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Biomedical subjects

X Qi

Publications and source records attributed to X Qi.

At least 37 records · Page 2Linked to original sources

Saposins A, B, C, and D in plasma of patients with lysosomal storage disorders.

BACKGROUND: Early diagnosis of lysosomal storage disorders (LSDs), before the onset of irreversible pathology, will be critical for maximum efficacy of many current and proposed therapies. To search for potential markers of LSDs, we measured saposins A, B, C, and D in patients with these disorders. METHODS: Four time-delayed fluorescence immunoquantification assays were used to measure each of the saposins in plasma from 111 unaffected individuals and 334 LSD-affected individuals, representing 28 different disorders. RESULTS: Saposin A was increased above the 95th centile of the control population in 59% of LSD patients; saposins B, C, and D were increased in 25%, 61%, and 57%, respectively. Saposins were increased in patients from several LSD groups that in previous studies did not show an increase of lysosome-associated membrane protein-1 (LAMP-1). CONCLUSION: Saposins may be useful markers for LSDs when used in conjunction with LAMP-1.

Adolescent↗

Hepatotropism of nonenveloped DNA virus in rhesus monkey infected by transfusion-transmitted virus.

OBJECTIVE: To study wether the nonenveloped DNA virus transmitted via blood transfusion is hepatotropic. METHODS: Total DNA was extracted from tissues of 5 experimentally infected Rhesus monkeys. A dot hybridization was done with virus double DNA strand probe or single antisense strand probe. RESULTS: Both single- and double-strand probes were hybridized with DNA of the liver, spleen, stomach, small intestine and colon. The virus was conformed present in most of all the organs when double-strand probe was used. The positive was noted only in the liver and small intestine when single-strand antisense probe was used, which showed that in liver and small intestine might have replicative intermediates of the virus. CONCLUSION: It suggests that nonenveloped DNA virus replicate in the liver and small intestine, so it might be hepatotropic.

Animals↗

[Study on the inhibitory effect of antisense phosphorothioate oligodeoxynucleotide on coxsackie virus B replication in vitro].

OBJECTIVE: To investigate the antiviral effect of antisense phosphorothioate oligodeoxynucleotide (AODN) on CVB3 replication in vitro. METHODS: In this study, 21 mer antisense phosphorothioate oligodeoxynucleotide which complemented to nt 581-601 in 5' NCR of Coxsackie Virus B3 (CVB3) RNA was used to investigate antiviral activity in Vero cells as a specific inhibitor of CVB3 replication. Specific AODN of CVB3 RNA, sense oligodeoxynucleotide (SODN) and randomized nonsense-sequence RODN were synthesized for effect comparison among them. Vero cells infected by CVB3 were transfected with different concentrations of AODN mediated by lipofectamine reagent, so that the cells could take in more AODN. Cell control and viral control were set up. The inhibitory effect of AODN on CVB3 replication was evaluated with a number of variables, including inhibitory rates of cytopathic effect (CPE), cell survival rates by MTT assay, inhibitory rates of CVB3 antigen by ELISA, inhibitory rates of RNA by dot blotting and 50% tissue culture infective dose (TCID50). RESULTS: The specific AODN could significantly inhibit CPE of CVB3-infected Vero cells, decrease the production of antigen and RNA of CVB3 and viral titers, and increase cell survival rates, in a dose-dependent manner. The strongest inhibitory effect appeared at 48 hours after transfection, the most effective concentration of AODN was 10 micromol/L. On the other hand, 10 micromol/L SODN also showed weaker inhibitory effect on CPE of CVB3-infected cells, but no antiviral effect of 10 micromol/L RODN was shown. AODN showed no-inhibition on HSV-1 replication, but inhibited some enteroviruses such as CVB3, Polio-1 and Echo-6 to some extent. CONCLUSIONS: These results indicate that nt 581-601 in 5' NCR of CVB3 RNA may play an important role in regulating CVB3 replication and AODN may have inhibitory effect on CVB3 replication.

Animals↗

[Analysis of the clinical characteristics and prognostic factors with primary normal-sized epithelial ovarian carcinoma syndrome].

OBJECTIVE: To investigate the clinical characteristics and prognostic factors of the primary normal-sized epithelial ovarian carcinoma syndrome. METHODS: The clinical records and pathologic slides of the 10 patients who satisfied the diagnostic criteria were retrospectively analyzed. RESULTS: The primary normal-sized epithelial ovarian carcinoma syndrome was detected in approximately 1.92% of the patients with the epithelial ovarian carcinoma. The age of the patients at diagnosis ranged from 43-70 years, with a median age of 57 years. The most common presentations included anorexia, increasing abdominal girth and awareness of abdominal or pelvic mass. During the exploratory laparotomy although we often discovered the diffuse metastasis throughout the abdominal and pelvic cavity, the ovaries both appeared normal size and had a fine granularity on the external surface. The survival time of patients with remained tumors smaller than 2.0 cm was longer than those with remained tumors larger than 2.0 cm, but the Log-rank evaluation indicated chi 2 = 0.61, P > 0.05. The patients who underwent postoperative chemotherapy have been noted to achieve some long-term survival. The median survival time was 20 months. CONCLUSION: The results predict that the size of the remained tumors may be one of the important factors to the survival and the disease is sensitive to the postoperative chemotherapy.

Adult↗

[Gene therapy with tumor suppressor gene p53 and(or) p16 on the nude mice models of NSCLC in vivo].

OBJECTIVE: To investigate the effect of tumor suppressor gene p53 and(or) p16 treatment on the nude mice models of non-small cell lung cancer (NSCLC). METHODS: Nude mice were injected subcutaneously with NSCLC cell line A549. 25 nude mice were randomly divided into 5 groups (control, SA, p53 gene, p16 gene, p53 + p16 genes), p53 and(or) p16 genes mediated by stearylamine/DOPE (SA liposome) were injected intratumorally alone or jointly. The size of tumor and survival period of nude mice were measured after treatment. RESULTS: p53 and(or) p16 genes can obviously inhibit the growth of tumor. The difference was significant between control and treated groups, among which the combined p53 and p16 genes enhance the inhibiting effect more markedly. The survival period of tumor-bearing nude mice was prolonged after transfecting p53 gene or p16 gene alone, p53 and p16 genes jointly can prolong the survival period significantly. CONCLUSIONS: Tumor suppressor gene p53 and(or) p16 in the replacement therapy of NSCLC are of potential clinical significance. The combination of p53 and p16 gene may have a greater antitumoral effect in vivo.

Animals↗

[Effects of selective preoperative intra-arterial infusion chemotherapy on apoptosis and proliferation of rectal cancer cells].

OBJECTIVES: To study the effects of anti-cancer drugs on apoptosis and proliferation of rectal cancer cells in vivo. METHODS: 114 patients with rectal cancer were treated by selective preoperative intra-arterial infusion chemotherapy. The rectal tumor tissues were derived before chemotherapy and 7 - 12 days after this treatment. In the tissues, apoptotic cells were examined by TUNEL method, and the expression of PCNA was examined by S-P staining. RESULTS: Before chemotherapy, the mean AI of tumor cells was 5.81 per thousand before chemotherapy and 10.99 per thousand 7 - 12 days after chemotherapy (P < 0.01). The mean PI of tumor cells before chemotherapy and 7 - 12 days after chemotherapy was 49.27% and 57.38% (P < 0.01). The mean AI of the high PI group increased more evidently than that of the low PI group. CONCLUSIONS: This treatment induced apoptosis of rectal cancer cells and inhibit tumor cell proliferation. The mean AI of the high PI group was higher than that of the low PI group. It is suggested that this operation should be performed shortly after chemotherapy.

Adult↗

New technique for vagal nerve stimulation.

INTRODUCTION: The vagus nerve travels in a neurovascular bundle with the carotid artery and internal jugular vein. The present study was designed to assess whether transvascular stimulation through the carotid artery of the dog can be used to directly stimulate the vagus nerve and increase parasympathetic tone. METHODS: In five anesthetized dogs, a steerable electrode catheter was positioned under fluoroscopic guidance in the right carotid artery in the mid neck via the femoral artery. Multipolar catheters were positioned transvenously through the femoral vein in the right atrium, across the tricuspid valve to record a His-bundle electrogram, and in the right ventricle. RESULTS: In all five animals, vagal nerve stimulation was successfully achieved with outputs ranging between 10 and 30 mA. Sinus cycle length increased from 473 +/- 113 ms at baseline to 894 +/- 315 ms (P < 0.025) during stimulation from the right carotid artery. There was an increase in the AH interval from 55 +/- 14 to 77 +/- 23 ms (P < 0.03), a shortening of the atrial effective refractory period from 136 +/- 8 to 126 +/- 6 ms (P < 0.01), and a fall in the systolic blood pressure from 135 +/- 20 to 117 +/- 20 mmHg (P < 0.005) with stimulation from the right carotid artery. A prolongation of the AV and VA block cycle lengths and the AV nodal effective refractory period was also noted with stimulation from the right carotid artery. Atrial fibrillation was not induced at baseline in any animal. During stimulation from the right carotid artery, atrial fibrillation was induced in three of five animals and persisted for the duration of stimulation from the right carotid artery. CONCLUSION: Cardiac parasympathetic stimulation can be achieved by positioning a catheter in the neurovascular bundle in the neck adjacent to the vagus nerve with resultant effects on cardiac electrophysiology.

Animals↗

Conformational and amino acid residue requirements for the saposin C neuritogenic effect.

Prosaposin is the precursor of four activator proteins, termed saposins A, B, C, and D, that are required for much of glycosphingolipid hydrolysis. The intact precursor also has neurite outgrowth activity ex vivo and in vivo that is localized to amino acid residues 22-31 of saposin C. Across species, this saposin C region has a high degree of identity and similarity with amino acids in the analogous region of saposin A. Wild-type and mutant saposins C and A from human and mouse were expressed in E. coli. Pure proteins, synthetic peptide analogues, conformation-specific antibodies, and CD spectroscopy were used to evaluate the basis of the ex vivo neuritogenic effect. Wild-type saposin A had no neuritogenic activity whereas reduced and alkylated saposin A did. Introduction of the conserved saposin A Tyr 30 (Y30) into saposin C at the analogous position 31, a conserved Ala(A)/Gly(G)31, diminished neuritogenic activity by 50-60%. Nondenatured saposin A with an introduced A30 acquired substantial neuritogenic activity. Polyclonal antibodies directed against the NH2-terminus of saposin C cross-reacted well with reduced and alkylated saposins C and A, wild-type saposin C, and saposin A [Y30A], poorly with saposin C [A31Y], and not at all with wild-type saposin A. CD spectra of wild-type and mutant saposins C and A, the corresponding neuritogenic region of saposin C, and the analogous region of saposin A showed that more "saposin C-like" molecules had neuritogenic properties. Those with more "saposin A-like" spectra did not. These studies show that the neuritogenic activity of saposin C requires specific placement of amino acids, and that Y30 of saposin A significantly alters local conformation in this critical region and suppresses neuritogenic activity.

Amino Acid Sequence↗

Effect of phosphorylation on activities of Rap1A to interact with Raf-1 and to suppress Ras-dependent Raf-1 activation.

Rap1A is phosphorylated by cAMP-dependent protein kinase (PKA), and this phosphorylation has been shown to modulate its interaction with other proteins. However, it is not known whether Rap1A phosphorylation is involved in regulation of its cellular functions, including suppression of Ras-dependent Raf-1 activation. We have previously shown that this suppressive activity of Rap1A is attributable to its greatly enhanced ability to bind to the cysteine-rich region (CRR, residues 152-184) of Raf-1 compared with that of Ras. Here, we show that phosphorylation of Rap1A by PKA abolished its binding activity to CRR. Furthermore, a mutant Rap1A(S180E), whose sole PKA phosphorylation residue, Ser-180, was substituted by an acidic residue, Glu, to mimic its phosphorylated form, failed to suppress Ras-dependent Raf-1 activation in COS-7 cells. These results indicate that the CRR binding activity and the Ras-suppressive function of Rap1A can be modulated through phosphorylation and suggest that Rap1A may function as a PKA-dependent regulator of Raf-1 activation, not merely as a suppressor.

Amino Acid Sequence↗

Adenoviral gene therapy with catalase suppresses experimental optic neuritis.

OBJECTIVE: To determine if adenoviral-mediated transfer of the gene for catalase (CAT), the reactive oxygen species scavenger, suppresses experimental optic neuritis. CLINICAL RELEVANCE: Gene therapy with CAT delivered by an adeno-associated viral vector was previously shown to suppress experimental optic neuritis. Because the transduction of protein expression with recombinant adeno-associated viral vector is relatively slow, taking weeks to reach full levels, we studied the effects of replication-deficient adenovirus containing CAT in suppressing experimental optic neuritis. Transduction with adenovirus occurs within days of inoculation, thus, it may be more applicable for the treatment of patients with acute optic neuritis. MATERIALS AND METHODS: Replication-deficient adenovirus containing CAT was injected above the right optic nerve heads of SJL/J mice that were simultaneously sensitized for experimental allergic encephalomyelitis. For controls, the left eyes were injected with the replication-deficient adenovirus without CAT or no virus. The histological effects of CAT on the lesions of experimental allergic encephalomyelitis were measured by computerized analysis of the myelin sheath area (for demyelination), optic disc area (for optic nerve head swelling), the extent of the cellular infiltrate, extravasated serum albumin labeled with immunogold (for disruption of the blood-brain barrier), and the in vivo hydrogen peroxide reaction product. RESULTS: After 1 month, cell-specific catalase activity, evaluated by the quantitation of catalase immunogold, was increased about 2-fold each in endothelia, oligodendroglia, astrocytes, and axons of the CAT-inoculated right optic nerves compared with the control left optic nerves. The increased cellular levels of catalase reduced demyelination by 30%, optic nerve head swelling by 25%, cellular infiltration by 26%, disruption of the blood-brain barrier by 61%, and in vivo levels of hydrogen peroxide by 81%. CONCLUSIONS: Adenoviral-mediated gene transfer increased catalase levels in all optic nerve cell types, and it persisted for 1 month after inoculation. The increased cellular levels of catalase suppressed demyelination and blood-brain barrier disruption at the foci in the optic nerve where prior magnetic resonance imaging and histopathologic studies have demonstrated the demyelinating inflammation of experimental and human optic neuritis. Together, they suggest that gene therapy with CAT may be helpful in the treatment of patients with optic neuritis.

Adenoviridae↗

Reporter expression persists 1 year after adeno-associated virus-mediated gene transfer to the optic nerve.

OBJECTIVE: To determine the foci and duration of protein expression following virus-mediated gene transfer to the optic nerve. METHODS: A cytomegalovirus (CMV) promoter was linked to a lacZ-SV40 polyA reporter gene or a humanized green fluorescent protein (hgfp) reporter gene, then inserted into a bacterial plasmid containing adeno-associated virus (AAV) terminal repeat sequences. The CMV-lacZ or the CMV-hgfp construct were injected into the vitreous cavity of strain-13 guinea pigs. Controls consisted of eyes injected with AAV without the promoter and reporter elements or eyes that received no injections. The eyes and optic nerves were processed for beta-galactosidase immunohistochemistry and hgfp fluorescence analyses. Cellular transduction at the messenger RNA (mRNA) level was evaluated by in situ reverse transcription-polymerase chain reaction. RESULTS: Weekly fundus photography, done for 1 month, documented the absence of any ocular abnormality due to the viral injections. No in vivo hgfp fluorescence of the retina was visualized. Beta-galactosidase histochemical analysis of eye cups that received the lacZ gene construct showed blue lacZ staining of the optic nerve head at 2 weeks. Light microscopy revealed the blue beta-galactosidase reaction product in fibers, glial cells, and blood vessels of the optic nerve head and retrobulbar nerve. Histochemistry showed absence of beta-galactosidase in the optic nerve at 3 to 12 months, but immunochemistry showed the persistence of beta-galactosidase in fibers, glial cells, and blood vessels as late as 1 year after a single ocular injection. In the retina, histochemical staining showed evidence of lacZ at 3 months, but not later. In situ reverse transcription-polymerase chain reaction revealed brown lacZ mRNA reaction product in ganglion cells of the retina. Control eyes that received AAV without the promoter and reporter elements and the eyes that received no viral injections and were processed for beta-galactosidase showed no reporter gene expression in any ocular tissue or cell type. CONCLUSIONS: Viral-mediated gene transfer can be successfully accomplished in the optic nerve. Further evaluation is needed to determine whether the level of protein expression at 1 year after injection, which is clearly reduced relative to shorter postinjection time, is sufficient for therapeutic purposes. CLINICAL RELEVANCE: We have previously shown that gene therapy with catalase suppressed experimental optic neuritis at 1 month after injection. Viral-mediated gene transfer may be a powerful technique for the treatment of optic neuropathies, particularly for recurrences of optic neuritis, if long-term expression of transduced protein can be demonstrated in the optic nerve.

Animals↗

[Study of transcription and cleavage in vitro of HDV with HBV-specific hammerhead ribozyme].

OBJECTIVE: To study the effect of hepatitis B virus(HBV) specific ribozyme(RZ) and recombinant hepatitis D virus(HDV) inserting hammerhead ribozyme(rHDVRZP and rHDVRZA). METHODS: 831 bp HBV C gene fragment was cloned under the control of T7 promoter, 32P-labeled HBV transcript was incubated with gel-purified RZ, rHDVRZA, rHDVRZP at different temperature and autoradiographed after denaturing gel-electrophoresis. RESULT: These results show that rRZ, rHDVRZA, rHDVRZP were active at 37 degrees C and more so at higher temperatures. CONCLUSION: Recombinant Delt virus could serve as a vector for the delivery of a ribozyme specific for hepatitis B virus cleavage. Our data demonstrate the value of recombinant ribozyme as potential therapeutic agents for treatment of HBV infection. Further study about cleavage in vitro and in vivo will continue.

Cloning, Molecular↗

Effects of acupuncture on the pituitary-thyroid axis in rabbits with fracture.

PURPOSE: To observe the effects of acupuncture on the pituitary-thyroid axis in rabbits with fracture. METHOD: 36 male rabbits with a 3-mm width experimental defect in the middle segment of the left radius were randomly divided into the treatment group and control group, and the changes in serum T3, T4 and TSH contents in different weeks were investigated. RESULTS: Serum T3, T4 and TSH contents in the treatment group all were higher than those in the control group, with statistically significant differences in the contents of T4 and TSH in the second week and T3 content in the fourth week (P < 0.01 or P < 0.05). CONCLUSION: The action of promoting union of fracture is possibly related with the pituitary-thyroid axis.

Animals↗

Antiarrhythmic drugs and ventricular defibrillation energy requirements.

PURPOSE: To understand the potential interaction between antiarrhythmic therapy and the implantable cardioverter-defibrillator (ICD) in patients who receive pharmacologic therapy as an adjunct to ICD therapy. DATA SOURCES: MEDLINE searching was employed and the information was indexed from approximately 3600 journals published world-wide from 1966 to 1998. STUDY SELECTION AND DATA EXTRACTION: Data were collected from 66 of approximately 455 originally identified articles and abstracts using explicit methodological criteria. RESULTS: The ICD therapy has been widely used for therapy of life-threatening ventricular arrhythmias (VT/VF) and prevention of recurrence of sudden cardiac death. Studies reported that 40%-70% or 10%-40% of ICD patients required concomitant antiarrhythmic medication to reduce the frequency of sustained arrhythmic episodes and to minimize the frequency of device discharges. Most studies on antiarrhythmic drug-ICD interactions have been performed in experimental animals. Antiarrhythmic drugs can influence the effectiveness of ICD to terminate arrhythmias through their effects on defibrillation threshold (DFT). Studies have demonstrated a rise in DFTs with class Ib agent lidocaine and class Ic agents encainide and flecainide. Class Ia agents, as well as amiodarone, bretylium and propafenone may have more variable effects on DFT probably because of the difference between acute and chronic drug dosing, dose-related changes, active metabolites, and reproducibility in determining DFT. Class III agents, with the exception of amiodarone, consistently decrease DFT. These drugs can be used as front-line agents in ICD patients. CONCLUSIONS: Antiarrhythmic drugs can increase, decrease, or have no effect on DFT. Class III agents except amiodarone can be safely administered in conjunction with ICD patients as long as the interaction between these therapeutic modalities is appreciated.

Animals↗

[The proper opportunity of surgery for rectal cancer after preoperative adjuvant chemotherapy].

OBJECTIVE: To discuss the proper opportunity of surgery for rectal cancer after preoperative intra-arterial chemotherapy. METHODS: Preoperative chemotherapy was performed on 27 rectal cancer cases at Dukes stage B and C. The therapy comprised of arterial infusion of 5-fluorouracil 600 mg/m(2), mitomycin 15 mg/m(2) and epirubicin 30 mg/m(2) for one course. Miles' or Dixon's operation was carried out 7 to 10 days later. The effects of chemotherapy were evaluated. Dynamic changes of proliferating cell nuclear antigen (PCNA) expression were studied by immunohistochemistry on paraffin-embedded sections. RESULTS: Hematochezia was remitted in 19 cases. Histologically, the effects of chemotherapy were considered as slight, moderate and marked in 9, 15 and 3 cases, respectively. Side effects were slight and recovered in 4 days. There was a high expression of PCNA in rectal cancer. On the 7th to the 10th day, proliferating index was significantly higher than that of before chemotherapy (46.48 +/- 10.62)%, P < 0.05. CONCLUSIONS: Preoperative adjuvant chemotherapy plays a role in the treatment of resectable rectal cancer. It is suggested that radical surgery should be carried out 5 to 6 days after intra-arterial chemotherapy.

Adult↗

[Timing changes of apoptosis and proliferating cells nuclear antigen after intra-arterial infusion chemotherapy for rectal cancer].

OBJECTIVE: To investigate the timing changes of apoptosis (APO) and PCNA after intra-arterial infusion chemotherapy for rectal cancer. METHODS: Twelve patients were subjected to percutaneous arterial femoralis catheterization by Seldinger's technique and infusion of anti-cancer drugs: 5-fluorouracil (5-Fu) 600 mg/m(2), mitomycin (MMC) C5 mg/m(2) and epirubicin (EDR) 35 mg/m(2). The biopsy of rectal tumor tissues was done before chemotherapy, and 24, 48, 72 hours and 7-10 days after chemotherapy. Apoptotic cells were examined by terminal-deoxynucleotidyl-transferase (TdT)-mediated dUTP-fluorescein and labeling. The expression of proliferating cells nuclear antigen (PCNA) was detected by immunohistologic staining. RESULTS: The apoptosis index (AI) of rectal cancer cells before chemotherapy, and 24, 48, 72 hours, and 7-10 days after chemotherapy was 6.84 per thousand, 19.53 per thousand, 13.15 per thousand, 11.85 per thousand and 11.86 per thousand respectively. The PCNA index (PI) was 45.56%, 40.68%, 39. 87%, 51.28% and 63.75% before and 24, 48, 72 hours, and 7-10 days after chemotherapy. CONCLUSIONS: Intra-arterial infusion chemotherapy not only induced apoptosis effectively, but also inhibited temporarily tumor cells proliferation in patients. The curative surgical treatment should be performed as soon as possible after chemotherapy.

Adult↗

[Relationship between insulin-like growth factor II and prognosis of colorectal cancer].

OBJECTIVE: To investigate the relationship between insulin-like growth factor II (IGF-II) and prognosis of colorectal cancer. METHODS: One hundred and forty-two colorectal cancer patients were enrolled. In colonoscopic biopsy specimens, the expression of IGF-II and PCNA were detected immunohistochemically, while TUNEL technique was used to detect apoptosis. All patients were followed up, and disease-free survival (DFS) and overall survival (OS) rate were calculated. RESULTS: The expression level of IGF-II was significantly higher in colorectal cancer than in normal colorectal mucosa. A correlation was observed between more IGF-II expression, high PCNA labeling index, and apoptotic index was demonstrated. Patients with lower expression level of IGF-II had higher DFS and OS. Multivariate analysis by means of the Cox proportional-hazards model revealed that the expression level of IGF-II was an independent prognostic predictor in colorectal cancer patients. CONCLUSION: The expression level of IGF-II is a new prognostic predictor for colorectal cancer.

Adenocarcinoma↗