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Biomedical subjects

E Abe

Publications and source records attributed to E Abe.

At least 19 recordsLinked to original sources
PubMed1992

A synthetic peptide corresponding to 86-93 of the human type I IL-1 receptor binds human recombinant IL-1 (alpha and beta) and inhibits IL-1 actions in vitro and in vivo.

A synthetic peptide corresponding to 86-93 of the human type I IL-1 receptor and its analogues bound human recombinant (hr) IL-1 (alpha and beta) and inhibited dose-dependently both Con A-stimulated proliferation of mouse spleen cells and hrIL-1 beta-stimulated formation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells in rat bone marrow cell cultures. Furthermore, hrIL-1 beta-induced mouse paw edema was dose-dependently inhibited by systemic administration (ip) of the synthetic peptide. These results suggest that one of the IL-1 binding sites of the human type I IL-1 receptor comes to the region of 86-93 and the synthetic peptide having the ability to bind hrIL-1 (alpha and beta) blocks the biological activities of exogenous hrIL-1 beta and endogenous mouse IL-1.

Amino Acid Sequence↗
PubMed1992

An 11-base-pair DNA sequence motif apparently unique to the human interleukin 4 gene confers responsiveness to T-cell activation signals.

We have identified a DNA segment that confers responsiveness to antigen stimulation signals on the human interleukin (IL) 4 gene in Jurkat cells. The human IL-4 gene, of 10 kilobases, is composed of four exons and three introns. A cis-acting element (P sequence) resides in the 5' upstream region; no additional DNA segments with enhancer activity were identified in the human IL-4 gene. For further mapping purposes, a fusion promoter was constructed with the granulocyte/macrophage colony-stimulating factor basic promoter containing 60 base pairs of sequence upstream from the cap site of the mouse granulocyte/macrophage colony-stimulating factor gene and various lengths of the 5' upstream sequence of the IL-4 gene. The P sequence was located between positions -79 and -69 relative to the transcription start site of the human IL-4 gene, and this location was confirmed by base-substitution mutations. The plasmids carrying multiple copies of the P sequence showed higher responsiveness to the stimulation. The binding protein(s) that recognize the P sequence of the IL-4 gene were identified by DNA-mobility-shift assays. The binding of NF(P) (a DNA binding protein that specifically recognizes the P sequence) to the P sequence was abolished when oligonucleotides carrying base substitutions were used, indicating that the NF(P) interaction is sequence-specific and that binding specificity of the protein paralleled the sequence requirements for IL-4 expression in vivo. The P sequence does not share homology with the 5' upstream sequence of the IL-2 gene, even though surrounding sequences of the IL-4 gene share high homology with the IL-2 gene. We conclude that a different set of proteins recognize IL-2 and IL-4 genes.

Animals↗
PubMed1992

Role of vitamin D in bone resorption.

The idea that vitamin D must function at the bone site to promote bone mineralization has long existed since its discovery as an anti-rachitic agent. However, the definite evidence for this is still lacking. In contrast, much evidence has accumulated that 1 alpha,25(OH)2D3 in involved in bone resorption. 1 alpha,25(OH)2D3 tightly regulates differentiation of osteoclast progenitors into osteoclasts. Osteoclast progenitors have been thought to belong to the monocyte-macrophage lineage. 1 alpha,25(OH)2D3 greatly stimulates differentiation and activation of mononuclear phagocytes. Recent reports have indicated that differentiation of mononuclear phagocytes into osteoclasts is strictly regulated by osteoblastic cells, the process of which is also stimulated by 1 alpha,25(OH)2D3. In the differentiation of mononuclear phagocytes into osteoclasts, the target cells for 1 alpha,25(OH)2D3 appear to be osteoblastic stromal cells. Osteoblastic cells produce several proteins such as BGP, MGP, osteopontin and the third component of complement (C3) in response to the vitamin. They appear to be somehow involved in osteoclast differentiation and functions. Thus, 1 alpha,25(OH)2D3 seems to be involved in the differentiation of osteoclast progenitors into osteoclasts directly and also by an indirect mechanism involving osteoblastic cells. The precise role of osteoblastic cells in osteoclast development has to be elucidated in the future.

Animals↗
PubMed1992

Leukemia inhibitory factor/differentiation-stimulating factor (LIF/D-factor): regulation of its production and possible roles in bone metabolism.

Leukemia inhibitory factor/differentiation-stimulating factor (LIF/D-factor), expression of its mRNA, and possible roles in bone metabolism were studied in murine primary and clonal osteoblast-like cells. Local bone-resorbing factors such as IL-1, TNF alpha, and LPS strongly induced expression of LIF/D-factor mRNA in both clonal MC3T3-E1 cells and primary osteoblast-like cells. Neither parathyroid hormone nor 1 alpha,25-dihydroxyvitamin D3 stimulated expression of LIF/D-factor mRNA. LIF/D-factor per se did not stimulate expression of its own mRNA. Appreciable amounts of LIF/D-factor were detected in synovial fluids from rheumatoid arthritis (RA) patients but not in those with osteoarthritis (OA). Simultaneous treatment with LIF/D-factor, IL-1, and IL-6 at the concentrations found in synovial fluids from RA patients greatly enhanced bone resorption, though these cytokines did not stimulate bone resorption when separately applied. This suggests that LIF/D-factor produced by osteoblasts is in concert with other bone-resorbing cytokines such as IL-1 and IL-6 involved in the bone resorption seen in the joints of RA patients. LIF/D-factor specifically bound to MC3T3-E1 cells with an apparent dissociation constant of 161 pM and 1,100 binding sites/cell. LIF/D-factor dose-dependently suppressed incorporation of [3H]thymidine into MC3T3-E1 cells. In addition, it potentiated the alkaline phosphatase activity induced by retinoic acid, though LIF/D-factor alone had no effect on enzyme activity. These results suggest that LIF/D-factor is involved in not only osteoclastic bone resorption but also osteoblast differentiation in conjugation with other osteotropic factors.

Acid Phosphatase↗
PubMed1992

Reversal by 3,3',5-triido-L-thyronine of the working memory deficit, and the decrease in acetylcholine, glutamate and gamma-aminobutyric acid induced by ethylcholine aziridinium ion in mice.

The effect of 3,3',5-triiodo-L-thyronine (T3) on working memory in ethylcholine aziridinium ion (AF64A)-treated mice was studied in a delayed non-matching to sample task using a T-maze. After behavioural testing was completed, mice were killed by microwave irradiation and regional brain levels of acetylcholine, aspartate, glutamate, glutamine, glycine, taurine, and gamma-aminobutyric acid (GABA) were measured by high-performance liquid chromatography with electrochemical detection. Treatment with AF64A (7 nmol, i.c.v.) produced a deficit in working memory performance in the non-matching to sample task at 30 s delay, and decreased acetylcholine, glutamate, and GABA levels in the hippocampus, but not in the septum and cerebral cortex. Administration of T3 (0.3 mg/kg, p.o., once daily for 6 days) to AF64A-treated animals improved the deficit in working memory performance and reversed the decrease in acetylcholine, glutamate, and GABA levels in the hippocampus. These results indicate that the deficit in performance induced by AF64A can be improved by T3 administration.

Acetylcholine↗
PubMed1992

A rapid assay for neurotransmitter amino acids, aspartate, glutamate, glycine, taurine and gamma-aminobutyric acid in the brain by high-performance liquid chromatography with electrochemical detection.

For simultaneous assay of the five neurotransmitter amino acids, Asp, Glu, Gly, Tau, and GABA in brain tissues, a very rapid and simple chromatographic method using high-performance liquid chromatography with electrochemical detection in combination with o-phthalaldehyde derivatization is described. Because the present method permits the determination of these five amino acids within less than five minutes in one chromatographic run, up to 100 samples a working day can be analyzed using an autosampler. Within-run coefficients of variation for these five amino acids were less than 2% (n = 20). The quantitative detection limit was 2.5 pmol for the 5 amino acids. The present method has been applied to the measurement of the five amino acid neurotransmitter levels in several discrete brain regions of mice treated with and without electroconvulsive shock.

Amino Acids↗
PubMed1992

Effects of nefiracetam, a novel pyrrolidone derivative, on brain monoamine metabolisms in mice.

The effects of acute and chronic administration of nefiracetam, a pyrrolidone derivative, on monoaminergic neurotransmitter systems in the mouse hippocampus, frontal cortex, hypothalamus, and striatum were studied. The levels of monoamines and of their metabolites were measured by high performance liquid chromatography with electrochemical detection on the first, 7th, and 14th days after nefiracetam was given. The neurochemical effects of nefiracetam were compared with those of oxiracetam and indeloxazine. Acute administration of nefiracetam (10 mg/kg, po) and oxiracetam (10 mg/kg, po) had no effect on the levels of noradrenaline (NA), dopamine (DA), or 5-hydroxytryptamine (5-HT), or on the levels of their metabolites, 3-methoxy-4-hydroxyphenylglycol (MHPG), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA), in any of the regions examined. In contrast, a single dose of indeloxazine (10 mg/kg, po) decreased the levels of MHPG, DOPAC, and 5-HIAA in all regions examined. After chronic administration of nefiracetam (10 mg/kg, po, once daily), the levels of MHPG, DOPAC, and 5-HIAA were higher than control in all regions on the 14th day only. Oxiracetam (10 mg/kg, po, once daily) similarly increased the levels of MHPG, DOPAC, and 5-HIAA in the hippocampus, frontal cortex, and striatum, but not in the hypothalamus. Conversely, indeloxazine (10 mg/kg, po, once daily) decreased the levels of MHPG and 5-HIAA in all regions and the levels of DOPAC and HVA in the hippocampus and striatum as measured on the 7th and 14th days. These results show that nefiracetam has a delayed effect on brain monoaminergic metabolism, and that its effects are similar to those of oxiracetam, but clearly different from those of indeloxazine.

Animals↗
PubMed1992

Pharmacological properties of ceruletide in the vertical and horizontal locomotor activities of mice.

To clarify the pharmacological properties of ceruletide (CER) and cholecystokinin-octapeptide (CCK-8) with respect to vertical (VLA) and horizontal (HLA) locomotor activities of mice, effects of pretreatment with CER (0.5, 5, and 50 micrograms/kg, IP) and CCK-8 (5, 50, and 500 micrograms/kg, IP) on apomorphine (0.1 mg/kg, SC)- and clonidine (0.1 mg/kg, SC)-induced hypo-VLA and -HLA and on apomorphine (1 mg/kg, SC)-induced hyper-VLA and -HLA were examined. CER and CCK-8 had a dose-dependent inhibitory effect on VLA and HLA in intact mice. Pretreatment with CER had a biphasic effect (increase and decrease) on apomorphine- and clonidine-induced hypo-VLA, as well as an effect on apomorphine-induced hypo-HLA, a decreased effect on clonidine-induced hypo-HLA, and a decreased effect on apomorphine-induced hyper-VLA and -HLA. On the other hand, pretreatment with CCK-8 had no effect on apomorphine- and clonidine-induced hypo-VLA and -HLA and a decreased effect on apomorphine-induced hyper-HLA but not on hyper-VLA. These results suggest that for apomorphine- and clonidine-induced locomotion in mice CER has pharmacological properties different from those of CCK-8.

Animals↗
PubMed1992

Rapid and simultaneous assay of monoamine neurotransmitters and their metabolites in discrete brain areas of mice by HPLC with coulometric detection.

For simultaneous assay of the three monoamine neurotransmitters, norepinephrine, dopamine, and serotonin, and four respective metabolites in brain tissue, a rapid and simple method using high-performance liquid chromatography with coulometric detection is described. Because the present method permits the determination of these target substrates within 10 min or less in one chromatographic run, 150 samples can be analyzed using an autosampler and an integrator in a 24-h period. Within-run coefficients of variation for the target substrates in the standard solution and the whole brain sample were less than 3% and 2% (n = 40), respectively. The quantitative detection limits were 0.01-0.1 pmol. The present procedure was applied to measure the target substrates in several discrete brain areas in mice.

Animals↗
PubMed1992

A simple T-maze method for estimating working memory in mice. Effect of ethylcholine mustard aziridinium ion (AF64A).

Mice were housed in a cage containing a T maze. A watering place was located at the entrance of the maze. The right and left arms of the maze each had two exits, one of which led to the home cage where food was placed, while the other led to the watering place via a bypass. The exit leading to the home cage in either the right or left arm was alternately closed every 90 min. One-way swinging doors were inserted at the entrance to each arm and between each bypass and the watering place. The mice were given a cholinergic neurotoxin--ethylcholine mustard aziridinium ion (AF64A)--(8 nmol) or saline as a control into the left ventricle 2 weeks before they were housed in the apparatus. Those mice housed in this apparatus mastered the alternation task at a 5-sec delay on day 3 in the sham group and on day 4 in the AF64A group. When a longer delay (5-90 sec) was introduced for the mice that mastered the alternation task at 5-sec delay, the AF64A group made significantly more errors than did the sham group at 60- and 90-sec delays. These results show that the apparatus is useful in estimating working memory in mice with little effort.

Animals↗
PubMed1992

1 alpha,25-dihydroxyvitamin D3 regulates in vivo production of the third component of complement (C3) in bone.

We previously reported that 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25-(OH)2D3] specifically stimulates production of the third component of complement (C3) by murine osteoblastic cells and marrow-derived stromal cells (ST2) in vitro. In the present study we examined tissue-specific production of C3 in vivo in vitamin D-deficient mice, some of which received supplemental 1 alpha,25-(OH)2D3. Western blot analysis indicated that the C3 protein band in bone was undetectable in vitamin D-deficient mice, but became distinct 48 h after 1 alpha,25-(OH)2D3 administration. The mRNA expression of C3 in bone was also undetectable in vitamin D-deficient mice and appeared as early as 24 h after 1 alpha,25-(OH)2D3 administration. mRNA expression apparently preceded the appearance of C3 protein. In contrast, there was no significant difference in the expression of hepatic C3 mRNA among normal mice fed laboratory chow and vitamin D-deficient mice with and without 1 alpha,25-(OH)2D3 administration. The serum concentration of C3 in vitamin D-deficient mice was almost identical to that in normal mice and was unchanged after 1 alpha,25-(OH)2D3 administration. 1 alpha,25-(OH)2D3 receptor (VDR) mRNAs were detected in the kidney and intestine, whereas no appreciable mRNA expression of VDR occurred in the liver. Osteopontin mRNA was expressed in response to 1 alpha,25-(OH)2D3 in the kidney, but not in the intestine. Immunohistochemical studies showed that in normal mice, the C3 protein was located mainly in the periosteal regions of calvaria and on the surfaces of bone trabeculae in the tibial metaphyses. These results demonstrate that 1 alpha,25-(OH)2D3 tissue-specifically regulates in vivo production of C3 in bone. The production of bone C3 cannot be attributed to the presence of VDR alone, and we speculate that other tissue-specific factors are required.

Animals↗
PubMed1992

Delayed suppressive effect of a low dose of caerulein on the grooming behavior induced by the D1-receptor agonist SKF 38393.

Caerulein (CLN, 0.8-80 micrograms/kg, s.c.) was administered to male rats 10 min or 24 hr before the injection of SKF 38393 (3 mg/kg, i.p.). The increased mouth movement and grooming behavior by SKF 38393 were suppressed dose-dependently by CLN 10 min before the SKF 38393. CLN at the dose of 0.8 micrograms/kg, given 24 hr before the SKF 38393, suppressed the grooming behavior by SKF 38393. These findings suggest that a low dose of CLN, but not a high dose, had a delayed suppressive effect on the grooming behavior induced by an excess of D1-activity.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1992

An improved assay method for UDP-glucuronyltransferase activity towards 5-hydroxytryptamine and the characteristic properties of the enzyme.

A simple and reproducible assay method for UDP-glucuronyltransferase (GT) towards 5-hydroxytryptamine (5-HT) was developed. It consists of the removal of unconjugated 5-HT by 0.6 N NH4OH-saturated n-amyl alcohol and the colorimetric estimation of 5-HT glucuronide. Using this assay method, some properties of the enzyme activity in rat liver microsomes were studied. Simple Michaelis-Menten kinetics was followed with respect to 5-HT and the apparent Km value for 5-HT was 0.1 mM. However, the deviation from this kinetics was observed with respect to UDP-glucuronic acid (UDPGA). The apparent Km values for UDPGA were 0.6 mM and 5 mM. The enzyme activity was stimulated by divalent cations. For Mg2+, the enzyme did not obey this kinetics, and the apparent Km values for Mg2+ were 1 mM and 10 mM. In the presence of Mg2+, the apparent Km value for 5-HT did not change but the Vmax value increased. On the other hand, the addition of a low concentration of Mg2+ decreased the apparent Km value for UDPGA and increased the Vmax value. The addition of a high concentration of Mg2+ did not change the apparent Km value for UDPGA but increased the Vmax value. These results indicate that the enzyme activity is stimulated by the formation of Mg(2+)-UDPGA complex which showed higher affinity for the enzyme than UDPGA at the low concentration of Mg2+ and further stimulated by the formation of Mg(2+)-enzyme complex at the higher concentration of Mg2+.

Animals↗
PubMed1992

Synovial fluid ferritin in traumatic hemarthrosis, rheumatoid arthritis and osteoarthritis.

Synovial fluid ferritin levels in patients with traumatic hemarthrosis (HA), rheumatoid arthritis (RA), and osteoarthritis (OA) were measured by double antibody radioimmunoassay. Synovial fluid ferritin levels were significantly higher in 60 patients with HA (mean +/- S.D., 536 +/- 536 ng/ml) and 39 patients with RA (614 +/- 486 ng/ml) than in 20 patients with OA (130 +/- 119 ng/ml) (p < 0.01). Individual levels, however, considerably varied. In HA patients, the synovial fluid ferritin level correlated well with the duration of hemarthrosis, but not with hemoglobin, hematocrit, or an inflammatory synovial fluid index such as the leukocyte count. In RA patients, there was no significant correlation between the synovial fluid ferritin levels and any inflammatory parameter, such as catalase activity, synovial leukocyte counts (including polymorphs and monocytes) or the duration of arthritis. Our results indicate that the synovial fluid ferritin level reflects primarily hemoglobin degradation and appears unrelated to inflammation in joint diseases.

Adolescent↗
PubMed1992

[A simple method using a maze task for estimating working memory in mice].

Mice were housed in a cage with a T-maze for 7-9 h a day. A watering place was equipped at one end of the maze. At the other end of the maze, the right and left arms each have two exits, one of which leads to the home cage where food is placed, and the other of which leads to the watering place via a bypass. The exit leading to the home cage in either the right or left was alternately closed every two hours. One-way swinging doors were inserted at the entrance to each arm and between each bypass and the watering place. The mice housed in this apparatus acquired the alternation task at 5 s delay on the 6th day. As the delay became longer (5-150 s), correct response rate showed gradual decrease. Scopolamine (0.1-0.4 mg/kg) did not decrease correct response rate at 5 s delay, but did at longer delay (30 s and 60 s). These results suggest that this method is useful in estimating working memory of mice.

Animals↗
PubMed1991

Granulocyte-macrophage colony-stimulating factor is a major macrophage fusion factor present in conditioned medium of concanavalin A-stimulated spleen cell cultures.

In 1983, we reported that the conditioned medium (CM) of spleen cell cultures treated with Con A greatly induced fusion of mouse alveolar macrophages within 2 to 3 days at a very high rate of more than 80% (Proc. Natl. Acad. Sci. USA 80:5583, 1983). In the course of examining macrophage fusion factors (MFF) present in Con A-CM, we found that IL-4 induced fusion of alveolar macrophages with a time course similar to that induced by Con A-CM. However, the maximal fusion rate induced by IL-4 (4 ng/ml) was about 35%. Furthermore, the fusion induced by Con A-CM was blocked only partially by adding IL-4 antibody, indicating that there are unknown MFF other than in Con A-CM. Of several other cytokines produced by Con A-stimulated spleen cells, IL-6 (20 ng/ml), IFN-gamma (45 ng/ml) and granulocyte-macrophage (GM)-CSF (10 ng/ml) greatly potentiated the fusion induced by 4 ng/ml of IL-4. The assay of these cytokines in Con A-CM proved that it contained 0.44 +/- 0.04 ng/ml of IL-4, 1.0 +/- 0.24 ng/ml of IL-6, 9.1 +/- 0.07 ng/ml of IFN-gamma, and 11.6 +/- 1.66 ng/ml of GM-CSF. When the potentiating effects of IL-6, IFN-gamma and GM-CSF on macrophage fusion were examined in the presence of 0.4 ng/ml of IL-4, only GM-CSF increased the fusion rate to the maximal level induced by Con A-CM at its physiologic concentration (10 ng/ml). The macrophage fusion induced by Con A-CM was greatly suppressed by adding antibody against GM-CSF. GM-CSF had a biphasic effect on growth and fusion, depending on its dose levels used: 0.01 to 0.1 ng/ml increased proliferation without inducing fusion and 10 ng/ml preferentially induced fusion. There was a negative relationship between macrophage growth and fusion. IL-4 was a potent inhibitor of proliferation of macrophages induced by GM-CSF. These results clearly indicate that GM-CSF is a major MFF present in Con A-CM.

Animals↗
PubMed1991

The specific production of the third component of complement by osteoblastic cells treated with 1 alpha,25-dihydroxyvitamin D3.

A 190 kDa protein was purified from conditioned media of mouse marrow-derived stromal cell (ST2) cultures treated with 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)2D3) and identified as the third component of mouse complement (C3). Northern and Western blot analysis revealed that the production of C3 by ST2 and primary osteoblastic cells was strictly dependent on 1 alpha,25(OH)2D3, but the production by hepatocytes was not. Adding 1 alpha,25(OH)2D3 together with mouse C3 antibody to bone marrow cultures greatly inhibited the formation of tartrate-resistant acid phosphatase (TRAP)-positive osteoclast-like multinucleated cells. Adding C3 alone induced no TRAP-positive cell formation. These results suggest that, in bone tissues, C3 is specifically produced by osteoblasts in response to 1 alpha,25(OH)2D3 and somehow involved in inducing differentiation of bone marrow cells into osteoclasts in concert with other factors produced by osteoblasts in response to 1 alpha,25(OH)2D3.

Acid Phosphatase↗