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  • Diffuse Lewy body disease  (2)
  • Human  (2)
  • Immunohistochemistry  (2)
  • 2000-2004
  • 1995-1999  (6)
  • 1980-1984
  • 1997  (6)
Collection
Publisher
Years
  • 2000-2004
  • 1995-1999  (6)
  • 1980-1984
Year
  • 1
    ISSN: 1619-7089
    Keywords: Key words: Dementia of the Alzheimer type ; Diffuse Lewy body disease ; Single-photon emission tomography ; Brain perfusion patterns ; Dopamine transporter
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Dementia of the Alzheimer-type (DAT) is characterized by progressive cognitive decline, variably combined with frontal lobe release signs, parkinsonian symptoms and myoclonus. The features of diffuse Lewy body disease (DLBD), the second most common cause of degenerative dementia, include progressive cognitive deterioration, often associated with levodopa-responsive parkinsonism, fluctuations of cognitive and motor functions, psychotic symptoms (visual and auditory hallucinations, depression), hypersensitivity to neuroleptics and orthostatic hypotension. A recent report suggests that positron emission tomography studies in patients with degenerative dementia may be useful in the differential diagnosis of DAT and DLBD. However, the diagnostic role of single-photon emission tomography (SPET) studies remains to be established. The aim of this study was therefore to evaluate regional cerebral perfusion [with either technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) or 99mTc-ethyl cysteinate dimer (99mTc-ECD) SPET] and striatal dopamine transporter density [using iodine-123 2β-carboxymethoxy-3β-[4-iodophenyl]tropane (123I-β-CIT) SPET] in patients with DAT and DLBD. Six patients with probable DAT and seven patients with probable DLBD were studied. Blinded qualitative assessment by four independent raters of 99mTc-HMPAO or 99mTc-ECD SPET studies revealed bilateral temporal and/or parietal hypoperfusion in all DAT patients. There was additional frontal hypoperfusion in two patients and occipital hypoperfusion in one patient. In the DLBD group, regional cerebral perfusion had a different pattern. In addition to temporoparietal hypoperfusion there was occipital hypoperfusion resembling a horseshoe defect in six of seven patients. In the DAT group, the mean 3-h striatal/cerebellar ratio of 123I-β-CIT binding was 2.5±0.4, with an increase to 5.5±1.1 18 h after tracer injection. In comparison, in the DLBD patients the mean 3-h striatal/cerebellar ratio of 123I-β-CIT binding was significantly reduced to 1.7±0.3, with a modest increase to 2.1±0.4 18 h after tracer injection (P〈0.05, Scheffe test, ANOVA). These results suggest that 99mTc-HMPAO or 99mTc-ECD and 123I-β-CIT SPET may contribute to the differential diagnosis between DAT and DLBD, showing different perfusion patterns and more severe impairment of dopamine transporter function in DLBD than in DAT.
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  • 2
    ISSN: 1619-7089
    Keywords: Dementia of the Alzheimer type ; Diffuse Lewy body disease ; Single-photon emission tomography ; Brain perfusion patterns ; Dopamine transporter
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Dementia of the Alzheimer-type (DAT) is characterized by progressive cognitive decline, variably combined with frontal lobe release signs, parkinsonian symptoms and myoclonus. The features of diffuse Lewy body disease (DLBD), the second most common cause of degenerative dementia, include progressive cognitive deterioration, often associated with levodopa-responsive parkinsonism, fluctuations of cognitive and motor functions, psychotic symptoms (visual and auditory hallucinations, depression), hypersensitivity to neuroleptics and orthostatic hypotension. A recent report suggests that positron emission tomography studies in patients with degenerative dementia may be useful in the differential diagnosis of DAT and DLBD. However, the diagnostic role of single-photon emission tomography (SPET) studies remains to be established. The aim of this study was therefore to evaluate regional cerebral perfusion [with either technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) or99mTc-ethyl cysteinate dimer (99mTc-ECD) SPET] and striatal dopamine transporter density [using iodine-123 2β-carboxymethoxy-3β-[4-iodophenyl]tropane (123I-β-CIT) SPET] in patients with DAT and DLBD. Six patients with probable DAT and seven patients with probable DLBD were studied. Blinded qualitative assessment by four independent raters of99mTc-HMPAO or99mTc-ECD SPET studies revealed bilateral temporal and/or parietal hypoperfusion in all DAT patients. There was additional frontal hypoperfusion in two patients and occipital hypoperfusion in one patient. In the DLBD group, regional cerebral perfusion had a different pattern. In addition to temporoparietal hypoperfusion there was occipital hypoperfusion resembling a horseshoe defect in six of seven patients. In the DAT group, the mean 3-h striatal/cerebellar ratio of123I-β-CIT binding was 2.5±0.4, with an increase to 5.5±1.1 18 h after tracer injection. In comparison, in the DLBD patients the mean 3-h striatal/cerebellar ratio of123I-β-CIT binding was significantly reduced to 1.7±0.3, with a modest increase to 2.1±0.4 18 h after tracer injection (P〈0.05, Scheffe test, ANOVA). These results suggest that99mTc-HMPAO or99mTc-ECD and123I-β-CIT SPET may contribute to the differential diagnosis between DAT and DLBD, showing different perfusion patterns and more severe impairment of dopamine transporter function in DLBD than in DAT.
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  • 3
    ISSN: 1432-1335
    Keywords: Immunohistochemistry ; p53 ; Soft-tissue sarcoma ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Most changes of tumor suppressor p53 and its pathway involve a protein with prolonged half-life that permits immunohistochemical detection. The goal of this study was to compare the prognostic relevance of five different p53 antibodies in primary soft-tissue sarcomas (STS) with known p53 mutation status, using a multivariate Cox regression model (adjusted to tumor grading, staging, localization, tumor type, and therapy). A group of 198 primary STS of six types were investigated for p53 overexpression, using p53 antibodies DO-1, DO-7, Pab1801, Pab240, and CM-1. A positive marker frequency between 36.2% and 62.6% was detected. Out of 65 patients whose primary tumor reacted positively to all five antibodies, 52 (80%) died within the study period. Only the N-terminal-binding monoclonal antibodies DO-1, DO-7 and Pab1801 showed a multivariate correlation with survival (P=0.0014, 0.0048 and 0.02). CM-1 and Pab240 had a univariate, but not a multivariate correlation, with a confounding effect of grading. The prognostic relevance for the five p53 antibodies was: DO-1〉Pab1801〉DO-7〉CM-1〉Pab240. This is the first study that investigates multivariately the prognostic relevance of p53 immunostaining in STS. If monoclonal antibodies with an epitope in the N-terminal region of the p53 protein (DO-1, Pab1801, DO-7) are applied, p53 immunohistochemistry provides an independent prognostic marker in STS.
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  • 4
    ISSN: 1432-1106
    Keywords: Key words Vision ; Locomotion ; Optic Flow Adaptation ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The effect of an optic flow pattern on human locomotion was studied in subjects walking on a self-driven treadmill. During walking an optic flow pattern was presented, which gave subjects the illusion of walking in a tunnel. Visual stimulation was achieved by a closed-loop system in which optic flow and treadmill velocity were automatically adjusted to the intended walking velocity (WV). Subjects were instructed to keep their WV constant. The presented optic flow velocity was sinusoidally varied relative to the WV with a cycle period of 2 min. The independent variable was the relative optic flow (rOF), ranging from −1, i.e., forward flow of equal velocity as the WV, and 3, i.e., backward flow 3 times faster than WV. All subjects were affected by rOF in a similar way. The results showed, firstly, an increase in stride-cycle variability that suggests a larger instability of the walking pattern than in treadmill walking without optic flow; and, secondly, a significant modulating effect of rOF on the self-chosen WV. Backward flow resulted in a decrease, whereas forward flow induced an increase of WV. Within the analyzed range, a linear relationship was found between rOF and WV. Thirdly, WV-related modulations in stride length (SL) and stride frequency (SF) were different from normal walking: whereas in the latter a change in WV is characterized by a stable linear relationship between SL and SF (i.e., an approximately constant SL to SF ratio), optic flow-induced changes in WV are closely related to a modulation of SL (i.e., a change of SL-SF ratio). Fourthly, this effect of rOF diminished by about 45% over the entire walking distance of 800 m. The results suggest that the adjustment of WV is the result of a summation of visual and leg-proprioceptive velocity informations. Visual information about ego-motion leads to an unintentional modulation of WV by affecting specifically the relationship between SL and SF. It is hypothesized that the space-related parameter (SL) is influenced by visually perceived motion information, whereas the temporal parameter (SF) remains stable. The adaptation over the entire walking distance suggests that a shift from visual to leg-proprioceptive control takes place.
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  • 5
    ISSN: 1432-2307
    Keywords: Cathepsins ; Immunohistochemistry ; Human soft tissue sarcomas ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Lysosomal proteases are known to enhance the spread of epithelial tumour cells, but little is known of the possible role of proteases in the growth of soft tissue sarcomas (STS). We investigated the expression of cathepsins D, B, S, H, L and procathepsin L in frozen sections of 34 STS from 34 patients by immunohistochemistry (IHC). Cathepsins D, B and H were relatively highly expressed in STS (77–91%). The expression rate of cathepsins S and L and of procathepsin L was lower (40–66%). Cathepsin S and L expression showed a moderate (P = 0.078 andP = 0.019) and procathepsin L a strong (P = 0.00001) correlation with the survival rate of STS patients. Cathepsin S expression is also correlated with the local recurrence rate (P 〈 0.01). Lysosomal proteases may play a role in STS progression, and cathepsin expression may also have, significance as a prognostic factor in STS.
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  • 6
    ISSN: 1432-0878
    Keywords: Key words: Interleukin-6 ; Interleukin-1β ; Tenidap ; Astrocytes ; Alzheimer’s disease ; Therapy ; Cell culture ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Tenidap is a structurally novel antirheumatic agent with anti-inflammatory and analgesic properties. Previous studies have shown that tenidap is able to inhibit the production and action of cytokines such as interleukin-1, interleukin-6 (IL-6) and tumour necrosis factor α. However, the mechanisms by which tenidap inhibits cytokine synthesis are not yet known. We investigated in the human astrocytoma cell line U373 whether tenidap inhibits IL-6 synthesis by inhibition of certain signal transduction processes leading to IL-6 synthesis. Cells were stimulated with different substances which have previously been shown to activate protein kinase A or C, reactive oxygen intermediates as well as transcription factors such as nuclear factor kappa B and AP-1 and which all result in IL-6 synthesis. Tenidap was a very potent inhibitor of IL-6 synthesis independent of the stimuli used, suggesting an inhibitory mechanism other than inhibition of a certain signal transduction pathway. Since IL-6 has been shown to be involved in the etiopathology of Alzheimer’s disease and since the use of nonsteroidal anti-inflammatory drugs appears to be of therapeutical benefit, it is concluded that tenidap should be tested in clinical trials in order to determine whether it may be useful for the treatment of Alzheimer’s disease.
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