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Biomedical subjects

M Son

Publications and source records attributed to M Son.

At least 19 recordsLinked to original sources

Protection by tetracyclines against ion transport disruption caused by nystatin in human airway epithelial cells.

Polyene antifungal antibiotics like nystatin form monovalent cation pores on the plasma membrane that perturb the intracellular electrolyte milieu, resulting in cell damage. In the present study, we investigated the effects of tetracyclines (minocycline and tetracycline) on ion transporters disrupted by nystatin in cultured human airway Calu-3 cells. Apical application of nystatin (50 microM) on a monolayer of the cells stimulated Na(+)-K(+) pump activity as estimated by ouabain (1 mM)-sensitive short-circuit current (I(sc)). The nystatin-potentiated I(sc) was inhibited by minocycline (IC(50) = 25 microM) or tetracycline (IC(50) = 150 microM) applied only from the apical (nystatin-treated) side. Nystatin increased monolayer conductance that was reversed by the application of tetracyclines. In contrast, ouabain potentiated the nystatin-induced change in the conductance. Further, Na(+)-glucose transport affected by nystatin was also normalized by tetracyclines from the nystatin-treated side of the membrane. These data suggest that tetracyclines may lower the cell permeability potentiated by nystatin, protecting cells against damage.

Cell Line↗

Novel effects of minocycline on Ca(2+)-dependent Cl(-) secretion in human airway epithelial Calu-3 cells.

The present study concerns previously unreported effects of the antibiotic minocycline on the transepithelial Cl(-) transport in Calu-3 cells, which display electrophysiological properties consistent with human airway serous cells. Basolateral 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS, 200 microM) augmented Cl(-) secretion, which was detected as a 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB, 100 microM, a Cl(-) channel blocker)-sensitive short-circuit current (I(sc)). The DIDS-induced I(sc) was composed of Ca(2+)-activated K(+) (K(Ca)) channel-dependent and -independent components. The former was selectively inhibited by 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetra(acetoxymethyl)ester (BAPTA/AM, 10 microM), charybdotoxin (ChTx, 100 nM), clotrimazole (10 microM), basolateral Ca(2+) removal, and basolateral minocycline (IC(50) = 20 microM). The latter was attenuated by basolateral BaCl (5 mM). In contrast, forskolin (10 microM)-induced I(sc), which is insensitive to BAPTA/AM and ChTx, was unaffected by minocycline (100 microM). ATP-induced I(sc) was partially inhibited by basolateral but not by apical minocycline. I(sc) due to basolateral application of ionomycin (1 microM) was markedly suppressed by NPPB and basolateral Ca(2+) removal. These inhibitory effects were mimicked by minocycline applied only from the basolateral side of the monolayer. In the basolateral absence of Ca(2+), 1-ethyl-2-benzimdazolinone (500 microM), a K(Ca) channel opener, generated a sustained I(sc) sensitive to ChTx. Minocycline had no significant effect on the ChTx-sensitive component of the I(sc). It is concluded that minocycline inhibits K(Ca) channel-dependent Cl(-) secretion via a blockade of Ca(2+) influx across the basolateral membrane from the extracellular side.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Lipiodol solution of a lipophilic agent, (188)Re-TDD, for the treatment of liver cancer.

Radiolabeled lipiodol has been used for targeting liver cancer. We developed a lipiodol solution of (188)Re-TDD (2,2,9,9-tetramethyl-4,7-diaza-1,10-decanedithiol) and investigated its feasibility for the treatment of liver cancer. The lipiodol solution of (188)Re-TDD was well-retained in the lipiodol phase in vitro. After injection through the tail veins of mice, high lung-uptake was investigated which is evidence of embolizing activity. We also found high accumulation in hepatoma after injection through the hepatic arteries of hepatoma-bearing rats. In conclusion, the lipiodol solution of (188)Re-TDD is a promising agent for liver cancer therapy.

Animals↗

[A case of tuberculous pericarditis developing constrictive pericarditis].

A case of constrictive pericarditis which developed after the onset of clinical manifestation of tuberculous pericarditis was reported. A 75-year-old male, complaining of anorexia, was admitted to our hospital. Adenosinedeaminase (ADA) level in pericardial effusion was found to be increased, and the culture of pericardial effusion was positive for tubercle bacilli. Diagnosed as having tuberculous pleuritis and pericarditis, he underwent chemotherapy for tuberculosis. However, massive pleural effusion developed later and pleural effusion drainage was carried out. Despite repeated drainage, pleural effusion continued to recur. Chest CT revealed apparent pericardial thickening, in addition, cardiac catheterization revealed elevation of mean right atrial pressure and marked deterioration of cardiac functions including decrease of cardiac output. These findings were compatible with constrictive pericarditis. After these investigations a diagnosis of constrictive pericarditis was established, and the patient underwent a pericardiectomy. Pathological examination of resected specimens revealed tuberculous inflammation.

Aged↗

[Bronchiolo-alveolar cell carcinoma arising after active pulmonary tuberculosis' report of two cases].

We report on two patients diagnosed as having active pulmonary tuberculosis who later developed lung cancer. In both cases, the lung cancer was detected during the treatment of pulmonary tuberculosis. Both patients were initially considered to be experiencing exacerbation of pulmonary tuberculosis. Case 1 was seen in a 74-year-old man. His chest roentgenogram revealed microscopic cavitary lesions with infiltration into both lung fields. His sputum tested positive for acid-fast bacilli. Although he was treated with isoniazid (INH), rifampicin (RFP), ethambutol (EB) and pyrazinamide (PZA), his general condition deteriorated, and the infiltrative shadows in the lung fields had expanded on subsequent chest radiography. Transbronchial lung biopsy (TBLB) yielded findings compatible with a diagnosis of bronchiolo-alveolar cell carcinoma. Case 2 occurred in a 52-year-old man. His chest radiograph revealed cavitary lesions with infiltration into both lung fields. His sputum also tested positive for acidfast bacilli. Despite medication with INH, RFP, EB and PZA, the infiltrative shadow in his chest radiograph increased in size. Bronchiolo-alveolar cell carcinoma was confirmed after examination of the sputum cytology. Case 1 was diagnosed as lung cancer 10 months after being admission to the hospital, and Case 2, seven months after hospitalization. Recent discussion concerning the simultaneous occurrence of pulmonary tuberculosis and bronchogenic carcinoma suggests a high frequency of coexistence of the two diseases. However, the coexistence of active tuberculosis with bronchiolo-alveolar cell carcinoma, as in our cases, is rare.

Adenocarcinoma, Bronchiolo-Alveolar↗

[A case of tuberculous peritonitis diagnosed by a direct smear of ascitic fluid complicated with an active pulmonary tuberculosis and intestinal tuberculosis].

We sometimes encounter difficulties in differentiating tuberculous peritonitis from other inflammatory disorders or ascites due to carcinomatous peritonitis. Acid-fast bacilli are very rarely detected in ascites. In this study, we reported a case of tuberculous peritonitis accompanied with active pulmonary tuberculosis in which acid-fast bacilli were detected in ascites. The patient was a 37-year-old single man who had been admitted to our hospital on February 28, 2000, because acid-fast bacilli were detected in sputum, faces and ascites by a direct smear. He had a lower abdominal distention and pain. His serum CA 125 level was high, 121 U/ml. Abdominal ultrasonography showed marked ascites in Douglas pouch. However adenosine deaminase level was not high in his ascites. During treatment by the combination chemotherapy with INH, RFP, EB, and PZA, serum CA 125 level was decreased.

Adult↗

[Two cases of multi-drug-resistant pulmonary tuberculosis with para-aminosalicylic acid (PAS)-induced hypothyroidism].

Two cases of multi-drug-resistant pulmonary tuberculosis with para-aminosalicylic acid (PAS)-induced hypothyroidism were reported. Case 1; a 73-year-old male, complaining of edema, was admitted to our hospital. He had been treated for his multi-drug-resistant pulmonary tuberculosis during the past 1 year with an antituberculous regimen consisting of ethambutol (EB), ethionamide (ETH) and PAS. A thyroid profile performed when he was admitted to our hospital showed several marked abnormalities: serum thyroid stimulating hormone (TSH) was elevated (69.4 microIU/ml: normal, 0.4-4.2 mIU/ml), free thyroxine level (T4) (0.01 ng/dl; normal, 0.70-1.60 ng/dl) and free triiodothyronine level (Ts) (0.60 pg/ml; normal, 2.3-4.1 pg/ml) were low. PAS was discontinued after he was admitted to our hospital, since PAS was believed to be the cause of the hypothyroidism. A thyroid profile that was repeated after the exclusion of PAS from treatment showed the following results: the TSH level was decreased (13.4 mIU/ml), the free T4 (0.93 ng/dl) were normal. During treatment with PAS, he had never received thyroid replacement therapy. Case 2; A 22-year-old female, complaining of hemosputum. She had been treated for her multi-drug-resistant pulmonary tuberculosis during the past 11 months with an antituberculous regimen consisting of EB, ETH and PAS. A thryoid profile performed when she was admitted to our hospital showed several marked abnormalities: elevated serum TSH (112.7 mIU/ml), and low T4 (2.0 micrograms/dl) and T3 (1.1 ng/ml). A thyroid profile that was repeated after the exclusion of PAS from treatment showed the following results: the TSH level was decreased (5.1 mIU/ml). Drug-induced hypothyroidism is an infrequent side effect of therapy with PAS, and only a few cases of PAS-induced hypothyroidism have been reported so far. In this report, we describe patients with hypothyroidism who were receiving therapy for multi-drug-resistant tuberculosis, tuberculosis namely, resistant to at least isoniazid (INH) and rifampicin (RFP), with a regimen that contained PAS.

Adult↗

[A case of pulmonary eosinophilic granuloma arising rapidly 30 years after the start of smoking and remitting spontaneously without smoking cessation].

A case of pulmonary eosinophilic granuloma which arose rapidly after 30 years of smoking and remitted spontaneously without smoking cessation is reported. The patient was a 54-year-old man complaining of a dry cough who had been smoking 30 cigarettes a day for 30 years. Chest roentgenography showed multiple nodular shadows and cystic lesions in the upper and middle fields of both lungs. Chest computed tomography revealed multiple small cysts and small nodular lesions, mainly in both upper lung fields. CT findings strongly suggested pulmonary eosinophilic granuloma. A transbronchial lung biopsy (TBLB) was performed and 4 specimens were obtained, of which 3 showed granulomatous lesions with eosinophils and histiocytes. Furthermore, the granulomatous lesions were positive for S-100 protein staining. The symptoms and radiographic findings improved markedly within about 6 months after the onset of symptoms without treatment. Many cases of this disease were diagnosed in the past by open lung biopsy, but the number of cases diagnosed by TBLB is now increasing. The effectiveness of open lung biopsy has been emphasized in the diagnosis of pulmonary eosinophilic granuloma, but TBLB is also useful for diagnosis, especially in the active or early stage of the disease.

Eosinophilic Granuloma↗

Cellular and molecular mechanism for Kilham rat virus-induced autoimmune diabetes in DR-BB rats.

Kilham rat virus (KRV) causes autoimmune diabetes in diabetes-resistant BioBreeding (DR-BB) rats; however, the mechanism by which KRV induces autoimmune diabetes without the direct infection of beta cells is not well understood. We first asked whether molecular mimicry, such as a common epitope between a KRV-specific peptide and a beta cell autoantigen, is involved in the initiation of KRV-induced autoimmune diabetes in DR-BB rats. We found that KRV peptide-specific T cells generated in DR-BB rats infected with recombinant vaccinia virus expressing KRV-specific structural and nonstructural proteins could not induce diabetes, indicating that molecular mimicry is not the mechanism by which KRV induces autoimmune diabetes. Alternatively, we asked whether KRV infection of DR-BB rats could disrupt the finely tuned immune balance and activate autoreactive T cells that are cytotoxic to beta cells, resulting in T cell-mediated autoimmune diabetes. We found that both Th1-like CD45RC+CD4+ and cytotoxic CD8+ T cells were up-regulated, whereas Th2-like CD45RC-CD4+ T cells were down-regulated, and that isolated and activated CD45RC+CD4+ and CD8+ T cells from KRV-infected DR-BB rats induced autoimmune diabetes in young diabetes-prone BioBreeding (DP-BB) rats. We conclude that KRV-induced autoimmune diabetes in DR-BB rats is not due to molecular mimicry, but is due to a breakdown of the finely tuned immune balance of Th1-like CD45RC+CD4+ and Th2-like CD45RC-CD4+ T cells, resulting in the selective activation of beta cell-cytotoxic effector T cells.

Acute Disease↗

Effect of DA-6034, a derivative of flavonoid, on experimental animal models of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a multifactorial disorder with unknown etiology and pathogenesis. DA-6034, 7-carboxymethyloxy-3', 4', 5-trimethoxy flavone, is a synthetic flavonoid known to possess anti-inflammatory activity. This study was performed to evaluate the oral therapeutic effect of DA-6034 in three experimental animal models of IBD: two chemical-induced IBD models of rats and the human leukocyte antigen (HLA)-B27 transgenic rat model known to develop spontaneous colitis without the use of exogenous agents. Acute chemical colitis was induced by intracolonic instillation of 1.2 ml of 4% acetic acid solution. Prednisolone (1 mg/kg), sulfasalazine (100 mg/kg) and DA-6034 (0.3 to approximately 3 mg/kg) were orally administered twice daily for 6 days in these rats. In addition, chronic chemical colitis was induced by intracolonic administration of trinitrobenzene sulfonic acid (TNBS) 30 mg in 50% ethanol and agents were orally administered for 6 or 20 days. In chemical-induced IBD models, all of these agents reduced the severity of colitis and specially, DA-6034 (3 mg/kg) showed more potent effect than other drugs in macroscopic lesion score. In HLA-B27 transgenic rats, DA-6034 (3 mg/kg) and prednisolone (0.5 mg/kg) were treated orally twice daily for 6 weeks. The HLA-B27 transgenic rats showed only mild colitis, compared with the chemical-induced colitis models. DA-6034 ameliorated the loose stool and decreased microscopic damage, which is the important indicator of this model. In conclusion, oral therapy of DA-6034 attenuated the macroscopic and histologic damages of the colon in all three experimental models of IBD, which suggest that DA-6034 could be a promising drug in the treatment of IBD.

Acetic Acid↗

Expression of Th1 and Th2 type cytokines responding to HBsAg and HBxAg in chronic hepatitis B patients.

The cytokine pattern on viral antigen recognition is believed to exert a profound influence on the resolution of viral infections and viral clearance. This study was initiated to investigate whether a cytokine imbalance oriented toward Th2 type response plays a role in chronic hepatitis B. Cytokine profiles of peripheral blood mononuclear cells associated with chronic hepatitis B were analysed by RT-PCR. Upon HBsAg stimulation, expression of IFN-gamma, IL-2, IL-4, and IL-10 was detected in 41%, 8%, 41%, and 50% of the patients, respectively. Among these cytokines, the expression of IFN-gamma was associated with high levels of serum AST/ALT. However, we could not prove that Th2 type cytokines had a protective effect on hepatocytes. Upon HBxAg stimulation, there was no recognizable association of cytokine patterns with AST/ALT levels. In conclusion, production of a Th1 cytokine, IFN-gamma, by HBsAg-reactive cells was associated with hepatocyte damage in chronic hepatitis B, while no counteracting effect of Th2 cytokines produced by those cells was observed.

Cytokines↗

Taurine can ameliorate inflammatory bowel disease in rats.

We previously reported that the protective effect of taurine against indomethacin-induced gastric mucosal injury was due to its antioxidant effects which inhibited lipid peroxidation and neutrophil activation. In this study, we examined the effect of taurine on reducing the inflammatory parameters of trinitrobenzene sulfonic acid (TNBS)-induced inflammatory bowel disease (IBD) in rats. To induce IBD, rats were given ethanolic TNBS intracolonically. The rats then received 500 mg/kg/day of taurine per orally. The rats were sacrificed one week after IBD induction. Ulceration and inflammation of the distal colon with formation of granuloma in the vehicle-treated IBD rats after two days of administration of TNBS were observed. Treatment with 0.5 g/kg of taurine by the oral route ameliorated colonic damage and decreased the incidence of diarrhea and adhesions. Colon weight (an index of tissue edema) was markedly increased in the IBD rats after administration of TNBS, but was significantly lower after taurine treatment. Myeloperoxidase (MPO) activity in the vehicle-treated IBD rats was substantially increased compared with that of the control. The taurine-treated animals showed reduced MPO activity (35% lower) when compared with that of the vehicle-treated animals. Taurine treatment decreased basal and formyl-methionyl leucyl phenylalanine (FMLP) stimulated reactive oxygen generation in colonic tissue of the IBD rat compared with vehicle treatment after one week. These results suggest that administration of taurine reduced the inflammatory parameters in this rat model of IBD by increasing the defenses against oxidative insult.

Animals↗

Heterogeneity of IgE response to TDI-HSA conjugates by ELISA in toluene diisocyanate (TDI) -induced occupational asthma (OA) patients.

Toluene diisocyanate (TDI), a low molecular weight reactive chemical, is known to be a main cause of occupational asthma (OA) in Korea. Although it is thought that inhaled TDI may act as a hapten, the precise mechanisms of TDI-induced OA are unknown. In this study, TDI-human serum albumin (HSA) conjugates (5, 10, 20 and 30 min) were prepared in the range of 1.5 to 5.0 TDI mole/HSA mole. Specific binding of serum IgE to TDI-HSA (30 min) was observed using IgE ELISA as well as ELISA inhibition assay. Around 40% of TDI-induced OA patients were positive for serum specific IgE by ELISA. Degrees of serum IgE binding were different depending on which TDI-HSA conjugate was used as an antigen. Moreover, binding patterns were different depending on the individuals. Interestingly, higher binding of IgE to TDI-HSA (5 min) than to TDI-HSA (30 min) which was more highly substituted was observed in some patients. Probably new antigenic epitopes on carrier proteins were targets of the specific IgE. The results of this study indicated that IgE responses to TDI-HSA conjugates were heterogeneous in TDI-induced OA patients and self-proteins modified by reactive chemicals can become a major target antigen of IgE in certain cases.

Antibody Specificity↗

Formation and cleavage of a DNA network during in vitro bacteriophage T7 DNA packaging: light microscopy of DNA metabolism.

To understand in vivo DNA metabolism, in vitro systems are developed that perform DNA metabolism, while maintaining in vivo (physiological) character. To determine the state of DNA during in vitro physiological metabolism, the present study develops procedures of fluorescence light microscopy for observation of stained DNA molecules during in vitro physiological metabolism in a crude extract of bacteriophage T7-infected cells. The extract inhibits illumination-induced breakage of DNA. The following DNA metabolism remains active for 2-3 min during microscopy: exonuclease-dependent end-to-end joining (concatemerization) of T7 DNA and subsequent cleavage of concatemers. When the T7 gene 3-encoded DNA debranching endonuclease is absent during in vitro T7 DNA concatemerization, DNA progressively partitions to form a continuous, mostly immobile (i.e., no detected Brownian motion) fibrous network that encloses the DNA-depleted solution; presumably because of reduced branching, a less extensive network forms when the gene 3-encoded debranching endonuclease is present. Most strands of the network consist of multiple DNA segments. After a time interval of 5-10 min, the DNA network undergoes cleavage that depends on the presence of both ATP, capsids, and the DNA packaging accessory proteins encoded by genes 18 and 19; multiple cleavages eventually disrupt the continuity of the DNA network. The dependence of the observed cleavage on these factors is explained by the hypothesis that this cleavage is the first of two cleavages known to occur during the packaging of T7 DNA concatemers both in vivo and in vitro. The first cleavage is also known to initiate entry of DNA into a T7 capsid. The cleavage observed here is usually preceded by an approximately 10 s burst of oscillatory motion of the DNA network near the point of eventual cleavage. If the in vivo presence of a similar concatemer-containing DNA network is assumed, requirement for DNA packaging-associated release of DNA from this network is a possible explanation for the evolution of a T7 DNA packaging pathway that is initiated by cleavage of a concatemer.

Adenosine Triphosphate↗

[Long-term late results of pericardiectomy for constrictive pericarditis].

Twenty-four cases of the constrictive pericarditis were operated on pericardiectomy from 1966 to 1990. One case died because of massive bleeding, LOS, and respiratory failure immediately after the operation. A long-term follow up study was performed up to 27 years (mean 13.1 years) in other cases. Ten cases died during the follow up period (cardiac: 6, non cardiac: 4). Five cases of the cardiac deaths had major complications: tabes dorsalis, chronic respiratory failure, pacemaker implantation, mitral regurgitation, emergency operation at high age (78 years old). The survival rates of 5, 10, and 15 years were 85%, 67%, and 58.2%, respectively (Kaplan-Meier). All of survival cases are now in NYHA I or II class in satisfactory. We concluded that pericardiectomy is a very effective treatment for constrictive pericarditis but a more careful follow up is required especially in cases complicated with other major problems because cardiac function is not so recovered as normal level after surgery due probably to readhesion and fibrotic changes of the myocardium.

Adult↗