RNA expression analysis of a congenital intracranial teratoma

Congenital intracranial tumors are extremely rare and account only for 0.5%-1.5% of brain tumors in children. We report a large intrauterine congenital teratoma in a female fetus at gestation weeks 37, which was diagnosed by detecting the tumor and associated craniomegaly with ultrasonography (US) and magnetic resonance (MR) imaging. The tumor had replaced the cerebral hemispheres and produced prenatal manifestations. Pathologic examination showed an immature teratoma, which was differentiated from all three germ layers. Microarray analysis revealed upregulation of ten genes and downregulation of three genes, as well as upregulation of 41 genes of ribosomal proteins in teratoma cells, compared to normal brain tissue of the patient. The data from the microarray analysis offer not only the potential to help define disease pathogenesis but may also provide clues to identify potential molecular therapeutic targets.     

Choice and administration sequence of antiepileptic agents for status epilepticus and frequent seizures in children

We investigated the sequence of the administration, the efficacy and the safety of antiepileptic drugs (AED) given intravenously for the treatment of status epilepticus and frequent seizures in children. Our institute has a recommended sequence of AED administration for treatment of status epilepticus: the first-line agent is diazepam (0.3 - 0.5 mg/kg administered intravenously, once or twice). The second-line drugs include midazolam (0.15 - 0.4 mg/kg intravenously, once or twice, and if necessary, followed by continuous infusion at 0.06 - 0.18 mg/kg/hour), lidocaine (1 - 2 mg/kg intravenously, once or twice, and if necessary, followed by continuous infusion at 2 - 4 mg/kg/hour) and phenytoin (10 - 20 mg/kg, infused slowly). For those patients who previously experienced a seizure which was refractory to diazepam but responsive to the second-line agent, it was recommended to use the second-line agent as a first-line agent. When seizures were refractory to the first and second-line agents, thiopental was administered (3 - 10 mg/kg intravenously, and if necessary, followed by continuous infusion at 2 -5 mg/kg/hour). The etiologies of 177 occasions of status epilepticus and frequent seizures were categorized into two groups:epilepsy (n = 95) and situation-related seizures (n = 82). Situation-related seizures included febrile seizures (n = 44), acute encephalopathy/encephalitis (n = 31) and benign infantile convulsions (n = 7). The ages of the patients ranged from 0.1 to 18.4 years (average +/- SD:3.69 +/- 3.15 years). Diazepam was administered as the first-line drug on 157 of 177 occasions (88.7%). On 116 occasions the second-line agents were administered. Midazolam and lidocaine were injected as the second-line agent on 54 (46.6%), and on 33 (28.4%) occasions, respectively, although both midazolam and lidocaine injections were off-label use for seizure control in Japan. Thiopental was used as the third to fifth-line agent. Effective ratios (effective occasions/total occasions) of each drug were the following: thiopental 19/21 (90.4%), midazolam 57/99 (57.6%), lidocaine 25/60 (41.7%), phenytoin 16/41 (39.0%), diazepam 59/164 (36.0%). Thiopental was statistically more effective than midazolam, lidocaine, diazepam or phenytoin (p < 0.01), and midazolam was statistically more effective than diazepam (p < 0.01) or phenytoin (p < 0.05). Administration of thiopental caused complications more frequently than the other agents (p < 0.01): The complications by thiopental were severe in some cases requiring intratracheal intubations and artificial ventilation. From the viewpoint of both efficacy and safety, midazolam should be recommended as one of the first-line agents for status epilepticus.     

Association of the Neprilysin gene with susceptibility to late-onset Alzheimer's disease

Neprilysin (NEP), also known as neutral endopeptidase, enkephalinase, CD 10, and common acute lymphoblastic leukemia antigen, is a 97-kD protein. NEP can degrade amyloid beta peptides, and its mRNA and protein levels are known to be reduced in the brains of patients with Alzheimer's disease (AD), making the NEP gene a substantial candidate for an AD risk factor. We examined the genetic association of three NEP polymorphisms, a GT-repeat polymorphism and two single nucleotide polymorphisms (SNPs, -1075A>G and -1284G>C) in its promoter region, with AD in a Japanese case-control sample (240 patients and 163 controls). The GT-repeat polymorphism, but not the SNPs, was significantly associated with late-onset AD (p = 0.0007). Our findings suggest that the GT-repeat polymorphism in the promoter region of the NEP gene or some other unknown polymorphisms, which are in a linkage disequilibrium, confer a susceptibility to late-onset AD.     

Cardiac failure caused by severe pre-eclampsia with placental abruption, and its treatment with anti-hypertensive drugs

Pre-eclampsia is the abnormality of blood circulation in late pregnancy, often caused by renal failure, hemolysis, elevated liver enzyme, low platelet syndrome, and eclampsia. We present a case of severe pre-eclampsia with placental abruption in a 24-year-old woman, pregnant for the first time. The patient was diagnosed with congestive heart failure, which came as a result of pre-eclampsia. Anti-hypertensive drugs were used for its treatment.     

Post-traumatic stress disorder in pre-school aged children after a gas explosion

To evaluate the sensitivity of diagnostic criteria for post-traumatic stress disorder (PTSD) in pre-school aged children involved in a gas explosion, post-traumatic symptoms of the children were investigated four times after the accident, immediately, 10 days, 6 months, and 1 year later. Using symptoms at 6 months after the accident, sensitivity of diagnostic criteria was assessed by comparing the fourth edition of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), and the alternative criteria for infants and young children [10]. In addition, the published Child Post-Traumatic Stress Disorder Reaction Index (CPTSD-RI) and its modified version proposed by us were also evaluated their sensitivity to rate the symptoms. Girls had a tendency to show more post-traumatic symptoms than boys. Although no children met DMS-IV criteria for PTSD, 8 children out of 32 were diagnosed as having PTSD with alternative criteria. With our modified CPTSD-RI, all eight children were decidedly more statistically distinguishable from those without PTSD than with original index. CONCLUSION: our data indicate that the sensitivity of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (4th edition) and the Child Post-Traumatic Stress Disorder Reaction Index in rating symptoms of pre-school aged children is not sufficient. The alternative criteria of the former and modified version of the latter would be the better choice in this age group.     

Topographical relationships between the brainstem auditory and somatosensory evoked potentials and the location of lesions in posterior fossa stroke

The topographical relationships between the location of brainstem lesions detected by magnetic resonance imaging and abnormality of brainstem auditory evoked potentials (BAEPs) and short-latency somatosensory evoked potentials (SSEPs) were studied in 57 patients with stroke in the posterior fossa. Abnormal BAEPs or SSEPs were associated with lesions involving the pontine tegmentum, and abnormal BAEPs also with lesions at the cerebellar peduncle. Absence of the V wave in BAEPs and N20 in SSEPs was associated with a localized overlapping area in the pontine tegmentum contralateral to stimulation. The overlapping area associated with loss of N20 coincided with the location of the medial lemniscus. Lesions widely involving the pontine tegmentum caused the disappearance of multiple waves in the BAEPs and SSEPs. Patients who entered prolonged coma or died had total loss of the III, IV, and V waves, bilateral absence to the contralateral response in BAEPs, or loss of N18 in SSEPs. The loss of N18 in SSEPs had a statistically significant correlation with bad outcome, which suggests the superiority of SSEPs for predicting the outcome of stroke and indicates the involvement of some system excluding the medial lemniscus in the generation of N18.     

The glutamate and neutral amino acid transporter family: physiological and pharmacological implications

The solute carrier family 1 (SLC1) is composed of five high affinity glutamate transporters, which exhibit the properties of the previously described system XAG-, as well as two Na+-dependent neutral amino acid transporters with characteristics of the so-called "ASC" (alanine, serine and cysteine). The SLC1 family members are structurally similar, with almost identical hydropathy profiles and predicted membrane topologies. The transporters have eight transmembrane domains and a structure reminiscent of a pore loop between the seventh and eighth domains [Neuron 21 (1998) 623]. However, each of these transporters exhibits distinct functional properties. Glutamate transporters mediate transport of L-Glu, L-Asp and D-Asp, accompanied by the cotransport of 3 Na+ and one 1 H+, and the countertransport of 1 K+, whereas ASC transporters mediate Na+-dependent exchange of small neutral amino acids such as Ala, Ser, Cys and Thr. Given the high concentrating capacity provided by the unique ion coupling pattern of glutamate transporters, they play crucial roles in protecting neurons against glutamate excitotoxicity in the central nervous system (CNS). The regulation and manipulation of their function is a critical issue in the pathogenesis and treatment of CNS disorders involving glutamate excitotoxicity. Loss of function of the glial glutamate transporter GLT1 (SLC1A2) has been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS), resulting in damage of adjacent motor neurons. The importance of glial glutamate transporters in protecting neurons from extracellular glutamate was further demonstrated in studies of the slc1A2 glutamate transporter knockout mouse. The findings suggest that therapeutic upregulation of GLT1 may be beneficial in a variety of pathological conditions. Selective inhibition of the neuronal glutamate transporter EAAC1 (SLC1A1) but not the glial glutamate transporters may be of therapeutic interest, allowing blockage of glutamate exit from neurons due to "reversed glutamate transport" of EAAC1, which will occur during pathological conditions, such as during ischemia after a stroke.