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Introduction: Squamous cell carcinoma of the temporal bone is extremely rare comprising 0.2% of all tumors of head and neck. Symptoms are nonspecific and may be mistaken for other more benign conditions as otitis, cholesteatoma and polyp. Hence, this condition may present as a diagnostic challenge. Case Discussion: We describe a case series of three patients who presented with external auditory canal (EAC) mass. The most common signs and symptoms are pruritus, decreased hearing and yellowish discharge. They were initially treated with otic antibiotics which afforded no relief. The first case is a 51 year-old female who underwent wide excision of the right ear canal and middle ear mass and right temporal craniotomy. Histopathology showed moderately differentiated squamous cell carcinoma with temporal tumor and subdural extension consistent with metastasis. The second case is a 53 year-old male who refused surgical management. He was non-compliant with work-up and follow-up and later on presented with left facial asymmetry and headache. CT scan showed a left inner and middle ear canal mass with extension to the auditory canal and protrusion into the left cerebellar hemisphere. Punch biopsy of the left EAC mass was done and pathologic report showed well-differentiated squamous cell carcinoma. Lastly, a 54 year old male who underwent Radical mastoidectomy with histopathology reports of a moderately differentiated squamous cell carcinoma. Conclusion: Standard treatment modality is still unclear because of the rarity of this condition. However, surgical resection with negative margins followed by concurrent chemotherapy and radiation is the most commonly performed approach1. For the above-mentioned patients, concurrent chemotherapy and radiation therapy was given which showed significant treatment response.

Aim: This study aimed to clarify the actual status of clinical trials and translational research activities in cancer immunology in the Asia-Pacific region, the most diverse and populous region with a large number of cancer patients. Methods: This questionnaire-based survey targeted researchers and healthcare professionals in the Asia-Pacific region. The questionnaire was sent to individuals who were involved in any collaboration with the National Cancer Center, Japan, or who belonged to the Asia-Pacific Blood and Marrow Transplantation group. Results: We received 122 responses from 20 Asia-Pacific countries and regions. Approximately 58% of the respondents were currently conducting clinical trials on cancer immunotherapy, with 25% having performed >10 phase 3 trials in the last 3 years. Half of the respondents (51.7%) belonged to institutions that conducted early phase clinical trials. In clinical trials, immune checkpoint inhibitors were used in most countries (81.8%), whereas chimeric antigen receptor T-cell (CAR-T) or T-cell receptor-modified T-cell (TCR-T) therapies were used in few countries (CAR-T, 22.7%; TCR-T, 2.3%). Importantly, 18% of respondents had referred their patients to facilities conducting suitable ongoing clinical trials in foreign countries. Some institutions provided hematopoietic stem cell transplantation (HSCT), including allogeneic HSCT (55.1%) and autologous peripheral blood stem cell transplantation (81.3%). Approximately 40% of the respondents belonged to institutions that conducted translational research on cancer immunotherapy using patient-derived samples. Conclusion: This survey revealed limited cancer immunotherapy accessibility and research activities in the Asia-Pacific region, especially for CAR-T and TCR-T therapies.

In the present study, four experimental groups were used: fresh embryos, cultured during in vitro maturation and in vitro culture in media supplemented with bovine serum albumin (BSA) (fresh BSA) o...

Diarrhea is one of the most important causes of mortality in the developing world, being responsible for 2.5 million deaths each year. Many of these deaths are caused by enterotoxigenic strains of bacteria, like Escherichia coli, that produce enterotoxins that cause acute watery diarrhea, commonly defined as secretory diarrhea. Studies on symptomatic patients indicate a high prevalence of enterotoxigenic E. coli strains producing the heat-stable toxin, STa. STa is a small, cysteine-rich peptide that binds to the extracellular receptor domain of guanylyl cyclase C (GCC), located at the luminal membrane of intestinal epithelial cells. GCC and its endogenous peptide ligands, guanylin and uroguanylin, play a key role in balancing water absorption and hydration of the intestinal lumen, as exemplified by the finding that loss of GCC function causes severe dehydration of the intestinal lumen, culminating in intestinal obstruction. From a mechanistic viewpoint, reduction of GCC activity offers an efficient approach to limit enterotoxigenic E. coli- provoked secretory diarrhea. Inhibition of GCC-mediated cGMP production would not only reduce anion secretion, but would also restore NHE3 activity, resulting in a comprehensive antidiarrheal action. In the present study, two novel phenylpyrimidinone derivatives were simultaneously synthesized and tested for their ability to block STa-induced CFTR activity in T84 cells.

This paper reports the synthesis of new norbornene and exo-N-hydroxy-7-oxabicyclo[2.2.1]hept-5-ene-2,3-dicarboximide derivatives and their binding to the 5-HT1A , 5-HT2A , and 5-HT2C receptors, in order to identify selective ligands for these 5-hydroxytryptamine (5-HT, serotonine) receptor subtypes. The combination of structural elements (heterocyclic nucleus, hydroxyalkyl chain, and 4-substituted piperazine) known to be critical for affinity to 5-HT1A receptors and the proper selection of substituents led to compounds with high specificity and affinity toward serotoninergic receptors. The most active compounds were selected and further evaluated for their binding affinities to D1 , D2 dopaminergic and α1 , α2 adrenergic receptors. 4-[3-[4-(2-Furoyl)piperazin-1-yl]propoxy-2-ol]-4-aza-tricyclo[5.2.1.02,6]dec-8-ene-3,5-dione 3e with Ki = 5.04 ± 0.227 nM was the most active and selective derivative for the 5-HT2C receptor with respect to other serotonin receptors, and the most selective derivative versus dopaminergic and adrenergic receptors.

雑誌掲載版, ラットにprednisolone 4mg/kg/日 4日間投与,または水浸拘束によるストレス潰瘍を作り,それに対するDHEA-Sの効果を検討した。prednisoloneによる胃粘膜病変は,同時に皮下注射したDHEA-S (50-200mg/kg)によって用量依存性に抑制され,prednisoloneによる胸腺萎縮も予防された。水浸拘束ストレス潰瘍の発生もDHEA-S前投与によって抑制された。ストレス潰瘍の外来患者30例について尿中17-KS-S (DHEA-S代謝産物),17-OHCS (Cortisol代謝産物)を測定した所,17-OHCSは上昇,17KS-Sおよび17KS-S/17-OHCS比は低値であった。ストレス状態ではcortisolとDHEA-S分泌バランスの変化が消化性潰瘍発生,胸腺萎縮に関与していると思われる

Homocysteinemia is a risk factor for cardiovascular diseases. Folic acid combined with vitamins B6 and B12 is effective in lowering homocysteine levels. This randomized placebo-controlled study was designed to determine the effect of a folic acid-based supplement on secondary prevention of clinical events in non-ST-segment elevation acute coronary syndromes. The study comprised 240 patients with either unstable angina or non-ST-elevation myocardial infarction in the previous 2 weeks who were randomized to a folate group ( n = 116) or a placebo group ( n = 124). The folate group received 1 mg folic acid, 400 μg vitamin B12, and 10 mg vitamin B6 daily. Clinical outcomes within 6 months were assessed. The composite endpoint of death, nonfatal acute coronary syndrome, and serious re-hospitalization was significantly higher in the folate group; serious re-hospitalization alone was significantly higher in this group. Advanced age and diabetes increased susceptibility to the composite outcome. Folic acid-based supplementation is not beneficial and may even be harmful in the secondary prevention of cardiovascular events in patients with unstable angina and non-ST-elevation myocardial infarction. Further studies on the safety of such supplements are suggested. Controlled Clinical Trials Registry no. ISRCTN30249553.

Background Unstable angina and non-ST elevation myocardial infarction (NSTEMI) are common acute coronary events. Homocysteine is a novel risk factor for coronary heart diseases. Together with the conventional risk factors, they may affect the outcome of non-ST coronary events. Objective This study aims to determine the effect of clinical risk factors that are responsible for the occurrence of mortality, and the composite outcome of mortality, nonfatal myocardial infarction and serious rehospitalization within 6 months after the onset of non-ST acute coronary syndromes. Methods A total of 124 Filipino patients were interviewed and tested for blood homocysteine levels and lipid profiles. Outcomes were assessed after 6 months. Results Homocysteinemia (>16 micromol/l) is associated with increased mortality and composite outcomes (mortality, nonfatal reinfarction, and serious rehospitalization), even if adjusted for conventional risk factors. No association was detected for the conventional risk factors. Earlier acute coronary syndrome was found to be positively associated with mortality and the composite outcomes. Early stroke is associated with increased composite outcomes, whereas greater mortality and adverse outcomes were observed in NSTEMI compared with intermediate-risk unstable angina. Conclusion Increased homocysteine level is associated with mortality and serious nonfatal outcomes in patients with unstable angina and NSTEMI.

Increase of VPAC receptor s binding to the (16)gamma-glutamyl diaminopropane vasoactive intestinal peptide (VIP-DAP) agonist, a vasoactive intestinal polypeptide (VIP) structural analogue containing a positive charge at position 16, has confirmed the importance of a positive charge at this site. By investigating the effect of distance from the peptide backbone Calpha of a positive charge in position 16, data are reported here concerning: (i) a novel chemical method used for the synthesis of a new family of (16)gamma-glutamyl diamine VIP derivatives differing among them for single carbon atoms and including diaminoethane (VIP-DAE2), diaminopropane (VIP-DAP3), diaminobutane (VIP-DAB4), diaminopentane (VIP-DAP5), and diaminohexane (VIP-DAH6); (ii) functional characterization of these compounds on human VPAC1 and VPAC2 receptors. In more detail, the EC50 and IC50 values, when measured as a function of the alkylic chain length, show in more detail, that the use of VIP-DAB4 derivative changes the IC50 but not the EC50, thus indicating on hVPAC2 receptor an unexpected relationship between binding and activity that differs from that obtained on hVPAC1.

Celiac disease (CD) is an autoimmune disease of the small bowel characterized by a strong genetic association with HLA - DQ2 and DQ8. Gluten is the etiological factor and the tissue enzyme transglutaminase (TGase) is its autoantigen. CD is associated with several autoimmune diseases such as type 1 diabetes, systemic lupus erythematous, rheumatoid arthritis, Sjögrens syndrome and autoimmune thyroid diseases. The aim of this study was to investigate the occurrence of serum IgA anti-endomysial and anti-human TGase antibodies in individuals with positive anti-thyroid antibody (ATA). The concordance between these two tests was also evaluated. Anti-endomysial antibodies were positive in 10 out of 456 (2.2%) and anti-human TGase were positive in 14 of 454 (3.1%) individuals with positive ATA. In control subjects they were positive in 1 of 197 (0.5%) and 2 of 198 (1%) for anti-endomysial and anti-human tissue TGase antibodies, respectively. The odds ratio (OR) for the anti-endomysial antibodies was 4.42 and for the anti-human TGase 3.12 in individuals with ATA when compared with controls. An elevated concordance index (k= 0.84) was observed between anti-endomisyal antibodies and anti-human TGase. We conclude that the determination of anti-TGase antibodies is a good test for DC screening.

Doença celíaca (DC) é uma doença autoimune do intestino delgado com importante associação com HLA-DQ2 e DQ8. Tem o glúten como fator etiológico e a enzima transglutaminase (TGase) tecidual como autoantígeno. A DC é associada a outras doenças autoimunes como diabetes mellitus tipo 1, lupus eritematoso sistêmico, artrite reumatóide, síndrome de Sjögren e doenças autoimunes da tireóide. O objetivo deste estudo foi investigar a ocorrência de anticorpos séricos da classe IgA anti-endomísio e anti-TGase tecidual humana em indivíduos com anticorpo anti-tireoidiano (AAT) positivo. Foi também pesquisada a concordância destes dois marcadores. Anticorpos anti-endomísio foram positivos em 10 de 456 (2,2%) e anti-TGase tecidual foi positiva em 14 de 454 (3,1%) dos indivíduos com AAT positivo. No grupo controle, 1 de 197 (0,5%) e 2 de 198 (1%) foram positivos para anticorpo anti-endomísio e anti-TGase tecidual humana, respectivamente. A chance de positividade dos anticorpos anti-endomísio foi de 4,42 e do anti-TGase tecidual humana 3,12 vezes maior nos indivíduos com positividade para AAT que nos controles. Um elevado índice de concordância (k= 0,84) foi obtido entre os testes para anticorpos anti-endomísio e anti-TGase. Os resultados obtidos neste trabalho não justificam uma triagem rotineira de DC em portadores de AAT. Concluímos que a pesquisa de anticorpos anti-TGase mostrou-se um teste útil para rastrear DC.

Doença celíaca (DC) é uma doença autoimune do intestino delgado com importante associação com HLA-DQ2 e DQ8. Tem o glúten como fator etiológico e a enzima transglutaminase (TGase) tecidual como autoantígeno. A DC é associada a outras doenças autoimunes como diabetes mellitus tipo 1, lupus eritematoso sistêmico, artrite reumatóide, síndrome de Sjögren e doenças autoimunes da tireóide. O objetivo deste estudo foi investigar a ocorrência de anticorpos séricos da classe IgA anti-endomísio e anti-TGase tecidual humana em indivíduos com anticorpo anti-tireoidiano (AAT) positivo. Foi também pesquisada a concordância destes dois marcadores. Anticorpos anti-endomísio foram positivos em 10 de 456 (2,2%) e anti-TGase tecidual foi positiva em 14 de 454 (3,1%) dos indivíduos com AAT positivo. No grupo controle, 1 de 197 (0,5%) e 2 de 198 (1%) foram positivos para anticorpo anti-endomísio e anti-TGase tecidual humana, respectivamente. A chance de positividade dos anticorpos anti-endomísio foi de 4,42 e do anti-TGase tecidual humana 3,12 vezes maior nos indivíduos com positividade para AAT que nos controles. Um elevado índice de concordância (k= 0,84) foi obtido entre os testes para anticorpos anti-endomísio e anti-TGase. Os resultados obtidos neste trabalho não justificam uma triagem rotineira de DC em portadores de AAT. Concluímos que a pesquisa de anticorpos anti-TGase mostrou-se um teste útil para rastrear DC. Celiac disease (CD) is an autoimmune disease of the small bowel characterized by a strong genetic association with HLA - DQ2 and DQ8. Gluten is the etiological factor and the tissue enzyme transglutaminase (TGase) is its autoantigen. CD is associated with several autoimmune diseases such as type 1 diabetes, systemic lupus erythematous, rheumatoid arthritis, Sjögren’s syndrome and autoimmune thyroid diseases. The aim of this study was to investigate the occurrence of serum IgA anti-endomysial and anti-human TGase antibodies in individuals with positive anti-thyroid antibody (ATA). The concordance between these two tests was also evaluated. Anti-endomysial antibodies were positive in 10 out of 456 (2.2%) and anti-human TGase were positive in 14 of 454 (3.1%) individuals with positive ATA. In control subjects they were positive in 1 of 197 (0.5%) and 2 of 198 (1%) for anti-endomysial and anti-human tissue TGase antibodies, respectively. The odds ratio (OR) for the anti-endomysial antibodies was 4.42 and for the anti-human TGase 3.12 in individuals with ATA when compared with controls. An elevated concordance index (k= 0.84) was observed between anti-endomisyal antibodies and anti-human TGase. We conclude that the determination of anti-TGase antibodies is a good test for DC screening.

Corticosteroids are effective in bringing about a clinical remission in patients with ulcerative colitis. However, in severely relapsed cases, corticosteroids are not always effective even when a high dosage is administered. In addition, the long-term use of corticosteroids often causes serious side effects. Therefore, an alternative treatment for active ulcerative colitis is necessary in order to avoid these clinical problems. In the present pilot study, the efficacy of leukocytapheresis using a centrifugal procedure was evaluated for corticosteroid-resistant, active ulcerative colitis. Fourteen patients with corticosteroid-resistant severely active ulcerative colitis were treated by leukocytapheresis. Thirteen patients (92.9%) achieved clinical remission within 4 weeks after the apheresis, and remained in remission for 8 months on average without any additional corticosteroid therapy. In the remaining patient, in whom remission was not induced, a total colectomy was performed immediately after the fourth course of leukocytapheresis. No significant side effects were noticed throughout the therapy. Both colonoscopic and histological examinations confirmed the beneficial effect of this procedure in terms of the reduction of severe inflammation of the affected colon. We found that the expression of two adhesion molecules, L-selectin and VLA4a, on the surface of peripheral leukocytes was decreased after this new therapy.