Interactions between proteins and genes are considered essential in
the description of biomolecular phenomena, and networks of interactions
are applied in a system's biology approach. Recently, many studies have
sought to extract information from biomolecular text using natural language
processing technology. Previous studies have asserted that linguistic
information is useful for improving the detection of gene interactions.
In particular, syntactic relations among linguistic information are good
for detecting gene interactions. However, previous systems give a reasonably
good precision but poor recall. To improve recall without sacrificing
precision, this paper proposes a three-phase method for detecting gene
interactions based on syntactic relations. In the first phase, we retrieve
syntactic encapsulation categories for each candidate agent and target.
In the second phase, we construct a verb list that indicates the nature of
the interaction between pairs of genes. In the last phase, we determine
direction rules to detect which of two genes is the agent or target. Even
without biomolecular knowledge, our method performs reasonably well using
a small training dataset. While the first phase contributes to improve
recall, the second and third phases contribute to improve precision. In
the experimental results using ICML 05 Workshop on Learning Language
in Logic (LLL05) data, our proposed method gave an F-measure of 67.2% for the test data, significantly outperforming previous methods. We also
describe the contribution of each phase to the performance.
Primary malignant melanoma of the anterior mediastinum is extremely rare, accounting for 0.1-0.5% of all primary malignant neoplasms. These tumors may be mistakenly diagnosed as lymphomas, thymic carcinomas and malignant germ-cell tumors of the mediastinum. We describe two cases of primary malignant melanomas of the anterior mediastinum and report their CT and pathology findings.
Mediastinal neoplasm; Mediastinal melanoma; Malignant melanoma; Anterior mediastinum; CT
The major inducible 70-kDa heat shock protein (hsp70) is host protective in a mouse model of measles virus (MeV) brain infection. Transgenic constitutive expression of hsp70 in neurons, the primary target of MeV infection, abrogates neurovirulence in neonatal H-2d congenic C57BL/6 mice. A significant level of protection is retained after depletion of T lymphocytes, implicating innate immune mechanisms. The focus of the present work was to elucidate the basis for hsp70-dependent innate immunity using this model. Transcriptome analysis of brains from transgenic (TG) and nontransgenic (NT) mice 5 days after infection identified type I interferon (IFN) signaling, macrophage activation, and antigen presentation as the main differences linked to survival. The pivotal role of type I IFN in hsp70-mediated protection was demonstrated in mice with a genetically disrupted type I IFN receptor (IFNAR−/−), where IFNAR−/− eliminated the difference in survival between TG and NT mice. Brain macrophages, not neurons, are the predominant source of type I IFN in the virus-infected brain, and in vitro studies provided a mechanistic basis by which MeV-infected neurons can induce IFN-β in uninfected microglia in an hsp70-dependent manner. MeV infection induced extracellular release of hsp70 from mouse neuronal cells that constitutively express hsp70, and extracellular hsp70 induced IFN-β transcription in mouse microglial cells through Toll-like receptors 2 and 4. Collectively, our results support a novel axis of type I IFN-dependent antiviral immunity in the virus-infected brain that is driven by hsp70.
To evaluate the additional effect of sonoelastography on the radiologist's ability for distinguishing benign from malignant complex breast masses and to decide whether to perform biopsy by B-mode US.
Materials and Methods
One hundred eighteen complex breast masses (15 malignant lesions, 103 benign lesions) were included. Five blinded readers independently assessed the likelihood of the malignancy score from 1 to 5 for two data sets (B-mode ultrasound alone and B-mode ultrasound with sonoelastography). Elasticity scores were categorized as 0, 1, or 2 based on the degree and distribution of strain of the echogenic component within complex masses. The readers were asked to downgrade the likelihood of the malignancy score when an elasticity score of 0 was assigned and to upgrade the likelihood of the malignancy score when an elasticity score of 2 was assigned. The likelihood of the malignancy score was maintained as it was for the lesions with an elasticity score of 1. The Az values, sensitivities, and specificities were compared.
The Az value of B-mode ultrasound with sonoelastography (mean, 0.863) was greater than that of B-mode ultrasound alone (mean, 0.731; p = 0.001-0.007) for all authors. The specificity of B-mode ultrasound with sonoelastography (mean, 37.1%) was greater than that of B-mode ultrasound alone (mean, 3.8%; p < 0.001) for all readers. The addition of sonoelastography led to changes in decisions. A mean of 33.6% of benign masses were recommended for follow-up instead of biopsy.
For complex breast masses, sonoelastography allows increase in both the accuracy in distinguishing benign from malignant lesions and the specificity in deciding whether to perform biopsy.
Breast; Neoplasm; Sonoelastography
Peroxisome proliferator-activated receptor gamma (PPARγ) belongs to a nuclear receptor superfamily; members of which play key roles in the control of body metabolism principally by acting on adipose tissue. Ligands of PPARγ, such as thiazolidinediones, are widely used in the treatment of metabolic syndromes and type 2 diabetes mellitus (T2DM). Although these drugs have potential benefits in the treatment of T2DM, they also cause unwanted side effects. Thus, understanding the molecular mechanisms governing the transcriptional activity of PPARγ is of prime importance in the development of new selective drugs or drugs with fewer side effects. Recent advancements in molecular biology have made it possible to obtain a deeper understanding of the role of PPARγ in body homeostasis. The transcriptional activity of PPARγ is subject to regulation either by interacting proteins or by modification of the protein itself. New interacting partners of PPARγ with new functions are being unveiled. In addition, post-translational modification by various cellular signals contributes to fine-tuning of the transcriptional activities of PPARγ. In this review, we will summarize recent advancements in our understanding of the post-translational modifications of, and proteins interacting with, PPARγ, both of which affect its transcriptional activities in relation to adipogenesis.
PPARγ; coregulator; post-translational modifications; transcriptional activity; adipogenesis; metabolic syndrome
To investigate CT and 18F-flurodeoxyglucose (18F-FDG) positron-emission tomography/CT findings of primary endobronchial marginal zone B-cell lymphoma of the bronchus-associated lymphoid tissue (BALT).
Materials and Methods
From June 2006 through April 2012, seven patients (six female, one male; age range, 21-61 years; mean age, 49 years) were examined who were pathologically diagnosed with the primary endobronchial marginal zone B-cell lymphoma of BALT. We evaluated the locations and characteristics of the lesions on CT and 18F-FDG-PET/CT scans. The lesions were classified into the following three patterns: 1) solitary intraluminal nodule; 2) several tiny nodular protrusions; and 3) diffuse wall thickening.
A solitary intraluminal nodule was observed in four patients (57.1%), several tiny nodular protrusion in two patients (28.6%), and diffuse wall thickening in one patient (14.3%). The lesions were categorized into 3 major locations: confined to the trachea (n = 3), confined to the lobar bronchus (n = 2), and diffuse involvement of the trachea and both main bronchi (n = 2). All lesions demonstrated homogeneous iso-attenuation as compared with muscle on pre- and post-enhancement scans. Secondary findings in the lungs (n = 3; 42.9%) included postobstructive lobar atelectasis (n = 1), air trapping (n = 1), and pneumonia (n = 1). On 18F-FDG-PET/CT (n = 5), 4 lesions showed homogeneous uptake with maximum standardized uptake values (mSUV), ranging 2.3-5.7 (mean mSUV: 3.3). One lesion showed little FDG uptake.
Primary endobronchial marginal zone B-cell lymphoma of the BALT manifests as three distinct patterns on CT, with the solitary intraluminal nodule presenting as the main pattern. Most lesions demonstrate homogeneous but weak FDG uptake on 18F-FDG-PET/CT.
Bronchial neoplasms; Lymphoma, non-Hodgkin/diagnosis; Lymphoma, non-Hodgkin/radiotherapy; Bronchus-associated lymphoid tissue; Tomography, X-ray computed; Positron-emission tomography
Bortezomib administration leads to a transient decrease in CD4+ T cells, increasing the susceptibility to opportunistic infections. The activation and proliferation of CD4+ T cells are particularly important in the host's defense against tuberculosis infection. The aim of this study was to determine the incidence and clinical significance of tuberculosis infection in patients with multiple myeloma (MM) treated with a bortezomib-containing regimen.
We retrospectively investigated the incidence of Mycobacterium tuberculosis in 115 patients with MM who were given a bortezomib-containing regimen and studied the disease prognosis.
All patients received chemotherapy prior to bortezomib administration, and the median duration from diagnosis to bortezomib administration was 12.4 months (range, 0.2-230). We diagnosed tuberculosis in 8 patients (8/115, 7%): 7 patients had a pulmonary granulomatous lesion prior to chemotherapy and 1 developed reactivation of tuberculosis, but none of them died of uncontrolled tuberculosis infection. In 50% of patients with tuberculosis, bortezomib-containing therapy was interrupted. This resulted in significantly lower response rates to the bortezomib-containing therapy (P<0.05) and significantly shorter overall survival times amongst tuberculosis vs. non-tuberculosis patients (P=0.017).
Tuberculosis infection was not uncommon among the patients with MM who were treated with bortezomib-containing therapy, and tuberculosis infection in these patients resulted in an interruption of bortezomib administration, which significantly affected patient outcomes. Therefore, early diagnosis and treatment of tuberculosis infection are critical to avoid worsening outcomes in such patients.
Bortezomib; Mycobacterium tuberculosis; Multiple myeloma
The role of extracellular 70 kDa heat shock protein 70 (ehsp70) in central nervous system inflammation is vastly understudied, despite evidence supporting the ability to drive a pro-inflammatory state. We investigated the presence of ehsp70 in cerebrospinal fluid (CSF) and serum of dogs with Steroid Responsive Meningitis-Arteritis (SRMA), with the hypothesis that an ehsp70 response would occur, and might play a role in the pathogenesis of this disease. Samples from 30 dogs acutely affected with SRMA, and 30 dogs treated with corticosteroids and currently in clinical remission from SRMA were compared with normal dogs. Serum and CSF concentrations of ehsp70 were quantified using an enzyme-linked immunosorbent assay. An ehsp70 response occurred in the CSF of dogs with SRMA and this response was attenuated by corticosteroid treatment. There was no correlation between serum and CSF concentrations of ehsp70, supporting local production and release of ehsp70 and not simply leakage from serum. Dogs with SRMA thus represent a powerful spontaneous model by which to study the role of ehsp70 in CNS inflammation.
Inflammation; Steroid Responsive Meningitis-Arteritis; Cerebrospinal fluid; Heat shock protein 70; Meningoencephalitis; Myelitis
Taurine is one of most abundant free amino acids in mammalian tissue. It has been used for various health functional foods as a main ingredient in food industry. A 33-year-old female patient repeatedly experienced generalized itching, urticaria, dyspnea and dizziness after drinking taurine-containing drinks. The patient showed positive response to oral challenge tests with taurine-containing drinks. The patient also showed positive response with synthetic taurine but not with natural taurine. Skin prick test and basophil activation test with the synthetic taurine were negative. To our knowledge, there has been no report of taurine-induced hypersensitivity reactions. We herein report the first case of taurine-containing drink induced anaphylaxis, especially by synthetic taurine.
Anaphylaxis; Taurine; Energy drinks
Wheat is a common cause of food allergy. Wheat-induced anaphylaxis (WIA) and wheat-dependent exercise induced anaphylaxis (WDEIA) are severe forms of immunoglobulin E (IgE) mediated allergic reaction to wheat protein. As the diagnosis of WIA or WDEIA is not easy because of the risk of oral challenge, identification of specific IgE of various wheat proteins is helpful for diagnosis. In Korea, there are only a few reports on WIA in adults. We report six cases of WIA diagnosed on the basis of clinical history and specific IgE of wheat proteins or provocation test. For immunologic evaluation of severe wheat allergy including WIA and WDEIA, it is important to measure specific IgE to each component of wheat including gluten and ω-5 gliadin not just measuring wheat-specific IgE.
Wheat allergy; Anaphylaxis; Immunoglobulin E
3T3-L1 adipocytes express the B-cell-activating factor (BAFF) and three different BAFF receptors (BAFF-Rs). Furthermore, BAFF expression is regulated by inflammatory modulators, such as tumor necrosis factor-α and rosiglitazone. Here we investigated the function of BAFF in 3T3-L1 adipocytes and RAW 264.7 macrophages. We examined adipokine expression in 3T3-L1 adipocytes treated with 10 ng ml−1 BAFF. We also examined inflammatory molecule expression in RAW 264.7 macrophages treated with 10 or 100 ng ml−1 BAFF. We examined BAFF expression in the coculture of 3T3-L1 adipocytes and RAW 264.7 macrophages, as well as in white adipose tissue (WAT) of diet-induced obese (DIO) mice. We found that BAFF decreases leptin and adiponectin expression, but increases the expression of proinflammatory adipokines monocyte chemotactic protein-1, interleukin-6 (IL-6), cyclooxygenase-2 (COX-2) and haptoglobin. Coculturing the two cell types resulted in increased BAFF mRNA and protein expression, as well as modulation of BAFF-R mRNA expression in both cell types. These data indicate that BAFF might mediate adipocyte and macrophage interaction. When RAW 264.7 macrophages were treated with BAFF, BAFF-R expression was modulated as in coculture, and nitric oxide synthase and IL-6 expression increased. BAFF expression also increased in WAT of DIO mice. We propose that BAFF can regulate adipokine expression and possibly mediate adipocyte and macrophage interaction.
3T3-L1 adipocytes; B-cell-activating factor; coculture; diet-induced obesity; inflammation
Osteosarcomas usually occur as secondary tumors after radiation therapy or chemotherapy. Without a history of irradiation to the head and neck area, primary osteosarcoma of the turbinate is extremely rare. We report here a rare case of primary turbinate osteosarcoma presenting as a relatively small, well-circumscribed, turbinate mass. Its appearance mimicked a benign nasal mass like mucocele and polyp. We also reviewed the previously reported cases of tumor arising from turbinate.
Osteosarcoma; Turbinate; Primary
IMR is useful for assessing the microvascular dysfunction after primary percutaneous coronary intervention (PCI). It remains unknown whether index of microcirculatory resistance (IMR) reflects the functional outcome in patients with anterior myocardial infarction (AMI) with or without microvascular obstruction (MO).This study was performed to evaluate the clinical value of the IMR for assessing myocardial injury and predicting microvascular functional recovery in patients with AMI undergoing primary PCI. We enrolled 34 patients with first anterior AMI. After successful primary PCI, the mean distal coronary artery pressure (Pa), coronary wedge pressure (Pcw), mean aortic pressure (Pa), mean transit time (Tmn), and IMR (Pd * hyperemic Tmn) were measured. The presence and extent of MO were measured using cardiac magnetic resonance image (MRI). All patients underwent follow-up echocardiography after 6 months. We divided the patients into two groups according to the existence of MO (present; n = 16, absent; n = 18) on MRI. The extent of MO correlated with IMR (r = 0.754; P < 0.001), Pcw (r = 0.404; P = 0.031), and Pcw/Pd of infarct-related arteries (r = 0.502; P = 0.016). The IMR was significantly correlated with the ΔRegional wall motion score index (r = -0.61, P < 0.01) and ΔLeft ventricular ejection fraction (r = -0.52, P < 0.01), implying a higher IMR is associated with worse functional improvement. Therefore, Intracoronary wedge pressures and IMR, as parameters for specific and quantitative assessment of coronary microvascular dysfunction, are reliable on-site predictors of short-term myocardial viability and Left ventricle functional recovery in patients undergoing primary PCI for AMI.
Acute Anterior Wall Myocardial Infarction; Coronary Occlusion; Capillary Resistance; Magnetic Resonance Imaging
A small subset of patients with nodular lymphocyte-predominant Hodgkin's lymphoma (NLPHLs) develop a non-Hodgkin lymphoma either concurrently or subsequently, usually T-cell/histiocyte-rich B-cell lymphomas (T/HRBCL), which are subtypes of diffuse large B-cell lymphomas (DLBCL). The standard treatment of DLBCL patients is rituximab-based chemotherapy with cyclophosphamide, adriamycin, vincristine and prednisolone. However, the administration of this chemotherapy regimen to patients with DLBCL arising in NLPHL brings concern about the cardiac toxicity of anthracycline because the majority of these patients had already received anthracycline-based chemotherapy with doxorubicin, bleomycin, vinblastine and dacarbazine at the time of NLPHL. Herein, we report 2 patients with sequential transformation of NLPHL to T/HRBCL. They initially presented with limited-stage NLPHL and subsequently developed T/HRBCL after 16 and 8 months, respectively. At the time of T/HRBCL, they were treated with rituximab, ifosfamide, carboplatin and etoposide, and complete responses were obtained.
Transformation; Nodular lymphocyte-predominant Hodgkin's lymphoma; T-cell/histiocyte-rich B-cell lymphoma; Chemotherapy
A 66-year-old female presented with a 1-month history of dyspepsia. An initial upper gastrointestinal endoscopy with biopsy revealed a low-grade mucosa-associated lymphoid tissue (MALT) lymphoma. A rapid urease test was positive for Helicobacter pylori. Endoscopic ultrasound (EUS) and computed tomography (CT) revealed a 30×15-mm lymph node (LN) in the subcarinal area. Histopathologic and phenotypic analyses of the biopsy specimens obtained by EUS-guided fine-needle aspiration revealed a MALT lymphoma, and the patient was diagnosed with a stage 4E gastric MALT lymphoma. One year after H. pylori eradication, the lesion had disappeared, as demonstrated by endoscopy with biopsy, CT, fusion whole-body positron emission tomography, and EUS. Here, we describe a patient with gastric MALT lymphoma that metastasized to the mediastinal LN and regressed following H. pylori eradication.
Marginal zone B-cell lymphoma; Stomach
Pumpkins have considerable variation in nutrient contents depending on the cultivation environment, species, or part. In this study, the general chemical compositions and some bioactive components, such as tocopherols, carotenoids, and β-sitosterol, were analyzed in three major species of pumpkin (Cucurbitaceae pepo, C. moschata, and C. maxima) grown in Korea and also in three parts (peel, flesh, and seed) of each pumpkin species. C. maxima had significantly more carbohydrate, protein, fat, and fiber than C. pepo or C. moschata (P < 0.05). The moisture content as well as the amino acid and arginine contents in all parts of the pumpkin was highest in C. pepo. The major fatty acids in the seeds were palmitic, stearic, oleic, and linoleic acids. C. pepo and C. moschata seeds had significantly more γ-tocopherol than C. maxima, whose seeds had the highest β-carotene content. C. pepo seeds had significantly more β-sitosterol than the others. Nutrient compositions differed considerably among the pumpkin species and parts. These results will be useful in updating the nutrient compositions of pumpkin in the Korean food composition database. Additional analyses of various pumpkins grown in different years and in different areas of Korea are needed.
Pumpkins; macronutrients; tocopherols; carotenoids; β-sitosterol
Abdominal computed tomography (CT) findings of malaria are not well-known even though malaria is a serious infectious disease. To identify abdominal CT findings, we selected 34 of 405 patients who had a positive peripheral blood smear for Plasmodium vivax and had underwent abdominal CT as the malaria group. We also selected 80 patients who had fever and a negative peripheral blood smear as the control group and 120 healthy people as the normal group. We reviewed and analyzed their medical records and CT findings retrospectively. The mean spleen and liver length were significantly larger in the malaria group and the incidence of splenomegaly, splenic focal low attenuation, and spontaneous splenic rupture were much higher in the malaria group (P < 0.05). Although abdominal CT is not an indispensable tool for diagnosis, these CT findings will help in the diagnosis of malaria in patients with fever.
Non-alcoholic fatty liver disease (NAFLD) is characterized by fat accumulation in the liver not due to alcohol abuse. NAFLD is accompanied by variety of symptoms related to metabolic syndrome. Although the metabolic link between NAFLD and insulin resistance is not fully understood, it is clear that NAFLD is one of the main cause of insulin resistance. NAFLD is shown to affect the functions of other organs, including pancreas, adipose tissue, muscle and inflammatory systems. Currently efforts are being made to understand molecular mechanism of interrelationship between NAFLD and insulin resistance at the transcriptional level with specific focus on post-translational modification (PTM) of transcription factors. PTM of transcription factors plays a key role in controlling numerous biological events, including cellular energy metabolism, cell-cycle progression, and organ development. Cell type- and tissue-specific reversible modifications include lysine acetylation, methylation, ubiquitination, and SUMOylation. Moreover, phosphorylation and O-GlcNAcylation on serine and threonine residues have been shown to affect protein stability, subcellular distribution, DNA-binding affinity, and transcriptional activity. PTMs of transcription factors involved in insulin-sensitive tissues confer specific adaptive mechanisms in response to internal or external stimuli. Our understanding of the interplay between these modifications and their effects on transcriptional regulation is growing. Here, we summarize the diverse roles of PTMs in insulin-sensitive tissues and their involvement in the pathogenesis of insulin resistance.
α-Lipoic acid and L-carnosine are powerful antioxidants and are often used as a health supplement and as an ergogenic aid. The objective of this study was to investigate the effects of α-lipoic acid and/or L-carnosine supplementation on antioxidant activity in serum, skin, and liver of rats and blood lipid profiles for 6 weeks. Four treatment groups received diets containing regular rat chow diet (control, CON), 0.5% α-lipoic acid (ALA), 0.25% α-lipoic acid + 0.25% L-carnosine (ALA + LC), or 0.5% L-carnosine (LC). Superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and lipid peroxidation products, malondialdehyde (MDA) concentrations, were analyzed in serum, skin, and liver. Blood lipid profiles were measured, including triglycerides (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C). Skin and liver SOD activities of the ALA and LC groups were higher than those of the CON group (P < 0.05), but serum SOD activity was higher only in the LC group compared to that in the CON group (P < 0.05). Additionally, only liver GSH-Px activity in the LC group was higher than that of the CON and the other groups. Serum and skin MDA levels in the ALA and LC groups were lower than those in the CON group (P < 0.05). Serum TG and TC in the ALA and ALA + LC groups were lower than those in the CON and LC groups (P < 0.05). The HDL-C level in the LC group was higher than that in any other group (P < 0.05). LDL-C level was lower in the ALA + LC and LC groups than that in the CON group (P < 0.05). Thus, α-lipoic acid and L-carnosine supplementation increased antioxidant activity, decreased lipid peroxidation in the serum, liver, and skin of rats and positively modified blood lipid profiles.
α-Lipoic Acid; L-carnosine; antioxidant activity; glutathione peroxidase; superoxide dism
Peroxiredoxins (Prxs) play an important role in regulating cellular differentiation and proliferation in several types of mammalian cells. This report examined the expression of Prx isotype I in the rat ovary after hormone treatment.
Immature rats were injected with 10 IU of pregnant mare's serum gonadotropin (PMSG) to induce the growth of multiple preovulatory follicles and 10 IU of human chorionic gonadotropin (hCG) to induce ovulation. Immature rats were also treated with diethylstilbestrol (DES), an estrogen analogue, to induce the growth of multiple immature follicles. Northern blot analysis was performed to detect gene expression. Cell-type specific localization of Prx I mRNA were detected by in situ hybridization analysis.
During follicle development, ovarian Prx I gene expression was detected in 3-day-old rats and had increased in 21-day-old rats. The levels of Prx I mRNA slightly declined one to two days following treatment with DES. A gradual increase in Prx I gene expression was observed in ovaries obtained from PMSG-treated immature rats. Furthermore, hCG treatment of PMSG-primed rats resulted in a gradual stimulation of Prx I mRNA levels by 24 hours (2.1-fold increase) following treatment, which remained high until 72 hours following treatment. In situ hybridization analysis revealed the expression of the Prx I gene in the granulosa cells of PMSG-primed ovaries and in the corpora lutea of ovaries stimulated with hCG for 72 hours.
These results demonstrate the gonadotropin and granulosa cell-specific stimulation of Prx I gene expression, suggesting its role as a local regulator of follicle development.
Peroxiredoxins; Gene Expression; Ovarian Follicle; Gonadotropin Regulation; Rats, Sprague-Dawley
Eotaxin is an important inflammatory chemokine in eosinophil chemotaxis and activation and, thus, is implicated in asthma. Recently, obesity was associated with an increased prevalence of asthma, but the relationship between obesity and eotaxin expression has only been partially understood in obese mice and human studies. Therefore, we studied the expression patterns of eotaxin in 3T3-L1 preadipocytes/adipocytes to determine whether eotaxin levels are influenced by body weight gain and/or reduction in diet-induced obese mice. First, we investigated eotaxin expression during differentiation in 3T3-L1 adipocytes. Then, we treated 3T3-L1 preadipocytes/adipocytes with tumor necrosis factor-alpha (TNF-α), eotaxin, interleukin (IL)-4, IL-5, or leptin. To examine the effects of weight loss in high-fat diet induced obese mice, we fed C57BL/6 mice a high-fat diet or a normal diet for 26 weeks. Then, half of the high-fat diet group were fed a normal diet until 30 weeks to reduce weight. Epididymal adipose tissue, visceral adipose tissue, serum, and bronchoalveolar fluid of mice were examined for eotaxin expression. The results showed that eotaxin expression levels increased with adipocyte differentiation and that more eotaxin was expressed when the cells were stimulated with TNF-α, eotaxin, IL-4, IL-5, or leptin. An in vivo study showed that eotaxin levels were reduced in visceral adipose tissues when high-fat diet fed mice underwent weight loss. Taken together, these results indicate a close relationship between eotaxin expression and obesity as well as weight loss, thus, they indirectly show a relation to asthma.
Eotaxin; 3T3-L1 adipocytes; obesity; weight loss; asthma
The dissemination of cancer cells from a primary tumor is conventionally viewed as a unidirectional process that culminates with the metastatic colonization of distant organs. Here we show that circulating tumor cells (CTCs) can also colonize their tumors of origin, in a process that we call “tumor self-seeding”. Self-seeding of breast cancer, colon cancer, and melanoma tumors in mice is preferentially mediated by aggressive CTCs, including those with bone, lung or brain metastatic tropism. The tumor-derived cytokines IL-6 and IL-8 acted as CTC attractants and the poor-prognosis markers MMP1/collagenase-1 and the actin cytoskeleton component fascin-1 as mediators of CTC infiltration into mammary tumors. Self-seeding can accelerate tumor growth, angiogenesis, and stromal recruitment through seed-derived factors including, in a breast cancer model, the chemokine CXCL1. Tumor self-seeding could explain the relationships between anaplasia, tumor size, vascularity and prognosis, and local recurrence seeded by disseminated cells following ostensibly complete tumor excision.
Benign bronchoesophageal fistula (BEF) is a rare condition that is usually treated surgically; however, less invasive endoscopy procedures have been attempted to overcome the disadvantages of surgery. The aim of this study was thus to determine the results of endoscopic management as a primary treatment in patients with BEF.
We retrospectively analyzed data from 368 patients with BEF who were treated at a tertiary care, academic medical center between January 2000 and August 2009.
Benign causes were found for only 18 of the 368 patients. Of these, seven were treated endoscopically and the others by surgery or other methods. The first endoscopy procedures failed in all seven patients, with second trials of endoscopy performed in four patients at a median of 8 days (range, 3 to 11 days) after the first procedure. The second endoscopic procedure was successful in two out of four patients; one patient showed no recurrence of the fistula, whereas the second patient experienced a recurrence after 24 months. All patients underwent successful surgical procedures after the failure of endoscopic treatment, with no further recurrences.
Although we observed a low rate of success for primary endoscopic treatment of benign BEF, the invasive nature of surgery suggests the need for a prospective study with a large number of patients to evaluate the efficacy of less invasive procedures such as endoscopic treatment.
Esophageal fistula; Endoscopy; Fibrin glue
Ventilating patients with acute respiratory distress syndrome (ARDS) in the prone position has been shown to improve arterial oxygenation, but prolonged prone positioning frequently requires continuous deep sedation, which may be harmful to patients. We evaluated the meaning of early gas exchange in patients with severe ARDS under prolonged (≥ 12 hours) prone positioning.
We retrospectively studied 96 patients (mean age, 60.1 ± 15.6 years; 75% men) with severe ARDS (PaO2/FiO2 ≤ 150 mmHg) admitted to a medical intensive care unit (MICU). The terms "PaO2 response" and "PaCO2 response" represented responses that resulted in increases in the PaO2/FiO2 ratio of ≥ 20 mmHg and decreases in PaCO2 of ≥ 1 mmHg, respectively, 8 to 12 hours after first placement in the prone position.
The mean duration of prone positioning was 78.5 ± 61.2 hours, and the 28-day mortality rate after MICU admission was 56.3%. No significant difference in clinical characteristics was observed between PaO2 and PaCO2 responders and non-responders. The PaO2 responders after prone positioning showed an improved 28-day outcome, compared with non-responders by Kaplan-Meier survival estimates (p < 0.05 by the log-rank test), but the PaCO2 responders did not.
Our results suggest that the early oxygenation improvement after prone positioning might be associated with an improved 28-day outcome and may be an indicator to maintain prolonged prone positioning in patients with severe ARDS.
Respiratory distress syndrome, acute; Prone position; PaO2 response; Mortality
Nurr1 is a transcription factor specific for the development and maintenance of the midbrain dopamine (DA) neurons. Exogenous Nurr1 in neural precursor (NP) cells induces the differentiation of DA neurons in vitro that are capable of reversing motor dysfunctions in a rodent model for Parkinson disease. The promise of this therapeutic approach, however, is unclear due to poor cell survival and phenotype loss of DA cells after transplantation. We herein demonstrate that Nurr1 proteins undergo ubiquitin-proteasome-system-mediated degradation in differentiating NP cells. The degradation process is activated by a direct Akt-mediated phosphorylation of Nurr1 proteins and can be prevented by abolishing the Akt-target sequence in Nurr1 (Nurr1Akt). Overexpression of Nurr1Akt in NP cells yielded DA neurons in which Nurr1 protein levels were maintained for prolonged periods. The sustained Nurr1 expression endowed the Nurr1Akt-induced DA neurons with resistance to toxic stimuli, enhanced survival, and sustained DA phenotypes in vitro and in vivo after transplantation.
Nurr1; Dopamine neuron; Ubiquitin-proteasome-system; Cell survival; Midbrain; Akt