PubMed Health⌕ Search

Biomedical subjects

X Su

Publications and source records attributed to X Su.

At least 109 records · Page 6Linked to original sources

Kappa, but not mu or delta, opioids attenuate responses to distention of afferent fibers innervating the rat colon.

BACKGROUND & AIMS: Discomfort and pain are the principal conscious sensations that arise from the viscera, and both are increased in frequency and intensity in patients with a functional bowel disorder. Visceral receptors, perhaps sensitized, may contribute to these altered sensations. The aim of this study was to evaluate the effects of opioid receptor-selective agonists on afferent fibers innervating the colon. METHODS: Mechanosensitive pelvic nerve afferent fibers were recorded from the decentralized S1 dorsal root in anesthetized rats. The effects of opioid agonists, given intra-arterially, were studied based on the fiber's responses to noxious colorectal distention (CRD) (80 mm Hg, 30 seconds). RESULTS: A total of 115 distention-sensitive fibers innervating the colon were studied, including 32 that were studied after colonic inflammation with 2.5% acetic acid. Neither mu-(morphine and fentanyl) nor delta- ([D-Pen2, D-Pen5]enkephalin- and SNC-80) opioid receptor agonists affected responses to CRD. In contrast, kappa- (U-50,488 and fedotozine) opioid receptor agonists dose-dependently attenuated responses to CRD. Acetic acid sensitized about half of the fibers studied, but neither the potency nor the efficacy of U-50, 488 or FDZ were changed after colonic inflammation. CONCLUSIONS: These results suggest a role for peripheral kappa-opioid receptors in the modulation of visceral nociception.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Cloning and characterization of a glycogen synthase cDNA from human endometrium.

One major human uterine response to post-ovulatory progesterone is the accumulation of glycogen by the endometrium. A temporally related increase in glycogen synthase activity has been documented, but the isozyme responsible has not yet been identified. We have amplified a glycogen synthase (GS) complementary DNA (cDNA) from human endometrium by reverse transcription-polymerase chain reaction (RT-PCR). Overlapping clones of the PCR products provided a cDNA that is 3534 base pairs (bp) long, including a 22-bp poly(A)+ tail, and an open reading frame that encodes a 737 amino acid protein with a molecular weight of 83936. This cDNA is almost identical to that of human striated muscle GS. Differences include a double nucleotide substitution at 1983-1984 and five single nucleotide substitutions located, respectively, at positions 379, 2457, 2470, 2477, and 2553. These differences only alter the predicted amino acid sequence from that of the striated muscle protein by a single substitution at position 608. A 5'-end fragment plus an internal fragment of human myometrial GS cDNA were also analysed and were shown to have identity with the endometrial GS cDNA. Northern blot hybridization, using a human muscle-derived cDNA probe, detected the presence of a 4.0-kb GS messenger RNA (mRNA) in the endometrium and myometrium. Our results establish that the GS of human Mullerian tissues is, essentially, identical to that reported for human striated muscle.

Amino Acid Sequence↗

[8 species of peroxidase isozymes and 2 varieties of Corydalis].

The peroxidase isozymes of 8 species and 2 varieties of Corydalis were analysed by means of polyacrylamide gel electrophoresis. According to the isozymic zymograms, these plants may be divided into 3 groups. The taxonomy based on isozymic zymograms is in accord with that by morphology. The problem that the action of enzymes of Corydalls species is easily weakened or lost is also discussed.

Electrophoresis, Polyacrylamide Gel↗

[Activation of proto-oncogenes induced by MNNG on primary culture of human gastric epithelium and immortalized human gastric epithelial cell line].

Epidemiologic study has shown the association of nitrosamide compounds with the high incidence of stomach cancer in south China. To study the mechanism of gastric carcinogenesis, we have established an immortalized human gastric epithelial cell line GES-1. GES-1 cells and the normal gastric tissues were treated with different concentrations of MNNG for 24 hours. Point mutation at codon 12 of c-Ha-ras gene was found in cells and tissues (43%) as demonstrated by PCR-RFLP. Rearrangement of c-met gene and amplification of c-erbB2 gene were detected by Southern blot assay on the MNNG treated GES-1 cells. The results indicate that MNNG treatment was intimately associated with the activation of certain oncogenes. H-ras and c-met genes, serving as early targets of carcinogens may play important role in the carcinogenesis of human gastric epithelial cells.

Cell Transformation, Neoplastic↗

Autoimmune disease results from multiple interactive defects in apoptosis induction molecules and signaling pathways.

Activation induced cell death (AICD) plays a critical role in eliminating autoimmune cells and limiting inflammation after activation. The two major signaling molecules for AICD are the Fas and TNF-R pathways of apoptosis. Defective Fas apoptosis in lpr/lpr mice results in a compensatory increase in TNF-R/TNF-mediated apoptosis. TNF/TNF-R has been shown to be a compensatory pathway of apoptosis in T cells and macrophages of lpr/lpr mice. Therefore, early production of TNF/TNF-R limit an immune response by inducing AICD in the absence of an intact Fas/Fas ligand apoptosis pathway. However, increased TNF production in lpr mice also lead to increased susceptibility to septic shock and autoimmune disease such as arthritis. Therefore TNF production during an inflammatory response can downmodulate this response, but this also results in the failure to downmodulate TNF production leading to septic shock and arthritis. A second pathway of AICD is mediated by Nur77 after T cell stimulation through the CD3 molecule. Mice with defective Nur77 signaling undergo AICD using the Fas-Fas ligand pathway to eliminate autoreactive T cells. A third defect of AICD is observed in HCP-mutant me/me (motheaten) mice which develop autoimmune disease related to defective Fas apoptosis signaling. Therefore, multiple interactive pathways play a role in limiting development of autoimmunity.

Animals↗

[Preparation and characterization of human monoclonal antibody to breast carcinoma].

With fusion of human heteromyeloma cells SHM-D33 and B lymphocytes obtained from axillary lymph nodes of a patient suffering from breast carcinoma, one hybridoma cell line which secretes human monoclonal antibody CM-1 to breast carcinoma was established. The hybridoma cells have been secreting human IgM (lambda light chain) stably for over 5 years. The CM-1 concentration of the supernatant of cell culture is 38.5 micrograms per ml and is the ascites that of 2 mg per ml. The reactivity of CM-1 to normal human tissues and several kinds of tumors was examined with immunohistochemical staining. The results showed that the CM-1 reacted strongly to breast carcinoma and weakly to myxoadenocarcinoma of the esophagus. CM-1 did not react to normal tissues or other kinds of tumors, such as breast fibroadenoma, medullary carcinoma of the thyroid, etc. After injection of 131I-CM-1 into abdominal cavity of the mice bearing breast carcinoma, the image of xenografted carcinoma can be obviously distinguished from the background of normal tissues. The inhibitory effect on growth of breast cancer xenograft in nude mice was 95% for CM-1-PYM conjugate and 58% for free drug. The above results showed that the hybridom cell line CM-1 stably secreting antibody reacted specificaly with breast carcinoma and it might be useful as a drug carrier in therapy of patients with breast carcinoma.

Animals↗

[Inhibition of rabbit lens epithelial cell proliferation].

OBJECTIVE: To study the ability of homoharringtonine, 5-fluorouracil and adriamycin on inhibiting the proliferation of rabbit lens epithelial cells (RLEC) and the prevention of after cataract by using homoharringtonine. METHODS: RLEC were isolated and cultured. (1) The passage RLEC were placed in 24-well tissue culture plates and incubated for 48 hours, then exposed to different concentrations of homoharringtonine, 5-fluorouracil and adriamycin for 24 and 72 hours; (2) The passage RLEC and homoharringtonine, 5-fluorouracil, adriamycin were placed and cultured for 24 hours to investigate the rate of attached cells; (3) The morphological changes of RLEC were studied under light microscope. RESULTS: The ID50 of homoharringtonine, 5-fluorouracil and adriamycin exposed to RLEC for 24 hours were 0.84 micrograms, 0.58 micrograms and 4.50 ng/ml and those for 72 hours were 0.49 micrograms, 0.33 micrograms and 3.85 ng/ml respectively. In the homoharringtonine group, the rate of attached cells was less than that of 5-fluorouracil and adriamycin groups. The study of the morphological changes showed that the different concentrations of antiproliferative drugs affected on RLEC at different regions. CONCLUSION: The authors consider that homoharringtonine may be more effective for the prevention of after cataract than 5-fluorouracil and adriamycin.

Animals↗

Myoblast and myotube nuclei display similar patterns of heterogeneous acetylcholine receptor subunit mRNA expression.

Muscle progenitor cells differentiate to myoblasts, and subsequently myotubes, upon expression of muscle specific genes. We and others have previously shown that myotube nuclei, even in the absence of nerve, express AChR alpha subunit RNA at varying levels, with a small subset (about ten percent) of the nuclei expressing at high levels. These findings raised two important questions: 1) is the observed heterogeneity a unique property of the alpha subunits, and 2) when does the heterogeneity begin? In particular, is it induced only at or after the time of fusion, or does it exist at the myoblast stage? We have, therefore, extended our observations to the gamma and delta subunits and we also have examined the distributions of AChR alpha, gamma, and delta subunit RNAs in both myoblasts and myotubes. We used intron and intron-exon probes to detect prespliced transcripts or mature mRNAs in the cells. Because intron-containing transcripts are not transported out of the nuclei, the distributions of these transcripts can indicate their expression patterns among nuclei in the same myotubes. Our results show that both myotubes and myoblasts have distributions of the AChR alpha, gamma, and delta subunit RNAs which differ sharply from that of the U1 RNA or Myo D. Thus, the heterogeneous expression of AChR genes is not only an intrinsic property of muscle cell nuclei (in the sense that it does not require the presence of nerves), but it also exists prior to fusion. Our results suggest that muscle nuclei attain individualized capacities for AChR subunit mRNA production early in their development. Conceptual models consistent with such individuality imply an additional level of regulation beyond the known diffusible transcriptional factors.

Animals↗

Autoimmunity, apoptosis defects and retroviruses.

Autoimmunity and AIDS both share the common feature of increased expression of retroviral protein products and abnormal apoptosis of immune cells (81). This leads to a more global immunomodulatory defect (82-84). The challenge in the future will be to devise compounds that can either regulate the effect of the retroviral products on apoptosis, or that can inhibit apoptosis pathways in order to restore normal immune system function.

Amino Acid Sequence↗

Self-complementary oligopeptide matrices support mammalian cell attachment.

A new class of ionic self-complementary oligopeptides is described, two members of which have been designated RAD16 and EAK16. These oligopeptides consist of regular repeats of alternating ionic hydrophilic and hydrophobic amino acids and associate to form stable beta-sheet structures in water. The addition of buffers containing millimolar amounts of monovalent salts or the transfer of a peptide solution into physiological solutions results in the spontaneous assembly of the oligopeptides into a stable, macroscopic membranous matrix. The matrix is composed of ordered filaments which form porous enclosures. A variety of mammalian cell types are able to attach to both RAD16 and EAK16 membranous matrices. These matrices provide a novel experimental system for analysing mechanisms of in vitro cell attachment and may have applications in in vivo studies of tissue regeneration, tissue transplantation and would healing.

Amino Acid Sequence↗

Defective expression of hematopoietic cell protein tyrosine phosphatase (HCP) in lymphoid cells blocks Fas-mediated apoptosis.

Protein tyrosine dephosphorylation after Fas cross-linking occurred in Fas apoptosis-sensitive CEM-6 cells but not in Fas apoptosis-resistant MOLT-4 cells, and apoptosis in the CEM-6 cells could be inhibited by the protein tyrosine phosphatase inhibitor, pervanadate. The time course and level of dephosphorylation were correlated with increased hematopoietic cell protein tyrosine phosphatase (HCP) activity, but not with the activity of two other tyrosine phosphatases. The level of expression of HCP was correlated with Fas apoptosis function in eleven human and murine Fas-positive lymphoid cell lines. Expression of recombinant HCP in the MOLT-4 cell line converted this Fas apoptosis-resistant cell line to Fas apoptosis sensitive. HCP-mutant mev/mev mice exhibited increased expression of Fas but decreased Fas-mediated apoptosis function in lymphoid organs after anti-mouse Fas antibody treatment in vivo. Thus, HCP-mediated protein dephosphorylation is involved in the delivery of the Fas apoptosis signal in lymphoid cells.

Animals↗

Expression of recombinant feline tumor necrosis factor is toxic to Escherichia coli.

The tumor necrosis factor (TNF) genes from cats, horses, and pigs have all been cloned into the pFLAG-1 fusion protein expression vector (International Biotechnologies, Inc., Kodak, New Haven, Conn.). Growth curves for Escherichia coli containing the pFLAG-1 vector alone and the pFLAG-1 vector containing the TNF gene from each species were determined by visible light spectrophotometry (at 600 nm). Porcine TNF, equine TNF, and feline TNF cultures had slower doubling rates than cultures containing the pFLAG-1 vector alone. Cultures of cells transformed with feline TNF reached peak densities at 3 to 4 h and then decreased to near initial densities prior to the recovery of growth. The induction of expression with isopropyl-beta-D-thiogalactopyranoside (IPTG) arrested the growth of fresh feline TNF cultures for 6 h, which was followed by complete recovery. This inhibition occurred in two strains of E. coli (LL308 and JM101). Induced feline TNF cultures expressed the TNF-FLAG fusion protein for the first 6.5 h. Uninduced cultures expressed low levels of fusion protein. The feline TNF-pFLAG-1 vector was purified from cells expressing fusion protein and from cells with recovered growth curves. Sequencing the vector demonstrated the complete feline TNF gene and tac promoter in cells expressing the fusion protein and a deletional mutation of the tac promoter site in recovered cells. In contrast to equine and porcine TNF, the expression of recombinant feline TNF is toxic to E. coli. Alterations in protein folding and the prevention of secretion of the feline protein may explain the toxic effect.

Animals↗

Role of cyclooxygenase metabolites in mediating platelet-induced baroreceptor dysfunction.

The goal of the study was to determine the role of cyclooxygenase metabolites in mediating platelet-induced suppression of baroreceptor activity. Exposure of the isolated carotid sinus of rabbits to thrombin-activated rabbit platelets (3 x 10(8) cells/ml Krebs buffer) decreased baroreceptor activity (P < 0.05) without significantly altering the slope of the pressure-activity relation (gain). The platelet-induced suppression of activity was not blocked but instead was even more pronounced after inhibition of cyclooxygenase with indomethacin; both maximum baroreceptor activity and gain were decreased markedly. The exacerbation of platelet-induced baroreceptor dysfunction contrasted with equivalent carotid vasoconstrictor responses to platelets before and after indomethacin. Furthermore, the stable thromboxane (TxA2) mimetic U-46619 caused similar vasoconstriction as platelets but did not influence baroreceptor gain or maximum activity. In contrast to indomethacin, the selective TxA2 synthesis inhibitor and receptor blocker CGS-22652 failed to influence platelet-induced suppression of activity. In summary, 1) rabbit platelet aggregating in carotid sinus suppress baroreceptor activity, which cannot be explained by the vasoconstriction, and 2) the suppression of activity is not mediated by TxA2 from platelets and is opposed by prostacyclin (PGI2) or other prostanoids produced in carotid sinus. The combination of impaired formation of PGI2 and platelet activation in atherosclerotic and thrombotic states may lead to profound baroreceptor dysfunction.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Proliferative inhibition of rabbit lens epithelial cell--preliminary investigation for prevention of after cataract.

PURPOSE: To study the ability of Homoharringtonine (Hh), 5-Fluorouracil (5-Fu), and Adriamycin (ADM) on inhibiting the proliferation of rabbit lens epithelium. METHODS: Whole rabbit lenses were removed from freshly enucleated eyes under sterile condition. The rabbit lens epithelia (RLE) were isolated and cultured: (1) The passage RLE were placed in 24-well tissue culture plates and incubated for 48 hours, then exposed to different concentrations of Hh, 5-Fu, and ADM for 24 and 72 hours; (2) The passage RLE and Hh (0.084 microgram/ml), 5-Fu (0.058 microgram/ml), ADM (0.45ng/ml) were placed and cultured for 24 hours; (3) The morphological changes of RLE exposed to different concentrations of Hh, 5-Fu and ADM were studied under light microscope. RESULTS: The ID50 of Hh, 5-Fu and ADM exposed to RLE for 24 hours were 0.84 microgram/ml, 0.58 microgram/ml and 4.50ng/ml, respectively, and those for 72 hours were 0.49 microgram/ml, 0.33 microgram/ml and 3.85ng/ml. The attachment rate of RLE after being cultured for 24 hours with Hh, 5-Fu and ADM were respectively 83.6%, 89.1% and 87.3%. The morphological changes of RLE demonstrated that obvious changes in the cell membrane and cytoplasm were found even in lower concentration, but changes in the nuclei could only be found in higher concentration of these drugs. CONCLUSION: Hh can not only inhibit the proliferation of RLE but also reduce the number of attached cells. It is suggested that Hh may be more useful for the prevention of after cataract than 5-Fu and ADM.

Animals↗