[Show abstract][Hide abstract] ABSTRACT: The case of a 12-year-old boy with anaplastic astrocytoma of the left thalamus is reported. Postoperative irradiation and chemotherapy could not repress tumor progression; therefore, treatment was undertaken with an oncolytic virus, MTH-68/H, an attenuated strain of Newcastle disease virus (NDV), and valproic acid (VPA), an antiepileptic drug, which also has antineoplastic properties. This treatment resulted in a far-reaching regression of the thalamic glioma, but 4 months later a new tumor manifestation, an extension of the thalamic tumor, appeared in the wall of the IVth ventricle, which required a second neurosurgical intervention. Under continuous MTH-68/H - VPA administration the thalamic tumor remained under control, but the rhombencephalic one progressed relentlessly and led to the fatal outcome. In the final stage, a third tumor manifestation appeared in the left temporal lobe. The possible reasons for the antagonistic behavior of the three manifestations of the same type of glioma to the initially most successful therapy are discussed. The comparative histological study of the thalamic and rhombencephalic tumor manifestations revealed that MTH-68/H treatment induces, similar to in vitro observations, a massive apoptotic tumor cell decline. In the rhombencephalic tumor, in and around the declining tumor cells, NDV antigen could be demonstrated immunohistochemically, and virus particles have been found in the cytoplasm of tumor cells at electron microscopic investigation. These findings document that the oncolytic effect of MTH-68/H treatment is the direct consequence of virus presence and replication in the neoplastic cells. This is the first demonstration of NDV constituents in an MTH-68/H -treated glioma.
[Show abstract][Hide abstract] ABSTRACT: Neurofibromas represent one of the hallmarks of neurofibromatosis 1 (NF1) patients. Tumor progression of neurofibromas to malignant peripheral nerve sheath tumors (MPNST) is a frequent and life threatening complication. To learn more about processes involved in malignant transformation, we evaluated differential gene expression in plexiform neurofibroma and MPNST from the same NF1 patient. Suppression subtractive hybridization (SSH) yielded 133 differentially expressed genes confirmed by reverse Northern blotting. Virtual Northern blots were employed to validate 23 genes. To independently verify differential expression, immunohistochemical analyses with antibodies to matrix metalloproteinase 13 (MMP13), platelet-derived growth factor receptor alpha (PDGFRA) and fibronectin (FN1) were performed on 9 dermal and 9 plexiform neurofibromas and 16 MPNST from 19 NF1 patients. All three proteins proved to be up-regulated in MPNST. MMP13 expression was observed in 44% of MPNST but was absent in neurofibromas. PDGFRA was expressed in all tumors, but the number of cells expressing it was below 30% in neurofibromas and over 50% in MPNST. Likewise, FN1 was expressed in all tumors, but less than 30% of the cells in neurofibromas and more than 70% of the cells in MPNST exhibited antibody binding. Our data point to several genes not previously recognized to be differentially expressed, and provide a framework for future studies on progression-associated gene expression in low- and high-grade nerve sheath tumors.
[Show abstract][Hide abstract] ABSTRACT: The June 2002 COM. A male patient presented at the age of 57 years with a benign meningeal melanocytoma. Eight years later, the patient had a local recurrence of the tumor, cerebral metastases and liver metastases. This demonstrates that a correct diagnosis of melanocytic CNS tumors remains a challenge together with elucidating predictive markers for biological behavior. To the best of our knowledge, this is the first case of a melanocytoma associated with hepatic metastasis.
[Show abstract][Hide abstract] ABSTRACT: The paravertebral muscle of 30 patients with spondylolisthesis and 30 control patients were investigated histologically.
To propose myopathologic paravertebral muscle changes in cases of degenerative lumbar spondylolisthesis.
The stability of the vertebral column is based on both active and passive systems. The passive system is composed of the vertebrae, the intervertebral discs, and the ligaments. Surrounding muscles and tendons constitute the active system. The autochthonous back muscles take over support functions if the passive system is ineffective. In some cases, muscles are overstrained for a long period, ultimately leading to muscular changes. This study was performed to determine the histopathologic correlates of this permanent strain.
Between July 1998 and July 1999, paravertebral muscle biopsies were performed for 30 patients with monosegmental degenerative spondylolisthesis undergoing posterior lumbar interbody fusion. The tissue samples were submitted to histologic analysis including immune and enzyme histochemistry and electron microscopy. In addition, the muscle fibers were submitted to morphometry.
Severe pathologic alterations were found. The findings showed that 22 patients (73.3%) had ragged red fibers with evident ultrastructural mitochondrial anomalies. The cristae appeared irregular in 12 patients (40%) Type 1 paracrystalline inclusions were detected in five samples (16.6%) and dense bodies in eight (26.6%). Fibers with ubiquitin-positive inclusions were detected by immunohistochemistry in 13 patients (43.3%). As shown by the electron microscope, these corresponded to granulofilamentous inclusions and polyglucosan bodies. The samples were submitted to genetical analysis because biochemical studies showed reduced activity of the respiratory chain enzymes. Normal mitochondrial deoxyribonucleic acids of unchanged length were detected.
Apart from nonspecific myopathic changes such as those observed in rimmed vacuoles and rods, increased numbers of polyglucosan bodies were detected. This increase in polyglucosan bodies currently has not been described in patients with otherwise normal muscles.
[Show abstract][Hide abstract] ABSTRACT: We present a novel large German kindred of fatal familial insomnia (FFI) consisting of three branches and comprising more than 800 individuals of 12 generations, the largest pedigree of any familial prion disease known today. There is a wide spectrum of clinical presentations leading to misdiagnoses of Olivo-Ponto-Cerebellar Atrophy (OPCA), Parkinson's or Alzheimer's disease in addition to Creutzfeldt-Jakob disease (CJD) and Gerstmann-Sträussler-Scheinker (GSS) syndrome. Molecular genetic analysis of the prion protein gene (PRNP) confirmed the mutation D178N segregating with methionine at the polymorphic codon 129 of PRNP in all 7 patients examined. This polymorphism at codon 129 is supposed to discriminate between familial CJD (fCJD) and FFI; the 129M allele determines FFI and 129V fCJD. Furthermore, heterozygosity at this site appears to induce prolonged disease duration as compared to the homozygous condition. The variability of the clinical and pathological findings documented for our patients indicates the difficulty in establishing the diagnosis of FFI on clinical and on pathological grounds alone. In three cases (IX-97, XI-21, V-2) followed up by us prospectively insomnia was an early and severe symptom; however, in case notes analyzed retrospectively this symptom was frequently missed. In contrast to previous reports and in agreement with recent studies we cannot confirm a clear relationship between the status of the M/V polymorphism at codon 129 and the age-of-onset of this disease.
American Journal of Medical Genetics 01/2000; 87(4):311-6.