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Biomedical subjects

S Miyake

Publications and source records attributed to S Miyake.

At least 55 records · Page 3Linked to original sources

Acute effects of smoke exposure on the cellular and cytokine profile in isolated perfused lungs.

The aim of this study was to assess the acute effects of cigarette smoke exposure on cellular and cytokine profile in BAL fluids in an isolated perfused rabbit assay. The experimental animals were categorized into four groups: (1) unexposed controls and (2) cigarette smoke-exposed animals perfused with autologous whole blood; (3) unexposed controls and cigarette smoke-exposed; (4) cigarette smoke-exposed animals perfused with Krebs' Ringer solution containing 5% bovine serum albumin and glucose. Cigarette smoke induced an increase in total cell numbers (mainly alveolar macrophages in BAL fluids) and an increase in the permeability index of BAL. Levels of interleukin 8 were also significantly decreased in BAL fluids due to acute effects of cigarette smoke exposure. The most likely explanation for cigarette smoke-induced increase of inflammatory cells in BAL in lungs is because of the release of pre-existing cells from reservoirs within the lungs. The acute effects of cigarette smoke-induced increase of pulmonary epithelial permeability may also play an important role in the cellular recruitment into airspaces from the lung reservoirs.

Animals↗

Self-organization of orientation maps in a formal neuron model using a cluster learning rule.

Self-organization of orientation maps due to external stimuli in the primary visual area of the cerebral cortex is studied in a two-layered neural network which consists of formal neuron models with a sigmoidal output function. A cluster learning rule is proposed as an extended Hebbian learning rule, where a modification of synaptic connections is influenced by an activation of neighboring output neurons. By making use of self-consistent Monte Carlo method, we evaluate output responses of neurons against explicit inputs after the learning. An orientation map calculated from the output responses reproduces characteristic features of biological ones. Moreover quantitative analysis of our results are consistent with those of experimental results. It is shown that the cluster learning rule plays an important role in forming smooth changes of preferred orientations.

Algorithms↗

Interferon-gamma increases IL-12 mRNA expression and attentuates allergic late-onset airway responses in the Brown Norway rat.

Interferon gamma is a T-helper cell (Th)-1-type cytokine that has been suggested to inhibit the development of an atopic Th2-type profile of cytokine expression. The aim of this study was to investigated the effect of exogenous rat interferon gamma on antigen-induced airway responses, and on Th1 and Th2-type cytokine messenger ribonucleic acid (mRNA) expression in the Brown Norway rat. Rats were actively sensitized to ovalbumin and 14 days later underwent an aerosolized ovalbumin challenge. Animals were intratracheally administered either interferon gamma (3,000 U) or control solvent 30 min prior to, and 2 and 4 h following, antigen challenge. Lung resistance was monitored over an 8-h time period. Using in situ hybridization and immunocytochemistry, the levels of Th1- (interleukin-12) and Th2-type (interleukin4 and -5) cytokine mRNA, and major basic protein expression in the bronchoalveolar lavage fluid of these rats 8 h after ovalbumin challenge were also determined. Administration of interferon gamma attenuated the development of the late-onset airways response in ovalbumin-sensitized antigen-challenged rats (p<0,05). The expression of interleukin-4 and -5 mRNA in the bronchoalveolar lavage fluid of interferon gamma treated rats was significantly attenuated compared to ovalbumin-challenged saline-treated controls (p<0.001). This was accompanied by a significant increase in the expression of interleukin-12 mRNA, and a reduction in eosinophil numbers. Intratracheal administration of interferon gamma modulates the allergic late-onset airways response in rats, and this is associated with a reduction in the expression of T-helper cell 2-type cytokines and an increase in interleukin-12 messenger ribonucleic acid expression within the airways. The present results support a role for interferon gamma in the pathophysiology of acute allergic airway responses, possibly by virtue of its ability to modulate T-helper cell 1- 2-type cytokine expression within the lungs.

Airway Resistance↗

A pathway of neuronal apoptosis induced by hypoxia/reoxygenation: roles of nuclear factor-kappaB and Bcl-2.

As a model of the reperfusion injury found in stroke, we have exposed neurons to hypoxia followed by reoxygenation. Neurons treated with hypoxia/reoxygenation (H/R) respond by activating nuclear factor-kappaB (NFkappaB), releasing cytochrome c from their mitochondria, and ultimately dying. Further supporting an apoptotic mechanism, expression of the antiapoptotic Bcl-2 and Bcl-x proteins was increased following H/R. In this model, adenoviral-mediated transduction of lkappaB expression inhibited NFkappaB activation and significantly accelerated cytochrome c release and caspase-dependent neuronal death. At the same time, expression of mutated lkappaB prevented the increased expression of endogenous Bcl-2 and Bcl-x. In the presence of mutated lkappaB, singular overexpression of only Bcl-2 by adenoviral-mediated transduction significantly inhibited cytochrome c release, caspase-3-like activation, and cell death in response to H/R. These findings suggest a pathway where NFkappaB activation induces overexpression of Bcl-2 and Bcl-x, which function to prevent apoptotic cell death following H/R treatments.

Aerobiosis↗

Increased insulin sensitivity and decreased insulin secretion in offspring of insulin-sensitive type 2 diabetic patients.

To investigate the early defects of glucose metabolism in insulin-sensitive type 2 diabetes, we performed oral and frequently sampled intravenous glucose tolerance tests (OGTT and FSIGT) with minimal model analysis in 15 offspring of Japanese type 2 diabetics with normal insulin sensitivity (insulin resistance index of homeostasis model assessment [HOMA-R] < 2.0) and in 20 healthy control subjects without a family history of type 2 diabetes. The frequency of impaired glucose tolerance (IGT) was 40% (6 of 15) in the offspring and 0% (0 of 20) in the controls. Fasting plasma glucose (4.8 +/- 0.1 v4.6 +/- 0.1 mmol/L, P = .18) and immunoreactive insulin ([IRI] 29.9 +/- 2.5 v 28.3 +/- 2.5 pmol/L, P = .64) were comparable between the offspring and the controls. The rate of glucose disappearance (KG) was significantly lower in the offspring versus the control group (2.00 +/- 0.22 v 2.60 +/- 0.17 min(-1), P= .03). The insulin sensitivity index (Si) was significantly greater in the offspring versus the controls (2.68 +/- 0.41 v 1.71 +/- 0.17 x 10(-4) min(-1) x pmol/L , P = .02). First-phase insulin secretion (FPI) to intravenous glucose was significantly lower in the offspring versus the control group (886 +/- 110 v 2,296 +/- 267 min x pmol/L, P< .01). Glucose effectiveness (SG) was comparable between the offspring and control groups. The disposition index (Si x FPI) was significantly lower in the offspring versus the controls (2,106 +/- 256 v 3,652 +/- 490 x 10(-4), P = .02). When the offspring were subdivided into 2 groups by glucose tolerance status, both normal glucose tolerance (NGT) offspring and IGT offspring showed a significant decrease in FPI and increase in Si. Thus, although the offspring of insulin-sensitive type 2 diabetics had increased insulin sensitivity, the impairment in insulin secretion was more dominant. Our results suggest that the early metabolic abnormality in insulin-sensitive type 2 diabetes is an insulin secretory dysfunction despite increased insulin sensitivity.

Adult↗

Evaluation of filtration leucocytapheresis for use in the treatment of patients with rheumatoid arthritis.

OBJECTIVES: To evaluate the efficacy of filtration leucocytapheresis (LCP) for rheumatoid arthritis (RA). METHODS: LCP was carried out three times, with 1 week separating each session, in 25 drug-resistant RA patients. RESULTS: During each session, 96, 98, 61, 84 and 8% of the granulocytes, monocytes, lymphocytes, platelets and erythrocytes, respectively, that entered the LCP filter were removed. The number of granulocytes, monocytes and lymphocytes in the peripheral blood significantly decreased during each session of LCP. However, there was no significant decrease in the number of circulating blood cells during the study period. On average, 110 x 10(8) granulocytes, 5.23 x 10(8) monocytes, and 20.5 x 10(8) lymphocytes were removed during LCP therapy. Assessment of RA before and after LCP showed a substantial and rapid improvement in the tender joints counts, swollen joint counts, and patient's and physician's assessments. No adverse reactions or complications were noted. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels decreased following LCP, although the change in the latter parameter was statistically insignificant. The concentrations of serum albumin, gamma-globulin, IgG, IgM, CH50 and rheumatoid factor titres did not change during or after LCP. Careful analysis indicated that 16 of 25 patients with RA showed > or =20% improvement following LCP therapy. CONCLUSIONS: Our results suggest that filtration LCP to remove leucocytes from the peripheral blood exerts an immunomodulatory effect in patients with RA.

Arthritis, Rheumatoid↗

Role of DBP in the circadian oscillatory mechanism.

Transcript levels of DBP, a member of the PAR leucine zipper transcription factor family, exhibit a robust rhythm in suprachiasmatic nuclei, the mammalian circadian center. Here we report that DBP is able to activate the promoter of a putative clock oscillating gene, mPer1, by directly binding to the mPer1 promoter. The mPer1 promoter is cooperatively activated by DBP and CLOCK-BMAL1. On the other hand, dbp transcription is activated by CLOCK-BMAL1 through E-boxes and inhibited by the mPER and mCRY proteins, as is the case for mPer1. Thus, a clock-controlled dbp gene may play an important role in central clock oscillation.

ARNTL Transcription Factors↗

Cells degrade a novel inhibitor of differentiation with E1A-like properties upon exiting the cell cycle.

Control of proliferation and differentiation by the retinoblastoma tumor suppressor protein (pRB) and related family members depends upon their interactions with key cellular substrates. Efforts to identify such cellular targets led to the isolation of a novel protein, EID-1 (for E1A-like inhibitor of differentiation 1). Here, we show that EID-1 is a potent inhibitor of differentiation and link this activity to its ability to inhibit p300 (and the highly related molecule, CREB-binding protein, or CBP) histone acetylation activity. EID-1 is rapidly degraded by the proteasome as cells exit the cell cycle. Ubiquitination of EID-1 requires an intact C-terminal region that is also necessary for stable binding to p300 and pRB, two proteins that bind to the ubiquitin ligase MDM2. A pRB variant that can bind to EID1, but not MDM2, stabilizes EID-1 in cells. Thus, EID-1 may act at a nodal point that couples cell cycle exit to the transcriptional activation of genes required for differentiation.

Acetyltransferases↗

Inhalation provocation tests in chronic bird fancier's lung.

BACKGROUND: Patients with chronic bird fancier's lung (BFL) can be classified into two types. One group of patients develops chronic disease with fluctuating acute episodes, including low-grade fever, mild exertional dyspnea, and cough (fluctuating chronic BFL; formerly termed recurrent and relapsing chronic BFL). The other group of patients shows no history of acute episodes (insidious chronic BFL). The diagnosis of chronic BFL is difficult, since the onset of chronic BFL may be insidious, with few if any symptoms during the early stages of the disease process. STUDY OBJECTIVE: To attempt to diagnose the conditions of these patients more precisely, inhalation provocation tests were conducted using avian dropping extracts. DESIGN: Retrospective chart review. SETTING: The Tokyo Medical and Dental University Hospital in Japan. PATIENTS: Eleven patients with chronic BFL (6 with fluctuating chronic BFL and 5 with insidious chronic BFL) and 6 control subjects (4 asymptomatic bird owners and 2 idiopathic pulmonary fibrosis patients) were evaluated. MEASUREMENTS AND RESULTS: Inhalation provocation tests using avian dropping extracts were conducted. All BFL patients were evaluated as positive or probable by inhalation challenge, whereas control subjects were evaluated as negative. A peripheral leukocytosis, an increase of alveolar-arterial oxygen pressure difference, an increase of body temperature, and the development of respiratory symptoms including cough and dyspnea were more frequently observed in chronic BFL patients than in control subjects. All the BFL patients had an increase in neutrophils in BAL fluids following inhalation challenge. CONCLUSIONS: We validated the utility of inhalation challenge for the diagnosis of chronic BFL, including fluctuating and insidious BFL. We also demonstrated that neutrophilia in BAL fluids following inhalation challenge could be added to the diagnostic criteria for chronic BFL.

Acute Disease↗

Transient thyrotoxicosis and hypothyroidism following administration of the GnRH agonist leuprolide acetate.

A 45-year-old women with chronic idiopathic thrombocytopenic purpura was given monthly injections of the GnRH agonist leuprolide acetate for the treatment of uterine leiomyoma. Two weeks after the fifth injection, she showed mild symptoms of thyrotoxicosis. At that time, serum thyroxin (T4) and triiodothyronine (T3) levels were elevated whereas TSH level was suppressed. Anti-thyroglobulin (anti-Tg) and anti-thyroid peroxidase (anti-TPO) antibodies were positive, whereas TSH binding inhibitory immunoglobulin (TBII) was undetectable. Two months later, serum T4 and T3 levels spontaneously decreased below the normal ranges. Five months after the onset of the disease, they returned to normal without any treatment. Anti-TPO and anti-Tg antibodies gradually decreased during the clinical course. Thus, the present case was indicated to be an instance wherein silent thyroiditis developed after leuprolide acetate administration. This is the first report to demonstrate the association of thyroid disorder with leuprolide injection.

Antineoplastic Agents, Hormonal↗

The effects of temperature on the mechanical performance in fatigued single muscle fibers of the frog induced by twitch and tetanus.

Muscle fatigue induced by consecutive twitches or tetani was studied in single skeletal muscle fibers of the frog, Rana japonica. The fatigue by twitch appeared sooner after the start of stimulation at lower temperatures (2-5 degrees C) than at higher ones (15-20 degrees C), while the fatigue by tetanus appeared sooner at higher temperatures. When a twitch-fatigued fiber was bathed in a solution with caffeine (15 mM), the contracture force was much higher than the fatigued force, while in tetanus fatigue, the force by caffeine was not different from the fatigued force. The length-force relation in fatigued fibers was compared with that in pre-fatigue at low and high temperatures. It was noticed that the ascending limb of the length-force curve in fatigued fibers by twitch was lower than that in pre-fatigue at the low temperatures; namely, the fatigue by twitch was more marked in shorter muscle length, while no marked change in the length-force relation was detected in the tetanus fatigue at the low and high temperatures. The maximum shortening velocity, measured by the slack test, decreased in both types of fatigue. These results suggest that the fatigue by twitch may be mainly due to the failure of activation of the contractile system, while in the fatigue by tetanus, the rate of the interaction between actin and myosin may be impaired due to the change in intracellular chemical environment.

Adenosine Triphosphate↗

Purification and characterization of the allergenic components of shimeji mushroom (Tricholoma conglobatum) spore for shimeji workers' hypersensitivity pneumonitis.

Respiratory symptoms and hypersensitivity pneumonitis (HP) among mushroom workers have been well documented. Inhalation of shimeji mushroom (Tricholoma conglobatum) spore has been assumed to be the cause of HP among indoor shimeji cultivating workers. We isolated and partially characterized the allergenic components of shimeji. The sera from 9 HP patients, 10 asymptomatic shimeji workers and 15 normal individuals were examined for shimeji specific IgG and IgA antibodies by ELISA using crude shimeji extract. Shimeji specific IgG- and IgA-antibodies were higher in sera from HP patients than in sera from control subjects. Crude shimeji spore extract was separated and purified by HPLC followed by SDS-PAGE, and their antigenic activity was studied by immunoblotting with a pool of sera from patients. Sera from all HP patients showed IgG and IgA antibody activities to 21, 16 and 14 kD proteins extracted from shimeji spore. The 21 kD protein contained internal peptide amino acid sequence of Gly-Gly-Thr-Val-Ile-Asn-Leu-Leu-Gly, Gln-Arg-Phe-Glu-Glu and Gln-Gly-Ile-Tyr. These results demonstrate that shimeji spore extract contains multiple proteinous components, which have antigenic activity to react with the sera from HP patients among shimeji workers. These proteins may be the potent sensitizing allergens to cause HP among shimeji cultivating workers.

Adult↗

Photic induction of mPer1 and mPer2 in cry-deficient mice lacking a biological clock.

Mice lacking mCry1 and mCry2 are behaviorally arrhythmic. As shown here, cyclic expression of the clock genes mPer1 and mPer2 (mammalian Period genes 1 and 2) in the suprachiasmatic nucleus and peripheral tissues is abolished and mPer1 and mPer2 mRNA levels are constitutively high. These findings indicate that the biological clock is eliminated in the absence of both mCRY1 and mCRY2 (mammalian cryptochromes 1 and 2) and support the idea that mammalian CRY proteins act in the negative limb of the circadian feedback loop. The mCry double-mutant mice retain the ability to have mPer1 and mPer2 expression induced by a brief light stimulus known to phase-shift the biological clock in wild-type animals. Thus, mCRY1 and mCRY2 are dispensable for light-induced phase shifting of the biological clock.

Animals↗

Idiopathic spinal cord herniation. Report of two cases and review of the literature.

The authors describe two occurrences of idiopathic spinal cord herniation, an entity that has been reported previously in only 11 cases. The patients described in this report presented in midlife with Brown-Sequard syndrome. Computerized tomography myelography and magnetic resonance (MR) imaging showed ventral displacement of the spinal cord with no apparent dorsal mass. Intraspinal cerebrospinal fluid (CSF) flow studies in which phase-contrast pulse sequence cine MR imaging was used displayed a normal pattern dorsal to the spinal cord. Percutaneous intrathecal endoscopic observation did not disclose dorsal intradural cysts, but ventral adhesions were seen between the spinal cord and the dura. Microsurgical intradural exploration revealed ventrolateral herniation of the cord and a ventral root through a dural defect into an epidural arachnoid cyst. The adhesions were released, the cord was repositioned intradurally, and the dural defect was patched. The patients showed gradual improvement postsurgery, as did most of the patients in the previously reported cases. The CSF flow and endoscopic studies were found to be particularly informative, and dural patching with surgical membrane is recommended.

Journal Article↗

Cbl-mediated negative regulation of platelet-derived growth factor receptor-dependent cell proliferation. A critical role for Cbl tyrosine kinase-binding domain.

The Cbl proto-oncogene product has emerged as a novel negative regulator of receptor and non-receptor tyrosine kinases. Our previous observations that Cbl overexpression in NIH3T3 cells enhanced the ubiquitination and degradation of the platelet-derived growth factor receptor-alpha (PDGFRalpha) and that the expression of oncogenic Cbl mutants up-regulated the PDGFRalpha signaling machinery strongly suggested that Cbl negatively regulates PDGFRalpha signaling. Here, we show that, similar to PDGFRalpha, selective stimulation of PDGFRbeta induces Cbl phosphorylation, and its physical association with the receptor. Overexpression of wild type Cbl in NIH3T3 cells led to an enhancement of the ligand-dependent ubiquitination and subsequent degradation of the PDGFRbeta, as observed with PDGFRalpha. We show that Cbl-dependent negative regulation of PDGFRalpha and beta results in a reduction of PDGF-induced cell proliferation and protection against apoptosis. A point mutation (G306E) that inactivates the tyrosine kinase binding domain in the N-terminal transforming region of Cbl compromised the PDGF-inducible tyrosine phosphorylation of Cbl although this mutant could still associate with the PDGFR. More importantly, the G306E mutation abrogated the ability of Cbl to enhance the ligand-induced ubiquitination and degradation of the PDGFR and to inhibit the PDGF-dependent cell proliferation and protection from apoptosis. These results demonstrate that Cbl can negatively regulate PDGFR-dependent biological responses and that this function requires the conserved tyrosine kinase binding domain of Cbl.

3T3 Cells↗

Tumor necrosis factor induces Bcl-2 and Bcl-x expression through NFkappaB activation in primary hippocampal neurons.

Emerging data indicate that tumor necrosis factor (TNF) exerts a neuroprotective effect in response to brain injury. Here we examined the mechanism of TNF in preventing neuronal death in primary hippocampal neurons. TNF protected neurons against hypoxia- or nitric oxide-induced injury, with an increase in the anti-apoptotic proteins Bcl-2 and Bcl-x as determined by Western blot and reverse transcriptase-polymerase chain reaction analysis. Treatment of neurons with an antisense oligonucleotide to bcl-2 mRNA or that to bcl-x mRNA blocked the up-regulation of Bcl-2 or Bcl-x expression, respectively, and partially inhibited the neuroprotective effect induced by TNF. Moreover, adenovirus-mediated overexpression of Bcl-2 significantly inhibited hypoxia- or nitric oxide-induced neuronal death. To examine the possible involvement of a transcription factor, NFkappaB, in the regulation of Bcl-2 and Bcl-x expression in TNF-treated neurons, an adenoviral vector capable of expressing a mutated form of IkappaB was used to infect neurons prior to TNF treatment. Expression of the mutant NFkappaB completely inhibited NFkappaB DNA binding activity and inhibited both TNF-induced up-regulation of Bcl-2 and Bcl-x expression and neuroprotective effect. These findings indicate that induction of Bcl-2 and Bcl-x expression through NFkappaB activation is involved in the neuroprotective action of TNF against hypoxia- or nitric oxide-induced injury.

Animals↗

Latanoprost accelerates disruption of the blood-aqueous barrier and the incidence of angiographic cystoid macular edema in early postoperative pseudophakias.

OBJECTIVE: To study the effect of latanoprost, a prostaglandin analog, on the blood-aqueous barrier and angiographic cystoid macular edema (CME) formation in early postoperative pseudophakias. PATIENTS AND METHODS: Included in the study were eyes with ocular hypertension, normal-tension glaucoma, or primary open-angle glaucoma undergoing surgery for cataract. The study consisted of a randomized double-masked trial for latanoprost and an open-label controlled trial for determining the effects of diclofenac sodium or fluorometholone eyedrop use on latanoprost or its placebo. We compared 4 groups of eyes with concurrent application of latanoprost and diclofenac (group A), latanoprost and fluorometholone (group B), latanoprost placebo and diclofenac (group C), and latanoprost placebo and fluorometholone (group D). A laser flare cell meter was used to determine the severity of blood-aqueous barrier disruption, and fluorescein angiography was performed to determine angiographic CME formation. Mean diurnal intraocular pressure differences were compared on the preoperative baseline day and in the fifth postoperative week. Latanoprost (0.005%) or its placebo was given once a day starting 2 days before surgery until the fifth postoperative week. Diclofenac or fluorometholone eyedrops were given 4 times a day before surgery on the day of surgery and 3 times a day until the fifth postoperative week. RESULTS: In group B compared with group D, the amount of flare 3 days and 1 and 2 weeks after surgery and the incidence of angiographic CME in the fifth postoperative week were significantly higher. These 2 factors were significantly higher in group B than in group A (P < .05) and in group D than in group C (P < .01). There was no significant difference in these factors between groups A and C. The intraocular pressure decline was significant in groups A and B compared with groups C and D (P < .05), but there was no significant difference between groups A and B and between groups C and D. CONCLUSIONS: Latanoprost therapy enhances disruption of the blood-aqueous barrier and increases the incidence of angiographic CME formation in early postoperative pseudophakias. Because administration of nonsteroidal eyedrops such as diclofenac seems to prevent the adverse effects of latanoprost therapy while maintaining its effect to lower intraocular pressure, we suggest their concurrent application.

Aged↗

Application of a newly developed, highly sensitive camera and a 3-dimensional high-definition television system in experimental ophthalmic surgeries.

OBJECTIVE: To apply a new television system, which displays highly sensitive, high-quality 3-dimensional (3-D) images, in performing experimental ophthalmic surgeries. METHODS: By combining a high-gain avalanche rushing-amorphous photoconductor (HARP) camera, recently developed in Japan, which has 600 times greater sensitivity than conventional television cameras, and a single-camera, 3-D high-definition television system, which displays high-quality 3-D images, we performed cataract/intraocular lens surgeries and pars plana vitrectomies under various illumination intensities in pig cadaver eyes. RESULTS: Cataract/intraocular lens surgeries were performed using 7.3% the intensity of ordinary surgical microscopic illumination; vitrectomies were performed using 30.2% the intensity of an ordinary endoillumination probe with the HARP camera and by observing the stereoscopic display of the single-camera 3-D high-definition television system. Images identical to those observed by the surgeon were displayed on the stereoscopic display monitor. CONCLUSION: The system not only allowed surgeries to be performed under lower intensities of operating light but also provided real-time, highly sensitive 3-D images identical to those observed by the surgeon; thus, the device may be effectively used for education, team surgery, and telesurgery. CLINICAL RELEVANCE: The new television system for ocular surgeries to be performed under lower intensities of operating light as well as providing real-time, highly sensitive 3-D images identical to those observed by the surgeon may be effectively used for education and telesurgery.

Animals↗