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Biomedical subjects

S Chun

Publications and source records attributed to S Chun.

At least 55 records · Page 3Linked to original sources
PubMed1998

Immune induction and modulation by topical ocular administration of plasmid DNA encoding antigens and cytokines.

In this article, the authors investigated if administration of eukaryotic expression plasmid DNA delivered to the ocular surface provided a means of inducing and modulating the immune response to herpes simplex virus (HSV). Topical application of gB DNA led to the development of HSV specific systemic humoral and cellular immunity. In addition, mucosal antibody was induced at both proximal and distal locations. Topically gB DNA immunized animals were protected against lethal challenge via either the systemic or the vaginal mucosal routes. Ocular pre-exposure to DNA encoding the cytokines interleukin (IL)-4 or IL-10, but not IL-2 or interferon-gamma, modulated the severity of the immunoinflammatory response to subsequent corneal infection with HSV. The present results indicate that the ocular surface provides a readily accessible site for DNA immunization and is suitable for both immune induction and modulation of the nature of the immune response that is induced.

Adjuvants, Immunologic↗
PubMed1998

Modulation of virus-induced delayed-type hypersensitivity by plasmid DNA encoding the cytokine interleukin-10.

This report evaluates the efficacy of eukaryotic expression plasmids encoding cytokines at modulating the induction and expression of cutaneous delayed-type hypersensitivity (DTH) responses to virus infections. Mice given a single intramuscular administration of cytokine DNA were subsequently infected with either herpes simplex virus (HSV) or vaccinia virus, then tested for DTH. Responses in animals given interleukin-10 DNA were markedly suppressed for at least 5 weeks after pretreatment. Animals also expressed diminished T-cell proliferative responses and modest changes in the balance of T helper type 1 and 2 T-cell reactions. Treatment of animals already sensitized to express DTH, also showed inhibited responses, these taking 6-7 days after treatment to become apparent. Our results show the potency and convenience of plasmid DNA encoding cytokines to modulate inflammatory reactions. Advantages and risks of the cytokine DNA approach are briefly discussed.

Animals↗
PubMed1998

Effects of a hybrid recombinant human alpha interferon (A/D) on in vitro cytotoxicity and in vivo localization of monoclonal antibody L6-cytosine deaminase conjugate in a colon cancer model.

L6 is an IgG2a murine monoclonal antibody which we have demonstrated binds well to HT29 human colon carcinoma cells by flow cytometry, whole cell ELISA, and mixed hemadsorption. In vitro cytotoxicity studies revealed that the monoclonal antibody L6-cytosine deaminase (L6-CD) immunoconjugate plus the nontoxic prodrug, 5-fluorocytosine (5-FC), is equivalent to 5-fluorouracil (5-FU) in its ability to kill HT29 cells. Human alpha-interferon (A/D) was able to enhance this cytotoxic effect. The I.C.50's revealed that very small amounts of L6-CD are needed for this cytotoxic effect (approximately, 5 pg/ml resulted in 50% viability). The limiting factor was the amount of 5-FC employed with L6-CD (3 microM yielded 50% cell viability). alpha-Interferon (A/D) lowered the requirement of 5-FC to 1 microM to achieve 50% cell lethality. In vivo biodistribution experiments indicated that 1 microgram of L6-CD is nonspecifically taken up by the liver and spleen and cleared rapidly from the blood. Significant localization of L6-CD to HT29 tumors occurred only when 99 micrograms of unlabeled L6-CD was added to 1 microgram of 125I-labeled immunoconjugate injected intravenously. Further augmentation of tumor/blood ratios without reduction in percent injected dose per gram of tumor was possible with the intravenous injection of 100 micrograms of anti-idiotypic monoclonal antibody 13B, 24 hours after L6-CD, which bound unreacted L6-CD and cleared it from the blood. The addition of 100,000 U of alpha-interferon (A/D) given intraperitoneally every day increased the clearance of L6-CD by the liver and spleen, but impaired tumor localization (percent injected dose per gram). These studies demonstrated that in vivo localization of the L6-CD conjugate to HT29 tumors could be optimized by injecting excess L6-CD followed by an equal amount of L6 anti-idiotype mAb 13B, 24 hours after L6-CD.

Adenosine Deaminase↗
PubMed1998

Microwave catheter ablation using a clinical prototype system with a lateral firing antenna design.

Microwave has been considered a potentially more effective and more versatile form of energy than radiofrequency. Its feasibility has been tested using various prototype systems and catheter designs. This study assessed the safety and efficacy of a clinically-suitable prototype microwave power supply and catheter system with a lateral-firing antenna design for atrioventricular (AV) junction ablation in canines and to correlate with tissue histopathology. The system consisted of a deflectable catheter with a 6-mm antenna and a thermocouple; and a 2.45-GHz frequency generator with power, time, and temperature controls. AV junction ablations were performed using 75 W energy for up to 60 seconds. Effective heating was confirmed by a rise in catheter temperature to 69.3 +/- 8.8 degrees C. Complete AV nodal block was accomplished in all canines after an average of 4.1 +/- 2.8 applications at 66.8 +/- 7.7 degrees C, and persisted after 28 days in all chronic animals. Lesions were consistent with thermal necrosis, were hemispherical to semi linear in shape and have distinct borders. Acute lesions were 3.4 +/- 1.5 mm wide, 4.8 +/- 2.1 long, and 2.0 +/- 0.9 deep. Chronic lesions showed typical healing and were smaller in size. Ablations did not cause any transvalvular, vascular or other cardiac structural damage, and no coagulum formation was noted on the antenna or catheter tip. Microwave AV junction ablation using this clinical prototype system specifically designed for it was safe and effective. Lesion's depth was limited to 5 mm with 60-second heating while its shape corresponded to the antenna's length. Microwave energy may provide greater versatility for producing discrete or linear ablation.

Animals↗
PubMed1998

Modulation of viral immunoinflammatory responses with cytokine DNA administered by different routes.

The efficacy of plasmid DNA encoding cytokine administered by different routes, systemic or surface exposure, was evaluated and compared for their modulating effects on subsequent lesions caused by infection with herpes simplex virus (HSV). Systemic or topical administration of both interleukin-4 (IL-4) and IL-10 DNA but not IL-2 DNA caused a long-lasting suppression of HSV-specific delayed-type hypersensitivity response. IL-4 or IL-10 DNA preadministration also modulated the expression of immunoinflammatory lesions associated with corneal infection of HSV. Suppression of ocular lesions required that the DNA be administered to the nasal mucosa or ocular surfaces and was not evident after intramuscular administration. The modulating effect of IL-10 DNA was most evident after topical ocular administration, whereas the effects of IL-4 DNA given by both routes appeared to be equal. Preexposure of IL-4 DNA, but not IL-10 DNA, resulted in a significant change in Th subset balance following HSV infection. Our results indicate that the modulating effect of IL-4 or IL-10 DNA may proceed by different mechanisms. Furthermore, our results suggest that surface administration of cytokine DNA is a convenient means of modulating immunoinflammatory lesions.

Animals↗
PubMed1997

The role of intravenous amiodarone in the management of cardiac arrhythmias.

PURPOSE: To review the electropharmacology, clinical applications, side effects, and hemodynamic profile of intravenous amiodarone. DATA SOURCES: The MEDLINE database was searched for English-language material, including reports of clinical trials and in vivo studies, review articles, and abstracts presented at national symposia, that was published between 1985 and 1996. Bibliographies of textbooks and articles were also examined. STUDY SELECTION: Studies that reported on the efficacy, toxicity, and hemodynamic profile of intravenous amiodarone and studies that examined the pharmacologic behavior of intravenous amiodarone in laboratory models were reviewed. DATA EXTRACTION: Study design and quality and relevant data on efficacy of suppression and treatment of arrhythmias with oral and intravenous amiodarone therapy, the reported mechanisms of antiarrhythmic effect, and hemodynamic changes seen with therapy were analyzed. DATA SYNTHESIS: Amiodarone is a unique antiarrhythmic agent that is now available in oral and intravenous forms in the United States. The use of intravenous amiodarone in the short-term treatment of life-threatening or hemodynamically unstable rhythm disturbances has generated much interest. Amiodarone has many electropharmacologic actions, some of which differ between the oral and intravenous forms. The wide clinical application of amiodarone includes treatment and prevention of supraventricular and ventricular arrhythmias and arrhythmias related to myocardial infarction. Intravenous amiodarone is effective for supraventricular and ventricular arrhythmias that are resistant to other antiarrhythmic agents. The effectiveness of intravenous amiodarone as short-term treatment also suggests that the drug has an important role in protocols of advanced cardiac life support. Intravenous amiodarone seems to have an overall favorable hemodynamic profile and does not produce many of the unwanted long-term side effects associated with oral therapy. CONCLUSION: Intravenous amiodarone shows much promise for the short-term treatment of unstable arrhythmias. Its favorable hemodynamic effects and minimal short-term side effects make it an attractive option in the management of cardiac arrhythmias.

Amiodarone↗
PubMed1997

Constitutive expression of the HTLV-I pX and env regions in Jurkat T-cells induces differential activation of SRE, CRE and NF kappa B pathways.

Human T-cell leukemia virus type I (HTLV-I) causes adult T-cell leukemia/lymphoma (ATLL). HTLV Tax, the viral transcriptional activator, can activate a variety of cellular genes. HTLV-mediated T-cell transformation, however, may involve additional viral proteins expressed from singly- as well as doubly-spliced viral mRNA. To determine the combined effect of these viral proteins on cellular gene expression in Jurkat T-cells, we derived stable transfectants that constitutively express the HTLV-I pX and env regions (J3.9). J3.9 cells show substantially increased mRNA levels of egr-1 and c-jun but no induction of either CD25 or GM-CSF by Northern blotting. This pattern corresponded to the activation of an egr-1 but not a GM-CSF promoter-driven reporter construct in transient gene expression assays. In DNA electrophoretic mobility shift assays (EMSA), nuclear extract from J3.9 cells has significantly increased binding to CRE and SRE but not nuclear factor kappa B (NF kappa B) DNA oligos, as compared to J-Neo cell extract. These results suggest that low level expression of pX and env region gene products in Jurkat T-cells stimulates persistent activation of CRE- and SRE- but not NF kappa B-induced cellular genes.

Cyclic AMP Response Element-Binding Protein↗
PubMed1997

Cyclooxygenase metabolites possibly produced by endothelial cells mediate the lung injury caused by mechanically stimulated leukocytes.

To determine whether mechanically stimulated leukocytes increase pulmonary vascular permeability and resistance and, if so, whether cyclooxygenase metabolites mediate the increase, we assessed the effects of stimulated and unstimulated leukocytes, and of a cyclooxygenase inhibitor on pulmonary vascular permeability and resistance in isolated perfused lungs from Sprague-Dawley rats. Leukocytes were stimulated by gentle agitation in a glass container for 10 seconds. After baseline measurements were made, stimulated or unstimulated leukocytes were added to the perfusate. The effects of the cyclooxygenase inhibitor, meclofenamate, on the pulmonary vascular filtration coefficient and pulmonary vascular resistance were measured. In the rats that received stimulated leukocytes, the pulmonary vascular filtration coefficient and the vascular resistance were about 2.5 times and 3.3 times higher, respectively, than those in the rats that received unstimulated leukocytes. These increases were completely and partly blocked by meclofenamate. Histological examination indicated that meclofenamate did not prevent the adhesion of leukocytes to the pulmonary vascular endothelium. These findings suggest that mechanically stimulated leukocytes increase pulmonary vascular permeability and that cyclooxygenase metabolites produced by endothelial cells may injure the cells.

Animals↗
PubMed1996

Negative regulation of gene expression from the HTLV type II long terminal repeat by Rex: functional and structural dissociation from positive posttranscriptional regulation.

Regulation of human T cell leukemia virus type II (HTLV-II) gene expression by Rex is mediated by cis-acting elements in the 5' viral long terminal repeat (LTR). Rex acts posttranscriptionally to enhance cytoplasmic accumulation of incompletely spliced viral mRNAs encoding structural proteins. We report a distinct negative regulatory function mediated by Rex affecting expression from the viral 5' LTR. Using both LTR-driven CAT reporters and a full-length HTLV-II proviral construct, we demonstrate that Rex decreases total cellular levels of LTR-containing mRNA in a dose-dependent manner. Negative regulation is an independent function as demonstrated by structural and functional dissociation from Rex positive posttranscriptional regulation. This negative regulatory action was dependent on nuclear localization sequences, but did not require the previously defined Rex-responsive element (RxRE). Negative regulation was observed in T cell lines but not in B cell lines, suggesting the involvement of cell type-specific factors distinct from those involved in posttranscriptional regulation. An internal deletion mutant of Rex removing aa 38-80 retained the ability to repress, but did not posttranscriptionally increase expression, while negative regulation requires a previously uncharacterized carboxy-terminal region (aa 154-170). These findings suggest that Rex may serve two simultaneous functions: to decrease overall levels of transcribed viral mRNA, and to facilitate nuclear to cytoplasmic export of mRNAs encoding structural proteins. The negative regulatory function of Rex may play a role in viral latency.

Base Sequence↗
PubMed1996

Specific binding of polypyrimidine tract binding protein and hnRNP A1 to HIV-1 CRS elements.

The human immunodeficiency virus (HIV) Rev and human T-cell leukemia virus (HTLV) Rex proteins regulate viral RNA processing. Both proteins act to overcome the block to viral structural gene expression, at least in part, by reversing the inhibitory effect of intronic RNA sequences, termed cis-acting repressive (CRS) sequences. Using HTLV type II (HTLV-II) as a model, we recently showed that the function of a 5' long terminal repeat (LTR) CRS correlates with in vitro binding by both polypyrimidine tract binding (PTB) protein (also known as hnRNP I) and hnRNP A1 to CRS RNA (1,2). Using radioimmunoprecipitation of proteins ultraviolet (UV) crosslinked to each HIV CRS RNA with monoclonal anti-hnRNP antibodies, we now demonstrate that hnRNP I and hnRNP A1 bind to two different HIV-1 CRS RNAs. In addition, we show that hnRNP I and hnRNP A1 binding to HIV-1 CRS RNAs can be specifically competed by HTLV-II CRS RNAs using electrophoretic mobility shift assay (EMSA)/UV crosslinking assays. Binding by both hnRNP I and hnRNP A1 to HIV-1 and HTLV-II CRS RNAs suggests a role for these proteins in CRS function that may be influenced by the Rev and Rex proteins, respectively.

Electrophoresis, Polyacrylamide Gel↗
PubMed1996

MK-801 reduces uptake and stimulates efflux of excitatory amino acids via membrane depolarization.

MK-801 and related compounds reduce excitotoxic neuronal injury by blocking N-methyl-D-aspartate (NMDA) receptorgated ion channels. These agents also cause neuronal vacuolization and block glutamate-induced astrocyte swelling, effects that may be unrelated to actions at the NMDA receptor. In the present study, high concentrations of MK-801 (100-1,000 microM) caused uncompetitive inhibition of glutamate uptake in astrocyte and neuronal cultures and stimulated D-aspartate efflux from astrocytes. MK-801 (500 microM) reduced the maximal velocity for glutamate uptake in astrocytes from 31 to 17 nmol.mg protein-1.min-1, whereas competitive NMDA receptor antagonists did not affect glutamate uptake. MK-801 also inhibited uptake of gamma-aminobutyric acid (GABA). Because both GABA uptake and glutamate uptake are electrogenic, one mechanism by which MK-801 could inhibit uptake is by membrane depolarization. Whole cell patch-clamp recording confirmed that MK-801 in the range of 100-1,000 microM caused dose-dependent and reversible depolarization. These concentrations are far higher than necessary to block NMDA receptors, and the findings suggest that actions at sites other than NMDA receptors could contribute to the effects of high doses of MK-801 in some experimental and clinical settings.

Amino Acids↗
PubMed1996

Sudden Death During Flecainide Therapy for Atrial Fibrillation Complicating Wolff-Parkinson-White Syndrome.

The Wolff-Parkinson-White syndrome can be complicated by atrial fibrillation that may increase morbidity and mortality. Different pharmacologic therapy, includes class IA, IC, and III agents, has been used in such cases with variable success. We now use less pharmacologic intervention with development of an electrode catheter ablation for accessory pathways. However, antiarrhythmic agents are still being used, especially when an electrode catheter ablation is unavailable or if a patient refuses such a procedure. Therefore, it is prudent that one understands each antiarrhythmic agents' electropharmacologic properties as well as its potential proarrhythmic effect in order to accurately assess each drug's risk-benefit ratio. We present a case that illustrates electropharmacologic properties of quinidine, flecainide, sotalol, and amiodarone on various cardiac tissues, as well as possible proarrhythmic effect of flecainide on a structurally normal heart.

Journal Article↗
PubMed1995

Polypyrimidine tract-binding protein and heterogeneous nuclear ribonucleoprotein A1 bind to human T-cell leukemia virus type 2 RNA regulatory elements.

Efficient expression of human T-cell leukemia virus (HTLV) and human immunodeficiency virus structural proteins requires Rx and Rev proteins, respectively. Decreased expression of Gag and Env appears to be due, in part, to intragenic RNA sequences, termed cis-acting repressive sequences (CRS), and may be mediated by binding of specific cellular factors. We demonstrated previously that two cellular proteins, p60CRS and p40CRS, interact with HTLV type 2.5' long terminal repeat CRS RNA and that the interaction of both proteins with CRS RNA correlates with function (A. C. Black, C. T. Ruland, J. Luo, A. Bakker, J. K. Fraser, and J. D. Rosenblatt, Virology 200:29-41, 1994). By radioimmunoprecipitation of HeLa nuclear proteins UV cross-linked to CRS RNAs with murine monoclonal antibodies, we now show that p40CRS is heterogeneous nuclear ribonucleoprotein (hnRNP) A1 and p60CRS is polypyrimidine tract-binding protein or hnRNP I. These immunoprecipitation results were confirmed by an immunobinding assay with hnRNP I and hnRNP AI antibodies and by cross-competition electrophoretic mobility shift experiments. In addition, we mapped a putative hnRNP A1 binding site in U5 RNA and demonstrated that p40CRS (hnRNP A1) binding to that site correlates with CRS function. Since both hnRNP I and hnRNP A1 have been shown to influence splicing and potentially other steps in RNA processing, the binding of both hnRNP I and hnRNP A1 to HTLV RNA regulatory elements may alter retrovirus RNA processing and may be involved in regulation by Rex.

Base Sequence↗
PubMed1994

Expression of human tumor mucin-associated carbohydrate epitopes, including sialylated Tn, and localization of murine monoclonal antibodies CC49 and B72.3 in a syngeneic rat colon carcinoma model.

Using immunohistochemical techniques and whole-cell enzyme-linked immunosorbent assay, we have determined that monoclonal antibodies (mAbs) B72.3 and CC49, which are widely used in the diagnosis and treatment of several human epithelial cancers, are expressed in a transplantable rat colon carcinoma cell line, K12-TRb. MAbs B72.3 and CC49 react with tumor-associated glycoprotein-72 (TAG-72) which is a carcinoma mucin molecule expressed in colon, breast, pancreatic, ovarian, lung, and gastric cancers. The carbohydrate epitope for mAb B72.3 is sialylated Tn (sTn), whereas CC49 reacts with an unknown carbohydrate epitope. K12-TRb is a transplantable rat colon carcinoma cell line derived from a dimethylhydrazine tumor which grows as progressive tumors in syngeneic BD IX rats. We found that the carbohydrate epitopes for mAbs B72.3 and CC49, including sTn, were more tumor-restricted in the rat than in humans. The only binding these had mAbs to normal rat tissue was to small-intestinal mucosa. MAbs B72.3 and CC49 were radiolabeled with iodine-125 (125I) and injected intravenously into BD IX rats containing subcutaneously grown syngeneic K12-TRb tumors. Biodistribution experiments were conducted by dissecting groups of three rats on days 2, 4, 7, and 14 after injection of radiolabeled mAbs. These experiments confirmed that maBs B72.3 and CC49 localize to K12-TRb tumors in vivo, and that the higher affinity mAb CC49 localized better than mAb B72.3. Gamma-camera imaging of subcutaneous K12-TRb tumors was successfully performed using 125I-labeled mAb CC49. The importance of this model is that mAbs B72.3 and CC49, immunoconjugates of these mAbs, and vaccines containing their corresponding carbohydrate epitopes, including sTn, can be studied in a relevant immunocompetent syngeneic rat colon carcinoma model.

Animals↗
PubMed1994

Comparison of sympathetic skin response and digital infrared thermographic imaging in peripheral neuropathy.

It is well known that the SSR (sympathetic skin response) is to evaluate the function of sudomotor activity and Digital infrared thermal imaging (DITI) is to evaluate the function of vasomotor activity of the sympathetic nerve. To assess the sympathetic nerve impairment in the patients with peripheral neuropathy, the SSRs and DITIs were tested in 35 cases. Twenty-four (68.6%) patients were abnormal on SSR test and twenty-nine (82.9%) patients were abnormal on DITI test. In the relationship between DITI and SSR, 19 (54.3%) cases were abnormal and 1 case was normal finding in both of these two tests. And the remaining 25 (42.9%) patients were abnormal on only either one of both tests. Frequency of abnormal SSR and DITI findings were correlated with severity of axonal involvement in peripheral nerve lesion. The results of this study revealed DITI to be more sensitive test in assessing sympathetic dysfunction in peripheral neuropathy than the SSR. However DITI has very limited values in the patients with symmetrically involved peripheral neuropathy because thermal asymmetry is considered as abnormal on DITI. Therefore, in assessing the function of sympathetic nerve in peripheral neuropathy, combined tests of SSR and DITI are useful.

Adolescent↗
PubMed1993

A survey of ciguatera: assessment of Puako, Hawaii, associated with ciguatera toxin epidemics in humans.

A survey for the assessment of the ciguatera problem has been determined in Puako, South Kohala, on the Island of Hawaii. This is in the area of persistent ciguateric outbreaks during the months of January through March, caused by a specific species of fish (Cheilinus rhodochrous, red rose wrasse, or po'ou). Analyses of algae, Gambierdiscus toxicus, and various species of fish, including herbivores and carnivores, gave positive indications of Puako as a potential ciguateric area. Algae associated with Gambierdiscus toxicus blooms and the dinoflagellate itself were found in transects A and D. Transects A and D showed 291 G. toxicus per gram of Tolycarpidia glomurata and 9 G. toxicus per gram of Turbinaria sp. with epiphytic Jania sp., respectively. No G. toxicus was found in transects B and C. This may be attributed to the low salinity from intrusion of freshwater in this vicinity. Examinations of the fish, kole, manini, Hawaiian kole, roi, and po'ou by the solid-phase immunoassay showed 89% of fish in the borderline and positive categories from all transects. Extracts of viscera and flesh showed high levels of toxicity in mouse (13 of 23 deaths), particularly in the viscera (gut) of both herbivores and carnivores. The guinea pig atrial analysis generally showed a few ciguatoxin-like, but most were nonciguateric type responses. The data presented in this Puako survey showed evidence of toxic fish associated with ciguatoxin-like and most probably other toxins, either polyethers or non-polyethers as yet unidentified.

Animals↗
PubMed1993

The ulnar impaction syndrome: follow-up of ulnar shortening osteotomy.

Thirty wrists of 27 patients with ulnar impaction syndrome who underwent ulnar shortening osteotomy were retrospectively reviewed. The average follow-up was 51 months. The wrists were graded preoperatively and postoperatively according to a wrist-grading system modified from Gartland and Werley. The parameters of grading included pain, function, range of motion, grip strength, radiographic analysis, bony union, and complications. Twenty-four wrists were graded excellent, 4 good, 1 fair, and 1 poor after the surgery in comparison with 28 poor and 2 fair before the operative treatment. Complications were rare, with no ulnar nonunions. This long-term follow-up study revealed that distal ulnar shortening osteotomy is an excellent procedure for the treatment of ulnar impaction syndrome.

Adolescent↗