Biomedical subjects

K Inoue

Publications and source records attributed to K Inoue.

At least 811 records · Page 45Linked to original sources

PubMed1998

Muscle pathology in the early stage of Guillain-Barré syndrome.

Although many studies have been performed on nervous tissue pathology in Guillain-Barré syndrome (GBS), much less is known about pathological changes in skeletal muscle in this disorder. We have studied muscle biopsies from 5 patients with GBS, 5 patients with amyotrophic lateral sclerosis (control A), and 5 patients with polyarteritis nodosa (control B). We also examined muscle obtained after death from 7 patients without neurologic or muscular diseases (control C). By light microscopy, all specimens from patients with GBS exhibited necrosis and/or phagocytosis, none of which was observed in the other three controls. Neither small angulated fibers nor small group atrophy was found in patients with GBS and in control C, by contrast with controls A and B. Ultrastructurally, filamentous bodies, subsarcolemmal aggregates of mitochondria, accumulation of glycogen particles, and concentric laminated bodies were present much more frequently in patients with GBS than in all controls. Only GBS patients showed cytoplasmic bodies. These observation suggests that there is muscle involvement in the early stage of GBS and that these muscle changes may have an intimate and important relationship to the pathogenesis of GBS.

Adult↗

PubMed1998

Effects of a novel antihypertensive drug, cilnidipine, on catecholamine secretion from differentiated PC12 cells.

Effects of a novel dihydropyridine type of antihypertensive drug, cilnidipine, on the regulation of the catecholamine secretion closely linked to the intracellular Ca2+ were examined using nerve growth factor (NGF)-differentiated rat pheochromocytoma PC12 cells. By measuring catecholamine secretion with high-performance liquid chromatography coupled with an electrochemical detector, we showed that high K+ stimulation evoked dopamine release from PC12 cells both before and after NGF treatments. Cilnidipine depressed dopamine release both from NGF-treated and untreated PC12 cells in a concentration-dependent manner. In contrast, inhibition by nifedipine was markedly decreased in the differentiated PC12 cells. With intracellular Ca2+ concentration ([Ca2+]i) measurements using fura 2, the elevation of high K+-evoked [Ca2+]i was separated into nifedipine-sensitive and -resistant components. The nifedipine-resistant [Ca2+]i increase was also blocked by cilnidipine, as well as omega-conotoxin-GVIA. By the use of the conventional whole-cell patch-clamp technique, the compositions of the high-voltage-activated Ca2+ channel currents in the NGF-treated PC12 cells were divided into types: L-type, N-type, and residual current components. It was also estimated that cilnidipine at 1 and 3 micromol/L strongly blocked the N-type current without affecting the residual current. These results suggest that cilnidipine inhibits catecholamine secretion from differentiated PC12 cells by blocking Ca2+ influx through the N-type Ca2+ channel, in addition to its well-known action on the L-type Ca2+ channel.

Animals↗

PubMed1998

Effects of N-methacryloyl amino acid applications on hybrid layer formation at the interface of intertubular dentin.

To understand the role of NMAA in the bonding of composite resin to a dentin surface, we investigated the effects of N-methacryloyl amino acid (NMAA) application on the expansion of aggregated collagen fibers, formation of a hybrid layer, and the tensile bond strength between composite resin and dentin. Four NMAA derivatives--N-methacryloyl-alpha-glycine (NMGly), N-methacryloyl-gamma-amino n-butyric acid (NMBu), N-methacryloyl-alpha-hydroxyproline (NMHPro), and N-methacryloyl-alpha-glutamic acid (NMGlu)--were prepared and applied to dentin surfaces which had been etched with 40% by mass H3PO4 and air-blown. The shrunken collagenous layer expanded by approximately 50% to 70% by volume of the original collagenous layer thickness after application of the NMAA primers. Application of the bonding agent and composite resin after NMAA treatment resulted in the formation of a hybrid layer. The thickness of the hybrid layer was somewhat smaller than the collagenous layer formed by the NMAA treatment only, regardless of the type of NMAA used. The thickness of the hybrid layer was approximately ten times larger than that formed without NMAA treatment. Although all NMAA primers formed hybrid layers of similar thickness, higher tensile bond strengths, from 13 to 15 MPa, were obtained when etched and air-blown dentin was treated with NMBu, NMGly, or NMGlu. NMHPro gave only 6.6 MPa, a value similar to that obtained when no NMAA was used. We concluded, therefore, that formation of the hybrid layer is a necessary but insufficient condition for high bond strength.

Analysis of Variance↗

PubMed1998

Increased anticoagulant activity of recombinant thrombomodulin modified with glycosaminoglycan.

Thrombomodulin (TM) is a thrombin receptor on the endothelial cell surface, effective as an anticoagulant by changing procoagulant thrombin to an anticoagulant one. As rabbit TM with glycosaminoglycan (GAG) has a more potent anticoagulant activity than that without GAG, we expressed recombinant GAG-modified urinary thrombomodulin (GAG-UTM) in C-127 cells. The effect of an additional GAG chain on anticoagulant activity was investigated in comparison with unmodified recombinant UTM (r-UTM). In vitro, the activity of cleavage of fibrinogen by thrombin or prothrombinase activity was more potently depressed by GAG-UTM than by r-UTM, and the generation of activated protein C by TM-thrombin complex was accelerated by GAG modification. The acceleration of antithrombin III-dependent anticoagulant activity was shown only by GAG-UTM. Parameters like thrombin time, prothrombin time and activated partial thromboplastin time in human plasma were prolonged by GAG-UTM more than by r-UTM. In vivo, the effect of GAG-UTM and r-UTM in endotoxin-induced disseminated intravascular coagulation (DIC) rats was investigated using hematological parameters. GAG-UTM and r-UTM significantly reduced the decrease in fibrinogen and platelet number induced by endotoxin at the dosage of 0.1 and 1.0 mg/kg/h, respectively, suggesting that the antithrombotic effect of GAG-UTM in endotoxin-induced DIC rats was 10-fold as potent as that of r-UTM. GAG-UTM reduced the prolongation of the bleeding time induced by endotoxin, while r-UTM accelerated it. These results suggest that the addition of a GAG chain may increase availability as an anticoagulant.

Angiotensin III↗

PubMed1998

Improved cardiac function after catheter ablation in a patient with type B Wolff-Parkinson-White syndrome with an old myocardial infarction.

A 67-year-old man was admitted to hospital for the treatment of exertional dyspnea. He suffered from congestive heart failure due to an old inferior myocardial infarction with type B Wolff-Parkinson-White syndrome. Asynchronous wall motion caused by pre-excitation through a right-side bypass tract caused his cardiac function to deteriorate. Catheter ablation of the bypass tract increased the ejection fraction, and improved his symptoms, prior to surgical revascularization.

Aged↗

PubMed1998

[Signal transduction through ATP receptors in brain and the development of new drugs].

The possible involvement of adenosine 5'-triphosphate (ATP) receptors in the function of the hippocampus and of pain transmission is discussed. Involvement of these receptors in the function of the hippocampus has been suggested by several reports. In the paper we presented the data that ATP inhibits the glutamate release in cultured hippocampal neurons. This and the report revealing that ATP protected against cell death by glutamate suggest that ATP may be playing a role in the protection of the hippocampus from over-stimulation. Microglia cells are activated by the stimulation of ATP and releases plasminogen which is well known to promote the development of mesencephalic dopaminergic neurons and enhance neurite outgrowth from explants of neocortical tissue. Therefore, ATP may have a role in repairing the damaged neuronal networks as well as protection.

Adenosine Triphosphate↗

PubMed1998

ATP receptors for the protection of hippocampal functions.

The inhibitory effects of extracellular adenosine 5'-triphosphate (ATP) are reviewed in the present paper. ATP inhibits the release of the excitatory transmitter glutamate and stimulates the release of the inhibitory transmitter GABA from hippocampal neurons. Also, ATP activates potassium conductance directly through G protein, resulting in hyperpolarization of membrane potential. ATP activates microglia to secrete plasminogen that promotes the development of mesencephalic dopaminergic neurons and enhances neurite outgrowth from explants of neocortical tissue. Moreover, ATP may protect hippocampal neurons from excitotoxic cell death by preserving mitochondrial function. Thus, ATP may have a role in the protection of the function of hippocampus from over-stimulation by glutamate.

Adenosine Triphosphate↗

PubMed1998

Inhibition by a capsaicin antagonist (capsazepine) of capsaicin-induced swimming capacity increase in mice.

We investigated the endurance swimming capacity of mice injected with CAP antagonist (capsazepine). The increase of endurance swimming capacity by the administration of CAP was significantly suppressed by the injection of capsazepine. At the same time, serum adrenaline secretion, which was induced by CAP, was depressed by capsazepine. These findings suggested that the increase in endurance swimming capacity by CAP was mediated by the CAP receptor.

Animals↗

PubMed1998

Suppression of the lethal effect of acidic-phospholipid deficiency in Escherichia coli by Bacillus subtilis chromosomal locus ypoP.

An acidic-phospholipid deficiency caused by the pgsA3 allele that encodes a defective phosphatidylglycerophosphate synthase in Escherichia coli is lethal. The only known mutations that suppress this lethality fully have been related to the major outer-membrane lipoprotein. We isolated a Bacillus subtilis chromosomal locus that suppresses the lethality when harbored in a low copy-number plasmid, without restoring the synthase activity or phospholipid composition to normal. The locus was first recognized to suppress the conditional lethality of E. coli YA5512 (pgsA3) that harbored an unidentified mutation(s), allowing its growth in LB medium but not in media of lower osmolarities. The locus was then found to suppress the lethality of pgsA3 in wild-type E. coli W3110. This locus, named ypoP in the database, had 37% nucleotide identity with the E. coli mprA gene, but the amplification of mprA had no suppressive effect. Plasmid pPOP1 containing ypoP completely prevented the decrease in the amount of a porin protein, OmpF, in the outer membrane and also cell mucoidy caused by pgsA3. The mechanisms underlying these unusual effects are discussed in relation to a putative stress signal(s) generated by the acidic-phospholipid deficiency.

Alleles↗

PubMed1998

Potentiated decrease of plasma folate levels caused by the coadministration of folic acid in rats treated with methotrexate.

The decrease of plasma 5-methyltetrahydrofolic acid (5-MF) levels, postulated as an indicator of folate status, was studied following the administration of both methotrexate (MTX) alone and MTX with folic acid (FA) using rats as our experimental model. Blood and urine samples were serially collected over a 9 hr period after the administration of MTX, MTX with FA and from a control group to examine the plasma kinetics and the renal clearance of 5-MF. The pharmacokinetics of MTX and the plasma protein binding of 5-MF were also examined. The concentrations of these analytes were assayed using high performance liquid chromatography (HPLC). MTX administration produced decreased plasma 5-MF levels. This observed decrease was potentiated by oral FA administration, suggesting that the folate status was more severely altered by the coadministration of FA. The renal clearance of 5-MF also increased dose-dependently with FA (0.05-5 mg/kg) coadministration. The plasma protein binding of 5-MF was not affected by the FA administration, which indicates that the fraction of 5-MF that was filtered through the glomerular apparatus appeared to be unchanged. In addition, the pharmacokinetic profiles of MTX also appeared not to be affected by the addition of FA. We conclude that the inhibition of reabsorption of 5-MF in the renal tube by concurrent administration of MTX and FA must be one of the causal factors for the demonstrated decrease in the plasma 5-MF levels in rats.

Animals↗

PubMed1998

Magnesium as a regulator of thrombin formation in bovine ovarian follicular fluid.

In the ovarian follicular fluid (FF) of Holstein cows, calcium (Ca) and magnesium (Mg) levels and their roles on thrombin generation were examined and compared with the blood samples. Total Ca levels in FF increased while the total Mg levels decreased with follicular development from preantral to preovulatory stage of follicles. These changes resulted in Ca values being significantly (p < 0.05) higher in FF from the most developed follicles and the Mg values being significantly higher (p < 0.05) in the least developed follicles. To determine whether the high level of Mg might function to regulate thrombin generation in FF as occurs in plasma, the influence of Mg supplementation of FF from various types of follicles was examined. In FF from small size follicles, Mg accelerated the prothrombin time, an estimation of the overall rate of thrombin production, although a similar effects was not observed in FF from medium and large size follicles. The addition of Mg to FF from all sizes of follicles resulted an inhibition in factor X activation. Since activation of factor X is a precursor step for thrombin formation it is concluded that Mg can function as a slow accelerator of thrombin generation in FF from follicles at the antral stage of development. It is likely to have a more important role in regulating the rate of thrombin generation as the follicle develops.

Animals↗

PubMed1998

Prolactin-producing cells differentiate from G0/G1-arrested somatotrophs in vitro: an analysis of cell cycle phases and mammotroph differentiation.

In order to analyze the relationship between cell proliferation and mammotroph differentiation, we studied a somatotrophic cell line, MtT/S. MtT/S cell is known to differentiate into PRL-producing cells in response to stimulation with insulin or insulin-like growth factor-1 (IGF-1). Double immunostaining for bromodeoxyuridine (BrdU), which labels proliferating cells, and for GH or PRL showed that most BrdU-labeled cells were GH-immunopositive, whereas considerably few PRL-positive cells were labeled with BrdU. This was confirmed by immunostaining of proliferating cells with antibody to proliferating cell nuclear antigen (PCNA). Furthermore, flow-cytometry analysis indicated that most of the PRL-producing cells were in the G0/G1 phase of the cell cycle. In order to determine whether cell cycle changes are required for transdifferentiation of PRL-producing cells, MtT/S cells were cultivated in serum restricted medium for 7 days to reduce their mitotic activity and then treated with insulin and epidermal growth factor (EGF). Under these conditions, the cell cycle of MtT/S cells was significantly delayed, but the percentage of PRL-producing cells induced was almost identical to that under control conditions, showing that mitosis is not required for PRL- producing cell differentiation. We also labeled MtT/S cells with BrdU for 24 h during PRL-producing cell induction by insulin and EGF, and as a result BrdU-labeled proliferative cells were specifically absent from PRL-producing cell populations. These data, taken as whole, suggest that PRL cells differentiated from G0/G1 arrested somatotrophs and the PRL cells which appeared had their cell proliferation activity significantly declined. In conclusion, this is the first report showing the relationship cell between proliferation and differentiation of PRL cells.

Animals↗

PubMed1998

Overexpression of c-Met/hepatocyte growth factor receptors in human prostatic adenocarcinoma.

Hepatocyte growth factor (HGF) and c-met proto-oncogene product (c-Met) have varied biological functions in different tissues and have been implicated in mitogenic, motogenic and morphogenic responses in both organ regeneration and carcinogenesis. Some studies have suggested that the overexpression of c-Met and epidermal growth factor receptor (EGFR) are associated with growth advantage, while transforming growth factor-beta receptor II (TGF beta R II) is associated with growth disadvantage of human prostatic adenocarcinoma. However, it is unclear if the expression of c-Met correlates with the expression of EGFR and TGF beta R II, and with the proliferative status of human prostatic adenocarcinoma. Using immunohistochemical staining with anti-c-Met (C-12), anti-EGFR (NCL-EGFR) and anti-TGF beta R II (L-21) antibodies, we determined the frequency of expression of c-MET, EGFR, and TGF beta R II respectively in a series of 134 radical prostatectomy specimens. We evaluated the relationship between the expression of these receptors and clinicopathological characteristics. Overall, c-Met immunostaining was detected in 54 of 134 (40.3%) cases, EGFR in 45 (33.6%) and TGF beta R II in 64 (48.4%). The overexpression of c-Met was significantly more common in poorly differentiated (P < 0.0001) and in the diffusely infiltrated specimens (P < 0.0005). In contrast, TGF beta R II was significantly overexpressed in the well differentiated specimens (P < 0.0001) and associated negatively with c-Met (P < 0.0001). Overall, these data suggest that c-Met/HGF receptor and TGF beta R II overexpression may be involved in the differentiation of human prostatic adenocarcinoma, c-Met with de-differentiation and TGF beta R II with differentiation.

Adenocarcinoma↗

PubMed1998

[A single dose toxicity study of magnesium sulfate in rats and dogs].

A single dose toxicity study of magnesium sulfate by intravenous administration was conducted in rats and dogs. The results are summarized in the following. Magnesium sulfate was administered once at dose levels of 90, 130, 200, 300 and 450 mg/kg to Crj:CD(SD) rats at 6 weeks of age. Deaths occurred in the 200 mg/kg and above groups in both sexes. The LD50 values were 206 mg/kg for males and 174 mg/kg for females. In the surviving animals, in the 130 mg/kg and above groups, tonic convulsions, abnormal gait and tachypnea were seen. However, these signs disappeared gradually and all animals returned to a normal state by 15 min after dosing. There were no treatment-related changes in the body weight or gross pathology. Magnesium sulfate was infused for 6 hr at dose levels of 75, 300 and 1200 mg/kg (12.5, 50 and 200 mg/kg/hr) to female beagle dogs at 6 months of age. No deaths were observed in any of the dose groups and it was considered that the lethal dose level would be higher than 1200 mg/kg(200 mg/kg/hr). In the 1200 mg/kg group, vomiting, decreased spontaneous movement, staggering gait, prone position and flush of the conjunctiva and ear auricles were seen. However, these signs disappeared gradually and animals returned to a normal state by 1 hr after dosing. There were no treatment-related changes in the body weight, food consumption or gross pathology.

Animals↗

PubMed1998

[A 2-week toxicity study of magnesium sulfate administered by 24-hr intravenous infusion in beagle dogs followed by 2-week recovery period].

A 2-week toxicity study of magnesium sulfate administered by a 24-hr intravenous infusion at the dosage levels of 0, 12.5, 50, 100 and 200 mg/kg/hr in female beagle dogs was conducted, with 2-week follow-up observation after drug withdrawal. One of 2 animals in the 200 mg/kg/hr group died approx. 32 hr after the start of infusion. At the same time, the remaining 1 animal of the same group was sacrificed in a moribund state. Changes attributable to the treatment of magnesium sulfate were decreased food consumption and body weight gain, anemia, mild prolongation of conduction time in electrocardiogram and tubular basophilia in the kidneys in the animals treated with 100 mg/kg/hr. Furthermore, decreased calcium level was recorded in the animals treated with 50 mg/kg/hr or more. However, these changes disappeared after drug withdrawal, and reversibility was suggested. Judging from the mode of occurrence, since the change in calcium level observed in the group treated with 50 mg/kg/hr was slight, it was considered to be toxicologically insignificant. In conclusion, the nontoxic dosage level of magnesium sulfate was judged to be 50 mg/kg/hr under the condition of the present study.

Anemia↗

PubMed1998

[A 4-week toxicity study of magnesium sulfate administered by 24-hr intravenous infusion in beagle dogs].

A 4-week toxicity study of magnesium sulfate administered by 24-hr intravenous infusion at the dosage levels of 0, 12.5, 50 and 100 mg/kg/hr in female beagle dogs was conducted. No death occurred in any group. Changes attributable to the treatment with magnesium sulfate were decreased food consumption and body weight gain, anemic change, increased urine volume, decreased serum calcium level, increased inorganic phosphorus level, slight prolongation of conduction time in electrocardiogram and tubular basophilia in the kidneys in the group treated with 100 mg/kg/hr. In addition, essentially similar changes were also observed at the same dosage level in the 2-week study of this drug, in which recoverability was recognized with 2-week follow-up observation after drug withdrawal. In conclusion, the nontoxic dosage level was judged to be 50 mg/kg/hr under the condition of the present study.

Anemia↗

PubMed1998

[A study for effects on pre- and postnatal development, including maternal function in rats treated subcutaneously with magnesium sulfate].

Magnesium sulfate, at dose levels of 250, 500 and 1000 mg/kg, was administered subcutaneously three times daily to Crj:CD(SD) female rats from day 15 through day 20 of gestation. The effects of the compound on dams and F1 animals were examined. In the dams, decreased food consumption was observed in the 500 and 1000 mg/kg groups. Hypolocomotion, pronation, bradypnea and decreased body weight gain were observed in the 1000 mg/kg group. But there were no effects on the delivery or lactation conditions and necropsy from administration of the test article. In the F1 animals, low body weight, delays in differentiation (eruption of lower incisor, opening of eyelid) and reversible change in ribs (wavy rib) were observed in the 1000 mg/kg group. But there were no effects from administration of the test article in viability, functional examinations, behavior tests or reproductive ability. Based on the above results, under the conditions of this study, it was concluded that the non-toxic dose levels for general toxicological effects on dams was 3 x 250 mg/kg/day, for reproductive ability of dams was 3 x 1000 mg/kg/day, and for development of F1 animals was 3 x 500 mg/kg/day.

Animals↗

PubMed1998

[Mutagenicity studies of magnesium sulfate--reverse mutation test with bacteria and chromosomal aberration test with mammalian cells in culture].

The mutagenicity potential of magnesium sulfate was re-assessed using the current procedure of the reverse mutation test with bacteria and chromosomal aberration test with mammalian cells (a Chinese hamster lung fibroblast cell line; CHL/IU) in culture. In the reverse mutation test with bacteria, Salmonella typhimurium TA100, TA98, TA1535 and TA1537 and Escherichia coli WP2 uvrA were use and the maximum dose level was set at 5000 micrograms/plate irrespective of the absence or presence of metabolic activation. Five dose levels (313-5000 micrograms/plate) were selected for all strains except for TA98 without metabolic activation and for TA1537 with metabolic activation, for which 6 dose levels (156-5000 micrograms/plate) were selected. Magnesium sulfate induced no increase in the number of colonies with reverse mutation in any of the strains irrespective of the absence of presence of metabolic activation in the dose-range-finding study or in the main study. In the chromosomal aberration test with mammalian cells, a Chinese hamster lung fibroblast cell line (CHL/IU) in culture was used and the maximum dose level was set at 5.0 mg/mL both in the direct and metabolic activation methods. Three dose levels (1.25-5.0 mg/mL) were selected. Magnesium sulfate induced no increase in the incidence of cells with chromosomal aberration or those with genome mutation (polyploidy) in any of the strains irrespective of the absence of presence of metabolic activation. Thus, it is concluded that magnesium sulfate does not have mutagenic potential under the presence experimental conditions.

Animals↗