Biomedical subjects

N Satoh

Publications and source records attributed to N Satoh.

At least 91 records · Page 5Linked to original sources

PubMed1999

Temporal expression patterns of 39 Brachyury-downstream genes associated with notochord formation in the Ciona intestinalis embryo.

Expression of the Brachyury (Ci-Bra) gene of the ascidian Ciona intestinalis is initiated at the 64-cell stage. Gene expression is restricted to notochord precursor cells, and Ci-Bra plays a key role in notochord differentiation. In a previous study, nearly 50 cDNA clones for potential Ci-Bra-downstream genes that are expressed in notochord cells were isolated. The present determination, by whole-mount in situ hybridization, of the temporal expression patterns of 19 notochord-specific and 20 notochord-predominant genes demonstrated that the timings of initiation of the expression of various genes was not identical. The expression of several genes was initiated as early as the gastrula stage. However, the expression of most of the notochord-specific genes commenced at the neural plate stage. Partial nucleotide sequence data of these clones suggest that genes expressed earlier encode potential transcriptional factors and/or nuclear proteins, while those expressed later encode proteins implicated in cell adhesion, signal transduction, regulation of the cytoskeleton, and components of the extracellular matrix. These gene activities may be associated with changes in cell shape and adhesion during the intercalation and extension of the notochord cells.

Animals↗

PubMed1999

Comparison of thermodynamic stabilities between PNA (peptide nucleic acid)/DNA hybrid duplexes and DNA/DNA duplexes.

We have examined quantitatively stabilities of PNA/DNA hybrid duplexes with identical nearest-neighbor base pairs and compared stabilities between PNA/DNA and DNA/DNA. The average difference of stabilization energy of the short PNA/DNA was 0.9 kcal mol(-1), which suggests that the stability of the hybrids with identical nearest-neighbor base pairs can be predicted with the nearest-neighbor model as well as those of nucleic acid duplexes.

Base Pairing↗

PubMed1999

Positional effect of single bulge nucleotide on PNA(peptide nucleic acid)/DNA hybrid stability.

We report positional effect of bulge nucleotide on PNA/DNA hybrid stability. CD spectra showed that PNA/DNA hybrids required at least seven base pairings at a stem region to form a bulged structure. On the other hand, DNA/DNA could form bulged structure when there are only four base pairings adjacent to the bulge nucleotide. We discuss why PNA requests such a many base pairings to form bulged structure from a nearest neighbor standpoint.

Base Sequence↗

PubMed1999

Three types of retinal bleeding as a complication of hypotony after trabeculectomy.

Although small retinal bleeding has been evaluated as a complication of filtering surgery, long-standing retinal bleeding is rare. We report 3 rare cases of young patients with massive retinal hemorrhages following trabeculectomy with 5-fluorouracil or mitomycin C. The bleeding in 1 case resolved spontaneously, whereas the bleeding in the other 2 cases did not resolve and the visual acuity remained poor. Every patient showed markedly delayed retinal circulation. Possible dysfunction of the retinal blood vessels may be responsible for the development of the other two types of massive bleeding, especially in advanced glaucoma with a total cup disk: one is decompression retinopathy and another central retinal vein occlusion or hemorrhagic retinopathy.

Adolescent↗

PubMed1999

Plasma platelet-activating factor acetylhydrolase deficiency in Japanese patients with asthma.

Platelet-activating factor (PAF), a phospholipid with a wide range of proinflammatory actions, is immediately degraded and inactivated in vivo by PAF acetylhydrolase (PAF-AH). Surprisingly, 4% of the Japanese population lacks the extracellular isoform of this enzyme, plasma PAF-AH, due to a genetic missense (V279F) mutation. We studied the association of this mutation with asthma prevalence and phenotypes in the Japanese adult population. The allele frequency of V279F mutation was 18.6% in 279 patients with asthma (28.7% heterozygotes and 4.3% homozygotes) and 21.7% in 217 healthy subjects (32.3% heterozygotes and 5.5% homozygotes). V279F mutant allele prevalence was consistent regardless of asthma type (16.3% in atopic [n = 156] and 21.6% in nonatopic [n = 123]), or the severity of disease (21.7% in patients with mild [n = 97], 17.5% in those with moderate [n = 131], and 15.8% in those with severe [n = 51] asthma). Plasma PAF-AH activity was inversely proportional to the number of mutant alleles, and did not correlate with asthma prevalence, type, or severity. We concluded that plasma PAF-AH deficiency due to V279F mutation is not essential to the pathophysiology of asthma in the Japanese adult population.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

PubMed1999

A comparative molecular approach to mesodermal patterning in basal deuterostomes: the expression pattern of Brachyury in the enteropneust hemichordate Ptychodera flava.

This work concerns the formation of mesoderm in the development of an enteropneust hemichordate, Ptychodera flava, and the expression of the Brachyury gene during this process. Brachyury expression occurs in two distinct phases. In the embryo, Brachyury is transcribed during gastrulation in the future oral and anal regions of the gut, but transcripts are no longer detected by 2 weeks of development. Brachyury expression is not detected during the 5 months of larval planktonic existence. During this time, the adult coeloms begin to develop, originating as coalescences of cells that appear to delaminate from the wall of the gut. Brachyury expression cannot be detected again until metamorphosis, when transcripts appear in the mesoderm of the adult proboscis, collar and the very posterior region of the trunk. It is also expressed in the posterior end of the gut. At no time is Brachyury expressed in the stomochord, the putative homologue of the chordate notochord. These observations illuminate the process of maximal indirect development in Ptychodera and, by comparison with patterns of Brachyury expression in the indirect development of echinoderms, their sister group, they reveal the evolutionary history of Brachyury utilization in deuterostomes.

Animals↗

PubMed1999

Developmental expression of Pax1/9 genes in urochordate and hemichordate gills: insight into function and evolution of the pharyngeal epithelium.

The epithelium of the pharynx contributes to the formation of gills in hemichordates, urochordates, cephalochordates and primitive vertebrates, and is therefore a key structure for understanding developmental mechanisms underlying the establishment of chordate body plans. Pax1- and Pax9-related genes encode transcription factors which are expressed in the pharyngeal region of cephalochordates as well as in the vertebrate pharyngeal pouch epithelium that forms the thymus and parathyroid glands. To explore the molecular basis underlying the occurrence and modifications of the pharyngeal epithelium during evolution, we isolated cDNA clones for Pax1- and Pax9-related genes of urochordates (HrPax1/9 of Halocynthia roretzi and CiPax1/9 of Ciona intestinalis) and a hemichordate (PfPax1/9 of Ptychodera flava) from gill cDNA libraries. Each gene is present as a single copy per haploid genome. All of the cDNAs encode typical paired domains and octapeptides but not a homeodomain, as is also true of other Pax1- and Pax9-related genes. Molecular phylogenetic analysis based on comparison of the paired domain amino-acid sequences suggests that HrPax1/9, CiPax1/9 and PfPax1/9 belong to the Pax1/9 subfamily, and that they are descendants of a single precursor of Pax1/Pax9. Screening of HrPax1/9 cDNA clones yielded six different types of transcripts which were generated by alternative splicing. Northern blot, RT-PCR/Southern and in situ hybridization analyses revealed that HrPax1/9, CiPax1/9 and PfPax1/9 are not expressed during early embryogenesis but are expressed in the epithelia of differentiating gills, suggesting that these genes encode gill-specific transcription factors. The Pax1/9 genes therefore might provide the first developmental genetic corroboration of hypotheses of organ-level homology that unifies hemichordates, urochordates and cephalochordates.

Alternative Splicing↗

PubMed1999

Initiation of shoot apical meristem in rice: characterization of four SHOOTLESS genes.

The regulatory mechanism of shoot apical meristem (SAM) initiation is an important subject in developmental plant biology. We characterized nine recessive mutations derived from four independent loci (SHL1-SHL4) causing the deletion of the SAM. Radicles were produced in these mutant embryos. Concomitant with the loss of SAM, two embryo-specific organs, coleoptile and epiblast, were lost, but the scutellum was formed normally. Therefore, differentiation of radicle and scutellum is regulated independently of SAM, but that of coleoptile and epiblast may depend on SAM. Regeneration experiments using adventitious shoots from the scutellum-derived calli showed that no adventitious shoots were regenerated in any shl mutant. However, small adventitious leaves were observed in both mutant and wild-type calli, but they soon became necrotic and showed no extensive growth. Thus, leaf primordia can initiate in the absence of SAM, but their extensive growth requires the SAM. An in situ hybridization experiment using a rice homeobox gene, OSH1, as a probe revealed that shl1 and shl2 modified the expression domain of OSH1, but normal expression of OSH1 was observed in shl3 and shl4 embryos. Accordingly, SHL1 and SHL2 function upstream of OSH1, and SHL3 and SHL4 downstream or independently of OSH1. These shl mutants are useful for elucidating the genetic program driving SAM initiation and for unraveling the interrelationships among various organs in grass embryos.

Gene Deletion↗

PubMed1999

Evolutionary alterations of the minimal promoter for notochord-specific Brachyury expression in ascidian embryos.

The Brachyury genes of two divergent ascidians, As-T of Halocynthia roretzi and Ci-Bra of Ciona intestinalis, are expressed exclusively in notochord precursor cells. A previous study showed that the notochord-specific expression of Ci-Bra is controlled by a minimal promoter that is composed of three distinct regions: a region responsible for repression of expression in non-notochord mesoderm cells, a region for activation of expression in notochord cells, and a region for activation of expression in non-notochord mesoderm cells, distal to proximal to the transcription initiation site, respectively. We examined various deletion constructs of the As-T/lacZ fusion gene and demonstrate that a module between -289 and -250 bp of the 5'-flanking region is responsible for notochord-specific expression of the reporter gene. Gel-shift assays suggested the binding of nuclear protein(s) to this module. The 5'-flanking region of As-T contains a potential T-binding motif (-ACCTAGGT-) around -160 bp. Deletion of this motif from the p(-289)As-T/lacZ diminished the reporter gene expression. In addition, coinjection of p(-289)As-T/lacZ and synthetic As-T mRNA resulted in ectopic expression of lacZ in non-notochord cells, suggesting that the T-binding motif is responsible for autoactivation of the gene. These findings revealed striking differences between the minimal promoters of As-T and Ci-Bra so far revealed, with respect to their notochord-specific expression. Furthermore, reciprocal injections of reporter gene constructs, namely As-T/lacZ into Ciona eggs and Ci-Bra/lacZ into Halocynthia eggs, suggest alterations in the cis-regulatory elements and trans-activation factors that have occurred during evolution of the two ascidian species.

Animals↗

PubMed1999

Involvement of agouti-related protein, an endogenous antagonist of hypothalamic melanocortin receptor, in leptin action.

To understand the role of agouti-related protein (AGRP), an endogenous antagonist of hypothalamic melanocortin receptor, in leptin action, we produced a full-length recombinant AGRP and examined its effect on the satiety effect of leptin. We also studied leptin's regulation of hypothalamic AGRP mRNA expression. A single intracerebroventricular (i.c.v.) injection of AGRP significantly increased cumulative food intake and body weight in a dose-dependent manner in rats. The leptin-induced inhibition of food intake and body weight was reversed by co-injection of AGRP in a dose-dependent manner. Hypothalamic AGRP mRNA expression was upregulated in leptin-deficient ob/ob mice and leptin receptor-deficient db/db mice and downregulated in lethal yellow agouti mice (KKAy mice) with hyperleptinemia. A single i.c.v. injection of leptin reversed the increased AGRP mRNA levels in ob/ob mice but not in db/db mice. In control mice and KKAy mice, AGRP mRNA expression was upregulated during fasting, when plasma leptin concentrations were decreased. No significant increase in AGRP mRNA expression was noted during fasting in control mice and KKAy mice treated with leptin. This study provides the first direct evidence that AGRP is a negative regulator of leptin action, and leptin downregulates hypothalamic AGRP production. Because leptin is shown to increase hypothalamic alpha-melanocyte stimulating hormone (alpha-MSH) production, our data suggest that its action via the hypothalamic melanocortin system is determined by the balance between the levels of its agonist and antagonist, alpha-MSH and AGRP.

Agouti-Related Protein↗

PubMed1999

Glucose metabolism and insulin sensitivity in transgenic mice overexpressing leptin with lethal yellow agouti mutation: usefulness of leptin for the treatment of obesity-associated diabetes.

Leptin acts as an adipocyte-derived blood-borne satiety factor that can increase glucose metabolism. To elucidate the therapeutic implications of leptin for obesity-associated diabetes, we crossed transgenic skinny mice overexpressing leptin (Tg/+), which we have developed recently, and lethal yellow KKAy mice (Ay/+), a genetic model for obesity-diabetes syndrome, and examined the metabolic phenotypes of F1 animals. At 6 weeks of age, plasma leptin concentrations in Tg/+ mice with the Ay allele (Tg/+:Ay/+) were significantly higher than those in Ay/+ mice. Although no significant differences in body weight were noted among Tg/+:Ay/+ mice, Ay/+ mice, and their wild-type lean littermates (+/+), glucose and insulin tolerance tests revealed increased glucose tolerance and insulin sensitivity in Tg/+:Ay/+ compared with Ay/+ mice. However, at 12 weeks of age, when plasma leptin concentrations in Ay/+ mice were comparable to those in Tg/+:Ay/+ mice, Tg/+:Ay/+ mice developed obesity-diabetes syndrome similar to that of Ay/+ mice. Body weights of 12-week-old Tg/+:Ay/+ and Ay/+ mice were reduced to those of +/+ mice by a 3-week food restriction; when plasma leptin concentrations remained high in Tg/+:Ay/+ mice but were markedly reduced in Ay/+ and +/+ mice, glucose tolerance and insulin sensitivity in Tg/+:Ay/+ mice were markedly improved as compared with Ay/+ and +/+ mice. The present study demonstrates that hyperleptinemia can delay the onset of impaired glucose metabolism and accelerate the recovery from diabetes during caloric restriction in Tg/+:Ay/+ mice, thereby suggesting the potential usefulness of leptin in combination with a long-term caloric restriction for the treatment of obesity-associated diabetes.

Aging↗

PubMed1999

Sympathetic activation of leptin via the ventromedial hypothalamus: leptin-induced increase in catecholamine secretion.

Leptin is an adipocyte-derived blood-borne satiety factor that acts directly on the hypothalamus, thereby regulating food intake and energy expenditure. We have demonstrated that the hypothalamic arcuate nucleus (Arc) is a primary site of the satiety effect of leptin (Neurosci Lett 224:149-152, 1997). To explore the hypothalamic pathway of sympathetic activation of leptin, we examined the effects of a single intravenous or intracerebroventricular injection of recombinant human leptin on catecholamine secretion in rats. We also examined the effects of direct microinjection of leptin into the ventromedial hypothalamus (VMH), Arc, paraventricular nucleus (PVN), and dorsomedial hypothalamus (DMH) in rats. To further assess whether sympathetic activation of leptin is mediated via the VMH, we also examined the effects of a single intravenous injection of leptin in VMH-lesioned rats. A single injection of leptin (0.25-1.0 mg i.v./rat or 0.5-2.0 pg i.c.v./rat) increased plasma norepinephrine (NE) and epinephrine (EPI) concentrations in a dose-dependent manner. Plasma NE and EPI concentrations were increased significantly when leptin was injected directly into the VMH but were unchanged when injected into the Arc, PVN, and DMH. Plasma NE and EPI concentrations were unchanged in VMH-lesioned rats that received a single intravenous injection of leptin. The present study provides evidence that a leptin-induced increase in catecholamine secretion is mediated primarily via the VMH and suggests the presence of distinct hypothalamic pathways mediating the satiety effect and sympathetic activation of leptin.

Animals↗

PubMed1999

Increased glucose metabolism and insulin sensitivity in transgenic skinny mice overexpressing leptin.

Excess of body fat, or obesity, is a major health problem and confers a higher risk of cardiovascular and metabolic disorders such as diabetes, hypertension, and coronary heart disease. Leptin is an adipocyte-derived satiety factor that plays an important role in the regulation of energy homeostasis, and its synthesis and secretion are markedly increased in obese subjects. To explore the metabolic consequences of an increased amount of leptin on a long-term basis in vivo, we generated transgenic skinny mice with elevated plasma leptin concentrations comparable to those in obese subjects. Overexpression of leptin in the liver has resulted in complete disappearance of white and brown adipose tissue for a long period of time in mice. Transgenic skinny mice exhibit increased glucose metabolism accompanied by the activation of insulin signaling in the skeletal muscle and liver. They also show small-sized livers with a marked decrease in glycogen and lipid storage. The phenotypes are in striking contrast to those of recently reported animal models of lipoatrophic diabetes and patients with lipoatrophic diabetes with reduced amount of leptin. The present study provides evidence that leptin is an adipocyte-derived antidiabetic hormone in vivo and suggests its pathophysiologic and therapeutic implications in diabetes.

Animals↗

PubMed1999

[Transient evoked otoacoustic emission measurement in infants].

Transient evoked otoacoustic emissions (TEOAEs) were measured and evaluated in 194 ears of 101 subjects under 4 years old who were suspected of hearing loss, using a ILO88 Otoacoustic Emission Analyzer, to study the basic characteristics of this measure and its utility for hearing screening. The mean time necessary to record TEOAEs in both ears was short, about 3 minutes. In 58 ears judged as normal hearing within 30 dB in ABR, TEOAE levels in infants aged less than 2 months were significantly higher than in those aged more than 1 year, especially in the high frequency bands (4-kHz and 5-kHz bands). One case which had been judged as bilateral moderate-to-profound hearing impairment in initial ABR testing showed good responses in TEOAEs, indicating normal cochlear function, and obvious wave Vs in follow-up ABRs recorded at 30 dB nHL confirmed normal auditory function. Therefore, in a case like this one, suspected of retardation in brain stem maturation, TEOAE is more useful than ABR as a hearing screening technique. Since external and middle-ear factors caused poor TEOAE responses in some cases which had been judged as normal hearing by ABR. TEOAE seems to be more sensitive in detecting external and middle ear problems than ABR. Moreover, TEOAE measurement of infants was easy and noninvasive. We conclude that TEOAE is an excellent tool for screening auditory function in infants.

Child, Preschool↗

PubMed1999

Firing shrinkage of porcelain-resin composites prepared by laser lithography.

Using porcelain and resin-mixed composites as experimental materials, cubic polymerized composites were prepared by the accumulation of thin slices cured by laser scanning. The composites were then fired, and bulk ceramic bodies were made. The optimal firing conditions of polymerized composites and firing shrinkage were investigated. The results showed that cubic ceramic bodies in a form homologous to that before firing could be reproduced. The volume shrinkage of fired ceramic bodies consisting of 1 g of ceramic powders and 0.3 g of epoxy resin was about 30% under all firing conditions, and there were no significant differences between specimens. It was suggested that with further research and development, three-dimensional forms for clinical use in dentistry could be manufactured by the proposed method.

Dental Porcelain↗

PubMed1999

Identification and characterization of maternally expressed genes with mRNAs that are segregated with the endoplasm of early ascidian embryos.

Endoderm cells of the ascidian embryo are specified autonomously dependent on maternal cytoplasmic information or determinants that are localized in the endoplasm. In the present study, we identified three maternally expressed genes (CsEndo-1, CsEndo-2 and CsEndo-3) by screening a cDNA library of Ciona savignyi fertilized egg mRNAs subtracted with gastrula mRNAs. CsEndo-1 encoded a protein with nuclear localization signals, CsEndo-3 predicted a protein containing both a potential transmembrane domain and the PDZ domain, and CsEndo-2 suggested a protein with no similarity to known proteins. The maternal transcripts of all of these genes were not concentrated during early stages of embryogenesis up to the 8-cell stage, but were concentrated at the endoplasmic region by the 16-cell stage and then segregated later with the endoplasm. At the 110-cell stage, the maternal transcript of CsEndo-1 was evident only in the primordial endoderm cells, while those of CsEndo-2 and CsEndo-3 were found in the primordial endoderm cells as well as the primordial notochord cells. All of the transcripts became barely detectable during gastrulation and neurulation. Later, zygotic expression of the three genes became evident again in the endoderm and notochord cells, suggesting developmental roles in the formation of these types of cell. Although we were not able to deduce their functions, this is the first report of maternal genes with mRNAs that are segregated with the endoplasm of ascidian embryos.

Amino Acid Sequence↗

PubMed1999

[Surgical removal of large cavernous angioma in the pontomedullary junction: a case report].

Recent advances in neuroradiology have enabled us to approach cavernous angioma in the brain stem. A case of large cavernous angioma, which was located in the pontomedullary junction, was removed surgically. A 24-year-old female was admitted with occipitalgia, dizziness, nausea, gait disturbance. On neurologic examination, the patient had right hemiparesis, slight right facial palsy and paresthesia, right hemiparesthesia, dysphagia. T1 weighted Gd enhanced MRI revealed a mixed intensity lesion. These findings were thought to be consistent with a cavernous angioma. Follow up MRI findings demonstrated progressive increase in cavernous angioma. Vertebral angiograms showed a mass sign and a venous angioma in the midline of the pontomedullary junction. Therefore, the operation was performed in an attempt to remove the cavernous angioma through the midline of the fouth ventricle. The operation was performed under monitoring of electromyogram of facial muscle and external ocular muscle. The cavernous angioma was removed totally, and addition neurogical deficits were minimal.

Adult↗

PubMed1999

[A case report of double roentgenographically occult lung cancer revealed by postsurgical pathological study].

A 66-year-old man admitted to our hospital as a roentgenographically occult lung cancer (ROLC) detected by sputum cytology of class IV. A differential brushing of all branches of the bronchi was performed and squamous cell carcinoma was detected only from the right B8 segmental bronchus. Right lower lobectomy was performed and the microscopic findings of surgical specimen revealed the squamous cell carcinomas were seen at not only B8 bronchus but also B7 bronchus. The frequency of multicentricity of ROLC is reported to be high, and a differential bronchial brushing of all bronchi is a very powerful method to diagnose synchronous multiple lung cancer. However, we failed to detect a cancer lesion of B7 segmental bronchus in this case. Since, the outcomes of surgical treatments for either synchronous or metachronous multiple primary lung cancer are satisfactory, limited surgical treatments might be appropriate as an initial treatment for a ROLC.

Aged↗