Keratinocyte Responsive Element 3: Analysis of a Keratinocyte-specific Regulatory Sequence in the 230-kDa Bullous Pemphigoid Antigen Gene Promoter

The 230-kDa bullous pemphigoid antigen gene is expressed primarily, if not exclusively, in basal keratinocytes of the epidermis. Keratinocyte responsive element 3, a cis-element at position –216 to –197 of the human 230-kDa bullous pemphigoid antigen gene promoter, confers tissue-specific expression to this gene (Tamai et al: J Biol Chem 270:7609–7614, 1995). In this study, we investigated the functional characteristics of keratinocyte responsive element 3 on the 230-kDa bullous pemphigoid antigen gene core promoter by transient transfections of cultured normal human keratinocytes and normal human fibroblasts, as well as of lung carcinoma (A549), osteosarcoma (OST), and gastric adenocarcinoma (GT3TKB) cell lines. A 230-kDa bullous pemphigoid antigen gene core promoter/luciferase reporter gene plasmid construct, pBPL, was modified to develop a series of constructs (pKBPL–p4KBPL), which have insertions of one, two, three, or four tandem repeats of keratinocyte responsive element 3, and these plasmids were used in transient transfections of the cultured cells. The promoter activities of pKBPL–p4KBPL constructs, relative to pBPL, in normal human keratinocytes were 7.6-, 15.5-, 4.6-, and 2.7-fold higher, respectively, whereas no upregulatory effect by keratinocyte responsive element 3 insertion was observed in other cell lines tested. prKBPL, a plasmid constructed with keratinocyte responsive element 3 in reverse orientation, showed essentially no activity in normal human keratinocytes. Insertion of a random 20 bp sequence between keratinocyte responsive element 3 and the 230-kDa bullous pemphigoid antigen gene core promoter resulted in about 40% reduction of luciferase activity in normal human keratinocytes. These data suggest that keratinocyte responsive element 3 functions as a position-, copy number-, and orientation-dependent cis-element contributing to tissue-specific regulation of the 230-kDa bullous pemphigoid antigen gene

Prediction of Indocyanine Green Retention Rate at 15 Minutes by Correlated Liver Function Parameters before Hepatectomy.

Indocyanine green retention rate at 15 min (ICGR15) is a useful marker of liver function in deciding on the extent of hepatectomy. To determine ICGR15 regardless of liver condition, we sought to establish a formula for converted ICGR15 based on conventional blood tests and technetium-99 m galactosyl human serum albumin ((99m)Tc-GSA) scintigraphy

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016)

Background and purposeThe Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in February 2017 and published in the Journal of JSICM, [2017; Volume 24 (supplement 2)] https://doi.org/10.3918/jsicm.24S0001 and Journal of Japanese Association for Acute Medicine [2017; Volume 28, (supplement 1)] http://onlinelibrary.wiley.com/doi/10.1002/jja2.2017.28.issue-S1/issuetoc.This abridged English edition of the J-SSCG 2016 was produced with permission from the Japanese Association of Acute Medicine and the Japanese Society for Intensive Care Medicine.MethodsMembers of the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine were selected and organized into 19 committee members and 52 working group members. The guidelines were prepared in accordance with the Medical Information Network Distribution Service (Minds) creation procedures. The Academic Guidelines Promotion Team was organized to oversee and provide academic support to the respective activities allocated to each Guideline Creation Team. To improve quality assurance and workflow transparency, a mutual peer review system was established, and discussions within each team were open to the public. Public comments were collected once after the initial formulation of a clinical question (CQ) and twice during the review of the final draft. Recommendations were determined to have been adopted after obtaining support from a two-thirds (> 66.6%) majority vote of each of the 19 committee members.ResultsA total of 87 CQs were selected among 19 clinical areas, including pediatric topics and several other important areas not covered in the first edition of the Japanese guidelines (J-SSCG 2012). The approval rate obtained through committee voting, in addition to ratings of the strengths of the recommendation, and its supporting evidence were also added to each recommendation statement. We conducted meta-analyses for 29 CQs. Thirty-seven CQs contained recommendations in the form of an expert consensus due to insufficient evidence. No recommendations were provided for five CQs.ConclusionsBased on the evidence gathered, we were able to formulate Japanese-specific clinical practice guidelines that are tailored to the Japanese context in a highly transparent manner. These guidelines can easily be used not only by specialists, but also by non-specialists, general clinicians, nurses, pharmacists, clinical engineers, and other healthcare professionals

Effects of prehospital epinephrine administration on neurological outcomes in patients with out-of-hospital cardiac arrest

Background: To determine if the effects of epinephrine administration on the outcome of out-of-hospital cardiac arrest (OHCA), patients are associated with the duration of cardiopulmonary resuscitation (CPR) performed by Emergency Medical Service (EMS) personnel. Methods: This retrospective, nonrandomized, observational analysis used the All-Japan Utstein Registry, a prospective, nationwide population-based registry of all OHCA patients transported to the hospital by EMS staff as the data source. We stratified all OHCA patients for quartile of EMSs' CPR duration. Group 1 consisted of patients who fell under the 25th percentile of EMSs' CPR duration (under 15 min); group 2, patients who fell into the 25th to 50th percentile (between 15 and 19 min); group 3, patients who fell into the 50th to 75th percentile (between 20 and 26 min); and group 4, patients who fell at or above the 75th percentile (over 26 min). The primary endpoint was a favorable neurological outcome 1 month after cardiac arrest. The secondary endpoints were ROSC before arrival at the hospital and 1-month survival. Results: A total of 383,811 patients aged over 18 years who had experienced OHCA between 2006 and 2010 in Japan, when stratified for quartile of EMSs' CPR duration, the epinephrine administration increased the rate of return of spontaneous circulation (ROSC) approximately tenfold in all groups. However, the beneficial effects of epinephrine administration on 1-month survival disappeared in patients on whom EMSs' CPR had been performed for more than 26 min, and the beneficial effects of epinephrine administration on neurological outcomes were observed only in patients on whom EMSs' CPR had been performed between 15 and 19 min (odds ratio, 1.327, 95 % confidence intervals, 1.017-1.733 P = 0.037). Conclusions: Epinephrine administration is associated with an increase of ROSC and with improvement in the neurological outcome on which EMSs' CPR duration is performed between 15 and 19 min

ジダツ コンバイン ノ ソウコウセイ コウジヨウ ニ カンスル ケンキユウ

筑波大学農学博士学位論文・昭和58年3月25日授