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Biomedical subjects

Z Q Chen

Publications and source records attributed to Z Q Chen.

At least 19 recordsLinked to original sources

Localization of the human CXC chemokine subfamily on the long arm of chromosome 4 using radiation hybrids.

All 12 of the human CXC chemokine genes were physically mapped using gene-specific PCR primers and the GenBridge 4 radiation hybrid panel. Nine genes, PF4, PF4V1, GRO1, GCP2, PPBP, IL8, GRO2, GRO3, and SCYB5, were assigned within a 1.8-cR interval of one another on 4q. Two additional genes, MIG and INP10, map within 0.5 cR of each another and 6 cR distal to the above-mentioned group. The final gene, SDF1, is localized on 10q. Phylogenetic analyses of amino acid sequences revealed that SDF1 is the most divergent member and that the physically separated MIG-INP10 pair constitutes a distinct evolutionary lineage.

Chemokines, CXC

Human S mu binding protein-2 binds to the drug response element and transactivates the human apoA-I promoter: role of gemfibrozil.

Previously, we demonstrated that protein-DNA interactions at the drug response element (DRE) in the human apoA-I promoter were important for the induction of apoA-I gene expression by gemfibrozil. We now report the cloning and characterization of a DRE transactivating factor. The cloned protein is identical to the putative helicase and potential transcription factor human S mu binding protein-2 (HSmuBP2). It is also related to glial factor-1 (GF1), an incomplete version of HSmuBP2 lacking the first 494 and the last 128 amino acids. Gel mobility shift assays demonstrated that HSmuBP2 binds apoA-I DRE oligomers and forms a specific protein-DNA complex. Northern blot analysis showed that HSmuBP2 mRNA is expressed at various levels in a wide range of human tissues. Transient cotransfection experiments performed in HepG2 cells demonstrated that overexpression of HSmuBP2 or GF1 induced apoA-I proximal promoter activity by 3-fold and that the apoA-I DRE was necessary for transactivation. Additionally, we demonstrated that transactivation was increased a further 2- to 3-fold by exposing the cells to gemfibrozil. Together these observations indicate that HSmuBP2 acts as a transcription factor that regulates apoA-I gene expression in hepatoma cells and whose activity may be stimulated by gemfibrozil treatment.

Apolipoprotein A-I

The development of neurobehavioral toxicology in China: the 1994 Hänninen Lecture.

With the rapid growth of industrialization in China, occupational and environmental exposure to chemicals has increased in frequency and in types of chemical exposures. A growing number of Chinese researchers are showing a special interest in exploring the effects of chemicals on the central nervous system. This paper presents a comprehensive review of neurobehavioral toxicology in China. It describes research into the "reference values" of the Neurobehavioral Core Test Battery (NCTB) tests, the development and improvement of the computer-administered Chinese version of the Neurobehavioral Evaluation System (NES-C), and exploration of related biomarkers. On the basis of this research, baseline data for the reference values for six subtests of the NCTB were preliminarily recommended. The upgraded NES-C2 has proven to possess higher stability and validity compared with the previous version, NES-C. Biomarkers derived from the changes in levels of neurotransmitter metabolites might be used as supplementary biomarkers of Pb-induced neurotoxicity.

Adolescent

Human hematopoietic cell express two forms of the cytokine receptor common gamma-chain (gamma c).

Recent studies have revealed that the gamma-chain of the IL-2 receptor is shared by the receptors for IL-4, IL-7, IL-9, IL-13, and IL-15, and it is therefore also referred to as the common gamma-chain (gamma c). Mutations of gamma c result in X-linked severe combined immunodeficiency syndrome in humans, indicating that gamma c is essential for normal development and function of the immune system. We demonstrate that human hematopoietic cells express two gamma c transcripts differing in their carboxyl terminal coding region. One transcript is the previously reported sequence (gamma c-long), whereas the newly identified sequence exhibits a deletion of 72 nucleotides close to the 3'-end of the open reading frame (gamma c-short). This alteration predicts a loss of 24 amino acids including a conserved tyrosine residue which is shared by several members of the cytokine receptor family. The presence of these two distinct forms of gamma c transcripts was demonstrated by sequencing of reversely transcribed and polymerase chain reaction (RT-PCR) amplified mRNA, restriction digestion of the RT-PCR products, RNAse protection, and Northern blotting from human cell lines and human peripheral blood lymphocytes. Furthermore, the two variants were present in peripheral blood lymphocytes from both female and male donors, which rules out allelic variants since gamma c is a single copy gene located on the X chromosome. A truncation mutant at a site near the observed changes in gamma c-short has been reported by others to alter biochemical events activated by cytokines. This combined with the loss of a potential SH2 "docking" site in gamma c-short suggests that gamma c-long and gamma c-short may link to different signaling pathways and may play an important role in determining the cellular response to IL-2, IL-4, IL-7, IL-9, IL-13, IL-15.

Alternative Splicing

Nutritional evaluation of women in urban areas in continental China.

In 1993-1995, a nutritional survey was conducted in China, in which 50 women each in three cities of Beijing, Shanghai and Nanning (thus 150 in total) volunteered to offer 24-hr total food duplicates and peripheral blood samples. People daily took 1,776 kcal (7,431 kJ) energy, 57 g protein, 75 g lipid, 218 g carbohydrate, 439 mg calcium, 24 mg iron, 3,398 mg sodium and 1,521 mg potassium. When compared with the recommended dietary allowance for Chinese, intakes of energy, iron and possibly vitamin C were sufficient in a majority of the participants, but not so in cases of calcium, and several vitamins. The lipid energy ratio was 38% on an average and was higher than 30% in a majority (73%) of the people. BMI, but not the lipid energy ratio, correlated with the serum triglyceride level. In accordance with high iron intake, the prevalence of anemia was low. Inter-city differences were evident in nutrient sources. Thus, Beijing people took more amounts of protein and lipid from meats (including eggs and milk), whereas plant-based foods were important sources of lipid in Shanghai and that of protein in Nanning. Furthermore, consumption of rice was significantly lower in Beijing than in Shanghai and Nanning, whereas wheat consumption was higher in Beijing than in Shanghai and Nanning.

Adult

Protein-DNA interactions at a drug-responsive element of the human apolipoprotein A-I gene.

Previously, we demonstrated that when two human hepatoma cell lines, Hep3B and HepG2, were exposed to gemfibrozil, a hypolipidemic drug, a 2-fold induction in apolipoprotein A-I (apoA-I) mRNA levels resulted. To determine if mRNA stabilization was responsible for the changes in apoA-I mRNA levels, the half-lives for apoA-I mRNA were measured in the presence of actinomycin D with and without gemfibrozil. These experiments revealed no differences in stability. However, nuclear run-off assays indicated that the transcription rate of the apoA-I gene was increased 2-fold in gemfibrozil-treated cells. Transient transfection experiments also indicated that the induction of apoA-I mRNA level in response to gemfibrozil is mediated at the transcriptional level. We have identified two copies of the "drug-responsive element" (DRE) in the apoA-I promoter region that may be responsible for the increase in apoA-I transcriptional activity by gemfibrozil. Using gel mobility shift assays with a synthetic DRE oligonucleotide, we have demonstrated that exposure of Hep3B and HepG2 cells to gemfibrozil resulted in strong induction of a protein-DNA complex. The formation of this complex is highly sequence-specific as indicated by the DNA competition experiments. The drug-inducible nuclear proteins bind to the DRE of the human apoA-I gene with an apparent Kd of 4.1 nM. Methylation interference experiments have localized the contact sites of nuclear factors to the DRE region. Southwestern blot analyses have identified two groups of drug-inducible nuclear proteins with molecular masses of approximately 30 and 15 kDa. When a copy of synthetic DRE oligonucleotide was inserted upstream of the thymidine kinase promoter and luciferase reporter construct, a significant 2-fold induction in luciferase activity was observed in the presence of gemfibrozil following transient transfection of two human hepatoma cell lines, HepG2 and Hep3B. However, a plasmid containing one copy of mutated apoA-I-DRE oligomer did not confer responsiveness to gemfibrozil treatment. Furthermore, pGL2 (apoA-I -250 mutant DRE), which carried an internal mutation of the DRE in the human apoA-I proximal promoter region, showed no increase in luciferase activity in response to gemfibrozil. These results implicate protein-DNA interactions at the DRE region in the transcriptional induction of human apoA-I gene expression by gemfibrozil.

Apolipoprotein A-I

Changes in cervical canal spinal volume during in vitro flexion-extension.

STUDY DESIGN: Quasistatic flexion and extension loads were applied in vitro to lower cervical spines. The flexion-extension motion produced was checked for physiologic relevance. OBJECTIVES: To examine the changes in the volume of the cervical spinal canal in flexion-extension motion. SUMMARY OF BACKGROUND DATA: Many papers have been published concerning the cervical canal volume as inferred from standard lateral radiographs. This study compares the inferred (radiographic) volumes and their changes to the physical changes within the spinal canal. METHODS: The lower cervical spines (C2-C7) from 10 cadavers were subject to stepwise flexion and extension in a purpose-built rig. Before this testing, the spinal cord was removed from the canal space of each specimen and replaced by a thin latex tube stoppered and secured at the opening of the canal (at C2) so that the volume of liquid displaced from the tube could be measured. This was done at each loading stage by means of a graduated glass column, and a radiograph of the spine was also taken to allow angular and displacement readings to be taken from C2 to C7. RESULTS: The average recorded change in volume of the spinal canal with flexion-extension motion was 1.9 ml, and showed a significant linear correlation with the dynamic canal width (r = 0.868, P < 0.05) and also with the total angle of flexion or extension (r = 0.979, P < 0.005). The volume of liquid displaced from the canal in lateral bending was much lower than that in flexion-extension motion, and only amounted to about 0.2 ml. The angular ranges of motion produced at each level were compared to previous results obtained in vivo, and no significant differences between the angular displacements found in vivo and in vitro under this experimental arrangement were seen. CONCLUSIONS: The loading regime described in this study causes angular displacements similar to those in vivo, and on this basis is a physiologically relevant loading pattern. The change in the volume of the spinal canal between C2 and C7 shows linear relationships with the angle of flexion and the dynamic canal width.

Adult

Identification of two regulatory elements within the promoter region of the mouse connexin 43 gene.

To define the minimal sequences required for expression of the connexin 43 gene (cx43) in myometrial cells, we generated 5' deletion constructs of a fragment extending 1686 base pairs upstream and 162 base pairs downstream of the transcription start site and determined their ability to drive expression of the chloramphenicol acetyltransferase reporter gene in transfected myometrial cell lines. Our investigation revealed two cis-acting regulatory elements within this fragment. Deletion of a region extending from -102 to -92 led to an increase of the promoter activity by greater than 10-fold, indicating a presence of a repressor element. Deletion of a region extending from -72 to -62 caused a decrease of the promoter activity of a similar extent, implying the existence of a positive element. Electrophoretic mobility shift assays demonstrated that synthetic oligonucleotides derived from these two small regions can each bind with a nuclear protein(s) prepared from myometrial cells, and an introduction of three and two base substitutions into each of these oligomers was sufficient to abolish their protein binding capability. These same mutations, when incorporated in the chloramphenicol acetyltransferase constructs, diminished regulatory functions of the negative and positive elements, and the protein(s) that bind to these functional elements was found in several tissues known to express cx43 gene.

Animals

Defining the breakpoint of a multigene deletion in the immunoglobulin heavy chain gene cluster.

The constant region of the human immunoglobulin heavy chain (IGHC) is encoded by a cluster of genes near the telomere of chromosome 14q. Deletions and duplications of single or multiple genes in the cluster have been identified, but little information about the breakpoint junctions has been available, in part due to the high degree of sequence similarity between the genes in this region. We report an intensive study of a homozygous deletion, using Southern hybridization and polymerase chain reaction techniques. We found that the deleted DNA includes the functional epsilon gene, and that the breakpoints are located within a 2 kilobase Bam HI/Sac I region of both the IGHEP1 and IGHE genes. These results revise a previous conclusion regarding the deleted region. Definition of breakpoints occurring within this cluster may shed light on recombination mechanisms.

Base Sequence

Myometrial transcriptional regulation of the gap junction gene, connexin-43.

The mechanisms that enable the myometrium to switch from a state of relative quiescence during pregnancy to a muscle that is spontaneously active, very responsive to endogenous uterotonins and exhibits a high degree of cell-cell coordination are poorly understood. It is hypothesized that this switch or 'activation' of the myometrium results from the coordinated expression of a cassette of 'contraction-associated proteins'. The molecular mechanisms that regulate the expression of one of these, namely the myometrial gap junction protein connexin-43 (Cx-43), have been analysed. Myometrial Cx-43 expression is significantly increased during labour, associated with an increase in plasma oestrogen:progesterone, and positively regulated by oestrogen in non-pregnant rats. The genomic structure of the murine Cx-43 gene and the sequence of its 5' flanking sequence are reported here. This region functions as a promoter and contains several putative cis-acting elements which may be important in the regulation of Cx-43 transcription. Among these elements are several half-palindromic sequences that may function as oestrogen response elements and several AP-1 sites that may bind the transcription factors Fos and Jun. Oestrogen treatment of cells transiently transfected with a plasmid containing the Cx-43 promoter linked to the chloramphenicol acetyl transferase (CAT) gene, increased CAT activity indicating that the murine Cx-43 gene is oestrogen responsive. In addition, treatment of rats with oestrogen significantly increased mRNA encoding c-fos and c-jun in the myometrium and this occurred before any increase in Cx-43 mRNA. These data suggest that oestrogen may increase transcription of the Cx-43 gene through direct mechanisms (via the putative oestrogen response elements) or indirect mechanisms (by increased expression of c-fos and c-jun acting via the putative AP-1 sites). Since oestrogen may be an important modulator of myometrial activation, these mechanisms may be critical to the processes leading to increased synthesis of gap junctions at term and, hence, to the onset of labour.

Animals

[Clinical significance of endogenous digitalis-like substances in patients with pregnancy-induced hypertension].

We measured plasma endogenous digitalis-like substances (EDLS), angiotensin II concentrations and plasma renin activity (PRA) by radioimmunoassay in 30 patients with pregnancy-induced hypertension (PIH), 30 normal pregnant women during the third trimester, and 23 non-pregnant women. Compared to the normal pregnant women, the concentration of plasma EDLS was significantly increased in patients with PIH (P < 0.05). There were significant positive correlations among plasma EDLS level, mean arterial pressure (r = 0.615; P < 0.01), the score index of PIH patients (r = 0.818; P < 0.01), hematocrit (r = 0.853; P < 0.01) and uric gravity (r = 0.764; P < 0.01). There was a significant negative correlation between plasma EDLS level and PRA in patients with PIH (r = -0.718; P < 0.01). Severe proteinuria and edema were related to a significant higher plasma EDLS level than the mild in patients with PIH (P < 0.001). After magnesium sulfate was administered in 9 severe patients of PIH, plasma EDLS levels were decreased (P > 0.05). These findings suggest that EDLS may play an important role in the pathogenesis of PIH and severe as an indicator of the severity of PIH. Its secretion may not be influenced after the administration of magnesium sulfate. There may be a close relationship between EDLS and renin-angiotensin system. When the medicine of digitalis type was administered in patients with PIH, the influence of EDLS must be considered to prevent digitalism.

Adult

[Urinary nicotine and intervention test for absorption of nicotine in female workers in tobacco industry].

The concentration of urinary nicotine of non-smoking female workers, 56 from shredding workshop, 65 from packing workshop and 54 from beverage factory (as controls), was determined, and intervention test for the absorption of nicotine was carried out in female workers from shredding workshop. The mean geometric concentration of urinary nicotine of shredding workers and packing workers at the end of shift was 44.8 +/- 5.1 ng/ml and 9.9 +/- 5.4 ng/ml, and was significantly higher than that of the controls (1.0 +/- 1.0 ng/ml) (P < 0.01). The concentration of urinary nicotine of shredding workers was significantly higher at the end of shift than pre-exposure period (11.46 +/- 6.73 ng/ml). The intervention test for the absorption of nicotine showed that there were good protection effects for the absorption of nicotine when glove and mask were used simultaneously and ventilator was used in summer.

Female

Psychological effects of low exposure to mercury vapor: application of a computer-administered neurobehavioral evaluation system.

A computer-administered neurobehavioral evaluation system in a Chinese language version (NES-C) and a mood inventory of the profile of mood states (POMS) were applied to assess the psychological effects of low-level exposure to mercury vapor in a group of 88 workers (19 males and 69 females, with mean age of 34.2 years) exposed to mercury vapor (average duration of exposure 10.4 years). The well-matched group of 97 nonexposed workers was treated as the control. The intensity of current mercury vapor was relatively mild as reflected by the average level of mercury in the air of the workplace (0.033 mg/m3) and in urine (0.025 mg/liter). The results indicated that the profile of mood states posed was moving to the negative side in Hg-exposed group and most of the NES-C performances, in particular, the mental arithmetic, two-digit search, switching attention, visual choice reaction time, and finger tapping, were also significantly affected compared with those obtained from controls (P < 0.05-0.01). The present study and the previous study on the validation of the system suggest that the NES-C we developed is valid for the neurotoxicity screening among the working population exposed to neurotoxic agents.

Adult

The binding capacity is a probability density function.

The binding capacity of a system, or equivalently, the fluctuations of the number of ligands bound around the average value defined by the binding isotherm, can be regarded as a probability density function for the chemical potential of the ligand. The first moment of this density function is the mean ligand activity as defined by Wyman and gives the average free energy (in kT units) of binding per site. The second moment is directly related to the cooperativity of the system. These and higher moments can be obtained from numerical integration of experimental data in a direct way. An analytical expression for the moment generating function shows that the N independent coefficients of the partition function of a system containing N sites are uniquely defined by the first N moments of the binding capacity.

Binding Sites

Studies on the toxicity and maximum allowable concentration of chloroform.

Chloroform has obvious hepato-, nephro-toxicity and carcinogenicity. In order to get necessary data for recommendation of maximum allowable concentration of chloroform in workplace, a series of studies were carried out. The results showed that exposed workers mainly distributed in the industries of perspex processing, production of refrigerants, drugs and pesticides. The exposure level ranged 4.27-147.91 mg/m3 in 119 air samples collected from 3 representative worksites, with 45.4% air samples below 20 mg/m3. The workers exposed to chloroform at 29.51 mg/m3 had slight liver damage indicated by the higher rates of abnormal serum prealbumin and transferrin levels than those of control workers. The neurobehavioral functions of these workers were also obviously affected, manifested as increases in scores of passive mood states and dose-related negative changes in neurobehavioral testing. The observed effect threshold concentration of subacute inhalation in rats was 592 mg/m3 according to the observation on the biochemical changes in liver tissue and abnormal activities of serum enzymes. Mainly based on the above results, we recommended 20 mg/m3 as the Maximum Allowable Concentration in workplace in China at present.

Adult

Capacity of adipose tissue to promote growth and metastasis of a murine mammary carcinoma: effect of estrogen and progesterone.

Previously we have shown that a murine mammary carcinoma cell line, designated SPI, grows and metastasizes more efficiently in the mammary gland than in the subcutis. In this report, we examine the tissue specificity of this phenomenon. Our results show that SPI cells grow best in the mesenteric and ovarian fat pads and well in the mammary gland, but very poorly in the subcutis or peritoneal cavity. Massive dissemination of tumors from the ovarian and mesenteric sites occurs to the liver, spleen and diaphragm. In contrast, metastases from the mammary site occur primarily in the lung. Co-transplantation of a threshold number of SPI cells with mammary or ovarian fat fragments into the subcutis results in increased tumor growth, whereas very few tumors form in sham controls receiving no fat fragments. Removal of the ovaries of donor and recipient mice abrogates tumor growth in adipose tissue transplants. Estrogen can stimulate growth of SPI in adipose tissue sites, whereas progesterone inhibits growth. In contrast, in vivo growth of a stable metastatic variant selected from SPI cells was not inhibited by progesterone. SPI cells growing in ovarian and mesenteric fat pads showed increased expression of estrogen receptors and progesterone receptors, as well as detectable levels of epidermal-growth-factor receptors, whereas receptor levels decreased to baseline on tumors in the subcutis. The levels of estrogen-receptor mRNA reflect the corresponding functional expression of receptors; this finding suggests that the regulation of estrogen-receptor expression in this system is, at least in part, at the mRNA level. Our results are consistent with the model that adipose tissue exerts an estrogen-dependent positive regulatory effect on primary SPI tumor growth, and promotes the formation of metastases.

Adipose Tissue