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Biomedical subjects

X He

Publications and source records attributed to X He.

458 records · Page 26Linked to original sources

Percutaneous implantation of a Port-Catheter System using the left subclavian artery.

PURPOSE: To evaluate the safety and feasibility of a percutaneous Port-Catheter System (PCS) implanted via the subclavian artery (SCA) for regional chemotherapy or chemoembolization of thoracic, abdominal, and pelvic malignant tumors. METHODS: Percutaneous puncture of the SCA was performed in 256 patients with thoracic, abdominal, or pelvic malignant tumors; then a catheter was inserted into the target artery. After the first transcatheter chemotherapy or chemoembolization with an emulsion of lipiodol and anticancer agents, an indwelling catheter was introduced with its tip placed in the target artery and its end subcutaneously connected to a port. RESULTS: The procedure was successfully completed in all 256 cases (100%). The indwelling catheter tip was satisfactorily placed in the target arteries in 242 cases (98%). Complications attributable to the procedure occurred in 20 (7.8%) cases, including pneumothorax (n = 10, 4%), hemothorax (n = 1, 0.4%), infections in the pocket (n = 4, 1.6%), and hematoma at the puncture site (n = 5, 2%). There were no severe sequelae or deaths. The duration of PCS usage was 1-36 months (median 9.5 months). During the course of treatment, occlusion of the target artery occurred in 20 cases (7.8%). Dislocation of the tip of the indwelling catheter occurred in 12 cases (4.7%); in 10 of the 12, the tip of the indwelling catheter was repositioned into the target artery. In all 10 cases no large symptomatic hematomas developed after the PCS was removed. CONCLUSION: Percutaneous PCS implantation via the left SCA, a relatively new procedure, is a safe and less invasive treatment approach than surgical placement for malignancies.

Abdominal Neoplasms↗

Flow in T-bifurcations: effect of the sharpness of the flow divider.

The local geometry of a bifurcation has been hypothesized to be a potential geometrical risk factor for the development of atherosclerosis. While flow division and branch area ratios clearly affect the flow field, the importance of the flow divider shape is not as clear. A fast spectral element computational fluid mechanics (CFD) solver was used to simulate flow through 90 degrees T-bifurcations with three different flow divider shapes. Other factors, such as flow partition, area ratio, and bifurcation angle, were kept constant. A Reynolds number range of 15 to 350 was studied to bracket experimental results in the literature. The variation in the sharpness of the corners had a dramatic effect on both the flow field and wall shear stress distribution in the side branch, but little effect on the flow in the main tube. The magnitude of reverse velocities and wall shear stress in the side branch increased linearly over a physiological range of Reynolds number and corner shape. This paper verifies the accuracy and usefulness of spectral element CFD in studying three-dimensional hemodynamics.

Arteriosclerosis↗

High-yield affinity alkylation of the atrial natriuretic factor receptor binding site.

To facilitate characterization of the atrial natriuretic factor (ANF) receptor, we have developed an affinity labeling procedure, stepwise affinity labeling, which allows specific labeling of ANF binding sites in adrenal plasma membranes at high yields. An iodoacetyl (IAc-), bromoacetyl (BrAc-), or maleimidobenzoyl group was attached to the amino-terminal alpha-amino group of the ANF(4-28) peptide, and the peptide derivatives were radioiodinated at Tyr-28 to obtain affinity reagents, N4alpha-IAc-[125I]ANF(4-28), N4alpha-BrAc-[125I]ANF(4-28), and N4alpha-(maleimidobenzoyl)-[125I]ANF(4-28). Receptor labeling was carried out in a stepwise fashion as follows: (1) Membranes were treated with p-chloromercuriobenzenesulfonic acid (PCMBS) or N-ethylmaleimide to block sulfhydryl groups; (2) the affinity reagent was allowed to bind to the receptor at 0 degrees C for 1 h; and (3) the membranes were washed to remove unbound reagent and were incubated at room temperature to effect alkylation reaction. Sodium dodecylsulfate (SDS)-polyacrylamide gel electrophoresis (PAGE) followed by autoradiography revealed specific labeling of a 130-kDa ANF receptor. On the basis of 125I-radioactivity incorporated, the labeling yields were estimated to be 70%, 52%, and 21% for the reactions with IAc-[125I]ANF(4-28), BrAc-[125I]ANF(4-28), and (maleimidobenzoyl)-[125I]ANF(4-28), respectively. The efficiency of receptor labeling by the stepwise procedure using IAc-[125I]ANF(4-28) was 27-fold greater than that obtained by photoaffinity labeling using N3Bz-[125I]ANF(4-28) and 63-fold greater than that by direct cross-linking using disuccinimidylsuberate and [125I]ANF(4-28) under comparable conditions. Digestion of the membrane protein labeled with IAc-[125I]ANF(4-28) by BrCN, endoproteinase Glu-C, and endoproteinase Lys-C gave single radiolabeled bands with apparent masses of 40, 18, and 29 kDa, respectively. Reversed-phase HPLC separation of the digests also gave single major peaks. The confinement of the affinity label to one major fragment in each digest suggests that the cross-linking occurred at a single or a limited number of sites. The stepwise affinity labeling with the high cross-linking yield and specificity may be useful for analyzing the ANF receptor binding site structure.

Adrenal Cortex↗

Modeling chemoattractant-elicited relocalization of myosin filaments in Dictyostelium.

Dictyostelium myosin is able to assemble into filaments that, when visualized under normal conditions, appear to be uniformly distributed throughout the cytoplasm. After stimulation by the chemoattractant cAMP, these filaments quickly diminish in the cellular medulla and accumulate in the cortex. A general hypothesis to explain the mechanism of this relocalization proposes that one or more of the chemical coefficients governing filament polymerization is precisely regulated by some sort of intracellular second messenger. To investigate this hypothesis we formulated a simple theoretical model of myosin polymerization and then used this model to analyze the resting state of the cell and various scenarios for initializing a transition to the activated state. In general, we found that the relocalization of filaments could be realized if a second messenger increased the elongation and (or) the nucleation coefficients for filament assembly in cortical ectoplasm and (or) if the messenger decreased these parameters in the cellular medulla. By comparing these limiting cases with experimental observations, we concluded that models in which redistribution of myosin is achieved by decreasing filament stability in the medulla are the most likely candidates.

Animals↗

A safe, effective in vivo gene therapy for melanoma using tyrosinase promoter-driven cytosine deaminase gene.

This study was designed to develop a safe, effective gene therapy for disseminated melanoma. We constructed retroviral vectors containing a tyrosinase promoter-cytosine deaminase expression cassette (Tyr/CD), and demonstrated that the tyrosinase promoter conferred a selective expression of cytosine deaminase (CD) gene in B16 melanoma cells, especially when the Tyr/CD cassette inserted in 3'LTR region of a retroviral vector. In vivo gene therapy for the intraperitoneally disseminated melanoma using Tyr/CD retrovirus-producing cells and 5-fluorocytosine (5-FC) showed that retroviruses produced in situ were capable of infecting tumor xenografts and bone marrow cells in animal model, and survival rates were prolonged significantly as compared with those treated with CD2 retrovirus-producing cells and 5-FC. Importantly, the treatment-related bone marrow suppression was not observed in the former treatment, while profound bone marrow suppression was observed in the latter treatment. In vivo gene therapy using retrovirus-producing cells containing suicide gene under the control of a tissue-specific promoter and 5-FC administration is safer and more effective for the treatment of disseminated melanoma, as compared with retrovirus-producing cells containing the gene under the control of a universal promoter and 5-FC.

Animals↗

Detection of p53 protein accumulation in sputum and lung adenocarcinoma associated with indoor exposure to unvented coal smoke in China.

Lung cancer in Xuan Wei (XW), China has been linked to exposure to unvented coal smoke and adenocarcinoma, especially bronchioloalveolar carcinoma, is most common. p53 mutations occur commonly in lung cancers and usually generate detectable levels of p53 protein accumulation. Sputum is noninvasive to collect and ideal for screening p53 abnormalities. p53 protein accumulation was detected by immunohistochemistry in lung tumors and sputa from XW lung cancer patients to determine (1) the role of p53 in lung pathogenesis, and (2) feasibility of detecting p53 protein accumulation in sputum, p53 protein accumulation was detected in 73% (22/30) of lung adenocarcinomas from XW females exposed to coal emissions and significantly higher than the control cases (33%, p < 0.05). In sputum, we detected p53 overexpression in tumor cells in 54% (13/24) of XW cases and also in dysplastic cells (50% or 4/8). These findings suggest that p53 abnormalities is important in XW lung cancer etiology.

Adenocarcinoma↗

Application of a panel of antiganglioside monoclonal antibodies to cytologic specimens.

The cytologic evaluation of poorly differentiated tumors frequently poses a diagnostic dilemma as to the tissue of origin. To assess the diagnostic utility of monoclonal antibodies (MAbs) in these situations, we applied a panel of three highly purified MAbs specific for tumor-associated ganglioside epitopes to a diverse series of cytologic specimens. The panel was composed of DMAb-3, reactive with the epitope GalNAc beta 1-4 (NeuAc alpha 2-3)Gal- of GM2; DMAb-7, reactive with the epitope (NeuAc alpha 2-8NeuAc alpha 2-3)Gal beta 1-4(Glc or GlcNAc)- of GD3 and 3'8'-LD1; and DMAb-20, reactive with the epitope GalNAc beta 1-4(NeuAc alpha 2-8NeuAc alpha 2-3)Gal- of GD2. The cytologic material consisted of air-dried Cytospin preparations prepared predominantly from fine needle aspirates and stained with the ABC immunohistochemical method. Positive reactivity was recognized when greater than 5% of tumor cells stained with the antibody; lesser reactivity was called negative. DMAb-3 stained 9/14 (64%) glial tumors, 4/13 (31%) nonglial central nervous system tumors, 1/21 (5%) melanomas, 7/38 (18%) non-small cell carcinomas (NSCC), 1/15 (7%) small cell carcinomas (SCC), 0/9 (0%) lymphomas/leukemias, 2/10 (20%) sarcomas, 1/7 (14%) miscellaneous tumors and 2/2 (100%) reactive fluids. DMAb-7 recognized 14/14 (100%) glial tumors, 9/13 (69%) non-glial central nervous system tumors, 19/22 (86%) melanomas, 19/43 (44%) NSCC, 5/15 (33%) SCC, 2/9 (22%) lymphomas/leukemias, 6/10 (60%) sarcomas, 1/7 (14%) miscellaneous tumors and 4/4 (100%) reactive fluids. DMAb-20 stained 6/14 (43%) glial tumors, 2/13 (15%) nonglial central nervous system tumors, 1/21 (5%) melanomas, 4/38 (10%) NSCC, 0/15 (0%) SCC, 0/9 (0%) lymphomas/leukemias, 1/10 (10%) sarcomas, 1/7 (14%) miscellaneous tumors and 1/3 (33%) reactive fluids. The GD3-reactive DMAb-7 recognized a large portion of many tumor types and thus is not diagnostically useful alone. DMAb-3 and DMAb-20 were more selective and showed the strongest reactivity for glial tumors and minimal reactivity for melanomas, small cell carcinomas, and lymphomas or leukemias. DMAb-3 and DMAb-20 may be useful as components of a larger panel of MAbs in distinguishing between poorly differentiated tumors in samples derived from the central nervous system.

Antibodies, Monoclonal↗

Synthesis and resolution of novel 3'-substituted phenylalanine amides.

A convenient approach to the synthesis of ring-substituted phenylalanine amides is described. Phase transfer alkylation of N-(diphenylmethylene)amino acetonitrile or N-(diphenylmethylene)glycine ethyl ester provides alpha-substituted imines 2 and 6. After acid hydrolysis and esterification, resolution with alpha-chymotrypsin provided 3'-substituted phenylalanine analogs 9a-d which could easily be converted to N alpha-t-butyloxycarbonyl-phenylalanine amides for use in the synthesis of peptide analogs. The approach described here is amenable to the synthesis of 3-substituted phenylalanines with a wide variety of substituents for determination of structure-activity relationships of peptides.

Amides↗