The feasibility of Cep55/c10orf3 derived peptide vaccine therapy for colorectal carcinoma

In our previous study, we demonstrated that a peptide derived from the novel centrosome residing protein Cep55/c10orf3 can be targeted by the cytotoxic T lymphocytes (CTLs) in peripheral blood mononuclear cells (PBMCs) of breast carcinoma patients. In this report, we evaluated the feasibility of cancer immunotherapy using Cep55/c10orf3 peptide for colorectal carcinoma (CRC). To evaluate the expression of Cep55/c10orf3 in CRC tissues, we performed immunohistochemical staining of using anti-Cep55/c10orf3 monoclonal antibody. Sixty-three percent cases showed weak positive for Cep55/c10orf3 in total 70 CRC cases. The Cep55/c10orf3 expression intention was collated with high histological grade of CRC. Thus, we hypothesized that Cep55/c10orf3 can also be the target of CTLs in CRC cases. We generated CTLs from PBMCs of human leukocyte antigen (HLA)-A24-positive colorectal carcinoma patients using HLA-A24-restricted Cep55/c10orf3 peptides. Two of 6 colorectal cancer patients were reactive for the Cep55/c10orf3_193(10) peptide, which was the only immunogenic peptide in breast carcinoma patients. CTL clone specific for Cep55/c10orf3_193(10) recognized and lysed HLA-A24 (+) and Cep55/c10orf3 (+) colorectal carcinoma cell lines. In addition, 1 of 6 colorectal carcinoma patients was reactive for the Cep55/c10orf3_402(11) and Cep55/c10orf3_283(12) peptides, but not for Cep55/c10orf3_193(10) with the ELISPOT assay. These observations suggest that the antigenic peptide repertoire presented by HLA-A24 in colorectal carcinoma might be different from that in breast carcinoma. Thus, these peptide vaccination peptide mixture of Cep55/c10orf3_193(10), Cep55/c10orf3_402(11) and Cep55/c10orf3_283(12) might be more effective than a single peptide in the treatment of colorectal carcinoma patients.     

Fast radio-frequency enforced steady state (FRESS) spin echo MRI for quantitative T2 mapping: minimizing the apparent repetition time (TR) dependence for fast T2 measurement

Transverse relaxation time (T(2)) is a basic but very informative MRI parameter, widely used in imaging to examine a host of diseases, including multiple sclerosis, stroke, and tumor. However, short repetition time (TR) is often used to minimize scan time, which may introduce non-negligible errors in T(2) measurement. Specifically, due to the use of refocusing pulse, the steady state magnetization depends not only on TR but also on the TE. Hence, if the TE dependence is not properly accounted for, it may be mistaken as T(2)-induced signal attenuation, leading to non-negligible T(2) underestimation. Our study proposed a fast radio-frequency enforced steady state (FRESS) spin echo (SE) MRI sequence, which saturates the magnetization after the echo and ensures a TE-independent steady state. The proposed FRESS-SE MRI was evaluated with numerical simulation, implemented with echo planar imaging readout, and validated by both phantom and in vivo experiments. In summary, FRESS-SE T(2) MRI technique was developed for fast and accurate T(2) imaging, suitable for in vivo applications.     

18F-fluorodeoxyglucose positron emission tomography in a case of retroperitoneal fibrosis

A patient with recurrent abdominal pain was admitted to our hospital. Computed tomography showed a soft dense mass surrounding the abdominal aorta at the infrarenal level, which was compatible with retroperitoneal fibrosis. (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography showed abnormal uptake of (18)F-FDG into these lesions. Two months after the initiation of corticosteroid therapy, the abnormal uptake of (18)F-FDG had ceased along with a reduction in the fibrous mass surrounding the abdominal aorta.     

Inhibition of 12/15‐lipoxygenase as therapeutic strategy to treat stroke

Targeting newly identified damage pathways in the ischemic brain can help to circumvent the currently severe limitations of acute stroke therapy. Here we show that the activity of 12/15‐lipoxygenase was increased in the ischemic mouse brain, and 12/15‐lipoxygenase colocalized with a marker for oxidized lipids, MDA2. This colocalization was also detected in the brain of 2 human stroke patients, where it also coincided with increased apoptosis‐inducing factor. A novel inhibitor of 12/15‐lipoxygenase, LOXBlock‐1, protected neuronal HT22 cells against oxidative stress. In a mouse model of transient focal ischemia, the inhibitor reduced infarct sizes both 24 hours and 14 days poststroke, with improved behavioral parameters. Even when treatment was delayed until at least 4 hours after onset of ischemia, LOXBlock‐1 was protective. Furthermore, it reduced tissue plasminogen activator‐associated hemorrhage in a clot model of ischemia/reperfusion. This study establishes inhibition of 12/15‐lipoxygenase as a viable strategy for first‐line stroke treatment. Ann Neurol 2013     

A Favipiravir-induced Fever in a Patient with COVID-19

We herein report the first case of a fever induced by favipiravir, a potential coronavirus disease 2019 therapeutic drug. An 82-year-old man diagnosed with bilateral pneumonia was transferred to our hospital following a positive severe acute respiratory syndrome coronavirus 2 polymerase chain reaction test. He was treated with compassionate use of favipiravir. Both his oxygen demand and fever gradually improved after admission; however, his fever relapsed, and the C-reactive protein (CRP) levels increased on day 7. We diagnosed his fever as being favipiravir-induced. The fever resolved a few days after favipiravir discontinuation, demonstrating the accuracy of the diagnosis. This case revealed that favipiravir can induce a fever.     

Support system of activities of daily living for the elderly]

People with severe disabilities use many assistive devices, such as computers and robots, to improve their quality of life. However, the elderly use only limited assistive devices, such as canes, wheelchairs, walkers, or handrails. This state is caused by two characteristics of the elderly: first, the elderly generally have difficulties in learning the operation of new equipment, especially equipment with digital interfaces. Secondly, the elderly have limited desire to improve their lives if it takes considerable effort. To solve these problems, speech recognition, gesture recognition and power assist technology have been proposed for various useful devices. Virtual reality technology and pet robots may encourage the elderly to use assistive devices to improve the quality of their lives.     

In vivo quantification of transvascular water exchange during the acute phase of permanent stroke

Mechanisms that underlie early ischemic damages to the blood‐brain‐barrier (BBB) are not well understood. This study presents a novel magnetic resonance imaging (MRI) technique using a widely available pulse sequence and a long‐circulating intravascular contrast agent to quantify water movements across the BBB at early stages of stroke progression. We characterized the integrity of the BBB by measuring the flip angle dependence of the water exchange‐affected MRI signal intensity, to generate an efficient quantitative index of vascular permeability (WEI, or water exchange index). We performed in vivo MRI experiments to measure the transvascular WEI immediately after the permanent filament occlusion of the middle cerebral artery of mice (n = 5), in which we monitored changes in blood volume (V_b), apparent diffusion coefficient (ADC), and intra‐/extravascular WEI for 4 hours. Statistically significant elevations (P < 0.05) of WEI in the ischemic tissue were observed as early as 1 hour after ischemic onset. Initial reduction of the apparent blood volume (V_app) in the infarct cortex was followed by a continuous increase of V_app over time. Although the measured ADC in the ipsilesional cortex continuously decreased, the abnormally high intra‐/extravascular WEI remained constant at a significantly elevated level, indicating apparent BBB injury at this early stage of stroke. Magn Reson Med 60:813–821, 2008. © 2008 Wiley‐Liss, Inc.     

Primary Duodenal Adenocarcinoma without Stenosis: A Case Report with a Brief Literature Review

This article focuses on the symptomatic and diagnostic problems of primary duodenal adenocarcinoma (PDA) by way of two case reports and a literature review. An 85-year-old woman with an adenocarcinoma in the 1st duodenal portion was offered palliative care. A 90-year-old woman with an adenocarcinoma in the 3rd duodenal portion was also offered palliative care. A unique finding in the two cases reported herein is that PDA did not cause stenosis and occlusion of the lumen. As no reports of PDA without stenosis have been published so far, these cases may add to our knowledge of PDA. The diagnosis of PDA is often delayed because its symptoms may be absent until the tumor has progressed, thus leading to a delay of several months. Patients typically present with a long history of variable and vague symptoms, and many are diagnosed with advanced disease. As regards clinical manifestations, abdominal pain is the most frequent symptom. The majority of these tumors are found to have infiltrated the duodenal wall at presentation, with many being unresectable due to local and distal invasion. Esophagogastroduodenoscopy and gastrointestinal barium radiography are the main diagnostic tests for PDA, detecting 88.6 and 83.3% of tumors, respectively. In some cases, ultrasonography or computed tomography are useful for detecting PDA and determining vascular invasion.Key words: Primary duodenal adenocarcinoma, without stenosis; Primary duodenal adenocarcinoma, first portion; Primary duodenal adenocarcinoma, third portion; Best supportive care; Symptoms; Clinical manifestations