concentration when the three concentrations were compared. This result indicated that selection of suitable inactivator was very important. The practical concentration of disinfectant should be decided under the basis of the result from capacity test.

Animals↗

Use of yeast artificial chromosomes (YACs) in studies of mammalian development: production of beta-globin locus YAC mice carrying human globin developmental mutants.

To test whether yeast artificial chromosomes (YACs) can be used in the investigation of mammalian development, we analyzed the phenotypes of transgenic mice carrying two types of beta-globin locus YAC developmental mutants: (i) mice carrying a G-->A transition at position -117 of the A gamma gene, which is responsible for the Greek A gamma form of hereditary persistence of fetal hemoglobin (HPFH), and (ii) beta-globin locus YAC transgenic lines carrying delta- and beta-globin gene deletions with 5' breakpoints similar to those of deletional HPFH and delta beta-thalassemia syndromes. The mice carrying the -117 A gamma G-->A mutation displayed a delayed gamma- to beta-globin gene switch and continued to express A gamma-globin chains in the adult stage of development as expected for carriers of Greek HPFH, indicating that the YAC/transgenic mouse system allows the analysis of the developmental role of cis-acting motifs. The analysis of mice carrying 3' deletions first provided evidence in support of the hypothesis that imported enhancers are responsible for the phenotypes of deletional HPFH and second indicated that autonomous silencing is the primary mechanism for turning off the gamma-globin genes in the adult. Collectively, our results suggest that transgenic mice carrying YAC mutations provide a useful model for the analysis of the control of gene expression during development.

Animals↗

[Evaluation of acute flaccid paralysis (AFP) surveillance system in 1994].

Increased by 40.2% compared with 1993, 3142 acute flaccidparalysis cases were reported from AFP surveillance system in 1994. A total number of 1297 counties had AFP cases reported, accounting for 45.1% of total amount of counties. Out of 3142 AFP cases, 307 were confirmed, coming from 225 counties. For children under 15 years old, the reported AFP incidence was 1.1/10(5), non-polio AFP rate was 0.83/10(5), much higher than 0.37/10(5), in 1993. 48.5% of the total AFP cases had double stool specimen taken within 0-14 days after paralysis. 79% AFP cases had been investigated within 48 hours after being reported. Some of the major monitoring indicators of AFP surveillance system were close to the WHO criterion, but the percentage of AFP cases reported within 48 hours of careseeking and AFP cases with follow-up visit after 60-70 days of paralysis were very low. Furthermore, 77.9% of the confirmed cases were diagnosea clinically by residual paralysis, so did the 46.4% of discarded cases. It is in urgent need to increase the percentage of cases classified by laboratory test.

Acute Disease↗

Ligand (T3) dependent and independent effects of thyroid hormone receptors upon human TRH gene transcription in neuroblastoma cells.

Thyrotropin releasing hormone (TRH) gene is regulated negatively at the transcriptional level by thyroid hormone (T3) in rat anterior hypothalamus. The actions of T3 upon other target genes are known to be mediated through the thyroid hormone receptors (TR), TR alpha and TR beta. To explore whether the inhibitory regulation of human (h) TRH gene transcription by T3 is TR isoform specific and whether TRH gene transcription can be modulated as well by unliganded TR isoforms, transient gene expression studies have been carried out using hTRH-luciferase (TRH-Luc) chimeric constructs and TR expression constructs, co-transfected into a human neuroblastoma cell line (HTB-11). Data herein demonstrate T3-dependent inhibitory regulation of the hTRH gene promoter by TR-T3 complexes. Moreover, significant inhibition (39%-60%) could be achieved by T3 bound to either hTR alpha 1, hTR beta 1, or rTR beta 1, beta 2 and was comparable quantitatively, indicating an absence of TR isoform specificity for T3 inhibition. Conversely, basal promoter activity of the hTRH gene could be activated significantly by unliganded hTR alpha 1, beta 1, rTR beta 1, and beta 2 (150% to 334%), but not by hTR alpha 2. Thus, TRs appear to exert opposite effects on hTRH gene transcription, depending on the presence or absence of ligand (T3). These dual effects of TR suggest that the addition of the T3 ligand effects conformational changes that can abrogate the initiation of transcription.

Animals↗

Pneumoconiosis: the changes of peripheral airways.

Ultrathin bronchofiberscope (Olympus BF-1.8T) was applied to the observation of the peripheral airways of total 87 cases, including 73 cases of quartz-exposed and asbestos-exposed workers with/without pneumoconiosis (exposure groups), and 14 cases of controls. The changes of peripheral airways in exposure group of non-smokers was found, mainly to be pigmentation, elevation, irregularity and lustlessness on the surface of the bronchiole walls, and predominantly stenosis and ectasis of the lumen. The detectable rate was higher in peripheral airways than in central airways. Some changes existed in early stage and some had a tendency of increasing detectable rate with category progressing. Some factors such as smoking could influence the results of analysis.

Adult↗

[Studies on electrochemical behaviour of antiepilepsirine and its adsorptive voltammetry].

Antiepilepsirine is a kind of new antiepileptic drug. In this paper, a new method, adsorptive voltammetry (ADV) has been established for the determination of antiepilepsirine. In 0.20 mol/L H2SO4 solution, a sensitive reduction wave of antiepilepsirine was obtained by ADV after preconcentration on the surface of hanging mercury drop electrode (HMDE) (Ei = 0.7V, v = 100 mV/s), the peak potential was -0.94V (vs Ag/AgCl). The linear range between the peak current and the concentration of antiepilepsirine was 3.0 x 10(-9)-3.0 x 10(-6) mol/L with a detection limit of 1.0 x 10(-9) mol/L. Antiepilepsirine in tablet and urine samples was determined by using this method. The electrochemical behaviour of the system and its electrode reaction mechanism were studied by means of linear sweep and cyclic voltammetry, constant potential coulometry, normal pulse polarography (NPP), etc. The diffusion coefficient D was 7.7 x 10(-6) cm2/s. The electrode reaction rate constant was 1.5 x 10(-3) cm/s. The number of reduction electron n was 2. The electron transfer coefficient was 0.52. The electrode reduction process was shown to be irreversible with the adsorptive characteristics.

Anticonvulsants↗

[A comparison between diltiazem SR and diltiazem HCL in the treatment of angina pectoris].

This study included 168 patients with angina pectoris, who were divided into two groups, the diltiazem SR (No. 88) group and diltiazem HCL (No. 80) group. The two groups were comparable in age and duration of coronary heart disease. The results were as follows: (1) The total clinical effect of diltiazem SR (94.3%) was slightly greater than that of diltiazem HCL (82.5%), the effect in ECG improvement was 53.3% and 53.4% respectively. (2) The rate of adverse effect was 12.5% in diltiazem SR group and 14.4% in diltiazem HCL group. It is concluded that the two different types of diltiazem have similar effect in the treatment of angina pectoris. However, it is more convenient to take diltiazem SR than diltiazem HCL as the former needs only twice a day.

Adult↗

Loss of thyroid hormone receptor activity in primary cultured rat hepatocytes is reversed by 2-mercaptoethanol.

In primary cultures of rat hepatocytes, specific thyroid-hormone-binding activity diminished with time and was hardly detectable at 24 h. In accordance with the loss of 3,5,3'-tri-iodothyronine (T3) binding, responses to the hormone disappeared, as indicated by low induction of the thyroid-hormone-responsive gene S14. In contrast, thyroid hormone receptor proteins were present, as determined by immunostaining with a specific antibody against the receptor. Thus the loss of T3 binding was due to receptor inactivation. After various attempts to restore the T3-binding activity, we found that 2-mercaptoethanol, a reducing agent, when added to the culture medium restored the hormone binding activity in a dose- and time-dependent manner. The observed kinetics and experiments using cycloheximide suggested that mercaptoethanol prevented inactivation of the newly synthesized receptors. Oxidoreductive conditions within cells may have a role in determining the level of activity of thyroid hormone receptors.

Animals↗

[The choice of treatment in acute hemorrhagic necrotic pancreatitis: medical or surgical?].

In recent ten years, physicians and surgeons in Beijing Tong Ren Hospital cooperated well in the treatment of acute hemorrhagic necrotic pancreatitis. Twenty four cases were chosen to determine whether medical conservative or surgical operative treatment should be given. In the surgical operation group there were fourteen cases. Twelve cases survived and the remaining two died. In the medical conservative group only one of the ten cases died. The overall mortality of the twenty four cases of acute hemorrhagic pancreatitis was 12.5%. In our study, the indications for operation were as follows: (1) Presence of more than five positive diagnostic criteria. (2) Accompaniment of gall stone. (3) Inability to differentiate with other acute surgical abdominal emergencies such as intestinal obstruction.

Acute Disease↗

[Regulatory effect of insulin on glucocorticoid receptor in human peripheral leukocytes].

The regulatory effect of insulin on the specific binding power of glucocorticoid receptor (GR) of human leukocytes was assessed by the unoccupied receptor sites capable of combining with [3H] labelled dexamethasone measured at 3 and 24 h after incubation with various concentrations of insulin added to the medium. After 3 h incubation the specific binding power with [3H] Dex was decreased by 23.3 +/- 10.0, 32.2 +/- 13.2 and 54.3 +/- 9.2% (P greater than 0.05, P greater than 0.05 and P less than 0.01 as compared with the control value of 100 in the absence of insulin) respectively in the presence of 20 mU/L (physiological testing concentration), 200 mU/L (physiological upper limit) and 2,000 mU/L (pharmacological concentration) insulin in the incubation medium. After 24 h incubation the decrease of these values increased respectively to 43.5 +/- 19.0, 56.1 +/- 20.7 and 80.2 +/- 15.5 (P less than 0.05, P less than 0.01 and P less than 0.01 compared with control). Thus the inhibitory effect of insulin on the GR binding power is both dose- and time-dependent, which strongly suggests that GR is tonically controlled by insulin concentration change under physiological conditions.

Cells, Cultured↗

Beta-globin locus activation regions: conservation of organization, structure, and function.

The human beta-globin locus activation region (LAR) comprises four erythroid-specific DNase I hypersensitive sites (I-IV) thought to be largely responsible for activating the beta-globin domain and facilitating high-level erythroid-specific globin gene expression. We identified the goat beta-globin LAR, determined 10.2 kilobases of its sequence, and demonstrated its function in transgenic mice. The human and goat LARs share 6.5 kilobases of homologous sequences that are as highly conserved as the epsilon-globin gene promoters. Furthermore, the overall spatial organization of the two LARs has been conserved. These results suggest that the functionally relevant regions of the LAR are large and that in addition to their primary structure, the spatial relationship of the conserved elements is important for LAR function.

Animals↗

Fatty acyl-CoAs are potent inhibitors of the nuclear thyroid hormone receptor in vitro.

We report that long-chain fatty acyl-CoAs are potent inhibitors of the thyroid hormone (T3) receptor isolated from rat liver nuclei. Both saturated and unsaturated fatty acyl-CoAs were similarly potent. Fifty per cent inhibition of T3 binding by the receptor was observed at an oleoyl-CoA concentration as low as 1.3 microM, and the affinity of oleoyl-CoA for the receptor (Ki) was estimated to be 0.45 microM. Fatty acyl-CoAs also promoted dissociation of the hormone bound to the receptor. The action of fatty acyl-CoAs was competitive for the hormone binding site, resulting in a reduction in the receptor's affinity for T3. These observations suggest that fatty acyl-CoAs modulate the binding of the thyroid hormone to its nuclear receptor, in vitro. Whether or not such events occur in vivo remains to be determined.

Acyl Coenzyme A↗