Biomedical subjects

H Xue

Publications and source records attributed to H Xue.

At least 55 records · Page 3Linked to original sources

PubMed1999

Bis(7)-tacrine, a novel dimeric AChE inhibitor, is a potent GABA(A) receptor antagonist.

Heptylene-linked bis-(9-amino-1,2,3,4-tetrahydroacridine) (bis(7)-tacrine) is a potential palliative therapeutic agent for Alzheimer's disease (AD), on the basis of its superior acetylcholinesterase (AChE) inhibition and memory-enhancing potency relative to tacrine. In this study we report that bis(7)-tacrine exhibits a potentially complementary central nervous system action, antagonism of GABA(A) receptor function. Bis(7)-tacrine displaced [3H]muscimol from rat brain membranes with an apparent Ki of 6.0 microM; tacrine and physostigmine were shown to be 18 and 170 times less potent, respectively. In whole-cell patch-clamp recordings, bis(7)-tacrine inhibited GABA-induced inward current with an IC50 of 5.6 microM, and shifted the GABA concentration-response curve to the right in a parallel manner. These results suggest that bis(7)-tacrine is a competitive antagonist of the GABA(A) receptor.

Alzheimer Disease↗

PubMed1999

[Pathogenic gene linkage analysis and hemopoietic characteristics in a kindred with sideroblastic anemia].

OBJECTIVE: Analysis of pathogenic gene linkage and hemopoietic characteristics in a kindred with sideroblastic anemia. METHODS: PCR amplification of the microsatellites DXS991,DXS1199 in chromosome Xp11.22 linked gene ALAS2 and of the microsatellite DXS1226 in Xp22. 13 linked another irrelevant gene and analysis of gene linkage in a kindred with 2 patients and 7 normal persons. The bone marrow hemopoietic cells from 2 patients were cultured in condition culture matrix with various cytokines added in and the CFU-E, CFU-GM and CFU-Meg formations were observed at different times. RESULTS: The kindred study revealed that pathogenic gene linked with DXS991 and DXS1199 but did not link with DXS1226.Hemopoietic cell culture showed that erythroid colonies of the two patients grew more vigorously than controls and they could grew in the absence of Epo except in common condition matrix. The erythroid colonies withered after a week and were smaller than the controls after 13 days. CONCLUSION: The kindred is subject to an X-linked sideroblastic anemia(XLSA) with the pathogenic gene ALAS2 involved. In XLSA,the function of stem cells is primarily normal before erythropoiesis, then the erythroid progenitors become dysplasia.

Adult↗

PubMed1999

Delineation of a membrane-proximal beta-rich domain in the GABAA receptor by progressive deletions.

The type A gamma-aminobutyric acid (GABAA) receptor plays a major inhibitory role in the central nervous system. Structural elucidation of the GABAA receptor has been impeded by the large size of the receptor. We present here the delineation of a minimal structural domain as the first step of dissecting the receptor structure. This was achieved through prediction-assisted progressive deletions: the prediction of a candidate structural domain rich in beta-strands with no close similarity to known structures was tested by deleting putative secondary structure elements from the ends of the proposed domain, as well as mutations within the terminal secondary structures. Such progressive deletions revealed the limits of an integral domain, spanning Cys180 to Met293 (numbering of human alpha1 subunit). Below these limits the intact domain structure, as indicated by its circular dichroism, collapses. Based on its putative position, this domain is provisionally designated the membrane-proximal beta-rich domain of GABAA receptor. The inclusion of sequences from the first two out of four previously suggested transmembrane segments and one of the two conserved Cys residues in this domain defines important constraints to the receptor structure.

Amino Acid Sequence↗

PubMed1999

Meconium stimulates a pro-inflammatory response in peritoneal macrophages: implications for meconium peritonitis.

BACKGROUND/PURPOSE: Although meconium peritonitis is a rare condition, the mortality rate can be as high as 40%. Meconium peritonitis is a result of intestinal perforation in utero, which leads to dense inflammation in the peritoneal cavity. The fetus has relatively immature peritoneal defense mechanisms, so the cause of this dense inflammation is unclear. The peritoneal macrophage is a key cell in the peritoneal inflammatory response in adults. The purpose of this investigation was to determine if sterile meconium had a direct stimulatory effect on the peritoneal macrophage. METHODS: Peritoneal macrophages were harvested from adult C3H/HEN mice. The cells were placed in microtiter wells at 10(5) cells per well. Sterile human meconium was diluted in media and placed in the wells at varying concentrations for 8 hours. Lipopolysaccharide (LPS) (10 microg/mL) served as a positive control. Supernatants were harvested and assayed for tumor necrosis factor alpha (TNF-alpha) using a commercial ELISA kit. Separate cells were assayed for TNF-alpha message using polymerase chain reaction (PCR). In another series of experiments, procoagulant activity (PCA) was determined on freeze-thawed cells using a two-stage amidolytic assay. To test for the role of protein kinase C (PKC) in the PCA response H7, a PKC inhibitor, was used as well. RESULTS: Meconium stimulation resulted in a significant increase in TNF-alpha compared with negative controls with a peak at 0.1% meconium (121 pg/mL v 11 pg/mL, P<.05). There was a significant increase in PCA, with a 10-fold increase with 1% meconium compared with controls (P<.05). This response was limited to less than 5% by PKC inhibition. CONCLUSIONS: Sterile meconium results in a marked proinflammatory response in the peritoneal macrophage with elevations of both PCA and TNF-alpha. The TNF response is likely mediated at a pretranscriptional level because there is a marked increase in TNF mRNA. These data suggest that the PCA response is regulated by a PKC mechanism similar to LPS. Stimulation of the peritoneal macrophage by meconium is a possible cause of the marked inflammation seen in meconium peritonitis.

Animals↗

PubMed1999

Effects of FK506 in rat and human resistance arteries.

BACKGROUND: FK506 is widely used in organ transplantation and causes hypertension. However, little is known about the impact of the drug on the cardiovascular system. METHODS: We therefore investigated the effect of FK506 on resistance artery and blood pressure responsiveness to vasoconstrictors and vasodilators. Studies were conducted in vitro using human and murine resistance artery, ex vivo in resistance artery isolated from rats treated with FK506 (6 mg/kg/day), and in vivo in conscious, treated animals. RESULTS: In vitro exposure (24 hr) of human and rat resistance artery to FK506 (1000 ng/ml) increased the sensitivity to norepinephrine (NE) and impaired the response to acetylcholine (Ach) and sodium nitroprusside (SNp). In contrast, arteries isolated from rats given FK506 for eight days showed a reduced sensitivity to NE (P < 0.05) and a normal endothelium-dependent relaxation. Their incubation with L-arginine caused a significant reduction in Ach sensitivity in the FK506 group (P < 0.05) but not in controls, suggesting enhancement of nitric oxide production by the drug. The sensitivity to SNp was reduced, as in the in vitro experiments (P < 0.05). Rats given FK506 for eight days presented blood pressure similar to that in controls but also presented signs of a compensatory response to excess vasodilation: tachycardia (P < 0.01), reduced blood pressure sensitivity to NE and Ach, blunted heart rate response to both agonists, and exaggerated hypotension at high doses of Ach. After 21 days of treatment, blood pressure remained similar to that in controls, but resistance artery showed further functional deterioration, with significant impairment of the maximum responses to Ach and to SNp. CONCLUSION: FK506 presents significant vascular toxicity affecting mainly smooth muscle relaxation and alters vascular hemodynamics. The data suggest that similar cardiovascular changes may occur in transplant patients and represent the forerunner of hypertension often seen with more prolonged use of the drug.

Adult↗

PubMed1999

Tentative association of the serotonin transporter with schizophrenia and unipolar depression but not with bipolar disorder in Han Chinese.

The serotonin transporter gene (SERT) plays an important role in the serotonin uptake into neurons. Recently, several polymorphisms including a variable-number-tandem-repeat (VNTR) in the second intron and an insertion/deletion polymorphism (5-HTT linked polymorphic region, 5-HTTLPR) were identified and reported to be associated with a variety of mental illnesses, including major depression, bipolar disorder, anxiety-related traits, and autism. In our study, we performed an association study between the SERT VNTR polymorphism and schizophrenia (n = 260), bipolar disorder (n = 137), and unipolar depression (n = 33) in the Han Chinese. A large group of ethnically matched control individuals (n = 362) were also genotyped. Allele 12 of the VNTR polymorphism was associated with schizophrenia (P = 0.007) and unipolar depression (P = 0.011). Bipolar disorder was not associated with the VNTR (P = 0.93). Thus, we conclude that the SERT VNTR polymorphism may be a risk factor for both schizophrenia and unipolar depression, but not for bipolar disorder, in the Han Chinese.

Alleles↗

PubMed1999

Enzyme-linked immunoelectrotransfer blotting analysis of human serologic responses to infective hookworm larval antigen.

OBJECTIVE: To explore the possibility of using specific antigens for immunodiagnosis of hookworm disease in endemic area. METHOD: Infective third-stage larvae of the canine hookworm, Ancylostoma caninum (A. caninum), were prepared as the source of antigen. Enzyme-linked immunoelectrotransfer blotting (EITB) was employed as an immunodiagnostic method. RESULTS: Two immunodominant bands of hookworm antigens (42 kDa and 55 kDa) were recognized by the sera of hookworm-infected patients (serum dilution 1:200; antigen centrifuged at 36,000 r/m for 20 minutes, but not by sera from negative controls. CONCLUSION: The 42 kDa and 55 kDa A. caninum antigens might be the specific antigens that could be used for immunodiagnosis of hookworm disease in endemic area.

Ancylostoma↗

PubMed1999

[Experimental study of the anti-tumor effects of directly administered packaging cell line of retroviral vector carrying IL-12 gene on hepatoma].

OBJECTIVE: To study the inhibitory effects of vivo directly administered packaging cell line of retroviral vector carrying mouse interleukin-12(mIL-12) on the growth of the vivo established hepatoma and to explore a new way for hepatoma gene therapy. METHODS: Retroviral vector carrying mIL-12 gene was constructed. The vector was transfected to retroviral packaging cell line. Then the cell was injected intra-peritoneally and locally into hepatoma tissues or intrasplenally to observe its effects on the growth of hepatoma and the changes of immunological function in rats. Its toxic effects were also documented. RESULTS: In treatment group, the rats survived permanently with the ratio of the packaging cell to hepatoma cell being less than 1:10, while the survival time of rats was only prolonged when the ratio was more than 1:10. In groups treated locally in the hepatoma tissue or intrasplenally, the rats survived permanantly with the packaging cell line given on the first or the third day, while the rats survived only longer with the packaging cell line given on the fifth or the seventh day. The immunological study showed that the number of hepatoma infiltrating lymphocytes, mainly composed of NK cell and cytotoxic T cell, was increased in the treatment group. The pathological study showed thicking of the vascular wall and sternosis of vascular cavity in hepatoma tissue in the treatment group. CONCLUSION: The directly injected packaging cell line in vivo carrying mIL-12 gene via retroviral vector inhibits the growth of hepatoma. The therapeutical effects of early administration are superior to later one. Direct injection via spleen is a new, safe and effective way for hepatoma therapy with.

Animals↗

PubMed1999

Length of protection by murine vaccination with living infective third-stage hookworm larvae.

OBJECTIVE: To determine the length of protection by murine immunization with living third-stage hookworm larvae (L3) as measured by reduction in worm burden and host serologic antibody responses. METHODS: Outbred male (Kunming strain) mice were immunized subcutaneously with 500 L3 once every 2 weeks for a total of immunization for 3 times, and then challenged orally with 1000 L3 for 1 to 8 weeks after the final immunization. Host protective immunity was determined both by the reduction in worm burden as measured by the number of L3 recovered from murine lungs 48-hour post-challenge, as well as by measurement of circulating antibodies. Histopathological responses were also examined. Non-immunized mice served as negative controls. RESULTS: The protection by L3 immunization declined over time. One or 2 weeks after the final immunization, worm burdens were reduced 72% and 77.5% after challenge respectively. In contrast, only 37% reduction in worm burden was observed when the L3 challenge was delayed by 4 weeks and protection was almost entirely lost when there was an 8 week delay between the time of final immunization and challenge. The reduced level of protection over time partially correlated with diminishing L3-specific antibody responses. Host inflammation in the lungs of immunized mice also diminished. CONCLUSION: The protection afforded by living L3 immunization is maximal for the first two weeks after immunization, but then declines significantly over the ensuing weeks.

Ancylostoma↗

PubMed1999

[IL-12 gene treatment of hepatocellular carcinoma: experimental study].

OBJECTIVE: To investigate the inhibitory effects of retrovirus vector containing IL-12 gene on hepatoma growth in vivo and to explore a new approach of gene therapy to hepatocellular carcinoma (HCC). METHODS: Retrovirus vector containing IL-12 gene was constructed and transfected into packaged cell PA317. Positive PA317 was injected into the rat which suffered from experimental HCC and its anti-tumor effects and immunity changes were recorded. RESULTS: The packaged cell PA317 containing IL-12 gene could inhibit the proliferation of hepatocellular cell line CBRH3. The rats injected at day 1 or 3 can survive permanently, while those injected at day 5 or 7 can survive longer than those not injected. However, tumor generated in rats injected with blank control or package cells containing retroviral vector without IL-12 gene (P < 0.01). CONCLUSIONS: Package cells transfected with retroviral vector containing IL-12 either injected to the hepatoma tissue locally or given splenic exercises anti-hepatoma effects efficiently. The direct intrasplenic injection route is new, safe and effective.

Animals↗

PubMed1999

[Internal drainage combined with intraoperative radiotherapy and chemotherapy for pancreatic head carcinoma].

OBJECTIVE: To improve the palliative effect on intermediate or advanced pancreatic head carcinoma. METHODS: 26 patients with intermediate or advanced pancreatic head carcinoma underwent cholecystojejunostomy combined with intraoperative radiotherapy with an electron beam on carcinoma from May 1996 to May 1998. The catheter of multifunctional implantable drug delivery system was inserted via gastroduodenal artery for postoperative perfusion chemotherapy. RESULTS: Follow-up for 3 - 27 months showed that all carcinomas shrunk with pain released in different degrees after a course of treatment. The 6-month, 12-month and 24-month survival rates were 100%, 93.9% and 20% respectively. Five patients survived on the average for 17.8 months. CONCLUSIONS: This protocol is effective to prolong the life of the patients with intermediate or advanced pancreatic head carcinoma.

Adult↗

PubMed1999

[Antagonistic effects of metallothionein on genetic damage caused by gamma-rays and mitomycin C].

OBJECTIVE: To study the antagonistic effects of metallothionein (Zn-MT)on genetic damage caused by gamma-rays and mitomycin C (MMC) in the liver of rabbits. METHODS: Micronucleus test and DNA strand breaks were determined in vitro and in vivo with single-cell gel electrophoresis assay to observe the effects of Zn-MT on the micronucleus formation and cleavage of DNA chain before and after gamma-rays radiation and MMC treatment. RESULTS: A dose of 664 microg/kg of Zn-MT could inhibit micronucleus formation in the bone marrow of the mice induced by 5 Gy gamma-rays radiation (P < 0.05). Concentrations of 10 and 50 microg/ml Zn-MT could antagonize the increase in bimicronucleus frequency in g12 cells induced by 1 and 3 Gy gamma-rays radiation and 0.3 microg/ml MMC treatment (P < 0.05 or P < 0.01). A dose of 50 microg/ml Zn-MT could reduce the DNA single strand breaks caused by 1 Gy gamma-rays radiation, but without statistical significance (P > 0.05). CONCLUSION: Zn-MT could antagonize the genetic damage to certain extent in the liver of the rabbits caused by gamma-rays radiation and MMC treatment.

Animals↗

PubMed1999

[Studies on DNA single strand breaks induced by sodium nitroprusside-nitric oxide donor].

OBJECTIVE: To study the effect of sodium nitroprusside (SNP), a nitric oxide (NO) donor, on DNA single strand breaks (SSBs). METHODS: A modified method was used to isolate and prepare the single cell suspension from the organs of mice. Alkaline single-cell gel electrophoresis (SCGE) was performed to examine DNA damage of the cells treated by SNP in vivo and in vitro. RESULTS: Treatment with 0.5 - 2.0 micromol/ml of SNP with S(9) for 1 h induced a concentration-dependent increase in DNA SSBs in g12 cells. Significant increase in DNA migration and comet frequency in the spleen, thymus and peritoneal macrophage were induced after intraperitoneal injection of SNP at a dose of 0.67 - 6.0 mg/kg. No obvious increase in DNA single strand breaks was observed in the liver, kidney and lung of the mice with same treatment. CONCLUSION: DNA SSBs could be induced by NO in some cells in vivo and in vitro. There was difference in sensitivity of various organs in the mice to NO. Cells of spleen and thymus and macrophage may be the important target cells of NO.

Animals↗

PubMed1999

[A study on the ultrastructure of plant cell under simulated microgravity].

OBJECTIVE: To study the effects of microgravity on plant cell ultrastructure. METHOD: Analyzing the biological and physiological differences between the plants grown in the simulated microgravity conditions and their correspondent ground controls. RESULT: Various variances in cell walls, chloroplasts and mitochondria were observed with electron microscope. Those ultrastructure changes included plasmolysis, twist, contraction and deformation of cell walls, curvature and loose arrangement of chloroplast lamellae, breach of mitochondria, overflow of inclusions, disappearance of cristae, and significant increase in number of starch grains per cell. CONCLUSION: Simulated microgravity conditions exert some coerce influence on the plant growth and the changes above-mentioned were the responses in cell level.

Cell Wall↗

PubMed1999

[SDS-PAGE and EITB analysis of the protein components of different isolates of Schistosoma japonicum in China and Japan].

AIM: To make a supplementary observation on the protein components prepared from adult S. japonicum of 4 different isolates from Zhejiang, Jiangxi, Taiwan Provinces of China and Japan in origin and to observe antigen reactivity of the above-mentioned isolates together with adult worms from Anhwi, Hubei, Sichuan and Yunnan isolates against heterologous anti-Oncomelania h. hupensis (collected from Guangxi, China and Japan) sera by EITB. METHODS: SDS-PAGE and EITB. RESULTS AND CONCLUSION: SDS-PAGE showed that by Coomassie blue staining, male S. japonicum from Jiangxi, Zhejiang, Taiwan Provinces and Japan isolales revealed 7-17 bands while female worms revealed 1-6 bands. The protein patterns of Taiwan and Zhejiang male worm were similar, but slight difference could be seen above 81 kDa. By silver staining, male worms of the 4 isolates revealed 10-23 bands while female worms revealed 1-19 bands. Male worms from Japan not only showed less bands but also differed in their pattern as compared to those of other Chinese isolates. Results of EITB revealed that each of the 4 isolates had slightly different pattern but all of the tested isolates had common antigens with their heterologous snail hosts i.e., Oncomelania h. hupensis from Guangxi, China and Japan.

Animals↗

PubMed1998

[The microsatellite instability and loss of heterozygosity in chromosome translocation breakpoint in leukemia].

OBJECTIVE: To investigate the microsatellite instability (MSI) and loss of heterozygosity (LOH) near the chromosome translocation breakpoints of various types of leukemia. METHODS: PCR amplification of 11 microsatellite loci closely linked to chromosome translocation breakpoints in 30 leukemia patients. RESULTS: Twenty one in 30 cases of leukemia had MSI in from 1 to 14 microsatellite loci. Eleven in 15 cases of acute leukemia had microsatellite instability (MSI) in more than 1 locus; among them 4 cases had MSI in from 7 to 11 loci. In order of MSI presence rate were D22S315>D9S179>D16S515>D8S559>D12S89. In six cases of chronic myeloid leukemia, 4 cases had MSI in more than 3 loci. Thirteen (2/15) percent of acute leukemia patients had loss of heterozygosity (LOH); the rate was higher than that in other leukemia types. CONCLUSION: The results of MSI and LOH in many cases indicate that there are a lot of allelic alterations in leukemia patients, but those changes have no special relationship with chromosome translocation breakpoints in various leukemia types.

Chromosome Breakage↗

PubMed1998

Genotoxicity of nitric oxide produced from sodium nitroprusside.

Induction of mutation and micronucleus (MN) formation by nitric oxide (NO) was investigated in mammalian cells using sodium nitroprusside (SNP) as a drug donor of NO. Results showed that the concentration of NO2- in the tested solution rose according to time- and concentration-exposure to SNP. The treatment of SNP (0.5-8 micromol/ml with S9 or 2-8 micromol/ml without S9) induced a concentration-dependent increase in the mutation frequency at the gpt gene locus in g12 cells and caused a 13- (-S9) to 25- (+S9) fold increase above the background level at the highest concentration. A statistically significant increase in the number of micronucleated binucleated cells (MNBN) was also observed in treated groups. MNBN per thousand, MN per thousand and the proportion of the multiple micronuleated cells increased in a concentration-dependent manner in the concentration range of SNP (0.5-4 micromol/ml with S9 or 2-8 micromol/ml without S9). Our results indicate that SNP, an NO releasing drug, is genotoxic in g12 cells.

Cell Line↗

PubMed1998

Fragment of GABA(A) receptor containing key ligand-binding residues overexpressed in Escherichia coli.

GABA(A) receptor plays a major role in inhibitory synaptic transmission in the central nervous system and is the target of drugs such as the benzodiazepine tranquilizers. The polymeric membrane protein nature of GABA(A) receptor has rendered structural elucidation of the receptor a formidable task, greatly hampering structure-based drug design. We report here the first expression in Escherichia coli of a fragment of GABA(A) receptor. This 131-residue fragment, spanning Cys166 to Leu296 of human GABAA receptor alpha1 subunit, contains residues previously suggested to be involved in benzodiazepine binding. The overexpressed non-fusion recombinant protein was purified to near homogeneity and characterized by circular dichroism (CD), which showed that the recombinant protein has well defined secondary structures where beta-strands are dominant. The stability of the secondary structures was demonstrated by CD spectra at high pH and elevated temperature. Excluding part of the sequences from the carboxyl terminal of the fragment resulted in dramatic changes in the secondary structures comparable to the effects caused by SDS denaturation. Our results therefore suggest that the 131-residue fragment harbors an integral structural domain of the receptor. The overexpression of the recombinant protein fragment thus opens the way to the biochemical and structural studies of a functionally important region of the receptor, and exemplifies an effective approach of expression and characterization that potentially may be extended to other members of the ligand gated channel receptor superfamily, to which the GABA(A) receptor belongs.

Binding Sites↗