Successful Intervention for Pressure Ulcer by Nutrition Support Team: A Case Report

A 23-year-old woman with heart failure developed pressure ulcer on her sacral area due to a long-term bed rest and impaired hemodynamics. The ulcer improved only slightly after 2 months with povidone-iodine sugar ointment because of severe nausea and anorexia. Then, the nutrition support team (NST) started intervention and estimated the patient's malnutrition from her body weight (30.1 kg), body mass index (BMI) (13.9), triceps skinfold thickness (TSF) (3.5 mm), arm circumference (AC) (17.2 cm) and serum albumin (2.6 g/dl). The NST administrated an enteral nutrition formula through a nasogastric tube and tried to provide meals according to the patient's taste. Although DESIGN score improved to 7 (DESIGN: d2e1s2i1g1n0 = 7) 2 months later, severe nausea prevented the patient from taking any food perorally. However, after nasogastric decannulation, her appetite improved and 1 month later her body weight increased to 32.8 kg, her BMI to 15.2, TSF to 7.5 mm, AC to 19.7 cm and serum albumin to 4.1 g/dl, and the wound completely healed

Co-culturing of follicles with interstitial cells in collagen gel reproduce follicular development accompanied with theca cell layer formation

<p>Abstract</p> <p>Background</p> <p>The mechanism of theca cell layer formation in mammalian ovaries has not been elucidated; one reason is that there is no follicle culture system that can reproduce theca cell layer formation in vitro. Therefore, a three-dimensional follicle culture system that can reproduce theca cell layer formation is required.</p> <p>Methods</p> <p>A collagen gel was used in the follicle culture system. To determine the optimum conditions for follicle culture that can reproduce theca cell layer formation, the effects of hormonal treatment and cell types co-cultured with follicles were examined. In addition, immunohistochemistry was used to examine the properties of the cell layers formed in the outermost part of follicles.</p> <p>Results</p> <p>Follicles maintained a three-dimensional shape and grew in collagen gel. By adding follicle-stimulating hormone (FSH) and co-culturing with interstitial cells, the follicles grew well, and cell layers were formed in the outermost part of follicles. Immunohistochemistry confirmed that the cells forming the outermost layers of the follicles were theca cells.</p> <p>Conclusion</p> <p>In this study, follicle culture system that can reproduce theca cell layer formation <it>in vitro </it>was established. In our opinion, this system is suitable for the analysis of theca cell layer formation and contributes to our understanding of the mechanisms of folliculogenesis.</p

Roles of MED1 in Quiescence of Hair Follicle Stem Cells and Maintenance of Normal Hair Cycling

MED1 (mediator complex subunit 1) is expressed by human epidermal keratinocytes and functions as a coactivator of several transcription factors. To elucidate the role of MED1 in keratinocytes, we established keratinocyte-specific Med1-null (Med1epi−/−) mice using the K5Cre/LoxP system. Development of the epidermis and appendages of Med1epi−/− mice were macroscopically and microscopically normal until the second catagen of the hair cycle. However, the hair cycle of Med1epi−/− mice was spontaneously repeated after the second telogen, which does not occur in wild-type (WT) mice. Hair follicles of Med1epi−/− mice could not enter anagen after 6 months of age, resulting in sparse pelage hair in older Med1epi−/− mice. Interfollicular epidermis (IFE) of Med1epi−/− mice was acanthotic and more proliferative than that of WT mice, whereas these findings were less evident in older Med1epi−/− mice. Flow cytometric analysis revealed that the numbers of hair follicle bulge stem cells were reduced in Med1epi−/− mice from a few months after birth. These results suggest that MED1 has roles in maintaining quiescence of keratinocytes and preventing depletion of the follicular stem cells

限局性腎細胞癌における腫瘍浸潤性リンパ球と関連サイトカインの予後因子としての意義

Renal cell carcinoma (RCC) is an immunogenic tumor and pathological specimen generally contain large quantities of tumor-infiltrating lymphocytes (TILs). Numerous cell types and cytokines could affect the immune escape mechanism of tumor cells. The aim of the present study was to investigate the prognostic impact of TILs and the associated circulating cytokines on localized clear cell RCC following radical nephrectomy. A total of 87 patients who had undergone radical nephrectomy and were pathologically diagnosed with localized clear cell RCC were included. The present study evaluated the profile of TILs with immunohistochemical analysis of tumor specimens using a panel of antibodies [cluster of differentiation (CD)-4, CD8, CD80, CD86, CD276, and Forkhead box p3 (Foxp3)]. Counts of each TIL were compared with clinicopathological variables. Based on the results of immunohistochemical analyses, putative cytokines, including interleukin (IL)-6, IL-10, IL-17, interferon-γ, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β, were selected, and their levels in preoperative serum were measured by ELISA. The levels were compared with TIL counts in tumor specimens. High counts of the CD276+ and Foxp3+ TILs were identified as independent factors for poor prognosis for metastasis and local recurrence following radical nephrectomy (P=0.033 and 0.006, respectively). A high CD276+ TIL count was associated with preoperative serum levels of TNF-α and IFN-γ (P=0.027 and P=0.035, respectively), whereas a high count of Foxp3+ TILs was associated with preoperative serum levels of TGF-β (P=0.021). High levels of TNF-α and TGF-β were associated with recurrence-free survival (P=0.035 and P=0.031, respectively). Topical intra-tumoral immunoreaction and systemic immune status may be associated with patients with localized RCC. The topical induction of the CD276+ and Foxp3+ TILs was suggested to be associated with high levels of serum TNF-α and IFN-γ. Preoperative serum levels of TNF-α and TGF-β could be simple and non-invasive biomarkers for risk stratification before radical surgery.博士（医学）・甲第741号・令和2年3月16日Copyright © Spandidos Publications 2019. All rights reserved.Articles from Oncology Letters are provided here courtesy of Spandidos Publications

Mice with defects in HB-EGF ectodomain shedding show severe developmental abnormalities

Heparin-binding EGF-like growth factor (HB-EGF) is first synthesized as a membrane-anchored form (proHB-EGF), and its soluble form (sHB-EGF) is released by ectodomain shedding from proHB-EGF. To examine the significance of proHB-EGF processing in vivo, we generated mutant mice by targeted gene replacement, expressing either an uncleavable form (HBuc) or a transmembrane domain–truncated form (HBΔtm) of the molecule. HBuc/uc mice developed severe heart failure and enlarged heart valves, phenotypes similar to those in proHB-EGF null mice. On the other hand, mice carrying HBΔtm exhibited severe hyperplasia in both skin and heart. These results indicate that ectodomain shedding of proHB-EGF is essential for HB-EGF function in vivo, and that this process requires strict control

Survey of imaging dose in HDR brachytherapy

Institutional imaging protocols for the verification of brachytherapy applicator placements were investigated in a survey study of domestic radiotherapy institutions. The survey form designed by a free on-line survey system was distributed via the mailing-list system of the Japanese Society for Radiation Oncology. Survey data of 75 institutions between August 2019 and October 2019 were collected. The imaging modalities used were dependent on resources available to the institutions. The displacement of a brachytherapy applicator results in significant dosimetric impact. It is essential to verify applicator placements using imaging modalities before treatment. Various imaging modalities used in institutions included a computed tomography (CT) scanner, an angiography X-ray system, a multi-purpose X-ray system and a radiotherapy simulator. The median total exposure time in overall treatment sessions was ≤75 s for gynecological and prostate cancers. Some institutions used fluoroscopy to monitor the brachytherapy source movement. Institutional countermeasures for reducing unwanted imaging dose included minimizing the image area, changing the imaging orientation, reducing the imaging frequency and optimizing the imaging conditions. It is worth noting that half of the institutions did not confirm imaging dose regularly. This study reported on the usage of imaging modalities for brachytherapy in Japan. More caution should be applied with interstitial brachytherapy with many catheters that can lead to potentially substantial increments in imaging doses for monitoring the actual brachytherapy source using fluoroscopy. It is necessary to share imaging techniques, standardize imaging protocols and quality assurance/quality control among institutions, and imaging dose guidelines for optimization of imaging doses delivered in radiotherapy should be developed

尿路上皮癌微小環境内におけるDisabled Homolog 2 (DAB2) は腫瘍細胞上皮間葉転換を介して遊走能・浸潤能を高める

Disabled homolog-2 (DAB2) has been reported to be a tumor suppressor gene. However, a number of contrary studies suggested that DAB2 promotes tumor invasion in urothelial carcinoma of the bladder (UCB). Here, we investigated the clinical role and biological function of DAB2 in human UCB. Immunohistochemical staining analysis for DAB2 was carried out on UCB tissue specimens. DAB2 expression levels were compared with clinicopathological factors. DAB2 was knocked-down by small interfering RNA (siRNA) transfection, and then its effects on cell proliferation, invasion, and migration, and changes to epithelial-mesenchymal transition (EMT)-related proteins were evaluated. In our in vivo assays, tumor-bearing athymic nude mice subcutaneously inoculated with human UCB cells (MGH-U-3 or UM-UC-3) were treated by DAB2-targeting siRNA. Higher expression of DAB2 was associated with higher clinical T category, high tumor grade, and poor oncological outcome. The knock-down of DAB2 decreased both invasion and migration ability and expression of EMT-related proteins. Significant inhibitory effects on tumor growth and invasion were observed in xenograft tumors of UM-UC-3 treated by DAB2-targeting siRNA. Our findings suggested that DAB2 expression was associated with poor prognosis through increased oncogenic properties including tumor proliferation, migration, invasion, and enhancement of EMT in human UCB.博士（医学）・甲第768号・令和3年3月15日© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)

Induction of transforming growth factor-beta 1 by androgen is mediated by reactive oxygen species in hair follicle dermal papilla cells

The progression of androgenetic alopecia is closely related toandrogen-inducible transforming growth factor (TGF)-β1 secretionby hair follicle dermal papilla cells (DPCs) in bald scalp.Physiological levels of androgen exposure were reported toincrease reactive oxygen species (ROS) generation. In thisstudy, rat vibrissae dermal papilla cells (DP-6) transfected withandrogen receptor showed increased ROS production followingandrogen treatment. We confirmed that TGF-β1 secretion isincreased by androgen treatment in DP-6, whereas androgeninducibleTGF-β1 was significantly suppressed by the ROSscavenger,N-acetyl cysteine. Therefore, we suggest that inductionof TGF-β1 by androgen is mediated by ROS in hair follicleDPCs.This study was supported by a grant from the Korea Healthcare Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (Grant No. A103017) and partially by a research agreement with AmorePacific Corporation, Republic of Korea.OAIID:oai:osos.snu.ac.kr:snu2013-01/102/0000045457/8SEQ:8PERF_CD:SNU2013-01EVAL_ITEM_CD:102USER_ID:0000045457ADJUST_YN:NEMP_ID:A079130DEPT_CD:801CITE_RATE:1.634FILENAME:(460-464)bmb 12-228.pdfDEPT_NM:의학과EMAIL:[email protected]_YN:YCONFIRM:

Extracellular Release of HMGB1 as an Early Potential Biomarker for the Therapeutic Response in a Xenograft Model of Boron Neutron Capture Therapy

Boron neutron capture therapy (BNCT) is a non-invasive therapeutic technique for treating malignant tumors, however, methods to evaluate its therapeutic efficacy and adverse reactions are lacking. High mobility group box 1 (HMGB1) is an inflammatory molecule released during cell death. Therefore, we aimed to investigate HMGB1 as a biomarker for BNCT response, by examining the early responses of tumor cells to 10B-boronophenylalanine (BPA)-based BNCT in the Kyoto University Nuclear Reactor. Extracellular HMGB1 release was significantly increased in human squamous carcinoma SAS and melanoma A375 cells 24 h after neutron irradiation but not after γ-irradiation. At 3 days post-BPA-based BNCT irradiation in a SAS xenograft mouse model, plasma HMGB1 levels were higher than those in the non-irradiation control, and HMGB1 was detected in both nuclei and cytoplasm in tumor cells. Additionally, increased plasma HMGB1 levels post-BNCT irradiation were detected even when tumors decreased in size. Collectively, these results indicate that the extracellular HMGB1 release occurs at an early stage and is persistent when tumors are reduced in size; therefore, it is a potential biomarker for evaluating the therapeutic response during BNCT