Induction of Anti-Aquaporin 5 Autoantibody Production by Immunization with a Peptide Derived from the Aquaporin of Prevotella melaninogenica Leads to Reduced Salivary Flow in Mice

Sjögren's syndrome (SS) is an autoimmune disease characterized by dryness of the mouth and eyes. The glandular dysfunction in SS involves not only T cell-mediated destruction of the glands but also autoantibodies against the type 3 muscarinic acetylcholine receptor or aquaporin 5 (AQP5) that interfere with the secretion process. Studies on the breakage of tolerance and induction of autoantibodies to these autoantigens could benefit SS patients. To break tolerance, we utilized a PmE-L peptide derived from the AQP5-homologous aquaporin of Prevotella melaninogenica (PmAqp) that contained both a B cell “E” epitope and a T cell epitope. Repeated subcutaneous immunization of C57BL/6 mice with the PmE-L peptide efficiently induced the production of Abs against the “E” epitope of mouse/human AQP5 (AQP5E), and we aimed to characterize the antigen specificity, the sequences of AQP5Especific B cell receptors, and salivary gland phenotypes of these mice. Sera containing anti-AQP5E IgG not only stained mouse Aqp5 expressed in the submandibular glands but also detected PmApq and PmE-L by immunoblotting, suggesting molecular mimicry.Characterization of the AQP5E-specific autoantibodies selected from the screening of phage display Ab libraries and mapping of the B cell receptor repertoires revealed that the AQP5E-specific B cells acquired the ability to bind to the Ag through cumulative somatic hypermutation. Importantly, animals with anti-AQP5E Abs had decreased salivary flow rates without immune cell infiltration into the salivary glands. This model will be useful for investigating the role of anti-AQP5 autoantibodies in glandular dysfunction in SS and testing new therapeutics targeting autoantibody production.

Usefulness of delta neutrophil index to predict neurologic outcome in patients with aneurysmal subarachnoid hemorrhage

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.

Usefulness of delta neutrophil index to predict neurologic outcome in patients with aneurysmal subarachnoid hemorrhage

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.

Stereotypic Neutralizing VH Clonotypes Against SARS-CoV-2 RBD in COVID-19 Patients and the Healthy Population

In six of seven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients, VH clonotypes, encoded by either immunoglobin heavy variable (IGHV)3-53 or IGHV3-66 and immunoglobin heavy joining (IGHJ)6, were identified in IgG1, IgA1, and IgA2 subtypes, with minimal mutations, and could be paired with diverse light chains, resulting in binding to the SARS-CoV-2 receptor-binding domain (RBD). Because most human antibodies against the RBD neutralized the virus by inhibiting host cell entry, we selected one of these clonotypes and demonstrated that it could potently inhibit viral replication. Interestingly, these VH clonotypes pre-existed in six of 10 healthy individuals, predominantly as IgM isotypes, which could explain the expeditious and stereotypic development of these clonotypes among SARS-CoV-2 patients.One Sentence Summary Stereotypic-naïve SARS-CoV-2 neutralizing antibody clonotypes, encoded by IGHV3-53/IGHV3-66 and IGHJ6, were identified in most patients and pre-exist in the majority of the healthy population, predominantly as an IgM isotype.Competing Interest StatementThe authors have declared no competing interest.View Full Text

Loss of Heterozygosity at Chromosome 16q Is a Negative Prognostic Factorin Korean Pediatric Patients with Favorable Histology Wilms Tumor:A Report of the Korean Pediatric Hematology Oncology Group (K-PHOG) / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Loss of heterozygosity (LOH) at chromosomes 1p and 16q is a poor prognostic factor infavorable histology Wilms tumor (FHWT). This study investigated the prevalence of LOH at1p and 16q and evaluated its prognostic value in Korean children with FHWT. @*Materials and Methods@#We analyzed 101 FHWT patients who were diagnosed between 1996 and 2016 in KoreanSociety of Pediatric Hematology Oncology Group hospitals. Using paraffin-embedded kidneytissue samples sent from each center, we reviewed LOH at 1p and 16q in each patient andassessed the prognostic value of LOH status for clinical parameters affecting event-freesurvival (EFS). @*Results@#Of the 101 patients, 12 (11.9%) experienced recurrence; the 3-year EFS was 87.6%. LOHat 1p or 16q was detected in 19 patients (18.8%), with five having LOH at both 1q and 16q.The frequency of LOH at 1p was higher among younger patients (p=0.049), but there wasno difference in LOH prevalence according to tumor stage. In the multivariate analysis, LOHat 16q was a significant negative prognostic factor affecting EFS (3-year EFS, 73.7% vs.91.1%; hazard ratio, 3.95; p=0.037), whereas LOH at 1p was not (p=0.786). @*Conclusion@#LOH at 16q was a significant negative prognostic factor affecting outcome in Korean pediatricFHWT patients. Due to the small sample size of this study, large-scale multicenter trialsare warranted to investigate the prognostic value of LOH at 1p and 16q in Korean childrenwith FHWT.

Use of Cream Containing Mucus Secreted by Snails Has an Anti-aging Effect on Skin / 대한피부과학회지

BACKGROUND: A cream made from mucus secreted by snails contains 80% mucin, as well as glycosaminoglycan, allantoin for skin rejuvenation, glycolic acid for keratin removal, and collagen and elastin, which are components of dermis. OBJECTIVE: The goal of the present study was to evaluate the efficacy of using cream containing mucus secreted by snails to reduce wrinkles, improve skin elasticity, restore dermal density, and lift the skin. METHODS: Cream containing mucus secreted by snails was applied to the lateral epicanthal areas and the left cheek of 10 subjects for 4 weeks twice per day. Wrinkles, skin elasticity, dermal density, and skin tightening were evaluated at baseline and 2 and 4 weeks. A patient survey was conducted at 4 weeks. RESULTS: There were statistically significant differences between baseline and 4 weeks after applying the cream in terms of wrinkles, skin elasticity, dermal density, and skin tightening (p<0.05). CONCLUSION: Use of cream containing mucus secreted by snails seems to be effective for anti-aging of the skin. Long term follow up studies, such as 3 or 6 months, to confirm the efficacy of the cream should be conducted involving a larger number of patients.

Risk group criteria for tailoring adjuvant treatment in patients with endometrial cancer: a validation study of the Gynecologic Oncology Group criteria / 부인종양

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.

Neoadjuvant and postoperative chemotherapy with paclitaxel plus cisplatin for the treatment of FIGO stage IB cervical cancer in pregnancy

Cervical cancer is one of the most common malignancy diagnosed during pregnancy. The experience of the use of neoadjuvant chemotherapy (NACT) with paclitaxel plus cisplatin during pregnancy is limited. Three pregnant women with International Federation of Gynecology and Obstetrics (FIGO) stage IB cervical cancer received NACT with paclitaxel plus cisplatin until fetal lung maturity, and then underwent cesarean delivery and radical hysterectomy. Two of our patients had intermediate pathologic risk factors, and received adjuvant chemotherapy with the same regimen used in NACT. All patients did not have any evidence of disease recurrence for follow-up of 3, 4, and 8 years, respectively. NACT with paclitaxel plus cisplatin followed by radical hysterectomy and adjuvant chemotherapy could be considered as one of feasible alternatives to primary radical surgery or concurrent chemoradiation therapy with the termination of pregnancy in pregnant women with FIGO stage IB cervical cancer who have two or more intermediate pathologic-risk factors.

Formulation Characteristics of Three Kinds of Elravie(R) Fillers / 대한피부과학회지

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.

Characterization of Two Kinds of Filler for the Formulation / 대한피부과학회지

BACKGROUND: Hyaluronic acid (HA) is a carbohydrate, occurring naturally throughout the human body. With linear polysaccharide structure, it is (HA) found in soft connective tissues, cartilage and joinfluids. Hyaluronic acid filler is used for treatment of depth of the fold or volume of filler needed and performed for wrinkle improvement and cosmetic. We did property of matter for the Perfectha(R) fillers. OBJECTIVE: Our purpose is to describe and comment on our experiences with two kinds of Perfectha(R) fillers. METHODS: We obtained image of the shape of fillers using a folliscope, VC98 and particle size using the Scanning electron microscope (SEM). We tested to make sure that affinity both fillers with water. We mixed the fillers and distilled water. We the PARKER ink added to the mixture. Viscosity and elasticity were measured using a rheometer. RESULTS: The test revealed that a particle sized Perfectha(R) derm deep is bigger than a Perfectha(R) derm. We were confirmed as hydrophile. While Perfectha(R) derm deep filler has high viscosity and elasticity, Perfectha(R) derm filler has high viscosity only, not elasticity. CONCLUSION: Two kinds of Perfectha(R) fillers act as space filler by binding to water and thus keeping the skin wrinkle-free.

Practice guidelines for the early detection of cervical cancer in Korea: Korean Society of Gynecologic Oncology and the Korean Society for Cytopathology 2012 edition / 부인종양

The consensus guideline development committee of Korean Society of Gynecologic Oncology was reconvened in March 2012. The committee consisted of 36 experts representing 12 university hospitals and professional organizations. The objective of this committee was to develop standardized guidelines for cervical cancer screening tests for Korean women and to distribute these guidelines to every clinician, eventually improving the quality of medical care. Since the establishment of the consensus guideline development committee, evidence-based guidelines have either been developed de novo considering specific Korean situations or by adaptation of preexisting consensus guidelines from other countries. Recommendations for cervical cancer screening tests, management of atypical squamous and glandular cells, and management of low-grade and high-grade squamous intraepithelial lesions were developed. Additionally, recommendations for human papillomavirus DNA testing and recommendations for adolescent and pregnant women with abnormal cervical screening test results were also included.

Diagnostic Utility of the JAZF1/JJAZ1 Gene Fusion in Endometrial Stromal Sarcomas and Their Histologic Variants

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.

Histological and Immunohistochemical Findings of the Intermediate Trophoblasts in Normal Full Term and Pre-eclamptic Placentas

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.

Metastatic Tumors to the Breast from Extramammary Malignancies

BACKGROUND: Metastases to the breast from extramammary malignancies are very rare. We describe here the clinicopathologic features of the metastatic breast tumors that were identified in Korean patients at a single institute. METHODS: We analyzed the clinicopathologic data of the patients who were diagnosed between January 1989 and April 2009 at Asan Medical Center. RESULTS: Only 31 (0.21%) patients with metastases to the breast from extramammary malignancies were diagnosed over a 20-year period, and 29 of them had available data. The mean time to the diagnosis of metastasis after the diagnosis of the primary malignancy was 21 months (range, 0 to 102 months). The most common primary site was the stomach, followed by the uterus and lung. The most common histologic type was adenocarcinoma. A common clinical presentation was a unilateral palpable mass. Most metastatic tumors had morphological features that were similar to those of their respective primary tumors. However, in situ carcinoma, microcalcification and desmoplastic reactions were rarely observed. CONCLUSIONS: Metastatic breast lesions from extramammary sites are extremely rare, and the stomach, uterus and lung could be considered as the common primary sites in Korean patients. The clinical history and comparing the morphology of the primary tumor with the morphology of the metastatic tumor are important for achieving the proper diagnosis.

Liquid-Based Cytology in Gynecologic Cytology

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.

Epidural Granulocytic Sarcoma involving the Thoracic Spine and Sternum in Acute Myelogenous Leukemia / 대한혈액학회지

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.