Sarcoidosis, a systemic granulomatous disease of unknown etiology. The presentation of sarcoidal granuloma in neck nodes without typical manifestations of systemic sarcoidosis is difficult to diagnose. We describe the case of a 37-year-old woman with an increasing mass on the right side of neck. The excisional biopsy from the neck mass showed noncaseating epithelioid cell granuloma of the lymph nodes. No evidence of mycobacterial or fungal infection was noted. Thoracic evaluations did not show enlargement of mediastinal lymph nodes or parenchymal abnormalities. Immunohistochemistry showed abundant expression of tumor necrosis factor-α in the granuloma. However, transforming growth factor-β was not expressed, although interleukin-1β was focally expressed. These immunohistochemical findings supported characterization of the granuloma and the diagnosis of sarcoidosis. Sarcoidosis can present with cervical lymph node enlargement without mediastinal or lung abnormality. Immunohistochemistry may support the diagnosis of sarcoidosis and characterization of granuloma.
Sarcoidosis; Lymphatic Diseases; Neck; Immunohistochemistry
The tumour-suppressor gene CDKN1A (encoding p21Waf/Cip1) is thought to be epigenetically repressed in cancer cells. FBI-1 (ZBTB7A) is a proto-oncogenic transcription factor repressing the alternative reading frame and p21WAF/CDKN1A genes of the p53 pathway. FBI-1 interacts directly with MBD3 (methyl-CpG–binding domain protein 3) in the nucleus. We demonstrated that FBI-1 binds both non-methylated and methylated DNA and that MBD3 is recruited to the CDKN1A promoter through its interaction with FBI-1, where it enhances transcriptional repression by FBI-1. FBI-1 also interacts with the co-repressors nuclear receptor corepressor (NCoR), silencing mediator for retinoid and thyroid receptors (SMRT) and BCL-6 corepressor (BCoR) to repress transcription. MBD3 regulates a molecular interaction between the co-repressor and FBI-1. MBD3 decreases the interaction between FBI-1 and NCoR/SMRT but increases the interaction between FBI-1 and BCoR. Because MBD3 is a subunit of the Mi-2 autoantigen (Mi-2)/nucleosome remodelling and histone deacetylase (NuRD)-HDAC complex, FBI-1 recruits the Mi-2/NuRD-HDAC complex via MBD3. BCoR interacts with the Mi-2/NuRD-HDAC complex, DNMTs and HP1. MBD3 and BCoR play a significant role in the recruitment of the Mi-2/NuRD-HDAC complex– and the NuRD complex–associated proteins, DNMTs and HP. By recruiting DNMTs and HP1, Mi-2/NuRD-HDAC complex appears to play key roles in epigenetic repression of CDKN1A by DNA methylation.
Inhalation of toxic gases can lead to pneumonitis. It has been known that methane gas intoxication causes loss of consciousness or asphyxia. There is, however, a paucity of information about acute pulmonary toxicity from methane gas inhalation. A 21-year-old man was presented with respiratory distress after an accidental exposure to methane gas for one minute. He came in with a drowsy mentality and hypoxemia. Mechanical ventilation was applied immediately. The patient's symptoms and chest radiographic findings were consistent with acute pneumonitis. He recovered spontaneously and was discharged after 5 days without other specific treatment. His pulmonary function test, 4 days after methane gas exposure, revealed a restrictive ventilatory defect. In conclusion, acute pulmonary injury can occur with a restrictive ventilator defect after a short exposure to methane gas. The lung injury was spontaneously resolved without any significant sequela.
Methane; Smoke Inhalation Injury; Respiratory Insufficiency
Polycomb group (PcG) proteins maintain the spatial expression patterns of genes that are involved in cell-fate specification along the anterior-posterior (A/P) axis. This repression requires cis-acting silencers, which are called PcG response elements (PREs). One of the PcG proteins, Pleiohomeotic (Pho), which has a zinc finger DNA binding protein, plays a critical role in recruiting other PcG proteins to bind to PREs. In this study, we characterized the effects of a pho mutation on embryonic segmentation. pho maternal mutant embryos showed various segmental defects including pair-rule gene mutant patterns. Our results indicated that engrailed and even-skipped genes were misexpressed in pho mutant embryos, which caused embryonic segment defects.
eve; Drosophila melanogaster; GAGA; pleiohomeotic; Polycomb group genes; PRE; segmentation genes
Tuberculous pleural effusion (TPE) is one of the most common forms of extrapulmonary tuberculosis. Because most studies of TPE focused on the pleural space, little information regarding lung parenchyma is available. We therefore aimed to investigate immune responses in the lung parenchyma of TPE patients without pulmonary tuberculosis.
Patients with any evidence of pulmonary tuberculosis, either from radiologic or bacteriologic evaluation, were excluded. Bronchoalveolar lavage fluid (BALF) was collected from 10 newly diagnosed, untreated, HIV-negative TPE patients and 10 healthy controls. We analyzed T-lymphocyte subpopulations and measured 10 cytokines in BALF. Cytokine levels in BALF were standardised using urea.
The concentrations of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), and the CD4+/CD8+ ratio of T-lymphocytes were significantly higher in TPE patients without pulmonary tuberculosis than in the controls. Of the cytokines measured in BALF, VEGF showed the highest concentration. No difference was observed in T-helper type 2 cytokines between the 2 groups.
There were significant immune responses and increases in IFN-γ, TNF-α, and VEGF in the lung parenchyma of TPE patients without pulmonary tuberculosis. This result suggests that TPE may induce a significant immune response in lung parenchyma.
Interferon-γ; Tuberculosis; Tumor necrosis factor-α; Vascular endothelial growth factor
We investigated effects of short- and long-term exposure to sidestream smoke on the bronchiolar and alveolar cells in Sprague-Dawley rats.
Rats were divided into five experimental groups: groups 1, 2, and 3 (1-month exposure to 3, 5, and 7 cigarettes a day, respectively), groups 4 and 5 (3- and 6 month exposure to five cigarettes a day, respectively). We examined the morphologic changes, the expressions of tumor necrosis factor α (TNF-α), tumor growth factor β1 (TGF-β1), interlekin (IL)-1α, IL-1β, Ki-67, and cytokeratin 14 and in situ apoptosis in the bronchiolar and alveolar cells on light microscopy (LM) and electron microscopic (EM) terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining.
LM showed the respiratory bronchiolar dilatation and alveolar wall collapse. In groups 3, 4, and 5, EM showed loss of the cilia and Clara cells with irregular size, more prominent alveolar wall collapse and dilation of alveolar duct than those of groups 1 and 2. Bronchiolar and alveolar cells showed increased expressions of TNF-α and TGF-β in groups 4 and 5. LM and EM TUNEL stains showed increased apoptosis in groups 3, 4, and 5.
Sidestream smoke causes a bronchiolar and alveolar cell injury and the severity correlates strongly the volume and duration of exposure to sidestream smoke.
Bronchiolar cells; Alveolar cells; Sidestream smoke; Immunohistochemistry; TUNEL staining
Pandemic influenza A (H1N1) disproportionately affects different age groups. The purpose of the current study was to describe the age and gender difference of pandemic influenza A (H1N1) cases that lead to pneumonia, hospitalization or ICU admission.
Data were collected retrospectively between May 2009 and December 2009. All of the diagnoses of H1N1 were confirmed by real-time reverse-transcription polymerase chain reaction (RT-PCR).
During the study period there were 3402 cases of RT-PCR positive H1N1, among which 1812 were males and 1626 were adults (> 15 years of age). 6% (206/3402) of patients required hospitalization, 3.6% (122/3402) had infiltrates on chest radiographs, and 0.70% (24/3402) were admitted to intensive care unit (ICU). The overall fatality rate was 0.1% (4/3402). The rate of hospitalization was sharply increased in patients ≥ 50 years of age especially in male. Out of 122 pneumonia patients, 68.8% (84 patients) were male. Among the patients admitted to the ICU, 70.8% (17 patients) were male. Approximately 1 of 10 H1N1-infected patients admitted to the ICU were ≥ 70 years of age.
Among the confirmed cases of H1N1, the ICU admission rate was < 1% and the case fatality rate was 0.1%. Male had a significantly higher rate of pneumonia and hospital admission. These findings should be taken into consideration when developing vaccination and treatment strategies.
Influenza; H1N1; Gender; Pneumonia; Admission
We experienced a case of primary pulmonary biphasic synovial sarcoma, which was confirmed by immunohistochemistry and molecular testing of SYT-SSX2 fusion transcripts. The patient was a 61-year-old man who presented with a well-defined mass in the left upper lung field on chest radiography. Left upper lobectomy with lymph node dissection was performed. Histological and immunophenotypic features were consistent with biphasic synovial sarcoma. Reverse transcriptase polymerase chain reaction, performed using RNA extracted from frozen tumor samples for the detection of SYT-SSX fusion gene, amplified a single 331-bp fragment that was characteristic of the SYT-SSX2 fusion transcripts. We report a case of primary pulmonary biphasic synovial sarcoma, which was confirmed by SYT-SSX2 fusion transcripts, and present a brief review of the literature on Korean cases.
Sarcoma, synovial; Lung neoplasms; Gene fusion
Acute kidney injury frequently accompanies sepsis. Endotoxin is known to reduce tissue levels of cAMP and low levels of cAMP have been associated with renal injury. We, therefore, hypothesized that endotoxin induced renal injury by activating phosphodiesterase 3 (PDE3) which metabolizes cAMP and that amrinone an inhibitor of PDE3 would prevent the renal injury.
Animals were divided into three groups (n = 7/group): 1) Control (0.9% NaCl infusion without LPS); 2) LPS (0.9% NaCl infusion with LPS); 3) Amrinone+LPS (Amrinone infusion with LPS). Either lipopolysaccharide (LPS) or vehicle was injected via the jugular vein and the rats followed for 3 hours. We explored the expression of PDE3 isoenzymes and the concentrations of cAMP in the tissue.
The PDE3B gene but not PDE3A was upregulated in the kidney of LPS group. Immunohistochemistry also showed that PDE3B was expressed in the distal tubule in the controls and LPS caused PDE3B expression in the proximal as well. However, PDE3A was not expressed in the kidney either in the control or LPS treated groups. Tissue level of cAMP was decreased after LPS and was associated with an increase in blood urea nitrogen, creatinine, ultrastructural proximal tubular changes, and expression of inducible nitric oxide synthase (iNOS) in the endotoxemic kidney. In septic animals the phosphodiesterase 3 inhibitor, amrinone, preserved the tissue cAMP level, renal structural changes, and attenuated the increased blood urea nitrogen, creatinine, and iNOS expression in the kidney.
These findings suggest a significant role for PDE3B as an important mediator of LPS-induced acute kidney injury.
Atelectasis can impair arterial oxygenation and decrease lung compliance. However, the effects of atelectasis on endotoxemic lungs during ventilation have not been well studied. We hypothesized that ventilation at low volumes below functional residual capacity (FRC) would accentuate lung injury in lipopolysaccharide (LPS)-pretreated rats. LPS-pretreated rats were ventilated with room air at 85 breaths/min for 2 hr at a tidal volume of 10 mL/kg with or without thoracotomy. Positive end-expiratory pressure (PEEP) was applied to restore FRC in the thoracotomy group. While LPS or thoracotomy alone did not cause significant injury, the combination of endotoxemia and thoracotomy caused significant hypoxemia and hypercapnia. The injury was observed along with a marked accumulation of inflammatory cells in the interstitium of the lungs, predominantly comprising neutrophils and mononuclear cells. Immunohistochemistry showed increased inducible nitric oxide synthase (iNOS) expression in mononuclear cells accumulated in the interstitium in the injury group. Pretreatment with PEEP or an iNOS inhibitor (1400 W) attenuated hypoxemia, hypercapnia, and the accumulation of inflammatory cells in the lung. In conclusion, the data suggest that atelectasis induced by thoracotomy causes lung injury during mechanical ventilation in endotoxemic rats through iNOS expression.
Atelectasis; Functional Residual Capacity; Lung Injury; Nitric Oxide Synthase; Nitric Oxide Synthase Inhibitor
This study was performed to produce transgenic Korean native goat (Capra hircus) by laparoscopic embryo transfer (ET) to overcome the limitations of ET performed by laparotomy. Transgenic embryos were produced by DNA pronuclear microinjection of in vivo zygotes. The recipient goats were synchronized for estrus by using an introvaginal progesterone devices as a controlled internal drug-releasing insert (CIDR) for 13 days and injection of 400 IU PMSG 48 h before removal of the insert. Embryos were transferred on day 3 and 4 after removal of the insert. Recipient goats were deprived of feed for 48 h, then suspended in a laparotomy cradle at an angle of 45°. After obtaining a sufficient pneumoperitoneum, the laparoscope and forceps were inserted abdominally through 5 mm trocar sleeves. Examination of the ovaries and uterus was performed and then 213 embryos were transferred into the oviducts via the infundibula of 76 recipient goats. To compare pregnancy rates, ET was also performed by laparotomy in 82 recipient goats. The pregnancies in the recipient goats were diagnosed by ultrasound on day 30 after embryo transfer. The pregnancy rate with laparoscopic ET was significantly higher than with ET performed by laparotomy (46.1% vs. 28.6%, p < 0.05). In addition, the pregnancy rates were compared between ovulated and non-ovulated ovaries of the recipient goats in the laparoscopic ET group. No significant difference was observed between the pregnancy rates of ovulated and non-ovulated ovaries (41.3% vs. 33.3%, p < 0.05) suggesting that ET may also be possible in non-ovulated recipients through artificial rupture of Graafian follicles. These results suggest that laparoscopic ET is a highly efficient method for the transfer of goat embryos.
embryo transfer; goat; laparoscopy; laparotomy; transgenic
In 2010, we proposed the first Korean Guidelines for the Prevention of Venous Thromboembolism (VTE). It was applicable to Korean patients, by modifying the contents of the second edition of the Japanese guidelines for the prevention of VTE and the 8th edition of the American College of Chest Physicians (ACCP) evidence-based clinical practice guidelines. From 2007 to 2011, we conducted a nationwide study regarding the incidence of VTE after major surgery using the Health Insurance Review and Assessment Service (HIRA) database. In addition, we have considered the 9th edition of the ACCP Evidenced-Based Clinical Practice Guidelines, published in 2012. It emphasized the importance of clinically relevant events as opposed to asymptomatic outcomes with preferences for both thrombotic and bleeding outcomes. Thus, in the development of the new Korean guidelines, three major points were addressed: 1) the new guidelines stratify patients into 4 risk groups (very low, low, moderate, and high) according to the actual incidence of symptomatic VTE from the HIRA databases; 2) the recommended optimal VTE prophylaxis for each group was modified according to condition-specific thrombotic and bleeding risks; 3) guidelines are intended for general information only, are not medical advice, and do not replace professional medical care and/or physician advice.
Guideline; Prevention; Venous Thromboembolism; Bleeding
Aberrant activation of the Wnt pathway contributes to human cancer progression. Antagonists that interfere with Wnt ligand/receptor interactions can be useful in cancer treatments. In this study, we evaluated the therapeutic potential of a soluble Wnt receptor decoy in cancer gene therapy. We designed a Wnt antagonist sLRP6E1E2, and generated a replication-incompetent adenovirus (Ad), dE1-k35/sLRP6E1E2, and a replication-competent oncolytic Ad, RdB-k35/sLRP6E1E2, both expressing sLRP6E1E2. sLRP6E1E2 prevented Wnt-mediated stabilization of cytoplasmic β-catenin, decreased Wnt/β-catenin signaling and cell proliferation via the mitogen-activated protein kinase, and phosphatidylinositol 3-kinase pathways. sLRP6E1E2 induced apoptosis, cytochrome c release, and increased cleavage of PARP and caspase-3. sLRP6E1E2 suppressed growth of the human lung tumor xenograft, and reduced motility and invasion of cancer cells. In addition, sLRP6E1E2 upregulated expression of epithelial marker genes, while sLRP6E1E2 downregulated mesenchymal marker genes. Taken together, sLRP6E1E2, by inhibiting interaction between Wnt and its receptor, suppressed Wnt-induced cell proliferation and epithelial-to-mesenchymal transition.