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Biomedical subjects

C Cho

Publications and source records attributed to C Cho.

At least 19 recordsLinked to original sources
PubMed2001

Protective role of cyclooxygenase inhibitors in the adverse action of passive cigarette smoking on the initiation of experimental colitis in rats.

Clinical and experimental findings had indicated that cigarette smoke exposure, and cyclooxygenase-2, are strongly associated with inflammatory bowel disease. The present study aimed to evaluate the role of cyclooxygenase-2 in the pathogenesis of experimental inflammatory bowel disease as well as in the adverse action of cigarette-smoke exposure. Rats were pretreated with different cyclooxygenase-2 inhibitors (indomethacin, nimesulide, or SC-236 (4-[5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide)) along with cigarette-smoke exposure before 2,4,6-trinitrobenzenesulfonic acid-enema. Results indicated that pretreatment with cyclooxygenase-2 inhibitors not only protected against 2,4,6-trinitrobenzenesulfonic acid-induced inflammatory bowel disease, but also attenuated the potentiating effect of cigarette-smoke exposure on colonic damage. Furthermore, the colonic cyclooxygenase-2 protein and mRNA expression was markedly induced by 2,4,6-trinitrobenzenesulfonic acid-enema, and it was potentiated further by cigarette-smoke exposure, while the cyclooxygenase-1 expression was not changed. The present study suggests that the highly induced cyclooxygenase-2 expression not only plays a pathogenic role in 2,4,6-trinitrobenzenesulfonic acid-induced inflammatory bowel disease, but also contributes to the adverse action of cigarette-smoke exposure on this disorder.

Animals↗
PubMed2000

A role for a TIMP-3-sensitive, Zn(2+)-dependent metalloprotease in mammalian gamete membrane fusion.

During fertilization, sperm and egg plasma membranes adhere and then fuse by a mechanism that is not well understood. Zinc metalloproteases are necessary for some intercellular fusion events, for instance, cell-cell fusion in yeast. In this study we tested the effects of class-specific and family-specific protease inhibitors on mouse gamete fusion. Capacitated, acrosome-reacted sperm and zona-free eggs were used in assays designed to define the effects of inhibitors on sperm-egg plasma membrane binding or fusion. Inhibitors of the aspartic, cysteine, and serine protease classes had no effect on sperm-egg binding or fusion. Both a synthetic metalloprotease substrate (succinyl-Ala-Ala-Phe-amidomethylcoumarin) and the zinc chelator 1,10-phenanthroline inhibited sperm-egg fusion but did not decrease sperm-egg binding. The fusion-inhibition effect of phenanthroline was reversible and activity of the inhibitable zinc metalloprotease was shown to be required during a short time window, the first 15 min after insemination. Tissue inhibitor of metalloprotease-3 and Ro 31-9790, specific inhibitors of zinc metalloproteases in the matrixin and adamalysin families, also inhibited sperm-egg fusion but not sperm-egg binding. These data indicate a role in gamete fusion for one or more zinc metalloproteases of the matrixin and/or adamalysin families that act after plasma membrane binding and before sperm-egg membrane fusion.

Animals↗
PubMed2000

Analysis of mouse fertilin in wild-type and fertilin beta(-/-) sperm: evidence for C-terminal modification, alpha/beta dimerization, and lack of essential role of fertilin alpha in sperm-egg fusion.

The sperm surface protein fertilin functions in sperm-egg interaction. On guinea pig and bovine sperm, fertilin is a heterodimer of alpha and beta subunits. Both subunits are initially synthesized as precursors and then proteolytically processed by removing N-terminal domains. Since the mouse is currently the main mammalian species in which fertilization is studied, in the present report, we analyzed the structure, processing, and expression of fertilin in mouse. We found that the processing of mouse fertilin beta occurs during epididymal maturation and involves changes in the cytoplasmic tail domain as well as the N-terminal domains. Although we (R. Yuan et al., 1997, J. Cell Biol. 137, 105-112) and others (M. S. Chen et al., 1999, J. Cell Biol. 144, 549-561) have previously reported that mature fertilin beta is 55-57 kDa, here we show that 55 kDa is an unrelated protein in the sperm extract which cross-reacts with an antibody that recognizes precursor, but not mature, fertilin beta. Comparison of Western blots of wild-type and fertilin beta knockout sperm revealed that authentic, mature fertilin beta is 45 kDa. We also obtained direct evidence that mouse fertilin alpha and beta exist as a heterodimer. In addition, we found that in mice lacking the fertilin beta subunit, fertilin alpha is absent from mature sperm. A widely proposed model for sperm-egg fusion suggests that fertilin alpha is the sperm component that promotes membrane fusion by undergoing a conformational change that exposes a virus-like, hydrophobic fusion peptide. Because sperm lacking fertilin alpha and fertilin beta can fuse with eggs at 50% the wild-type rate, this model is called into question. The results suggest instead that other gamete surface molecules act to promote membrane fusion and that fertilin's role in gamete fusion is in sperm-egg plasma membrane adhesion.

ADAM Proteins↗
PubMed2000

Enhanced efficacy by percutaneous absorption of piroxicam from the poloxamer gel in rats.

The pharmacokinetics and anti-inflammatory activity of piroxicam from the poloxamer 407 gel were determined to investigate percutaneous absorption of piroxicam from poloxamer gels in rats. The poloxamer 407 gel containing 1% piroxicam showed significant inhibition of carragenin-induced rat foot swelling when compared to the control group. The extent of inhibition of swelling (%) showed a linear relationship with the logarithm of piroxicam dose within approximately 0.4-3.2 mg/kg. The enhancing effect of polyoxyethylene-2-oleyl ether, non-ionic surfactant on the percutaneous absorption of piroxicam from poloxamer 407 gel was evaluated in rats. The piroxicam gel containing polyoxyethylene-2-oleyl ether increaesd the relative bioavailability approximately 1.8-fold compared with the gel without enhancer. Percutaneous administration of piroxicam gel containing polyoxyethylene-2-oleyl ether to rats showed a relatively constant, sustained blood concentration with minimal fluctuation.

Algorithms↗
PubMed2000

A lesion of the anterior thalamus producing dystonic tremor of the hand.

BACKGROUND: Thalamic tremor is typically characterized by resting and intention components; a postural element is often present as well. Previously reported cases of acquired thalamic tremor have demonstrated lesions in the posterior thalamus or dentatorubrothalamic tract. OBJECTIVES: To report a case of dystonic-postural tremor of the upper extremity that occurred after a contralateral anterior thalamic infarct, and to discuss potential tremorigenic mechanisms. DESIGN: Case report. SETTING: Municipal hospital neurology clinic. PATIENT: A 65-year-old right-handed woman suddenly developed a dystonic tremor in her left hand after undergoing coronary bypass surgery. The tremor persisted unchanged for 8 months, at which time she was evaluated by us. Cranial magnetic resonance imaging scans demonstrated a right anterior thalamic infarct. CONCLUSION: To our knowledge, this is the first report of focal tremor caused by a lesion of the anterior thalamus.

Aged↗
PubMed2000

Development of screening systems for drugs against human papillomavirus-associated cervical cancer: based on E6-E6AP binding.

Human papillomavirus (HPV) E6 protein forms a ternary complex with the cell-cycle regulator p53 and the E6-associated protein (E6AP) known as an E3 ubiquitin protein ligase, leading to the degradation of p53 via the ubiquitination pathway. As an attempt to employ interaction between HPV viral oncogene E6 and a cellular protein E6AP for in vitro screening system of drugs against HPV infection, we primarily investigated the E6AP-E6 binding through pull down assay and enzyme-linked immunosorbent assay (ELISA). E6AP immobilized on the resin produced specifically complexes with bacterially expressed E6 in a dose-dependent manner, as determined by immunoblot analysis. This result was collinear with that shown in ELISA, which is a useful system for mass-screening potential drugs with rapidity and cheapness. Screening system based on the interaction between E6AP and E6 may be a promising system in the development of drugs against cervical cancer caused by HPV infection.

Blotting, Western↗
PubMed2000

Increased interleukin-8 expression by cigarette smoke extract in endothelial cells.

It has been reported that cigarette smoking worsens alcohol-induced gastric lesions through neutrophil infiltration. We hypothesize that IL-8, a potent chemotactic factor for neutrophil is likely to be involved in this ulcerogenic process. To evaluate this phenomenon, the ability of cigarette smoke extract (CSE) to induce endothelial cell expression of IL-8 was examined. Two different fractions (ethanol or chloroform soluble extracts) of CSE with their chemical types identified showed a time- and dose-dependent increase on IL-8 secretion from ECV304 cell line. Protein kinase C (PKC) inhibitor GF109203X had no effect on IL-8 response in basal secretion and also to these stimuli. Protein tyrosine kinase (PTK) inhibitor genistein and protein kinase A (PKA) inhibitor H8 at respective concentrations significantly reduced chloroform and ethanol soluble extract-induced IL-8 expression by about 34 and 35% respectively at 8 h after incubation. It is concluded that CSE increases IL-8 release from human endothelial cells through PTK and PKA activation.

Journal Article↗
PubMed2000

The role of IL-12 in inflammatory activity of patients with rheumatoid arthritis (RA).

The aim of this study was to investigate the role of IL-12 in patients with RA. IL-12 (p70) and its associated cytokines were measured in sera and synovial fluid (SF) using an enzyme-linked immunosorbent method. Seven American College of Rheumatology (ACR) core set measures as well as IL-12 levels were sequentially monitored at the commencement and 4 months after treatment with a low-dose steroid and disease-modifying anti-rheumatic drugs (DMARDs). In sera, 64 (42.2%) of 152 RA patients had detectable concentrations of IL-12 (p70), whereas one (1.4%) of 69 osteoarthritis (OA) patients and five (10%) of 50 healthy controls had detectable IL-12 (P < 0.001). The median level of circulating IL-12 was also higher in RA patients (P < 0.001). In SF, the number of patients with detectable IL-12 and the median IL-12 levels were significantly higher in RA patients (n = 53) than in OA patients (n = 22). In paired samples (n = 53) of sera and SF from RA patients, IL-12 levels were higher in the SF than in sera (P < 0.001). Patients with detectable IL-12 (n = 51) in sera had higher tender joint scores (P = 0.003), swollen joint scores (P < 0.001) and C-reactive protein (CRP; P = 0.036), than those without (n = 55). Four months after treatment with DMARDs, the improved group showed a larger IL-12 decrease than the non-improved group (P = 0.017). The levels of IL-12 correlated positively with those of IL-2, interferon-gamma, IL-6, and tumour necrosis factor-alpha, but were correlated inversely with those of IL-10. Our results demonstrate that IL-12 levels reflect RA disease activity and that IL-12 is involved in the production of proinflammatory cytokines. An IL-12 blockade could be useful for the treatment of RA.

Adult↗
PubMed2000

Enhanced effect of sulfonylurea (SU) in copolymer comprising a sugar moiety and SU derivative as double ligands on insulin secretion from MIN6 cells.

Copolymers composed of sulfonylurea (SU) as an antagonist of ATP-sensitive K+ channel and sugar moieties as double ligands were synthesized. Insulin secretion from MIN6 cells (insulinoma cell line) in contact with the copolymers was evaluated. MIN6 cells attached to the poly(N-p-vinylbenzyl-D-maltonamide-co-SU) [P(VMA-co-SU)]-coated dishes were in the more aggregated form as compared to other polymer-coated surfaces. By introducing SU into the sugar bearing homopolymer, an enhanced effect on insulin secretion from MIN6 cells was observed due to the specific interaction between SU ligands and SU receptors on the beta-cell membrane. P(VMA-co-SU) composed of SU and non-reducing glucose moieties demonstrated enhanced insulin secretion from MIN6 cells and faster proliferation of MIN6 cells as compared to poly(N-p-vinylbenzyl-D-lactonamide-co-SU) [P(VLA-co-SU)] probably owing to the glucose transporters presence on the MIN6 cell membrane. Insulin secretion from MIN6 cells pretreated with diazoxide as an agonist of ATP-sensitive K+ channel was suppressed.

Adenosine Triphosphate↗
PubMed1999

Mouse-to-rat testicle transplantation.

This report details mouse-to-rat testicular transplantation with immediate revascularization. Donor preparation involved grafting a long segment of aorta and inferior vena cava (IVC) containing the testicular artery and vein. The graft aorta and IVC were anastomosed to the rat aorta and IVC, respectively. Vasovasostomy was completed and the scrotal epithelia were anastomosed to draw the graft toward the host scrotal sac. Twenty-nine of 53 transplants were determined to be viable. Histologically, 6- to 18-hr-old grafts displayed moderate to minimal polymorphonuclear neutrophil (PMN) infiltrates. Ischemia set in somewhere between 18-24 hr postoperatively. Beyond 24 hr the grafts displayed progressive infiltration of PMN and perivascular and intertubular lymphocytes, disorganization of the germinal epithelium, and cessation of spermatogenesis.

Animals↗
PubMed1999

Update on sequential isologous rat organ transplantation: pancreaticoduodenal and kidney transplantations.

This periodic report includes intermittent results of consecutive pancreaticoduodenal (Pd) and kidney (Kt) transplants in inbred rats and results on double kidney transplants that did not follow sequential transplant protocol. Eight 24-month-old Lewis pancreas, kidney, and aorta served histological controls showing normal histological architecture with no atherosclerosis developed in the aorta. Thirty-four month old pancreas and thirty-two month old kidneys, which resided in young hosts for at least three occasions, appeared as youthful Pd and Kt grafts. They show normal histological appearance for more than the expected life span of a Lewis rat. The fact that not only pancreases but also kidneys outlived their host leads to the study of other different organs' viability as aged valuable grafts. Nevertheless, the threats by the development of atherosclerosis in graft-associated aortas resulted in slow progression of the follow-ups.

Animals↗
PubMed1999

[Elastase 1].

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Acute Disease↗
PubMed1998

Fertilization defects in sperm from mice lacking fertilin beta.

Fertilin, a member of the ADAM family, is found on the plasma membrane of mammalian sperm. Sperm from mice lacking fertilin beta were shown to be deficient in sperm-egg membrane adhesion, sperm-egg fusion, migration from the uterus into the oviduct, and binding to the egg zona pellucida. Egg activation was unaffected. The results are consistent with a direct role of fertilin in sperm-egg plasma membrane interaction. Fertilin could also have a direct role in sperm-zona binding or oviduct migration; alternatively, the effects on these functions could result from the absence of fertilin activity during spermatogenesis.

ADAM Proteins↗
PubMed1998

XeCl laser surgery of the vocal cords: a histologic comparison with CO2 laser in a porcine model.

Fresh cadaveric pig larynxes were ablated with a CO2 (lambda = 10.6 microm) and a XeCl excimer (lambda = 308 nm) laser. Histologic comparison of the ablation craters created by the two lasers was performed, and ablation crater depth and marginal tissue damage were measured. Crater depth for both laser treatments is correlated with energy deposition and exposure time. The CO2 laser creates three times more nonspecific, marginal tissue damage than the XeCl laser at the ranges of total energy and exposure times used. This study demonstrates the potential of the XeCl laser as an alternative to the CO2 laser in microlaryngeal surgery.

Animals↗
PubMed1998

Induction of an ATPase inhibitor protein by propylthiouracil and protection against paracetamol (acetaminophen) hepatotoxicity in the rat.

1. The purpose of the present study was to test the following hypothesis: propylthiouracil (PTU) treatments of rats induces an increase in the concentration and activity of the mitochondrial ATPase (m-ATPase) inhibitor protein (IF1). The PTU-induced elevated baseline levels of this inhibitor protein inactivated m-ATPase, and prevented hepatotoxicity by a toxic dose of acetaminophen (AAP) (paracetamol), by maintaining hepatic adenosine 5'-triphosphate (ATP) levels. 2. Male Wistar rats were either gavaged with a toxic dose of AAP alone, or after pretreatment with PTU for periods of 3 and 12 days. 3. Twenty four hours after acetaminophen treatment alone, toxicity was manifested by: an approximately 10 fold increase in serum transaminase levels (serum glutamic oxaloacetic transaminase and serum glutamic pyruvic transaminase); depletion of hepatic reduced glutathione (GSH) and ATP levels; loss of inhibitor protein activity, and extensive pericentral necrosis of the hepatocytes. Propylthiouracil pretreatment for 12 days enhanced the concentration of the following metabolites in the liver: ATP (1.5 fold), ATPase inhibitor protein (IF1) (4.5 fold), and reduced glutathione (1.3 fold), while the activity of the inhibitor protein increased 2 fold. When the PTU treated rats were challenged with AAP, transaminases were not elevated, and only sporadic areas of necrosis were detected by histological examination of the liver tissue. In contrast to the 12 day treatment with PTU the 3 day treatment had no protection against AAP. No histological evidence of protection was manifested and the transaminases were not different from AAP treated controls. Most of the protective metabolites were depleted. 4. Our findings suggest that PTU-induced increased concentration of inhibitor protein and GSH, are contributing factors in the prevention of hepatotoxicity by maintaining hepatic m-ATP levels and reducing the harmful effect of the toxic metabolite of AAP.

Acetaminophen↗
PubMed1997

Effects of the tyrosine-kinase inhibitor geldanamycin on ligand-induced Her-2/neu activation, receptor expression and proliferation of Her-2-positive malignant cell lines.

Geldanamycin belongs to the family of benzoquinoid ansamycin tyrosine-kinase inhibitors. We have examined its effects on Her-2/neu kinase activity, protein expression level, and proliferation of Her-2+ malignant cells. In SK-BR-3 breast-cancer cells, short-time treatment with geldanamycin completely abrogated gp30-ligand-induced activation of Her-2 without a change of receptor-expression level. Longer treatment of intact cells with geldanamycin induced decreased steady-state Her-2 autophosphorylation activity, which correlated with reduction of Her-2 protein expression and phosphotyrosine content of several proteins. The decrease was time- and dose-dependent, starting after 1 hr at 100 nM concentration and reaching completion by 24 hr. The reduction of the Her-2 protein level probably resulted from increased degradation, since the Her-2 mRNA level remained constant. Geldanamycin effects were not specific for Her-2, since the non-receptor tyrosine-kinase fyn was inhibited equally. In contrast to these results, protein-kinase-C activity was not affected. In 3 other malignant cell lines expressing different amounts of Her-2 (SK-BR-3 > SK-OV-3 > OVCAR3 > MCF7), geldanamycin also effectively reduced Her-2-kinase activity proportionally to the decrease of protein expression. In contrast, in a [3H]-thymidine-uptake assay, cell growth was meaningfully inhibited by geldanamycin at nanomolar concentrations only in SK-BR-3 (IC50 2 nM) and MCF7 (IC50 20 nM), while OVCAR3 was only moderately sensitive (IC50 2 microM) and SK-OV-3 was clearly resistant to geldanamycin. In direct comparison with herbimycin A, another benzoquinoid ansamycin that has been more thoroughly characterized, the biologic effects of geldanamycin were more pronounced.

Adenocarcinoma↗
PubMed1997

Sequential isologous organ transplantation in inbred rats: pancreaticoduodenal transplants.

A total of 847 inbred Lewis rats of mixed sex were used in this pancreaticoduodenal (Pd) donor aging study. Pd grafts were taken from 9- to 12-month-old donors and transplanted into 3-month-old recipients (thus, the first generation Pd graft, or 1 Pd). After 9 to 12 months, the same Pd grafts were again harvested and transplanted into 3-month-old rats (thus the 2 Pd generation). This cycle was repeated to obtain the 3, 4, and 5 Pd series. Sequential transplantation was able to extend the Pd grafts' mean survival time to 32 months for fourteen 4 Pd grafts, and to 39.2 months for four 5 Pd grafts (the longest lived graft survived for 42 months). The pancreas and duodenal sections of the grafts remained normal throughout the entire study. However, the aortic sections of the grafts (which were harvested to include the superior mesenteric and celiac arteries) all exhibited moderate to massive atherosclerotic changes by the 5 Pd mean survival age of 39.2 months. Such histological changes commenced even before 21 months of Pd graft age in some animals, gradually progressing to dilation of the aorta (and subsequent narrowing of aortic tributaries), as well as formation of an eggshell-like inner membrane shielding the aortic intima, by 42 months. Such atherosclerotic changes precluded transplantations beyond the 5 Pd series.

Age Factors↗