Journal of Pathology and Translational Medicine

Original Article

Uncoupling Protein 2 (UCP2) and p53 Expression in Invasive Ductal Carcinoma of Breast.: Kyu Yeoun Won, Gou Young Kim, Youn Wha Kim, Sung Jig Lim, Jeong Yoon Song; Korean J Pathol. 2010;44(6):565-570.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.6.565

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BACKGROUND
Uncoupling protein 2 (UCP2) is a recently identified mitochondrial inner membrane anion carrier and a negative regulator of reactive oxygen species production. In this study, we evaluated the characteristics and relationships of UCP2 and p53 expression in breast cancer tissues.
METHODS
Tissue microarray slides from 107 cases of invasive ductal carcinoma of the breast were constructed, UCP2 and p53 immunohistochemical staining was conducted, and clinicopathological correlations were investigated.
RESULTS
UCP2 expression in invasive ductal carcinoma was high in 53 cases (49.5%), while p53 expression in invasive ductal carcinoma was high in 37 cases (34.6%). UCP2 expression was correlated significantly with histological grade (p = 0.038) and mitotic count (p = 0.050). UCP2 expression was correlated significantly with p53 expression in invasive ductal carcinoma of the breast (p = 0.045). UCP2 expression (p = 0.8308) and p53 expression (p = 0.3292) showed no significant difference for the overall survival rate in patients with invasive ductal carcinoma.
CONCLUSIONS
UCP2 expression in invasive ductal carcinoma increased proportionally with histological grade and mitotic count. High UCP2 expression in invasive ductal carcinoma was observed in conjunction with high p53 expression.

Citations

Citations to this article as recorded by

Forkhead box protein A1 inhibits the expression of uncoupling protein 2 in hydrogen peroxide-induced A549 cell line
Lan Song, Zhaojun Xu, Ling Li, Mei Hu, Lijuan Cheng, Lingli Chen, Bo Zhang
Cell Stress and Chaperones.2014; 19(1): 53. CrossRef
New Aspects of Mitochondrial Uncoupling Proteins (UCPs) and Their Roles in Tumorigenesis
Delira Robbins, Yunfeng Zhao
International Journal of Molecular Sciences.2011; 12(8): 5285. CrossRef

Case Report

Myopathy due to Chronic Clevudine Therapy: A Case Report.: Jee Young Kim, Young Shin Yoon, Kee Duk Park, Heasoo Koo; Korean J Pathol. 2009;43(6):575-579.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.6.575

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Abstract PDF

A 40-year-old man with chronic hepatitis B complained of progressive weakness of the proximal muscles and edema of both legs. He had been receiving long-term clevudine (nucleoside analogue reverse transcriptase inhibitor, NRTI) therapy for his hepatitis. The serum creatine kinase level was increased on the laboratory tests. His electromyography showed a generalized myopathic process. The muscle biopsy showed numerous ragged-red fibers, degenerating myofibers with variable sized cytoplasmic bodies, the prominence of type 1 fibers with type 2 fiber atrophy and an endomysial mononuclear cell infiltration. The electron microscopic examination revealed necrotic myofibers, including extremely dysmorphic mitochondria with extensive loss, blunting and focal clumping of the cristae and concentric cristae. Although clevudine is known to be a less cytotoxic agent among the various NRTIs, careful clinical attention should be paid to the patients who are receiving long-term clevudine therapy for the occurrence of myopathy.

Citations

Citations to this article as recorded by

A randomized phase 1b trial of the active site polymerase inhibitor nucleotide ATI‐2173 in patients with chronic hepatitis B virus infection
Katherine E. Squires, Lauren Ogilvie, Alina Jucov, Igor Anastasiy, Nelli Ghicavii, Jade Huguet, Rebeca Melara, Martin Constantineau, Abel De La Rosa, Douglas L. Mayers
Journal of Viral Hepatitis.2023; 30(1): 19. CrossRef
Active site polymerase inhibitor nucleotides (ASPINs): Potential agents for chronic HBV cure regimens
Robert G Gish, Tarik Asselah, Katherine Squires, Douglas Mayers
Antiviral Chemistry and Chemotherapy.2022; 30: 204020662211387. CrossRef
Clevudine Induced Mitochondrial Myopathy
Soo-Hyun Park, Kyung-Seok Park, Nam-Hee Kim, Joong-Yang Cho, Moon Soo Koh, Jin Ho Lee
Journal of Korean Medical Science.2017; 32(11): 1857. CrossRef
In silico elucidation of the inclusion phenomenon and permeation behavior of a zidovudine–cyclodextrin complex via static lattice atomistic simulation
Pradeep Kumar, Yahya E. Choonara, Lisa C. Toit, Viness Pillay
Journal of Inclusion Phenomena and Macrocyclic Chemistry.2014; 78(1-4): 445. CrossRef

Original Articles

Ultrastructural Changes of Lead Acetate Induced Liver Injury in Rats.: Eun Sook Chang, Jin Seok Oh; Korean J Pathol. 1996;30(3):184-198.

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Abstract PDF: To evaluate the ultrastructural changes and the mechanism causing liver injury by lead, light and electron microscopic(LM and EM) examination using Timm sulphide silver method(TSM) was done. Sprague-Dawley rats were divided into a control and 3 experimental groups. The experimental groups were orally administered 0.5% lead acetate(LA). Group 1 received a one time dose of 10 ml of LA by gastric intubation. Groups 2 and 3 continuously received LA instead of drinking water. The control group was composed of 3 rats in each group which did not receive any treatment. Rats of group 1, 2 and 3 and control were sacrificed at 1/2, 1, 1 1/2 hours, 2 days, and at 1, 2, 4, 6 and 8 weeks later, except group 3. Before sacrifice, they were perfused with 0.1% sodium sulphide and 2.5% glutaraldehyde through the abdominal aorta for TSM. The liver was taken for LM and EM examinations. Blood lead concentration began to increase from the 2nd day up to 3.29 microgram/ml at 2nd week, and the urinary delta-ALA level showed a steady increase from the 2nd day. LM and EM examination of liver revealed that absorbed lead granules in group 1 were transported into sinusoidal spaces, Kupffer cells, and the hepatocytes within 1 hour and then disappeared 1/2 hour thereafter. In group 2 deposited lead was found in the hepatocytic cytosol bound to mitochondria. That in turn inhibited mitochondrial respiration with resultant mitochondrial swelling at the 1st week and thereafter at 6th week myelin figure formation and condensation of mitochondria, and peroxisomes were increased at 8th week. Based on these results it can be concluded that a transient intake of subletal dose of LA is biotransformed completely by periportal hepatocytes within 1 1/2 hours, but excessively accumulated lead can induce liver cell injury due to lipid peroxidation of membrane by direct toxic effect of lead and by products of lipid peroxidation. We postulate that lead acetate triggers presumably primarily mitochondrial membrane injury and then other organellar changes may play a role in disturbance of a network of interacting of key events capable of causing cell death.

Clinicopathologic Comparison between Autoimmune Cholangitis and Primary Biliary Cirrhosis.: Gyeong Hoon Kang, So Dug Lim, Eun Sil Yu, On Ja Kim, Geun Chan Lee, Neung Hwa Park, Dong Jin Suh; Korean J Pathol. 1998;32(2):115-124.

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Abstract PDF: Primary biliary cirrhosis (PBC) is characterized by histological findings of an immunoinflammatory destruction of small- and medium-sized bile ducts with progressive portal fibrosis, and the presence of anti-mitochondrial antibody (AMA) with a laboratory evidence of chronic cholestasis. The term "autoimmune cholangitis" (AIC) is used for a disease with the clinical and pathologic features of primary biliary cirrhosis (PBC) but with negative AMA and positive anti-nuclear antibody (ANA) tests. Eight cases of AIC and ten cases of PBC were reviewed in order to determine whether there was any difference between two diseases in clinico-pathologic aspects. All of the patients were female and the mean ages of AIC and PBC patients were 48 and 47 years, respectively. ANA test was positive in six of ten PBC paients and their mean titer was lower than that of AIC patients. IgM level was significantly higher in PBC group than in AIC group. No significant difference was found between two groups with respect to biochemical and histopathological features. Since the only consistently distinguishing features between these two conditions are the autoantibody profile (AMA vs ANA) and immunoglobulin level (IgM), these two conditions might be part of a spectrum. PBC can be considered to be the same as AMA-positive AIC or alternatively AIC to be the same as AMA-negative PBC.

Relationship between Insulin Secretory Capacity and Mitochondrial Morphology in Pancreatic beta-Cell.: Seung Won Yang, Jae Hyuk Lee, Chang Soo Park, Min Young Chung; Korean J Pathol. 1999;33(5):326-336.

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Abstract PDF: To investigate the relationship between insulin response and morphometric changes of the mitochondria of pancreatic beta-cell, this study was performed using hyperglycemia and streptozotocin as oxidative stresses. Adult and neonatal rats were used. Intravenous glucose tolerance test (IVGTT) and morphologic examination of pancreas using immunohistochemical stain, in situ end-labeling method and electron microscopic study were performed. Various mitochondrial parameters were measured by image analyzer. Immunohistochemical stain revealed a markedly reduced islet size and decreased number of beta-cells and the increased number of non-beta-cell in adult and neonatoal streptozotocin group, and the appearance of insulin positive cells throughout the exocrine parenchyma in neonatal streptozotocin group. Three days after injection of streptozotocin in adult streptozotocin group, TUNEL stain showed increased apoptotic cells in islets. Ultrastructurally, beta-cells in adult streptozotocin group showed increase in number and size of mitochondria, and disruption of mitochondrial structures. Hyperglycemic group and neonatal streptozotocin group showed preserved mitochondrial ultrastructure. Ultrastructural morphometric study revealed increase in size and number of mitochondria and decrease in mitochondrial contour index in adult streptozotocin-treated rats, which suggested mitochondrial degeneration. Hyperglycemic group showed mild increase in size of mitochondria. Increased number of mitochondria was also observed in neonatal streptozotocin group. IVGTT revealed marked decrease in insulin response in adult streptozotocin group, and non-insulin-dependent diabetes mellitus pattern in glucose and insulin response in neonatal streptozotocin group. Hyperglycemic group showed a glucose and insulin response similar to control group. The above results suggest that a severe oxidative injury may cause degeneration and disruption of mitochondria of pancreatic beta-cell, and may be associated with substantial apoptotic cell death. The changes in the morphology and the number of mitochondria may result from streptozotocin treatment within neonatal period and hyperglycemia treatment, which may be associated with changes in insulin response.

Case Report

Adrenocortical Oncocytoma: A case report.: Hee Joung Cha, Yeon Lim Suh, Jung Hyun Yang; Korean J Pathol. 1999;33(6):463-466.

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Abstract PDF: Adrenal gland is a rare location for an oncocytic neoplasm. In English literature less than 10 cases of adrenocortical oncocytoma have been reported. We have experienced a case of adrenocortical oncocytoma in a 35-year-old man which was detected incidentally during the ultra-sonographic evaluation of the abdomen for a routine physical examination. This case did not demonstrate any clinical evidence of adrenocortical abnomalities, such as virilization or hypertension. Grossly, the tumor was light to dark tan on cut surface. Light-microscopic examination revealed tumor cells with abundant lipid- sparse eosinophilic cytoplasm and occasional pleomorphic nuclei. Mitotic figures were less than 5/50 HPFs. Tumor cells were positive for vimentin but negative for pancytokeratin, CAM 5.2, chromogranin and synaptophysin. Ultrastructural examination demonstrated abundant mitochondria containing occasional intramitochondrial dense bodies or inclusions.

Original Articles

Pathologic Findings of Mitochondrial Myopathy.: Lucia Kim, Tai Seung Kim; Korean J Pathol. 2000;34(1):77-84.

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Abstract PDF: Mitochondrial myopathy (MM) has been applied to muscle disease in which mitochondria have abnormal structure, function or both. To characterize the pathologic findings of MM, we examined the ultrastructural and histochemical findings of 24 cases of MM. The ultrastructures of the MM were characterized by abnormal mitochondria in number (pleoconia) and size (megaconia), and showed predominant accumulation of mitochondria in the subsarcolemmal space of myofibers in all cases. Mitochondria contained abnormally shaped cristae (concentric form and gyriform) in 79% of cases. Paracrystalline inclusion which was known to be a characteristics of MM were seen only in 7 cases (29%). Electron dense deposits were more frequently found (77%) in abnormal mitochondria of chronic progressive external opthalmoplegia and Kearn-Sayre syndrome. But, other findings were not specific for the specific clinical entities. On succinate dehydrogenase (SDH) stain, ragged red fibers (RRF) showed more intense positivity than modified Gomori-trichrome stain and definite strong reactive products were present along the periphery of myofibers which showed normal findings on modified Gomori-trichrome stain. In conclusion, ultrastructural findings such as mitochondria showing pleoconia with megaconia, and bizarre shaped cristae may be helpful for the diagnosis of MM and SDH stain is more useful for identification of RRF than modified Gomori-trichrome stains.

Effect of Lysodren(R) on the Ultrastructural Changes in the Rat Adrenal Corex: Immunohistochemical staining for anti-ACTH antibody on the adenohypophysis.: Ho Jong Chun, Hae Chang Cho, Hae Sook Song, Kyu Ho Park; Korean J Pathol. 1989;23(1):94-110.

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Abstract PDF: The toxicity and adrenostatic effect of o,p'-DDD, a derivative of the insecticidal DDT, on the adrenal cortex were well known. It known that the toxicity was based on the blocking of steroid biopsynthesis when cholesterol was converted to pregnenolone. Lysodren(R) was also known to be capable of producing a regression of adrenocortical carcinoma and its metastases, and this drug became one of useful choice for the treatment of unoperable adrenocortical carcinomas. Recently, fine structural effect of o,p'-DDD on the adrenocortical carcinoma show that the mitochondria is the primary target organelle. o,p'-DDD was dissolved in corn oil and it was orally administered for 28 days to investigate the ultrastructural effects of zona fasciculata of rat adrenal cortex. The results obtained were as follow: 1) The body weight was decreased after feeding o,p'-DDD. 2) Light microscopic examination showed no remarkable change except increased fine lipid droplets of zona fasciculata in group I (o,p'-DDD 75 mg/kg feeding). Moderately increased intracytoplasmic lipid droplets and pyknotic nuclei bearing membrane indentations were seen in group II (o,p'-DDD 150 mg/kg feeding). Large sized lipid droplet aggregates, pyknotic nuclei with severe nuclear membrane indentations and karyorrhexis in focal area were evident in group III. 3) Immunohistochemical staining for ACTH in pituitary gland showed increasing number of ACTH secretory cell and increasing intensity of staining property according to the dosage of o,p'-DDD. 4) Ultrastructural examination showed increased intracytoplasmic lipid droplets and mild increased peroxisome. There was no remarkable ultrastructural changes in mitochondria in group I. Moderately increased lipid droplets and clusters formation, compressed mitochondria, partial disappearance of mitochondrial cristae, increased peroxisome and nuclear membrane indentations were seen in group II. In group III, nuclear membrane showed prominent indentation. Numberous cytoplasmic vacuolation, double membrane ring in mitochondria, disappearance of mitochondrial cristae, myelin figure formation in mitochondrial matrix, and fatty changes in mitochondrial matrix were seen. These findings showed that the primary target organelle of attack by o,p'-DDD on zona fasciculata of adrenal gland in rat is mitochondria and it was developed from double ring formation in mitochondrial matrix.

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