• Clinical and Experimental Pediatrics
• /
• v.51 no.11
• /
• pp.1165-1171
• /
• 2008

Purpose : This study aimed to identify the true extent of non-responsiveness in full-term infants born from HBsAg-negative or HBsAg-positive mothers and vaccinated against hepatitis B virus (HBV) at 0, 1, and 6 months of age and to evaluate the effect of revaccination among non-responders. Methods : The study included 716 full-term infants born in 2004-2007. Of 716, 662 infants (A group) were born to HBsAg-negative mothers and 54 infants (B group: 50, except HBsAg-positive infants) were born to HBsAg-positive mothers. All infants were administered DNA recombinant vaccines at 0, 1, and 6 months of age. B group infants received hepatitis B immunoglobulin at birth. Anti-HBs titers were tested at 7-12 and 9-15 months in A and B groups, respectively. Three revaccination doses were administered to non-responders whose anti-HBs titers were under 10 mIU/ml; revaccinated infants were retested at 1-3 months after last vaccination. The association between HBeAg seropositivity of mother and the failure of HBV immunoprophylaxis was evaluated. Results : The seroconversion rates after primary hepatitis B vaccination were higher in A group (94.1%) than in B group (78%, P<0.001). The seroconversion rates were high in revaccinated infants (A group non-responders: 96.9%, B group non-responders: 87.5%). The failure of HBV immunoprophylaxis was significantly associated with maternal HBeAg seropositivity (P<0.001). Conclusion : The seroconversion rates after primary hepatitis B vaccination were low in B group infants. Revaccination of non-responders in B group was very effective. Therefore, anti-HBs testing and revaccination of B group is very important. Revaccination of non-responders in A group was also very effective. Thus, testing the immune status of infants born to HBsAg-negative mothers even after primary hepatitis B vaccination should be considered. However, to realize this, further studies on the cost-effectiveness of anti-HBs testing in healthy full-term infants are necessary.

• Radiation Oncology Journal
• /
• v.12 no.1
• /
• pp.81-90
• /
• 1994

Purpose : The aim of this study is to analyze the clinical results of thermo-irradiation treatment for surgically unresectable advanced hepatoma with or without hepatic arterial chemo-embolization (HACE), chemotherapy (CT) and interferon (IFN) therapy. Materials and Methods : Between February 1990 and December 1992, 45 Patients with surgically unresectable advanced hepatomas were treated by thermo-irradiation with or without hepatic arterial chemo-embolization and other treatment modalities. Among them, We analyzed retrospectively 25 patients who received more than three times of hyperthermias. Mean age was 50 years (range : 18-71 years) and male to female ratio was 20 : 5. In the study, treatment was administered as follows : 3 patients received radiation therapy(RT) and hyperthermia (HT). 3 received RT+HT+CT. 3 received RT+HT+HACE. 1 received RT+HT+CT+HACE. 2 received RT+HT+CT+IFN. 10 received RT+HT+HACE+IFN. 3 received RT+HT+CT+HACE+IFN. Radiation therapy was done by a 6 MV linear accelerator Patients were treated with daily fractions of 180 cGy to doses of 11Gy-50Gy (median 30Gy). Local hyperthermia was done by HEH-500C(Omron Co. Japan), 30-45 min/session, 2 sessions/wk and the number of HT sessions ranged from 3 to 17 (median 7 times). 15 patients of 25 were followed by abdominal CT scan or abdominal ultra-sonogram. The following factors were analyzed :Age, histologic grade, sex. number of hyperthermia, total RT dose, hepatic arterial chemo-embolization. Results : Of 25 patients. there were observed tumor regression (partial response and minimal response) in 6 (24$ \% $), no response in 8 (32$ \% $), progression in 1 (4$ \% $) and not evaluable ones in 10 (40$ \% $) radiographically. The over all 1-year survival was 25$ \% $, with a mean survival of 33 weeks. The treatment modes of partial and minimal responsive patients (PR+MR)were as follows : Two were treated with RT+HT+HACE, 2 were done with RT+HT+HACE+IFN Remaining 2 were treated with RT+HT+CT+HACE+IFN. The significant factor affecting the survival rate were RT dose (more than 25 Gy), HACE, number of HT (above 6 times), responsiveness after treatment (PR + MR). Age, sex, histologic differentiation, chemotherapy, interferon therapy were not statistically significant factors affecting the survival rate. Conclusion : Although follow-up duration was short, the thermo-irr3diBtion with/without hepatic arterial chemo-embolization was well tolerated and there were no serious complicatons. In future, it is considered the longer follow up and prospective, well controlled trials should be followed to evaluate the efficacies of survival advantage.

• Journal of Life Science
• /
• v.19 no.6
• /
• pp.735-743
• /
• 2009

The common word flavonoids is often used to classify a family of natural compounds, highly abundant in all higher plants, that have received significant therapeutic interest in recent years. Naringin is associated with a reduced risk of heart disease, neurodegenerative disease, cancer and other chronic diseases; however the molecular basis of this effect remains to be elucidated. Thus we attempted to elucidate the anti-allergic effect of Naringin in ovalbumin (OVA)-induced asthma model mice. The OVA-induced mice showed allergic reactions in the airways. These included an increase in the number of eosinophils in bronchoalveolar lavage (BAL) fluid, an increase in inflammatory cell infiltration into the lung around blood vessels and airways, airway luminal narrowing, and the development of airway hyper-responsiveness (AHR). The administration of Naringin before the last airway OVA challenge resulted in a significant inhibition of all asthmatic reactions. Accordingly, this study may provide evidence that Naringin plays a critical role in the amelioration of the pathogenetic process of asthma in mice. These findings provide new insight into the immunopharmacological role of Naringin in terms of its effects on asthma in mice.

• Toxicological Research
• /
• v.8 no.2
• /
• pp.343-357
• /
• 1992

Tumor necrosis factor-${\alpha}$(TNF), a polypeptide hormone secreted primarily by activated macrophages, was originally identified on the basis of its ability to cause hemorrhagic necrosis and tumor regression in vivo. Subsequently, TNF has been shown to be an important component of the host responses to infection and cancer and may mediate the wasting syndrome known as cachexia. These systemic actions of TNF are reflected in its diverse effects on target cells in vitro. TNF initiates its diverse cellular actions by binding to specific cell surface receptors. Although TNF receptors have been identified on most of animal cells, regulation of these receptors and the mechanisms which transduce TNF receptor binding into cellular responses are not well understood. Therefore, in the present study, the mechanisms how TNF receptors are being regulated and how TNF receptor binding is being transduced into cellular responses were investigated in rat liver plasma membranes (PM) and ME-180 human cervical carcinoma cell lines. $^{125}I$-TNF bound to high ($K_d=1.51{\pm}0.35nM$)affinity receptors in rat liver PM. Solubilization of PM with 1% Triton X-100 increased both high affinity (from $0.33{\pm}0.04\;to\;1.67{\pm}0.05$ pmoles/mg protein) and low affinity (from $1.92{\pm}0.16\;to\;7.57{\pm}0.50$ pmoles/mg protein) TNF binding without affecting the affinities for TNF, suggesting the presence of a large latent pool of TNF receptors. Affinity labeling of receptors whether from PM or solubilized PM resulted in cross-linking of $^{125}I$-TNF into $M_r$ 130 kDa, 90 kDa and 66kDa complexes. Thus, the properties of the latent TNF receptors were similar to those initially accessible to TNF. To determine if exposure of latent receptors is regulated by TNF, $^{125}I$-TNF binding to control and TNF-pretreated membranes were assayed. Specific binding was increased by pretreatment with TNF (P<0.05), demonstrating that hepatic PM contains latent TNF receptors whose exposure is promoted by TNF. Homologous up-regulation of TNF receptors may, in part, be responsible for sustained hepatic responsiveness during chronic exposure to TNF. As a next step, the post-receptor events induced by TNF were examined. Although the signal transduction pathways for TNF have not been delineated clearly, the actions of many other hormones are mediated by the reversible phosphorylation of specific enzymes or target proteins. The present study demonstrated that TNF induces phosphorylation of 28 kDa protein (p28). Two dimensional soidum dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE) resolved the 28kDa phosphoprotein into two isoforms having pIs of 6.2 and 6.1. The pIs and relative molecular weight of p28 were consistent with those of a previously characterized mRNA cap binding protein. mRNA cap binding proteins are a class of translation initiation factors that recognize the 7-methylguanosine cap structure found on the 5' end of eukaryotic mRNAs. In vitro, these proteins are defined by their specific elution from affinity columns composed of 7-methylguanosine 5'-triphosphate($m^7$GTP)-Sepharose. Affinity purification of mRNA cap binding proteins from control and TNF treated ME-180 cells proved that TNF rapidly stimulates phosphorylation of an mRNA cap binding protein. Phosphorylation occurred in several cell types that are important in vitro models of TNF action. The mRNA cap binding protein phosphorylated in response to TNF treatment was purifice, sequenced, and identified as the proto-oncogene product eukaryotic initiation factor-4E(eIF-4E). These data show that phosphorylation of a key component of the cellular translational machinery is a common early event in the diverse cellular actions of TNF.

• Neonatal Medicine
• /
• v.16 no.2
• /
• pp.146-153
• /
• 2009

Purpose: The aim of this study is to investigate the current use of dexamethasone rescue therapy (DRT) for bronchopulmonary dysplasia (BPD). Methods: This is a retrospective study of 251 BPD patients managed in the neonatal intensive care units at Seoul National University Childrens Hospital and Seoul National University Bundang Hospital between March 2004 and August 2008. The demographic data and clinical characteristics of the mothers and infants were analyzed. The infants were compared based on DRT responsiveness. The DRT complications were investigated. Results: Ninety-three patients (37.1%) were classified with severe BPD, DRT was only given to patients with severe BPD. Dexamethasone was administered to 24 patients (9.6%) whose respiratory status had precluded extubation, which indicated that conventional BPD management had failed. Fourteen patients (58.3%) who received DRT were responsive. DRT non-responders required more oxygenation and more complicated with pulmonary arterial hypertension (PAH). Responder had shorter length's of hospitalization and lower mortality rates. High dose dexamethasone was no more effective in weaning neonates from the ventilatior than low dose dexamethasone. Sepsis was the most common complication of DRT. Conclusion: DRT is a valuable treatment for severe BPD ahead of PAH development. DRT should not be performed in BPD patients with PAH due to the possibility of complications.

• Tuberculosis and Respiratory Diseases
• /
• v.55 no.5
• /
• pp.459-466
• /
• 2003

Background : Asthma and eosinophilic bronchitis(EB) are eosinophilic inflammatory diseases of the airway. However, EB differs from asthma in that there is no variable airway obstruction or airway hyper-responsiveness. Pathologically, asthma is characterized by the accumulation of eosinophils and CD4+ T lymphocytes in the submucosa. A recent study showed that there was no significant difference between asthma and EB in terms of the submucosal eosinophil and T lymphocyte count. However, it is not known whether or not an infiltration of CD4+ and CD8+ T lymphocytes occurs in the airways of EB patients. The aim of this study was to identify the difference between the two conditions by measuring the submucosal CD4+ and CD8+ T lymphocyte count. Methods : Immunohistochemical analysis of bronchial-biopsy specimens was performed in 17 subjects with asthma and 24 subjects with EB. Results : The CD4+ T lymphocytes count in the asthma subjects and the EB subjects was similar (median, 58.6 vs 50.0 $cells/mm^2$, respectively; P=0.341). In contrast, the number of CD8+ T lymphocytes in the EB subjects was higher than that in the asthma subjects (median, 46.7 vs 11.8 $cells/mm^2$, respectively; P=0.003). Conclusion : The infiltration of submucosal CD8+ T lymphocytes may be associated with the pathophysiology of EB.

• Tuberculosis and Respiratory Diseases
• /
• v.49 no.2
• /
• pp.217-224
• /
• 2000

Background : It is well known that when macrophages are stimulated with endotoxin, they produce a wide variety of cytokine mediators, including TNF-$\alpha$ and IL-1$\beta$. However, there is an alteration in the macrophages' responsiveness when they are challenged with repeated bouts of endotoxin, termed "endotoxin tolerance" which is regarded as a self-protective phenomenon from continuous stimulation. In this study, endotoxin tolerance in the peripheral blood monocytes of sepsis patients was evaluated. Methods : Fourteen patients with organism-documented sepsis were included. The severity of illness was evaluated by APACHE II score. Peripheral blood monocytes were isolated from the patients and diluted to $1{\times}10^5$ well. After stimulation with endotoxin (LPS of E. coli O114 : B4, 100 ng/ml), they were incubated at $37^{\circ}C$ in 5% $CO_2$ incubator for 24 hours. Supernatant was collected for the measurement of TNF-$\alpha$ and IL-1$\beta$ with ELISA method. Peripheral blood monocytes of seven healthy volunteers were used as control. Results : The APACHE II score (mean$\pm$SD) of the patients at the time of blood sampling was 12.2$\pm$5.7. The primary infection foci were urinary tract infection, pneumonia, subacute bacterial endocarditis, and catheter related infection, etc. The causative organisms were gram negative rods (10 cases), gram positive cocci (6 cases) with two cases of mixed infection. Serum TNF-$\alpha$ could be measured in 4 cases with 29.9$\pm$27.7 pg/ml. Serum IL-1$\beta$was measurable in only one patient. The TNF-$\alpha$ level of supernatant of cultured peripheral blood monocytes was 2,703$\pm$2,066 pg/ml in patients and 2,102$\pm$1914 pg/ml in controls. The IL-1$\beta$level of supernatant was 884$\pm$1,050 pg/ml in patients and 575$\pm$558 pg/ml in controls. There was no difference of TNF-$\alpha$ and IL-1$\beta$ level between patients and controls. Conclusion : We cannot prove the phenomenon of endotoxin tolerance in this study. Future study needs to be focused on the more severe sepsis patients who were taken for sampling earlier. Addition of serum to the culture medium could be an another valuable option for the success of this study.

• Tuberculosis and Respiratory Diseases
• /
• v.49 no.5
• /
• pp.585-593
• /
• 2000

Background : International consensus guidelines have recently been developed to improve the assessment and management of asthma. One of the major recommendation of these guidelines is that asthma severity should be assessed through the recognition of key symptoms, such as nocturnal waking, medication requirements, and objective measurements of lung function. Differential classification of asthma severity would lead to major differences in both long term pharmacological management and the treatment of severe exacerbation. Methods : This study examined the relationship between the symptom score and measurements of $FEV_1$ and PEF when expressed as a percentage of predicted values in asthmatics (n=107). Results : The correlation of $FEV_1$ % with PEFR% was highly significant (r=0.83, p<0.01). However, there was agreement in terms of the classification of asthma severity in 76.6% of the paired measurements of $FEV_1$ % and PEFR%. Agreement in the classification of asthma severity was also found in 57.1% of the paired analysis of $FEV_1$ % and symptom score. 39% of the patients classified as having moderate asthma on the basis of $FEV_1$ % recording would be considered to have severe asthma if symptom score alone were used. Low baseline $FEV_1$ and high bronchial responsiveness were associated with a low degree of perception of airway obstruction. Conclusion : The relationships between the symptom score, PEFR and $FEV_1$ were generally poor. When assessing asthma severity, age, duration, $PC_{20}$, and baseline $FEV_1$ should be considered.

• Korean Journal of Biological Psychiatry
• /
• v.3 no.1
• /
• pp.46-50
• /
• 1996

This study was designed to examine the basal cyclic AMP levels and the $10^{-5}mol/L$ isoproterenol-stimulated cyclic AMP levels of lymphocytes, by which ${\beta}$-adrenoceptor function was shown, between to normal controls and 17 drug free patients(8 major depresive patients and 9 dysthymic patients), who were diagnosed by DSM-III-R. The severity of depression was assessed by Hamilton Rating Scale for Depression (HDRS). Cyclic AMP levels were measured by radioimmunoassay(double antibody). The results were as follows ; 1) HDRS score was significantly higher in major depressive patients($41.8{\pm}4.6$) than in dysthymic patients($24.0{\pm}4.2$)(p<005). 2) There was no Significant difference in basal cyclic AMP levels among normal controls($3.9{\pm}1.7pmol/10^6cells/10min$), major depressive patients($2.1{\pm}0.5pmol/10^6cells/10min$), and dysthymic patients($3.9{\pm}1.8pmol/10^6cells/10min$). 3) There was significant difference in net cyclic AMP levels($10^{-5}mol/L$ isoproterenol-stimulated cyclic AMP levels minus basal cyclic AMP levels) among normal controls($16.5{\pm}6.0pmol/10^6cells/10min$), major depressive patients($3.0{\pm}1.4pmol/10^6cells/10min$), dysthymic patients($10.9{\pm}4.4pmol/10^6cells/10min$)(p <005). 4) The net cyclic AMP levels were significantly correlated with HDRS scores in major depressive patients(${\gamma}=-0.8^6$, p<0.05), but not in dysthymic patients(${\gamma}=0.43$, p=0.25). In conclusion, we suggested that the dysthymic disorder might differ from the molar depressive disorder not only in the severity of depressive symptoms but also in ${\beta}$-adrenergic responsiveness of lymphocytes, which was regarded as a biological marker of depressive disorder.

• Korean Journal of Biological Psychiatry
• /
• v.14 no.3
• /
• pp.167-176
• /
• 2007

Objectives:A considerable number of pharmacogenetic studies have been performed in recent years to define the association of antipsychotic drug response with dopamine receptor polymorphisms. The purpose of this study was to investigate the relationship between the therapeutic response to antipsychotic drugs and the polymorphisms of the dopamine D2, D3, and D4 receptor genes(DRD2, DRD3 and DRD4, respectively). Methods:We conducted retrospective chart review of 200 consecutively hospitalized patients with the diagnosis of schizophrenia(DSM-IV) who were treated with various antipsychotics(94% atypical antipsychotics) at Bugok National Hospital, Korea. The patients were divided into two groups, responders and non-responders, by responsiveness to antipsychotic drugs according to a four-point scale used in previous studies; responders included moderate to marked responded patients and non-responders included none to minimal responded patients. We analyzed the Ser311Cys polymorphism in the DRD2, the Ser9Gly polymorphism in the DRD3, and the exon III 48 bp repeat polymorphism in the DRD4. Results:Among the total patients of 200, 141(70.5%) were categorized as responders. There were no significant differences in the frequencies of the DRD2, DRD3, and DRD4 alleles and genotypes between responders and non-responders. Conclusion:These results suggest that the Ser311Cys polymorphism in the DRD2, the Ser9Gly polym- orphism in the DRD3, and the exon III 48bp repeat polymorphism in the DRD4 are not associated with the therapeutic response to antipsychotic drugs in Korean schizophrenic patients. A larger prospective study is needed to elucidate the association between antipsychotic response and dopamine receptor gene polymorphism.