• Biomolecules & Therapeutics
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• v.20 no.1
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• pp.43-49
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• 2012

Stimulation of mast cells through the high affinity IgE receptor (Fc${\varepsilon}$RI) induces degranulation, lipid mediator release, and cytokine secretion leading to allergic reactions. Although various signaling pathways have been characterized to be involved in the Fc${\varepsilon}$RI-mediated responses, little is known about the precious mechanism for the expression of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) in mast cells. Here, we report that rapamycin, a specific inhibitor of mammalian target of rapamycin (mTOR), reduces the expression of TNF-${\alpha}$ in rat basophilic leukemia (RBL-2H3) cells. IgE or specific antigen stimulation of RBL-2H3 cells increases the expression of TNF-${\alpha}$ and activates various signaling molecules including S6K1, Akt and p38 MAPK. Rapamycin specifically inhibits antigeninduced TNF-${\alpha}$ mRNA level, while other kinase inhibitors have no effect on TNF-${\alpha}$ mRNA level. These data indicate that mTOR signaling pathway is the main regulation mechanism for antigen-induced TNF-${\alpha}$ expression. TNF-${\alpha}$ mRNA stability analysis using reporter construct containing TNF-${\alpha}$ adenylate/uridylate-rich elements (AREs) shows that rapamycin destabilizes TNF-${\alpha}$ mRNA via regulating the AU-rich element of TNF-${\alpha}$ mRNA. The antigen-induced activation of S6K1 is inhibited by specific kinase inhibitors including mTOR, PI3K, PKC and $Ca^{2+}$chelator inhibitor, while TNF-${\alpha}$ mRNA level is reduced only by rapamycin treatment. These data suggest that the effects of rapamycin on the expression of TNF-${\alpha}$ mRNA are not mediated by S6K1 but regulated by mTOR. Taken together, our results reveal that mTOR signaling pathway is a novel regulation mechanism for antigen-induced TNF-${\alpha}$ expression in RBL-2H3 cells.

• The Korean Journal of Nuclear Medicine
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• v.32 no.4
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• pp.354-364
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• 1998

Purpose: Simple X-ray study and bone scan have limitations for early diagnosis of bone or bone marrow lesions in multiple myeloma. The purpose of this study was to evaluate the diagnostic usefulness of bone marrow immunoscintigraphy using anti-granulocyte monoclonal antibody for the evaluation of bone involvement in multiple myeloma. Materials and Methods: In 22 patients (Male: 15, Female: 7) with multiple myeloma, we performed whole-body immunoscintigraphy using $^{99m}Tc$-labelled antigranulocyte antibody (BW 250/183, Scintimum $Granulozyt^{(R)}$ CIS, France) and compared the findings with those of simple bone radiography and $^{99m}Tc$-MDP bone scan. Abnormal findings in bone marrow scintigraphy were, considered to be present in case of expansion of peripheral bone marrow or focal photon defect in axial bones. Results: Marrow expansion was noted in 15 of 22 patients (68%). Focal photon defects were found in 18 patients (82%). While one (33%) of 3 patients with Stage II disease showed focal defects in bone marrow scan, abnormal focal defects were observed in 17 of 19 (90%) patients with Stage III. Among 124 focal abnormal sites which were observed in bone marrow scan, bone scan or simple bone radiography, bone marrow scan detected 92 sites (74%), whereas 82 sites (66%) were observed in simple bone radiography(58 sites, 47%) or bone scan(40 sites, 32%). Fifty-one (41%) out of 124 bone lesions were detected by bone marrow scan only, and located mostly in thoracolumbar spine. Conclusion: Bone marrow scan using $^{99m}Tc$-labelled antigranulocyte antibody seems to be a more sensitive procedure for the detection of pathologic bone lesions than simple bone X-ray or bone scan in patients with multiple myeloma.

• The Korean Journal of Nuclear Medicine
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• v.32 no.2
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• pp.143-150
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• 1998

Purpose: T1-201 SPECT has been used in differentiating benign and malignant pulmonary lesions. While its sensitivity may be high, the specificity and predictive values are reported to be variable depending on the type of benign lung lesion. The purpose of this study was to prospectively assess the efficacy of T1-201 SPECT for differentiating benign and malignant single pulmonary lesion in a population with a high prevalence of benign pulmonary lesion, especially, tuberculosis. Materials and Methods: One-hundred thirty-three patients, having 89 malignant and 44 benign lesions(23 active tuberculosis, 5 inactive tuberculosis, 3 aspergil-loma, 3 focal pneumonia, 2 thymoma, and 8 others), were imaged using a dual-headed system at 15 minute(early) and 3 hour (delayed) following administration of 111MBq T1-201. The images were read visually and lesion-to-background ratios(L/B) were obtained from transverse tomographic slices. Retention index was expressed as [(delayed L/B- early L/B) $\div$ early L/B]. Results: 82/89(92%) and 83/89(93%) of the malignant lesions were visually positive on the early and delayed images, and 27/44(61%) and 26/44(59%) of the benign lesions were also visually positive on both images. Although a statistically significant difference was found between the mean L/B's of the malignant and benign lesions, L/B was not useful for differentiating the two due to a large overlap. There was no difference in retention indices. Conclusion: Despite of its high sensitivity, the specificity of T1-201 SPECT was unacceptably low in patients with active benign lesions. The positive and negative predictive values for lung cancer in a population with a high prevalence of the benign single pulmonary lesion was only marginal.

• The Korean Journal of Nuclear Medicine
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• v.29 no.4
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• pp.484-491
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• 1995

It is well known that hepatobiliary agent are taken up by metastatic hepatocellular carcinoma(HCC) as well as primary HCC. But the reported cases of the extrahepatic metastasis of HCC diagnosed by hepatobiliary scintigraphy are for the most part hematogenous ones. The relation of the uptake pattern of hepatobiliary agent in the primary and metastatic HCC is also still remains unknown. So we undertook this study to evaluate the relation of the hepatobiliary scintigraphic patterns of primary and metastatic HCC with different metastatic routes. Nine patients with primary HCC and twelve cases of metastatic HCC including four lung metastases, one bone metastasis, one right atrial metastasis, one peritoneal wall metastasis, and five lymph node metastases were studied with $^{99m}Tc-DISIDA$ scintigraphy. The images were taken on 10, 30 minutes, 1, 2, 4-6 hours. The overall detection rates of hematogenous metastases(lung and bone) is 60%(3 of 5), direct metastasis(right atrium and peritoneal wall), 100%(2 of 2) and lymphatic metastases, 0%(0 of 5). In four of five metastatic cases demonstrated with hepatobiliary scintigraphy, biliary agent is also taken up by primary HCC lesions. And the appearing time of the radioactivity in the direct metastatic HCC lesioin is same as that of primary HCC and in the cases of hematogenous metastasis, earlier than that of primary HCC. Hepatobiliary scintigraphy is more useful in the diagnosis of the metastatic HCC than primary HCC, in the cases of hematogenous and direct metastasis.

• The Korean Journal of Nuclear Medicine
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• v.37 no.3
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• pp.178-189
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• 2003

Purpose: Cellular uptakes of $^{99m}Tc-sestamibi(MIBI)\;and\;\;^{99m}Tc-tetrofosmin$ into cancer cell lines expressing multidrug resistance(MDR) were investigated and compared. The effects of verapamil and cyclosporin A, well-known multidrug resistant reversing agents, on cellular uptakes of both tracers were also compared. Materials and Methods: Doxorubicin-resistant HCT15/CL02 human colorectal cell and doxorubicin-resistant K562(Adr) and vincristine-resistant K562(Vcr) human leukemic cells were studied. RT-PCR analysis was used for the detection of mdr1 mRNA expression. MDR-reversal effects with verapamil and cyclosporine A were evaluated at different drug concentrations after incubation with MIBI and tetrofosmin for 1, 15, 30, 45 and 60 min, using single-cell suspensions at $1{\times}10^6cells/ml$ incubated at $37^{\circ}C$. Radioactivity in supernatants and pellets were measured with gamma well counter. Results: The cellular uptakes of MIBI and tetrofosmin in K562(Adr) and K562(Vcr) were lower than those of parental K562 cell. In HCT15/CL02 cells and K562(Adr) cells, there were no significant difference in cellular uptakes of both tracers, but cellular uptake of MIBI was higher than that of tetrofosmin in K562(Vcr) cells. Coincubation with verapamil resulted in a increase In cellular uptakes of MIBI and tetrofosmin. Verapamil increased cellular uptakes of MIBI and tetrofosmin by HCT15/CL02 cell by 11.9- and 6.8-fold, by K562(Adr) cell by 14.3- and 8-fold and by K562(Vcr) cell by 7- and 5.7-fold in maximum, respectively. Cyciosporin A increased cellular uptakes of MIBI and tetrofosmin by HCT15/CL02 cell by 10- and 2.4-fold, by K562(Adr) cell by 44- and 13-fold and by K562(Vcr) cell by 18.8- and 11.8-fold in maximum, respectively Conclusion: Taking together, MIBI and tetrofosmin are considered as suitable radiopharmaceuticals for defecting multidrug resistance. However, MIBI seems to be a better tracer than tetrofosmin for evaluating MDR reversal effect of the modulators. Since cellular uptakes of both tracers might differ in different cell types, further experiments regarding differences in cellular uptakes between cell types should be explored.

• The Korean Journal of Nuclear Medicine
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• v.31 no.3
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• pp.320-329
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• 1997

Neuroanatomic substrate of autism has been the subjects of continuing investigation. Because previous studies had not demonstrated consistent and specific neuroimaging findings in autism and most studies comprised adults and school-aged children, we performed a retrospective review in search of common functional and anatomical abnormalities with brain SPECT using Tc-99m ECD and correlative MRI The patient population was composed of 18 children aged 28 to 89 months(mean age : 55 months) who met the diagnostic criteria of autism as defined in the DSM-IV and CARS. Brain SPECT was performed after intravenous injection of 185-370MBq of Tc-99m ECD using brain dedicated annular crystal gamma camera. MRI was performed in all patients including T1, T2 axial and T1 sagittal sequences. SPECT data were visually assessed. Thirteen patients had abnormal SPECT scan revealing focal areas of decreased perfusion. Decreased perfusion of cerebellar vermis(12/18), cerebellar hemisphere(11/18), thalami(13/18), basal ganglia(4/18), posterior parietal(7/18), and temporal(4/18) area were noted on brain SPECT. Whereas, only 3 patients had abnormal MR findings which were subtle volume loss of parieto-occipital white matter in 3 and mild thinning of posterior body of corpus callosum in 2 and slightly decreased volume of cerebellar vermis in 1. Comparison of the numbers of abnormal findings revealed that regional cerebral blood flow (rCBF) abnormalities seen on SPECT were more numerous than anatomical abnormalities seen on MRI. In conclusion, extensive perfusion impairment involving cerebellum, thalami and parietal lobe were found in this study. SPECT may be more sensitive in reflecting pathophysiology of autism than MRI. However, further studies are mandatory to determine the significance of thalamic and parietal perfusion impairment in autism.

• Journal of Yeungnam Medical Science
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• v.16 no.1
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• pp.60-68
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• 1999

A nationwide survey was conducted to investigate the annual occurrence rate of neonatal sepsis, maternal risk factors in neonatal sepsis, localized infection in neonates, causative organisms in nosocomial infection and the most common causative organism for neonatal sepsis in Korea. Clinical and bacteriological data wele collected from 37 neonatal units to perform retrospective review of the medical records of the newborn infants who were confirmed as having neonatal sepsis and whose blood culture was collected to isolate organisms for one year study period from January to December in 1997. 78,463 neonates were born at 37 hospital in 1997, and 20,869 neonates were admitted to the neonatal units, During this period, 772 episodes of neonatal sepsis were recorded in 517 neonates. The occurrence rate of neonatal sepsis was 0.73%(0~2.95%). Male to female ratio was 1.15:1, and 303 cases(42.1%) were born prematurely. The main pathogens of early onset of sepsis were S. aureus(20%), S. epidermidis(14.4%) and coagulase negative staphylococcus(14. 4%). Gram negative bacilli including Enterobacter spp (7.2%), E. coli(5.1%), Klepstella(4.5%), Pseudomonas(3.7%) and Enterobacter faectum(3.6%) accounted for 24.1% of sepsis. Group B beta-hemolytic streptococcus were isolated only in two cases. Common obstetric factors were PROM(21.1%), difficulty delivery(18.7%), fetal tachycardia(5.3%), chorioamnionitis(4.9%), and maternal fever(4.7%). The main pathogens of late-onset sepsis were S. aureus(22.3%), S. epidermidis(20.4%) and CONS(9.9%). There were 6 cases(1.0%) of Candida sepsis, Frequent focal infections accompanying sepsis were pneumonia(26.1%), urinary tract infection(10.5%), meningitis(8.2%), and arthritis(3.6%), S. epidermidis(22.0%) and s. aureus(21.7%) were also the most common pathogens in 373 nosocomial infection.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.9 no.2
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• pp.210-217
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• 2006

Purpose: Crohn disease (CD) in children is frequently complicated by malnutrition and growth retardation. Conventional treatment with corticosteroid may also affect the growth of children, which may be alleviated by nutritional therapy. Therefore, we performed this study to evaluate the role of nutritional therapy in the treatment of CD in children. Methods: The study cohort consisted of thirty children under the age of 17 years, admitted to the Asan Medical Center from 2001 to 2005. While 11 children received nutritional therapy (NT) with an elemental diet, 19 received conventional corticosteroid therapy (ST). Comparative analysis was performed for the rate of the induction of remission, recurrence, disease activity index of pre and post-treatment, and changes of the growth using mean standard deviation score for weight (zW) and height (zH). Results: Ten of 11 children with NT and 18 of 19 children with ST completed the therapy. Two of them were lost to follow-up during the treatment. All 10 children with NT and 15 of 18 children with ST achieved remission. While there was no recurrence in children with NT, 7 with ST showed recurrence within 1 year. Pre- and post treatment Pediatric Crohn disease Activity Index (PCDAI) did not show a difference between the two groups. There were no differences in zW and zH between the two groups after 1 year of follow-up. Conclusion: This study showed that nutritional therapy could be considered instead of steroid therapy for treatment of children with CD. However, a long-term study will be needed to determine the long-term efficacy.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.9 no.2
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• pp.193-199
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• 2006

Purpose: The proper diagnosis of Meckel's diverticulum (MD) is difficult and delayed because of the variety of clinical manifestations. We reviewed clinical characteristics of symptomatic MD to facilitate early detection. Methods: We analyzed retrospectively the clinical manifestations, diagnostic tools, histopathological findings, and operative findings in 58 patients with symptomatic MD. Results: The male to female ratio was 2.8 : 1. The most common symptom of MD was bleeding. Others symptoms included: vomiting, abdominal pain, irritability, abdominal distension and fever in the order of frequency. The clinical manifestations of symptomatic MD were lower gastrointestinal bleeding, intestinal obstruction, perforation, diverticulitis and hemoperitoneum, in the order of frequency. The causes of intestinal obstruction were intussusception, internal hernia, band, volvulus, invagination, in the order of frequency. Seventy five percent of patient with MD were diagnosed prior to 5 years of age. The most frequently used diagnostic tool was the Meckel's scan. The diverticulum was located 2 cm to 120 cm proximal to the ileocecal valve. The length of the diverticulum ranged from 1 cm to 10 cm and 94% were less than 5 cm. The most common ectopic tissue found in the MD was gastric mucosa. Ileal resection was more frequently performed than diverticulectomy. Conclusion: In cases of unexplained gastrointestinal bleeding, obstruction and repeated intussusception, the meckel's scan, ultrasound and computed tomography shoud be considered to rule out MD, and if clinically necessary, an exploratory laparotomy when needed.

• Journal of Applied Biological Chemistry
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• v.55 no.1
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• pp.47-53
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• 2012

Increasing concerns over green farming technology, plant growth promoting rhizobacterium (PGRP) having growth promoting as well as plant disease suppressing properties was recently preferred to use for biological control of plant pathogens infecting plant. We measured the influence of the selected microbial consortium agents-a mixture of PGPR strains-, commercial bio-fungicide, and chemical pesticides on soil microbial community in red pepper field. The activities of soil enzyme such as dehydrogenase, urease, phosphatase, ${\beta}$-glucosidase, and cellulase were analyzed to investigate that of soil microbial community. We also measured plant length, main stem, stem diameter, number of branches and yields of red-pepper in order to observe the red pepper growth promotion. The results of measuring enzyme activities were dehydrogenase 3.5584 ${\mu}g$ TPF $g^{-1}h^{-1}$, urease 15.8689 ${\mu}g$ $NH_4{^-}N$ $g^{-1}h^{-1}$, phosphatase 0.5692 ${\mu}g$ PNP $g^{-1}h^{-1}$, ${\beta}$-glucosidase 2.4785 ${\mu}g$ PNP $g^{-1}h^{-1}$, and cellulase 86.1597 ${\mu}g$ glucose $g^{-1}h^{-1}$ in the soil treated with the microbial consortium agents, so it came out to be very active in the soil. Observing the growth of red-peppers, the main-stem length and the stem diameter were 6.1% and 8.1% higher in the soil treated with the selected microbial consortium agent than the chemical pesticides. After harvesting, yields were 7.3% higher in the soil treated with selected microbial consortium agents than the chemical pesticides. These results showed that microbial consortium agents contribute to increasing soil microbial diversity, growth promoting, and yield of red pepper.