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1.
Phys Rev Lett ; 124(25): 253201, 2020 Jun 26.
Article in English | MEDLINE | ID: mdl-32639753

ABSTRACT

We study an array of ultracold atoms in an optical lattice (Mott insulator) excited with a coherent ultrashort laser pulse to a state where single-electron wave functions spatially overlap. Beyond a threshold principal quantum number where Rydberg orbitals of neighboring lattice sites overlap with each other, the atoms efficiently undergo spontaneous Penning ionization resulting in a drastic change of ion-counting statistics, sharp increase of avalanche ionization, and the formation of an ultracold plasma. These observations signal the actual creation of electronic states with overlapping wave functions, which is further confirmed by a significant difference in ionization dynamics between a Bose-Einstein condensate and a Mott insulator. This system is a promising platform for simulating electronic many-body phenomena dominated by Coulomb interactions in the condensed phase.

2.
Eur Radiol ; 26(2): 547-55, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26017736

ABSTRACT

OBJECTIVES: To compare 3D-inversion-recovery balanced steady-state free precession (IR-bSSFP) non-contrast-enhanced magnetic resonance angiography (MRA) with 3D-contrast-enhanced MRA (CE-MRA) for assessment of renal artery stenosis (RAS) using digital subtraction angiography (DSA) as the reference standard. METHODS: Bilateral RAS were surgically created in 12 swine. IR-bSSFP and CE-MRA were acquired at 1.5 T and compared to rotational DSA. Three experienced cardiovascular radiologists evaluated the IR-bSSFP and CE-MRA studies independently. Linear regression models were used to calibrate and assess the accuracy of IR-bSSFP and CE-MRA, separately, against DSA. The coefficient of determination and Cohen's kappa coefficient were also generated. RESULTS: Calibration of the three readers' RAS grading revealed R(2) values of 0.52, 0.37 and 0.59 for NCE-MRA and 0.48, 0.53 and 0.71 for CE-MRA. Inter-rater agreement demonstrated Cohen's kappa values ranging from 0.25 to 0.65. Distal renal artery branch vessels were visible to a significantly higher degree with NCE-MRA compared to CE-MRA (p < 0.001). Image quality was rated excellent for both sequences, although image noise was higher with CE-MRA (p < 0.05). In no cases did noise interfere with image interpretation. CONCLUSIONS: In a well-controlled animal model of surgically induced RAS, IR-bSSFP based NCE-MRA and CE-MRA accurately graded RAS with a tendency for stenosis overestimation, compared to DSA. KEY POINTS: • IR-bSSFP and CE-MRA are accurate methods for diagnosis of renal artery stenosis • IR-bSSFP and CE-MRA demonstrate excellent agreement with DSA • Both IR-bSSFP and CE-MRA have a tendency to overestimate renal artery stenosis.


Subject(s)
Angiography, Digital Subtraction/methods , Magnetic Resonance Angiography/methods , Renal Artery Obstruction/pathology , Animals , Contrast Media , Disease Models, Animal , Imaging, Three-Dimensional/methods , Renal Artery/pathology , Renal Artery Obstruction/diagnosis , Reproducibility of Results , Swine
3.
Water Sci Technol ; 72(7): 1234-42, 2015.
Article in English | MEDLINE | ID: mdl-26398040

ABSTRACT

This study aims to explore the influential sources of organic matter in first flush runoff from urban roadways by comparing organic carbon content and particle size distribution in road dust with those from discharge from vehicles during rainfall. Samples on first flush runoff and road dust were collected from urban roadways. In addition, vehicle drainage was assumed to flow from vehicles during rainfall events, so vehicle wash-off water was collected by spraying water onto the top and from the underside of vehicles to simulate accumulation during a vehicle run. In road dust, the organic carbon content in the <0.2 mm fraction was about twice that of the 0.2-2 mm fraction. The particle size distributions of both first flush runoff and vehicle wash-off water were similar, and particles <0.2 mm contributed to over 95% of the total volume. The dissolved organic carbon concentration in the vehicle wash-off water was considerably higher than that in the road dust/water mixture. The total organic carbon content in road dust was positively correlated with annual daily traffic. Therefore, vehicles were thought to strongly influence the nature of road dust.


Subject(s)
Dust/analysis , Organic Chemicals/analysis , Rain , Vehicle Emissions/analysis , Water Pollutants, Chemical/analysis , Environmental Monitoring/methods , Japan , Particle Size , Urbanization
5.
J Dev Orig Health Dis ; 1(3): 158-73, 2010 Jun.
Article in English | MEDLINE | ID: mdl-25141784

ABSTRACT

Autism spectrum disorders (ASD) are life-long neurodevelopmental conditions. The pathophysiology is poorly understood, and the clinical diagnosis can only be made through behavioural assessments. The prevalence of ASD has increased eight-fold over the last three decades. Paralleling this rise, research interest in the disorder has been accumulating, centering on two aspects: risk factors that would explain the increase in prevalence, and precursors that could predict an emergence of ASD prior to 2 years of age. As regard factors responsible for the increased prevalence, an increasing trend of low birthweight (4.2% in 1980 v. 9.6% in 2006 at Japan) and advanced paternal age at birth are potentially implicated. To explore these issues, and to yield an early diagnostic algorithm for ASD, the authors initiated the ongoing Hamamatsu Birth Cohort for Mothers and Children (HBC) in 2007. The strengths of the HBC include frequent, direct face-to-face assessments of all the participating mothers and children during the first 4 years of life (12 assessments); this depth of assessments will disclose subtle changes in the developmental domains of individuals with ASD, which might otherwise be overlooked. A total of 1200 pregnant women are to be recruited by the end of 2010. Assembled information comprises a range of variables related to the mother's characteristics and child development. The comprehensiveness of the HBC will provide an informative data source that will elucidate early trajectories of children with ASD in addition to revealing detailed, developmental properties of typically developing children.

6.
Br J Psychiatry ; 193(4): 338-9, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18827301

ABSTRACT

Immune dysfunction has been proposed as a mechanism for the pathophysiology of autistic-spectrum disorders. The selectin family of adhesion molecules plays a prominent role in immune/inflammatory responses. We determined the serum levels of three types of soluble-form selectin (sP, sL and sE) in 15 men with high-functioning autism and 22 age-matched healthy controls by enzyme-linked immunosorbent assay. Levels of sP-selectin and sL-selectin were significantly lower in patients than in controls. Furthermore, sP-selectin levels were negatively correlated with impaired social development during early childhood.


Subject(s)
Autistic Disorder/blood , P-Selectin/blood , Case-Control Studies , E-Selectin/blood , Enzyme-Linked Immunosorbent Assay , Humans , L-Selectin/blood , Male , Young Adult
7.
Acta Psychiatr Scand ; 118(6): 503-4, 2008 Dec.
Article in English | MEDLINE | ID: mdl-18764838

ABSTRACT

OBJECTIVE: Burning mouth syndrome (BMS) is an orofacial pain disorder characterized by a chronic, idiopathic burning sensation of the oral mucosa that mostly affects middle-aged women. Although both psychological and neuropathological factors have been postulated to underlie BMS, the pathogenic mechanism of the condition remains controversial, as do the treatment strategies. METHOD: A single case was reported. RESULTS: Ms A, a 66-year-old woman with BMS type 1, which is characterized by daily burning pain associated with circadian variation, underwent electroconvulsive therapy (ECT). After the completion of 12 ECTs, the pain markedly diminished and the pronounced ECT effect persisted over the subsequent 24-week period of observation. CONCLUSION: To our knowledge, this is the first clinical report on the efficacy of ECT for treating pain associated with BMS. ECT can be considered to be an option for treating individuals with enduring and intractable intraoral burning pain.


Subject(s)
Burning Mouth Syndrome/therapy , Electroconvulsive Therapy , Aged , Burning Mouth Syndrome/diagnosis , Burning Mouth Syndrome/psychology , Female , Humans , Pain Measurement
8.
J Neural Transm (Vienna) ; 115(3): 521-30, 2008.
Article in English | MEDLINE | ID: mdl-18301953

ABSTRACT

Abnormality in cytokine signaling is implicated in the neuropathology of schizophrenia. Previously, we established an animal model for schizophrenia by administering epidermal growth factor (EGF) to neonatal rats. Here we investigated effects of the anthraquinone derivatives emodin (3-methyl-1,6,8-trihydroxyanthraquinone) and sennoside (bis-[D: -glucopyranosyl-oxy]-tetrahydro-4,4'-dihydroxy-dioxo[bianthracene]-2,2'-dicarboxylic acid) on behaviors of this model and EGF signaling. Subchronic oral administration of emodin (50 mg/kg) suppressed acoustic startle responses and abolished prepulse inhibition (PPI) deficits in this rodent model. ANCOVA revealed that emodin had distinct effects on PPI and startle responses. In contrast, sennoside (50 mg/kg) had no effects. Emodin attenuated weight gain initially during treatment but had no apparent effect on weight gain and locomotor activity thereafter. Application of emodin to neocortical cultures attenuated the phosphorylation of ErbB1 and ErbB2. We conclude that emodin can both attenuate EGF receptor signaling and ameliorate behavioral deficits. Therefore, emodin might be a novel class of a pro-drug for anti-psychotic medication.


Subject(s)
Antipsychotic Agents/pharmacology , Behavior, Animal/drug effects , Emodin/pharmacology , Schizophrenia/drug therapy , Animals , Anthraquinones/pharmacology , Blotting, Western , Cathartics/pharmacology , Disease Models, Animal , Epidermal Growth Factor/toxicity , Neural Inhibition/drug effects , Protein Kinase Inhibitors/pharmacology , Rats , Rats, Sprague-Dawley , Reflex, Startle/drug effects , Schizophrenia/chemically induced , Senna Extract , Sennosides
9.
Br J Psychiatry ; 187: 589-90; author reply 590, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16353414
10.
Neuroscience ; 136(4): 1037-47, 2005.
Article in English | MEDLINE | ID: mdl-16226841

ABSTRACT

Scaffolding proteins containing postsynaptic density-95/discs large/zone occludens-1 (PDZ) domains interact with synaptic receptors and cytoskeletal components and are therefore implicated in synaptic development and plasticity. Little is known, however, about what regulates the expression of PDZ proteins and how the levels of these proteins influence synaptic development. Here, we show that ligands for epidermal growth factor receptors (ErbB1) decrease a particular set of PDZ proteins and negatively influence synaptic formation or maturation. In short-term neocortical cultures, concentrations of epidermal growth factor and amphiregulin (2-9 pM) decreased the expression of glutamate receptor interacting protein 1 (GRIP1) and synapse-associated protein 97 kDa (SAP97) without affecting postsynaptic density-95 (PSD-95) levels and glial proliferation. In long-term cultures, epidermal growth factor treatment resulted in a decrease in the frequency of pan-PDZ-immunoreactive aggregates on dendritic processes. A similar activity on the same PDZ proteins was observed in the developing neocortex following epidermal growth factor administration to rat neonates. Immunoblotting revealed that administered epidermal growth factor from the periphery activated brain ErbB1 receptors and decreased GRIP1 and SAP97 protein levels in the neocortex. Laser-confocal imaging indicated that epidermal growth factor administration suppressed the formation of pan-PDZ-immunoreactive puncta and dispersed those structures in vivo as well. These findings revealed a novel negative activity of ErbB1 receptor ligands that attenuates the expression of the PDZ proteins and inhibits postsynaptic maturation in developing neocortex.


Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Carrier Proteins/metabolism , Gene Expression Regulation, Developmental/drug effects , Glycoproteins/pharmacology , Intercellular Signaling Peptides and Proteins/pharmacology , Membrane Proteins/metabolism , Neocortex/cytology , Nerve Tissue Proteins/metabolism , Neurons/drug effects , Age Factors , Amphiregulin , Animals , Blotting, Northern/methods , Blotting, Western/methods , Cells, Cultured , Dose-Response Relationship, Drug , Drug Administration Schedule , EGF Family of Proteins , Embryo, Mammalian , Epidermal Growth Factor/pharmacology , ErbB Receptors/physiology , Immunohistochemistry/methods , Intracellular Signaling Peptides and Proteins , Neurons/metabolism , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain Reaction/methods , Time Factors
11.
Acta Psychiatr Scand ; 111(1): 74-6; discussion 76-7, 2005 Jan.
Article in English | MEDLINE | ID: mdl-15636597

ABSTRACT

OBJECTIVE: To discuss the relationship between obsessive-compulsive symptoms and a right orbitofrontal lesion. METHOD: Single case report. RESULTS: A 59-year-old man developed obsessive-compulsive disorder (OCD) symptoms after his head injury. Magnetic resonance imaging brain scans showed a small contusion in the right orbitofrontal region, and single-photon emission computed tomography revealed hypoperfusion in blood flow at the same region. CONCLUSION: The OCD symptoms that developed in the present case may be attributable primarily to hypofunction in the lesion localized to the right orbitofrontal area. Although caution is needed for interpretation of the observation because of our experience of only a single case, it suggests that the right orbitofrontal region may be important in forming OCD symptoms.


Subject(s)
Brain Concussion/complications , Dominance, Cerebral/physiology , Frontal Lobe/injuries , Obsessive-Compulsive Disorder/etiology , Brain Concussion/diagnosis , Brain Concussion/physiopathology , Brain Injury, Chronic/diagnosis , Brain Injury, Chronic/physiopathology , Frontal Lobe/blood supply , Humans , Intelligence/physiology , Magnetic Resonance Imaging , Male , Mental Status Schedule , Middle Aged , Neuropsychological Tests , Obsessive-Compulsive Disorder/diagnosis , Obsessive-Compulsive Disorder/physiopathology , Positron-Emission Tomography , Regional Blood Flow/physiology , Stereotyped Behavior , Tomography, X-Ray Computed , Wechsler Scales
12.
Acta Psychiatr Scand ; 110(4): 257-63, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15352926

ABSTRACT

OBJECTIVE: We investigated whether antenatal factors in mothers would increase the risk of schizophrenia in the offspring, and also examined any relationship between these factors and histories of obstetric complications (OCs). METHOD: Using the Mother and Child Health Handbooks of 52 patients with schizophrenia and 284 healthy subjects, we evaluated the risk-increasing effects of the frequency of antenatal care visits and mothers' body mass index (BMI) at both early and late pregnancy. RESULTS: In logistic regression analysis, there was a significant association between the number of antenatal care visits and the risk of the disorder; an increase in a unit of visits corresponds to a reduction of the risk by 12%. We also found a 24% increase in the risk with a one-unit increase of BMI at the early pregnancy, and a 19% increase at the late pregnancy. These antenatal factors were found to contribute, in part, to an excess of OCs in individuals with schizophrenia. CONCLUSION: Poor maternal care during pregnancy and comparatively high maternal BMI especially at early pregnancy may cause a predisposition to schizophrenia in the offspring.


Subject(s)
Maternal Behavior , Prenatal Care/statistics & numerical data , Schizophrenia/epidemiology , Adolescent , Adult , Body Mass Index , Female , Health Behavior , Humans , Infant, Newborn , Logistic Models , Male , Pregnancy , Risk Factors
13.
Acta Psychiatr Scand ; 109(2): 150-5; discussion 155, 2004 Feb.
Article in English | MEDLINE | ID: mdl-14725599

ABSTRACT

OBJECTIVE: Olfactory reference syndrome (ORS) in the Western literature is characterized as preoccupation with the idea that the body emits a foul odor. Japanese patients with a feature similar to ORS have long been recognized as jiko-shu-kyofu, which is believed to be a culture-bound syndrome and specific to Japan. The aim of the study was to clarify the relationship between the two separate syndromes that had independently been recognized in culturally different settings. METHOD: The phenomenology and treatment of seven patients with jiko-shu-kyofu were described. A feature of jiko-shu-kyofu was then compared with that of ORS. RESULTS: In our cases, clinical characteristics of jiko-shu-kyofu such as symptomatology, insight, and pharmacotherapy response were found identical to those of ORS except for the onset at relatively younger ages. CONCLUSION: Jiko-shu-kyofu and ORS may share a common clinical entity, hence the former is not a culturally distinctive disorder.


Subject(s)
Delusions , Odorants , Phobic Disorders/diagnosis , Social Behavior , Somatoform Disorders/diagnosis , Adolescent , Adult , Diagnosis, Differential , Female , Humans , Japan , Male , Phobic Disorders/therapy , Somatoform Disorders/therapy , Syndrome
14.
Seishin Shinkeigaku Zasshi ; 106(12): 1585-92, 2004.
Article in Japanese | MEDLINE | ID: mdl-15770961

ABSTRACT

The increased incidence of minor physical anomalies (MPAs) in schizophrenia is the fundamental basis for the neurodevelopmental hypothesis of schizophrenia etiology. Ocular misalignment falls into the category of MPAs, but this phenotype has not been assessed in schizophrenia. This study reveals that constant exotropia displays marked association with schizophrenia. To assess the genetic mechanisms, we examined the transcription factor genes ARIX and its paralogue, PMX2B. We identified frequent deletion/insertion polymorphisms in the 20-alanine homopolymer stretch of PMX2B, with a modest association between these functional polymorphisms and constant exotropia in schizophrenia. The polymorphisms were also associated with overall schizophrenia and more specifically with schizophrenia manifesting strabismus. These results suggest a possible interaction between PMX2B and other schizophrenia-precipitating factors, increasing the risk of the combined phenotypes. This study also highlights the unique nature of the polyalanine length variations found in PMX2B.


Subject(s)
Exotropia/genetics , Schizophrenia/genetics , Exotropia/complications , Genotype , Homeodomain Proteins/chemistry , Homeodomain Proteins/genetics , Humans , Mutation , Peptides/genetics , Phenotype , Polymorphism, Genetic , Schizophrenia/complications , Transcription Factors/chemistry , Transcription Factors/genetics
15.
Neuroscience ; 122(3): 637-46, 2003.
Article in English | MEDLINE | ID: mdl-14622907

ABSTRACT

Transforming growth factor-alpha (TGFalpha), a member of the epidermal growth factor family, has neurotrophic actions on postmitotic neurons. We examined the chronic effects of TGFalpha on the electrophysiological properties of one type of GABAergic neuron, identified by its bipolar morphology, in neocortical primary culture. Approximately 85% of the bipolar neurons were GABA-immunoreactive. In response to depolarizing current injection, the bipolar neurons usually showed tonic firing of action potential under control conditions. After treatment with TGFalpha (20 ng/ml) for 2 days, these neurons failed to generate trains of action potentials. Furthermore, the treatment altered the action potential waveforms of the bipolar neurons, including the duration and amplitude of the fast after-hyperpolarization, which implies a reduction in voltage-gated potassium currents. In contrast, TGFalpha did not affect the firing properties of pyramidal-shaped non-GABAergic neurons. Voltage-clamp recordings from the bipolar neurons indicated that chronic treatment with TGFalpha markedly decreased the current densities of slow delayed rectifier (IK) and transient voltage-gated potassium currents, whereas the treatment had no effect on voltage-gated sodium current and fast delayed rectifier potassium current densities. Reverse transcription-polymerase chain reaction analysis of potassium channel mRNA in the bipolar neurons revealed that the reduction in the IK current density was caused by Kv2.2 mRNA down-regulation. Thus, chronic treatment with TGFalpha down-regulated slow delayed rectifier and transient voltage-gated potassium currents, and in parallel, suppressed repetitive generation of action potentials in the cortical GABAergic neurons.


Subject(s)
Neocortex/cytology , Neurons/drug effects , Potassium Channels, Voltage-Gated , Potassium Channels/metabolism , Transforming Growth Factor alpha/pharmacology , gamma-Aminobutyric Acid/metabolism , 4-Aminopyridine/pharmacology , Action Potentials/drug effects , Anesthetics, Local/pharmacology , Animals , Cadmium/pharmacology , Delayed Rectifier Potassium Channels , Dose-Response Relationship, Radiation , Drug Interactions , Electric Stimulation , Embryo, Mammalian , Gene Expression Regulation/drug effects , Humans , Neurons/classification , Neurons/physiology , Organ Culture Techniques , Potassium/pharmacology , Potassium Channel Blockers/pharmacology , Potassium Channels/drug effects , Potassium Channels/genetics , Potassium Channels/physiology , Pyramidal Cells/drug effects , Pyramidal Cells/physiology , RNA, Messenger/biosynthesis , Rats , Reaction Time , Reverse Transcriptase Polymerase Chain Reaction/methods , Shab Potassium Channels , Tetrodotoxin/pharmacology
16.
Mol Cell Neurosci ; 24(2): 340-56, 2003 Oct.
Article in English | MEDLINE | ID: mdl-14572457

ABSTRACT

The regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors is implicated in synaptic plasticity. Although we have found that brain-derived neurotrophic factor (BDNF) triggers surface translocation of AMPA receptor proteins, the physiological significance of the BDNF effect remained to be determined. The present immunohistochemical studies revealed that cortical GABAergic neurons exhibited the most striking response to BDNF. Accordingly, we monitored AMPA-triggered currents through GABAergic neurons: Chronic BDNF treatment increased the AMPA-triggered currents but not NMDA-triggered currents in culture. In parallel, the amplitude, but not frequency, of spontaneous miniature excitatory postsynaptic currents (mEPSCs) was elevated in GABAergic neurons. In agreement, BDNF enhanced GABA release triggered by AMPA compared to the amount triggered by high potassium. Conversely, there was a significant decrease in the mEPSC amplitude of GABAergic neurons in heterozygous BDNF-knockout mice. These findings indicate that the neurotrophin enhances the input sensitivity of GABAergic neurons to facilitate their inhibitory function in the neocortex.


Subject(s)
Brain-Derived Neurotrophic Factor/deficiency , Neocortex/metabolism , Receptors, AMPA/biosynthesis , Up-Regulation/physiology , gamma-Aminobutyric Acid/metabolism , Animals , Brain-Derived Neurotrophic Factor/pharmacology , Cells, Cultured , Excitatory Postsynaptic Potentials/drug effects , Excitatory Postsynaptic Potentials/physiology , Membrane Potentials/drug effects , Membrane Potentials/physiology , Mice , Mice, Inbred C57BL , Mice, Knockout , Neocortex/drug effects , Neurons/drug effects , Neurons/metabolism , Rats , Rats, Sprague-Dawley , Up-Regulation/drug effects
17.
West Indian Med J ; 52(2): 124-6, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12974062

ABSTRACT

It has been shown that an excess of pregnancy and birth complications (PBCs) does not contribute to the excess rates of schizophrenia reported for the population of Caribbean origin in Britain compared with the native Caucasian British population. We therefore attempted to compare the rate of PBCs between a sample of schizophrenics in Britain with that of a sample from Trinidad where some of the Caribbean migrants to Britain originated. First contact patients with schizophrenia according to the CATEGO system diagnosis were identified in Trinidad and London. Their mothers, where available, were interviewed using the Lewis-Murray scale for pregnancy and birth complications. Data from Trinidad and Tobago concerning 56 patients were compared with those of the Caucasian (n = 61) and African-Caribbean (n = 50) patients in London. The rate of PBCs was similar for the Caucasian British patients (24.6%) and the patients in Trinidad and Tobago (21.7%). The rates were lowest in the African-Caribbean patients in London (14.0%), though this difference was not statistically significant. These findings suggest that pregnancy and birth complications are a risk factor for a substantial minority of patients with schizophrenia in Trinidad and London. It also confirms that the excess rates of schizophrenia reported for the Caribbean population in Britain are not due to these complications.


Subject(s)
Black People , Obstetric Labor Complications/epidemiology , Pregnancy Complications/epidemiology , Pregnancy Outcome , Schizophrenia/epidemiology , White People , Adolescent , Adult , Age Distribution , Age of Onset , Birth Injuries/epidemiology , Birth Weight , Chi-Square Distribution , Cohort Studies , Emigration and Immigration , Female , Humans , Incidence , Infant, Newborn , Infant, Premature , London/epidemiology , Male , Middle Aged , Odds Ratio , Pregnancy , Risk Factors , Sampling Studies , Schizophrenia/diagnosis , Sex Distribution , Trinidad and Tobago/epidemiology , Urban Population
18.
Mol Psychiatry ; 8(2): 217-24, 2003 Feb.
Article in English | MEDLINE | ID: mdl-12610654

ABSTRACT

Brain-derived neurotrophic factor (BDNF) plays a critical role in synaptic plasticity such as long-term potentiation (LTP), a form of synaptic correlate of learning and memory. BDNF is also implicated in learning and memory. We have demonstrated that radial arm maze training in rats for spatial learning and memory results in a significant increase in the BDNF mRNA expression in the hippocampus. Moreover, antisense BDNF oligonucleotide treatment impaired not only acquisition, but also maintenance and/or recall of spatial memory in the maze. Although these results suggest a role of BDNF for spatial memory processes, the signal transduction mechanisms that mediate the actions of BDNF remain unknown. Here we show that phosphorylation of BDNF receptor tyrosine kinase B (TrkB), phosphatidylinositol 3-kinase (PI3-K) and Akt, a target of PI3-K, in the hippocampus increased in parallel with spatial memory formation. Moreover, an activation of translational processes was suggested in the hippocampus after the maze training. When spatial learning was inhibited by antisense BDNF oligodeoxynucleotide, the activation was diminished. Chronic treatment with PI3-K inhibitor wortmannin impaired spatial learning. Our findings suggested that activation of TrkB/PI3-K and protein synthesis signaling pathway by BDNF in the hippocampus is important for spatial memory.


Subject(s)
Brain-Derived Neurotrophic Factor/metabolism , Memory/physiology , Phosphatidylinositol 3-Kinases/metabolism , Space Perception/physiology , Androstadienes/pharmacology , Animals , Brain-Derived Neurotrophic Factor/genetics , Enzyme Inhibitors/pharmacology , Hippocampus/enzymology , Male , Maze Learning/drug effects , Maze Learning/physiology , Memory/drug effects , Oligonucleotides, Antisense/pharmacology , Rats , Rats, Wistar , Wortmannin
19.
Ann Hematol ; 82(1): 53-6, 2003 Jan.
Article in English | MEDLINE | ID: mdl-12574967

ABSTRACT

It is now well recognized that hemophagocytic syndrome (HPS) is occasionally associated with malignant lymphomas. However, its association with Hodgkin's disease has been only rarely reported. We present here a 72-year-old woman manifesting with HPS as the primary and solitary clinical symptom of Hodgkin's disease. She had been suffering from high-grade fever and anemia for more than a month. Based on the findings in bone marrow aspirates, she was diagnosed as having HPS. In spite of extensive surveys including various cultures, serological tests for collagen disease, abdominal and cardiac sonography, chest computed tomography (CT), and renal biopsy, the origin of the fever was not determined. She was treated with steroid pulse therapy and then referred. Radiological studies revealed only mild hepatosplenomegaly and small lymph node swellings around celiac and common hepatic arteries. Reevaluation of the bone marrow specimen revealed the infiltration of small numbers of CD30-, CD15-, and EBER-1-positive large-sized lymphocytes with bizarre nucleus. Under the diagnosis of Hodgkin's disease, she was treated with combination chemotherapy containing pirarubicin, cyclophosphamide, vincristine, and prednisolone. However, it was not effective and she died of rapidly progressive hepatic failure on the 5th day of the chemotherapy. Autopsy was performed, which showed proliferation of lymphoma cells in para-aortic lymph nodes. We believe that diagnostic survey to rule out the underlying lymphoma should be vigorously performed for patients with hemophagocytic syndrome of unknown origin.


Subject(s)
Histiocytosis, Non-Langerhans-Cell/complications , Hodgkin Disease/complications , Aged , Bone Marrow Examination , Cytokines/blood , Fatal Outcome , Female , Fever/etiology , Histiocytosis, Non-Langerhans-Cell/diagnosis , Hodgkin Disease/diagnosis , Hodgkin Disease/drug therapy , Humans , Lymph Nodes/pathology
20.
Eur J Haematol ; 69(2): 101-4, 2002 Aug.
Article in English | MEDLINE | ID: mdl-12366713

ABSTRACT

Hepatitis B virus (HBV) is a well known pathogen that sometimes causes fulminant hepatitis in patients undergoing cytotoxic chemotherapy. Fibrosing cholestatic hepatitis (FCH) is a recently recognized unique variant of viral hepatitis, which has been occasionally reported in HBV-infected recipients of liver, renal, or bone marrow transplantation. We present here a 48-yr-old male in whom HBV was reactivated during post-remission chemotherapy for acute myelogenous leukemia, which resulted in rapidly fatal outcome. He manifested with deterioration of liver function in association with enormous replication of HBV. Liver biopsy showed marked ballooning of hepatocytes, cholestasis, and periportal fibrosis with minimum infiltrates. Immunostaining revealed that hepatocytes were strongly positive for hepatitis B surface antigen. Under the diagnosis of FCH, he was treated with lamivudine and interferon beta, which was not effective. Autopsy showed severe atrophy of the liver and marked degeneration of hepatocytes. Hematologists should be aware that FCH is a fatal complication that can develop under post-chemotherapy immunosuppressed conditions. Although there is no convincing evidence, prophylactic administration of lamivudine seems to be a reasonable strategy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Chemical and Drug Induced Liver Injury, Chronic , Hepatitis B virus , Leukemia, Myeloid, Acute/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemical and Drug Induced Liver Injury, Chronic/physiopathology , Chemical and Drug Induced Liver Injury, Chronic/virology , Cholestasis , Fatal Outcome , Hepatitis B virus/drug effects , Hepatitis B virus/growth & development , Humans , Leukemia, Myeloid, Acute/pathology , Leukemia, Myeloid, Acute/physiopathology , Liver Cirrhosis , Male , Middle Aged , Recurrence , Virus Activation/drug effects
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