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Aims This study aimed to evaluate the changes in left ventricular remodelling with time in patients with hypertrophic cardiomyopathy (HCM) using thallium‐201 myocardial scintigraphy. Methods and results Forty‐eight patients with HCM participated in the study. The extent score (ES) and a newly devised index termed the ‘mean count change’ (MCC) were used to evaluate the myocardial perfusion defects. Using the amount of thallium‐201 uptake (TU), MCC (%) was calculated using the following formula: (last TU − initial TU)∕initial TU × 100. To confirm the site of the lesion, the left ventricle was divided into five segments: anterior, septal, inferior, lateral, and apex. Cardiovascular complications and deaths were recorded. The mean follow‐up period was 8.6 ± 2.0 years. ES increased from 17.4 ± 13.7% to 44.0 ± 22.3% (P

Aims Traditional criteria for heart transplantation by cardiopulmonary exercise testing (CPX) include peak oxygen uptake (VO2)

BACKGROUNDS The relative apical sparing pattern (RASP) of left ventricular (LV) longitudinal strain (LS) is frequently associated with cardiac amyloidosis (CA). However, the visual assessment of RASP is inconsistent, and the quantitative assessment of RASP is time-consuming. This study aimed to compare assessments of RASP for the identification of CA with conventional assessments and investigate their reproducibility and relevance on the assessments. METHODS Forty patients with biopsy-proven CA were compared with 80 hypertrophied patients matched for mean LV wall thickness. We compared the discriminative abilities of three assessments of RASP to identify CA (visual, quantitative, and semiquantitative). Nine patterns of semiquantitative RASP were investigated; finally, it was defined as "reduction of LS" (≥ -10%) in ≥5 (of 6) basal segments, relative to "preserved LS" (

Epigenetic modifications established in the early developmental stages can have long-term consequences throughout life. This concept encompasses the possibility of controlling livestock health and diseases by epigenetic regulation during early development. To explore the candidates of epigenetic modifications in early embryos that might exert long-lasting effects in adulthood, we aimed to obtain genome-wide histone H3 lysine 27 trimethylation (H3K27me3) profiles of bovine blastocysts and compare these data with those from adult somatic tissues in order to extract common and typical features between them. Bovine blastocysts were produced in vitro and subjected to chromatin immunoprecipitation-sequencing analysis of H3K27me3. Comparative analysis of the blastocyst-derived H3K27me3 profile performed using publicly available data from adult muscle, fat, and liver tissues revealed that (1) blastocyst-specific modifications against somatic tissues were enriched in immune function-related genes, (2) somatic modifications "sieved" by blastocyst modifications were enriched in biological processes in tissue-specific trends, (3) the modifications common in blastocyst and each somatic tissue were largely overlapped and enriched in developmentally important genes, including homeobox and imprinted genes. The results of this study produced a genome-wide H3K27me3 profile of bovine blastocysts and revealed its common and typical features in relation to the profiles of adult somatic tissues.

Data from 26 Japanese Black cows were collected to clarify the effects of supplemental β-carotene on colostral immunoglobulin (Ig) and plasma β-carotene and Ig in the cows. Cows were assigned to control or β-carotene groups from 21 days before the expected calving date to 60 days after parturition. Supplemental β-carotene was provided at 500 mg/day in the β-carotene group. Supplemental β-carotene drastically increased plasma β-carotene concentrations in the cows from parturition to 60 days after parturition, and plasma β-carotene concentrations in the control and β-carotene groups at parturition were 202 and 452 μg/dl, respectively. Supplemental β-carotene had no effects on plasma IgG1 , IgA or IgM concentrations at parturition. Supplemental β-carotene increased colostral IgG1 concentrations in the cows, but colostral β-carotene, IgA and IgM concentrations were not affected by supplemental β-carotene. These results indicate that supplemental β-carotene is effective to enhance colostral IgG1 concentrations and plasma β-carotene concentrations in Japanese Black cows.

PURPOSE Hypertrophic cardiomyopathy (HCM) impairs left ventricular (LV) diastolic function leading to left atrial (LA) dilatation. Because Doppler echocardiography cannot accurately assess LV diastolic function in hearts with heterogeneous hypertrophy, assessment of LA function might be useful for risk stratification of patients with HCM. This study aimed to elucidate the impact of LA function on outcome in patients with patients. METHODS Seventy-six patients with HCM who underwent echocardiographic and cardiac magnetic resonance imaging were retrospectively enrolled. Twenty-six control subjects were also included. Using speckle tracking echocardiography, LA function was divided into active and passive strain indices based on the timing of the second positive peak of LA strain rate that occurred during LV systole. RESULTS Left atrial strain indices of active and passive function were significantly impaired concomitantly with increased LA volume index in HCM patients compared with controls. During follow-up (2.6 ± 1.7 years), 14 patients with HCM developed cardiac events (heart failure hospitalization or atrial fibrillation). The association of LA active strain with cardiac events was independent of and incremental to clinical and echocardiographic parameters (age, gender, E/e', LV global longitudinal strain, and LA volume index) in sequential models. Cardiac events were more frequent in HCM patients with LA active strain

Aim This study investigated the relationship between the initial diuretic response to tolvaptan and clinical predictors for tolvaptan responders in patients with acute decompensated heart failure (ADHF). Methods and results Patients (153) with ADHF (clinical scenario 2 or 3 with signs of fluid retention) who were administered tolvaptan were enrolled. Tolvaptan (15 or 7.5 mg) was administered for at least 7 days to those patients in whom fluid retention was observed even after standard treatment. The maximum urine volume immediately after tolvaptan administration showed good correlations with the ejection fraction and estimated glomerular filtration rate that were independent predictors of the urine volume (UV) responders (≥1500 mL increase in urine volume). The diuretic response (in terms of maximum diuresis) diminished with advancing chronic kidney disease (CKD) stage and concomitant deterioration of the renal function. Furthermore, advanced CKD was a significant negative predictor for the body weight (BW) responders (2.0% decrease in the body weight within 1 week after starting tolvaptan). As compared with non-CKD, the presence of advanced CKD predicts poor diuretic response for both UV and BW responders. Conclusions The diuretic response following tolvaptan administration gradually diminished with progressive deterioration of the CKD stage. Worsening renal function was not observed. Tolvaptan is effective in treating CS2 or CS3 ADHF patients who present fluid retention and congestion, suggesting its potential efficacy for fluid management in the ADHF patients with CKD without worsening the renal function.

Data from 18 β-carotene-deficient Japanese Black cows were collected to clarify the effects of feeding β-carotene-enriched dry carrots on β-carotene status and colostral immunoglobulin (Ig) in cows. Cows were assigned to control or carrot groups from 3 weeks before the expected calving date to parturition, and supplemental β-carotene from dry carrots was 138 mg/day in the carrot group. Plasma β-carotene concentrations in the control and carrot groups at parturition were 95 and 120 μg/dL, and feeding dry carrots slightly improved plasma β-carotene at parturition. Feeding dry carrots increased colostral IgA concentrations in cows and tended to increase colostral IgG1 , but colostral IgM, IgG2 , β-carotene and vitamin A were not affected by the treatment. Feeding dry carrots had no effects on plasma IgG1 , IgA and IgM concentrations in cows, but plasma IgG1 concentrations decreased rapidly from 3 weeks before the expected calving date to parturition. These results indicate that feeding β-carotene-enriched dry carrots is effective to enhance colostral IgA and IgG1 concentrations in β-carotene-deficient cows.

This study was conducted to clarify the relationships among immunoglobulin (Ig)M, IgG, IgA, β-carotene, vitamin A and α-tocopherol contents in colostrum of 24 Japanese Black multiparous cows in order to evaluate the role of IgM on colostral IgG and IgA production. Compared with colostral IgG, colostral IgM and IgA were very low but varied widely. There was positive correlation between colostral IgM and IgG, but colostral IgM was not related with colostral IgA. There was no relationship between colostral IgM and age of cows, although colostral IgG was increased with aging. There were positive correlations among colostral β-carotene, vitamin A and α-tocopherol and these vitamins were positively correlated with colostral IgM and IgG. These results indicate that fat-soluble vitamins may affect colostral IgG and IgM in cows and colostral IgG increases with the increase of colostral IgM.

Data from 19 Japanese Black multiparous cows were collected to clarify the relationships among immunoglobulin (Ig) G, IgA, β-carotene, vitamin A and α-tocopherol contents in colostrum of cows in order to evaluate the role of fat-soluble vitamins on colostral IgG and IgA production. Mean colostral IgG was 141 mg/mL, ranging from 65 to 208 mg/mL, whereas mean colostral IgA was 8.7 mg/mL, ranging from 1.0 to 34.6 mg/mL. Colostral IgG increased with aging in multiparous cows. There were positive correlations between colostral IgG and colostral vitamin A or colostral α-tocopherol in cows, and the higher adjusted R(2) was obtained in the prediction model of colostral IgG from age and colostral vitamin A. Colostral vitamin A was positively correlated with colostral β-carotene or colostral α-tocopherol in cows, but there were no relationships between colostral IgA and colostral IgG or colostral fat-soluble vitamins. These results indicate that fat-soluble vitamin contents in colostrum of cows may change in similar patterns and high colostral vitamin A is related with high colostral IgG.

Midkine (MK) was originally characterized as a member of a distinct family of neurotrophic factors functioning in the CNS. However, it was later discovered that MK is abundantly expressed in ovarian follicles. Since then, the physiological roles of this molecule in the ovary have been steadily investigated. During the in vitro maturation (IVM) of oocytes MK was shown to promote the cytoplasmic maturation of oocytes, as indicated by post-fertilization development. This effect of MK could be mediated via its pro-survival (anti-apoptotic) effects on the cumulus-granulosa cells that surround oocytes. The oocyte competence-promoting effects of MK are discussed in the context of the recently discovered involvement of MK in the full maturation of ovarian follicles. MK was at the frontline of a new paradigm for neurotrophic factors as oocytetrophic factors. MK may promote the developmental competence of oocytes via common signalling molecules with the other neurotrophic factor(s). Alternatively or concomitantly, MK may also interact with various transmembrane molecules on cumulus-granulosa cells, which are important for ovarian follicle growth, dominance and differentiation, and act as a unique pro-survival factor in ovarian follicles, such that MK promotes oocyte competence. MK, along with other ovarian neurotrophic factors, may contribute to the optimization of the IVM system. Linked Articles This article is part of a themed section on Midkine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-4

The present study was conducted to clarify the effects of astaxanthin-enriched yeast on the concentration of immunoglobulin A (IgA), the numbers of IgA antibody-secreting cells (ASC) and the messenger RNA (mRNA) expression of IgA C-region in the jejunum and ileum of weanling mice. Weanling mice were fed rodent feed or astaxanthin-enriched yeast-supplemented rodent feed for 7, 14 or 21 days. Supplemental astaxanthin-enriched yeast increased the numbers of IgA ASC in the jejunum and ileum after 7, 14 and 21 days of treatment. Supplemental astaxanthin-enriched yeast increased IgA concentrations in the jejunum after 21 days of treatment, but IgA concentrations in the ileum were not affected by the treatment. The mRNA expressions of IgA C-region in the jejunum after 14 and 21 days of treatment and the ileum after 14 days of treatment were enhanced by supplementation of astaxanthin-enriched yeast. These results indicate that supplementation of astaxanthin-enriched yeast is effective to enhance the numbers of IgA ASC in the jejunum and ileum and IgA concentrations in the ileum of weanling mice.

Thirty-one ICR pregnant mice were assigned to a control or a potassium chloride (KCl) diet group to clarify the effects of KCl supplementation on water intake, bodyweight gains and serum components in pregnant and lactating mice, and 5% KCl was supplemented in KCl diets from 6.5 days post coitus to 1 or 14 days after parturition. Feed intake was not affected by treatment, but supplemental KCl decreased bodyweight gains of lactating mice and their neonatal mice. Water intake and urine volume of KCl supplemented mice were significantly higher than those of control mice during pregnancy and supplemental KCl decreased serum urea N in pregnant mice. Supplemental KCl increased water intake drastically in lactating mice immediately after parturition and increased serum K at 14 days after parturition. Histological alteration using hematoxylin-eosin was not found in the kidney of each mouse at 1 or 14 days after parturition. These results indicate that high KCl supplementation accelerates water intake in lactating mice and prevents bodyweight gains of maternal and neonatal mice during lactation.

Mortality and morbidity of neonates continue to be major problems in humans and animals, and immunoblogulin A (IgA) provides protection against microbial antigens at mucosal surfaces. The present study was conducted to clarify the effects of coumestrol administration to maternal mice during pregnancy and lactation on IgA antibody-secreting cells (ASC) in mammary glands in lactating mice. From 6.5 to 16.5 days post coitus and 1 to 13 days post partum (dpp), maternal mice were administered coumestrol at 200 μg/kg body weight/day. Coumestrol administration increased the number of IgA ASC and the messenger RNA expression of IgA C-region and vascular cell adhesion molecule-1 in mammary glands of maternal mice at 14 dpp, but coumestrol administration had no effect on the number of IgA ASC in the ileum. Coumestrol administration increased serum IgA concentration in maternal mice at 14 dpp, but IgA concentrations in serum, stomach contents, intestine and feces of neonatal mice were not affected by treatment. These results imply that coumestrol administration to maternal mice during pregnancy and lactation is effective in increasing the numbers of IgA ASC in mammary glands during lactation owing to the activated messenger RNA expressions of IgA C-region and vascular cell adhesion molecule-1 in mammary gland.

The development of mammalian pre-implantation embryos is inhibited by heat stress, and the inhibitory effect is associated with excess reactive oxygen species (ROS). Folate is a nutrient with various physiological functions including antioxidative effects. We first investigated the transcript expression for 10 enzymes in the cycle of folate metabolism (folate-methionine cycle) in mouse embryos at the 1-cell, 2-cell, 4- to 8-cell, morula and blastocyst stages using reverse transcription-polymerase chain reaction. All of the transcripts were consistently expressed, except for Mat1a, which was not detected from the 4- to 8-cell stage onward. Next, the effects of folic acid (the synthetic form of folate) on the development and ROS levels of heat-stressed embryos were investigated. One-cell mouse embryos were cultured with or without 1000 ng/ml folic acid basically at 38°C, and in the heat-stressed groups, embryos were exposed to 39.5°C/10 h/day on the first two days of culture. The heat stress significantly (p < 0.05) decreased blastocyst development and cell number and increased ROS levels compared to those in the group not subjected to heat stress; however, among the heat-stressed groups, blastocyst development and cell number were increased and the ROS level was decreased by the addition of folic acid. These results indicate that the mRNA of folate-methionine cycle enzymes are expressed in mouse pre-implantation embryos, suggesting they can independently utilize folate, and the inhibitory effects of heat stress on the development of mouse pre-implantation embryos are ameliorated by folic acid. The ameliorating effects of folic acid may be partly due to its antioxidative property.

The present study was conducted to clarify the effects of coumestrol administration to maternal mice during pregnancy and lactation on serum Ca and Ca metabolism in their neonatal mice. From 6.5 to 16.5 days post coitus and from 3 to 10 days after parturition, maternal mice were administered at 200 µg/kg body weight/day of coumestrol. Coumestrol administration did not affect weight gains, serum Ca and the expression of vitamin D receptor (VDR) protein in the kidney of neonatal mice, but weight gains of maternal mice were decreased by coumestrol administration. Coumestrol administration increased the messenger RNA (mRNA) expressions of epithelial Ca channels 1 (ECaC1) and VDR in the kidney of neonatal mice, and also increased the mRNA expressions of ECaC2 in the kidney and small intestine of male neonatal mice. The mRNA expressions of ECaC1, ECaC2, calbindin-D(9k) (CaBP-9k) and estrogen receptor (ER)α in the kidney and VDR in the small intestine of male neonatal mice were higher than those of female mice. Thus, coumestrol administration to maternal mice during pregnancy and lactation may affect renal Ca metabolism in neonatal mice, especially male neonatal mice via maternal milk.

Bisphenol A (BPA) is a xenoestrogen commonly used in food storage plastics. The present study was conducted to clarify the effects of BPA administration to pregnant mice on serum calcium (Ca) and Ca metabolism of the gut and kidney. From 6.5 to 16.5 days post coitus (dpc), pregnant mice were administered at 2 mg or 20 mg/kg body weight/day of BPA. Serum Ca was decreased in mice treated with 20 mg BPA at 17.5 dpc, but no remarkable differences were detected in the alkaline phosphatase activity and vitamin D receptor protein expression in the duodenum and jejunum. The messenger RNA (mRNA) expressions of calcium binding protein (CaBP-9k) and active vitamin D synthesis enzyme (CYP27B1) in the kidney were increased in mice treated with 20 mg BPA. The mRNA expressions of occludin and junction adherence molecular A (JAM-A) in the duodenum and ileum, which regulate paracellular transport, were increased in mice treated with 20 mg BPA. However, the administration of 2 mg BPA had no effect on serum Ca and mRNA expressions of relative genes in Ca metabolism. These results imply that BPA administration at 20 mg/kg body weight/day during pregnancy decreases serum Ca in pre-delivery mice, which may be partly due to decreased paracellular Ca absorption.

The present study was conducted to clarify the effects of coumestrol administration on Ca metabolism during pregnancy and in lactating mice. From 6.5 to 16.5 days post coitus (dpc), pregnant mice were administered coumestrol at 200 µg/kg body weight/day. The duodenum, jejunum and blood samples were obtained at 17.5 dpc or 10 days after parturition (dap). Coumestrol administration decreased alkaline phosphatase (ALP) activity and mRNA expression of IAP and estrogen responsive genes, c-fos and vascular endothelial growth factor (VEGF), in the duodenum and jejunum of pre-delivery mice. In lactating mice, the ALP activity and mRNA expression of IAP were not changed, although coumestrol administration decreased mRNA expression of c-fos in the duodeum and VEGF in the jejunum. Coumestrol did not affect serum Ca and the expression of vitamin D receptor protein in the duodenum and jejunum. Thus, coumestrol administration during pregnancy may decrease the mRNA expression of IAP and the ALP activity in the intestine of the pre-delivery mice through ERα, but coumestrol had little effect on intestinal ALP activity at 10 days after parturition. Copyright © 2010 John Wiley & Sons, Ltd.

In mammalian blastocysts, the inner cell mass (ICM) differentiates into the epiblast and the hypoblast. In vitro culture of bovine pre-implantation embryos is generally carried out for a limited duration at most up to the blastocyst formation, therefore, it is unclear whether and when the differentiation of ICM occurs in vitro. In bovine species, epiblast formation is characterized by the expression of the intermediate filament protein vimentin. In the present study, the spatial and temporal expression of vimentin in bovine blastocysts maintained under extended in vitro culture (EIVC) was investigated. Bovine blastocysts produced by in vitro maturation, fertilization, and culture were further cultured in vitro in modified synthetic oviduct fluid up to day 12 (fertilization = day 0). Early, expanded, or hatched blastocysts on day 8 and hatched blastocysts on days 9 and 12 were individually subjected to indirect immunofluorescence analysis with an anti-vimentin monoclonal antibody and to semi-quantitative reverse transcription-polymerase chain reaction analysis to examine the vimentin expression. Most of the blastocysts (25/26) did not exhibit any significant immunostaining for the vimentin protein on day 8. On the other hand, the vimentin protein was observed in 59.1% (13/22) and 86.4% (19/22) of the hatched blastocysts on days 9 and 12, respectively. Vimentin was detected as filaments localized within a portion of the ICM, and its expression levels varied among the embryos. Vimentin transcript could not be detected in 50% (3/6) of the blastocysts on day 8, whereas it was detected in all the blastocysts on days 9 and 12. Examination of the day 8 blastocysts revealed that compared with the slow developers, the fast developers (blastocysts which had already expanded by 168 h post-insemination) had significantly higher levels of vimentin transcripts. These results indicate that the ICM differentiates dynamically in bovine blastocysts maintained under EIVC, as reflected by the expression of vimentin and that the higher vimentin expression may reflect the higher developmental competence of embryos.

Contents Early bovine embryos are vulnerable to heat stress during the first few days after fertilization. The inhibitory effect of heat stress on embryonic development is known to be associated with oxidative stress, which can be attenuated by antioxidants. In the present study, we focused on the use of astaxanthin as an antioxidant and examined the effects of astaxanthin-containing oil (Ax) on post-fertilization development of bovine embryos subjected to heat stress in vitro and the expression of stress-related genes. Bovine 1-cell embryos were in vitro produced by in vitro maturation and fertilization (IVF) of oocytes recovered from abattoir-derived ovaries. At 20 h post-insemination (hpi, 0 h = the start of IVF), the embryos were introduced in modified synthetic oviduct fluid supplemented with 25 ppm of Ax (concentration of astaxanthin was 0.25 ppm) or vehicle (dimethyl sulfoxide) up to 72 hpi. The embryos were basically cultured at 38.5°C, and in the heat stress group, embryos were exposed twice to 40.5°C for 10 h (at 20–30 and 44–54 hpi). Under the condition without the Ax treatment, the cleavage rate, rate of development to the 5–8 cell stage, blastocyst yield from cultured embryos and that from cleaved embryos were lower in the heat stress group than in the group not subjected to heat stress (p

In the present study, we cloned bovine midkine (bMK) cDNA by RT- and RACE-PCR, and determined its nucleotide sequence. The nucleotide and deduced amino acid sequences of bMK showed a high degree of homology to those of mouse and human MK. Moreover, a large amount of recombinant bMK (rbMK) was produced using a baculovirus expression system and the protein was purified to homogeneity by heparin affinity chromatography. To examine whether treatment with rbMK during in vitro maturation (IVM) of bovine cumulus-enclosed oocytes affects their nuclear maturation and postfertilization development to the blastocyst stage, bovine cumulus-enclosed oocytes obtained from slaughterhouse-derived ovaries were cultured for 24 hr in IVM medium without (control) or with various concentrations (50-400 ng/ml) of rbMK, followed by in vitro fertilization (IVF) and culture. Although rbMK treatment during IVM did not affect the rates of nuclear maturation and postfertilization cleavage of oocytes, rbMK at all experimental concentrations significantly (P < 0.05) increased the blastocyst yields per tested and per cleaved oocyte compared to the control. Next, it was examined whether heparitinase (HTN) treatment of cumulus-enclosed oocytes would affect the enhancing activity of rbMK during IVM on the developmental competence of oocyte after IVF. The enhancing activity of rbMK was completely suppressed by HTN (1.0 mU/ml) treatment. These results indicate that the presence of rbMK during IVM of bovine cumulus-enclosed oocytes can enhance their developmental competence to the blastocyst stage after IVF and suggest that heparan sulfate chains on the cell surface of cumulus cells and/or oocytes are required for bMK to exert its effect.

In multiple ovulation and embryo transfer (MOET) programmes in cattle, a considerable number of morphologically poor-quality embryos continue to be produced; this is one of the limiting factors of the technique. Apoptosis has often been implicated in developmental arrest and fragmentation; these are regarded as poor traits of embryonic quality in mammalian pre-implantation embryos. In the present study, apoptosis was assessed in morphologically poor-quality embryos in comparison with good-quality embryos that were recovered from a MOET programme. Retarded embryos (two to 16 cell stage), morulae with severe fragmentation and morphologically good-quality morulae recovered from superstimulated cows at day 7 post-insemination were subjected to TdT-mediated dUTP nick-end labelling (TUNEL) and Hoechst staining. Cell nuclei that showed both TUNEL staining and apoptotic morphology were considered to be apoptotic. Apoptotic index (AI) was calculated as the percentage of apoptotic cells per embryo. Fifteen of 17 retarded embryos and 10 of 15 morphologically poor-quality morulae did not show signs of apoptosis. The mean AIs in the morphologically poor-quality embryos (two to 16 cell stage, 2.2%; poor morulae, 1.3%) were as low as that in the good-quality embryos (2.9%). These results suggest that another mode of developmental arrest and/or fragmentation that is independent of apoptosis occurs in morphologically poor-quality embryos recovered from MOET programmes.