Esophageal leiomyosarcoma is a rare tumor that accounts for less than 1% of all malignant esophageal tumors. Esophageal leiomyosarcoma combined with squamous cell carcinoma is even rarer than solitary leiomyosarcoma. We experienced a case of leiomyosarcoma combined with squamous cell carcinoma that progressed very rapidly.
Leiomyosarcoma; Carcinoma; Squamous cell; Esophagus; Sarcoma
A 38-year-old female with a history of alcoholic liver cirrhosis visited our hospital with a massive hematochezia. An esophagogastroduodenoscopy did not demonstrate any bleeding source, and a colonoscopy showed a massive hemorrhage in the ascending colon but without an obvious focus. The source of the bleeding could not be found with a mesenteric artery angiography. We performed an enhanced abdominal computed tomography, which revealed a distal ascending colonic varix, and assumed that the varix was the source of the bleeding. We performed a venous coil embolization and histoacryl injection to obliterate the colon varix. The intervention appeared to be successful because the vital signs and hemoglobin laboratory data remained stable and because the hematochezia was no longer observed. We report here on a rare case of colonic variceal bleeding that was treated with venous coil embolization.
Colon ascending; Varicose veins; Liver cirrhosis; Therapeutic embolization
Myostracum, which is connected from the umbo to the edge of a scar, is not a single layer composed of prismatic layers, but a hierarchically complex multilayered shape composed of minerals and an organic matrix. Through the analysis of the secondary structure, the results revealed that a β-antiparallel structure was predominant in the mineral phase interface between the myostracum (aragonite) and bottom folia (calcite). After the complete decalcification and deproteinization, the membrane obtained from the interface between the myostracum buried in upper folia, and the bottom folia was identified as chitin. The transitional zone in the interface between the adductor muscle scar and folia are verified. The myostracum disappeared at the edge of the scar of the posterior side. From this study, the entire structure of the myostracum from the adult oyster shell of Crassostrea gigas could be proposed.
Angiosarcoma is a rare tumor that account for less than 1% of all sarcomas. Although hepatic angiosarcoma usually presents with unspecific symptoms, it rapidly progresses and has a high mortality. We report a rare case of primary hepatic angiosarcoma manifested as recurrent hemoperitoneum.
Angiosarcoma; Hemoperitoneum; Primary hepatic tumor
AIM: To evaluate the efficacy of short-term overlap lamivudine therapy with adefovir in patients with lamivudine-resistant and naïve chronic hepatitis B, we compared patients receiving overlap therapy with those receiving adefovir alone.
METHODS: Eighty patients who had received lamivudine treatment for various periods and had a lamivudine-resistant liver function abnormality were enrolled. Forty of these patients received adefovir treatment combined with lamivudine treatment for ≥ 2 mo, while the other 40 received adefovir alone. We assessed the levels of hepatitis B virus (HBV) DNA at 0, 12 and 48 wk and serum alanine aminotransferase (ALT) levels after 0, 12, 24 and 48 wk of adefovir treatment in each group.
RESULTS: We found serum ALT became normalized in 72 (87.5%) of the 80 patients, and HBV DNA decreased by ≥ 2 log10 copies/mL in 60 (75%) of the 80 patients at the end of a 48-wk treatment. HBV DNA levels were not significantly different between the groups. The improvements in serum ALT were also not significantly different between the two groups.
CONCLUSION: These findings suggest short-term overlap lamivudine treatment results in no better virological and biological outcomes than non-overlap adefovir monotherapy.
Adefovir dipivoxil; Chronic hepatitis B; Hepatitis B virus DNA; Overlap
Dendritic cells (DC) in the gut promote immune tolerance by expressing retinal dehydrogenase (RALDH), an enzyme that promotes retinoic acid (RA), which aids differentiation of inducible Foxp3+ Treg (iTreg) in the intestinal mucosa. How RALDH expression is regulated is unclear. We found that 4-1BB (CD137), a member of the TNFR family, together with CD103, marked mesenteric lymph node DC with the highest level of RALDH activity, and ligation of 4-1BB maintained RALDH expression in these gut DC. Moreover, 4-1BB signals synergized with those through TLR2 or GM-CSFR to promote RALDH activity in undifferentiated DC. Correspondingly, 4-1BB-deficient mice were impaired in their ability to generate iTreg in the GALT when exposed to oral antigen, and 4-1BB-deficient mesenteric lymph node DC displayed weak RALDH activity and were poor at promoting iTreg development. Thus, our data demonstrate a novel activity of 4-1BB in controlling RALDH expression and the regulatory activity of DC.
A variety of telomere protection programs are utilized to preserve telomere structure. However, the complex nature of telomere maintenance remains elusive. The Timeless protein associates with the replication fork and is thought to support efficient progression of the replication fork through natural impediments, including replication fork block sites. However, the mechanism by which Timeless regulates such genomic regions is not understood. Here, we report the role of Timeless in telomere length maintenance. We demonstrate that Timeless depletion leads to telomere shortening in human cells. This length maintenance is independent of telomerase, and Timeless depletion causes increased levels of DNA damage, leading to telomere aberrations. We also show that Timeless is associated with Shelterin components TRF1 and TRF2. Timeless depletion slows telomere replication in vitro, and Timeless-depleted cells fail to maintain TRF1-mediated accumulation of replisome components at telomeric regions. Furthermore, telomere replication undergoes a dramatic delay in Timeless-depleted cells. These results suggest that Timeless functions together with TRF1 to prevent fork collapse at telomere repeat DNA and ensure stable maintenance of telomere length and integrity.
TRF1; replication efficiency; telomere; telomere aberration; the fork protection complex; timeless
To report the three-year outcomes of macular laser photocoagulation following intravitreal injection of triamcinolone acetonide (IVTA) for diffuse diabetic macular edema (DME).
A prospective, randomized controlled study was completed. Eighty-six eyes of 74 patients with diffuse DME were randomized into two groups. Eyes assigned to the combination group (n = 48) were subjected to macular laser photocoagulation three weeks after IVTA. Eyes in the IVTA group (n = 38) underwent IVTA alone. Central macular thickness was measured by optical coherence tomography, and the number of additional treatments and mean time to recurrence were assessed.
Thirty-seven eyes in the combination group and 26 eyes in the IVTA group completed the three-year follow-up. Recurrence of DME after initial treatment was not observed for nine of the 37 (24.3%) eyes in the combination group or for one of the 26 (3.9$) eyes in the IVTA group (p = 0.028). DME was absent for 19.9 months after treatment in the combination group compared to 10.3 months in the IVTA group (p = 0.027). The mean number of additional treatments was 0.92 in the combination group and 1.88 in the IVTA group (p = 0.001).
Results in the subset of subjects who completed the three-year follow-up demonstrated that laser photocoagulation following IVTA is more effective than IVTA monotherapy for diffuse DME. Combination therapy required fewer additional treatments and resulted in a lower recurrence rate than IVTA monotherapy.
Diabetic retinopathy; Intravitreal injections; Laser therapy; Macular edema; Triamcinolone
A laparoscopic transperitoneal approach allowed for resection of a pulmonary sequestration avoiding an open thoracoabdominal incision.
Pulmonary sequestration is a rare cystic malformation composed of bronchopulmonary tissue that is discontinuous from the tracheobronchial tree and has an anomalous systemic blood supply. We present a case of a 40-y-old male who presented with an extralobar pulmonary sequestration and underwent a laparoscopic retroperitoneal mass excision. Preoperative imaging revealed a large 11.3-cm retroperitoneal tumor consisting of a multiloculated cystic lesion. The patient was discharged home, and at 3-mo follow-up no complaints were reported.
Laparoscopy; Bronchopulmonary sequestration
The Bosniak renal cyst classification has been accepted by urologists and radiologists as a way of diagnosing cystic renal masses and determining the management approach. We report two cases of a renal cystic mass that showed a category change from category II on the basis of enhanced computed tomography to category IV after further gadolinium-enhanced magnetic resonance imaging. In both cases, the cysts were later confirmed as kidney cancer by pathology.
Cysts; Kidney; Magnetic resonance imaging
TGF-β can induce Foxp3+ inducible regulatory T cells (Treg) and also synergize with IL-6 and IL-4 to induce Th17 and Th9 cells. We now report that NO modulates TGF-β activity away from Treg but toward the Th1 lineage. NO potentiated Th1 differentiation in the presence of TGF-β in both IL-12–independent and –dependent fashions by augmenting IFN-γ–activated STAT-1 and T-bet. Differentiation into Treg, Th1, and Th17 lineages could be modulated by NO competing with other cofactors, such as IL-6 and retinoic acid. NO antagonized IL-6 to block TGF-β–directed Th17 differentiation, and together with IL-6, NO suppressed Treg development induced by TGF-β and retinoic acid. Furthermore, we show that physiologically produced NO from TNF and inducible NO synthase-producing dendritic cells can contribute to Th1 development predominating over Treg development through a synergistic activity induced when these cells cocluster with conventional dendritic cells presenting Ag to naive Th cells. This illustrates that NO is another cofactor allowing TGF-β to participate in development of multiple Th lineages and suggests a new mechanism by which NO, which is associated with protection against intracellular pathogens, might maintain effective Th1 immunity.
Here we report a case of central retinal artery occlusion after chiropractic manipulation on the neck. A 49-year old man presented at the hospital because of sudden visual loss in his right eye after chiropractic neck manipulation. He had received chiropractic manipulation of the neck by a chiropractor eight days prior. When he first visited us, his best corrected visual acuity in his right eye was hand motion. A full ophthalmic examination was performed. There was cherry-red spot in the macula in his right eye. We performed a fluorescein angiogram and cervical color Doppler. The arterio-venous transit time in the fluorescein angiogram was delayed, and we detected stenosis of the right internal carotid artery with diffuse atherosclerotic plaques in the right common carotid artery. We prescribed ginko biloba extract (Tanamin). Three years after his first visit, the best corrected visual acuity of his right eye was 20 / 200.
Chiropractic manipulation; Retinal artery occlusion
Signal transducers and activators of transcription (STATs) are a family of transcription factors that are activated in response to cytokines and growth factors. STAT3 activation has been implicated in modulating the activity of downstream mediators, such as Bcl-xL and matrix metalloproteinase-2 (MMP-2). The aim of this study was to investigate the immunohistochemical expression of STAT3, B-cell lymphoma-extra large (Bcl-xL), and MMP-2 proteins according to histopathological parameters in colon adenocarcinomas, including lymph node metastasis, tumor differentiation, the TNM stage and the tumor size.
Immunohistochemical staining with monoclonal STAT3, Bcl-xL, and MMP-2 antibodies was performed on paraffin-embedded specimens from 20 colon adenomas and 39 adenocarcinomas.
The expression of STAT3, Bcl-xL, and MMP-2 was increased in the adenocarcinomas as compared with the adenomas (p<0.001). STAT3 expression was stronger in tumors with a distant metastasis than in tumors without a distant metastasis (p=0.012). A larger tumor size was related to an increase in STAT3 expression (p=0.035).
STAT3, Bcl-xL, and MMP-2 may play important roles in the tumorigenesis of colorectal carcinoma. STAT3 may be indicative of a poor prognosis due to its correlation with distant metastases and a larger tumor size.
Colon; Signal transducers and activators of transcription 3; B-cell lymphoma-extra large; Matrix metalloproteinase-2
Two-component triblock magnetic nanorods with gold end blocks and nickel interior blocks have been synthesized and used as affinity templates for the simultaneous and efficient separation of a three component protein mixture. The gold blocks were selectively functionalized with 11-amino-1-undecanethiol, and then glutaraldehyde was used to covalently attach nitrostreptavidin to them. His-tagged proteins bind to the nickel block and biotin-tagged proteins bind to the functionalized gold ends, allowing one to separate a mixture of three proteins with a single material. Each surface bound protein can be released selectively using imidazole for the His-tagged protein and biotin for the biotinylated protein.
Biotin tagged protein; Histidine tagged protein; Magnetic nanorod; Protein separation
The initial requirement for the emergence of CMV-specific CD8+ T cells is poorly understood. Mice deficient in the cosignaling TNF superfamily member, 4-1BB, surprisingly developed exaggerated early CD8+ T-cell responses to mouse CMV (MCMV). CD8+ T cells directed against acute MCMV epitopes were enhanced, demonstrating that 4-1BB naturally antagonizes these primary populations. Paradoxically, 4-1BB-deficient mice displayed reduced accumulation of memory CD8+ T cells that expand during chronic/latent infection. Importantly, the canonical TNF-related ligand, 4-1BBL, promoted the accumulation of these memory CD8+ T cells, whereas suppression of acute CD8+ T cells was independent of 4-1BBL. These data highlight the dual nature of the 4-1BB/4-1BBL system in mediating both stimulatory and inhibitory cosignaling activities during the generation of anti-MCMV immunity.
4-1BB; CD8+ T cells; CMV; Memory
To describe the clinical characteristics of idiopathic juxtafoveal telangiectasis (IJT) in Koreans.
Medical records of 16 patients with IJT were analyzed during the period from 1997 to 2009. Diagnosis was based on biomicrosopic and fluorescein angiographic findings and the group was determined according to the Gass and Blodi classification.
We analyzed eight patients in group 1A (50%), two in group 1B (12.5%), and six in group 2A (37.5%). Diverse treatment modalities, such as macular laser photocoagulation, photodynamic therapy, intravitreal antiangiogenic agent, and steroid injection, were applied for macular edema in nine eyes; however, only two eyes showed visual improvement.
In this case series, group 1A was the most common. For macular edema related to IJT, current treatment strategies had no consistent effect.
Idiopathic Juxtafoveal Retinal Telangiectasia; Intravitreal Injection; Macular edema; Photochemotherapy
A respiratory monitoring system based on a quartz crystal microbalance (QCM) sensor with a functional film was designed and investigated. Porphyrins 5,10,15,20-tetrakis-(4-sulfophenyl)-21H,23H-porphine (TSPP) and 5,10,15,20-tetrakis-(4-sulfophenyl)-21H, 23H-porphine manganese (III) chloride (MnTSPP) used as sensitive elements were assembled with a poly(diallyldimethyl ammonium chloride) (PDDA). Films were deposited on the QCM resonators using layer-by-layer method in order to develop the sensor. The developed system, in which the sensor response reflects lung movements, was able to track human respiration providing respiratory rate (RR) and respiratory pattern (RP). The sensor system was tested on healthy volunteers to compare RPs and calculate RRs. The operation principle of the proposed system is based on the fast adsorption/desorption behavior of water originated from human breath into the sensor films deposited on the QCM electrode.
respiratory monitoring; quartz crystal microbalance; porphyrin based thin films; layer-by layer approach; sensor array
We here in report a case of bilateral endogenous endophthalmitis caused by Pantoea agglomerans (P. agglomerans) in a patient who had interstitial lung disease and was treated with oral corticosteroids. A 72-year-old man presented with decreased visual acuity in both eyes nine days after he received oral corticosteroids. He had marked uveitis, cataracts, and vitreous opacities. Cultures were taken of blood, aqueous humor, and vitreous. We initially suspected a fungal etiology and treated him with antifungal drugs; however, the intraocular disease progressed without improvement. Vitreous culture was positive for P. agglomerans. The patient underwent pars plana vitrectomy with cataract surgery bilaterally, followed by a 2-week course of antibiotics. The final visual acuity was 20/25 in the right eye and 20/200 in the left eye. This is the first report of bilateral endogenous endophthalmitis caused by P. agglomerans in Korea; it is also the first case reported outside of the United States.
The deleterious side-effects associated with a recent clinical trial with anti-CD28 super-agonist antibodies have questioned the use of reagents to costimulatory molecules in human therapy. We now show that sustained signaling from an agonist antibody to 4-1BB, a member of the tumor necrosis factor receptor (TNFR) superfamily, results in detrimental effects on immune cell homeostasis. Repeated anti-4-1BB treatment during the reconstitution of hematopoietic cells in irradiated mice engrafted with bone marrow, or in mice infected with vaccinia virus, induced abnormal apoptosis of pre- and immature-B cells in the bone marrow, and led to peripheral B cell depletion. Inhibition of B cell development was indirect and due to costimulation of CD8 T cells and dependent on IFN-γ. Moreover, anti-4-1BB also suppressed the development of NK and NKT cells, but in this case independently of T cells and IFN-γ. The altered NK cell homeostasis resulted from activation-induced cell death triggered by anti-4-1BB. These results show that hyper-costimulation elicits strong T cell immunity, but it can simultaneously distort immune homeostasis, suggesting that careful attention to activity, dose, and periodicity of treatment will be needed in any immunotherapeutic strategy with agonist antibodies to costimulatory molecules.
Costimulation; Hematopoiesis; T cells; B cells; Natural Killer cells
An enzymatic reaction was employed as a means to enhance the sensitivity of an immunosensor based on localized surface plasmon resonance (LSPR). The reaction occurs after intermolecular binding between an antigen and an antibody on gold nano-island (NI) surfaces. For LSPR sensing, the gold NI surface was fabricated on glass substrates using vacuum evaporation and heat treatment. The interferon-γ (IFN-γ) capture antibody was immobilized on the gold NIs, followed by binding of IFN-γ to the antibody. Subsequently, a biotinylated antibody and a horseradish peroxidase (HRP) conjugated with avidin were simultaneously introduced. A solution of 4-chloro-1-naphthol (4-CN) was then used for precipitation; precipitation was the result of the enzymatic reaction catalyzed the HRP on gold NIs. The LSPR spectra were obtained after each binding process. Using this method, the enzyme-catalyzed precipitation reaction on the gold NI surface was found to effectively amplify the change in the signal of the LSPR immunosensor after intermolecular binding.
immunosensor; localized surface plasmon resonance (LSPR); gold nano-island; enzyme-catalyzed precipitation
4-1BB and 4-1BBL can control adaptive immunity, but we demonstrated that their interaction also suppressed myelopoiesis. 4-1BBL was found to be expressed on hematopoietic stem cells, and differentiating common myeloid (CMPs) and granulocyte-macrophage progenitors (GMPs), and 4-1BB was inducible on activated myeloid progenitors. Steady state numbers of GMPs, myeloid-lineage cells, and mature dendritic cells, were elevated in 4-1BB- and 4-1BBL-deficient mice, indicative of a negative functional role, and this was confirmed in bone marrow chimeras and in vitro where the absence of 4-1BB/4-1BBL interactions led to enhanced differentiation into dendritic cell lineages. The regulatory activity was mediated through 4-1BBL, with binding by 4-1BB inhibiting differentiation of myeloid progenitors. Thus, 4-1BB and 4-1BBL have a novel function in limiting myelopoiesis and dendritic cell development.
The TNFR family members OX40 (CD134) and 4-1BB (CD137) have been found to play major roles as costimulatory receptors for both CD4 and CD8 T cells. In particular, in many situations, they can control proliferation, survival, and cytokine production, and hence are thought to dictate accumulation of protective T cells during anti-viral and anti-tumor responses and pathogenic T cells during autoimmune reactions. As opposed to simply controlling the activity of naïve, effector, and memory T cells, recent data have suggested that both molecules are also instrumental in controlling the generation and activity of so-called regulatory or suppressor T cells (Treg), perhaps in both positive and negative manners. Part of the action on Treg might function to further promote protective or pathogenic T cells, but alternate activities of OX40 and 4-1BB on Treg are also being described that suggest there might be control by these molecules at multiple levels that will alter the biological outcome when these receptors are ligated. This review specifically focuses on recent studies of regulatory T cells, and regulatory or suppressive activity, that are modulated by OX40 or 4-1BB.
OX40; 4-1BB; Treg; T cells
A 46-year-old man had chronic granulomatous gastritis characterized by giant gastric folds with noncaseating epithelioid granulomas including giant cells in the corpus. No definite etiologic factors were detected. Histology and the rapid urease test indicated that H. pylori was present in both the antrum and corpus. The granulomatous gastritis with giant gastric folds improved after H. pylori eradication. This case suggests an association between isolated granulomatous gastritis and H. pylori infection.
Granulomatous gastritis; Helicobacter pylori; Hypertrophic gastritis
In the present study, in order to investigate the anti-proliferative phenomenon of PLME, the effects of mycelial extract of Phellinus linteus (PLME) on the growth of human lung carcinoma cell line A549 was examined. We studied on the effects of PLME on the release of nitric oxide (NO) in mouse macrophage Raw 264.7 cells. Treatment of PLME to A549 cells resulted in the growth inhibition, morphological change and induction of apoptotic cell death in a dose-dependent manner as measured by MTT assay. We found that PLME stimulated a dose-dependent increase in NO production. These findings suggest that PLME enhances the anti-tumoral activity of macrophage and may be a potential therapeutic agent for the control of human lung carcinoma cells.
A549; Nitric oxide; Phellinus linteus; PLME; Raw 264.7
The induction of strong cytotoxic T-lymphocyte (CTL) and humoral responses appear to be essential for the elimination of persistently infecting viruses, such as hepatitis C virus (HCV). Here, we tested several vaccine regimens and demonstrate that a combined vaccine regimen, consisting of HCV E2 DNA priming and boosting with recombinant E2 protein, induces the strongest immune responses to HCV E2 protein. This combined vaccine regimen augments E2-specific immunoglobulin G2a (IgG2a) and CD8+ CTL responses to a greater extent than immunizations with recombinant E2 protein and E2 DNA alone, respectively. In addition, the data showed that a protein boost following one DNA priming was also effective, but much less so than those following two DNA primings. These data indicate that sufficient DNA priming is essential for the enhancement of DNA encoded antigen-specific immunity by a booster immunization with recombinant E2 protein. Furthermore, the enhanced CD8+ CTL and IgG2a responses induced by our combined vaccine regimens are closely associated with the protection of BALB/c mice from challenge with modified CT26 tumor cells expressing HCV E2 protein. Together, our results provide important implications for vaccine development for many pathogens, including HCV, which require strong antibody and CTL responses.