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Biomedical subjects

K Abe

Publications and source records attributed to K Abe.

At least 973 records · Page 54Linked to original sources

A water channel closely related to rat brain aquaporin 4 is expressed in acid- and pepsinogen-secretory cells of human stomach.

We isolated a cDNA clone encoding a water channel protein, aquaporin ( AQP), from human stomach. The encoded protein consisted of 323 amino acid residues, containing six putative transmembrane domains. The protein was designated human aquaporin 4 (hAQP4) because of its 94% sequence similarity to rat brain AQP4. Expression of hAQP4 cRNA in Xenopus oocytes resulted in a significant increase in osmotic water permeability, indicating that this protein functions as a water channel. Northern blot analysis demonstrated a strong signal of hAQP4 mRNA in brain, lung, and skeletal muscle as well as in stomach. Immunohistochemical experiments with human stomach tissues showed that hAQP4 as a protein is expressed mainly in cells located in the glandular portion of the fundic mucosa. These include chief cells which secrete pepsinogen and parietal cells which secrete hydrochloric acid. These results strongly indicate that hAQP4 is a principal factor involved in the osmotic regulation of pepsinogen and acid secretion in the stomach.

Amino Acid Sequence↗

A novel two-base mutation in the Cu/Zn superoxide dismutase gene associated with familial amyotrophic lateral sclerosis in Japan.

We have identified a novel two-base mutation in exon 1 of the Cu/Zn superoxide dismutase (SOD1) gene (TGC to TTT), which resulted in Cys6 to Phe substitution in a Japanese family with amyotrophic lateral sclerosis (ALS). This is the first case of familial ALS-associated two-base change of the SOD1 gene. Similar to several mutations in exon 1 of the SOD1 gene such as Ala4 to Val, Ala4 to Thr and Val14 to Met, affected members of the present family showed a rapid progression of motor dysfunction. Although Ala4, Cys6 and Val7 reside in the middle of the first beta-strand of the SOD1, a family with a mutation of Val7 to Glu associates with slow progression of the disease. These findings suggest that clinical courses are variable with each mutation, even in the same exon.

Amino Acid Sequence↗

Differential role of nitric oxide in long-term potentiation in the medial and lateral amygdala.

The effects of nitric oxide (NO) donors on the induction of long-term potentiation in the amygdala were investigated using rat brain slice preparations in vitro. In the medial amygdala synapses, sodium nitroprusside (10 microM) and hydroxylamine (100 microM), when applied together with a weak tetanic stimulation, significantly facilitated the induction of long-term potentiation. The NO donors showed no effect in the lateral amygdala synapses. These results suggest that NO plays a role in facilitating the induction of long-term potentiation in the medial amygdala but not in the lateral amygdala.

Amygdala↗

Exchange of aspartate and alanine. Mechanism for development of a proton-motive force in bacteria.

We examined the idea that aspartate metabolism by Lactobacillus subsp. M3 is organized as a proton-motive metabolic cycle by using reconstitution to monitor the activity of the carrier, termed AspT, expected to carry out the electrogenic exchange of precursor (aspartate) and product (alanine). Membranes of Lactobacillus subsp. M3 were extracted with 1.25% octyl glucoside in the presence of 0. 4% Escherichia coli phospholipid and 20% glycerol. The extracts were then used to prepare proteoliposomes loaded with either aspartate or alanine. Aspartate-loaded proteoliposomes accumulated external [3H]aspartate by exchange with internal substrate; this homologous self-exchange (Kt = 0.4 mm) was insensitive to potassium or proton ionophores and was unaffected by the presence or absence of Na+, K+, or Mg2+. Alanine-loaded proteoliposomes also took up [3H]aspartate in a heterologous antiport reaction that was stimulated or inhibited by an inside-positive or inside-negative membrane potential, respectively. Several lines of evidence suggest that these homologous and heterologous exchange reactions were catalyzed by the same functional unit. Thus, [3H]aspartate taken up by AspT during self-exchange was released by a delayed addition of alanine. In addition, the spontaneous loss of AspT activity that occurs when a detergent extract is held at 37 degrees C prior to reconstitution was prevented by the presence of either aspartate (KD(aspartate) = 0.3 mm) or alanine (KD(alanine) > or = 10 mm), indicating that both substrates interact directly with AspT. These findings are consistent with operation of a proton-motive metabolic cycle during aspartate metabolism by Lactobacillus subsp. M3.

Adenosine Triphosphate↗

Molecular cloning and functional expression of the alpha1A-adrenoceptor of Medaka fish, Oryzias latipes.

A genomic DNA encoding a subtype adrenoceptor (AR) was cloned from Medaka fish, Oryzias latipes, using an oligonucleotide probe corresponding to the consensus sequence of mammalian alpha-AR and beta-AR. The gene spans at least 9kbp, and the coding region consists of two exons split by an intron of 7.2 kbp located at the same position as those of mammalian alpha1B-AR genes. The gene encodes 470 amino acid residues, the sequence of which shows the highest similarity to that of mammalian alpha1A-AR (61%) and significant but lower similarities to other alpha-AR and beta-AR proteins (31-45%), indicating that the gene encodes a Medaka homolog of alpha1A-AR. To characterize the encoded protein, the mRNA was synthesized in vitro and injected into Xenopus oocytes. As a result, the oocytes responded to 100 nM epinephrine evoking a Ca2 + -dependent C1- current in the order of microamperes, which was not observed for oocytes injected with water alone. The response was reversibly inhibited by an alpha1-selective antagonist, WB4101 (2-[2,6-dimethoxphenoxyethyl]aminomethyl)-1,4-benzodioxane). Similar experiments using several adrenergic agonists revealed that Medaka alpha1A-AR responds to the following agonists in the order: epinephrine > or = (-)norepinephrine > oxymetazoline > or = methoxamine, which is similar to the responses of rat alpha1A receptor expressed in COS cells. The results indicate that fish contains adrenoceptor systems similar to those of mammals in terms of primary structure and pharmacological properties.

Amino Acid Sequence↗

The possible role of hydrogen sulfide as an endogenous neuromodulator.

Hydrogen sulfide (H2S), which is well known as a toxic gas, is produced endogenously from L-cysteine in mammalian tissues. H2S is present at relatively high levels in the brain, suggesting that it has a physiological function. Two other gases, nitric oxide and carbon monoxide, are also endogenously produced and have been proposed as neuronal messengers in the brain. In this work we show the following: (1) an H2S-producing enzyme, cystathionine beta-synthase (CBS), is highly expressed in the hippocampus; (2) CBS inhibitors hydroxylamine and amino-oxyacetate suppress the production of brain H2S; and (3) a CBS activator, S-adenosyl-L-methionine, enhances H2S production, indicating that CBS contributes to the production of endogenous H2S. We also show that physiological concentrations of H2S selectively enhance NMDA receptor-mediated responses and facilitate the induction of hippocampal long-term potentiation. These observations suggest that endogenous H2S functions as a neuromodulator in the brain.

Aminooxyacetic Acid↗

Effects of indium and iron ions on in vitro calcium phosphate precipitation and crystallinity.

The elution characteristics of indium and iron ions from six kinds of dental casting alloys were studied in vitro. A certain amount of indium (0.01-1.70 mg/cm2) was solubilized from the surface of only one prosthetic semiprecious brand (Miro Bright) in either 1% lactic acid or 0.05% hydrochloric acid solutions. The elution of iron was below the detection limit or < 0.01 mg/cm2. We also studied the stimulatory effects of indium and ferric ions on the calcium phosphate precipitation in the absence and presence of an inhibitor (phosvitin, a phosphoprotein purified from egg yolks). Indium and ferric ions promoted the reaction, and their stimulatory effects were stronger than the inhibitory effects of phosvitin (250 micrograms/ml). These facts suggest that indium, but not iron, could be eluted into the mouth, and that the eluted indium may stimulate the formation of oral calcium phosphate precipitates, counteracting the inhibition by saliva-derived phosphoproteins. The effects of these metal ions on calcium phosphate precipitates were also studied using both X-ray diffractometry and infrared spectrophotometry. It was shown that both indium and ferric ions decreased the grade of crystallinity of the calcium phosphate precipitates (hydroxyapatite).

Chelating Agents↗

The clinical phenotype of two missense mutations in the presenilin I gene in Japanese patients.

We report the clinical and neuropathologic phenotypes associated with two different missense mutations in the presenilin 1 (PS-1) gene in Japanese patients with early-onset familial Alzheimer's disease (FAD). In the AM/JPN1 pedigree a missense mutation (C-->T) was found at nucleotide 1102, which is predicted to cause an alanine-to-valine missense substitution at codon 260. In this family, the disease had a mean age of onset of 40.3 years and an indolent course (range, 8-19 years). Neuropathologic studies in 3 members of this pedigree showed widespread senile plaques, neurofibrillary tangles, and neuronal loss, as well as abundant perivascular subpial amyloid deposits in the Virchow-Robin spaces and the presence of Pick-like intraneuronal inclusions in the dentate gyrus. In the second pedigree, transmitting a C-->T nucleotide substitution at position 1027, leading to the missense mutation of alanine to valine at codon 285, the disease had a later onset (mean, 51 years) but a more rapid course. Comparison of the disease phenotypes associated with other missense mutations in exon 9 of PS-1 reveals no clinical or pathological phenotype, which uniquely distinguishes Alzheimer's disease associated with PS-1 mutations from other forms of early-onset FAD, implying that direct mutation screening is required to identify these cases.

Adult↗

Transgenic rice established to express corn cystatin exhibits strong inhibitory activity against insect gut proteinases.

Corn cystatin (CC), a phytocystatin, shows a wide inhibitory spectrum against various cysteine proteinases. We produced transgenic rice plants by introducing CC cDNA under CaMV 35S promoter as a first step to obtain a rice plant with insecticidal activity. This attempt was based on the observation that many insect pests, especially Coleoptera, have cysteine proteinases, probably digestive enzymes, and also that oryzacystatin, an intrinsic rice cystatin, shows a narrow inhibition spectrum and is present in ordinary rice seeds in insufficient amounts to inhibit the cysteine proteinases of rice insect pests. The transgenic rice plants generated contained high levels of CC mRNA and CC protein in both seeds and leaves, the CC protein content of the seed reaching ca. 2% of the total heat soluble protein. We also recovered CC activity from seeds and found that the CC fraction efficiently inhibited both papain and cathepsin H, whereas the corresponding fraction from non-transformed rice seeds showed much lower or undetectable inhibitory activities against these cysteine proteinases. Furthermore, CC prepared from transgenic rice plants showed potent inhibitory activity against proteinases that occur in the gut of the insect pest, Sitophilus zeamais.

Animals↗

Hemiparkinsonism following haemorrhage in the contralateral substantia nigra.

We report a patient with right hemiparkinsonism following haemorrhage in the left substantia nigra. The hemiparkinsonism responded to treatment with trihexyphenidyl hydrochloride and deteriorated after temporary discontinuation of the drug. Single photon emission computed tomography using technetium 99m d, l-hexamethylpropyleneamine oxide showed reduced uptake in the left putamen, globus pallidus and thalamus.

Cerebral Hemorrhage↗

Lazy gene (la) responsible for both an agravitropism of seedlings and lazy habit of tiller growth in rice (Oryza sativa L.).

Using an isogenic line of rice having lazy gene (la), we studied the correlation between the agravitropic response at the young seedling stage and the lazy habit (prostrate growth of tillers) at the more advanced stage of growth. In this study, it was found that both agravitropism and lazy habit were controlled by the single recessive la gene. That is, F2 segregants of Kamenoo x lazy-Kamenoo, which had an agravitropic response at their young seedling stage, showed a lazy habit of growth in the more advanced stage of vegetative growth. On the other hand, seedlings that showed normal gravitropic curvature at their early stage of growth had an upright growth in the mature stage.

Genes, Plant↗

Down-regulation of S-adenosylhomocysteine hydrolase in the active methyl transfer system in the brain of genetically epileptic El mice.

To study the role of cerebral methylation in epileptogenesis, we investigated the active methyl transfer pathway in the brain of genetically epileptic El mice. We examined S-adenosylhomocysteine (AdoHcy) hydrolase activity (by high performance liquid chromatography), the corresponding mRNA levels (by competitive reverse transcription-polymerase chain reaction), as well as S-adenosylmethionine (AdoMet) and AdoHcy levels in epileptic El and non-epileptic control ddY mice. The level of AdoHcy, a potent feedback inhibitor in the methyl transfer system, was relatively high throughout growth, particularly in 15 week old El mice where it was increased approximately 20% compared to control ddY mice. AdoHcy hydrolase activity in the El mice brain did not increase during growth, which was confirmed by the finding that mRNA synthesis from the hydrolase gene behaved likewise. In contrast, ddY mice exhibited a gradual increase in the mRNA synthesis up to three fold and 20% increase in the enzyme activity at 15 weeks of age compared to those of El mice in which the seizure frequency was 100%. The levels of AdoMet, a versatile methyl donor, did not change throughout growth. We concluded that the down-regulation of AdoHcy hydrolase results in the accumulation of AdoHcy, possibly inducing an unstable state including seizures in the El mouse brain. El mice predisposed to epilepsy may be characterized by disordered feedback regulation of the AdoMet-dependent methyl transfer pathway.

Adenosylhomocysteinase↗