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  • 2000-2004  (275)
  • 1920-1924
  • 1830-1839
  • Magnetic resonance imaging  (158)
  • apoptosis  (117)
  • 101
    ISSN: 1432-1920
    Keywords: Key words Hemimegalencephaly ; Positron emission tomography ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report hemimegalencephaly in a 44-year-old woman with mental retardation, epilepsy and a mild hemiparesis. In addition to typical findings on MRI, 2-deoxy-2[18F]fluorodeoxyglucose positron-emission tomography (PET) demonstrated glucose hypometabolism of the affected hemisphere. The results of PET have been coregistered with morphological information from the MRI studies by image fusion.
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  • 102
    ISSN: 1432-1920
    Keywords: Key words Cerebral palsy ; Birth asphyxia ; Magnetic resonance imaging ; Single-photon emission computed tomography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We describe the findings on single-photon emission computed tomography (SPECT) in patients with perinatal asphyxia at term, with perirolandic cortico-subcortical changes on MRI, and to correlate them with clinical features. SPECT of 7 patients was obtained after injection of 185–370 MBq of Tc-99m-ECD (ethyl cysteinate dimer). The patients had spastic quadriplegia (7/7) with perinatal asphyxia (6/7) at term (7/7). The results were correlated with the MRI findings. Hypoperfusion of the perirolandic cortex was clearly seen on SPECT in all patients, even in two with subtle changes on MRI. SPECT demonstrated a more extensive area of involvement than MRI, notably in the cerebellum (in 4), the thalamus (in 7) and basal ganglia (in 5), where MRI failed to show any abnormalities.
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  • 103
    Electronic Resource
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    Springer
    Neuroradiology 42 (2000), S. 917-922 
    ISSN: 1432-1920
    Keywords: Key words Mouth, cysts ; Neck, cysts ; Glands, salivary ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We reviewed the MRI of 20 patients with a ranula (8 simple and 12 plunging) and ten with other cystic masses in the floor of the mouth and/ or suprahyoid portion of the neck (three haemangiomas, two neuromas, one monomorphic adenoma, one lipoma, two lateral cervical cysts and one dermoid cyst). Histological diagnoses were obtained in all cases with the exception of one presumed haemangioma. Ranulas were all well-defined, homogeneous masses giving low signal on T1-and markedly high signal on T2-weighted images. While simple ranulas were all confined to the sublingual space, plunging ranulas were centered on the submandibular space and tended to spill into one or more adjacent spaces. They extended into the sublingual space anteriorly (producung a so-called tail sign) in eight of 12 cases and into the parapharyngeal space superiorly in five. Although they sometimes filled a considerable part of the parapharyngeal space, displacement of surrounding muscles or vessels was usually slight, which was thought to reflect the nature of extravasation pseudocysts. All other cystic masses in our study had one or more MRI finding different from those of ranulas and could be easily differentiated from them.
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  • 104
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    Springer
    Neuroradiology 42 (2000), S. 112-114 
    ISSN: 1432-1920
    Keywords: Key words Hypophosphataemia ; Brain ; Myelinolysis, extrapontine ; Computed tomography ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report a 38-year-old woman with extreme hypophosphataemia in whom CT and MRI disclosed bilateral lesions within the basal ganglia, thalamus and occipital lobes. After adequate substitution of phosphate the lesions grossly resolved and the patient recovered. This case is the first to demonstrate that profound changes of serum phosphate may be associated with reversible brain lesions.
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  • 105
    ISSN: 1432-1920
    Keywords: Key words Carcinoma nasopharyngeal ; Radionecrosis ; Magnetic resonance imaging ; Pulse sequences
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We examined nine patients with histologically proven nasopharyngeal carcinoma (NPC), treated with radiotherapy, using dynamic susceptibility contrast MRI (DSC-MRI). In eight there was clinical evidence of radionecrosis of the temporal lobe, and one was examined for local recurrence in the nasopharynx. All patients had either high-signal finger-like or cystic lesions in the temporal lobes on T2-weighted images. Heterogeneous contrast enhancement occurred in all patients. Relative regional cerebral blood volume (rrCBV) mapping revealed marked hypoperfusion in all patients. One underwent bilateral temporal lobectomy and radionecrosis was confirmed histologically.
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  • 106
    ISSN: 1432-1920
    Keywords: Key words Dysplasia, focal cortical ; Hamartomas ; Epilepsy ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Focal cortical dysplasia (FCD) is a pathological entity first described in 1971. Other more subtle cortical malformations found in patients with epilepsy include microdysgenesis (MD), and glioneuronal hamartias. Although these glial and neuronoglial malformations have distinct histological features, there is terminological confusion in the radiological literature. Few cases have been reported in adults with both imaging and histology. We address these issues, giving a radiological-pathological correlation of histologically proven cortical malformations in adults. We describe clinical, radiological and histological features of 12 cases (five FCD, five MD with glioneuronal hamartias, and two hamartomas), unassociated with other conditions, and discuss them in the light of the literature. FCD is usually seen on MRI as cortical thickening, with or without signal change, which may extend into the adjacent white matter. On histology, abnormal neurons and/or glial cells, blurring of the grey-white matter interface, myelin pallor, demyelination, and gliosis may be found. Glioneuronal hamartias and hamartomas usually appear as complex masses on MRI. FCD and hamartias may be associated, and a combination of imaging findings may be seen on MRI. Atrophy of the ipsilateral hippocampus may be present on MRI in patients with hamartias, and minor cell loss on histology, but not definitive hippocampal sclerosis. Although the imaging findings of cortical malformations are protean, some characteristic MRI features, with histological correlates, may be found. The relevance of most of these observations remains unclear.
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  • 107
    ISSN: 1432-1920
    Keywords: Key words Acquired immunodeficiency syndrome ; Magnetic resonance imaging ; Contrast-enhancement
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Our purpose was to determine whether triple-dose delayed contrast-enhanced images would improve lesion detection in patients with symptomatic human immunodeficiency virus (HIV) infection. We reviewed 33 MRI studies on 29 patients. Single-dose immediate T 1-weighted spin-echo (1x-T 1) images were compared with delayed triple-dose images (D3x-T 1). Two neuroradiologists decided which technique showed more lesions, increased lesion conspicuity and/or altered the radiologic diagnosis. The D3x-T 1 technique improved lesion detection in 14 of 29 patients (48 %). In two patients (7 %), the improvement changed the radiologic diagnosis by showing new meningeal lesions.
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  • 108
    ISSN: 1432-1920
    Keywords: Key words Cerebral autosomal dominant arteriopathy ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Clinical data and MRI findings are presented on 18 subjects from two families with neuropathologically confirmed CADASIL. DNA analysis revealed mutations in exon 4 of Notch 3 gene in both families. All family members with mutations in Notch 3 gene had extensive abnormalities on MRI, principally lesions in the white matter of the frontal lobes and in the external capsules. Of several family members in whom a diagnosis of CADASIL was suspected on the basis of minor symptoms, one had MRI changes consistent with CADASIL; none of these cases carried a mutation in the Notch 3 gene. MRI and clinical features that may alert the radiologist to the diagnosis of CADASIL are reviewed. However, a wide differential diagnosis exists for the MRI appearances of CADASIL, including multiple sclerosis and small-vessel disease secondary to hypertension. The definitive diagnosis cannot be made on MRI alone and requires additional evidence, where available, from a positive family history and by screening DNA for mutations of Notch 3 gene.
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  • 109
    ISSN: 1432-1920
    Keywords: Key words Rhombencephalosynapsis ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rhombencephalosynapsis is an unusual disorder characterised by maldevelopment of the rhombencephalon, sometimes with supratentorial midline anomalies. We report MRI findings in a 39-year-old woman, the oldest in the literature. MRI demonstrated hypoplasia of the cerebellar vermis, with fusion of the cerebellar hemispheres and abnormally oriented folia. Supratentorial anomalies were also seen.
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  • 110
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    Neuroradiology 42 (2000), S. 360-362 
    ISSN: 1432-1920
    Keywords: Key words Cyst, cavum septi pellucidi ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A 20-year-old woman with secondary amenorrhoea and an empty sella turcica was found to have a cyst of the cavum septi pellucidi (CSP) on MRI. The cyst had regressed spontaneously on follow-up MRI.
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  • 111
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    Springer
    Neuroradiology 42 (2000), S. 406-412 
    ISSN: 1432-1920
    Keywords: Key words Lymphoma, primary central nervous system ; Chemotherapy ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract On MRI, primary brain tumors are commonly seen as contrast-enhancing masses surrounded by areas of abnormal signal on T2-weighted images. Following successful treatment tumors may no longer show contrast enhancement. The residual abnormalities are assumed to be represent “edema” and infiltrating tumor cells. We report nine patients with primary lymphoma of the central nervous system who had complete responses to intravenous methotrexate, but did not receive intrathecal chemotherapy or cranial irradiation. After complete resolution of contrast-enhancing lesions, persistent abnormalities on T2-weighted images in the region of prior tumor were initially assumed to reflect residual viable tumor. As they remained unchanged for years, however, this may not hold true in the cases in which primary central nervous system lymphoma responds to chemotherapy alone.
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  • 112
    ISSN: 1432-1920
    Keywords: Key words Corpus callosum ; White matter lesions ; Cerebral ischaemia ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Many studies of white matter high signal (WMHS) on T2-weighted MRI have disclosed that it is related to cerebral ischaemia and to brain atrophy. Atrophy of the corpus callosum (CC) has also been studied in relation to ischaemia. Our objective was to test the hypothesis that CC atrophy could be due to ischaemia. We therefore assessed CC, WMHS and brain atrophy in patients with risk factors without strokes (the risk factor group) and in those with infarcts (the infarct group), to investigate the relationships between these factors. We studied 30 patients in the infarct group, 14 in the risk factor group, and 29 normal subjects. Using axial T1-weighted MRI, cortical atrophy and ventricular enlargement (brain atrophy) were visually rated. Using axial T2-weighted MRI, WMHS was assessed in three categories: periventricular symmetrical, periventricular asymmetrical and subcortical. Using the mid-sagittal T1-weighted image, the CC was measured in its anterior, posterior, midanterior and midposterior portions. In the normal group, no correlations were noted between parameters. In the infarct group, there were significant correlations between CC and brain atrophy, and between CC atrophy and WMHS. After removing the effects of age, gender and brain atrophy, significant correlations were noted between some CC measures and subcortical WMHS. In the risk factor group, there were significant correlations between CC and brain atrophy and between CC atrophy and WMHS. After allowance for age, gender and brain atrophy, significant correlations between some CC measures and periventricular WMHS remained. The hypothesis that CC atrophy could be due to cerebral ischaemia was supported by other analyses. Namely, for correlations between the extent of infarcts and partial CC atrophy in patients with anterior middle cerebral artery (MCA) and with posterior MCA infarcts, there were significant correlations between the extent of infarct and midanterior CC atrophy in the former, and posterior CC atrophy in the latter. Our findings could indicate that CC atrophy is associated with cerebral ischaemia.
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  • 113
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    Neuroradiology 42 (2000), S. 551-563 
    ISSN: 1432-1920
    Keywords: Key words Acquired immune deficiency syndrome ; Spine ; infections ; Spine ; neoplasms ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Our purpose was to describe the range of MRI findings in infectious and neoplastic involvement of the spine and spinal cord in symptomatic patients with the acquired immunodeficiency syndrome (AIDS). MRI studies in 55 patients with AIDS and neurological signs and symptoms thought to be related to the spine or spinal cord were reviewed. We categorized the findings according to the spinal compartment involved. There were 29 patients with extradural, 11 with intradural-extramedullary and 9 with intramedullary disease. In 6 patients more than one compartment was involved simultaneously, and patients presented with multiple lesions in the same compartment. The most common causes of extradural disease were bone lesions (28); an epidural mass was seen in 14 and spondylodiscitis in 4 patients. Cytomegalovirus polyradiculitis was the most common cause of intradural-extramedullary disease (in 10 cases); herpes radiculitis was seen in two, and tuberculous infection in another two. In three cases leptomeningeal contrast enhancement was due to lymphoma. Human immunodeficiency virus (HIV) myelitis was seen in two patients, presumed vacuolar myelopathy in two, toxoplasma myelitis in four, intramedullary lymphoma in one, and herpes myelitis in one. Familiarity with the various potential pathological entities that can affect the spine and spinal cord in the AIDS population and their imaging characteristics is crucial for initiation of further diagnostic tests and appropriate medical or surgical treatment.
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  • 114
    ISSN: 1432-1920
    Keywords: Key words Progressive supranuclear palsy ; Magnetic resonance imaging ; Diffusion-weighted imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We measured the apparent diffusion coefficient (ADC), using diffusion-weighted imaging (DWI) and signal intensity on T2-weighted MRI in the cerebral white matter of patients with progressive supranuclear palsy (PSP) and age-matched normal subjects. In PSP, ADC in the prefrontal and precentral white matter was significantly higher than in controls. There was no significant difference in signal intensity on T2-weighted images. The ADC did correlate with signal intensity. The distribution of the elevation of ADC may be the consequence of underlying pathological changes, such as neurofibrillary tangles or glial fibrillary tangles in the cortex. Our findings suggest that ADC measurement might be useful for demonstrating subtle neuropathological changes.
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  • 115
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    Neuroradiology 42 (2000), S. 676-678 
    ISSN: 1432-1920
    Keywords: Key words. Syringomyelia, spontaneous drainage ; Cerebrospinal fluid, hydrodynamics ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. We present five cases of syringomyelia associated with Chiari I or other causes of partial obstructions at the cervicomedullary junction, with spontaneous disruption of the wall of a cervical syrinx and formation of a communication between the cavity and the subarachnoid space, shown on axial MRI. MRI can be used to investigate the hydrodynamics, showing the liquid inside the disrupted syrinx wall and the pathway of drainage. The finding of spontaneous drainage may be important for understanding the pathogenesis of syringomyelia and may be helpful for choosing a surgical approach.
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  • 116
    ISSN: 1432-198X
    Keywords: Key words Henoch-Schönlein purpura ; Methylprednisolone ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Neurological complications are rare during the course of Henoch-Schönlein purpura (HSP). We report a 7-year-old girl with HSP who presented with seizures, loss of vision and disturbance of consciousness. Magnetic resonance imaging (MRI) showed high signal intensity in the gray and white matter over the left parietal and both occipital lobes, compatible with MRI findings of cerebral vasculitis. The eye fundi revealed multiple branches of retinal artery occlusion. Intravenous pulse methylprednisolone (MTP) followed by oral steroid therapy was initially administered for HSP nephritis. Cerebral vasculitis developed 10 days post-MTP treatment, with progressive worsening of consciousness. Oral steroid was discontinued and plasmapheresis was performed alone. Her level of consciousness dramatically improved after plasmapheresis. The brain MRI and eye fundi findings were consistent with her clinical improvement. To the best of our knowledge, this is the first description of MRI abnormalities and multiple retinal artery branch occlusion of cerebral vasculitis in a patient with HSP that was successfully treated by plasmapheresis alone. In conclusion, we propose that plasmapheresis may be used as a first-line therapy or rescue therapy for cerebral vasculitis in HSP.
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  • 117
    ISSN: 1432-198X
    Keywords: Key words Hemolytic uremic syndrome ; Cerebral hypoxia ; Magnetic resonance imaging ; Central nervous system lesions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We report a 20-month-old girl with post- diarrheal (Shiga toxin) hemolytic uremic syndrome and severe encephalopathy. Magnetic resonance (MR) images were obtained in the acute phase of the disease and after 10 months. The first MR images showed widespread high signal intensity on T2-weighted and low signal intensity on T1-weighted images, in deep and subcortical white matter; the splenium of the corpus callosum was also involved, as well as cerebellar hemispheres. Neurological symptoms and signs gradually disappeared within 35 days. Follow-up MR imaging showed almost complete resolution of the previous findings, and the patient recovered without central nervous system impairment. The neurological lesions were probably due to hypoxia, although several other mechanisms could be involved, such as metabolic derangements and the action of Shiga toxin. In spite of the dramatic clinical manifestations, we observed a good outcome, indicating that patients with similar lesions do not necessarily have a poor prognosis.
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  • 118
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    Der Radiologe 40 (2000), S. 904-915 
    ISSN: 1432-2102
    Keywords: Schlüsselwörter Leber ; Sonographie ; Computertomographie ; Magnetresonanztomographie ; Szintigraphie ; Positronenemissionstomographie ; Keywords Liver ; Ultrasonography ; Computed tomography ; Magnetic resonance imaging ; Radionuclide imaging ; Positron emission tomography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Highly specific methods are required for the diagnostic workup of focal hepatic lesions, since benign circumscribed liver changes are very common. Although cross-sectional imaging techniques have a high diagnostic accuracy, radionuclide imaging techniques such as colloid, red blood cell, or hepatobiliary scan are commonly performed when a benign lesion is assumed since these permit a definite diagnosis with high specificity. The diagnosis of a primary or secondary malignant liver tumor, however, usually relies on radiological imaging techniques alone, supported by needle biopsy. Whether positron emission tomography as a primary or supplementary diagnostic tool will have a role in the routine staging of malignant tumors remains to be determined.
    Notes: Zusammenfassung Die Abklärung umschriebener Leberveränderungen erfordert den Einsatz von Methoden hoher Spezifität, da die Prävalenz benigner, fokaler Läsionen sehr hoch ist. Hierfür sind radiologische Schnittbildtechniken grundsätzlich gut geeignet. Wenn aufgrund der sonographischen, computertomographischen oder magnetresonanztomographischen Befunde eine gutartige Läsion anzunehmen ist, werden jedoch häufig ergänzend die Kolloiderythrozyten- oder hepatobiliäre Szintigraphie – ggf. in Kombination – eingesetzt, da hiermit rasch eine abschließende Diagnose mit hoher Spezifität gestellt werden kann. Bei malignen primären oder sekundären Lebertumoren hingegen werden nuklearmedizinische Zusatzuntersuchungen seltener angefordert, da der radiologische Befund, ggf. gestützt durch eine Ultraschall- oder CT-gezielte Biopsie, eine Diagnose in den meisten Fällen erlaubt. Inwieweit sich der primäre oder ergänzende Einsatz der Positronenemissionstomographie im Vergleich zu radiologischen Schnittbildtechniken beim Staging bösartiger Tumoren bewährt, ist noch nicht abschließend geklärt.
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  • 119
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    Der Radiologe 40 (2000), S. 1064-1076 
    ISSN: 1432-2102
    Keywords: Schlüsselwörter Sarkoidose ; Neurosarkoidose ; Granulom ; MRT ; Keywords Sarcoidosis ; Sarcoidosis complications ; Neurosarcoidosis ; Granuloma ; Brain diseases complications ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract The central nervous system is frequently affected during the course of sarcoidosis. Many of these lesions remain without clinical correlates. Unenhanced and contrast enhanced CT and MRI play an important role during the diagnostic work-up of patients with sarcoidosis and suspected or proved CNS involvement. This article summarizes the most frequent manifestations of neurosarcoidosis and provides illustrative examples of MRI findings.
    Notes: Zusammenfassung Das Nervensystem ist bei der Sarkoidose häufiger mitbeteiligt als nach klinischen Gesichtspunkten zu vermuten wäre. Den bildgebenden Untersuchungsverfahren kommt eine große Bedeutung beim Nachweis der pathologischen Veränderungen zu. Insbesondere die Kernspintomographie sichert die Diagnosestellung und dient der Verlaufsbeurteilung. In dieser Übersichtsarbeit werden die typischen klinischen und bildgebenden Befunde bei der Neurosarkoidose vorgestellt.
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  • 120
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    Der Radiologe 40 (2000), S. 870-877 
    ISSN: 1432-2102
    Keywords: Schlüsselwörter Lunge ; Perfusion ; Ventilation ; Computertomographie (CT) ; Magnetresonanztomographie (MRT) ; Keywords Lung ; Perfusion ; Ventilation ; Computed tomography ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Radiological cross-sectional imaging modalities, particularly computed tomography (CT) have become the mainstays for diagnosing lung disease in recent years. These enable morphological visualization of pathological processes with the greatest possible spatial resolution. Modern technical developments and complementary strategies have led to new applications and new functional assessments which need to be reviewed together with state-of-the-art techniques in nuclear imaging. The diagnosis of pulmonary embolism using spiral CT angiography and magnetic resonance (MR) angiography certainly belongs in this category. CT has become the an alternative modality of first choice, and it is also challenging pulmonary angiography as the gold standard. Direct visualization of patent pulmonary arteries and thromboembolic material is complemented by that of effects on the pulmonary parenchyma and right heart function; it also provides perfusion studies and MR-based flow measurement to assess hemodynamic compromise. Ventilation studies have long been a domain of nuclear imaging, and new techniques for the direct visualization of ventilation are emerging from recent developments in the field of MR imaging, for example, using hyperpolarized inert gases. New functional parameters of ventilation can be derived from these studies. For the diagnosis of metabolically active disease, such as tumor and pneumonia, CT offers very high sensitivity, for example, in screening for intrapulmonary nodules using low-dose CT and in the early detection of pulmonary infiltrates in high-risk patients. Especially for characterizing pulmonary nodules there is a need to combine nuclear medicine techniques, such as in positron-emission tomography.
    Notes: Zusammenfassung Die radiologischen Schnittbildverfahren, insbesondere die CT, haben sich innerhalb kurzer Zeit einen herausragenden Stellenwert in der Diagnostik von Lungenerkrankungen erworben. Dies umfasst in erster Linie die morphologische Darstellung pathologischer Prozesse mit hoher räumlicher Auflösung. Moderne technische Entwicklungen und kombinierte Untersuchungsstrategien eröffnen neue Einsatzgebiete und auch funktionelle Aussagen, die nach einer aktuellen Standortbestimmung gemeinsam mit den nuklearmedizinischen Verfahren verlangen. Dazu gehört die Diagnostik der Lungenembolie mittels Spiral-CT-Angiographie und MR-Angiographie der Pulmonalarterien. Hier hat sich mittlerweile die CT als alternatives Verfahren der Wahl etabliert und die Rolle der Pulmonalisangiographie als Goldstandard infrage gestellt. Die reine direkte Darstellung der durchströmten Pulmonalarterien und des thromboembolischen Materials wird durch Diagnostik intrapulmonaler und kardialer Veränderungen, Perfusionsuntersuchungen sowie MR-basierte Flussmessungen zur hämodynamischen Beurteilung erweitert. Nachdem Untersuchungen der Ventilation lange Zeit eine Domäne der Nuklearmedizin waren, eröffnen aktuelle Entwicklungen in der MRT neue Verfahren zur direkten Visualisierung der Lungenbelüftung, z. B. mittels polarisierter Edelgase. Aus diesen Verfahren lassen sich auch neue funktionelle Parameter der Ventilation ableiten. In der Diagnostik von Tumoren und Entzündungen überzeugt die CT insbesondere durch ihre hohe Sensitivität, z. B. beim Screening auf intrapulmonale Rundherde mittels Niedrigdosis-CT oder bei der Früherkennung pneumonischer Infiltrate bei Risikopatienten. Insbesondere bei der Charakterisierung intrapulmonaler Rundherde ist eine Kombination mit nuklearmedizinischen Verfahren (PET) grundsätzlich anzustreben.
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  • 121
    ISSN: 1432-2102
    Keywords: Schlüsselwörter ; Koronare Herzkrankheit ; Magnetresonanztomographie ; Myokardperfusion ; SPECT ; Key words ; Coronary artery disease ; Magnetic resonance imaging ; Myocardial perfusion ; SPECT
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Aim: Performance of combined rest/stress MR perfusion studies and the analysis of qualitative signal intensity parameters in comparison with 99mTc-SestaMIBI SPECT in patients with known coronary artery disease (CAD). Methods: Sixteen patients with CAD underwent MR myocardial perfusion assessment at rest and after dipyridamole-induced hyperemia. Qualitative parameters (SI increase, SI upslope) of the SI time-curves were evaluated and characteristics of normal, reversible and persistent hypoperfused myocardium as assessed by 99mTc-SestaMIBI SPECT were compared. Results: Compared with the rest values, normal myocardium showed a significant increase of the SI upslope during hyperemia (P〈0.001), whereas persistent (P=0.07) and reversible (P=0.15) hypoperfusions showed only minor changes. SI increase over baseline also showed a significant increase only in normal myocardium (P〈0.001). At rest, reversible ischemic areas showed no significant differences from normal myocardium, whereas during hyperemia SI increase was significantly lower (P=0.02). Conclusions: Qualitative SI parameters of a combined rest/stress MR myocardial perfusion study allow to differentiate normal from reversibly or persistently hypoperfused myocardium.
    Notes: Zusammenfassung Fragestellung: Die kombinierte Ruhe- und Belastungsuntersuchung der myokardialen Durchblutung in der MRT sowie die Analyse qualitativer SI-Parameter der MR-Myokardperfusion bei Patienten mit koronarer Herzkrankheit wurden mit der 99mTc-SestaMIBI SPECT verglichen. Methode: Bei 16 Patienten mit koronarer Herzkrankheit (KHK) wurde in der MRT mit einer Mehrschichtgradientenechotechnik die Myokardperfusion unter Ruhe- und Belastungsbedingungen untersucht. Qualitative Signalintensitätsparameter der Kontrastmittelanflutung wurden berechnet und die Parameter in normalen, reversibel und persistierend minderperfundierten Myokardarealen miteinander verglichen. Ergebnisse: Normales Myokard zeigte im Gegensatz zu reversiblen (P=0,15) und persistierenden (P=0,07) Ischämien eine signifikante Zunahme der SI-Anstiegssteilheit unter Belastung (P〈0,001). Die SI-Zunahme zeigte ebenfalls nur in normal perfundierten Arealen eine signifikante Zunahme (P〈0,001) nach Belastung. Unter Belastung zeigte sich bei reversiblen Ischämien eine signifikant niedrigere SI-Zunahme als in normalem Myokard (P=0,02), während sich in Ruhe kein Unterschied zeigte. Schlussfolgerung: Qualitative SI-Parameter der kombinierten MR-Perfusionsuntersuchung des Myokards in Ruhe und unter Belastung erlauben die Differenzierung zwischen normalem sowie reversibel oder persistierend minderperfundiertem Myokard.
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  • 122
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    Der Radiologe 40 (2000), S. 465-468 
    ISSN: 1432-2102
    Keywords: Schlüsselwörter Fäkale Inkontinenz ; Magnetresonanztomographie ; Endoanalspule ; Key words Faecal incontinence ; Magnetic resonance imaging ; Endoanal coil
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Purpose. Within the recent years several studies have been performed to determine the value of endoanal magnetic resonance imaging (MRI) in faecal incontinence. Methods. MRI is performed using a 0.5 – 1.5T unit. A surface coil with a maximum diameter of 19 mm is placed in the anal canal. T2* 3D gradient-echo-sequences and T2-weighted turbo-spin-echo-sequences in coronal, axial und sagittal orientation are acquired. Results. Compared to endoanal ultrasound (EUS), which is the gold standard for diagnosis in faecal incontinence, endoanal MRI is better in visualization of the external sphincter. The accurate delineation of the external sphincter has led to the possibility to evaluate sphincter atrophy. Preliminary results have shown, that endoanal MRI has an accuracy of 90–95% in the demonstration of lesions in the external sphincter. In detection of lesions of the internal sphincter EUS is still superior to endoanal MRI. Conclusion. EUS and endoanal MRI are currently the optimal imaging techniques for faecal incontinenc, with the advantage of detecting external sphincter atrophy with endoanal MRI.
    Notes: Zusammenfassung Zielsetzung. In den letzten Jahren wurden mehrere Studien durchgeführt, deren Ziel es war, den Stellenwert von Endoanalspulen in der Magnetresonanztomographie (MRT) zur Abklärung von Sphinkterdefekten bei fäkaler Inkontinenz (FI) zu bestimmen. Methode. Die endoanale MRT wird an 0,5–1,5-Tesla-Geräten durchgeführt. Zur Darstellung der Sphinkteren werden Oberflächenspulen mit einem maximalen Querdurchmesser von 19 mm endoanal appliziert. T2*-gewichtet 3D-Gradientenechosequenzen und T2-gewichtete Turbospinechosequenzen in koronaler, axialer und sagittaler Schnittführung werden zur Darstellung des Analkanals angefertigt. Ergebnisse. Im Vergleich zum endoanalen Ultraschall (EUS), der den Goldstandard bei der Abklärung einer FI darstellt, kann mit der endoanalen MRT v. a. der M. sphincter externus besser abgegrenzt werden. Die exakte Differenzierung des M. sphincter externus vom ischiorektalem Fettgewebe ermöglicht die Diagnose einer Atrophie des äußeren Schließmuskels. Erste Studienergebnisse haben gezeigt, daß die endoanale MRT eine Treffsicherheit von 90–95% bei der Detektion von Defekten im M. sphincter externus erreicht. Die Abklärung einer Kontinuitätsunterbrechung im M. sphincter internus ist nach wie vor eine Domäne des EUS. Schlussfolgerung. Die endoanale MRT stellt eine ergänzende Methode zum EUS dar und ist diesem in der Beurteilung der Morphologie des M. sphincter externus überlegen.
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  • 123
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    Der Radiologe 40 (2000), S. 625-631 
    ISSN: 1432-2102
    Keywords: Schlüsselwörter Computertomographie ; Magnetresonanztomographie ; Pharynx ; Tumoren ; Key words Computed tomography ; Magnetic resonance imaging ; Pharynx ; Tumors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Background. Malignant tumors of the head and neck region are amongst the six most often occurring tumors of the body. They can be associated with the different anatomical compartments as well as different histologic types. The way of tumor spread of these malignancies depends on their histologic type and on the region. These compartments can be separated into the nasopharynx, the oropharynx, and the hypopharynx. Most of the malignant tumors belong to the squamous cell carcinomas, other histologic types are depicted less frequently. The histologic types of the other groups which are seen more often comprise of lymphomas and adenoidcystic carcinomas. The undifferentiated carcinoma of the nasopharynx is supposed to be a special type of tumor. The malignant tumors of the pharynx can also involve all three compartments. Beside these tumors, malignancies of mesenchymal origin can also be delineated. Imaging modalities. The imaging modalities most frequently used to detect these tumors and to clarify their extension are contrast enhanced computed tomography, magnetic resonance imaging, nuclearmedicine imaging modalities such as positron emission tomography. Other scintigraphic imaging methods play a less important role. Conclusion. The different imaging modalities of malignant pharyngeal tumors and of potentially infiltrated lymphnodes with the weightness on computed tomography and magnetic resonance imaging and their appearance in these imaging techniques shall be enhanced in this paper.
    Notes: Zusammenfassung Hintergrund. Der Kopf-Hals-Bereich zählt weltweit zu den 6 am häufigsten von malignen Tumoren befallenen Körperregionen. Maligne Tumoren des Pharynx können dabei entsprechend der anatomischen Unterteilung – d. h. Nasopharynx, Oropharynx und Hypopharynx – diesen Regionen zugeordnet werden. Neben der grundsätzlich heterogenen Wachstumstendenz weisen diese Tumoren je nach histologischer Herkunft ein recht unterschiedliches Ausbreitungsmuster auf. Bei der überwiegenden Mehrzahl handelt es sich um Plattenepithelkarzinome, die anderen histologischen Typen – wie adenoidzystische Karzinome oder Lymphome – sind weitaus seltener vertreten. Daneben kommen sehr selten auch noch maligne Tumoren mesenchymalen Ursprungs wie z. B. die Rhabdomyosarkome vor. Bildgebung. Die bildgebende Abklärung erfolgt mit der kontrastmittelverstärkten CT, der MRT und in jüngster Zeit mit nuklearmedizinischen Methoden, z. B. PET. Andere szintigraphische Untersuchungsmethoden spielen eine untergeordnete Rolle. Resümee. Verschiedene bildgebende Methoden (schwerpunktmäßig CT und MRT) und die entsprechenden Erscheinungsbilder sowie Lokalisations- bzw. Ausbreitungsdiagnostik der malignen Tumoren und evtl. befallener Lymphknoten dieser Regionen werden vorgestellt.
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  • 124
    ISSN: 1432-2102
    Keywords: Schlüsselwörter Zerebrovaskuläre Erkrankung ; Arteriosklerose ; Magnetresonanztomographie ; Magnetresonanzangiographie ; Digitale Subtraktionsangiographie ; A. carotis ; Keywords Cerebrovascular disease ; Arteriosclerosis ; Magnetic resonance imaging ; Magnetic resonance angiography ; Digital subtraction angiography ; Carotid artery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Purpose. To compare high resolution contrast-enhanced MR angiography (MRA) and digital subtraction angiography (DSA) in the assessment of supraaortic vessel stenosis. Methods. 14 patients with suspicion of cerebrovascular disease or upper limb ischemia underwent selective DSA and high resolution contrast enhanced MRA employing a new Panoramic-Array coil. Stenosis assessment in comparison to DSA followed NASCET criteria. Additionally signal-/noise ratios (SNR) were evaluated to assess contrast enhancement. Results. Diagnostic image quality was achieved in all patients. Sensitivity and specificity for assessing high-grade stenosis of the supraaortic vessels were 100% and 96% respectively. In the assessment of high-grade common or internal carotid artery stenosis sensitivity and specificity was 100%. Conclusion. High resolution contrast enhanced supraaortic MRA combined with new coil sytems allow for a reliable assessment of stenoses along the whole vessel course including the aortic arch. Previous stent procedures limit its use in post-interventional follow-up.
    Notes: Zusammenfassung Fragestellung. Ziel der Studie war ein Vergleich zwischen hochauflösender kontrastverstärkter MR-Angiographie (MRA) und digitaler Subtraktionsangiographie (DSA) in der Diagnostik von Stenosen der supraaortalen Gefäße. Methoden. 14 Patienten mit Verdacht auf eine zerebrovaskuläre Erkrankung oder Durchblutungsstörung der oberen Extremität wurden mit DSA und hochaufgelöster, kontrastverstärkter MR-Angiographie mit Verwendung einer Panoramic-Array-Spule untersucht. Neben der Beurteilung der Kontrastierung erfolgte die Bestimmung der Stenosegrade im Vergleich zur selektiven DSA nach den NASCET-Kriterien. Ergebnisse. Bei allen Patienten konnte mit der MRA eine diagnostisch ausreichende Bildqualität erzielt werden. In der Diagnostik hochgradiger Stenosen der supraaortalen Gefäße ergab sich eine Sensitivität von 100% und eine Spezifität von 96%. In der Erkennung hochgradiger Stenosen der A. carotis communis oder interna lagen Sensitivität und Spezifität bei 100%. Schlussfolgerung. Die ultraschnelle MRA der supraaortalen Gefäße in Kombination mit einer geeigneten Spulenkombination ermöglicht die zuverlässige Erkennung stenotischer Veränderungen im gesamten Gefäßverlauf einschließlich des Aortenbogens. Stentimplanationen limitieren derzeit den Einsatz in der postinterventionellen Kontrolle.
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  • 125
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    Journal of neurology 247 (2000), S. 943-948 
    ISSN: 1432-1459
    Keywords: Key words Transverse myelitis ; Motor evoked potentials ; Somatosensory evoked potentials ; Electromyography ; Prognosis ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A systematic evaluation of anterior horn cell, motor and sensory pathways is possible by electromyography (EMG), motor (MEPs) and somatosensory (SEPs) evoked potentials, respectively, which may provide valuable information on acute transverse myelitis (ATM). In a prospective hospital-based study, EMG, MEP and SEP studies were carried out on admission and after 3 months in 39 patients with ATM. All the patients also underwent detailed clinical evaluation, and spinal magnetic resonance imaging (MRI) was performed in 28. Outcome was defined at the end of 3 months as poor, partial or complete recovery on the basis of functional status. Spinal MRI revealed hyperintense signal changes in T2 extending for two segments to the entire spinal cord. Central motor conduction time to tibialis anterior (CMCT-TA) was more frequently abnormal (90%), followed by tibial SEP (77%). CMCT to abductor digiti minimi (ADM) was abnormal in 30% and median SEP in 15% of patients. Evidence of denervation on EMG was present in 51% of patients. The CMCT-TA improved in 48% patients and tibial SEP in 32%. Median SEP improved in all patients, and CMCT-ADM remained prolonged in two. At 3 months 2 patients had died, and 18 had poor, 10 partial and 9 complete recovery. CMCT was correlated with miscle power, tone, reflec and MRI changes. Patients' outcome of was correlated with CMCT, SEP and EMG. These results are consistent with pronounced involvement of dorsal region of spinal cord in ATM. MEP is more frequently abnormal than SEP.
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  • 126
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    Journal of neurology 247 (2000), S. 252-258 
    ISSN: 1432-1459
    Keywords: Key words Cerebral venous ¶thrombosis ; Dural sinuses ; Magnetic resonance imaging ; Heparin ; Thrombolysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In contrast to arterial stroke, cerebral venous thrombosis (CVT) is an infrequent condition which presents with a wide spectrum of signs and with a highly variable mode of onset. The clinician must therefore consider it systematically in all brain syndromes and perform the appropriate neuroimaging investigations: computed tomography (CT) with computed tomography angiography and/or magnetic resonance imaging with magnetic resonance angiography and, if necessary intra-arterial angiography. Once the diagnosis is established, a wide investigation for should be carried out in search of the cause, and treatment started as soon as possible. Treatment is based on the combination of intravenous heparin (followed by oral anticoagulants for 3–6 months), symptomatic treatment (anticonvulsants, analgesics, treatment of increased intracranial pressure) and treatment of the cause. Local thrombolysis is indicated if there is deterioration due to thrombosis extension despite adequate anticoagulation. Diagnosis and treatment of CVT should be considered as an emergency because of the considerable potential for full recovery in this condition.
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  • 127
    ISSN: 1432-1459
    Keywords: Key words Multiple sclerosis ; Neuropsychological ; Cognitive ; Magnetic resonance imaging ; Lesion load
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Neuropsychological deficits and the relationship to brain pathology were examined in 13 primary progressive (PP) and 12 secondary progressive (SP) multiple sclerosis patients with a similar duration of the progressive phase and comparable physical disability. A battery of neuropsychological tests to assess attention, short-term and working memory was administered to the patients, and their performance was compared to that of 20 healthy controls matched for age and premorbid IQ. Total cerebral lesion load on T2-weighted magnetic resonance imaging was measured in the patients. Both PP and SP patients performed significantly worse than controls in most of the neuropsychological tests. There were only subtle differences between SP and PP on the working memory task although magnetic resonance imaging lesion load was significantly higher in SP than in PP patients. In this exploratory study only subtle differences in cognitive impairment were detected between SP and PP patients matched for physical disability and relevant illness features. The results also suggest that the severity of cognitive impairment cannot be fully explained by the extent of abnormalities detected on conventional T2-weighted magnetic resonance images, and that other pathological abnormalities such as in normal-appearing white matter are likely to be involved.
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  • 128
    ISSN: 1432-1459
    Keywords: Key words Leukoaraiosis ; Aged ; Atherosclerosis ; Magnetic resonance imaging ; Carotid artery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cerebral white matter lesions are frequently observed on magnetic resonance imaging of elderly, nondemented persons. There is evidence that white matter lesions are involved in the pathophysiology of cognitive decline and dementia. White matter lesions can be divided into those in the periventricular and those in the subcortical region. Pathological and epidemiological studies suggest that atherosclerosis is involved in the pathogenesis of these lesions. Our study reports on the association between atherosclerosis in the carotid arteries and white matter lesions in a population-based study among 1077 elderly subjects. We randomly sampled 1077 subjects aged between 60–90 years from two prospective population-based studies. All subjects underwent ultrasonography of the carotid artery. In addition, 1.5 T magnetic resonance imaging was performed; white matter lesions in the subcortical and periventricular regions were rated separately. With increasing number of plaques in the carotid artery the severity of periventricular white matter lesions increased (P trend = 0.03), but not the severity of subcortical white matter lesions (P trend = 0.19). In addition, an increase in intima media thickness was borderline significantly associated with an increased severity of periventricular white matter lesions (P trend = 0.09), but not of subcortical white matter lesions (P trend = 0.68). These findings suggest that partly dissimilar pathogenetic mechanisms are involved in the etiology of periventricular and subcortical white matter lesions.
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  • 129
    ISSN: 1432-1459
    Keywords: Key words Multiple sclerosis ; Fatigue ; Magnetic resonance imaging ; Motor evoked potentials
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Fatique is a common symptom of multiple sclerosis (MS) even in the early phases of the disease, when neurological disability is usually still not present. To investigate the pathophysiology of fatigue we compared neurophysiological (motor evoked potentials of the four limbs, MEPs) and brain magnetic resonance imaging (MRI) findings in two groups of nondisabled MS patients, those with (n=15) and those without (n=15) fatigue. Fatigue was assessed by an interview and scored by the Fatigue Severity Scale. The two groups were matched for sex, age, disease duration, Expanded Disability Status Scale score, pyramidal Functional System (FS) score, and depression score. MEPs were abnormal in five patients with fatigue and in one patient without fatigue. A significant association was found between the patient scores on the Fatigue Severity Scale, and the burden of MRI lesions (r=0.5; P〈0.005). Significantly higher parietal lobe (P〈0.05), internal capsule (P〈0.05), and periventricular trigone (P〈0.05) lesion loads were found in patients with fatigue than in those without. Our results agree with a central nervous system origin of fatigue in MS patients. This symptom might be a consequence either of a functional deafferentation of the cortex due to cortico-subcortical interconnection damage or of a demyelination in critical sites of the CNS, such as the cortico-spinal tract.
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  • 130
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    Keywords: Key words Small subcortical ¶infarction ; Large-vessel disease ; Magnetic resonance imaging ; Silent white-matter hyperintensity ; Lacunar infarction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Small subcortical infarctions resulting from large-vessel disease are often observed. It is important to distinguish these from pure lacunar infarction resulting from small-vessel disease because the investigations and examinations differ. We investigated the differences on brain magnetic resonance imaging (MRI) between small subcortical ¶“lacunar-like” infarcts resulting from large-vessel disease and pure lacunar infarcts. Thirteen subjects with small lacunar-like infarcts (size 〈 2 cm), resulting from large-vessel disease, ¶and 30 subjects with lacunar infarcts (〈 2 cm), without large-vessel disease were studied. We measured infarction size using a 1.5-T MRI device and evaluated silent subcortical hyperintensity lesions using the modified Scheltens’ score. Large-vessel lesion was confirmed by conventional angiography, duplex carotid scan, and magnetic resonance angiography. There was no difference in the mean age of the two groups. Cerebrovascular risk factors and atherosclerotic complications were also comparable for the two groups. Progressive stroke was more common ¶in the lacunar-like infarction group than in the lacunar infarction group ¶(P = 0.004). Scores for periventricular hyperintensity, white matter hyperintensity, basal ganglia hyperintensity, and total subcortical hyperintensity scores were significantly higher in the lacunar infarction group than in the lacunar-like infarction group. The difference in basal ganglia hyperintensity scores was remarkable (P = 0.001). The enlargement of the perivascular space was also significantly greater in the lacunar infarction group than in the lacunar-like infarction group. These findings seem to reflect differences in the pathogenesis of infarction between the two groups. Silent subcortical hyperintensity lesions and enlargement of perivascular space are useful for between distinguishing small lacunar-like infarct resulting from large-vessel disease and pure lacunar infarction. This may have significant implications for the management of patients with lacunar-sized infarctions. It suggests that the pathogenesis of lacunar-sized infarction is variable.
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  • 131
    ISSN: 1432-1459
    Keywords: Key words Sarcoidosis ; Spinal cord ; Magnetic resonance imaging ; Corticosteroid therapy ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Spinal cord sarcoidosis is a rare disorder whose natural history and therapeutic outcome are not fully known. We examined four patients with spinal cord sarcoidosis both clinically and radiologically, particularly in relation to corticosteroid treatment. The initial manifestation was cervical myelopathy in three and uveitis in one. All four patients progressed slowly until corticosteroid therapy was initiated. The cervial spine was involved in all patients. Magnetic resonance imaging (MRI) showed spinal cord swelling with T2-weighted high intensity and linear leptomeningeal and patchy or diffuse intramedullary enhancement with gadolinium diethylene triaminepentaacetic acid. With corticosteroid therapy, dramatic improvement was seen on MRI, including disappearance or marked reduction of swelling and enhancement. Plasma levels of angiotensin-converting enzyme (ACE) were also markedly improved. In contrast, the clinical symptoms were little improved in one patient, unchanged in two, and rather worsened in one patient. Recurrence was seen on MRI at the maintenance dose in all four patients, without any dramatic change in clinical manifestation. MRI findings and plasma ACE are well correlated with active leasion of the spinal cord sarcoidosis, providing a useful marker for recurrence, but do not parallel the clinical manifestations.
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  • 132
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    Skeletal radiology 29 (2000), S. 726-728 
    ISSN: 1432-2161
    Keywords: Keywords Developmental dysplasia ; Hip ; Membrane ; Interposition ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Intra-articular membranous interposition was detected by MRI in the hip joint with residual subluxation of a girl aged 5 years 10 months. This structure, which had low signal intensity on both T1- and T2-weighted images, separated the femoral head from the acetabulum. Histological examination revealed chondrometaplasia, which suggested that this interposition might be transformed to a surface cartilaginous tissue of the secondary acetabulum often observed in residual subluxation of the hip.
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  • 133
    ISSN: 1432-2161
    Keywords: Key words Rheumatoid arthritis ; Cervical spine ; Magnetic resonance imaging ; Dynamic imaging ; Flexion views
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Objective. To determine whether MR imaging in flexion adds value relative to imaging in the neutral position with respect to displaying involvement of the subarachnoid space, brainstem and spinal cord. Design and patients. T1-weighted MR images of the cervical spine in 42 rheumatoid arthritis patients with cervical spine involvement were obtained and analyzed prospectively. We assessed changes between images obtained in the neutral position and following active flexion, especially horizontal atlantoaxial and subaxial motion, presence or absence of brainstem compression, subarachnoid space involvement at the atlantoaxial and subaxial level and the cervicomedullary angle. Vertical atlantoaxial subluxation and the amount of pannus were correlated with motion and change in subarachnoid space. Results. The flexion images showed horizontal atlantoaxial motion in 21 patients and subaxial motion in one patient. The flexion view displayed brainstem compression in only one patient. Involvement of the subarachnoid space increased at the atlantoaxial level in eight (19%) patients (P=0.004) and at the level below C2 in five (12%) patients (P=0.03). There were no patients with a normal subarachnoid space in neutral position and compression in the flexed position. The cervicomedullary angle changed significantly with flexion. Vertical atlantoaxial subluxation and the amount of pannus did not show a significant correlation with motion or subarachnoid space involvement. Conclusion. MR imaging in the flexed position shows a statistically significant narrowing of the subarachnoid space at the atlantoaxial level and below C2. Cord compression is only observed on flexion views if the subarachnoid space in neutral position is already decreased. MR imaging in the flexed position might be useful, since subarachnoid space involvement may be an indicator for the development of neurologic dysfunction.
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  • 134
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    Skeletal radiology 29 (2000), S. 104-108 
    ISSN: 1432-2161
    Keywords: Key words Adult teratoma ; Dumb-bell type tumor ; Lumbar spine ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We report a case of a lumbar teratoma in a 50-year-old woman. The teratoma showed a dumb-bell-type expansion at the level of the left L3/4 foramen with massive erosion of the L3 vertebral body. MRI revealed inhomogeneous signal changes in the tumor, which were histologically compatible with a mixture of bone, muscle, fat, and cyst containing sebaceous material. Complete resection of the tumor and spinal arthrodesis with pedicle screw fixation was necessary to obtain stability of the affected spinal segment.
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  • 135
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    Child's nervous system 16 (2000), S. 138-142 
    ISSN: 1433-0350
    Keywords: Key words Craniopharyngioma ; Posterior fossa tumors ; Microsurgery ; Magnetic resonance imaging ; Computerized tomography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Between 1991 and 1998, 24 patients underwent surgery for a craniopharyngioma in our department. This group included two patients who had tumors with extensive growth along the midline, and along the posterior fossa in particular. In both cases suprasellar calcifications were typical features on magnetic resonance imaging (MRI) and computed tomography (CT). A 7-year-old boy presented with a 6-month history of headache, nausea, and progressive unilateral hearing loss. With a suboccipital approach it was possible to remove the main part of the tumor. In a 13-year-old boy headache and visual deterioration led to the diagnosis of a craniopharyngioma, which was removed with a pterional approach. For the neuroimaging work-up in such cases of atypically growing craniopharyngiomas MRI is the method of choice. Additional CT scanning is recommended, which provides valuable information about bony changes at the skull base due to space-occupying growth. CT substantiates the differential diagnosis if typical calcifications are seen.
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  • 136
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    Child's nervous system 16 (2000), S. 398-401 
    ISSN: 1433-0350
    Keywords: Keywords Primitive neuroectodermal tumor ; Diffuse leptomeningeal neoplasia ; Magnetic resonance imaging ; Pseudotumor cerebri ; Sinus thrombosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Primitive neuroectodermal tumors are easily detected by neuroradiologic imaging, as a rule. We report on two patients with early diffuse leptomeningeal primitive neuroectodermal tumors which escaped detection by contrast-enhanced magnetic resonance imaging.
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  • 137
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    Child's nervous system 16 (2000), S. 551-554 
    ISSN: 1433-0350
    Keywords: Keywords Acute myelitis of childhood ; Fibrocartilaginous embolism ; Magnetic resonance imaging ; Spinal cord infarction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Fibrocartilaginous embolus causing acute spinal cord infarction is a rare cause of acute-onset paraplegia or quadriplegia. Few cases of survivors have been reported in the neurosurgical literature, with most reports involving post-mortem or biopsy findings. There is little information on MRI findings in such patients. We present the youngest patient ever reported, and discuss the important differences between fibrocartilaginous embolus and acute myelitis of childhood. A 6-year-old girl with a history of back pain presented with sudden-onset nontraumatic paraplegia, with a clinical anterior spinal artery syndrome. Initial MRI scan revealed intervertebral disc disease at L1–2 and an incidental thoracic syrinx, but no cause for her acute-onset paraplegia was identified. Cerebrospinal fluid and other investigations were all negative. Sequential MRI scans revealed development of spinal cord expansion from T10 to the conus medullaris, with increased cord signal in the anterior aspect of the spinal cord. The intervertebral disc disease was unchanged. The imaging and clinical findings were caused by fibrocartilaginous embolus, which meant there was no need for spinal cord biopsy. The report describes the clinical and imaging criteria for diagnosis of fibrocartilaginous embolus, highlighting the case for avoiding an unnecessary biopsy. The clinical pattern in the paediatric group is discussed, with features differentiating it from acute myelitis of childhood.
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  • 138
    ISSN: 1433-0350
    Keywords: Keywords Cavernous angioma ; Cerebral angiography ; Dynamic scan ; Magnetic resonance imaging ; Sinus pericranii
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Objects: Sinus pericranii is only a symptom complex, and it can have a variety of etiologies. Therefore, it is important to differentiate these etiologies preoperatively by means of radiological examinations. A 5-year-old boy was admitted with a soft and fluctuant tumor in the right parietal region near the midline. The tumor appeared when the child was in a recumbent position, distending noticeably with the Valsalva maneuver and disappearing completely when the patient was in the sitting position. Methods: Magnetic resonance imaging showed the lesion with honeycomb-like heterogeneous iso- and low-intensity signals on the T1-weighted image and with heterogeneous high- and iso- intensity signal on the T2-weighted image. Dynamic study with an injection of gadolinium diethylene-triaminopentaacetic acid demonstrated and nodular peripheral enhancement at early phase and subsequent progressive enhancement towards the center of tumor. The internal carotid angiogram was normal. The external carotid angiogram, however, showed a tumor stain fed by the superficial temporal arteries. The stain was retained until the late phase and drained into the scalp veins and into the superior sagittal sinus. Following direct injection of contrast medium into the tumor there was prolonged retention of the medium in the tumor and leakage into scalp veins and the superior sagittal sinus. The mass under the periosteum was totally removed and proved to be a cavernous angioma. Conclusions: Scalp cavernous angioma is one of the etiologies of sinus pericranii and may be diagnosed preoperatively by cerebral angiography or magnetic resonance imaging. Serial dynamic magnetic resonance imaging will be particularly helpful for this diagnosis.
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  • 139
    ISSN: 1432-2102
    Keywords: Schlüsselwörter Diffusionsgewichtete Kernspintomographie ; Wirbelkörpermetastasen ; Diffusionskoeffizient ; Keywords Diffusion weighted imaging (DWI) ; Magnetic resonance imaging ; Vertebral metastases ; Diffusion coefficient ; ADC
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Aim of the study. The aim of the study was the evaluation of the diffusion coefficient (ADC) of vertebral metastasis and regular vertebral bodies with diffusion weighted MRI (DWI). DWI evaluates the tissue-specific molecular diffusion of protons. In tissues with high cell densities (neoplasm) a decreased ADC can be expected due to restricted diffusion according to an exaggerated amount of intra- and intercellular membranes (i. e. diffusion barriers). Methods. In 5 breast cancer patients the ADC of both known vertebral metastases and of adjacent regular vertebral bodies were measured with DWI (1.0 T; Phased-Array-Body-Coil; b: 880 and 440 s/mm2). Results. The ADC of regular vertebral bodies (1.3±0.23×10–,3s/mm2) was significantly (p≤0.0002) higher than in vertebral metastases (0.39±0.11×10–3s/mm2). Conclusions. These data demonstrate that the ADC can be reliably measured in vertebral bodies. The quantitative evaluation of the ADC in vertebral bodies seems to be an objective and comparable parameter for differentiating malign from benign vertebral tissue.
    Notes: Zusammenfassung Ziel. Ziel der Arbeit war die Messung des Diffusionskoeffizienten (ADC) mittels diffusionsgewichteter (DW) MRT in Wirbelkörpermetastasen und in MR-morphologisch unauffälligen Wirbelkörpern. Die DW-MRT misst den für ein Gewebe spezifischen ADC, welcher der Eigendiffusion von Wasserstoffmolekülen entspricht. In zellreichem Tumorgewebe mit zahlreichen intra- und interzellulären Membranen (d. h. Diffusionsbarrieren) ist ein niedriger, in zellarmen oder nekrotischem Gewebe, ein hoher ADC zu erwarten. Methode. Bei 5 Patientinnen mit Mammakarzinom wurde der ADC von Lendenwirbelkörpermetastasen sowie von angrenzenden, MR-morphologisch unauffälligen Wirbelkörpern ermittelt (1,0 T; Phased-Array-Body-Coil; b: 880 und 440 s/mm2). Ergebnisse. Der ADC in MR-morphologisch unauffälligen Wirbelkörpern (1,3±0,23×10–3s/mm2) war signifikant (p≤0,0002) höher als in Wirbelkörpermetastasen (0,39±0,11×10–3s/mm2). Schlussfolgerung. Anhand dieser Daten konnte gezeigt werden, dass der ADC von Wirbelkörpern verlässlich gemessen werden kann, und dass durch die quantitative Bestimmung des ADC ein objektiv vergleichbarer Parameter zur Verfügung steht, der zur Differenzierung von malignem und benignem Gewebe gut geeignet erscheint.
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  • 140
    ISSN: 1432-2102
    Keywords: Schlüsselwörter Diffusion ; Magnetresonanztomographie ; Encephalitis disseminata ; Keywords Diffusion ; Magnetic resonance imaging ; Multiple sclerosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Magnetic resonance (MR) imaging is one of the best methods in diagnosis of multiple sclerosis, particularly in disclosure of active demyelinating lesions. Aim of this study was to compare diffusion weighted imaging and contrast enhancement in the detection of active lesions. A MR study with a contrast enhanced T1-weighted pulse sequence with magnetization transfer presaturation and a diffusion weighted echoplanar pulse sequence (b=1000 s/mm2) was performed in 17 patients (11 women, 6 men) with multiple sclerosis. 29 of 239 lesions showed an increased signal intensity in diffusion weighted imaging, 24 lesions a contrast enhancement, but only 16 lesions were visible in both pulse sequences. In patients with short clinical symptomatology significant more lesions could be detected with diffusion-weighted pulse sequence in comparison to patients with long standing symptomatology showing more lesions with contrast enhancement. Hence it is likely, that both pulse sequences detect different histopathologic changes. The early detection of demyelinating lesions in diffusion weighted imaging is attributed to the extracellular edema, however the contrast enhancement is caused by a blood brain barrier abnormality. It can be expected that diffusion weighted imaging will have a high impact on imaging of multiple sclerosis not only in therapeutic trials, but also in clinical routine.
    Notes: Zusammenfassung Die Magnetresonanztomograpie ist eine der wichtigsten Untersuchungsmethoden in der Diagnostik der Encephalitis disseminata, insbesondere im Nachweis aktiver Entmarkungsherde. Ziel der Untersuchung war es, diffusionsgewichtete und kontrastverstärkte Untersuchungen bezüglich der Erkennung aktiver Läsionen zu vergleichen. Bei 17 Patienten (11 Frauen, 6 Männer) mit bekannter Encephalitis disseminata wurden sowohl eine kontrastverstärkte T1-gewichtete Sequenz mit Magnetization-Transfer-Sättigung als auch eine diffusionsgewichtete Echoplanar-Sequenz (b=1000 s/mm2) durchgeführt. 29 der 239 Läsionen zeigten eine Signalsteigerung in der diffusionsgewichteten Sequenz, 24 eine Kontrastmittelaufnahme, jedoch waren nur 16 Läsionen in beiden Techniken nachweisbar. Bei Patienten mit kurzzeitig bestehender Symptomatik zeigten sich signifikant mehr Entmarkungsherde mit Signalsteigerung in der Diffusionswichtung im Vergleich zu Patienten mit länger bestehender neurologischer Symptomatik, die mehr kontrastmittelaffine Läsionen aufwiesen. Dies lässt darauf schließen, dass mit beiden Verfahren unterschiedliche histopathologische Veränderungen beobachtet werden. Das sehr frühe Auftreten der Diffusionsänderung in den Entmarkungsherden wird auf das Ödem zurückgeführt, während die Kontrastmittelaufnahme durch eine Blut-Hirnschranken-Störung verursacht wird. Es ist zu erwarten, dass die diffusionsgewichtete Magnetresonanztomographie einen hohen Stellenwert in der Bildgebung der Encephalitis disseminata nicht nur in Therapiestudien, sondern auch in der klinischen Routinediagnostik erlangen wird.
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  • 141
    ISSN: 1433-7347
    Keywords: Key words Osteonecrosis ; Bone marrow edema ; Knee ; High tibial osteotomy ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Sports Science
    Notes: Abstract Symptoms in patients suffering from spontaneous osteonecrosis of the knee (SONK) may be reduced by high tibial osteotomy (HTO). However, the fate of the necrotic lesion is unknown and needs further investigation. We conducted a prospective study to evaluate magnetic resonance imaging (MRI) changes after operative and nonoperative treatment. Ten consecutive patients suffering from SONK of the medial compartment were given two treatment options: either HTO (n = 6) or conservative treatment with partial weight bearing for 3 months (n = 4). We measured the greatest extent of well-defined subchondral low signal intensity abnormality, considered to represent necrosis, and the surrounding area of intermediate signal intensity, considered to represent perifocal bone marrow edema, on T1-weighted coronal MRI images before and after treatment. The MRI follow-up period was 17.5 months (range 12–¶27) in the HTO group and 14.5 months (range 8–25) in the nonoperative group. At follow-up the MRI evaluation revealed a decrease in the low signal intense areas (necrosis) in five of the six patients in the HTO group. Only one of the four nonoperative patients showed a decrease in the low signal intense area. The intermediate intense areas (edema) decreased in all patients in the HTO group and in three of four in the nonoperative group. The mean decrease in the area of perifocal edema was significantly greater in the HTO group than in the nonoperative group (P = 0.019). No statistically significant difference was found for the area of necrosis between the two groups (P = 0.171). A clinical improvement was observed in all patients of the HTO group but in only two of the four patients of the nonoperative group. We conclude that the decrease in perifocal bone marrow edema seems to be associated with improved patient comfort. The MRI appearance of the necrotic lesion does not alter with either treatment mode.
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  • 142
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    Child's nervous system 16 (2000), S. 829-831 
    ISSN: 1433-0350
    Keywords: Keywords Intraoperative imaging ; Magnetic resonance imaging ; Anatomical and functional neuronavigation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The Erlangen-concept of image-guided-surgery is based on the installation of an open magnetic resonance (MR) scanner (Magnetom Open, 0.2 T, Siemens AG) in a twin operating room in combination with two neuronavigation systems (Stealth NeuroStation, Sofamor Danek, MKM Zeiss). Since March 1996 this method has been used for a total of 402 patients, among them 44 children. In 214 patients, mainly with gliomas or pituitary adenomas or who needed surgery for epilepsy, we performed intraoperative MR imaging to monitor the extent of resection, allowing a second look for possible tumor remnants and also compensating for brain shift by an intraoperative update of neuronavigation. Functional neuronavigation, i.e. the combination of anatomical neuronavigation with functional imaging [e.g. magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI)] was used in patients with lesions in brain areas such as the motor and speech areas. For MEG we used a MAGNES II biomagnetometer (Biomagnetic Technologies, San Diego, Calif.) and for fMRI a 1.5 T Siemens Symphony MR scanner. So far we have treated 89 patients with functional neuronavigation. Our preliminary experience indicates that intraoperative MR imaging, especially in combination with functional neuronavigation, allows more radical resections with lower morbidity.
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  • 143
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    European archives of psychiatry and clinical neuroscience 250 (2000), S. 76-78 
    ISSN: 1433-8491
    Keywords: Key words Septum pellucidum ; Developmental ¶disorder ; Schizophrenia ; Magnetic resonance imaging ; Cavum veli interpositi ; Cavum septi pellucidi
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The case of monocygotic twins discordant for a psychotic disorder is presented. An anomaly of the septum pellucidum, a so-called cavum veli interpositi was found in the psychotic twin while his brother showed no such anomaly. Previous studies have shown a higher prevalence of septum pellucidum anomalies in schizophrenic patients. Abnormalities of the septum pellucidum may be associated with disturbed neuronal development in distinct limbic brain areas which cannot yet be visualized yet by brain imaging techniques. The finding of the cavum veli interpositi in the psychotic twin could be incidental; however, it may indicate a dysgenic process in early brain development and, thus, play a significant role in the etiology of psychosis.
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  • 144
    ISSN: 1432-2013
    Keywords: Key words vitamin C (L-ascorbic acid) ; apoptosis ; human articular chondrocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Chondrocytes present in articular cartilage survive as a resident cell population throughout the lifespan of the individual organism. However, articular chondrocytes as other cells also undergo apoptosis and there is an ever increasing list of diverse stimuli that can induce this phenomenon in vitro. Our main interest was to investigate potential cytotoxic effects of vitamin C (L-ascorbic acid) on human articular chondrocytes. The present study suggests that vitamin C can induce apoptosis in a cell culture of chondrocytes after 18 h of cultivation. Apoptosis-inducing activity of L-ascorbic acid is dose dependent and significantly affected by the presence of serum. The increased number of vitamin C induced apoptotic cells was associated with DNA fragmentation and morphological changes of the cells.
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  • 145
    ISSN: 1569-8041
    Keywords: 5-fluorouracil ; antifolates ; apoptosis ; DNA repair ; p53 ; thymidylate synthase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Thymidylate synthase (TS) is an essential enzyme for the de novo synthesis of thymidylate and subsequently DNA synthesis. TS has been usedas a target for cancer chemotherapy in the development of fluoropyrimidinessuch as 5-fluorouracil (5-FU) and 5-fluorodeoxyuridine and of novelfolate-based TS inhibitors such as ZD1694 (Tomudex, Raltitrexed), ZD9331,LY231514 (ALIMTA, Pemetrexed), AG337 (Thymitaq, Nolatrexed) and AG331.Although TS has been considered as a target for chemotherapy, the precisemechanism by which TS inhibition leads to cell death is still not completelyresolved. TS inhibition results in depletion of dTTP, an essential precursorfor DNA, and an increase in dUTP. This results in the so-called thymine-lessdeath due to misincorporation of dUTP into DNA; its excision, catalysed byuracil-DNA glycosylase, results in DNA damage. Both this imbalance indTTP/dUTP and DNA damage can result in induction of downstream events, leadingto apoptosis. On the other hand a specific interaction exists betweenoncogenes and TS, by binding of TS protein to the p53and c-mycRNA, while wt p53can also inhibit TS promotor activity. TSinhibition by either 5-FU or antifolates can also result in a depression ofTS protein mediated inhibition of TS mRNA translation leading to induction ofmore TS protein synthesis, and p53protein may further deregulatethis process. These complex indirect and direct interactions between oncogenesand TS may have as yet unclear clinical implications, since most data arebased on in vitroor in vivo studies and some results arecontradictive. In some preliminary clinical studies evidence was postulatedfor a combined prognostic role for TS and p53.This knowledge shouldbe used to design clinical studies with the aim to deliver effective treatmentto potentially sensitive patients both in the adjuvant setting and in advancedstage disease.
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  • 146
    ISSN: 1573-4919
    Keywords: endosulfan ; cytotoxicity ; mitochondria ; apoptosis ; Jurkat cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Several organochlorinated pesticides including DDT, PCBs and dieldrin have been reported to cause immune suppression and increase susceptibility to infection in animals. Often this manifestation is accompanied by atrophy of major lymphoid organs. It has been suggested that increased apoptotic cell death leading to altered T-B cell ratios, and loss of regulatory cells in critical numbers leads to perturbations in immune function. The major objective of our study was to define the mechanism by which endosulfan, an organochlorinated pesticide, induces human T-cell death using Jurkat, a human T-cell leukemic cell line, as an in vitro model. We exposed Jurkat cells to varying concentrations of endosulfan for 0-48 h and analyzed biochemical and molecular features characteristic of T-cell apoptosis. Endosulfan lowered cell viability and inhibited cell growth in a dose- and time-dependent manner. DAPI staining was used to enumerate apoptotic cells and we observed that endosulfan at 10-200 μM induced a significant percentage of cells to undergo apoptotic cell death. At 48 h, more than 90% cells were apoptotic with 50 μM of endosulfan. We confirmed these observations using both DNA fragmentation and annexin-V binding assays. It is now widely being accepted that mitochondria undergo major changes early during the apoptotic process. We examined mitochondrial transmembrane potential (ΔΨm) in endosulfan treated cells to understand the role of the mitochondria in T-cell apoptosis. Within 30 min of chemical exposure, a significant percentage of cells exhibited a decreased incorporation of DiOC6(3), a cationic lipophilic dye into mitochondria indicating the disruption of ΔΨm. This drop in ΔΨm was both dose- and time-dependent and correlated well with other parameters of apoptosis. We also examined whether this occurred by the down regulation of bcl-2 protein expression that is likely to increase the susceptibility of Jurkat cells to endosulfan toxicity. Paradoxically, the intracellular expression of bcl-2 protein was elevated in a dose dependent manner suggesting endosulfan-induced apoptosis occurred by a non-bcl-2 pathway. Based on these data, as well as those reported elsewhere, we propose the following sequence of events to account for T-cell apoptosis induced by endosulfan: uncoupling of oxidative phosphorylation → excess ROS production → GSH depletion → oxidative stress → disruption of ΔΨm → release of cytochrome C and other apoptosis related proteins to cytosol → apoptosis. This study reports for the first time that endosulfan can induce apoptosis in a human T-cell leukemic cell line which may have direct relevance to loss of T cells and thymocytes in vivo. Furthermore, our data strongly support a role of mitochondrial dysfunction and oxidative stress in endosulfan toxicity.
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  • 147
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    Molecular and cellular biochemistry 204 (2000), S. 83-88 
    ISSN: 1573-4919
    Keywords: FHIT ; cell cycle ; ecdysone ; tumor suppressor ; apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The mechanism of tumor suppressor action of the fragile histidine triad (FHIT) gene is unknown. Disruption of cell cycle regulation leads to the tumor formation and many tumor suppressor genes suppress tumorigenesis through their effect on cell cycle regulation. We examined the expression of FHIT during the cell cycle, and determined whether overexpression of FHIT affects cell cycle kinetics and apoptosis. The FHIT cDNA was cloned into the ecdysone-inducible expression vector in both the sense and antisense orientations. Overexpression of the sense or antisense construct did not affect cell proliferation, cell cycle distribution or apoptosis in human 293T cells. Analysis of the FHIT expression in 293T cells collected at various cell cycle phases showed that the expression of FHIT is not under cell cycle regulation. These results indicate that the tumor suppressor activity of the FHIT gene may be independent of an effect on the cell cycle and apoptosis mechanisms.
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  • 148
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    Molecular and cellular biochemistry 212 (2000), S. 19-28 
    ISSN: 1573-4919
    Keywords: melanoma ; transcription factors ; CREB ; invasion ; apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The purpose of this study was to determine the role of CREB and its associated proteins in melanoma progression. We used MeWo human melanoma cells transfected with a dominant negative construct of CREB, KCREB. KCREB has a mutation in its DNA-binding domain and can not bind the CRE element. Expression of KCREB yields proper heterodimerization with CREB and its associated proteins, but the proteins associated with KCREB do not confer the same degree of transcriptional activity as they would in the case of wild-type CREB. Here, we demonstrate that expression of KCREB in MeWo melanoma cells leads to a decrease in their tumorigenicity and metastatic potential in nude mice. We identified two mechanisms that explain at least partially this effect of KCREB. The first, is one in which CREB and its associated proteins play an essential role in invasion. We showed that the invasive properties of KCREB-transfected MeWo cells were reduced due to the downregulation of the CRE-dependent expression of the type IV collagenase MMP-2 and the adhesion molecule MCAM/MUC18. In the second mechanism, CREB and its associated proteins act as survival factors for human melanoma cells. Here we demonstrated that expression of KCREB in MeWo cells rendered them susceptible to apoptosis induced by thapsigargin, which in turn increased the intracellular level of Ca2+. Thapsigargin induced CREB and ATF-1 phosphorylation and activated CRE-dependent transcription in MeWo cells. Collectively, our data demonstrate that CREB and its associated proteins play an important role in tumor growth and metastasis of human melanoma.
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  • 149
    ISSN: 1573-4919
    Keywords: T-type Ca2+ channel ; polyglutamine-expanded androgen receptor ; CAG trinucleotide repeats ; spinobulbar muscular atrophy ; apoptosis ; motorneuron ; cell lines ; neuroblastoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract We have analyzed Ca2+ currents in two neuroblastoma-motor neuron hybrid cell lines that expressed normal or glutamine-expanded human androgen receptors (polyGln-expanded AR) either transiently or stably. The cell lines express a unique, low-threshold, transient type of Ca2+ current that is not affected by L-type Ca2+ channel blocker (PN 200-110), N-type Ca2+ channel blocker (ω-conotoxin GVIA) or P-type Ca2+ channel blocker (Agatoxin IVA) but is blocked by either Cd2+ or Ni2+. This pharmacological profile most closely resembles that of T-type Ca2+ channels [1-3]. Exposure to androgen had no effect on control cell lines or cells transfected with normal AR but significantly changed the steady-state activation in cells transfected with expanded AR. The observed negative shift in steady-state activation results in a large increase in the T-type Ca2+ channel window current. We suggest that Ca2+ overload due to abnormal voltage-dependence of transient Ca2+ channel activation may contribute to motor neuron toxicity in spinobulbar muscular atrophy (SBMA). This hypothesis is supported by the additional finding that, at concentrations that selectively block T-type Ca2+ channel currents, Ni2+ significantly reduced cell death in cell lines transfected with polyGln-expanded AR.
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  • 150
    ISSN: 1573-4919
    Keywords: retinoic acid ; RARβ ; protein kinase A ; apoptosis ; caspase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Both cAMP and retinoids play a role in cell differentiation and the control of cell growth. A site-selective cAMP analog, 8-Cl-cAMP and retinoic acid synergistically inhibit growth and induce apoptosis in certain cancer cells. In advanced or recurrent malignant diseases, retinoic acid (RA) is not effective even at doses that are toxic to the host. The objective of our present study was to examine the mechanism(s) of synergistic effects of retinoic acid (9-cis, 13-cis or all-trans RA) and 8-Cl-cAMP on apoptosis in human ovarian cancer NIH: OVCAR-3 and OVCAR-8 cells. RA induced growth inhibition and apoptosis in OVCAR-3 and OVCAR-8 cells. 8-Cl-cAMP acted synergistically with RA in inducing and activating retinoic acid receptor β (RARβ) which correlates with growth inhibition and apoptosis in both cell types. In addition, induction of apoptosis by RA plus 8-Cl-cAMP requires caspase-3 activation followed by cleavage of anti-poly(ADP-ribose) polymerase. Furthermore, mutations in CRE-related motif within the RARβ promoter resulted in loss of both transcriptional activation of RARβ and synergy between RA and 8-Cl-cAMP. RARβ expression appears to be associated with induction of apoptosis. Introduction of the RARβ gene into OVCAR-3 cells resulted in gain of RA sensitivity. Loss of RARβ expression, therefore, may contribute to the tumorigenicity of human ovarian cancer cells. Thus, combined treatment with RA and 8-Cl-cAMP may provide an effective means for inducing RARβ expression leading to apoptosis in ovarian cancer cells.
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  • 151
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    Molecular and cellular biochemistry 203 (2000), S. 59-71 
    ISSN: 1573-4919
    Keywords: PTEN tumor suppressor ; cyclin-dependent kinase inhibitors ; apoptosis ; chemosensitivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The recently discovered tumor suppressor gene PTEN has been found mutated in many types of advanced tumors. When introduced into tumor cells that lack the wild-type allele of the gene, PTEN was able to suppress the growth of these cells. Here, we have analyzed how PTEN might alter cell cycle-regulatory controls to achieve this growth-inhibitory effect. We found that overexpression of PTEN stimulates the synthesis of three inhibitors of cyclin-dependent kinases, p21WAF1, p27KIP1, and p57,KIP2. This effect is very specific, as the expression of other components of the cell cycle engine, various cyclins and cyclin-dependent kinases, is not affected. For p21WAF1 we show that this induction is due to the p53-independent transcriptional activation of its promoter. In addition, increased expression of PTEN rendered the cells more sensitive to apoptotic cell death. Therefore, our data suggest a two-fold mechanism of growth inhibition by PTEN: one that acts via the increased expression of CKIs such as p21WAF1, and another that augments the cellular propensity for apoptotic cell death.
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  • 152
    ISSN: 1573-4919
    Keywords: tumour necrosis factor ; receptors ; subtypes ; calcium ; apoptosis ; cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Tumour necrosis factor-α (TNF) receptors mediate a variety of effects dependent on cell type. A role for Ca2+ in TNF-induced death remains uncertain. Here we investigated restricting intracellular/extracellular Ca2+ in HeLa epithelial carcinoma cells expressing low and high levels of p75TNFR receptor subtype and KYM-1 rhabdomyosarcoma cells, models of rapid TNF-induced apoptosis. Ca2+-chelators EGTA and BAPTA-AM as well as microsomal Ca2+-ATPase inhibitor thapsigargin, did not alter TNF-induced death. TNF was also unable to alter resting [Ca2+]i levels which remained 〈 200 nM even during times when these cells were undergoing apoptotic cell death. These findings indicate no role for modulated Ca2+ concentrations in TNF-induced apoptotic cell death.
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  • 153
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    Journal of clinical immunology 20 (2000), S. 229-239 
    ISSN: 1573-2592
    Keywords: Aging ; apoptosis ; TNF receptor ; Fas ; Fas ligand ; mitochondria
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The cellular and molecular basis of immune senescence is unclear. A number of mechanisms have been proposed. In this issue of the Journal of Clinical Immunology, some of the mechanisms for various immunologic abnormalities in aging are presented. In this article, various molecular steps of both death receptor and mitochondrial pathways of apoptosis in general are reviewed. In particular, the role of apoptosis in T-cell immune senescence is discussed.
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  • 154
    ISSN: 1573-4919
    Keywords: etoposide ; Bcl-XL ; Bax ; apoptosis ; K562 cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Etoposide is a potent anticancer agent that is used to treat various tumors. We have investigated the dose-dependent effect of etoposide on apoptosis using chronic myeloid leukemia K562 cells treated with low (5 μM) or high (100 μM) concentrations of the drug. At a low concentration, etoposide induced little apoptosis at 24 h, while about 20% of the cells showed apoptosis morphologically at a high concentration. Processing of caspase-3 was slightly detected from 12 h and became obvious at 24 h with 100 μM etoposide. Caspase-3-like protease activity was detected at 24 h with a high concentration. Moreover, these changes were accompanied by cleavage of poly ADP ribose polymerase (PARP). Changes of the mRNA levels of most apoptosis-regulating genes were not prominent at both concentrations, except for the rapid induction of c-IAP-2/HIAP-1 and the down-regulation of Bcl-XL by 100 μM etoposide. The downregulation of Bcl-XL protein occurred from 6 h, while Bax protein conversely showed a slight increase from 6 h. Taken together, the present findings show that the dose-dependent apoptotic effect of etoposide is based on a change in the balance between Bcl-XL and Bax, which precedes the activation of caspase-3.
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  • 155
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    Molecular and cellular biochemistry 207 (2000), S. 19-27 
    ISSN: 1573-4919
    Keywords: PKC ; apoptosis ; bile acid ; hepatocyte
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The effect of GCDC-induced apoptosis on PKC activity and PKC's role in GCDC-induced hepatocyte apoptosis is unclear. The specific aims of this study were to determine if GCDC-induced apoptosis changed intracellular PKC activity and if modulation of PKC activity affected GCDC-induced hepatocyte apoptosis. Apoptosis was induced in isolated hepatocytes using GCDC. PKC activity was measured and specific PKC and calpain inhibitors were used to study the effects of PKC and calpain modulation on GCDC-induced apoptosis. After 4 h exposure, 50 μM GCDC induced apoptosis in 42% of hepatocytes. Intracellular PKC activity decreased to 44% of controls 2 h after exposure of hepatocytes to GCDC (p 〈 0.001). Pre-incubation of hepatocytes with the calpain protease inhibitor restored PKC activity in GCDC exposed hepatocytes to 91± 5% of control cells. Pre-incubation of hepatocytes with a calpain inhibitor decreased GCDC-induced apoptosis as did pre-incubation with the PKC activating phorbol ester, PMA. The combination of calpain inhibition and PMA further reduced GCDC-induced apoptosis but caused low level hepatic apoptosis. Inhibition of PKC with chelerythrine also substantially reduced GCDC-induced hepatocyte apoptosis. GCDC-induced apoptosis is associated with decreases in total cellular PKC activity, which appear to be dependent on intracellular calpain-like protease activity. The combination of protease inhibition and phorbol ester pretreatment preserved total cellular PKC activity and decreased GCDC-induced apoptosis but induced low level apoptosis in the absence of GCDC exposure. PKC inhibition also decreased GCDC-induced hepatocyte apoptosis highlighting the complex interactions of PKC and proteases during GCDC-induced apoptosis.
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  • 156
    ISSN: 1573-4919
    Keywords: phosphatidylserine ; base exchange ; apoptosis ; thymocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The exposure of phosphatidylserine toward the external surface of the membrane is a well-established event of programmed cell death. The possibility that an apoptotic stimulus influences the metabolism of this phospholipid could be relevant not only in relation to the previously mentioned event but also in relation to the capability of membrane phosphatidylserine to influence PKC activity. The present investigation demonstrates that treatment of mouse thymocytes with the apoptotic stimulus dexamethasone, enhances the incorporation of [3H]serine into phosphatidylserine. Cell treatment with dexamethasone also enhanced the activity of serine base exchange enzyme, assayed in thymocyte lysate. Both the effects were observed at periods of treatment preceding DNA fragmentation. The addition of unlabelled ethanolamine, together with [3H]serine to the medium containing dexamethasone-treated thymocytes lowered the radioactivity into phosphatidylserine. Serine base exchange enzyme activity was influenced by the procedure used to prepare thymocyte lysate and was lowered by the addition of fluoroaluminate, that is widely used as a G-protein activator. The increase of serine base exchange enzyme activity induced by dexamethasone treatment was observed independently by the procedure used to prepare cell lysate and by the presence or absence of fluoroaluminate.
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  • 157
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    Molecular and cellular biochemistry 212 (2000), S. 35-43 
    ISSN: 1573-4919
    Keywords: cAMP ; CRE ; Cox-2 ; NO ; apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Previous studies revealed that expression and activation of cyclooxygenase-2 (Cox-2) conveyed a protective principle in murine macrophages, thus attenuating pro-apoptotic actions of chemotherapeutic agents or programmed cell death as a result of massive nitric oxide (NO) generation. Expression of Cox-2 was achieved by treatment of cells with lipopolysaccharide/interferon-γ or nontoxic doses of NO releasing agents. We reasoned E-type prostanoid formation, and in turn an intracellular cAMP increase as the underlying protective mechanism. To prove our hypothesis, we analyzed the effects of lipophilic cAMP-analogs on NO, cisplatin, or etoposide induced apoptosis in RAW 264.7 macrophages. Selected apoptotic parameters comprised DNA fragmentation (diphenylamine assay), annexin V staining of phosphatidylserine, caspase activity (quantitated by the cleavage of a fluorogenic caspase-3-like substrate Ac-DEVD-AMC), and mitochondrial membrane depolarisation (ΔΨ). Western blots detected accumulation of the tumor suppressor protein p53, relocation of cytochrome c to the cytosol, and expression of the anti-apoptotic protein Bcl-xL. Prestimulation with lipophilic cAMP-analogs attenuated apoptosis with the notion that cell death parameters were basically absent. To verify gene induction by cAMP in association with protection we established activation of cAMP response element binding protein (CREB) by gel-shift analysis and moreover, treated macrophages with oligonucleotides containing a cAMP-responsive element (CRE) in order to scavenge CREB. Decoy oligonucleotides, but not control oligonucleotides, attenuated cAMP-evoked protection and reestablished pro-apoptotic parameters. We conclude that gene induction by cAMP protects macrophages towards apoptosis that occurs as a result of excessive NO formation or addition of chemotherapeutica. Attenuating programmed cell death by the cAMP-signaling system may be found in association with Cox-2 expression and tumor formation.
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  • 158
    ISSN: 1573-4978
    Keywords: apoptosis ; CD95 ; human hepatoma cell ; hydrogen peroxide ; p53
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Reactive oxygen species (ROS) play an important role in cell death induced by many different stimuli. Direct exposure of human hepatoma cell line SMMC-7221 to hydrogen peroxide (H2O2) can induce apoptosis characterized by morphological evidence and fragmentation of DNA assayed by terminal deoxynucleotidyl transferase assay (TUNEL assay). Analysis of flow cytometry indicated that H2O2 can decrease the level of CD95(APO-1/Fas), and it is confirmed that H2O2 can also activate the differential expression of some specific gene such as p53 by means of RT-PCR technique. The results indicated that CD95 signal transduction system may be involved in the H2O2-induced apoptosis, and can regulate some specific genes associated with apoptosis in transcription and translation levels such as p53.
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  • 159
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    Molecular biology 34 (2000), S. 875-887 
    ISSN: 1608-3245
    Keywords: antisense oligonucleotides ; oncogenesis ; therapy of cancer ; apoptosis ; bcl family
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Members of the bcl-2 family genes are thought to be central regulators of apoptosis. Overexpression of antiapoptotic proteins, such as Bcl-2 and Bcl-xL, contributes not only to the development of cancer but also to its resistance against a wide variety of anticancer agents. Thus, downregulation of Bcl-2 and Bcl-xL can potentially be used to improve therapeutic approaches to advanced cancer. The use of antisense biotechnology to downregulate antiapoptotic bcl family members in diverse cancers in vitro and in vivo is reviewed. The effects and potential limitations of antisense strategies are also discussed in the context of a critical view of recent research in the field.
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  • 160
    ISSN: 1618-2545
    Keywords: apoptosis ; caspase-3 ; E2F factor ; Lentinula edodes ; mycelial culture broth
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Extracts fromshiitake (Lentinula edodes) mycelial culture broth, by an organic solvent ethyl acetate, inhibited the proliferation of cultured cells. At lower concentrations (1.25–15 μg/ml), this inhibition, measured by the MTT assay, was dose- and cell line-dependent. Inhibition of tumor cells, such as Caski, SiHa, HeLa, HP-1 and A375, byL. edodes-436 extracts was stronger than inhibition of normal cells (3T3). At 20 μg/ml, the extracts induced changes in cell shape, DNA-fragmentation and the activation of caspase-3. The extracts also inhibited the binding of E2F protein to its promoter. The results suggest that extracts ofL. edodes culture broth contain substances that have the ability to induce apoptosis in the cultured cells.
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  • 161
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    Herz 25 (2000), S. 384-391 
    ISSN: 1615-6692
    Keywords: Key Words Cardiomyopathy ; Magnetic resonance imaging ; Schlüsselwörter Kardiomyopathie ; Magnetresonanztomographie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die kardiale Magnetresonanztomographie (MRT) bietet als nichtinvasives Verfahren die Möglichkeit, innerhalb einer Untersuchung die für die verschiedenen Formen der Kardiomyopathien charakteristischen funktionellen und morphologischen Veränderungen darzustellen. In dieser Übersicht werden die Einsatzmöglichkeiten der MRT bei den verschiedenen Formen dieser Erkrankung diskutiert. Die geringe Variabilität der MRT-Messungen gestattet ge-naue Verlaufskontrollen im klinischen Alltag, eröffnet aber auch die Möglichkeit, Therapiestudien mit einer geringeren Anzahl von einzuschließenden Patienten zu sicheren Ergebnissen zu führen. Damit erweitert sich das Spektrum der Indikationen über die Präzisierung unklarer Befunde hinaus auf die Verlaufsbeobachtung während einer pharmakologischen Intervention und auf alle wissenschaftlichen Fragestellungen. Der Vorzug der MRT, nichtinvasiv Gewebe charakterisieren zu können, verdeutlicht das Potential dieser Technik bei sekundären Kardiomyopathien sowie bei entzündlichen und infiltrativen Formen myokardialer Erkrankungen.
    Notes: Abstract Cardiac magnetic resonance imaging (MRI) is a noninvasive tool which is able to diagnose and differentiate cardiomyopathies in a single study. The assessment of essential information such as alterations of myocardial and ventricular geometry and function is possible with a high degree of accuracy and reproducibility, based on a small inter- and intraobserver variability. Thus, very small morphological and functional changes in different types of cardiomyopathy are detectable, thereby enabling the cardiologist to increase the safety of therapeutic decisions. Furthermore, MRI bears the potential to characterize tissue transformation in the different types of myocardial affections including ischemic, toxic, infiltrative or inflammatory forms.
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  • 162
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    Heart and vessels 15 (2000), S. 44-45 
    ISSN: 1615-2573
    Keywords: Key words Pericardial hydatid cyst ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 163
    ISSN: 1615-2573
    Keywords: Key words Three-dimensional echocardiography ; Magnetic resonance imaging ; Left ventricular volume ; Stereology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The objective of this study was to investigate the degree of bias with coaxial three-dimensional echocardiography in an experimental animal setup and to establish the minimum number of sections needed for estimation of left ventricular (LV) volume. Epicardial coaxial echocardiography and magnetic resonance imaging (MRI) was used to measure LV volume in 14 pigs, with chronic remodeled left ventricles induced by repeated intracoronary microembolizations. In addition, six animals underwent serial MRI at baseline, immediately after intracoronary microembolization, and after 119–165 days (mean 129 days). Coaxial echocardiography was performed by rotational acquisition of long-axis sections starting from an arbitrary angle. Planimetered MRI contours of LV endocardial borders were analyzed to investigate the relationship between the number of coaxial sections, and the precision of volume estimates. The mean ± 2SD of the differences between coaxial epicardial echocardiography with six sections and MRI were −2.5 ± 16.4 ml, 0.8 ± 13. 1 ml, and 2% ± 14% for end-diastolic volume (EDV), end-systolic volume (ESV), and ejection fraction (EF), respectively. Numerical analysis conducted on MRI contours of LV endocardial borders showed that with six coaxial sections the average coeffi-cient of error was 〈1% for the EDV and ESV. Three-dimensional echocardiography with six coaxial sections provides unbiased LV volume estimation with minimal geometric error.
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  • 164
    ISSN: 1439-6327
    Keywords: Key words Human ; Muscle function ; Physiological cross-sectional area ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The purpose of the present study was to investigate the effect of recruitment on the relationship between peak torque and physiological cross-sectional area (PCSA) in human muscle. A group of 11 healthy men participated in this study. Isokinetic knee extension torques at seven (0, 30, 60, 120, 180, 240, and 300° · s−1) velocities were determined. Magnetic resonance imaging (MRI) was performed to calculate PCSA of right quadriceps femoris (QF) muscle. Exercise-induced contrast shifts in spin-spin relaxation time (T2)-weighted MRI were taken at rest and immediately after repetitive knee-extension exercise and T2 of QF were calculated. The MRI pixels with T2 values more than 1 SD greater than the means at rest were considered to represent QF muscle that had contracted. The area of activated PCSA within the total in QF was expressed as percentage activated PCSA and used as an index of muscle recruitment. The PCSA correlated with peak torque at 0° · s−1 (r=0.615, P 〈 0.05); in contrast, activated PCSA correlated with peak torque at 120° · s−1 (r=0.603, P 〈 0.05) and 180° · s−1 (r=0.606, P 〈 0.05). Additionally, there was a significant difference in correlation coefficients between the activated PCSA-peak torque relationship and the PCSA-torque relationship (P 〈 0.05). These results suggested that muscle recruitment affects the PCSA-torque relationship.
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  • 165
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    European journal of applied physiology 82 (2000), S. 391-396 
    ISSN: 1439-6327
    Keywords: Key words B-mode ultrasound ; Bioelectrical impedance ; Data acquisition system ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study aimed to investigate the validity of bioelectrical impedance and ultrasonographic methods for predicting the muscle volume of the upper arm. Bioelectrical impedance of the right upper arm and the thickness of elbow flexor and extensor muscles were measured from 26 healthy young adult men using a specially designed bioelectrical impedance data acquisition system and brightness-mode ultrasound apparatus, respectively. As reference data, the muscle volume (MVMRI) of the right upper arm was determined using a magnetic resonance imaging method. The impedance index was calculated as L 2/Z, where L is the upper arm length and Z is the impedance of the shoulder to the elbow. The muscle volume (MVULT) was calculated as π·(d/2)2·L, where d is muscle thickness. L 2/Z and MVULT were significantly correlated with MVMRI with correlation coefficients of 0.971 and 0.962, respectively. In these relationships, the standard errors of estimation were 44.2 cm3 (6.3%) for L 2/Z and 50.7 cm3 (7.2%) for MVULT. There was no significant difference between the absolute errors of muscle volumes estimated by L 2/Z and MVULT: 36.2 (4.8, SEM) cm3 for L 2/Z versus 40.3 (5.8) cm3 for MVULT. The present results suggest that both bioelectrical impedance and ultrasonographic methods may be useful for predicting the muscle volume of the upper arm.
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  • 166
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    Cytotechnology 34 (2000), S. 131-139 
    ISSN: 1573-0778
    Keywords: apoptosis ; bcl-xL ; cell growth ; cell viability ; hybridoma ; myeloma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract While the ectopic expression of the anti-apoptoticprotein Bcl-2 has been shown to significantly increaseboth cell viability and antibody production in batchculture, some cell lines are refractory to thesemanipulations. For example, the NS/O and theP3x63Ag8.653 murine myelomas, which express highendogenous levels of the Bcl-2 homologue Bcl-xL, areboth resistant to the anti-apoptotic effect of Bcl-2.This indicates that, in these cells, Bcl-2 and Bcl-xLmay be functionally redundant. In order to define therole which Bcl-xL plays in hybridoma cultures, we usedthe Sp2/0-Ag14 cell line. This murine hybridomaexpresses low levels of Bcl-xL and is highly sensitiveto apoptosis induction by cycloheximide (CHX) and byamino acid depletion. Bcl-xL-transfected Sp2/0-Ag14cells were more resistant than the wild type and theplasmid-containing cells to apoptosis induced by CHXand by glutamine depletion. Moreover, when compared tothe vector-transfected control, Bcl-xL-Sp2/0 cellsexhibited a substantial increase in viability instationary batch culture. Interestingly, Sp2/0-Ag14cells overexpressing Bcl-xL showed a growth behaviourthat was similar to the parent myeloma cell lineP3x63Ag8.653. Our results suggest that Bcl-xLexpression levels are sufficient to account for therelative robustness of some hybridoma cell lines instationary batch cultures.
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  • 167
    ISSN: 1573-0778
    Keywords: antisense ; apoptosis ; cell cycle ; c-jun ; protein production
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract Expression of c-jun gene induces apoptosis ofcells cultured in serum-free medium. It also promotescell-cycling in serum-containing medium, leading cellsto die by overgrowth. Previously, we established anapoptosis-suppressible, cell-cycle arrestable cellline, c-jun AS, by transfecting Friend murineerythroleukemia (F-MEL) cells with adexamethasone-inducible antisense c-jun gene.Induction of the antisense c-jun transcriptionwith dexamethasone suppressed c-jun expression.As a result, c-jun AS cells survived inserum-free medium containing dexamethasone for a longtime, while F-MEL cells died quickly in the presenceor absence of dexamethasone. In serum-containingmedium, the growth of c-jun AS cells was viablyblocked by inducing antisense c-juntranscription, and the cells survived at thenon-growth state avoiding overgrowth. In the presentstudy, protein productivity of c-jun AS cellswas examined in comparison with that of wild typeF-MEL cells. C-jun AS and F-MEL cells werefurther transfected with a vector for expressingalkaline phosphatase as a protein to be produced, andnamed c-jun AS-SEAP and F-MEL-SEAP cells,respectively. In the serum-free medium withdexamethasone, c-jun AS-SEAP cells produced theprotein for up to 6 days, while F-MEL-SEAP cellsstopped production on day 3 due to cell death causedby serum deprivation. In the serum-containing mediumwith dexamethasone, c-jun AS-SEAP cells wereviably arrested in the cell cycle, and cell death dueto overgrowth was avoided. As the result, they couldproduce the protein for up to 18 days, whileF-MEL-SEAP cells stopped production within 7 days dueto cell death caused by overgrowth.
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  • 168
    ISSN: 1573-4986
    Keywords: sialidase ; sialyltransferase ; apoptosis ; Jurkat cells ; etoposide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The present study investigated the mechanism underlying alterations of cell surface sugar chains of Jurkat cells by inducing apoptosis with etoposide, an inhibitor of topoisomerase II. Within 3[emsp4 ]h of etoposide treatment, flowcytometric analysis revealed a decrease in Maackia amurensis agglutinin recognized α2,3-linked sialic acid moieties and an increase in Ricinus communis agglutinin recognized galactose. The results suggested that asialo-sugar chains on glycoconjugates were rapidly induced on the etoposide-treated cell surface. To clarify the desialylation mechanism, we studied α2,3-sialyltransferase mRNA expression and the activity of sialidase on the cell surface during etoposide-induced apoptosis. The expression of hST3Gal III and hST3Gal IV mRNAs were down-regulated and sialidase activity on the cell surface increased threefold within 2[emsp4 ]h of etoposide treatment. Moreover, the decrease in α2,3-linked sialic acid levels was significantly suppressed in the presence of 2,3-dehydro-2-deoxy-N-acetylneuraminic acid, an inhibitor of sialidase. These results suggested that activation or exposure of sialidase on the cell surface was induced by etoposide treatment and was the main cause of the decrease in sialic acids.
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  • 169
    ISSN: 1573-7276
    Keywords: apoptosis ; Bcl-2 ; cell cycle ; invasion ; metastasis ; mobility ; melanoma B16-BL6 cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Quercetin has been known to have anti-tumor and anti-oxidation activities. In the present study, we have investigated its in vitro anti-metastatic activity. Quercetin inhibited the invasion and mobility of murine melanoma B16-BL6 cells in a dose-dependent manner but did not affect their adhesion to either laminin, fibronectin, or type VI collagen. Moreover, quercetin significantly inhibited the proliferation of B16-BL6 cells only in the case of time incubation longer than 48 h. Quercetin dose-dependently decreased the cell rates in S and G2–M phases of cell cycle. The effect of quercetin to cause a remarkable apoptosis of B16-BL6 cells was also demonstrated by flow cytometric assay as well as DNA fragmentation with a typical 180-bp ladder band in agarose electrophoresis and a quantitative analysis. Furthermore, quercetin markedly inhibited the expression of anti-apoptotic protein Bcl-2 but hardly influenced Bcl-XL. These results suggest that the inhibition of quercetin on invasiveness and migration of B16-BL6 cells are closely associated with the arrest of cell cycle as well as the induction of apoptosis by decreasing the Bcl-2 expression.
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  • 170
    ISSN: 1573-7276
    Keywords: apoptosis ; butyrate ; cell cycle ; cholesteryl butyrate ; drug delivery ; melanoma ; solid lipid nanospheres
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Literature data show that butyric acid derivatives bear a dose-dependent differentiative anti-proliferative activity on cancer cell lines and that apoptosis induction may play a major role. Although it was recently shown that solid lipid nanospheres (SLNs) are a suitable tool for several in vivo drug administration routes, there is little available information on melanoma cell lines. This study was aimed at evaluating the anti-proliferative and apoptotic in vitro effects of cholesteryl butyrate (chol-but) SLNs on melanoma cells. Increasing concentrations of chol-but SLNs were used to test two melanoma cell lines. Both cell lines were treated with Na-butyrate (Na-but) and chol-but SLNs for viability. Those tested with chol-but SLNs were more effective than Na-butirate (3 to 72 h). The apoptotic effects of chol-but SLNs were evaluated between 3 and 72 h by annexin-V (ANX-V)/propidium iodide (PI) staining and the antiproliferative effect by PI staining. Apoptosis anti-proliferative-regulatory proteins as bcl-2, Fas/APO1 (CD95) and PCNA (PC10) were also investigated. Flow cytometric analyses evidenced a G0/1-S transition block and a `sub-G0/1' apoptotic peak from 0.5 to 1.0 mM butyric acid. In ANX-V/PI flow cytometric staining, a dose- and time-dependent increase in the apoptotic cell percentage (ANX-V+) coupled with a down-regulation of PC10 and bcl-2 and a parallel up-regulation of Fas/APO1 (CD95) were found in both lines started after 3 to 24 h of chol-but SLNs treatment. Results show that chol-but SLNs exerts a dose/time-dependent effect in melanoma cell apoptosis induction between 3 and 24 h and a dose but not time-dependent effect after 24 h of treatment.
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  • 171
    ISSN: 1573-7373
    Keywords: apoptosis ; DNA ; glioma ; estramustine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The drug effect of estramustine phosphate (EMP), an anti-microtubule agent on human glioma cells has been studied with the focus being mainly its cytotoxity or its targeting of organelles. However, the pharmacological knowledge of estramustine with respect to its cytotoxity and mechanism is limited. To acquire such knowledge, the present study investigates the ability of EMP to induce apoptosis in a human malignant glioma cell line. Transmission electron microscope (TEM) images were examined to monitor periodic changes. Agarose gel electrophoresis was also examined. Cellular DNA fragmentation ELISA was performed to investigate the DNA fragmentation rates and an MTT assay was studied to evaluate the ID50. A TEM study revealed condensing and fragmentation of the chromatin. Laddering of the bands was observed in all EMP exposure groups in agarose gel electrophoresis. DNA fragmentation in all EMP groups began at 0.5 h following an exposure with EMP and increased in a dose- and time-dependent manner as revealed by DNA ELISA fragmentation. ID50 at 24 h was 5.0 µM according to the MTT assay, a value close to 4.8 µM of ID50 was revealed by the DNA fragmentation assay. None of the above mentioned changes was observed in the control group. These results indicated that EMP caused a drug-induced apoptosis in the human malignant glioma cell line, U87MG.
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  • 172
    ISSN: 1573-7373
    Keywords: selenium ; human glioma cells ; mitochondria ; apoptosis ; fibroblasts ; ultrastructure ; MTT
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We examined the effect of the trace element selenium on human glioma cell lines: T98G, U373MG, and U87MG, in addition to dermal fibroblast cells. Cultures were incubated with sodium selenite, and the following parameters were studied: cell growth, mitochondrial function, and ultrastructure. Cell growth was assayed by counting the number of viable cells after treatment with selenium. Mitochondrial function was analyzed using the MTT (tetrazolium salt reduction) assay. Apoptosis was determined by evaluating nuclear chromatin condensation by electron microscopy. The results indicated that selenium had a significant inhibitory effect on the growth of the tumor cells but had little effect upon dermal fibroblasts which had been passaged numerous times. Selenium also induced mitochondrial damage as shown by MTT assay in two brain tumor cell lines and in minimally passaged fibroblasts, but it had little effect upon the high-passage fibroblasts. Ultrastructurally, mitochondria had electron-dense inclusions resulting from selenium treatment. High rates of apoptosis were induced by selenium in the tumor cell lines and in the minimally passaged fibroblasts, whereas the fibroblasts with a high number of passages had some resistance to selenium treatment. This study correlates the adverse effects of selenium on mitochondrial function, inhibition of cell growth, and apoptosis and shows that selenium similarly affects three different brain tumor cell lines and minimally passaged fibroblasts. Further, the results with fibroblasts show that some types of cells after repeated passages can develop resistance to selenium damage.
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  • 173
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    Journal of neuro-oncology 47 (2000), S. 31-38 
    ISSN: 1573-7373
    Keywords: glioma ; apoptosis ; vitamin K ; reactive oxygen intermediates ; Fas/APO-1 ; flow cytometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Congeners of vitamin K have been found to inhibit growth in various rodent and human tumor cells, but the mechanisms of the inhibitory action are still not well understood. To investigate the modes of actions of vitamin K, we used several vitamin K analogs and examined their cytotoxic effect for human glioma cell lines RBR17T and U251. The analogs included vitamin K1 (VK1), vitamin K2 (VK2), vitamin K3 (VK3), and geranylgeraniol (GGO) which form an unsaturated side chain of VK2. Cell viability was estimated by MTT assay. DNA fragmentation was demonstrated by gel electrophoresis and flow cytometry. In order to study the mechanism of apoptosis, we measured the changes of intracellular reactive oxygen intermediates (ROI) and Fas/APO-1 expression by flow cytometry. The results showed: (1) VK2, VK3, and GGO inhibited cell growth; (2) VK3 had a more potent cytotoxic effect than VK2, and VK3 enhanced the cytotoxic effect of antitumor agents (ACNU and IFN-beta) in RBR17T cells; (3) VK2, VK3, and GGO induce apoptosis; (4) VK3 increased the expression of Fas/APO-1 although VK2 and GGO did not increase its expression in glioma cells; (5) VK3 increased the production of intracellular ROI. Catalase and reduced glutathione (GSH) inhibited production of intracellular ROI and antagonized inhibition of cell-growth induced by VK2, but failed to antagonize that of VK2 and GGO. We hypothesize that VK3 induces apoptosis by promoting the generation of intracellular ROI and Fas/APO-1 expression. On the other hand, VK2 and GGO induce apoptosis but most likely by some other unknown pathway.
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  • 174
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    Journal of neuro-oncology 47 (2000), S. 153-160 
    ISSN: 1573-7373
    Keywords: tumour ; apoptosis ; incidence ; p53 ; bax ; immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We sought to determine the relative incidence of meningiomas compared to other central nervous system tumours in an Asian surgical series, as well as the demographic and biological characteristics of these meningiomas. A review of 655 consecutive cases of central nervous system tumours from 583 patients representing the last five years admissions to one hospital in Singapore was undertaken. A total of 33 malignant/atypical tumours from 19 patients and 196 benign meningiomas from 187 patients were identified. Twenty malignant/atypical and 20 benign tumours were selected at random and subjected to histochemical and immunohistochemical analysis using antibodies directed against p53, bax and 3′-DNA hydroxy groups (TUNEL). Meningiomas comprised some 35.2% of all central nervous system tumours with malignant/atypical meningiomas representing 9.2% of meningiomas. Histochemically, necrosis was the predominant finding. However, peri-necrotic areas displayed p53 positivity in 10% of cases and bax positivity in 25% of cases. Apoptotic cells were detected in the peri-necrotic areas in 90% of benign and 75% of malignant/atypical meningiomas. Meningiomas represent the predominant form of central nervous system tumour in the Singaporean population, and aberration of p53 expression is not associated with tumour formation or progression. There was a slight but non-significant reduction in apoptosis in the progression from benign to malignant meningioma, suggesting that in contrast to many other tumour types disruption of cellular apoptosis is not a predominant driving force in Asian meningioma tumourigenesis.
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  • 175
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    Journal of neuro-oncology 46 (2000), S. 135-144 
    ISSN: 1573-7373
    Keywords: apoptosis ; cRGDfV ; human gliomas ; integrin αVβ3 ; mouse glioma model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Glioblastoma multiforme (GBM) is the most frequent malignant brain tumor in adults and is invariably fatal. We have investigated the effect of cyclo-(Arg-Gly-Asp-D-Phe-Val) (cRGDfV) peptide on survival of human malignant glioma cells in vitro and in vivo. Immunofluorescent analyses revealed the presence of αVβ3 integrin on U-87MG and U-373MG cells, but minimal expression on U-251MG cells. Treatment of U-87MG and U-373MG cells in vitro with cRGDfV (20 µg/ml), but not the linear peptide, resulted in the appearance of rounded and loosely attached cells with subsequent cell death. By comparison, neither this cyclic peptide nor its linear homolog had any significant effect on growth and morphology of U-251MG cells. The death of cRGDfV-treated (20 µg/ml) glioma cells was blocked by pretreatment (10 µM) of cells with DEVD-FMK and LEHD-FMK, inhibitors of caspase-3 and caspase-9, respectively. Moreover, when glioma cells grown as spheroids were treated with cRGDfV (50 µg/ml), spheroid formation was markedly reduced. Further, treatment of intracranial U-87MG tumors in scid mice with cyclic peptide significantly (p〈0.001) prolonged their survival. These results indicated (i) that cRGDfV induced apoptosis of human glioma cells by binding αVβ3 integrin expressed on their cell surfaces and (ii) that cRGDfV may be an effective and non-toxic direct anti-tumor therapy for αVβ3-expressing GBMs.
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  • 176
    ISSN: 1573-7373
    Keywords: apoptosis ; proliferation ; p53 ; Bcl-2 ; transglutaminase ; immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Several protocols for the adjuvant treatment of glioblastoma multiforme (GBM) are currently being evaluated. In this context, little is known about the influence of radiochemotherapy on apoptosis and the expression of apoptosis-related proteins in vivo. We have analyzed the incidence of apoptosis using in situ nick translation (ISNT) and expression of Ki-67 (MIB-1), p53 (DO-1 and DO-7), Bcl-2 and transglutaminase II (TGase II) by immunohistochemistry in 41 patients with GBM and their matched relapses. Sixteen patients received radiochemotherapy, 18 irradiation and 7 no treatment. Radiochemotherapy resulted in an increase in Bcl-2+ cells (p=0.013). Irradiation caused the reduction of MIB-1+ (p=0.0015), DO-7+ (p=0.0043) and the increase of Bcl-2+ cells (p=0.016). We calculated a positive correlation between high TGase II scores in patients preceding radiochemotherapy (p=0.0186) and no treatment (p=0.0158), low ISNT scores (p=0.0018) and high DO-1 scores (p=0.0233) in patients preceding irradiation and short time to progression. These data show that distinct postsurgical radiochemotherapy protocols differentially alter cellular proliferation and expression of p53 and Bcl-2 in GBM relapses. Furthermore, we show that ISNT, DO-1 and TGase II labeling scores are therapy-specific predictors of time to progression in GBM patients.
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    Journal of neuro-oncology 49 (2000), S. 117-129 
    ISSN: 1573-7373
    Keywords: apoptosis ; chemotherapy resistance ; bcl-2 ; bax ; glioma ; nucleolus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To investigate the role of apoptosis suppression in glioma chemotherapy resistance, protein levels and subcellular localization of bcl-2 family members were investigated in 2 pairs of sensitive cell lines and their in vitro generated resistant derivatives. The alkylating agent, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), induced apoptosis in both sensitive cell strains and apoptosis was suppressed in both resistant derivatives. Both resistant cell lines contained altered regulation of a bcl-2 related protein consistent with the suppression of apoptosis. Independent of which bcl-2 family member was dysregulated, resistance was associated with altered regulation in the subcellular localization of bax protein. Following BCNU treatment, bax accumulated in nucleoli and a nuclei containing fraction of sensitive cells but not their resistant derivatives. Nuclear accumulation was an early event in apotosis induction. These data indicates altered subcellular localization of bax may play a role in resistance. In addition, the association between an early, nucleolar localization of bax and the induction of apoptosis suggests that localization of bax to nucleoli may play a role in apoptosis-induction of glioma cells.
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  • 178
    ISSN: 1573-8469
    Keywords: apoptosis ; bacteria ; chromatin condensation ; DNA degradation analysis ; plant ; programmed cell death
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Ultrastructural details of the hypersensitive reaction induced by infiltration with avirulent race 2 Xanthomonas campestris pv. vesicatoria in pepper ‘Early Calwonder-10R’ leaves (incompatible interaction) are reported. Affected cells displayed plasmalemma undulations and disruption, lysis of the chloroplast membrane, degeneration of other organelles, general cytoplasm disorganisation and, often, protoplast shrinkage. The nuclei contained large masses of electron-dense material, apparently formed by chromatin aggregation. In many cases a single chromatin-like layer was deposited on the inner side of the nuclear envelope leaving a finely granular matrix in the centre of the nucleus; the nucleolus usually disappeared. The nuclear envelope was sometimes ruptured and the internal matrix leaked into the cytoplasm. The content of many affected cells eventually coagulated and became very electron-dense. The walls often collapsed. All these alterations were especially visible in spongy mesophyll cells at sites where bacteria occurred in the intercellular spaces. Although some of the nuclear and cytoplasmic alterations recall certain aspects of apoptotic cell death, molecular determinations did not reveal any DNA degradation in hypersensitively reacting tissues. The first cell alterations in leaves infected with the virulent bacterial race 1 (compatible interaction) were observed only 27 h after inoculation, when the cytoplasm of some cells showed limited internal disorganisation and plasmolysis at sites where bacterial colonies developed.
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  • 179
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    Cancer and metastasis reviews 19 (2000), S. 97-107 
    ISSN: 1573-7233
    Keywords: angiogenesis ; angiostatin ; cancer biology ; cancer therapy ; proteolysis ; apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The study of angiogenesis, and the promise of angiogenesis inhibition as a means of cancer therapy, has dramatically accelerated in the last several years. The discovery and publication of angiostatin by O'Reilly and colleagues in Judah Folkman's lab in 1994 has greatly contributed to this progress. Angiostatin is a kringle-containing fragment of plasminogen, which is a potent inhibitor of angiogenesis in-vivo, and selectively inhibits endothelial cell proliferation and migration in-vitro. There have been a number of proposed proteolytic mechanisms by which plasminogen is cleaved to form angiostatin, and the resulting cleavage products contain different NH2 and COOH termini of the angiostatin. Therefore, it is possible that there are more than one angiostatin isoforms (or angiostatin-related proteins) which occur in one or more normal or pathophysiological situations. It is also possible that some of the proteolytic processes which can convert plasminogen to angiostatin-like proteins are simply laboratory artifacts. Angiostatin-related proteins exert potent endothelial cell inhibitory activity, including the induction of apoptosis, and inhibition of migration, and the intact kringle structures are believed to be necessary for the antiangiogenic activity. Efforts are now underway to translate the understanding of the biology of angiostatin to clinical practice, which includes phase 1 clinical trials with recombinant angiostatin K1–3 (kringles 1–3) as well as phase 1 trials of an Angiostatin Cocktail, which induces the direct in vivo conversion of plasminogen to angiostatin 4.5 (kringles 1–4, plus most of kringle 5). The translation of the basic science of angiostatin and angiostatin-related proteins to clinical trial promises to provide an important new tool in the treatment of cancer by inhibition of angiogenesis.
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  • 180
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    Apoptosis 5 (2000), S. 203-209 
    ISSN: 1573-675X
    Keywords: apoptosis ; lens development ; organelle loss ; denucleation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The lens represents an ideal model system for studying many of the cellular and molecular events of differentiation. It is composed of two ectodermally-derived cell types: the lens epithelial cells and the lens fibre cells, which are derived from the lens epithelial cells by differentiation. Programmed removal of nuclei and other organelles from the lens fibre cells ensures that an optically clear structure is created, while the morphology of the degenerating nuclei is similar to that observed during apoptosis and is accompanied by DNA fragmentation. These observations suggest the existence of biochemical parallels between the process of lens fibre cell organelle loss and classical apoptosis. For example, proteins encoded by the bcl-2 and caspase gene families are expressed in developing lenses and nuclear degeneration in lens fibre cells can be inhibited in vivo by overexpression of bcl-2 and in vitro by incubation of differentiating lens epithelial cell cultures with caspase inhibitors. Thus, the developing lens may represent a particularly useful model system for researchers interested in apoptosis. In this review, the recent literature pertaining to lens fibre cell organelle loss and its relationship to apoptosis is reviewed and possible future research directions are suggested.
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  • 181
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    Apoptosis 5 (2000), S. 217-220 
    ISSN: 1573-675X
    Keywords: Daxx ; apoptosis ; Fas ; PML ; ND10
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Several reports describing Daxx and its putative role have emerged without a unifying theme. While Daxx has been implicated in apoptosis, it remains unclear whether Daxx is pro- or anti-apoptotic, and whether its role in apoptosis is direct or indirect. Moreover, whether Daxx plays alternative or additional roles in regulating transcription, centromere binding or any number of other activities within the cell, is uncertain. The ability of Daxx to interact with a wide variety of molecules in yeast-interaction trap systems (Table 1) has allowed for this range of speculation. The fact that Daxx contains no significant homology to other known proteins has rendered its study all the more challenging.
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  • 182
    ISSN: 1573-675X
    Keywords: apoptosis ; cyclin B1/CDC 2 ; G2/M arrest ; MAD 2 ; paclitaxel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Paclitaxel (Taxol™) is a microtubule-interfering agent that induced persistent and transient G2/M arrest before apoptosis in human nasopharyngeal carcinoma (NPC) cells at high and low concentrations, respectively. In this study, we intended to explore the underlying molecular events and found that cellular cyclin B1/CDC 2 kinase activity was increased and persisted for 〉6 h upon paclitaxel treatment both at high and low concentrations. Furthermore, activation of MAD 2 checkprotein could account for the loss of cyclin B1 ubiquitination and the persistence of cyclin B1/CDC 2 activation in the cases. To investigate the involvement of cyclin B1 and MAD 2 activation in paclitaxel-induced apoptosis, we introduced affinity-purified anti-cyclin B1 and MAD 2 antibodies into NPC cells by electroporation before the further paclitaxel treatment. The antibodies against cyclin B1 and MAD 2 indeed attenuated paclitaxel-induced cytotoxicity and DNA fragmentation. Our study suggests that activation of cyclin B1/CDC 2 and MAD 2 were the M-phase events required for paclitaxel-induced apoptosis in NPC cells. The dys-regulated cyclin B1/CDC 2 activation could enhance the prometaphase progression, but activation of MAD 2 rendered cells inable to exit from the metaphase. Under this circumstance, cells were probably going to “mitotic catastrophe” and ultimately, destined to apoptosis.
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  • 183
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    Apoptosis 5 (2000), S. 211-215 
    ISSN: 1573-675X
    Keywords: adenovirus ; E4orf4 ; apoptosis ; protein phosphatase 2A (PP2A) ; caspases ; cancer ; gene therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Adenovirus E4orf4 protein is a multifunctional viral regulator that induces p53-independent apoptosis in transformed cells, but not in normal cells. E4orf4-induced apoptosis can occur without activation of known caspases, although E4orf4 induces caspase activity in some cell lines. The interaction of E4orf4 with a specific subpopulation of protein phosphatase 2A (PP2A) molecules that contain B subunits, but not with those that contain B′ subunits, is required for induction of apoptosis. This review suggests the potential use of E4orf4 in cancer therapy, and discusses whether E4orf4-induced apoptosis plays a role in the viral life cycle. Future research directions are also highlighted.
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  • 184
    ISSN: 1573-675X
    Keywords: Amphibia ; apoptosis ; cancer ; cell cycle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Spontaneous and induced cancers are rare in non-isogeneic or inbred amphibians. Neoplastic cells become immortalized through loss of a normal capacity to die by apoptosis. Mature lymphocytes of mammals require activation and entry into the cell cycle in order to become susceptible to apoptosis. Whether Xenopus lymphocytes differ from mammalian lymphocytes in this regard is examined. In vitro exposure of PMA, or its analogue, MPMA, to adult splenocytes of Xenopus laevis was used to affect apoptosis. Flow cytometric analysis of FITC-Annexin V/propidium iodide (PI) fluorescence (apoptosis) and BrdU uptake (DNA synthesis) were assayed concurrently in the same lymphocyte population over time. Significant increases in apoptotic levels were induced throughout a 72 hour period in PMA-treated cells only. Lymphocytes were also separated by size for analysis. Several sub-populations of lymphocytes were identified, the most interesting of which was small and apoptotic within 4 hours, after PMA exposure. PMA-induced DNA synthesis did not become elevated until after 24 hours. “Direct” apoptosis, i.e. without cell cycle entry, was found only in these small, mature lymphocytes. Since small lymphocytes make up the vast majority of those being analyzed, “direct” apoptosis may be a determining mechanism in the resistance to neoplasia observed in Amphibia. Cells that die more readily are less likely to transform into neoplastic cells.
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  • 185
    ISSN: 1573-675X
    Keywords: apoptosis ; caspase-3 ; nuclease ; endo-exonuclease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Single-strand DNase and poly rAase, activities characteristic of endo-exonuclease, were co-activated in nuclear fractions of HL-60 cells by caspase-3. Activation was accompanied by cleavages of large soluble polypeptides (130–185 kDa) and a 65 kDa inactive chromatin-associated polypeptide related to the endo-exonuclease of Neurospora crassa as detected on immunoblots. The major products seen in vitro were a 77 kDa soluble polypeptide and an active chromatin-associated 34 kDa polypeptide. When HL-60 cells were induced to undergo apoptosis by treating with 50 μM etoposide (VP-16) for 4 hours, 77 kDa and 40 kDa polypeptides accumulated in nuclear fractions. Chromatin DNA fragmentation activity was also activated in cytosol and nuclear extract either by pre-treating the cells in vivo with VP-16 or by treating the cytosol in vitro with caspase-3 or dATP and cytochrome c. Endo-exonuclease activated by caspase-3 in cytosol-derived fractions augmented chromatin DNA fragmentation activity in vitro. Endo-exonuclease is proposed to act in vivo in conjunction with the caspase-activated DNase (CAD) to degrade chromatin DNA during apoptosis of HL-60 cells.
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  • 186
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    Apoptosis 5 (2000), S. 307-314 
    ISSN: 1573-675X
    Keywords: apoptosis ; cancer ; cross-priming ; cross-tolerance ; dendritic cells ; T lymphocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Induction of cell death by apoptosis, also called programmed cell death, and clearance of apoptotic bodies by scavenger cells has long thought to be an efficient means to dispose of unwanted cells without causing inflammatory responses able to mediate specific reactions. However, a number of evidences have been accumulated suggesting that apoptotic cell death is implicated in the pathogenesis of systemic and organ specific autoimmune diseases. In addition, recognition and engulfement of apoptotic cells by professional antigen presenting cells, such as dendritic cells, and their interaction with effector immune cells have been recently described to result in apoptotic cell-derived antigen specific tolerance. This review will summarise the most recent findings on the immunogenic potential of cells undergoing programmed death.
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  • 187
    ISSN: 1573-675X
    Keywords: Angiogenesis ; angiopoietins ; apoptosis ; integrins ; vascular endothelial growth factor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Angiogenesis is essential for the growth and metastasis of solid tumors. The balance of endothelial cell (EC) proliferation and apoptosis is a major determinant in tumor angiogenesis. Recently, several studies demonstrated that numerous angiogenic factors not only induce angiogenesis but also function as EC survival factors. Vascular endothelial growth factor (VEGF), a potent angiogenic factor, is also an EC survival factor in embryonic vasculogenesis and tumor angiogenesis. VEGF activates specific intracellular survival pathways in ECs including Bcl-2, A1, IAP, Akt, and Erk. Integrins may function as EC survival factors by preventing anoikis by enhancing binding to the extracellular matrix. In addition, integrins may function in concert with VEGF to promote EC survival. Angiopoietin-1 (Ang-1) has recently been shown to stabilize EC networks by binding to the EC-specific tyrosine kinase receptor Tie-2. Pericytes also function as EC survival factors, by cell-cell contact, secretion of survival factors, or both. Targeting any of the above mechanisms for EC survival may provide novel antineoplastic strategies.
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  • 188
    ISSN: 1573-675X
    Keywords: apoptosis ; antimicrotubule agent ; cell cycle ; dolastatin 10 ; TZT-1027
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract TZT-1027, a newly synthesized dolastatin 10 derivative, is a potent antitumor agent which inhibits microtubule polymerization and perturbs microtubule dynamics. In this report, we investigated whether TZT-1027 inhibited the growth of various human cancer cells, and the cell death caused by TZT-1027 was due to apoptosis. In addition, we elucidated the apoptosis machinery induced by treatment with TZT-1027. The 50% growth-inhibitory concentrations (IC50 values) of TZT-1027 on cancer cells derived from various sources were not more than 5.9 ng/ml. TZT-1027 showed superior cytotoxicity than any other antitumor agents. Next, we evaluated morphological nuclear change, namely, chromatin condensation and DNA fragmentation. We used three cancer cell lines derived from different types in view of having apoptosis related protein, human leukemia HL-60 (in the presence of both Caspase-3 and Bcl-2), human breast cancer MCF-7 (in the absence of Caspase-3), and human prostate cancer DU145 (in the absence of Bcl-2). TZT-1027 induced DNA fragmentation in the presence but not absence of Caspase-3. Nevertheless, apoptic chromatin condensation was observed in all cancer cells even if there was no Caspase-3. Furthermore, we examined whether TZT-1027, microtubule-disrupting agent, influenced cell cycle progression. Flow cytometric analysis revealed the cells treated with TZT-1027, and with the other antimicrotubule agents, to be arrested at the G2/M phase and subsequently to show fragmented DNA smaller than that of G1 phase cells. Moreover, we tested TZT-1027 for its ability to induce Bcl-2 phosphorylation in human cancer cell lines. TZT-1027 and other agents which interacted with microtubules induced Bcl-2 phosphorylation, whereas DNA-damaging agents did not. The present results suggested an association of the growth-inhibitory effect of TZT-1027 with the induction of apoptosis and indicated that the apoptosis induced by TZT-1027 was followed by G2/M arrest even if there was no Caspase-3 or Bcl-2.
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  • 189
    ISSN: 1573-675X
    Keywords: apoptosis ; chemotherapy resistance ; clonogenicity ; ras
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Mutationally activated Ras is involved in tumor progression and likely also in drug resistance. Using survival, viability and apoptosis assays, we have here compared the cisplatin sensitivities of FR3T3 rat fibroblasts and a 12V-H-ras transformed subline (Ras2:3). Around 24 h after cisplatin treatment Ras2:3 cells showed higher apoptosis levels and lower viability than FR3T3. This increased sensitivity correlated with weaker cisplatin-induced activation of Jun N-terminal kinase (JNK). In contrast to apoptosis assays, colony formation assays showed that Ras2:3 were more resistant to cisplatin than were FR3T3. This was partly due to the increased cisplatin sensitivity of FR3T3 seeded at low densities, as required in colony formation assays. In addition, Ras2:3 cisplatin survivors had a higher relative proliferative capacity. Cell cycle analyses showed that FR3T3 cells initially responded with a dose-dependent G2 arrest, while Ras2:3 accumulated in S-phase. Experiments with an anti-apoptotic mutant of MEKK1 suggested that the apoptotic response of Ras2:3 cells is not specific to the S-phase fraction. In summary, the cisplatin response of ras-transformed fibroblasts is distinct from that of parental cells, in that they show increased apoptosis, a different cell cycle response and increased post-treatment proliferative capacity. The results illustrate the need to carefully consider methods and protocols for in vitro studies on chemotherapy sensitivity.
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  • 190
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    Apoptosis 5 (2000), S. 415-418 
    ISSN: 1573-675X
    Keywords: apoptosis ; death receptors ; inflammation ; reactive oxygen species (ROS)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Reactive oxygen species (ROS) and mitochondria play an important role in apoptosis induction under both physiologic and pathologic conditions. Interestingly, mitochondria are both source and target of ROS. Cytochrome c release from mitochondria, that triggers caspase activation, appears to be largely mediated by direct or indirect ROS action. On the other hand, ROS have also anti-apoptotic effects. This review focuses on the role of ROS in the regulation of apoptosis, especially in inflammatory cells.
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  • 191
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    Apoptosis 5 (2000), S. 419-424 
    ISSN: 1573-675X
    Keywords: apoptosis ; diabetes ; Fas ; organ-specific auto-immunity ; thyroiditis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract CD95 (Fas/Apo-1) is a broadly expressed death receptor involved in a variety of physiological and pathological apoptotic processes. Since its discovery, defects in CD95/CD95L system have been proposed as major pathogenic factors responsible for impaired immunological tolerance to self antigens and autoimmunity. Later, analysis of altered sensitivity to CD95-induced apoptosis in cells targeted by the immune response has revealed an unexpected role for CD95 and CD95L in organ-specific autoimmunity. CD95 has been shown to be expressed and functional in virtually all cell types that are target of the organ-specific autoimmune response. Here we review some of the major findings concerning the role of CD95 in autoimmunity, in dysfunctions due to increased or decreased CD95-induced apoptosis.
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  • 192
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    Apoptosis 5 (2000), S. 443-449 
    ISSN: 1573-675X
    Keywords: apoptosis ; autoimmunity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Apoptosis is a physiological form of cell death required to ensure that the rate of cell division is balanced by the rate of cell death in multicellular organisms. Dysregulation of apoptosis is associated with the pathogenesis of a wide array of diseases: cancer, neurodegeneration, autoimmunity, heart disease and others. In this review we collect arguments supporting a hypothesis of a dysregulated apoptosis leading to development of autoimmunity like systemic lupus erythematosus (SLE). This notion is supported by occurence of known autoantigens in apoptotic blebs, in vitro findings of an increased rate of apoptotic lymphoblasts despite optimal cytokine stimulation combined with a defective in vitro clearance of apoptotic bodies by SLE phagocytes. Moreover, we and others could generate histone-specific lymphocytic cell lines from cells after activation with autologous apoptotic material. These lymphocytes could stimulate autologous B-lymphocytes to produce of anti-dsDNA antibodies, a diagnostic hallmark for SLE. Finally, antibodies against phospholipids like phosphatidylserine are often associated with systemic autoimmunopathies like SLE and others. Phosphatidylserine is exposed on apoptotic cells as early sign of programmed cell death and serves as phagocyte recognition molecule for apoptotic cells. Formation of immune complexes and deposition in tissues might lead to organ damage and disease. This scenario will be discussed in this review in detail.
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  • 193
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    Apoptosis 5 (2000), S. 9-16 
    ISSN: 1573-675X
    Keywords: Aging ; Alzheimer's disease ; amyloid precursor protein ; apoptosis ; Bcl-2 ; caspase ; presenilin ; transcription factor ; β amyloid.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Alzheimer's disease (AD) is the most common human neurodegenerative disorder characterized by the progressive deterioration of cognition and memory in association with the presence of senile plaques, neurofibrillary tangles, and massive loss of neurons. Most cases of AD are late-onset and sporadic, but in some cases the disease is inherited as an autosomal dominant trait. Four different genes, the amyloid precursor protein, apolipoprotein E, and presenilins 1 and 2 have been implicated in the etiology of familial AD. It is now generally accepted that massive neuronal death due to apoptosis is a commmon characteristic in the brains of patients suffering from neurodegenerative diseases, and apoptotic cell death has been found in neurons and glial cells in AD. This review summarizes the current findings regarding the evidence for apoptosis in AD and discusses the possible involvement of apoptosis-regulating factors in the pathology of AD. Modification of the apoptotic cascade could be considered as a primary therapeutic strategy for the disease.
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  • 194
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    Keywords: Anti-tumor drugs ; apoptosis ; cancer ; caspases ; necrosis.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The majority of current anticancer therapies induce tumor cell death through the induction of apoptosis. Alterations in the apoptotic pathways may determine tumor resistance to these therapies. Activation of the proteolytic cascade involving caspase family members is a critical component of the execution of cell death in apoptotic cells. However, recent studies suggest that cell death can proceed in the absence of caspases. In this review we describe the role of caspase-dependent and -independent pathways as targets for anticancer treatment; better understanding of diverse modes of tumor cell death will help to avoid ineffective treatment and provide a molecular basis for the new strategies targeting caspase-independent death pathways in apoptosis-resistant forms of cancer.
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  • 195
    ISSN: 1573-675X
    Keywords: Anti-Fas antibody ; antisense homology box-derived peptide ; apoptosis ; Fas ligand ; ovarian cancer.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract We found that a short synthetic peptide corresponding to the “antisense homology box” of Fas ligand induced apoptotic cell death of Fas-expressing human ovarian cancer cell lines. The peptide was deduced from residues 256–265 of human Fas ligand, based on the hypothesis that it should contain a specific binding site to the corresponding Fas. Interestingly, the ovarian cancer cell line NOS4, which was sensitive to anti-Fas antibody induced apoptosis, was not affected by the peptide, whereas another cell line, SKOV-3, which was insensitive to anti-Fas antibody, was killed by the peptide. Thus, this short peptide was shown to have a unique activity to induce apoptosis in human ovarian cancer cells in a manner different from anti-Fas antibody.
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  • 196
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    Keywords: apoptosis ; Bax ; ceramide ; mitochondria ; pH
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Ceramide can induce apoptosis through a caspase independent pathway. Bax has been described as able to kill cells in the absence of caspase activity, therefore we measured Bax in situ during ceramide-induced apoptosis using anti-Bax antibodies and flow cytometry analysis. An early (〈30 min) increase in Bax labeling was observed after the addition of several ceramide species to several hemopoietic-related cell types. On U937, this increase was not due to antigens synthesis or processing, but rather an increased accessibility or reactivity of Bax antigens for antibodies. This increased immuno-reactivity of Bax was not inhibited by Z-VAD-fmk nor leupeptin, and preceded nuclear fragmentation by several hours. Such an increase in immuno-reactivity was also observed after Fas ligation, but it occurred later (〉2 h) accompanying nuclear apoptosis, and was inhibited by Z-VAD-fmk. Bax immuno-reactivity was found to be related to intracellular pH (pHi), and C2-Ceramide (C2-Cer) induced a very early (〈10 min) transitory increase in pHi. Both Bax immuno-reactivity and pHi increases were dependent on the mitochondrial permeability transition pore (PTP) status. It was concluded from these results that C2-Cer induced a transitory increase in pHi in relation to the PTP. This rise in pHi led to conformational changes in Bax which could be responsible for further apoptosis in the C2-Cer pathway while it was a consequence of caspase activation in the Fas pathway.
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  • 197
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    Keywords: apoptosis ; macrophages ; Chagas disease ; Trypanosoma cruzi ; T lymphocytes ; vitronectin receptor ; transforming growth factor-beta ; prostaglandins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
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  • 198
    ISSN: 1573-675X
    Keywords: anesthetics ; apoptosis ; barbiturates ; benzodiazepines ; ethanol ; GABAA receptors ; ketamine ; NMDA receptors ; phencyclidine ; synaptogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract It has been known for three decades that ethanol, the most widely abused drug in the world, has deleterious effects on the developing human brain, but progress has been slow in developing animal models for studying this problem, and the underlying mechanisms have remained elusive. Recently, we have shown that during the synaptogenesis period, also known as the brain growth spurt period, ethanol has the potential to trigger massive neuronal suicide in the in vivo mammalian brain. The brain growth spurt period in humans spans the last trimester of pregnancy and first several years after birth. The NMDA antagonist and GABAmimetic properties of ethanol may be responsible for its apoptogenic action, in that other drugs with either NMDA antagonist or GABAmimetic actions also trigger apoptotic neurodegeneration in the developing brain. Our findings provide a likely explanation for the reduced brain mass and neurobehavioral disturbances associated with the human fetal alcohol syndrome. Furthermore, since NMDA antagonist and GABAmimetic drugs are sometimes abused by pregnant women and also are used as anticonvulsants, sedatives or anesthetics in pediatric medicine, our findings raise several complex drug safety issues. In addition, the observation that ethanol and several other drugs trigger massive neuronal apoptosis in the developing brain provides an unprecedented opportunity to study both neuropathological aspects and molecular mechanisms of apoptotic neurodegeneration in the in vivo mammalian brain.
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  • 199
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    Apoptosis 5 (2000), S. 379-388 
    ISSN: 1573-675X
    Keywords: apoptosis ; ATP depletion ; cell acidification and shrinkage ; CpG-specific megabase fragmentations ; DCNP (2,6-dichloro-4-nitrophenol) ; housekeeping genes ; microarray (genechip) ; zVAD-fmk
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Previous suggestions of CpG-specific apoptotic commitment implied critical epigenetic modulation of house-keeping genes which have canonical CpG islands at 5′ promoter regions. Differential housekeeping gene activity however has not been shown. Using a focussed microarray (genechip) of 22 housekeeping genes we show this in apoptosis induced in human Chang liver cells by DCNP (2,6-dichloro-4-nitrophenol), a non-genotoxic inhibitor of sulfate detoxification. 3–7 folds downregulation of 9 genes in glycolysis, tricarboxylic acid cycle and the respiratory electron transport chain suggested gene-directed energy depletion which was correlated with observed ATP depletion. 4 folds downregulation of the pyruvate dehydrogenease gene suggested gene-directed metabolic acidosis which was correlated with observed cell acidification. Other differential housekeeping gene activity, including 4 folds upregulation of microtubular alpha-tubulin gene, and 2 folds upregulation of ubiquitin, also had a bearing on apoptosis. Broadspectrum zVAD-fmk caspase inhibition abolished 200 bp DNA ladder fragmentations but not the CpG-specific megabase fragmentations and other hallmarks of cell destruction, suggesting a caspase-independent cell death. Death appeared committed at gene-level.
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  • 200
    ISSN: 1573-675X
    Keywords: apoptosis ; concanavalin A ; cytochrome c release ; mitochondria
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Concanavalin A (ConA), normally a mitogen of T-lymphocytes, was found to be a cell cycle-independent apoptosis-inducing agent in cultured murine macrophage PU5-1.8 cells. This assertion is based on the following observations: (1) ConA increased the number of cells with hypo-diploid DNA in a dose dependent manner as revealed by flow cytometry; (2) ConA elicited DNA fragmentation and the cytotoxicity of ConA was suppressed by α-D-methylmannoside which blocks the lectin site of ConA; (3) ConA was able to release cytochrome c (cyto c) into the cytosol of PU5-1.8 cells. When isolated mitochondria were incubated with ConA, release of cyto c was observed too. Interestingly, clustering of mitochondria was found in the cytosol under a confocal microscope after ConA treatment. When cells were incubated with ConA-FITC and subsequently with mitotracker red (a probe for mitochondria), co-localization of fluorescence signals was observed. These results suggest that ConA was delivered to the mitochondria, induced mitochondrial clustering and released cyto c. Our results also show that introduction of exogenous cyto c electroporationally into ConA-untreated cells elicited DNA fragmentation. On the other hand, introduction of specific antibody against cyto c into PU5-1.8 cells suppressed the ConA-mediated cell death. Taken together, our results indicate that ConA induced apoptosis in PU5-1.8 cells through mitochondrial clustering and release of cyto c and the release of cyto c was sufficient to elicit apoptosis in PU5-1.8 cells.
    Type of Medium: Electronic Resource
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