SYNTHESIS OF PROCYANIDINS C2 AND C1 USING LEWIS ACID MEDIATED EQUIMOLAR CONDENSATION

Synthesis of procyanidins C2 and C1 was achieved via a stereoselective intermolecular condensation of equimolar amount of dimeric catechin or epicatechin nucleophile and monomeric catechin or epicatechin electrophile using Lewis acid. In the case of synthesis of procyanidin C2, AgBF4 and AgOTf afforded condensed product in excellent yield. As to the synthesis of procyanidin C1, Yb(OTf)(3) was effective for equimolar condensation.ArticleHETEROCYCLES. 85(9):2241-2250 (2012)journal articl

Efficacy of Corrected Rapid Turnover Protein Increment Index (CRII) for Early Detection of Improvement of Nutrition Status in Patients with Malnutrition

Serum prealbumin level is useful for assessment of changes in nutritional status but it is markedly affected by the inflammation. In this study, we examined the efficacy of the corrected rapid turnover protein increment index (CRII) for prealbumin, which is calculated as [prealbumin level/C-reactive protein (CRP) level on the assessment day]/[prealbumin level/CRP level on the day of starting nutritional care], for prediction of improvement of nutritional status in patients with malnutrition. The subjects were 50 hospitalized patients with low albuminemia, who were receiving nutritional care. Serum concentrations of albumin, prealbumin and CRP were measured every week for 5 weeks. We defined patients whose serum albumin level was elevated by more than 0.2 g/dl after 5 weeks as those showing improved nutritional status. There was a significant difference in the prealbumin level between improved and unimproved patients at 5 weeks after the start of nutritional support. On the other hand, the prealbumin CRII value showed a significant difference between the groups at 1 and 2 weeks after the start of nutritional support. In conclusion, assessment of prealbumin CRII is useful for early prediction of improved nutritional status in patients with malnutrition

TIMP3 promotes the maintenance of neural stem-progenitor cells in the mouse subventricular zone

Adult neural stem cells (NSCs) in the mouse subventricular zone (SVZ) serve as a lifelong reservoir for newborn olfactory bulb neurons. Recent studies have identified a slowly dividing subpopulation of embryonic neural stem-progenitor cells (NPCs) as the embryonic origin of adult NSCs. Yet, little is known about how these slowly dividing embryonic NPCs are maintained until adulthood while other NPCs are extinguished by the completion of brain development. The extracellular matrix (ECM) is an essential component of stem cell niches and thus a key determinant of stem cell fate. Here we investigated tissue inhibitors of metalloproteinases (TIMPs)—regulators of ECM remodeling—for their potential roles in the establishment of adult NSCs. We found that Timp2, Timp3, and Timp4 were expressed at high levels in slowly dividing NPCs compared to rapidly dividing NPCs. Deletion of TIMP3 reduced the number of adult NSCs and neuroblasts in the lateral SVZ. In addition, overexpression of TIMP3 in the embryonic NPCs suppressed neuronal differentiation and upregulated the expression levels of Notch signaling relating genes. These results thus suggest that TIMP3 keeps the undifferentiated state of embryonic NPCs, leading to the establishment and maintenance of adult NSCs

Synthesis of Procyanidins C2 and C1 Using Lewis Acid Mediated Equimolar Condensation

Synthesis of procyanidins C2 and C1 was achieved via a stereoselective intermolecular condensation of equimolar amount of dimeric catechin or epicatechin nucleophile and monomeric catechin or epicatechin electrophile using Lewis acid. In the case of synthesis of procyanidin C2, AgBF4 and AgOTf afforded condensed product in excellent yield. As to the synthesis of procyanidin C1, Yb(OTf)(3) was effective for equimolar condensation.ArticleHETEROCYCLES. 85(9):2241-2250 (2012)journal articl

Vastus lateralis oxygenation during prolonged cycling in healthy males

This study examined the relationship between the acute cardiorespiratory and muscleoxygenation/blood volume changes during prolonged exercise. Eight healthy male volunteers (mean VO2max = 41.6 ± 2.4 ml/kg/min) performed 60 minutes submaximal cycling at 500f VO2max. Oxygen uptake (VO2) was measured by indirect spirometry, cardiac output (CO) was estimated via Portapres, and right vastus lateralis oxyhemoglobin/myoglobin (OxyHb/Mb), deoxyhemoglobin/myoglobin (DeoxyHb/Mb) and total hemoglobin/myoglobin (Total Hb/Mb) were recorded using near infrared spectroscopy. After 40 minutes of exercise, there was a significant increase in VO2 due to a significantly higher (a – v)O2diff. After 30 mins of exercise CO was unchanged, but there was a significant decrease in stroke volume and a proportionate increase in heart rate indicating the occurrence of cardiovascular drift. During the first few minutes of exercise, there was a decline in OxyHb/Mb and Total Hb/Mb while DeoxyHb/Mb remained unchanged. Thereafter OxyHb/Mb and Total Hb/Mb increased systematically until the termination of exercise while DeoxyHb/Mb declined. After 40 minutes of exercise, these changes were significantly different from the baselines values. There were no significant correlations between the changes in the NIRS variables and systemic VO2 or mixed (a – v)O2diff during exercise. These results suggest that factors other than localized changes in muscle oxygenation and blood volume account for the increased VO2 during prolonged submaximal exercise

Protocol for a multicentre, prospective, cohort study to investigate patient satisfaction and quality of life after immediate breast reconstruction in Japan: the SAQLA study

Introduction The aim of breast reconstruction (BR) is to improve patients' health-related quality of life (HRQOL). Therefore, measuring patient-reported outcomes (PROs) would clarify the value and impact of BR on a patient's life and thus would provide evidence-based information to help decision-making. The Satisfaction and Quality of Life After Immediate Breast Reconstruction study aimed to investigate satisfaction and HRQOL in Japanese patients with breast cancer who undergo immediate breast reconstruction (IBR). Methods and analysis This ongoing prospective, observational multicentre study will assess 406 patients who had unilateral breast cancer and underwent mastectomy and IBR, and were recruited from April 2018 to July 2019. All participants were recruited from seven hospitals: Okayama University Hospital, Iwate Medical University Hospital, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Showa University Hospital, University of Tsukuba Hospital, Osaka University Hospital and Yokohama City University Medical Center. The patients will be followed up for 36 months postoperatively. The primary endpoint of this study will be the time-dependent changes in BREAST-Q satisfaction with breast subscale scores for 12 months after reconstructive surgery, which will be collected via an electronic PRO system. Ethics and dissemination This study will be performed in accordance with the Ethical Guidelines for Medical and Health Research Involving Human Subjects published by Japan's Ministry of Education, Science and Technology and the Ministry of Health, Labour and Welfare, the modified Act on the Protection of Personal Information and the Declaration of Helsinki. This study protocol was approved by the institutional ethics committee at the Okayama University Graduate School of Medicine, Dentistry, on 2 February 2018 (1801-039) and all other participating sites. The findings of this trial will be submitted to an international peer-reviewed journal

Analysis of the MYD88 L265P mutation in IgM monoclonal gammopathy by semi-nested polymerase chain reaction-based restriction fragment length polymorphism method

MYD88 L265P mutation causes constitutive activation of NF-κB and possible driver mutation in B-cell lymphoid malignancies. It is frequently detected in Waldenstrom’s macroglobulinemia （WM） （50％-100％）, and its detection is important in diagnostic and therapeutic targets of this syndrome. Standard detection method of MYD88 L265P mutation in clinical practice has yet to be established. We developed semi-nested PCR-based restriction fragment length polymorphism （snPCR-RFLP） to detect the mutation. The snPCR-RFLP method is a modification of the PCR-RFLP method, which uses the restriction enzyme BsiEI that recognizes CGACT/CG, intending to increase detection sensitivity by amplification of mutated allele in the DNA sample using semi-nested PCR before enzyme digestion. The detection sensitivity of snPCR-RFLP was estimated as 0.1％, by detecting mutated allele in wild-type allele in the cloned plasmid DNA, which is comparable with allele-specific （AS） PCR method widely used as sensitive detection method. By analyzing 40 cases with IgM monoclonal gammopathy, snPCR-RFLP detected 29/40 （70％） of all cases, 22/31 （70.9％） of WM, and 6/9 （66.6%） of IgM-type monoclonal gammopathy with undetermined significance （IgMMGUS）, including five cases （three cases of WM and two cases of IgMMGUS） in which the mutation was detected only by snPCR-RFLP but not by Sanger sequencing method. Regarding DNA sample status, particularly five cases, a case was extracted from formalin-fixed paraffin-embedded tissue and four cases were extracted from cells by Ficoll-Hypaque density gradient. In correlation with clinical features, the MYD88 mutation detected by snPCR-RFLP method was associated with the adverse prognostic index （WMIPSS） of WM using patient age, hemoglobin （Hb） level, platelet count, β2MG level, and serum IgM level （p＝0.055）. The snPCR-RFLP method is a clinically useful MYD88 mutation detection method that can be performed in general laboratories

Forebrain Ptf1a Is Required for Sexual Differentiation of the Brain

The mammalian brain undergoes sexual differentiation by gonadal hormones during the perinatal critical period. However, the machinery at earlier stages has not been well studied. We found that Ptf1a is expressed in certain neuroepithelial cells and immature neurons around the third ventricle that give rise to various neurons in several hypothalamic nuclei. We show that conditional Ptf1a-deficient mice (Ptf1a cKO) exhibit abnormalities in sex-biased behaviors and reproductive organs in both sexes. Gonadal hormone administration to gonadectomized animals revealed that the abnormal behavior is caused by disorganized sexual development of the knockout brain. Accordingly, expression of sex-biased genes was severely altered in the cKO hypothalamus. In particular, Kiss1, important for sexual differentiation of the brain, was drastically reduced in the cKO hypothalamus, which may contribute to the observed phenotypes in the Ptf1a cKO. These findings suggest that forebrain Ptf1a is one of the earliest regulators for sexual differentiation of the brain

Japanese translation and linguistic validation of the US National Cancer Institute’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)

Abstract Background The US National Cancer Institute (NCI) has developed the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) to capture patients’ self-reported symptomatic adverse events in cancer clinical trials. The aim of this study was to develop and linguistically validate a Japanese translation of PRO-CTCAE. Forward- and back-translations were produced, and an independent review was performed by the Japan Clinical Oncology Group (JCOG) Executive Committee and the US NCI. We then conducted cognitive interviews with 21 patients undergoing cancer treatment. Participants were asked to complete the PRO-CTCAE and were interviewed using semi-structured scripts and predetermined probes to investigate whether any items were difficult to understand or answer. The interviews were recorded and transcribed, and a thematic analysis was performed. The data were split into two categories: 1) remarks on the items and 2) remarks on the questionnaire in general. Results Twenty-one cancer patients undergoing chemotherapy or hormone therapy were interviewed at the University of Tokyo Hospital and the Kansai Medical University Hirakata Hospital during 2011 and 2012. Thirty-three PRO-CTCAE items were evaluated as “difficult to understand,” and 65 items were evaluated as “difficult to answer” by at least one respondent. However, on further investigation, only 24 remarks were categorized as “comprehension difficulties” or “clarity” issues. Most of these remarks concerned patients’ difficulties with rating their experience of individual symptomatic events. Conclusions The study provides preliminary evidence supporting the linguistic validity of the Japanese version of PRO-CTCAE. Further cognitive interviewing is warranted for PRO-CTCAE items relating to sexuality and anxiety and for response options on severity attribute items

禁煙支援教育を受講した看護学生を対象とした支援方法の内容分析 －妊娠期および産褥期の女性に対する支援方法－

　周産期にある女性の禁煙支援は母児の健康管理のために重要である．本研究では，将来，医療職者となっていく看護学生に対して「女性の喫煙」と題した講義を行うことで，看護学生自らが考える禁煙支援について明らかにすることを目的とする．　研究方法は，専門学校の看護学生2年次生34名に対して1コマ90分の講義をおこなった．そののち，看護学生が自ら考える妊婦･褥婦に対する禁煙支援方法について自由記述質問用紙を用いて記述を求め，その結果について内容分析した．その結果，7の行動技法のカテゴリーに該当する記述が認められ，新たな１つのカテゴリーが抽出された．とりわけ，妊婦･褥婦に対して重要だとされている「社会的サポート」に該当する【周囲の人々を活用する支援】カテゴリーでは，82コードと最も多いコード数となった．「社会的サポート」の中でも，妊婦･褥婦だけを捉えるのではなく，彼女らを取り巻く周囲の人々を資源として活用する視点を有していた．一方で，妊婦･褥婦への禁煙支援指導として適切ではない記述もみられており，今後の教育方法において更なる工夫の必要性が示唆された