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Biomedical subjects

Makoto Inoue

Publications and source records attributed to Makoto Inoue.

At least 55 records · Page 3Linked to original sources
PubMed2006

[A case of exacerbation of ulcerative colitis induced by combination therapy with PEG-interferon alpha-2b and ribavirin for chronic hepatitis C].

A 55-year-old man with chronic hepatitis C had diarrhea with bloody stool in July, 2003 and ulcerative colitis was suspected. However, he quickly improved. He was treated with percutaneous radiofrequency ablation therapy for adenomatous hyperplasia in S5 of the liver in December, 2004. After the ablation therapy, he was treated with combination therapy of PEG-interferon alpha-2b and ribavirin for chronic hepatitis C. Because exacerbation of ulcerative colitis appeared 10 weeks after beginning of the treatment for hepatitis C, the combination therapy of PEG-interferon and ribavirin was discontinued. He was treated with mesalazine and steroid therapy for ulcerative colitis, and improved. We report the first case in Japan of the exacerbation of ulcerative colitis induced by the combination therapy of PEG-interferon and ribavirin for chronic hepatitis C.

Antiviral Agents↗
PubMed2005

Changes in reflex responses of the genioglossus muscle during sleep in rabbits.

Changes in reflex responses in the genioglossus (GG) muscle evoked by electrical stimulation of the inferior alveolar nerve and GG muscle tone (background activity, BGA) were investigated during sleep-wakefulness stages in rabbits. The GG muscle showed two types of electromyographic activity patterns: a respiration-related phasic activity and non-respiration-related activity. GG reflex responses and BGA exhibited a stage-dependent decrease as they were constantly suppressed from quiet wakefulness to non-rapid eye movement sleep to rapid eye movement sleep (REMS). Degree of suppression of reflexes was much larger than that of BGA regardless of GG activity patterns. When amplitude of reflex responses was compared between with and without rapid eye movements during REMS, no difference between the conditions was noted. These results suggest that excitability of the GG muscle is affected by sleep stages by not only a modulation of excitability in motoneurons but also in interneurons involved in the reflex arc.

Animals↗
PubMed2005

Diabetic microangiopathy in ischemic limb is a disease of disturbance of the platelet-derived growth factor-BB/protein kinase C axis but not of impaired expression of angiogenic factors.

Diabetic foot is caused by microangiopathy and is suggested to be a result of impaired angiogenesis. Using a severe hindlimb ischemia model of streptozotocin-induced diabetic mice (STZ-DM), we show that diabetic foot is a disease solely of the disturbance of platelet-derived growth factor B-chain homodimer (PDGF-BB) expression but not responses of angiogenic factors. STZ-DM mice frequently lost their hindlimbs after induced ischemia, whereas non-DM mice did not. Screening of angiogenesis-related factors revealed that only the expression of PDGF-BB was impaired in the STZ-DM mice on baseline, as well as over a time course after limb ischemia. Supplementation of the PDGF-B gene resulted in the prevention of autoamputation, and, furthermore, a protein kinase C (PKC) inhibitor restored the PDGF-BB expression and also resulted in complete rescue of the limbs of the STZ-DM mice. Inhibition of overproduction of advanced-glycation end product resulted in dephosphorylation of PKC-alpha and restored expression of PDGF-BB irrespective of blood sugar and HbA1c, indicating that advanced-glycation end product is an essential regulator for PKC/PDGF-BB in diabetic state. These findings are clear evidence indicating that diabetic vascular complications are caused by impairment of the PKC/PDGF-B axis, but not by the impaired expression of angiogenic factors, and possibly imply the molecular target of diabetic foot.

Angiogenesis Inducing Agents↗
PubMed2005

A free radical scavenger but not FGF-2-mediated angiogenic therapy rescues myonephropathic metabolic syndrome in severe hindlimb ischemia.

The therapeutic use of angiogenic factors shows promise in the treatment of critical limb ischemia; however, its potential for myonephropathic metabolic syndrome (MNMS), a fatal complication caused by arterial reconstruction, has not been elucidated. The objective of this study was to evaluate the effectiveness of recombinant Sendai virus-mediated gene transfer of fibroblast growth factor-2 (FGF-2) directly compared with that of a radical scavenger, MCI-186, in a rat model of MNMS. MNMS was surgically induced by aortic occlusion below renal arteries for 4 h, followed by 6 h of reperfusion. Administration of MCI-186 (twice; iv 5 min before induced ischemia and ip 5 min before reperfusion; 10 mg/kg, respectively), but not FGF-2 gene transfer (once, 48 h before induced ischemia), dramatically prevented the increase of serum biochemical markers as well as the edema of the gastrocnemius muscle. The effect of MCI-186 was accompanied by the marked suppression of the neutrophilic infiltration into the local (muscle) and remote (lung) organs. Although serum and muscular levels of a neutrophil-chemoattractant (growth-related oncogene/cytokine-induced neutrophil chemoattractant-1) were not affected by any treatment, the serum level of soluble intercellular adhesion molecule-1 was decreased by treatment with MCI-186 but not by treatment with FGF-2. These results suggest the distinct mechanism of MNMS from critical limb ischemia without reperfusion. Therefore, radical scavenging should be paid more attention than therapeutic angiogenesis when arterial circulation is reconstructed.

Angiogenesis Inducing Agents↗
PubMed2005

Unilateral application of an inflammatory irritant to the rat temporomandibular joint region produces bilateral modulation of the jaw-opening reflex.

The aim of this study was to determine the effect of unilateral acute inflammation of craniofacial deep tissues on the ipsilateral and contralateral jaw-opening reflex (JOR). The effects of mustard oil (MO), injected into the temporomandibular joint region, were tested on the JOR recorded in the digastric muscle and evoked by low-intensity electrical stimulation of the ipsilateral and contralateral inferior alveolar nerve in anesthetized rats. The MO injection induced a long-lasting suppression of the amplitude of both ipsilaterally and contralaterally evoked JOR, although the latency and duration of the JOR were unaffected. The suppressive effect was more prominent for the contralaterally evoked JOR, and observed even when background activity in the digastric muscle was increased by the MO injection. The results indicate that changes in the JOR amplitude following MO injection do not simply reflect alterations in motoneuronal excitability, and suggest that inflammation of deep craniofacial tissues modulates low-threshold sensory transmission to the motoneurons.

Analysis of Variance↗
PubMed2005

Royal jelly has estrogenic effects in vitro and in vivo.

Royal jelly (RJ) from honeybees (Apis mellifera) is traditionally thought to improve menopausal symptoms. The potential estrogenic activities of RJ were investigated using various approaches. RJ competed for binding of 17beta-estradiol to the human estrogen receptor alpha and beta but its affinities were weak compared with diethylstilbestrol and phytoestrogens. The reporter gene expression assays suggested that 0.1-1 mg/ml RJ activated estrogen receptors, leading to enhanced transcription of a reporter gene through an estrogen-responsive element. 1 mg/ml RJ stimulated the mRNA expression of estrogen-responsive pS2 and vascular endothelial growth factor (VEGF) by increasing gene transcription in MCF-7 cells. Treatment with RJ at concentrations ranging from 0.5 to 1 mg/ml enhanced MCF-7 cell proliferation, but concomitant treatment with 1 microM tamoxifen blocked this effect. In vivo studies using ovariectomized rats showed that 17beta-estradiol (20 mg/kg, s.c.) treatment restored VEGF expression in both uterus and brain, whereas RJ (1 g/kg, s.c.) restored it in uterus but not in brain. These findings provide evidence that RJ has estrogenic activities through interaction with estrogen receptors followed by endogenous gene expressions.

Animals↗
PubMed2005

Time course of dopamine D2 receptor occupancy by clozapine with medium and high plasma concentrations.

Most antipsychotics were thought to induce antipsychotic action at an excess of 70% striatal dopamine D2 receptor occupancy, while the clinical dose of clozapine was reported to show less than 60% occupancy. High-dose clozapine could occupy as high as 80% of striatal dopamine D2 receptor in monkey PET studies. Although the time course of dopamine D2 receptor occupancy is an important property of antipsychotics, that by clozapine has not been investigated in a clinical setting. We measured the time course of extrastriatal dopamine D2 receptor occupancy with different doses of clozapine and evaluated whether the measured occupancies fitted the binding theory. Three consecutive PET scans with [11C]FLB 457 were performed for two patients with schizophrenia, chronically taking 600 mg/day and 200 mg/day of clozapine, respectively. Series of occupancies were also measured in combination with fluvoxamine or paroxetine in one patient. Dopamine D2 receptor occupancies were also simulated using individual clozapine plasma data and previously determined in vivo ED50 value. The occupancy of one patient with high plasma concentration (1207 ng/ml at peak time) was around 75% at peak and around 60% after 26 h. Another patient with medium plasma concentration (649 ng/ml at peak time) showed less than 50% occupancy at peak, decreasing to 15% after 25 h. The measured occupancy values fitted well with the simulated occupancy values. At high plasma concentration, clozapine can induce high extrastriatal dopamine D2 receptor occupancy in the human brain, and this finding fitted well with the theoretical estimation.

Adult↗
PubMed2005

Massive bilateral vitreoretinal hemorrhage in patient with chronic refractory idiopathic thrombocytopenic purpura.

BACKGROUND: We describe a patient with chronic, refractory idiopathic thrombocytopenic purpura (ITP) who developed massive vitreoretinal hemorrhages in both eyes. METHODS: A 49-year-old woman complained of an acute decrease of vision, and ophthalmoscopy revealed bilateral preretinal and subretinal hemorrhages around the optic disc. Her platelet counts were less than 5000/mul in spite of repetitive administration of corticosteroids and immunoglobulins with splenectomy for the chronic refractory ITP. One month later, she developed massive vitreoretinal hemorrhages bilaterally, and vision decreased to hand-motion. RESULTS: Vitrectomy was performed on both eyes after medical treatment to increase platelet counts. The intraretinal hemorrhages were absorbed from the area around the disc and vision recovered to 20/100 in the right eye and 20/2000 in the left after one month. CONCLUSION: Massive vitreoretinal hemorrhages can develop in patients with chronic refractory ITP, and vitrectomy can be beneficial for this condition.

Chronic Disease↗
PubMed2005

Recombinant Sendai virus vector induces complete remission of established brain tumors through efficient interleukin-2 gene transfer in vaccinated rats.

PURPOSE: Sendai virus (SeV), a murine parainfluenza virus type I, replicates independent of cellular genome and directs high-level gene expressions when used as a viral vector. We constructed a nontransmissible recombinant SeV vector by deleting the matrix (M) and fusion (F) genes from its genome (SeV/DeltaMDeltaF) to enhance its safety. We also estimated the therapeutic efficacy of the novel vector system against a rat glioblastoma model. EXPERIMENTAL DESIGN: We administered the recombinant SeV vector carrying the lacZ gene or the human interleukin-2 (hIL-2) gene into established 9L brain tumors in vivo simultaneous with peripheral vaccination using irradiated 9L cells. Sequential monitoring with magnetic resonance imaging was used to evaluate the therapeutic efficacy. RESULTS: We found extensive transduction of the lacZ gene into the brain tumors and confirmed sufficient amounts of interleukin 2 (IL-2) production by hIL2-SeV/DeltaMDeltaF both in vitro and in vivo. The magnetic resonance imaging study showed that the intracerebral injection of hIL2-SeV/DeltaMDeltaF brought about significant reduction of the tumor growth, including complete elimination of the established brain tumors. The (51)Cr release assay showed that significant amounts of 9L-specific cytotoxic T cells were induced by the peripheral vaccination. Immunohistochemical analysis revealed that CD4(+) T cells and CD8(+) T cells were abundantly infiltrated in the target tumors. CONCLUSION: The present results show that the recombinant nontransmissible SeV vector provides efficient in vivo gene transfer that induces significant regression of the established brain tumors and suggest that it will be a safe and useful viral vector for the clinical practice of glioma gene therapy.

Animals↗
PubMed2005

Abnormal effective connectivity of dopamine D2 receptor binding in schizophrenia.

Receptor binding has been examined region by region in both in vitro and in vivo studies, but less attention has been paid to the connectivity of regional receptor binding despite the fact that neurophysiological studies have indicated an extensive inter-regional connectivity. In this study, we investigated the connectivity of regional dopamine D2 receptor binding in positron emission tomography data from 10 drug-naive patients with schizophrenia and 19 healthy controls. We applied a structural equation method to regional receptor binding. The results indicated that the network models of the patients and normal subjects were significantly different. As to the individual path coefficients, (a) connectivity between cortical regions was different between groups; (b) connectivity from the prefrontal cortex, parietal cortex, and thalamus to the anterior cingulate differed from that in controls; and (c) connectivity from the prefrontal cortex to the anterior cingulate and thalamus via the hippocampus was observed in normal subjects but not in patients. These results suggest that a systems-level change reflected in the connectivity of D2 receptor binding is present in schizophrenia.

Adult↗
PubMed2005

Solution structure of the major DNA-binding domain of Arabidopsis thaliana ethylene-insensitive3-like3.

Ethylene-insensitive3 (EIN3) and EIN3-like (EIL) proteins are essential transcription factors in the ethylene signaling of higher plants. The EIN3/EIL proteins bind to the promoter regions of the downstream genes and regulate their expression. The location of the DNA-binding domain (DBD) in the primary structure was unclear, since the proteins show no sequence similarity to other known DBDs. Here, we identify the major DBD of an EIN3/EIL protein, Arabidopsis thaliana EIL3, containing a key mutational site for DNA binding and signaling (ein3-3 site), and determine its solution structure by NMR spectroscopy. The structure consists of five alpha-helices, possessing a novel fold dissimilar to known DBD structures. By a chemical-shift perturbation analysis, a region including the ein3-3 site is suggested to be involved in DNA binding.

Amino Acid Sequence↗
PubMed2005

Coordination of cranial motoneurons during mastication.

Mastication is the first stage of digestion and involves several motor processes such as food intake, intra-oral food transport, bolus formation and chewing in its broad sense. These complicated motor functions can be accomplished by the well-coordinated activities in various cranial motoneurons innervating the jaw, hyoid, tongue and facial muscles. The brainstem masticatory central pattern generator (CPG) plays a crucial role in generating basic activity patterns of these cranial motoneuron groups. However, descending inputs from higher brain (e.g., cerebral cortex) and mastication-generated peripheral sensory inputs also play important roles in modulating the activity pattern of each motoneuron so that the final motor outputs fit the environmental demand. In this review, we focus on the coordination of the trigeminal, facial and hypoglossal motoneurons during mastication. We first summarize findings showing the activity patterns of muscles innervated by these motoneurons during natural mastication, and then discuss the possible neural mechanisms underlying their coordinated activities during mastication.

Animals↗
PubMed2005

Modulation of jaw reflexes induced by noxious stimulation to the muscle in anesthetized rats.

Previous studies have shown that jaw reflexes and activity patterns of the jaw muscles were modulated in the presence of jaw muscle pain. However, there is no study comparing the modulatory effects on the jaw reflexes induced by noxious stimulation to the jaw muscle. To clarify this, effects of the application of mustard oil (MO), an inflammatory irritant, into the temporalis (jaw-closing) muscle on (1) jaw-opening reflex evoked by tooth pulp stimulation (TP-evoked JOR) as a nociceptive reflex, (2) jaw-opening reflex evoked by inferior alveolar nerve stimulation as a non-nociceptive reflex and (3) jaw-closing reflex evoked by trigeminal mesencephalic nucleus stimulation as a proprioceptive reflex were investigated in anesthetized rats. The MO application induced suppression of all reflexes, and the effect on the TP-evoked JOR was more prominent than on the other reflexes. To elucidate the involvement of endogenous opioid system for the suppressive effect, a systemic administration of naloxone following the MO application was conducted. The MO-induced suppressive effect on the TP-evoked JOR was reversed by the naloxone administration. The results suggest that noxious stimulation to the jaw muscle modulate jaw reflexes particularly for the nociceptive jaw-opening reflex, and the modulatory effect includes both facilitatory and inhibitory aspects. The results also suggest that pain modulatory systems such as the endogenous opioid system play a crucial role in the suppression of the nociceptive transmissions related to nociceptive reflexes, and in some pathological states, defense reflexes may not be evoked properly.

Analysis of Variance↗
PubMed2005

Acute and chronic changes in cholesterol modulate Na-Pi cotransport activity in OK cells.

We previously showed an inverse correlation between membrane cholesterol content and Na-P(i) cotransport activity during the aging process and adaptation to alterations in dietary P(i) in the rat (Levi M, Jameson DM, and van der Meer BW. Am J Physiol Renal Fluid Electrolyte Physiol 256: F85-F94, 1989). The purpose of the present study was to determine whether alterations in cholesterol content per se modulate Na-P(i) cotransport activity and apical membrane Na-P(i) protein expression in opossum kidney (OK) cells. Acute cholesterol depletion achieved with beta-methyl cyclodextrin (beta-MCD) resulted in a significant increase in Na-P(i) cotransport activity accompanied by a moderate increase in apical membrane Na-P(i) protein abundance and no alteration of total cellular Na-P(i) protein abundance. Conversely, acute cholesterol enrichment achieved with beta-MCD/cholesterol resulted in a significant decrease in Na-P(i) cotransport activity with a moderate decrease in apical membrane Na-Pi protein abundance and no change of the total cellular Na-P(i) protein abundance. In contrast, chronic cholesterol depletion, achieved by growing cells in lipoprotein-deficient serum (LPDS), resulted in parallel and significant increases in Na-P(i) cotransport activity and apical membrane and total cellular Na-P(i) protein abundance. Cholesterol depletion also resulted in a significant increase in membrane lipid fluidity and alterations in lipid microdomains as determined by laurdan fluorescence spectroscopy and imaging. Chronic cholesterol enrichment, achieved by growing cells in LPDS followed by loading with low-density lipoprotein, resulted in parallel and significant decreases in Na-P(i) cotransport activity and apical membrane and total cellular Na-P(i) protein abundance. Our results indicate that in OK cells acute and chronic alterations in cholesterol content per se modulate Na-P(i) cotransport activity by diverse mechanisms that also include significant interactions of Na-P(i) protein with lipid microdomains.

Animals↗
PubMed2005

Solution structure of an Arabidopsis WRKY DNA binding domain.

The WRKY proteins comprise a major family of transcription factors that are essential in pathogen and salicylic acid responses of higher plants as well as a variety of plant-specific reactions. They share a DNA binding domain, designated as the WRKY domain, which contains an invariant WRKYGQK sequence and a CX4-5CX22-23HXH zinc binding motif. Herein, we report the NMR solution structure of the C-terminal WRKY domain of the Arabidopsis thaliana WRKY4 protein. The structure consists of a four-stranded beta-sheet, with a zinc binding pocket formed by the conserved Cys/His residues located at one end of the beta-sheet, revealing a novel zinc and DNA binding structure. The WRKYGQK residues correspond to the most N-terminal beta-strand, kinked in the middle of the sequence by the Gly residue, which enables extensive hydrophobic interactions involving the Trp residue and contributes to the structural stability of the beta-sheet. Based on a profile of NMR chemical shift perturbations, we propose that the same strand enters the DNA groove and forms contacts with the DNA bases.

Amino Acid Sequence↗
PubMed2005

Solution structure of the PWWP domain of the hepatoma-derived growth factor family.

Among the many PWWP-containing proteins, the largest group of homologous proteins is related to hepatoma-derived growth factor (HDGF). Within a well-conserved region at the extreme N-terminus, HDGF and five HDGF-related proteins (HRPs) always have a PWWP domain, which is a module found in many chromatin-associated proteins. In this study, we determined the solution structure of the PWWP domain of HDGF-related protein-3 (HRP-3) by NMR spectroscopy. The structure consists of a five-stranded beta-barrel with a PWWP-specific long loop connecting beta2 and beta3 (PR-loop), followed by a helical region including two alpha-helices. Its structure was found to have a characteristic solvent-exposed hydrophobic cavity, which is composed of an abundance of aromatic residues in the beta1/beta2 loop (beta-beta arch) and the beta3/beta4 loop. A similar ligand binding cavity occurs at the corresponding position in the Tudor, chromo, and MBT domains, which have structural and probable evolutionary relationships with PWWP domains. These findings suggest that the PWWP domains of the HDGF family bind to some component of chromatin via the cavity.

Amino Acid Motifs↗
PubMed2005

Pars plana vitrectomy with internal limiting membrane removal for macular hole associated with proliferative diabetic retinopathy.

BACKGROUND: We describe the outcome of vitreous surgery in three eyes of three patients with macular hole associated with proliferative diabetic retinopathy (PDR) in the absence of fibrovascular proliferation, a combination of conditions where efficacy is incompletely known. METHODS: The patients, all male were 62, 65, and 66 years old. Panretinal photocoagulation had been performed preoperatively in all, and one eye had undergone vitreous surgery. No fibrovascular tissue causing macular traction was observed in any case. Fluorescein angiography and optical coherence tomography (OCT) demonstrated persistent diabetic macular edema surrounding the hole. Affected eyes were treated with vitrectomy including internal limiting membrane (ILM) peeling; 20% sulfur hexafluoride gas (SF(6)) was introduced for tamponade. RESULTS: Anatomical closure of the macular hole as well as resolution of macular edema was achieved in all cases, and vision improved considerably by more than two Snellen lines. CONCLUSIONS: Vitreous surgery with ILM peeling was effective for macular hole associated with PDR, attaining not only macular hole closure but also resolution of persistent diabetic macular edema.

Aged↗