RNA tumor virus specific sequences in nuclear DNA of several avian species.

Nucleic acid sequences complementary to single-stranded DNA prepared from the endogenous chicken (C-type) RNA tumor virus, RAV-O, were detected in nuclear DNA from five different avian species. The RAV-O probe hybridized almost completely to DNA from helper factor positive and negative chicken cells. DNA from quail, duck, pigeon and pheasant cells contained nucleotide sequences complementary to a varying degree (5–50%) to the RAV-O genome. Rous sarcoma virus-related sequences were also detected in all avian species, except pigeon. Thus, it appears likely that most if not all species of fowl contain RNA tumor virus sequences in their DNA.     

The heterogeneity of frontotemporal dementia with regard to initial symptoms, qEEG and neuropathology

OBJECTIVES/METHODS: Ten patients with neuropathologically verified frontotemporal dementia (FTD) were analysed for neuropathological features in relation to first presenting and dominating symptoms, age at onset and duration of dementia, as well as to EEG/quantitative EEG. RESULTS: Cases with a late onset (> 65 years) initially presented language disturbances, while the early onset group (< 65 years) showed predominantly behavioural symptoms and mood alterations as early features. The late onset group presented combined cortical-subcortical degeneration including white matter pathology, while early onset cases showed pathology predominantly in the cortex. EEG was normal in the late onset group, while it was mildly and variably abnormal in those with early onset. CONCLUSIONS: Within this small sample of clinical and neuropathological FTD, cases with late vs early onset differed with respect to initial symptoms, EEG findings and regional distribution of brain pathology.     

White matter lesions as a risk factor for stroke and dementia. A population-based study in 85-year-olds

AIM: This study was performed to determine whether white matter lesions on cranial computed tomography (cCT) are associated with increased prevalence and incidence of stroke, dementia, and mortality. METHODS: A representative sample of 239 85-year-olds living in Gothenburg, Sweden, was examined in a population-based study. Stroke was defined by information from patient reports, key informants, and an inpatient register system. Dementia was diagnosed according to DSM-III-R. White matter lesions (WML) and infarcts were determined by cCT. Follow-up examinations were performed 3 years later. RESULTS: White matter lesions doubled the odds of previous stroke (OR 1.8, 95% CI 1.03-3.3). Individuals with WML and stroke showed higher prevalence of dementia (OR 16.5, 95% CI 6.5-41.8) and mortality (OR 12.4, 95% CI 5.1-30.0) than those without WML and stroke. CONCLUSION: White matter lesions are common in the elderly, and these changes have clinical consequences increasing the risk of stroke. Whether preventive mechanisms could lead to risk reduction should be clarified in further studies.     

Familial presenile dementia with bitemporal atrophy

This study describes the clinical, neuropsychological, neuroimaging and genetic characteristics in two generations of a Swedish family affected by presenile dementia. The pedigree includes 5 cases (mother and 4 of 5 children) of progressive dementia with onset between 54 and 62 years. The clinical picture is characterized by insidious onset and progressive decline in episodic memory without spatial impairment or dyspraxia, followed by changes in personality and behaviour, with signs of disinhibition, irritability, impulsivity and loss of social awareness. Three siblings, examined after 10 years of duration, showed moderate language deficits but preserved spatial function and praxis. CT and MRI showed progressive bilateral temporal atrophy and moderate frontal white matter changes. Regional cerebral blood flow measurements showed hypoperfusion in temporal areas bilaterally. Quantitative EEG was normal within 5 years after symptom onset and thereafter showed a moderate increase in relative theta power. Sequencing of the tau gene (chromosome 17) revealed the previously described R406W mutation in exon 13 as a likely cause of the disease. This mutation was identified in all affected cases. The clinical picture of this family shows striking similarities not only to frontotemporal dementia but also to Alzheimer's disease.     

CD34-immunoreactive balloon cells in cortical malformations

Balloon cells are histopathological hallmarks of various cortical malformations, i.e., focal cortical dysplasia (Taylors type, FCD IIb), hemimegalencephaly (HME) or cortical tubers (tuberous sclerosis, TSC). Whether this intriguing cell type results from similar pathogenetic pathways remains to be shown. Here, we analyzed the immunohistochemical distribution pattern of the CD34 epitope in surgical specimens from 34 patients with FCD IIb, compared to that of 6 patients with TSC and 3 patients with HME. In normal brain, CD34 occurs only transiently during neurulation, but cannot be detected in mature neuroectodermal cell progenies. In contrast, 58% of our patients showed CD34 immunoreactivity within a subpopulation of balloon cells. Interestingly, CD34-positive balloon cells were confined to the white matter, but never observed in neocortical layers. Furthermore, balloon cells expressing neurofilament protein were also restricted to white matter, whereas GFAP-positive balloon cells were observed either in white or gray matter location. Clinical characteristics did not significantly differ between patients with CD34-positive versus CD34-negative lesions. No significant correlation was found between CD34 expression and genetic alterations of the TSC1 gene, which is affected in many FCD and TSC patients and which plays a role in the regulation of cell size. Further studies are warranted to clarify the restricted expression of CD34 in balloon cells of the white matter.     

Regulation of matrix metalloproteinase 13 expression by androgen in prostate cancer

The matrix metalloproteinases (MMPs) are members of a family of endopeptidases that are able to degrade extra-cellular matrix. MMPs and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs), play a key role in the migration of normal and malignant cell. Interaction of MMPs and TIMPs has been involved in the process of tumor invasion and metastasis. Using cDNA microarray as a screening tool to find androgen regulated gene in prostate cancer, we have found that expression of MMP-13 is regulated by androgen in prostate cancer derived cell line LNCaP. This regulation was further confirmed and quantified by real-time RT-PCR. In addition, the upregulation of MMP-13 mRNA by androgen could be abolished by the androgen antagonist Casodex but not the protein inhibitor cycloheximide. Western blot and immunohistochemistry of MMP-13 confirmed the androgen regulation at the protein level. We have furthermore shown that MMP-13 expression is presented in human prostate cancer obtained from aspiration biopsy. In summary, MMP-13 is androgen regulated and detectable in prostate cancer. Further study of MMP-13 in prostate cancer may help us to understand the progression of the cancer and can lead to new therapeutic options.