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Biomedical subjects

N Satoh

Publications and source records attributed to N Satoh.

At least 163 records · Page 9Linked to original sources

Early evolution of the Metazoa and phylogenetic status of diploblasts as inferred from amino acid sequence of elongation factor-1 alpha.

To understand the early evolution of the Metazoa, it is necessary to determine the correct phylogenetic status of diploblastic animals (poriferan, cnidaria, and ctenophora). Despite clasdistic studies of morphological characters and recent molecular phylogenetic studies, it remains uncertain whether diploblasts are monophyletic or paraphyletic, and how these three phyla of diploblasts are phylogenetically related. To obtain insight into these phylogenetic problems, we sequenced almost the entire nucleic acid sequence of elongation factor-1 alpha from a sponge, two cnidarians, a ctenophora, and a turbellarian. We then investigated the phylogenetic status of the diploblasts. We compared the amino acid sequences, nucleotide sequences at the first and second codon positions, and those at the second positions. Phylogenetic trees were inferred by neighbor-joining, maximum likelihood, and maximum parsimony, and they supported the monophyly of the Metazoa. However, the phylogenetic relationships of the diploblast groups were not significantly resolved, although the trees preferred the monopoly of the diploblasts.

Amino Acid Sequence↗

Mitochondrial rDNA phylogeny of the asteroidea suggests the primitiveness of the paxillosida.

Asteroids display four distinct modes of developmental patterns: the indirect mode, the nonbrachiolarian mode, the direct mode, and the mode with a barrel-shaped larva. Among them the former two are planktotrophic, whereas the latter two are lecithotrophic. The direct mode and the mode with a barrel-shaped larva are thought to have evolved from the more primitive planktotrophic mode, the nonbrachiolarian and the indirect mode, respectively. However, whether the nonbrachiolarian mode or the indirect mode is the more primitive in asteroids is unresolved, despite discussion since early this century. A key aspect of this problem is the phylogenetic status of paxillosidans, since the nonbrachiolarian mode and the mode with a barrel-shaped larva are seen only in paxillosidans. To resolve this problem, we performed a molecular phylogenetic study of asteroids, based on the nucleotide sequences of mitochondrial rDNAs. Phylogenetic trees support a close relationship between the Asterinidae and the Solasteridae. We suggest that the paxillosidans are not a monophyletic group; rather, the Luidiidae (one family of Paxillosida) is a sister group to the rest of the asteroids. Although some aspects of our results contradict a recent study by Lafay et al. (1995, Syst. Biol. 44: 190-208) based on 28S rRNA sequences, both studies agree on a paraphyletic nature for the paxillosidans. We conclude that characters shared by paxillosidans are primitive; hence the primitive mode of development in asteroids is the nonbrachiolarian mode.

Animals↗

Electrophysiological evidence suggesting that sensory stimuli of unknown origin induce spontaneous K-complexes.

The present study was performed to determine whether or not spontaneous K-complexes are induced by sensory stimuli. In the first part of the present study, sound stimuli were prescribed during sleep in 7 healthy, young, adult subjects. EEG segments in stage 2 sleep were averaged separately according to the presence or absence of an evoked K-complex appearing after each stimulus. The sound stimulus induced N100 and P200 components in averaged EEGs regardless of K-complex appearance. The appearance of N100 and P200 components was considered to be an indicator of the presence of sensory stimuli. In the second part of the present study, EEG segments in stage 2 sleep containing an evoked K-complex or spontaneous K-complex were separately averaged with respect to the peak of N300, one of the main components constituting the K-complex. Small negative and positive components were found just before the main components of spontaneous K-complexes in averaged EEGs. These two components were judged to correspond to N100 and P200 components induced by the sound stimulus, as they appeared just before the main components of the spontaneous K-complex with almost the same lag time between the two components, or between each of the two components and the main components of K-complex, as in the case of N100 and P200 appearing just before the evoked K-complex. The present findings suggest that the spontaneous K-complex is not a spontaneous phenomenon, but that it is induced by sensory stimuli, probably of extracerebral origin.

Adult↗

Comparison of the antiplatelet agent potential of the whole molecule, F(ab)2 and Fab fragments of humanized anti-GPIIb/IIIa monoclonal antibody in monkeys.

1. The potential antiplatelet agent use of the whole molecule, F(ab)2 and Fab fragments of humanized antiglycoprotein (GP) IIb/IIIa monoclonal antibody, hC4G1, were investigated in rhesus monkeys. 2. Fab completely inhibited platelet aggregation 1 hr after an i.v. bolus administration of 1 mg/kg without a decrease in platelet count or prolongation of bleeding time, and the duration of inhibition was much shorter than that of F(ab)2. 3. These results suggest that the Fab fragment of hC4G1 may be a more useful antiplatelet agent in patients with acute thromboembolic diseases than the whole molecule or F(ab)2 fragments.

Animals↗

An ascidian homologue of vertebrate BMPs-5-8 is expressed in the midline of the anterior neuroectoderm and in the midline of the ventral epidermis of the embryo.

The ascidian tadpole larva is thought to be the prototype for the ancestral chordate. Although ascidians show a highly determinate mode of development, recent studies suggest significant roles of cell-cell interaction during embryogenesis. To elucidate the signaling molecules responsible for the cellular interaction, we investigated an ascidian homologue of the transforming growth factor beta (TGF-beta) superfamily. HrBMPa is an ascidian member of the 60A subclass of the BMP subfamily. Molecular phylogenetic analysis suggested that HrBMPa branched prior to further divergence of vertebrate BMPs-5-8. The zygotic expression of HrBMPa was initiated around gastrulation. HrBMPa transcripts were first evident in precursor cells of the spinal cord, notochord, epidermis and nervous system, although signals in the first two regions quickly disappeared. In neurulae and early tailbud embryos, transcripts were evident in the adhesive organ, midline of the anterior dorsal neuroectoderm and midline of both ventral and dorsal ectoderm, suggesting that HrBMPa plays a major role in neuroectodermal cell differentiation during embryogenesis. This HrBMPa expression profile resembled that of Xenopus BMP-7, implying a primordial function of BMP-7 among vertebrate BMPs-5-8.

Amino Acid Sequence↗

A distribution study of 11C platelet-activating factor (PAF) analogs in normal and tumor-bearing mice.

As a preliminary study to image platelet-activating factor (PAF) receptors in vivo, comparative study of biodistribution between 1-O-hexadecy1-2-O-N, N-dimethylcarbamoyl-sn-glycero-3-phosphocholine [choline-methyl-11C](L-[11C]dimethylcarbamoyl-PAF) and nonspecific PAF analog, 3-O-hexadecyl-2-O-N,N-dimethylcarbamoyl-sn-glycero-1-phosphocholine [choline-methyl-11C](D-[11C]-dimethylcarbamoyl-PAF) was carried out in both normal and tumor-bearing mice. Higher accumulation of L-[11C]dimethylcarbamoyl-PAF than D-[11C]dimethylcarbamoyl-PAF was observed in normal mice spleen. The co-administration of PAF antagonists dose-dependently reduced the radioactivity level of the L-isomer only in the spleen. In mice bearing Ehrlich tumors and Sarcoma 180, more L-than the D-[11C]-isomer was accumulated in the tumor and spleen. We found that specific accumulation sites for L-[11C]dimethylcarbamoyl-PAF exist in the spleen and tumors than in other tissues. Moreover, the comparison of accumulation between L- and D-[11C] dimethylcarbamoyl-PAF would be a useful procedure for estimation of PAF receptors in vivo.

Animals↗

Spatial expression of a forkhead homologue in the sea urchin embryo.

Echinoderms are the sister group of the chordates and hemichordates within the deuterostomes. They lack a notochord or any structures obviously homologous with it. To gain insight into developmental mechanisms important in the origin and early evolution of chordates, we investigated sea urchin homologues of chordate genes that are implicated in notochord formation, viz. Brachyury and HNF-3 beta. Here we report the pattern of expression of a sea urchin orthologue of forkhead, Hphnf3 which is present as a single copy per haploid genome. An Hphnf3 transcript of 3.0 kb was first detected at the swimming blastula stage, accumulated maximally at the gastrula and prism-embryo stages, and decreased at the pluteus-larva stage. In situ hybridization signals were found in cells of the vegetal plate of the swimming blastula. During gastrulation, intense staining was evident in the cells surrounding the blastopore, whereas weak staining was detected in the invaginating archenteron. At the prism-embryo stage, the entire archenteron stained intensely; then, at pluteus stage, the larva staining decreased in intensity. The forkhead and Brachyury genes begin to be expressed almost simultaneously in sea urchin embryos, in the vegetal plate at the late blastula stage. After the onset of gastrulation, however, Hphnf3 is expressed in the posterior part of the archenteron, whereas the Brachyury orthologue, HpTa, is expressed in the secondary mesenchyme founder cells, which occupy the anterior tip of archenteron. Hphnf3 may contribute to specification of embryonic cells as archenteron, and the role of HpTa may be directed towards specification of mesodermal founder cells. Except for the basal character of expression in endoderm and endomesoderm, these transcription factors are clearly utilized differently in chordates.

Amino Acid Sequence↗

Common deleted region on the long arm of chromosome 5 in esophageal carcinoma.

BACKGROUND & AIMS: The existence of an unknown tumor-suppressor gene on 5q for esophageal carcinoma other than the APC gene has been suggested. The location of the putative tumor-suppressor gene on 5q, distinct from the APC gene, was examined. METHODS: Sixty-one primary esophageal carcinomas were examined for nine microsatellite loci by the polymerase chain reaction followed by polyacrylamide gel electorophoresis. Loss of heterozygosity at the APC gene locus also was examined by the polymerase chain reaction-restriction fragment length polymorphisms. RESULTS: Thirty-five of 61 esophageal carcinomas (57%) showed loss of heterozygosity at single or multiple loci on 5q, and the smallest common deleted region was identified at 5q31.1, the location of the IRF-1 gene locus. All tumors showing loss of heterozygosity at the APC gene locus showed complete or large interstitial deletions on 5q. CONCLUSIONS: Deletion at the APC gene locus may just be the result of large deletions on 5q and may not be important in esophageal carcinogenesis, and the IRF-1 gene or other gene(s) on 5q31.1 may be the true target of frequent deletions on 5q that may play an important role in the pathogenesis of the majority of esophageal carcinomas.

Carcinoma↗

Posterior end mark, a novel maternal gene encoding a localized factor in the ascidian embryo.

Ascidian embryogenesis is regarded as a typical 'mosaic' type. Recent studies have provided convincing evidence that components of the posterior-vegetal cytoplasm of fertilized eggs are responsible for establishment of the anteroposterior axis of the embryo. We report here isolation and characterization of a novel maternal gene, posterior end mark (pem). After fertilization, the pem transcript is concentrated in the posterior-vegetal cytoplasm of the egg and later marks the posterior end of developing ascidian embryos. Despite its conspicuous localization pattern, the predicted PEM protein shows no significant homology to known proteins. Overexpression of this gene by microinjection of synthesized pem mRNA into fertilized eggs results in development of tadpole larvae with deficiency of the anteriormost adhesive organ, dorsal brain and sensory pigment-cells. Lineage tracing analysis revealed that the anterior epidermis and dorsal neuronal cells were translocated posteriorly into the tail region, suggesting that this gene plays a role in establishment of anterior and dorsal patterning of the embryo. The ascidian tadpole is regarded as a prototype of vertebrates, implying a similar function of pem in vertebrate embryogenesis.

Amino Acid Sequence↗

Basic fibroblast growth factor induces notochord formation and the expression of As-T, a Brachyury homolog, during ascidian embryogenesis.

The tadpole larva of an ascidian develops 40 notochord cells in the center of its tail. Most of the notochord cells originate from the A-line precursors, among which inductive interactions are required for the subsequent differentiation of notochord. The presumptive-endoderm blastomeres or presumptive-notochord blastomeres themselves are inducers of notochord formation. Notochord induction takes place during the 32-cell stage. In amphibia, mesoderm induction is thought to be mediated by several growth factors, for example, activins and basic fibroblast growth factor (bFGF). In the ascidian, Halocynthia roretzi, treatment with bFGF of presumptive-notochord blastomeres that had been isolated at the early 32-cell stage promoted the formation of notochord at a low concentration of bFGF (0.02 ng/ml), while activin failed to induce notochord differentiation. The effect of bFGF reached a maximum at the end of the 32-cell stage and rapidly faded at the beginning of the subsequent cleavage, the time for full induction of notochord being at least 20 minutes. The expression of As-T, a previously isolated ascidian homolog of the mouse Brachyury (T) gene, starts at the 64-cell stage and is detectable exclusively in the presumptive-notochord blastomeres. The present study showed that presumptive-notochord blastomeres, isolated at the early 32-cell stage, neither differentiated into notochord nor expressed the As-T gene. However, when the presumptive-notochord blastomeres were coisolated or recombined with inducer blastomeres, transcripts of As-T were detected. When presumptive-notochord blastomeres were treated with bFGF, the expression of the As-T gene was also detected. These results suggest that inductive interaction is required for the expression of the As-T gene and that the expression of the As-T gene is closely correlated with the determined state of the notochord-precursor cells.

Activins↗

Cleavage specificity of coxsackievirus 3C proteinase for peptide substrate (2): Importance of the P2 and P4 residues.

Coxsackievirus 3C proteinase (3Cpro) cleaves between Gln and Gly, but additional amino acids are required to constitute a cleavage site. To investigate the additional sequence requirements, cleavages of the peptide substrate, and its derivatives were examined. Substitutions of each residue from the P2 to P5 positions showed the importance of the P2 Phe and P4 Ala for recognition by 3Cpro.

3C Viral Proteases↗

Cleavage specificity of coxsackievirus 3C proteinase for peptide substrate.

The substrate requirements of coxsackievirus 3C proteinase (3Cpro) were investigated on the C-terminal side of the scissile bond using C-terminal truncated peptides of the substrate peptide Ac-EALFQGPPV. Not only the Gln-Gly bond of Ac-EALFQG-NH2 but also the C-terminal amide group of Ac-EALFQ-NH2 was hydrolyzed by 3Cpro, suggesting that the essential residues for cleavage by coxsackievirus 3Cpro would exist within the N-terminal 5 residues.

Amino Acid Sequence↗

[Otoacoustic emissions of full-term and preterm neonates].

Transiently evoked otoacoustic emission (TEOAE), distortion product otoacoustic emission (DPOAE), and spontaneous otoacoustic emission (SOAE) were measured in 45 full-term neonates (68 ears) and 12 preterm neonates (20 ears) with ILO88 & 92. Measurements were performed in the nursery of the obstetrics ward or NICU (not sound proof room) under natural sleeping condition after nursing. No sedating agent was used. TEOAEs were rated "good response" in 61 (89.7%) of 68 full-term neonate ears. DPOAEs were rated "good response" in 40 (71.4%) of 56 full-term neonate ears. SOAEs were detectable in 25 (62.5%) of 40 full-term neonate ears. Considering the high positive rate of TEOAE in full-term neonates and the easy and noninvasive method of measurement, we concluded that TEOAE is useful for auditory screening in neonates. There was failure to detect TEOAEs in 7 ears and the measurements were all performed within 6 days after birth. Some reports claim that residual amnion in the external auditory canal or the middle ear in the first few days after birth causes slight hearing loss. Thus, we expected that making the measurements more than 7 days after birth might yield higher "good response" rates. We sometimes found that the Total Echo Powers of TEOAEs were reduced by the poor condition of the ear probe. Thus, we must be very careful in regard to this technical problem in order to perform accurate examinations. Because of its lower "good response" rate, DPOAE was not as useful for screening as TEOAE. Because of the movements or respiratory noises of the newborn infants, it was hard to detect reliable DPOAEs, particularly in the low frequency range. On the other hand, because of its frequency specificity, particurally at high frequencies, DPOAE will be useful for detecting the partial hearing impairment such as congenital high-tone hearing impairment. It would be difficult to use SOAE as a clinical test. Because it is not an evoked response, its mechanism of generation is not well understood. We expect that following longitudinal changes in SOAE in neonates may yield some information about it. We measured mainly TEOAE in preterm neonates because we had to complete the measurements as soon as possible. High Total Echo Powers of TEOAEs were recorded in most infants over 38 weeks of PCA (post conceptional age). The earliest case showed reliable TEOAE at 35 weeks PCA. In most cases that could be measured twice on different days, the Total Echo Powers of TEOAE, were higher in the second time. We therefore concluded that TEOAE might serve as an examination for monitoring the maturation of preterm neonate hearing.

Female↗

Antiplatelet and antithrombotic effects of YM337, the Fab fragment of a humanized anti-GPIIb/IIIa monoclonal antibody in monkeys.

The antiplatelet and antithrombotic effects of the Fab fragment of the humanized antiplatelet glycoprotein (GP) IIb/IIIa monoclonal antibody C4G1 (YM337) were investigated in monkeys. First, the relationship between the inhibition of platelet aggregation and the prolongation of bleeding time was studied in rhesus monkeys. YM337 dose-dependently inhibited ex vivo platelet aggregation, with complete inhibition at doses higher than 0.25 mg/kg intravenous injection or 1.5 micrograms/kg/min infusion. At 0.25 mg/kg bolus injection followed by 1.5 micrograms/kg/min infusion, YM337 immediately and continuously inhibited platelet aggregation during the 6-h infusion period with platelet aggregation rapidly returning to over 50% of baseline within 1 h after the cessation of infusion. Template-bleeding time was significantly prolonged during the period of complete inhibition of platelet aggregation. Second, the antithrombotic effects of YM337 were investigated in a photochemically-induced thrombosis model in squirrel monkeys. YM337 at a dose of 1 mg/kg intravenous injection followed by 6 micrograms/kg/min infusion for 60 min prevented occlusive thrombus formation in all 4 monkeys. In contrast, time to occlusive thrombus formation did not change on intravenous bolus injection of aspirin 17 mg/kg (11.3 +/- 5.2 min) or sodium ozagrel (9.4 +/- 3.0 min) compared with saline (13.3 +/- 4.0 min). YM337 but not aspirin or sodium ozagrel significantly inhibited ex vivo ADP-induced platelet aggregation, while all drugs completely inhibited arachidonic acid-induced platelet aggregation. However, while aspirin and sodium ozagrel inhibited the thromboxane B2 generation accompanying arachidonic acid-induced platelet aggregation, YM337 had no effect on this variable. Platelet counts and bleeding time showed no significant change in any group in this squirrel monkey model. These results indicate that YM337, with a short half-life, may be a useful therapeutic agent in patients with thrombotic disorders.

Animals↗

[A case of progressive hemifacial and hemispheric atrophy with multiple hemi-intracerebral calcifications presenting with occipital lobe epilepsy].

A 30-year-old man with progressive hemifacial atrophy is described. He had right hemifacial atrophy and epileptic seizures first noted at the age of about 15 years. Examination revealed atrophy of the right half of the tongue, skin pigmentation in the right neck, grizzled hair on the right side of the head, and left upper temporal homonymous hemianopsia. CT and MRI revealed multiple intracerebral calcifications, and EEG showed spike discharges predominantly in the right occipital lobe, ipsilateral to the hemifacial atrophy. The epileptic seizures were associated with visual hallucinations that are characteristic of occipital epilepsy. A skin biopsy obtained from the pigmented region in the right neck showed chronic inflammatory changes consisting of severe atrophy of the epidermis, dermis, and fatty tissue, marked proliferation of collagen fibers, and perivascular infiltration by round cells and giant phagocytes. Previous descriptions on the pathogenesis of hemiatrophy of the face and brain were reviewed in relation to the present case.

Adult↗

[Role of reservoirs in intraarterial chemotherapy for recurrent hepatocellular carcinoma after hepatectomy].

We conducted a retrospective study on the role of reservoirs in intraarterial chemotherapy for recurrent hepatocellular carcinoma (HCC) after hepatectomy. Ninety-two out of 170 patients with HCC who underwent hepatectomy from 1987 to 1992 in our institute were enrolled in this study. HCC recurred in 55 patients. A rate of good patency of the catheter of the reservoir at the time of recurrence was found in 72.7% of the patients. Transcatheter arterial embolization (TAE) for recurrent tumor was not feasible in 3 patients, because of occlusion of the hepatic artery (3.3% of patients with reservoir, 5.5% of patients with recurrence). Eleven patients were treated by intraarterial chemotherapy using the reservoir and TAE or TAE and PEIT (group R), and 11 patients were treated only with TAE and/or PEIT (group NR). Although there were no significant differences between the two groups in the number of recurrent lesions and operative procedures, tumor-free interval was shorter in group R. Cumulative survival rates after recurrence were not significant. The frequency of TAEs was lower in group R, which shortened the hospitalization for postrecurrence therapy. Thus, intraarterial chemotherapy using reservoir contributed to improvement of the quality of life of patients with recurrent HCC.

Carcinoma, Hepatocellular↗

[Suppression of experimental autoimmune uveitis by energy restriction].

The effects of energy restriction on experimental autoimmune uveitis (EAU) were investigated. Seven-week-old, male Lewis rats were divided into three groups. Experiment A) A control group was fed ad libitum, a second group was given 50% calorie restricted food from the day of immunization, and a third group was given 50% calorie restricted food from 2 weeks before immunization. Experiment B) A control group was fed ad libitum, a second group was given 25% calorie restricted food from 4 weeks before immunization, and a third group was given 50% calorie restricted food 4 weeks before immunization. All rats were immunized with interphotoreceptor retinoid-binding protein (IRBP). In experiment A), in the group given 50% calorie restricted food from 2 weeks before immunization, and in experiment B), in the group given 50% calorie restricted food from 4 weeks before immunization, the onset of EAU was significantly delayed, the clinical symptoms were lessened, and delayed hypersensitivity against IRBP was suppressed. Clinically and histologically, the severity was also low. In the group given 50% calorie restricted food from 4 weeks before immunization, the titer of anti-IRBP antibody was also significantly lower than in the control group.

Animals↗

[Difference in expression of epithelial adhesion molecules between primary and metastatic lesions in small-cell lung cancer].

One crucial step in tumor metastasis is detachment of cells from the primary lesion. This involves down-regulation of homophilic binding intercellular adhesion molecules. To determine whether this occurs in metastasis of human small-cell lung cancer to lymph nodes, we examined expression of E-cadherin, carcinoembryonic antigen (CEA), and neural cell adhesion molecule (NACM) on cells from patients with small-cell lung cancer, some cells were obtained from primary lesions and others from lymph-node metastases. Cells in all of the five lines from primary lesions expressed E-cadherin, unlike those in all of the five lines from lymph-node metastases. Cells in all of the five lines from primary lesions expressed CEA, as did those in only one of the five cell lines from lymph-node metastases. Cells in lines from primary and metastatic lesions did not differ in the expression of NCAM (4/5 positive). Expression of E-cadherin and of CEA were closely correlated. Because E-cadherin and CEA are involved in the binding of epithelial cells, these findings demonstrate that metastasis of small-cell lung cancer to lymph nodes is associated with a lack of the epithelial intercellular adhesion molecules E-cadherin and CEA. The expression of these molecules is involved in the metastasis of small-cell lung cancer to lymph nodes.

Cadherins↗