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Bee Venom Inhibits Angiogenesis by Decreasing HIF-1α Expression in HCT116 Cells (봉독의 HIF-1α 발현감소를 통한 혈관신생 억제효과)

  • Shin, Jae-Moon;Jeong, Yun-Jeong;Park, Kwan-Kyu;Choe, Jung-Yoon;Han, Sang-Mi;Lee, Kwang-Gill;Yeo, Joo-Hong;Chung, Il-Kyung;Chang, Young-Chae
    • Journal of Life Science
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    • v.22 no.1
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    • pp.41-48
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    • 2012
  • Bee venom (BV) has been used in medicine to treat a variety of diseases including arthritis, rheumatism, and various cancers. Recent reports indicate that BV has anti-angiogenic effects, but the precise molecular mechanism underlying the effects of BV against colorectal cancer remains to be elucidated. We examined the effects of BV and its major components (melittin and apamin) on tumor angiogenesis and found that BV significantly decreased protein levels of hypoxia-inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$), an important factor involved in angiogenesis and tumor progression, in human colorectal carcinoma HCT116 cells. BV also suppressed the transcription of HIF-$1{\alpha}$ under hypoxia, leading to a decrease in the expression of vascular endothelial growth factor (VEGF), a major target gene of HIF-$1{\alpha}$. We also found that these effects were mainly elicited by apamin, but not melittin. BV specifically inhibited the phosphorylation of ERK1/2 without changing the total levels of this protein, but had no effect on kinases of p38/JNK and AKT. Our results suggest that BV may inhibit human colorectal cancer progression and angiogenesis by inhibiting HIF-$1{\alpha}$ and VEGF expression, thereby providing a novel potential mechanism for the anticancer action of BV.

Morphological study on abdominal organs of healthy cats using omnidirectional radiography and fluoroscopy (다각도 방사선촬영 및 투시법을 이용한 정상 고양이 장기의 형태학적 연구)

  • Shin, Sa-kyeng;Hirose, Tsuneo;Sato, Motoyoshi;Miyahara, Kazuro
    • Korean Journal of Veterinary Research
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    • v.36 no.4
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    • pp.949-966
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    • 1996
  • To establish the method for the most effective radiography and fluoroscopy, the abdominal organs of cats were investigeted using omnidirectional angles with the center of the body as the axis using an omnidirectional protective shielding X-ray system and a $360^{\circ}$ rotary restraint unit for use in small animals. The organs examined were the diaphragm, liver, stomach, colon, spleen and kidney. The results obtained in the present study were as follows: 1. Regardless of gas in the stomach present or not, it was feasible to distinguish the left and right crura in the lumbar portion of diaphragm in the oblique projection inclined over $30^{\circ}$ and under $90^{\circ}$ from the lateral projection. 2. Outlines of the exterior left lobe and the interior right lobe of the liver were observed in the oblique image inclined up to $60^{\circ}$ from the lateral image, while that of the exterior right lobe was noted in the oblique image inclined up to $60^{\circ}$ from the ventrodorsal-dorsoventral images. 3. It was necessary to have gas present in the stomach for detailed morphological observations of the stomach. It was most clearly observed in the right $30^{\circ}$ ventral-left dorsal oblique projection($120^{\circ}$ image) and the left $60^{\circ}$ dorsal-right ventral oblique projection($300^{\circ}$ image). 4. Morphology of the colon was observable in detail by the oblique projection inclined over $30^{\circ}$ from the lateral projection. 5. To observe the whole spleen it was required to have images from the ventrodorsal projection ($90^{\circ}$ image) to the right $60^{\circ}$ ventral-left dorsal oblique projection ($150^{\circ}$ image) as well as those from the dorsoventral projection ($270^{\circ}$ image) to the left-right lateral projection $0^{\circ}$ image). 6. Dorsal and ventral sides of the kidney were observable in the oblique images inclined $30^{\circ}$ from the lateral image. 7. Considering above findings collectively, it was thought that the results of present study might be useful for the analysis of abnormalies in each organ of cat.

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Clinical Features of Dietary Protein Induced Proctocolitis (식이 단백 유발 직결장염의 임상적 고찰)

  • Im, Sun Ju;Kim, Seong Heon;Bae, Sang Nam;Park, Jae Hong
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.8 no.2
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    • pp.157-163
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    • 2005
  • Purpose: Dietary protein induced proctocolitis (DPIPC) can be considered as a cause of rectal bleeding or blood streaked stool in otherwise healthy-looking infants in the first several months of life. Failure to appreciate this entity may lead to inappropriate diagnostic or therapeutic intervention. This study aimed to ascertain the clinical features, treatment and prognosis of DPIPC. Methods: We reviewed 13 infants retrospectively, presented with bloody stool in early infancy. They were diagnosed as DPIPC clinically in Pusan National University Hospital from May 2002 to June 2004. Results: Seven males and six females were included. The mean age at onset of bleeding was $96.8{\pm}58.8days$. The mean frequency of hematochezia was $2.6{\pm}2.5$ times a day. Duration from onset of symptom to diagnosis was $35.5{\pm}55.0days$ and duration from onset of symptom to resolution of bleeding was $58.7{\pm}67.0days$. Nine (69.2%) were exclusively breast-fed infants and two (15.4%) were formula-fed infants. All but one infant did not have family history of other allergic diseases. A dietary history of ingestion of cow's milk, nut or shellfish was present in three mothers. Peripheral eosinophil count was normal to slightly elevated (total WBC count $10,555{\pm}3,145/mm^3$, relative eosinophil count $6.3{\pm}3.0%$, absolute eosinophil count $659.0{\pm}532.2/mm^3$). Sigmoidoscopy revealed lymphonodular hyperplasia with surrounding hemorrhagic spots in the rectosigmoid colon in 6 infants. Histopathologic finding of colonic biopsies in 5 infants showed chronic inflammation with lymphoid follicular hyperplasia (5 infants), crypt abscess (3 infants), or mild infiltration of eosinophils (less than 20/high power field) in the lamina propria. Spontaneous resolution of rectal bleeding occurred in all infants without dietary change or medicine. Conclusion: Most infants with DPIPC experience a very benign course and have spontaneous resolution of rectal bleeding without changes in the mother's diet. In the case of strong evidence for DPIPC we suggest deferring further invasive investigation and continuing breast feeding.

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Clinical Features of Eosinophilic Colitis Developed in Early Infancy (영아 초기에 발생한 호산구성 대장염의 임상적 고찰)

  • Kwak, Jeong Won;Park, Jae Hong
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.8 no.2
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    • pp.122-129
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    • 2005
  • Purpose: Eosinophilic colitis is a disease characterized by gastrointestinal symptoms, peripheral eosinophilia, eosinophilic infiltration of the colonic wall. The etiology and pathogenesis of this disease is not clear and it is considered to be idiopathic. This study aimed to ascertain the clinical features, treatment and prognosis of eosinophilic colitis in early infancy. Methods: We reviewed 6 infants retrospectively, presented with bloody stool in early infancy, who were diagnosed with eosinophilic colitis in Pusan National University Hospital between August 2002 and February 2004. Results: Five males and one female were included. The mean age when bloody stool was identified was $79.2{\pm}56.1$ days (10~145 days). All but one infant with atopic dermatitis did not have other allergic diseases. Nobody had a family history of allergic disease. No specific dietary history in infants and their mothers related to food allergy was identified. Peripheral eosinophilia (total WBC count $11,763{\pm}3,498/mm^3$, eosinophils $17.0{\pm}4.3%$, absolute eosinophil count $2,044{\pm}996/mm^3$) was observed in all infants. Colonoscopy in six infants revealed diffuse erythema, congestion and granulation pattern of mucosa in the rectosigmoid colon. Histopathologic findings of colononic biopsies showed chronic inflammation with severe eosinophilic infiltration in the mucosa. Two infants were treated with hydrolyzed casein-based formula and four infants with prednisolone. Gastrointestinal symptoms and peripheral eosinophilia resolved completely with prednisolone and partially with a hydrolyzed casein-based formula. Relapse was not observed during the follow-up period. Conclusion: Our study demonstrated that there is no evidence of a definite relationship between eosinophilic colitis and food-allergic disorders. Clinical course and prognosis of infantile form of eosinophilic colitis is very favorable and treatment with prednisone was effective.

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Clinical Spectra of Auto-amputated Polyps: Comparison of Juvenile Polyps and Meckel's Diverticula (자동절제 대장 용종의 임상 양상: 연소성 용종 및 멕켈 게실과의 비교)

  • Kim, Jae-Young;Park, Jae-Hong;Choi, Gwang-Hae;Choe, Byung-Ho
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.12 no.1
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    • pp.10-15
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    • 2009
  • Purpose: The manner of rectal bleeding of auto-amputated polyps (AP) is similar to juvenile polyps (JP) or Meckel's diverticula (MD). We conducted this study to characterize the clinical spectrum of AP. Methods: Fourteen patients were enrolled this study who were diagnosed AP due to painless rectal bleeding. The clinical data of AP was assessed and then compared with the clinical data of JP and MD retrospectively. Results: The prevalence of AP was 10.4% (14/135) and high in younger patients compared with that of JP (p=0.042 below 2 years). Whereas JP was more common in patients aged 2 to 5 years (p=0.005). Male was predominant in AP (p=0.008 AP vs JP). The manner of rectal bleeding in AP group was sudden and transient. There was no significant difference in time interval between onset of rectal bleeding and diagnosis between the 3 groups. However AP was diagnosed in 9 patients (64.3%) within 7 days after onset of rectal bleeding, but JP was diagnosed in 5 patients (4.1%) in the same period (p<0.001). All of AP were located in the rectum and the sigmoid colon. The mean hemoglobin was 11.3${\pm}$1.5 g/dL in AP, 11.8${\pm}$1.3 g/dL in JP, and 8.4${\pm}$1.2 g/dL in MD (p<0.001, only significant in MD). Conclusion: AP may be considered in male older than 1 year with transient and sudden onset or increase of painless rectal bleeding without drop of hemoglobin level.

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Studies on the Organo-mercury Residus in Rice Grain -3. Studies on the histopathological changes of the chief organ in rabbit influenced by PMA administration and the fate of mercury- (수도(水稻)에 처리(處理)된 유기수은제(有機水銀劑)의 잔류성(殘留性)에 관(關)한 연구(硏究) -제3보(第3報) : 가토(家兎)에 있어서 PMA투여(投與)에 의(依)한 주요장기(主要臟器)의 병리조직학적(病理組織學的) 변화(變化) 및 체내(體內)에서의 동태(動態)에 관(關)한 연구(硏究)-)

  • Lee, Dong-Suk
    • Applied Biological Chemistry
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    • v.8
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    • pp.101-111
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    • 1967
  • Daily doses of phenylmercuric acetate arranged in $30{\gamma}\;(group\;I)$, 3{\gamma}\;(group\;II)$ and $0.3{\gamma}\;(group\;III)$ were administered respectively to rabbits for 90 days. The chief histopathological changes in the organs and the analytical data on mercury residues in the excretion and liver were as follows. 1. Kidney: In group I, severe degrees of vacuolization and cloudy swelling were occurred in the epithelial cells of proximal convoluted tubules and severe cloudy swelling and coagulative necrosis were observed in the proximal straight tubules. There were many hyaline casts in the collecting tubules. In group II, moderate degrees of vacuolization and cloudy swelling were observed in the epithelial cells of proximal convoluted tubules and moderate cloudy swelling and coagulative necrosis were encountered in the proximal straight tubules. A little numbers of hyaline casts were located in the lumen of collecting tubules. In group III, slight degree of cloudy swelling were observed in the epithelial cells of proximal convoluted and straight tubules. 2. Liver: In group I, cloudy swelling, fatty changes and coagulative necrosis were observed in the central zone of hepatic lobules. Dissociation of hepatic cell cords was encountered. Hyperplsia of hepatic cells were remarkable in group II. No Pathological changes were observed in group III. 3. Spleen: Deposition of hemosiderin pigment was prominant in group I and small amount of the pigment was observed in group II. There were no pathological changes in group III. 4. Adrenal, colon and heart: No pathological changes were detected in all 3 groups. 5. In an average about 76.5% of mercury was excreted from group I, 85.4% from group II and 79.8% from group III. 6. Mercury content in the liver was 0.0348 g in group I, 0.00378 g and 0.00066 g in group II and group III respectively. 7. In general, as to increased mercury doses the concentration of mercury accumulation in the liver became higher, how·ever, the accumulation quantity against a total amount of mercury doses showed an adverse trend. In other word, the quantity of mercury accumulation was not increased proportionately by higher dose of mercury.

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Histopathological and Serological Observations on Experimental Anisakiasis of Rabbits (실험적 토끼 아니사키스증에서의 조직학적 병변과 혈청 항체가의 경시적 변동 양상)

  • 홍성태;이손형
    • Parasites, Hosts and Diseases
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    • v.25 no.2
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    • pp.168-180
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    • 1987
  • This study was performed to observe histopathological changes and serological reactions in chronic anisakiasis of rabbits. Each rabbit was infected per os with 30 larvae of Anisakis type I. Their sera were collected chronologically and the rabbits were killed for histopathological examination, 3, 13, 20, 30, 60, 90 and 150 days after the infection. The results were summarized as below. 1. Most of the larvae were recovered from the stomach, but a few from the omentum, intestine, mesentery and abdominal wall. The recovery rates and distribution of worms by organ were not differed by duration of infection. 2. Histologically the lesion was abscess type on 13 days, i.e., the dead worms were surrounded by fibrinous exudate, histiocytes and thick zone of numerous inflammatory cells. After 30 days, histiocytes were found to invade the worms and the lesion was changing into abscessgranulomatous type. Also a calcified worm was found on the 30th day. After then the worms were observed to be dissolved slowly until 90 days. On 150 day, only one calcified worm was observed. 3. The levels of serum IgG antibody by ELISA reached their maximum 30 days after the infection. After then, it decreased slowly until 150 days after the infection. Above serological and histopathological findings indicated that antigenic stimulation from degenerating Anisakis larvae was the greatest during the first 30 days after infection. This period was corresponding with the beginning of worm resolution or calcification. Serologic test by ELISA would be a valuable tool for confirming chronic anisakiasis.

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Clinical Features and the Natural History of Dietary Protein Induced Proctocolitis: a Study on the Elimination of Offending Foods from the Maternal Diet (식품 단백질 유발성 직결장염의 임상 소견과 식이 조절에 관한 연구)

  • Choi, Seon Yun;Park, Moon Ho;Choi, Won Joung;Kang, Una;Oh, Hoon Kyu;Kam, Sin;Hwang, Jin-Bok
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.8 no.1
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    • pp.21-30
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    • 2005
  • Purpose: The aim of this study was to identify the clinical features and natural history of dietary protein induced proctocolitis (DPIPC) and to detect the causative foods of DPIPC, and to evaluate the effect of elimination of the foods on the course of the disease. Methods: Between March 2003 and July 2004, data from 30 consecutive patients with DPIPC who were followed for over 6 months, was reviewed. The diagnostic criterion used for DPIPC was an increase in the number of eosinophils in the lamina propria (${\geq}60per$ 10 high-power fields). In breast feeding mothers, 5 highly allergenic foods were eliminated from the maternal diet for 7 days, namely, allergenic food groups such as dairy products, eggs, nuts and soybean, fish and shellfish, and wheat and buckwheat. We observed the disappearance or appearance of hematochezia after elimination or challenge with the offending foods. Results: Before diagnosis infants were breast-fed (93.3%) or formula-fed (6.7%). Mean age at symptom onset was $11.5{\pm}5.1$ (5~24) weeks, and mean age at diagnosis was $17.8{\pm}9.5$ (8~56) weeks. Duration from symptom onset to diagnosis was $6.3{\pm}6.7$ (0~36) weeks. Mean peripheral blood eosinophil count was $478{\pm}320$ (40~1,790)/$mm^3$ and eosinophilia (> $250/mm^3$) was observedin 90.0% of patients. None of patients were found to have an increased serum IgE level. Of 15 patients that received sigmoidoscopy, nodular hyperplasia with erosion was observed in 93.3%. Of 27 patients whose mother ate the diet eliminated the 5 food groups, hematochezia diappeared in 74.1% of patients. Offending foods were identified as dairy products (37.5%), wheat and buckwheat (27.5%), fish and shellfish (20.0%), nuts and soybean (7.5%) and eggs (7.5%). A free maternal diet without patient's clinical symptoms was achieved at $29.4{\pm}8.7$ (9~44) weeks of patient's age, and a free baby diet without blood in stools was achieved at $37.5{\pm}9.7$ (12~56) weeks of age. Conclusion: DPIPC commonly occurs in exclusively breast-fed babies. Elimination of the above-mentioned 5 hyper-allergenic food groups from the maternal diet for 7days enables the detection of the offending foods. DPIPC is a transient disorder and 96.0% of patients can tolerate the offending foods at 12 months of age.

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