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Biomedical subjects

X Ding

Publications and source records attributed to X Ding.

At least 91 records · Page 5Linked to original sources
PubMed1999

Anti-inflammatory effects of U74389F in a rat model of intestinal ischemia/reperfusion injury.

OBJECTIVE: To investigate the role of eicosanoid generation and neutrophilic infiltration in the protective effects of U74389F against ischemia/reperfusion injury in the small intestines of rats. DESIGN: Prospective, randomized, controlled study. SETTING: University research laboratory. SUBJECTS: Adult, male Sprague-Dawley rats weighing between 200 and 300 g. INTERVENTIONS: Groups (5-8) of rats treated with U74389F or vehicle were subjected to a sham operation and 30 mins of ischemia by occlusion of the superior mesenteric artery or 30 mins of ischemia followed by 60 or 120 mins of reperfusion. U74389F (2.5 mg/kg i.v.) or vehicle (citrate buffer) were slowly injected 2 mins before ischemia. MEASUREMENTS AND MAIN RESULTS: Ischemia significantly (p < .05) increased mucosal injury (0 [normal] to 5) in both U74389F and untreated rats. In contrast, U74389F significantly (p < .05) attenuated the severity of injury after reperfusion. In vehicle-treated rats, ischemia/reperfusion significantly reduced villus height in both U74389F and untreated groups. However, the surface epithelial layer was intact in the U74389F but not in the vehicle-treated group. In addition, compared with the vehicle-treated group, U74389F significantly reduced neutrophil infiltration and prevented the increase in leukotriene B4 and prostaglandin E2 in response to ischemia and reperfusion. CONCLUSIONS: This study demonstrates that the mechanism of U74389F against mesenteric ischemia/reperfusion includes a delay and reduction of neutrophilic infiltrate, an inhibition of leukotriene B4 production, and a facilitation of mucosal restitution.

Animals↗
PubMed1999

Providencia stuartii genes activated by cell-to-cell signaling and identification of a gene required for production or activity of an extracellular factor.

By utilizing reporter transposons, five Providencia stuartii genes that are activated by the accumulation of self-produced extracellular signals have been identified. These genes have been designated cma for conditioned medium activated. The presence of conditioned medium from stationary-phase cultures grown in rich media resulted in the premature activation of each gene in cells at early log phase, with activation values ranging from 6- to 26-fold. Preparation of conditioned medium from an M9 salts medium and fractionation by gel filtration chromatography resulted in fractions within the included volume which activated three of the cma fusions. In addition, depending on the reporter fusion, peak activity was found in different fractions. The partially purified factors activated in a dose-dependent manner. Characterization of the factors activating the cma fusions indicated that they were stable to heat, alkali, and acid. Furthermore, for each cma fusion, factor activity was not reproduced by the addition of homoserine lactone, homocysteine thiolactone, pyruvate, Casamino Acids, or alpha-ketoglutarate. The identities of three cma genes have been determined and revealed physiological roles in amino acid biosynthesis and nutrient import. To begin to address the pathways for production of or response to the extracellular factors, we have identified a locus, aarA, that is required for the activation of four cma fusions. The AarA product was required for factor activity in extracellular supernatants, indicating a possible role in biosynthesis or export.

Amino Acids↗
PubMed1999

Islet amyloid polypeptide tonally inhibits beta-, alpha-, and delta-cell secretion in isolated rat pancreatic islets.

Islet amyloid polypeptide (IAPP, or amylin) is produced in pancreatic beta-cells. The intraislet significance of IAPP is still uncertain. In the present study, paracrine effects of endogenous IAPP and somatostatin were investigated in isolated rat pancreatic islets. The intraislet IAPP activity was inhibited with an IAPP antiserum or a specific antagonist [IAPP-(8-37)]. Somatostatin activity was inhibited by immunoneutralization. Basal insulin and glucagon secretion were not affected by the somatostatin and/or IAPP blockade. Arginine-stimulated insulin and glucagon secretion were dose dependently increased by IAPP antiserum, IAPP-(8-37), and somatostatin antiserum, respectively. Arginine-stimulated somatostatin secretion was dose dependently potentiated by IAPP antiserum. Insulin secretion induced by 16.7 mM glucose was enhanced by IAPP antiserum and IAPP-(8-37), respectively. A combination of somatostatin antiserum with IAPP antiserum or IAPP-(8-37) further enhanced the arginine-stimulated insulin and glucagon secretion compared with effects when the blocking reagents were used individually. These results indicate that endogenously produced IAPP tonally inhibits stimulated insulin, glucagon, and somatostatin secretion. Furthermore, the paracrine effects of IAPP and somatostatin are additive.

Amyloid↗
PubMed1999

Male reproductive toxicity and beta-luteinizing hormone gene expression in sexually mature and immature rats exposed to 2-bromopropane.

1. The reproductive effects of 2-bromopropane (2-BP) in sexually mature and immature male Sprague-Dawley rats were investigated. The animals were randomly divided into three treatment groups and one control group each of which comprised six mature and six immature rats. The treated groups were injected s.c. 200, 600 and 1800 mg/kg of 2-BP on 5 days a week for 5 - 7 weeks and the control group received the vehicle. 2. The absolute and relative testis weights were significantly reduced in 600 and 1800 mg/kg b.w. dose groups in both mature and immature rats. The absolute epididymis, prostate, seminal vesicle, and pituitary weights and the relative epididymis weights, however, were significant only at the highest dose level used in both mature and immature rats. 3. The sperm concentration and sperm viability in epididymal duct decreased and the percentage of abnormal sperm increased in a dose-dependent manner in both mature and immature rats. Additionally, serum testosterone level was significantly decreased in all dose groups in mature rats, and was significantly reduced only in the group treated with the middle and highest dose in immature rats. 4. In both mature and immature rats treated with 200 and 600 mg/kg, the seminiferous tubules were atrophied and all types of germ cells were decreased in number. At the highest dose level, the effect was more marked showing severely atrophied seminiferous tubules and a complete loss of all types of germ cells. 5. The mating, pregnancy and fertility indices were significantly reduced in the 600 and 1800 mg/kg groups. Additionally, at the highest dose group the number of implantations and viable fetuses per litter were reduced and the resorption rate was increased significantly. 6. In the mature rats, the beta-LH gene expression increased significantly in the 1800 mg/kg group when compared to the control group. 7. It can be concluded that 2-BP induces alterations in both neuro-endocrine axis and the reproductive tract under the present experimental conditions. The no observed adverse effect level (NOAEL) in this study could be estimated to be lower than 200 mg/kg/b.w. based on the alteration in testicular morphology as well as on sperm parameters observed at the dose level of 200 mg/kg.

Animals↗
PubMed1999

Induction of rat small intestinal cytochrome P-450 2J4.

Cytochrome P-450 (CYP) 2J4 is a member of the recently identified CYP2J subfamily-part of the CYP superfamily-and is primarily expressed in rat small intestinal epithelium (enterocytes). Studies to determine small intestinal CYP2J4 inducibility by prototypic CYP inducers have been undertaken. Immunoblot analysis of enterocyte microsomes from rats treated with beta-naphthoflavone, dexamethasone, or phenobarbital revealed unchanged, diminished, or slightly increased levels of CYP2J4 protein, respectively, relative to vehicle-treated rats, whereas rats treated with pyrazole (200 mg/kg) had 3- to 4-fold increased levels of CYP2J4. Pyrazole administration also increased CYP2J4 metabolic activity, as probed by retinoic acid formation from retinal, approximately 3-fold, and the activity was inhibited by 90% by a polyclonal anti-CYP2J4 antibody. CYP2J4 mRNA levels were increased 2.5-fold by pyrazole administration. The route of pyrazole administration-oral or i.p.-did not affect the extent or time course of intestinal CYP2J4 induction. However, at >300 mg/kg pyrazole, oral administration produced higher levels of CYP2J4 activity than i.p. administration. Pyrazole also produced increased hepatic and olfactory mucosal levels of CYP2J4. We speculate, based on our data and on published mechanisms of pyrazole induction, that pyrazole induces rat intestinal CYP2J4 by stabilization of mRNA primarily, and by stabilization of protein to a lesser extent. This study documents for the first time the induction of a CYP2J subfamily member by a xenobiotic and provides the basis for a mechanism by which xenobiotics could modulate biological processes.

Animals↗
PubMed1999

[Determination of trisomy 9p by molecular cytogenetic technology].

OBJECTIVE: To use molecular cytogenetic techniques for the determination of complex chromosomal aberrations that could not be distinguished by conventional cytogenetic method. METHODS: Chromosome painting, comparative genomic hybridization (CGH) and color banding chromosome analysis (RxFISH) were used to identify a case with chromosome 9 aberration by G-banding. RESULTS: The patient has a karyotype of 46,XX,9p+ by G-banding. Both chromosomes 9 were uniformly painted, including the extra segment on one of the 9p alleles. CGH revealed a duplication of the entire 9p short arm. After analysis with RxFISH the patient's karyotype could be accurately described as 46,XX,dup9p (p11-->p24::p24-->qter). CONCLUSION: The present report shows that some late technological developments in the field of cytogenetics can facilitate the study of the diseases linked to complex chromosomal aberrations and may find significant application in basic and clinical medical studies.

Child, Preschool↗
PubMed1999

[Recurrent epithelial ovarian cancer].

OBJECTIVE: To evaluate the factors of influence on recurrent epithelial ovarian cancer and to make strategy of treatment. METHODS: Retrospective study of 189 cases of ovarian cancer admitted in our hospital from Jan, 1987 to Dec, 1997. All of these cases had postoperative pathological diagnosis. RESULTS: Of 31 recurrent cases, 19 cases had first cytoreductive surgery in our hospital, while other 12 cases were done in other hospitals. According to FIGO criteria, stage I, II 4 cases (12.9%), III, IV 27 cases (87.1%). The mean recurrent time of no-residual disease was 17.2 months, while that of residual disease < or = 2 cm was 10.1 months (P < 0.01). The mean recurrent time of those having chemotherapy > or = 6 cycles was 13.1 months, while that of those having chemotherapy < 6 cycles was 10.1 months (P > 0.05). The five-year survival rate of 18 cases having secondary cytoreductive surgery was 27.3%, while that of 4 cases having chemotherapy only was 7.1% (P < 0.01). The five-year survival rate of 7 cases abandoning any therapy was 4.8% (P < 0.01). 2 cases had only irradiation therapy. CONCLUSIONS: Histology, stage, degree of tumor differentiation, chemotherapy and the residual disease of cytoreductive surgery all influence recurrence of epithelial ovarian cancer. Secondary cytoreductive surgery along with chemotherapy can raise recurrent epithelial ovarian cancer's five-year survival rate.

Antineoplastic Agents↗
PubMed1999

[Detection of lipoarabinomannan-IgG in cerebrospinal fluid with enzyme-linked immunosorbent assay for diagnosis of tuberculous meningitis].

OBJECTIVE: To ascertain the value of lipoarabinomannan-IgG (LAM-IgG) determination in the diagnosis of tuberculous meningitis. METHODS: LAM-IgG in cerebrospinal fluid was detected with enzyme-linked immunosorbent assay. RESULTS: The positive rate of LAM-IgG in 73 patients with tuberculous meningitis was 51%, 36 control cases were all negative. The specificity was 100%. CONCLUSIONS: Detection of LAM-IgG in cerebrospinal fluid is a useful tool for diagnosis of tuberculous meningitis.

Antibodies, Bacterial↗
PubMed1999

[Studies on chemical constituents of the roots of Gypsophila oldhamiana Miq].

OBJECTIVE: To separate compounds from the root of Gypsophila oldhamiana. METHOD: Chemical and chromatographic methods were used to separate the compounds. IR, MS, NMR were used to determine the structures of compounds. RESULT: Compound pentacosanoic acid, lacceroic acid, beta-sitosterol, alpha-spinasterol, daucosterol and sucrose were identified. CONCLUSION: All the above compounds were obtained from this genus for the first time.

Caryophyllaceae↗
PubMed1999

Biotransformation of coumarin by rodent and human cytochromes P-450: metabolic basis of tissue-selective toxicity in olfactory mucosa of rats and mice.

Coumarin was previously found to cause tissue-selective toxicity in the olfactory mucosa (OM) of rats and mice, with rats being the more sensitive species. The aim of this study was to explore the role of target tissue biotransformation in OM-selective toxicity and the metabolic basis of the species differences in coumarin toxicity. At least six coumarin metabolites were detected in OM microsomal reactions, with o-hydroxyphenylacetaldehyde (o-HPA) being the most abundant. Formation of o-HPA was inhibited by reduced glutathione, confirming its origin from a reactive intermediate. There were significant differences in the rates and metabolite profiles of coumarin metabolism in the livers of Wistar rats and C57BL/6 mice. The rates of metabolic activation of coumarin, as indicated by the formation of o-HPA, were comparable in OM microsomes of the two species but about 25- and 3-fold higher in OM than in liver microsomes of rats and mice, respectively. Thus, target tissue activation seems to play an important role in the tissue-selective toxicity, whereas differences in the rates of hepatic metabolism may be responsible for the species difference in olfactory toxicity. Purified, heterologously expressed mouse CYP2A5 and CYP2G1 produced 7-hydroxycoumarin and o-HPA as the predominant products, respectively. Kinetic analysis and immunoinhibition studies indicated that the OM-specific CYP2G1 plays the major role in metabolic activation of coumarin. Furthermore, of 13 human cytochrome P-450s (P-450s) examined, five (CYP1A1, CYP1A2, CYP2B6, CYP2E1, and CYP3A4) were active in the metabolic activation of coumarin, suggesting a potential risk of coumarin toxicity in humans.

Animals↗
PubMed1998

Synthesis and biological activity of [Tic5] didemnin B.

A didemnin B analog containing a Tic (1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) as a conformationally restrained replacement for tyrosine has been synthesized and shown to have comparable potency as a protein biosynthesis inhibitor. Synthetic highlights include an oxidation of an alcohol to an acid in the presence of the sensitive Tic heterocycle and a modified Schmidt-type one-pot macrocyclization.

Animals↗
PubMed1998

Identification and characterization of a novel tissue-specific transcriptional activating element in the 5'-flanking region of the CYP2A3 gene predominantly expressed in rat olfactory mucosa.

CYP2A3 is expressed preferentially in rat olfactory mucosa and is believed to play important roles in maintaining cellular homeostasis in the chemosensory tissue. DNase I footprinting analysis revealed a single protected region in the proximal promoter of the CYP2A3 gene with nuclear extracts from olfactory mucosa, but not from liver, lung, kidney, or brain. The core sequence of the binding site, named the nasal predominant transcriptional activating (NPTA) element, is similar to that of nuclear factor 1, but it interacted with unique proteins detected only in the olfactory mucosa in electrophoretic mobility shift assays or on Southwestern blots. The NPTA element is conserved in rat CYP2A3, mouse Cyp2a5, and human CYP2A6 genes and was found to be essential for transcriptional activity of the CYP2A3 promoter in in vitro transcription assays. NPTA-binding proteins were detectable at day 1 and were much more abundant at day 8 than at day 60 after birth. Furthermore, their levels decreased dramatically during chemically induced degeneration of the olfactory epithelium, paralleling the disappearance of CYP2A3 protein, and rebounded to higher than pretreatment levels during recovery. Thus, we have identified a novel transcriptional activation element potentially responsible for the olfactory mucosa-predominant expression of the CYP2A3 gene in rats and orthologous genes in mice and humans.

Animals↗
PubMed1998

Structure of the metal-ion-activated diphtheria toxin repressor/tox operator complex.

The virulent phenotype of the pathogenic bacterium Corynebacterium diphtheriae is conferred by diphtheria toxin, whose expression is an adaptive response to low concentrations of iron. The expression of the toxin gene (tox) is regulated by the repressor DtxR, which is activated by transition metal ions. X-ray crystal structures of DtxR with and without (apo-form) its coordinated transition metal ion have established the general architecture of the repressor, identified the location of the metal-binding sites, and revealed a metal-ion-triggered subunit-subunit 'caliper-like' conformational change. Here we report the three-dimensional crystal structure of the complex between a biologically active Ni(II)-bound DtxR(C102D) mutant, in which a cysteine is replaced by an aspartate at residue 102, and a 33-base-pair DNA segment containing the toxin operator toxO. This structure shows that DNA interacts with two dimeric repressor proteins bound to opposite sides of the tox operator. We propose that a metal-ion-induced helix-to-coil structural transition in the amino-terminal region of the protein is partly responsible for the unique mode of repressor activation by transition metal ions.

Bacterial Proteins↗
PubMed1998

Role of CYP2A5 and 2G1 in acetaminophen metabolism and toxicity in the olfactory mucosa of the Cyp1a2(-/-) mouse.

Acetaminophen (AP) is a widely-used analgesic agent that has been linked to human liver and kidney disease with prolonged or high-dose usage. In rodents, the target organs that are affected include liver, kidney, and the olfactory mucosa. AP toxicity requires cytochrome P450(CYP)-mediated metabolic activation, and the isozymes CYP1A2, 2E1, and 3A are known to activate AP in the human. In the present study, we determined that olfactory mucosal toxicity of AP was not different between the Cyp1a2(+/+) wild-type and the Cyp1a2(-/-) knockout mouse, whereas the hepatic toxicity of AP was significantly diminished in Cyp1a2(-/-) mice. Western blots of olfactory mucosa revealed that CYP2E1 and CYP3A levels are similar between untreated Cyp1a2(+/+) and Cyp1a2(-/-) mice. Diallyl sulfide (DAS), a known inhibitor of CYP2E1 and of CYP2A10/2A11 (the rabbit orthologue of mouse CYP2A5), completely eliminated olfactory toxicity of AP in both the Cyp1a2(-/-) and wild-type mouse olfactory mucosa. We found that heterologously expressed mouse CYP2A5 and CYP2G1 enzymes (known to be present in olfactory mucosa) form 3-hydroxyacetaminophen (3-OH-AP) and 3-(glutathion-S-yl)acetaminophen (GS-AP); CYP2A5 is considerably more active than 2G1. Addition of GSH caused increases in GS-AP proportional to decreases in 3-OH-AP, suggesting that these two metabolites arise from a common precursor or are formed by way of competing pathways. We also found that both CYP2A5 and CYP2G1 are inhibitable by DAS in vitro. These studies provide strong evidence that, in addition to CYP2E1, CYP2A5 and 2G1 are important in AP bioactivation in the mouse olfactory mucosa and that CYP1A2 appears to be of minor importance for AP olfactory toxicity.

Acetaminophen↗
PubMed1998

Characterization of the cytochrome P450 CYP2J4: expression in rat small intestine and role in retinoic acid biotransformation from retinal.

The sites of expression in the small intestine and the function of CYP2J4, a recently identified rat cytochrome (P450) isoform found to be predominantly expressed in the small intestine, were characterized. Immunoblot analysis with a polyclonal antibody to heterologously expressed CYP2J4 revealed that expression of CYP2J4 was at the highest level in the distal duodenum and jejunum and decreased toward the ileum. Villous cells expressed higher levels of CYP2J4 than crypt cells. Isoform-specific RNA polymerase chain reaction indicated that a related P450 isoform, CYP2J3, was only a minor form in rat small intestine. Since the intestinal mucosa is exposed to high levels of dietary nutrients, we hypothesized that CYP2J4 may be active toward diet-derived factors. We determined that purified, heterologously expressed CYP2J4 is active toward all-trans- and 9-cis-retinal in reconstituted systems, producing the corresponding retinoic acids as the major products. Apparent K(m) values for the formation of retinoic acids were 54 and 49 microM, respectively, and apparent Vmax values were 20 and 21 nmol/min/nmol P450, respectively. These activities were readily inhibited by a polyclonal anti-CYP2J4 antibody. Rat enterocyte microsomes were also active with all-trans-retinal to produce all-trans-retinoic acid in the presence of NADPH, and the majority of retinoic acid synthesis activity was inhibited by the polyclonal anti-CYP2J4 antibody. These findings suggest that CYP2J4 plays a major role in intestinal microsomal metabolism of retinal to retinoic acid and may be involved in the maintenance of retinoid homeostasis in the small intestine in vivo.

Animals↗
PubMed1998

Electrophoretic coating of multilayered apatite composite on alumina ceramics.

By means of an electrophoretic deposition technique followed by sintering, alumina and zirconia ceramics were coated with apatitic composites composed of porous surface and intermediate layers of hydroxyapatite and an adhesive calcium phosphate layer. The electrophoretic deposition of these layers was attained by the use of a mixed solvent of acetylacetone and alcohol as well as the mixed powders of the calcium phosphates and alumina. The adhesive layer was formed by the codeposition of calcium phosphate glass powders (Ca/P = 1/2) with hydroxyapatite, while the open porosity of the surface layer was increased with the addition of alumina to the hydroxyapatite layers. The resultant phases of sintered composite layers were tricalcium phosphate and alumina with a small amount of hydroxyapatite.

Aluminum Oxide↗
PubMed1998

Formation of plasmid DNA strand breaks induced by low-energy ion beam: indication of nuclear stopping effects.

Plasmid pGEM 3zf(+) was irradiated by nitrogen ion beam with energies between 20 and 100 keV and the fluence kept as 1x10(12)ions/cm2. The irradiated plasmid was assayed by neutral electrophoresis and quantified by densitometry. The yields of DNA with single-strand and double-strand breaks first increased then decreased with increasing ion energy. There was a maximal yield value in the range of 20-100 keV. The relationship between DNA double-strand breaks (DSB) cross-section and linear energy transfer (LET) also showed a peak-shaped distribution. To understand the physical process during DNA strand breaks, a Monte Carlo calculation code known as TRIM (Transport of Ions in Matter) was used to simulate energy losses due to nuclear stopping and to electronic stopping. It can be assumed that nuclear stopping plays a more important role in DNA strand breaks than electronic stopping in this energy range. The physical mechanisms of DNA strand breaks induced by a low-energy ion beam are also discussed.

DNA Damage↗