Reciprocal Cytokine-Mediated Cellular Interactions in Mouse Epidermis: Promotion of γ δ T-Cell Growth by IL-7 and TNFα and Inhibition of Keratinocyte Growth by γIFN

A unique subset of γδ T cells, termed dendritic epidermal T cells (DETC), resides in symbiosis with keratinocytes in mouse epidermis. We have shown previously that interleukin 7 (IL-7) which is produced by keratinocytes, promotes growth and prevents apoptosis in DETC. To extend this observation, we examined 12 cytokines, each of which is expressed by epidermal cells at mRNA and/or protein levels, for their capacities to modulate the growth of DETC. Cytokines examined included IL-1α, IL-2, IL-3, IL-4, IL-6, IL-7, IL-8, IL-10, tumor necrosis factor-α (TNFα), interferon-γ (IFNγ) granulocyte/macrophage-colony stimulating factor (GM-CSF) and macrophage inflammatory protein-1γ (MIP-1γ). When tested individually, IL-2 and IL-7 promoted maximal growth of the long-term cultured DETC line 7-17. When tested in combinations, synergistic growth- promoting effects were seen with IL-2 and IL-4 or IL-7, and with IL-7 and IL-4 or TNFγ. Dose-response experiments demonstrated that TNFγ, which is produced by keratinocytes, enhances IL,-7-induced DETC proliferation, but inhibits IL-2 – induced proliferation. The mouse keratinocyte-derived cell line Pam 212 was used to test these cytokines for their capacities to regulate keratinocyte growth. Only γIFN, which is produced by DETC, inhibited proliferation in a dose-dependent fashion. These results illustrate three reciprocal pathways by which epidermal cytokines regulate the growth of epidermal cells: 1) a paracrine mechanism by which keratinocyte-derived cytokines (e.g., IL-7 and TNFα) promote the growth of DETC, 2) an autocrine mechanism by which DETC-derived cytokines (e.g., IL-2 and IL-4) support their own growth, and 3) a reciprocal pathway in which a cytokine produced by resident epidermal leukocytes (e.g., γIFN) modulates the growth of keratinocytes

Plasma level of oxidized low-density lipoprotein is an independent determinant of coronary macrovasomotor and microvasomotor responses induced by bradykinin

AbstractObjectivesWe examined the relationship between coronary endothelium-dependent vasodilation in response to bradykinin (BK) and plasma levels of oxidized low-density lipoprotein (oxLDL) in subjects with normal coronary arteries.BackgroundIt is unclear whether the plasma oxLDL level is a determinant of coronary endothelial function. Bradykinin plays an important role in regulating resting coronary tone and flow-mediated coronary vasomotion.MethodsCoronary blood flow (CBF) in the left anterior descending (LAD) coronary artery was assessed by quantitative angiography and a Doppler flow wire in 94 consecutive subjects with normal coronary arteries. The plasma oxLDL level was measured by enzyme-linked immunosorbent assay using DLH3R, a specific antibody against oxLDL.ResultsPlasma levels of oxLDL in diabetic subjects (n = 13) were higher than those in non-diabetic subjects (n = 81). Plasma levels of oxLDL correlated with body mass index (BMI). Bradykinin at doses of 0.2, 0.6, and 2.0 μg/min caused dose-dependent increases in diameter and CBF in the LAD coronary artery. By a univariate analysis, oxLDL levels significantly correlated with epicardial (r = −0.30, p < 0.0001) and resistant (r = −0.36, p = 0.003) coronary vasodilator responses to BK at 2.0 μg/min, whereas total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides were not associated with these coronary responses. In a stepwise multivariate analysis, oxLDL levels were significantly correlated with epicardial and resistant coronary vasomotor responses to BK, independent of age, gender, smoking status, other lipid levels, BMI, hypertension, and diabetes.ConclusionsThe plasma level of oxLDL is an appropriate surrogate for assessing coronary endothelial-dependent vasomotor function as estimated by responses to BK compared with conventional risk factors for atherosclerosis

Type A thymoma : a rare cause of neoplastic cardiac tamponade with long-term survival

Background: The prognosis of thymoma with cardiac tamponade is generally poor. Most of the reported thymomas with cardiac tamponade were type B or type AB (mixed thymoma), and cardiac tamponade due to type A thymoma, which has a better prognosis compared to type B thymoma, is extremely rare. Case presentation: We encountered a case of cardiac tamponade in a 71-year-old male. He visited our emergency department due to exacerbation of fatigue and dyspnea on exertion that lasted for two weeks. Chest imaging revealed a large amount of pericardial fluid and a contrast-enhanced tumor with calcification in the anterior mediastinum. The patient underwent thoracoscopic tumor biopsy and pathological examinations revealed type A thymoma. In this case, long-term disease-free survival (7.5 years) was achieved by multidisciplinary treatment (preoperative chemotherapy, surgical excision, and postoperative radiation therapy), in accordance with the histological type. Conclusions: This case indicates that neoplastic cardiac tamponade, even in elderly patients, should not necessarily be regarded as a terminal cancer and requires a systematic investigation for underlying causes

Two-photon Bio-imaging with a Mode-locked Semiconductor Laser

Abstract: We demonstrated two-photon imaging of biological tissues by employing a mode-locked semiconductor laser. Kilowatt-peak-power second-harmonic pulses were obtained from amplified 1.55-µm optical pulses, and were used for two-photon excitation. ©2006 Optical Society of America OCIS codes: (140.5960) Semiconductor lasers; (170.3880) Medical and biological imaging. 1

Evaluation of the Upper Gastrointestinal Tract in Ulcerative Colitis Patients

To analyze the clinical characteristics of patients with ulcerative colitis who have upper gastrointestinal lesions, we retrospectively reviewed the data of 216 patients with ulcerative colitis who underwent esophagogastroduodenoscopy at our institute in April 2008-March 2016. We investigated the endoscopic features and compared the clinical characteristics between the patients with and without upper gastrointestinal lesions. Forty-two patients (19.4%) had upper gastrointestinal lesions, including multiple erosions (n=18), bamboo joint-like appearance (n=17), mucosa with white spots (n=4), friable mucosa (n=2), ulcer (n=1), and purulent deposits within the mucosa (n=1) in the stomach and/or duodenum. Compared to the patients without upper gastrointestinal lesions, those with upper gastrointestinal lesions showed significantly more frequent extraintestinal manifestations (19.0% vs. 8.0%, p<0.05) and a significant history of colectomy (33.3% vs. 12.1%, p<0.01). There were no significant differences with regard to the sex ratio, age at esophagogastroduodenoscopy, gastrointestinal symptoms, time since the diagnosis of ulcerative colitis, type of colitis at the initial diagnosis of ulcerative colitis, or gastric atrophy between the groups. In conclusion, gastroduodenal lesions were identified in 19.4% of the patients with ulcerative colitis. Esophagogastroduodenoscopy is particularly recommended for ulcerative colitis patients who show extraintestinal manifestations and for those who have undergone a colectomy

The novel latex agglutination turbidimetric immunoassay system for simultaneous measurements of calprotectin and hemoglobin in feces

Background/Aims Fecal calprotectin (Fcal) as well as the fecal immunochemical test (FIT) are useful biomarkers for detecting activity and mucosal healing in inflammatory bowel diseases. Here, we report the performance of simultaneous measurements of Fcal and FIT for ulcerative colitis (UC) patients using the newly-developed latex agglutination turbidimetric immunoassay (LATIA) system. Methods Fcal and hemoglobin were measured by the LATIA system in 152 UC patients who underwent colonoscopy. Fcal was also quantified with a conventional enzyme-linked immunosorbent assay (ELISA). Fecal markers were evaluated in conjunction with the mucosal status of UC, which was assessed via the Mayo endoscopic subscore (MES) classification. Results The LATIA system could quantify calprotectin and hemoglobin simultaneously with the same fecal samples within 10 minutes. The values of the Fcal-LATIA closely correlated with those of the Fcal-ELISA (Spearman rank correlation coefficient, r=0.84; P Conclusions The performance of the novel Fcal-LATIA was equivalent to that of the conventional Fcal assay. Simultaneous measurements with FITs would promote the clinical relevance of fecal biomarkers in UC

Prevalence and Intra-Family Phylogenetic Divergence of Burkholderiaceae-Related Endobacteria Associated with Species of Mortierella.

Endofungal bacteria are widespread within the phylum Mucoromycota, and these include Burkholderiaceae-related endobacteria (BRE). However. the prevalence of BRE in Mortierellomycotinan fungi and their phylogenetic divergence remain unclear. Therefore, we examined the prevalence of BRE in diverse species of Mortierella. We surveyed 238 isolates of Mortierella spp. mainly obtained in Japan that were phylogenetically classified into 59 species. BRE were found in 53 isolates consisting of 22 species of Mortierella. Among them, 20 species of Mortierella were newly reported as the fungal hosts of BRE. BRE in a Glomeribacter-illycoavidus Glade in the family Burkholderiaceae were separated phylogenetically into three groups. These groups consisted of a group containing Mycoavidus cysteinexigens, which is known to be associated with M. elongata, and two other newly distinguishable groups. Our results demonstrated that BRE were harbored by many species of Mortierella and those that associated with isolates of Mortierella spp. were more phylogenetically divergent than previously reported

Iso-α-Acids, Bitter Components in Beer, Suppress Inflammatory Responses and Attenuate Neural Hyperactivation in the Hippocampus

Due to the growth in aging populations worldwide, prevention and therapy for age-related cognitive decline and dementia are in great demand. We previously demonstrated that long-term intake of iso-α-acids, which are hop-derived bitter compounds found in beer, prevent Alzheimer’s pathology in a rodent model. On the other hand, the effects of iso-α-acids on neural activity in Alzheimer’s disease model mice have not been investigated. Here, we demonstrated that short-term intake of iso-α-acids suppresses inflammation in the hippocampus and improves memory impairment even after disease onset. Importantly, we demonstrated that short-term administration of iso-α-acids attenuated the neural hyperactivation in hippocampus. In 6-month-old 5 × FAD mice exhibiting hippocampus inflammation and memory impairment, oral administration of iso-α-acids for 7 days reduced inflammatory cytokines, including MIP-1α and soluble Aβ and improved object memory in the novel object recognition test. In 12-month-old J20 mice, intake of iso-α-acids for 7 days also suppressed inflammatory cytokines and soluble Aβ in the brain. Manganese-enhanced magnetic resonance imaging (MEMRI) of hippocampi of J20 mice showed increased manganese compared with wild type mice, but iso-α-acids canceled this increased MEMRI signal in J20 mice, particularly in the hippocampus CA1 and CA3 region. Taken together, these findings suggest that short-term intake of iso-α-acids can suppress hippocampus inflammation even after disease onset and improve hyper neural activity in Alzheimer’s disease model mice

Ten Initial Cases of Peroral Endoscopic Myotomy for Treatment of Esophageal Motility Disorders at Okayama University Hospital

Peroral endoscopic myotomy (POEM) for treatment of esophageal motility disorders has recently been reported to be highly effective and less invasive than other treatment. POEM was recently introduced in Okayama University Hospital under the supervision of a physician from a high-volume center. To verify the safety and efficacy of POEM during its introduction in our institution. We examined 10 cases in whom POEM was performed between January 2016 and April 2017. The patients included 7 men and 3 women, with a median age (range) of 49 years (17-74) and median symptom duration of 6 years (1-21). Seven patients had a straight esophagus, and the remaining 3 had a sigmoid esophagus. According to the Chicago classification, 6 patients were diagnosed with type I achalasia, 2 with type II achalasia, and 2 with distal esophagus spasm. Treatment outcomes and adverse events were evaluated. Treatment success was defined as a > 3 decrease in Eckardt score or a score of <3 at the time of discharge. The treatment success rate was 90%, with the average Eckardt score decreasing significantly, from 4.7 to 0.9 (p<0.05). No mucosal perforation, severe infection, mediastinitis, severe bleeding, or gastroesophageal reflux occurred intraoperatively or postoperatively. POEM was introduced to Okayama University Hospital, and the first 10 cases were accomplished safely and effectively under the supervision of an expert physician from a high-volume center