A common Ile 823 Met variant of ATP-binding cassette transporter A1 gene (ABCA1) alters high density lipoprotein cholesterol level in Japanese population

Recently, variants in ATP-binding cassette transporter A1 (ABCA1) were demonstrated to be associated with increased level of high density lipoprotein cholesterol (HDL-C) and decreased risk of coronary artery disease (CAD) in Caucasians. However, this is not universally applicable due to the ethnic or environmental differences. In this context, to clarify the effect of ABCA1 in Japanese, we evaluated the phenotypic effects of I/M 823 and R/K 219 variants on the plasma level of HDL-C in 410 patients recruited in our hospital. Subjects with M 823 allele had significantly higher level of HDL-C than those without M823 allele (49.0+/-15.1 vs. 44.9+/-11.5 mg/dl, respectively, P<0.05). This statistical significance did not change even after multiple regression analysis. In contrast, there was no difference in HDL-C level among the genotypes in R/K 219 polymorphism. Further, in our study population an inverse relationship was shown to exist between HDL-C level and incidence of CAD. However, no positive association was observed between those variants and susceptibility to CAD. In this study, we provide evidence that I/M 823 variant, not R/K 219 variant, in ABCA1 is one of the determinants of HDL-C level, suggesting the importance of this gene on lipid metabolism in Japanese.     

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.     

Rapid shrinkage of remnant central neurocytoma after gamma knife radiosurgery: a case report

Central neurocytomas are typically benign tumors that have high local control rates after gross total resection. Radiotherapy for residual or recurrent central neurocytomas is controversial.We report a 30-year-old male with a central neurocytoma in the lateral ventricle. The tumor was subtotally resected through a transcallosal approach, and subsequently treated with gamma knife radiosurgery. The tumor had shrunken markedly by 2 months after radiosurgery and remained unchanged during the one year follow-up period.Gamma knife radiosurgery may be an option for effective treatment of patients with residual or recurrent central neurocytomas.     

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.     

A Collision Tumor Composed of Adenocarcinoma and Malignant Lymphoma in the Remnant Stomach After Pancreatoduodenectomy: Report of a Case

The occurrence of a collision tumor in the stomach, consisting of adenocarcinoma and malignant lymphoma, is extremely rare. We report herein the case of a patient who had undergone a pancreatoduodenectomy for bile duct cancer 5 year earlier, in whom an ulcerating tumor of the remnant stomach developed and grew rapidly within 5 months. Surgical exploration revealed a tumor in the remnant stomach, multiple liver metastases, and multiple lymph node metastases. Total resection of the remnant stomach was performed, and pathological examination revealed a collision tumor consisting of adenocarcinoma and malignant lymphoma. The patient died of liver metastases and lymph node metastases 7 months after his second operation. The coexistence of both adenocarcinoma and malignant lymphoma of the remnant stomach and the etiology of this unusual combination, never previously reported, is discussed. Received: December 20, 1999 / Accepted: November 20, 2000