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Biomedical subjects

X Su

Publications and source records attributed to X Su.

At least 55 records · Page 3Linked to original sources
PubMed2000

[Iodine-125 labeled monoclonal antibody 3H11: in radioimmunoguided surgery for primary gastric cancer].

OBJECTIVE: To evaluate the clinical usefulness of iodine-125 labeled monoclonal antibody (MAb) 3H11 in radioimmunoguided surgery (RIGS) for patients with gastric cancer. METHODS: Thirty-five patients with primary gastric cancer were enrolled. Via endoscopy, iodine-125 labeled MAb 3H11 was injected into submucosa around the tumor. All patients underwent surgery 4 to 11 days after administration. Intraoperative radioimmunodetection was performed using a hand-held gamma-detecting probe. The counts of target sites were obtained, and tumor-to-normal tissue (T/NT) ratios were calculated. The T/NT ratio of 3.5:1 was taken as the lowest threshold value of positive gastric wall infiltration, and 3.0:1 for lymph node metastasis. Serial sections of those RIGS-positive lymph nodes, which were originally diagnosed as negative by routine histology, were made. Immunohistochemical staining was performed to detect the existence of lymphatic micrometastasis. RESULTS: Of thirty-five patients, 33 underwent RIGS successfully. The accuracy rate in detecting tumor infiltration of the incision margins was 97.0%, and the specificity 98.5%. In the group of patients with an interval of 6 to 8 days between injection and operation (n = 25), the RIGS results were satisfying. For the detection of lymphatic metastasis, the sensitivity of RIGS was 83.6%, the specificity 95.0%, and the accuracy 91.3%. The existence of lymphatic micrometastasis were verified immunohistochemically in 52.6% (10/19) of those RIGS positive but histologically negative lymph nodes. CONCLUSION: This study validates the use of iodine-125 labeled monoclonal antibody 3H11 for the intraoperative detection of carcinomatous lesions in gastric cancer.

Adult↗
PubMed2000

[The contrast study of preoperative flash visual evoked potential test and the postoperative resumed visual acuity in senile cataract patients].

PURPOSE: To study the using value of flash visual evoked potentials (FVEP) in predicting the resumed visual acuities in senile cataract patients. METHODS: Forty-three eyes with senile cataract had been conducted extracapsular cataract extraction combined with posterior chamber intraocular lens implantation. The contrast study had been carried out in this research between preoperative FVEP, light projection and color discrimination tests with the postoperative regained visual acuities. RESULTS: There were significant correlations between the regained visual acuities and the amplitudes of FVEP (X1), the latencies of P1 wave (X2) as well as color discriminations (P < 0.01). The coefficients were 0.7277, -0.5678 and 0.4302 in sequence. There was no correlation between the resumed visual acuities and the light projection test before operation. The formula of linear regression between the visual acuities (Y) and the indexes of FVEP was Y = 0.2255 +0.047X1 -0.0026X2. CONCLUSION: FVEP is an effective method to evaluate the visual function before the cataract operation. It may predict the resumed visual acuity.

Aged↗
PubMed1999

Molecular characterization of Plasmodium falciparum S-adenosylmethionine synthetase.

S-Adenosylmethionine (AdoMet) synthetase (SAMS: EC 2.5.1.6) catalyses the formation of AdoMet from methionine and ATP. We have cloned a gene for Plasmodium falciparum AdoMet synthetase (PfSAMS) (GenBank accession no. AF097923), consisting of 1209 base pairs with no introns. The gene encodes a polypeptide (PfSAMS) of 402 amino acids with a molecular mass of 44844 Da, and has an overall base composition of 67% A+T. PfSAMS is probably a single copy gene, and was mapped to chromosome 9. The PfSAMS protein is highly homologous to all other SAMS, including a conserved motif for the phosphate-binding P-loop, HGGGAFSGKD, and the signature hexapeptide, GAGDQG. All the active-site amino acids for the binding of ADP, P(i) and metal ions are similarly preserved, matching entirely those of human hepatic SAMS and Escherichia coli SAMS. Molecular modelling of PfSAMS guided by the X-ray crystal structure of E. coli SAMS indicates that PfSAMS binds ATP/Mg(2+) in a manner similar to that seen in the E. coli SAMS structure. However, the PfSAMS model shows that it can not form tetramers as does E. coli SAMS, and is probably a dimer instead. There was a differential sensitivity towards the inhibition by cycloleucine between the expressed PfSAMS and the human hepatic SAMS with K(i) values of 17 and 10 mM, respectively. Based on phylogenetic analysis using protein parsimony and neighbour-joining algorithms, the malarial PfSAMS is closely related to SAMS of other protozoans and plants.

Amino Acid Sequence↗
PubMed1999

A genetic map and recombination parameters of the human malaria parasite Plasmodium falciparum.

Genetic investigations of malaria require a genome-wide, high-resolution linkage map of Plasmodium falciparum. A genetic cross was used to construct such a map from 901 markers that fall into 14 inferred linkage groups corresponding to the 14 nuclear chromosomes. Meiotic crossover activity in the genome proved high (17 kilobases per centimorgan) and notably uniform over chromosome length. Gene conversion events and spontaneous microsatellite length changes were evident in the inheritance data. The markers, map, and recombination parameters are facilitating genome sequence assembly, localization of determinants for such traits as virulence and drug resistance, and genetic studies of parasite field populations.

Animals↗
PubMed1999

Identification of a novel actin binding motif in smooth muscle myosin light chain kinase.

Phosphorylation of the 20-kDa regulatory light chain of myosin catalyzed by a Ca(2+)/calmodulin-dependent myosin light chain kinase is important in the initiation of smooth muscle contraction and other contractile processes in non-muscle cells. It has been previously shown that residues 1-142 of smooth muscle myosin light chain kinase are necessary for high-affinity binding to actin-containing filaments in cells (1). To further localize the region of the kinase required for binding, a series of N-terminal deletion mutants as well as several N-terminal glutathione S-transferase fusion proteins were constructed. Cosedimentation assays showed that a peptide containing residues 1-75 binds to purified smooth muscle myofilaments. Furthermore, the N-terminal peptide was sufficient for high-affinity binding to actin stress fibers in smooth muscle cells in vivo. Alanine scanning mutagenesis in the fusion protein identified residues Asp-30, Phe-31, Arg-32, and Leu-35 as important for binding in vitro. There are two additional DFRXXL motifs located at residues 2-7 and 58-63. The DFR residues in these three motifs were individually replaced by alanine residues in the full-length kinase. Each of these mutations significantly decreased myosin light chain kinase binding to myofilaments in vitro, and each abolished high-affinity binding to actin-containing filaments in smooth muscle cells in vivo. These results identify a unique structural motif comprised of three repeat consensus sequences in the N terminus of myosin light chain kinase necessary for high-affinity binding to actin-containing filaments.

Actin Cytoskeleton↗
PubMed1999

Self-assembled monolayer-based piezoelectric crystal immunosensor for the quantification of total human immunoglobulin E.

This work presents a piezoelectric (Pz) immunosensor for the quantification of total human IgE in serum samples. The anti-human IgE is deposited on the surface of the 10 M Hz AT-cut gold coated crystal resonator by self-assembled technique, and serves as a receptor layer. The highly ordered self-assembled monolayers (SAMs) ensure well-controlled surface structure and offer many advantages to the performance of the sensor. The fabricated Pz sensor can quantitatively detect human serum IgE in the range of 5-300 IU/ml with high precision (CV < 8%). A total of 28 patient serum samples are detected by the Pz sensor, and the results agree well with those given by two commercially provided test kits (Total IgE FAST Test, Pharmacia-CAP). The correlation coefficients are 0.94 between FAST and Pz sensor, and 0.90 between CAP and Pz sensor, respectively. After regeneration with urea and glycine buffer the coated crystal can be reused five times without appreciable loss of activity. Compared with conventional cross-linking methods, nonspecific binding caused by the SAM binding method is three to five times less.

Antigen-Antibody Reactions↗
PubMed1999

Induction of specific T cell tolerance by Fas ligand-expressing antigen-presenting cells.

Autocrine interaction of Fas and Fas ligand leads to apoptosis of activated T cells, a process that is critical for the maintenance of peripheral T cell tolerance. Paracrine interactions of Fas ligand with T cells also may play an important role in the maintenance of tolerance, as Fas ligand can create immune-privileged sites and prevent graft rejection by inducing apoptosis in T cells. We surmised that APCs that express Fas ligand might directly induce apoptosis of T cells during presentation of Ag to the T cells, thus inducing Ag-specific, systemic T cell tolerance. Here, we show that profound, specific T cell unresponsiveness to alloantigen was induced by treatment of H-2k mice with H-2b APCs that expressed Fas ligand and that profound T cell unresponsiveness specific for the H-Y Ag was induced by treatment of H-2Db/H-Y TCR transgenic female mice with H-2Db/H-Y APCs that expressed Fas ligand. The induction of this systemic T cell tolerance required the expression of Fas ligand on the APCs as well as the expression of Fas on the T cells. The tolerance was restricted to the Ag presented by the APCs. The rapid and profound clonal deletion of the Ag-specific, peripheral T cells mediated by the Fas ligand-expressing APCs contributed to the induction of tolerance. These findings demonstrate that Ag-specific T cell tolerance can be induced by APCs that express Fas ligand and suggest a novel function for APCs in the induction of T cell apoptosis. Furthermore, they indicate a novel immunointervention strategy for treatment of graft rejection and autoantigen-specific autoimmune diseases.

Animals↗
PubMed1999

Ca(2+)- and protein kinase C-dependent stimulation of mitogen-activated protein kinase in detergent-skinned vascular smooth muscle.

Protein kinase C and mitogen-activated protein (MAP) kinase are expressed in all smooth muscle cells and believed to be important in several physiologically relevant properties of this muscle. Our goal was to determine if protein kinase C and MAP kinase are activated by a simple increase in cellular Ca(2+) and to determine if protein kinase C is an upstream activator of MAP kinase. These studies were performed in the Triton X-100 detergent-skinned preparation of the swine carotid artery, which allows control of the intracellular environment without influence from membrane or receptor-mediated modulation. The p42 and p44 isoforms of MAP kinase were activated in a concentration-dependent fashion by an increase in Ca2+. This was shown by in-the-gel kinase assay and direct measurement of MAP kinase phosphotransferase activity. Protein kinase C was also activated by an increase in Ca2+, as shown by a novel assay that measures total active protein kinase C in the tissue. Inhibition of protein kinase C activity completely abolished MAP kinase activity. Additionally, inhibition of Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) also abolished MAP kinase activity. Using intact swine carotid arteries, we showed p42 and p44 MAP kinase to be activated by both histamine and phorbol dibutyrate, but only the p42 isoform was calcium-sensitive. Our results suggest that a Ca(2+)-dependent isoform of protein kinase C and CaM kinase II are upstream activators of MAP kinase in the swine carotid artery.

Animals↗
PubMed1999

Differential expression of angiotensin-converting enzyme and chymase in dogs with chronic mitral regurgitation.

The current study tested the hypothesis that angiotensin-converting enzyme (ACE) and chymase expression are subject to different regulatory processes in the heart, as well as the lungs and kidneys and, as a result, have an important effect on the efficacy of ACE inhibitor treatment in modulating tissue angiotensin II (ANG II) levels in heart failure. A total of 18 dogs underwent the induction of mitral regurgitation and were followed for 5 months. Eleven dogs were untreated and seven received the ACE-inhibitor ramipril at a dose of 10 mg PO BID. Seventeen dogs underwent a sham-operation: six of these dogs were treated with ramipril for 3 months (10 mg PO BID) and 11 were untreated and followed for 3 months prior to sacrifice. In mitral regurgitation dogs, ANG II levels were increased >2-fold in left ventricle, lungs, and kidney, but were normalized with ACE inhibitor-treatment only in the left ventricle. In the left ventricle and lungs steady state ACE mRNA levels and ACE activities were increased 2-fold in treated and untreated mitral regurgitation dogs compared to shams (P<0.05, ANOVA). In contrast, chymase mRNA levels were decreased by >50% and chymase activity was increased in left ventricle (LV) of mitral regurgitation dogs (P<0.05). Neither chymase mRNA nor chymase activity could be detected in the kidney; however, kidney ACE mRNA and ACE activity were significantly upregulated in treated and untreated mitral regurgitation dogs (P<0. 05). These results suggest that ACE and chymase expression are regulated differentially in the dog in response to chronic mitral regurgitation and ACE inhibitor treatment. Further, these responses, as well as regulation of ANG II formation, are organ specific.

Animals↗
PubMed1999

Differential expression of natriuretic peptides and their receptors in volume overload cardiac hypertrophy in the rat.

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) upregulation are genetic markers for the chronic hypertrophic phenotype but also have important acute physiologic effects on salt and water balance and blood pressure control. The presence of a dual NP-system led us to hypothesize a differential expression of ANP and BNP in response to an acute hemodynamic stress of volume overload in the left ventricle (LV) and right ventricle (RV). Accordingly, we examined the temporal relationship between the RV and LV expression of ANP and BNP mRNA and NP receptor mRNA levels on days 1, 2, 3, and 7 after induction of aortocaval fistula in the rat. LV end-diastolic pressure was increased 1.5-fold by day 3 and 2.0-fold by day 7 compared to control (P<0.05). LV weight increased by day 7 compared to control (2.34+/-0.04 vs 3.07+/-0.10 mg/g, P<0.05) while RV weight did not change over the 7 days. There was a 7-fold increase of ANP mRNA in LV at day 1, which was sustained through day 7, while LV BNP mRNA levels did not differ from controls over the 7 days. In contrast, RV mRNA transcript levels for ANP and BNP were increased >2-fold by day 2 and this increase was sustained throughout 7 days. NP clearance receptor was decreased by 75% by day 7 in the LV but did not change in the RV. Thus, LV ANP mRNA levels increased before the onset of LV hypertrophy and RV BNP mRNA levels increased in the absence of RV hypertrophy. The disparate response of BNP and the NP clearance receptor transcript levels in the LV and RV may be related to differences in load and/or differential expression of the NP system in the LV and RV in response to acute haemodynamic stress.

Animals↗
PubMed1999

Role of neurokinin 3 receptors on responses to colorectal distention in the rat: electrophysiological and behavioral studies.

BACKGROUND & AIMS: Tachykinins contribute to the control of gastrointestinal motility and modulation of somatic and visceral pain. The role of neurokinin (NK) B and NK3 receptors in visceral pain and gastrointestinal disorders has not been determined. METHODS: Using electromyographic recordings of both abdominal and colonic muscle and electrophysiological recordings of pelvic nerve afferent fibers, we studied drug effects on responses to colorectal distention. RESULTS: In awake rats, intraperitoneal administration of the NK3-receptor antagonist SR 142,801 reduced, whereas the NK3-receptor agonist senktide increased, both the rectocolonic inhibitory reflex and abdominal contractions produced by colorectal distention. In contrast, intracerebroventricular administration of SR 142,801 increased the number of abdominal contractions without affecting the rectocolonic inhibitory reflex produced by colorectal distention. In a similar manner, intracerebroventricular injection of senktide diminished the number of abdominal contractions. In electrophysiological experiments, SR 142,801 decreased responses of pelvic nerve afferent fibers to colorectal distention. Responses of pelvic nerve fibers to urinary bladder distention, however, were unaffected by SR 142,801. CONCLUSIONS: These results suggest that peripheral NK3 receptors are involved in the mediation of both visceral nociception and gastrointestinal disorders. Also, central NK3 receptors seem to play a role in the modulation of visceral nociception.

Animals↗
PubMed1999

Ethylenediamine-palladium(II) complexes with pyridine and its derivatives: synthesis, molecular structure and initial antitumor studies.

The synthesis of four mononuclear palladium complexes of general formula [Pd(en)Cl(L)]NO3 (en = ethylenediamine; L = pyridine (I), 4-methylpyridine (II), 4-hydroxypyridine (III) or 4-aminopyridine (IV) has been achieved. The structure of these compounds was studied by elemental analysis, IR, far-IR and 1H NMR; complex I was analyzed by X-ray diffraction. The crystal of [Pd(en)(pyridine)Cl]NO3 is monoclinic, space group P21/c (a = 7.990(2), b = 16.058(3), c = 9.846(2) A, beta = 103.81(3) degrees, Z = 4, R = 0.067, Rw = 0.066). The Pd(II) atom exhibits an approximately square planar coordination with bond lengths in the range 2.017-2.042 A for Pd-N and 2.320 A for Pd-Cl. In order to determine the donor strength of the aromatic pyridine ligands, the stability constants of binary complex ML2+ (M = [Pd(en) (H2O)2]2+; L = pyridine, 4-Me-pyridine, 4-OH-pyridine and 4-NH2-pyridine) were determined by potentiometric pH titration in aqueous solution (T = 25 degrees C, I = 0.1 mol l-1 NaNO3). The results show that the stability constants of the binary complexes systematically increase with increasing pKa of the pyridines. The above four palladium complexes, [Pt(en)(pyridine)Cl]NO3 and cis-diamminedichloroplatinum (II) (cis-DDP) were assayed for cytotoxicity in vitro against the human leukemia cell line HL-60, and compounds I, II, III and cis-DDP show significant cytotoxic activity against HL-60.

Antineoplastic Agents↗
PubMed1999

Effects of kappa opioids in the inflamed rat colon.

The objective of this study was to examine the antinociceptive effects of peripherally restricted kappa-opioid receptor agonists (ORAs) in a rat model of inflammatory bowel disease produced by intracolonic instillation of trinitrobenzine sulfonic acid (TNBS). Antinociceptive effects of mu-(morphine) and kappa-ORAs (EMD 61,753 and ICI 204,488) were evaluated in a behavioral model of visceral nociception. The effects of these agonists and a delta-ORA (SNC 80) on responses of pelvic nerve afferent fibers innervating the colon were also tested. In the behavioral study, systemic injections of morphine and both kappa-ORAs dose-dependently inhibited the visceromotor response to colorectal distension in rats with uninflamed or inflamed colons. The inhibitory effects of kappa-ORAs, but not morphine, were significantly greater in rats with colons inflamed 4 days previously by TNBS. A mu-receptor-selective dose (30 microg/kg) of naloxone methiodide (NLXM) blocked the inhibitory effect of morphine, but not of EMD 61,753. In the single-fiber study, neither morphine nor the delta-ORA SNC 80 attenuated the responses of pelvic nerve afferent fibers, whereas kappa-ORAs dose-dependently inhibited responses of pelvic nerve afferent fibers with significantly greater potency in the inflamed colon. Pretreatment with a non-opioid receptor-selective dose (2 mg/kg) of NLXM produced a rightward shift in the dose-response function of EMD 61,753. The greater potency of kappa-ORAs in the TNBS-inflamed condition suggests a peripheral upregulation of kappa-opioid receptors in colonic inflammation.

Acetamides↗
PubMed1999

Differential activation of phosphoinositide 3-kinase by endothelin and ceramide in colonic smooth muscle cells.

We have investigated the hypothesis that different contractile agonists activate distinct catalytic subunits of phosphoinositide (PI) 3-kinase in smooth muscle cells. Endothelin (10(-7) M) induced a sustained increase in PI 3-kinase activity at both 30 s and 4 min of stimulation (151.5 +/- 8.5% at 30 s and 175.8 +/- 8.7% at 4 min, P < 0.005). Preincubation of smooth muscle cells with the tyrosine kinase inhibitor genistein (3 microM) resulted in a significant inhibition of both C2 ceramide-induced and endothelin-induced PI 3-kinase activation and contraction. Preincubation with herbimycin A, an Src kinase inhibitor (3 microM), inhibited only C2 ceramide-induced PI 3-kinase activation and contraction. Western blotting using Src kinase antibody showed that C2 ceramide, not endothelin, stimulated the phosphorylation of Src kinase. Western blotting and immunoprecipitation with PI 3-kinase antibodies to the regulatory subunit p85 and the catalytic subunits p110alpha and p110gamma indicated that both endothelin and C2 ceramide interacted with the regulatory subunit p85; endothelin interacted with the catalytic subunits p110alpha and p110gamma, whereas C2 ceramide interacted only with the catalytic subunit p110alpha. In summary, C2 ceramide activated PI 3-kinase p110alpha subunit by a tyrosine kinase-mediated pathway, whereas endothelin-induced contraction, unlike C2 ceramide, was not mediated by the activation of Src kinase but was mediated by G protein activation of both p110alpha and p110gamma subunits (type IA and IB) of PI 3-kinase.

Animals↗
PubMed1999

Capsaicin sensitivity and voltage-gated sodium currents in colon sensory neurons from rat dorsal root ganglia.

DiI-labeled colon sensory neurons were acutely dissociated from S1 rat dorsal root ganglia (DRG) and studied using perforated whole cell patch-clamp techniques. Forty-six percent (54/116) of labeled sensory neurons responded to capsaicin (10(-8)- 10(-5) M) with an increase in inward current, which was a nonspecific cation conductance. Responses to capsaicin applied by puffer ejection were dependent on dose, with a half-maximal response at 4.9 x 10(-7) M; bath application was characterized by marked desensitization. Voltage-gated Na(+) currents in 23 of 30 DRG cells exhibited both TTX-sensitive and TTX-resistant components. In these cells, capsaicin induced an inward current in 11 of 17 cells tested. Of the cells containing only a TTX-sensitive component, none of six cells tested was sensitive to capsaicin. In all cells that responded to capsaicin with an increase in inward current, capsaicin abolished voltage-gated Na(+) currents (n = 21). Capsazepine (10(-6) M) significantly attenuated both the increase in inward current and the reduction in Na(+) currents. Na(+) currents were not significantly altered by adenosine, bradykinin, histamine, PGE(2), or serotonin at 10(-6) M and 10(-5) M. These findings may have important implications for understanding both the irritant and analgesic properties of capsaicin.

Action Potentials↗
PubMed1999

Effect of Mg2+ on stress, myosin phosphorylation, and ATPase activity in detergent-skinned swine carotid media.

Smooth muscle contraction has a relatively high requirement for free magnesium (Mg2+). In this study we examined the effect of Mg2+ concentration ([Mg2+]) on Ca2+-dependent stress development and stress maintenance, myosin ATPase activity, and myosin light chain (MLC) phosphorylation levels in Triton X-100 detergent-skinned fibers of the swine carotid media. Increasing [Mg2+] in a stepwise fashion from 0.1 to 6 mM 1) decreased the magnitude and Ca2+ sensitivity of stress development but augmented the amount of stress maintained without proportional MLC phosphorylation, 2) produced a greater decrease in the Ca2+ sensitivity of MLC phosphorylation than that of stress development, and 3) decreased myosin ATPase activity. These findings demonstrate that Mg2+ differentially modulates the MLC phosphorylation-dependent development of stress and the MLC phosphorylation-independent maintenance of stress. We suggest that increases in [Mg2+] enhance stress maintenance by increasing [MgADP], thus increasing the number of cross bridges in a force-generating state, and by a direct effect on the pathway responsible for Ca2+-dependent, MLC phosphorylation-independent contractions.

Adenosine Triphosphatases↗
PubMed1999

[Study of TEL-AML1 fusion gene in childhood B-lineage acute lymphoblastic leukemia].

OBJECTIVE: To determine the incidence of TEL-AML1 fusion gene and its role in clinical diagnosis and prognosis of childhood B-lineage acute lymphoblastic leukemia (B-ALL), and to compare the two techniques: nested RT-PCR and dual-color fluorescence in situ hybridization (FISH). METHODS: Nested RT-PCR and dual-color FISH techniques were used to detect TEL-AML1 fusion gene. RESULTS AND CONCLUSION: TEL-AML1 fusion transcript was found in 22.5%(9/40) of patients with B-ALL by RT-PCR. The prognosis of these TEL-AML1 positive patients was relatively good and the complete remission rate was 100%. Both RT-PCR and FISH techniques were proved to be useful for detecting TEL-AML1 fusion gene and suitable for clinical diagnosis and prognosis evaluation.

Adolescent↗