Post-traumatic diffuse brain swelling: isolated or associated with cerebral axonal injury

Eighteen children with severe head injuries and diffuse brain swelling were studied. They were separated into two groups based on the computed tomography (CT) findings. Seven patients had small ventricles in the normal location and small or absent cisterns. Eleven had these signs plus small deep-seated intraparenchymal hemorrhagic foci and/or intraventricular hemorrhage. Patients in the first group were in relatively good neurological condition; their intracranial pressure was easily controlled and all had a favourable outcome. On contrast, children in the second group had a more severe clinical presentation, frequently had uncontrollable intracranial hypertension, and more than 50% died.     

Occurrence of diffuse amyloid deposits in the presubicular parvopyramidal layer in Alzheimer's disease

Summary Silver staining by a modified Bielschowsky's technique and immunostaining for -amyloid protein BAP have revealed the occurrence of diffuse amyloid deposits bilaterally in the presubiculum in each of fourteen Alzheimer's disease cases examined. Observations on serial blocks show these deposits to be localized in the parvopyramidal layer of the presubiculum proper and the transsubiculum. They are also observed in the cellular islands within the molecular layer of the subiculum but not in the parasubiculum. These amyloid deposits are not accompanied by neurofibrillary tangles, neuropil threads, or the aggregated microglial reaction which is characteristically associated with classic senile plaques. Convergence of input from limbic and cortical areas might play a significant role in the formation of these diffuse amyloid deposits.Supported by grants from the MRC of Canada, the Alzheimer's Society of B.C., the American Health Assistance Foundation and the McLean Foundation     

Characterization of a shared epitope in cortical Lewy body fibrils and Alzheimer paired helical filaments

The straight fibrils of the Lewy body contain an epitope related to phosphorylation of the KSPV motif common to the C termini of the 200- and 170-kDa neurofilament subunits and . To further characterize this phosphorylated neurofilament/ epitope in Lewy bodies and to analyze the constituents of isolated Lewy bodies we used a combined biochemical and immunochemical approach. In formalin-fixed paraffin-embedded tissue cortical Lewy bodies were labelled by monoclonal antibodies directed to phosphorylation-dependent KSPV epitopes in the sequences of neurofilament and phosphorylation-independent epitopes. Immunoblotting of solubilized Lewy body fibrils with the same antibodies which stained Lewy bodies in tissue sections revealed that the immunoreactive Lewy body proteins were phosphorylated neurofilament subunits. An antibody to the 68-kDa neurofilament subunit labelled Lewy bodies and Lewy body protein at 50–68 kDa. We conclude that the shared phosphorylated epitope in Lewy body fibrils and paired helical filaments is related to the common KSPV sequence in neurofilament and , and that all three neurofilament subunits are present in the Lewy body. This result indicates that although Lewy bodies and neurofibrillary tangles share epitopes they are comprised of distinct structural subunits.Supported by grants from the Parkinson Foundation of Canada and the Alzheimer Society of Canada to C.B. M.S.P. is a recipient of a Medical Research Council of Canada Studentship     

Association of apolipoprotein ɛ4 allele and neuropathologic findings in patients with dementia

Apolipoprotein E (APOE) is a lipoprotein expressed in liver and brain as one of three isoforms (APOE 2, APOE 3 and APOE 4). Recent findings suggest that the presence of APOE 4 is associated with an increased risk for both familial Alzheimer's disease and late-onset Alzheimer's disease. We extended these observations by determining the frequency of APOE alleles in patients with pathologically confirmed Alzheimer's Disease (AD), Parkinson's disease (PD), diffuse Lewy Body disease (DLBD), AD with concomitant PD pathology, demented PD patients without or with concomitant AD pathology and in schizophrenics with a progressive dementia (SCHIZ+DEM). The APOE genotype was determined by restriction digestion of polymerase chain reaction-amplified DNA isolated from frozen brain samples. The frequency of the APOE 4 allele was highest among sporadic AD and DLBD patients (0.30 and 0.38, respectively) and lowest in the SCHIZ+DEM and non-demented PD patients (0.06 and 0.1, respectively). Thus, the APOE 4 allele is over-represented selectively in patients with dementias associated with plaques and tangles and/or cortical Lewy bodies, but not in demented schizophrenics or non-demented PD patients.     

Neuron-specific enolase as an effective immunohistochemical marker for injured axons after fatal brain injury

Recently, it has been reported that a diagnosis of diffuse axonal injury in cases with a short survival period can be made with the use of immunolabelling for β-amyloid precursor protein (APP). We examined whether immunostaining for neuron-specific enolase (NSE) can also be a useful marker for the detection of axonal injury in its early stages. Sections of the corpus callosum from 19 cases of head injury and from 9 cases of no head injury were immunostained for NSE and stained by the standard Holmes’ silver method. For comparison, serial sections from several cases were immunostained for APP. Immunostaining for NSE as well as for APP, labelled injured axons in head injury cases with as early as 1.5 h survival where Holmes’ staining failed to detect any changes of axons. Since NSE and APP labelled only injured axons but not normal axons, the results were readily interpretable. These findings indicate that NSE should be an effective marker for the detection of axonal injury in its early stages. Received: 7 December 1998 / Received in revised form: 11 March 1999     

磁共振成像诊断脑弥漫性轴索损伤

目的　探讨MRI诊断脑弥漫性轴索损伤 (DAI)的方法及价值。方法　回顾性分析 38例临床诊断脑弥漫性轴索损伤患者的MRI资料 ,对其病灶的分布特点、信号特征及不同序列对病灶的显示能力进行统计分析。结果　 38例DAI患者 ,共发现病灶 1338个 ,其中双侧大脑半球皮髓交界处病灶 4 6 9个 ,脑叶白质 4 6 0个 ,基底节区 2 0 2个 ,胼胝体 89个 ,小脑 70个 ,脑干 4 8个。DAI病灶在不同序列中的信号特征不同 ,所显示病灶T1WI为等、低信号 ,T2 WI及FLAIR为高信号 ,SE EPI弥散像为稍高信号或高信号 ,FLASH为显著低信号。病灶在不同序列的显示程度不同 ,FLASH序列能得到显示的病灶 ,SET1WI仅能显示 15 3% ,FSET2 WI能显示 38 9% ,FLAIR能显示 5 4 7% ,SE EPI能显示 6 3 6 %。DAI合并症的显示各序列有着大致相同的特异性 ,但敏感性略有差异。结论　MRI对DAI有非常高的诊断价值 ,不同序列对DAI病灶的显示能力不同 ,FLASH序列能显示常规序列所不能显示的出血灶 ,可作为MRI诊断DAI的首选序列。     

Identification of potential drugs for diffuse large b-cell lymphoma based on bioinformatics and Connectivity Map database

Diffuse large B-cell lymphoma (DLBCL) is the most main subtype in non-Hodgkin lymphoma. After chemotherapy, about 30% of patients with DLBCL develop resistance and relapse. This study was to identify potential therapeutic drugs for DLBCL using the bioinformatics method. The differentially expressed genes (DEGs) between DLBCL and non-cancer samples were downloaded from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DEGs were analyzed using the Database for Annotation, Visualization, and Integrated Discovery. The R software package (SubpathwayMiner) was used to perform pathway analysis on DEGs affected by drugs found in the Connectivity Map (CMap) database. Protein–protein interaction (PPI) networks of DEGs were constructed using the Search Tool for the Retrieval of Interacting Genes online database and Cytoscape software. In order to identify potential novel drugs for DLBCL, the DLBCL-related pathways and drug-affected pathways were integrated. The results showed that 1927 DEGs were identified from TCGA and GEO. We found 54 significant pathways of DLBCL using KEGG pathway analysis. By integrating pathways, we identified five overlapping pathways and 47 drugs that affected these pathways. The PPI network analysis results showed that the CDK2 is closely associated with three overlapping pathways (cell cycle, p53 signaling pathway, and small cell lung cancer). The further literature verification results showed that etoposide, rinotecan, methotrexate, resveratrol, and irinotecan have been used as classic clinical drugs for DLBCL. Anisomycin, naproxen, gossypol, vorinostat, emetine, mycophenolic acid and daunorubicin also act on DLBCL. It was found through bioinformatics analysis that paclitaxel in the drug-pathway network can be used as a potential novel drug for DLBCL.     

Subcutaneous Dissemination from an Orbital Diffuse Large B Cell Lymphoma

Secondary cutaneous dissemination from an orbital diffuse large B cell lymphoma has not been described before. The authors report an unusual case of anaplastic variant of diffuse large B cell lymphoma which primarily presented in the orbit and during the course of disease had subcutaneous dissemination.