• Journal of Preventive Medicine and Public Health
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• v.32 no.1
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• pp.88-94
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• 1999

Objectives. In order to gain a better understanding of the mechanism of DMF toxicity, recent studies have focused on hepatic drug metabolizing enzymes. In this study, we investigated the effects of DMF on the induction of P450 and the activities of other related enzymes in rat liver microsomes. Methods. DMF was administered to male Sprague Daweley rats by intraperitoneal injection at 0(control), 450(D1), 900(D2), 1,800(D3) mg DMF/kg body weight in olive oil once a day for three days. Hepatic P450 was measured by method of Omura and Sato. We evaluated selective assays for the three drug metabolizing cytochrome P450 isoenzymes 1A1, 2B1 and 2E1. Results. The content of microsomal protein, P450 and b5 were tended to be decreased in DMF treated group, but they were not statistically significant. The activity of NADPH-cytochrome P450 reductase was significantly increased dose dependently(p<0.01), but the activity of NADH-b5 reductase was decreased in the treated group(p<0.01). The activities of PROD and EROD were not significant between control and treated group. The activities of pNPH in the DMF treated groups were higher than that of the control group(p<0.01). When Western immunoblottings were carried out utilizing three monoclonal antibodies which were specific against P4501A1/1, P4502B1/2 and P4502E1, the strong density band corresponding to P4502E1 was observed with the microsomes obtained from the rats treated with DMF. But there were no significant increased in the P4501A1/2 and P4502B1/2 band densities in immunoblotting. Conclusions. These result suggested that P4502E1 was inducible by DMF and P4502E1 isozyme might be responsible for the hydroxylation of DMF to HMMF.

• Proceedings of the KSAR Conference
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• 2000.10a
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• pp.10-12
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• 2000

Members of the glycoprotein family, which includes CG, LH, FSH and TSH, comprise two noncovalently linked $\alpha$- and $\beta$-subunits. Equine chorionic gonadotropin (eCG), known as PMSG, has a number of interesting and unique characteristics since it appears to be a single molecule that possesses both LH- and FSH-like activities in other species than the horse. This dual activity of eCG in heterologous species is of fundamental interest to the study of the structure-function relationships of gonadotropins and their receptors. CG and LH $\beta$ genes are different in primates. In horse, however, a single gene encodes both eCG and eLH $\beta$-subunits. The subunit mRNA levels seem to be independently regulated and their imbalance may account for differences in the quantities of $\alpha$ - and $\beta$ -subunits in the placenta and pituitary. The dual activities of eCG could be separated by removal of the N-linked oligosaccharide on the $\alpha$-subunit Asn 56 or CTP-associated O-linked oligosaccharides. The tethered-eCG was. efficiently secreted and showed similar LH-like activity to the dimeric eCG. Interestingly, the FSH-like activity of the tethered-eCG was increased markedly in comparison with the native and wild type eCG. These results also suggest that this molecular can implay particular models of FSH-like activity not LH-like activity in the eCG/indicate that the constructs of tethered molecule will be useful in the study of mutants that affect subunit association and/or secretion. A single-chain analog can also be constructed to include additional hormone-specific bioactive generating potentially efficacious compounds that have only FSH-like activity. The LH/CG receptor (LH/CGR), a membrane glycoprotein that is present on testicular Leydig cells and ovarian theca, granulosa, luteal, and interstitial cells, plays a pivotal role in the regulation of gonadal development and function in males as well as in nonpregnant and pregnant females. The LH/CGR is a member of the family of G protein-coupled receptors and its structure is predicted to consist of a large extracellular domain connected to a bundle of seven membrane-spanning a-helices. The LH/CGR phosphorylation can be induced with a phorbol ester, but not with a calcium ionophore. The truncated form of LHR also was down-regulated normally in response to hCG stimulation. In contrast, the cell lines expressing LHR-t63I or LHR-628, the two phosphorylation-negative receptor mutant, showed a delay in the early phase of hCG-induced desensitization, a complete loss of PMA-induced desensitization, and an increase in the rate of hCG-induced receptor down-regulation. These results clearly show that residues 632-653 in the C-terminal tail of the LHR are involved in PMA-induced desensitization, hCG-induced desensitization, and hCG-induced down-regulation. Recently, constitutively activating mutations of the receptor have been identified that are associated with familial male-precocious puberty. Cells expressing LHR-D556Y bind hCG with normal affinity, exhibit a 25-fold increase in basal cAMP and respond to hCG with a normal increase in cAMP accumulation. This mutation enhances the internalization of the free and agonist-occupied receptors ~2- and ~17-fold, respectively. We conclude that the state of activation of the LHR can modulate its basal and/or agonist-stimulated internalization. Since the internalization of hCG is involved in the termination of hCG actions, we suggest that the lack of responsiveness detected in cells expressing LHR-L435R is due to the fast rate of internalization of the bound hCG. This statement is supported by the finding that hCG responsiveness is restored when the cells are lysed and signal transduction is measured in a subcellular fraction (membranes) that cannot internalize the bound hormone.

• Clinical and Experimental Pediatrics
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• v.49 no.3
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• pp.278-286
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• 2006

Purpose : Although suprapubic bladder aspiration(SBA) is the most reliable technique for identifying bacteriuria in young infant, no report has been published about the clinical manifestations of urinary tract infection(UTI) diagnosed by aspirated urine in Korea. This study was performed to examine clinical manifestations and related factors of UTI confirmed by a positive urine culture obtained by SBA in young infants. Methods : We reviewed medical records of 159 infants younger than six months of age, who had been admitted for UTI to Korea University Ansan Hospital from January 2002 to June 2005. Results : The male:female ratio was 5.1 : 1. The most common pathogen in urine culture was Escherichia coli(92.5 percent). Most of the gram-negative pathogens had high sensitivity to amikacin, or third generation cephalosporins and had low sensitivity to ampicillin, trimethoprim-sulfamethoxazole, or gentamicin. Hydronephrosis and vesicoureteral reflux(VUR) were present in 32.7 percent and 27.7 percent respectively. Renal cortical defects observed on DMSA scans were detected in 37.1 percent. Prolonged fever duration and hospital day, high erythrocyte sedimentation rate(ESR) and C-reactive protein(CRP) levels, hydronephrosis and VUR were related to the renal cortical defects(P<0.05). Rates of UTI-associated bacteremia and aseptic meningitis were 8.3 percent and 6.6 percent. Conclusion : Early differential diagnosis is very important in infants younger than 6 months of age with UTI because the clinical findings are non-specific and UTI-associated bacteremia and aseptic meningitis are concomitantly found. Because prolonged fever and higher ESR and CRP levels are risk factors of the renal cortical defects, radiologic evaluations and nephrologic follow-up were needed in identifying the predisposing congenital abnormalities and chronic renal scarring.

• Korean Journal of Animal Reproduction
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• v.24 no.4
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• pp.357-364
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• 2000

Members of the glycoprotein family, which includes CG, LH, FSH and TSH, comprise two noncovalently linked $\alpha$- and $\beta$-subunits. Equine chorionic gonadotropin (eCG), known as PMSG, has a number of interesting and unique characteristics since it appears to be a single molecule that possesses both LH- and FSH-like activities in other species than the horse. This dual activity of eCG in heterologous species is of fundamental interest to the study of the structure-function relationships of gonadotropins and their receptors. CG and LH $\beta$ genes are different in primates. In horse, however, a single gene encodes both eCG and eLH $\beta$ -subunits. The subunit mRNA levels seem to be independently regulated and their imbalance may account for differences in the quantities of $\alpha$ - and $\beta$-subunits in the placenta and pituitary. The dual activities of eCG could be separated by removal of the N-linked oligosaccharide on the $\alpha$-subunit Asn 56 or CTP-associated O-linked oligosaccharides. The tethered-eCG was efficiently secreted and showed similar LH-like activity to the dimeric eCG. Interestingly, the FSH-like activity of the tethered-eCG was increased markedly in comparison with the native and wild type eCG. These results also suggest that this molecular can implay particular models of FSH-like activity not LH-like activity in the eCG/indicate that the constructs of tethered molecule will be useful in the study of mutants that affect subunit association and/or secretion. A single-chain analog can also be constructed to include additional hormone-specific bioactive generating potentially efficacious compounds that have only FSH-like activity. The LH/CG receptor (LH/CGR), a membrane glycoprotein that is present on testicular Leydig cells and ovarian theca, granulosa, luteal, and interstitial cells, plays a pivotal role in the regulation of gonadal development and function in males as well as in nonpregnant and pregnant females. The LH/CGR is a member of the family of G protein-coupled receptors and its structure is predicted to of a large extracellular domain connected to a bundle of seven membrane-spanning a-helices. The LH/CGR phosphorylation can be induced with a phorbol ester, but not with a calcium ionophore. The truncated form of LHR also was down-regulated normally in response to hCG stimulation. In contrast, the cell lines expressing LHR-t631 or LHR-628, the two phosphorylation-negative receptor mutant, showed a delay in the early phase of hCG-induced desensitization, a complete loss of PMA-induced desensitization, and an increase in the rate of hCG-induced receptor down-regulation. These results clearly show that residues 632~653 in the C-terminal tail of the LHR are involved in PMA-induced desensitization, hCG-induced desensitization, and hCG-induced down-regulation. Recently, constitutively activating mutations of the receptor have been identified that are associated with familial male-precocious puberty. Cells expressing LHR-D556Y bind hCG with normal affinity, exhibit a 25-fold increase in basal cAMP and respond to hCG with a normal increase in cAMP accumulation. This mutation enhances the internalization of the free and agoinst-occupied receptors ~2- and ~17- fold, respectively. We conclude that the state of activation of the LHR can modulate its basal and/or agonist-stimulated internalization. Since the internalization of hCG is involved in the termination of hCG actions, we suggest that the lack of responsiveness detected in cells expressing LHR-L435R is due to the fast rate of internalization of the bound hCG. This statement is supported by the finding that hCG responsiveness is restored when the cells are lysed and signal transduction is measured in a subcellular fraction (membranes) that cannot internalize the bound hormone.

• Korean Journal of Poultry Science
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• v.39 no.2
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• pp.121-131
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• 2012

To investigate the effect of dietary supplementation of freeze-dried plum (Prunus mume Siebold and Zucc., PMS) or omija meal (Schizandra chinensis Baill.; SCB) on growth performance, organ weights, blood biochemical profiles and antioxidant defense system, a total of 96, 3-day-old male broiler chickens were assigned to three dietary groups: (1) control diet, (2) control diet supplemented with PMS at 0.2%, (3) control diet supplemented with SCB at 0.2%. In vitro antioxidant activity, plum and omija extracts showed a significantly higher radical scavenging activity (RSA). In particular, omija extract showed much higher RSA than plum extract. Dietary addition of plum or omija did not affect body weight, feed intake, feed conversion and the relative weight of digestive organ in birds. Plasma triglyceride significantly (P<0.05) increased in birds fed the diet supplemented with omija compared with those fed control diet without affecting the other blood biochemical components. Furthermore, reduced form of glutathione (GSH) in the liver or muscle significantly (P<0.05) increased in birds fed the diet fortified with plum and omija. However, the specific activities of superoxide dismutase (SOD), glutathione peroxidase (GPX) and glutathione-S-transferase (GST) and MDA (malondealdehyde) in the intestine, liver and muscle were not altered by dietary antioxidant sources. In conclusion, dietary plum and omija resulted in a positive effect on some antioxidant indicators such as increased in vitro RAS in extracts and in vivo GSH level in the liver and muscle without affecting growth performance. Therefore, dietary addition of 0.2% of plum or omija could be applicable as potential antioxidant sources in broiler chick production.

• Korean Journal of Poultry Science
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• v.39 no.3
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• pp.223-232
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• 2012

The effects of dietary supplementation of dried coffee meal (CM) on growth performance, blood biochemical profiles, the weights of immune-related organs, and the antioxidant defense system in broiler chicks were examined. A total of 162, 3-day-old male broiler chickens were assigned to three dietary groups: control group (CON), control diet added with 0.5% CM (CM0.5), and control diet added with 1.0% CM (CM1.0). In vitro antioxidant activity test, coffee extracts showed concentration-dependent increase in radical scavenging activity. Dietary addition of 0.5 and 1.0% of CM did not have negative effects on growth performance and feed conversion during the experimental periods, whereas dietary CM significantly (P<0.05) increased the relative weight of thymus without changes in the other organ weights. In addition, birds fed the diet supplemented with CM (0.5 and 1.0%) significantly increased blood albumin without affecting other components including glucose, triglyceride and cholesterol compared with those fed control diet. In antioxidant defense system, the specific activities of superoxide dismutase, glutathione peroxidase and glutathione S-transferase and the level of glutathione in the small intestine and liver were not affected by dietary supplementation of CM. However, hepatic lipid peroxidation in birds fed the diet supplemented with 0.5% CM was significantly (P<0.05) decreased compared with that in control birds. In conclusion, dietary supplementation of CM(0.5~1.0%) has potential for use as a natural antioxidant source without negative effect on growth performance in broiler chickens.

• Tuberculosis and Respiratory Diseases
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• v.51 no.6
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• pp.559-569
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• 2001

Background : Pleural effusion is one of the most common clinical manifestations associated with a variety of pulmonary diseases such as malignancy, tuberculosis, and pneumonia. However, there are no useful laboratory tests to determine the specific cause of pleural effusion. Therefore, an attempt was made to analyze the various types of pleural effusion and search for useful laboratory tests for pleural effusion in order to differentiate between the diseases, especially between a malignant pleural effusion and a non-malignant pleural effusion. Methods : 93 patients with a pleural effusion, who visited the Severance hospital from January 1998 to August 1999, were enrolled in this study. Ultrasound-guided thoracentesis was done and a confirmational diagnosis was made by a gram stain, bacterial culture, Ziehl-Neelsen stain, a mycobacterial culture, a pleural biopsy and cytology. Results : The male to female ratio was 56 : 37 and the average age was $47.1{\pm}21.8$ years. There were 16 cases with a malignant effusion, 12 cases with a para-malignant effusion, 36 cases with tuberculosis, 22 cases with a para-pneumonic effusion, and 7 cases with transudate. The LDH2 fraction was significantly higher in the para-malignant effusion group compared to the para-pneumonic effusion group [$30.6{\pm}6.4%$ and $20.2{\pm}7.5%$, respectively (p<0.05)] and both the LDH1 and LDH2 fraction was significantly in the para-malignant effusion group compared to those with tuberculosis [$16.4{\pm}7.2%$ vs. $7.6{\pm}4.7%$, and $30.6{\pm}6.4%$ vs.$17.6{\pm}6.3%$, respectively (p<0.05)]. The pleural effusion/serum LDH4 fraction ratio was significantly lower in the malignant effusion group compared to those with tuberculosis [$1.5{\pm}0.8$ vs. $2.1{\pm}0.6$, respectively (p<0.05)]. The LDH4 fraction and the pleural effusion/serum LDH4 fraction ratio was significantly lower in the para-malignant effusion group compared to those with tuberculosis [$17.0{\pm}5.8%$ vs. $23.5{\pm}4.6%$ and $1.3{\pm}0.4$ vs. $2.1{\pm}0.6$, respectively (p<0.05)]. Conclusion : These results suggest that the LDH isoenzyme was the only useful biochemical test for a differential diagnosis of the various diseases. In particular, the most useful test was the pleural effusion/serum LDH4 fraction ratio to distinguish between a para-malignant effusion and a tuberculous effusion.