Imaging Findings of Breast Metastasis from Squamous Cell Carcinoma of the Cervix: A Case Report

Metastasis from extramammary malignancy to the breast is rare, and metastasis of cervical cancer to the breast is quite uncommon. We report atypical sonographic findings of a rapid growing, single, and circumscribed mass with complex cystic and solid echo pattern in a 50-year-old female. The mass confirmed a metastasis from cervical cancer. It is rare, but the possibility of breast metastasis should be considered when a rapidly growing breast mass is located in between the parenchyma and subcutaneous fat layer.

Optimization of Microenvironments Inducing Differentiation of Tonsil-Derived Mesenchymal Stem Cells into Endothelial Cell-Like Cells

BACKGROUND: Stem cell engineering is appealing consideration for regenerating damaged endothelial cells (ECs) because stem cells can differentiate into EC-like cells. In this study, we demonstrate that tonsil-derived mesenchymal stem cells (TMSCs) can differentiate into EC-like cells under optimal physiochemical microenvironments.METHODS: TMSCs were preconditioned with Dulbecco's Modified Eagle Medium (DMEM) or EC growth medium (EGM) for 4 days and then replating them on Matrigel to observe the formation of a capillary-like network under light microscope. Microarray, quantitative real time polymerase chain reaction, Western blotting and immunofluorescence analyses were used to evaluate the expression of gene and protein of EC-related markers.RESULTS: Preconditioning TMSCs in EGM for 4 days and then replating them on Matrigel induced the formation of a capillary-like network in 3 h, but TMSCs preconditioned with DMEM did not form such a network. Genome analyses confirmed that EGM preconditioning significantly affected the expression of genes related to angiogenesis, blood vessel morphogenesis and development, and vascular development. Western blot analyses revealed that EGM preconditioning with gelatin coating induced the expression of endothelial nitric oxide synthase (eNOS), a mature EC-specific marker, as well as phosphorylated Akt at serine 473, a signaling molecule related to eNOS activation. Gelatin-coating during EGM preconditioning further enhanced the stability of the capillary-like network, and also resulted in the network more closely resembled to those observed in human umbilical vein endothelial cells.CONCLUSION: This study suggests that under specific conditions, i.e., EGM preconditioning with gelatin coating for 4 days followed by Matrigel, TMSCs could be a source of generating endothelial cells for treating vascular dysfunction.

Intracellular Remodeling and Accumulation of Aberrant Lysosomes in Differentiation of Tonsil-Derived Mesenchymal Stem Cells into Parathyroid-Like Cells

Differentiation of mesenchymal stem cells (MSC) into a variety of cell lineages such as adipocytes, osteocytes, and chondrocytes is often accompanied up-regulation of autophagy. In our study, we demonstrated that the expression of autophagy-associated proteins (p-Beclin 1, LC3A, LC3B, p-AMPK, p-mTOR and ATG3, ATG7, and ATG12-5) over a period of time was hardly distinguishable from control tonsil-derived MSC (TMSC). Despite the unnoticeable difference in autophagy activation between differentiated TMSC (dTMSC) and the control (cTMSC), we reported significant changes in intracellular compositions in differentiated TMSC into functional parathyroid-like cells secreting parathyroid hormone (PTH). By using transmission electron microscopy (TEM), we observed accumulation of multivesicular bodies (MVB) comprising small, degraded compartments densely accumulated as dark granular or amorphous clumps, multilamellar bodies and lipid droplets in dTMSC. However, no such structures were found in cTMSC. These results suggest that differentiation of TMSC into parathyroid-like cells producing PTH hormone is hardly dependent on autophagy activation in the beginning of our conditions. Furthermore, our results of intracellular remodeling and accumulated endo-lysosomal storage bodies in the later stages of TMSC differentiation present a possible role of the structures in PTH secretion.

A Case of Drug-Induced Autoimmune Hepatitis after Glucosamine Ingestion / 대한내과학회지

Herbal remedies and health foods are widely used, and their side effects have been reported. Glucosamine is a naturally occurring amino-monosaccharide and a safe health food; rarely, however, it can cause cholestatic and hepatocellular hepatitis. We describe a case of drug-induced autoimmune hepatitis after ingestion of glucosamine. A middle-aged woman who had no history of liver disease complained of jaundice after taking glucosamine. The diagnosis of drug-induced acute autoimmune hepatitis was made using the Roussel Uclaf Causality Assessment Method score based on the patient's history and laboratory data, and percutaneous liver biopsy. After supportive care and administering prednisolone and azathiprine, the patient showed rapid improvement in clinical symptoms and laboratory findings.

A Case of Drug-Induced Autoimmune Hepatitis after Glucosamine Ingestion / 대한내과학회지

Herbal remedies and health foods are widely used, and their side effects have been reported. Glucosamine is a naturally occurring amino-monosaccharide and a safe health food; rarely, however, it can cause cholestatic and hepatocellular hepatitis. We describe a case of drug-induced autoimmune hepatitis after ingestion of glucosamine. A middle-aged woman who had no history of liver disease complained of jaundice after taking glucosamine. The diagnosis of drug-induced acute autoimmune hepatitis was made using the Roussel Uclaf Causality Assessment Method score based on the patient's history and laboratory data, and percutaneous liver biopsy. After supportive care and administering prednisolone and azathiprine, the patient showed rapid improvement in clinical symptoms and laboratory findings.

A Case of Papillary Thyroid Carcinoma Combined with Multiple Endocrine Neoplasia Type 2A / 대한내분비학회지

Multiple endocrine neoplasia (MEN) type 2A is a syndrome of medullary thyroid carcinomas, pheochromocytomas and parathyroid hyperplasia. The simultaneous occurrence of medullary, and papillary, thyroid carcinomas is rare because they are derived from, apparently, different germ layers, the former from the neuroectoderm and the latter from the endoderm. We report a case of a papillary thyroid carcinoma, combined with a medullary thyroid carcinoma, in a patient with MEN type 2A. Molecular genetic studies for screening a RET proto-oncogene mutation revealed a point mutation in codon 631 on chromosome 10, which is reported as highly uncommon in MEN type 2A.

Radiation-Induced Proctitis in Rat and Role of Nitric Oxide / 대한방사선종양학회지

PURPOSE: Proctitis is one of acute complications encountered when radiotherapy was applied to the pelvis. Radiation-induced proctitis represents similar microscopic findings that are observed in inflammatory bowel disease (IBD). Nitric oxide (NO) plays an important role in the inflammatory process and many data suggest a close relationship between NO production and gastrointestinal inflammation. This study was aimed to establish the optimal radiation dose for radiation-induced proctitis in rat and to find a relationship between radiation proctitis and NO production. MATERIALS AND METHODS: Female Wistar rats, weighing from 150 to 220 g, received various doses(10-30 Gy) of radiation to the rectum. On the 5th and 10th day after irradiation, rectal specimens were evaluated grossly and microscopically. In addition, the degree of NO production by irradiation dose was evaluated by study with NOS expression and nitrite production in the irradiated rectal tissue. To evaluate relationship between radiation proctitis and NO, we administered aminoguanidine, iNOS inhibitor and L-arginine, substrate of NOS to rats from 2 days before to 7 days after the irradiation. RESULTS: There were obvious gross and histological changes after 17.5 Gy or higher radiation dose but not with 15 Gy or less radiation dose. Twenty Gy or higher dose of radiation caused Grade 4 damage in most of rectal specimens which were more likely to be related to the late complications such as fibrosis, rectal bleeding and rectal obstruction. A single fraction of 17.5 Gy to the rat rectum is considered to be an optimal dose to produce commonly experienced proctitis in the clinic. The result demonstrated that severity of microscopic damage of rectal mucosa from irradiation significantly correlated with iNOS overexpression. However, administration of iNOS inhibitor or substrate of iNOS did not influence the degree of rectal damage. CONCLUSION: A single fraction of 17.5 Gy irradiation to the rat rectum considered to be an optimal dose for radiation induced proctitis model. These results indicated that an excess production of NO contributes to pathogenesis of radiation-induced proctitis in part but was not the direct cause of rectal damage.

A rat model for radiation-induced proctitis

Radiation proctitis is a frequent acute complication encountered with pelvic irradiation. This study was aimed at establishing the optimal radiation dose for radiation-induced proctitis in rats. Female Wistar rats were used. The rectal specimens were examined morphologically at 5th and 10th day following 10-30 Gy irradiation in single fraction. With increasing dose, mucosal damage became worse, and there was a prominent reaction after > or =15 Gy. We selected 17.5 Gy as an optimal dose for radiation proctitis and examined specimens at day 1-14 and at week 4, 6, 8, and 12 after 17.5 Gy. The rectal mucosa revealed characteristic histological changes with time. An edema in lamina propria started as early as 1-2 days after irradiation and progressed into acute inflammation. On day 7 and 8, regeneration was observed with or without ulcer. Four weeks later, all regeneration processes have been completed with end result of either fibrosis or normal appearing mucosa. This study showed that the radiation injury of the rectum in rat develops in dose-dependent manner as it has reported in previous studies and suggested that 17.5 Gy in single fraction is the optimum dose to evaluate the protective effect of various medications for radiation proctitis in face of the clinical situation.

Maximal Diagnostic Accuracy in Virtual Telepathology System according to Input Device and Video Signal

Varieties of telepathology system had been developed and in use, but their functional capability and diagnostic accuracy are considered to be inferior to those of conventional optical microscope. This study is intended to find out: 1) the diagnostic accuracy and reproducibility rate according to the input devices and the video signals; 2) any potential technical problems of the telepathology system; 3) any possible physical and psychological impacts. We devised a virtual telepathology system using our existing microscope equipped with CCD camera unit that has no restriction of network speed. Total fifty-five surgical pathology cases from 11 different organs were selected. Three pathologists were involved in making diagnoses. The resulting diagnostic accuracies were: 1 CCD camera with composite video signal was 86.2%; 3 CCD camera with composite video signal was 93.1%; 3 CCD camera with component video signal was 95.0%. The 3 CCD camera with component video signal resulted in 95.0% diagnostic accuracy and was superior to 1 CCD camera with composite video signal. Some technical problems noted during this study were: the visual field of the virtual telepathology system was smaller by 43% than that of microscope; the difference of cell sizes between microscope and monitor; low resolution of image. Some physical and psychological symptoms were noted.

Production and Gene Cloning of Monoclonal Antibodies Directed Against S Antigen of Hepatitis B virus / 대한면역학회지

We produced two murine monoclonal antibodies designated S2E1 and S2C11, which recognize S antigen of hepatitis B virus (HBsAg). S2E1 could bind to denatured form of recombinant HBsAg as well as native form of HBsAg, but S2C11 could bind only to native form of HBsAg. Both antibodies reacted with HBsAg in the hepatocyte of patient infected with hepatitis B virus. Analyses of the nucleotide sequences encoding the variable regions of these antibodies revealed that S2E1 and S2C11 utilize variable gene segment which belong to V4/5 gene family and utilize the J5 and Jk4 gene segments, respectively. In addition, the heavy chain of S2E1 express a member of V14 gene family and a member of DSP2.9 and Jh3 gene families. S2C11 is related to the V1 gene family and expresses DFL16.1 gene regions in conjunction with the Jh3 gene segment.

The Effects of Intrasplenic Transplantation of Hepatocytes on Rats with Acute Liver Failure Induced by a 90% Hepatectomy

BACKGROUND: Acute liver failure either after liver resection or as part of underlying liver disease is still associated with high mortality. Various treatments have been tried to improve liver function during acute liver failure, including metabolic and nutritional support, hemodialysis, hemoperfusion, plasmapheresis, and hepatocyte and liver transplantation. Hepatocyte transplantation in various forms has attracted attention recently. We investigated whether allogeneic isolated hepatocytes transplanted in the spleen would prolong survival, facilitate liver regeneration, and improve biochemical parameters in rats with acute liver failure induced by a 90% hepatectomy. METHODS: Allogeneic male Sprague-Dawley rats were used. Group I rats (n=26) received an intrasplenic injection of 2 107 hepatocytes in 0.3 ml of Dulbecco's modified Eagle's medium (DMEM), and 1 days later acute liver failure was induced. Group II acute-liver-failure rats (n=24) received an intrasplenic injection of DMEM. The survival time was determined for 22 rats in Group I and for 20 rats in Group II. The remaining 8 (4/each group) acute liver failure rats were used to assess the liver function and regeneration. RESULTS: The survival was longer and the number of long-term survivors was greater for Group I rats than for the Group II controls. At 24 hour after the hepatectomy, Group I rats had lower ammonia, lower total bilirubin, lower activities of liver enzymes, and higher glucose levels than did Group II rats. In Group I, there was significant increase in the ratio of the weight of the remnant liver lobes to the body weight. CONCLUSION: Compared with the Control group intrasplenic hepatocyte transplantation in acute liver failure rats acts as a bridge to support experimental rats in going from acute or fulminant liver failureto liver regeneration or compensation, prolongs survival in rats with acute liver failure induced by a 90% hepatectomy, and improves the biochemical parameters, except for the albumin levels and prothrombin time. Transplantation of hepatocytes may be beneficial in supporting a liver which has been acutely devastated by a 90% hepatectomy.

Dimethylnitrosamine-Induced Liver Cirrhosis and Expression of Hepatocyte Growth Factor (HGF), its Receptor c-Met, and the Transforming Growth Factor (TGF)-beta1 in Sprague-Dawley Rats

BACKGROUND: Liver fibrosis and cirrhosis are the ultimate histologic consequences of chronic liver damage. Efforts have been made to study the mechanisms of cirrhosis and to discover effective therapeutic strategies. However, to date, no animal model reproduces the disease in man. The purpose of this work is to establish a model of DMN-induced liver cirrhosis for treatment of liver cirrhosis, to understand the basic characteristics of DMN-induced liver cirrhosis, and to confirm the expression of HGF, its receptor c-Met, and TGF-beta1 in Sprague-Dawley rats. METHODS: Five-week-old male Sprague-Dawley rats (n=56) were used for this study. Liver cirrhosis was induced in the rats by using DMN (1 ml/kg body weight, i.p.) given 3 consecutive days a week for 6 weeks. Changes in the portal vein pressure were measured by a venous catheter during the duration of the DMN-treatment. The levels of serum albumin, bilirubin, and ammonia were determined in a clinical laboratory by routive methods. Pieces of the median lobe were cut and fixed in 10% buffered neutral formalin, embedded in paraffin, and stained by hematoxylin-eosin (H&E) & masson-trichrome (M&T). Changes in the extracellular matrix were measured by image analysis and hydroxyproline content. Immunohistochemical staining of alpa-smooth muscle actin was performed to confirm the activation ofhepatic stellate cells. Northern blot analyses were performed to confirm the expression of HGF and TGF-beta1 and western blotting was performed c-Met, HGF receptor. RESULTS: Pressures in the portal vein were significantly increased during the DMN-treatment time (p<0.05). Biochemical parameters were significantly correlated with the progression of liver cirrhosis. H&E staining of 4-week DMN-treated rats demonstrated fibrous tissue bridging between the periportal and the pericentral areas with gradual widening of fibrous bands. Both the extracellular matrix measured by image analysis of the M&T staining and the hydroxyproline content rose continuously throughout the 6 weeks of DMN treatment. alpa-smooth muscle actin was observed in the stellate cells of DMN-treated rats. The northern blot analyses showed that the expression of HGF mRNA decreased with the progression of DMN-induced liver cirrhosis but that of TGF-beta1 mRNA did not. The western blot analyses showed that the expression of the c-Met receptor protein increased continuously, but the expression of HGF mRNA a decreased. CONCLUSION:The model of cirrhosis induced by chronic, discontinuous treatment with a low dose of DMN in rats was simple and predictable and displayed many of the features of human cirrhosis. The decrease in the expression of HGF mRNA may be responsible for the reduced hepatocyte regeneration in liver cirrhosis. The expression of the c-Met protein was related with the decreased expression of HGF. The exact significance of TGF-beta1 was not determined in this study.

The Preliminary Report of Rapid Production of Pancreas Cancer and Cholangiocarcinoma by Cyclic Injection of Carcinogens in Syrian Hamster initiated with N-nitrosobis(2-oxopropyl)amine / 한국간담췌외과학회지

BACKGROUND/AIMS: It is well known that N-nitrosobis(2-oxopropyl)amine(BOP)-induced pancreas cancer and cholangiocarcinoma in Syrian hamster is similar to that of humans in morphological, biological and immunological aspects. The cyclic administration of BOP and ethionine, choline-deficient diet and methionine is known to rapidly induce the ductal type of carcinoma in pancreas and bile duct. Authors studied whether the rapid production of this cancer can occur in Syrian hamster and what its features are. METHODS: Sixteen Syrian hamsters aged 6-7 weeks and weighing 100 gm were used. All hamsters received 70 mg/kg body weight of BOP followed by three cycles of dl-ethionine, choline-deficient diet, l-methionine and 20mg/kg BOP. Hamsters were killed 9, 10 and 11 weeks after the beginning of the experiment and their gross and histologic features were observed. RESULTS: Nine cases, killed withan 10weeks after the begining of experiment, showed no development of cancer. Of seven Syrian hamsters, killed more than 10weeks after the begining of experiment, the incidences of BOP-induced cancer included one case(14.3%) of pancreas cancer and five cholangiocarcinomas( 71.4%). The morphological change of pancreas carcinogenesis was shown at first in cell mitosis and atypia(6 weeks) and then in atypical ductal hyperplasia(9 weeks) and carcinoma in situ(10 weeks). The change in cholangiocarcinoma, first progressed with ductular proliferation and surrounding fibrosis(6 weeks) followed by focal cholangiocarcinoma(10 weeks) and multiple invasive cholangiocarcinomas( 11 weeks). CONCLUSION: Pancreas cancer and intrahepatic cholangiocarcinomas can be induced rapidly within 10 weeks by cyclic injections of carcinogens in Syrian hamsters initiated with Nnitrosobis( 2-oxopropyl)amine and the morphologic changes can be observed.

Internet Use for the Evaluation of Medical Learning / 한국의학교육

There are many ways to evaluate the learning achievement of medical students. We are familiar with the problems related to the traditional laboratory course practical examinations of pathology and histology courses, which deal with morphology heavily. In order to overcome the limitations inherent to the traditional evaluation methods, we used Internet for the written and practical examinations for the pathology course. Two tests were conducted on the internet with thirty medical students. Each student used his/her personal computer, which was connected to Local Area Network(LAN), in the computer laboratory. The examinee entered the Pathology Department home page(address: http://ajoupath. ajou.ac.kr) and took their tests made up of descriptive and multiple choice questions including related gross and microscopic images. Common Gateway Interface(CGI) program of Perl language was used for automatic scoring and analysis of the multiple choice questions. The server computer in the Pathology Department scored the results instantaneously upon the answer selection and push down of the "send" button by the examinee. Furthermore, the computer program was capable of providing data regarding how many students got the correct answer and the degree of difficulty for each item. The students were requested to provide hand-written descriptions for the questions requiring descriptive answers, because of the technical limitation. We believe that the tests on the internet were performed successfully. The "dreadful" old fashioned examination using timer were no longer needed because high quality gross and microscopic images on the monitor were available for the examinee. We believe that the internet is very useful for the comprehensive evaluation of the medical students' learning achievement.

Clinicopathological Study of Resected Gallbladders and Bile Ducts with Anomalous Pancreaticobiliary Ductal Union (APBDU)

BACKGROUND : Anomalous pancreaticobiliary ductal union (APBDU) is a congenital defect defined as a union of the pancreatic and the biliary ducts located outside the duodenal wall. Accordingly, this anomalous connection between the choledochus and the pancreatic duct is considered to be a factor in the development of biliary tract diseases such as choledochal cysts, pancreatitis, cholangitis, gallbladder cancer, and bile duct cancer. Our purpose is to analyze combined disease, especially biliary neoplasm, and to evaluate biliary tract microscopic changes in the biliary tract. METHODS : To study the clinical characteristics of APBDU, we reviewed 21 APBDU cases which were treated from June 1994 to January 1998. We studied the associated diseases, the surgical treatment, histological findings and the PCNA expression. We also analyzed the gallbladder epithelium in 10 control patients without APBDU. RESULTS : Among the 21 cases, 12 cases were accompanied by a choledochal cyst. A gallbladder carci noma occurred in 5 cases. Of the 13 operations, 4 involved a cholecystectomy only, and 9 involved a cholecystectomy, bile duct resection and hepaticojejunostomy. The histologic findings were reviewed in 13 cases. Bile duct metaplasia was found in 8 of the 9 cases with a bile duct resection, and gallbladder metaplasia was found in 8 of the 12 cases whereas metaplasia was detected in 1 of the 10 control patients. The PCNA expression was significantly high in APBDU group. CONCLUSIONS : The patients with APBDU showed a high incidence of gallbladder carcinoma and meta plasia in the epithelium of the gallbladder and the bile duct. This metaplasia in the gallbladder and the bile duct was thought to be related to the cancerous change.

Two Cases of Villous Adenoma of the Common Bile Duct: Endoscopic Diagnosis and Treatment / 대한소화기내시경학회지

Villous adenomas of the common bile duct are rare and accordingly it is difficult to render a firm preoperative diagnosis. They are the unusual cause of bile duct obstruction and can mimic malignant extrahepatic biliary tumors or stones. Until recently, only a few cases had been reported in the medical literature. Although some authors advocate open surgical excision, especially with recurrence or carcinomatous change, an endoscopic resection of a distal common bile duct adenoma is a viable alternative for those patients considered poor surgical risks. We present two cases of villous adenoma of the common bile duct diagnosed by an endoscopic biopsy and endoscopically resected, with review of the relevant literature on the subject.

Pancreatic serous cystadenoma mimicking pseudocyst

The serous cystadenoma of the pancreas is a rare lesion that is usually found incidentally. It is mostly observed as a spongy microcystic mass but rare variants such as macrocystic, unicystic, or multicentric are also seen. We recently experienced a unique case of unicystic serous cystadenoma mimicking a pseudocyst. It was grossly a unilocular cyst with surrounding dense fibrosis resembling a pseudocyst. Microscopically, the cyst was partly lined by low columnar-to-cuboidal cells with clear cytoplasm containing glycogen.

A Case of Familial Medullary Thyroid Carcinoma / 대한이비인후과학회지

Medullary thyroid carcinoma(MTC) is a malignancy of the thyroid C-cells, and it compromises 5-10% of all thyroid cancers. MTC occurs in both sporadic and hereditary types, the latter making up 25% of all MTCs and being compromised of three distinct syndromesmultiple endocrine neoplasia type IIa(MEN IIa), multiple endocrine neoplasia type IIb(MEN IIb), and familial medullary thyroid carcinoma(FMTC). To date, screening for MTC subtype is important for proper diagnosis and treatment. Recently, the authors experienced a case of FMTC. So, we report this case with the review of the literatures.

A Case of Graves' Disease associated with Myasthenia Gravis treated by Bilateral Subtotal Thyroidectomy and Total Thymectomy / 대한내분비학회지

Graves disease occur in association with myasthenia gravis is rare. We report a case of Graves disease and myasthenia gravis treated by bilateral subtotal thyroidectomy and total thymectomy simultaneously. A 37 year old woman was admitted with anterior neck mass and ptosis. Various examinations were compatible with combined Graves disease and myasthenia gravis. The bilateral subtotal thyroidectomy and total thymectomy were done simultaneously. The pathologic diagnosis was Graves disease and thymic hyperplasia. The patients postoperative course was uneventful. The thyroid function of patient became euthyroid and the clinical symptoms related with myastenia gravis resolved during follow up period.

Cyclin E expression in benign and malignant epithelial neoplasms of the gallbladder

Cyclins are the regulatory subunits of cyclin-dependent kinase and play an important role in cell proliferation. Many tumors, such as colon, breast and gastric carcinomas are known to be involved in the deregulation or amplification of cyclins, especially cyclin E, which involves the restriction point of G1-S transition. We investigated the expression of cyclin E in benign and malignant epithelial tumors of the gallbladder and compared the results with the activity of cell proliferation by the Ki67 antigen using immunohistochemical staining. Cyclin E was expressed in the adenocarcinoma tissue in 33.3% of patients (4 out of 12 cases), whereas only one out of 8 cases of adenoma expressed cyclin E (12.5%). There was a correlation between cyclin E expression and the Ki67 labeling index. These results suggest that the high expression of cyclin E in adenocarcinoma of the gallbladder is related to a high rate of cell proliferation.