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Biomedical subjects

A Wang

Publications and source records attributed to A Wang.

At least 109 records · Page 6Linked to original sources

A physical map of the mouse shaker-2 region contains many of the genes commonly deleted in Smith-Magenis syndrome (del17p11.2p11.2).

We report the construction of a physical map of the region of mouse chromosome 11 that encompasses shaker-2 (sh2), a model for the human nonsyndromic deafness DFNB3. DFNB3 maps within the common deletion region of Smith-Magenis syndrome (SMS), del(17)(p11.2p11.2). Eleven of the genes mapping within the SMS common deletion region have murine homologs on the sh2 physical map. The gene order in this region is not perfectly conserved between mouse and human, a finding to be considered as we engineer a mouse model of Smith-Magenis syndrome.

Abnormalities, Multiple↗

Predictors and significance of atrial rhythm before and six months after percutaneous balloon mitral commissurotomy.

Clinical, echocardiographic, and cardiac catheterization data were evaluated in 263 patients with mitral stenosis who were undergoing balloon commissurotomy to determine the predictors of atrial rhythm and its effect on functional status. Conversion from atrial fibrillation to sinus rhythm at 6 months after the procedure occurred in 16 of 86 patients (19%) and was predicted by the duration of atrial fibrillation, baseline functional class, and antiarrhythmic therapy; patients who remained in atrial fibrillation had a poorer functional status compared with those in sinus rhythm despite similar procedural results.

Adult↗

A human anti-HIV autoantibody enhances EBV transformation and HIV infection.

A highly specific, human IgG mAb, F223, which reacts with both HIV-1-infected cells and uninfected lymphoid cells, has been derived. F223 reacts with gp120 but fails to neutralize viral infection. The antibody does enhance HIV-1 infection in a complement-dependent manner. The autoantigen recognized by F223 is expressed on a small percentage of T cells and NK cells and the majority of B cells. Immunoprecipitation demonstrates F223 reactivity with an as of yet unidentified 159-kDa protein in uninfected lymphoid cells. This reactivity with uninfected cells is inhibited by free gp120 demonstrating the cross-reactive nature of this antibody. The F223 light chain demonstrates strong homology to VLlambda2 family genes whereas the heavy chain is most homologous (84%) to the germline gene VH3-H.11. In vivo usage of VH3 family genes by F223 and an anti-HIV-1 (gp41) human mAb, 3D6, with related autoreactivity, suggests that VH3 sequences may be important components of potentially pathogenic human anti-HIV-1 envelope autoantibodies. F223 was isolated from an HIV-1 infected individual with lymphoma and in vitro F223 significantly enhances EBV transformation of normal B cells and increases immunoglobulin production without affecting B cell proliferation. Characterization of this antibody response may provide important insights and mechanistic information on HIV pathogenesis.

Antibodies, Blocking↗

Stress reinstates nicotine seeking but not sucrose solution seeking in rats.

RATIONALE: Intermittent footshock stress effectively reinstates extinguished heroin-, cocaine- and alcohol-taking behaviors, but not behaviors previously maintained by food reinforcers. Here we tested further the generality of the phenomenon of stress-induced reinstatement by determining the effect of footshock on reinstatement of operant responding previously maintained by nicotine or palatable sucrose solutions. METHODS: Groups of rats were trained to self-administer either nicotine (0.03 mg/kg per infusion, 14 days) or sucrose (10 or 30% w/v, 14-20 days). After extinction of the nicotine- or the sucrose-reinforced behaviors for 5-15 days, the rats were exposed to intermittent footshock stress (5 and 15 min, 0.8 mA) during tests for reinstatement. RESULTS: Footshock reliably reinstated nicotine seeking after extinction of the drug-reinforced behavior. In contrast, the same parameters of footshock stress did not consistently reinstate operant responding previously maintained by sucrose solutions. CONCLUSIONS: These and previous data suggest that stressors may be more effective stimuli for reinstatement of behaviors previously maintained by drug reinforcers as compared with non-drug reinforcers.

Animals↗

Assessing the severity of mitral stenosis: variability between noninvasive and invasive measurements in patients with symptomatic mitral valve stenosis.

BACKGROUND: This study evaluated the correlation and variability between noninvasive and invasive measures of mitral stenosis severity before and after balloon mitral commissurotomy (BMC) in a large group of patients with symptomatic mitral stenosis. Factors related to variability between measurements were determined. METHODS: The Doppler transmitral gradient, Doppler half-time valve area, and 2-dimensional echocardiographic (2D) mitral valve area (MVA) were measured immediately before and 1 day after BMC in 272 consecutive patients with mitral stenosis and compared with their respective measures during cardiac catheterization. RESULTS: The correlation coefficient for the comparison of noninvasive and invasive measurements of the transmitral gradient was 0.63 before BMC and 0.60 after the procedure; for 2D versus Gorlin-derived MVA, 0.39 and 0.57, respectively; and for Doppler half-time versus Gorlin-derived MVA, 0.31 and 0.18, respectively. A large degree of variability in the measurement of MVA was present among the 3 techniques before BMC and increased after BMC. Before BMC, for the comparison of 2D and Gorlin-derived MVA, variables predictive of the discrepancy were age, echocardiographic score, transmitral gradient during catheterization, and cardiac index. For the comparison of Doppler half-time versus Gorlin-derived MVA, age, heart rate during cardiac catheterization and echocardiography, cardiac output and left ventricular end-diastolic pressure predicted the difference between the 2 measures. CONCLUSIONS: In symptomatic patients with mitral stenosis, there is significant variability between noninvasive and invasive measures of mitral stenosis severity despite careful, reproducible measurements. The difference between noninvasive and invasive measures of MVA before BMC is strongly related to cardiac output.

Cardiac Catheterization↗

Heparan sulfate chains with antimitogenic properties arise from mesangial cell-surface proteoglycans.

Heparan sulfate (HS) chains accumulate in both the medium and the cell layer of mesangial cell cultures. When given in fresh medium to quiescent cultures at naturally occurring concentrations, they suppress entry into the cell cycle and progression to DNA synthesis. We have attempted to identify the proteoglycan (PG) source of the antimitogenic HS chains from mesangial cell layers (HS(c)) and medium (HS(c)). When cells were labeled for 16 hours with [35S]sulfate, 25% of the label was found in intracellular HS chains and 5% in extracellular HSPGs. Cell-surface HSPGs accounted for the remaining 70% of the label associated with cell-layer HS and were released by either trypsin or 2% Triton X-100. About 20% of this cell-surface fraction was released by treatment with phosphatidylinositol-specific phospholipase C (PI-PLC), and probably represents glypican-like PG; glypican mRNA was present in the cells. The remainder of this fraction could be incorporated into liposomes, indicating the presence of hydrophobic transmembrane regions suggestive of syndecans. Upon purification and deglycosylation, an antiserum to rat liver HSPGs that reacts primarily with syndecan-2 showed a strong signal corresponding to this protein and three weaker bands that may represent additional syndecans. mRNAs for syndecan-1, -2, and -4 were present in the cultures. Syndecan-1 and -2 mRNAs were increased 30 minutes after stimulation of quiescent rat mesangial cells (RMCs) with serum. Heparin, HS(c), and HS(m) all prevented this increase. Syndecan-4 mRNA was not affected by serum, heparin, or HS. In pulse-chase experiments, the amount of 35S appearing in the cellular protein-free HS fraction was accounted for almost entirely by cell-surface PGs, as matrix-associated label was a minor contribution at the end of the pulse-labeling. The appearance of [35S]HS in cell extracts was unaffected by phospholipase C treatment, indicating that turnover of the newly labeled syndecan fraction is the source of the antimitogenic HS chains.

Animals↗

Effective treatment of murine leukemia with antisense poly-2'O-(2,4-dinitrophenyl)-oligoribonucleotides.

Two antisense poly-2'-O-(2,4-dinitrophenyl)-oligoribonucleotides (poly-DNP-RNA) have been synthesized and tested for the treatment of murine leukemia. Compound I was designed as a bifunctional inhibitor of either the reverse transcriptase (RT) activity or viral envelope synthesis in Moloney murine leukemia virus (MMLV). Compound II was designed as a trifunctional inhibitor of either RT activity or envelope synthesis or protease synthesis in MMLV. Administration of either I or II to MMLV-infected mice for 3 weeks decreased viremia gradually to below the level detectable by RT-PCR. Viremia did not reappear 8 weeks after termination of treatment, when most of the mice were killed for autopsy. All infected but untreated mice died within 6 months with enlarged spleens that exhibited abnormal histologic signs and were found by PCR to contain the DNA of integrated viral genome. The infected mice that had been treated subsequently with adequate dosage of compound I or II had normal spleens, continued to live on, and had no integrated MMLV genome in their spleen and bone marrow samples. The effective i.p. dosage (ED50) for compounds I and II are 0.25 and 0.1 mg/kg, respectively, which are 200-fold to 500-fold lower than that of the monofunctional RT inhibitor poly-DNP-oligo A. The estimated effective oral dosage of compound II is 1.2 mg/kg.

2,4-Dinitrophenol↗

Proteolytic processing of tomato ringspot nepovirus 3C-like protease precursors: definition of the domains for the VPg, protease and putative RNA-dependent RNA polymerase.

Tomato ringspot nepovirus (TomRSV) RNA-1 encodes a putative NTP-binding protein (NTB), a putative viral genome-linked protein (VPg), a putative RNA-dependent RNA polymerase (Pol) and a serine-like protease (Pro), which have been suggested to be involved in viral RNA replication. Proteolytic processing of protease precursors containing these proteins was studied in Escherichia coli and in vitro. The TomRSV protease could cleave the precursor proteins and release the predicted mature proteins or intermediate precursors. Although processing was detected at all three predicted cleavage sites (NTB-VPg, VPg-Pro and Pro-Pol), processing at the VPg-Pro cleavage site was inefficient, resulting in accumulation of the VPg-Pro intermediate precursor in E. coli and in vitro. In addition, the presence of the VPg sequence in the precursor resulted in increased cleavage at the Pro-Pol cleavage site in E. coli and in vitro. Direct N-terminal sequencing of the genomic RNA-linked VPg, of the mature protease purified from E. coli extracts and of radiolabelled mature polymerase purified from in vitro translation products revealed the sequences of the NTB-VPg, VPg-Pro and Pro-Pol dipeptide cleavage sites to be Q/S, Q/G and Q/S, respectively. In vitro processing at the NTB-VPg and Pro-Pol cleavage sites was not detected upon mutation or deletion of the conserved glutamine at the -1 position of the cleavage site. These results are discussed in light of the cleavage site specificity of the TomRSV protease.

3C Viral Proteases↗

Effect of a single bout of acute exercise on plasma human immunodeficiency virus RNA levels.

Acute exercise is known to activate the immune system and thus could lead to increased human immunodeficiency virus (HIV) replication. We sought to determine whether a single acute bout of exercise, similar to what people experience when starting an intensive exercise program, has a detrimental effect on plasma HIV RNA levels. Twenty-five patients with HIV infection performed one 15-min bout of acute exercise. Absolute neutrophil counts, serum creatine phosphokinase, and 72-h urinary 3-methylhistidine (a marker of muscle protein breakdown) were measured before and after the exercise, along with plasma HIV RNA levels. There were increases in neutrophil counts (P < 0.06), serum creatine phosphokinase (P < 0. 01), and urinary 3-methylhistidine (P < 0.01) in response to exercise, indicating a mild acute-phase response with muscle proteolysis. However, mean HIV RNA, which was elevated at baseline in 22 of the 25 subjects (mean of 4 x 10(5) +/- 0.7 x 10(5) copies/ml), did not increase during the week after exercise (P = 0. 12). Small changes in RNA were seen in the three subjects with initially undetectable HIV RNA, but the significance of these changes is unclear. Acute exercise does not have a deleterious effect on HIV replication in adults with high viral loads. Because regular exercise training has not been shown to activate the acute-phase response, the lack of increased viral loads in response to an acute exercise intervention suggests that exercise training is safe in people with HIV infection.

Adult↗

Assessing the Winning Teams program of interactive satellite-based training.

This research assessed an interactive satellite-based training program integrating interactive audiovisual experiences with face-to-face interactions. Key elements were content created by experts, high-quality video segments, satellite-based interaction, off-line interactions among teams of parents and caregivers, workshops, and team building exercises. For pragmatic reasons, it was necessary to develop brief assessment instruments concurrently with training. A large set of survey items were created from draft materials and reduced empirically through piloting to those with the best psychometric properties. To avoid the appearance of traditional testing, knowledge was assessed with Likert items. Surveys measured participant satisfaction, knowledge, attitudes, and the application and articulation of concepts. Participant satisfaction was high. Participants increased positive attitudes and learned appropriate vocabulary. Training was more effective than no training or watching videotapes. The program appears to represent a viable model of training that could successfully be applied to Internet technologies.

Consumer Behavior↗

[Study of the plasma adrenomedullin value in pregnancy induced hypertension patients].

OBJECTIVE: To investigate the relationship between adrenomedullin(ADM) and pregnancy induced hypertension(PIH). METHOD: The ADM values in the plasma from 12 normal term-pregnant women and 26 women with PIH were determined by specific radioimmunoassay. RESULT: (1) The ADM value in the PIH (24.67 +/- 1.27) ng/L increased significantly than that of normal pregnancy (19.16 +/- 1.17) ng/L (P < 0.05). (2) There were significant difference between severe(30.00 +/- 1.17) ng/L moderate (24.80 +/- 0.70) ng/L and mild (19.38 +/- 2.65) ng/L PIH groups (P < 0.001). (3) Significant positive correlation was found between plasma ADM value and mean arterial pressure (r = 0.775, P < 0.001). CONCLUSION: The ADM level is closely associated with PIH and may plan an important role in PIH.

Adrenomedullin↗

[Alterations of platelet membrane glycoproteins in patients with diabetes mellitus and their clinical significance].

OBJECTIVE: To investigate changes of platelet glycoproteins in patients with diabetes mellitus(DM) type II and their clinical significance. METHODS: Seventy DM patients and 28 normal individuals entered in this study. The platelet glycoproteins Ib, IIb, IIIa and P-selectin were analyzed by flow cytometry (FCM). Platelet surface P-selectin was measured by Immunoradiometric analysis (IRMA), and plasma P-selectin concentration by ELISA. RESULTS: On FCM, the P-selectin expression on platelets of patients with vascular diseases [(10.28 +/- 4.86)%] was higher than that of normal subjects [(3.75 +/- 1.83)%] (P < 0.01) and patients without vascular diseases [(4.25 +/- 2.29)%] (P < 0.01). Similar results were obtained using IRMA. Plasma P-selectin concentration in patients with vascular diseases [(6.18 +/- 3.20) ng/ml] was higher than that of control group [(3.43 +/- 1.56) ng/ml](P < 0.05) and that of patients without vascular diseases [(3.71 +/- 2.12) ng/ml] (P < 0.05). On the contrary, the platelet surface GP Ib expression in patients with vascular diseases [(86.35 +/- 11.00)%] was remarkably lower than that of normal subjects [(92.63 +/- 7.55)%] (P < 0.05), while platelet GP IIb and IIIa were not changed in any cases. CONCLUSION: The P-selectin levels in plasma and on platelet surface were increased while platelet membrane GP Ib was decreased in DM type II patients with vascular events.

Adult↗

[The expression of MRP gene relates to the pathological features of lung cancer].

OBJECTIVE: To evaluate the expression of MRP gene and its relation to pathological features in lung carcinoma. METHODS: A series of 35 resected primary lung cancer tissues from 9 post-chemotherapy and 26 untreated patients and adjacent normal lung tissues and 28 lymph node tissues were analyzed for MRP gene expression by RT-PCR method. RESULTS: Positive expression rate of MRP gene was 54% in 35 cases with primary lung cancer, 14% in tissues adjacent to the carcinoma site and the difference was significant (P < 0.005), the positive rate of MRP gene expression in metastatic lymph node tissues was 53%. In 9 cases of pre-operative chemotherapy, the positive expression rate of MRP gene was higher than that in 26 cases without chemotherapy. Nineteen of 35 tumors were found to show positive expression of MRP gene, comprising 11 of 18 adenocarcinoma, 9 of 15 squamous cell cancer. The relapse or metastasis rate with MRP-positive cases was higher(55%) than that with MRP-negative (15%) by follow-up of these patients. CONCLUSIONS: There are overexpression of MRP gene in primary lung cancer tissues. Preoperative chemotherapy may play inductive role in lung cancer multidrug resistance. The positive expression of MRP gene in lung cancer tissues is in accord with its lymph node tissues. Positive expression of MRP gene does not necessarily be associated with tumor size, clinical type and TNM stages, but it could be regarded as one poor prognostic factor.

Biomarkers, Tumor↗

[The use of intervention chemotherapy in comprehensive treatment of advanced nasopharyngeal carcinoma].

OBJECTIVE: To study the application of intervention chemotherapy in the comprehensive treatment of advanced nasopharyngeal carcinoma (NPC). METHODS: In 30 patients with advanced NPC, combined intervention chemotherapy with cisplatin (100 mg), 5-fluoro-uracil (1,000 mg) and bleomycin (16 mg) was given by Seldinger's selective unilateral catheterization of the ascending pharyngeal artery or superior maxillary artery. If the lesion had extended over the midline, the intervention chemotherapy encompassed both sides: 2/3 of the dose infused to the side with the major lesion and 1/3 to the other side. Radiotherapy started one week after intervention chemotherapy. A total dose of 60-70 Gy was given to the primary tumor or 50-60 Gy to the cervical metastases in 8 weeks. Fifty patients with advanced NPC treated in the same period of time with radiotherapy alone served as the control. Both groups of patients were treated with 60Co, the duration of treatment and dose splitting were the same. RESULTS: After intervention chemotherapy, the primary tumor mass reduced in size in 16 patients and the enlarged cervical lymph nodes shrank or became loosened in 12 patients. The radiation dose required to achieve complete response of the primary and metastatic lesions was significantly less as compared to that of patients receiving radiotherapy alone (P < 0.05). At four weeks following completion of radiotherapy, complete response rate in the two groups of patients was 83.3% and 72.0%, respectively (P < 0.05). CONCLUSION: Intervention chemotherapy combined with radiotherapy is an effective treatment for patients with advanced NPC.

Adult↗

[Clinical study on treatment of mid-late stage gastric carcinoma by composite xiansu capsule combined with chemotherapy].

OBJECTIVE: To assess the effect and mechanism of composite Xiansu Capsule (CXSC) combined with chemotherapy in treating gastric carcinoma of mid-late stage. METHODS: The 61 patients of the test group were treated by CXSC combined with chemotherapy and 30 patients of the control group treated with chemotherapy alone. The effect of treatment and cell mediated immunity of patients were observed. RESULTS: The effective rate of the test group and the control group was 32.8% and 13.3% respectively (P < 0.05), the chemotherapy caused toxic reaction occurrence was less in the former than that in the latter group (P < 0.01). The CD3 level of patients in the test group was decreased, and CD4/CD8 level was raised obviously, which suggested that CXSC had immuno-regulating effect on T-cells. CONCLUSION: CXSC could enhance the efficacy and reduce the toxic side-effect of chemotherapy. To regulate the cell mediated immunity of patients is possibly its mechanism.

Adenocarcinoma↗