Conventional cervical smears have been a great tool to reduce the incidence of cervical cancer; however, many studies have revealed significant false negative rates. To resolve this problem, the liquid based cytology (LBC) method was developed. The LBC method reduces the number of false positive and false negative smear results because LBC achieves an even distribution of monolayered cells, eliminated the obscuring effects of inflammation and blood. Although the LBC method has many advantages, there are several drawbacks. The LBC method requires an adaptation period for cytopathologists and cytotechnicians. Another drawback is the expense of the method. Thus, the LBC method has been questioned, and criticism has been raised regarding the design of the studies that assert its superiority. With a focus on the cytomorphologic and technical differences of LBC compared with conventional cervical smears, a review of the clinical and cost effectiveness of LBC, a brief comparison of two popular LBC methods, and the basic concepts of study design with respect to LBC are presented in this review.
Cervix Uteri ; Cost-Benefit Analysis ; Female ; Incidence ; Inflammation ; Vaginal Smears

Ubiquitination of proteins plays an essential role in various cellular processes, including protein degradation, DNA repair, and cell signaling pathways. Previous studies have shown that protein ubiquitination is implicated in regulating pluripotency as well as fate determination of stem cells. To identify how protein ubiquitination affects differentiation of embryonic stem cells, we analyzed microarray data, which are available in the public domain, of E3 ligases and deubiquitinases whose levels changed during stem cell differentiation. Expression of pja2, a member of the RING-type E3 ligase family, was up-regulated during differentiation of stem cells. Wnt/β-catenin signaling is one of the most important signaling pathways for regulation of the self-renewal and differentiation of embryonic stem cells. Pja2 was shown to bind to TCF/LEF1, which are transcriptional factors for Wnt/β-catenin signaling, and regulate protein levels by ubiquitination, leading to down-regulation of Wnt signaling activity. Based on these results, we suggest that E3 ligase Pja2 regulates stem cell differentiation by controlling the level of TCF/LEF1 by ubiquitination.
DNA Repair ; Down-Regulation ; Embryonic Stem Cells ; Humans ; Ligases ; Proteolysis ; Public Sector ; Stem Cells ; Ubiquitin ; Ubiquitin-Protein Ligases ; Ubiquitin-Specific Proteases ; Ubiquitination

BACKGROUND: Recent studies have suggested that implantation site intermediate trophoblasts (ISITs) and chorionic type intermediate trophoblasts (CTITs) show different immunohistochemical findings, and that each type has specific location in placentas. However, we observed that both subtypes are intimately admixed in many areas of the placentas and both types are proliferated around the infarcts. METHODS: In order to examine the site specificity in their distribution and the changes of intermediate trophoblasts (ITs), if any, in the pre-eclamptic placentas, quantitative analyses of ISITs and CTITs using p63, CD146, placental alkaline phosphatase, human placental lactogen, and alpha-inhibin were performed in normal and pre-eclamptic placentas containing infarcts. RESULTS: In the fetal membranes of both normal and pre-eclamptic placentas, CTITs and ISITs were equally identified, forming distinct layers. ISITs were predominant in the intervillous septum and basal plate, while CTITs were predominant in the subchorionic area. At the margin of infarcts in pre-eclamptic placentas, both subtypes were increased in number, forming distinct layers. CONCLUSIONS: The subtypes of ITs do not have site specificity in placentas. Increased number of ITs and zonal distribution around infarcts suggest that CTITs and ISITs have differentiation associated relationship, and the differentiation might be related to the microenvironment of placenta, such as intraplacental oxygen concentration.
Alkaline Phosphatase ; Chorion ; Extraembryonic Membranes ; Fluconazole ; Immunohistochemistry ; Inhibins ; Oxygen ; Placenta ; Placental Lactogen ; Pre-Eclampsia ; Sensitivity and Specificity ; Trophoblasts

OBJECTIVE: The purpose of this study is to validate the Gynecologic Oncology Group (GOG) criteria for adjuvant treatment in a different cohort of patients and to evaluate the simplified risk criteria predicting the prognosis and tailoring adjuvant treatment in patients with surgically staged endometrial cancer. METHODS: We performed a retrospective analysis of 261 consecutive patients with surgically staged endometrial cancer between January 2000 and February 2013. All patients had complete staging procedures and were surgically staged according to the 2009 International Federation of Gynecology and Obstetrics staging system. Clinical and pathologic data were obtained from medical records. We designed the simplified risk criteria for adjuvant treatment according to the risk factors associated with survival. The patients were divided into low and low-intermediate, high-intermediate, and high-risk groups according to the GOG criteria and simplified criteria and their survivals were compared. Receiver-operating characteristic curve analysis was used to evaluate the prognostic significance of both criteria. RESULTS: Median follow-up time was 48 months (range, 10 to 122 months). According to the GOG criteria, we identified 197 low and low-intermediate risk patients, 20 high-intermediate risk patients, and 44 high-risk patients. There were significant differences in disease-free (p<0.001) and overall survival (p<0.001) among the three groups. Using the simplified risk criteria, we identified 189 low and low-intermediate risk patients, 28 high-intermediate risk patients, and 44 high-risk patients. There were significant differences in disease-free (p<0.001) and overall survival (p<0.001) among the three groups. The performance of the simplified criteria (area under the curve [AUC]=0.829 and 0.916 for disease recurrences and deaths, respectively) was as good as the GOG criteria (AUC=0.836 and 0.921 for disease recurrences and deaths, respectively). CONCLUSION: The simplified criteria may be easily applicable and offer useful information for planning strategy of adjuvant treatment in patients with surgically staged endometrial cancer as the GOG criteria.
Adult ; Aged ; Aged, 80 and over ; Chemotherapy, Adjuvant ; Endometrial Neoplasms/pathology/surgery/*therapy ; Female ; Humans ; Middle Aged ; Neoplasm Staging ; Prognosis ; Radiotherapy, Adjuvant ; Retrospective Studies ; Risk Factors ; Survival Analysis

Granulocytic sarcoma is a localized tumor composed of immature cells of the granulocytic series. Most granulocytic sarcomas occur in the course of acute leukemia and the blast crisis of chronic leukemia. Rarely, however, it may present before leukemia becomes clinically apparent. It may also occur in patients with myeloproliferative disorders. It has been reported that it occurs in 3% to 9% of patients with acute myelogenous leukemia (AML) and the incidence of granulocytic sarcoma is reported to be higher in patients with t (8;21). However, epidural granulocytic sarcoma associated with t (8;21) is very rare. In this report, we describe a patient with AML associated with t (8;21) in whom the cord compression occurred due to epidural granulocytic sarcoma. In addition, this case present infiltration of both pleura by blast cells. She was treated with local irradiation and chemotherapy successfully.
Blast Crisis ; Drug Therapy ; Humans ; Incidence ; Leukemia ; Leukemia, Myeloid, Acute* ; Myeloproliferative Disorders ; Pleura ; Sarcoma, Myeloid* ; Spine* ; Sternum*

Background and Objectives: Tcfs and Lef1 are DNA-binding transcriptional factors in the canonical Wnt signaling pathway. In the absence of β-catenin, Tcfs and Lef1 generally act as transcriptional repressors with co-repressor proteins such as Groucho, CtBP, and HIC-5. However, Tcfs and Lef1 turn into transcriptional activators during the interaction with β-catenin. Therefore, the activity of Tcfs and Lef1 is regulated by β-catenin. However, the intrinsic role of Tcfs and Lef1 has yet to be examined. The purpose of this study was to determine whether Tcfs and Lef1 play differential roles in the regulation of self-renewal and differentiation of mouse ES cells. Methods: and Results: Interestingly, the expression of Tcfs and Lef1 was dynamically altered under various differentiation conditions, such as removal of LIF, EB formation and neuronal differentiation in N2B27 media, suggesting that the function of each Tcf and Lef1 may vary in ES cells. Ectopic expression of Tcf1 or the dominant negative form of Lef1 (Lef1-DN) contributes to ES cells to self-renew in the absence of leukemia inhibitory factor (LIF), whereas ectopic expression of Tcf3, Lef1 or Tcf1-DN did not support ES cells to self-renew. Ectopic expression of either Lef1 or Lef1-DN blocked neuronal differentiation, suggesting that the transient induction of Lef1 was necessary for the initiation and progress of differentiation. ChIP analysis shows that Tcf1 bound to Nanog promoter and ectopic expression of Tcf1 enhanced the transcription of Nanog. Conclusions The overall data suggest that Tcf1 plays a critical role in the maintenance of stemness whereas Lef1 is involved in the initiation of differentiation.

Objective: Aneurysmal subarachnoid hemorrhage (SAH) is a common emergency condition, resulting in high morbidity and mortality. The delta neutrophil index (DNI), which reflects the fraction of circulating immature granulocytes, is significantly associated with systemic inflammation after infection or sterile injury. Aneurysmal SAH also leads to systemic inflammation after a brain injury. This study aimed to evaluate the relationship between the DNI and poor neurologic outcomes in patients with aneurysmal SAH. Methods: We retrospectively identified patients (>18 years old) with aneurysmal SAH consecutively admitted to the emergency department (ED) between January 1, 2011, and November 30, 2018. The diagnosis of aneurysmal SAH was confirmed using clinical and radiological findings. DNI was determined at 0, 24, 48, and 72 hours after ED admission. The primary result was a poor neurologic outcome using the modified Rankin scale. Results: A total of 352 patients with aneurysmal SAH were included in this study. A multivariable logistic regression model revealed that a high value of DNI at 24 hours after ED admission was a strong independent predictor of poor neurologic outcome upon discharge (odds ratio [OR], 1.471; 95% confidence interval [CI], 1.081-2.001; P=0.014). Among patients with aneurysmal SAH, DNI >1.0% at 24 hours was significantly associated with poor neurologic outcomes upon discharge (OR, 5.037; 95% CI, 3.153-8.044; P<0.001). Conclusion DNI can be determined easily and rapidly after ED admission without any additional cost or time burden. A high DNI value at 24 hours after ED admission is significantly associated with a poor neurologic outcome upon discharge among patients with aneurysmal SAH.

Objective: Aneurysmal subarachnoid hemorrhage (SAH) is a common emergency condition, resulting in high morbidity and mortality. The delta neutrophil index (DNI), which reflects the fraction of circulating immature granulocytes, is significantly associated with systemic inflammation after infection or sterile injury. Aneurysmal SAH also leads to systemic inflammation after a brain injury. This study aimed to evaluate the relationship between the DNI and poor neurologic outcomes in patients with aneurysmal SAH. Methods: We retrospectively identified patients (>18 years old) with aneurysmal SAH consecutively admitted to the emergency department (ED) between January 1, 2011, and November 30, 2018. The diagnosis of aneurysmal SAH was confirmed using clinical and radiological findings. DNI was determined at 0, 24, 48, and 72 hours after ED admission. The primary result was a poor neurologic outcome using the modified Rankin scale. Results: A total of 352 patients with aneurysmal SAH were included in this study. A multivariable logistic regression model revealed that a high value of DNI at 24 hours after ED admission was a strong independent predictor of poor neurologic outcome upon discharge (odds ratio [OR], 1.471; 95% confidence interval [CI], 1.081-2.001; P=0.014). Among patients with aneurysmal SAH, DNI >1.0% at 24 hours was significantly associated with poor neurologic outcomes upon discharge (OR, 5.037; 95% CI, 3.153-8.044; P<0.001). Conclusion DNI can be determined easily and rapidly after ED admission without any additional cost or time burden. A high DNI value at 24 hours after ED admission is significantly associated with a poor neurologic outcome upon discharge among patients with aneurysmal SAH.

BACKGROUND: Hyaluronic acid (HA) is a mucopolysaccharide that occurs naturally throughout the human body, where it attaches to collagen and elastin to form cartilage, and also helps maintain the strength and flexibility of the cartilage that cushions joints. A decline in HA synthesis may lead to a variety of symptoms, ranging from joint discomfort, to wrinkles. Cross-linked HA is a viscoelastic solid that resists in vivo degradation by hyaluronidase for much longer than endogenous HA, and which is also a key ingredient in various cosmetics. OBJECTIVE: To describe our experience with three kinds of Elravie(R) fillers. METHODS: We obtained images of filler shape using a folliscope. Scanning electron microscopy (SEM) was used to compare particle sizes. Hydrophilic filler is a hydroxyl, and for this reason, we mixed the filler with water. Next, PARKER ink was added to the mixture, and viscosity and elasticity were measured using a rheometer. RESULTS: Among the tested fillers, particle size was largest in the Restylane(R) SubQ. Elravie(R) ultra volume filler was greater in volume than Elravie(R) deep line, and Elravie(R) light fillers. We confirmed Elravie(R) fillers to be hydrophilic. Elravie(R) ultra volume filler was found to have the highest viscosity and elasticity, whilst Elravie(R) light filler had the lowest. CONCLUSION: All three kinds of Elravie(R) fillers were found to be suitable for human cosmetic use.
Cartilage ; Collagen ; Elasticity ; Elastin ; Human Body ; Humans ; Hyaluronic Acid ; Hyaluronoglucosaminidase ; Ink ; Joints ; Microscopy, Electron, Scanning ; Particle Size ; Pliability ; Viscosity ; Water

BACKGROUND: The diagnosis of endometrial stromal sarcoma (ESS) is often difficult in cases showing diverse histological differentiation or in undifferentiated endometrial sarcoma (UES). Recently, JAZF1/JJAZ1 gene fusion has been described as a defining feature of low-grade ESS (LGESS). However, its prevalence is variably reported, and the diagnostic utility has rarely been examined for cases showing various histological differentiation. METHODS: To test the diagnostic utility of JAZF1/JJAZ1 gene fusion in difficult cases, we compared the prevalence of the JAZF1/JJAZ1 fusion gene in LGESS with and without histological differentiation. RESULTS: The JAZF1/JJAZ1 fusion transcript was detected in 18 of 21 LGESS (85.7%), including 14 classical LGESS (93%), four LGESS with diverse histological differentiation (67%), and two with UES (28.6%). Positive cases included two LGESS with sex cord-like differentiation, one with osseous differentiation, and two UES. LGESS showing smooth muscle differentiation revealed the fusion transcript only in the classic area. Direct sequencing analysis of two LGESS revealed a previously reported breakpoint at t(7;17)(p15;q21). CONCLUSIONS: The JAZF1/JJAZ1 fusion gene was identified in a significant proportion of LGESS showing secondary histological differentiation except in cases with smooth muscle differentiation. Thus, this fusion gene may be useful to confirm the diagnosis in difficult cases of LGESS.
Gene Fusion ; Muscle, Smooth ; Prevalence ; Sarcoma ; Sarcoma, Endometrial Stromal