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Biomedical subjects

Z Fan

Publications and source records attributed to Z Fan.

195 records · Page 11Linked to original sources
PubMed1989

Amantadine-induced afterpotentials and automaticity in guinea pig ventricular myocytes.

The ionic mechanisms of amantadine-induced changes in membrane potential and automatic activity in guinea pig ventricular myocytes were studied using the suction-pipette whole-cell clamp method. While 25-100 microM amantadine decreased the action potential amplitude and duration, 200 and 400 microM amantadine lengthened the action potential duration and decreased the maximum diastolic potential with an appearance of diastolic depolarization and automaticity. In the presence of 25-100 microM amantadine, the preparations developed an afterpotential due to incomplete repolarization and a delayed afterdepolarization that eventually brought about triggered automaticity. The former type of afterpotential was abolished by tetrodotoxin (TTX) and the latter by Co2+. Spontaneous activity from the diastolic depolarization was also abolished by Co2+ but not by Cs+. Amantadine suppressed the calcium current to as much as half of the control at the concentrations used (25-200 microM). The drug also produced a depression of the inward rectifier K+ current. The outward current showing time-dependent decay was activated at the plateau voltages by concentrations lower than 100 microM, whereas the delayed outward K+ current was depressed by the drug in a concentration-dependent manner at more positive potentials. Amantadine activated the TTX-sensitive and TTX-insensitive inward currents on repolarization from depolarized states, without producing the transient inward current. These results indicate that the amantadine-induced diastolic depolarization and afterpotentials are caused by changes in multiple ionic currents and that, therefore, the drug can be used as a unique model for the study of arrhythmogenesis.

Amantadine↗
PubMed1989

Activation of ATP-sensitive outward K+ current by nicorandil (2-nicotinamidoethyl nitrate) in isolated ventricular myocytes.

The vasodilatory agent, nicorandil (2-nicotinamidoethyl nitrate) activates an outward K+ current in cardiac and vascular smooth muscle. This current was studied with the patch clamp technique using isolated guinea pig and rabbit ventricular myocytes. Nicorandil (10(-5) and 10(-4) M) shortened the action potential duration without any significant change in the resting membrane potential. Under voltage clamp, nicorandil increased the time-independent outward current at potentials positive to -80 mV, and decreased the inward current at potentials negative to -90 mV. The drug did not affect Ca++ current activated upon depolarization from the holding potential of -30 mV, or did it influence delayed outward K+ current on repolarization. In rabbit myocytes, nicorandil did not increase the Ca++-sensitive and -insensitive transient outward K+ currents. When the ATP concentration of the pipette solution was reduced from 5 to 2 to 3 mM, nicorandil produced a large increase in outward current, which decreased slightly with time. The increased outward current was antagonized by raising the intracellular ATP concentration. Nicorandil increased the probability of opening of the ATP-sensitive single channel current without affecting its unitary amplitude. These results indicate that nicorandil activates the ATP-sensitive K+ current, which is responsible for shortening of the action potential duration.

Action Potentials↗
PubMedDate not supplied

Treatment of unresectable primary liver cancer: with reference to cytoreduction and sequential resection.

Unquestionably, progress has been made in the early detection and early treatment of primary liver cancers (PLCs), although most remain unresectable, mainly because the cancer is advanced and coexists with liver cirrhosis, particularly in Oriental patients. Thanks to the progress of regional cancer therapy, a multidisciplinary approach, and changing concepts about surgical oncology, it has been proved that some unresectable but not far advanced PLCs are potentially convertible to being resectable, particularly those cancers confined to the right lobe of a cirrhotic liver. A retrospective analysis of 571 unresectable PLCs revealed the following: (1) There was an increase in 5-year survivals in the series, from 0% during the 1960s (n = 61), to 4.8% during the 1970s (n = 163), to 21.2% during the 1980s (n = 347). It might be a result of the increase in double- or triple-modality treatments in these series (from 9.8%, to 19.6%, to 70.3%, respectively) and in the sequential resection rate after cytoreduction (from 0%, to 2.5%, to 14.7%). (2) The combination of hepatic artery ligation, hepatic artery cannulation and infusion, and intrahepatic arterial radioimmunotherapy has resulted in better shrinkage of the tumor, a higher sequential resection rate, and a higher 5-year survival (28.2%). (3) Of the 55 patients who had initially unresectable PLCs and yielded "cytoreduction and sequential resection," the 5-year survival was 58.5%. It is concluded that cytoreduction and sequential resection might be an important approach to improving the prognosis of patients with unresectable PLCs.

Adolescent↗
PubMedDate not supplied

Poly(ethylene glycol)-conjugated anti-EGF receptor antibody C225 with radiometal chelator attached to the termini of polymer chains.

Several biological barriers, including significant liver uptake, limit the clinical application of radiolabeled antibodies in radioimmunoscintigraphy. Here, a general approach is described for radiolabeling of monoclonal antibodies conjugated with poly(ethylene glycol) (PEG). This strategy is demonstrated with C225, a monoclonal antibody directed against epidermal growth factor (EGF) receptor. We synthesized a heterofunctional PEG with one end attached to a radiometal chelator, diethylenetriaminepentaacetic acid (DTPA), and the other end to a protected thiol group, S-acetylthioacetate. After a deprotection step, the resulting DTPA-PEG-SH was conjugated to maleimide-activated C225 to yield DTPA-PEG-C225 conjugate. Characterization of DTPA-PEG-C225 with immunoprecipitation and Western blot analysis revealed that the conjugate was biologically active in binding to the EGF receptor in A431 cells. Competitive EGF receptor binding assay in MDA-MB-468 cells showed that DTPA-PEG-C225, with up to 60% of the amino groups in C225 substituted, retained 66% of C225's binding affinity. Moreover, DTPA-PEG-C225 with increasing degrees of NH(2) substitution from 20% to 70% retained the activity of C225 to induce apoptosis in DiFi cells. More importantly, DTPA-PEG-C225 demonstrated less nonspecific interaction than DTPA-C225. Pharmacokinetic analysis using (111)In-labeled compounds revealed narrower steady-state distribution of (111)In-DTPA-PEG-C225 than (111)In-DTPA-C225, probably due to reduced nonspecific binding of PEG-modified antibody to tissues. The terminal half-life (t(1/2,)(gamma)) of (111)In-DTPA-PEG-C225, 21.1 h, was shorter than that of (111)In-DTPA-C225, 52.9 h. These data suggest that (111)In-DTPA-PEG-C225 may provide better imaging characteristics than (111)In-DTPA-C225, and that using PEG as a linker between the monoclonal antibody and DTPA may be a promising strategy in optimizing the imaging characteristics of immunoscintigraphic agents.

Antibodies, Monoclonal↗
PubMedDate not supplied

Measurement of access flow during hemodialysis using the constant infusion approach.

With reversed placement of blood lines and with a peripheral arteriovenous access, hemodialysis recirculation (R) consists of a local access component, and a central cardiopulmonary component that must be separated for the calculation of access flow (Qac) using indicator dilution principles. With indicator injections that follow constant infusion principles Qac = (1 - Rx)/(Rx(1 - CPR)) x (Qb,x - UFR), where Qb is the extracorporeal blood flow, where UFR is the ultrafiltration rate, and where the index x indicates reversed placement of blood lines. CPR, the amount of cardiopulmonary recirculation (CPR = Qac/CO) is determined from two recirculation measurements with correct (index n) and with reversed (index x) placement of blood lines CPR = Rn(1 - Rx)/Rx(1 - Rn) x (Qb,x - UFR)/Qb,n. Qac was measured in 11 hemodialysis (HD) patients using a thermodilution device tested in an in vitro set-up based on constant infusion principles. Mean Qac was 1.135 L/min and 1.054 L/min for measurements done early and late in dialysis. The coefficient of variation was +/-7.3% and +/-8.6%, respectively. Repeated measurements of access flow in HD patients showed good reproducibility (Qac.1 = 1.01*Qac.0, r2 = 0.98), with the regression line not different from the line of identity; however, in vivo results remain to be validated by an independent technique.

Arteriovenous Shunt, Surgical↗
PubMedDate not supplied

Involvement of p21Waf1 in mediating inhibition of paclitaxel-induced apoptosis by epidermal growth factor in MDA-MB-468 human breast cancer cells.

Paclitaxel (Taxol) is currently one of the most widely used anti-cancer drugs for human breast cancer. In this study, we investigated how epidermal growth factor (EGF) modulated paclitaxel-induced apoptosis in MDA-MB-468 human breast adenocarcinoma cells. Pulse-exposure of the cells to paclitaxel resulted in cell death through apoptosis. When EGF was present during the post-paclitaxel culture period, this paclitaxel-induced apoptosis was inhibited in an EGF dose-dependent manner. The induction of apoptosis by paclitaxel was accompanied by an elevated level of p34cdc2 kinase activity, which was inhibited in the presence of EGF during the post-paclitaxel culture period. Exposure of MDA-MB-468 cells to EGF induced expression of the cyclin-dependent kinase inhibitor p21Waf1. Incubation of paclitaxel-treated MDA-MB-468 cell extracts with EGF-treated MDA-MB-468 cell extract, which exhibited elevation of p34cdc2 activity, inhibited the kinase activity. This inhibition was not observed with p21Waf1-immunodepleted EGF-treated cell extract. Transfection of the cells with p21Waf1 antisense oligonucleotide abolished the induction of p21Waf1 and also significantly reduced inhibition by EGF of paclitaxel-induced apoptosis. These studies demonstrate that p21Waf1 plays a key role in the inhibition of paclitaxel-induced apoptosis by EGF in MDA-MB-468 cells.

Adenocarcinoma↗
PubMedDate not supplied

Regulation of anabolic and catabolic gene expression in normal and osteoarthritic adult human articular chondrocytes by osteogenic protein-1.

OBJECTIVE: Osteoarthritis is characterized by dramatic changes in chondrocyte metabolism including the overexpression of catabolic enzymes, but also a lack of anabolic activity. In this respect, osteogenic protein 1 (OP-1) appears to be one of the most potent anabolic factors of chondrocytes. In this study, we were interested in: (1) whether recombinant human OP-1 exerts its anabolic effects also on osteoarthritic chondrocytes, (2) whether OP-1 modulates the expression of catabolic genes, and (3) whether the BMP effects are related to the expression levels of its intracellular mediators (R- and I-Smads). METHODS: Chondrocytes were isolated from cartilage of either normal (n = 5) or osteoarthritic (n = 8) human knee joints and cultured in short-term high-density monolayer cultures with and without recombinant OP-1. RNA was isolated and analyzed for mRNA expression levels of anabolic (aggrecan, collagen type II), catabolic (MMP-1, -3, -13, ADAMTS-4), and intracellular signaling mediators (Smad 1, 4, 5, 6, 7, and 8) by quantitative online PCR. RESULTS: After OP-1 stimulation, the anabolic genes were significantly up-regulated in osteoarthritic chondrocytes in comparison to normal chondrocytes. Neither in normal nor osteoarthritic chondrocytes were significant changes observed for the matrix degrading enzymes. Smads were also expressed in both normal and osteoarthritic cells at roughly the same level with and without stimulation with OP-1. CONCLUSION: Osteoarthritic chondrocytes are not hypo-responsive to anabolic stimulation by OP-1. Thus, human recombinant OP-1 could be a suitable anabolic activator of osteoarthritic chondrocytes. This might be of particular interest as chondrocytes themselves showed very low levels of OP-1 expression.

ADAM Proteins↗
PubMedDate not supplied

[Isolation and characterization of a novel dehydrin gene from Capsella bursa-pastoris].

A novel dehydrin gene designated as Cbcor29 was cloned from Capsella bursa-pastoris by rapid amplification of cDNA ends (RACE) and genome walker technique. The full-length cDNA of Cbcor29 was 1101 bp long with a 783 bp open reading frame (ORF), encoding a putative protein of 261 amino acids. Like other dehydrin proteins, CbCOR29 contained a high percentage of charged and polar amino acids, in which Cys and Trp amino acids were absent. Besides, predicted CbCOR29 protein possesses three conserved repeats of the characterized Lys-rich domains (K-segments), and a Ser-rich domain (S-segment) prior to the first Lys-rich domain, which presented a typical SK3 structure of dehydrins. Analysis of Cbcor29 genomic DNA revealed that it contained 2 exons and 1 intron, which was a typical character of dehydrin genes. Subsequent bioinformatic analysis also showed that the sequence of CbCOR29 had high homology with other dehydrin proteins, especially with cor47 from Arabidopsis thaliana. Moreover, semi-quantitative RT-PCR revealed that the expression of Cbcor29 could be induced by exposure to drought, low-temperature, NaCl and exogenous ABA treatment respectively. Our study implied that the Cbcor29 gene was a new member of the dehydrin gene family and might exert functions in drought-, cold- and salt- responsiveness in Capsella bursa-pastoris.

Amino Acid Sequence↗