分子遺伝学的手法を用いたわが国メロン品種の多様性と分類

For the breeding of Japanese netted melon, various types of foreign cultivars have been utilized for improving adaptability, disease and pest resistance, fruit quality and so on. However, little is known about their genetic diversity and relationships, since most cultivars derived from crosses between various horticultural groups. To figure out the genetic structure of Japanese melon, in this study, 57 melon accessions from three horticultural groups were examined using 55 RAPD markers produced by 24 RAPD primers. Genetic diversity of the Japanese netted melon was as high as those of cultivar groups of Groups Cantalupensis and Inodorus, while it was low in Group Conomon irrespective of large variations in fruit traits. Cluster analysis and PCO analysis based on genetic distance showed that Group Conomon was distantly related to other melon accessions. Among the latter, European cantaloupe (nonnetted) and American open-field type (netted) proved to be genetically close, while England glasshouse melon (netted) including ‘Earl’s Favourite’ is distantly related to these two groups and closely related with Group Inodorus. It was therefore suggested that England glasshouse type was established from hybrids between European cantaloupe and Group Inodorus. Japanese netted melon was most closely related with England glasshouse type, irrespective of the fact that various kinds of melon accessions have been crossed to improve adaptability, disease resistance and so on. In contrast, pure line cultivars of the Japanese netted melon bred by pure line selection from ‘Earl's Favourite’ or by crossing ‘Earl’s Favourite’ with ‘British Queen’ were confirmed to be mostly homogenous, and it was difficult to establish RAPD markers to discriminate each cultivar. Group Conomon var. makuwa and var. conomon, which have been cultivated and utilized as different crops, proved to be genetically indistinguishable and were considered to share the same gene pool

Polaprezinc Protects Mice against Endotoxin Shock

Polaprezinc (PZ), a chelate compound consisting of zinc and l-carnosine (Car), is an anti-ulcer drug developed in Japan. In the present study, we investigated whether PZ suppresses mortality, pulmonary inflammation, and plasma nitric oxide (NO) and tumor necrosis factor (TNF)-α levels in endotoxin shock mice after peritoneal injection of lipopolysaccharide (LPS), and how PZ protects against LPS-induced endotoxin shock. PZ pretreatment inhibited the decrease in the survival rate of mice after LPS injection. PZ inhibited the increases in plasma NO as well as TNF-α after LPS. Compatibly, PZ suppressed LPS-induced inducible NO synthase mRNA transcription in the mouse lungs. PZ also improved LPS-induced lung injury. However, PZ did not enhance the induction of heat shock protein (HSP) 70 in the mouse lungs after LPS. Pretreatment of RAW264 cells with PZ suppressed the production of NO and TNF-α after LPS addition. This inhibition likely resulted from the inhibitory effect of PZ on LPS-mediated nuclear factor-κB (NF-κB) activation. Zinc sulfate, but not Car, suppressed NO production after LPS. These results indicate that PZ, in particular its zinc subcomponent, inhibits LPS-induced endotoxin shock via the inhibition of NF-κB activation and subsequent induction of proinflammatory products such as NO and TNF-α, but not HSP induction

Geranylgeranylacetone Ameliorates Inflammatory Response to Lipopolysaccharide (LPS) in Murine Macrophages: Inhibition of LPS Binding to The Cell Surface

We investigated whether pretreatment with geranylgeranylacetone (GGA), a potent heat shock protein (HSP) inducer, could inhibit proinflammatory cytokine liberation and nitric oxide (NO) production in lipopolysaccharide (LPS)-treated murine macrophages. The levels of NO and tumor necrosis factor-α (TNF-α) released from murine macrophage RAW 264 cells were increased dose- and time-dependently following treatment with LPS (1 µg/ml). GGA (80 µM) treatment 2 h before LPS addition significantly suppressed TNF-α and NO productions at 12 h and 24 h after LPS, respectively, indicating that GGA inhibits activation of macrophages. However, replacement by fresh culture medium before LPS treatment abolished the inhibitory effect of GGA on NO production in LPS-treated cells. Furthermore, GGA inhibited both HSP70 and inducible NO synthase expressions induced by LPS treatment despite an HSP inducer. When it was examined whether GGA interacts with LPS and/or affects expression of Toll-like receptor 4 (TLR4) and CD14 on the cell surface, GGA inhibited the binding of LPS to the cell surface, while GGA did not affect TLR4 and CD14 expressions. These results indicate that GGA suppresses the binding of LPS to the cell surface of macrophages, resulting in inhibiting signal transduction downstream of TLR4

The effect of isoflavone-daidzein oral medication on cutaneous wound healing in female ovariectomized mice

This study investigated the influence of oral administration of isoflavone-daidzein on the cutaneous wound healing process in female ovariectomized mice. Eight-week-old female mice were divided into groups of ovariectomized mice and mice administered daidzein after an ovariectomy. Two full-thickness wounds on the dorsum were made in mice in both groups. There was no significant difference between wound areas of the two groups from wounding to healing during 15 days. The area in the group administered daidzein tended to be smaller than that in the ovariectomized group during the inflammatory phase 4 and 5 days after wounding . The rate of re-epithelialization in the group administered daidzein tended to be higher than that in the ovariectomized group in the inflammatory phase on day 3 (40.7 ± 17.6% and 21.0 ± 16.8%, respectively). Therefore, the administration of daidzein under lack of estrogen is expected to reduce the inflammation period and promote re-epithelialization. この研究は、卵巣摘出した雌マウスに皮膚創傷を作製し、経口投与したイソフラボン の一種であるダイゼインが、創傷治癒にどのような影響を与えるかを観察したもので ある。8 週令の雌マウスを卵巣摘出群と卵巣摘出し創作製した後にダイゼインを与え た2 群に分けた。両群共、卵巣摘出後、ダイゼインを含まない精製飼料で２週間飼育 後に、左右の背部に直径4mm の皮膚全層欠損層を作製した。創作製後、ダイゼインを 含まない飼料とダイゼインを含む飼料で2 週間飼育した。ダイゼインは、飼料1g に 0.01mg 含むように作製した。両群の創面積は、2 週間の間の毎日において、有意差は 見られなかった。しかし、炎症期である創作製後4 と5 日では、ダイゼイン食で飼育 した群が無ダイゼイン食で飼育した群が、やや創面積が小さい傾向がみられた（それ ぞれ、p 値が0.061、0.083 であった）。創作製後の3 日での、再上皮化の割合は、ダイゼイン群で40.7 ± 17.6%、無ダイゼイン群で21.0 ± 16.8%となり、ダイゼイ ン群はより上皮化が進んでいる傾向が見られた (p = 0.07)。これらの結果は、エス トロゲン欠乏状態で、ダイゼインの経口投与が、創傷治癒において、炎症を抑制し上 皮化を促進することを示唆している

Immunological Microenvironment Predicts the Survival of the Patients with Hepatocellular Carcinoma Treated with Anti-PD-1 Antibody

Introduction: Although immune checkpoint inhibitors (ICIs) have been considered as promising agents for the treatment of advanced hepatocellular carcinoma (HCC), previous clinical trials revealed that the response to anti-programmed cell death protein 1 (anti-PD-1) monotherapy was as low as 20%. Identifying subgroups that respond well to ICIs is clinically important. Here, we studied the prognostic factors for anti-PD-1 antibody treatment based on the molecular and immunological features of HCC. Methods: Patients who were administered anti-PD1 antibody for advanced HCC at Kindai University Hospital were included. Clinicopathological backgrounds and antitumor responses were examined in 34 cases where tumor tissues before treatment were available. Transcriptome analysis was performed using 40 HCC samples obtained from surgical resection, and immune status was compared between 20 HCCs with activating mutations in β-catenin and those without the mutations using transcriptome-based immunogram. Results: Univariate analysis showed that the disease control rate was significantly better in patients with α-fetoprotein < 400 ng/mL, negative for β-catenin/glutamate synthetase (GS) staining, high combined positive score (CPS) of programmed death-ligand 1 (PD-L1), and increased infiltration of CD8+ cells in tumor tissues. Among them, negative staining of β-catenin/GS, CPS of PD-L1 ≥ 1, and high degree of CD8+ tumor-infiltrating lymphocytes (TILs) were significantly associated with longer survival in both progression-free survival (PFS) and overall survival (OS). The combination of these factors well stratified the survival of the patients on anti-PD-1 antibody in both PFS and OS (p < 0.0001 and p = 0.0048 for PFS and OS, respectively). In addition, the immunogram revealed that tumor-carrying mutations in β-catenin showed downregulation of immune-related genes, especially in those related to priming and activation by dendritic cells, interferon-γ response, inhibitory molecules, and regulatory T cells. Discussion/Conclusion: The combined score including Wnt/β-catenin activation, CPS of PD-L1, and degree of CD8+ TILs in HCC is informative for predicting the response to ICI in HCC cases. Constitutive activation of β-catenin can induce an immune cold phenotype with downregulation of immune-related genes, and immunohistochemistry-based evaluation is beneficial for identifying the subgroup that shows a good response to ICI

Body mass index and colorectal cancer risk : A Mendelian randomization study

Traditional observational studies have reported a positive association between higher body mass index (BMI) and the risk of colorectal cancer (CRC). However, evidence from other approaches to pursue the causal relationship between BMI and CRC is sparse. A two-sample Mendelian randomization (MR) study was undertaken using 68 single nucleotide polymorphisms (SNPs) from the Japanese genome-wide association study (GWAS) and 654 SNPs from the GWAS catalogue for BMI as sets of instrumental variables. For the analysis of SNP-BMI associations, we undertook a meta-analysis with 36 303 participants in the Japanese Consortium of Genetic Epidemiology studies (J-CGE), comprising normal populations. For the analysis of SNP-CRC associations, we utilized 7636 CRC cases and 37 141 controls from five studies in Japan, and undertook a meta-analysis. Mendelian randomization analysis of inverse-variance weighted method indicated that a one-unit (kg/m2) increase in genetically predicted BMI was associated with an odds ratio of 1.13 (95% confidence interval, 1.06-1.20; P value <.001) for CRC using the set of 68 SNPs, and an odds ratio of 1.07 (1.03-1.11, 0.001) for CRC using the set of 654 SNPs. Sensitivity analyses robustly showed increased odds ratios for CRC for every one-unit increase in genetically predicted BMI. Our MR analyses strongly support the evidence that higher BMI influences the risk of CRC. Although Asians are generally leaner than Europeans and North Americans, avoiding higher BMI seems to be important for the prevention of CRC in Asian populations

Prevalence of inappropriate medication using Beers criteria in Japanese long-term care facilities

BACKGROUND: The prevalence and risk factors of potentially inappropriate medication use among the elderly patients have been studied in various countries, but because of the difficulty of obtaining data on patient characteristics and medications they have not been studied in Japan. METHODS: We conducted a retrospective cross-sectional study in 17 Japanese long-term care (LTC) facilities by collecting data from the comprehensive MDS assessment forms for 1669 patients aged 65 years and over who were assessed between January and July of 2002. Potentially inappropriate medications were identified on the basis of the 2003 Beers criteria. RESULTS: The patients in the sample were similar in terms of demographic characteristics to those in the national survey. Our study revealed that 356 (21.1%) of the patients were treated with potentially inappropriate medication independent of disease or condition. The most commonly inappropriately prescribed medication was ticlopidine, which had been prescribed for 107 patients (6.3%). There were 300 (18.0%) patients treated with at least 1 inappropriate medication dependent on the disease or condition. The highest prevalence of inappropriate medication use dependent on the disease or condition was found in patients with chronic constipation. Multiple logistic regression analysis revealed psychotropic drug use (OR = 1.511), medication cost of per day (OR = 1.173), number of medications (OR = 1.140), and age (OR = 0.981) as factors related to inappropriate medication use independent of disease or condition. Neither patient characteristics nor facility characteristics emerged as predictors of inappropriate prescription. CONCLUSION: The prevalence and predictors of inappropriate medication use in Japanese LTC facilities were similar to those in other countries

三重県地域住民に対するみそ汁の減塩指導の実践についての検討

昭和55年において,三重県地域住民に対する各保健所の健康教室,集団検診などの参加者1,201世帯を対象とし,参加者に持参させたみそ汁の食塩濃度を測定した。その結果について検討をおこなった。(1)三重県下地域住民のみそ汁の食塩濃度の平均値は1.08%であったが,各保健所ともにその値に著しいバラツキがみられた。(2)上記みそ汁の適正濃度(0.8%)以上のからずき世帯率を保健所別にみた場合は,桑名では67.8%,四日市では62.5%,鈴鹿では79.5%,津では74.6%,松阪では72.8%,上野では81.2%であった。このからすぎ世帯率において,高血圧者在宅世帯と非高血圧者在宅世帯との間には相関関係はみられなかった。(3)ついで,保健所別脳血管疾患死亡率とからずき世帯率との間には相関関係は認められなかった。In 1980 having 1,201 families participated in the health school and mass examination was held by the Regional Health Centers in Mie Prefecture. And, salt concentrations of miso soup brought by those participants were measured. The results were analyzed as follows: (1) The mean concentration of salt in miso soup referring to the regional inhabitants in Mie Prefecture was 1.08%, however, the values were markedly fluctuated by Health Centers. (2) Those families in favor of the saltier taste than the adequate concentration (0.8%) of the miso soup were noted at 67.8% in Kuwana, 62.5% in Yokkaichi, 79.5% in Suzuka, 74.6% in Tsu, 72.8% in Matsuzaka and 81.2% in Ueno. Among those families of salty taste lovers, no correlation was observed between hypertension and nonhypertension. (3) When classified by Health Centers, no correlation was observed between the mortality from cerebrovascular diseases and the percentage of salty taste loving families

Vrn-D4 is a vernalization gene located on the centromeric region of chromosome 5D in hexaploid wheat.

Natural variation in wheat requirement of long exposures to cold temperatures to accelerate flowering (vernalization) is mainly controlled by the Vrn-1, Vrn-2, Vrn-3, and Vrn-4 loci. The first three loci have been well characterized, but limited information is available for Vrn-4. So far, natural variation for Vrn-4 has been detected only in the D genome (Vrn-D4), and genetic stocks for this gene are available in Triple Dirk (TDF, hereafter). We detected heterogeneity in the Vrn-1 alleles present in different TDF stocks, which may explain inconsistencies among previous studies. A correct TDF seed stock from Japan carrying recessive vrn-A1, vrn-B1, and vrn-D1 alleles was crossed with three different winter cultivars to generate F(2) mapping populations. Most of the variation in flowering time in these three populations was controlled by a single locus, Vrn-D4, which was mapped within a 1.8 cM interval flanked by markers Xcfd78 and Xbarc205 in the centromeric region of chromosome 5D. A factorial ANOVA for heading time using Vrn-D4 alleles and vernalization as factors showed a significant interaction (P &lt; 0.0001), which confirmed that the Vrn-D4 effect on flowering time is modulated by vernalization. Comparison of the different Triple Dirk stocks revealed that Vrn-B1, Vrn-D1, and Vrn-D4 all have a small residual response to vernalization, but Vrn-D4 differs from the other two in its response to short vernalization periods. The precise mapping and characterization of Vrn-D4 presented here represent a first step toward the positional cloning of this gene

Usefulness of Respiratory Mechanics and Laboratory Parameter Trends as Markers of Early Treatment Success in Mechanically Ventilated Severe Coronavirus Disease: A Single-Center Pilot Study

Whether a patient with severe coronavirus disease (COVID-19) will be successfully liberated from mechanical ventilation (MV) early is important in the COVID-19 pandemic. This study aimed to characterize the time course of parameters and outcomes of severe COVID-19 in relation to the timing of liberation from MV. This retrospective, single-center, observational study was performed using data from mechanically ventilated COVID-19 patients admitted to the ICU between 1 March 2020 and 15 December 2020. Early liberation from ventilation (EL group) was defined as successful extubation within 10 days of MV. The trends of respiratory mechanics and laboratory data were visualized and compared between the EL and prolonged MV (PMV) groups using smoothing spline and linear mixed effect models. Of 52 admitted patients, 31 mechanically ventilated COVID-19 patients were included (EL group, 20 (69%); PMV group, 11 (31%)). The patients’ median age was 71 years. While in-hospital mortality was low (6%), activities of daily living (ADL) at the time of hospital discharge were significantly impaired in the PMV group compared to the EL group (mean Barthel index (range): 30 (7.5–95) versus 2.5 (0–22.5), p = 0.048). The trends in respiratory compliance were different between patients in the EL and PMV groups. An increasing trend in the ventilatory ratio during MV until approximately 2 weeks was observed in both groups. The interaction between daily change and earlier liberation was significant in the trajectory of the thrombin–antithrombin complex, antithrombin 3, fibrinogen, C-reactive protein, lymphocyte, and positive end-expiratory pressure (PEEP) values. The indicator of physiological dead space increases during MV. The trajectory of markers of the hypercoagulation status, inflammation, and PEEP were significantly different depending on the timing of liberation from MV. These findings may provide insight into the pathophysiology of COVID-19 during treatment in the critical care setting