Biomedical subjects

M Araki

Publications and source records attributed to M Araki.

At least 73 records · Page 4Linked to original sources

PubMed1998

Localization of Six4/AREC3 in the developing mouse retina; implications in mammalian retinal development.

The Six4/AREC3 gene was originally isolated as a regulatory factor which bound to the positive regulatory region of the Na, K-ATPase alpha 1 subunit. It is a murine homologue of the Drosophila sine oculis (so) gene, which is essential for the development of the entire insect visual system. In this study, we attempted to determine the localization of the Six4/AREC3 gene product in the developing mouse retina in order to examine its role in retinal cell differentiation. Immunohistochemistry with anti-SIX4/AREC3 and anti-Na, K-ATPase alpha 1 subunit antisera was performed on developing mouse retinas, and immunoblotting analysis with anti-SIX4/AREC3 was also performed. The localization of Six4-like immunoreactivity (Six4-LI) showed a temporally regulated pattern: During embryonic development, Six4-LI was found in the nuclei of cells located at the inner neuroblastic layer of the retina as early as on ED12, nearly corresponding to the onset of retinal cell differentiation. In the PD1 retina, Six4-LI was observed in the nuclei of the ganglion cells, and increased its intensity until PD4, and thereafter kept its intensity until PD7 when Six4-LI was often found in the cytoplasm. On PD4, the presumptive amacrine cells found in the inner portion of the inner nuclear layer appeared to be immunostained in their nuclei. On PD7, the presumptive bipolar cells located in the outer portion were immunostained in the nuclei. After that, Six4-LI gradually decreased, and in the mature retina no detectable Six4-LI was observed in the nuclei. This pattern of Six4-LI localization during retinal development seemed to correlate with retinal cell differentiation, but did not correlate with the distribution pattern of Na, K-ATPase alpha 1 subunit protein-like immunoreactivity. These results suggest that the Six4 gene may play a role in the differentiation of neural retinal cells during mouse retinal development, rather than regulating the expression of the Na, K-ATPase alpha 1 subunit gene.

Animals↗

PubMed1998

Microwave Spectrum of the SD+3 Ion: Molecular Structure.

The J = 1-0 to 4-3 spectral lines of SD+3 were measured in the 152-610 GHz region using a source-modulated microwave spectrometer. The SD+3 ion was generated in a free space absorption cell by a hollow-cathode discharge in a gas mixture of D2S and D2. The rotational constant B0 and the centrifugal distortion constants DJ and DJK were determined from the measured frequencies. A vibration-rotation analysis was carried out and the rz structures of SH+3 and SD+3 were derived from their zero point averaged rotational constants, expressed as SH+3: rz = 1.36512(22) Å and thetaz = 94.098(26) degrees, and SD+3: rz = 1.36086(16) Å and thetaz = 94.1211(195) degrees, where the difference between thetaz(HSH) and thetaz(DSD) was assumed to be the same as that between thetaz(HPH) of PH3 and thetaz(DPD) of PD3. From the shift between the rz structures of SH+3 and SD+3, the re structure of SH+3 was estimated to be re = 1.35001(113) Å, thetae = 94.181(135) degrees. Copyright 1998 Academic Press.

Journal Article↗

PubMed1998

Region-specific expression of murine Hox genes implies the Hox code-mediated patterning of the digestive tract.

BACKGROUND: Hox genes encode transcription factors which are involved in the establishment of regional identities along the anteroposterior (AP) body axis. To elucidate the AP patterning of the digestive tract, we have systematically examined the expression patterns of Hox genes belonging to paralogue groups 6, 7, 8 and 9 by whole-mount in situ hybridization and by section in situ hybridization analyses. RESULTS: The expression patterns of these genes showed co-linearity along the wall of the digestive tract, thereby yielding the Hox code of the gut. The expression boundaries of the Hox genes at later stages (12.5 d.p.c.) corresponded to the morphological boundaries of individual gut subdomains. CONCLUSIONS: The visceral mesoderm-restricted expression suggested that the Hox code primarily functions in the mesenchymal specification which eventually leads to the regional differentiation of gut subdomains as the result of epithelial-mesenchymal interactions. Overlapping expression patterns were found among the paralogous Hox genes, indicating that the paralogues may have redundant functions in the specification of the gut.

Animals↗

PubMed1998

Early embryonic interaction of retinal pigment epithelium and mesenchymal tissue induces conversion of pigment epithelium to neural retinal fate in the silver mutation of the Japanese quail.

The neural retina and retinal pigment epithelium (RPE) diverge from the optic vesicle during early embryonic development. They originate from different portions of the optic vesicle, the more distal part developing as the neural retina and the proximal part as RPE. As the distal part appears to make contact with the epidermis and the proximal part faces mesenchymal tissues, these two portions would encounter different environmental signals. In the present study, an attempt has been made to investigate the significance of interactions between the RPE and mesenchymal tissues that derive from neural crest cells, using a unique quail mutant silver (B/B) as the experimental model. The silver mutation is considered to affect neural crest-derived tissues, including the epidermal melanocytes. The homozygotes of the silver mutation have abnormal eyes, with double neural retinal layers, as a result of aberrant differentiation of RPE to form a new neural retina. Retinal pigment epithelium was removed from early embryonic eyes (before the process began) and cultured to see whether it expressed any phenotype characteristic of neural retinal cells. When RPE of the B/B mutant was cultured with surrounding mesenchymal tissue, neural retinal cells were differentiated that expressed markers of amacrine, cone or rod cells. When isolated RPE of the B/B mutant was cultured alone, it acquired pigmentation and did not show any property characteristic of neural retinal cells. The RPE of wild type quail always differentiated to pigment epithelial cells. In the presence of either acidic fibroblast growth factor (aFGF) or basic FGF (bFGF), the RPE of the B/B mutant differentiated to neural retinal cells in the absence of mesenchymal tissue, but the RPE of wild type embryos only did so in the presence of 10-40 times as much aFGF or bFGF These observations indicate that genes responsible for the B/B mutation are expressed in the RPE as well as in those cells that have a role in the differentiation of neural crest cells. They further suggest that development of the neural retina and RPE is regulated by some soluble factor(s) that is derived from or localized in the surrounding embryonic mesenchyme and other ocular tissues, and that FGF may be among possible candidates.

Animals↗

PubMed1998

Evidence for involvement of two isoforms of Syk protein-tyrosine kinase in signal transduction through the high affinity IgE receptor on rat basophilic leukemia cells.

Recent evidence suggests a critical role for Syk in mast cell activation upon high affinity IgE receptor (FcepsilonRI) aggregation. A rat basophilic leukemia cell line, RBL-2H3, expresses similar levels of two Syk isoforms that differ with respect to the presence of a 23-amino acid insert within the "linker" region located between the second Src homology 2 and the catalytic domain. Although they exhibit comparable intrinsic enzymatic activity, functional differences between the two isoforms are unknown. Here we report that the deleted Syk isoform can mediate signal transduction in RBL-2H3 cells. Aggregation of chimeric kinase, consisting of either form of Syk fused to the transmembrane and extracellular domains of guinea pig type II IgG Fc receptor, on RBL transfectants resulted in degranulation, release of leukotrienes, and enhanced gene expression of tumor necrosis factor-alpha. The chimeras as well as phospholipase C-gamma1 and Vav became tyrosine-phosphorylated upon aggregation of chimeras. We also found that both Syk isoforms from transiently transfected COS-7 cells were capable of binding to phosphorylated FcepsilonRI, and their kinase activities were similarly up-regulated in the presence of tyrosine-phosphorylated synthetic peptides based on the sequence of the gamma subunit of FcepsilonRI. Thus, these results establish that both isoforms of Syk can mediate signal transduction in mast cells and suggest that the 23-amino acid insert in the linker region of Syk may not be obligatory for FcepsilonRI signaling.

Animals↗

PubMed1998

A family with Liddle's syndrome caused by a new missense mutation in the beta subunit of the epithelial sodium channel.

Liddle's syndrome is an autosomal dominant form of salt sensitive hypertension caused by mutations in the beta or gamma subunit of the epithelial sodium channel. Systematic mutagenesis studies revealed that a conserved PPPXY sequence (PY motif) of the C-terminus of the alpha, beta, or gamma subunits might be involved in the regulation of the channel activity. However, only two missense mutations in the PY motif of the beta subunit have been reported to cause Liddle's syndrome. We sequenced the C-termini of the beta and gamma subunits of the epithelial sodium channel in a Japanese family clinically diagnosed as having Liddle's syndrome and found a new missense mutation in the PY motif of the beta subunit, P615S. Expression studies with P615S mutant in Xenopus oocytes resulted in an about 3-fold increase in the amiloride-sensitive sodium current compared to the wild type (p = 0.001). These findings provide further clinical evidence for the hypothesis that a conserved PY motif may be critically important for the regulation of the epithelial sodium channel.

Adult↗

PubMed1998

Use of temporary vena cava filters after catheter-directed fragmentation and thrombolysis in patients with acute pulmonary thromboembolism.

Acute pulmonary thromboembolism is a life-threatening disease and in almost all cases originates from deep venous thrombosis in the proximal deep venous system of the legs. In order to prevent further episodes of thromboembolism in 2 patients with acute pulmonary thromboembolism, we inserted an Antheor temporary vena cava filter after catheter-directed fragmentation and thrombolysis. No complications occurred during the insertion of the filters and our results suggest that this filter device may be clinically safe and effective for temporary protection against pulmonary thromboembolism.

Aged↗

PubMed1998

Spinal meningeal melanocytoma presenting with superficial siderosis of the central nervous system. Case report and review of the literature.

Meningeal melanocytoma is a benign melanocytic tumor that originates most frequently from the melanocytes in the posterior fossa or along the spinal cord. This tumor generally occurs as an extraaxial mass that compresses adjacent neural structures to produce various neurological signs. The authors describe an unusual case in which a patient with a meningeal melanocytoma located at the thoracic spinal cord presented with superficial siderosis of the central nervous system (CNS). Extensive neuroradiological studies identified the presence of a spinal cord tumor, and postsurgical histological examination revealed the meningeal melanocytoma as a bleeding source. After surgery, lumbar puncture demonstrated normalization of the patient's cerebrospinal fluid; however, no neurological improvement occurred. The neurological deficits seem irreversible. Meningeal melanocytoma is biologically benign and can be cured by complete surgical resection; therefore, this tumor should be included in the differential diagnosis of pigmented lesions of the CNS. The authors reviewed 14 cases of well-documented meningeal melanocytoma in the literature and discuss the clinical, radiological, and pathological features of the present case to emphasize the importance of early diagnosis and identification of the source of bleeding in patients with superficial siderosis.

Brain Diseases↗

PubMed1997

Diffusible factors produced by cultured neural retinal cells enhance in vitro differentiation of pineal cone photoreceptors of developing quail embryos.

The avian pineal is a photoreceptive organ and is believed to function as a circadian clock. Avian pineal cells are secretory rudimentary photoreceptors, and previous studies have demonstrated that there are two types of photoreceptors in developing quail pineals, one of which is rhodopsin-like immunoreactive and the other iodopsin-like immunoreactive. Much larger number of rhodopsin-like immunoreactive cells than of iodopsin-like immunoreactive cells were found in quail pineals, both in vivo and in vitro. In the present study we co-cultured pineal cells of embryonic quails with retinal cells but separated the two with a bio-membrane filter. We found that diffusible material produced by the cultured retinal cells intensely promotes the appearance of pineal iodopsin-like immunoreactive cells in vitro. This effect of retina-derived factor(s) is cell-type specific, since there is no effect on the differentiation of pineal rhodopsin-like immunoreactive cells. Retinal cell cultures had much more intensive iodopsin-promoting effect than other embryonic brain cultures such as cerebral cell cultures. The production of the retinal factor(s) seems to be developmentally regulated, since retinal cells from older embryos (E13 and older) did not have such effects. The factor(s) possibly act on pineal precursor cells by stimulating the expression of the iodopsin-like immunoreactive phenotype. Preliminary characterization of conditioned medium obtained from cultured retinal cells shows that the factor is a stable polypeptide, probably of low molecular weight. The pineal-retina culture system will provide a good experimental system to analyze the effect of extrinsic environments on cell differentiation.

Animals↗

PubMed1997

The hydrophobic region of signal peptides is involved in the interaction with membrane-bound SecA.

The positive charges of signal peptides are important for the interaction with SecA, a translocation ATPase. To examine whether or not the hydrophobic region of signal peptides also interacts with SecA, we constructed model preproteins, proOmpF-Lpps, possessing no positively charged amino acid residues at the amino-terminus and different numbers of alanine/leucine residues in the hydrophobic region of signal peptides. When the hydrophobic stretch was sufficiently long, amino-terminal positively charged residues were not required for the translocation of preproteins across the cytoplasmic membrane of Escherichia coli both in vitro and in vivo. Chemical cross-linking between SecA and preproteins possessing no positively charged residues at the amino-terminus was observed only in the presence of liposomes containing acidic phospholipids. The degree of cross-linking increased as the length of the hydrophobic stretch increased irrespective of whether positively charged residues were present or not. A preprotein possessing no positively charged residues at the amino-terminus, which is competent in the presence of liposomes, competitively inhibited the cross-linking of wild-type proOmpF-Lpp with SecA under the same conditions. It is concluded that both the amino-terminal positive charges and central hydrophobic domains are involved in the interaction with SecA in the initial stage of translocation in addition to their possible roles in transmembrane movement of preproteins.

Adenosine Triphosphatases↗

PubMed1997

Chromosomal localization of the human arginase II gene and tissue distribution of its mRNA.

Liver-type arginase (arginase I) is expressed almost exclusively in the liver and catalyzes the last step of urea synthesis, whereas the nonhepatic type (arginase II) is expressed in extrahepatic tissues and is probably involved in down-regulation of nitric oxide synthesis. We isolated cDNA for human arginase II (T. Gotoh et al., 1996, FEBS Lett. 395, 119-122). Fluorescence in situ hybridization mapping and PCR mapping studies with somatic cell hybrid panels and a radiation hybrid panel localized the arginase II gene to chromosome 14q24.1-24.3. Dot-blot analysis showed that arginase II mRNA is expressed strongly in the adult human kidney and weakly in the prostate, pituitary gland, lung, liver, thyroid gland, and small intestine. The mRNA was either at very low levels or not detectable in the fetal kidney, lung, and liver. Thus, expression of the human arginase II gene is regulated both tissue-specifically and developmentally.

Adult↗

PubMed1997

Targeted integration of DNA using mutant lox sites in embryonic stem cells.

Site-directed DNA integration has been achieved by using a pair of mutant lox sites, a right element (RE) mutant lox site and a left element (LE) mutant lox site [Albertet al. (1995)Plant J., 7, 649-659], in mouse embryonic stem (ES) cells. We established ES cell lines carrying a single copy of the wild-type lox Por LE mutant lox site as a target and examined the frequency of site-specific integration of a targeting vector carrying a loxP or RE mutant lox site induced by Cre transient expression. Since our targeting vector contains a complete neo gene, random integrants can form colonies as in the case of a gene targeting event through homologous recombination. With our system, the frequency of site-specific integration via the mutant lox sites reached a maximum of 16%. In contrast, the wild-type loxP sites yielded very low frequencies (<0.5%) of site-specific integration events. This mutatedloxsystem will be useful for 'knock-in' integration of DNA in ES cells.

Animals↗

PubMed1997

An expanded histatin gene polymorphism and test of a possible disease resistant phenotype.

Histatins are small molecular weight salivary proteins that are important in the non-immune host defense system. Two frequent cis-linked coding-change mutations were previously described in exon 5 of the HIS2 gene of Blacks. The polymorphic mutant allele was termed HIS2(2) and the wild-type allele HIS2(1). We here describe two new non-coding change polymorphisms of the HIS2 gene: a deletion in intron 5 (7183-7198 del) and a C-->T mutation in exon 5 [C-->T (7104)] that characterize two new HIS2 alleles, HIS2(3) and HIS2(4) respectively. Both mutations occur on a HIS2(1) background. The HIS2(3) allele occurred only in Afro-Americans, but not in 67 Japanese, 51 Chinese and 50 Whites. Among 66 random DNA samples from Afro-Americans, frequencies of HIS2(1), HIS2(2), HIS2(3) and HIS2(4) were 0.67, 0.22, 0.05 and 0.07 respectively, with a heterozygosity of 0.45. The frequencies of the HIS2(4) allele in 50 Whites and 50 Chinese were 0.06, and 0.1 respectively. In a comparison of 60 matched saliva and DNA samples from the Afro-American population, the DNA-based mutation analysis reliably identified salivary histatin phenotypes. The salivary histatin polymorphism (inferred from PCR analysis) was used to test a biologically plausible hypothesis, that the mutant histatin phenotype (coded by the HIS2(2) allele) confers relative resistance to severe and fatal malaria. In a study of 185 Black Tanzanian subjects, there were no significant differences in HIS2(2) allelic frequencies between the various test groups: for 86 cerebral malaria subjects, 54 uncomplicated malaria subjects, and 45 combined asymptomatic parasitemia and health controls, HIS2(2) frequencies were 0.16, 0.17 and 0.17 respectively. Thus, there was no support for the hypothesis in this population.

Black People↗

PubMed1997

A newly identified membrane protein localized exclusively in intracellular organelles of neurons.

We report here cloning of the cDNA of a novel membrane protein, termed p24, which, of the eight mouse tissues tested, was found only in brain where it is localized exclusively in neurons. The cDNA encodes 196 amino acids with a molecular weight of approximately 24000. P24 contains two putative membrane spanning domains and a sequence in the hydrophilic tail homologous to the microtubule-binding domain of microtubule-associated proteins, such as TAU and MAP-2. We prepared antibodies to p24 and demonstrated that the protein is rich in nerve fibers of the cerebral cortex, anterior cerebral nuclei and hypothalamus. When neuroblastoma Neuro 2a cells were treated with retinoic acid to induce differentiation, p24 mRNA increased but the p24 protein was not detected. The protein expressed from the p24 cDNA in non-neuronal Cos-7 cells was 24 kDa in size and were localized only in lysosomes. These findings indicate that p24 is a neuron-specific membrane protein localized in intracellular organelles of highly differentiated neural cells and suggest that it may play a role in the neural organelle transport system.

Amino Acid Sequence↗

PubMed1997

Selective cleavages of tRNAPhe with secondary and tertiary structures by enediyne antitumor antibiotics.

Some enediyne antitumor antibiotics induce site-selective cleavages for yeast tRNA(Phe) with three-dimensional structure. Of special interest is the fact that tRNA(Phe) is specifically cleaved at the anticodon arm regions by C-1027 and esperamicin A1 in the presence of Mg2+ ions. Although neocarzinostatin strongly breaks tRNA(Phe) at 5'-GPu steps in the absence of magnesium ions, its cleavage ability is completely lost in the presence of 100 microM Mg2+ ions. Dynemicin A, which favors an intercalative binding, causes no strand scissions for the RNA with secondary and tertiary structures. This cutting of tRNA(Phe) may reveal that RNA as well as DNA constitutes a therapeutically relevant target for certain enediyne antitumor antibiotics.

Antibiotics, Antineoplastic↗

PubMed1997

Chronic intractable headache in a patient with Marfan's syndrome.

A 30-year-old woman with Marfan's syndrome had chronic intractable headaches and spontaneous intracranial hypotension. The pain was concentrated over the occipitonuchal region, had elements of both migraine and tension headache, and was often aggravated by postural change. Myelography showed multiple, large, lumbosacral arachnoid diverticula. Radioisotope cisternography revealed a halolike accumulation in the lumbosacral region and rapid uptake of isotope in the urinary bladder, indicating cerebrospinal fluid leakage. Epidural blood patching brought immediate relief from the positional headaches. We concluded that patients with Marfan's syndrome and undifferentiated chronic headaches should be radiologically evaluated for spinal meningeal defects.

Adult↗

PubMed1997

Effects of volatile anesthetics on the calcium ionophore A23187-mediated alterations in hepatic flow and metabolism in the perfused liver in fasted rats.

Alterations in intracellular calcium homeostasis have been implicated in heptic injury. Volatile anesthetics modulate the homeostasis of intracellular calcium. The effects of volatile anesthetics on the hemodynamic and metabolic alterations induced by the calcium ionophore A23187 were studied using isolated liver perfusion in fasted rats. The liver was isolated from 24 hr-fasted male Sprague-Dawley rats, and perfused through the portal vein at a constant pressure of 1.2 kPa in a recirculating perfusion-aeration system. Halothane, isoflurane and sevoflurane were administered at 2%, 3% and 4.4%, respectively. All volatile anesthetics maintained basal hepatic flow, reduced oxygen consumption, and transiently enhanced net lactate production. A23187 at initial concentrations of 0.8 to 3.2 microM decreased hepatic flow and oxygen consumption in a dose-dependent manner, and enhanced lactate production. All anesthetics significantly attenuated the decreases in hepatic flow and oxygen consumption after administration of A23187 at 1.6 microM. None of the anesthetics significantly influenced the A23187-induced enhancement of net lactate production. Volatile anesthetics may attenuate the hepatic vasoconstriction and oxygen debt induced by intracellular calcium overload.

Anesthetics, Inhalation↗

PubMed1997

Radiofrequency catheter ablation of an accessory pathway in dextrocardia.

A 60-year-old woman with situs inversus and paroxysmal supraventricular tachycardias utilizing an AV accessory pathway underwent successful, uncomplicated RF ablation. Using biplane fluoroscopy, accessory pathway catheter ablation in dextrocardia is as safe, easy, and useful as that for normal heart structure cases, and does not require a lengthy procedure.

Catheter Ablation↗