Radiologic-histopathologic correlation of fatty island sign with fat necrosis in atypical lipomatous tumor and lipoma.

AIM: This study aimed to assess the imaging features of atypical lipomatous tumors (ALTs) and lipoma with fat necrosis. METHODS: This study included patients with histopathologically proven fat necrosis within adipocytic tumors who underwent preoperative imaging. Magnetic resonance imaging (MRI) and/or computer tomography (CT) findings of fat necrosis associated with lipomatous tumors were retrospectively reviewed, emphasizing the "fatty island sign (FIS)." FISs were defined as well-demarcated, focal fat-containing areas surrounded by more thickened septa compared with other intratumoral septa. Imaging findings of FIS were compared between ALT and lipoma. RESULTS: Fat necrosis was histopathologically confirmed in 17 patients (6 ALTs and 11 lipomas). Among them, 18 FISs were observed in 10 lesions (59%). Multiple FISs within a lesion were observed in 4 (40%) patients. The median maximum diameter of the FISs was 37 mm. Hypointense areas within FISs relative to the subcutaneous fat on T1- and T2-weighted images were observed in 8 (80%) and 9 (90%), respectively, whereas hyperintense areas within FISs on fat-suppressed T2-weighted images were observed in 2 (20%). Nonfatty solid components within FISs were observed in 2 (20%). On CT, increased fat attenuation and pure fat attenuation within FISs were observed in 6 (86%) and 1 (14%), respectively. The imaging findings of FIS were not significantly different between ALT and lipoma. CONCLUSION: FISs were observed in 59% of the histologically proven ALT and lipoma patients with fat necrosis. The hypointense areas relative to the subcutaneous fat on T1- and T2-weighted images and increased fat attenuation on CT were usually observed within FISs.

CT and MRI characteristics for differentiating mediastinal Müllerian cysts from bronchogenic cysts.

AIM: To evaluate how computed tomography (CT) and magnetic resonance imaging (MRI) characteristics can be used to differentiate immunohistochemically confirmed mediastinal Müllerian cysts (MMCs) from bronchogenic cysts (BCs). MATERIALS AND METHODS: Sixteen patients with histopathologically and immunohistochemically confirmed mediastinal cysts (four with MMCs and 12 with BCs) were included in this study. CT and MRI images were reviewed retrospectively and the location, size, CT attenuation, and MRI signal intensity of the two pathologies were compared. RESULTS: On review of CT images, cysts could be located to the anterior mediastinum in four BCs, middle mediastinum in three MMCs and seven BCs, and posterior mediastinum in one MMC and one BC. Contact with a vertebral body was observed in 4/4 MMCs (100%) and 6/12 BCs (50%). The ratios of minimum-to-maximum diameter (0.57±0.09 versus 0.74±0.11, p<0.01), CT attenuation (7.8±6 versus 44.3±12 HU, p<0.01), and cyst-to-spinal cord signal intensity ratios (SIRs) on T1-weighted images (0.56±0.2 versus 1.31±0.4, p<0.01) were significantly lower for MMCs than BCs. No significant differences in maximum diameter, minimum diameter, and SIRs on T2-weighted images were found between MMCs and BCs. CONCLUSION: In characterising mediastinal cysts in a middle-aged female patient, contact with a vertebral body, flattened configuration, hypodensity on CT, and hypointensity compared to spinal cord on T1-weighted images are features that are specific to MMCs.

Inchworm sign of endometrial cancer on diffusion-weighted MRI: radiology-pathology correlation.

AIM: To perform radiology-pathology correlation of the inchworm sign on diffusion-weighted imaging (DWI) in patients with endometrial cancer. MATERIALS AND METHODS: Consecutive patients (345) with histopathologically proven endometrial cancer who underwent preoperative magnetic resonance imaging (MRI), including DWI images, and hysterectomy were included in the present study. The inchworm sign was defined as a hypointense stalk between hyperintense endometrial cancer and hypointense myometrium on DWI images. A genitourinary pathologist reviewed the resected specimen at the site of the inchworm sign. RESULTS: The inchworm sign on DWI images was observed in 32 (9.3%) patients. On T2-weighted images, areas of hypointense stalk on DWI images showed hypointensity in 31 (97%) patients and hyperintensity in one (3%). Among them, the depth of myometrial invasion at histopathology was superficial (<50% myometrial invasion) in 28 (87.5%) patients and deep (≥50% myometrial invasion) in four (12.5%). As a result of histopathological investigation, the hypointense stalk of the inchworm sign was mainly composed of various degrees of stromal proliferation, including smooth muscle cells and metaplastic fibromuscular stroma, with or without intervening endometrial cancer. CONCLUSION: The inchworm sign of endometrial cancer on DWI images usually indicated superficial myometrial invasion and was caused by a stalk composed of stromal proliferation with or without intervening endometrial cancer.

Rebamipide, an anti-ulcerative drug, inhibits induction of salivary dysfunction by benzodiazepines.

OBJECTIVES: The purpose of this study was to determine whether rebamipide, an antistomach ulcer agent, ameliorated benzodiazepine-induced hyposalivation in rat parotid gland (PG) and submandibular gland (SMG). METHODS: Saliva was collected from PG and SMG through a capillary cannula inserted into the parotid duct and sublingual papillae, respectively, every 15 min for 1 h after stimulation with pilocarpine dissolved in physiological saline and intraperitoneally administered at 1 mg kg-1 . Diazepam (DZP) was administered intraperitoneally at a dose of 0.2 mg kg-1 twice daily for 7 days. Rebamipide was administered at 10, 20, 30, or 100 mg kg-1 concomitantly with DZP to determine its effect on hyposalivation. The effect of rebamipide on movement of intracellular calcium ([Ca2+ ]i) in isolated parotid acinar cells was analyzed using Fluo4, a fluorescent dye used to detect Ca2+ . RESULTS: Repetitive administration of DZP decreased salivary secretion in PG and SMG. This inhibitory effect was weakened by administration of rebamipide. Prior administration of DZP (10-6 M) significantly suppressed carbachol (10-7 M)-induced increase in [Ca2+ ]i. This inhibitory effect was ameliorated by combined use with rebamipide (5 × 10-4 M). CONCLUSION: This findings suggest that rebamipide weakens the downregulatory effect of DZP on salivary secretion by preventing DZP-induced suppression of increase in [Ca2+ ]i.

Tracheal intubation by trainees does not alter the incidence or duration of postoperative sore throat and hoarseness: a teaching hospital-based propensity score analysis.

BACKGROUND: Postoperative throat complications, such as sore throat and hoarseness, are frequent complications of tracheal intubation. To assess whether severity of throat complications is related to the experience of physicians performing tracheal intubation, we compared the incidence and duration of postoperative sore throat and hoarseness and patient satisfaction between tracheal intubation performed by trainees and experienced consultant anaesthetists. METHODS: This is a retrospective review of an institutional registry containing records of 21 606 patients undergoing general anaesthesia and was conducted with ethics board approval. All tracheal intubations by trainees were performed under the supervision of consultant anaesthetists. To avoid channel bias, the propensity score analysis was used to generate a set of matched cases (intubations by trainees) and controls (intubations by anaesthetists), yielding 3465 (sore throat) and 3267 (hoarseness) matched patient pairs. The incidence and sustained rate of symptoms were compared as primary outcomes. We also compared patient satisfaction with perioperative care. RESULTS: After propensity score matching, there was no difference between tracheal intubation by trainees and tracheal intubation by consultant anaesthetists in the incidences of sore throat (32.9 vs 32.6%, P=0.84) or hoarseness (35.8 vs 35.2%, P=0.60). Odds ratios and 95% confidence intervals for tracheal intubation by trainees were 1.01 (0.91-1.12) for sore throat and 1.03 (0.93-1.14) for hoarseness. The rates of sustained sore throat and hoarseness over the course were low (P=0.85 and P=0.67, respectively). Hazard ratios and 95% confidence intervals for tracheal intubation by trainees were 0.99 (0.94-1.05) for sustained sore throat and 0.99 (0.93-1.05) for sustained hoarseness. Patient satisfaction did not differ between matched groups (P=0.66 and P=0.83). CONCLUSIONS: Tracheal intubation by trainees under the supervision of consultant anaesthetists did not worsen the postoperative airway outcomes, such as sore throat and hoarseness.

A comparison of airway dimensions, measured by acoustic reflectometry and ultrasound before and after general anaesthesia.

Changes in airway dimensions can occur during general anaesthesia and surgery for a variety of reasons. This study explored factors associated with postoperative changes in airway dimensions. Patient airway volume was measured by acoustic reflectometory and neck muscle diameter by ultrasound echography in the pre- and post-anaesthetic periods in a total of 281 patients. Neck circumference was also assessed during these periods. A significant decrease in median (IQR [range]) total airway volume (from 63.8 (51.8-75.7 [14.7-103]) ml to 45.9 (33.5-57.2 [6.4-96.3]) ml, p < 0.0001), and a significant increase in muscle diameter (from 4.3 (3.3-5.6 [2.2-9.0]) mm to 5.8 (4.7-7.3 [2.8-1.3]) mm, p < 0.0001) and neck circumference (from 34.0 (32.5-37.0 [29.5-49.0]) cm to 35.0 (33.5-38.0 [30.5-50.5]) cm, p < 0.0001) were observed. It may be possible that changes in airway volume and neck circumference were influenced by surgical duration or peri-operative fluid management (ρ) = -0.31 (95% CI -0.24 to -0.01), p = 0.0301, -0.17 (-0.23 to -0.06), p = 0.0038, 0.23 (0.12-0.34), p < 0.0001, and 0.16 (0.05-0.27), p = 0.0062, respectively). The intra-oral space can significantly decrease and neck thickness increase after general anaesthesia, and might increase the risk of difficult laryngoscopy and intubation if airway management is required after extubation following general anaesthesia.

Identification of hemiclonal reproduction in three species of Hexagrammos marine reef fishes.

Natural hybrids between the boreal species Hexagrammos octogrammus and two temperate species Hexagrammos agrammus and Hexagrammos otakii were observed frequently in southern Hokkaido, Japan. Previous studies revealed that H. octogrammus is a maternal ancestor of both hybrids; the hybrids are all fertile females and they frequently breed with paternal species. Although such rampant hybridization occurs, species boundaries have been maintained in the hybrid zone. Possible explanations for the absence of introgressions, despite the frequent backcrossing, might include clonal reproduction: parthenogenesis, gynogenesis and hybridogenesis. The natural hybrids produced haploid eggs that contained only the H. octogrammus genome (maternal ancestor) with discarded paternal genome and generated F1 -hybrid type offspring by fertilization with the haploid sperm of H. agrammus or H. otakii (paternal ancestor). This reproductive mode was found in an artificial backcross hybrid between the natural hybrid and a male of the paternal ancestor. These findings indicate that the natural hybrids adopt hybridogenesis with high possibility and produce successive generations through hybridogenesis by backcrossing with the paternal ancestor. These hybrids of Hexagrammos represent the first hybridogenetic system found from marine fishes that widely inhabit the North Pacific Ocean. In contrast with other hybridogenetic systems, these Hexagrammos hybrids coexist with all three ancestral species in the hybrid zone. The coexistence mechanism is also discussed.

Comparison between the effects of epidural and intravenous patient-controlled analgesia on postoperative disability-free survival in patients undergoing thoracic and abdominal surgery: A post hoc analysis.

BACKGROUND: Thoracic epidural analgesia (TEA) and intravenous patient-controlled analgesia (IV-PCA) are widely used to mitigate immediate postoperative pain; however, their effects on long-term disability-free survival are poorly documented. This study aimed to compare the effects of postoperative TEA and IV-PCA on disability-free survival in patients who underwent thoracic or abdominal surgery. METHODS: This post hoc analysis of a prospective observational study included 845 inpatients aged ≥55 years that underwent elective thoracic and abdominal surgery between 1 April 2016 and 28 December 2018 in a tertiary care hospital. Inverse probability of treatment weighted (IPTW) using stabilized inverse propensity scores was adopted to minimize bias. The primary outcome in this study was disability-free survival, defined as survival with a 12-item World Health Organization Disability Assessment Schedule 2.0 score of <16%, assessed at 3 months and 1 year after surgery. RESULTS: The final analysis included 601 patients who received TEA and 244 who received IV-PCA. After IPTW, the weighted incidence of disability-free survival at 3 months and 1 year was 60.5% and 61.4% in the TEA group and 78.3% and 66.2% in the IV-PCA group, respectively. The adjusted OR for disability-free survival at 3 months and 1 year was 0.84 (95% confidence interval [CI]: 0.50-1.39) and 1.21 (95% CI: 0.72-2.05), respectively, for the TEA group. CONCLUSION: No significant differences were observed in the disability-free survival at 3 months and 1 year after elective thoracic and abdominal surgery in patients aged ≥55 years who received TEA or IV-PCA. SIGNIFICANCE STATEMENT: This study is the first in our setting to document the long-term effects of patient-controlled analgesia. In a post hoc analysis of our prospective cohort study, we show that although differences in chronic postsurgical pain exist at 3 months post-surgery, disability-free survival rates at 1 year do not differ irrespective of the choice of patient-controlled analgesia. The findings of this study highlight the need for shared decision-making between clinicians and patients.

Computed Tomography and 18F-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography Imaging Biomarkers of Lung Invasive Non-mucinous Adenocarcinoma: Prediction of Grade 3 Tumour Based on World Health Organization Grading System.

AIMS: To evaluate computed tomography (CT) and 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT) findings of invasive non-mucinous adenocarcinoma (INMA) of the lung as a predictor of histological tumour grade according to 2021 World Health Organization (WHO) classification. MATERIALS AND METHODS: This retrospective study included consecutive patients with surgically resected INMA who underwent both preoperative CT and 18F-FDG-PET/CT. A three-tiered tumour grade was performed based on the fifth edition of the WHO classification of lung tumours. CT imaging features and the maximum standardised uptake value (SUVmax) were compared among the three tumour grades. RESULTS: In total, 214 patients with INMA (median age 70 years; interquartile range 65-76 years; 123 men) were histologically categorised: 36 (17%) as grade 1, 102 (48%) as grade 2 and 76 (35%) as grade 3. Pure solid appearance was more frequent in grade 3 (83%) than in grades 1 (0%) and 2 (26%) (P < 0.001). The SUVmax of the entire tumour was higher in grade 3 than in grades 1 and 2 (P < 0.001). Multivariable analysis revealed that pure solid appearance (odds ratio = 94.0; P < 0.001), round/oval shape (odds ratio = 4.01; P = 0.001), spiculation (odds ratio = 2.13; P = 0.04), air bronchogram (odds ratio = 0.40; P = 0.03) and SUVmax (odds ratio = 1.45; P < 0.001) were significant predictors for grade 3 INMAs. CONCLUSION: Pure solid appearance, round/oval shape, spiculation, absence of air bronchogram and high SUVmax were associated with grade 3 INMAs. CT and 18F-FDG-PET/CT were potentially useful non-invasive imaging methods to predict the histological grade of INMAs.

Interleukin-33 induces interleukin-17F in bronchial epithelial cells.

BACKGROUND: IL-33 is clearly expressed in the airway of patients with asthma, but its role in asthma has not yet been fully understood. IL-17F is also involved in the pathogenesis of asthma. However, the regulatory mechanisms of IL-17F expression remain to be defined. To further indentify the role of IL-33 in asthma, we investigated the expression of IL-17F by IL-33 in bronchial epithelial cells and its signaling mechanisms. METHODS: Bronchial epithelial cells were stimulated with IL-33. The levels of IL-17F expression were analyzed using real-time PCR and ELISA. Next, the involvement of ST2, MAP kinases, and mitogen- and stress-activated protein kinase1 (MSK1) was determined by Western blot analyses. Various kinase inhibitors and anti-ST2 neutralizing Abs were added to the culture to identify the key signaling events leading to the expression of IL-17F, in conjunction with the use of short interfering RNAs (siRNAs) targeting MSK1. RESULTS: IL-33 significantly induced IL-17F gene and protein expression. The receptor for IL-33, ST2, was expressed in bronchial epithelial cells. Among MAP kinases, IL-33 phosphorylated ERK1/2, but not p38MAPK and JNK. It was inhibited by the pretreatment of anti-ST2 neutralizing (blocking) Abs. MEK inhibitor significantly blocked IL-17F production. Moreover, IL-33 phosphorylated MSK1, and MEK inhibitor diminished its phosphorylation. Finally, MSK1 inhibitors and transfection of the siRNAs targeting MSK1 significantly blocked the IL-17F expression. CONCLUSIONS: IL-33 induces IL-17F via ST2-ERK1/2-MSK1 signaling pathway in bronchial epithelial cells. These data suggest that the IL-33/IL-17F axis is involved in allergic airway inflammation and may be a novel therapeutic target.

Effects of diazepam and flumazenil on forebrain ischaemia in a rat model of benzodiazepine tolerance.

BACKGROUND: Post-ischaemic benzodiazepine administration is neuroprotective, but chronic administration of benzodiazepines can induce tolerance, such that the neuroprotective effect may be reduced. This study investigated whether benzodiazepine tolerance can worsen ischaemic injury and whether neuroprotection by post-ischaemic benzodiazepine administration is affected by benzodiazepine tolerance. We also investigated whether antagonism of benzodiazepine receptors by flumazenil was able to restore neuroprotection during benzodiazepine tolerance. METHODS: Experiments were performed in both benzodiazepine-tolerant and naive rats. Benzodiazepine tolerance was indeed by 4 weeks administration of flurazepam. Bilateral carotid artery occlusion (BCAO) was performed to cause cerebral ischaemia. Four experiments were performed: (1) BCAO with no further interventions; (2) BCAO followed by administration of diazepam; (3) administration of flumazenil before BAO; and (4) administration of flumazenil before and diazepam after BCAO. Neurological and histological assessment was performed 5 days after BCAO. RESULTS: Benzodiazepine tolerance did not affect neuronal injury in the CA1 and CA3 regions and dentate gyrus of the hippocampus after severe ischaemic insult, but did worsen neuronal damage when mild ischaemia was applied (P<0.05). Neuroprotective efficacy of post-ischaemic diazepam was not observed under conditions of benzodiazepine tolerance. Flumazenil treatment before BCAO reduced ischaemic neuronal damage exacerbated by benzodiazepine tolerance (P<0.05), and restored neuroprotection by post-ischaemic diazepam (P<0.05), the effect of which was reduced by benzodiazepine tolerance (P<0.05). However, pre-ischaemic flumazenil treatment in naive animals reduced neuroprotection provided by post-ischaemic diazepam (P<0.01-0.05). CONCLUSIONS: Benzodiazepine tolerance can worsen ischaemic neuronal injury and abolish the neuroprotection provided by post-ischaemic diazepam. Pre-treatment with flumazenil treatment reversed benzodiazepine tolerance and restored neuroprotection by post-ischaemic diazepam. These findings may suggest that management of patient's risk of developing cerebral ischaemia may need to take into account current use.

Anesthetic management using costoclavicular brachial plexus block with patient-controlled analgesia in Pediatrics: A case report.

The costoclavicular brachial plexus block (CBPB) has been receiving increasing attention as an effective technique for upper arm surgery conducted without phrenic paralysis. However, studies in children are lacking. CBPB was applied to a 10 year-old girl undergoing scheduled radial and ulnar osteotomy due to multiple cartilaginous exostoses and ulnar lengthening. CBPB was performed with a bolus administration of 10 mL of 0.25% levobupivacaine, and the catheter was sequentially replaced in the right costoclavicular space. After surgery, a continuous infusion of 0.17% levobupivacaine through a catheter was initiated at 2 mL/h, along with patient-controlled analgesia (PCA) of 3 mL 0.17% levobupivacaine with a 60-min lock out. The patient complained of 5/10 pain on the numerical rating scale (NRS) 2 h after surgery, which improved immediately after bolus administration. The analgesia induced by CBPB was otherwise effective (NRS ≤ 2). CBPB with PCA may provide adequate analgesia in paediatric cases.

Blockade of cysteinyl leukotriene-1 receptors suppresses airway remodelling in mice overexpressing GATA-3.

BACKGROUND: We demonstrated previously that GATA-3 overexpression markedly enhanced allergen-induced airway inflammation and airway remodelling, including subepithelial fibrosis, and smooth muscle cell hyperplasia, in transgenic mice. OBJECTIVE: Because cysteinyl leukotrienes (cysLTs) have been shown to be involved in such structural changes, the effects of a specific cysLT1 receptor antagonist, montelukast, were evaluated in a mouse model of chronic asthma. METHODS: GATA-3-overexpressing mice and wild-type Balb/c mice were sensitized and repeatedly challenged by ovalbumin (OVA) or saline. The effects of montelukast on the development of airway remodelling were compared between the two mouse genotypes. RESULTS: CysLTs in the lung were increased after repeated allergen challenges, and significantly enhanced in GATA-3-overexpressing mice. The enhanced cysLT levels were accompanied by the development of eosinophilia, smooth muscle cell hyperplasia, and increased stromal cell-derived factor-1 gene expression with a small increase in pro-collagen gene expression in OVA-challenged GATA-3-overexpressing mice, but not in wild-type mice. Montelukast significantly decreased lung cysLT levels and inhibited the GATA-3-overexpression-related airway remodelling, potently preventing smooth muscle cell hyperplasia, but partially suppressed the increased pro-collagen gene expression and eosinophilic inflammation. Increases in the levels of IL-4, IL-5, IL-13, and eotaxin in bronchial lavage and TGF-ß gene expression in the lungs were induced by OVA in both mouse genotypes. Montelukast treatment also significantly reduced these levels to the levels seen after saline challenges in GATA-3-overexpressing mice. CONCLUSION: Montelukast efficaciously prevented airway inflammation and remodelling in a GATA-3-overexpression antigen challenge mouse model by decreasing the cysLT-driven Th2 cytokine cycle of amplification of airway pathologies.

Anesthetic management using costoclavicular brachial plexus block with patient-controlled analgesia in Pediatrics: A case report. / Tratamiento anestésico mediante bloqueo del plexo braquial costoclavicular con analgesia controlada por el paciente en Pediatría: caso clínico.

Anesthetic management using costoclavicular brachial plexus block with patient-controlled analgesia in pediatrics: a case report Abstract The costoclavicular brachial plexus block (CBPB) has been receiving increasing attention as an effective technique for upper arm surgery conducted without phrenic paralysis. However, studies in children are lacking. CBPB was applied to a 10 year-old girl undergoing scheduled radial and ulnar osteotomy due to multiple cartilaginous exostoses and ulnar lengthening. CBPB was performed with a bolo administration of 10 mL of 0.25% levobupivacaine, and the catheter was sequentially replaced in the right costoclavicular space. After surgery, a continuous infusion of 0.17% levobupivacaine through a catheter was initiated at 2 mL/h, along with patient-controlled analgesia (PCA) of 3 mL 0.17% levobupivacaine with a 60-minute lock out. The patient complained of 5/10 pain on the numerical rating scale (NRS) 2 hours after surgery, which improved immediately after bolus administration. The analgesia induced by CBPB was otherwise effective (NRS ≤ 2). CBPB with PCA may provide adequate analgesia in pediatric cases.

Preoperative underweight is associated with adverse postoperative events in patients undergoing microvascular reconstruction surgery for oral and maxillofacial cancer.

We aimed to describe the prevalence of postoperative complications and evaluate its relationship with underweight, obesity, preoperative nutritional status, and systemic inflammation status in patients undergoing microvascular reconstruction for oral and maxillofacial cancer. Patients who were ≥20 years old and underwent microvascular reconstruction surgery between January 2009 to June 2019 were investigated. Patient demographics including body mass index, prognostic nutritional status, and neutrophil-lymphocyte ratio were collected. Logistic regression analysis was applied to evaluate these impacts on postoperative complications. A postoperative complication was defined as a Clavien-Dindo classification more than or equal to II. Of the 145 patients included in the analysis, 83 patients (57.2%) experienced postoperative complications, belonging to a Clavien-Dindo classification Ⅱ (n=71), Ⅲb (n=11), and Ⅳa (n=1). Multiple logistic regression revealed that a body mass index less than 18.5 kg/m2 (odds ratio 6.19, 95% confidential interval 1.34-28.6, P=0.02) was related to postoperative complications. Another multiple logistic regression model including all explanatory factors found that underweight (P=0.03) was related to postoperative complications. This retrospective study showed that preoperative underweight was associated with postoperative complications as evaluated by the Clavien-Dindo classification.

Induction of insulin-like growth factor-I by interleukin-17F in bronchial epithelial cells.

BACKGROUND: Increased expression of IL-17F has been noted in the airway of asthmatic patients, but its role in asthma has not been fully elucidated. Insulin-like growth FACTOR-I (IGF-I) is known to be involved in airway remodelling and inflammation, while its regulatory mechanisms remain to be defined. OBJECTIVE: To further clarify the biological function of IL-17F, we investigated whether IL-17F is able to regulate the expression of IGF-I in bronchial epithelial cells. METHODS: Bronchial epithelial cells were stimulated with IL-17F in the presence or absence of T-helper type 2 cytokines. Various kinase inhibitors were added to the culture to identify the key signalling events leading to the expression of IGF-I, in conjunction with the use of short interfering RNAs (siRNAs) targeting mitogen- and stress-activated protein kinase (MSK) 1, p90 ribosomal S6 kinase (p90RSK), and cyclic AMP response element-binding protein (CREB). RESULTS: IL-17F significantly induced IGF-I gene and protein expression, and co-stimulation with IL-4 and IL-13 augmented its production. MAP kinase kinase (MEK) inhibitors and the Raf1 kinase inhibitor significantly inhibited IGF-I production, and the combination of PD98059 and Raf1 kinase inhibitor showed further inhibition. Overexpression of Raf1 and Ras dominant-negative mutants inhibited its expression. MSK1 inhibitors significantly blocked IL17F-induced IGF-I expression. Moreover, transfection of the siRNAs targeting MSK1, p90RSK, and CREB blocked its expression. CONCLUSIONS: In bronchial epithelial cells, IL-17F is able to induce the expression of IGF-I via the Raf1-MEK1/2-ERK1/2-MSK1/p90RSK-CREB pathway in vitro.

Transforming growth factor-ß stimulates the expression of eotaxin/CC chemokine ligand 11 and its promoter activity through binding site for nuclear factor-κß in airway smooth muscle cells.

BACKGROUND: Chemokines ligands of CCR3 including eotaxin/CC chemokine ligand 11 (CCL11) may contribute to the pathogenesis of asthma. These chemokines and a growth factor (TGF-beta) may be involved in the process of airway remodelling. OBJECTIVE: We analysed the effects of TGF-beta on the expression of CCR3 ligands in human airway smooth muscle (HASM) cells and investigated the mechanisms. METHODS: HASM cells were cultured and treated with TGF-beta and Th2 cytokines IL-4 or IL-13. Expression of mRNA was analysed by real-time PCR. Secretion of CCL11 into the culture medium was analysed by ELISA. Transcriptional regulation of CCL11 was analysed by luciferase assay using CCL11 promoter-luciferase reporter plasmids. RESULTS: IL-4 or IL-13 significantly up-regulated the expression of mRNAs for CCL11 and CCL26. TGF-beta alone did not increase the expression of chemokine mRNAs, but enhanced the induction of only CCL11 by IL-4 or IL-13 among CCR3 ligands. Activity of the CCL11 promoter was stimulated by IL-4, and this activity was enhanced by TGF-beta. Activation by IL-4 or IL-4 plus TGF-beta was lost by mutation of the binding site for signal transducers and activators of transcription-6 (STAT6) in the promoter. Cooperative activation by IL-4 and TGF-beta was inhibited by mutation of the binding site for nuclear factor-kappaB (NF-kappaB) in the promoter. Pretreatment with an inhibitor of NF-kappaB and glucocorticoid fluticasone propionate significantly inhibited the expression of CCL11 mRNA induced by IL-4 plus TGF-beta, indicating the importance of NF-kappaB in the cooperative activation of CCL11 transcription by TGF-beta and IL-4. CONCLUSION: These results indicate that Th2 cytokines and TGF-beta may contribute to the pathogenesis of asthma by stimulating expression of CCL11. The transcription factors STAT6 and NF-kappaB may play pivotal roles in this process.

Effects of xenon on ischemic spinal cord injury in rabbits: a comparison with propofol.

BACKGROUND: Xenon has been shown to reduce cellular injury after cerebral ischemia. However, the neuroprotective effects of xenon on ischemic spinal cord are unknown. The authors compared the effects of xenon and propofol on spinal cord injury following spinal cord ischemia in rabbits. METHODS: Thirty-two male New Zealand white rabbits were randomly assigned to one of three groups. In the xenon and propofol group, 70% of xenon and 0.8 mg/kg/min of propofol were administered 30 min before an aortic occlusion and maintained until the end of the procedure. The aortic occlusion was performed for 15 min. In the sham group, the aorta was not occluded. After an assessment of the hind limb motor function using the Tarlov score (0=paraplegia, 4=normal) at 48 h after reperfusion, gray and white matter injuries were evaluated based on the number of normal neurons in the anterior spinal cord and the percentage areas of vacuolation in the white matter, respectively. RESULTS: In the xenon and propofol groups, the Tarlov score and the number of normal neurons were significantly lower than those in the sham group, whereas the percentage areas of vacuolation were similar among the three groups. There were no significant differences in Tarlov scores and the number of normal neurons between the xenon and the propofol groups. CONCLUSION: The results indicated that 70% of xenon has no additional neuroprotective effects on ischemic spinal cord injury in rabbits compared with propofol.

Concomitant expression of HER2 and HIF-1alpha is a predictor of poor prognosis in uterine cervical carcinoma treated with concurrent chemoradiotherapy: prospective analysis (KGROG0501).

BACKGROUND: In previously reported retrospective analyses of uterine cervical carcinoma cases, HER2 was correlated with poor radiation sensitivity and poor treatment outcomes and HIF-1alpha was found to be an indicator of poor prognosis. To date, no prospective studies have been performed to evaluate the radiation sensitivity and treatment outcomes of patients with uterine cervical carcinoma relative to HER2 and HIF-1alpha expressions. We conducted a prospective evaluation of HER2 and HIF-1alpha in cases of locally advanced uterine cervical carcinoma treated with concurrent chemoradiotherapy. METHODS: Between June 2005 and April 2008, 25 patients with locally advanced uterine cervical carcinoma were registered in this study, KGROG0501. Their clinical stages were Ib2/IIb/IIIb/IVa in 1/2/22/1 cases, respectively. Nineteen cases had squamous cell carcinoma and six had adenocarcinoma. HER2 expression and HIF-1alpha expression were analyzed using an immunohistochemical kit on pretreatment biopsied specimens. HIF-1alpha expression was studied using another commercial immunohistochemical kit on pretreatment biopsied specimens. The survival rates were compared between patients with and without positive HER2 and HIF-1alpha expressions. RESULTS: The 20-month survival of HER2(-) and HIF-1alpha(-) cases (n = 6) was 100% and that of HER2(+) and HIF-1alpha(+) cases (n = 4) was 37.5% (p = 0.0032). CONCLUSIONS: In this first prospective analysis of patients with uterine cervical carcinoma treated with concurrent chemoradiotherapy, concomitant expression of HER2 and HIF-1alpha was suggested to be a strong indicator of poor prognosis. A novel therapy including molecular targeted therapy such as anti-HER2 and anti-HIF-1alpha may be worth considering in patients with concomitant expression of HER2 and HIF-1alpha.