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Coordinated proliferation between clonally distinct cells via inter-cell-layer signaling largely determines the size and shape of plant organs. Nonetheless, the signaling mechanism underlying this coordination in leaves remains elusive because of a lack of understanding of the signaling molecule (or molecules) involved. ANGUSTIFOLIA3 (AN3, also called GRF-INTERACTING FACTOR1) encodes a putative transcriptional coactivator with homology to human synovial sarcoma translocation protein. AN3 transcripts accumulate in mesophyll cells but are not detectable in leaf epidermal cells. However, we found here that in addition to mesophyll cells, epidermal cells of an3 leaves show defective proliferation. This spatial difference between the accumulation pattern of AN3 transcripts and an3 leaf phenotype is explained by AN3 protein movement across cell layers. AN3 moves into epidermal cells after being synthesized within mesophyll cells and helps control epidermal cell proliferation. Interference with AN3 movement results in abnormal leaf size and shape, indicating that AN3 signaling is indispensable for normal leaf development. AN3 movement does not require type II chaperonin activity, which is needed for movement of some mobile proteins. Taking these findings together, we present a novel model emphasizing the role of mesophyll cells as a signaling source coordinating proliferation between clonally independent leaf cells., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Primary retroperitoneal transitional cell carcinomas (TCCs) are extremely rare neoplasms for which prognosis is very poor. We present a case that underwent complete remission after radiotherapy and concurrent oral chemotherapy. A 68-year-old woman presented with acute onset of bloody stool. Urgent colonoscopy only detected haemorrhoids. Subsequent abdominal ultrasonography revealed a mass of 7 cm in maximal diameter in the left iliac fossa. Laparotomy disclosed a retroperitoneal mass that could not be dissected and therefore only incision biopsy was performed. After a final diagnosis of primary retroperitoneal TCC, chemotherapy with tegafur-uracil (UFT) was initiated but was not effective. Subsequently, radiotherapy was initiated concurrently with UFT at a total dose of 50 Gy in 25 fractions. At 20 months after radiotherapy, the tumour seemed to have completely remitted. At the last follow-up, ten years from radiotherapy, computed tomography revealed no recurrence. We identified only three single case reports regarding primary retroperitoneal TCC over the last five decades. All patients died from the tumour 8-24 months after diagnosis or treatment. Based on the success of our case, radiotherapy with concurrent oral chemotherapy should be considered as an option for unresected cases.

Background: Both neuropeptide Y (NPY) and ghrelin can enhance the feeding behavior. The purpose of this study was to determine whether NPY and ghrelin are involved in hyperphagia and obesity induced by lesions of the hypothalamic paraventricular nucleus (PVN)., Methods: Sham-operated control rats and rats subjected to bilateral electrolytic lesions of the PVN were administered NPY (5 μg/rat) by intracerebroventricular infusion or ghrelin (20 μg/kg) by intraperitoneal (i.p.) injection. Control rats were administered the appropriate vehicle by the same route as the drug. We measured the cumulative food intake (FI) for 2 h after infusion of NPY and for 4 h after ghrelin injection., Results: NPY significantly increased the cumulative FI in sham-operated rats. In PVN-lesioned rats, however, the cumulative FI at each time point (15 min, 30 min, 1 h, and 2 h) after NPY infusion was not significantly different from vehicle infusion, showing that NPY lost its orexigenic effect in PVN-lesioned rats. Following ghrelin injection, the cumulative FI was greater in PVN-lesioned rats than sham-operated rats, indicating that PVN lesions enhanced the orexigenic effects of ghrelin., Conclusion: These results suggest that the hyperphagia and obesity induced by PVN lesions may be related to an increased orexigenic action of ghrelin, but not NPY.

Objectives: This study examines the countermeasures taken by restaurants to prevent passive smoking and the impact of smoking prohibition on both the number of customers and sales volume in restaurants., Methods: An interview-based survey was administered to 8,558 restaurant managers in Aichi prefecture. The survey questions concerned the countermeasures taken against passive smoking within each restaurant and the effect of the prohibition of smoking on both the number of customers and sales volume between November 1, 2009, and February 26, 2010., Results: Seven thousand and eighty managers responded to the survey (response rate 83%). The proportion of managers of restaurants with a complete smoking ban was 16.4%, of restaurants with a smoking and non-smoking room or section was 20.2%, and of restaurants where no countermeasures were taken was 63.4%. The results showed that among the restaurants with a complete smoking ban, the number of customers and sales volume increased in 1.5%, decreased in 3.9%, and did not change in 95%. Differences in countermeasures were seen according to the type of restaurant. A high proportion of restaurants with a complete ban were curry shops and fast food restaurants, while few such restaurants were bars or Izakaya (Japanese style bars) and Yakiniku (Korean style BBQ) restaurants., Conclusion: The results of this large-scale survey in Aichi prefecture suggest that the economic impact of smoking prohibition in restaurants, in terms of the number of customers and sales volume, is small.

The study of the pearl oyster Pinctada fucata is key to increasing our understanding of the molecular mechanisms involved in pearl biosynthesis and biology of bivalve molluscs. We sequenced ~1150-Mb genome at ~40-fold coverage using the Roche 454 GS-FLX and Illumina GAIIx sequencers. The sequences were assembled into contigs with N50 = 1.6 kb (total contig assembly reached to 1024 Mb) and scaffolds with N50 = 14.5 kb. The pearl oyster genome is AT-rich, with a GC content of 34%. DNA transposons, retrotransposons, and tandem repeat elements occupied 0.4, 1.5, and 7.9% of the genome, respectively (a total of 9.8%). Version 1.0 of the P. fucata draft genome contains 23 257 complete gene models, 70% of which are supported by the corresponding expressed sequence tags. The genes include those reported to have an association with bio-mineralization. Genes encoding transcription factors and signal transduction molecules are present in numbers comparable with genomes of other metazoans. Genome-wide molecular phylogeny suggests that the lophotrochozoan represents a distinct clade from ecdysozoans. Our draft genome of the pearl oyster thus provides a platform for the identification of selection markers and genes for calcification, knowledge of which will be important in the pearl industry.

Fungal plant pathogens secrete effector molecules to establish disease on their hosts, and plants in turn use immune receptors to try to intercept these effectors. The tomato immune receptor Ve1 governs resistance to race 1 strains of the soil-borne vascular wilt fungi Verticillium dahliae and Verticillium albo-atrum, but the corresponding Verticillium effector remained unknown thus far. By high-throughput population genome sequencing, a single 50-Kb sequence stretch was identified that only occurs in race 1 strains, and subsequent transcriptome sequencing of Verticillium-infected Nicotiana benthamiana plants revealed only a single highly expressed ORF in this region, designated Ave1 (for Avirulence on Ve1 tomato). Functional analyses confirmed that Ave1 activates Ve1-mediated resistance and demonstrated that Ave1 markedly contributes to fungal virulence, not only on tomato but also on Arabidopsis. Interestingly, Ave1 is homologous to a widespread family of plant natriuretic peptides. Besides plants, homologous proteins were only found in the bacterial plant pathogen Xanthomonas axonopodis and the plant pathogenic fungi Colletotrichum higginsianum, Cercospora beticola, and Fusarium oxysporum f. sp. lycopersici. The distribution of Ave1 homologs, coincident with the presence of Ave1 within a flexible genomic region, strongly suggests that Verticillium acquired Ave1 from plants through horizontal gene transfer. Remarkably, by transient expression we show that also the Ave1 homologs from F. oxysporum and C. beticola can activate Ve1-mediated resistance. In line with this observation, Ve1 was found to mediate resistance toward F. oxysporum in tomato, showing that this immune receptor is involved in resistance against multiple fungal pathogens.

The gobiid fish Trimma okinawae changes its sex bi-directionally according to its social status. Morphological changes in the urinogenital papillae (UGP) of this fish have been reported during sex change. However, there have been no detailed observations of such changes. Here, we histologically examined the UGP structure of male- and female-phase fish. UGPs of fish in female and male phase contained both oviducts and sperm ducts. Both ducts were coalesced into one duct within the posterior region of the UGP. Female-phase fish had many longitudinal folds in the hypertrophied tunica mucosa of the oviduct, which was found to be responsible for the transport of eggs and the removal of follicular cells from the oocyte. In contrast, male-phase fish had an immature oviduct and a mature sperm duct in the UGP. In the male-phase fish, the co-existence of spermatozoa and fibrillar secretions was observed in the sperm duct during spermiation.

The pea pathogen Fusarium oxysporum f. sp. pisi is able to detoxify pisatin produced as a defense response by pea, and the gene encoding this detoxification mechanism, FoPDA1, was 82% identical to the cytochrome P450 pisatin demethylase PDA1 gene in Nectria haematococca. A survey of F. oxysporum f. sp. pisi isolates demonstrated that, as in N. haematococca, the PDA gene of F. oxysporum f. sp. pisi is generally located on a small chromosome. In N. haematococca, PDA1 is in a cluster of pea pathogenicity (PEP) genes. Homologs of these PEP genes also were found in the F. oxysporum f. sp. pisi isolates, and PEP1 and PEP5 were sometimes located on the same small chromosomes as the FoPDA1 homologs. Transforming FoPDA1 into a pda(?) F. oxysporum f. sp. lini isolate conferred pda activity and promoted pathogenicity on pea to some transformants. Different hybridization patterns of FoPDA1 were found in F. oxysporum f. sp. pisi but these did not correlate with the races of the fungus, suggesting that races within this forma specialis arose independently of FoPDA1. FoPDA1 also was present in the formae speciales lini, glycines, and dianthi of F. oxysporum but they had mutations resulting in nonfunctional proteins. However, an active FoPDA1 was present in F. oxysporum f. sp. phaseoli and it was virulent on pea. Despite their evolutionary distance, the amino acid sequences of FoPDA1 of F. oxysporum f. sp. pisi and F. oxysporum f. sp. phaseoli revealed only six amino acid differences, consistent with a horizontal gene transfer event accounting for the origin of these genes.

Leaves are the most important, fundamental units of organogenesis in plants. Although the basic form of a leaf is clearly divided into the leaf blade and leaf petiole, no study has yet revealed how these are differentiated from a leaf primordium. We analyzed the spatiotemporal pattern of mitotic activity in leaf primordia of Arabidopsis (Arabidopsis thaliana) in detail using molecular markers in combination with clonal analysis. We found that the proliferative zone is established after a short interval following the occurrence of a rod-shaped early leaf primordium; it is separated spatially from the shoot apical meristem and seen at the junction region between the leaf blade and leaf petiole and produces both leaf-blade and leaf-petiole cells. This proliferative region in leaf primordia is marked by activity of the ANGUSTIFOLIA3 (AN3) promoter as a whole and seems to be differentiated into several spatial compartments: activities of the CYCLIN D4;2 promoter and SPATULA enhancer mark parts of it specifically. Detailed analyses of the an3 and blade-on-petiole mutations further support the idea that organogenesis of the leaf blade and leaf petiole is critically dependent on the correct spatial regulation of the proliferative region of leaf primordia. Thus, the proliferative zone of leaf primordia is spatially differentiated and supplies both the leaf-blade and leaf-petiole cells.

Knowledge of pathogen biology and genetic diversity is a cornerstone of effective disease management, and accurate identification of the pathogen is a foundation of pathogen biology. Species names provide an ideal framework for storage and retrieval of relevant information, a system that is contingent on a clear understanding of species boundaries and consistent species identification. Verticillium, a genus of ascomycete fungi, contains important plant pathogens whose species boundaries have been ill defined. Using phylogenetic analyses, morphological investigations and comparisons to herbarium material and the literature, we established a taxonomic framework for Verticillium comprising ten species, five of which are new to science. We used a collection of 74 isolates representing much of the diversity of Verticillium, and phylogenetic analyses based on the ribosomal internal transcribed spacer region (ITS), partial sequences of the protein coding genes actin (ACT), elongation factor 1-alpha (EF), glyceraldehyde-3-phosphate dehydrogenase (GPD) and tryptophan synthase (TS). Combined analyses of the ACT, EF, GPD and TS datasets recognized two major groups within Verticillium, Clade Flavexudans and Clade Flavnonexudans, reflecting the respective production and absence of yellow hyphal pigments. Clade Flavexudans comprised V. albo-atrum and V. tricorpus as well as the new species V. zaregamsianum, V. isaacii and V. klebahnii, of which the latter two were morphologically indistinguishable from V. tricorpus but may differ in pathogenicity. Clade Flavnonexudans comprised V. nubilum, V. dahliae and V. longisporum, as well as the two new species V. alfalfae and V. nonalfalfae, which resembled the distantly related V. albo-atrum in morphology. Apart from the diploid hybrid V. longisporum, each of the ten species corresponded to a single clade in the phylogenetic tree comprising just one ex-type strain, thereby establishing a direct link to a name tied to a herbarium specimen. A morphology-based key is provided for identification to species or species groups.

In the teleost fish, medaka (Oryzias latipes), the sex is genetically determined at the time of fertilization. The males are heterogametic with XY chromosome composition, while females are of XX chromosome composition. The male sexual differentiation is initiated in XY embryos of medaka by the sex-determining gene Dmy. In this study, we have cloned the gonadal soma derived factor (Gsdf) from medaka and characterized its expression pattern during the initiation of morphological testicular differentiation. By real-time PCR, an XY-specific up-regulation was detected in the expression levels of Gsdf in the whole embryos of medaka at 6days post fertilization (dpf), coincident with the initiation of testicular differentiation in the XY gonads. Whole mount and section in situ hybridizations reaffirmed that Gsdf was expressed exclusively in primordial gonads of only the genetic males at 6dpf. Conversely, the expression of Gsdf was found to be very weak in the XX gonads during embryogenesis. Importantly, Gsdf and Dmy were found to be co-localized in the same somatic cells in the XY gonads. When the XY embryos were treated with estradiol-17beta, in order to reverse their phenotypic sex, a decline was observed in the expression of Gsdf in these embryos by real-time PCR., (Copyright 2010 Elsevier B.V. All rights reserved.)

Heart diseases are the most common causes of morbidity and death in humans. Using cardiac-specific RNAi-silencing in Drosophila, we knocked down 7061 evolutionarily conserved genes under conditions of stress. We present a first global roadmap of pathways potentially playing conserved roles in the cardiovascular system. One critical pathway identified was the CCR4-Not complex implicated in transcriptional and posttranscriptional regulatory mechanisms. Silencing of CCR4-Not components in adult Drosophila resulted in myofibrillar disarray and dilated cardiomyopathy. Heterozygous not3 knockout mice showed spontaneous impairment of cardiac contractility and increased susceptibility to heart failure. These heart defects were reversed via inhibition of HDACs, suggesting a mechanistic link to epigenetic chromatin remodeling. In humans, we show that a common NOT3 SNP correlates with altered cardiac QT intervals, a known cause of potentially lethal ventricular tachyarrhythmias. Thus, our functional genome-wide screen in Drosophila can identify candidates that directly translate into conserved mammalian genes involved in heart function., (Copyright 2010 Elsevier Inc. All rights reserved.)

This study was carried out to investigate whether the personal advocacy of influenza vaccination by community pharmacists to people aged 65 years and above affected the vaccination rate and number of influenza patients. A cluster randomized controlled trial was conducted with the cooperation of 84 community pharmacies in the wards of Suginami and Nerima, Tokyo. Participants were aged 65 years and above living in Suginami and Nerima wards, Tokyo, receiving dispensing services in their community pharmacies. The intervention was that pharmacists in the intervention pharmacy group provided information on the risk of influenza and benefits of influenza vaccination. Main outcome measures were the self-reported influenza vaccination rate in January 2004, and the number of participants with influenza, as confirmed by inspection of their prescriptions from January to May 2004. The vaccination rate in the intervention pharmacy group (81.6%) was significantly higher than that in the control pharmacy group (64.9%). The number of participants with influenza among the intervention group (2/881) was significantly lower than that among the control group (11/895). The personal advocacy of influenza vaccination by community pharmacists among people aged 65 years and above increases the vaccination rate and decreases the number of influenza patients.

Obese adipose tissue is markedly infiltrated by macrophages, suggesting that they may participate in the inflammatory pathways that are activated in obese adipose tissue. Evidence has suggested that saturated fatty acids released via adipocyte lipolysis serve as a naturally occurring ligand that stimulates Toll-like receptor (TLR)4 signaling, thereby inducing the inflammatory responses in macrophages in obese adipose tissue. Through a combination of cDNA microarray analyses of saturated fatty acid-stimulated macrophages in vitro and obese adipose tissue in vivo, here we identified activating transcription factor (ATF)3, a member of the ATF/cAMP response element-binding protein family of basic leucine zipper-type transcription factors, as a target gene of saturated fatty acids/TLR4 signaling in macrophages in obese adipose tissue. Importantly, ATF3, when induced by saturated fatty acids, can transcriptionally repress tumor necrosis factor-alpha production in macrophages in vitro. Chromatin immunoprecipitation assay revealed that ATF3 is recruited to the region containing the activator protein-1 site of the endogenous tumor necrosis factor-alpha promoter. Furthermore, transgenic overexpression of ATF3 specifically in macrophages results in the marked attenuation of proinflammatory M1 macrophage activation in the adipose tissue from genetically obese KKA(y) mice fed high-fat diet. This study provides evidence that ATF3, which is induced in obese adipose tissue, acts as a transcriptional repressor of saturated fatty acids/TLR4 signaling, thereby revealing the negative feedback mechanism that attenuates obesity-induced macrophage activation. Our data also suggest that activation of ATF3 in macrophages offers a novel therapeutic strategy to prevent or treat obesity-induced adipose tissue inflammation.

Regulation of cell number and cell size is essential for controlling the shape and size of leaves. Here, we report a novel class of Arabidopsis thaliana mutants, more and smaller cells 1 (msc1)-msc3, which have increased cell number and decreased cell size in leaves. msc1 has a miR156-resistant mutation in the SQUAMOSA PROMOTER BINDING PROTEIN-LIKE 15 (SPL15) gene. msc2 and msc3 are new alleles of paused and squint mutants, respectively. All msc mutants showed accelerated heteroblasty, a phenomenon in which several morphological traits of leaves change along with phase change. Consistent with this finding, in the wild type, leaves at higher nodes (adult leaves) also have increased cell number and reduced cell size compared with those at lower nodes (juvenile leaves). These facts indicate that precocious acquisition of adult leaf characteristics in the msc mutants may cause alterations in the number and size of cells, and that heteroblasty plays an important role in the regulation of cell number and size. In agreement with this suggestion, such heteroblasty-associated changes in cell number and size are severely inhibited by the constitutive overexpression of miR156 and are promoted by the elevated expression of miR156-insensitive forms of SPL genes. By contrast, rdr6, sgs3, zip, arf3 and arf4 mutations, which affect progression of heteroblasty, had little or no effect on number or size of cells. These results suggest that cell number and size are mainly regulated by an SPL-dependent pathway rather than by a tasiR-ARF-dependent pathway.

Sex-changing fish Trimma okinawae can change its sex back and forth from male to female and then to male serially, depending on the social status in the harem. T. okinawae is well equipped to respond to its social status by possessing both ovarian and testicular tissues even though only one gonad remains active at one time. Here we investigated the involvement of gonadotropins in sex change by determining the changes in gonadotropin receptor (GtHR) gene expression during the onset of sex change from female to male and male to female. The expression of the GtHR was found to be confined to the active gonad of the corresponding sexual phase. During the sex-change from female to male, initially the ovary had high levels of FSHR and LHR, which eventually went up in the testicular tissue if the fish was bigger. Changing of the gonads started with switching of GtHR expression discernible within 8-12 h of the visual cue. Further in vitro culture of the transitional gonads with a supply of exogenous gonadotropin (human chorionic gonadotropin) revealed that the to-be-active gonad acquired the ability to produce the corresponding sex hormone within 1 d of the activation of GtHR. Conversely, the to-be-regressed gonad did not respond to the exogenous gonadotropin. Our findings show that the gonads of successive sex-changing fish possess the intrinsic mechanism to respond to the social cue differentially. Additionally, this location switching of GtHR expression also could substantiate the importance of the hypothalamo-pituitary-gonadotropic axis.

A serious disease of the ascidian Halocynthia roretzi has been spread extensively among Korean aquaculture sites. To reveal the cause of the disease and establish a monitoring system for it, we constructed a cDNA microarray spotted with 2,688 cDNAs derived from H. roretzi hemocyte cDNA libraries to detect genes differentially expressed in hemocytes between diseased and non-diseased ascidians. We detected 21 genes showing increased expression and 16 genes showing decreased expression in hemocytes from diseased ascidians compared with those from non-diseased ascidians. RT-PCR analyses confirmed that the expression levels of genes encoding astacin, lysozyme, ribosomal protein PO, and ubiquitin-ribosomal protein L40e fusion protein were increased in hemocytes from diseased ascidians, while those of genes encoding HSP40, HSP70, fibronectin, carboxypeptidase and lactate dehydrogenase were decreased. These genes were expressed not only in hemocytes but also in various other tissues in ascidians. Furthermore, the expression of glutathione-S transferase omega, which is known to be up-regulated in H. roretzi hemocytes during inflammatory responses, was strongly increased in hemocytes from diseased ascidians. These gene expression profiles suggest that immune and inflammatory reactions occur in the hemocytes of diseased ascidians. These genes will be good markers for detecting and monitoring this disease of ascidians in Korean aquaculture sites.

Bilateral lesions of the hypothalamic paraventricular nuclei (PVN) induce hyperphagia and obesity, and ghrelin stimulates appetite in rodents and humans. Conversely, corticotrophin-releasing hormone (CRH) and melanotan-II (MT-II, a synthetic structural homologue of alpha-melanocyte-stimulating hormone, alphaMSH) inhibit feeding behavior. The purpose of the present study was to determine whether these peptides are involved in the hyperphagia and obesity induced by PVN lesions. After bilateral electrolytic lesions of the PVN, rats were given ghrelin intraperitoneally (i. p.), or intracerebroventricular (i. c. v.) infusion of CRH or MT-II. We measured the cumulative food intake (FI) for 4 h after ghrelin injection in rats fed AD LIB, and the changes in FI at 15 min, 30 min, 1 h, and 2 h after infusion of CRH and MT-II in rats fasted for 24 h. Ghrelin significantly increased cumulative FI, with maximal response 3 h and 4 h after injection, and at these times, the FI of PVN-lesioned rats was greater than that of sham-operated rats. CRH significantly decreased FI in all experimental animals, but at 1 h, there was a more powerful inhibitory effect on FI in the PVN-lesioned group than in the sham-operated group. MT-II decreased FI in sham-operated, but not in PVN-lesioned rats. Thus, ghrelin and CRH showed more potent orexigenic and anorectic effects in PVN-lesioned rats, respectively, but MT-II lost its inhibitory action on feeding behavior. These results suggest that the hyperphagia and obesity induced by PVN lesions may be related to an increased orexigenic action of ghrelin due to the destruction of endogenous CRH and alphaMSH receptors.

Sjögren's syndrome (SS) is caused by an autoimmune sialodacryoadenitis, and up to 5% of patients with SS develop malignant B cell growth. The IQI mouse is a spontaneous model of primary SS in which B cells are the dominant cellular subpopulation among mononuclear infiltrates in sialitis lesions. Understanding the genetic control of aberrant B cell growth in IQI mice may help elucidate the genetic mechanisms involved in B-lineage hyperplasia leading to malignant transformation in human SS. B cell-dominant infiltration in the submandibular glands of 6-month-old IQI and C57BL/6 (B6) mice and their F1 and F2 progenies was quantified as B-lymphocytic sialitis score, and a genome-wide scan of 179 (IQI x B6) F2 females was performed to identify a quantitative trait locus (QTL) controlling this phenotype. A QTL significantly associated with variance in B-lymphocytic sialitis score was mapped to the D6Mit138 marker (position of 0.68cM) on proximal chromosome 6, with a logarithm of odds score of 4.3 (p = 0.00005). This QTL, named autoimmune sialitis in IQI mice, associated locus 1 (Asq1), colocalized with Islet cell autoantigen 1 (Ica1), which encodes a target protein of the immune processes that define the pathogenesis of primary SS in humans and in the nonobese diabetic mouse model.

Recent whole-genome studies and in-depth expressed sequence tag (EST) analyses have identified most of the developmentally relevant genes in the urochordate, Ciona intestinalis. In this study, we made use of a large-scale oligo-DNA microarray to further investigate and identify genes with specific or correlated expression profiles, and we report global gene expression profiles for about 66% of all the C. intestinalis genes that are expressed during its life cycle. We succeeded in categorizing the data set into 5 large clusters and 49 sub-clusters based on the expression profile of each gene. This revealed the higher order of gene expression profiles during the developmental and aging stages. Furthermore, a combined analysis of microarray data with the EST database revealed the gene groups that were expressed at a specific stage or in a specific organ of the adult. This study provides insights into the complex structure of ascidian gene expression, identifies co-expressed gene groups and marker genes and makes predictions for the biological roles of many uncharacterized genes. This large-scale oligo-DNA microarray for C. intestinalis should facilitate the understanding of global gene expression and gene networks during the development and aging of a basal chordate.

Objective: We recently showed regional differences in the incidence of end-stage renal disease (ESRD) within Japan, which is generally ethnically homogenous, suggesting that factors other than genetic may contribute to the difference. We examined regional differences in the amounts of dietary nutrient intake, especially protein in our search for an explanation., Design and Setting: Annually, the Japanese Society for Dialysis Therapy reports the numbers of patients entering maintenance dialysis in each prefecture of Japan. We used these numbers from 1984 to 2002 to calculate the annual ESRD incidence in each of 12 regions of Japan. The regional differences were analyzed in relation to the amounts of nutrient intake reported annually by National Nutrition Survey in corresponding regions for these 19 years. Each year, approximately 15,000 subjects from 5000 households in randomly selected 300 districts were included to obtain a representative sample of the entire population of Japanese in a manner of age, sex, and body mass matched., Results: There were marked regional differences in the annual ESRD incidence and small regional differences in dietary intake of each nutrient. Multiple regression analysis showed that the annual ESRD incidence was negatively correlated with energy intake (r = -0.65, F = 240, n = 228) and positively correlated with animal protein intake (r = 0.25, F = 30). Across 12 regions in the values averaged for 19 years in each region, however, the incidence of ESRD was negatively correlated only with the amounts of energy intake (r = -0.74, F = 12, n = 12), but not with animal protein (r = 0.07, F = 0.04)., Conclusion: The present study, relating regional differences between ESRD dynamics and the amounts of nutrient intake in a nationwide population of Japan, revealed that the renal protective effects of dietary restriction of protein, suggested by animal models of progressive nephropathies but yet unproved by large-scale clinical trials, remained unestablished even on a macro level of whole Japan through mapping approaches.

Plants fine-tune light responses through interactions between photoreceptors. We have previously reported that the greening of Arabidopsis thaliana roots is regulated synergistically by phytochromes and cryptochromes. In the present study, we investigated the functions of the N- and C-terminal domains of phytochrome B (phyB) in the interactions between phyB and cryptochrome signaling cascades. Transgenic Arabidopsis expressing the phyB N-terminal domain fused to green fluorescent protein (GFP), beta-glucuronidase (GUS) and the nuclear localization signal (NLS) showed intense root greening under blue light, indicating that the C-terminal domain was dispensable for the synergistic interaction in the induction of root greening. However, root greening under red light was substantially reduced in the absence of the C-terminal domain. This effect was opposite to the previous observation that removal of the C-terminal domain enhanced the signaling activity of phyB in the inhibition of hypocotyl elongation. In addition, we found that overexpression of the isolated C-terminal domain of phyB enhanced the blue light response not only for root greening but also for the inhibition of hypocotyl elongation. Analysis of this activity on various photoreceptor mutant backgrounds demonstrated that the isolated C-terminal domain enhanced cryptochrome signaling. In summary, these results demonstrate that different domains of phyB can play various roles which are dependent on light conditions as well as on the specific physiological response.

A statistical survey of 3932 nationwide hemodialysis (hereafter, dialysis) facilities was carried out at the end of 2004, and 3882 facilities (98.73%) responded. The population undergoing dialysis at the end of 2004 was 248 166, an increase of 10 456 patients (4.4%) from that at the end of 2003. The number of dialysis patients per million people was 1943.5. The crude death rate of dialysis patients from the end of 2003 to the end of 2004 was 9.4%. The mean age of patients who underwent dialysis in 2004 was 65.8 years, and that of the total dialysis population was 63.3 years. The percentage distribution of patients who underwent dialysis according to a newly underlying disease showed that 41.3% of patients had diabetic nephropathy and 28.1% had chronic glomerulonephritis. The frequency of calcium carbonate use for dialysis patients was 75.1% and that of sevelamer hydrochloride use was 26.2%. The frequency of sevelamer hydrochloride use does not necessarily have a strong correlation with the dose of calcium carbonate. Patients who received high doses of sevelamer hydrochloride tended to have a low concentration of arterial blood HCO(3-). Approximately 15% of dialysis patients used an intravenous vitamin D preparation, generally maxacalcitol. The longer the patients had been on dialysis, the higher the frequency of use of an intravenous vitamin D preparation. When the concentration of serum intact parathyroid hormone (PTH) was more than 200 pg/mL, the frequency of use of an orally administered vitamin D preparation decreased; but that of intravenous vitamin D preparation increased. The percentage of dialysis patients who received percutaneous ethanol injection therapy (PEIT) was 1.4%. The percentage was more than 50% in the patients who had been on dialysis for more than 10 years. The percentage of patients who received PEIT again was 35.0%. The percentage of patients who had been on hemodialysis for more than 10 years and received PEIT again was more than 50%.

The pond snail Lymnaea stagnalis is capable of learning conditioned taste aversion (CTA) and then consolidating that learning into long-term memory (LTM) that persists for at least 1 month. LTM requires de novo protein synthesis and altered gene activity. Changes in gene activity in Lymnaea that are correlated with, much less causative, memory formation have not yet been identified. As a first step toward rectifying this situation, we constructed a cDNA microarray with mRNAs extracted from the central nervous system (CNS) of Lymnaea. We then, using this microarray assay, identified genes whose activity either increased or decreased following CTA memory consolidation. We also identified genes whose expression levels were altered after inhibition of the cyclic AMP response element-binding protein (CREB) that is hypothesized to be a key transcription factor for CTA memory. We found that the molluscan insulin-related peptide II (MIP II) was up-regulated during CTA-LTM, whereas the gene encoding pedal peptide preprohormone (Pep) was down-regulated by CREB2 RNA interference. We next examined mRNAs of MIP II and Pep using real-time RT-PCR with SYBR Green. The MIP II mRNA level in the CNS of snails exhibiting "good" memory for CTA was confirmed to be significantly higher than that from the CNS of snails exhibiting "poor" memory. In contrast, there was no significant difference in expression levels of the Pep mRNA between "good" and "poor" performers. These data suggest that in Lymnaea MIP II may play a role in the consolidation process that forms LTM following CTA training.

Patients with infective endocarditis (IE) often have renal complications which may include infarcts, abscesses and glomerulonephritis (GN). Furthermore, it is generally accepted that there is an association between IE and anti-neutrophil cytoplasmic antibody (ANCA). Here, we report the case of a 24-year-old man who developed rapidly progressive GN in the course of IE due to infection with alpha-streptococcus. The initial clinical manifestation of the condition was severe sacroiliitis without fever. Sandwich ELISA showed that the patient was positive for PR3-ANCA at low titer, and the classical complement pathway was also activated. Renal biopsy demonstrated several lesions: focal embolic GN, GN with immune deposits and focal and segmental crescentic necrotizing GN. Treatment with antibiotics and steroids led to eradication of the infection, and resolution of the renal disease was accompanied by immediate disappearance of PR3-ANCA and hypocomplementemia. During a 4-year follow-up period, no recurrence was observed. There have only been 7 case reports of GN associated with IE and PR3-ANCA in which the renal pathology has been described, and the current report is the first to document renal pathology in a patient with isolated pulmonic valve IE and PR3-ANCA. Moreover, this report is the first to show a change in renal biopsy findings in response to treatment. A review of the 7 literature cases and that of our patient showed that none involved pauci-immune GN. Hence, further studies are needed to clarify the prevalence of pauci-immune GN in ANCA-positive IE patients.

Background: Nocturnal polyuria has been well known in renal insufficiency. Recently, we found that as renal function deteriorated in chronic kidney disease (CKD), natriuresis was enhanced during the night with nocturnal blood pressure elevation. In the present study, we investigated whether nocturnal polyuria in CKD was due to the inability to concentrate urine, as previously proposed, or based on osmotic diuresis mainly by natriuresis., Methods: In 27 CKD patients, circadian rhythms of urinary sodium, potassium, urea and osmolar excretion rates (U(Na)V, U(K)V, U(urea)V, U(osm)V) as well as of urinary volume (V) and free-water clearance (C(H(2)O)) were estimated during both daytime (6:00 to 21:00) and nighttime (21:00 to 6:00). Then, the night/day ratios of these parameters were analysed in relation to creatinine clearance (C(cr)) as a marker of glomerular filtration rate., Results: C(cr) had significantly negative relationships with night/day ratios of V (R = -0.69; P < 0.0001), U(osm)V (R = -0.54; P = 0.004) and U(Na)V (R = -0.63; P = 0.0005), but no correlation with night/day ratios of C(H(2)O) (R = -0.33; P = 0.1), U(K)V (R = -0.29; P = 0.1) or U(urea)V (R = -0.31; P = 0.1). Linear and multiple regression analysis identified nocturnal natriuresis rather than urea excretion as an independent determinant of nocturia., Conclusion: As renal function deteriorated, nocturnal polyuria was seen, being consistent with classical recognition. Furthermore, this increase in nocturnal urine volume seemed related to osmotic diuresis mainly by natriuresis rather than to water diuresis or urea excretion.

In view of the importance of the peptide linkage in structural biology, we have carried out intensive investigations on peptide molecules consisting of a peptide linkage with one or two substituents in the gas phase by Fourier transform microwave spectroscopy, paying special attention to the internal rotation of the substituents relative to the central linkage framework. We have found that, in sharp contrast with the stiff structure around the central C-N bond of the linkage, the internal rotations of the substituents are of low frequency and thus of large amplitude and are extremely susceptible to their local environment such as the presence of other substituents.

Remarkable regional differences in the annual incidence of endstage renal disease (ESRD) was found within Japan, which has a relatively homogeneous ethnic composition. In addition, there existed no regional difference in the incidence of ESRD due to polycystic kidney disease, the major genetic disorder of the kidneys. These findings suggest that the presence of factors other than genetic disposition contribute to the differences. On the other hand, there were similar regional variations in the incidences of ESRD between two causes of ESRD: chronic glomerulonephritis and diabetic nephropathy. Because it is unlikely that the regional distribution of underlying disease incidence and the disease-specific progression rate would be similar for two different causes, this observation suggests that factors governing the progression rate, which operate commonly for all causes of ESRD but differ among regions, may play an important role in generating the regional differences. Finally, we examined regional differences in the amounts of inhibitors of the renin-angiotensin system used, especially angiotensin-converting enzyme (ACE) inhibitors, in our search for an explanation of the regional differences in ESRD dynamics. Among antihypertensive agents examined, only ACE inhibitors were negatively correlated with the annual incidence of ESRD. The renal protective effects of ACE inhibitors have been established by results with animal models of progressive nephropathy and by large-scale clinical trials. Our epidemiological results for Japan as a whole show the same protective effects still more convincingly from a different approach. It is not completely clear yet at present, however, how regional variations in the incidence of ESRD are generated. If we could identify in future the factors that contribute to the regional differences, strategies for the treatment of renal disease will become available from different angles. Thus, much effort will be encouraged for the further analysis of regional differences in ESRD dynamics.

By comparing mammalian genomes, we and others have identified actively transcribed Ty3/gypsy retrotransposon-derived genes with highly conserved DNA sequences and insertion sites. To elucidate the functions of evolutionarily conserved retrotransposon-derived genes in mammalian development, we produced mice that lack one of these genes, Peg10 (paternally expressed 10), which is a paternally expressed imprinted gene on mouse proximal chromosome 6. The Peg10 knockout mice showed early embryonic lethality owing to defects in the placenta. This indicates that Peg10 is critical for mouse parthenogenetic development and provides the first direct evidence of an essential role of an evolutionarily conserved retrotransposon-derived gene in mammalian development.

This study was conducted to clarify the characteristics of small-scale enterprises (SSEs) with fewer than 50 workers, which employ 62.2% of all Japanese workers. Subjects were 71,183 workers employed at 1,761 workplaces in Tochigi, Japan, in 2002. Frequencies of abnormal lifestyle and health check-up data were described according to the category of the enterprise. Adjusted odds ratios (ORs) of the abnormal findings were calculated by logistic regression analysis. Dose-response relationships were calculated by trend tests. The frequency of abnormal findings was higher in SSEs than in other categories of enterprises. The ORs of work intensity, alcohol consumption, current smoker, and the Brinkmann index were higher in SSEs than in large-scale enterprises (LSEs) and were also significant in trend tests. The ORs of audiometry, hypertension, glucose in urine and ECG in males and females, BMI, liver function, lipid metabolism, and blood sugar in females, chest X-ray, and anemia in males were higher in SSEs. Audiometry, hypertension, anemia, ECG in both males and females; chest X-ray, and glucose in urine in males, and liver function, lipid metabolism and blood sugar in females showed significant results in trend tests. Overall health and healthy lifestyle in SSEs were worse than in LSEs.

NFATc1 and NFATc2 are functionally redundant in the immune system, but it was suggested that NFATc1 is required exclusively for differentiation of osteoclasts in the skeletal system. Here we provide genetic evidence that NFATc1 is essential for osteoclast differentiation in vivo by adoptive transfer of NFATc1(-/-) hematopoietic stem cells to osteoclast-deficient Fos(-/-) mice, and by Fos(-/-) blastocyst complementation, thus avoiding the embryonic lethality of NFATc1(-/-) mice. However, in vitro osteoclastogenesis in NFATc1-deficient cells was rescued by ectopic expression of NFATc2. The discrepancy between the in vivo essential role of NFATc1 and the in vitro effect of NFATc2 was attributed to selective autoregulation of the NFATc1 gene by NFAT through its promoter region. This suggested that an epigenetic mechanism contributes to the essential function of NFATc1 in cell lineage commitment. Thus, this study establishes that NFATc1 represents a potential therapeutic target for bone disease and reveals a mechanism that underlies the essential role of NFATc1 in bone homeostasis.

ABSTRACT Efficiency of nonpathogenic Fusarium oxysporum Fo-B2 for the biological control of Fusarium wilt of tomato, caused by F. oxysporum f. sp. lycopersici CU1, was examined in different environments: a growth chamber with sterile soil-less medium, a greenhouse with fumigated or nonfumigated soil, and nonfumigated field plots. Inoculation of Fo-B2 onto tomato roots significantly reduced the severity of disease, but the efficiency of disease suppression decreased as the experimental environment became less controlled. Relationships between the recovery of Fo-B2 from hypocotyls and the disease severity indicated that the biocontrol agent was most effective when it colonized vascular tissues intensively. Moreover, the degree of Fo-B2 colonization was greatly reduced when the seedlings were grown in nonfumigated soil. Dose-response models (negative exponential, hyperbolic saturation, and logistic) were fit to observed data collected over a range of inoculum densities of the pathogen and the antagonist; the logistic model provided the best fit in all environments. The ratios of an 50% effective dose parameter for Fo-B2 to that of CU1 increased as the environment became less controlled, suggesting that environmentally related efficiency reduction impacted the antagonist more than the pathogen. The results suggest that indigenous soil microbes were a primary factor negatively influencing the efficiency of Fo-B2. Therefore, early establishment of the antagonist in a noncompetitive environment prior to outplanting could improve the efficacy of biological control.

Pathogenicity-impaired mutants, B02 and H15, of Fusarium oxysporum f. sp. lycorpersici (FOL) were obtained using restriction enzyme-mediated integration. Disease severities of Fusarium wilt caused by these mutants were significantly reduced, and their disease development rates were correlated with their colonization rates in tomato vessels. Both B02 and H15 produced significantly smaller amounts of extracellular proteins as well as fusaric acid than the wild-type. Southern blot analyses suggested that B02 and H15 likely contain a single and three copies of transformation vector, respectively. These mutants may thus be useful in isolating genes involved in pathogenicity of FOL.

Background: We recently showed that there were clear regional differences in the dynamics of end-stage renal disease (ESRD) within Japan, which has an ethnically homogenous population. We speculate on the reason for these regional differences by correlating the regional distributions in the incidence of ESRD due to each of the following individual causes of ESRD: chronic glomerulonephritis (CGN), diabetic nephropathy (DMN) and polycystic kidney disease (PKD)., Methods: The number of ESRD patients entering maintenance dialysis therapy due to individual causes of renal disease in each prefecture was reported annually for a 6-year period by the Japanese Society for Dialysis Therapy. After combining data from several prefectures into 11 geopolitical regions in Japan, the mean annual incidence of ESRD across the 11 regions was correlated among the three causes of ESRD., Results: There were significant regional differences in the incidence of ESRD due to CGN (P<0.0001) and DMN (P=0.0015), the distributions of which were similar to each other across the 11 regions. In contrast, no regional differences were found in the incidence of ESRD due to PKD (P=0.6) as the major genetic disorder of the kidneys, suggesting that genetic backgrounds are relatively uniform throughout Japan. The regional distributions due to PKD were not correlated with those due to other causes: CGN and DMN., Conclusion: Risk factors common to nephropathy progression, rather than an underlying disease incidence and genetic predisposition, might contribute to regional differences in the overall ESRD incidence in Japan. Other possibilities such as the prevalence of underlying diseases, and acceptance or rejection rates into treatment programmes must be considered further for better explanations.

Oligonucleotide-based microarray analyses were carried out to identify retinoic acid target genes in embryos of the ascidian Ciona intestinalis. Of 21,938 spots, 50 (corresponding to 43 genes) showed over twofold up-regulation in retinoic acid-treated tail bud embryos. In situ hybridization verified retinoic acid-induced up-regulation of 23 genes. Many of them were expressed in the anterior tail region, where a retinaldehyde dehydrogenase homolog is expressed. Homologs of vertebrate genes involved in neurogenesis and/or neuronal functions (e.g., COUP-TF, Ci-Hox1, and SCO-spondin) were expressed in the central nervous system of Ciona embryos, and activated by retinoic acid. Genes encoding transcription factors (e.g., Ci-lmx1.2, vitamin D receptor, and Hox proteins) and apoptosis-related proteins (e.g., transglutaminase and an apoptosis-inducing factor homolog) were also activated by retinoic acid. Simultaneous treatment of embryos with retinoic acid and puromycin revealed a few direct targets, including genes encoding Ci-Hox1, Ci-Cyp26, and an Rnf126-like ring finger protein., ((c) 2005 Wiley-Liss, Inc.)

We present the case of a 69-year-old man with nephrotic syndrome and renal insufficiency, who developed lobular glomerulonephritis. An electron microscopy examination of a renal biopsy showed microtubular structures of 24 nm in diameter in the subendothelial space and the paramesangial area. These deposits were PAS-positive and Congo red-negative, and revealed predominantly positive staining for kappa light chain. There was no evidence of diseases with highly organized glomerular deposits, such as amyloidosis, cryoglobulinemia, systemic lupus erythematosus or paraproteinemia. Therefore, the patient was diagnosed to have immunotactoid glomerulopathy (ITG). During a seven-year course he has not developed any disease known to be associated with organized glomerular immune deposits. Hence, we believe ITG occurred as a primary glomerular disease in this case. We also highlight cases of ITG with microtubular deposits that have been reported in Japan, compare these cases to previous reports, and show that the characteristics of the Japanese cases are male predominance; a high incidence of membranoproliferative glomerulonephritis (MPGN); a low incidence of monoclonal gammopathy and hematological malignancies and a higher incidence of hypocomplementemia.

To increase their fitness, plants sense ambient light conditions and modulate their developmental processes by utilizing multiple photoreceptors such as phytochrome, cryptochrome and phototropin. Even roots, which are normally not exposed to light, express photoreceptors and can respond to light by developing chloroplasts. In the present study, root greening was observed in Arabidopsis thaliana. Seedlings were grown under monochromatic light and chlorophyll levels in the roots were determined. It was found that blue light was far more effective at inducing chloroplast development in Arabidopsis roots than was red light, and this response was under the control of a strong synergistic interaction between phytochromes and cryptochromes. As expected, the cry1 mutant was deficient in this response. Interestingly, the phyAphyB double mutant failed to respond to blue light under these conditions. This strongly suggests that either phytochrome A or phytochrome B, in addition to cryptochrome, was required for this blue light response. It was further demonstrated that the expression of photosynthetic genes was regulated in the same way. Dichromatic irradiation experiments indicated that this interaction depends on the level of phyB P(FR). Analysis of the cop1, det1 and hy5 mutants indicated that the corresponding factors were involved in the response.

Background: In order to improve enzymatic glycated albumin measurement, we studied the endogenous glycated amino acid elimination reaction and the new bromocresolpurple (BCP) method for albumin measurement., Methods: In the assay, endogenous glycated amino acids are first eliminated by oxidation by ketoamine oxidase. Second, glycated albumin is hydrolyzed to glycated amino acids by proteinase digestion, and glycated amino acids are oxidized to produce hydrogen peroxide, which is quantitatively measured. Third, albumin is measured by the new BCP method. Finally, glycated albumin value is calculated as the percentage of glycated albumin in total albumin., Results: Glycated amino acid concentrations in prepared total parenteral nutrition products were increased in direct proportion to storage time and temperature. The glycated amino acid elimination reaction using ketoamine oxidase may be able to eliminate more than 15 mmol/l glycated amino acids. The glycated albumin values of samples calculated from the albumin concentrations using the new BCP method accorded with those calculated with the HPLC method. Fundamental performances (linearity, dilution test, analytical recovery, within-run and between-run CVs, interference study) of the present method were good. Detection of glycated albumin by the present method was significantly correlated with detection of glycated albumin by the high-performance liquid chromatography method (r(p) = 0.995)., Conclusions: This new improved method is free of interference by endogenous glycated amino acids and is unaffected by albumin concentration, and enables more accurate analysis of glycated albumin.

We present a red-green-blue laser source with average powers of 8 W in the red, 23 W in the green, and 10.1 W in the blue. The entire pump power for the nonlinear conversion stages is provided by a single laser oscillator without any amplifier stages. Our system does not require any synchronized cavities, and all nonlinear crystals except one are critically phase matched at room temperature.

The effects of steroid hormones on in vitro IgM-secreting cells (IgMSC) and IgM secretion by lymphocytes of the lymphoid organs in common carp, Cyprinus carpio were examined by ELISPOT and ELISA assay, respectively. Cells isolated from peripheral blood (PB), spleen and head kidney were cultured for 12, 24 and 48 h either in the absence or in the presence of steroid hormones, i.e. cortisol, testosterone, 11-ketotestosterone (11-KT), and estradiol-17beta (E(2)) at doses of 1, 10 and 100 ng/ml. Cortisol reduced the IgMSC numbers and IgM secretion by cells from all organs. In addition, cortisol induced apoptosis in lymphocytes from all organs. High dose of testosterone showed tissue-specific functions; it reduced the number of IgMSC and amount of IgM secretion by cells from spleen and head kidney, but not in PB, though IgM secretion was suppressed. However, no effects of sex steroids were observed in this study. The results show that sex-specific steroid hormones may have no immunosuppressive effects in common carp.

To analyze global gene expressions, we constructed a cDNA microarray from a basal chordate, the ascidian Ciona intestinalis. Ciona is a cosmopolitan species and a genomic analysis of Ciona revealed that ascidians had approximately 15,500 protein-coding genes. Our "Ciona intestinalis cDNA chip version 1 (Ci cDNA chip ver. 1)" has arrayed 13,400 unique Ciona cDNAs. To establish a detection system for gene expression profiles in wild ascidians using a cDNA microarray, we analyzed gene expressions in the whole body of Ciona adults after exposure to 100 nM tributyltin (TBT) for 24 h. In our preliminary array data using Ci cDNA chip ver. 1, we found more than 200 genes that showed strong differential expressions. These genes encoded proteins that were concerned with stress response, detoxification, oxidoreduction reaction, biosynthesis, and catabolism. This, the first large cDNA microarray of this animal, should facilitate analyses of global gene expressions following exposure to TBT.

We demonstrate a synchronously pumped high-gain optical parametric oscillator with feedback through a fiber, using a passively mode-locked Yb:YAG thin-disk laser as a pump source. We obtain as much as 19-W average signal power at a wavelength of 1.45 microm in 840-fs pulses and 7.8 W of idler power at 3.57 microm. The repetition rate of the pulses is 56 MHz, and the transverse beam quality of the generated signal is M2 < 1.6.

The characteristics and primary structure of AJL-1, one of the lectins in the skin mucus of the Japanese eel (Anguilla japonica), were examined. This lectin exhibited beta-galactoside specific activity in a Ca2+ independent manner. We previously reported that its molecular mass was 16,091Da, although it was approximately 30 kDa as determined by gel filtration, indicating that it is a homodimer having non-covalent bonds. This lectin was composed of 142 amino acid residues having no half-cystinyl residues, and showed homology to members of the galectin family, especially to proto-type galectins. Gene expression of this lectin was detected in skin only, and relative expression was high in an individual that exhibited resistance to infectious disease. AJL-1 showed agglutinating activity against pathogenic bacteria, Streptococcus difficile. This suggests that AJL-1 functions as an important defensive factor at the body surface.

Background: We reported that patients with sodium sensitive type of hypertension exhibited the lack of nocturnal fall in blood pressure with enhanced natriuresis during night. Sodium sensitivity is caused by diminished glomerular filtration capability and/or augmented tubular reabsorption of sodium, and seems tightly linked with glomerular capillary hypertension. In the present study, we investigated the relationship between glomerular filtration rate and circadian rhythms of these parameters in patients with glomerulopathy., Methods: Twenty six patients (15 men and 11 women; aged 17 to 72 years; mean age 47 +/- 3 years), whose diagnosis was confirmed as glomerulopathy with renal biopsy, were studied during hospitalization. Ambulatory blood pressure for 24 hours was monitored, while urinary samples were collected for both daytime (6:00 a.m. to 9:00 p.m.) and nighttime (9:00 p.m. to 6:00 a.m.) to estimate circadian rhythms of urinary sodium and protein excretion rates (UNaV, UproV). Then night/day ratios of mean arterial blood pressure (MAP), UNaV, and UproV were analyzed in relation to 24-hour creatinine clearance as a marker of glomerular filtration rate., Results: Serum creatinine and creatinine clearance were 1.1 +/- 0.1 mg/dL and 89 +/- 7 mL/min/1.73 m2. There were significant day-night differences in MAP (96 +/- 2 mm Hg vs. 92 +/- 2 mm Hg; P= 0.006), UNaV (6.7 +/- 0.9 mmol/hour vs. 3.6 +/- 0.3 mmol/hour; P= 0.003), and UproV (161 +/- 27 mg/hour vs. 128 +/- 28 mg/hour; P= 0.02). Creatinine clearance had significantly negative relationships with night/day ratios of MAP (r=-0.49; P= 0.01), UNaV (r=-0.43; P= 0.03,) and UproV (r=-0.41; P= 0.04). In addition, night/day ratio of MAP had significantly positive relationships with night/day ratios of UNaV (r= 0.49; P= 0.01) and UproV (r= 0.45; P= 0.02)., Conclusion: Our results show that as renal function deteriorates in glomerulopathy the nocturnal dip in blood pressure is lost, resulting in enhanced urinary sodium and protein excretions during night. These findings are compatible with our proposal that impaired natriuresis during daytime makes nocturnal blood pressure elevated to compensate for diminished natriuresis by pressure natriuresis. We speculate that nocturnal glomerular capillary hypertension contributes, at least in part, to enhanced urinary sodium and protein excretions during night.

A cDNA microarray was constructed from a basal chordate, the ascidian Ciona intestinalis. The draft genome of Ciona has been read and inferred to contain approximately 16,000 protein-coding genes, and cDNAs for transcripts of 13,464 genes have been characterized and compiled as the "Ciona intestinalis Gene Collection Release I". In the present study, we constructed a cDNA microarray of these 13,464 Ciona genes. A preliminary experiment with Cy3- and Cy5-labeled probes showed extensive differential gene expression between fertilized eggs and larvae. In addition, there was a good correlation between results obtained by the present microarray analysis and those from previous EST analyses. This first microarray of a large collection of Ciona intestinalis cDNA clones should facilitate the analysis of global gene expression and gene networks during the embryogenesis of basal chordates.

Background: We recently found regional differences in the incidence of end-stage renal disease (ESRD) in Japan, which is generally ethnically homogeneous, suggesting that factors other than genetic may contribute to the difference. Here, we examined regional differences in the amounts of expenses spent on antihypertensives, especially angiotensin-converting enzyme (ACE) inhibitors, in our search for an explanation., Methods: Annually, the Japanese Society for Dialysis Therapy reports the numbers of patients entering maintenance dialysis in each prefecture of Japan since 1982. We used the findings for 1995 to 2000 to calculate the annual incidence of ESRD in each of the 11 regions of Japan. In addition, regional differences in annual amounts paid for antihypertensive drugs, presumably corresponding to the amounts used, during the same 6 years, corrected for population, were estimated., Results: As in our 1982 to 1998 study, the incidence of ESRD was high in Okinawa, Kyushu, and Shikoku, while low in Hokuriku, Koshinetsu, and Tohoku (P < 0.0001) [one-way repeated measures analysis of variance (ANOVA)]. We found regional differences in the corrected sum paid for total antihypertensive drugs, ACE inhibitors and calcium antagonists. Only ACE inhibitors were negatively correlated with the incidence of ESRD by linear and multiple regression analyses., Conclusion: The renal protective effects of ACE inhibitors have been established by results with animal models of progressive nephropathy and large-scale clinical trials. Our epidemiologic results for Japan as a whole show the same protective effects still more convincingly from a different approach.