• The Korean Journal of Nuclear Medicine
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• v.30 no.3
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• pp.332-337
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• 1996

Purpose : It has been known that the activity of extracellular matrix degradative enzymes such as collagenase correlate well with the metastatic potential of various tumor cells in experimental study. This study was aimed at comparing the activities of type IV collagenase with bone scan findings in patients with breast cancer. Materials and Methods : We retrospectively correlated bone scan findings with the results of immunohistochemical staining for 92kDa, 72kDa type IV collagenase in 28, and 30 patients with metastatic breast cancer, respectively, as well as 23, and 27 patients with primary breast cancer, respectively. The immunohistochemical staining was performed with tissue specimens obtained from primary or metastatic breast tumor lesions. The amounts of the enzyme were graded from 0 to 4 and scored by multiplication with the percentage of tumor cells. The confidence of bone scan interpretation for metastasis was also scored from 1 to 5 with increasing probability. Results : There was a significant difference in enzyme scores between patients with and without metastasis. In patients with primary breast cancer group, the frequency of patients with enzyme score of less than 170 were 96%(26/27) and 100%(26/26) with 92kDa and 72kDa collagenase, respectively. In contrast, in patients with metastatic breast cancer group, the frequency of patients with enzyme score of more than 200 were 93%(28/30) and 87%(26/30) with 92kDa and 72kDa collagenase, respectively. All patients with each enzyme score of less than 170 show no active bony metastasis, however, there were variable bone scan findings in patients with each enzyme score of more than 200. Conclusion : Bone scan is useful to confirm, localize or follow up of bony metastasis in patients with each enzyme scores of more than 200. Acitve metastatic lesions were hardly seen on the bone scintigraphy in patients with collagenase scores of less than 170.

• Clinical and Experimental Pediatrics
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• v.52 no.8
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• pp.938-943
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• 2009

Purpose : We performed this study in order to investigate the effect of direct renin inhibition on an experimental animal model with nephrotoxic serum nephritis and tried to give useful information for clinical research and renin inhibitor treatment. Methods : Thirty BALB/c 6-week-old male mice were divided into 4 groups: control group (CO, n=5), control-treatment group with aliskiren (CT, n=5), disease group (DO, n=10), and disease treatment group with aliskiren (DT, n=10). Nephritis was induced by an intravenous injection of 0.25 mg/g weight of rabbit anti-GBM immunoglobulin G. Model 2002 Alzet mini-osmotic pumps (Durect Corp.) for aliskiren infusion were implanted into CT and DT. Each group strain was sacrificed serially one at a time on day 14. We estimated the protein-creatinine ratio in 12-hour-collected urine (UP/Cr) and measured the mesangial matrix score in the PAS-stained kidney of each strain. Results : One strain at CT and DT died on day 6 and 7, respectively. Each group strain was sacrificed serially at a time on day 10 because DO were seriously ill. The UP/Cr of each group is as follows: CO, $31.24{\pm}6.54mg/mg$, CT, $23.38{\pm}13.60mg/mg$, DO, $112.72{\pm}10.97mg/mg$, DT $114.07{\pm}32.30mg/mg$. There was no significant difference between DO and DT. The mesangial matrix score of each group was CO, $0.23{\pm}0.10$; CT, $0.13{\pm}0.03$; DO, $1.90{\pm}0.48$; and DT, $1.28{\pm}0.41$, respectively, and there was a significant difference between DO and DT in the extent of mesangial matrix expansion (P=0.008). Conclusion : We found that renin inhibition was able to suppress the mesangial matrix expansion in experimental mice with acute nephritis, although there were no significant differences in UP/Cr.

• Childhood Kidney Diseases
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• v.5 no.2
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• pp.164-175
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• 2001

Purpose : Alport syndrome is a hereditary nephrotic disease characterized by progressive nephrotic symptom, sensorineural hearing loss, ophthalmic abnormality, typical microscopic findings, and familial occurrence. In this study, we tried to find the risk factors related with its prognosis by taking a close observation on clinical symptoms of children with Alport syndrome reviewing retrospectively. Materials & methods : We chose children diagnosed as Alport syndrome in renal biopsy during 20 years(from 1980, Jan. until 1999, Dec.) who could receive follow up studies in tile department of pediatrics. They were divided into two groups by comparing renal function at the time of diagnosis and at current status. We compared several clinical aspects in them, and applied nonparametric test for statistical analysis. Results : The sex ratio(male:female) of 24 children was 3:1. The most common clinical symptom presented at their first visit was gross hematuria. Among those 24 children, 11 cases($46\%$) of progressing into chronic renal failure(Group II) were observed. Hypertension, proteinuria and edema were seen much frequently in group II. The level of serum protein, albumin, and creatinine clearance were decreased while BUN, creatinine were relatively increased. All the results were statistically significant. Conclusion Clinically significant risk factors related to prognosis in Alport syndrome were the presence of hypertension, edema, and proteinuria at the time of diagnosis. Also, the level of serum protein, albumin, BUN, creatinine, and glomerular filtration rate were proved to be important factors in predicting prognosis. We believe that studies on these possible risk factors would be of great help in treating and predicting prognosis of children suffering with Alport syndrome. (J Korean Soc Pediatr Nephrol 2001;5 : 164-75)

• Journal of Chest Surgery
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• v.38 no.1 s.246
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• pp.38-43
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• 2005

Matrix metalloproteinase-2 (MMP-2) is a class of proteolytic enzymes that digest collagen type IV and other components of the basement membrane. It plays a key role in the local invasion and the formation of distant metastases by various malignant tumors. The aim of this study was to evaluate the activity of MMP-2 and its significance as a prognostic marker in resected stage I non-small cell lung cancer (NSCLC). Material and Method: In this study we obtained fresh-frozen samples of tumor and non-tumor tissues from 34 patients with stage I NSCLC who underwent resection without preoperative radiotherapy or chemotherapy. After the extraction of total protein from tissue samples, MMP-2 activities were assessed by gelatin-substrate-zymography. The activities were divided into the higher or lower groups. Result: The MMP-2 activities were higher in tumor tissues than in non-tumor tissues. The MMP-2 activity of non-tumor tissues in recurrent group was higher than in non-recurrent group (p<0.01). Also the patients with higher MMP-2 activity of non-tumor tissues showed poor 5 year survival (p<0.01). Conclusion: This result indicates that the higher level of MMP-2 activity in the non-tumor tissue is associated with the recurrence and survival after the resection of stage I NSCLC. Therefore, MMP-2 activity in the non-tumor tissue could be used as a potential prognostic marker for the resected stage I-NSCLC.

• Clinical and Experimental Pediatrics
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• v.52 no.2
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• pp.227-233
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• 2009

Purpose : Growth hormone (GH) replacement after retesting is necessary because impairment of body composition and cardiovascular health has been more severe in adult patients with persistent GH deficiency (GHD) from childhood to adulthood. This study aimed to investigate the factors for persistent GHD and define a highly probable group of persistent GHD in young adults with childhood-onset GHD. Methods : GHD was reassessed by insulin tolerance test (ITT) in 55 adult patients (39 males, 16 females) with childhood-onset GHD. Twelve patients presented with idiopathic GHD and 43 patients presented with organic GHD caused by tumors involving the hypothalamus-pituitary (H-P) region (n=33), other brain tumors (n=3), meningitis (n=3), leukemia (n=2) and others (n=2). Results : Forty-nine (89.1%) of 55 patients had persistent GHD. IGF-I was positively correlated with log of peak GH (r=0.57, P<0.001). There was no difference in the proportion of persistent GHD between idiopathic and organic GHD. The percentage of patients with persistent GHD was 40%, 80%, and 95.6% for patients with zero, one, two or more additional pituitary hormone deficiencies (PHDs), respectively (P=0.002). The probability of persistent GHD was higher in patients with diseases involving the H-P region (P=0.003). GHD persisted in 15 of 18 patients treated with cranial irradiation. Conclusion : We suggest that the probability of persistent GHD in adulthood was high in patients with 2 or more additional PHDs, and diseases involving the H-P region.

• Applied Biological Chemistry
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• v.43 no.2
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• pp.86-94
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• 2000

In order to develop the enzymatic hydrolysis system concerned with taste and flavor, strains having the high hydrolyzing activity on the soy protein were selected from some traditional Mejus. Two molds and one bacterium producing enzymes which were different in character of hydrolysis were isolated and identified. Leucine and azodye enzyme activities of both M4 and M5 were relatively high among in the isolated molds. And, leucine enzyme activity of B16 was the lowest in the isolated bacteria. These strains were isolated as microorganisms having a dissimilar hydrolysis pattern on the soy protein by enzymatic reactions. Mold M4 on the culture solid media was mycelium colors of white and its sclerotia colors were changed from white to black. According to the result of slide culture, radial conidial head, subclavate vesicle, conidia of subglobose, stipes of uncolored with smooth walls and metula and phialides were existed. Because M4 was taxonomically similar to the characteristics of Aspergillus oryzae (ahlburg) species, M4 was identified and named as Aspergillus oryzae M4.Mold M5 showed white and black mycelium on the MEA medium. Mold M5 colony exhibited grayish-green color and have long(7 mm) sporangiophores at slide culture. Sporangia became brownish-gray and the wall of larger sporangia was broken to form small collars, and smaller sporangia were fomed continually from large basal membrane. Columella is globose and hyaline, and sporangiospores are ellipsoidal of small diameter$(80\;{\mu}m)$. Because M5 was taxonomically similar to the Mucor circinelloides of zygomycetes, M5 was was identified and named as Mucor circinelloides M5. Bacteria B16 colony was opaque white, circular and lobate, and had rod shaped endospore. B16 was found positive in stain, catalase, ${\beta}-glucosidse$ and V-P tests. B16 was found to utilize D-fructose, ${\alpha}-D-glucose$, maltose, D-mannose, D-raffinose, stachyose and sucrose. By the morphological and physiological results, the characteristics of B16 was thought to correspond to that of Bacillus megaterium. However, fatty acid composition was similar to Paenibacillus marcerans, requiring further study for the definite identification. Accordingly, Bacteria B16 was provisionally classified and named as Bacillus megaterium B16.

• Childhood Kidney Diseases
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• v.14 no.2
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• pp.143-153
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• 2010

Purpose: Recently, massive proteinuria has been observed in some transplant patients after switching cyclosporine A (CsA) to sirolimus. To evaluate the pathogenesis of sirolimus-associated proteinuria, we investigated the early changes in slit diaphragm molecules by various administrative conditions of sirolimus and CsA. Methods: In vitro-Mouse podocytes were incubated with buffer (C), sirolimus ($10\;{\mu}g/mL$) after CsA ($10\;{\mu}g/mL$) (C-S), sirolimus only (S) and CsA and sirolimus simultaneously (C+S) for 12, 24, and 48 hours. In vivo- twenty four SPF female Wistar rats were divided into 4 groups buffer (C), sirolimus after 2 weeks of CsA (C-S), sirolimus only (S) and CsA and sirolimus simultaneously (C+S). All groups were treated by intraperitoneal injection every other day for 4 weeks (CsA: 25 mg/kg, sirolimus: 0.5 mg/kg). The changes in mRNA of slit diaphragm molecules were examined by RT-PCR. Results: The mRNA of nephrin was significantly decreased in group C-S and C+S in vitro. In vivo, the mRNA of nephrin in all groups using sirolimus and the mRNA of podocin in group C-S and C+S were decreased. Microscopically, group C-S and C+S showed small vacuolization and calcification in proximal tubular epithelial cells. Immunohistochemistry using nephrin and podocin antibodies did not show remarkable decrease of staining along the glomerular capillaries. Electron-microscopically, focal fusion of foot processes was seen in group C-S and C+S. Conclusion: This study suggests the decrease of slit diaphragm molecules (nephrin and podocin) in podocyte may be one of the causes of sirolimus associated proteinuria, and podocyte injury by sirolimus may need a primary hit by CsA to develop the proteinuria.

• Applied Microscopy
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• v.32 no.1
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• pp.67-80
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• 2002

This study was carried out to investigate the effects of deer antler extract on the regeneration of peripheral nerves. Sprague-Dawley male rats weighing about 300 gm were fed deer antler extract for 1, 2, and 3 weeks per oral (1.5 ml/100 gm B.W.), respectively, once a day and transected both sides of sciatic nerve of each leg. After keeping for 6 hours, sciatic nerves taken from proximal part of transected region were treated with conventional transmission electron microscopical method and then observed with electron microscope. The results obtained were summarized as follows; 1. Sciatic nerves of normal control group were not showing any sprouts and electron dense axolemmal projections were frequently observed. 2. Sciatic nerves of saline treated groups were showing axonal sprouts at the nodes of Ranvier. The length of them was usually short, and numerous vesicles, vacuoles and organelles including neurofilament were contained. The number of nodes of Ranvier containing sprouts from 100 longitudinal sectioned nerve fibers was 29 (29%) in 1 week treated group, 32 (32%) in 2 weeks treated group, and 30 (30%) in 3 weeks treated group, respectively. 3. Sciatic nerves of deer antler treated groups were showing axonal sprouts at the node of Ranvier as well. Although most of the sprouts were short, some sprouts of 2 weeks and 3 weeks treated groups were quite long. Sprouts usually contained numerous vesicles, vacuoles and cell organelles such as neurofilaments and mitochondria. The number of nodes of Ranvier containing sprouts from 100 longitudinal sectioned nerve fibers was 38 (38%) in 1 week treated group, 46 (46%) in 2 weeks treated group, and 48 (48%) in 3 weeks treated group respectively. The results described above explain pretreatment of deer antler extract improves the sprout formation of transected sciatic nerves, and then it suggests deer antler may be effective for the regeneration of peripheral nerves.

• Applied Microscopy
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• v.29 no.3
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• pp.383-403
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• 1999

This study was performed to investigate the immunohistochemical and ultrastructural characterization of the choline acetyltransferase (ChAT)-immunoreactive nerve cells in the diagonal band of Broca of the rat basal forebrains, utilizing techniques of immunohistochemical and immunocytochemical microscopy. The ChAT-immunoreactivities were shown within neuronal cell bodies and processes by the light micoscope. According to cell shape and ratio of long axis vs short axis of cell body, the ChAT-immunoreaclive nerve cells in both vertical and horizontal limbs of the diagonal band of Broca were classified into 6 types. at the light microscopic level; round, oval, elongated, fusiform, triangular and polygonal types. As a result of the electron microscopic observation, the ChAT-immunoreactivated products appeared on the outer nuclear envelope, membranes of rough endoplasmic reticula (rER), free ribosomes and polysomes. Each cell type was subdivided into subtype I and II according to the several criteria such as volume of cell body, nuclear size relative to the cytoplasm, kinds and distribution of cell organelles and numbers and sorts of synapses. The subtype I of immnunoreactive nerve cells had large cell body and a small nucleus showing shallow indentations of nuclear evelope. In this subtype I with abundant cytoplasm, rER were well differentiated. Their long cisternae were parallelly ditributed and lamellated. One or two lamellar bodies and nematosomes were observed. The subtype II cell had small cell body and a large nucleus with deep indentations of nuclear envelope. In this subtype II with small cytoplasm, the rER were irregularly distributed and the lamellar body and nematosome were not found. A few axosomatic synapses in the subtype I and II were shown to be symmetric or asymmetric. The ratios of the symmetric synapse to the asymmetric one were investigated to be 1 : 2 and 1 : 4 in the subtype I and II, respectively. The axodendritic ones were almost asymmetric. But, the fusiform and triangular immunoreactive nerve cells were shown only to be subtype I. According to observations in this study, it is considered that the ultrastructural characterization in the 2 subtypes of each cell type may reflect the differences of the metabolic activities and projecting distances to the target cells.

• Tuberculosis and Respiratory Diseases
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• v.52 no.2
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• pp.107-116
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• 2002

Background: Matrix metalloproteinases(MMP) are essential enzymes for tumor invasion and metastasis. Among the MMP family, elevated MMP-9 and stromelysin-3(STR-3) expression have been reported to be poor prognostic factors in lung cancer patients. To evaluate the possibility of a molecular diagnosis of lung cancer using peripheral blood, the mRNA expression level of MMP-9 and STR-3 was measured using a reverse transcriptase-polymerase chain reaction (RT-PCR) in patients with lung cancer. Methods : Ninety six patients(44 patients with lung cancer, 19 pulmonary infection, and 33 control) were included. To detect MMP-9 and STR-3 mRNA expression, RT-PCR was performed in peripheral blood mononuclear cells. ELISA was also used to measure the serum level of MMP-9. Results : MMP-9 was expressed more frequently in patients with a pulmonary infection(18/19, 94.7%) compared to lung cancer patients(26/44, 59.1%) or the controls (23/33, 69.7%) (p=0.018). On the other hand, STR-3 expression was observed more frequently in patients with lung cancer(37/44, 84.1%) compared to the lung infection patients(8/19, 42.1%) or control(20/33, 60.6%) (p=0.003). Among the lung cancer patients, MMP-9 was expressed more frequently when a tumor invaded the lymph nodes(17/24, 70.8%) compared to when a tumor did not(3/13, 23.1%) (p=0.005). The MMP-9 and STR-3 expression levels had no relationship with age, sex, tumor size, distant metastasis, or tumor histology. The serum MMP-9 concentration was not higher in lung cancer patients compared to patients with a pulmonary infection or the control subjects. Conclusion : STR-3 may be used as a diagnostic marker in the peripheral blood of lung cancer patients using RT-PCR. Further studies to evaluate the clinical significance of elevated STR-3 expression in lung cancer patients is recommended.