The purpose of this study is to investigate whether acoustic radiation force impulse (ARFI) elastography with ARFI quantification and ARFI 2-dimensional (2D) imaging is useful for differentiating hepatic hemangiomas from malignant hepatic tumors.
Materials and Methods
One-hundred-and-one tumors in 74 patients were included in this study: 28 hemangiomas, 26 hepatocellular carcinomas (HCCs), three cholangiocarcinomas (CCCs), 20 colon cancer metastases and 24 other metastases. B-mode ultrasound, ARFI 2D imaging, and ARFI quantification were performed in all tumors. Shear wave velocities (SWVs) of the tumors and the adjacent liver and their SWV differences were compared among the tumor groups. The ARFI 2D images were compared with B-mode images regarding the stiffness, conspicuity and size of the tumors.
The mean SWV of the hemangiomas was significantly lower than the malignant hepatic tumor groups: hemangiomas, 1.80 ± 0.57 m/sec; HCCs, 2.66 ± 0.94 m/sec; CCCs, 3.27 ± 0.64 m/sec; colon cancer metastases, 3.70 ± 0.61 m/sec; and other metastases, 2.82 ± 0.96 m/sec (p < 0.05). The area under the receiver operating characteristics curve of SWV for differentiating hemangiomas from malignant tumors was 0.86, with a sensitivity of 96.4% and a specificity of 65.8% at a cut-off value of 2.73 m/sec (p < 0.05). In the ARFI 2D images, the malignant tumors except HCCs were stiffer and more conspicuous as compared with the hemangiomas (p < 0.05).
ARFI elastography with ARFI quantification and ARFI 2D imaging may be useful for differentiating hepatic hemangiomas from malignant hepatic tumors.
Acoustic radiation force impulse imaging; ARFI; Elastography; Ultrasound; Liver; Tumors
Orthorhombic crystals of DtxR from T. acidophilum have been obtained. X-ray data were collected to 1.8 Å resolution using synchrotron radiation.
The diphtheria toxin repressor (DtxR) is a metal-ion-dependent transcriptional regulator which regulates genes encoding proteins involved in metal-ion uptake to maintain metal-ion homeostasis. DtxR from Thermoplasma acidophilum was cloned and overexpressed in Escherichia coli. Crystals of N-terminally His-tagged DtxR were obtained by hanging-drop vapour diffusion and diffracted to 1.8 Å resolution. DtxR was crystallized at 296 K using polyethylene glycol 4000 as a precipitant. The crystals belonged to the orthorhombic space group P21212, with unit-cell parameters a = 61.14, b = 84.61, c = 46.91 Å, α = β = γ = 90°. The asymmetric unit contained approximately one monomer of DtxR, giving a crystal volume per mass (V
M) of 2.22 Å3 Da−1 and a solvent content of 44.6%.
DtxR; transcriptional regulators; metalloregulatory proteins; Thermoplasma acidophilum
The potential role of Nogo-66 Receptor 1 (NgR1) on immune cell phenotypes and their activation during neuroinflammatory diseases such as multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), is unclear. To further understand the function of this receptor on haematopoietically-derived cells, phenotypic and functional analyses were performed using NgR1-deficient (ngr1-/-) animals. Flow cytometry-based phenotypic analyses performed on blood, spleen, thymus, lymph nodes, bone marrow and central nervous-system (CNS)-infiltrating blood cells revealed no immunological defects in naïve ngr1-/- animals versus wild-type littermate (WTLM) controls. EAE was induced by either recombinant myelin oligodendrocyte glycoprotein (rMOG), a model in which B cells are considered to contribute pathogenically, or by MOG35–55 peptide, a B cell-independent model. We have demonstrated that in ngr1-/- mice injected with MOG35–55, a significant reduction in the severity of EAE correlated with reduced axonal damage present in the spinal cord when compared to their WTLM controls. However, despite a reduction in axonal damage observed in the CNS of ngr1-/- mice at the chronic stage of disease, no clinical differences could be attributed to a specific genotype when rMOG was used as the encephalitogen. Following MOG35–55-induction of EAE, we could not derive any major changes to the immune cell populations analyzed between ngr1-/- and WTLM mice. Collectively, these data demonstrate that NgR1 has little if any effects on the repertoire of immune cells, their activation and trafficking to the CNS.
Background and Objectives
Survivors of pediatric hematopoietic stem cell transplantation (HSCT) are at risk for developing hypertension. The objectives of this study are to evaluate the prevalence and risk factors of early onset hypertension during the engraftment period after HSCT.
Subjects and Methods
This is a retrospective study of 157 consecutive patients (mean age at HSCT: 9.1±5.1 years) who underwent HSCT for acute myeloid leukemia (n=47), acute lymphoblastic leukemia (n=43), severe aplastic anemia (n=41), and other reasons (n=26). Blood pressure data were collected at five time points: 0, 7, 14, 21, and 28 days after HSCT. Hypertension was defined as having systolic and/or diastolic blood pressure ≥95th percentile according to age, gender, and height. To analyze the risk factors related to hypertension, data, including patients' demographic and transplant characteristics, were reviewed.
Hypertension developed in 59 patients (38%), among whom 12 (7.6%) required long term therapy. Thirty-two (54%) patients had systolic and diastolic, 8 (14%) had only systolic, and 19 (32%) had only diastolic hypertension. Younger age, acute graft-versus-host disease, sinusoidal obstruction syndrome, treatment with antifungal agent, and greater increase in serum creatinine (Cr) levels were associated with hypertension. Multivariate analysis showed that younger age at HSCT and greater increase in serum Cr level were independent risk factors for hypertension.
Prevalence of hypertension during immediate post-HSCT period is high, especially in younger children. A greater increase in Cr after HSCT was significantly associated with hypertension. Further study is needed to elucidate long-term cardiovascular complications in pediatric HSCT survivors.
Hematopoletic stem cell transplantation; Child; Incidence; Blood pressure; Hypertension
The risk of mortality and morbidity of patients with congenital heart defects (CHDs) is highest during neonatal period and increases when diagnosis and proper management are delayed. Neonates with critical CHDs may present with severe cyanosis, respiratory distress, shock, or collapse, all of which are also frequent clinical presentations of various respiratory problems or sepsis in the newborn. Early diagnosis and stabilization and timely referral to a tertiary cardiac center are crucial to improve the outcomes in neonates with CHDs. In this review, the clinical presentation of critical and potentially life-threatening CHDs is discussed along with brief case reviews to help understand the hemodynamics of these defects and ensure proper decision-making in critically ill patients.
Congenital heart defect; Ductal-dependent lesions; Cyanosis; Shock
As pet ownership increases, sensitization to animal allergens due to domestic exposure is a concern. Sensitization to animal allergens may occur from indirect exposure, as well as direct ownership of animals. However, there have been conflicting results regarding the association between pet ownership and sensitization to animal allergens in adults.
In total, 401 patients with various allergic diseases were enrolled in this study. We performed skin prick tests with 55 common inhalant and food allergens, including dog, cat, and rabbit allergens. A mean wheal diameter of 3 mm or greater was considered a positive reaction. The exposure modality to each animal allergen was investigated using a questionnaire and included present ownership, past ownership, occupational exposure, occasional exposure, contact with pet owner, and no contact. Present ownership, past ownership, occupational, and occasional exposure were regarded as direct exposure.
The sensitization rate for animal allergens was 20.4% for dog, 15.0% for cat, and 9.0% for rabbit. Direct exposure to dogs (72.0%) was significantly higher than that of other animals (18.4% for cats and 16.7% for rabbits), whereas 'no contact' with cats (78.3%) and rabbits (83.3%) was significantly higher than with dogs (26.8%; P<0.0001). Independent risk factors for sensitization to animal allergens were sensitization to Dermatophagoides pteronyssinus (OR=2.4, P=0.052), Dermatophagoides farinae (OR=5.1, P<0.001), cat (OR=4.4, P<0.0001), and direct exposure to dogs (OR=1.5, P=0.029) for dog, and sensitization to dog (OR=4.4, P<0.0001) and rabbit (OR=2.6, P=0.036) for cats. Finally, for rabbits, the independent risk factor was sensitization to Alternaria (OR=6.0, P<0.002).
These results suggest that direct exposure to dogs contributes to the sensitization to dog allergens in patients with allergic diseases, whereas indirect exposure to cats and rabbits may induce sensitization to each animal's allergen.
Cats; dogs; rabbits; pets; ownership; sensitization
The crystal structure of M. tuberculosis
l,d-transpeptidase (LdtMt2; Rv2518c) has been determined in both ligand-free and meropenem-bound forms. The detailed view of the interactions between meropenem and LdtMt2 will be useful in structure-guided discovery of new antituberculosis drugs.
Difficulty in the treatment of tuberculosis and growing drug resistance in Mycobacterium tuberculosis (Mtb) are a global health issue. Carbapenems inactivate l,d-transpeptidases; meropenem, when administered with clavulanate, showed in vivo activity against extensively drug-resistant Mtb strains. LdtMt2 (Rv2518c), one of two functional l,d-transpeptidases in Mtb, is predominantly expressed over LdtMt1 (Rv0116c). Here, the crystal structure of N-terminally truncated LdtMt2 (residues Leu131–Ala408) is reported in both ligand-free and meropenem-bound forms. The structure of meropenem-inhibited LdtMt2 provides a detailed structural view of the interactions between a carbapenem drug and Mtb
l,d-transpeptidase. The structures revealed that the catalytic l,d-transpeptidase domain of LdtMt2 is preceded by a bacterial immunogloblin-like Big_5 domain and is followed by an extended C-terminal tail that interacts with both domains. Furthermore, it is shown using mass analyses that meropenem acts as a suicide inhibitor of LdtMt2. Upon acylation of the catalytic Cys354 by meropenem, the ‘active-site lid’ undergoes a large conformational change to partially cover the active site so that the bound meropenem is accessible to the bulk solvent via three narrow paths. This work will facilitate structure-guided discovery of l,d-transpeptidase inhibitors as novel antituberculosis drugs against drug-resistant Mtb.
Rv2518c; Mt2594; LdtMt2; l,d-transpeptidases; Mycobacterium tuberculosis; meropenem; carbapenem; peptidoglycans; antituberculosis drug discovery
Triclinic crystals of a self-complementary DNA heptacosamer with 20-base-pair duplexes flanked by 3′-terminal seven-nucleotide overhangs have been obtained. X-ray data were collected to 2.8 Å resolution using synchrotron radiation.
The self-complementary DNA heptacosamer (a 27-mer oligonucleotide) with sequence d(CGAGCACTGCGCAGTGCTCGTTGTTAT) forms a 20-base-pair duplex flanked by seven-nucleotide overhangs at the 3′-terminus. Crystals of the oligonucleotide were obtained by sitting-drop vapour diffusion and diffracted to 2.8 Å resolution. The oligonucleotide was crystallized at 277 K using polyethylene glycol as a precipitant in the presence of magnesium chloride. The crystals belonged to the triclinic space group, with unit-cell parameters a = 48.74, b = 64.23, c = 79.34 Å, α = 91.37, β = 93.21, γ = 92.35°.
DNA heptacosamer; oligonucleotides
Two case reports discussing Korean ginseng-induced allergic reactions have been published; both were inhalation-induced respiratory allergies in occupational settings. In this report we discuss the first case of anaphylaxis that developed after an oral intake of ginseng, confirmed by an open oral challenge, a skin prick test (SPT), and a basophil activation test (BAT). A 44-year-old man experienced rhinorrhea and nasal stiffness, followed by respiratory difficulty with wheeze and abdominal pain 10 minutes after oral intake of fresh ginseng. He had suffered from episodes of allergic rhinitis during the spring season for several years. Upon presentation, a physical examination, chest radiograph, and routine laboratory tests were unremarkable. Total serum IgE level was 41 IU/mL. The SPT results showed strong positive responses to alder, birch pollens, and ginseng extracts (1:500 w/v). The methacholine bronchial challenge test revealed a positive result at PC20 of 5.83 mg/mL. The open oral challenge was performed using 50 g of fresh ginseng and showed immediate onset of facial flushing, cough, respiratory difficulty with wheeze, and abdominal pain combined with a significant decrease in FEV1 levels (54% from the baseline). Serum-specific IgE and IgG4 antibodies were not detectable by enzyme-linked immunosorbent assay. BAT showed a remarkable increase in the expression of CD203c and CD63 with the addition of ginseng extract in a dose-dependent manner, while no changes were noted in the controls. In conclusion, oral intake of Korean ginseng could induce anaphylaxis, which is mediated by non-IgE-dependent direct activation of basophil/mast cells.
Anaphylaxis; basophil; flow cytometry; Panax
There is a need for new anti-asthmatic medications with fewer side effects. NDC-052, an extract of the medicinal herb Magnoliae flos, which has a long history of clinical use, was recently found to have anti-inflammatory effects. Herein, we evaluated the effects of NDC-052 as an add-on therapy in patients with mild to moderate asthma using inhaled corticosteroids (ICS).
In a non-comparative, multi-center trial, 148 patients taking ICS received NDC-052 for eight weeks. We evaluated their forced expiratory volume in one second (FEV1), morning and evening peak expiratory flow rate (AM and PM PEFR), AM/PM asthma symptom scores, visual analogue symptom (VAS) scores, night-time wakening, frequency of short-acting β2-agonist usage, and adverse events.
After eight weeks, both AM and PM PEFRs were significantly improved. Asthma symptom scores, VAS scores, the frequency of nights without awakening, and the frequency of β2-agonist use were also reduced. Most of the adverse drug reactions were mild and resolved spontaneously.
The addition of NDC-052 to ICS had a beneficial effect on asthma control in patients with mild to moderate asthma, with good tolerability and fewer side effects. Further studies are necessary to evaluate the effects of NDC-052 in patients with severe and/or refractory asthma.
Asthma; Drugs; Chinese herbal; Magnolin; Magnoliae
To prospectively evaluate the safety and short-term therapeutic efficacy of switching monopolar radiofrequency ablation (RFA) with multiple electrodes to treat medium-sized (3.1-5.0 cm), hepatocellular carcinomas (HCC).
Materials and Methods
In this prospective study, 30 patients with single medium-sized HCCs (mean, 3.5 cm; range, 3.1-4.4 cm) were enrolled. The patients were treated under ultrasonographic guidance by percutaneous switching monopolar RFA with a multichannel RF generator and two or three internally cooled electrodes. Contrast-enhanced CT scans were obtained immediately after RFA, and the diameters and volume of the ablation zones were then measured. Follow-up CT scans were performed at the first month after ablation and every three months thereafter. Technical effectiveness, local progression and remote recurrence of HCCs were determined.
There were no major immediate or periprocedural complications. However, there was one bile duct stricture during the follow-up period. Technical effectiveness was achieved in 29 of 30 patients (97%). The total ablation time of the procedures was 25.4 ± 8.9 minutes. The mean ablation volume was 73.8 ± 56.4 cm3 and the minimum diameter was 4.1 ± 7.3 cm. During the follow-up period (mean, 12.5 months), local tumor progression occurred in three of 29 patients (10%) with technical effectiveness, while new HCCs were detected in six of 29 patients (21%).
Switching monopolar RFA with multiple electrodes in order to achieve a sufficient ablation volume is safe and efficient. This method also showed relatively successful therapeutic effectiveness on short-term follow up for the treatment of medium-sized HCCs.
Liver; Interventional procedures; Radiofrequency ablation; Preliminary clinical study
The addition of thoracic epidural anesthesia to general anesthesia during cardiac surgery may have a beneficial effect on clinical outcome. However, epidural catheter insertion in a patient anticoagulated with heparin may increase the risk of epidural hematoma. We report a case of epidural hematoma in a 55-year-old male patient who had a thoracic epidural placed under general anesthesia preceding uneventful mitral valve replacement and tricuspid valve annular plasty. During the immediate postoperative period and first postoperative day, prothrombin time (PT) and activate partial thromboplastin time (aPTT) were mildly prolonged. On the first postoperative day, he complained of motor weakness of the lower limbs and back pain. An immediate MRI of the spine was performed and it revealed an epidural hematoma at the T5-6 level. Rapid surgical decompression resulted in a recovery of his neurological abnormalities to near normal levels. Management and preventing strategies of epidural hematoma are discussed.
Analgesia; Epidural; Hematoma; Postoperative complications; Spinal
Surface modification of electrically conductive biomaterials has been studied to improve biocompatibility for a number of applications, such as implantable sensors and microelectrode arrays. In this study, we electrochemically coated electrodes with biocompatible and non-cell adhesive hyaluronic acid (HA) to reduce cellular adhesion for potential use in neural prostheses. To this end, pyrrole-conjugated hyaluronic acid (PyHA) was synthesized and employed for electrochemical coating of platinum, indium-tin-oxide, and polystyrene sulfonate-doped polypyrrole electrodes. This PyHA conjugate consists of (1) a pyrrole moiety that allows the compound to be electrochemically deposited onto a conductive substrate and (2) non-adhesive HA to minimize cell adhesion and to potentially decrease inflammatory tissue responses. Our characterization results showed the presence of a hydrophilic p(PyHA) layer on the modified electrode, and impedance measurements revealed impedance that was statistically the same as the unmodified electrode. We found that the p(PyHA)-coated electrodes minimized adhesion and migration of fibroblasts and astrocytes for a minimum of up to 3 months. Also, the coating was stable in physiological solution for 3 months and also stable against enzymatic degradation by hyaluronidase. These studies suggest that this p(PyHA)-coating has the potential to be used to mask conducting electrodes from adverse glial responses that occur upon implantation. In addition, electrochemical coating with PyHA can be potentially extended for the surface modification of other metallic and conducting substances such as stents and biosensors.
pyrrole; surface modification; hyaluronic acid; conducting materials
We wanted to assess the safety and efficacy of performing radiofrequency ablation (RFA) in patients with non-colorectal liver metastases.
Materials and Methods
In this retrospective study, 25 patients with 40 hepatic metastases (M:F = 17:8; mean age, 57 years; tumor size, 0.5-5.0 cm) from a non-colorectal origin (stomach, biliary, breast, pancreas, kidney and skin) were treated with RFA. The RFA procedures were performed using either an internally cooled electrode or a clustered electrode under ultrasound or CT guidance. Contrast-enhanced CT scans were obtained immediately after RFA and follow-up CT scans were performed within three months after ablation and subsequently at least every six months. The intrahepatic disease-free interval was estimated and the overall survival from the time of the initial RFA was analyzed using the Kaplan-Meier method.
No intraprocedural deaths occurred, but four major complications developed, including abscesses (n = 3) and pneumothorax (n = 1). Technical effectiveness was determined on the initial follow-up images. During the follow-up period (range, 5.9-68.6 months; median time, 18.8 months) for 37 tumors in 22 patients where technical effectiveness was achieved, 12 lesions (32%, 12 of 37) showed local tumor progression and new intrahepatic metastases occurred in 13 patients (59%, 13 of 22). The median intrahepatic disease-free interval was 10.1 months. The 1-year, 3-year and 5-year overall survival rates after RFA were 86%, 39% and 19%, respectively.
RFA showed intermediate therapeutic effectiveness for the treatment of non-colorectal origin liver metastases.
Liver; Interventional procedures; Radiofrequency ablation; Preliminary clinical study
In this study, aloe fermentation products were derived from mycelia from 3 mushrooms: Ganoderma lucidum (AG), Hericium erinaceum (AH), and Phellinus linteus (AP). Levels of aloin A and B increased with fermentation time. The highest levels were measured on the fifth day of fermentation. β-Glucan levels decreased with fermentation time. The safety of aloe fermentation products were examined in male and female Sprague-Dawley rats. Rats were orally administered the three aloe fermentation products at dose levels of 1, 2 or 5 g/kg for single-dose toxicity test and 0.5, 1, or 2 g/kg for repeated-dose toxicity test. There were no significant differences in body weight gain between vehicle control and AG-, AH- or AP-treated rats. Also, significant changes in daily feed intake and water consumption were not observed. In hematological analysis, none of the parameters were affected by aloe fermentation products with mushroom mycelia. This suggests that there are no negative effects on homeostasis and immunity. In blood biochemistry analysis, none of the markers were affected by feeding rats with AG, AH or AP. Similarly, there were no significant effects on markers for liver, kidney, skeletal and heart muscle functions. No remarkable lesions were observed in these organs at histopathology. Since there were no adverse effects of AG, AH and AP in single- or repeated-dose toxicity tests, even at higher doses than normal, we conclude that the aloe fermentation products with mushroom mycelia possess long-term safety and could be candidates as multifunctional nutrients for the improvement of intestinal function and immunity.
Aloe fermentation; aloin; β-glucan; Ganoderma lucidum; Phellinus linteus; Hericium erinaceum; single-dose toxicity test; repeated-dose toxicity; Sprague-Dawley rat
Elevated peak inspiratory airway pressure (PIP) can occur during general anesthesia and is usually easily rectified. In rare circumstances it can lead to potentially fatal conditions such as tension pneumothorax. We report on a 77-year-old male patient admitted for a cervical laminoplasty. The preoperative chest radiograph showed normal findings and there was no medical history of allergy or underlying airway inflammation. Anesthesia induction and maintenance progressed uneventfully. However, 5 minutes after prophylactic antibiotic administration, PIP suddenly increased and blood pressure dropped. The operation was abandoned and the patient was moved to a supine position to perform chest radiography. Cardiac arrest occurred, and cardiopulmonary resuscitation was performed. The radiograph showed bilateral tension pneumothorax. Needle aspiration was immediately performed, and chest tubes were inserted. Ventilation rapidly improved and the vital signs normalized. The patient was discharged without sequelae on postoperative day 36.
Anaphylaxis; Cardiac arrest; Peak inspiratory airway pressure; Tension pneumothorax
Torsade de pointes (TdP) is a devastating form of polymorphic ventricular arrhythmia associated with corrected QT (QTc) interval prolongation. TdP usually terminates spontaneously but frequently recurs and may degenerate to ventricular fibrillation. The present report describes a case of TdP in a patient being transferred to the postanesthetic care unit following an emergency laparoscopic appendectomy. The patient had undergone open heart surgery 1 week before. Retrospective electrocardiogram analysis revealed the patient had QTc and Tpeak-Tend interval prolongation that had gone unrecognized. We believe TdP may have been induced by accentuation of sympathetic nervous system during emergence from general anesthesia.
Long QT syndrome; Torsade de pointes; Tpeak-Tend interval; Ventricular fibrillation
Electrospun fibers have been fabricated for wide use as artificial tissue engineering scaffolds. In particular, fibers smaller than a cell body have been extensively employed to mimic natural extracellular matrix (ECM) and to explore specific responses by various cell types. We investigated the effects of various poly(lactic acid-co-glycolic acid) (PLGA) fiber features on embryonic hippocampal neurons in the early developmental stages in terms of initial axon formation (i.e., polarization) and axon orientation. We produced PLGA fibers that have average diameters ranging from 0.44 µm to 2.2 µm and different degrees of fiber alignment (16–58° in angular standard deviation). After 22 h in culture, embryonic hippocampal neurons grown on PLGA fibers exhibited more axon formation with a 30–50% increase over those on spin-coated smooth PLGA films. This improvement was independent of fiber diameter and alignment; however, slightly more polarization was observed on the smaller fibers and the more aligned fibers. In addition, average axon length of the polarized embryonic hippocampal neurons was not significantly different among the PLGA fibers when compared to cells grown on spin-coated PLGA films. These findings suggest that fibers of subcellular diameters stimulate initial axon establishment and guide the direction of axonal extension; however these fibers do not appear to affect overall axon length. This information will be valuable in understanding the roles of subcellular features on neuron development and for the design of biomaterials for neural tissue interfacing.
hippocampal neuron; polarization; electrospinning; PLGA fibers; nerve tissue engineering
This study was performed to evaluate the potential clinical value of concurrent chemotherapy and pulsed high intensity focused ultrasound (HIFU) therapy (CCHT), as well as the safety of pulsed HIFU, for the treatment of unresectable pancreatic cancer.
Materials and Methods
Twelve patients were treated with HIFU from October 2008 to May 2010, and three of them underwent CCHT as the main treatment (the CCHT group). The overall survival (OS), the time to tumor progression (TTP), the complications and the current performance status in the CCHT and non-CCHT groups were analyzed. Nine patients in the non-CCHT group were evaluated to determine why CCHT could not be performed more than twice.
The OS of the three patients in the CCHT group was 26.0, 21.6 and 10.8 months, respectively, from the time of diagnosis. Two of them were alive at the time of preparing this manuscript with an excellent performance status, and one of them underwent a surgical resection one year after the initiation of CCHT. The TTP of the three patients in the CCHT group was 13.4, 11.5 and 9.9 months, respectively. The median OS and TTP of the non-CCHT group were 10.3 months and 4.4 months, respectively. The main reasons why the nine patients of the non-CCHT group failed to undergo CCHT more than twice were as follows: pancreatitis (n = 1), intolerance of the pain during treatment (n = 4), palliative use of HIFU for pain relief (n = 1) and a poor physical condition due to disease progression (n = 3). No major complications were encountered except one case of pancreatitis.
This study shows that CCHT is a potentially effective and safe modality for the treatment of unresectable pancreatic cancer.
Pancreatic cancer; High-intensity focused ultrasound ablation; Gemcitabine; Chemotherapy
The variant form of human xeroderma pigmentosum syndrome (XPV) is caused by a deficiency in DNA polymerase η (Pol η) that enables replication through sunlight-induced pyrimidine dimers. We report high-resolution crystal structures of human Pol η at four consecutive steps during DNA synthesis through cis-syn cyclobutane thymine dimers. Pol η acts like a molecular splint to stabilize damaged DNA in a normal B-form conformation. An enlarged active site accommodates the thymine dimer with excellent stereochemistry for two-metal ion catalysis. Two residues conserved among Pol η orthologs form specific hydrogen bonds with the lesion and the incoming nucleotide to assist translesion synthesis. Based on the structures, eight Pol η missense mutations causing XPV can be rationalized as undermining the “molecular splint” or perturbing the active-site alignment. The structures also shed light on the role of Pol η in replicating through D loop and DNA fragile sites.
Electrically conductive and biologically active scaffolds are desirable for enhancing adhesion, proliferation and differentiation of a number of cell types such as neurons. Hence, the incorporation of neuroactive molecules into electroconductive polymers via a specific and stable method is essential for neuronal tissue engineering applications. Traditional conjugation approaches dramatically impair conductivities and/or stabilities of the scaffolds and ligands. In this study, we developed copolymers (PPy-NSE) of N-hydroxyl succinimidyl ester pyrrole and regular pyrrole, which can be immobilized with nerve growth factor (NGF) without significantly hindering electroconductivity. The presence of active ester groups was confirmed using reflectance infrared spectroscopy and X-ray photoelectron spectroscopy (XPS) from the copolymers prepared from different monomer compositions. We selected PPy-NSE50 (polymerized from a 50 : 50 monomer ratio of pyrrole : pyrrole-NSE) for further modification with NGF because this copolymer retains good conductivity (approx. 8 S cm−1) and presents active ester groups for NGF immobilization. We tethered NGF on the PPy-NSE50 surface, and found that PC12 cells extended neurites similarly to cells cultured in NGF-containing medium. XPS and enzyme-linked immunosorbent assay confirmed that NGF immobilized via the active ester on the PPy-NSE50 film was stable for up to 5 days in phosphate-buffered saline solution. Also, application of an external electrical potential to NGF-immobilized PPy films did not cause a significant release of NGF nor reduce their neurotrophic activity. This novel scaffold, providing electroconductive and neurotrophic activities, has potential for neural applications, such as tissue engineering scaffolds and biosensors.
polypyrrole; nerve growth factor; PC12 cells; nerve tissue engineering
Electrospinning is a promising approach to create nanofiber structures that are capable of supporting adhesion and guiding extension of neurons for nerve regeneration. Concurrently, electrical stimulation of neurons in the absence of topographical features also has been shown to guide axonal extension. Therefore, the goal of this study was to form electrically conductive nanofiber structures and to examine the combined effect of nanofiber structures and electrical stimulation. Conductive meshes were produced by growing polypyrrole (PPy) on random and aligned electrospun poly(lactic-co-glycolic acid) (PLGA) nanofibers, as confirmed by scanning electron micrographs and X-ray photon spectroscopy. PPy-PLGA electrospun meshes supported the growth and differentiation of rat pheochromocytoma 12 (PC12) cells and hippocampal neurons comparable to non-coated PLGA control meshes, suggesting that PPy-PLGA may be suitable as conductive nanofibers for neuronal tissue scaffolds. Electrical stimulation studies showed that PC12 cells, stimulated with a potential of 10 mV/cm on PPy-PLGA scaffolds, exhibited 40–50% longer neurites and 40–90% more neurite formation compared to unstimulated cells on the same scaffolds. In addition, stimulation of the cells on aligned PPy-PLGA fibers resulted in longer neurites and more neurite-bearing cells than stimulation on random PPy-PLGA fibers, suggesting a combined effect of electrical stimulation and topographical guidance and the potential use of these scaffolds for neural tissue applications.
polypyrrole; nanofibers; nerve tissue engineering; electrical stimulation; PC12 cells; hippocampal neurons
Tpa1 (for termination and polyadenylation) from Saccharomyces cerevisiae is a component of a messenger ribonucleoprotein (mRNP) complex at the 3′ untranslated region of mRNAs. It comprises an N-terminal Fe(II)- and 2-oxoglutarate (2OG) dependent dioxygenase domain and a C-terminal domain. The N-terminal dioxygenase domain of a homologous Ofd1 protein from Schizosaccharomyces pombe was proposed to serve as an oxygen sensor that regulates the activity of the C-terminal degradation domain. Members of the Tpa1 family are also present in higher eukaryotes including humans. Here we report the crystal structure of S. cerevisiae Tpa1 as a representative member of the Tpa1 family. Structures have been determined as a binary complex with Fe(III) and as a ternary complex with Fe(III) and 2OG. The structures reveal that both domains of Tpa1 have the double-stranded β-helix fold and are similar to prolyl 4-hydroxylases. However, the binding of Fe(III) and 2OG is observed in the N-terminal domain only. We also show that Tpa1 binds to poly(rA), suggesting its direct interaction with mRNA in the mRNP complex. The structural and functional data reported in this study support a role of the Tpa1 family as a hydroxylase in the mRNP complex and as an oxygen sensor.
Chitin, the second most abundant polysaccharide in nature, is commonly found in lower organisms such as fungi, crustaceans and insects, but not in mammals. Although the non-specific anti-viral and anti-tumor activities of chitin/chitin derivatives were described two decades ago, the immunological effects of chitin have been only recently been addressed. Recent studies demonstrated that chitin has complex and size-dependent effects on innate and adaptive immune responses including the ability to recruit and activate innate immune cells and induce cytokine and chemokine production via a variety of cell surface receptors including macrophage mannose receptor, toll-like receptor 2 (TLR-2), and Dectin-1. They also demonstrated adjuvant effects of chitin in allergen-induced Type 1 or Type 2 inflammation and provided insights into the important roles of chitinases and chitinase-like proteins (C/CLP) in pulmonary inflammation. The status of the field and areas of controversy are highlighted.
chitin; chitinases; chitinase-like protein; innate and adaptive immunity
An inflammatory myofibroblastic tumor (IMT) is an uncommon, benign lesion characterized by the mesenchymal proliferation and infiltration of inflammatory cells composed primarily of lymphocytes and plasma cells. A percutaneous radiofrequency ablation (RFA) is an effective and safe therapeutic modality used for the management of liver malignancies. Here we report, for the first time, a case of IMT as a complication of RFA for hepatocellular carcinoma in a 61-year-old man with a Child's class A hepatitis B-related liver cirrhosis. Gastrohepatic fistula formation was pathologically proven and associated with the RFA. Such a longstanding inflammation of the fistula might have been a possible cause of the development of IMT in this case.
Inflammatory myofibroblastic tumor; Radiofrequency ablation, complication