Morphologically and karyotypically atypical cells of 'normal' human bronchial epithelial cell line (Beas-2B).

Beas-2B is an adenovirus 12-SV40-transfected cell line of "normal" human bronchial epithelial cells. This cell line was able to replace normal human bronchial epithelial cells, which are currently unavailable, and served as a model for related studies in numerous toxicology and cancer transformation experiments. In any experiment involving toxins or carcinogens, the basic morphology of Beas-2B should be well characterized prior to exposure, but this has never been properly reported. In this study, atypical cells of the Beas-2B cell line in early passage culture were observed using light and electron microscopy, and the cells were further investigated for abnormal karyotypes by flow cytometry. This Beas-2B cell line could be morphologically categorized into two cell types, A and B. Type A contains a large nucleus and abundant cytoplasm (type A > 95%) and type B contains a small nucleus with dense and scarce cytoplasm (type B < 5%). Both atypical cell types had atypical and multilobed/multinucleated cells, including a high percentage (>30%) of mitotic figures, and were Ki-67 positive (100%). Karyotyping also revealed that 40.4% of the cells had atypical karyotyped chromosomes. In light of these findings, this cell line is no longer a "normal" cell, and experiments performed using this cell line can be questioned for non-default results. Experimenters should consider this error in future experiments.

Association between interstitial cells of Cajal and anti-vinculin antibody in human stomach.

Interstitial cells of Cajal (ICC) are known as the pacemaker cells of gastrointestinal tract, and it has been reported that acute gastroenteritis induces intestinal dysmotility through antibody to vinculin, a cytoskeletal protein in gut, resulting in small intestinal bacterial overgrowth, so that anti-vinculin antibody can be used as a biomarker for irritable bowel syndrome. This study aimed to determine correlation between serum anti-vinculin antibody and ICC density in human stomach. Gastric specimens from 45 patients with gastric cancer who received gastric surgery at Kangwon National University Hospital from 2013 to 2017 were used. ICC in inner circular muscle, and myenteric plexus were counted. Corresponding patient's blood samples were used to determine the amount of anti-vinculin antibody by enzyme-linked immunosorbent assay. Analysis was done to determine correlation between anti-vinculin antibody and ICC numbers. Patients with elevated anti-vinculin antibody titer (above median value) had significantly lower number of ICC in inner circular muscle (71.0 vs. 240.5, p = 0.047), and myenteric plexus (12.0 vs. 68.5, p < 0.01) compared to patients with lower anti-vinculin antibody titer. Level of serum anti-vinculin antibody correlated significantly with density of ICC in myenteric plexus (r = -0.379, p = 0.01; Spearman correlation). Increased level of circulating anti-vinculin antibody was significantly correlated with decreased density of ICC in myenteric plexus of human stomach.

Pediatric appendectomy: the outcome differences between pediatric surgeons and general surgeons.

PURPOSE: The aim of this study was to review our experience of pediatric appendectomy performed by either a general surgeon (GS) or a pediatric surgeon (PS) to determine any differences in outcomes. METHODS: We reviewed the medical records of pediatric appendicitis patients, 4 years before (GS group, 2007-2010) and after (PS group, 2011-2014) the introduction of a pediatric surgical practice. The records were reviewed for the following variables: operation time, length of hospital stay, complications, readmission in ≤30 days, type of operation, negative for appendicitis, drainage, open conversion, and reoperation in ≤30 days. RESULTS: Over 8 years, 400 patients were operated on for acute appendicitis, with the PS group comprising 61 % (N = 244) of patients. The operation time (55.1 vs 43.2 min, p = 0.0001) and postoperative length of hospital stay (3.5 vs 2.7 days, p = 0.001) were shorter, more patients were treated by laparoscopy (61.3 vs 91.2 %, p = 0.0001), and a fewer patients required peritoneal drainage (29.5 vs 63.2 %, p = 0.023) in the PS group than in the GS group. The negative appendectomy rate was slightly lower in the PS group, but not to a statistically significant degree. CONCLUSION: The patients in the PS group enjoyed a reduced operation time and length of hospital stay, greater likelihood of laparoscopic operation, and less peritoneal drainage than the patients in the GS group.

Analysis of human tissue management models for medical research: preparation for implementation of the 2012 revision of the Bioethics and Safety Act of Korea.

Efficient management of human tissue samples is a critical issue; the supply of samples is unable to satisfy the current demands for research. Lack of informed consent is also an ethical problem. One of the goals of the 2012 revision of Korea's Bioethics and Safety Act was to implement regulations that govern the management of human tissue samples. To remain competitive, medical institutions must prepare for these future changes. In this report, we review two tissue management models that are currently in use; model 1 is the most common system utilized by hospitals in Korea and model 2 is implemented by some of the larger institutions. We also propose three alternative models that offer advantages over the systems currently in use. Model 3 is a multi-bank model that protects the independence of physicians and pathologists. Model 4 utilizes a comprehensive single bioresource bank; although in this case, the pathologists gain control of the samples, which may make it difficult to implement. Model 5, which employs a bioresource utilization steering committee (BUSC), is viable to implement and still maintains the advantages of Model 4. To comply with the upcoming law, we suggest that physicians and pathologists in an institution should collaborate to choose one of the improved models of tissue management system that best fits for their situation.

Embryonal rhabdomyosarcoma arising from a mediastinal teratoma: an unusual case report.

We report an unusual case of 9.5-cm-sized embryonal rhabdomyosarcoma arose from a mediastinal mature teratoma in a 46-yr-old man. A man presented with chest trauma as a result of an accident at 10 September 2011. On chest X-ray, an anterior mediastinal mass was detected. To obtain further information, chest computed tomography (CT) with contrast enhancement was performed, revealing an anterior mediastinal mass. Complete surgical excision was performed and entire specimen was evaluated. Pathologic diagnosis was embryonal rhabdomyosarcoma arising in mature cystic teratoma. After surgical excision, two cycles of dactinomycin-based chemotherapy were performed. Lung metastasis was detected on follow up CT in September 2012, and wedge resection was performed. Pathological finding of the lung lesion showed same feature with that of primary rhabdomyosarcoma.

Comparison of the ultrastructural and immunophenotypic characteristics of human umbilical cord-derived mesenchymal stromal cells and in situ cells in Wharton's jelly.

The umbilical cord contains mucinous connective tissue, called Wharton's jelly. It consists of stromal cells, collagen fibers, and amorphous ground substances composed of proteoglycan. Recently, these stromal cells have been redefined as a new cell therapy source, named human umbilical cord-derived mesenchymal stromal cells (hUCMSCs). However, there are few studies on the ultrastructural features and immune-phenotypic characteristics of isolated hUCMSCs and comparisons with the cells found in original cord tissues. In this study, the authors describe and compare the phenotypic characteristics of hUCMSCs with cells in the umbilical cord in order to know the kinds of cells and ultrastructural changes. Isolated hUCMSCs showed similar ultrastructure with few structural differences from in situ stromal cells, and they are relatively homogenous and well-developed mesenchymal cells that demonstrate a myofibroblastic phenotype.

An XYZ-axis Matrix Approach for the Integration of Neuroscience and Neuroethics.

The recent, unprecedented advancement in neuroscience has led to new discoveries about the human brain and its function. Yet at the same time, it has spurred novel ethical and regulatory issues, and the field of neuroethics has emerged as an interdisciplinary endeavor to address these issues. Across the globe, extensive efforts have been underway to achieve the integration of neuroscience and Neuroethics, with active engagement not only from academia but also from the government, the public, and industry. However, in some countries, integrating neuroscience and neuroethics has proved to be a particularly challenging task. For example, in South Korea, the government has primarily driven the integration effort, and only a small group of researchers is properly trained for conducting an interdisciplinary evaluation of ethical, legal, social, and cultural implications (ELSCI) of neurotechnology. On the basis of the last few years of experience pursuing a government-funded neuroethics project in South Korea, we developed a new operational framework to provide practical guidance on ELSCI research. This framework consists of the X, Y, and Z axes; the X-axis represents a target neurotechnology, the Y-axis represents different developmental stages of the technology, and the Z-axis represents ELSCI issues that may arise from the development and use of the neurotechnology. Here we also present a step-by-step workflow to apply this matrix framework, from organizing a panel for a target neurotechnology to facilitating stakeholder discussion through public hearings. This framework will enable meaningful integration of neuroscience and neuroethics to promote responsible innovation in neuroscience and neurotechnology.

Epithelial-mesenchymal transition in breast cancer correlates with high histological grade and triple-negative phenotype.

AIMS: Epithelial-mesenchymal transition (EMT) is characterized by a loss of epithelial nature and the acquisition of a mesenchymal form. The aim of this study was to assess the role of EMT in human mammary carcinogenesis, by performing immunohistochemical studies of EMT markers with tissue microarrays. METHODS AND RESULTS: A total of 492 cases were evaluated and classified as hormone receptor (HR)-positive type, HER2 type and triple-negative (TN) type by the use of immunohistochemistry and in-situ hybridization. We compared these groups in terms of epithelial and mesenchymal marker expression patterns. Of the 102 cases of TN-type breast cancer, 24.5% expressed vimentin, 13.7% expressed N-cadherin, and 9.8% expressed smooth muscle actin (SMA). Of the 221 cases of HR-type breast cancer, 4.1% expressed vimentin, 5.9% expressed N-cadherin, and 0.4% expressed SMA. Regarding epithelial markers, decreased expression was seen in 16.7% of cases for E-cadherin, in 45.1% for cytokeratin (CK)19 and in 60.8% for CK8 and CK18 (CAM5.2) in TN-type breast cancer cases. Decreased expression was seen in 11.8% of cases for E-cadherin, in 6.8% for CK19 and in 3.2% for CAM5.2 in HR-type cases. CONCLUSIONS: EMT features were particularly seen in TN-type breast cancer (P < 0.001). EMT was also significantly associated with high histological grade (P < 0.001).

A Study of Human Papillomavirus Genotypes Specificity and the Vaccines Introducing System for Korean-Chinese Women in the Yanbian Autonomous Region.

OBJECTIVES: Human papillomavirus (HPV) is a major cause of cervical cancer in women. The characteristics of HPV infection vary; therefore, it is necessary to identify the most common HPV genotypes among a group of subjects when introducing a vaccine program. Currently, in the Yanbian Autonomous Region, no HPV vaccinations are not provided, and no data has been reported regarding HPV rates or genotype prevalence. We aimed to find the most suitable HPV vaccine for this region and reasons why no vaccine has been introduced. METHODS: HPV genotyping of 200 Korean-Chinese women living in the Yanbian Autonomous Region who visited the hospital for annual health examination was done. We also checked main factors necessary for HPV vaccine administrative system; (1) vaccine manufacturers in China, (2) vaccine importers, (3) vaccine suppliers, (4) applicable vaccine laws, (5) the HPV vaccine permit system in Jilin Province, and (6) vaccination hospital facilities-were assessed by direct inquiry and search. RESULTS: The results showed that HPV genotypes 52, 58, 16, 53, and 33 were the most common among Korean-Chinese women. These results differed from those previously reported for Korean or Chinese women. All elements necessary for introduction of HPV vaccine were prepared, but there is no HPV vaccination plan based on epidemiological investigation. CONCLUSIONS: Gardasil® 9 should be the most suitable vaccine for Korean-Chinese women with HPV infection and cervical cancer in this region considering the prevalence of certain genotypes. Governments and medical institutions should take an active stance on HPV vaccination to lower the incidence of cervical cancer here. Our study may serve as an important reference for introducing a Chinese government program designed to prevent cervical cancer.

Solitary colonic metastasis from primary lung adenocarcinoma first presenting as intestinal obstruction: A case report.

RATIONALE: The brain, liver, adrenal glands, and bone are the most common sites of metastatic disease in patients with lung cancer. Symptomatic gastrointestinal metastases are rare. In the present report, we describe a rare case of a patient with intestinal obstruction due to solitary colonic metastasis from primary lung adenocarcinoma, wherein the intestinal obstruction was the first symptom of lung cancer. PATIENT CONCERNS: A 74-year-old man was admitted to the emergency room with abdominal pain and vomiting, and abdominal computed tomography (CT) indicated obstruction of the ascending colon due to a huge mass. DIAGNOSIS: The ascending colon cancer was found to be a metastatic adenocarcinoma based on the results of the pathology report. Chest CT and positron emission tomography-CT were performed to identify the cancer origin site. Moreover, immunohistochemical staining of the tissue specimen for thyroid transcription factor 1, cytokeratin 7 (CK7), and CK20 and CT-guided gun biopsy of the lung mass confirmed the presence of an adenocarcinoma that originated from the lung. INTERVENTION: Right hemicolectomy was performed as the primary treatment. OUTCOMES: The patient recovered without any problems due to the surgery itself. However, malignant pleural effusion deteriorated, and no additional palliative chemotherapy was performed. LESSONS: Patients with malignant bowel obstruction along with lung infiltration should be suspected of not only colon cancer with lung metastasis, but also lung cancer with colon metastasis.

Korea Brain Initiative: Emerging Issues and Institutionalization of Neuroethics.

Neuroscience research has become a national priority for the Korean government. Korean scholars have dedicated interest in the societal ramifications of neurotechnologies; neuroethics is an integral component of the Korea Brain Initiative and to the formation of its growing neuroscience community.

ACN9 Regulates the Inflammatory Responses in Human Bronchial Epithelial Cells.

BACKGROUND: Airway epithelial cells are the first line of defense, against pathogens and environmental pollutants, in the lungs. Cellular stress by cadmium (Cd), resulting in airway inflammation, is assumed to be directly involved in tissue injury, linked to the development of lung cancer, and chronic obstructive pulmonary disease (COPD). We had earlier shown that ACN9 (chromosome 7q21), is a potential candidate gene for COPD, and identified significant interaction with smoking, based on genetic studies. However, the role of ACN9 in the inflammatory response, in the airway cells, has not yet been reported. METHODS: We first checked the anatomical distribution of ACN9 in lung tissues, using mRNA in situ hybridization, and immunohistochemistry. Gene expression profiling in bronchial epithelial cells (BEAS-2B), was performed, after silencing ACN9. We further tested the roles of ACN9, in the intracellular mechanism, leading to Cd-induced production, of proinflammatory cytokines in BEAS-2B. RESULTS: ACN9 was localized in lymphoid, and epithelial cells, of human lung tissues. ACN9 silencing, led to differential expression of 216 genes. Pathways of sensory perception to chemical stimuli, and cell surface receptor-linked signal transduction, were significantly enriched. ACN9 silencing, further increased the expression of proinflammatory cytokines, in BEAS-2B after Cd exposure. CONCLUSION: Our findings suggest, that ACN9 may have a role, in the inflammatory response in the airway.

Posttraumatic Intracranial Tuberculous Subdural Empyema in a Patient with Skull Fracture.

Intracranial tuberculous subdural empyema (ITSE) is extremely rare. To our knowledge, only four cases of microbiologically confirmed ITSE have been reported in the English literature to date. Most cases have arisen in patients with pulmonary tuberculosis regardless of trauma. A 46-year-old man presented to the emergency department after a fall. On arrival, he complained of pain in his head, face, chest and left arm. He was alert and oriented. An initial neurological examination was normal. Radiologic evaluation revealed multiple fractures of his skull, ribs, left scapula and radius. Though he had suffered extensive skull fractures of his cranium, maxilla, zygoma and orbital wall, the sustained cerebral contusion and hemorrhage were mild. Eighteen days later, he suddenly experienced a general tonic-clonic seizure. Radiologic evaluation revealed a subdural empyema in the left occipital area that was not present on admission. We performed a craniotomy, and the empyema was completely removed. Microbiological examination identified Mycobacterium tuberculosis (M. tuberculosis). After eighteen months of anti-tuberculous treatment, the empyema disappeared completely. This case demonstrates that tuberculosis can induce empyema in patients with skull fractures. Thus, we recommend that M. tuberculosis should be considered as the probable pathogen in cases with posttraumatic empyema.

Recurrent renal cell carcinoma manifesting as a large intrathoracic fibrotic mass: A case report.

Renal cell carcinomas (RCCs) have a strong tendency to metastasize, and the most common sites are the lungs, bones and liver. Late recurrence is another feature of the RCC, with lesions appearing ≥10 years after surgical treatment. However, fibrosis has rarely been associated with the disease. The present study reports a case of recurrent RCC that manifested as a fibrotic mass within the thorax. A 48-year-old man presented with dyspnea that had persisted for 3 days. The patient had undergone a right radical nephrectomy for stage II clear cell carcinoma of the kidney 6 years previously. The patient was a current smoker, with a smoking history of 20 pack-years. Chest radiography showed pleural effusion in the right thorax with an egg-sized mass shadow within the right upper lung (RUL) field. Computed tomography (CT) showed a main mass, 7 cm in diameter, within the RUL, with heterogeneous enhancement and multiple nodules of various sizes in the lungs, suggestive of primary lung cancer or metastatic RCC. A CT-guided percutaneous needle aspiration biopsy was obtained from the main mass, but histology revealed dense fibrous tissue without any malignant cells. Positron emission tomography-CT demonstrated an irregular hypermetabolic RUL mass, with a standardized uptake value (SUV) of 5.0, along the right pleura, and small pulmonary nodules (SUV, 2.0). Ultrasound-guided biopsy was attempted for a smaller hypermetabolic pleural nodule and the result was clear cell adenocarcinoma, consistent with the previous renal histology. The present study describes the case, along with a review of the relevant literature.

The Autoclaving of Autologous Bone is a Risk Factor for Surgical Site Infection After Cranioplasty.

BACKGROUND: This retrospective study was designed to evaluate the effectiveness of autoclaving for the prevention of surgical site infection (SSI) after cranioplasty. METHODS: Patients who underwent cranioplasty with autologous bone were enrolled. SSI was defined as an infection requiring bone flap removal. Risk factors of SSI, as reported by other researchers, and microbiologic features of SSI were analyzed. All bone flaps were preserved in a deep freezer (-70°C). Autoclaving of the preserved autologous bone flap before cranioplasty was performed for 5 minutes at 135°C in the 26 patients. RESULTS: Eighty patients were enrolled. The mean age was 53.3 years and the male/female ratio was 3:2. Causes of craniectomy included trauma (n = 37) and nontrauma (n = 43). The mean time interval between craniectomy and cranioplasty was 49.7 days. The SSI rate after cranioplasty with autologous bone was 17.5% (n = 14). In univariate analysis, the cranioplasty operation time (P = 0.09) and the use of autoclaved bone (P = 0.00) were supposed to be risk factors for SSI. The use of autoclaved autologous bone was found to be the only risk factor of SSI (P = 0.01; hazard ratio = 8.88) in binary logistic regression analysis. Non-methicillin-resistant Staphylococcus aureus (MRSA) causes were more frequent in the autoclaved group (MRSA, 30%; non-MRSA, 70%) compared with the nonautoclaved group (MRSA, 100%) (P = 0.07). A microscopic examination showed that autoclaving after long-term cryopreservation may result in a loss of bone viability. CONCLUSIONS: Autoclaving of autologous bone causes SSI after cranioplasty and it seems to increase the risk of non-MRSA infection by normal skin flora.

Occult gastric cancer with distant metastasis proven by random gastric biopsy.

Krukenberg tumor, a rare metastatic ovarian tumor arising from gastrointestinal adenocarcinoma mainly, tends to occur in premenopausal females. Finding the origin of a Krukenberg tumor is crucial for determining prognosis. In Eastern countries, the most common origin of Krukenberg tumor is stomach cancer, which is generally diagnosed via endoscopic biopsy to investigate an abnormal mucosal lesion. Here, we describe a case of huge adnexal mass in a 33-year-old woman who presented with abdominal distension. Two independent endoscopic examinations performed by experts in two tertiary university hospitals revealed no abnormal mucosal lesion. The patient was diagnosed with a Krukenberg tumor according to findings from random endoscopic biopsies taken from normal-looking gastric mucosa in our hospital. It is very rare to be diagnosed via a random biopsy in cases where three well-trained endoscopists had not found any mucosal lesion previously. Thus, in this case, random biopsy was helpful in finding the origin of a Krukenberg tumor.

Investigation of the origin of stromal and endothelial cells at the desmoplastic interface in xenograft tumor in mice.

Carcinoma-associated fibroblasts found at the interface between a tumor and the normal stroma play several roles in the development of cancer, including cancer initiation, growth, and progression, thereby also affecting patient prognosis. Although recent studies have focused on carcinoma-associated fibroblasts as potential treatment targets, the origin of these fibroblasts remains unclear. One theory suggests that these cells arise from tumor cells undergoing the epithelial-mesenchymal transition, i.e., tumor cells transform into carcinoma-associated fibroblasts. Therefore, in this study, we aimed to elucidate the cellular origin of carcinoma-associated fibroblasts in a mouse xenograft model. Mice were transplanted with human lung cancer cells (H226 and A549 cells). After sacrifice, tumor masses and surrounding tissues were excised. Interestingly, the excised xenograft tissues contained a significant proportion of desmoplastic fibroblasts that exhibited strong expression of α-smooth muscle actin (SMA). Immunohistochemical staining with pan-cytokeratin, vimentin, ß-catenin, E-cadherin, and CD34 showed no evidence of the epithelial-mesenchymal transition. Additional evaluation using dual-color silver in situ hybridization with dinitrophenyl-labeled human epidermal growth factor receptor 2 (HER2) and digoxigenin-labeled chromosome 17 centromere probes also showed similar results. In conclusion, our results revealed that the epithelial-mesenchymal transition may not occur in tumor xenograft models, regardless of evidence supporting this phenomenon in humans.

Gastric inverted hyperplasic polyp composed only of pyloric glands: a rare case report and review of the literature.

Inverted hyperplastic polyp (IHP) in stomach is a rare benign gastric polypoid lesion, characterized by downward growth of hyperplastic mucosal glands into the submucosal layer. In most previous reported cases, gastric IHP showed mixtures of fundic-type gland, pyloric-type gland, and foveolar-type epithelium. Also, a case of IHP composed of only one type of gland is extremely rare. This report describes a case of a 70-year-old man with gastric IHP, composed only of pyloric-type gland. It was removed completely by endoscopic submucosal dissection, and patient showed no recurrence over 2 years after treatment.

Overexpressions of Vimentin and Integrins in Human Metastatic Spine Tumors.

OBJECTIVE: To comparatively investigate the expression of several integrins in specimens of human bone metastases and degenerative bone tissue. METHODS: Degenerative cancellous tissue was obtained from a sample of human degenerative spine. Thirteen human specimens were obtained from metastatic spine tumors, whose primary cancer was colon cancer (n=3), hepatocellular cancer (n=3), lung cancer (n=4), and breast cancer (n=3). The expression of vimentin and integrins αv, ß1, and ß3 was assessed in metastatic and degenerative specimens by immunohistochemistry and real-time reverse transcription-polymerase chain reaction (qRT-PCR). RESULTS: Immunohistochemical staining showed that vimentin and integrin αv was broadly expressed in all tissues examined. By contrast, integrin ß1 was weakly expressed only in 38.4% (5/13) of tissues. Integrin ß3 was consistently negative in all cases examined. qRT-PCR analysis showed that vimentin gene expression was higher in all metastatic specimens, as compared to degenerative bone. The gene expression of integrin αv in breast specimen was significantly higher than others (p=0.045). The gene expression of integrin ß1 was also higher in all metastatic specimens than in degenerative bone tissue. The gene expression of integrin ß3 was variable. CONCLUSION: Spinal metastatic tumors have mesenchymal characteristics such as increased expression of vimentin. The increased expression of integrin αv and ß1 in spine metastatic tumors suggests that adhesive molecules such as integrin may have implications for the prevention of spine metastasis.