Biomedical subjects

K Eto

Publications and source records attributed to K Eto.

At least 109 records · Page 6Linked to original sources

PubMed1994

Simple and sensitive assay of zonisamide in human serum by high-performance liquid chromatography using a solid-phase extraction technique.

A rapid and sensitive method for the assay of zonisamide in serum was developed using a solid-phase extraction technique followed by high-performance liquid chromatography. A 20-microliter volume of human serum was first purified with a Bond-Elut cartridge column. Then, the methanol eluate was injected onto a reversed-phase HPLC column with a UV detector. The mobile phase was acetonitrile-methanol-distilled water (17:20:63, v/v) and the detection wavelength was 246 nm. The detection limit was 0.1 micrograms/ml in serum. The coefficients of variation were 4.2-5.6% and 5.1-9.1% for the within-day and between-day assays, respectively. This method can be used for clinical pharmacokinetic studies of zonisamide in serum even in infant patients with epilepsy.

Anticonvulsants↗

PubMed1994

Cloning of a complete protein-coding sequence of human platelet-type phosphofructokinase isozyme from pancreatic islet.

We have cloned a full length protein-coding sequence of human platelet-type phosphofructokinase (PFK) from pancreatic islet cDNA library. The platelet-type PFK was composed of 784 amino acids and had a deduced molecular weight of 85,590. Homologies in the primary structure with muscle- and liver-type PFK were 71 and 67%. Clear similarities of the amino and carboxyl halves with a prokaryotic PFK indicated an evolutionary event that duplicated genes of a prototype PFK fused into larger genes of eukaryotic PFKs. Amino acid residues constituting the binding sites for various allosteric modulators were well conserved, while a couple of different residues at the inhibitory ATP sites among three isozymes may partly explain their varied degree of sensitivities to ATP. Considerable amount of platelet-type PFK expression was demonstrated in brain, heart, kidney, colon and testis.

Amino Acid Sequence↗

PubMed1994

Antisense retinoic acid receptor gamma-1 oligonucleotide enhances chondrogenesis of mouse limb mesenchymal cells in vitro.

Retinoic acid receptor (RAR) gamma gene is expressed in the precartilaginous cells during chondrogenesis in mouse embryos, but the role of the gene products is still unclear. To examine the role during chondrogenesis, we isolated mesenchymal cells from the limb bud of mouse embryos and exposed them to antisense RAR gamma-1 oligodeoxynucleotide in micromass culture. The antisense oligodeoxynucleotide inhibited RAR gamma-1 protein expression and enhanced chondrogenesis in the exposed cells. These results suggest that the complex of RAR gamma-1 protein and its ligand RA acts as a suppressor of the chondrogenesis in the limb development.

Animals↗

PubMed1994

Antisense c-myc oligonucleotide promotes chondrogenesis and enhances RA responsiveness of mouse limb mesenchymal cells in vitro.

To examine the role of c-myc protein during chondrogenesis, we exposed 11 day p.c. mouse limb mesenchymal cells to the antisense c-myc oligonucleotide in micromass culture. The antisense oligonucleotide inhibited the c-myc protein expression, and intensely promoted chondrogenesis in the exposed cells. Most of the cells differentiated into cartilaginous cells, whereas they differentiated into cartilaginous and fibrous cells under the control conditions. The antisense oligonucleotide increased the inhibitory efficiency of all-trans retinoic acid (RA) to the chondrogenesis. These results suggest that the c-myc protein suppress the chondrogenesis and reduces RA responsiveness in the limb mesenchymal cells.

Animals↗

PubMed1994

First-pass metabolism of omeprazole in rats.

To clarify the in vivo first-pass metabolism of omeprazole, the pharmacokinetics were examined after oral, intraduodenal (i.d.), intraportal venous (i.p.v), and intravenous (i.v.) administration at various doses to rats. Extraction ratios in the liver and intestinal tract were determined from the areas under the concentration-time curve (AUC) for i.p.v. and i.v. administration and from those for id and ipv administration, respectively. Assuming that the drug was absorbed from the gastrointestinal tract completely, the hepatic and intestinal extraction ratios were 0.80, 0.63, and 0.59 at doses of 2.5, 5, and 10 mg/kg and 0.70 and 0.73 at doses of 5 and 10 mg/kg, respectively. The bioavailability of orally administered omeprazole was 6.4, 9.6, and 12.6% at the doses of 10, 20, and 40 mg/kg, respectively. There were no differences in the distribution volume of steady state, total clearance, or elimination half-life at any doses. In addition, the AUC value after oral administration (20 mg/kg) in rats acutely intoxicated with CCl4 was 2.4 times larger than that in the control. These findings suggest that omeprazole undergoes a first-pass metabolism in the intestinal mucosa and/or lumen, as well as in the liver, and that the major contribution to the dose-dependent increase in bioavailability is a saturation of the first-pass metabolism in the liver.

Administration, Oral↗

PubMed1994

The contribution of both forebrain and midbrain crest cells to the mesenchyme in the frontonasal mass of mouse embryos.

Migration of cranial neural crest cells is a crucial event in the formation of facial organs such as the frontonasal mass and branchial arches. However, the source of the populating crest cells that occupy the frontonasal mass remains unclear in mammalian embryos. To elucidate this, we performed focal DiI injections at various sites in the prosencephalon (forebrain, including the future telencephalon and diencephalon), mesencephalon (midbrain), and the anterior part of the rhombencephalon (hindbrain) separated posteriorly by the preotic sulus (i.e., rhombomere A; future rhombomere 1 and 2) of cultured mouse embryos from the 3- to 10-somite stage. Results directly revealed that during these stages the lateral edge of the prosencephalon produced crest cells which migrated to the frontonasal mass. On the other hand, labeled cells at the anterior neural ridge in the prosencephalon contributed mainly to the head epithelium, including the nasal placode, Rathke's pouch, and oral epithelium. As for the crest cells of the mesencephalon and rhombomere A, their destinations were significantly dependent on the injection site and somite stage. At the 3- to 4-somite stage, the crest cells emigrating from both the mesencephalon and rhombomere A migrated to the first branchial arch. Moreover, the mesencephalic region, but never rhombomere A, produced another group of crest cells that migrated to the frontonasal mass. In the 5- to 10-somite stage, the destinations of late-emigrating crest cells were restricted depending on their premigratory positions, i.e., the region producing crest cells migrating toward the frontonasal mass was restricted to the anterior portion of the mesencephalon, and the crest cells from the posterior portion of the mesencephalon primarily migrated to the first branchial arch, while those from the rhombomere A predominantly migrated to the trigeminal ganglion. Migration toward the frontonasal mass from the mesencephalon ceased at the earliest in the 7-somite stage, followed by termination of mesencephalic and rhombencephalic crest cell migration toward the first branchial arch at the 8-somite stage, whereas the contribution from rhombomere A to the trigeminal ganglion continued even at the 10-somite stage. This behavior suggests that both the prosencephalic and mesencephalic crest contribute to the mesenchymal cells in the frontonasal mass and also that the migration patterns of crest cells released from the prosencephalon, mesencephalon, and rhombencephalon depend on their axial level and developmental stage at initial emigration.

Animals↗

PubMed1994

Apical cell escape from the neuroepithelium and cell transformation during terminal lip fusion in the house shrew embryo.

The house shrew embryo has many cells in the ventricular lumen and on the luminal surface of the fusing terminal lip of the cephalic neural tube. The origin and fate of these cells were studied by means of light and electron microscopy, and by DiI labeling in a whole-embryo culture system. The cells appeared at stage 11A and persisted until stage 12A. Most of the cells seemed to originate from the neuroepithelium, as shown by frequent observations of epithelial cell escape and DiI labeling analysis. The cells on the luminal surface sometimes showed apoptotic features, but were not subjected to phagocytosis. Some of the escaping cells seemed to migrate to the ventral part of the prosencephalic neuropore and insert themselves into it. Others separated from the luminal surface and floated into the lumen. It seems likely that the floating cells either become autolyzed, or else change into macrophage-like cells, the latter alternative being supported by the results of DiI labeling. The macrophage-like cells actively phagocytosed the other degenerating cells and apoptotic bodies. These observations suggest that the apical escape of cells may play an important role in the remodeling of the neural fold during the terminal lip fusion, and that early neuroepithelial cells may have the potential to become cells with vigorous phagocytic activity, like macrophages.

Animals↗

PubMed1994

Uchida rat (rSey): a new mutant rat with craniofacial abnormalities resembling those of the mouse Sey mutant.

A new mutant rat with small eyes (rSey) which was found in the course of breeding Sprague-Dawley rats is described. Genetic analysis demonstrates that rSey is inherited as an autosomal dominant mutation. Heterozygotes (rSey/+) have small eyes, while homozygotes (rSey/rSey) do not develop lens and nasal placodes, resulting in lack of eyes and the nose and perinatal death. rSey does not affect any other cranial regions including the maxilla, mandible, hyoid arch and otic vesicles. The genetics and phenotype of the mutant rat closely resemble the Sey mutation in the mouse, suggesting that rSey is the rat counterpart of the Sey mouse. Tissue recombination studies indicate that ectoderm from homozygotes (rSey/rSey) never differentiates into lens tissue even if it is cultured with normal optic vesicles from rSey/+ or +/+ embryos. In contrast, lens differentiation occurs when ectoderm from rSey/+ or +/+ as well as rSey/rSey embryos. These results suggest that the failure of head ectoderm from rSey/rSey embryos to differentiate into lens results from defects in the early differentiation signaling from the neural plate or underlying mesenchyme before the optic vesicle grows out to contact the head ectoderm.

Abnormalities, Multiple↗

PubMed1994

Thimerosal induces toxic reaction in non-sensitized animals.

The effects of injection of thimerosal solution on nonsensitized animals was investigated. Intrafootpad injection of thimerosal solution in nonsensitized mice resulted in a swelling response which peaked 1 h after injection and lasted for more than 24 h. Histopathological examination showed that there were severe edema and infiltration of polymorphonuclear neutrophils at the site of injection. An increased vascular permeability was observed after cutaneous injection of thimerosal solution on the back of nonsensitized rats. Since mercuric chloride and methyl mercury induced severer reactions, and thiosalicylic acid had no effect, mercury contained in thimerosal would have caused the reactions observed in this study. These results suggest that part of these hypersensitivity reactions against thimerosal observed among patients were possibly induced by the toxic effect of thimerosal. Therefore, thimerosal contained as a preservative in vaccine may augment the side-effects of the vaccination.

Animals↗

PubMed1994

Analysis of the glucokinase gene promoter in Japanese subjects with noninsulin-dependent diabetes mellitus.

Glucokinase plays an important role in glucose metabolism in pancreatic beta-cells and liver. Recently, several mutations responsible for noninsulin-dependent diabetes mellitus (NIDDM) have been identified within the coding regions of the glucokinase gene. We screened the promoter regions using polymerase chain reaction followed by single strand conformation polymorphisms in 240 Japanese NIDDM and 111 control subjects. In the beta-cell promoter, two kinds of sequence variations were detected. One variation, in which 2 nucleotides at position -282 (C-->T) plus -194 (A-->G) were changed simultaneously, was found in 23 NIDDM (9.6%) and 12 control (10.8%) subjects. The other variation [e.g. -30 (G-->A)] was identified in 87 NIDDM (36.3%) and 40 control (36.0%) subjects. In the liver promoter, in addition to the -603 (G-->T) substitution in 1 NIDDM (0.4%) and 2 control (1.8%) subjects, the -120 (G-->T) substitution in 1 control (0.9%) subject was found. However, there were no differences in these allele frequencies between NIDDM and control subjects. We conclude that the prevalence of mutations in the promoter of the glucokinase gene responsible for NIDDM is rare among Japanese patients.

Adolescent↗

PubMed1994

CD4+ CD8+ granular lymphocytic leukemia arising in a patient with acute myeloblastic leukemia.

A 59-year-old woman who had an 8-year history of acute myeloblastic leukemia (AML) developed granular lymphocytic leukemia (GLL). She had a small number of granular lymphocytes (GL) in her bone marrow (BM) at the onset of AML. The GL increased during complete remission (CR) of AML, but not at the relapse. During the third CR state of AML, GL increased to 4.0 x 10(9)/l in the peripheral blood (PB). The GL were T-cell receptor (TCR) alpha beta+ T cells and expressed both CD4 and CD8 antigens. Rearrangements of TCR beta and gamma chain genes were detected in the peripheral blood mononuclear cells (PBMNC), confirming that this patient had GLL. The PBMNC from the patient responded weakly to PHA or ConA, yet they responded to her own bone marrow mononuclear cells (BMMNC) or CD4-depleted BMMNC that contained AML cells stronger than her own PBMNC or normal PBMNC. These observations suggest that monoclonal proliferation of GL developed after the reactive proliferation of GL in response to AML cells.

CD4-Positive T-Lymphocytes↗

PubMed1994

[An adult case of congenital myopathy--coexistence of nemaline rods and core-like structures].

A 42-year-old female complained of exertional dyspnea and sleep disturbance. Her face was elongated longitudinally and the hard palate was narrow and high-arched. She has slender musculature and kyphoscoliosis. She was dysphonic and could not walk on her heels. Muscles in the face, upper arm, pelvic girdle and thigh were atrophic. Muscle weakness was detected in the neck, tibialis anterior, ilipsoas and other hip muscles, and ranged between 3- and 4 by the manual muscle testing. Electromyography showed definite myogenic abnormalities in all the muscle examined. No abnormality was found on the routine examination of blood, as was the motor and sensory nerve conduction velocity. Her vital capacity was 0.91 L, i.e., 35% of the expected value, suggesting a severe restrictive respiration. The arterial blood gas analysis revealed hypoxia, hypercapnia and desaturation. The blood gas data worsened when she was asleep, because of increased hypoventilation. Muscle biopsy of the biceps brachii showed a marked variation in the muscle fiber size. The type 1 muscle fiber was predominant. Many fibers contained nemaline rods and/or core-like structures. Some fibers contained both nemaline and core-like structures. This core-like structures were not stained with NADH-TR and ATPase reactions, and about 40-100 microns in the longitudinal extension. In this context, typical central cores have not been observed in the present case. No association of nemaline rods and core-like structures in the same muscle fiber has been reported, although a close relationship of the two structures has been suggested.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Oligopeptides of three to five residues derived from uveitopathogenic sites of retinal S-antigen induce experimental autoimmune uveitis (EAU) in Lewis rats.

We have previously reported that microbial peptides having 3 to 6 amino acid sequence homology with uveitopathogenic peptide of retinal S-antigen (S-Ag) are capable of inducing experimental autoimmune uveitis (EAU) in Lewis rats and subhuman primates. T-cells obtained from animals immunized with these microbial peptides proliferate when stimulated with S-Ag peptide in culture and vice versa. We were interested to know whether these 3 to 6 identical amino acid residues by themselves were sufficient to induce EAU in susceptible animals under optimal conditions. For this purpose we have determined the response of synthetic oligopeptides of 3 to 18 amino acid residues for their ability to indice EAU. Here, we report that small synthetic oligopeptides of 3 to 5 amino acid residues of the two uveitopathogenic peptides of S-Ag induced EAU in Lewis rats, although with a higher dose (2000 micrograms/rat) than that of the larger peptides (50 micrograms/rat). These results define the core sequences in the uveitopathogenic peptides of retinal S-Ag.

Amino Acid Sequence↗

PubMed1993

Immunization with recombinant Escherichia coli expressing retinal S-antigen-induced experimental autoimmune uveitis (EAU) in Lewis rats.

Previously we have reported that microbial proteins having sequence homology with uveito-pathogenic peptide (peptide M) of retinal S-antigen (S-Ag) induced experimental autoimmune uveitis (EAU) in Lewis rats and subhuman primates. In order to evaluate the role of natural microbial infections in causing autoimmune diseases we have constructed a recombinant Escherichia coli expressing retinal S-Ag when injected it into Lewis rats which developed EAU. Control animals immunized with E. coli JM105 transfected with only plasmid DNA did not induce EAU. Similarly, baker's yeast (Saccharomyces cerevisiae), which has six amino acid residues in histone H3 identical with peptide M of S-Ag, induced EAU when injected into rats. Lymph node cells of rats immunized with recombinant E. coli or with the yeast show significant proliferative responses against peptide G and peptide M of S-Ag, respectively. The animals immunized with recombinant E. coli also produced antibody to S-Ag.

Animals↗

PubMed1993

Studies on the toxicities of aluminium hydroxide and calcium phosphate as immunological adjuvants for vaccines.

Aluminium hydroxide (Al) and calcium phosphate (Ca) have been used for many years as immunological adjuvants for biologicals. We investigated the toxic effects of both adjuvants with different physical properties. Al-gel elicited vascular permeability-increasing and toxic effects to macrophages (M phi), while its haemolytic effect was weak. Ca-gel elicited a significantly stronger haemolytic effect, but no other toxic effect. Incubation of M phi or polymorphonuclear leucocytes with Al-suspension resulted in the largest release of lactate dehydrogenase. Ca-suspension caused haemolysis of about 50% of that caused by Ca-gel.

Adjuvants, Immunologic↗

PubMed1993

Perirenal hematomas caused by SWL with EDAP LT-01 lithotripter.

A total of 419 calculi in the upper urinary tract of 402 patients were treated by SWL with the EDAP LT-01 lithotripter from July 1988 to September 1989. Subcapsular hematomas resulted in 17 kidneys of 16 patients, an incidence of 4.1%. On CT scan, fractures with subcapsular hematomas were observed in nine kidneys, and a retroperitoneal hematoma was observed in one patient. There was no significant difference in stone location and size, grade of hydronephrosis, number of shock waves, applied energy, or post-treatment fever between the groups with and without hematomas. However, the hematoma group revealed significantly (P < 0.01) higher incidences of pretreatment hypertension (> 160/95 mm Hg) and use of antiplatelet agents. It is difficult to detect some disorders of blood coagulation in ordinary laboratory studies in patients receiving low dosages of antiplatelet agents; and many drugs including analgesic and anti-inflammatory agents, calcium antagonists, coronary vasodilators, antiplatelet agents, beta-blockers, and lipid-regulating agents have antiplatelet actions. Therefore, particular care should be taken in SWL when a patient is using those drugs.

Adolescent↗

PubMed1993

Sequence variations of the glucokinase gene in Japanese subjects with NIDDM.

Mutations in the glucokinase gene have been identified recently in patients with maturity-onset diabetes of the young, a subtype of NIDDM. The proposed role of glucokinase as a glucose sensor, combined with the low insulin response to glucose found in most Japanese with NIDDM, prompted us to speculate that mutations in the glucokinase gene might be one of the major causes of NIDDM in Japanese subjects. To determine the prevalence of mutations and sequence variations in the glucokinase gene, we screened all 12 exons of the glucokinase gene, including exon/intron junctions, by polymerase chain reaction followed by single-strand conformation polymorphism in 209 Japanese NIDDM subjects. In addition to the mutation in exon 7, which substituted Arg (AGG) for Gly (GGG) at codon 261 (10), a silent mutation of Pro (CCC-->CCG) in exon 4 at codon 145 and several new sequence variations in intervening sequences and the 5'-untranslated region of exon 1 beta (beta-cell-specific exon 1) were identified. Because we identified only one subject who had a structurally abnormal glucokinase molecule, we conclude that the prevalence of structural mutations in the glucokinase gene responsible for NIDDM appears to be rare among Japanese patients. To our knowledge, this is the first thorough study describing the ethnic prevalence of mutations and sequence variations in the glucokinase gene in NIDDM.

Adolescent↗

PubMed1993

[Preoperative evaluation of malignant potential in esophageal carcinoma by nuclear DNA contents].

Employing surgically resected specimens from patients without preoperative radiation therapy, we measured the nuclear DNA contents in order to evaluate the malignant potential of esophageal carcinoma. The association of the DNA index (DI) > or = 1.7 and the intratumoral DNA heterogeneity of biopsy specimens from patients with or without preoperative radiotherapy was also analyzed in relation to problems related to preoperative evaluation of nuclear DNA contents using biopsy specimens and the influence of irradiation on nuclear DNA contents. Esophageal carcinomas in 128 cases were studied. Nuclear DNA content was measured for biopsy specimens as well as surgically resected tumors by flow cytometry according to the method of Hedley and colleagues. HET was found in 42% of surgically resected specimens, but in only 18% of biopsy specimens. In 90% of cases, dominant DI of the resected tumor was also found in the biopsy specimens. Cases of DI > or = 1.7 showed a poorer prognosis than those with DI < 1.7 in cases with preoperative radiotherapy (p < 0.05) as well as in those without it. These results indicated that DI can be an indicator for highly malignant potential of esophageal carcinoma when measuring nuclear DNA contents using not only biopsy specimens but also specimens from irradiated cases.

Cell Division↗