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Context: Pheochromocytoma and paraganglioma (PPGL) may appear as a complication of cyanotic congenital heart disease (CCHD-PPGL) with frequent EPAS1 mutations, suggesting a close link between EPAS1 mutations and tissue hypoxia in CCHD-PPGL pathogenesis., Objective: Our aim is to further investigate the role of EPAS1 mutations in the hypoxia-driven mechanism of CCHD-PPGL pathogenesis, particularly focusing on metachronous and/or multifocal CCHD-PPGL tumors., Methods: We performed whole-exome sequencing (WES) for somatic and germline mutations in 15 PPGL samples from 7 CCHD patients, including 3 patients with metachronous and/or multifocal tumors, together with an adrenal medullary hyperplasia (AMH) sample., Results: We detected EPAS1 mutations in 15 out of 16 PPGL/AMH samples from 7 cases. Conspicuously, all EPAS1 mutations in each of 3 cases with multifocal or metachronous tumors were mutually independent and typical examples of parallel evolution, which is suggestive of strong positive selection of EPAS1-mutated clones. Compared to 165 The Cancer Genome Atlas non-CCHD-PPGL samples, CCHD-PPGL/AMH samples were enriched for 11p deletions (13/16) and 2p amplifications (4/16). Of particular note, the multiple metachronous PPGL tumors with additional copy number abnormalities developed 18 to 23 years after the resolution of hypoxemia, suggesting that CCHD-induced hypoxic environments are critical for positive selection of EPAS1 mutants in early life, but may no longer be required for development of PPGL in later life., Conclusion: Our results highlight a key role of activated hypoxia-inducible factor 2α due to mutated EPAS1 in positive selection under hypoxic environments, although hypoxemia itself may not necessarily be required for the EPAS1-mutated clones to progress to PPGL., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Dental pulp is known to play crucial roles in homeostasis of teeth and periodontal tissue. Although resorption of bone around the roots of nonvital teeth is occasionally observed in clinical practice, little is known about the role of dental pulp in osteoclastogenesis. Here we evaluated the effects of conditioned medium (CM) from rat dental pulp on osteoclastogenesis. It was found that the CM reduced the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclasts, but did not alter the mRNA levels of nuclear factor of activated T-cells, cytoplasmic 1 and TRAP. To further understand the mechanism behind these results, we evaluated the effects of CM on osteoclast precursors and found that the CM removed cell processes, resulting in a significant reduction in the number of attached cells and an increase in the number of freely floating cells. Furthermore, the CM suppressed the mRNA levels of focal adhesion kinase and paxillin, which are involved in cell adhesiveness and spreading. Collectively, the present results show that CM from dental pulp serves as an inhibitor of osteoclastogenesis by reducing the number and adhesiveness of osteoclast precursors, suggesting novel therapeutic applicability for osteoporosis.

Objective: To determine the utility of the post-/preoperative anti-p53 antibody (p53 Ab) ratio as a prognostic factor for colorectal cancer (CRC) recurrence., Methods: A total of 737 nonmetastatic CRC patients who had undergone R0 resection were retrospectively analyzed. p53 Ab levels were measured within 1 month prior to and at least every 3 months after surgery. Post-/preoperative p53 Ab ratios were calculated, and the optimal ratio cutoff values for predicting recurrence were determined using the Kaplan-Meier method and the log-rank test., Results: Preoperative p53 Ab elevation was observed in 194 patients (pre-p53 high). Preoperative p53 Ab levels correlated with TNM stage. Re-elevation of p53 Ab levels occurred on recurrence in the pre-p53 high group, but not in the pre-p53 low group (n = 543). In the pre-p53 high group, patients who experienced tumor recurrence exhibited a slow postoperative reduction of p53 Ab levels, and a post-/preoperative p53 Ab ratio >0.4 at postoperative 3 months predicted relapse-free survival. In other words, a p53 Ab level remaining higher than 40% of the preoperative level was an independent and strong risk factor for recurrence in multivariate analyses., Conclusion: In CRC patients with preoperative p53 Ab elevation, the rate of p53 Ab reduction in the early postsurgical period is a promising prognostic factor for recurrence., (© 2016 S. Karger AG, Basel.)

Precise directional control of pollen-tube growth by pistil tissue is critical for successful fertilization of flowering plants [1-3]. Ovular attractant peptides, which are secreted from two synergid cells on the side of the egg cell, have been identified [4-6]. Emerging evidence suggests that the ovular directional cue is not sufficient for successful guidance but that competency control by the pistil is critical for the response of pollen tubes to the attraction signal [1, 3, 7]. However, the female molecule for this competency induction has not been reported. Here we report that ovular methyl-glucuronosyl arabinogalactan (AMOR) induces competency of the pollen tube to respond to ovular attractant LURE peptides in Torenia fournieri. We developed a method for assaying the response capability of a pollen tube by micromanipulating an ovule. Using this method, we showed that pollen tubes growing through a cut style acquired a response capability in the medium by receiving a sufficient amount of a factor derived from mature ovules of Torenia. This factor, named AMOR, was identified as an arabinogalactan polysaccharide, the terminal 4-O-methyl-glucuronosyl residue of which was necessary for its activity. Moreover, a chemically synthesized disaccharide, the β isomer of methyl-glucuronosyl galactose (4-Me-GlcA-β-(1→6)-Gal), showed AMOR activity. No specific sugar-chain structure of plant extracellular matrix has been identified as a bioactive molecule involved in intercellular communication. We suggest that the AMOR sugar chain in the ovary renders the pollen tube competent to the chemotropic response prior to final guidance by LURE peptides., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Described herein is the case of a rare combination of congenital left ventricular (LV) aneurysm and left ventricular non-compaction (LVNC) in a newborn. The patient developed refractory heart failure soon after birth and died at 5 months of age. The etiology of both congenital LV aneurysm and LVNC seems to be maldevelopment of the ventricular myocardium during early fetal life. Treatment should be individually tailored depending on clinical severity, and treatment options are limited. Given that this combination of congenital LV aneurysm and LVNC is significantly associated with poor prognosis, it appears that patients with congenital LV aneurysm and LVNC are candidates for early, aggressive intervention, including surgical aneurysmectomy and evaluation for transplantation. It is important to be aware of this combination of congenital LV aneurysm and LVNC, and to make earlier decisions on therapeutic strategy., (© 2014 Japan Pediatric Society.)

Aim: To compare the acute effects of shortly pre- vs. postprandial exercise on postprandial lipid metabolism in healthy but sedentary young Japanese women., Methods: Healthy young Japanese women with a sedentary lifestyle, normal weight (18.5 ≤ BMI < 25), normal ovarian cycle, and apolipoprotein E3/3 were selected as participants. A single bout of walking exercise was performed 20 min after (Exp. 1) or 50 min before (Exp. 2) the intake of oral fat tolerance test (OFTT) cream (1 g/kg body weight) at about 50% Vo(2)max for 30 min on a motorized treadmill. A control trial without exercise was also performed in each experiment. Each subject performed 2 trials in a randomized, cross-over design. Venous blood samples were drawn before the preprandial exercise (-1 h, Exp. 2 only) [corrected] and before (0 h) and 1, 2, 4 and 6 h after the fat intake for the determination of triglyceride (TG), apolipoprotein B-48 (apoB48), remnant-like particle-TG (RLP-TG), lactate, free fatty acid (FFA), insulin, and glucose., Results: In both experiments, postprandial serum TG concentrations in the exercise group were lower, but not significantly, than those in the control. In Exp. 1, incremental areas under the curve (IAUC) for TG and RLP-TG were slightly, but not significantly, smaller in the postprandial exercise group than the control. The values of apoB48, a marker of the chylomicron particle number, at 2, 4, and 6 h after the fat intake and IAUC for apoB48 were significantly lower in the postprandial exercise group than the control. In Exp. 2, IAUC for TG, RLP-TG, and apoB48 were not significantly different between the two groups., Conclusion: The present findings suggest that postprandial, but not preprandial, exercise may reduce the number of chylomicrons and chylomicron remnants and improve exogenous lipoprotein metabolism. Postprandial exercise is more effective for improving postprandial lipoprotein metabolism than preprandial exercise.

A putative virulence factor, SabA, a sialic acid-binding adhesin, has recently been characterized in Helicobacter pylori from European isolates. However, little genetic information is available for sabA genes in strains isolated from Japanese patients. Here, we investigated the presence of the sabA gene in 23 H. pylori clinical isolates using polymerase chain reaction detection. It was found that 91.3% of H. pylori isolates examined contain the sabA gene. Sequence comparison and phylogenetic analysis based on the deduced amino acid sequence of sabA in nine H. pylori isolates from Japanese patients and three H. pylori strains from Western individuals suggested that sabA is genetically diverse and the clustering of the strains based on SabA is related to their geographical origin. It needs to be further assessed whether the genetic diversity of sabA is associated with the clinical outcomes of H. pylori infection.

Although well over 200 viral agents have been implicated in acute respiratory infections (ARIs) among children, no system able to detect such a wide range of viruses has been established. Between January 2004 and December 2005, a modified microplate method, including HEF, HEp-2, Vero E6, MDCK, RD-18S, and GMK cell lines (HHVe6MRG plate), was adopted to isolate viruses. A total of 1,551 viruses were isolated, representing both outbreaks and sporadic cases, from 4,107 nasopharyngeal specimens, at monthly isolation rates of 22.3 to 52.6%. Influenza, parainfluenza, respiratory syncytial (RS), and mumps viruses, and human metapneumovirus, enterovirus, parechovirus, rhinovirus, adenovirus, herpesvirus, and cytomegalovirus were all isolated. The use of multiple cell lines increased the isolation rates of most of these viruses. The findings showed that ARIs due to a number of respiratory viruses occurred across all seasons in succession and/or concurrently in children in the community. These data will help clinicians determine in which seasons and for which age groups they should use the rapid diagnostic test kits available for influenza virus, RS virus, and adenovirus. In conclusion, we verified that the modified microplate method was able to clarify the etiology and epidemiology of numerous viruses isolated from children with ARI.

We have continued the epidemiological study on adenovirus type 7 (Ad7), which re-emerged in 1995 in Yamagata, Japan. Between 1999 and 2004, we isolated only four strains from 10,778 throat swab specimens among children with acute respiratory infections. A serological survey of 303 specimens revealed the antibody-positive rate against Ad7 to be 0-7.4% in children under 10 years of age in 2005, although it was 3.3-16.7% in 1997 and 0% in 1993. Our results suggest that a re-emergence does not always provoke a sudden major outbreak, even if the antibody-positive rate against Ad7 is low in the local community.

Between September 2000 and March 2003 healthy subjects in 10 prefectures of Japan were investigated to identify carriers of Neisseria meningitidis. Twenty-five N. meningitidis strains were isolated from 5886 throat swab specimens collected from healthy persons, such as students, elderly, and foreigners. Of the 25 carriers, 9 were teenagers, 15 were in their twenties, and only one was in the fifties. The male-female ratio of the carriers was 17 to 8, showing male dominance. The serogroups of the 25 strains were B (9 strains), Y (4 strains) and non-groupable (12 strains). One of the strains was found to be deficient in gamma-glutamyl aminopeptidase activity, which is an identification marker for N. meningitidis.

Objectives: To analyze the prevalence of echovirus type 13 (Echo13) in Yamagata, Japan., Methods: Virus isolation was performed from 6514 clinical specimens using six cell lines between January 1999 and December 2002. We also carried out a seroepidemiological study against Echo13, using 234 serum samples collected in 2001., Results: In 2002, we isolated a total of 50 Echo13 strains, which had not been detected from 1981 until 2001 in Japan. The antibody positive rate was higher (57.2-62.0%) in subjects 50 years or over than in those under 50 years (0-14.4%)., Conclusions: Serological study suggested that Echo13 had been present in Yamagata until around 1960, at which time the antibody positive persons were exposed to Echo13 in their childhood. Furthermore, results of virus isolation demonstrated that Echo13 re-emerged in around 2002 after a hiatus of several decades.

A technique for detecting Raphidophycean, a bloom-forming genus of algae, was developed using a specific DNA probe. The design of the probe was based on a sequence polymorphism within the small subunit (SSU) ribosomal RNA gene (rDNA) of this strain by using fluorescence polarization (FP) analysis and the BIAcore 2000 biosensor, which utilized surface plasmon resonance (SPR). The specific sequence in SSU rDNA for Heterosigma carterae was determined by sequence data analysis. One pair of polymerase chain reaction (PCR) probes was designed for use in making the identification. H. carterae SSU rDNA was amplified by PCR. Using a fluoroscein isothiocyanate-labeled or biotin-labeled oligonucleotide probe, the PCR-amplified rDNA was selectively detected as an FP-intensity change via FP analysis or as a resonance-unit change via SPR. Although total time for final detection after sampling was within 3 hours, specific rDNA could be detected within 10 minutes after PCR through these detection methods.

The effect of glucagon on macronutrient selection was studied using rats. Continuous infusion of glucagon (5 ng/microliters/h) into the lateral cerebral ventricle increased total caloric intake and protein selection, and decreased carbohydrate selection. Continuous infusion of glucagon subcutaneously induced similar changes. Since a hyperglycemic response to the intracranial injection of 2-deoxy-D-glucose (2DG) disappeared in rats either with bilateral lesions of the hypothalamic suprachiasmatic nucleus (SCN) (17) or with acquired (21) and congenital (10) blindness, and bilateral lesions of the SCN eliminated the hyperglucagonemic response to the 2DG-injection (19), changes in the plasma glucagon concentration after 2DG injection were examined in acquired and congenital blind rats. Consequently, it was found that the hyperglucagonemic response to 2DG was not observed in those blind rats which lacked the hyperglycemic response. In those SCN-lesioned and blind rats lacking the hyperglucagonemic response to 2DG, the protein selection was lower, and carbohydrate selection tended to be higher, than those selections found in the control rats. Considering the neural connection between the retina and the SCN, these findings suggest that glucagon may have a stimulatory effect on protein intake and a suppressive one for carbohydrate intake; and that the SCN may be involved in such a regulatory mechanism of feeding behavior through controlling the blood glucagon level.

In 50 patients from 41 families of Duchenne muscular dystrophy (DMD) born between 1956 and 1980 in the San-in area of Japan, the changes in DMD incidence rate were analyzed through five periods of time: 1956-1960, 1961-1965, 1966-1970, 1971-1975 and 1976-1980. The overall incidence decreased from 22.31 X 10(-5) live male births in the first period to 14.51 X 10(-5) in the last. This decrease was mainly related to the group of mothers who were definite carriers (p less than 0.005), and was probably due to genetic counselling of definite carrier families. For a further decrease in the incidence of DMD, the newborn male screening system for creatine phosphokinase (CPK) and appropriate genetic counselling might be effective. From an analysis of 28 families without previous family history, the expected proportion of maternal carriers was 0.57.