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Biomedical subjects

N Wang

Publications and source records attributed to N Wang.

At least 271 records · Page 15Linked to original sources
PubMed1997

[Cloning of BRCA1 cDNA and detection of BRCA1 mRNA expression in breast cancer cells].

The fragment of BRCA1 cDNA obtained by reverse transcription and polymerase chain reaction(RT-PCR) was inserted into plasmid pUC118 and demonstrated by DNA sequencing. Nucleotide sequence analysis demonstrated that the cloned cDNA for BRCA1 includes zinc finger domain. Two differences in nucleotides were found as compared with the sequence published. One occurs at nucleotide number 409 where Creplaced by A (Asp-->Glu). Another difference occurs at nucleotide number 879 where A replaced by T (samesense mutation). In order to further study the relationship-between BRCA1 function and breast cancer, the probe was prepared from the recombinant plasmid and then hybridized to total RNAs from 6 cases of breast cancer. Compared with normal cells, the expression level of BRCA1 mRNA was normal in 4, decreased markedly in 1, and in one patient there was no any expression of BRCA1 mRNA at all. The results suggested that the expression of BRCA1 mRNA was relatively low in some breast cancer cells.

Amino Acid Sequence↗
PubMed1997

Loss of heterozygosity at chromosome segment Xq25-26.1 in advanced human ovarian carcinomas.

To determine whether a tumor suppressor gene of importance to epithelial ovarian cancer resides on the X chromosome, we examined loss of heterozygosity (LOH) in 123 epithelial ovarian cancer cases. In 54 such cases, we examined LOH at 26 loci on the human X chromosome. In eight cases, we examined LOH in 14 loci and in 61 cases we examined LOH in 13 loci. Matched DNA samples from tumors and corresponding normal tissues were analyzed by polymerase chain reaction (PCR) amplification of microsatellite markers. Frequent losses were found in epithelial carcinomas at the Xq25-26.l region, including DXS1206 (34.5% loss in informative cases), DXS1047 (27.7%), HPRT (24.1%), and DXS1062 (33.3%). The minimum overlapping region of LOH was approximately 5 megabases (Mb), flanked by DXS1206 (Xq25) and HPRT (Xq26.1). The methylation status of the remaining allele of the androgen receptor gene in the tumors exhibiting LOH at the Xq25-26.1 region suggested that the loss was exclusively in the inactive X chromosome. We next determined whether a significant relationship exists between Xq LOH and other parameters, including histologic grade and/or clinical stage of the tumors and LOH at TP53. The Xq LOH had a significant association with grade 2 to 3 tumors at stages II to IV. Sixteen of 18 cases that showed Xq LOH revealed LOH at the TP53 locus, and 45% of tumors exhibiting LOH at TP53 showed Xq LOH. These results suggest that there may be a tumor suppressor gene or genes which escape inactivation of the X chromosome at Xq25-26.1, and that the loss of the gene(s) at Xq25-26.1 is frequently accompanied by loss of the TP53 or loss of another gene on chromosome 17. These losses may contribute to the progression from a well-differentiated to a more poorly differentiated state or to metastatic aggressiveness.

Carcinoma↗
PubMed1997

[Follow-up study on children with obesity and hypertension].

OBJECTIVE: To study obesity development and its relationship between obesity and hypertension of children in China. METHOD: A 8-year follow-up study was conducted in 468 children aged 6 years by the criteria of hight, weight, thickness of skin fat and blood pressure. RESULTS: Obesity morbidity rose from 6 years (4.9%) to 13 years (16.2%), with the peak at 9 to 11 years. Both sexes developed obesity, which dominated in males. Children with obesity developed hypertension at age 13, the morbidity increased 3.5 times than that of those without obesity. CONCLUSION: Prevention of malnutrition is important in China but interventions to children with obesity in China are in urgent need.

Adolescent↗
PubMed1997

[The application of transposition of pectoralis major muscle or myocutaneous flap in the repair of long-standing wound over the mandibulo-cervico-thoracic area].

The pectoralis major muscle or myocutaneous flap is characterized by its easy dissection and free rotation, as well as abundance of blood supply and tissue mass of the flap, so that it was often used in repairing the wound over the mandibulo-cervico-thoracic area. From 1989 to 1996, 11 cases with long-standing wound of this area were difficult to repair with the traditional method, but were treated with transposition of this type of myocutaneous flap. The myocutaneous flap was applied in 8 case and muscle flap in 3 case. The flap area ranged from 12 cm x 8 cm to 26 cm x 18 cm. All the flaps survived, and excellent results were achieved. The technique and design of the operation were reported in details. It was concluded that the process was easy to perform, and the flap had abundant blood supply and high resistance to infection.

Adolescent↗
PubMed1996

Scavenger receptor BI (SR-BI) is up-regulated in adrenal gland in apolipoprotein A-I and hepatic lipase knock-out mice as a response to depletion of cholesterol stores. In vivo evidence that SR-BI is a functional high density lipoprotein receptor under feedback control.

Scavenger receptor BI (SR-BI), a putative high density lipoprotein (HDL) receptor, mediates the selective uptake of HDL cholesteryl ester into cells and is highly expressed in adrenal gland (Acton, S., Rigotti, A., Landschulz, K.T., Xu, S., Hobbs, H.H., and Krieger, M. (1996) Science 271, 518-520). Apolipoprotein A-I knock-out (apoA-I0) mice have decreased HDL cholesterol, depleted adrenal cholesterol stores and impaired corticosteroid synthesis (Plump, A.S., Erickson, S.K., Weng, W., J. Clin. Invest. 97, 2660-2671). We now show up-regulation of adrenal SR-BI mRNA and protein in apoA-I0 mice, but not in apoA-II0, LDL receptor 0, apoE0, or cholesteryl ester transfer protein transgenic mice. Adrenal SR-BI mRNA and protein are also increased and cholesterol stores decreased in female mice with knockout of hepatic lipase, and enzyme previously shown to increase selective uptake in cell culture. SR-BI mRNA is increased in stressed wild type mice and in Y1 adrenal cells treated with adrenocorticotropic hormone; the latter effect is inhibited by HDL. These findings provide in vivo evidence showing SR-BI is a functional HDL receptor under feedback control. The action of hepatic lipase on apoA-I-containing lipoproteins may facilitate the SR-BI-mediated uptake of HDL lipid.

Adrenal Glands↗
PubMed1996

A two-component histidine kinase gene that functions in Dictyostelium development.

A mutant which failed to complete development was isolated from a population of cells that had been subjected to insertional mutagenesis using restriction enzyme-mediated integration. The disrupted gene, dhkA, encodes the conserved motifs of a histidine kinase as well as the response regulator domain. It is likely that the histidine in DhkA is autophosphorylated and the phosphate passed to one or more response regulators. Such two-component systems function in a variety of bacterial signal transduction pathways and have been characterized recently in yeast and Arabidopsis. In Dictyostelium, we found that DhkA functions both in the regulation of prestalk gene expression and in the control of the terminal differentiation of prespore cells.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1996

A microstructural approach to cytoskeletal mechanics based on tensegrity.

Mechanical properties of living cells are commonly described in terms of the laws of continuum mechanics. The purpose of this report is to consider the implications of an alternative approach that emphasizes the discrete nature of stress bearing elements in the cell and is based on the known structural properties of the cytoskeleton. We have noted previously that tensegrity architecture seems to capture essential qualitative features of cytoskeletal shape distortion in adherent cells (Ingber, 1993a; Wang et al., 1993). Here we extend those qualitative notions into a formal microstructural analysis. On the basis of that analysis we attempt to identify unifying principles that might underlie the shape stability of the cytoskeleton. For simplicity, we focus on a tensegrity structure containing six rigid struts interconnected by 24 linearly elastic cables. Cables carry initial tension ("prestress") counterbalanced by compression of struts. Two cases of interconnectedness between cables and struts are considered: one where they are connected by pin-joints, and the other where the cables run through frictionless loops at the junctions. At the molecular level, the pinned structure may represent the case in which different cytoskeletal filaments are cross-linked whereas the looped structure represents the case where they are free to slip past one another. The system is then subjected to uniaxial stretching. Using the principal of virtual work, stretching force vs. extension and structural stiffness vs. stretching force relationships are calculated for different prestresses. The stiffness is found to increase with increasing prestress and, at a given prestress, to increase approximately linearly with increasing stretching force. This behavior is consistent with observations in living endothelial cells exposed to shear stresses (Wang & Ingber, 1994). At a given prestress, the pinned structure is found to be stiffer than the looped one, a result consistent with data on mechanical behavior of isolated, cross-linked and uncross-linked actin networks (Wachsstock et al., 1993). On the basis of our analysis we concluded that architecture and the prestress of the cytoskeleton might be key features that underlie a cell's ability to regulate its shape.

Animals↗
PubMed1996

Interleukin 8 is induced by cholesterol loading of macrophages and expressed by macrophage foam cells in human atheroma.

In order to identify novel genes expressed in macrophage-derived foam cells, we used a multigene assay to examine the expression of genes in control versus cholesterol-loaded macrophages. We compared THP-1 macrophages incubated with or without acetylated LDL (acLDL) +/- acyl-CoA:cholesterol O-acyltransferase (ACAT) inhibitor (compound 58035) for 20 h and assessed changes in mRNA of chemokines, growth factors, interleukins, and adhesion molecules. Among 49 genes examined, an increase in mRNA was observed only for interleukin 8 (IL-8) in THP-1 macrophages. Northern analysis confirmed a 3- to 4-fold increase of IL-8 mRNA and an enzyme-linked immunosorbent assay (ELISA) revealed a corresponding increase in IL-8 in conditioned medium. Oxidized LDL (oxLDL) also induced IL-8 mRNA, but native LDL had no effect. 58035 had a moderate effect on IL-8 induction by acLDL. AcLDL-induced IL-8 expression was concentration- and time-dependent. The time course of IL-8 induction paralleled that of cholesterol loading. MCP-1, a chemokine implicated in recruiting monocytes in atherogenesis, was also induced by acLDL. The induction of MCP-1, however, peaked at 1 h after addition of acLDL and returned to basal level by 20 h while IL-8 induction peaked at 8 h and was still 2-fold higher than basal level at 20 h. IL-8 induction was also observed in fresh human monocyte-derived macrophage cells treated with acLDL. Finally, immunohistochemistry and in situ hybridization studies using specimens of human coronary atheromas showed expression of IL-8 mRNA in a macrophage-rich area. We conclude that IL-8 is induced in macrophage foam cells as a response to cholesterol loading. The chemoattractant and/or mitogenic effects of IL-8 on neutrophils, T cells, smooth muscle, or vascular endothelial cells may contribute to the progression and complications of atherosclerosis.

Arteriosclerosis↗
PubMed1996

Effects of renin gene transfer on blood pressure and renin gene expression in a congenic strain of Dahl salt-resistant rats.

To investigate whether a BP-regulatory locus exists in the vicinity of the renin locus on rat chromosome 13, we transferred this chromosome segment from the Dahl salt-sensitive (S) rat onto the genetic background of the Dahl salt-resistant (R) rat. In congenic Dahl R rats carrying the S renin gene and fed an 8% salt diet, systolic BP was significantly lower than in progenitor Dahl R rats: 127 +/- 1 mmHg versus 138 +/- 4 mmHg, respectively (P < 0.05). Moreover, the decreased BP in the congenic Dahl R strain was associated with decreased kidney renin mRNA and decreased plasma renin concentration. These findings demonstrate that the Dahl S strain carries alleles in or near the renin locus that confer lower plasma renin concentration and lower BP than the corresponding alleles in the Dahl R strain, at least when studied on the genetic background of the Dahl R rat and in the environment of a high salt diet. The occurrence of coincident reductions in kidney renin mRNA, plasma renin concentration, and BP after interstrain transfer of naturally occurring renin gene variants strongly suggests that genetically determined variation in renin gene expression can affect BP.

Alleles↗
PubMed1996

Detection of 11q13 amplification as the origin of a homogeneously staining region in small cell lung cancer by chromosome microdissection.

Chromosomal homogeneous staining region (hsr), which is a cytogenetic indication of gene amplification, was found in the pleural effusion (BHII) of a patient with small cell lung cancer (SCLC) after failure of multiple drug treatments. Amplification of band 11q13 was identified as the origin of the hsr by means of chromosomal microdissection combined with G-banding, DNA amplification by polymerase chain reaction, and fluorescence in situ hybridization (micro-FISH). In situ hybridization with the biotin-labeled DNA probe generated from the hsrs of BHII to the cell line BHI, which was established from the lymph node metastasis prior to chemotherapy, revealed the preexistence of 11q13 amplification. This ruled out the possibility of therapeutic induction of the 11q13 amplification. However, the hsr-bearing marker chromosomes were identified by the micro-FISH approach as der(21)(Xqter-->Xq24::hsr(11)(q13)::21p11-->21qter+ ++) in BHII but as der(11)t(3;11)(q21;q13)hsr(11)(q13) in BHI. This suggests that 11q13 DNA sequence amplification may occur first and is then followed by various types of structural rearrangements. FISH analysis with INT2/FGF3 and HST1/FGF4 probes revealed that these protooncogenes were coamplified in the hsrs of BHI and BHII. The results obtained suggest that 11q13 amplification and the successive structural rearrangement may play an important role in the progression of the disease and its therapeutic response.

Carcinoma, Small Cell↗
PubMed1996

Uniformity of perfusion in all regions of the human heart by warm continuous retrograde cardioplegia.

BACKGROUND: Animal models have suggested that retrograde cardioplegia may be poorly distributed to septal and right ventricular regions of the heart; if true, this may have dangerous implications for warm continuous retrograde cardioplegia in humans. We have previously shown that blood gases from coronary arteries during warm continuous retrograde cardioplegia represent postcapillary "venous" gases and are reflective of myocardial perfusion. METHODS: To determine regional differences in perfusion during warm continuous retrograde cardioplegia we obtained blood gases from three regions of the heart in 141 consecutive patients undergoing coronary artery bypass grafting, aortic valve replacement, or both. Right heart perfusion was determined by blood gases from the right coronary artery orifice, acute marginal, or posterior descending coronary arteries; circumflex or lateral wall perfusion was determined by samples from obtuse marginal or intermediate coronary arteries; and anterior wall/septal perfusion was determined by left anterior descending and diagonal coronary artery blood gases. Warm continuous retrograde cardioplegia flow ranged from 150 to 300 mL/min depending on heart size. A mean of 4 +/- 1 samples/patient were obtained. RESULTS: There were no regional differences in postcapillary pH, carbon dioxide tension, or CO2 production during warm continuous retrograde cardioplegia. Oxygen tensions were lower in the right and anterior/septal regions of the heart, implying more O2 uptake. No regional acidosis, consistent with poor perfusion, could be detected. CONCLUSIONS: We conclude that, unlike experimental models, regional myocardial perfusion, including the right heart, is uniform during "high-flow" warm continuous retrograde cardioplegia in humans.

Carbon Dioxide↗
PubMed1996

Delayed primary repair of intrathoracic esophageal perforation: is it safe?

The management of intrathoracic esophageal perforation with delayed diagnosis is a subject of controversy. Because of the obvious advantages of primary repair as a simple single-stage operation, this technique was preferentially used to treat 18 of 22 consecutive patients with esophageal perforation. These patients were stratified into three groups according to the time interval between perforation and repair: group A, less than 6 hours, five patients (28%); group B, 6 to 24 hours, six patients (33%); and group C, more than 24 hours, seven patients (39%). Group A patients were older (p < 0.05) and group B had fewer iatrogenic perforations (B, 17%; A, 80%; C, 57%, p < 0.1). Additional tissue was used to buttress the repair site in all three groups (A, 3/5 patients, 60%; B, 4/6 patients, 67%; C, 6/7 patients, 86%; p = not significant). In seven patients (39%), a fundic wrap was used to reinforce the site of primary repair. The outcomes of the three groups were analyzed. Group A had the lowest proportion of postoperative leaks (A, 0/4 patients, 0%; B, 4/6 patients, 67%; C, 5/6 patients, 83%; p < 0.05) and postoperative morbidity (A, 2/5 patients, 40%; B, 6/6 patients, 100%; C, 6/7 patients, 86%; p < 0.1). However the increased incidence of leak and morbidity did not lead to an increase in mortality. One death occurred in each group, with an overall mortality of 17% (A, 1/5 patients, 20%; B, 1/6 patients, 17%; C, 1/7 patients, 14%; p = not significant). We conclude that in the era of advanced intensive care capabilities, primary repair of intrathoracic esophageal perforation can be safely accomplished in most patients regardless of the time interval between perforation and operation. Leakage at the suture site is common unless primary repair is carried out without delay. Postoperative leakage, however, is usually inconsequential and does not necessarily result in an adverse outcome.

Aged↗
PubMed1996

Leukocyte adhesion to vascular endothelium induces E-selectin linkage to the actin cytoskeleton.

We have examined functions of the cytoplasmic domain of E-selectin, an inducible endothelial transmembrane protein, especially its ability to associate with the cytoskeleton during leukocyte adhesion. Confocal microscopy of interleukin-1 beta (IL-1 beta)-activated human umbilical vein endothelial cells (HUVEC) visualized clustering of E-selectin molecules in the vicinity of leukocyte-endothelial cell attachment sites. A detergent based extraction and Western blotting procedure demonstrated an association of E-selectin with the insoluble (cytoskeletal) fraction of endothelial monolayers that correlated with adhesion of leukocytes via an E-selectin-dependent mechanism. A mutant form of E-selectin lacking the cytoplasmic domain (tailless E-selectin) was expressed in COS-7 cell and supported leukocyte attachment (in a nonstatic adhesion assay) in a fashion similar to the native E-selectin molecule, but failed to become associated with the cytoskeletal fraction. To identify the cytoskeletal components that associate with the cytoplasmic domain of E-selectin, paramagnetic beads coated with the adhesion-blocking anti-E-selectin monoclonal antibody H18/7 were incubated with IL-1 beta-activated HUVEC, and then subjected to detergent extraction and magnetic separation. Certain actin-associated proteins, including alpha-actinin, vinculin, filamin, paxillin, as well as focal adhesion kinase (FAK), were copurified by this procedure, however talin was not. When a mechanical stress was applied to H18/7-coated ferromagnetic beads bound to the surface of IL-1 beta-activated HUVEC, using a magnetical twisting cytometer, the observed resistance to the applied stress was inhibited by cytochalasin D, thus demonstrating transmembrane cytoskeletal mechanical linkage. COS-7 cells transfected with the tailless E-selectin failed to show resistance to the twisting stress. Taken together, these data indicate that leukocyte adhesion to cytokine-activated HUVEC induces transmembrane cytoskeletal linkage of E-selectin through its cytoplasmic domain, a process which may have important implications for cell-cell signaling as well as mechanical anchoring during leukocyte-endothelial adhesive interactions.

Actins↗
PubMed1996

Cross-validation of non-exercise predictions of VO2peak in women.

The purpose of this investigation was to cross-validate non-exercise (N-Ex %fat and N-Ex BMI) models for predicting VO2peak in females, and to evaluate the validity of these models in estimating fitness status, based on a < 9 METs cardiovascular fitness/health-risk criterion. Subjects were 165 females who completed the PA-R activity scale and were evaluated for VO2peak and body composition. The cross-validation statistics for the N-Ex %fat and N-Ex BMI models were: ryy' = 0.86, E = 6.3 (ml.kg-1.min-1), and ryy' = 0.81, E = 6.9 (ml.kg-1.min-1), respectively. Both models were found to accurately identify 87% of the subjects with VO2peak < 9 METs. The statistics associated with the < 9 MET criterion were: ryy' = 0.73, E = 3.4 (ml.kg-1.min-1), and ryy' = 0.80, E = 4.5 (ml.kg-1.min-1), for N-Ex %fat and N-Ex BMI, respectively. The N-Ex models yielded values similar to those reported previously (Jackson, A. S., S. N. Blair, M. T. Mahar, L. T. Wier, R. M. Ross, and J. E. Stuteville. Prediction of functional aerobic capacity without exercise testing. Med. Sci. Sports Exerc. 22:863-870, 1990). When exercise testing is not an option, the present N-Ex models provide an alternative method for predicting VO2peak in females.

Adolescent↗