[Gene hunting for Fukuyama-type congenital muscular dystrophy by positional cloning].
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Chromosome Mapping↗
Biomedical subjects
T Toda
Publications and source records attributed to T Toda.
Effect of particle sizes in India ink on its use in evaluation of apical seal.
We investigated the use of India ink as an indicator of root canal sealing ability. Sealing ability is one of the most important factors required of root canal cements. Various dyes have been used for this purpose. Methylene blue, radioisotopes and India ink have all been tried. However, there is no evidence that India ink is suitable as an indicator. We measured the particle size distribution of India ink to determine how this factor affects test results. In addition, we observed the surface texture of an experimentally developed calcium phosphate sealer and a commercially available root canal sealer using SEM. We found that a portion of the India ink particles were smaller than cracks on the two sealer surfaces, indicating, that India ink could pass through these cracks. We concluded that India ink is suitable as an indicator of root canal seal.
Calcium Phosphates↗
Prenatal diagnosis of Fukuyama type congenital muscular dystrophy by polymorphism analysis.
Fukuyama type congenital muscular dystrophy (FCMD) is an autosomal recessive disorder characterized by a combination of primary muscular dystrophy of early infantile onset and brain malformation (lissencephaly type II). The identification of the FCMD gene locus at 9q31 opened the theoretical possibility of prenatal diagnosis. The authors conducted prenatal diagnosis in two unrelated FCMD families by analysis using nine microsatellite CA-repeat polymorphic markers flanking the FCMD locus, and calculated phenotype probabilities in fetuses with a computer program, LINKAGE. The fetus in family 1 showed a 99% probability of being healthy either as a normal homozygote or a heterozygote carrier and was born without signs of FCMD. In family 2, the fetus was diagnosed to have FCMD with at least 86% probability. The parents of this family decided to terminate the pregnancy and an abortus showed brain malformations characteristic of an FCMD fetus.
Brain↗
Requirement for PP1 phosphatase and 20S cyclosome/APC for the onset of anaphase is lessened by the dosage increase of a novel gene sds23+.
Ubiquitin-dependent proteolysis is required for the onset of anaphase. We show that protein dephosphorylation by protein phosphatase 1 (PP1) is also essential for initiating anaphase in fission yeast. PP1 may directly or indirectly regulate the 20S cyclosome/APC (anaphase-promoting complex) required for anaphase-promoting proteolysis. Using anti-phosphopeptide antibodies, PP1 is shown to be dephosphorylated at the C-terminus, upon the onset of anaphase, for reactivation. sds23+, a novel gene, is a multicopy suppressor for mutations in PP1 and the 20S cyclosome/APC, implying that the gene dosage increase can relieve the requirement for PP1 and the cyclosome/APC for the onset of anaphase. The sds23+ gene is not essential for cell viability, but a mutant with the gene deleted cannot form colonies at 22 and 36 degrees C. In the sds23 deletion mutant, the progression of anaphase and cytokinesis is retarded and cell shape is aberrant. These defects are overcome by plasmids carrying the genes encoding subunits of the 20S cyclosome/APC or PP1. These results demonstrate functions other than promoting anaphase for the components of the 20S cyclosome/APC and also a close functional relationship of Sds23 with PP1 and 20S cyclosome/APC.
Amino Acid Sequence↗
Microtubules mediate mitochondrial distribution in fission yeast.
The Schizosaccharomyces pombe mutant, ban5-4, displays aberrant mitochondrial distribution. Incubation of this conditional-lethal mutant at the nonpermissive temperature led to aggregated mitochondria that were distributed asymmetrically within the cell. Development of this mitochondrial asymmetry but not mitochondrial aggregation required progression through the cell division cycle. Genetic analysis revealed that ban5-4 is an allele of atb2 encoding alpha 2-tubulin. Consistent with this finding, cells with the cold-sensitive nda3 mutation in beta-tubulin displayed aggregated and asymmetrically distributed mitochondria after incubation at lowered temperatures. These results indicate that microtubules mediate mitochondrial distribution in fission yeast and provide the first genetic evidence for the role of microtubules in mitochondrial movement.
Cell Cycle↗
A new group of conserved coactivators that increase the specificity of AP-1 transcription factors.
The Jun proteins are nuclear proteins that combine with Fos proteins to form a gene-regulatory protein, AP-1. They have highly conserved DNA-binding and dimerization domains, resulting in almost identical sequence-recognition properties. Nevertheless, there are many indications that each Jun protein activates a distinct and only partially overlapping set of AP-1 target genes. Using the more variable activation domain of c-Jun as a bait, we identified a protein, JAB1, that interacts with c-Jun and JunD, but not with JunB or v-Jun. As a result, JAB1 selectively potentiates transactivation by only c-Jun or JunD. In vitro, JAB1 specifically stabilizes complexes of c-Jun or JunD with AP-1 sites and does not affect binding of either JunB or v-Jun. The amino-terminal half of JAB1 is very similar to the amino terminal region of Pad1 from fission yeast, which was identified genetically as a coactivator of a subset of AP-1 target genes. JAB1 and Pad1 are also functionally interchangeable. They define a new group of coactivators that increase the specificity of target gene activation by AP-1 proteins.
Amino Acid Sequence↗
The Atf1 transcription factor is a target for the Sty1 stress-activated MAP kinase pathway in fission yeast.
The atf1+ gene of Schizosaccharomyces pombe encodes a bZIP transcription factor with strong homology to the mammalian factor ATF-2. ATF-2 is regulated through phosphorylation in mammalian cells by the stress-activated mitogen-activated protein (MAP) kinases SAPK/JNK and p38. We show here that the fission yeast Atf1 factor is also regulated by a stress-activated kinase, Sty1. The Sty1 kinase is stimulated by a variety of different stress conditions including osmotic and oxidative stress and heat shock. Deletion of the atf1+ gene results in many, but not all, of the phenotypes associated with loss of Sty1, including sensitivity to environmental stress and inability to undergo sexual conjugation. Furthermore, we identify a number of target genes that are induced rapidly in a manner dependent upon both the Sty1 kinase and the Atf1 transcription factor. These genes include gpd1+, which is important for the response of cells to osmotic stress, the catalase gene lambda important for cells to combat oxidative stress, and pyp2+, which encodes a tyrosine-specific MAP kinase phosphatase. Induction of Pyp2 by Atf1 is direct in that it does not require de novo protein synthesis and results in a negative feedback loop that serves to control signaling through the Sty1/Wis1 pathway. We show that Atf1 associates stably and is phosphorylated by the Sty1 kinase in vitro. Taken together, these results indicate that the interaction between AM and Sty1 is direct. These findings highlight a remarkable level of conservation in transcriptional control by stress-activated MAP kinase pathways between fission yeast and mammalian cells.
Activating Transcription Factor 1↗
Expression of thymopoietin beta/lamina-associated polypeptide 2 (TP beta/LAP2) and its family proteins as revealed by specific antibody induced against recombinant human thymopoietin.
An expression vector was constructed to produce a common region of human thymopoietin family proteins. The recombinant protein was expressed in Escherichia coli as a fusion protein with a biotinylated tag region and purified by affinity chromatography on a monomeric avidin resin. The thymopoietin family-specific antibody was induced in rabbits by immunization with the recombinant fusion protein. Western blotting analysis using the antibody revealed that the expression of thymopoietin family proteins was remarkably tissue specific. Among those, thymopoietin beta/lamina-associated polypeptide 2 appears to be specifically expressed in tissues with high proliferative activity.
Amino Acid Sequence↗
Structure and chromosomal assignment of the human S1-5 gene (FBNL) that is highly homologous to fibrillin.
The human S1-5 gene (fibrillin-like; FBNL) was originally isolated from a subtractively enriched cDNA library established from a subject with Werner syndrome (WS). We isolated genomic clones containing the entire S1-5 gene and determined its genomic structure including the exon-intron organization. The gene spanned approximately 18 kb of genomic DNA and consisted of 12 exons. Its expression was abundant in all tissues examined except brain and peripheral leukocytes, where it was undetectable. In addition, we have mapped S1-5 by fluorescence in situ hybridization to chromosome 2p16, a position that excludes it as a candidate for WS. Our data should facilitate an understanding of the function and regulation of S1-5 in human tissues.
Base Sequence↗
Caffeine-resistance in fission yeast is caused by mutations in a single essential gene, crm1+.
Caffeine is a base analogue and is known to affect a wide variety of cellular processes. In order to dissect genetically molecules which mediate the biological effects of caffeine, temperature-sensitive (ts) and caffeine-resistant mutants were isolated from fission yeast, Schizosaccharomyces pombe. Surprisingly, all twelve ts isolates contained a mutation in the same locus, crm1. Cells of the ts crm1 mutant showed an abnormal chromosome structure at the restrictive temperature, an elevated expression of Pap1-dependent transcription, and cross-resistance to an unrelated drug such as staurosporine. Overproduction of pap1+ also conferred caffeine resistance, whilst the resistance of the crm1 mutant is abolished in the pap1- background. These results show that the crm1+ gene is a major locus for caffeine resistance, which arises from Pap1-dependent transcriptional activation.
Alkaloids↗
Plexiform leiomyoma of the esophagus: a peculiar gross variant simulating plexiform neurofibroma.
A plexiform variant of leiomyoma of the esophagus in a 51-year-old woman is reported. The patient was diagnosed with a tumor of the esophagus in an X-ray mass survey of the upper gastrointestinal tract. She was referred to the Ryukyu University Hospital for further examination. She appeared healthy with no complaints. Upper gastrointestinal series revealed an oval, well-defined filling defect in the lower esophagus just above the esophagogastric junction. Endoscopy revealed an undulating bulge covered with normal esophageal mucosa. Endoscopic ultrasonography showed a sharply demarcated hypoechoic mural tumor with internal linear pattern, with no evidence of penetration into the surrounding tissue. These findings were evaluated as consistent with a leiomyoma. Removing the tumor by enucleation was easily accomplished. Unexpectedly, on gross inspection, the tumor was a plexiform type, mimicking a plexiform neurofibroma. Light and electron microscopic examination and immunohistochemistry of the tumor tissue confirmed leiomyoma. Since the enucleation of the tumor, the patient has been free of recurrence and symptoms for 1.5 years at the time of this report.
Diagnosis, Differential↗
A novel (CA)n polymorphism on 6p21.1-21.2.
A novel highly polymorphic CA repeat locus D6S2213 was identified on human chromosome 6p21.1-21.2. It should be a useful marker for linkage studies on chromosome 6 and also in forensic use.
Alleles↗
Are breaches in the glia limitans the primary cause of the micropolygyria in Fukuyama-type congenital muscular dystrophy (FCMD)? Pathological study of the cerebral cortex of an FCMD fetus.
A light and electron microscopic study of the brain of an 18-week fetus with a prenatal genetic diagnosis of Fukuyama-type congenital muscular dystrophy revealed a widespread mantle of abnormal neurogliomesenchymal tissue that covered a dysplastic cerebral cortex. In this area alone, the glia limitans that adjoined the abnormal mantle via one or two layers of basal lamina had frequent breaches, through which neuroglial elements extruded. In the most severely affected cortical region, which had only a rudimentary and fragmentary glia limitans, the majority of cortical neurons had migrated into the neurogliomesenchymal tissue. The massive overmigrated neurons still maintained a somewhat columnar arrangement, and the marked dysplasia abruptly shifted to a neurogliomesenchymal tissue-free normal cortical structure with an intact glia limitans, thus indicating essentially vertical overmigration of neurons without significant tangential migration of them. Together the above findings imply that breaches in the glia limitans may be the primary cause of the micropolygyria seen in this genetic disorder.
Cerebral Cortex↗
Beneficial effects of electrical stimulation before round spermatid nuclei injections into rabbit oocytes on fertilization and subsequent embryonic development.
OBJECTIVE: To evaluate the effects of electrical stimulation of rabbit oocytes before round spermatid nuclear injection procedure on oocyte activation and fertilization. DESIGN: The ratio of activated oocytes to the number of successfully injected oocytes and the proportion of offspring to the number of activated oocytes after round spermatid nuclear injections into oocytes stimulated via mechanical stimulation (group A) or a combination of electrical and mechanical stimulation (group B) was compared. INTERVENTIONS: Round spermatid nuclei were isolated from mature male rabbits and microinjected into the oocytes of groups A and B. Injected oocytes were cultured for 24 hours. The embryos developed from groups A and B were transferred to synchronized recipient does. RESULTS: Embryos that developed normally through implantation in groups A and B were carried successfully through complete gestation in the recipient does. The ratio of the activated oocytes to the number of successfully injected oocytes and the proportion of offspring to the number of activated oocytes were significantly higher in group B. CONCLUSION: Electrical stimulation of oocytes before ooplasmic spermatid nuclear injections and ET procedures has beneficial effects on oocytes activation, fertilization, and subsequent embryonic development.
Animals↗
Altering the timing of human chorionic gonadotropin injection according to serum progesterone (P) concentrations improves embryo quality in cycles with subtle P rise.
OBJECTIVE: To investigate the effect of earlier administration of hCG according to serum concentrations of P on the outcome of IVF-ET in cycles in which a subtle rise in serum P (1.0 to 2.0 ng/mL; conversion factor to SI unit, 3.180) occurred during the follicular phase. DESIGN: Retrospective study. PATIENTS: A total of 110 infertile women underwent 124 cycles of IVF-ET at Tottori University Hospital. MAIN OUTCOME MEASURES: Serum was obtained daily or every 12 hours from day 7 until the administration of hCG. Serum E2 and P concentrations were measured by RIA. In 19 of 36 subtle P rise cycles, hCG injection was given when the levels of serum P exceeded 1.0 ng/mL ("rescued" subtle P rise). Parameters of IVF outcomes for the no P rise, the subtle P rise, and the rescued subtle P rise cycles were compared. RESULTS: The mean day of hCG administration in the rescued cycles was 1 day earlier than those of the subtle P rise and no P rise cycles. The mean number of oocytes collected was significantly higher in the subtle P rise and rescued P rise cycles than in the no P rise cycles. The mean follicular diameter on the day of hCG administration was 13.9 mm in the rescued cycles, significantly smaller than those of the no P rise and subtle P rise cycles. However, there was no significant difference in the cleavage rates between the three groups. The rate of embryonic development beyond four-cell stage was increased significantly in the rescued cycles and no P rise cycles versus the subtle P rise cycles. Embryos obtained in the no P rise and rescued cycles were of better morphological quality than those obtained in the P rise cycles. The implantation rate was significantly higher in the rescued cycles than in the P rise cycles. CONCLUSION: The data suggest that, if hCG is administered when a subtle P rise is detected, embryo quality and subsequent implantation rate can be improved.
Adult↗
Removal of smear layer in the root canal using oxidative potential water.
We investigated oxidative potential water (OPW) for its ability to remove the smear layer using a scanning electron microscope. OPW has been studied mainly in Japan and is known to suppress bacteria and viruses without harming living systems. We found that OPW used as in irrigant during and after root canal instrumentation is as effective as 5% NaOCl or 17% EDTA for opening and keeping patent the dentinal tubules.
Acid Etching, Dental↗
Cardiac rhabdomyoma of a neonate: an autopsy case report.
A primigravida delivered a cyanosed female infant with a very low Apgar score. Cardiac anomaly of the fetus was detected at 32 weeks of gestation by ultrasonography. The baby died on the day of delivery. Autopsy revealed multiple tumor masses in the interventricular septum and ventricular walls. The tumor originating from the interventricular septum was the largest and measured 3.7 x 3 cm. Histologically, the tumor was composed of large polygonal glycogen-laden cells and 'spider-cells'. Eosinophilic giant histiocytic cells were also observed in the spleen. Ultrastructural features of the tumor cells correlated with those of typical cardiac muscle cells.
Fatal Outcome↗
Mixed gonadal dysgenesis with gonadoblastoma in a female with Y chromosome: case report.
A young female with primary amenorrhea and male karyotype (46/XY) is reported. Physical examination and clinical investigation of the patient suggested mixed gonadal dysgenesis (MGD). After gonadectomy, a tumor was found on the left side and histologically diagnosed gonadoblastoma. Postoperative decreased level of testosterone and estradiol reflected the activities of the tumor.
Amenorrhea↗