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Biomedical subjects

S Xiao

Publications and source records attributed to S Xiao.

At least 109 records · Page 6Linked to original sources

In vitro and in vivo effect of levopraziquantel, dextropraziquantel versus racemic praziquantel on different developmental stages of Schistosoma japonicum.

AIM: To compare the antischistosomal effect of racemic praziquantel (Pra) and its enantiomers, levopraziquantel (L-Pra) and dextropraziquantel (D-Pra), on different developmental stages of Schistosoma japonicum. METHODS: The in vitro effects of the drugs were determined in different stages of schistosomes maintained in RPMI 1640 supplemented with 20% calf serum. In vivo study mice infected with schistosome cercariae were treated intragastrically (ig) with Pra, L-Pra or D-Pra at different intervals after infection. The efficacy of the drugs was evaluated by residual mean worm number. RESULTS: Based on the degree of tegument damage induced by L-Pra, d28 and d35 schistosomes were most susceptible to L-Pra, while d14 schistosomules being least susceptible. At comparable concentrations of 0.1-1 g/ml, L-Pra was more active than Pra even when the concentration of L-Pra was reduced to one-half of the minimum effective concentration of Pra. At above-mentioned concentrations D-Pra exhibited no apparent in vitro effect on different stages of schistosomes. When infected mice were treated ig with L-Pra, Pra or D-Pra at a single dose of 300 mg/kg or 500 mg/kg, only the former two drugs showed apparent effect on d0, d21, d28 and d35 schistosomes and less or much less effect on d3, d7 and d14 schistosomules. D-Pra only exhibited a negligible effect on d35 adult schistosomes as compared with L-Pra and Pra. When mice infected with d35 adult schistosmes were treated ig with L-Pra 150 mg/kg, the efficacy was similar to that of mice treated with Pra 300 mg/kg. CONCLUSION: L-Pra is the principal active component against schistosomes in racemic Pra.

Animals↗

Structural organization and characterization of the promoter region of the rat gonadotropin-releasing hormone receptor gene.

The gene encoding the rat gonadotropin-releasing hormone (GnRH) receptor was isolated, and its structural organization and promoter region were characterized. The gene was found to consist of three exons that encode the receptor protein, and spanned about 20 kb. Of two genomic clones analyzed, one contained the 5'-untranslated region and the first exon, and the other contained the second and third exons. The sizes of the first, second, and third exons are 625, 217, and 1476 nt, respectively. The first intron is at least 12 kb in length and is located between nucleotides 522 and 523 of the cDNA reading frame, in the middle of the fourth transmembrane domain. The second intron is about 2.5 kb and is also located in the reading frame between nucleotides 739 and 740, separating the fifth and sixth transmembrane domains. Genomic blots in combination with cloning and sequencing suggested that a single GnRH receptor gene is present in the rat genome. Primer extension indicated that the transcription start site is located 103 nt upstream of the translational start codon. A putative TATA box is positioned 23 nt in front of the transcription initiation site. The 1.8 kb 5' flanking sequence contains an SF-1 site, an AP-1 site, CCAAT sequences, a Pit-1 binding site, and a potential CRE-like sequence. To evaluate promoter activity, the 1.8 kb and two 5' deleted fragments of 1.2 and 0.6 kb were fused to the luciferase reporter gene and transiently expressed in immortalized pituitary gonadotrophs (alphaT3-1 cells) and hypothalamic neurons (GT1-7 cells), and in nonpituitary (COS-7) cells. Luciferase gene expression was significantly increased by all three fragments in pituitary and hypothalamic cells, but not in COS-7 cells. The promoter activity of the 1.2 kb fragment was higher than that of the other fragments. Forskolin and cAMP analogs increased luciferase gene expression in both alphaT3-1 and GT1-7 cells, but activation of protein kinase C by phorbol myristate acetate had no effect. These studies indicate that positive and negative regulatory elements are present within the 1.8 kb 5' flanking sequence of the GnRH receptor. Knowledge of the genomic organization and analysis of the promoter region of the rat GnRH receptor gene will facilitate the elucidation of its transcriptional control in pituitary gonadotrophs and hypothalamic neurons.

Amino Acid Sequence↗

Pharmacokinetics and pharmacodynamics of 15-deoxyspergualin in a canine renal allograft model of local immunosuppression.

Local immunosuppression is based on the rationale that one can simultaneously prevent rejection and reduce systemic side effects by administering appropriately chosen immunosuppressive agents directly into the allograft. We utilized a mongrel canine renal transplant model with a programmable, implantable pump/catheter system to estimate the first-pass extraction of 15-deoxyspergualin (DSG) during renal artery infusion and to compare the efficacy and toxicity of continuous intraarterial (ia) versus intravenous (iv) DSG delivery. Six autotransplanted dogs were given DSG by both iv bolus (1 mg/kg) and ia infusion (1.0 mg/kg/d). DSG was administered to allograft recipients by continuous ia infusion at 0.5 (n = 11) and 0.75 (n = 8) mg/kg/day and by continuous iv infusion at 0.5 (n = 12) and 0.75 (n = 6) mg/kg/day. Mean +/- SD elimination half-life was 0.6 +/- 0.1 hr, and the transplanted kidney removed as much as 55-88% (mean 66%) of locally infused DSG. When compared with untreated controls [mean survival time (MST) = 8 days], low-dose (0. 5 mg/kg/day) DSG produced a significant antirejection effect when given ia (MST = 12 days; P = 0.04) but not iv (MST = 9 days; P = 0. 09), with equivalent overall mean drug levels during normal renal function. However, two of the four longest-surviving animals in the ia group died from severe systemic toxicity, manifested by anorexia, diarrhea, leukopenia, and sepsis. High-dose (0.75 mg/kg/day) DSG significantly prolonged survival via both local (MST = 12 days; P = 0.04) and systemic (MST = 11 days; P = 0.02) routes, but half of the iv-treated dogs died from, and four of the longer-surviving ia-treated animals manifested signs of, systemic toxicity, with significantly higher mean drug levels in the iv group. DSG significantly suppressed vascular rejection at both doses when administered locally and systemically, dose-dependently affected the severity of tubulointerstitial rejection and graft edema, and was not nephrotoxic. Our autotransplant pharmacokinetic data overestimated the allografted kidney's ability to extract DSG during local infusion of slightly lower, but immunosuppressive, doses, so that death from systemic toxicity was not prevented and a direct survival benefit of ia vs iv therapy was not realized. Local DSG administration might be combined with other immunosuppressants to therapeutic advantage.

Animals↗

Study on antifertility effect of a novel LHRH antagonist in male rats.

The potential of a novel LHRH antagonist, TX54, to inhibit reproductive function in male rats was evaluated. After subcutaneous injection at a dosage of 200 micrograms/rat, once a week for 2 weeks, all the drug-treated male rats maintained mating behavior. But, only one out of seven female rats mated to treated males was pregnant with two fetuses. At the end of medication, sperm count and motility of caudal epididymal spermatozoa of the treated rats were reduced significantly (TX54 vs. control: 11.3 +/- 3.2 x 10(8)/mg epididymal plasma, 66.4 +/- 13.4% vs 18.4 +/- 2.4 x 10(8)/mg epididymal plasma, 83.0 +/- 2.7%). Suppression of serum testosterone by TX54 was not observed 48 h after drug injection and at the end of experiment. Morphological examination revealed that at the IX stage of seminiferous epithelium cycle, spermiation was impaired in TX54-treated rats. Less elongated spermatids were found in the lumen of seminiferous tubules of the treated rats. The size of Leydig cells decreased; psychosis and apoptosis features occurred.

Animals↗

Characterization of three loci controlling resistance of Arabidopsis thaliana accession Ms-0 to two powdery mildew diseases.

Arabidopsis thaliana accession La-er was susceptible, and accession Ms-0 was resistant, to powdery mildew diseases caused by Erysiphe cruciferarum UEA1 and E. cichoracearum UCSC1. The resistance reaction phenotype of A. thaliana Ms-0 to both pathogens was characterized, and the resistance loci were genetically mapped. Growth of E. cruciferarum UEA1 on Ms-0 leaves was arrested after formation of the first appressorium: the underlying host epidermal cell collapsed, and occasionally there was necrosis of one or two host mesophyll cells. Growth of E. cichoracearum UCSC1 on Ms-0 leaves was arrested after emergence of several germ tubes from the conidium, and there was necrosis of host mesophyll cells at the sites of infection. Examination of F2 progeny of a cross La-er x Ms-0 indicated that two independently-segregating dominant loci were required for resistance to E. cruciferarum UEA1. One locus, named RPW6, was genetically mapped to chromosome 5, in a 5.6 cM interval flanked by pCITf16 and PI. The other locus, named RPW7, mapped to chromosome 3 in a 8.5 cM interval flanked by CDC2A and AFC1. Independent effects of RPW6 and RPW7 on E. cruciferarum UEA1 could be detected by quantitative measurements of growth of mycelium and production of conidia. Resistance to E. cichoracearum UCSC1 mapped to a single locus, named RPW8, at a location on chromosome 3 which we could not distinguish from RPW7. Evidently, RPW7 and RPW8 define either a complex resistance locus, or a common resistance gene with dual specificity.

Arabidopsis↗

[Effect of eosinophil major basic protein on histamine release from nasal epithelial mast cells].

Eosinophils and nasal epithelial mast cells (NEMCs) are closely related in nasal allergy. The activity of the eosinophil cationic protein, major basic protein (MBP) on histamine release from human NEMCs has not been documented. We examined the effects of MBP on histamine release from NEMCs. Nasal scrapings (containing NEMCs) from 59 patients with house dust mite nasal allergy were incubated with MBP or alkylated MBP. Specimens were also pre-incubated with MBP followed by incubation with house dust mite allergen (HDM) or preincubated with HDM followed by incubation with MBP or HDM. Histamine released in incubated media and remained in incubated mast cells was quantified by radio-immunoassay. MBP at the concentration of 10(-5) mol/L induced mild but statistically significant histamine release from the NEMCs. Preincubation with MBP at the concentration of 1.57 x 10(-5) mol/L produced slight inhibition of subsequent HDM-induced histamine release but preincubation with HDM showed no effect on the subsequent MBP-induced or HDM-induced histamine release from NEMCs. These results suggest that accumulated and activated eosinophils may release MBP resulting in clinical symptoms by interaction with NEMCs and inhibit of histamine release from NEMCs by subsequent interaction with allergen.

Adolescent↗

HMGI(Y) activation by chromosome 6p21 rearrangements in multilineage mesenchymal cells from pulmonary hamartoma.

The chromosome band 6p21 high-mobility group gene, HMGI(Y), encodes DNA-binding proteins with both chromatin structural and gene regulatory roles. Although HMGI(Y) expression is associated with neoplastic transformation, no oncogenic HMGI(Y) mutations have been identified. We report pulmonary chondroid hamartoma chromosome 6p21 aberrations targeting HMGI(Y). Several pulmonary chondroid hamartomas had chromosome rearrangements mapping within 100 kb of HMGI(Y), and one pulmonary chondroid hamartoma contained an intragenic fusion juxtaposing HMGI(Y) A.T book DNA-binding domains with a laminin alpha 4 chain epidermal-growth-factor-like/ zinc-finger-like motif. These findings demonstrate an oncogenic role for HMGI(Y) and for laminin chain transcriptional regulatory motifs.

Amino Acid Sequence↗

Immunoreactive growth hormone in human peripheral T lymphocytes: encoding sequence of cDNA identical to that of the pituitary human growth hormone.

OBJECTIVE: To detect the cDNA sequence of immunoreactive growth hormone (irGH) in human lymphocytes and to compare it with that of human growth hormone (hGH) in the pituitary. METHODS: The mRNA of irGH in human peripheral blood mononuclear cells (PBMC) was detected by Northern blot analysis. The cDNA of irGH was obtained by reverse-transcriptase and polymerase chain reaction amplification and obtained by screening from a cDNA library of human T lymphocytes. The sequence of irGH cDNA was determined and compared with that of the pituitary hGH. RESULTS: Very low level of irGH mRNA was detected in human PBMCs by Northern blot analysis. The cDNA sequence of the entire open reading frame of human irGH was 651 bp, which is identical to that of pituitary hGH. CONCLUSIONS: The same hGH molecule can be produced by human pituitary somatotrophic cells and human peripheral lymphocytes.

Amino Acid Sequence↗

Muscle fatigue monitoring using wavelet decomposition of surface EMG.

Monitoring the local muscle fatigue in maximum voluntary isometric contraction is successful using median frequency and mean power frequency of the surface EMG. However, it has very limited success in maximum voluntary dynamic contraction. We showed that the relaxation electromechanical delay was a reliable fatigue indicator during the maximum voluntary isokinetic concentric contraction. In this paper, we use wavelet decomposition to generate fatigue indicators including contraction delay (WCD), relaxation delay (WRD), and the power ratio related to high frequency and low frequency regions (HF/LF) of the power spectrum of surface electromyogram (SEMG). Eight subjects were asked to perform right knee isokinetic contractions at two angular velocities (120 and 240 degrees/sec). Total work (TW), knee angle, and four channels of quadriceps SEMGs were sampled simultaneously. The results indicate that the initial slopes of WCD and WRD increase and are correlated with TW significantly, the initial slope of HF/LF declines and is correlated with TW significantly, and the WRD is more stable than the WCD. It concludes that wavelet decomposition enhances the features of surface EMG, and that power ratio (HF/LF) and contraction and relaxation delays obtained with the EMG wavelet decomposition can be used to monitor the muscle fatigue during the maximum voluntary isokinetic concentric contraction.

Electromyography↗

An elbow joint movement control model with visual feedback.

A motor program generator control model is proposed to simulate neuromuscular control. Three muscles (Biceps, Triceps, Brachialis) driving elbow joint flexion in a plane are simulated by integrating their nonlinear dynamic property and spinal neural circuitry. The motor descending commands are described by a visual feedback signal from the joint and an excitation signal for the motor neuron pool. The visual feedback signal mimics the gamma command whereas the excitation signal mimics another descending co-activation command. The gamma command is expressed as the output of a PID controller with the visual feedback error signal as the input. The gamma command and the motoneuron pool background activity are the inputs to the motoneuron pool model coupled with the Renshaw cell recurrent inhibitions. The output of the motoneuron pool model mimics the alpha command feeding directly to the muscle dynamics. A movement is produced by reducing the error signal between goal position and actual position and altering excitation signal properly. The simulation results show that a burst pattern of excitation signal and a PID controller can accurately trace the terminal goal and generate a smooth movement with a bell shaped velocity profile. The muscle activation signals have the characteristic similar to the smoothed EMG. Changing different parameters of the PID can cause the same effects as the stimulus pulse intensity or duration modulation.

Elbow Joint↗

Effects of limb perturbation on surface recorded nerve action potentials.

The field action potentials are a convolution of source strength and the propagating-point source responses (PPSRs). Surface-recorded peripheral nerve potentials are strongly influenced by the volume-conductor properties of the limb. In this paper the PPSRs are solved based on finite-element formulation, which allows solutions to forward volume-conductor problems involving curved nerves in arbitrarily shaped, inhomogeneous, anisotropic limbs. Effects of limb perturbation on surface-recorded nerve action potentials are simulated based on circular and elliptic cylinders with a uniform cross-section consisting of multiple inhomogeneous and anisotropic regions (fat, muscles, and bone layers). The simulations show that a simple homogeneous model is adequate only for a very superficial nerve that lies completely in the subcutaneous fat layer. Deeper nerves that lie on or within the muscle require a multiple-layer model that takes both the muscle and the fat into account. The cross section only needs to be modeled accurately between the recording site and the nerve location. A circular limb model is adequate for clinical recordings. However, an accurate knowledge of the nerve path is essential for accurate modeling of the action potentials, in both needle and surface recordings.

Action Potentials↗

[Evaluation of effectiveness of comprehensive control for diarrhea diseases in rural areas of east Fujian and analysis of its cost-benefit].

An intervention trial with comprehensive prevention and control for diarrhea diseases was carried out in the rural areas of East Fujian, China during 1991 to 1993, focusing on improvement of drinking water, health education, and supervision and direction to villagers to improve their environmental and family health. Results showed the intervention could reduce the incidence of diarrhea diseases by 55.1 percent in average. Economic benefit analysis of the effectiveness of the intervention showed ratios of cost to benefit were 1:5.6, 1:4.9 and 1:6.5 in 1991, 1992 and 1993, respectively, and net benefit amounted to 13,674,000 Chinese yuan. It suggests that effectiveness of this comprehensive control was significant and cost-effective.

China↗

Selectivity in tyrosyl iodination sites in human thyroglobulin.

Previous studies indicate that when low iodine thyroglobulin (Tg) is iodinated enzymatically with thyroid peroxidase (TPO), the tyrosyl residues that are used for the formation of thyroid hormone (hormonogenic sites) are selected for early iodination. The aim of the present study was to assess the relative importance of the substrate (Tg) and the enzyme (TPO) in the selection of the early tyrosyl sites that undergo iodination. For this purpose, low iodine human Tg (2.0 atoms I per 660,000 dimer) was iodinated chemically with (125)I-(3) and enzymatically with TPO + 125I- to a matched low level of iodination (approximately 8 added I atoms per molecule). After reduction and alkylation, the two Tg preparations were digested with trypsin, and the tryptic digests were separated by reverse-phase HPLC into 10 125I-containing pools. Each pool was further fractionated by HPLC to provide purified 125I-peptides suitable for sequence analysis. From the sequence information and the known amino acid sequence of Tg, it was possible to define the location of the iodinated tyrosyl residues. Surprisingly, almost identical results were obtained with chemically and enzymatically iodinated Tg. Not only were the 125I-peptide maps very similar, but all of the recovered 125I in the purified peptides from both samples was located in only three different tyrosyl sites, 5, 2553, and 2520. Tyr 5 and Tyr 2553 are well-established sites of thyroxine formation, while Tyr 2520 has previously been proposed by us to be a donor site. Our observation that the same hormonogenic tyrosyl sites are iodinated by chemical as well as enzymatic iodination indicates that preferential iodination of hormonogenic sites is dependent primarily on the native structure of Tg. TPO plays a minor role, if any, in the selection of early tyrosyl iodination sites in Tg. Consistent with this conclusion was our finding that chemical iodination, as well as enzymatic iodination, led to formation of uniformly iodinated Tg, as determined by isopycnic centrifugation in rubidium chloride. However, we observed a slightly higher diiodotyrosine (DIT) content and a correspondingly lower monoiodotyrosine content in enzymatically iodinated Tg, compared to matched chemically iodinated Tg. This was not observed with two other proteins, bovine serum albumin and trypsinogen, or with free tyrosine, as substrates for iodination. The same preferential formation of DIT in Tg was, however, observed when lactoperoxidase was substituted for TPO. Preferential formation of DIT, therefore, appears to involve interaction between Tg and the peroxidase.

Amino Acid Sequence↗

Glucose-induced phosphorylation of the insulin receptor. Functional effects and characterization of phosphorylation sites.

Elevated glucose concentrations have been reported to inhibit insulin receptor kinase activity. We studied the effects of high glucose on insulin action in Rat1 fibroblasts transfected with wild-type human insulin receptor (HIRcB) and a truncated receptor lacking the COOH-terminal 43 amino acids (delta CT). In both cell lines, 25 mM glucose impaired receptor and insulin receptor substrate-1 phosphorylation by 34%, but IGF-1 receptor phosphorylation was unaffected. Phosphatidylinositol 3-kinase activity and bromodeoxyuridine uptake were decreased by 85 and 35%, respectively. This was reversed by coincubation with a protein kinase C (PKC) inhibitor or microinjection of a PKC inhibitor peptide. Phosphopeptide mapping revealed that high glucose or PMA led to serine/threonine phosphorylation of similar peptides. Inhibition of the microtubule-associated protein (MAP) kinase cascade by the MAP kinase kinase inhibitor PD98059 did not reverse the impaired phosphorylation. We conclude that high glucose inhibits insulin action by inducing serine phosphorylation through a PKC-mediated mechanism at the level of the receptor at sites proximal to the COOH-terminal 43 amino acids. This effect is independent of activation of the MAP kinase cascade. Proportionately, the impairment of insulin receptor substrate-1 tyrosine phosphorylation is greater than that of the insulin receptor resulting in attenuated phosphatidylinositol 3-kinase activation and mitogenic signaling.

Animals↗

Construction and expression of single-chain Fv antibody against human bladder carcinoma.

We designed two sets of oligonucleotide primers to amplify the immunoglobulin heavy- and light-chain variable-region genes from genomic DNA by polymerase chain reaction (PCR). The genomic DNA was extracted from hybridoma BDI-1 cells, which secreted a monoclonal antibody (mAb) against human bladder carcinoma. The primers contained special restriction sites that allowed the variable-region genes to be easily cloned for sequencing and expression. The recombinants were sequenced by Sanger's method. It was proved that the full lengths of the VH and VK genes were 366 and 324 bp, respectively. Compared with other published sequences, the VH gene was a member of mouse heavy-chain VH subgroup II and originated from the rearrangement of VH, Dsp2.2 and JH4. The VK gene was VK subgroup IV and from VK and JK4. The VH and VK genes was inserted expression vector pWAI80. By inducement, the ScFv antibodies were expressed and secreted from Escherichia coli. Binding activities against the bladder carcinoma cells were detected. We suggest that ScFv antibody recognized the antigen specifically.

Amino Acid Sequence↗

[Cloning and sequencing of VH and VL genes of an anti-human lung adenocarcinoma monoclonal antibody].

By comparing the conserved regions at each end of the nucleotide sequences of murine germ-line genes encoding FR1 and FR4 regions of immunoglobulin heavy and light chain variable regions, we designed two sets of primer for amplification of VH and VL genes. Hybridoma cell WLA-2C4, secreting an antihuman lung adenocarcinoma McAb, was cultured and the genome DNA was extracted and used as template for PCR. After PCR the desired VH and VL fragments were amplified. The PCR products were then cloned into pUC19 vector. By screening and identification, several recombinants that had been inserted with the target fragments were obtained. Then they were sequenced with Sanger's method. It was confirmed by computer-assisted comparative sequence analysis that clones of full-length and potentially functional VH and VL genes from the hybridoma cell line WLA-2C4 were ob-tained.

Adenocarcinoma↗

[ACNU and methyl-CCNU in combination chemotherapy for advanced gastric cancer: a randomized comparative study. Shanghai ACNU Collaborative Study Group].

The study was conducted to compare the efficacy between a combined chemotherapy of ACNU (Nimustine hydrochloride, brand name Nidran), a new nitrosourea agent, and a combined chemotherapy of methyl-CCNU for advanced gastric cancer. One hundred and three cases of advanced gastric cancer were randomly allocated into Group A (Me-CCNU, 5-Fu and ADM) and Group B (ACNU, 5-Fu and ADM). The results showed that in Group A there was no CR or PR, while in Group B, although no CR, there were 8 PR (8/64 cases), denoting the response rate of 0% in Group A and 17.4% in Group B. The median survival period in Group A was 108 days and in Group B 112 days. Both groups well tolerated the treatment and there were no serious adverse effects. Quality of life (QOL) was better in Group B than in Group A. It is concluded that ACNU combination is superior to Me-CCNU combination for advanced gastric cancer.

Adenocarcinoma↗