Biomedical subjects

Yasushi Ito

Publications and source records attributed to Yasushi Ito.

At least 19 recordsLinked to original sources

PubMed2006

Sphingosine 1-phosphate causes airway hyper-reactivity by rho-mediated myosin phosphatase inactivation.

In the present study, we investigated whether extracellular sphingosine 1-phosphate (S1P) is involved in airway hyper-reactivity in bronchial asthma. The effects of S1P on the response to methacholine was examined in the fura-2-loaded strips of guinea pig tracheal smooth muscle using simultaneous recording of the isometric tension and the ratio of fluorescence intensities at 340 and 380 nm (F(340)/F(380)). A 15-min pretreatment with S1P (>100 nM) markedly enhanced methacholine-induced contraction without elevating F(340)/F(380). This effect of S1P was suppressed in the presence of Y-27632 [(R)-(+)-trans-N-(4-pyridyl)-4-(1-aminoethyl)-cyclohexane-carboxamide], a selective inhibitor of Rho-kinase, in a concentration-dependent manner. Moreover, pretreatment with pertussis toxin caused an inhibition in S1P-induced hyper-reactivity to methacholine in a time- and concentration-dependent manner. In contrast, although S1P-induced Ca(2+) mobilization was attenuated by SKF96365 and verapamil, the subsequent response to methacholine was unaffected. A 15-min pretreatment with lower concentrations of S1P (<100 nM), which is clinically attainable, did not increase methacholine-induced contraction. However, when the incubation was lengthened to 6 h, S1P (<100 nM) enhanced the subsequent response to methacholine. Next, application of S1P to cultured human bronchial smooth muscle cells increased the proportion of active RhoA (GTP-RhoA) and phosphorylation of myosin phosphatase target subunit 1 (MYPT1). This phosphorylation of MYPT1 was significantly inhibited by application of Y-27632 and by pretreatment with pertussis toxin. Our findings demonstrate that exposure of airway smooth muscle to S1P results in airway hyper-reactivity mediated by Ca(2+) sensitization via inactivation of myosin phosphatase, which links G(i) and RhoA/Rho-kinase processes.

Animals↗

PubMed2006

Direct effects of hydrogen peroxide on airway smooth muscle tone: roles of Ca2+ influx and Rho-kinase.

Reactive oxidant species are implicated in the chronic airway inflammation related to asthma and chronic obstructive pulmonary disease. This study was designed to determine mechanisms underlying contraction induced by hydrogen peroxide (H(2)O(2)), a clinical marker of oxidative stress, in airway smooth muscle. Isometric tension and fluorescent intensities of fura-2, an index of intracellular Ca(2+) concentrations ([Ca(2+)](i)), were measured in epithelium-denuded tracheal smooth muscle tissues isolated from guinea pigs. H(2)O(2) (0.01-1 mM) caused contraction with an augmentation of [Ca(2+)](i) in a concentration-dependent manner in the normal physiological solution containing 2.4 mM of extracellular Ca(2+) concentrations. The contractile force and [Ca(2+)](i) by H(2)O(2) (1 mM) were approximately half of those in response to 1 microM methacholine. However, contraction by H(2)O(2) was not generated under the condition that extracellular Ca(2+) concentrations were less than 0.15 mM. Verapamil (10 microM), an inhibitor of voltage-operated Ca(2+) channels, partially but significantly inhibited the H(2)O(2)-induced contraction. In contrast, SKF-96365 (1-{beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl}-1H-imidazole hydrochloride) (100 microM), a non-selective inhibitor of Ca(2+) channels, completely abolished both the contraction and the increase in [Ca(2+)](i) elicited by H(2)O(2). Moreover, Y-27632 ((R)-(+)-trans-N-(4-Pyridyl)-4-(1-aminoethyl)-cyclohexanecarboxamide) (0.03-10 microM), an inhibitor of Rho-kinase, caused a concentration-dependent inhibition of the H(2)O(2)-induced contraction. In conclusion, both the Ca(2+) influx from the extracellular side and the Ca(2+) sensitization by Rho-kinase are involved in the regulation of airway smooth muscle tone induced by H(2)O(2). An inhibition of the Rho/Rho-kinase pathway may be beneficial for the treatment of airflow limitation mediated by oxidative stress.

Amides↗

PubMed2006

Modified buddy wire technique for coil embolization of posterior circulation aneurysms.

INTRODUCTION: In coil embolization of a posterior circulation aneurysm, tortuosity or a small vessel caliber frequently prevents placement of a guiding catheter in the vertebral artery. Even in such difficult situations, however, coil embolization is the only treatment option when the patient's clinical condition is very poor, or the aneurysm is inaccessible by microsurgery. METHODS: Three patients with a posterior circulation aneurysm were treated by coil embolization with the use of a modified buddy wire technique to stabilize a guiding catheter that could not be placed into the vertebral artery. RESULTS: The guiding catheter was stabilized in the subclavian artery and the microcatheter was firmly supported. As a result, coil embolization was performed safely in all patients. There were no procedural complications. CONCLUSION: The modified buddy wire technique could provide patients with a chance to undergo endovascular surgery despite having a tortuous or narrow vertebral artery.

Aged↗

PubMed2006

Lig-8, a bioactive lignophenol derivative from bamboo lignin, protects against neuronal damage in vitro and in vivo.

Lig-8, a lignophenol derivative from bamboo lignin, potently suppresses oxidative stress-induced apoptosis. Here, we first examined in vitro whether lig-8 protects against neuronal damage induced by oxygen-glucose deprivation (OGD) followed by reoxygenation, tunicamycin [endoplasmic reticulum (ER)-stress inducer], or PSI (proteasome inhibitor). In pheochromocytoma (PC12) cell cultures, lig-8 (1 to 30 microM) concentration-dependently inhibited OGD- and tunicamycin (2 microg/ml)-induced cell deaths (significant at >/=3 microM and >/=1 microM, respectively). In human neuroblastoma (SH-SY5Y) cell culture, the PSI-induced apoptotic cell death and fusion protein accumulation (revealing reduced proteasome activity) was inhibited by lig-8 (30 microM). On the other hand, lig-8 at 30 microM alone did not affect any proteasome activity under resting conditions. In vivo, lig-8 (0.1 nmol/eye) reduced intravitreal N-methyl-D-aspartate (NMDA, 20 nmol)-induced retinal damage (decreases in retinal ganglion cells and inner plexiform layer thickness). Hence, lig-8 protects, partly by inhibiting excessive ER-stress, against neuronal damage in vitro and in vivo.

Animals↗

PubMed2006

Roles of stretch-activated cation channel and Rho-kinase in the spontaneous contraction of airway smooth muscle.

In guinea pigs, it is well-known that mechanical stretch of airway smooth muscle exhibits spontaneous tone which is mediated by cyclooxygenase (COX) activation. We tested the hypothesis that this spontaneous contraction of airway smooth muscle is mediated by stretch-activated non-selective cation channels and the Rho/Rho-kinase pathway, as well as COX-2 using a pharmacological approach. Isometric force and intracellular Ca(2+) concentrations ([Ca(2+)](i)) were assessed in isolated guinea pig tracheal smooth muscle tissues. The samples were stretched to a given level and the muscle behavior was monitored under isometric conditions. We observed an increase in [Ca(2+)](i) and subsequent force generation over a 15-min period. The augmented [Ca(2+)](i) and spontaneous contraction due to the stretch were markedly attenuated by application of Gd(3+), an inhibitor of stretch-activated channels, and removal of extracellular Ca(2+). In contrast, nifedipine only had a mild inhibitory effect on the contraction. (R)-(+)-trans-N-(4-pyridyl)-4-(1-aminoethyl)-cyclohexane-carboxamide (Y-27632; a Rho-kinase inhibitor) abolished the spontaneous contraction with no changes in [Ca(2+)](i). Simvastatin, which down-regulates Rho activity, also significantly inhibited the contraction. Moreover, indomethacin, an inhibitor of COX-1 and -2, and N-[2-(cyclohexyloxy)-4-nitrophenyl]-methanesulfonamide (NS-398; a COX-2 inhibitor) abolished the stretch-induced contraction without affecting [Ca(2+)](i), whereas the inhibitory effect of 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole (SC560; a COX-1 inhibitor) on the contraction was much less. These findings demonstrated that Ca(2+) entry via stretch-activated channels, the Rho/Rho-kinase pathway, and COX-2 are involved in the mechanotransduction in guinea pig tracheal smooth muscle. Additionally, while the Rho/Rho-kinase pathway and COX-2 regulate the spontaneous contraction independently of [Ca(2+)](i), COX-1 is not involved in the stretch-induced force generation.

Amides↗

PubMed2006

Role of RhoA inactivation in reduced cell proliferation of human airway smooth muscle by simvastatin.

Enhanced proliferation of smooth muscle cells contributes to airway remodeling of bronchial asthma. Recently, statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, have been shown to inhibit proliferation of both vascular and airway smooth muscle cells independently of lowering cholesterol. However, the mechanisms remain to be elucidated. The purpose of this study was to determine molecular processes by which statins inhibit proliferation of human bronchial smooth muscle cells. Simvastatin (0.1-1.0 muM) significantly inhibited cell proliferation and DNA synthesis induced by FBS in a concentration-dependent manner. The inhibitory effects of simvastatin were antagonized by mevalonate and geranylgeranylpyrophosphate, whereas the effects were not affected by squalene and farnesylpyrophosphate. The antiproliferative effects of simvastatin were mimicked by GGTI-286, a geranylgeranyltransferase-I inhibitor, C3 exoenzyme, an inhibitor of Rho, and Y-27632, an inhibitor of Rho-kinase, a target protein of RhoA. Western blot analysis showed that the level of membrane localization of RhoA (active Rho) was markedly increased by FBS, and that the level of active RhoA increased by FBS was reduced by simvastatin. Moreover, the inhibitory effect of simvastatin on FBS-induced RhoA activation was also antagonized by geranylgeranylpyrophosphate, but not by farnesylpyrophosphate. Because these isoprenoids are required for prenylation of small G proteins RhoA and Ras, respectively, the present results demonstrate that an inhibition in airway smooth muscle cell proliferation by simvastatin is due to prevention of geranylgeranylation of RhoA, not farnesylation of Ras. Therefore, statins may have therapeutic potential for prohibiting airway remodeling in bronchial asthma.

ADP Ribose Transferases↗

PubMed2006

TRH therapy in a patient with juvenile Alexander disease.

Alexander disease is a rare disorder of the central nervous system caused by a de novo mutation in the glial fibrillary acidic protein (GFAP) gene. Unlike the much more common infantile form, the juvenile form is slowly progressive with bulbar, pyramidal and cerebellar signs. Herein, we report a 9-year old Japanese girl suffering from frequent vomiting, slurred speech and truncal ataxia. Juvenile Alexander disease was diagnosed by genetic analysis, which detected a novel GFAP mutation, D360V. We also describe our clinical success in treating this patient with thyrotropin releasing hormone (TRH).

Alexander Disease↗

PubMed2006

Tyrosine kinase inhibitors and ATP modulate the conversion of smooth muscle L-type Ca2+ channels toward a second open state.

Properties of smooth and cardiac L-type Ca2+ channels differ prominently in several physiological aspects, including sympathetic modulation. To assess the possible underlying mechanisms, we applied the whole cell patch-clamp technique to guinea pig detrusor smooth muscle cells, in which only L-type Ca2+ channel currents are observed in practice. During depolarization to large positive potentials, the conformation of the majority of L-type Ca2+ channels is converted from the normal (O1) to a second open state (O2), which undergoes little inactivation during depolarization. Extracellular application of genistein, a known tyrosine kinase inhibitor, significantly attenuated the voltage-dependent conversion of Ca2+ channels to O2, accompanied by reduction of availability, whereas genistin, an inactive analog, had little effect. In the absence of ATP in the patch pipette, intracellular application of either genistein or tyrphostin-47 suppressed the conversion to O2. Computer calculation revealed that the acceleration of the O1 to an inactivated state qualitatively reconstructs the unique effects of PTK inhibitors antagonized by ATP. We concluded that under normal conditions smooth muscle L-type Ca2+ channels are already modulated by tyrosine-kinase and ATP-related mechanism(s) and thereby easily achieve the second conversion, which yields voltage-dependent modulation of L-type Ca2+ current analogous to that in cardiac myocytes during beta-adrenoceptor stimulation.

Adenosine Triphosphate↗

PubMed2006

Paradoxical effects of hydrogen peroxide on human airway anion secretion.

The present study concerns intriguing effects of hydrogen peroxide (H2O2) on cAMP-mediated anion secretion in polarized human airway epithelia. Although H2O2 applied to the apical and basolateral membrane increases short-circuit currents (ISC) with analogous properties, it has opposite effects on subsequent cAMP-activated ISC responses. Namely, forskolin (FK)-induced ISC responses were down-regulated by the apical presence of H2O2, whereas they were up-regulated by its basolateral presence. Despite this contrasting effect, oxidative stimuli from either aspect of the monolayer hindered FK-induced increments in cytosolic cAMP levels and apical membrane Cl- conductance. The site-dependent effects of H2O2 were reproduced in the responses to 8-bromo-cAMP. Estimation of the anionic composition of the ISC revealed that the FK up-regulated both bumetanide [an Na+-K+-2Cl- cotransporter (NKCC1) inhibitor]-sensitive and 4,4'-dinitrostilbene-2,2'-disulfonic acid [an HCO3--dependent anion transporter (NBC1/AE2) inhibitor]-sensitive ISC in the control, whereas the up-regulation evidently favored bumetanide-sensitive ISC in the basolateral presence of H2O2. The FK-induced NKCC1 augmentation after exposure to basolateral H2O2 was counteracted by cytochalasin D, an inhibitor of microfilament function, but not by charybdotoxin, a blocker of the intermediate conductance Ca2+-activated K+ channel, whose activation could be related to NKCC1-mediated Cl- secretion. These observations suggest that basolaterally but not apically applied H2O2 potentiates subsequent cAMP-mediated Cl- secretion by an increase in Cl- uptake via basolateral NKCC1, whose sensitivities to cAMP/protein kinase A are up-regulated, overcoming the H2O2-induced inhibition of cAMP-mediated apical anion conductance. The basolateral membrane-specific effects of H2O2 may be relevant to the basolateral cytoskeleton, which is believed to interact with NKCC1.

Anions↗

PubMed2006

[Examination of formula for enhanced dynamic wedge factors in half fields].

The method presented by Liu et al. in 1998 has generally been used in Japan to calculate the wedge factor of the enhanced dynamic wedge (EDW). When the points used to evaluate the dose exist outside the central beam axis in the half field (HF), however, a difference of about 3% can occur between the values calculated by this method and the measured values. In 2003, Liu et al. presented a new general formula for calculating MU using the EDW. We modified the formula for calculating the wedge factor by combining the conventional calculation formula and the formula of Liu et al., presented in 2003, and compared the calculated values of the wedge factor of the EDW in the HF with the measured values. Our formula employs a very simple method in which only the normalized golden segmented treatment table (NGSTT) on the center of the radiation field and the central beam axis are added to the existing formula. The values calculated by our formula and the measured values were consistent within 1% in most combinations of energy, wedge angle, and size of radiation field. When the EDW was used for irradiation to the tangent line of the HF breast, in particular, the values calculated by our formula and the measured values were consistent within 0.5%, and it was possible to calculate the wedge factor with a higher degree of accuracy than that calculated with the existing formula.

Calibration↗

PubMed2006

[Successful antiemetic treatment of TSUMURA Rikkunshi-to Extract Granules for ethical use in addition to other antiemetic agents in neoadjuvant chemotherapy for an advanced breast cancer patient].

A 45-year-old woman who suffered from left breast cancer, 8 cm in diameter, with skin invasion and axillary lymph node involvement but no distant metastasis, underwent neoadjuvant chemotherapy. FEC100 consisting of 5-FU (500 mg/m(2)), epirubicin (100 mg/m(2)) and cyclophosphamide (500 mg/m(2)), were given intravenously for tumor reduction in connection with breast conserving surgery. Although antiemetic agents such as granisetron hydrochloride,metoclopramide and dexamethasone failed to prevent frequent emesis and loss of appetite in the first course, TSUMURA Rikkunshi-to Extract Granules (Rikkunshi-to) in addition to those antiemetic agents from the second course remarkably well controlled nausea and vomiting. Consequently, 6 courses of neoadjuvant chemotherapy were carried out successfully and brought about complete tumor remission. Rikkunshi-to was first medicated for non-ulcer dyspepsia, but now we suggest that it is possibly a good new antiemetic agent.

Antiemetics↗

PubMed2005

Sulphonylurea receptors differently modulate ICC pacemaker Ca2+ activity and smooth muscle contractility.

Appropriate gastrointestinal motility is essential to properly control the body energy level. Intracellular Ca2+ ([Ca2+]i) oscillations in interstitial cells of Cajal (ICCs; identified with c-Kit immunoreactivity) are considered to be the primary mechanism for the pacemaker activity in gastrointestinal motility. In the present study, RT-PCR examinations revealed predominant expression of the type 1 isoform of sulphonylurea receptors (SUR1) in ICCs of the mouse ileum, but expression of SUR2 was predominant in smooth muscle. In cell clusters prepared from the same tissue, smooth muscle contractility and pacemaker [Ca2+]i activity in ICCs were found to be differentially modulated by K(ATP) channel openers and sulphonylurea compounds, in accordance with the expression of SUR isoforms. 1 microM cromakalim nearly fully suppressed the mechanical activity in smooth muscle, whereas ICC pacemaker [Ca2+]i oscillations persisted. Greater concentrations (approximately 10 microM) of cromakalim attenuated pacemaker [Ca2+]i oscillations. This effect was not reversed by changing the reversal potential of K+, but was prevented by glibenclamide. Diazoxide at 30 muM terminated ICC pacemaker [Ca2+]i oscillations, but again treatment with high extracellular K+ did not restore them. These results suggest that SUR can modulate pacemaker [Ca2+]i oscillations via voltage-independent mechanism(s), and also that intestinal pacemaking and glucose control are closely associated with SUR.

ATP-Binding Cassette Transporters↗

PubMed2005

Evaluation of in-stent stenosis by magnetic resonance phase-velocity mapping in nickel-titanium stents.

PURPOSE: To evaluate different grades of in-stent stenosis in a nickel-titanium stent with MRI. MATERIALS AND METHODS: Magnetic resonance phase velocity mapping (MR-PVM) was used to measure flow velocity through a 9-mm NiTi stent with three different degrees of stenosis in a phantom study. The tested stenotic geometries were 1) axisymmetric 75%, 2) axisymmetric 90%, and 3) asymmetric 50%. The MR-PVM data were subsequently compared with the velocities from computational fluid dynamic (CFD) simulations of identical conditions. RESULTS: Good quantitative agreement in velocity distribution for the 50% and 75% stenoses was observed. The agreement was poor for the 90% stenosis, most likely due to turbulence and the high-velocity gradients found in the small luminal area relative to the pixel resolution in our imaging settings. CONCLUSION: The accuracy of the MRI velocities inside the stented area renders MRI a modality that may be used to assess moderate to severe in-stent restenosis (ISR) in medium-sized vascular stents in peripheral vessels, such as the iliac, carotid, and femoral arteries. Advances in MR instrumentation may provide sufficient resolution to obtain adequate velocity information from smaller vessels, such as the coronary arteries, and allow MRI to substitute for invasive and expensive catheterization procedures currently in clinical use.

Constriction, Pathologic↗

PubMed2005

Autonomic dysfunction in cases of spinal muscular atrophy type 1 with long survival.

In Japan, quite a few patients with spinal muscular atrophy type 1 (SMA type 1) survive with mechanical ventilation. Since a patient with SMA type 1 and continuous artificial ventilation exhibited excessive perspiration and tachycardia, we examined the autonomic functions in three cases of SMA type 1, undergoing mechanical ventilation. Two cases exhibited the common sympathetic-vagal imbalance on R-R interval analysis involving 24-h Holter ECG recordings in addition to an abnormality in finger cold-induced vasodilatation. Furthermore, one case showed blood pressure and heart rate fluctuation with the paroxysmal elevation, and a high plasma concentration of norepinephrine during tachycardia. These findings suggest that autonomic dysfunction should be examined in SMA type 1 patients with long survival, although the pathogenesis remains to be clarified.

Autonomic Nervous System↗

PubMed2005

Ion transport regulated by protease-activated receptor 2 in human airway Calu-3 epithelia.

We examined the mechanisms underlying anion secretion mediated by protease-activated receptor 2 (PAR2) and its role in the regulation of ion transport, using polarized human airway Calu-3 cells. PAR2 stimulation by trypsin and a PAR2-activating peptide (PAR2AP), especially from the basolateral aspect, caused transient Cl(-) secretion due to cytosolic Ca(2+) mobilization. Antagonists of PI-PLC (U73122, ET-18-OCH(3)) and inositol 1,4,5-triphosphate (xestospongin C (Xest C)) were without effect on the PAR2AP-mediated Cl(-) secretion, whereas it was attenuated by D609 (a PC-PLC inhibitor) and phorbol 12-myristate 13 acetate (PMA, a PKC activator). Even 30 min after removal of PAR2AP after a 10-min-exposure, cells were still poorly responsive to PAR2 stimulation, but the reduced responsiveness was upregulated by a PKC inhibitor, GF109203X (GFX). Pretreatment with PAR2AP did not affect responses to anion secretagogues, such as isoproterenol, forskolin, thapsigargin, 1-ethyl-2-benzimdazolinone, and adenosine, but ATP-induced responses were significantly reduced. Nystatin permeabilization studies revealed that the presence of PAR2AP prevented ATP-induced increments in basolateral membrane K(+) conductance without affecting apical membrane Cl(-) conductance. ATP-elicited Ca(2+) mobilization, which was sensitive to D609 and PMA, was inhibited by the pretreatment with PAR2AP, and this inhibition was blunted by the presence of GFX. Collectively, stimulation of PAR2 generates a brief response of Cl(-) secretion through PC-PLC-mediated pathway, followed by not only auto-desensitization of PAR2 itself but also cross-desensitization of a PC-PLC-coupled purinoceptor. The two types of desensitization seem likely to have PKC-mediated downregulation of PC-PLC in common.

Calcium↗

PubMed2005

Blood pressure in the artery distal to an intraarterial embolus during thrombolytic therapy for occlusion of a major artery: a predictor of cerebral infarction following good recanalization.

OBJECT: The aim in this study was the investigation of back pressure in arteries distal to the occlusion site during intraarterial thrombolysis as well as the usefulness of back pressure measurement in combination with diffusion-weighted (DW) magnetic resonance (MR) imaging to predict the occurrence of ischemic lesions following good recanalization. METHODS: . Twenty-five consecutive patients with severe hemiparesis caused by embolism of the internal carotid artery (10 patients) and the proximal middle cerebral artery (15 patients) were treated using intraarterial thrombolysis. Systolic back pressure, measured through a microcatheter in the artery just distal to the emboli, ranged from 22 to 78 mm Hg. According to an angiographic inclusion criterion for good recanalization--that is, recanalization of the M2 or more distal arteries at the end of thrombolysis--21 of 25 patients underwent evaluation in this study. In 14 patients volumes of low-density areas on computerized tomography (CT) scans obtained 2 months postthrombolysis were smaller in comparison with volumes of hyperintense areas on DW MR images acquired before treatment, whereas these low-density areas were larger in seven patients. Compared with those on initial DW MR images, the volume of abnormalities on CT scans obtained 2 months posttreatment were significantly reduced in patients with a systolic back pressure greater than 30 mm Hg (16 patients) than in those with a back pressure of 30 mm Hg or less (five patients) (p < 0.05). Systolic back pressures greater than 30 mm Hg were associated with significantly better modified Rankin Scale scores than those 30 mm Hg or less (p < 0.05). CONCLUSIONS: Back pressure measurement in combination with DW MR imaging can be used to predict the occurrence of infarction as demonstrated on CT scans following thrombolysis.

Aged↗

PubMed2004

Clinical presentation, EEG studies, and novel mutations in two cases of GLUT1 deficiency syndrome in Japan.

We report the first two Japanese children diagnosed with glucose transporter type 1 (GLUT1) deficiency syndrome. Both boys had been treated under the initial diagnosis of epilepsy and were reinvestigated for previously unexplainable hypoglycorrhachia. Myoclonic seizures developed at 4 months of age in Patient #1 (7 years old), and at 2 months of age in Patient #2 (11 years old), followed by cerebellar ataxia, spastic diplegia, and mental retardation. Both patients had hypoglycorrhachia, and the symptoms were more severe in the latter. CSF and serum glucose levels determined simultaneously showed a CSF/serum glucose ratio of below 0.4 in both patients. In mildly affected Patient #1, the postprandial waking EEG showed improvement in the background activity, as compared to that recorded after overnight fasting, while no significant changes were observed in severely affected Patient #2. In both patients, the functional GLUT1 defect was confirmed by 3-O-methyl-D-glucose uptake into erythrocytes. Molecular analyses identified heterozygous novel mutations in both patients, within exons 6 and 2 of the GLUT1 gene, respectively. The ketogenic diet was refused in Patient #1, but started in Patient #2 with significant clinical benefit. Fasting CSF analysis and pre-/postprandial EEG changes in children with epileptic seizures and unexplainable neurological deterioration help in diagnosing this potentially treatable disorder.

Base Sequence↗

PubMed2004

Soluble Fas and Fas ligand provide new information on metastasis and response to chemotherapy in SCLC patients.

BACKGROUND: The Fas/Fas ligand (FasL) system is a major regulator of apoptosis. Chemotherapeutic drugs have been shown to induce Fas expression on the surface of lung cancer cells, and cancer cell apoptosis. However, this mechanism is not considered to be associated with Fas expressed on lung cancer cells. Soluble Fas and FasL concentrations are reportedly elevated in the peripheral blood of patients with lung cancer, but the roles of circulating soluble Fas and FasL in that disease have not been clarified. MATERIALS AND METHODS: We measured the circulating soluble Fas and FasL levels in 21 patients with small cell lung cancer (SCLC), and 12 healthy matched controls, in order to examine whether such ligands could provide any important information and/or reveal any new clinical features of SCLC. RESULTS: In the CR patients, the neuronal specific enolase (NSE), soluble Fas and soluble FasL concentrations were 21.26+/-3.65 ng/ml, 3.58+/-0.19 ng/ml and 0.50+/-0.15 ng/ml, while in the partial response (PR)/no change (NC)/progressive disease (PD) group of patients they were 33.96+/-7.86 ng/ml, 5.29+/-0.29 ng/ml and 0.59+/-0.07 ng/ml, respectively. The NSE, soluble Fas and soluble FasL concentrations were all elevated in the PR/NC/PD patients, however, significant differences were only seen in Fas concentration between CR and PR/NC/PD patients and CR patients and the controls (p<0.001). CONCLUSIONS: Serum soluble Fas and FasL play important roles in the proliferation and metastasis of SCLC, as well as in the cytotoxic reaction and apoptosis induced by anticancer drugs in SCLC. Further study of the mechanisms and participation of circulating soluble Fas and FasL is necessary to develop treatment strategies for SCLC.

Aged↗