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Biomedical subjects

Y H Tan

Publications and source records attributed to Y H Tan.

At least 91 records · Page 5Linked to original sources
PubMed1989

[Negative inotropic effect of 3,6-dimethamidodibenzopyriodonium citrate (I-65) on guinea pig papillary muscles].

The effects of 3,6-dimethamidodibenzopyriodonium citrate (I-65) on the contractile response of electrically paced guinea pig papillary muscles in vitro were studied. I-65 (0.1-300 mumol/L) decreased the contractile force and inhibited isoprenaline-induced restoration of the contractile response in papillary muscles rendered inexcitable by KCl 22 mmol/L. Both effects were concentration-dependent, and the IC50 were 36.0 and 7.3 mumol/L, respectively. I-65 antagonized the positive inotropic effects of Iso and CaCl2 in a non-competitive manner. Like verapamil, I-65 had a frequency-dependent negative inotropic effect, and delayed the recovery of post-rest potentiation. It is concluded that the negative inotropic effect of I-65 results not only from the reduction of Ca2+-influx through the sarcolemmal membrane, but also from the inhibition of Ca2+ translocation in the sarcoplasmic reticulum.

Animals↗
PubMed1989

[Effects of 3,6-dimethamidodibenzopyriodonium citrate (I-65) on action potentials and contractions in guinea pig papillary muscles].

Synchronous recordings of action potentials and contractile force in isolated guinea pig papillary muscles administered 3,6-dimethamidodibenzopyriodonium citrate (I-65) 30 mumol/L showed excitation-contraction uncoupling, ie, the contractile force was markedly depressed although the Vmax and amplitudes of the action potentials were unaffected. At the same concentration, I-65 shortened the duration of the action potentials at 50% and 90% repolarization. However, I-65 at lower concentrations (1-10 mumol/L) decreased Vmax and the amplitude of the slow action potentials which were elicited by isoprenaline in papillary muscles were rendered partially depolarized by KCl 25 mmol/L Tyrode solution. These effects were partially reversed by elevation of the concentration of Ca2+ from 2.7 to 5.4 mmol/L. I-65 also suppressed the abnormal automaticity elicited by BaCl2 and DAD and triggered activity induced by ouabain. The results suggest that I-65 may be a calcium channel blocker.

Action Potentials↗
PubMed1988

Preparation and characterization of biotinylated probes for the beta-interferon receptor.

1. Recently we described the isolation of the beta-interferon receptor [Zhang et al. (1986) J. biol. Chem. 261, 8017-8021]. A highly purified product was obtained but in low quantities. 2. The use of biotinylated beta-interferon as a ligand represents an alternate approach to receptor isolation. 3. We have prepared and characterized the derivatives N-(biotinyl)- and N-(biotinyl-epsilon-aminocaproyl)-recombinant human [Ser17]-interferon beta (B- and BC-recHuIFN beta). 4. Biotin incorporation does not result in any loss of antiviral activity, demonstrating the recognition of the derivative by the cell receptor. 5. The biotinylated recHuIFN beta binds specifically and reversibly to succinoylavidin or guanidine thiocyanate-stripped succinoylavidin linked to a Sepharose matrix. 6. Comparison of the competition curves obtained with [14C]biotin and [3H]biotinyl recHuIFN, in the presence of increasing concentrations of biotin suggests that the IFN moiety of the derivative has little effect on the affinity of biotin for avidin. 7. Biotinylated recHuIFN beta derivatives represent useful probes for the beta-IFN receptor.

Avidin↗
PubMed1988

Natural human interferon-beta in metastatic malignant melanoma. A phase II study.

A phase II trial of natural human fibroblast interferon (HuIFN-beta) in 15 previously untreated patients with advanced metastatic malignant melanoma is reported. It was given as out-patient treatment by 30 min i.v. infusion of 60 x 10(6) U/m2/day on 4 consecutive days each week. Systemic toxicity was acceptable to all patients except one who declined further treatment. Performance status of treated patients was good. Three patients had a partial response and 3 patients had stable disease. The median time to response was 13.3 weeks and the duration of response was 22.6 weeks. Responses were seen in lungs and soft tissues only and relapses were seen particularly in the central nervous system and the liver. Overall survival of the patients was only 20.7 weeks. Those who achieved a partial remission had a median survival of 34.7 weeks and those with disease stabilisation a survival of 22.0 weeks. HuIFN-beta is shown to have anti-tumour activity in advanced metastatic melanoma, although the unit dose of HuIFN-beta is much larger than that required to achieve similar anti-tumour activity with interferon-alpha.

Adult↗
PubMed1986

An early event in the interferon-induced transmembrane signaling process.

Human interferon stimulates a transient two- to threefold increase in the concentration of diacylglycerol and inositol tris-phosphate within 15 to 30 seconds of cell exposure to interferon. Antibodies to interferon inhibit this effect. The stimulation was measurable in isolated cell membranes exposed to interferon. Human alpha and beta, but not gamma, interferon stimulate this increase in cells containing the appropriate interferon receptor. The effect was proportional to the number of interferon receptors. Both the diacylglycerol increase and antiviral effects induced by interferon could be correlated in terms of dose dependence. Thus, a transient diacylglycerol increase is an early event in the interferon-induced transmembrane signaling process.

Animals↗
PubMed1986

The isolation of human beta-interferon receptor by wheat germ lectin affinity and immunosorbent column chromatographies.

Radioiodinated human beta-interferon-Ser 17 (Betaseron) was reversibly cross-linked to Daudi cells by dithiobis(succinimidylpropionate). The radioactive ligand was cross-linked to three macromolecules forming labeled complexes of apparent Mr values of 130,000, 220,000, and 320,000. Betaseron, human alpha-interferon, human interleukin 2 but not recombinant human gamma-interferon competed with the labeled ligand for binding to these putative receptor(s). Human leukocyte-produced gamma-interferon competed weakly with 125I-Betaseron for binding to Daudi cells. The Betaseron-receptor complex(es) was purified by passage through a wheat germ lectin column followed by chromatography on an anti-interferon immunosorbent column and semipreparative gel electrophoresis. The cross-linked ligand-receptor complex was shown to be highly purified by sodium dodecyl sulfate and acetic acid:urea:Triton X-100 polyacrylamide gel electrophoresis. It can be dissociated into the labeled Betaseron (Mr = 17,000) ligand and a receptor moiety which has an apparent molecular weight of 110,000. The chromatographic behavior of the ligand-receptor complex on wheat germ lectin column suggests that the receptor is a glycoprotein. The described procedure yielded about 1 microgram of Betaseron receptor from 10(10) Daudi cells, estimated to contain a maximum of about 15 micrograms of the receptor.

Binding, Competitive↗
PubMed1986

Rapid and transient rise in diacylglycerol concentration in Daudi cells exposed to interferon.

Human beta-interferon stimulates a 4-fold increase in the concentration of diacyglycerol and a 2-fold increase in the concentration of inositol monophosphate in Daudi (human B-lymphoblastoid) cells within 30 sec of exposure of the cells to interferon. The increase in diacylglycerol and in inositol monophosphate is transient and the concentrations of these compounds decrease to basal levels within 10 min. Preincubation of human beta-interferon with anti-interferon antibodies inhibits this effect as well as the binding of interferon to Daudi cells. Diacylglycerol concentrations were unaffected in mouse A9 cells (fibroblasts) incubated with human beta-interferon and in Daudi cells incubated with human gamma-interferon. Mouse A9 cells are insensitive to human interferon and Daudi cells are insensitive to human gamma-interferon. The magnitude of the increase in diacylglycerol concentration stimulated by interferon can be correlated to the interferon-induced inhibition of Daudi cell division in a dose-responsive manner. Phorbol 12-myristate 13-acetate also inhibits Daudi cell division in a dose-responsive manner. It is likely that the sharp and transient increase in diacylglycerol concentration represents one of the early biochemical changes in Daudi cells exposed to interferon.

B-Lymphocytes↗
PubMed1986

Combination of fibroblast interferon (HuIFN beta), carboxamide (DTIC), and cimetidine for advanced malignant melanoma.

In vitro synergism between interferons (IFNs) and chemotherapeutic drugs has been demonstrated, and an enhancement of IFN's antiproliferative effects when combined with cimetidine has been suggested in melanoma patients. In this pilot study, 12 patients with advanced malignant melanoma received HuIFN beta by 30 min i.v. infusion at 30 X 10(6) u/m2 day for 4 days, followed by i.v. decarbazine (DTIC) 1.0 g/m2 on day 5, repeated every 4 weeks. Oral cimetidine, 300 mg q.i.d., was given continuously. All the patients had visceral (bulky) metastases. No objective responses were observed; however, two patients had stable diseases for 16 and 20 weeks, respectively. Mild chills and fever with IFN, and mild to moderate emesis with DTIC, were noted. No additive haemopoietic or hepatic toxicity was observed. Combination of HuIFN beta, DTIC, and cimetidine is relatively nontoxic, but does not appear to have a significant antitumor activity in patients with advanced malignant melanoma.

Adult↗
PubMed1986

Extended phase I study of human beta-interferon in human cancer.

Ten patients with advanced cancer were treated with weekly intravenous escalating doses of human beta-interferon (HuIFN beta) 4 days each week. The starting dose of HuIFN beta was 3.0 X 10(6) units/m2 and the dose was doubled each week until dose-limiting toxicity was observed. Subjective toxicity included mild fevers and chills, malaise and flu-like symptoms. The lowest dose which caused suppression of the platelet and/or white cell count was 64 X 10(6) units daily, and the maximum dose given was 320 X 10(6) units daily. Both subjective and objective toxicity were not dose-related, easily managed and reversible. Serum interferon levels and the duration of measurable interferon activity on natural killer cells was in general dose-dependent. Two patients had an objective partial response, and two others showed stable disease while receiving HuIFN beta.

Adult↗
PubMed1986

Cervical intraepithelial neoplasia treated by perilesional injection of interferon.

Twelve patients with cervical intraepithelial neoplasia (CIN) were studied by colposcopy and cervical smears to elucidate the local response to interferon alpha and beta given by perilesional injections and to assess long-term disease remission. In all patients, local inflammatory response was seen and persisted throughout the treatment period. Selective toxic effect was evident by exfoliation of increasing proportion of degenerate to viable dyskaryotic cells, while the normal epithelial cells appeared unaffected, and by the progressive regression of the lesion. Interferon alpha induced complete remission in six of seven (85.7%) patients but three had recurrence 12 to 24 months later, while interferon beta induced complete remission in only two of five (40%) patients.

Colposcopy↗
PubMed1985

Characterization of human beta-interferon-binding sites on human cells.

Radioiodinated recombinant human beta-interferon (rHuIFN beta Ser), with almost full (greater than 90%) biological activity, was used to study the binding of human beta-interferon to Daudi cells. Specific binding was not observed with less biologically active (less than or equal to 10%) radioiodinated interferon. The bound radioiodinated interferon was shown to compete with human beta-interferon (HuIFN beta), rHuIFN beta Ser, human alpha-interferon (HuIFN alpha) and with human gamma-interferon (HuIFN gamma). Scatchard plot analyses suggest the presence of about 10,000 binding sites for HuIFN beta/Daudi cell. About 6,600 of these sites can be blocked by HuIFN alpha and 3,700 sites can be blocked by HuIFN gamma. The apparent Kd for HuIFN beta is 2.7 nM. The apparent Kd values for HuIFN alpha and HuIFN gamma are 3.7 and 1.1 nM, respectively. It was possible to demonstrate the cross-linking of HuIFN beta to two macromolecular components of Mr = 128,000 and 103,000. We propose the existence of at least two binding sites for HuIFN beta in Daudi cells, one site recognizing both HuIFN beta and HuIFN gamma, the other site recognizing both HuIFN beta and HuIFN alpha. Each site is capable of recognizing only HuIFN gamma or HuIFN alpha.

Binding, Competitive↗
PubMed1985

Human beta:alpha but not gamma interferon binding site is a product of the chromosome 21 interferon action gene.

The binding of human interferons to their binding site(s) was measured by the amount of radioiodinated human beta interferon (HuIFNbeta) displaceable by unlabeled human beta, alpha, and gamma interferon (HuIFNbeta, alpha, and gamma). By this approach, HuIFNbeta and HuIFNalpha were found to interact with specific binding sites in cell membranes derived from human cells and mouse-human cell hybrids containing chromosome 21 as their only human chromosome. Specific binding was not observed with cell membranes derived from parental mouse cells or from mouse-human cell hybrids in subsequent generations that have lost human chromosome 21. Although the chromosome 21-positive mouse-human cell hybrids are sensitive to the antiviral effects of HuIFNbeta and HuIFNalpha, they are found to be insensitive to the antiviral effect of HuIFNgamma and to lack specific HuIFNgamma binding sites. These results suggest that the HuIFNbeta and HuIFNalpha but not HuIFNgamma binding sites are coded for by genes located on chromosome 21. The lack of a chromosome 21 gene dosage effect on the inducibility of the antiviral state by HuIFNgamma is consistent with this hypothesis.

Animals↗
PubMed1984

Detection of human beta-2 interferon using a radioimmunoassay.

Does the human "beta 2 interferon" (HuIFN-beta 2) mRNA of length 1.3 kb obtained from poly(I) X poly(C) and cycloheximide-induced human diploid fibroblasts (FS-4) code for an interferon per se, or for a protein which, in turn, induces IFN-beta in the cell culture assay that is usually used to detect the antiviral activity of the translation product (obtained from Xenopus laevis oocytes) of this mRNA? This question has been resolved by demonstrating that the IFN derived from the 1.3 kb mRNA can be detected by the direct assay of the oocyte translation product in a highly sensitive radioimmunoassay based on a high-affinity polyclonal antibody raised against N-terminal aminoacid sequence pure IFN-beta 1.

Animals↗
PubMed1984

Immunologic differentiation between E. coli and CHO cell-derived recombinant and natural human beta-interferons.

The products of the human IFN-beta gene expressed in E. coli, Chinese hamster ovary (CHO) cells, and human fibroblasts appear similar when purified on a monoclonal antibody column and analyzed by reverse-phase HPLC, indicating little difference in their hydrophobic nature. SDS-PAGE differentiates E. coli-rHuIFN-beta ser (Mr = 17,000) from CHO-rHuIFN-beta and HuIFN-beta (Mr = 23,000), with glycosylation accounting for 26% of the apparent m.w. of the latter two proteins. CHO-rHuIFN-beta is preferentially neutralized by mouse monoclonal and monospecific rabbit polyclonal anti-HuIFN-beta antibodies, whereas E. coli-rHuIFN-beta ser is preferentially neutralized by goat polyclonal anti-E. coli-rHuIFN-beta antibodies. Adsorption measurements by a sensitive radioimmunoassay indicate that the binding of the three proteins to anti-HuIFN-beta antibodies is similar. The results show that all three molecules can be differentiated by the heteroclitic cross-reactivities of anti-HuIFN-beta and anti-E. coli-rHuIFN-beta antibodies to the antigens.

Animals↗
PubMed1984

Spontaneous production of human gamma interferon in vitro by splenic lymphocytes of patients with idiopathic thrombocytopenic purpura.

Lymphocytes derived from spleens of traffic trauma victims do not appear to produce human interferon (IFN) activity, spontaneously, in vitro. However, lymphocytes derived from spleens of four ITP patients were found to produce significant amounts of human IFN activity. The IFN activity produced by the splenic lymphocytes of ITP patients was neutralized by anti-gamma-IFN antisera but not anti-alpha or anti-beta antisera. The IFN activity was found to be unstable at pH 2.0 and at 56 degrees C. Thus the human IFN activity of splenic lymphocytes is characterized as human gamma-IFN. No human IFN activity was detectable in the serum of the ITP patients and it is not known whether the splenic lymphocytes of ITP patients also produce human gamma-IFN in vivo. The observations suggest that conditions prevail in the ITP state that predispose the splenic lymphocytes to produce human gamma-IFN without stimulation by exogenously added inducer.

Cells, Cultured↗