Analysis of Prognoses according to Breast MRI Results in Patients with Axillary Lymph Node Metastases from an Unknown Primary Origin

Purpose@#To compare the prognosis of patients with axillary adenocarcinoma from an unknown primary (ACUPax) origin with negative MRI results and those with MRI-detected primary breast cancers. @*Materials and Methods@#The breast MRI images of 32 patients with ACUPax without signs of primary breast cancer on mammography and ultrasound (US) were analyzed. Spot compression-magnification mammography and second-look US were performed for the area of MRI abnormality in patients with positive results; any positive findings corresponding to the MRI abnormality were confirmed by biopsy. If suspicious MRI lesions could not be localized on mammography or US, MR-guided biopsy or excision biopsy after MR-guided localization was performed. We compared the prognosis of patients with negative breast MRI with that for patients with MRI-detected primary breast cancers. @*Results@#Primary breast cancers were confirmed in 8 (25%) patients after breast MRI. Primary breast cancers were not detected on MRI in 24 (75%) patients, including five cases of false-positive MRI results. Twenty-three patients underwent axillary lymph node dissection (ALND) followed by whole breast radiation therapy (WBRT) and chemotherapy (n=17) or subsequent chemotherapy only (n=2). Recurrence or distant metastasis did not occur during follow up in 7/8 patients with MRI-detected primary breast cancers and 22/24 patients with negative MRI results. Regional recurrence or distant metastasis did not occur in any MR-negative patient who received adjuvant chemotherapy after ALND and WBRT. @*Conclusion@#The prognoses of MR-negative patients with ACUPax who received ALND and WBRT followed by chemotherapy were as good as those of patients with MRI-detected primary breast cancers.

The Expression of Epidermal Stem Cell Marker and SIRT1 in Atopic Dermatitis: A Discussion of Regenerative Potential

No abstract available.

Interactive Roles of Activin A in Epidermal Regeneration

No abstract available.

Decreased Galectin-3 and -7 Expressions in Old-Aged Skin and Their Differential Expression in Skin Equivalents

No abstract available.

The Effects of the 3-OH Group of Kaempferol on Interfollicular Epidermal Stem Cell Fate

BACKGROUND: Kaempferol (3,4′,5,7-tetrahydroxyflavone) is a flavonoid known to have a wide range of pharmacological activities. The 3-OH group in flavonoids has been reported to determine antioxidant activities. OBJECTIVE: We tested whether kaempferol can affect the expression of integrins and the stem cell fate of interfollicular epidermal stem cells. METHODS: Skin equivalent (SE) models were constructed, and the expression levels of stem cell markers and basement membrane-related antigens were tested. The immunohistochemical staining patterns of integrins, p63, and proliferating cell nuclear antigen (PCNA) were compared between kaempferol- and apigenin-treated SE models. Reverse transcription-polymerase chain reaction (RT-PCR) was used to evaluate the mRNA expression of integrins. RESULTS: Kaempferol increased the thickness of the epidermis when added to prepare SEs. In addition, the basal cells of kaempferol- treated SEs appeared more columnar. In the immunohistological study, the expression of integrins α6 and β1 and the numbers of p63- and PCNA-positive cells were markedly higher in the kaempferol-treated model. However, apigenin showed no effects on the formation of three-dimensional skin models. RT-PCR analysis also confirmed that kaempferol increased the expression of integrin α6 and integrin β1. CONCLUSION: Our findings indicated that kaempferol can increase the proliferative potential of basal epidermal cells by modulating the basement membrane. In other words, kaempferol can affect the fate of interfollicular epidermal stem cells by increasing the expression of both integrins α6 and β1. These effects, in particular, might be ascribed to the 3-OH group of kaempferol.

Immunogenic Cell Death Induced by Ginsenoside Rg3: Significance in Dendritic Cell-based Anti-tumor Immunotherapy

Cancer is one of the leading causes of morbidity and mortality worldwide; therefore there is a need to discover new therapeutic modules with improved efficacy and safety. Immune-(cell) therapy is a promising therapeutic strategy for the treatment of intractable cancers. The effectiveness of certain chemotherapeutics in inducing immunogenic tumor cell death thus promoting cancer eradication has been reported. Ginsenoside Rg3 is a ginseng saponin that has antitumor and immunomodulatory activity. In this study, we treated tumor cells with Rg3 to verify the significance of inducing immunogenic tumor cell death in antitumor therapy, especially in DC-based immunotherapy. Rg3 killed the both immunogenic (B16F10 melanoma cells) and non-immunogenic (LLC: Lewis Lung Carcinoma cells) tumor cells by inducing apoptosis. Surface expression of immunogenic death markers including calreticulin and heat shock proteins and the transcription of relevant genes were increased in the Rg3-dying tumor. Increased calreticulin expression was directly related to the uptake of dying tumor cells by dendritic cells (DCs): the proportion of CRT+ CD11c+ cells was increased in the Rg3-treated group. Interestingly, tumor cells dying by immunogenic cell death secreted IFN-gamma, an effector molecule for antitumor activity in T cells. Along with the Rg3-induced suppression of pro-angiogenic (TNF-alpha) and immunosuppressive cytokine (TGF-beta) secretion, IFN-gamma production from the Rg3-treated tumor cells may also indicate Rg3 as an effective anticancer immunotherapeutic strategy. The data clearly suggests that Rg3-induced immunogenic tumor cell death due its cytotoxic effect and its ability to induce DC function. This indicates that Rg3 may be an effective immunotherapeutic strategy.

ABO*Ael03/O Genotype with ABO Discrepancy: The First Case in Korea

The Ael subgroup expresses the least amount of A antigens and could only be detected by performing the adsorption-elution test. The frequency of the Ael subgroup is about 0.001% in Koreans, and the Ael02 allele, which originates from A102, is the most frequently identified allele in the Korean population. We report a Korean family with the Ael03 allele identified by molecular genetic analysis. To the best of our knowledge, this is the first such report in Korea to date.

A Choice and Precautions of Replacement Fluids for Therapeutic Plasma Exchange / 대한수혈학회지

BACKGROUND: Therapeutic plasma exchange (TPE) is an effective and practical treatment for separation and removal of harmful antibodies or pathogenic substances from the blood. The volume of plasma removed must be replaced by a replacement fluid such as 4~5% albumin solution or Fresh frozen plasma (FFP). We conducted a study of coagulopathy using albumin solution and checked the chemical composition of fresh frozen plasma. METHODS: We measured pre- and post-TPE PT/aPTT for evaluation of the effect of albumin replacement on coagulation from 192 TPE sessions of 19 patients. We also investigated routine chemistry test items including glucose and electrolytes from 10 randomly selected FFP. RESULTS: The post PT and aPTT within four hours after TPE were prolonged due to a transient decrease in coagulation factors, but were normalized within 2 days after TPE. All coagulation time was corrected to the level of the pre-TPE status within four hours before the next TPE except the patients who received TPE 6 times or more. FFP showed higher level in glucose, sodium and inorganic phosphate. CONCLUSION: Albumin exchange produces temporary coagulation factor deficiency. However, this transient factor deficiency rarely causes clinical problems and the factors are rapidly corrected by redistribution and resynthesis. We should be careful about hypocalcemia, hyperglycemia, and hypernatremia when using FFP replacement.

Analysis Survey on Changes in Hospital Blood Donation Center and Satisfaction Level with the Korean Red Cross / 대한수혈학회지

BACKGROUND: Blood supply circumstances in Korea have changed in recent decades because of blood supplier diversification and restructuring of hospital blood donation centers. The purpose of this study is to understand the current status of hospital blood donation centers and their satisfaction levels with the Korean Red Cross Blood Center (KRCBC) and compare with the previous results for sustainable development of the blood supply system. METHODS: During one month in November 2014, we conducted a questionnaire survey through e-mail in 64 hospital blood donation centers which are approved by government. The response rate was 97% (62/64 hospitals). Responses from 62 hospitals were analyzed. RESULTS: The number of hospital blood donation centers were reduced by half from 129 in 2004 to 64 in 2014. There was no blood donation center in hospitals less than 400 beds, except 2 hospitals; 23 hospital (37.1%) blood banks collected no blood components. More than 80% of hospitals were satisfied with the KRCBC service such as donor record lookup and nucleic acid amplification Test (NAT) results lookup. Hospitals with more than 1,000 beds replied that they would not take account of transferring the collection services to KRCBC because of the directed and autologous donation and unexpected emergency blood transfusion. CONCLUSION: The government should be the subject of national blood policy and establish a committee or agency for its comprehensive and consistent execution through close cooperation with the KRCBC and hospitals.

Fucoidan Promotes the Reconstruction of Skin Equivalents

In this study we investigated the effects of fucoidan on the proliferation of fibroblasts and the reconstruction of a skin equivalent (SE). Fucoidan significantly stimulated the proliferation of CCD-25Sk human fibroblasts and Western blot analysis demonstrated that fucoidan markedly increased the expression of cyclin D1 and decreased the expression of p27. Fucoidan was used to reconstruct SE. Immunohistochemical staining showed that the addition of fucoidan to dermal equivalents increased expression of proliferating cell nuclear antigen (PCNA) and p63. In addition, expression of alpha6-integrin was significantly increased by fucoidan, whereas expression of beta1-integrin, type 1 collagen, elastin, fibronectin did not markedly change. These results suggest that fucoidan has positive effects on epidermal reconstruction and will therefore be beneficial in the reconstruction of SE.

An Analytical Study for Cases associated with Massive Blood Transfusion at a Tertiary Referral Hospital / 대한수혈학회지

BACKGROUND: Massive transfusion (MT) is an unusual event and has been defined as replacement of total body fluid volume in less 24 hours or transfusion of 10 or more RBC units in 24 hours. MT is a high priority treatment for major blood loss. METHODS: We gathered 78 patients receiving MT from 2008 to 2013 at Severance hospital using electronic medical records and performed a retrospective review. For each case, we analyzed patients' characteristics, including sex, age, major causes of MT, and clinical outcome. We also calculated the ratio of each blood component transfused. RESULTS: Patient sex ratio of male and female was 1.60 and percentage of patients over age 40 was 58.4%. The individual diagnostic categories were 28.2% of cardiovascular surgery, 26.9% of liver transplantation, 11.5% of upper gastrointestinal bleeding, and 5.2% of trauma. The overall mortality rate was 47.3%. Mortality rate ranged from the lowest (52.3%) for liver transplantation to the highest (77.8%) for upper gastrointestinal tract bleeding. No correlation was observed between causes of MT and mortality rate. The average usage of FFP: RBC and platelet: RBC ratio was 0.83 and 0.68, respectively. However, recently, the ratio of two components transfused is close to 1.0. CONCLUSION: The highest priority in MT was rapidity and propriety for improvement of patient survival. By regularly reviewing MT cases, we could provide an improved massive transfusion service.

Stamp-Form Contact Plate: A Simple and Useful Culture Method for Microorganisms of the Skin

No abstract available.

Stamp-Form Contact Plate: A Simple and Useful Culture Method for Microorganisms of the Skin

No abstract available.

Dipeptides Inhibit Melanin Synthesis in Mel-Ab Cells through Down-Regulation of Tyrosinase

This study investigated the effects of proline-serine (PS) and valine-serine (VS) dipeptides on melanogenesis in Mel-Ab cells. Proline-serine and VS significantly inhibited melanin synthesis in a concentration-dependent manner, though neither dipeptide directly inhibited tyrosinase activity in a cell-free system. Both PS and VS down-regulated the expression of microphthalmia-associated transcription factor (MITF) and tyrosinase. In a follow-up study also described here, the effects of these dipeptides on melanogenesis-related signal transduction were quantified. Specifically, PS and VS induced ERK phosphorylation, though they had no effect on phosphorylation of the cAMP response element binding protein (CREB). These data suggest that PS and VS inhibit melanogenesis through ERK phosphorylation and subsequent down-regulation of MITF and tyrosinase. Properties of these dipeptides are compatible with application as skin-whitening agents.

Topical Hypopigmenting Agents for Pigmentary Disorders and Their Mechanisms of Action

Melanin is produced in melanocytes and stored in melanosomes. In spite of its beneficial sun-protective effect, abnormal accumulation of melanin results in esthetic problems. Hydroquinone, competing with tyrosine, is a major ingredient in topical pharmacological agents. However, frequent adverse reactions are amongst its major limitation. To solve this problem, several alternatives such as arbutin, kojic acid, aloesin, and 4-n-butyl resorcinol have been developed. Herein, we classify hypopigmenting agents according to their mechanism of action; a) regulation of enzyme, which is subdivided into three categories, i) regulation of transcription and maturation of tyrosinase, ii) inhibition of tyrosinase activity, and iii) post-transcriptional control of tyrosinase; b) inhibition of melanosome transfer, and c) additional mechanisms such as regulation of the melanocyte environment and antioxidant agents.

A Simple Assay Method for Melanosome Transfer

Pigmentation is induced by production of melanin in specialized organelles termed melanosomes and by transfer of these organelles from melanocytes to surrounding keratinocytes. The chemical basis of melanogenesis is relatively well known but the mechanism of melanosome transfer is not well studied. Various pigmentary disorders and cosmetic applications require the use of depigmenting agents. Currently available topical agents used for the reduction of pigmentation mainly include tyrosinase inhibitors and/or melanocyte-cytotoxic agents. Recently, several agents have been introduced to inhibit melanosome transfer from melanocytes to keratinocytes. However, an experimental model for melanosome transfer is not well established. In this study, a simple assay method using flow cytometry is described.

Effects of Murine Dermal Cells on the Regulation of Hair Growth Is Dependent on the Cell Number and Post-Natal Age of Newborn Mice

Dermal cells from neonatal mice can initiate the formation of hair follicles (HFs) when combined with adult mouse epidermal cells and transplanted subcutaneously into athymic mice. In the present study, the effects of dermal cells on HF formation were tested in terms of total cell number and the time course of cell harvest. Results demonstrated that the number of dermal cells is critical to the formation of HF. Furthermore, hair forming ability is rapidly decreasing as the neonatal mice age. To examine potential differences in gene expression, cDNA array was performed. Results demonstrate that numerous molecules which are directly involved in receptor and signaling correlated with decreased hair inductivity in early time points after delivery. It is reported that bone morphogenic protein (BMP)-6 and Wnt3a treatment increased hair inductivity of dermal papilla cells. But in our study, no changes were observed in the expression levels of BMP-6 and Wnt3a. However, several Wnt related genes demonstrate increased or decreased expression levels. Thus, our results suggest that co-ordinated regulation of these molecules will be important in hair neogenesis within our model system.

Evaluation of ABO Antibody Titration Using Tube and Column Agglutination Techniques

BACKGROUND: ABO antibody titration is useful for the evaluation of ABO-incompatible bone marrow or solid organ transplantations, yet the results quite vary between different test methods used. We compared the results of microcolumn agglutination and tube methods. METHODS: Anti-A and anti-B isoagglutionin titers were determined in 63 healthy individuals (23 O, 20 A, and 20 B blood groups) using 4 different methods: immediate spin tube (tube), microcolumn agglutination without anti-human globulin (AHG) (CAT), tube with AHG (tube-AHG) and microcolumn agglutination with AHG (CAT-AHG). RESULTS: The median (range) titers of anti-A and anti-B in group O individuals by tube, CAT, tube-AHG, and CAT-AHG methods were 64 (8-512), 64 (8-512), 128 (8-2,048), and 128 (16-2,048); 64 (16-128), 128 (16-256), 128 (16-512), and 256 (16-512), respectively. The median (range) titers of anti-A in group B and anti-B in group A individuals by the four methods were 64 (16-128), 128 (8-128), 128 (8-256), and 256 (8-256); 64 (8-128), 64 (8-128), 32 (8-128), and 64 (8-256), respectively. The isoagglutinin titer measured by CAT-AHGmethod was the highest. The titers measured by CAT and CAT-AHG methods were 0-1 titer higher than those by tube and tube-AHG methods, respectively. Whatever method was used, the isoagglutinin titers were higher in women than in men. CONCLUSIONS: CAT-AHG was the most sensitive method among the four methods tested. Since AHG titer values are critical for the clinical management and CAT has less manual procedures than tube method, CAT-AHG method could be used for the standardization of ABO antibody titration in different institutions.

Evaluation of the Automated Instrument QWALYS-3 for Unexpected Antibody Screening / 대한수혈학회지

BACKGROUND: The use of automated techniques reduces the impact of human errors in blood banking and it improves the standardization and the quality of the achieved results. Erythrocyte Magnetized Technology (EMT) is now being widely used due to its simplicity and efficiency for detecting alloantibody. We evaluated the antibody screening test of the QWALYS-3 (DIAGAST, Loos Cedex, France). METHODS: The evaluation focused on antibody screening using the QWALYS-3 as compared to the standard manual tube method and the Ortho BioVue system in clinical samples (n=100) and frozen stored samples (n=64), which had RBC alloantibody. RESULTS: Using the manual tube method, the sensitivity of antibody screening was 100% by the QWALYS-3 and 42.8% by the Ortho BioVue in the clinical samples (n=7) and 2 results were discrepant by the QWALYS-3 for negative samples. For the known antibodies from the frozen stored samples (n=64) this correspondence rate amounted to 93.7% (n=60). CONCLUSION: The QWALYS-3 system displayed a good match rate with the Ortho BioVue system (92%). It also showed reliable results for the general accuracy when compared to the manual method (concordance rate: 98%). The QWALYS-3 system will facilitate the automation of routine antibody screening with high reliability, sensitivity and specificity compared to the standard manual methods.

A Case of Hemophagocytic Lymphohistiocytosis with Clonal Karyotype Abnormalities

There have been a few reports of hemophagocytic lymphohistiocytosis (HLH) with chromosomal abnormalities. Clonal chromosomal abnormalities in HLH patients are usually found in association with hematologic malignancies and rarely with epstein-barr virus (EBV) infection. Here, we report a fatal case of HLH with clonal karyotype abnormalities. A 75-yr-old man was admitted with persistent anorexia and high fever. Laboratory data revealed pancytopenia, hypofibrinogenemia, hyperferritinemia, prolonged prothrombin time and activated partial thromboplastin time, and marked elevated level of serum transaminases. In real time-PCR using whole blood, EBV DNA was not detected but cytomegalovirus (CMV) DNA was detected. The bone marrow aspiration smear showed hyperplasia of mature histiocytes with prominent hemophagocytosis. In chromosomal analysis of bone marrow aspirates, complex chromosomal abnormalities were found. In spite of steroid pulse therapy and antibiotic treatment, he died of disseminated intravascular coagulopathy.