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T Maeda

Publications and source records attributed to T Maeda.

At least 469 records · Page 26Linked to original sources
PubMed1997

Nicotinic receptor stimulation protects neurons against beta-amyloid toxicity.

beta-Amyloid (A beta), a major constituent of senile plaques in Alzheimer's disease (AD), is thought to contribute to the neurodegeneration. We examined the effects of nicotinic receptor agonists on A beta cytotoxicity in cultured rat cortical neurons. The number of viable neurons decreased significantly when cultures were exposed to synthetic A beta peptides (25-35). Concomitant administration of nicotine with A beta markedly reduced the number of dead cells. This nicotine-induced neuroprotection was dependent on the concentration. When hexamethonium or mecamylamine, nicotinic antagonist, was added, neuroprotective effect of nicotine was blocked, which indicates that effect of nicotine was mediated by nicotinic receptors. In addition, a selective alpha7-receptor antagonist, alpha-bungarotoxin (alpha-BTX), blocked the neuroprotective effect of nicotine. Furthermore, incubation with 3-(2,4)-dimethoxybenzylidene anabaseine (DMXB), a selective alpha7-receptor agonist, protected against A beta-induced neuronal death. These results suggest that alpha7-receptor activation plays an important role in neuroprotection against A beta cytotoxicity. This study suggests that nicotinic receptor stimulation, especially alpha7-receptor activation, may be able to protect neurons from degeneration induced by A beta and may have effects that counter the progress of AD.

Amyloid beta-Peptides↗
PubMed1997

Direct evidence of high DNA binding activity of transcription factor AP-1 in rheumatoid arthritis synovium.

OBJECTIVE: To investigate the possible activation of transcription factor AP-1 in rheumatoid arthritis (RA) and its involvement in the pathogenesis of RA. METHODS: Synovial tissues and peripheral blood samples were obtained from 25 patients with RA and 5 patients with osteoarthritis (OA) during arthroplasty and synovectomy. The synovial tissue was digested with collagenase and separated into adherent and nonadherent cells by plastic-adhesion methods. Nuclear extracts obtained from each sample were examined by electrophoretic mobility shift assay to determine the DNA binding activity of AP-1. The expression of c-fos and c-jun messenger RNA (mRNA) was examined by in situ reverse transcription assay. RESULTS: A markedly high DNA binding activity of AP-1 was detected in the synovial tissues of RA patients, while virtually no activity or only a little activity was observed in OA patients. Following separation of adherent and nonadherent cells, the AP-1 activity was mainly detected in adherent cells, which consisted of synovial cells and macrophages. However, the activity was significantly higher in the mononuclear cells infiltrating into RA synovium than in RA peripheral blood mononuclear cells. The high DNA binding activity of AP-1 in RA correlated with the expression of c-fos and c-jun mRNA in situ. Furthermore, AP-1 binding activity also correlated with disease activity. CONCLUSION: In RA synovium, AP-1 DNA binding activity was constitutively up-regulated. These findings suggest that AP-1 may play an important role in the pathogenesis of RA, including synovial hyperplasia and abnormal immune responses.

Aged↗
PubMed1997

Transcriptional regulation of the HOX4C gene by basic fibroblast growth factor on rheumatoid synovial fibroblasts.

OBJECTIVE: To examine the expression of genes of the HOX D cluster in the synovial tissue of patients with rheumatoid arthritis (RA), and to determine whether basic fibroblast growth factor (bFGF) influences the expression and transcriptional regulation of the gene. METHODS: The expression of genes of the HOX D cluster, including HOX4C, HOX4D, HOX4H, and HOX4I, was determined in the synovium of 4 patients with RA and 4 with osteoarthritis (OA) by in situ reverse transcription (RT) and RT-polymerase chain reaction (RT-PCR). The induction of HOX4C messenger RNA (mRNA) by bFGF was determined by RT-PCR. The binding activity of a transcriptional regulator of the HOX4C gene, C2, was analyzed by the mobility shift assay. NIH-3T3 cells transfected with a construct containing C2 binding sequence were incubated with bFGF, and the activity of the reporter was measured by luciferase assay. RESULTS: Using an in situ RT assay, specific expression of HOX4C mRNA was detected in 3 of 4 RA synovial samples, whereas none of the OA synovia expressed HOX4C. HOX4D, HOX4H, and HOX4I genes were expressed in all synovial samples from RA and OA patients. The presence of HOX4C mRNA was also confirmed by RT-PCR and Southern blotting. Treatment with bFGF increased the expression of HOX4C mRNA in RA fibroblasts. The mobility shift assay and luciferase assay showed that bFGF enhanced C2 binding activity and significantly increased the transcriptional activity on RA fibroblasts. CONCLUSION: Our findings suggest that HOX4C is involved in synovial hyperplasia, and that the transcriptional regulation of HOX4C genes by bFGF may play a crucial role in the pathogenesis of RA.

Arthritis, Rheumatoid↗
PubMed1997

Calcitonin gene-related peptide, substance P, and tyrosine hydroxylase-immunoreactive innervation of rat bone marrows: an immunohistochemical and ultrastructural investigation on possible efferent and afferent mechanisms.

The presence of nerve fibers in bone marrow has been noted by various investigators, and recent developments in immunohistochemistry have enabled differential localization of the intramedullary nerve fibers. Much interest has been devoted to the efferent activities of the afferent fibers, which probably act on the target tissues by secreting a variety of neurotransmitters. The present study aimed to further characterize intramedullary substance P, calcitonin gene-related peptide, and tyrosine hydroxylase-immunoreactive nerve fibers of the rat lower limb by comparing those of the knee, ankle, and tarsal joints. The ultrastructural details of intramedullary calcitonin gene-related peptide-immunoreactive axons were also investigated to provide a morphological basis for their possible efferent actions. Intramedullary calcitonin gene-related peptide and substance P-immunoreactive fibers in the proximal tibia and the knee joint were found to be as reported earlier, but the marrow of the distal metaphysis was also noted to be richly innervated, and the tarsal joints displayed dense innervation at the subchondral regions that underlie the joint cartilage. The articular and intramedullary innervations that function for joint protection might participate in characteristic clinical features of joint damage secondary to the neuropathies. Ultrastructurally, the intramedullary calcitonin gene-related peptide-immunoreactive axons were minimally engulfed by the Schwann cell, and naked intramedullary calcitonin gene-related peptide-immunoreactive axons were noted along an extraordinarily long extension, suggesting much efferent activity.

Animals↗
PubMed1997

Detection and characterization of IL-1 receptor antagonist in tissues from healthy rabbits: IL-1 receptor antagonist is probably involved in health.

Interleukin 1 (IL-1) is postulated to function in maintaining homeostasis, however, over-action of this cytokine may lead to disruption of homeostasis due to it's wide spectrum of activities. To understand the endogenous regulation of this cytokine, we examined the existence of IL-1 receptor antagonist (IL-1Ra) in tissues from healthy rabbits. IL-1Ra was constitutively produced in all tissues examined (lung, liver, spleen, thymus, caecum, skin, kidney, heart, and brain), as estimated by ELISA. Immunoprecipitation, RT-PCR and immunohistochemical studies indicated that all tissues produced secreted form of IL-1Ra (sIL-1Ra), whereas thymus, caecum, skin and kidney produced both sIL-1Ra and intracellular of IL-1Ra. All tissue IL-1Ra purified using anti-IL-1Ra IgG affinity chromatography had inhibitory activity on the IL-1-induced thymocyte proliferative response, and the activity was totally abolished by anti-IL-1Ra mAb. No IL-1 activity was detected in any tissues except skin and heart, however, after preincubation of the samples with anti-IL-1Ra, the activity was first visible in the tissues. Under these conditions, IL-1 activity in skin and heart was enhanced to 170% and 280%, respectively. Taken together, we conclude that tissue IL-1Ra is involved in health maintenance by masking co-existing IL-1 activity present in tissues.

Animals↗
PubMed1997

Hemodynamic depression and microthrombosis in the peripheral areas of cortical contusion in the rat: role of platelet activating factor.

Cerebrovascular damages leading to subsequent reductions in regional cerebral blood flow (rCBF) may play an important role in secondary cell damages following traumatic brain injury (TBI). Recent studies have demonstrated that rCBF markedly decrease in experimental model of TBI (e.g. fluid percussion injury, acute subdural hematoma, contusion). However, precise mechanisms underlying post-traumatic CBF reduction remain unclear. In the present study, the rCBF changes and microthrombosis formation were investigated in a cortical contusional model in rats, and the effects of etizolam (platelet activating factor antagonist) on microthrombosis were tested. The rCBF in the peripheral areas increased transiently, and decreased to ischemic level 3 hours post- injury. The histological examinations revealed microthrombosis formation in the contused area, extending from the center to the peripheral areas within 6 hours post-injury. The rCBF decrease and the contusion necrosis volume were significantly attenuated by etizolam administration. These results indicate that platelet activating factor is involved in microthrombosis formation and hemodynamic depression, and resultant ischemic damages within areas surrounding the contusion.

Animals↗
PubMed1997

Antioxidant, OPC-14117, attenuates edema formation and behavioral deficits following cortical contusion in rats.

Oxygen free radicals may contribute to tissue injury processes in the central nervous system following ischemia or trauma. Recent studies have suggested that inhibition of free radicals improves the outcome in experimental models involving such conditions, and antioxidant therapy appears promising. In the present study, behavioral changes and edema formation in rat cortical contusion model were investigated, and the effects of a superoxide radical scavenger, OPC-14117, were tested. Wistar rats were anesthetized with halothane inhalation. Cortical contusion was induced in the parietal cortex employing a controlled cortical impact device. Immediately following injury induction, OPC-14117 was administered (300 mg/kg, p.o.). Edema formation was assessed in the center and peripheral areas of the contusion by the specific gravity method. Behavioral changes were evaluated by the Morris water maze test and the habituation of exploratory activity. The results revealed that the vehicle-administered control showed progressive edema formation and behavioral deficits following the injury. These changes were significantly attenuated by the OPC-14117 treatment (p < 0.05). Further, OPC-14117 reduced the size of contusional necrosis (p < 0.05). These findings suggest that superoxide free radicals are involved in contusion-induced edema formation, necrosis formation, and behavioral deficits, and that OPC-14117 has a therapeutic potential to prevent secondary cell damage following traumatic brain injury.

Animals↗
PubMed1997

Effect of antileukocyte adhesion molecule antibodies, nitric oxide synthase inhibitor, and corticosteroids on endotoxin shock in mice.

We compared the therapeutic effects of anti-leukocyte adhesion molecule antibodies (mAbs), a nitric oxide (NO) synthase inhibitor (monomethyl-L-arginine, NMLA), and methylprednisolone (MP) on experimental endotoxin-induced shock in mice. Lipopolysaccharide (LPS, 30 mg/kg) was administered to ICR mice intraperitoneally, While 1 mg/kg mAb, 5-20 mg/kg NMLA, or 30 mg/kg MP was administered intravenously. The placebo group received phosphate-buffered saline. The survival rate of the placebo group 48 h after LPS injection was 36%. The administration of anti-CD11a, anti-CD18, anti-lectin cell adhesion molecule-1 (anti-LECAM-1), and MP increased the survival rate to 70, 62, 64, and 100%, respectively; however, NMLA had no significant effect. A FACS analysis revealed that the CD18 expression of granulocytes increased 12-fold within 30 min after LPS administration. MP significantly suppressed its expression. The plasma level of nitrate/nitrite increased from 20 to 260 and 1000 microM 4 and 16 h, respectively, 20 mg/kg NMLA abolished NO production at 4 h, while MP inhibited it for up to 16 h. The hepatic malondialdehyde level increased from 0.50 to 2.46 nmol/mg protein at 4 h. Administration of anti-CD18 and MP reduced the level to 1.80 and 1.41 nmol/mg protein, respectively, whereas NMLA did not affect it. The mAbs and MP were concluded to be useful agents for endotoxin shock. The abolition of NO production had little influence on the hepatic cellular injury associated with endotoxemia.

Animals↗
PubMed1997

The appearance of a normal appendix on barium enema examination does not rule out a diagnosis of chronic appendicitis: report of a case and review of the literature.

We report herein the rare case of a 15-year-old girl with chronic appendicitis in whom the appendix was clearly depicted by a barium enema (BE) examination. The patient presented with a 4-month history of diffuse abdominal pain and tenderness in the lower abdomen. Neither computed tomography nor ultrasonography showed any abnormal findings in the lower abdomen or pelvic cavity. Furthermore, BE examination depicted an appendix filled with the contrast medium. However, at elective surgery, she was found to have chronic appendicitis which was later confirmed histologically. Following this case report, a discussion on the value and limitations of BE examination for the diagnosis of acute and chronic appendicitis is presented.

Abdominal Pain↗
PubMed1997

Distribution of serotonin-immunoreactive nerve cells and fibers in the rat gastrointestinal tract.

The distribution of serotonin-immunoreactive (5HT-IR) nerve cells and fibers was thoroughly investigated immunohistochemically in the rat stomach, duodenum, jejunum, ileum, and colon. The immunoreactivity of the 5HT neurons was compared between non-treated controls and animals treated with colchicine, colchicine plus 5-hydroxytryptophan (5HTP), colchicine plus pargyline, and reserpine. The intensity of immunoreactivity in nerve fibers as well as nerve cell bodies was enhanced mostly in colchicine plus pargyline treated animals, therefore these animals were used for an observation of precise localization of 5HT in the rat gastrointestinal (GI) tract. Immunoreactivity in the nerve cell bodies and fibers was completely abolished in the GI tract of reserpine treated animals. The pattern of localization and projection of 5HT-IR neurons was similar in all segments of the rat GI tract: 5HT-IR nerve cell bodies were located in the myenteric plexus and showed the distinctive features of Dogiel type I neurons. Prominent bundles of varicose fibers traversed the myenteric ganglia and some of them surrounded the cell bodies of immunopositive and immunonegative neurons. 5HT-IR nerve fibers were located in the submucous plexus, densely entwined about the submucosal blood vessels. Most characteristically, 5HT-IR nerve fibers invaded the lamina propria of mucosa where they underlay the crypt epithelium. In conclusion, the present study showed that 5HT-IR neurons located in the myenteric plexus projected fibers widely in the rat GI tract. The localization of fibers in the lamina propria of mucosa implies that this neuron may exert an important role in the epithelial function of the GI tract.

5-Hydroxytryptophan↗
PubMed1997

Clinical assessment of prolonged myocardial preservation for patients with a severely dilated heart.

BACKGROUND: The purpose of this study was to compare the myocardial protective effect of histidine-tryptophan-potassium and glucose-insulin-potassium cardioplegic solutions in patients with a dilated heart (left ventricular diastolic diameter > 55 mm, left ventricular systolic diameter > 45 mm) associated with prolonged cross-clamp time (longer than 200 minutes). METHODS: We selected 20 patients with dilated hearts due to severe aortic regurgitation. Glucose-insulin-potassium cardioplegia was used in 11 patients and histidine-tryptophan-potassium cardioplegia was used in 9 patients. RESULTS: After operation, the cardiac index was significantly increased in the histidine-tryptophan-potassium group (p < 0.05). Postoperative percent fractional shortening was 13.4% +/- 3.1% in the glucose-insulin-potassium group and 23.6% +/- 2.6% in the histidine-tryptophan-potassium group (p < 0.05). Creatine kinase levels were significantly lower in the histidine-tryptophan-potassium group than that in the glucose-insulin-potassium group (p < 0.05). The incidence of ventricular arrhythmia (higher than Lown's grade 2) was lower in the histidine-tryptophan-potassium group. CONCLUSIONS: These data support the superiority of the histidine-tryptophan-potassium method over the glucose-insulin-potassium method for protection of the dilated heart during prolonged ischemia in open heart operations.

Aortic Valve Insufficiency↗
PubMed1997

Expression of TrkB-like immunoreactivity in non-neural cells of rat periodontal ligament.

The Trk family, a group of high-affinity neurotrophin receptors, is divided into three subtypes, TrkA, TrkB and TrkC. These were originally found in neural elements, and are involved in neural development, maintenance and survival. Recent studies have shown that non-neural cells in vitro also express mRNA encoding some neurotrophin receptors. In our preliminary study, TrkB-like immunoreactivity (LI) was found in the various non-neural cells in the rat periodontal ligament. The present study was undertaken to clarify which cell types express Trk-LI, in particular two types of TrkB-LI, in the periodontal ligament of mature rats, using an immunocytochemical technique with polyclonal antibodies. Intense full-length TrkB-LI was clearly recognized in non-neural cells such as fibroblasts, osteoclasts, odontoclasts and cementoblasts as well as in neural elements. Relatively large cells with many cytoplasmic processes were also frequently immunopositive for full-length TrkB. Immunocytochemistry for TrkB[TK-], a truncated type, also demonstrated a similar immunostaining pattern to that of full-length TrkB in non-neural periodontal cells, and intense positive reactions in endothelial cells. Some non-neural cells were positive for TrkA and TrkC. These findings suggest that neurotrophic factors, the ligands of the Trk family, have certain effects on the proliferation and/or differentiation of non-neural cells, as well as on their neurotrophic functions.

Animals↗
PubMed1997

Protective effect of monoclonal antibodies to adhesion molecules on rat liver ischemia-reperfusion injury.

BACKGROUND: The source of reactive oxygen species in the liver remains to be elucidated. The present study was undertaken to determine whether polymorphonuclear neutrophils (PMNs) can contribute to hepatic ischemia-reperfusion injury, and pretreatment with monoclonal antibodies (mAbs) to intercellular adhesion molecule-1 (ICAM-1), lymphocyte function associated antigen-1 (LFA-1), and CD 18 could improve energy metabolism and prolong the viability of the organ. METHODS: Male Wistar rats were used. Rat liver ischemia was induced by clamping blood vessels supplying median and left lateral hepatic lobes. Monoclonal antibodies to ICAM-1, LFA-1, or CD18 were injected intravenously 5 minutes before inducing ischemia. To determine the effect of mAbs on the survival rate, total hepatic ischemia was induced by clamping the hepatic artery, portal vein, and bile duct after making a portafemoral shunt. RESULTS: Although ischemia of the liver for 90 minutes did not permit survival of the animals, pretreatment with mAbs to ICAM-1 plus LFA-1 increased the survival rate to 57%. Pretreatment with mAb to ICAM-1 failed to increase the survival rate. The number of PMNs in the liver increased continually up to 24 hours after reperfusion after 90 minutes of ischemia, and the expression of ICAM-1 was enhanced 4 hours after reperfusion. This is accompanied by a low recovery of hepatic adenosine triphosphate and, on the contrary, a marked increase in lipid-peroxide in the reperfused liver. Pretreatment with mAbs suppressed the infiltration of PMNs and the elevation of lipid peroxide and enhanced the recovery of hepatic adenosine triphosphate 6, 12, or 24 hours after reperfusion. Pretreatment with mAbs also prevented the rise in serum alanine aminotransferase level after reperfusion. CONCLUSIONS: These results suggest that PMNs contribute to ischemia-reperfusion injury in the liver 4 hours and more after reperfusion, and pretreatment with mAbs to adhesion molecules is useful for the prevention of ischemic liver cell injury.

Adenine Nucleotides↗
PubMed1997

Cognitive enhancers and hippocampal long-term potentiation in vitro.

We review our works on the pharmacological modulation of long-term potentiation (LTP) at guinea pig hippocampal mossy fiber-CA3 synapses in vitro. The magnitude of tetanus-induced LTP at the mossy fiber synapse was augmented by perfusion of slices with several cognitive enhancers, such as bifemelane (1 microM). The mossy fiber LTP was enhanced by somatostatin (0.32 microM) and inhibited in somatostatin-depleted slices from cysteamine-treated guinea pigs. An involvement of the 5-HT3 receptor also showed that granisetron (0.1 microM) enhanced the mossy fiber LTP. The above-mentioned enhancements by perfused agents were commonly reversed, at least in part, by muscarinic antagonists. However, the magnitude of mossy fiber LTP was bidirectionally modulated by muscarinic stimulations of slices with physostigmine or carbachol at different concentrations. The enhancing effects of high-concentration carbachol was antagonized by pirenzepine, and in contrast, the inhibition by low-concentration carbachol was antagonized in the presence of AF-DX116. When guinea pigs were preinjected with the cholinotoxin AF64A, the magnitude of LTP was decreased in the slices prepared from AF64A-treated animals. These results suggest that endogenous acetylcholine dominantly plays facilitatory roles through muscarinic M1 receptors in the induction of mossy fiber LTP. The pharmacological characterization of mossy fiber LTP may be of help to the evaluation of cognitive enhancers at a neuronal circuit level.

Animals↗
PubMed1997

Involvement of M2 receptor in an enhancement of long-term potentiation by carbachol in Schaffer collateral-CA1 synapses of hippocampal slices.

We examined effects of carbachol (CCh), muscarinic receptor agonist, on long-term potentiation (LTP) of field excitatory postsynaptic potential (fEPSP) at Schaffer collateral-CA1 synapse of guinea pig hippocampal slices using extracellular recording technique. Application of 0.1 microM CCh to the slices significantly augmented the magnitude of LTP without significant change in the amplitude of pretetanus fEPSP. The enhancement of LTP by 0.1 microM CCh was significantly attenuated by 0.1 microM AF-DX 116, M2 receptor antagonist, but not by 0.1 microM pirenzepine, M1 receptor antagonist. Ten micromolar of carbachol reduced the amplitude of pretetanus fEPSP, while the magnitude of LTP was significantly larger than that in control slices to which tetanus was applied in a stimulus intensity producing pretetanus fEPSPs with an amplitude comparable to those during administration of 10 microM CCh. Neither 0.1 microM pirenzepine nor 0.1 microM AF-DX 116 had significant effect on the enhancement of LTP by 10 microM CCh. These results suggest that the induction of LTP at Schaffer collateral-CA1 synapse was enhanced through the activation of M2 receptors by CCh at a lower concentration.

Animals↗
PubMed1997

Identification of an autoantibody against alpha-enolase in primary biliary cirrhosis.

BACKGROUND: Primary biliary cirrhosis is a chronic cholestatic liver disease in which autoreactive T cells may play an important role in the destruction of intrahepatic bile ducts. However, target antigens remain unknown. Alpha-enolase-derived peptide binds to human leukocyte antigen (HLA)-DR8, which is implicated in the development of primary biliary cirrhosis in Japanese patients. Partial homology between alpha-enolase and the inner lipoyl domain of E2 component of pyruvate dehydrogenase (PDH-E2) is also observed. METHODS: Using alpha, beta and gamma enolase isozymes obtained from humans and/or rabbits, we examined serum samples of 56 patients with primary biliary cirrhosis, 19 autoimmune hepatitis, 38 acute and chronic viral hepatitis and 36 healthy subjects by immunoblotting. RESULTS: Anti-alpha-enolase antibody was present in a significantly higher percentage of patients with primary biliary cirrhosis (16 of 56, 28.6%) and autoimmune hepatitis (6 of 19, 31.6%) than in normal subjects (p<0.005, p<0.01, respectively). Antibodies against beta and gamma-enolases were not detected in any serum sample. Although there was no significant correlation between the presence of anti-alpha-enolase antibody and clinical features of primary biliary cirrhosis, the mortality rate associated with hepatic failure in patients with positive autoantibody was significantly higher than that of antibody-negative PBC patients (6 of 16, 37.5% vs 5 of 40, 12.5%, p<0.05). CONCLUSIONS: Since alpha-enolase is expressed on the cell surface, our data suggest that the immunological reaction to alpha-enolase might be involved in biliary epithelial destruction and be relevant to the disease progression.

Acute Disease↗
PubMed1997

Uterine blood flow velocity waveforms during early postpartum course following caesarean section.

OBJECTIVE: To assess the change of uterine blood flow after Caesarean section. STUDY DESIGN: Doppler flow velocity waveforms were acquired from the uterine arteries and small arteries near the myometrial wound detected by transvaginal power Doppler ultrasonography in 23 patients on the 3rd, 6th and 9th postoperative days. RESULTS: The resistance index for the uterine artery did not show any change during the study period, while that for the small arteries slightly decreased. CONCLUSION: Uterine blood flow resistance after Caesarean section did not show any change during the early postpartum period.

Blood Flow Velocity↗