ABSTRACT
1. Accumulations of phosphorylated neurofilaments are seen in affected motor neurones in amyotrophic lateral sclerosis (ALS). 2. The authors demonstrate that cyclin dependent kinase-5 (cdk-5) will induce cellular phosphorylation of neurofilament heavy chain side-arms to generate epitopes for several antibodies that label these neurofilament accumulations. 3. By creating recombinant neurofilament fragments of NF-H side-arm domains, the authors also map the epitopes for several of these antibodies. 4. Finally, the authors demonstrate that cdk-5 is also present in affected motor neurones in ALS. These studies implicate cdk-5 in the pathogenesis of ALS.
Subject(s)
Amyotrophic Lateral Sclerosis/immunology , Cyclin-Dependent Kinases/metabolism , Epitopes/biosynthesis , Motor Neurons/metabolism , Neurofilament Proteins/metabolism , Aged , Aged, 80 and over , Amino Acid Sequence , Amyotrophic Lateral Sclerosis/enzymology , Animals , Blotting, Western , COS Cells , Cyclin-Dependent Kinase 5 , DNA Primers , Epitope Mapping , Female , Humans , Immunohistochemistry , Male , Middle Aged , Molecular Sequence Data , Motor Neurons/enzymology , Neurofilament Proteins/immunology , Peptide Fragments/chemical synthesis , PhosphorylationABSTRACT
We have studied the distribution of cyclin dependent kinase-5 (cdk-5) within spinal cord in sporadic and two superoxide dismutase type 1 (SOD1) familial cases of amyotrophic lateral sclerosis (ALS). Although most neurofilament accumulations in ALS motor neurones did not appear to contain high levels of cdk-5, intense cdk-5 immunoreactivity was observed in perikarya of degenerating neurones in many ALS cases. Here, cdk-5 co-localised with lipofuscin. Co-localisation of cdk-5 with lipofuscin was also observed in some aged non-affected controls although this labelling was less intense than the ALS cases. The biogenesis of lipofuscin is believed to be linked to oxidative stress and oxidative stress and free radical damage have been suggested to be part of the pathogenic process of ALS, possibly involving apoptotic mechanisms. cdk-5 has recently been associated with apoptosis. These observations suggest a role for cdk-5 in the pathogenesis of ALS.
Subject(s)
Amyotrophic Lateral Sclerosis/enzymology , Amyotrophic Lateral Sclerosis/pathology , Cyclin-Dependent Kinases , Lipofuscin/metabolism , Motor Neurons/enzymology , Protein Serine-Threonine Kinases/metabolism , Adult , Aged , Aged, 80 and over , Amyotrophic Lateral Sclerosis/genetics , Cyclin-Dependent Kinase 5 , Humans , Immunohistochemistry , Middle Aged , Superoxide Dismutase/genetics , Superoxide Dismutase/metabolismABSTRACT
AIMS: To establish the clinical and pathological aspects of teratoma affecting the spinal cord. METHOD AND RESULTS: We reviewed our neurosurgical records for the last 15 years and found seven cases of teratoma of the spinal cord. The cases were reviewed clinically, radiologically and pathologically using immunohistochemical markers to identify various tissue components. We found that spinal cord teratoma is an extremely rare tumour of spinal cord affecting patients aged 23-47 years and of approximately equal male to female distribution. The terminal portions of spinal cord and intradural location of the tumour are common. Three cases were associated with vertebral anomaly. Most tumours showed benign (mature) components derived from more than one germ cell layer; one showed malignant adenocarcinomatous component. All cases were treated by surgical resection and two recurred at 6 and 10 year intervals without malignant transformation. CONCLUSION: Spinal cord teratoma is a rare, mainly benign tumour, which could be associated with vertebral anomaly. The pathogenesis of this tumour is controversial, possibly due to germinal cell aberration.
Subject(s)
Spinal Cord Neoplasms/pathology , Teratoma/pathology , Adenocarcinoma/pathology , Adult , Female , Germ Layers/cytology , Germ Layers/pathology , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Radionuclide Imaging , Spinal Cord/diagnostic imaging , Spinal Cord/pathology , Spinal Cord Neoplasms/diagnostic imaging , Teratoma/diagnostic imaging , Tomography, X-Ray ComputedABSTRACT
In this article two cases of primary malignant extrarenal rhabdoid tumour are described. In the affected children the brain and the spinal cord were the primary sites of origin of the tumour. The imaging findings are presented and the pathology discussed. Although the imaging features are non-specific, rhabdoid tumour should be included in the differential diagnosis of childhood intracranial and spinal neoplasms.
Subject(s)
Brain Neoplasms/diagnosis , Magnetic Resonance Imaging , Rhabdoid Tumor/diagnosis , Spinal Cord Neoplasms/diagnosis , Acquired Immunodeficiency Syndrome/diagnosis , Acquired Immunodeficiency Syndrome/pathology , Acquired Immunodeficiency Syndrome/surgery , Biomarkers, Tumor/analysis , Biopsy , Brain/pathology , Brain Neoplasms/pathology , Brain Neoplasms/surgery , Child, Preschool , Diagnosis, Differential , Diseases in Twins , Humans , Infant , Male , Neurologic Examination , Rhabdoid Tumor/pathology , Rhabdoid Tumor/surgery , Spinal Cord/pathology , Spinal Cord Neoplasms/pathology , Spinal Cord Neoplasms/surgeryABSTRACT
A distinctive glial tumour in an 8-month-old child characterized by superficial location, attachment to the dura, desmoplasia and histological malignancy is described. The tumour differed from "desmoplastic cerebral astrocytoma of infancy" and "desmoplastic infantile ganglioglioma" by virtue of the presence of frequent mitoses and necrosis and lack of basal lamina. We have termed this tumour a "desmoplastic cerebral glioblastoma of infancy". The differential diagnosis and the origin of the desmoplasia are discussed.
