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SUMMARY: Although no consensus is available on the treatment of esophageal squamous cell carcinoma (ESCC) invading adjacent organs (T4), establishing effective induction treatments is crucial to altering an unresectable status and achieving curative resection. Here, we evaluated the efficacy of chemotherapy using 5-fluorouracil, cisplatin, and docetaxel (DCF) as the initial induction treatment for T4 ESCC. Fifty patients without distant metastasis who underwent initial induction chemotherapy using DCF for T4 ESCC were propensity score-matched with 50 patients who underwent radiotherapy concurrent with cisplatin and 5-fluorouracil (CRT). In the DCF group, 24 (48.0%) patients underwent surgery, achieving a 64% clinical response rate compared to 72.0% for induction CRT. CRT was also performed in another 24 (48.0%) patients in the DCF group in whom surgical resection was not indicated. The DCF group had significantly higher overall resectability than the CRT group (78.0% vs. 48.0%, P = 0.0017). The esophageal perforation rate during induction treatments was significantly lower in the DCF group than the CRT group (4.0% vs. 18.0%, P = 0.0205). Prognosis was significantly better in the DCF group than the CRT group (5-year cancer-specific survival 42.1% vs. 22.2%, P = 0.0146). Thus, induction DCF chemotherapy in patients with T4 ESCC reduced esophageal perforation and increased overall resectability, leading to better survival than CRT alone. Therefore, DCF chemotherapy may be an effective and safe option for initial induction treatment of T4 ESCC. [ABSTRACT FROM AUTHOR]

Although 3-field lymph node dissection (3-FLD) is often performed for thoracic esophageal squamous cell carcinoma (ESCC), the clinical effects of cervical lymph node dissection in addition to mediastinal and abdominal dissections on postoperative complications remain unclear. A total of 367 ESCC patients who underwent curative esophagectomy for thoracic esophageal cancer in our hospital from 2010 to 2015 were included in the study: 157 patients who underwent 2-field lymph node dissection (2-FLD) and 210 patients who underwent 3-FLD. Clinicopathological parameters and postoperative complications based on the Clavien-Dindo classification were compared between the two groups.We performed propensity score matching (PSM) analyses to compare the groups with wellbalanced backgrounds. In terms of patient background, clinical T (p<0.001), N (p<0.001), and M (p=0.002) stage of tumor was significantly more advanced; therefore, preoperative treatment was more frequently performed in the 3-FLD group than in the 2-FLD group (91.0% vs. 79.0%, P<0.001). However, perioperative parameters including operation time, blood loss, and the number of dissected mediastinal and abdominal lymph nodes did not differ between the groups. In terms of postoperative complications, the occurrence rate of pneumonia increased significantly in patients with 3-FLD compared to 2-FLD (grade III or higher: 10.5% vs. 3.2%, P = 0.025). Although the duration of systemic inflammatory response syndrome (SIRS) was longer in the 3-FLD group than in the 2-FLD group (median 3 days vs. 2 days, P=0.025), other postoperative parameters (including the highest level of postoperative serum C-reactive protein, intensive care unit stay, re-operation rate, and postoperative hospital stay) were similar between the groups. After PSM, the differences in the background between the groups disappeared. PSM analysis showed that there was no significant difference in each complication between the groups. The duration of SIRS tended to be longer in the 3-FLD group than in the 2-FLD group, but the difference was not significant. The field of lymphadenectomy negatively impacted the short-term outcome in ESCC patients in terms of pneumonia and inflammatory response. However, because the results of the PSM analyses indicate that the short-term outcome was similar between the two groups, 3-FLD could be as feasible as 2-FLD in ESCC patients. [ABSTRACT FROM AUTHOR]

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Differences in cytotoxic T lymphocyte activity in hepatitis C virus infection may account for the outcome of interferon monotherapy. To investigate this hypothesis, we analysed the response of peripheral CD8+ T cells that recognized epitopes presented by HLA-A*2402. We synthesized HLA/β2-microglobulin/peptide complexes using two epitopes. Production of interferon-γ by CD8+ T cells in response to plastic-bound monomeric HLA/peptide complex was observed frequently in sustained virus responders (SVR) ( n = 13) against all the peptides, NS31296–1304 (the percentage of responding patients, 61·5%) and core 129–137 (53·8%), while no interferon-γ production was observed in non-responders (NR) ( n = 13) for any of the peptides. Tetramer-staining showed the presence of CD8+ T cells specific for all the peptides except NS31296–1304 in two SVR at the end of interferon monotherapy, although hardly any such cells were found in four NR. Specific killing was observed against peptides NS31296–1304 (3/4) and core 129–137 (1/4) in sustained responders but none in non-responders. These results suggest that the responses of cytotoxic T lymphocytes (CTLs) were induced during interferon therapy in these patients and that interferon-γ production by CD8+ T lymphocytes against HCV NS31296–1304 and core 129–137 are well maintained in patients with SVR compared with those with NR. These findings emphasize the importance of the CD8+ T cell response in controlling HCV infection. [ABSTRACT FROM AUTHOR]

We established a mouse model in which fatal pneumonia was induced by pneumococcal superinfection following influenza virus infection in chronic Pseudomonas aeruginosa infected mice. In this mouse model, influenza virus infection caused a significant increase in inflammatory cells, cytokines and severe tissue damage in the lungs of these P. aeruginosa infected mice, before pneumococcal infection. Intra- pulmonary virus titres were significantly increased in mice with chronic P. aeruginosa infection, compared with control mice. Neutrophil function analysis showed significant reduction of myeloperoxidase (MPO) activity and lysozyme secretion by influenza virus infection in these mice. Our results suggest that influenza virus infection may play an important role in inducing pneumococcal pneumonia in chronic P. aeruginosa infected mice. Our results suggested that our mouse model is useful for investigating the pathogenesis of influenza virus infection in patients with chronic lung infection. [ABSTRACT FROM AUTHOR]

SUMMARY We previously reported the establishment of a mouse model system of contact hypersensitivity (CHS) to paraphenylemediamine (PPD). In order to analyse the functional contribution of Th2 cytokines, IL-4 and IL-5, in PPD induced CHS, STAT6 deficient (STAT6–/– ) and wild-type control (WT) mice (C57BL/6) were immunized by the topical application of a PPD solution, and then the subsequent skin reactions were examined. Ear swelling was significantly reduced with a delayed peak response in STAT6–/– mice as compared with that of WT mice. A histological analysis showed the infiltration of both eosinophils and neutrophils in the skin of STAT6–/– mice challenged 24 h previously to significantly decrease in comparison with that in the WT mice. The expression of Th2 cytokines (IL-4, IL-5) by ELISA in the PPD-challenged skin tissue specimens as well as the IgE and IgG1 response after challenge were also profoundly reduced in the STAT6–/– mice. The adoptive transfer of the serum obtained from sensitized WT mice for the putative IgE transfer induced a peak response at 3 h and 24 h after challenge. To further investigate the role of mast cells in the induction of PPD-CHS, mast cell deficient W/Wv mice were sensitized with PPD and then were challenged. Maximal ear swelling was detected from 12 to 24 h and another small peak response was observed at 1 h in+/+mice, whereas only a small peak response at 24 h was detected in W/Wv mice. These data indicate that not only Th2 cytokines and IgE but also mast cells play an essential role in the induction of PPD-CHS. [ABSTRACT FROM AUTHOR]

Primary Sjögren's syndrome (SS), sarcoidosis (SA), and psoriasis vulgaris (PV) are all chronic diseases of unknown etiology. Recent studies suggest that activated T cells play a central role in their pathogenesis. We describe a case of a Japanese woman with primary SS complicated by SA and PV. To our knowledge, this is the first case in which these three diseases coexist. Although these three disorders may have a common immunopathogenic mechanism, the extreme rarity of their coexistence suggests that distinct etiological mechanisms are also involved and appear to play an important role in triggering and developing each disease. [ABSTRACT FROM AUTHOR]

We investigated the role of inflammatory cytokines in a mouse model of chronic Pseudomonas aeruginosa infection mimicking diffuse panbronchiolitis (DPB), and determined the effects of clarithromycin therapy on the production of these cytokines. The concentrations of IL-1β, IL-2, IL-4, IL-5, interferon-gamma (IFN-γ) and tumour necrosis factor-alpha (TNF-α) were measured serially in the lungs of mice with experimentally induced chronic respiratory P. aeruginosa infection until 60 days after inoculation. The concentrations of these cytokines during the course of the disease were significantly higher than baseline (before inoculation, P < 0·01 for all cytokines). Clarithromycin significantly inhibited the production of IL-1β and TNF-α in the lung (P < 0·01). The same treatment also reduced the levels of other cytokines, albeit insignificantly. Treatment with anti-TNF-α antibody significantly reduced the number of pulmonary lymphocytes and concentration of IL-1β in the lung (P < 0·01), but did not change the number of viable bacteria. Our findings resemble those detected in bronchoalveolar lavage fluid of patients with DPB and indicate that inflammatory cytokines play an important role in chronic P. aeruginosa lung infection. Our results also show that macrolides modulated the production of these cytokines, ultimately reducing lymphocyte accumulation in the lung. Our data suggest that anti-TNF-α antibody might be a useful new strategy for the treatment of chronic respiratory P. aeruginosa infection. [ABSTRACT FROM AUTHOR]

We encountered a patient with Sjögren's syndrome (SS) associated with bilateral parotid salivary gland swelling. Histological analysis of biopsy specimens from both parotid glands showed myoepithelial islands and infiltration of small- and intermediate-sized lymphocytes but no cytological atypia. Using reverse transcriptase-polymerase chain reaction and subsequent single-strand conformational polymorphism analysis, monoclonal B-cell expansion was detected in samples from both right and left parotid glands, bone marrow, and peripheral blood (PB). Our case suggests that the circulating clonal lymphocytes represent clones that can repopulate tissue sites and may contribute to B-cell lymphomagenesis. Detection of monoclonal B cells in PB is therefore considered to be important in monitoring the disease course of SS. [ABSTRACT FROM AUTHOR]

Studies the effects of macrophage colony-stimulating factor on anti-fungal activity of mononuclear phagocytes against Trichosporon asahii. Enhancement of the phagocytic fungicidal activity of mononuclear cells; Concentration of tumor necrosis factor-alpha in the lung.

We investigated the increase of platelet-associated IgG and complement component, ³CO caused by the in vitro action of anti-platelet MoAbs, and the effect of mouse and human IgG on these events, Anti-glycoprotein IIb/IIIa and anti-glycoprotein Ib MoAbs caused a slight increase of C3, but not of platelet-associated IgG. In contrast, anti-CD9 and anti-Fey II receptor MoAbs caused an increase of both platelet-associated C3 and IgG. In particular, three MoAbs which activated the complement system caused a marked increase of C3. When platelet-rich plasma was treated with aspirin and prostaglandin, before incubation with antibodies, the increase of platelet-associated IgG was inhibited in all cases. In contrast, the increase of platelet-associated C3 was scarcely influenced. These results suggest that the binding to platelets of platelet-activating antibodies caused the increased expression of IgG molecules on the platelet surface and a possible increase of platelet-associated IgG, However, the increase of platelet-associated C3 appeared to depend on specific characteristics of the antibodies tested, such as a complement-activating effect. In addition, intact mouse or human IgG inhibited the increase of platelet-associated C3 caused by complement-activating antibodies, white F(ab') 2 mouse or human IgG had no such effect. This suggested that the Fc portion of IgG may block the increase of C3 mediated by anti-platelet antibodies. [ABSTRACT FROM AUTHOR]

A topical vitamin D3 ointment (tacalcitol) was prescribed for patients with long-lasting pruriginous lesions (four with prurigo nodularis and seven with subacute prurigo, four of whom had atopic dermatitis). Seven of 11 cases had not responded to a topical steroid ointment and even to occlusive application of the ointment. Nine of 11 cases showed a significant clinical response to this new regimen within 4 weeks. Epidermal Fce R1(+) dendritic cells were increased in number in prurigo nodularis and reduced to normal level after the therapy. Topical vitamin D3 ointment might be an alternative therapy for steroid-resistant prurigo. [ABSTRACT FROM AUTHOR]

Reflux following an esophagectomy with gastric conduit reconstruction in the posterior mediastinum is a clinically significant problem. In this study, we investigated the frequency and impact of reflux on the quality of life (QOL) among 158 patients who underwent an esophagectomy for esophageal cancer using an original questionnaire and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Version 3.0 (EORTC QLQ-C30). Reflux frequency was assessed using the original questionnaire. The number of patients who complained of reflux every day, two or three times a week, once a week, or less than once a week was 16 (10.1%), 21 (13.3%), 26 (16.5%), and 60 (38.0%), respectively. Out of 35 patients (22.2%) reported no reflux symptoms. Patients were divided into two groups: those with reflux ≥ once/week (63 patients) and those with low frequency of symptoms (95 patients). Time elapsed following surgery was the only factor to influence reflux frequency. Reflux frequency decreased within two years of surgery; however, the frequency plateaued after more than two years. QOL was assessed using the EORTC QLQ-C30. The ≥ once/week reflux group had a significantly lower global health status score than the low-frequency reflux group (59.6 ± 24.2 vs. 70.8 ± 20.7; P  = 0.007). In addition, the ≥ once/week reflux group had a significantly lower social functioning score than the low-frequency reflux group (81.6 ± 24.1 vs. 88.4 ± 19.8; P  = 0.035). Regarding symptoms, the ≥ once/week reflux group had significantly higher scores for fatigue, nausea, and vomiting, dyspnea and insomnia compared to the low-frequency reflux group (fatigue: 42.4 ± 21.9 vs. 28.9 ± 18.4, P  < 0.001; nausea and vomiting: 17.3 ± 17.1 vs. 4.9 ± 10.6, P  < 0. 001; dyspnea: 29.2 ± 26.0 vs. 21.7 ± 26.8, P  = 0.043; insomnia: 22.2 ± 31.1 vs. 10.5 ± 21.7, P  = 0.015). Thus, reflux after an esophagectomy was associated with a lower QOL. [ABSTRACT FROM AUTHOR]

The article discusses the case of a successful treatment of primary cutaneous mucormycosis by combining liposomal amphotericin B and surgical debridement. A 78-year-old man was presented with a history of recurrent multiple leg ulcers on both leg and a history of type 2 diabetes mellitus. Genetic sequencing shows that there is 99 percent of Rhizomucor variabilis in the patient's leg.

Para-phenylenediamine (PPD) is known to be a common sensitizer of allergic contact dermatitis and contact urticaria. To clarify the mechanism of contact hypersensitivity (CHS) to PPD, we established a mouse model of PPD-induced CHS. BALB/c mice were immunized for 3 consecutive days by painting topically a 2·5% PPD solution on their shaved abdominal skin. On days 5, 7 or 9 after the initial application, the mice were challenged by applications of a 2·5% PPD solution. Maximal ear swelling was determined at 24 h but another statistically significant and smaller ear swelling was observed 1 h after challenge with PPD in a hapten-specific manner. Adoptive cell transfer experiments demonstrated that the ear swelling of the adoptive cell transferred mice displayed an early response at 6 h and a late response from 12 h to 24 h when the recipient mice were challenged immediately after transfer. Both MoAbs and complement treatment of the transferred cells demonstrated that the phenotype of the early response cells which elicited a response at 6 h after challenge was Thy1[sup +], B220[sup +], αβ TCR[sup ], γδ TCR[sup ], CD3[sup ], CD4[sup ], CD5[sup +] and CD8[sup ]. The in vitro treatment of effector cells with MoAbs against not only αβ TCR but also γδ TCR, together with complement, was found to diminish substantially the late response, elicited 12–24 h after challenge. γδ T cells reconstituted the ability of αβ T cells to transfer 24 h CHS responsiveness. The phenotype of the γδ T cells that assist CHS effector αβ T cells was CD3[sup +], CD4[sup ] and CD8[sup +] and these regulatory γδ T cells were neither Ag-specific nor MHC-restricted. Furthermore, γδ T cells from normal spleen could also assist αβ T cells in adoptive transfer of the 24 h CHS response in a non-MHC-restricted manner. RT-PCR demonstrated that αβ T cells strongly ex... [ABSTRACT FROM AUTHOR]