ymptoms of Parkinson’s disease (PD) caused by loss of dopaminergic neurons are accompanied by movement disorders, including tremors, rigidity, bradykinesia, and akinesia. Non-human primate (NHP) models with PD play an essential role in the analysis of PD pathophysiology and behavior symptoms. As impairments of hand dexterity function can affect activities of daily living in patients with PD, research on hand dexterity function in NHP models with chronic PD is essential. Traditional rating scales previously used in the evaluation of animal spontaneous behavior were insufficient due to factors related to subjectivity and passivity. Thus, experimentally designed applications for an appropriate apparatus are necessary. In this study, we aimed to longitudinally assess hand dexterity function using hand dexterity task (HDT) in NHP-PD models. To validate this assessment, we analyzed the alteration in Parkinsonian tremor signs and the functionality of presynaptic dopaminergic neuron using positron emission tomography imaging of dopamine transporters in these models. In addition, a significant inverse correlation between HDT and DAT level was identified, but no local bias was found. The correlation with intention tremor signs was lower than the resting tremor. In conclusion, the evaluation of HDT may reflect behavioral symptoms of NHP-PD models. Furthermore, HDT was effectively used to experimentally distinguish intention tremors from other tremors.

With recent advances in molecular diagnostic methods and targeted cancer therapies, several molecular tests have been recommended for gastric cancer (GC) and colorectal cancer (CRC). Microsatellite instability analysis of gastrointestinal cancers is performed to screen for Lynch syndrome, predict favorable prognosis, and screen patients for immunotherapy. The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor has been approved in metastatic CRCs with wildtype RAS (KRAS and NRAS exon 2–4). A BRAF mutation is required for predicting poor prognosis. Additionally, amplification of human epidermal growth factor receptor 2 (HER2) and MET is also associated with resistance to EGFR inhibitor in metastatic CRC patients. The BRAF V600E mutation is found in sporadic microsatellite unstable CRCs, and thus is helpful for ruling out Lynch syndrome. In addition, the KRAS mutation is a prognostic biomarker and the PIK3CA mutation is a molecular biomarker predicting response to phosphoinositide 3-kinase/AKT/mammalian target of rapamycin inhibitors and response to aspirin therapy in CRC patients. Additionally, HER2 testing should be performed in all recurrent or metastatic GCs. If the results of HER2 immunohistochemistry are equivocal, HER2 silver or fluorescence in situ hybridization testing are essential for confirmative determination of HER2 status. Epstein-Barr virus–positive GCs have distinct characteristics, including heavy lymphoid stroma, hypermethylation phenotype, and high expression of immune modulators. Recent advances in next-generation sequencing technologies enable us to examine various genetic alterations using a single test. Pathologists play a crucial role in ensuring reliable molecular testing and they should also take an integral role between molecular laboratories and clinicians.

No abstract available.
Joint Capsule* ; Joints* ; Thumb*

BACKGROUND: A few recent studies have demonstrated a possible role of transglutaminase 2 (TG2) in tumorigenesis or progression of renal cell carcinoma (RCC). The aim of this study was to examine TG2 expression and its clinicopathologic significance in a large number of human clear cell RCCs (CCRCCs). METHODS: We analyzed 638 CCRCC patients who underwent partial or radical nephrectomy between 1995 and 2005. The expression of TG2 was determined by immunohistochemistry and categorized into four groups, according to staining intensity: negative (0), mild (1+), moderate (2+), and strong (3+). RESULTS: TG2 staining intensity was negative in 8.5% of CCRCC (n=54), 1+ in 32.6% (n=208), 2+ in 50.5% (n=322), and 3+ in 8.5% (n=54). Strong TG2 expression was correlated with high Fuhrman nuclear grade (p=.011), high T category (p=.049), metastasis (p=.043) and male sex (p<.001) but not with N category.The survival analysis showed a significant association between strong TG2 expression and worse overall and cancer-specific survival (p=.027 and p=.010, respectively). On multivariate analysis, strong TG2 expression was a marginally significant prognostic indicator for Fuhrman nuclear grade and TNM staging (p=.054). CONCLUSIONS: Our study is the first to demonstrate the clinicopathologic significance of TG2 expression in a large number of human CCRCC samples. Strong TG2 expression was associated with high nuclear grade and poor prognosis.
Carcinogenesis ; Carcinoma, Renal Cell* ; Humans ; Immunohistochemistry ; Male ; Multivariate Analysis ; Neoplasm Metastasis ; Neoplasm Staging ; Nephrectomy ; Prognosis ; Transglutaminases

BACKGROUND: Many studies about the levator aponeurosis complex of the blepharoptosis have already been presented. However, the studies about the changes of the levator aponeurosis are relatively insufficient. So, this study was performed to observe histological changes of levator aponeurosis that arise depending on the severity of blepharoptosis and the age. METHODS: Twenty patients who have undergone surgical treatment for blepharoptosis from 2013 to 2014 were analyzed in this study. Patients were categorized mild or severe group according to the severity of blepharoptosis, and the age. Through the blepharoplasty incision, we harvested the specimens of the levator aponeurosis on the upper border of tarsal plate. After staining the specimens with the Verhoeff-van Gieson technique, the changes of elastin was analyzed in a histopathological manner. RESULTS: Light microscopy of the levator aponeurosis stained positively for elastic fibers using the Verhoeff-van Gieson technique. Elastic fibers appear to have direct connections with the collagen fiber of the levator aponeurosis. The amount of the elastin was decreased in the old age group. And the amount of elastin was decreased markedly in severe blepharoptosis group. CONCLUSIONS: The elastin of the levator aponeurosis was decreased in old age and elastin tended to decreased markedly in severe levator function group. The levator aponeurosis plays a greater role in the eyelid ptosis. Therefore, knowledge about the histologic changes of the levator aponeurosis may give more help us to understand the high recurrence rate of the blepharoptosis in old age. Also, considering this information, will be helpful to the blepharoptosis surgery.
Aging* ; Blepharoplasty ; Blepharoptosis* ; Collagen ; Elastic Tissue ; Elastin ; Eyelids ; Humans ; Microscopy ; Recurrence

BACKGROUND: This study investigates the prevalence of human papillomavirus (HPV) 52 and 58 genotypes among women residing in Busan, and the expression of p16 and p53 proteins in cervical neoplasia with HPV 52 and 58 infections. METHODS: A total of three hundred fifteen cases were analyzed using the HPV DNA chip test for HPV genotypes, and of these, we retrospectively examined p16 and p53 expression in 62 cases of cervical tissues infected with HPV 52 and 58 using immunohistochemistry. RESULTS: HPV 52 and 58 genotypes were identified in 62 (54.9%) out of 113 high-risk, HPV-infected cases. Of the cases examined, there were 19 single HPV 52 infections (16.8%), 23 single HPV 58 infections (20.4%), 4 multiple HPV 52 infections (3.5%), and 16 multiple HPV-58 infections (14.2%). Immunoreactivity of p16 and p53 was observed in 41 (66.1%) and 23 (37.1%) of the 62 cases of cervical neoplasia infected with HPV 52 and 58 genotypes, respectively. CONCLUSIONS: This study demonstrates a high prevalence of HPV 52 and 58 genotypes, in addition to HPV 16, among high-risk strains of cervical neoplasia in Korea. These findings suggest that development of more vaccines would be beneficial for the prevention of the various HPV genotypes.
Busan ; Cyclin-Dependent Kinase Inhibitor p16 ; Female ; Genotype* ; Human papillomavirus 16 ; Humans* ; Immunohistochemistry ; Korea ; Oligonucleotide Array Sequence Analysis ; Prevalence ; Retrospective Studies ; Tumor Suppressor Protein p53 ; Vaccines

\ OBJECTIVES: The tension on a wound is one of the important factors that determine the degree of fibrosis and scar formation. We hypothesized that local botulinum toxin type A (Botox) induced paralysis of the musculature subjacent to a surgical wound with a skin defect would minimize the repetitive tensile forces on the surgical wound's edges, and this will result in a decreased fibroplastic response and fibrosis of the wound. METHODS: This is a prospective randomized experimental study. Two distinct surgical wounds were made to the dorsum of 15 adult rats, respectively. One of the 2 wounds was injected with Botox, and the other wound was used as a control, and this was done for all the rats' wounds. We evaluated the wound size, the degree of fibrosis and inflammation, the blood vessel proliferation, the thickness of the wound and the expression of transforming growth factor (TGF)-beta1 in the wounds. RESULTS: There were significant differences of wound size at the 3rd and 4th week between the Botox and control groups (P<0.05). The Botox group showed less infiltration of inflammatory cells than the control group at the 2nd week (P<0.05). The Botox group showed a smaller number of fibroblasts and less fibrosis than the control group at the 4th week (P<0.05). The Botox group showed much strong collagen density than the control group at the 8th week (P<0.05). For the immunohistochemical staining, there was a lower transforming growth factor (TGF)-beta1 expression in the Botox group than that of the control group at the 4th week (P<0.05). CONCLUSION: The wounds of the Botox-treated group showed a larger wound size, less infiltration of inflammatory cells and less fibrosis, a much greater amount of collagen and a lower expression of TGF-beta1 than did the control group. Botox might be used to decrease the fibrosis of a surgical wound without damaging the epithelial growth in situations for which decreased fibrosis is necessary, such as for treating laryngeal, tracheal and nasal stenosis.
Adult ; Animals ; Blood Vessels ; Botulinum Toxins ; Botulinum Toxins, Type A ; Cicatrix ; Collagen ; Constriction, Pathologic ; Fibroblasts ; Fibrosis ; Glycosaminoglycans ; Humans ; Inflammation ; Paralysis ; Prospective Studies ; Rats ; Skin ; Transforming Growth Factor beta1 ; Transforming Growth Factors ; Wound Healing

Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome reflects a serious hypersensitivity reaction to drugs, characterized by skin rash, fever, lymph node enlargement, and internal organ involvement. So far, numerous drugs such as sulfonamides, phenobarbital, sulfasalazine, carbamazepine, and phenytoin have been reported to cause the DRESS syndrome. We report a case in a 29-yr-old female patient who had been on celecoxib and anti-tuberculosis drugs for one month to treat knee joint pain and pulmonary tuberculosis. Our patient's clinical manifestations included fever, lymphadenopathy, rash, hypereosinophilia, and visceral involvement (hepatitis and pneumonitis). During the corticosteroid administration for DRESS syndrome, swallowing difficulty with profound muscle weakness had developed. Our patient was diagnosed as DRESS syndrome with eosinophilic polymyositis by a histopathologic study. After complete resolution of all symptoms, patch tests were positive for both celecoxib and ethambutol. Although further investigations might be needed to confirm the causality, celecoxib and ethambutol can be added to the list of drugs as having the possibility of DRESS syndrome.
Adult ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects ; Antitubercular Agents/adverse effects ; Arthritis/complications/*drug therapy ; Drug Eruptions/*etiology/pathology ; Eosinophilia/*chemically induced/pathology ; Ethambutol/*adverse effects ; Female ; Humans ; Myositis/chemically induced/pathology ; Pyrazoles/*adverse effects ; Sulfonamides/*adverse effects ; Syndrome ; Tuberculosis, Pulmonary/complications/*drug therapy

Thymidine phosphorylase (TP) has shown to be up-regulated in several cancers and to play a role in angiogenesis and invasion. Most studies regarding TP have focused on cancer cells. Recently, evidences suggest that TP in cancer-infiltrating inflammatory cells (CIICs) also affect the cancer cell behavior. To evaluate the significance of TP expression of CIICs in gastric cancer, we assessed TP expression of cancer cells and CIICs separately using immunohistochemical assay on 116 paraffin-embedded tissue samples from stomach cancer patients and investigated their clinical significance. When subjects were divided into 4 groups according to the TP expression: cancer/matrix (+/+), C/M (+/-), C/M (-/+), and C/M (-/-), intratumoral microvessel density scores were higher in the C/M (+/-) group than in the C/M (-/-) group (p=0.02). For lymph node metastasis and survival, there were no significant differences among the 4 groups. However, there were significant differences in survival (p=0.035) and LN metastasis (p=0.023) between the two groups divided by TP expression of CIICs alone irrespective of TP expression of cancer cells. Taken together, this study suggested the TP expression in CIICs could affect lymph node metastasis and patients' survival in gastric cancer.
Adult ; Aged ; Female ; Humans ; Immunohistochemistry ; Inflammation/*enzymology/pathology ; Kaplan-Meiers Estimate ; Lymphatic Metastasis ; Lymphocytes, Tumor-Infiltrating/*enzymology/pathology ; Male ; Microcirculation/pathology ; Middle Aged ; Neovascularization, Pathologic ; Prognosis ; Stomach Neoplasms/blood supply/*enzymology/mortality/pathology ; Thymidine Phosphorylase/*metabolism

BACKGROUND: Disturbances of the cell cycle regulatory proteins are key events underlying the development and/or progression of human malignancies. The aim of this study was to evaluate the expression of G1/S cell cycle regulatory proteins in ovarian epithelial tumor. METHODS: We simultaneously evaluated the expression of cyclin D1, cyclin E, CDK4, CDK2, p16, Rb, E2F1, p53 and the Ki67 labelling index (LI) by immunohistochemical methods in 148 cases of ovarian epithelial tumor of the benign (n=47), borderline (n=29), and malignant type (n=72). RESULTS: The expression of cyclin E, CDK2, p16, Rb, E2F1, p53 and the Ki67 LI gradually increased from the benign type, through the borderline type, to the malignant tumors. Between the borderline and malignant tumors, the increased expression of cyclin E, E2F1, and p53, and the decreased expression of Rb were significantly associated with malignancy. The reduced Rb expression and the increased E2F1 expression were correlated with the FIGO stage and the histologic grade in the malignant ovarian epithelial tumors. CONCLUSIONS: Cyclin E, E2F1, and p53 overexpressions and the loss of Rb are the important components during carcinogenesis of ovarian epithelial tumors. Our results suggest that in- creased expression of E2F1 should be considered as a new parameter for the prognosis of patients with malignant ovarian epithelial tumors.
Carcinogenesis ; Cell Cycle Proteins* ; Cell Cycle* ; Cyclin D1 ; Cyclin E ; Cyclins ; E2F1 Transcription Factor ; Female ; Humans ; Neoplasms, Glandular and Epithelial ; Ovary ; Prognosis