Methods: HFCs were obtained from patients with LSS who had undergone decompression surgery. The cells were stimulated with TGF-β and pretreated with either the p38 mitogen-activated protein (MAP) kinase inhibitor SB203580 or the p44/42 MAP kinase inhibitor FR180204. IL-6 secretion in the cell culture medium and IL-6 messenger RNA (mRNA) expression levels were analyzed using an enzyme-linked immunoassay and real-time polymerase chain reaction, respectively. Results: TGF-β administration resulted in a dose- and time-dependent stimulation of IL-6 release. Treatment with SB203580 and FR180204 markedly suppressed TGF-β–induced IL-6 secretion from HFCs. Moreover, these inhibitors suppressed IL-6 mRNA expression in response to TGF-β stimulation. Conclusions Our findings indicate that TGF-β induces IL-6 protein secretion and gene expression in HFCs through the activation of p38 or p44/42 MAP kinases. These results suggest a potential association between IL-6–mediated inflammatory response and tissue hypertrophy in LSS, and we provide insights into molecular targets for therapeutic interventions targeting LSS-related inflammation through our analysis of the MAP kinase pathway using HFCs.

BACKGROUND: The canonical Wnt/β-catenin signaling pathway is a fundamental regulatory system involved in various biological events. ICG-001 selectively blocks the interaction of β-catenin with its transcriptional co-activator cyclic AMP response element-binding protein (CBP). Recent studies have provided convincing evidence of the inhibitory effects of ICG-001 on Wnt-driven disease models, such as organ fibrosis, cancer, acute lymphoblastic leukemia, and asthma. However, the effects of ICG-001 in atopic dermatitis (AD) have not been investigated. OBJECTIVE: To investigate whether β-catenin/CBP-dependent signaling was contributed in the pathogenesis of AD and ICG-001 could be a therapeutic agent for AD. METHODS: We examined the effects of ICG-001 in an AD-like murine model generated by repeated topical application of the hapten, oxazolone (Ox). ICG-001 or vehicle alone was injected intraperitoneally every day during the development of AD-like dermatitis arising from once-daily Ox treatment. RESULTS: Ox-induced AD-like dermatitis characterized by increases in transepidermal water loss, epidermal thickness, dermal thickness accompanied by increased myofibroblast and mast cell counts, and serum levels of thymic stromal lymphopoietin and thymus and activation-regulated chemokine, and decreases in stratum corneum hydration, were virtually normalized by the treatment with ICG-001. Elevated serum levels of periostin tended to be downregulated, without statistical significance. CONCLUSION: These results suggest that β-catenin/CBP-dependent signaling might be involved in the pathogenesis of AD and could be a therapeutic target.
Animals ; Asthma ; Chemokine CCL17 ; Cyclic AMP Response Element-Binding Protein ; Cyclic AMP ; Dermatitis ; Dermatitis, Atopic ; Fibrosis ; Mast Cells ; Mice ; Myofibroblasts ; Oxazolone ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Water

Objective: This study aimed to clarify outpatient nurses' awareness of their support for the decision-making of newly diagnosed cancer patients undergoing surgical therapy.Methods: Semi-structured interviews were conducted with eight outpatient nurses from two hospitals, and transcribed data were analyzed qualitatively.Results: The following four categories of outpatient nurses' awareness were extracted: "Difficult environment for supporting decision-making", "Identifying a patient in need of support", "Collaborating at the organizational level", and "Supporting the patient until a satisfying decision is made". Although the nurses recognized the need to support cancer patients' decision-making when undergoing surgical therapy, they were obliged to prioritize other duties and found it difficult to adequately provide the support needed. Although it was difficult, nurses tried to identify patients requiring support during their routine work, and to assist them until a satisfying decision was made by collaborating with colleagues at the organizational level.Conclusion: In order for outpatient nurses to more effectively support cancer patients' decision-making, it is necessary to allocate an adequate number of personnel, secure interview spaces, and provide training for nurses to improve their skills in decision-making support, in addition to implementing the necessary organizational changes.

Introduction: We started the gender-specific clinic for women to provide sufficient treatment for female patients. The purpose of this study was to clarify the characteristics of patients using the gender-specific clinic for women, and to assess the association among depression, physical and mental subjective symptoms.Methods: This observational study included female patients aged 16-84 years who visited our clinic between June 2012 and December 2015 (N=97). In addition to general attributes, we collected data on physical and mental symptoms, and depression status using the Cornell Medical Index (CMI) and Self-rating Depression Scale (SDS), respectively, at the first visit. We conducted analyses to assess patient characteristics and the association between subjective symptoms and depression, and between physical and mental symptoms by estimating odds ratios (ORs) and 95% confidence intervals (CIs).Results: The average age of subjects was 50.4 years. The average CMI score was 42.7 points and 55.9% of the subjects were suggested to be neurotic. The average SDS score was 45.0 points and 64.0% of them were suggested to be depressed. The association with depression by SDS was observed in subjective symptoms of CMI such as fatigue (OR [95%CI]: 7.66 [2.26-25.99], p-value: 0.001) and anxiety (OR [95%CI]: 11.73 [1.80-∞], p-value: 0.006). Physical symptoms in the cardiovascular system were positively association with some mental symptoms such as tension.Conclusion: As female patients often have mental symptoms, it is essential for doctors engaging in gender-specific medicine for women to approach patients while considering psychological and mental aspects.

OBJECTIVE: Recent investigations have revealed DNA mismatch repair (MMR) gene mutations are closely related with carcinogenesis of endometrial cancer; however the impact of MMR protein expression on prognosis is not determined. Correlations between MMR-related protein expression and clinicopathological factors of endometrial cancers are analyzed in the present study. METHODS: A total of 191 endometrial cancer tissues treated between 1990 and 2007 in our hospital were enrolled. Immunoreactions for MSH2, MLH1, MSH6, and PMS2 on tissue microarray specimens and clinicopathological features were analyzed retrospectively. RESULTS: Seventy-six cases (40%) had at least one immunohistochemical alteration in MMR proteins (MMR-deficient group). There were statistically significant differences of histology, International Federation of Gynecology and Obstetrics (FIGO) stage, and histological grade between MMR-deficient group and the other cases (MMR-retained group). Response rate of first-line chemotherapy in evaluable cases was slightly higher in MMR-deficient cases (67% vs. 44%, p=0.34). MMR-deficient cases had significantly better progression-free and overall survival (OS) compared with MMR-retained cases. Multivariate analysis revealed MMR status was an independent prognostic factor for OS in endometrial cancers. CONCLUSION: MMR-related proteins expression was identified as an independent prognostic factor for OS, suggesting that MMR was a key biomarker for further investigations of endometrial cancers.
Adaptor Proteins, Signal Transducing/deficiency/metabolism ; Adenosine Triphosphatases/deficiency/metabolism ; Adult ; Aged ; Aged, 80 and over ; Chemotherapy, Adjuvant ; *DNA Mismatch Repair ; DNA Repair Enzymes/deficiency/*metabolism ; DNA-Binding Proteins/deficiency/*metabolism ; Endometrial Neoplasms/*diagnosis/drug therapy/genetics/pathology ; Female ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; MutS Homolog 2 Protein/deficiency/metabolism ; Neoplasm Proteins/deficiency/metabolism ; Nuclear Proteins/deficiency/metabolism ; Prognosis ; Retrospective Studies ; Tumor Markers, Biological/*metabolism

We describe a case of meningeal carcinomatosis of the internal auditory meatus presenting as sudden deafness accompanied by dizziness. A 54-year-old woman complained of acute right-side hearing loss in October 2014. The pure tone audiometry test revealed right-side hearing loss of 47.5 dB. She was treated with oral steroids. Her hearing as well as her symptoms of dizziness worsened and she was admitted for further examination. Her right and left-side hearing had worsened to 105.0 dB and 47.5 dB, respectively. A magnetic resonance imaging scan of the head revealed bilateral enhancement of the internal auditory canal and multiple brain metastases. The chest radiograph revealed a mass in the left lung. Adenocarcinoma of the lung was diagnosed. Lumbar puncture yielded no evidence of carcinoma cells in the cerebrospinal fluid, but an increased number of lymphocytes was confirmed. A diagnosis of multiple brain metastases and leptomeningeal metastasis from the adenocarcinoma of the lung was considered. Whole-brain radiation therapy (30 Gr/10 fractions) was administered. Progressive bilateral hearing loss is a rare first manifestation of meningeal carcinomatosis. It is quite important to consider the possibility of this condition when patients present with sudden deafness.
Adenocarcinoma ; Audiometry ; Brain ; Cerebrospinal Fluid ; Diagnosis ; Dizziness ; Ear, Inner ; Female ; Head ; Hearing ; Hearing Loss ; Hearing Loss, Bilateral ; Hearing Loss, Sudden ; Humans ; Lung ; Lymphocytes ; Magnetic Resonance Imaging ; Meningeal Carcinomatosis ; Middle Aged ; Neoplasm Metastasis ; Radiography, Thoracic ; Spinal Puncture ; Steroids ; Temporal Bone

PURPOSE: It has been reported that the Pulse Contour Cardiac Output (PiCCO) is very useful mainly in the field of intensive care and treatment to grasp the pathophysiological conditions of pulmonary edema because of its capability of obtaining data such as Pulmonary Vascular Permeability Index (PVPI) and Extra Vascular Lung Water (EVLW). Furthermore, a high degree of usability of various markers has been reported for better understanding of the pathological conditions in cases with septicemia. MATERIALS AND METHODS: The correlation between the cardiorespiratory status based upon the PiCCO monitor (EVLW and PVPI) and inflammatory markers including C reactive protein, procalcitonin (PC), and Endotoxin Activity Assay (EAA) were evaluated in 11 severe cases that required treatment with a respirator in an intensive care unit. RESULTS: The EAA values were significantly higher in patients with abnormal EVLW at 0.46+/-0.20 compared to the normal EVLW group at 0.21+/-0.19 (p=0.0064). In a similar fashion, patients with abnormal PVPI values tended to have higher PC levels at 18.9+/-21.8 compared to normal PVPI cases at 2.4+/-2.2 (p=0.0676). On the other hand, PVPI was significantly higher in the abnormal EAA group at 3.55+/-0.48 in comparison with the normal EAA group at 1.99+/-0.68 (p=0.0029). The abnormal EAA group tended to have higher PVPI values than the normal EAA group. CONCLUSION: The EAA is a measurement method designed to estimate the activity of endotoxins in the whole blood. Our results suggest that the EAA value, which had the greatest correlation with lung disorders diagnosed by the PiCCO monitoring, reflects inflammatory reactions predominantly in the lungs.
Adult ; Aged ; Aged, 80 and over ; Cardiac Output/physiology ; Endotoxins/*blood ; Female ; Humans ; Lung Injury/*blood/*diagnosis/physiopathology ; Male ; Middle Aged ; Pulmonary Edema/blood/*diagnosis/physiopathology

A 68-year-old woman presented dizziness whenever she put her finger into the right ear and also complained of water-streaming tinnitus, which indicated she would have been suffering from perilymph fistula. An exploratory tympanotomy was conducted. Leakage of perilymph from the round window was suspected, although the cochlin-tomoprotein (CTP) results were negative. After the procedure, the patient's finger-induced dizziness, tinnitus, and vertigo spells disappeared completely. However, her dizzy symptom did not improve. The patient also complained of general fatigue, weight loss, and insomnia, which led us to suspect comorbid depression. Antidepressants and vestibular rehabilitation treatment resulted in a significant improvement in her dizziness. Although it is not apparent whether the patient had a perilymph fistula, this case demonstrates the importance of evaluating not only physical symptoms but also psychological comorbidity, especially when the physical symptoms are intractable despite treatment.
Aged ; Antidepressive Agents ; Comorbidity ; Depression* ; Dizziness ; Ear ; Fatigue ; Female ; Fingers ; Fistula* ; Humans ; Perilymph* ; Rehabilitation ; Sleep Initiation and Maintenance Disorders ; Tinnitus ; Vertigo ; Weight Loss

OBJECTIVE: Compared with serous adenocarcinoma (SAC), clear cell carcinoma (CCC) often shows chemo-resistance, which would potentially lead to a poor prognosis. On the other hand, there have been arguments over prognoses of CCC and SAC disease. In the present study, multivariate analysis to compare prognosis of CCC patients with that of SAC was aimed for the patients selected from central pathologic review. METHODS: Between 1984 and 2009, a total of 500 ovarian cancer patients were treated at our university hospital. Among them, 111 patients with CCC and 199 patients with SAC were identified through central pathological review. Overall survival and progression-free survival were compared using Kaplan-Meier method, and prognostic factors were investigated by multiple regression analyses. RESULTS: Median age was 52 years for CCC and 55 years for SAC (p=0.03). The ratio of stage I patients were significantly higher in CCC compared with SAC (55% vs. 13%, p<0.01). Among evaluable cases, response rate was significantly lower in CCC than that in SAC (32% vs. 78%, p<0.01). No significant differences of progression-free survival and overall survival were observed in stage I patients; however, prognoses of CCC were significantly poorer than those of SAC in advanced-stage disease. In stage II-IV patients, not only residual tumors and clinical stages, but also clear cell histology were identified as predictors for poor prognosis. CONCLUSION: Clear cell histology was identified as a prognostic factor for advanced-stage ovarian cancers. Histologic subtypes should be considered in further clinical studies, especially for advanced epithelial ovarian cancers.
Adenocarcinoma ; Adenocarcinoma, Clear Cell ; Chlormequat ; Cystadenocarcinoma, Serous ; Disease-Free Survival ; Hand ; Humans ; Multivariate Analysis ; Neoplasm, Residual ; Ovarian Neoplasms ; Prognosis

BACKGROUND/AIMS: The gastrointestinal motility effects of endogenous incretin hormones enhanced by dipeptidyl peptidase-IV (DPP-IV) inhibitors have not yet been sufficiently investigated. The aim of this study was to determine whether single pre-prandial sitagliptin, the DPP-IV inhibitor, administration might have an effect on the rate of liquid gastric emptying using the 13C-acetic acid breath test. METHODS: Ten healthy male volunteers participated in this randomized, two-way crossover study. The subjects fasted for overnight and were randomly assigned to receive 50 mg sitagliptin 2 hours before ingestion of the liquid test meal (200 kcal per 200 mL, containing 100 mg 13C-acetate) or the test meal alone. Under both conditions, breath samples were collected for 150 minutes following the meal. Liquid gastric emptying was estimated by the values of the following parameters: the time required for 50% emptying of the labeled meal (T1/2), the analog to the scintigraphy lag time for 10% emptying of the labeled meal (Tlag), the gastric emptying coefficient and the regression-estimated constants (beta and kappa), calculated by using the 13CO2 breath excretion curve using the conventional formulae. The parameters between the 2 test conditions were compared statistically. RESULTS: No significant differences in the calculated parameters, including T1/2, Tlag, gastric emptying coefficient or beta and kappa, were observed between the 2 test conditions. CONCLUSIONS: The present study revealed that single-dose sitagliptin intake had no significant influence on the rate of liquid gastric emptying in asymptomatic volunteers.
Breath Tests ; Cross-Over Studies ; Eating ; Gastric Emptying ; Gastrointestinal Motility ; Humans ; Incretins ; Male ; Meals ; Pyrazines ; Triazoles ; Sitagliptin Phosphate