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Biomedical subjects

A Sato

Publications and source records attributed to A Sato.

At least 37 records · Page 2Linked to original sources

Expression of inducible nitric oxide synthase messenger RNA, but not guanylate cyclase messenger RNA, depends on gestational age in rat myometrium.

We studied the expression of inducible nitric oxide (NO) synthase (iNOS) and soluble guanylate cyclase (sGC) mRNAs in pregnant rat myometrium. Expression of iNOS and sGC alpha1, beta1 and beta2 mRNA was analyzed in non-pregnant and pregnant (days 10, 14, 17 and 21) Wistar rats by reverse transcription-polymerase chain reaction. Expression of iNOS mRNA increased during pregnancy but decreased on day 21 of gestation. Expression of GC alpha1 mRNA was greater than GC beta1 mRNA at all time points. Expression of uterine GC alpha1 and GC beta1 mRNA did not change significantly during pregnancy and did not differ significantly from non-pregnant levels. The values of sGC beta2 mRNA were below the limit of detection. In conclusion, the expression of iNOS mRNA increased during pregnancy in the myometrium and decreased at term, while the expression of sGC mRNA was not affected by pregnancy. Thus, it is the changes in NO production, rather than changes in its target, that are responsible for uterine quiescence during pregnancy and initiation of labor.

Animals↗

The effects of veno-venous extracorporeal membrane oxygenation on hypoxic fetal lambs.

OBJECTIVE: The purpose of this study was to determine the applicability of veno-venous extracorporeal membrane oxygenation (V-V ECMO) to support fetal oxygenation in utero. METHODS: An ECMO system with a centrifugal pump was applied to ten chronically instrumented fetal lambs, at 126 or 127 days of gestation. Blood was obtained through a double-lumen catheter inserted into the right atrium. After oxygenation, the blood was returned through a single-lumen catheter into either the carotid artery (veno-arterial; V-A ECMO) or the right atrium (V-V ECMO). After fetal hypoxia had been experimentally produced, V-A ECMO or V-V ECMO was instituted to maintain fetal oxygenation. We compared fetal blood gases with both routes of ECMO. RESULTS: Oxygen partial pressure (pO(2)) in the fetal cranial carotid artery decreased to 12.9 +/- 0.6 mmHg after reducing the fraction inspiratory oxygen of the mother. After instituting V-A ECMO, pO(2) was found to be 23.5 +/- 2.6 mmHg; after instituting V-V ECMO, pO(2) was found to be 20.3 +/- 1.9 mmHg. Thus, fetal acidosis increased under both procedures. Fetal heart rate and blood pressure were not altered significantly during the experiments. CONCLUSIONS: This study indicates that V-V ECMO could more effectively and less traumatically maintain oxygenation in hypoxic fetal lambs.

Animals↗

Clustering of C-type lectin natural killer receptor-like loci in the bony fish Oreochromis niloticus.

The genome of the cichlid (teleost) fish Oreochromis niloticus contains a set of genes which encode group V C-type lectin proteins homologous to the mammalian NKG2/CD94 family of natural killer (NK) cell receptors. To determine the genomic organization of these killer cell-like receptor (KLR) genes, an O. niloticus BAC library was screened with a cDNA probe derived previously from an expressed sequence tag of the related cichlid species Paralabidochromis chilotes. Four distinct KLR-bearing BAC clones were analysed, three of which could be assembled into a contig. One of the clones was sequenced in its entirety, whereas the others were partially sequenced to identify the KLR loci borne by them. Altogether, 28 distinct KLR loci were identified, of which at least 26 occupy a single chromosomal region, the KLR complex. One half of the loci appear to be occupied by pseudogenes. Compared to the human NK cell receptor complex, the Oreochromis KLR complex is more compact and, apart from transposons, appears to contain only KLR loci. The gene density of the complex is one KLR locus per 18 kb of sequence. All the KLR loci constituting the complex are derived from a single most recent common ancestor, which is estimated to have existed 7.7 million years ago. The 180 kb of the determined sequence is a mosaic of blocks of similar segments reflecting a complex history of duplications, deletions and rearrangements. The transposons found in the sequenced part belong to the TC1, Xena, CR1 and TX1 families.

Amino Acid Sequence↗

Elemental diet modulates the growth of Clostridium difficile in the gut flora.

BACKGROUND AND AIMS: Tube feeding is regarded as a risk factor for Clostridium difficile-associated diarrhoea. Recently, we reported that C. difficile toxin was frequently found in patients receiving an elemental diet. The present study was conducted to clarify whether elemental diets are associated with the growth of C. difficile in the gut flora. METHODS: C. difficile was cultured for 72 h in various concentrations of elemental diet containing 3% thioglycollate, and the growth rate or activity of C. difficile was evaluated by Gram stain or by measuring optical density at 560 nm. Faecal samples from 10 healthy adults were cultured in elemental diet + 3% thioglycollate. RNA was extracted from faeces with glass powder, which can eliminate PCR inhibitors, and mRNA of C. difficile toxin B was measured by reverse transcription PCR. RESULTS: Maximum OD560 value during culture in thioglycollate-containing elemental diet was 2.4 times higher than that in thioglycollate alone (P = 0.0163). Viability of C. difficile was decreased in thioglycollate but not in thioglycollate-containing elemental diet. Toxin B mRNA was detected in five faecal samples (50%) before culture and in all samples after culture. CONCLUSIONS: Our results suggest that an elemental diet can modulate the growth of C. difficile in the gut flora.

Adult↗

The experience of Japan as a clue to the etiology of breast and ovarian cancers: relationship between death from both malignancies and dietary practices.

Although breast and ovarian cancers are rare in Japan compared with other developed countries, the death rates for both are increasing. In Japan, dramatic lifestyle changes occurred after World War II. Over the past 50 years (1947-1997), the age-standardized death rates of breast and ovarian cancers increased about 2- and 4-fold, respectively, and the respective intake of milk, meat, and eggs increased 20-, 10-, and 7-fold. The increase in the annual death rates from breast and ovarian cancers might be due to the lifestyle changes (increased consumption of animal-derived food) that occurred after 1945. Among the food, milk and dairy products should receive particular attention since they contain considerable amounts of estrogens.

Breast Neoplasms↗

The experience of Japan as a clue to the etiology of testicular and prostatic cancers.

In Japan dramatic lifestyle changes occurred after World War 2. To examine the experience of Japan as a clue to the etiology, trends in the mortality rates of testicular and prostatic cancers from 1947 to 1998 were related to changes in dietary practices. The male population born before 1945 had a peak in death from testicular cancer in their thirties or forties, whereas those born after 1946 had a peak in their twenties. The death rate of prostatic cancer increased 25-fold almost linearly after the war. The intake of milk, meat, and eggs increased 20-, 9-, and 7-fold, respectively, after the war. In connection with the development and growth of testicular and prostatic cancers in Japan, particular attention should be paid to milk, because the increase in its consumption in this country is a recent occurrence and because milk contains considerable amounts of estrogens plus saturated fats.

Food↗

Cytotoxicity of bisphenol A glycidyl methacrylate on cytochrome P450-producing cells.

Of the cytochrome P450 (CYP) family of carcinogen-activating enzymes, CYP3A is the major form found in human livers. The purpose of this study was to investigate the cytotoxic effects of dental resin monomers after being metabolized by CYP3A4 and CYP3A7, using a colony formation assay and a neutral red assay. Specimen wells were plated with transfected cells derived from the Chinese hamster lung at 100 cells well(-1). The experimental group consisted of CYP-producing 3A4-10 and 3A7-40 cells, while the control group consisted of non-CYP-producing CR-119 cells. Bisphenol A (BPA) and bisphenol A glycidyl methacrylate (Bis-GMA) and a positive control (Aflatoxine Bl) were added separately to each well and cultured for 7 days. After cultivation, the number of the colonies was counted and IC50 values were determined. The data were statistically analysed by a Student's t-test. The resultant of IC50 values indicated that the monomers were not metabolically activated by CYP3A4 or CYP3A7 as compared with the control (P < 0.05). We also confirmed that these monomers act neither as activators nor as inhibitors of CYP3A4 and CYP3A7.

Aflatoxins↗

Phylogeny of antigen-processing enzymes: cathepsins of a cephalochordate, an agnathan and a bony fish.

Cathepsins are enzymes that have been cleaving peptide bonds of lysosomal proteins probably since lysosomes appeared in early eucaryotes. When the adaptive system emerged in gnathostomes, cathepsins were recruited to produce peptides for loading onto the major histocompatibility complex class II molecules and for degrading the class II-associated invariant chain just before the loading. The circumstances under which this recruitment took place are unclear because the knowledge about vertebrate cathepsins is limited largely to mammals. To shed light on the recruitment, 10 amphioxus, one lamprey and one cichlid fish cathepsin cDNA clone were characterized and analysed phylogenetically. Disregarding cathepsin O, whose phylogenetic position is uncertain, the analysis confirms the existence of two old lines of descent, the B and the L lineages of cathepsins, which diverged from each other early in the evolution of eucaryotes. The B lineage encompasses cathepsins B, C and Z (X). The L lineage splits off sublineages encompassing cathepsins F and W before the plant-animal separation and cathepsin H early in the evolution of the metazoa. The remaining cathepsins belonging to the L lineage diverged from one another during the evolution of vertebrates: S, K and L before the emergence of bony fishes, and the group of rodent placentally expressed cathepsins [J (P), M, Q, R, 3, 6, 7 and 8] as well as the testis/ova-expressed cathepsins (testins) probably after the divergence of rodents from primates. The part possibly played by the adaptive immune system in some of these divergences is discussed.

Amino Acid Sequence↗

Lymph node hyalinization in elderly Japanese.

Lymph node hyalinization has been comprehensively investigated using specimens obtained from elderly Japanese and white Americans. Onion-peel lesions and associated meshwork areas were often found in the medullary sinus of the thoracic node (mediastinal-type hyalinization), while eosinophilic, glassy and spotty lesions were consistently seen in B lymphocyte areas of the pelvic node (pelvic-type hyalinization). The mediastinal-type hyalinization was comprised of thin collagen fibrils (ca 50 nm in diameter), whereas the pelvic-type hyalinization had thick fibrils (ca 150 nm in diameter). This difference seemed to be consistent with a difference in composite collagen fibrils of vascular walls between the thoracic and pelvic regions. The pelvic-type hyalinization was often or sometimes seen in other nodes, such as cervical, axillary, abdominal and inguinal nodes, especially in white Americans. The mediastinal-type hyalinization, usually in combination with a sinus filled with anthracotic macrophages, tended to be observed in Japanese more frequently than in white Americans. Anthracosis seemed to be connected to the pathogenesis of the hyalinization. On the other hand, because the lesion was weakly positive for Factor VIII immunohistochemistry and because lesions were located along thin vessels, the pelvic-type hyalinization seemed to originate from vascular degeneration in the nodal cortex. Due to the high incidence and large proportion in total volume of the node, the hyalinization seems to be one of the major events that diminish the nodal filtration function and ruin the node with aging.

Aged↗

Preliminary report of two-stage secondary alveolar bone grafting for patients with bilateral cleft lip and palate.

OBJECTIVE: To overcome the difficulties of one-stage secondary alveolar bone grafting for patients with bilateral cleft lip and palate (BCLP) who have a broad alveolar cleft, the value of two-stage alveolar bone grafting was examined. PATIENTS: Three patients (2 girls and 1 boy) with BCLP were treated by two-stage alveolar bone grafting. The procedure consisted of a first-stage surgery (mean age 8 year 6 months +/- 7.8 months), which consisted of alveolar bone grafting for one side of the BCLP, and second-stage surgery for the contralateral side several months later. For the postoperative assessment, radiographs of the operated site were examined. RESULTS: The average amount of implanted bone per operation and per patient was 6.8 +/- 1.1 g and 13.7 +/- 1.0 g, respectively. Postoperative clinical and radiographic examinations revealed that an appreciable alveolar bone ridge had formed, and there were no major complications. CONCLUSIONS: Two-stage alveolar bone grafting, which makes it possible to reduce the amount of implanted bone, could be an optional surgical procedure for patients with BCLP and a broad alveolar cleft.

Alveoloplasty↗

Simultaneous immunohistochemical localization of beta-catenin and cyclin D1 in differentiated but not in undifferentiated human endometrial carcinoma.

PURPOSE: Beta-catenin plays dual important roles in epithelial cell-cell adhesion in cytoplasm as well as in the nuclear T-cell factor (TCF)/lymphoid enhancing factor-1 (LEF-1) signaling pathway. Abnormal nuclear accumulation of beta-catenin promotes colorectal carcinogenesis by triggering the expression of cyclin D1 gene through the TCF/LEF-1 pathway. The purpose of this study was to investigate the possible involvement of the TCF/LEF-1 pathway in endometrial carcinogenesis. METHODS: Immunohistochemical localization of beta-catenin and cyclin D1 in normal endometrium, hyperplastic endometrium and endometrial carcinoma were assessed on serial tissue sections. RESULTS: Nuclear accumulation of beta-catenin was observed in endometrial carcinomas compared with normal endometria. Cyclin D1-positive endometrial cancer cases were beta-catenin-positive in the nuclei, especially in 70% (7/10) of G1 and 55.6% (5/9) of G2 differentiated endometrial carcinomas, but never in G3 undifferentiated ones. CONCLUSIONS: These results imply that the simultaneous nuclear accumulation of beta-catenin and cyclin D1--suggesting the activation of the TCF/LEF-1 pathway--may be a potential marker for the progression of Type 1 endometrial carcinogenesis.

Adult↗

Vector-averaged gravity regulates gene expression of receptor activator of NF-kappaB (RANK) ligand and osteoprotegerin in bone marrow stromal cells via cyclic AMP/protein kinase A pathway.

Bone loss due to unloading of the skeleton may be caused by an acceleration of osteoclastic bone resorption as well as a decline of osteoblastic bone formation. Recently, two molecular species that play important roles in osteoclastogenesis were discovered: (i) the receptor activator of NF-kappaB ligand (RANKL)/osteoprotegerin (OPG) ligand/osteoclast differentiation factor induces osteoclastogenesis; and (ii) the OPG/osteoclastogenesis inhibitory factor potently inhibits osteoclastogenesis. To investigate the effects of gravity on gene expression of RANKL and OPG, a mouse bone marrow-derived stromal cell line, ST2, was cultured on a single axis clinostat, which generates a vector-averaged gravity environment. Northern blot analysis revealed that RANKL mRNA was increased, whereas that of OPG decreased. The clinostat culture also caused an increase in intracellular cyclic (cAMP) level. Both forskolin and dibutyryl-cAMP mimicked the regulation of RANKL and OPG transcription in clinostat culture. These modulations of gene expression in clinostat culture were blocked by a protein kinase A (PKA) inhibitor, H89, but not by a cyclooxygenase inhibitor, indomethacin. The enhancement of RANKL gene expression under clinostat culture and its inhibition by H89 were confirmed by a reporter assay with the murine RANKL 5'-flanking region. These results suggest that modulations of RANKL and OPG expression in stromal cells might be one of the causes of bone loss during skeletal unloading. An elevation of intracellular cAMP level caused through an as yet undetermined pathway is involved in modulation of RANKL and OPG expression during clinostat culture.

Animals↗

Linkage relationships of genes coding for alpha2-macroglobulin, C3 and C4 in the zebrafish: implications for the evolution of the complement and Mhc systems.

The alpha2-macroglobulin (A2M) and the complement components C3 and C4 are related proteins derived from a common ancestor. Theoretically, this derivation could have occurred either by tandem duplications of their encoding genes or by polyploidization involving chromosomal segments, a chromosome or the whole genome. In tetrapods the A2M-, C3- and C4-encoding genes are generally each located on a different chromosome. This observation has been interpreted as supporting their origin by polyploidization. We identified and mapped (with the help of a radiation hybrid panel of cell lines) the A2M, C3 and C4 loci in the zebrafish, Danio rerio. Each of the three types of loci is present in the zebrafish in multiple copies, but all of the identified copies of a given type map to the same region in linkage groups 1 (C3) and 15 (A2M, C4). The A2M and C4 loci are mapped in the same region not linked to any of the class I or class II major histocompatibility complex (Mhc) loci. These observations are interpreted as supporting the origin of the A2M family of genes by tandem duplications, followed by the dispersal of the copies to different chromosomes. It is also argued that the association of C4 with the class I/II loci in tetrapods is accidental and without functional significance.

Animals↗

alpha-Tocopherol Inhibits IL-8 synthesis induced by thrombin and high glucose in endothelial cells.

It has been reported that alpha-tocopherol, an antioxidant agent, may play a role in preventing diabetic angiopathy. However, there is little evidence to show the effect of alpha-tocopherol on the production of pro-inflammatory cytokines in endothelial cells. Therefore, we examined the effect of alpha-tocopherol on the regulation of IL-8 synthesis induced by high glucose and/or thrombin in endothelial cells. Thrombin alone markedly increased the IL-8 release. Furthermore, high glucose levels and thrombin combined had additive effects on IL-8 synthesis, and alpha-tocopherol diminished their effect; alpha-tocopherol also inhibited the phosphorylation of IkappaB-alpha induced by high glucose levels and/or thrombin. Our results suggest that the administration of alpha-tocopherol to diabetic patients may have a beneficial effect for the prevention of diabetic vascular complications by the inhibition of IL-8 synthesis from endothelial cells.

Aorta↗

Homologous phases built by boron clusters and their vibrational properties.

We have found a series of new rare earth boron-rich solids in REBC(N) (RE: Y, Ho, Er, Tm, and Lu), systems and their structures are solved from single crystal and/or powder X-ray diffraction data. Structure analysis results show that they are homologous with B(4)C and also show trigonal symmetry. As the two basic structural units, boron icosahedra and octahedra in the new phases form in layers and stack in different sequences which form different phases. With increasing number of icosahedral layers stacking between two neighboring octahedral layers, the c-axis of the unit cell is increased and the other two edges of the unit cell are only changed slightly. Three monophases of the series have been synthesized both in powders and as single crystals. The vibrational modes of the homologous phases are analyzed from the Raman spectra and compared with that of B(4)C.

Journal Article↗

Evolution of Mhc class II B genes in Darwin's finches and their closest relatives: birth of a new gene.

The 15 extant species of Darwin's finches on the Galápagos and Cocos Islands are the products of an unfinished adaptive radiation from a founder flock of birds related to the South American species Tiaris obscura. Molecular characterization of their major histocompatibility complex ( Mhc) class II B genes has revealed the existence of several related groups of sequences (presumably encoded in distinct loci) from which one (group 5) stands out because of its low divergence over extended time periods. Analysis of group 5 exon 2 and intron 2 sequences has revealed that the encoding locus apparently arose 2-3 million years ago in the Tiaris group of South and Central American Thraupini. The locus shows no evidence of inactivation, but displays a very low degree of polymorphism, both in terms of number of alleles and genetic distances between alleles. Some of the polymorphism, however, appears to be trans-specific. All the observed intergenic differences can be explained by point mutations and most of the exon 2 changes represent non-synonymous substitutions, although the rate of non-synonymous and synonymous substitutions appears to be the same. The origin of the new locus is explained by the birth-and-death model of Mhc evolution with two important extensions. First, the ancestor of the group 5 genes may have arisen without new gene duplication and second, the birth of the new group may have been brought about by a switch from balancing to directional selection. The ancestor of the group 5 genes may have been a classical class II B allele (one of many) which directional selection fixed in the ancestral population and drove into the category of nonclassical genes.

Animals↗