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  • 2005-2009
  • 1995-1999  (1,006)
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  • 1940-1944
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  • 101
    Electronic Resource
    Electronic Resource
    Sudden unilateral deafness with endolymphatic sac adenocarcinoma: MRI (1999)
    Springer
    Neuroradiology 41 (1999), S. 799-801 
    Details
    ISSN: 1432-1920
    Keywords: Key words Endolymphatic sac ; adenocarcinoma ; Hearing loss ; sensorineural ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A 30-year-old man presented with sudden left deafness and vertigo. CT showed an osteolytic retrolabyrinthine tumour of the left temporal bone. High signal from the tumour and labyrinth was seen on fat-suppressed T 1-weighted images. At surgery, a haemorrhagic papillary-cystic adenocarcinoma of the endolymphatic sac was found.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002340050845
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  • 102
    Electronic Resource
    Electronic Resource
    Paragangliomas of the spinal canal (1999)
    Springer
    Neuroradiology 41 (1999), S. 788-794 
    Details
    ISSN: 1432-1920
    Keywords: Key words Paraganglioma spinal ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report the clinical MRI and histopathological features of five consecutive cases of spinal paraganglioma. Three intradural tumours were found in the typical location (two at the L4, one at the S2 level); one intradural extramedullary tumour arose at an unusual level, from the ventral C2 root, and one extradural tumour growing along the L5 nerve root sheath had an aggressive growth pattern with early, local paraspinal recurrence and, eventually, intradural metastatic spread. This type of growth pattern has not been described previously. Paragangliomas of the spinal canal are more common than previously thought and can be located anywhere along the spine, although the lumbosacral level is the most common. Their appearance on MRI can not disinguish them from other tumours in the spinal canal. Even though paragangliomas in general are benign and slowly growing their growth pattern can vary and be more aggressive, to the point of metastatic spread.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002340050843
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  • 103
    Electronic Resource
    Electronic Resource
    Proteus syndrome: craniofacial and cerebral MRI (1999)
    Springer
    Neuroradiology 41 (1999), S. 840-843 
    Details
    ISSN: 1432-1920
    Keywords: Key words Proteus syndrome ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The Proteus syndrome is a rare hamartoneoplastic syndrome that may affect the brain, skull, and extracranial head and neck. We present a case with severe, characteristic findings. Brain abnormalities are not common in Proteus syndrome; when present, hemimegalencephaly and migrational disorders are typically seen, commonly with an associated seizure disorder. Maxillary and mandibular dysmorphism may occur, including unilateral condylar hyperplasia. Subcutaneous fatty, fibrous, lymphangiomatous masses commonly seen in this syndrome may involve the neck and face, leading to disfigurement and potential airway compromise.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002340050853
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  • 104
    Electronic Resource
    Electronic Resource
    Persistent hyperplastic primary vitreous: MRI (1999)
    Springer
    Neuroradiology 41 (1999), S. 520-522 
    Details
    ISSN: 1432-1920
    Keywords: Key words Persistent hyperplastic primary vitreous ; Leukocoria ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Persistent hyperplastic primary vitreous (PHPV), a developmental cause of leukocoria, is due to incomplete regression of the fetal blood supply to the eye. We report the MRI features of PHPV of the dorsal type to facilitate differential diagnosis from other causes of leukocoria, namely retinoblastoma, which may have major therapeutic consequences.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002340050796
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  • 105
    Electronic Resource
    Electronic Resource
    Extraspinal dural arteriovenous fistula in a patient with lipomyelodysplasia: value of MRI and MRA (1999)
    Springer
    Neuroradiology 41 (1999), S. 579-583 
    Details
    ISSN: 1432-1920
    Keywords: Key words Spine ; dysraphism ; Fistula ; arteriovenous ; Magnetic resonance imaging ; Magnetic resonance angiography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Spinal dural arteriovenous fistulae are extremely rare in spinal dysraphism. A fistulous malformation within a lipomyelomeningocele has not been reported previously. A 50-year-old man presented with progressive paraparesis and bladder dysfunction. MRI revealed a large lumbar lipomyelomeningocele. A vascular malformation was indicated by abnormal signal in the thoracolumbar spinal cord and dilated perimedullary veins. Phase-contrast MRA demonstrated only the slow-flow veins of the fistula and an intradural ascending vein. Contrast-enhanced ultra-fast MRA gave excellent delineation of all parts of the fistula within the dysraphic lesion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002340050810
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  • 106
    Electronic Resource
    Electronic Resource
    Myeloneuropathy following nitrous oxide anesthaesia in a patient with macrocytic anaemia (1999)
    Springer
    Neuroradiology 41 (1999), S. 588-590 
    Details
    ISSN: 1432-1920
    Keywords: Key words Nitrous oxide anaesthesia ; Macrocytic anaemia ; Myeloneuropathy ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The neurological condition triggered by anaesthesia with nitrous oxide involves the cyanocobalamine pathway and is characterised by progressive demyelination and axonal lesions of the peripheral nerves and cervicothoracic spinal cord (posterior and anterolateral columns) giving a peripheral neuropathy and very frequently subacute combined degeneration of the spinal cord. It is possible to show these demyelinating lesions by MRI of the spine, allowing early diagnosis and follow-up. We describe a case of myeloneuropathy with onset a few hours after nitrous oxide anaesthesia in a patient with macrocytic anaemia and possible subclinical vitamin B12 deficiency and MRI evidence of a lesion of the cervical spinal cord. Neurological and haematological improvement followed cyanocobalamine replacement.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002340050812
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  • 107
    Electronic Resource
    Electronic Resource
    Posterior extradural migration of extruded thoracic and lumbar disc fragments: role of MRI (1999)
    Springer
    Neuroradiology 41 (1999), S. 630-635 
    Details
    ISSN: 1432-1920
    Keywords: Key words Disc ; intervertebral ; prolapsed ; Migration ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report three patients with a sequestrated disc fragment posterior to the thecal sac. The affected disc was lumbar in two cases and thoracic in the third. Disc fragment migration is usually limited to the anterior extra dural space. Migration of a disc fragment behind the dural sac is seldom encountered. MRI appears to be the method of choice to make this diagnosis. The disc fragments gave low signal on T1- and slightly high signal on T2-weighted images and showed rim contrast enhancement. The differential diagnosis includes abscess, metastatic tumour and haematoma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002340050815
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  • 108
    Electronic Resource
    Electronic Resource
    Choroid plexus papilloma of foramen of Luschka with multiple recurrences and cystic features (1999)
    Springer
    Neuroradiology 41 (1999), S. 654-656 
    Details
    ISSN: 1432-1920
    Keywords: Key words Angle cerebellopontine ; Papilloma choroid plexus ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We present a rare cerebellopontine angle choroid plexus papilloma arising at the foramen of Luschka, without an associated intraventricular component. Distinct features of the tumour on MRI, of multiple recurrences with cystic features, are described, with a review of the literature.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002340050819
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  • 109
    Electronic Resource
    Electronic Resource
    Fibro-osseous lesions involving the brain: MRI (1999)
    Springer
    Neuroradiology 41 (1999), S. 18-21 
    Details
    ISSN: 1432-1920
    Keywords: Key words Brain ; neoplasms ; Skull base ; neoplasms ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We present the MRI findings in two patients with “fibro-osseous lesions” involving the central nervous system. A left temporal lobe mass was present in one patient and an extra-axial mass at the skull base in the other. In both cases, calcification was present, with low signal intensity on T1- and T2-weighted images.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002340050697
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  • 110
    Electronic Resource
    Electronic Resource
    Pleomorphic xanthoastrocytoma with CT and MRI appearance of meningioma (1999)
    Springer
    Neuroradiology 41 (1999), S. 30-34 
    Details
    ISSN: 1432-1920
    Keywords: Key words Pleomorphic xanthoastrocytoma ; Computed tomography ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We describe a pleomorphic xanthoastrocytoma (PXA) in a young girl whose frontal lobe location, solid structure, dural tail and MRI signal characteristics led to a preoperative diagnosis of meningioma. PXA should be considered in differential diagnosis of tumours affecting young patients with neuroradiological characteristics suggestive of meningioma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002340050700
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  • 111
    Electronic Resource
    Electronic Resource
    Rathke's cleft cyst with pituitary apoplexy: case report (1999)
    Springer
    Neuroradiology 41 (1999), S. 832-834 
    Details
    ISSN: 1432-1920
    Keywords: Key words Pituitary tumor ; Cyst Rathke's cleft ; Pituitary apoplexy ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report a Rathke's cleft cyst which presented as pituitary apoplexy, a rare presentation. A 46-year-old woman suffered sudden headache and visual loss. T1-weighted MRI 3 weeks after this apoplectic episode demonstrated a cystic lesion between the anterior and posterior lobes of the pituitary, with some high-signal material layering in it. The mass showed spontaneous regression on an image 3 weeks later. Trans-sphenoidal surgery confirmed the diagnosis of a Rathke's cleft cyst with a haematoma within it.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002340050851
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  • 112
    Electronic Resource
    Electronic Resource
    Pial involvement in Wegener's granulomatosis shown on MRI (1999)
    Springer
    Neuroradiology 41 (1999), S. 847-849 
    Details
    ISSN: 1432-1920
    Keywords: Key words Granulomatosis ; Wegener's ; Meninges ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Involvement of the brain and meninges is rare in Wegener's granulomatosis (WG); it has been reported in 1.2–8 % of patients. Meningeal involvement in WG has been reported in imaging as being confined to the duramater, and is thought to represent granulomatous infiltration. We present a case of WG with abnormal pial enhancement and involvement of the perivascular spaces on MRI, pathologically proven to represent granulomatous infiltration due to the primary disease rather than to infection.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002340050855
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  • 113
    Electronic Resource
    Electronic Resource
    Unusual MRI findings in lymphocytic hypophysitis with central diabetes insipidus (1999)
    Springer
    Neuroradiology 41 (1999), S. 899-900 
    Details
    ISSN: 1432-1920
    Keywords: Key words Hypophysitis lymphocytic ; Pituitary tumour ; Diabetes insipidus ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report an unusual case of lymphocytic hypophysitis, which proved to be cystic at surgery.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002340050863
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  • 114
    Electronic Resource
    Electronic Resource
    Constructive interference in steady-state 3D Fourier-transform MRI in the management of hydrocephalus and third ventriculostomy (1999)
    Springer
    Neuroradiology 41 (1999), S. 117-123 
    Details
    ISSN: 1432-1920
    Keywords: Key words Hydrocephalus ; Ventriculostomy ; Magnetic resonance imaging ; Pulse sequences
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We describe the use of three-dimensional Fourier transform constructive imaging in the steady state (CISS) MRI in the assessment of patients with hydrocephalus. We have found it of value both as a diagnostic investigation and in the follow-up of patients treated by third ventriculostomy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002340050715
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  • 115
    Electronic Resource
    Electronic Resource
    Chronic spinal subdural haematoma associated with intracranial subdural haematoma: CT and MRI (1999)
    Springer
    Neuroradiology 41 (1999), S. 137-139 
    Details
    ISSN: 1432-1920
    Keywords: Key words Spinal subdural haematoma ; Magnetic resonance imaging ; Computed tomography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Chronic spinal subdural haematoma is a uncommon. We describe the CT and MRI appearances of chronic spinal and intracranial subdural haematomas following minor trauma. The aetiology, pathogenesis and differential diagnosis are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002340050719
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  • 116
    Electronic Resource
    Electronic Resource
    Cryptococcus meningoencephalitis in AIDS: parenchymal and meningeal forms (1999)
    Springer
    Neuroradiology 41 (1999), S. 129-133 
    Details
    ISSN: 1432-1920
    Keywords: Key words Cryptococcosi ; Acquired immunodeficiency syndrome ; Computed tomography ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract CT and MRI in one case of Cryptococcus neoformans infection showed contrast-enhancing parenchymal lesions resembling granulomata or abscesses. After an initial phase without contrast enhancement, the full extent of the lesions was visible within 2 weeks of presentation. The enhancing masses were assumed to represent intracerebral cryptococcomas. Despite evidence of massive meningeal infection on cerebrospinal fluid (CSF) examination, no radiological signs of meningitis, invasion of the Virchow-Robin spaces or ventriculitis could be demonstrated. With antimycotic treatment the contrast enhancement disappeared and cystic, partly calcified lesions remained. Recurrence of meningeal infection without radiological correlates was apparent in this stage. In a second case of proven cryptococcus meningitis, dilation of Virchow-Robin spaces or cysts in the adjacent parenchyma were the main abnormalities on MRI. Enhancing masses were not detected. These cases may represent two different reactions of the immunocompromised hosts to infection with C. neoformans: widening of the perivascular spaces as a correlate of the more typical meningeal infection and enhancing parenchymal lesions as a sign of further invasion from the CSF spaces. Enhancement of cryptococcomas, indicating an inflammatory response in the surrounding brain, is not typical in patients with impairment of immune function.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002340050717
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  • 117
    Electronic Resource
    Electronic Resource
    MRI characteristics of midbrain tumours (1999)
    Springer
    Neuroradiology 41 (1999), S. 158-162 
    Details
    ISSN: 1432-1920
    Keywords: Key words Midbrain ; tumours ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We diagnosed 60 cases of midbrain tumours by MRI between 1993 to 1997. There were 39 males and 21 females, aged 2–64 years, mean 25.6 years. We found 38 patients with true intramedullary midbrain tumours, 11 predominantly in the tectum, 20 in the tegmentum and 7 with a downward extension to the pons; there were 7 within the cerebral aqueduct. There were 22 patients with infiltrating midbrain tumours extending from adjacent structures, 11 cases each from the thalamus and pineal region. All patients received surgical treatment. Gross total resection was achieved in 42 cases, subtotal (〉 75 %) resection in 18. Pathological diagnoses included 16 low-grade and 15 high-grade astrocytomas; 5 oligodendroastrocytomas; 2 ependymomas; 11 glioblastomas; and 11 pineal parenchymal or germ-cell tumours. Midbrain tumours are a heterogeneous group of neoplasms, with wide variation in clinical and MRI features, related to the site and type of tumour. MRI not only allows precise analysis of their growth pattern, but also can lead to a correct preoperative diagnosis in the majority of cases.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002340050723
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  • 118
    Electronic Resource
    Electronic Resource
    Hyperacute infarction: a comparison of CT and MRI, including diffusion-weighted imaging (1999)
    Springer
    Neuroradiology 41 (1999), S. 175-178 
    Details
    ISSN: 1432-1920
    Keywords: Key words Infarct ; cerebral ; Computed tomography ; Magnetic resonance imaging ; diffusion-weighted
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We compared CT and MRI obtained within the first 3 h of onset of a cerebral infarct. Echo-planar diffusion-weighted MRI delineated the infarcted areas most clearly, and subtle low-density areas on CT were consistent with those shown to be abnormal by diffusion-weighted MR. The signal changes of affected areas on fast spin-echo proton-density, T2-weighted and fast FLAIR images were subtler than the low density on CT.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002340050727
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  • 119
    Electronic Resource
    Electronic Resource
    High-intensity basal ganglia lesions on T1-weighted images in two toddlers with elevated blood manganese with portosystemic shunts (1999)
    Springer
    Neuroradiology 41 (1999), S. 195-198 
    Details
    ISSN: 1432-1920
    Keywords: Key words Shunt ; portosystemic ; Globus pallidus ; Manganese ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report two toddlers with portosystemic shunts who had symmetrical high-signal globus pallidus lesions on T1- but not T2-weighted MRI, and measurement of whole blood manganese at 2 years of age. These cases suggest that portosystemic shunts can cause elevation of blood manganese and result in manganese accumulation in the globus pallidus, causing high signal on T1-weighted images even in asymptomatic toddlers.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002340050733
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  • 120
    Electronic Resource
    Electronic Resource
    MRI of acute cerebral infarcts: increased contrast enhancement with continuous infusion of gadolinium (1999)
    Springer
    Neuroradiology 41 (1999), S. 242-248 
    Details
    ISSN: 1432-1920
    Keywords: Key words Cerebral infarcts ; Magnetic resonance imaging ; Contrast enhancement
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We compared contrast enhancement on T1-weighted MRI of acute cerebral infarcts after conventional bolus administration and continuous infusion of gadolinium. We examined 12 patients with a history of acute stroke with contrast-enhanced MRI once a week for a 1 month. Only ischaemic lesions were investigated after cerebral haemorrhage had been excluded by CT. Each MRI study included T2- and proton density-weighted sequences for determination of the size and site of the infarct, immediate postinjection T1-weighted imaging after bolus administration of 0.1 mmol/kg gadolinium-DPTA and delayed T1-weighted imaging after additional continuous infusion of 0.1 mmol/kg over 2 h. A total of 42 MRI studies was performed. In the first week after the onset of stroke, most infarcts (8 of 10) did not enhance after bolus administration, whereas all showed distinct contrast enhancement after the infusion. In the following weeks all but two infarcts showed contrast enhancement after bolus administration; after continuous infusion contrast enhancement could be seen in all cases. While contrast enhancement after bolus administration showed the typical gyriform pattern, enhanced areas were more extensive after the infusion and usually covered the entire infarcted area shown on T2- and proton density-weighted images. We presume that the disturbed blood-brain barrier in ischaemic areas favours delivery of contrast medium to the infarcted tissue if it is offered continuously so that a steady state can develop.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002340050740
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  • 121
    Electronic Resource
    Electronic Resource
    Cortical tubers without other stigmata of tuberous sclerosis: imaging and pathological findings (1999)
    Springer
    Neuroradiology 41 (1999), S. 428-432 
    Details
    ISSN: 1432-1920
    Keywords: Key words Tuberous sclerosis ; Magnetic resonance imaging ; Focal cortical dysplasia ; Cortical dysgenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract There is immense variability in the clinical presentation of tuberous sclerosis and many incomplete forms (formes frustes) exist. To investigate the imaging characteristics of cortical tubers seen in tuberous sclerosis unaccompanied by other stigmata, we reviewed MRI and CT of six patients who met the criteria for a definitive diagnosis of TS, established solely by the presence of a histologically confirmed cortical tuber. Five of the patients had a solitary cortical tuber and the last had three lesions, one of which was resected and confirmed histologically. The other two lesions were included in our study. CT showed five tubers as low density, but three were not identified. No calcified or dense lesions were observed. MRI revealed peripheral components and inner cores of seven cortical tubers in five patients, with differing signal characteristics. The subcortical cores, with T1 and T2 prolongation, were separated from the overlying cortex. Abnormal inhomogeneous high signal was observed in both the cortex and subcortical white matter on proton-density weighted or FLAIR images. A radially orientated white-matter band was observed in one patient, and central depression of the expanded gyri in another. In one patient, a cortical tuber was atypical, with a thick cortex on T1-weighted images and a blurred grey/white matter junction with diffusely increased signal on T2-weighted images. Cortical tubers without other stigmata of tuberous sclerosis are shown to be distinct from focal cortical dysplasia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002340050777
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  • 122
    Electronic Resource
    Electronic Resource
    Cerebellar and basal ganglion involvement in Langerhans cell histiocytosis (1999)
    Springer
    Neuroradiology 41 (1999), S. 443-446 
    Details
    ISSN: 1432-1920
    Keywords: Key words Langerhans cell histiocytosis ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Langerhans cell histiocytosis (LCH) is a disease of unknown cause characterised by proliferation of histiocytic granulomas in tissues; the primary cerebral manifestation is diabetes insipidus caused by hypothalamic infiltration. We present a patient in whom, except for the absence of high signal on T 1 weighting in the posterior pituitary, consistent with central diabetes insipidus, MRI showed no evidence of hypothalamic involvement by histiocytosis, despite the long duration of the disease. However, there was bilateral, symmetrical involvement of the cerebellum and globus pallidus in addition to a calvarial lesion. High signal in the cerebellar white matter on T 2-weighted images may represent demyelination, gliosis and cell loss, as previously reported on pathologic examination.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002340050781
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  • 123
    Electronic Resource
    Electronic Resource
    Successful surgical treatment of a dural arteriovenous fistula at the craniocervical junction with reference to pre- and postoperative MRI (1999)
    Springer
    Neuroradiology 41 (1999), S. 463-467 
    Details
    ISSN: 1432-1920
    Keywords: Key words Dural arteriovenous fistula ; Craniocervical junction ; Magnetic resonance imaging ; Venous hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report a 62-year-old woman who presented with a myelopathy at the lower thoracic level. Left vertebral angiography revealed a dural arteriovenous fistula (DAVF) at the craniocervical junction, draining into an anterior spinal vein. Below the T 7 level, the spinal cord gave high signal on T 2-weighted images and enhanced with Gd-DTPA. The patient was successfully treated by simple clipping of vein draining the DAVF. The abnormal signal intensity and contrast enhancement rapidly regressed, except in the conus medullaris. Regression of the parenchymal abnormality on serial MRI following treatment corresponded closely with postoperative improvement of neurological function.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002340050785
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  • 124
    Electronic Resource
    Electronic Resource
    Die spontane intrazerebrale Blutung aus klinisch- neuroradiologischer Sicht (1999)
    Springer
    Der Radiologe 39 (1999), S. 828-837 
    Details
    ISSN: 1432-2102
    Keywords: Schlüsselwörter Zerebrovaskuläre Erkrankungen ; Intrazerebrale Blutung ; Magnetresonanztomographie ; Computertomographie ; Key Words Cerebrovascular diseases ; Intracerebral hemorrhage ; Magnetic resonance imaging ; Computed tomography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Intracerebral hemorrhage is a common cause of acute neurological deterioration and a frequent indication for emergency neuroimaging. Stroke symptoms are caused in 10 to 15% by intracerebral hemorrhage. It is often not possible to differentiate intracerebral hemorrhage from cerebral ischemia by clinical examination. The therapeutic decision between thrombolysis or conservative therapy is comprised by the etiology. To exclude intracerebral hemorrhage as the cause of clinical symptoms, a CT is usually performed. Localisation and extension of the acute intracerebral hemorrhage are easy to detect. Subacute and chronic intracerebral hemorrhage are better delineated with magnetic resonance imaging. The different signal of the hemorrhage can be used for the age of the intracerebral hemorrhage. The cause of a non-traumatic intracerebral hemorrhage is in over 60% hypertony, less frequent alcoholism, malformation, or amyloid angiopathy. Uncommon causes of hemorrhage are head trauma, blood dyscrasia, tumor or venous thrombosis. Non-traumatic intracerebral hemorrhage are most common in patients between 50 and 70 years. In younger patients a malformation should be excluded with a cerebral angiography. Intracerebral hemorrhages are usually conservatively treated, in some cases an operative decompression is performed.
    Notes: Zusammenfassung Die intrazerebrale Blutung ist eine häufige Ursache akut auftretender neurologischer Symptome und führt oft zu einer notfallmäßigen neuroradiologischen Untersuchung. Etwa 15% der „Schlaganfälle” sind auf eine intrazerebrale Blutung zurückzuführen. Intrazerebrale Blutungen sind klinisch oft nicht von ischämischen Infarkten zu unterscheiden. Eine Computertomographie ist zur Zeit für die Diagnosesicherung – und damit auch zur weiterführenden Therapie – unerläßlich. Ausdehnung und Lokalisation der akuten intrazerebralen Blutung können damit schnell und sicher erfaßt werden. Subakute und chronische Blutungen sind dagegen verläßlicher mit der Magnetresonanztomographie nachweisbar. Aus der unterschiedlichen Signalgebung in den verschiedenen MR-Sequenzen kann auf das Alter der Blutung geschlossen werden. Die Ursache einer nicht-traumatischen intrazerebralen Blutung ist in über 60% der Fälle eine Hypertonie, weniger häufig die Folgen des Alkoholismus, Gefäßfehlbildungen oder die Amyloidangiopathie. Seltener sind Blutgerinnungsstörungen, Traumen, Tumoren, Venenthrombosen oder Intoxikationen die Ursachen einer intrazerebralen Blutung. Nicht-traumatische intrazerebrale Blutungen treten am häufigsten zwischen dem 5.–7. Lebensjahrzehnt auf. Bei jüngeren Patienten sind vor allem Gefäßfehlbildungen als Ursache zu berücksichtigen. Insbesondere bei jüngeren Patienten sollte zur ätiopathogentischen Klärung eine zerebrale Angiographie durchgeführt werden. Spontane intrazerebrale Blutungen werden in der Regel konservativ behandelt, außer man verspricht sich von der operativen Dekompression eine Verbesserung des klinischen Zustandes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001170050719
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    Wertigkeit der Magnetresonanztomographie in der Diagnostik der Neurosarkoidose (1999)
    Springer
    Der Radiologe 39 (1999), S. 889-893 
    Details
    ISSN: 1432-2102
    Keywords: Schlüsselwörter Sarkoidose ; Neurosarkoidose ; Magnetresonanztomographie ; Key words Sarcoidosis ; Neurosarcoidosis ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Neurological involvement is a significant cause of morbidity and mortality in patients with sarcoidosis. The aim of this study was to evaluate the role of magnetic resonance imaging (MRI) in the diagnosis of patients with neurosarcoidosis. The MRI brain scans of 22 patients with sarcoidosis were retrospectively reviewed, along with the clinical information provided in the request form. All patients had signs and symptoms referable to the head and were examined with gadolinium enhancement. Cranial (facial) nerve paralysis was the most common clinical manifestation identified in 10 patients. A wide spectrum of MR findings was noted: periventricular and white matter lesions on T2 W spin echo images, mimicking multiple sclerosis (46%); multiple supratentorial and infratentorial brain lesions, mimicking metastases (36%); solitary intraaxial mass, mimicking high-grade astrocytoma (9%); solitary extraaxial mass, mimicking meningioma (5%); leptomeningeal enhancement (36%). The diagnosis of neurosarcoidosis is often difficult, particularly so in patients who lack either pulmonary or systemic manifestations of sarcoidosis. MRI shows a wide spectrum of brain abnormalities associated with neurosarcoidosis. These findings, however, are not specific for sarcoidosis and one must consider appropriate clinical circumstances in arriving at the correct diagnosis. In selected cases with isolated brain involvement, meningeal or cerebral biopsy may be required.
    Notes: Zusammenfassung Klinische Untersuchungen an Patienten mit systemischer Sarkoidose sprechen in 5%, Autopsieberichte in 25% für eine Beteiligung des Zentralnervensystems. Ziel der Studie ist eine Beurteilung der Beitrags der Magnetresonanztomographie (MRT) in der Diagnostik der Neurosarkoidose. Die MR-Tomogramme von 22 Patienten mit gesicherter Sarkoidose und neurologischer Symptomatik wurden retrospektiv ausgewertet. Häufigstes klinisches Symptom der Neurosarkoidose war eine Fazialisparese (10 Patienten). MR-tomographisch konnte eine Vielzahl verschiedener Befunde erhoben werden: periventrikuläre und Marklagerläsionen in T2-gewichteten Bildern in 46%, multiple bzw. miliare supratentorielle und infratentorielle Läsionen in 36%, solitäre intraaxiale Raumforderungen in 9%, solitäre extraaxiale Raumforderungen in 5% und meningeale Kontrastmittelanreicherung (nodulär oder diffus) in 36%. Schlußfolgerung: Die MR-tomographischen Befunde bei Neurosarkoidose sind oft wenig spezifisch. Die Diagnose wird meist bei gleichzeitigem Nachweis sarkoidosetypischer Granulome in anderen Organen gestellt, eine isolierte zerebrale Manifestation kann erhebliche diagnostische Schwierigkeiten bereiten. Die Neurosarkoidose sollte bei unklaren zerebralen Symptomen und Befunden stets in die Differentialdiagnose einbezogen werden, weil sie behandelbar ist.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001170050727
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  • 126
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    Rheumatische Erkrankungen des Sprunggelenkes und der Fußwurzel (1999)
    Springer
    Der Radiologe 39 (1999), S. 60-67 
    Details
    ISSN: 1432-2102
    Keywords: Schlüsselwörter Kalkaneus ; Talus ; Gelenkinstabilität ; Radiologische Diagnostik ; Ultraschall ; Magnetresonanztomographie ; Sprunggelenk ; Synovialmembran ; Arthritis ; Diagnose ; Bildgebende Diagnostik ; Key words Calcaneus ; Joint instability ; Plain film radiography ; Ultrasonography ; Magnetic resonance imaging ; Subtalar joint ; Ankle joint ; Arthritis ; Synovial membrane ; Synovitis ; Diagnosis ; Differential ; Diagnostic imaging ; Rheumatic disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Diseases of the hindfoot are associated with considerable functional impairment and therefore may hamper patients’ movements during gait considerably. Because of biomechanical overload, articular structures, tendons and ligaments are prone to early degenerative changes during the course of rheumatic diseases as visible with plain film radiography, sonography (US), or magnetic resonance imaging (MRI). Findings may occur as arthritis of major joints or in the form of fibroostitis and bursitis of the os calcis. Despite the progressive course of rheumatic diseases and characteristic imaging findings, high variability of X-ray signs may occur. Plain film radiograms and high-resolution ultrasonography play a key role in imaging rheumatic diseases of the hindfoot. MRI supports imaging diagnosis in selected cases. The principal goals of diagnostic imaging are precise and reproducible documentation of morphologic abnormalities and differentiated analysis for planning proper conservative or surgical treatment.
    Notes: Zusammenfassung Erkrankungen des Sprunggelenks und der Fußwurzel sind, da mit einer deutlichen Einschränkung der Beweglichkeit dieser Region einhergehend, für den Patienten meist sehr belastend. Bei rheumatischen Krankheitsbildern steht neben der Funktionseinschränkung vor allem in späteren Stadien die Destruktion biomechanisch stark beanspruchter Strukturen (hyaliner Knorpel, subchondraler Knochen, Bänder und Sehnen) im Vordergrund des klinischen wie auch des radiologischen Bildes. Grundsätzlich sind Arthritiden der großen Gelenke und die Calcaneopathia rheumatica zu beobachten. Trotz des meist stadienhaften Verlaufes mit charakteristischem Befallsmuster ist die bildgebende Diagnostik wegen der großen Formvariabilität der unterschiedlich ausgeprägten Veränderungen oft schwierig. Zusätzlich zu nativröntgenologischen Aufnahmen gehören die hochauflösende Sonographie, ergänzt durch die MRT, mit denen Gelenke und Sehnen direkt darstellbar sind, heute zur Standarddiagnostik. Ziel der Diagnostik ist einerseits die präzise reproduzierbare Dokumentation morphologischer Veränderungen zur Verlaufskontrolle, andererseits ihre möglichst differenzierte Analyse zur Einleitung adäquater konservativer oder operativer Therapiemaßnahmen, um Patienten zu einer aktiveren Lebensweise verhelfen zu können.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001170050478
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    Das kernspintomographische Erscheinungsbild der spontanen intrazerebralen Blutung (1999)
    Springer
    Der Radiologe 39 (1999), S. 838-846 
    Details
    ISSN: 1432-2102
    Keywords: Schlüsselwörter Intrazerebrale Blutung ; Kernspintomographie ; MR-Angiographie ; Key words Intracerebral hematoma ; Magnetic resonance imaging ; Magnetic resonance angiography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary We review the signal characteristics of intracerebral hematomas (ICH) on magnetic resonance imaging (MRI), with special emphasis on the diagnosis of intracerebral hemorrhage within the first hours after stroke. The detection of peracute ICH was evaluated in 42 patients of a prospective, MR randomized stroke trial. These patients underwent a protocol of T1 and T2 weighted sequences, diffusion weigthed sequences and MR – angiography within 6 hours after onset of acute hemiparesis. The signal behaviour of ICH in any stage after bleeding was additionally reviewed in a retrospective series of 63 patients, who were submitted for MRI over a 12 months period because of known ICH. MRI correctly identified 4 hyperacute ICH in the prospective group and 4 hyperacute ICH in the retrospective group. These ICHs had high signal on T2 weighted images, were isointense in T1 weighted images and had signal voids on the diffusion weighted sequences. The signal intensities of acute, subacute and chronic ICHs correlated to previous experiences as reported in the literature. In conclusion, MRI reliably identified all hematomas even in the hyperacute stage. Diffusion weighted images were most sensitive to the presence of deoxyhemoglobine and helpful for the differentiation and characterization of acute ischemia. Therefore, MRI at 1.5 T can be employed as an alternative to CT for the emergency diagnosis of acute stroke.
    Notes: Zusammenfassung In dieser Übersicht wird das kernspintomographische (KST) Erscheinungsbild der intrazerebralen Blutung (IZB) anhand eigener Erfahrungen und der Literatur diskutiert. Besonderes Gewicht wurde auf den KST Nachweis der hyperakuten IZB innerhalb der ersten Stunden gelegt. Es wurden einerseits die Befunde von 42 Patienten einer prospektiven, KST randomisierten Schlaganfallstudie ausgewertet, bei denen die KST als Erstuntersuchung innerhalb von 6 Stunden durchgeführt worden war. Andererseits werteten wir retrospektiv jene KST Untersuchungen aus, die im Jahr 1998 unter der Fragestellung einer IZB (n=63) erfolgten. Die KST erwies sich als sensitiv im Nachweis auch der hyperakuten IZB. Es wurden weder falsch-negative noch falsch-positive Befunde erhoben. Die hyperakute IZB kommt in der T2-Gewichtung hyperintens und in der T1-Gewichtung isointens zur Darstellung. Auf den diffusionsgewichteten Sequenzen führen minimale Deoxyhämoglobinkonzentrationen bereits in dieser Phase zu Signalauslöschungen. Das Erscheinungsbild der akuten, subakuten und chronischen IZB entsprach dem, in der Literatur mitgeteilten, Signalverhalten. Zusammenfassend waren alle IZB, unabhängig vom Stadium in der KST nachweisbar. Die Diffusionsgewichtung war in der hyperakuten Blutungsdiagnose und deren Abgrenzung von der akuten Ischämie hilfreich. Zumindest bei 1,5T erscheint die KST somit für die Diagnostik des akuten Schlaganfalls geeignet und sollte, da Ischämien besser als mit der Computertomographie charakterisiert werden können, für die Akutdiagnostik verfügbar gemacht werden.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001170050720
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    Vergleich der Wertigkeit der Computertomographie und der Magnetresonanztomographie in der Diagnostik der akuten intrazerebralen Blutung (1999)
    Springer
    Der Radiologe 39 (1999), S. 855-859 
    Details
    ISSN: 1432-2102
    Keywords: Schlüsselwörter Schlaganfall ; Intrazerebrale Blutung ; Magnetresonanztomographie ; Computertomographie ; Ratten ; Key words Cerebrovascular diseases ; Intracerebral hemorrhage ; Magnetic resonance imaging ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Background and Purpose: Stroke symptoms are caused in 10 to 15% by intracerebral hemorrhage. From the clinical examination it is often impossible to differentiate intracerebral hemorrhage from cerebral ischemia. To exclude intracerebral hemorrhage as the cause of clinical symptoms a CT is usually performed. The aim of our study was a direct comparison of the sensitivity of Computed Tomography and MRI using different MR sequences for the detection of acute intracerebral hemorrhage. Methods: In 8 male Wistar rats intracerebral hemorrhage was induced by infusion of collagenase into the caudate nucleus. After 1hour the brains were subsequently imaged with CT and MRI using T2- and T1-weighted Spin Echo sequences, diffusion-weighted sequences, T2*-weighted gradient echo sequences and FLAIR-sequences. Visibility of the intracerebral hemorrhage was examined using a scoring system from 1=not visible to 5=excellent visible. Finally, the intracerebral hemorrhage was verified by histological staining. Results: In all animals, intracerebral hemorrhage was visible in T2*-weighted gradient echo and diffusion weighted MR images 1 h after infusion of collagenase. T2- and PD-weighted SE images were positive in 7/8 rats. T1-weighted images revealed signal changes in 5/8 rats, and FLAIR sequence was positive in 8/8 rats. In CT intracerebral hemorrhage was only visible in 3/8 rats. When measuring the increase of Hounsfield units within the suspected hemisphere we saw a mean increase of 7% compared to the normal hemisphere in 3/8 rats. Conclusions: In this animal model, T2*-weighted magnetic resonance imaging proved to be the most sensitive imaging modality in the detection of acute intracerebral hemorrhage and is by far more sensitive than CT.
    Notes: Zusammenfassung Hintergrund und Ziel: Die Symptome eines Schlaganfalls sind in 10 bis 15% durch eine intrazerebrale Blutung verursacht. Oft ist es in der klinischen Untersuchung nicht möglich, zwischen einer intrazerebralen Blutung und einer zerebralen Ischämie zu differenzieren. Um eine intrazerebrale Blutung bei Schlaganfallsymptomatik auszuschließen, wird in der Regel zuerst eine Computertomographie (CT) durchgeführt. Ziel der vorliegenden Studie ist ein direkter Vergleich der Sensitivität der CT mit verschiedenen magnetresonanztomographischen (MR) Sequenzen in der Diagnostik der akuten intrazerebralen Blutung. Material und Methoden: Durch intrazerebrale Applikation von Kollagenase wurde bei 8 männlichen Wistar-Ratten eine intrazerebrale Blutung im linken Nucleus caudatus induziert. Nach einer Stunde wurden die Gehirne zunächst im CT und direkt anschließend in einem klinischen MR-Tomographen unter Verwendung von Protonendiche-, T2- und T1-gewichteten Spinechosequenzen, T2*-gewichten Gradientenechosequenzen, FLAIR-Sequenzen sowie diffusions- und perfusionsgewichteten Gradientenechosequenzen untersucht. Die Visibilität der Blutung wurde anhand einer Skala von 1 (=nicht sichtbar) bis 5 (=klar sichtbar) bewertet. Die Größe der Blutungsherde wurde für jede Untersuchungstechnik bestimmt und mit der Histologie verglichen. Ergebnisse: Bei allen Tieren konnte die Blutung in den T2*-gewichteten Gradientenecho-, FLAIR- sowie diffusionsgewichteten MRT-Bildern 1 h nach Kollagenaseinfusion erkannt werden. Auch in den T2- und Protonendichte-gewichteten Bildern konnte die Blutung bei 8/8 Ratten erkannt werden, wohingegen sie in den T1-gewichteten Aufnahmen nur bei 5/8 Ratten zu erkennen war. In der CT war die intrazerebrale Blutung nur bei 3/8 Ratten sichtbar, wobei bei diesen Tieren eine Zunahme der Dichte in Hounsfield-Einheiten (HE) in der Läsion um 15% auftrat. Schlußfolgerung: In dem verwendeten Tiermodell erwiesen sich T2*-und diffusionsgewichtete Aufnahmen sowie FLAIR-Sequenzen als sehr sensitive Methode in der Diagnostik der akuten intrazerebralen Blutung. Sie waren hierbei sensitiver als die CT. Deshalb sollte ein MR-tomographisches Untersuchungsprotokoll zur Diagnostik des akuten Schlaganfalls T2*- und diffusionsgewichtete Sequenzen beinhalten. Hierdurch gelingt eine rasche Unterscheidung zwischen der akuten intrazerebralen Blutung und der Frühphase der zerebralen Ischämie.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001170050722
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    Motor-learning-related changes in piano players and non-musicians revealed by functional magnetic-resonance signals (1999)
    Springer
    Experimental brain research 125 (1999), S. 417-425 
    Details
    ISSN: 1432-1106
    Keywords: Key words Motor learning ; Motor cortex ; Magnetic resonance imaging ; Musicians ; Hand motor skill
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In this study, we investigated blood-flow-related magnetic-resonance (MR) signal changes and the time course underlying short-term motor learning of the dominant right hand in ten piano players (PPs) and 23 non-musicians (NMs), using a complex finger-tapping task. The activation patterns were analyzed for selected regions of interest (ROIs) within the two examined groups and were related to the subjects’ performance. A functional learning profile, based on the regional blood-oxygenation-level-dependent (BOLD) signal changes, was assessed in both groups. All subjects achieved significant increases in tapping frequency during the training session of 35 min in the scanner. PPs, however, performed significantly better than NMs and showed increasing activation in the contralateral primary motor cortex throughout motor learning in the scanner. At the same time, involvement of secondary motor areas, such as bilateral supplementary motor area, premotor, and cerebellar areas, diminished relative to the NMs throughout the training session. Extended activation of primary and secondary motor areas in the initial training stage (7–14 min) and rapid attenuation were the main functional patterns underlying short-term learning in the NM group; attenuation was particularly marked in the primary motor cortices as compared with the PPs. When tapping of the rehearsed sequence was performed with the left hand, transfer effects of motor learning were evident in both groups. Involvement of all relevant motor components was smaller than after initial training with the right hand. Ipsilateral premotor and primary motor contributions, however, showed slight increases of activation, indicating that dominant cortices influence complex sequence learning of the non-dominant hand. In summary, the involvement of primary and secondary motor cortices in motor learning is dependent on experience. Interhemispheric transfer effects are present.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050698
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    Pseudomyxoma retroperitonei (1999)
    Springer
    European radiology 9 (1999), S. 457-459 
    Details
    ISSN: 1432-1084
    Keywords: Key words: Retroperitoneal neoplasms ; Retroperitoneal space ; Computed tomography ; Magnetic resonance imaging ; Ultrasonography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. We report a rare case of pseudomyxoma retroperitonei in a 58-year-old woman with a past history of severe appendicitis. The imaging showed a multicystic mass similar to pseudomyxoma peritonei, but the tumor was located in the retroperitoneal space.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003300050692
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    Depression in Parkinson’s disease: brainstem midline alteration on transcranial sonography and magnetic resonance imaging (1999)
    Springer
    Journal of neurology 246 (1999), S. 1186-1193 
    Details
    ISSN: 1432-1459
    Keywords: Key words Parkinson’s disease ; Depression ; Brainstem midline ; changes ; Transcranial sonography ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Recent studies using transcranial sonography (TCS) have provided evidence of alterations in the mesencephalic midline structures in patients with unipolar depression and depression in Parkinson’s disease (PD), suggesting an involvement of the basal limbic system in primary and secondary mood disorders. This study tested the hypothesis of brainstem midline abnormality in depression and investigated 31 PD patients by magnetic resonance imaging (MRI) and TCS. Signal intensity of the pontine and mesencephalic brainstem midline was rated on T2-weighted images and measured by relaxometry. In addition, two blinded investigators assessed the echogenicity of the brainstem midline by TCS. The severity of motor symptoms and depression were graded independently using standard research scales. Rating of signal intensity and T2 relaxometry of the pontomesencephalic midline structures revealed significant difference between depressed and nondepressed PD patients (P 〈 0.05). This corresponded to a significant reduction in mesencephalic midline echogenicity of depressed PD patients on TCS images. No correlation was found between raphe signal intensity, T2 relaxation times, or TCS echogenicity and the severity of motor symptoms or depression. This study is the first to show changes in signal intensity and T2 relaxation time of the pontomesencephalic midline structures on MRI in depressed PD patients confirming previous TCS findings. As these midline structures comprise fiber tracts and nuclei of the basal limbic system, the findings may support the hypothesis of an alteration in the basal limbic system in mood disorders.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004150050541
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  • 132
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    Magnetic resonance imaging outcome of new enhancing lesions in relapsing-remitting multiple sclerosis patients treated with interferon β1a (1999)
    Springer
    Journal of neurology 246 (1999), S. 443-448 
    Details
    ISSN: 1432-1459
    Keywords: Key words Multiple sclerosis ; Magnetic resonance imaging ; Enhancing lesions ; Interferon-β1a
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. We investigated whether interferon-β1a modifies the course of new enhancing lesions in relapsing-remitting multiple sclerosis. Sixty-eight patients were studied by monthly magnetic resonance imaging (MRI) in a pretest-posttest design including 6 months of observation and 6 months of treatment. We examined the course of new Gd-enhancing lesions on two consecutive scans during observation and during treatment. Lesions detected during treatment were also analyzed by MRI 1 year later for persistence of enhancement, persistence of T2 hyperintensity, development of T1 hypointensity, or disappearance. Among the enhancing lesions detected by observation and treatment MRI, respectively, Gd-enhancement persisted at 2 months in 20% and 3% (P 〈 0.001), T2 hyperintensity persisted in 86% and 63% (P 〈 0.03), and T1 hypointensity developed in 49% and 15% (P 〈 0.01). Progression to T1 hypointensity was significantly more frequent in larger lesions during both the observation and treatment periods (P 〈 0.01). No reenhancement of plaques was present at 1-year follow-up; a further reduction in T2 hyperintensity (63% vs. 39%) was observed while T1 hypointensity remained unchanged. Both the duration of Gd enhancement and the short-term MRI course of new enhancing lesions benefited by treatment with recombinant interferon-β1a treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004150050380
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    Multiple sclerosis: interobserver agreement in reporting active lesions on serial brain MRI using conventional spin echo, fast spin echo, fast fluid-attenuated inversion recovery and post-contrast T1-weighted images (1999)
    Springer
    Journal of neurology 246 (1999), S. 920-925 
    Details
    ISSN: 1432-1459
    Keywords: Key words Multiple sclerosis ; Magnetic resonance imaging ; Disease activity ; Fast spin echo ; Fast fluid-attenuated inversion ; recovery ; Reproducibility
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous studies have addressed the question of the precision in assessing multiple sclerosis (MS) activity by counting enhancing lesions on gadolinium enhanced brain magnetic resonance imaging (MRI). However, counting the active lesions on serial unenhanced MRI obtained by various pulse sequences has not been yet considered. We compared the interobserver levels of agreement in reporting active MS lesions on serial enhanced and unenhanced MRI to assess whether the use of various unenhanced techniques may change the degree of interobserver measurement reproducibility. Dual-echo conventional spin echo (CSE), dual-echo fast spin echo (FSE), fast fluid-attenuated inversion recovery (FLAIR) and Gd-enhanced T1-weighted brain MRI were obtained from five MS patients at baseline and monthly for 2 months. Six experienced observers independently identified and counted active MS lesions on the two follow-up MRI scans. Active lesions were considered to be all the enhancing lesions and any new or enlarging lesion on enhanced and unenhanced scans. Interobserver levels of agreement were calculated by weighted κ values. Very good agreement was reached only for counting total and new Gd-enhancing lesions. Good agreement was achieved for counting new lesions on the three unenhanced techniques, whereas the agreement for counting enlarging lesions was poor with all the MRI techniques. The level of agreement was significantly heterogeneous for various MRI techniques but not for various lesion sites. These results confirm that counting enhancing lesions is the most reliable method for assessing MS activity, but the use of any of the available unenhanced MRI techniques did not result in different levels of interobserver agreement when reporting new and enlarging MS lesions on serial scans.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004150050483
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    Detection of anterior horn lesions by MRI in central European tick-borne encephalomyelitis (1999)
    Springer
    Journal of neurology 246 (1999), S. 1169-1171 
    Details
    ISSN: 1432-1459
    Keywords: Key words European tick-borne encephalitis ; Magnetic resonance imaging ; Central nervous system
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report a case of central European tick-borne encephalitis with cervical myelitis presenting clinically as a lower motor neuron syndrome of the upper limbs with proximal asymmetrical pareses and atrophies. There were no sensory deficits nor signs of lesions of the spinal pathways or signs of encephalitis or meningitis. The affected motor fibers of the upper limbs were electrically inexcitable, but sensory findings were normal. Electromyography of the paralyzed muscles revealed pathological denervation activity without voluntary activation. The initial magnetic resonance imaging (MRI) showed a large hyperdense lesion in the anterior part of the cervical cord from C3 to T1. Despite the fact that MRI changes disappeared completely within 6 weeks the patient showed only little improvement in the paralyzed muscles after 6 months. To our knowledge, these MRI changes in patients with tick-borne encephalitis, consistent with an isolated anterior horn lesion, have never been reported previously. The course may have been aggravated by an initial antibiotic treatment with cephalosporins.
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    URL: http://dx.doi.org/10.1007/s004150050537
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    Bilateral reductions of hippocampal volume, glucose metabolism, and Wada hemispheric memory performance are related to the duration of mesial temporal lobe epilepsy (1999)
    Springer
    Journal of neurology 246 (1999), S. 926-933 
    Details
    ISSN: 1432-1459
    Keywords: Key words Temporal lobe epilepsy ; Hippocampus ; Magnetic resonance imaging ; Fluoro-2-deoxy-d-glucose positron-emission tomography ; Wada test
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In refractory temporal lobe epilepsy (TLE) temporal lobe structures and functions are continuously or intermittently affected by abnormal brain electrical events, noxious neurochemical agents, and metabolic disturbances. There is conflicting evidence regarding the relationship between the duration of refractory mesial TLE and quantitative measures of temporal lobe functions and volumes of the hippocampi. Twenty patients (aged 28 ± 7 years, 14 males) with an initial precipitating injury before the age of 5 years were subjected to high-resolution magnetic resonance imaging, fluoro-2-deoxy-d-glucose positron-emission tomography (PET), and the Wada test. We investigated whether the duration of unilateral refractory TLE (12 left, 8 right) affects hippocampal volume, glucose metabolism, or Wada hemispheric memory performance. Ipsilateral to the epileptogenic zone the hippocampal volume, metabolism, and Wada hemispheric memory performance were reduced compared to the corresponding contralateral measures. The duration of epilepsy controlled for age at investigation, side of seizure origin, underlying cause, and sex were negatively correlated with ipsi- and contralateral hippocampal volume, hippocampal metabolism, and Wada hemispheric memory performance. Moreover, ipsilateral Wada hemispheric memory performance and contralateral hippocampal glucose metabolism were correlated with the frequency of habitual seizures. Refractory TLE seems to be associated with a slow but ongoing bilateral temporal lobe damage. These cross-sectional results require verification by longitudinal studies carried out over a period of more than two decades.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004150050484
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  • 136
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    Electronic Resource
    Disease activity in multiple sclerosis studied by weekly triple-dose magnetic resonance imaging (1999)
    Springer
    Journal of neurology 246 (1999), S. 689-692 
    Details
    ISSN: 1432-1459
    Keywords: Key words Multiple sclerosis ; Magnetic resonance imaging ; Gadolinium-DTPA ; Triple dose ; Blood-brain barrier
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study assessed whether dysfunction of the blood-brain barrier is an obligatory early event in lesion formation in multiple sclerosis. Dual-echo and T1-weighted magnetic resonance imaging after the injection of a triple dose (0.3 mmol/kg) of gadolinium-DTPA were obtained from ten patients with relapsing-remitting multiple sclerosis every week for 2 months. Sixty-four newly active lesions were detected by the two techniques. All the 44 new lesions seen on dual-echo scans enhanced during the early phases of their formation: 33 at their first appearance, 10 1 week before their appearance on the dual-echo scans, and one the week thereafter. When the every fourth (monthly) scan was analyzed, a total of 55 newly active lesions were detected (i.e., 14% active lesions would have been missed compared to the number found on weekly scanning). Thirty-one of them were detected by both dual-echo and triple-dose scans, 15 only by enhanced scans, and nine only by dual-echo scans. This study confirms that with highly sensitive magnetic resonance imaging techniques dysfunction of the blood-brain barrier is an obligatory early event in new lesion formation in relapsing-remitting multiple sclerosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004150050433
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  • 137
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    Electronic Resource
    Contrast agents for magnetic resonance angiographic applications: 1H and 17O NMR relaxometric investigations on two gadolinium(III) DTPA-like chelates endowed with high binding affinity to human serum albumin (1999)
    Springer
    JBIC 4 (1999), S. 766-774 
    Details
    ISSN: 1432-1327
    Keywords: Gadolinium(III) complexes ; Contrast agents ; Magnetic resonance imaging ; Human serum albumin ; Proton relaxation enhancement
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: N,N′,N″,N‴ -pentaacetic acid) bearing different substituents for binding to human serum albumin (HSA) are compared. In spite of the structural differences of the recognition synthon and of the residual electric charge, the two chelates display an analogous binding affinity for the serum protein. Upon formation of the adducts with HSA, the exchange rates of the coordinated water appear slowed down by an amount corresponding to ca. 50% of the rates found for the free complexes. The relaxivity of [Gd(BOM)3DTPA (H2O)]2 −  is significantly higher than that of MS-325 either in the free complex or in the macromolecular adduct. Finally, the effect of pH on the stability of the HSA adducts and on the values of their relaxivities has been investigated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s007750050349
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  • 138
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    Electronic Resource
    Past, present and future of pediatric neuroradiology (1999)
    Springer
    Child's nervous system 15 (1999), S. 624-634 
    Details
    ISSN: 1433-0350
    Keywords: Key words Brain imaging ; Magnetic resonance imaging ; brain ; Magnetic resonance spectroscopy ; brain ; Computed tomography ; brain ; Diffusion imaging ; brain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The last century has seen the evolution of neuroimaging from nonexistent to a group of techniques that, in our eyes, appears to be highly sophisticated. The rapidity of advancement in imaging has been concentrated in the last quarter century. There is no reason to expect this continual forward expansion of neuroradiology to abate; rather it seems likely that it will continue to increase at an even faster rate. The near future is one of refinement in imaging, faster and higher resolution as well as a much greater emphasis on physiology and biochemistry.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003810050451
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  • 139
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    Electronic Resource
    Dermal sinus and intramedullary spinal cord abscess Report of two cases and review of the literature (1999)
    Springer
    Child's nervous system 15 (1999), S. 202-207 
    Details
    ISSN: 1433-0350
    Keywords: Key words Abscess ; Spinal cord ; Dermal sinus ; Epidermoid ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Intramedullary abscesses of the spinal cord are uncommon. Most of them occur in association with heart, pulmonary or urogenital infections. We report two cases of intramedullary spinal cord abscesses secondary to congenital dermal sinus. Only 14 cases of such an association have previously been reported. In our cases, dermal sinus was associated with an epidermoid tumour. The clinical presentation, pathogenesis, magnetic resonance imaging findings, surgical management and outcome are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003810050370
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  • 140
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    Electronic Resource
    Giant posterior fossa teratoma (1999)
    Springer
    Child's nervous system 15 (1999), S. 359-361 
    Details
    ISSN: 1433-0350
    Keywords: Key words Computerized tomography ; Intracranial tumor ; Magnetic resonance imaging ; Posterior fossa ; Teratoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In this study we report a rare case of a giant midline posterior fossa teratoma; its clinical presentation, radiological appearance, treatment and outcome, with an extensive review of the literature.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003810050413
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  • 141
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    Electronic Resource
    Magnetic resonance imaging features of allografts (1999)
    Springer
    Skeletal radiology 28 (1999), S. 383-389 
    Details
    ISSN: 1432-2161
    Keywords: Key words Allografts ; Osteoarticular ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Objective. To investigate the magnetic resonance imaging (MRI) features of allografts at various time intervals after surgery in patients with osteoarticular allografts. Design and patients. Sixteen patients who were treated with osteoarticular allografts and who were followed over time with MRI studies as part of their long-term follow-up were retrospectively selected for this study. T1-weighted images were obtained both before and after gadolinium administration along with T2-weighted images. All images were reviewed by an experienced musculoseletal radiologist, with two other experienced radiologists used for consultation. Imaging studies were organized into three groups for ease of discussion: early postoperative period (2 days to 2 months), intermediate postoperative period (3 months to 2 years), and late postoperative period (greater than 2 years). Results. In the early postoperative period, no gadolinium enhancement of the allograft was visible in any of the MR images. A linear, thin layer of periosteal and endosteal tissue enhancement along the margin of the allograft was visible in images obtained at 3–4 months. This enhancement apeared gradually to increase in images from later periods, and appears to have stabilized in the images obtained approximately 2–3 years after allograft placement. The endosteal enhancement diminished after several years, with examinations conducted between 6 and 8 years following surgery showing minimal endosteal enhancement. However, focal enhancement was noted adjacent to areas of pressure erosion or degenerative cysts. All the cases showed inhomogeneity in the marrow signal (scattered low signal foci on T1 with corresponding bright signal on T2), and a diffuse, inhomogeneous marrow enhancement later on. Conclusion. We have characterized the basic MRI features of osteoarticular allografts in 16 patients who underwent imaging studies at various time points as part of routine follow-up. We believe that the endosteal and periosteal enhancement observed on MRI during the first few months to 2 years following surgery represents vascular ingrowth and early skeletal repair. The zone of periosteal enhancement could also include the new bone laid on the surface of the allograft through which the soft tissues bind to the cortex. The exact reason for the inhomogeneity in the marrow signal, and the diffuse, inhomogeneous marrow enhancement is not clear. This may represent saponified and/or necrotic marrow fat interspersed with the fibrovascular tissue. The features noted here should provide radiologists with useful information regarding imaging characteristics they can expect to see in other allograft replacement patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002560050534
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  • 142
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    Electronic Resource
    The plantar fasciotomy: MR imaging findings in asymptomatic volunteers (1999)
    Springer
    Skeletal radiology 28 (1999), S. 447-452 
    Details
    ISSN: 1432-2161
    Keywords: Key words Plantar fascia ; aponeurosis ; Fasciitis ; Fasciotomy ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Objective. To determine the postoperative appearance of the plantar fascia on MR imaging after a fasciotomy has been performed, and to compare the postsurgical appearance of the fascia after an open and endoscopic procedure.〈@head-abs-p1.lf〉Design and patients. Fifteen asymptomatic volunteers (12 women, 3 men; age range 22–49 years, mean age 33 years) with prior fasciotomies for treatment of longstanding plantar fasciitis were studied. Fourteen volunteers had a unilateral release and one volunteer had bilateral releases, allowing for assessment of 16 ankles. Eight fasciotomies were performed through an open incision and eight were performed endoscopically. The average time between surgery and imaging was 24 months (range 11–46 months). The site of surgery was established from the operative reports. Proton density (PD)-weighted and T2-weighted images in three orthogonal planes were obtained on a 1.5-T magnet. In eight studies, T1-weighted sagittal and STIR sagittal images were included. The fascia in each ankle was assessed for morphology and signal intensity. Perifascial soft tissues and bone marrow were assessed for edema. Preoperative MR studies were available in five volunteers.〈@head-abs-p1.lf〉Results. There was no apparent difference in the postoperative appearance of the ankle after an open or endoscopic procedure except for scar formation in the subcutaneous fat which was common after an open procedure (P〈0.05). Three ankles had a gap in the fascia (one open, two endoscopic). The plantar fascia measured a mean of 7.0 mm (range 5–10 mm) at the fasciotomy, and 8.3 mm (range 6–12 mm) at the enthesis. At the fasciotomy, 11 of 13 ankles had an indistinct deep contour and 9 of 13 had an indistinct superficial contour. At the enthesis, 13 of 16 ankles had an indistinct deep contour and 6 of 16 had an indistinct superficial contour. Compared with preoperative MR studies there was an average reduction in the fascial thickness at the enthesis of 14% (range 9–20%), but the thickness at the fasciotomy nearly doubled. No edema was evident in the fascia, perifascial tissues, deep plantar muscles, or calcaneal bone marrow.〈@head-abs-p1.lf〉Conclusions. The average thickness of the plantar fascia in asymptomatic volunteers after surgery is nearly 2–3 times that of normal. While there is increased thickness at the site of surgery, the changes in morphology and signal intensity were most prominent at the enthesis. The key observation was absence of edema in the fascia and perifascial soft tissues. This baseline information may be of value when assessing MR studies of symptomatic patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002560050544
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  • 143
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    Electronic Resource
    Masses and pseudomasses of the hand and wrist: MR findings in 134 cases (1999)
    Springer
    Skeletal radiology 28 (1999), S. 498-507 
    Details
    ISSN: 1432-2161
    Keywords: Key words Hand ; Wrist ; Magnetic resonance imaging ; Soft tissue mass ; Neoplasm ; Tumour ; Tendon diseases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract   Objective. To assess the utility of magnetic resonance imaging (MRI) in the investigation of palpable masses in the hand or wrist.〈@head-abs-p1.lf〉Design and patients. We retrospectively reviewed the MRI examinations and case records of 134 patients referred because of a palpable mass in the hand or wrist. MRI was performed on a 1.0 T magnet using an extremity coil. Intravenous gadolinium-DTPA was injected when considered appropriate.〈@head-abs-p1.lf〉Results and conclusions. MRI demonstrated the cause of the palpable mass in 126 cases (94.02%). Soft tissue neoplasms were found in 34 cases (25.37%). The majority were benign and included giant cell tumours of tendon sheath, lipomas and hemangiomas and had a characteristic appearance. There were three malignant tumours (myxoid liposarcoma, malignant fibroushistiocytoma and rhabdomyosarcoma). Ganglia were found in 36 cases (26.86%) and non-tumour tendon pathology in 31 cases (23.13%). Less common causes included articular diseases (5.97%) and anatomical variants (4.47%). No focal lesion was present in 8 cases (5.97%). In conclusion, MRI is an accurate diagnostic technique in patients who present with a palpable mass of the hand and wrist.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002560050553
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  • 144
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    Electronic Resource
    Granular cell tumor of the subcutis: CT and MRI findings (1999)
    Springer
    Skeletal radiology 28 (1999), S. 96-99 
    Details
    ISSN: 1432-2161
    Keywords: Key words Computed tomography ; Granular cell tumor ; Magnetic resonance imaging ; Subcutis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Three cases of granular cell tumor (GCT) of the subcutis are presented. Computed tomography showed a mass isodense with muscle with an ill-defined margin. Magnetic resonance imaging showed a mass with inhomogeneous low signal intensity on both T1- and T2-weighted images. Another characteristic feature of subcutaneous GCT is its attachment in part to muscle. Histological examination confirmed the diagnosis in all cases.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002560050481
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  • 145
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    Electronic Resource
    Meningioma of the cavernous sinus in a child (1999)
    Springer
    Child's nervous system 15 (1999), S. 8-10 
    Details
    ISSN: 1433-0350
    Keywords: Key words Cavernous sinus ; Meningioma ; Child ; Ophthalmoplegia ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Intracranial meningiomas in children are rare, representing 1–4.2% of central nervous system tumors and 1.5–1.8% of all intracranial meningiomas. Meningiomas arising from the lateral wall of the cavernous sinus account for less than 1% of all intracranial meningiomas. To our knowledge, only one case of a meningioma arising from the cavernous sinus has been reported in childhood. A 6-year-old boy presented with left ophthalmoplegia. A slight drooping of the left eyelid was noted at the age of 1 year. Magnetic resonance imaging (MRI) with contrast administration revealed an enhancing mass lesion located in the left cavernous sinus. The tumor, arising from the lateral wall of the cavernous sinus, was totally removed and the oculomotor nerve was reconstructed with a sural nerve graft. MRI displayed total tumor removal 1 month after the surgery. The pathological diagnosis was of a psammomatous meningioma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003810050318
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  • 146
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    Electronic Resource
    Anterior sacral meningocele completely occupied by an epidermoid tumor (1999)
    Springer
    Child's nervous system 15 (1999), S. 209-211 
    Details
    ISSN: 1433-0350
    Keywords: Key words Anterior sacral meningocele ; Epidermoid tumor ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A 2-year-old girl presented with an anterior sacral meningocele completely occupied by an epidermoid tumor. Preoperative magnetic resonance imaging had shown the meningocele with contents of the same intensity as cerebrospinal fluid. Surgery via a posterior sacral approach disclosed the tumor beneath an unexpected membrane inside the meningocele. Additionally, the presence of pus inside epidermoid tumor suggested that possible episodes of asymptomatic meningitis or other infection might have occurred before treatment, these being the major complication in anterior sacral meningocele. Therefore, we recommend that surgical treatment should be performed at the earliest possible stage in childhood, once the diagnosis is established, and dural plasty carried out to prevent infectious complications.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003810050372
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  • 147
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    Electronic Resource
    Die intrazerebrale Blutung im Rahmen der Amyloidangiopathie (1999)
    Springer
    Der Radiologe 39 (1999), S. 847-854 
    Details
    ISSN: 1432-2102
    Keywords: Schlüsselwörter Zerebrale Amyloidangiopathie ; Intrazerebrale Blutung ; Computertomographie ; Kernspintomographie ; Key words Cerebral amyloid angiopathy ; Intracerebral hemorrhage ; Computed tomography ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The purpose of our study was to evaluate the characteristic findings of acute hemorrhage due to amyloid angiopathy with computed tomography. 14 patients of intracranial hemorrhage with histologically confirmed cerebral amyloid angiopathy were observed over a period of 4 years. Characteristic findings were a lobar hemorrhage in superficial localisation, cortical involvment, subarachnoid hemorrhage, the multiplicity of hemorrhages and repeated episodes. Severe cerebral amyloid angiopathy is often accompanied by multiple petechial hemorrhages, restricted to a cortical-subcortical distribution, detectable by magnetic resonance imaging. These findings suggest that cerebral amyloid angiopathy is not a rare cause of atraumatic lobar hemorrhage. Amyloid angiopathy should be considered in any elderly patient with superficial intracerebral hemorrhage in an atypical location.
    Notes: Zusammenfassung In der Arbeit werden die computertomographischen Befunde der intrazerebralen Blutung im Rahmen der Amyloidangiopathie untersucht. 14 Patienten mit Massenblutung und histologisch bestätigter Amyloidangiopathie wurden in einem Zeitraum von 4 Jahren beobachtet. Charakteristische Befunde waren eine lobäre, oberflächlich gelegene Blutung, eine kortikale Beteiligung, eine begleitende Subarachnoidalblutung sowie ein mehrfaches und mehrzeitiges Auftreten der Blutungen. Eine schwere Amyloidangiopathie geht oft mit multiplen petechialen Blutungen in kortiko-subkortikaler Lokalisation einher, die sich kernspintomographisch nachweisen lassen. Die Befunde zeigen, daß die Amyloidangiopathie keine seltene Ursache einer nicht traumatischen lobären Blutung ist. Sie sollte daher bei jedem älteren Patienten mit einer intrazerebralen, oberflächlich gelegenen Blutung in atypischer Lokalisation in Betracht gezogen werden.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001170050721
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  • 148
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    Radiologisches Staging von thorakalen und abdominalen Tumoren im Kindesalter (1999)
    Springer
    Der Radiologe 39 (1999), S. 538-545 
    Details
    ISSN: 1432-2102
    Keywords: Schlüsselwörter Staging thorakoabdominaler Tumoren ; Kinder ; Computertomographie (CT) ; Magnetresonanztomographie (MRT) ; Malignome ; Key words Staging of tumors ; Thoracoabdominal tumors ; Childhood ; Computed tomography ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Thoracoabdominal tumors in childhood can arise from all organs and affect children from the neonate to the adolescent. Better prognosis of childhood tumors, due to better biological understanding and improvement of chemotherapy, require sufficient radiological staging. Sufficiency in radiological staging needs modern cross-sectional techniques with high resolution, good availability and lower radiation dose. In general computed tomography (CT) is being used for radiological staging; increasingly MR imaging is being used because of multiplanar imaging techniques. Replacement of invasive techniques such as myelography and lymphography and modern cross-sectional techniques create painless staging conditions. Nevertheless, scintigraphy will always be a major examination technique, especially for evaluation of metastases and postoperative control examinations. The most common thoracoabdominal tumors in childhood and their staging are described.
    Notes: Zusammenfassung Thorakale und abdominale Tumoren im Kindesalter nehmen ihren Ausgang von allen Organsystemen und können vom Neugeborenen bis zum Adoleszenten auftreten. Verbesserte Prognose, bedingt durch das bessere biologische Verständnis der Tumorerkrankung, sowie der effiziente Einsatz von Chemotherapeutika machen ein radiologisches Staging unumgänglich. Üblicherweise wird zum Staging die Computertomographie (CT) eingesetzt. Durch die Möglichkeit der multiplanaren Schnittführung und die bessere Auflösung bei Tumoren mit Beteiligung des ZNS wird in zunehmendem Maße die Magnetresonanztomographie (MRT) eingesetzt. Diese modernsten Schnittbildverfahren haben invasive Methoden wie Lymphographie und Angiographie in den Hintergrund gedrängt. Im weiteren werden die häufigsten thorakalen und abdominalen Tumoren im Kindesalter besprochen und deren Stagingsysteme erläutert.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001170050548
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  • 149
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    Electronic Resource
    Präoperatives Staging des Kolorektalen Karzinoms (1999)
    Springer
    Der Radiologe 39 (1999), S. 562-567 
    Details
    ISSN: 1432-2102
    Keywords: Schlüsselwörter Kolorektales Karzinom ; Präoperatives Staging ; Endosonographie ; CT ; MRT ; Key words Colorectal cancer ; Preoperative staging ; Endosonography ; Computed tomography ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Carcinoma of the colorectum is one of the most frequent neoplasias, with an incidence of 40 in 100 000. For the effective use of new, differentiated, less invasive treatment options, exact preoperative staging of the tumor is essential. The introduction of endosonography in rectal tumor staging allows for exact differentiation of the rectal wall layers and thus of tumor stages 1–3 with median accuracy of 89%. Magnetic resonance imaging of the rectum, especially in double-contrast technique, can also be employed in high and stenosing tumors and leads to an average accuracy of 85% for the stages 1–4. Computed tomography is the method of choice in screening for metastases. In lymph node staging, all modalities show only moderate accuracy around 75%.
    Notes: Zusammenfassung Das kolorektale Karzinom stellt mit einer Inzidenz von 40 auf 100000 eine der häufigsten Neoplasien dar. Für den effektiven Einsatz neuer differenzierter Therapien mit geringerer Invasivität ist ein exaktes präoperatives Staging erforderlich. Die Einführung der Endosonographie im Tumorstaging erlaubt eine exakte Differenzierung der Wandschichten und damit der Tumorstadien 1–3 mit einer mittleren Genauigkeit von 89%, die Magnetresonanztomographie des Rektums, insbesondere in Doppelkontrasttechnik, kann auch bei hohen und stenosierenden Tumoren angewendet werden, bei einer Genauigkeit von durchschnittlich 85% für die Stadien 1–4. Die Computertomographie ist Methode der Wahl im Metastasenscreening. Im Lymphknotenstaging zeigen alle Modalitäten nur bescheidene Genauigkeiten um 75%.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001170050551
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  • 150
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    Electronic Resource
    Serial magnetic resonance imaging of the donor site after harvesting the central third of the patellar tendon A prospective study of 37 patients after arthroscopic anterior cruciate ligament reconstruction (1999)
    Springer
    Knee surgery, sports traumatology, arthroscopy 7 (1999), S. 20-24 
    Details
    ISSN: 1433-7347
    Keywords: Key words Donor site morbidity ; Anterior cruciate ligament ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Sports Science
    Notes: Abstract The aim of this prospective study was to follow the development of repair tissue in the donor-site area using serial magnetic resonance imaging (MRI) evaluation and to assess whether the MRI findings were correlated with donor-site morbidity. Thirty-seven consecutive patients with unilateral anterior cruciate ligament injuries undergoing elective reconstruction of the ligament were included in the study. They were aged 27 (range 14–50) years. The graft was harvested through two 25-mm vertical incisions with the aim of protecting the infrapatellar nerve and sparing the paratenon. The tendon defect was left open. The patients underwent MRI evaluation at 6 weeks, 6 months and 27 months postoperatively. A final clinical follow-up was made 25 (range 23–29) months postoperatively. MRI demonstrated that the donor-site gap, i.e. the area corresponding to a pathological non-tendinous-like tissue signal, was 9 (range 4–18) mm at 6 weeks, 5 (range 2–14) mm at 6 months and 2 (range 0–5) mm at 27 months. The size of the donor-site gap had significantly decreased at 6 months compared with 6 weeks (P = 0.0001), as well as at 27 months compared with 6 months (P = 0.0001). We conclude that the patellar tendon at the donor site healed gradually, as expressed by a decrease in the area of non-tendinous-like tissue signal on the serial MRI evaluations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001670050115
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  • 151
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    Magnetic resonance imaging of meniscal degeneration in torn menisci: a comparison between anterior cruciate ligament deficient knees and stable knees (1999)
    Springer
    Knee surgery, sports traumatology, arthroscopy 7 (1999), S. 274-277 
    Details
    ISSN: 1433-7347
    Keywords: Key words Meniscus ; Degeneration ; Magnetic resonance imaging ; Histology ; Chronicity of the meniscal tear
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Sports Science
    Notes: Abstract Signal anomalies observed in magnetic resonance imaging of the intrameniscal tissue adjacent to the tear were compared between stable knees (group 1, 54 menisci) and anterior cruciate ligament (ACL) deficient knees (group 2, 98 menisci). The histological significance of these signal anomalies was also studied (n = 25). The frequency of intrameniscal signal anomalies adjacent to the tear was significantly lower in ACL-deficient knees than in ACL-stable knees (P = 0.0022). There was a close correlation between the imaging anomalies and the presence of histological lesions (fissures, degeneration) within meniscal tissues adjacent to the tear (sensitivity: 0.95, specificity: 0.60). Our results suggest that the severity of intrameniscal degenerative changes adjacent to the tear are lower in ACL-deficient knees than in ACL-stable knees.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001670050163
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  • 152
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    Early diagnosis of dementia: neuroimaging (1999)
    Springer
    Journal of neurology 246 (1999), S. 16-20 
    Details
    ISSN: 1432-1459
    Keywords: Key words Dementia ; Alzheimer’s disease ; Neuroimaging ; Magnetic resonance imaging ; Single photon emission computed tomography ; Atrophy ; Hippocampus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The use of neuroimaging is reviewed in the diagnosis of dementia, especially Alzheimer’s disease (AD). Computed tomography (CT) may be used to exclude other causes of dementia than AD. The finding of cortical or subcortical atrophy on CT or magnetic resonance imaging (MRI) itself does not indicate AD. Hippocampal atrophy on CT/MRI provides a useful early marker, although further longitudinal and neuropathological study is required. CT- and MRI-based measurements of hippocampal atrophy show promise in providing useful diagnostic information for discriminating patients with probable AD from normal elderly individuals. Using a standardized imaging protocol, including some assessment of hippocampal atrophy, can save costs since patients with suspected AD must undergo a cross-sectional imaging study to exclude other (treatable) causes of dementia. Combining an assessment of hippocampal atrophy with cerebral blood flow measurements by single photon emission computed tomography is not warranted either from a clinical or from an economic point of view.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004150050300
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  • 153
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    Supratentorial atrophy in spinocerebellar ataxia type 2: MRI study of 20 patients (1999)
    Springer
    Journal of neurology 246 (1999), S. 383-388 
    Details
    ISSN: 1432-1459
    Keywords: Key words Spinocerebellar ataxia type 2 ; Magnetic resonance imaging ; Cerebral atrophy ; Disease duration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract There have been only few studies of brain magnetic resonance imaging (MRI) in spinocerebellar ataxia (SCA) type 2. We investigated 20 SCA2 patients, from 11 Sicilian families, and 20 age-matched control subjects using MRI. Our data confirm that olivopontocerebellar atrophy (OPCA) is the typical pattern in SCA2. We found no significant correlation between infratentorial atrophy, disease duration, or the number of CAG repeats in our SCA2 patients, but there was supratentorial atrophy in 12 patients, with a significant correlation between supratentorial atrophy and disease duration. OPCA appears to represent the “core” of the SCA2: however, central nervous system involvement is not limited to pontocerebellar structures. We therefore consider central nervous system degeneration in SCA2 as a widespread atrophy. MRI is helpful in diagnosing SCA, but it is not diagnostic in the absence of clinical and molecular studies. We suggest that serial MRI may play a role in evaluating “in vivo” the progressive steps of neurodegeneration in SCA2, for a better comprehension of the pathophysiology of this disorder.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004150050368
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  • 154
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    p53-Oriented cancer therapies: Current progress (1999)
    Springer
    Annals of oncology 10 (1999), S. 139-150 
    Details
    ISSN: 1569-8041
    Keywords: apoptosis ; chemotherapy ; clinical trials ; gene therapy ; p53
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Nearly twenty years after the initial discovery of p53, we are now in an ideal position to exploit our vast knowledge of p53 biology in the creation of novel cancer therapies. Disruption of p53 function through mutation, or other means, occurs very frequently in human cancer. Loss of p53 function has been linked with unfavourable prognosis in a large number of tumour types, as indicated by more aggressive tumours, early metastasis and decreased survival rates. Many different avenues of research have converged upon p53 to highlight this protein as being one of the foremost cellular responders to stress, in particular to DNA damage. Huge advances have been made in understanding the complex role p53 plays in the regulation of apoptosis and cell cycle arrest. This review is not meant to be a comprehensive description of p53 biology, but rather serves to highlight current progress in the development of p53- oriented cancer therapies. These may be categorised into three basic strategies: gene replacement therapy using wild-type p53, restoration of p53 function by other means and, finally, targeting of the p53 dysfunction itself. Rapid progress is expected to be made regarding the identification of conventional pharmaceutical agents which either work in a p53-independent manner or act preferentially in p53 defective cells. Gene replacement therapy with wild-type p53 also holds considerable potential for obtaining clinically relevant results quickly. The other forms of cancer therapies based around p53 are much further behind in the developmental process, but may prove to more efficacious in the long run, especially in terms of specificity. As with many other fields, the innovation of successful p53-oriented cancer therapies is only limited by our understanding of p53 biology and the creative use of such knowledge.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008368500557
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  • 155
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    Mechanisms of Biliary Carcinogenesis: A Pathogenetic Multi-Stage Cascade towards Cholangiocarcinoma (1999)
    Springer
    Annals of oncology 10 (1999), S. 122-126 
    Details
    ISSN: 1569-8041
    Keywords: apoptosis ; biliary carcinogenesis ; cholangiocarcinoma ; genotoxicity ; risk factors ; therapeutic strategies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Carcinomas of the biliary tract are rare cancers developing from the epithelial or blast-like cells lining the bile ducts. A variety of known predisposing factors and recent experimental models of biliary carcinogenesis (e.g., infection with the liver fluke Opisthorchis viverrini, models of chemically induced carcinogenesis and experimental models of pancreaticobiliary maljunction) have elucidated different stages of this complex system of biliary tumorigenesis. Chronic inflammatory processes, generation of active oxygen radicals, altered cellular detoxification mechanisms, activation of oncogenes, functional loss of tumor-suppressor genes and dysregulation of cell proliferation and cell apoptotic mechanisms have been identified as important contributors in the development of cholangiocarcinomas. In this review, the known mechanisms involved in the carcinogenesis of biliary epithelium are addressed. We will divide the topic into four stages: 1) Predisposition and risk factors of biliary cancer, 2) Genotoxic events and alterations leading to specific DNA damage and mutation patterns. 3) Dysregulation of DNA repair mechanisms and apoptosis, permitting survival of mutated cells and 4) Morphological evolution from premalignant biliary lesions to cholangiocarcinoma. Finally, established and hypothetical future therapeutic strategies directed towards specific pathogenetic events during biliary carcinogenesis will be addressed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008321710719
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  • 156
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    All-trans-retinoic acid increases cytosine arabinoside cytotoxicity in HL-60 human leukemia cells in spite of decreased cellular ara-CTP accumulation (1999)
    Springer
    Annals of oncology 10 (1999), S. 335-338 
    Details
    ISSN: 1569-8041
    Keywords: acute myelogenous leukemia ; apoptosis ; ara-CTP ; cytosine arabinoside ; HL-60 ; retinoic acid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Accumulation of the cytosine arabinoside (ara-C) metabolite ara-C-triphosphate (ara-CTP) in leukemic blast cells is considered to be the main determinant of ara-C cytotoxicity in vitro and in vivo. Retinoids such as all-trans-retinoic acid (ATRA) have been shown to increase the sensitivity of acute myelogenous leukemic (AML) blast cells to ara-C. To investigate the mechanism of this sensitisation, the hypothesis was tested that ATRA augments cellular ara-CTP levels in human-derived myelogenous leukemia HL-60 cells. Materials and methods: The effect of ATRA and 13-cis-retinoic acid on ara-CTP accumulation and ara-C-induced apoptosis was studied. Ara-CTP levels were measured by high-performance liquid chromatography (HPLC), cytotoxicity by the tetrazolium (MTT) assay, and apoptosis by occurrence of DNA fragmentation (gel electrophoresis), cell shrinkage and DNA loss (flow cytometry). Results: Pretreatment of HL-60 cells with ATRA (0.01–1 µM) caused a significant decrease in intracellular ara-CTP levels; e.g., incubation for 72 hours with ATRA 1 µM prior to one hour ara-C 10 µM reduced ara-CTP levels to 41% ± 4% of control. Similar results were obtained after preincubation with 13-cis-retinoic acid. In spite of decreased ara-CTP levels, the cytotoxicity of the combination was supraadditive and ATRA augmented ara-C-induced apoptosis. Conclusions: At therapeutically relevant concentrations ATRA increased ara-C cytotoxicity and ara-C induced apoptosis but this augmentation is not the corollary of elevated ara-CTP levels. The feasibility of ara-C treatment optimisation via strategies other than those involving elevation of ara-CTP levels should be investigated further.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008365714942
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  • 157
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    Regulation of cardiomyocyte apoptosis in ischemic reperfused mouse heart by glutathione peroxidase (1999)
    Springer
    Molecular and cellular biochemistry 196 (1999), S. 13-21 
    Details
    ISSN: 1573-4919
    Keywords: apoptosis ; DNA fragmentation ; GSHPx-1 knockout mice ; GSHPx-1 transgenic mice ; ischemia/repurfusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Apoptosis, a genetically controlled programmed cell death, has been found to play a role in ischemic reperfusion injury in several animal species including rats and rabbits. To examine whether this is also true for other animals, an isolated perfused mouse heart was subjected to 30 min of ischemia followed by 2 h of reperfusion. Experiments were terminated before ischemia (baseline), after ischemia, and at 30, 60, 90 and 120 min of reperfusion. At the end of each experiment, hearts were processed for the evaluation of apoptosis and DNA laddering. The in situ end labeling (ISEL) technique was used to detect apoptotic cardiomyocyte nuclei while DNA laddering was evaluated by subjecting the DNA obtained from the cardiomyocytes to 1.8% agarose gel electrophoresis followed by photographing under UV illumination. The results of our study revealed that apoptotic cells appear only after 60 min of reperfusion as demonstrated by the intense fluorescence of the immunostained genomic DNA when observed under fluorescence microscopy. None of the ischemic hearts showed any evidence of apoptosis. These results were corroborated with the findings of DNA fragmentation showing increased ladders of DNA bands in the same reperfused hearts representing integer multiples of the internucleosomal DNA length (about 180 bp). Since our previous studies showed a role of glutathione peroxidase (GSHPx) in apoptotic cell death, we performed identical experiments using isolated hearts from GSHPx-l knockout mice and transgenic mice overexpressing GSHPx-l. GSHPx-l knockout mice showed evidence of apoptotic cell death even after 30 min of reperfusion. Significant number of apoptotic cells were found in the cardiomyocytes as compared to non-transgenic control animals. To the contrary, very few apoptotic cells were found in the hearts of the transgenic mice overexpressing GSHPx-l. Hearts of GSHPx-l knockout mice were more susceptible to ischemia/reperfusion injury while transgenic mice overexpressing GSHPx- 1 were less susceptible to ischemia reperfusion injury compared to non-transgenic control animals. The results of this study clearly demonstrate a role of GSHPx in ischemia/reperfusion-induced apoptosis in mouse heart.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006905910140
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  • 158
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    Human DU145 prostate cancer cells overexpressing mitogen-activated protein kinase phosphatase-1 are resistant to Fas ligand-induced mitochondrial perturbations and cellular apoptosis (1999)
    Springer
    Molecular and cellular biochemistry 199 (1999), S. 169-178 
    Details
    ISSN: 1573-4919
    Keywords: MKP-1 ; Fas ligand ; Fas ; apoptosis ; prostate cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Recent studies have suggested that MAP kinase phosphatase 1 (MKP-1) is overexpressed in prostate cancer. To evaluate the role of MKP-1 in regulating cell death and tumor growth in prostate cancer, MKP-1 was conditionally overexpressed in the human prostate cancer cell line DU145. Overexpression of MKP-1 in DU145 cells blocked activation of stress-activated protein kinase (SAPK/JNK). MKP-1 overexpression in DU-145 cells was also found to inhibit Fas ligand (FasL)-induced apoptosis, as well as block the activation of caspases by Fas engagement. In addition, MKP-1 blocked the activation of apoptosis by transfected MEKK-1 and ASK-1, presumably through its inhibition of the SAPK/JNK family of enzymes. MKP-1 blocked the ability of FasL to induce loss of mitochondrial transmembrane potential (Δγm), suggesting that MKP-1 acts upstream of mitochondrial pro-apoptotic events induced by FasL and that the SAPK/JNK pathway may form the signaling link between Fas receptor and mitochondrial dysfunction. Thus, MKP-1 overexpression in prostate cancer may play a role in promoting prostate carcinogenesis by inhibiting FasL-induced cell death.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006980326855
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  • 159
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    Poly(ADP-ribosylation) and apoptosis (1999)
    Springer
    Molecular and cellular biochemistry 199 (1999), S. 125-137 
    Details
    ISSN: 1573-4919
    Keywords: apoptosis ; ADP-ribosylation ; caspases ; PARP ; PARG
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Poly(ADP-ribosylation) is a post-translational modification playing a relevant role in DNA damage recovery, DNA replication and viral integration. Several reports also suggest a modulation of this process during cell death by apoptosis. The aim of this review is to discuss the possible involvement of poly(ADP-ribosylation) during apoptosis, by dealing with general considerations on apoptosis, and further examining the correlation between NAD consumption and cell death, the regulation of poly(ADP-ribose) metabolism in apoptotic cells, the effect of poly(ADP-ribose) polymerase inhibition on cell death occurrence and the use of enzyme cleavage as a marker of apoptosis. Finally, the future prospects of the research in this area will be addressed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006962716377
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  • 160
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    A dual approach in the study of poly (ADP-ribose) polymerase: In vitro random mutagenesis and generation of deficient mice (1999)
    Springer
    Molecular and cellular biochemistry 193 (1999), S. 53-60 
    Details
    ISSN: 1573-4919
    Keywords: DNA binding protein ; NAD metabolism ; cellular response to DNA damage ; γ-rays ; alkylating agents ; genomic instability ; apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract A dual approach to the study of poly (ADP-ribose)polymerase (PARP) in terms of its structure and function has been developed in our laboratory. Random mutagenesis of the DNA binding domain and catalytic domain of the human PARP, has allowed us to identify residues that are crucial for its enzymatic activity. In parallel PARP knock-out mice were generated by inactivation of both alleles by gene targeting. We showed that: (i) they are exquisitely sensitive to γ-irradiation, (ii) they died rapidly from acute radiation toxicity to the small intestine, (iii) they displayed a high genomic instability to γ-irradiation and MNU injection and, (iv) bone marrow cells rapidly underwent apoptosis following MNU treatment, demonstrating that PARP is a survival factor playing an essential and positive role during DNA damage recovery and survival.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006947707713
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  • 161
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    Involvement of PARP and poly(ADP-ribosyl)ation in the early stages of apoptosis and DNA replication (1999)
    Springer
    Molecular and cellular biochemistry 193 (1999), S. 137-148 
    Details
    ISSN: 1573-4919
    Keywords: PARP ; poly(ADP-ribosyl)ation ; apoptosis ; DNA replication
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract We have focused on the roles of PARP and poly(ADP-ribosyl)ation early in apoptosis, as well as during the early stages of differentiation-linked DNA replication. In both nuclear processes, a transient burst of PAR synthesis and PARP expression occurs early, prior to internucleosomal DNA cleavage before commitment to apoptosis as well as at the round of DNA replication prior to the onset of terminal differentiation. In intact human osteosarcoma cells undergoing spontaneous apoptosis, both PARP and PAR decreased after this early peak, concomitant with the inactivation and cleavage of PARP by caspase-3 and the onset of substantial DNA and nuclear fragmentation. Whereas 3T3-L1, osteosarcoma cells, and immortalized PARP +/+ fibroblasts exhibited this early burst of PAR synthesis during Fas-mediated apoptosis, neither PARP-depleted 3T3-L1 PARP-antisense cells nor PARP -/- fibroblasts showed this response. Consequently, whereas control cells progressed into apoptosis, as indicated by induction of caspase-3-like PARP-cleavage activity, PARP-antisense cells and PARP -/- fibroblasts did not, indicating a requirement for PARP and poly(ADP-ribosyl)ation of nuclear proteins at an early reversible stage of apoptosis. In parallel experiments, a transient increase in PARP expression and activity were also noted in 3T3-L1 preadipocytes 24 h after induction of differentiation, a stage at which ~95% of the cells were in S-phase, but not in PARP-depleted antisense cells, which were consequently unable to complete the round of DNA replication required for differentiation. PARP, a component of the multiprotein DNA replication complex (MRC) that catalyzes viral DNA replication in vitro, poly(ADP-ribosyl)ates 15 of ~40 MRC proteins, including DNA pol α, DNA topo I, and PCNA. Depletion of endogenous PARP by antisense RNA expression in 3T3-L1 cells results in MRCs devoid of any DNA pol α and DNA pol δ activities. Surprisingly, there was no new expression of PCNA and DNA pol α, as well as the transcription factor E2F-1 in PARP-antisense cells during entry into S-phase, suggesting that PARP may play a role in the expression of these proteins, perhaps by interacting with a site in the promoters for these genes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006988832729
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  • 162
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    Bcl-2, survivin and variant CD44 v7-v10 are downregulated and p53 is upregulated in breast cancer cells by progesterone: Inhibition of cell growth and induction of apoptosis (1999)
    Springer
    Molecular and cellular biochemistry 202 (1999), S. 53-61 
    Details
    ISSN: 1573-4919
    Keywords: breast cancer cells ; anti-apoptotic genes ; apoptosis ; progesterone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Progesterone inhibits the proliferation of normal breast epithelial cells in vivo, as well as breast cancer cells in vitro. But the biologic mechanism of this inhibition remains to be determined. We explored the possibility that an antiproliferative activity of progesterone in breast cancer cell lines is due to its ability to induce apoptosis. Since p53, bcl-2 and survivin genetically control the apoptotic process, we investigated whether or not these genes could be involved in the progesterone-induced apoptosis. We found a maximal 90% inhibition of cell proliferation with T47-D breast cancer cells after exposure to 10 μM progesterone for 72 h. Control progesterone receptor negative MDA-231 cancer cells were unresponsive to 10 μM progesterone. The earliest sign of apoptosis is translocation of phosphatidylserine from the inner to the outer leaflet of the plasma membrane and can be monitored by the calcium-dependent binding of annexin V in conjunction with flow cytometry. After 24 h of exposure to 10 μM progesterone, cytofluorometric analysis of T47-D breast cancer cells indicated 43% were annexin V-positive and had undergone apoptosis and no cells showed signs of cellular necrosis (propidium iodide negative). After 72 h of exposure to 10 μM progesterone, 48% of the cells had undergone apoptosis and 40% were annexin V positive/propidium iodide positive indicating signs of necrosis. Control untreated cancer cells did not undergo apoptosis. Evidence proving apoptosis was also demonstrated by fragmentation of nuclear DNA into multiples of oligonucleosomal fragments. After 24 h of exposure of T47-D cells to either 1 or 10 μM progesterone, we observed a marked down-regulation of protooncogene bcl-2 protein and mRNA levels. mRNA levels of survivin and the metastatic variant CD44 v7-v10 were also downregulated. Progesterone increased p53 mRNA levels. These results demonstrate that progesterone at relative high physiological concentrations, but comparable to those seen in plasma during the third trimester of human pregnancy, exhibited a strong antiproliferative effect on breast cancer cells and induced apoptosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007081021483
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  • 163
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    Role of nitric oxide in the induction of apoptosis by smokeless tobacco extract (1999)
    Springer
    Molecular and cellular biochemistry 200 (1999), S. 51-57 
    Details
    ISSN: 1573-4919
    Keywords: smokeless tobacco ; apoptosis ; nitric oxide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Smokeless tobacco usage is, a growing public health concern in the United States. Lesions of the oral cavity have been clearly linked to smokeless tobacco use. The objective of this study was to determine the biochemical effects of smokeless tobacco extract (STE) exposure upon hamster cheek pouch cell (HCPC-1) cultures. HCPC-1 cells were exposed to a 5 -fold dose-range of STE (0.5, 1.0 and 2.5%) over a time-course of 24-96 h. Following each exposure we measured various biochemical parameters of cell proliferation and cell death. Cell viability, cell cycle progression and S-phase DNA synthesis were measured as markers of cell proliferation. We measured lactate dehydrogenase leakage as a marker of cell membrane damage and cell death due to necrosis. No significant alterations were observed in cell cycle progression and cell proliferation as a result of exposure to STE. LDH measured colorimetrically indicated no significant effect with the lower doses (0.5, 1.0 and 2.5% STE). Apoptosis measured as the A0 peak and by the TUNEL procedure revealed that STE caused significant rates of apoptosis. Maximal apoptosis was noted between 48-96 h. In order to probe the mechanism further we measured the levels of nitrites as an indicator of nitric oxide (NO) in the media. NO levels were significantly elevated at the doses that caused an induction of apoptosis. The results from this study indicate that STE causes a dose-dependent induction of apoptosis and that this is mediated by nitric oxide.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006985700851
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  • 164
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    Clostridial toxins: Molecular probes of Rho-dependent signaling and apoptosis (1999)
    Springer
    Molecular and cellular biochemistry 193 (1999), S. 37-42 
    Details
    ISSN: 1573-4919
    Keywords: Rho ; GTPase ; toxins ; Clostridium ; signal transduction ; apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The Rho family small GTPases are members of the Ras superfamily of small GTPases. Rho proteins were first determined to act as key regulators of many types of actin cytoskeletal-dependent cellular functions. Recent work by several investigators indicates that Rho GTPases are also critical modulators of several important intracellular and nuclear signal transduction pathways. Certain clostridial toxins and exoenzymes covalently modify, and thereby inactivate, specific types of Rho family GTPases. As such, these microbial enzymes have proven invaluable in helping to identify structural and functional attributes of Rho GTPases.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006939505896
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  • 165
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    Functional analysis of poly(ADP-ribose) polymerase in Drosophila melanogaster (1999)
    Springer
    Molecular and cellular biochemistry 193 (1999), S. 103-108 
    Details
    ISSN: 1573-4919
    Keywords: Poly(ADP-ribose) polymerase ; Drosophila melanogaster ; alternative splicing ; apoptosis ; DNA repair ; development
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Poly(ADP-ribose) polymerase (PARP) is conserved in eukaryotes. To analyze the function of PARP, we isolated and characterized the gene for PARP in Drosophila melanogaster. The PARP gene consisted of six translatable exons and spanned more than 50 kb. The DNA binding domain is encoded by exons 1-4. Although the consensus cleavage site of CED-3 like protease during apoptosis is conserved from human to Xenopus laevis PARPs, it is neither conserved in the corresponding region of Drosophila nor Sarcophaga peregrina. There are two cDNAs species in Drosophila. One cDNA could encode the full length PARP protein (PARP I), while the other is a truncated cDNA which could encode a partial-length PARP protein (PARP II), which lacks the automodification domain and is possibly produced by alternative splicing. The expression of these two forms of PARP in E. coli demonstrated that while PARP II has the catalytic NAD-binding domain and DNA-binding domain it is enzymatically inactive. On the other hand PARP I is active. A deletion mutant of PARP gene could grow to the end of embryogenesis but did not grow to the adult fly. These results suggest that the PARP gene plays an important function during the development of Drosophila.
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    URL: http://dx.doi.org/10.1023/A:1006920429095
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  • 166
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    Newly discovered anti-inflammatory properties of the benzamides and nicotinamides (1999)
    Springer
    Molecular and cellular biochemistry 193 (1999), S. 119-125 
    Details
    ISSN: 1573-4919
    Keywords: benzamides ; nicotinamides ; apoptosis ; inflammation ; NF-kB ; DNA repair
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Our laboratory has concentrated on the possible regulation the benzamides and nicotinamides may have on the processes of DNA repair and apoptosis. Recent reports [14-16] have suggested that both apoptosis and inflammation are regulated by the transcription factor NF-kB. We have initiated studies regarding the hypothesis that the benzamides and nicotinamides could inhibit the production of tumor necrosis factor alpha (TNFalpha) and the inflammatory response as well as induce apoptosis via inhibition of NF-kB. Our data have shown that nicotinamide and two N-substituted benzamides, metoclopramide (MCA) and 3-chloroprocainamide (3-CPA), gave dose dependent inhibition of lipopolysacharide induced TNFalpha in the mouse within the dose range of 10-500 mg/kg. Moreover, lung edema was prevented in the rat by 3 ï 50 mg/kg doses of 3-CPA or MCA, and 100-200 μM doses of MCA could also inhibit NF-kB in Hela cells. Taken together these data strongly support the notion that benzamides and nicotinamides have potent anti-inflammatory and antitumor properties, because their primary mechanism of action is regulated by inhibition at the gene transcription level of NF-kB, which in turn inhibits TNFalpha and induces apoptosis.
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    URL: http://dx.doi.org/10.1023/A:1006932714982
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  • 167
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    Growth arrest and induction of apoptosis in breast cancer cells by antisense depletion of protein kinase A-RIα subunit: p53-independent mechanism of action (1999)
    Springer
    Molecular and cellular biochemistry 195 (1999), S. 25-36 
    Details
    ISSN: 1573-4919
    Keywords: antisense oligonucleotide ; apoptosis ; cAMP-dependent protein kinase ; cancer cells ; growth inhibition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The enhanced expression of the RIα subunit of cyclic AMP-dependent protein kinase type 1 (PKA-I) has been correlated with cancer cell growth. We have investigated the effects of sequence-specific inhibition of RIα gene expression on the growth of MCF-7 human breast cancer cells. We report that RIα antisense treatment results in a reduction in RIα expression at both mRNA and protein levels and inhibition of cell growth. The growth inhibition was accompanied by changes in cell morphology, cleavage of poly(ADP-ribose) polymerase (PARP) and appearance of apoptotic nuclei. In addition, bcl-2 protein level was reduced and p53 expression increased in growth arrested cells. Interestingly, RIα antisense inhibited cell viability and induced apoptosis in the absence of p53, suggesting that these actions of RIα antisense are exerted independent of p53. In contrast, two- and four-base mismatched control oligonucleotides had no effect on either cell growth or morphology. These results demonstrate that the RIα antisense, which efficiently depletes the growth stimulatory molecule RIα, induces cell differentiation and apoptosis, providing a new approach to combat breast cancer cell growth.
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    URL: http://dx.doi.org/10.1023/A:1006990231186
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  • 168
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    TNF-α induced altered signaling mechanism in human neutrophil (1999)
    Springer
    Molecular and cellular biochemistry 197 (1999), S. 97-108 
    Details
    ISSN: 1573-4919
    Keywords: neutrophil ; PKC ; TNF-α ; apoptosis ; DNA fragmentation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract In the present study we investigated the TNF-α induced signal transduction mechanism in human neutrophil. Exogenously added TNF-α affects both PKC activity and its translocation from cytosol to the membrane. Endogenous protein phosphorylation pattern is inhibited in TNF-α induced neutrophil in Ca-dependent and Ca-independent manner, including a major 47 and 66 kDa cytosolic proteins, which may be implicated in superoxide anion generation. However TNF-α dose dependently enhances the expression of ζ-PKC isotype but not the β-PKC. Morphology and cell cytotoxicity are studied in TNF-α treated neutrophil to understand the TNF-α induced cell death or apoptosis and these experiment is further confirmed by DNA fragmentation analysis. These results clearly demonstrate that TNF-α induces cellular death of human neutrophil at least in part by enhanced expression of Ca-independent ζ-PKC. These observations provide an insight towards understanding the function of ζ-PKC in apoptotic pathway.
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    URL: http://dx.doi.org/10.1023/A:1006935114624
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  • 169
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    Diminished energy metabolism and enhanced apoptosis in livers of B6C3F1 mice treated with the antihepatocarcinogen rotenone (1999)
    Springer
    Molecular and cellular biochemistry 201 (1999), S. 25-32 
    Details
    ISSN: 1573-4919
    Keywords: rotenone ; apoptosis ; oncogenes ; liver cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Rotenone decreases the incidence of hepatocellular carcinoma and lowers rates of hepatocellular proliferation. In an effort to delineate mechanisms involved, the in vivo effect of rotenone on liver mitochondrial metabolism, apoptotic machinery as well as elements of the hepatic signal transduction pathways were investigated. Mitochondria from livers of male B6C3F1 mice fed a standard diet containing 600 ppm rotenone for 7 days were uncoupled or inhibited when succinate or glutamate plus malate were used as the substrate, respectively. These livers also showed a significant increase in apoptosis compared with control livers. Furthermore, rotenone increased the expression of c-myc mRNA to 5-fold of control values within 3 days, an effect which was still observed (3-fold) after 7 days. Levels of p53 mRNA were also increased 3-fold after 1 day, but declined to control levels by 7 days. Rotenone also caused a transient, yet marked increase in liver particulate glyceraldehyde phosphate dehydrogenase (GAPDH) protein expression, while it did not alter the expression of the cytosolic form of the enzyme. Conversely, mRNA of the proto-oncogene H-ras showed a decline of 35% after 3 days of rotenone treatment, and remained diminished for the duration of the experiment. These data suggest that rotenone may act as an anticancer agent by diminishing mitochondrial bioenergetics which prevents basal hepatocyte proliferation and lowers the threshold for liver cells with DNA damage to undergo apoptosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007024905046
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  • 170
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    Preparative High-Resolution Two-Dimensional Electrophoresis Enables the Identification of RNA Polymerase B Transcription Factor 3 as an Apoptosis-Associated Protein in the Human BL60–2 Burkitt Lymphoma Cell Line (1999)
    Springer
    The protein journal 18 (1999), S. 225-231 
    Details
    ISSN: 1573-4943
    Keywords: Two-dimensional electrophoresis ; MALDI-MS ; apoptosis ; RNA polymerase B transcription factor 3
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Apoptosis or programmed cell death is essential in the process of controlling lymphocyte growth and selection. We identified RNA polymerase B transcription factor 3 (BTF3), which is associated with anti-IgM antibody-mediated apoptosis, using a subclone of the human Burkitt lymphoma cell line BL60. To identify the transcription factor BTF3, which is expressed only in minor amounts, we used preparative high-resolution two-dimensional gel electrophoresis (2DE) employing carrier ampholytes for isoelectric focusing. Comparison of the 2DE protein patterns from apoptotic and nonapoptotic cells showed BTF3 as a predominantly altered protein spot. The characterization of the differentially expressed transcription factor and 13 marker proteins described in this study were performed by internal Edman microsequencing and/or by peptide mass fingerprinting using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). The proteome analysis was significantly improved by performing the newly developed preparative high-resolution two-dimensional gels employing high protein concentrations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1020636308270
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  • 171
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    Hochauflösende Kernspintomographie bei traumatischen Veränderungen an Fingergelenken (1999)
    Springer
    European journal of trauma 25 (1999), S. 224-229 
    Details
    ISSN: 1615-3146
    Keywords: Kerspintomographie ; Kollateralbandruptur ; Knorpelläsion ; Hochauflösende Oberflächenspule ; Magnetic resonance imaging ; Collateral ligament rupture ; Cartilage lesion ; High-resolution coil
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Aim of this study was the evaluation of a prototype of a new high-resolution MRI coil for the detection of finger trauma. The practicability of this new coil for the assessment of traumatic lesions of the finger joints and the diagnostic value of this new method in clinical practice was assessed. Twenty patients between 13 and 50 years of age (mean 28 years) were examined with a 1.5-T whole-body-imager Magnetom SP 63 scanner (Siemens, Erlangen, Germany). A prototype of a high-resolution MRI coil with a diameter of 2.5 cm was used. T1- and T2-weighted images with an in plane resolution of 0.I95 x 0.098 mm were acquired. Bone structures, joint cartilage and capsule, ligaments, tendons and soft tissue alterations were assessed. All 19 patients with pathological changes at the finger joints had a joint effusion. With MR imaging, fractures were detected in almost all patients, compared with the X-ray examinations. Cartilage contusion showed high signal intensity. The collateral ligaments could best be assessed in the transversal, and ligament ruptures in the coronal plane. Hemorrhage in the tendon showed an increased signal intensity in T1- and T2-weighted, edema only in T2-weighted images. Especially traumatic lesions of cartilage and of ligaments can be sufficiently assessed by the high-resolution MRI due to its high anatomic resolution compared to common methods like X-ray. High-resolution MRI is practicable in clinical routine.
    Notes: Zusammenfassung Ziel der vorliegenden prospektiven Untersuchung war es, die Wertigkeit der hochauflösenden Kernspintomographie mittels einer speziellen Oberflächenspule in der Beurteilung von traumatischen Veränderungen der Fingergelenke zu evaluieren. Ferner sollte die Praktikabilität der Methode in der klinischen Routine überprüft werden. Es wurden 20 Patienten im Alter zwischen 13 und 50 Jahren (im Mittel 28 Jahre) an einem 1,5-T-Ganzkörpertomographen (Magnetom SP 63, Firma Siemens, Erlangen) untersucht. Als Spule wurde ein Prototyp einer hochauflösenden Oberflächenspule mit einem Durchmesser von 2,5 cm benutzt. T1- und T2-gewichtete Sequenzen mit einer maximalen Auflbsung in der Bildebene von 0,195 x 0,098 mm wurden zur Beurteilung von Knochen, Gelenkknorpel und -kapsel, der Sehnen und des Weichteilgewebes akquiriert. Kernspintomographisch fand sich bei 19 Patienten ein pathologischer Befund. Bei all diesen Patienten konnte ein Gelenkerguß nachgewiesen werden. Knöcherne Absprengungen, die anhand konventioneller Röntgenaufnahmen diagnostiziert wurden, zeigten sich kernspintomographisch als dislozierte signalreiche Strukturen. Gelenkknorpelkontusionen stellten sich hyperintens dar. Zur Beurteilung der Kollateralbānder eignete sich vor allem die koronare Schichtebene, da in dieser die Kollateralbdnder per continuitatem darstellbar sind. Sehneneinblutungen wiesen eine Signalerhöhung in T1- und T2-Wichtung auf. Ödeme der Weichteile und Bandstrukturen imponierten in T2-gewichteten Aufnahmen als signalreiche Strukturveränderungen. Aufgrund der hohen anatomischen Detailerkennbarkeit eignet sich die hochauflbsende Kernspintomographie als ergänzendes diagnostisches Verfahren zur nichtinvasiven Diagnostik von traumatischen Knorpel- und Bandläsionen. Unter Berücksichtigung des Zeitaufwandes handelt es sich dabei um eine im klinischen Alltag praktikable Methode.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00596731
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  • 172
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    Perfusion impairments in infantile autism on technetium-99m ethyl cysteinate dimer brain single-photon emission tomography: comparison with findings on magnetic resonance imaging (1999)
    Springer
    European journal of nuclear medicine 26 (1999), S. 253-259 
    Details
    ISSN: 1619-7089
    Keywords: Key words: Autism ; Brain ; Technetium-99m ethyl cysteinate dimer ; Single-photon emission tomography ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. The neuro-anatomical substrate of autism has been the subject of detailed investigation. Because previous studies have not demonstrated consistent and specific neuro-imaging findings in autism and most such studies have been performed in adults and school-aged children, we performed a retrospective review in young children in search of common functional and anatomical abnormalities with brain single-photon emission tomography (SPET) using technetium-99m ethyl cysteinate dimer (ECD) and correlative magnetic resonance imaging (MRI). The patient population was composed of 23 children aged 28–92 months (mean: 54 months) who met the diagnostic criteria of autism as defined in the DSM-IV and CARS. Brain SPET was performed after intravenous injection of 185–370 MBq of 99mTc-ECD using a brain-dedicated annular crystal gamma camera. MRI was performed in all patients, including T1, T2 axial and T1 sagittal sequences. SPET data were assessed visually. Twenty patients had abnormal SPET scans revealing focal areas of decreased perfusion. Decreased perfusion of the cerebellar hemisphere (20/23), thalami (19/23), basal ganglia (5/23) and posterior parietal (10/23) and temporal (7/23) areas were noted on brain SPET. By contrast all patients had normal MRI findings without evidence of abnormalities of the cerebellar vermis, cerebellar hemisphere, thalami, basal ganglia or parietotemporal cortex. In conclusion, extensive perfusion impairments involving the cerebellum, thalami and parietal cortex were found in this study. SPET may be more sensitive in reflecting the pathophysiology of autism than MRI. However, further studies are necessary to determine the significance of thalamic and parietal perfusion impairment in autism.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002590050385
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  • 173
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    Effect of head-down tilt on brain water distribution (1999)
    Springer
    European journal of applied physiology 79 (1999), S. 367-373 
    Details
    ISSN: 1439-6327
    Keywords: Key words Cerebral edema ; Cerebrospinal fluid ; Head-down tilt ; Intracranial pressure ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Vascular and tissue fluid dynamics in the microgravity of space environments is commonly simulated by head-down tilt (HDT). Previous reports have indicated that intracranial pressure and extracranial vascular pressures increase during acute HDT and may cause cerebral edema. Tissue water changes within the cranium are detectable by T 2 magnetic resonance imaging. We obtained T 2 images of sagittal slices from five subjects while they were supine and during −13° HDT using a 1.5-Tesla whole-body magnet. The analysis of difference images demonstrated that HDT leads to a 21% reduction of T 2 in the subarachnoid cerebrospinal fluid (CSF) compartment and a 11% reduction in the eyes, which implies a reduction of water content; no increase in T 2 was observed in other brain regions that have been associated with cerebral edema. These findings suggest that water leaves the CSF and ocular compartments by exudation as a result of increased transmural pressure causing water to leave the cranium via the spinal CSF compartment or the venous circulation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004210050522
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  • 174
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    Protein Kinase C Targeting in Antineoplastic Treatment Strategies (1999)
    Springer
    Investigational new drugs 17 (1999), S. 227-240 
    Details
    ISSN: 1573-0646
    Keywords: apoptosis ; protein kinase C ; sphingoid bases ; safingol ; diglyceride ; bryostatin 1 ; staurosporine ; 7-hydroxy staurosporine (UCN-01) ; 4′-N-benzoyl staurosporine (CGP-41251) ; calphostin C (UCN-1028c)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Neoplastic cell survival is governed by a balance between pro-apoptotic and anti-apoptotic signals. Noteworthy among several anti-apoptotic signaling elements is the protein kinase C (PKC) isoenzyme family, which mediates a central cytoprotective effect in the regulation of cell survival. Activation of PKC, and subsequent recruitment of numerous downstream elements such as the mitogen-activated protein kinase (MAPK) cascade, opposes initiation of the apoptotic cell death program by diverse cytotoxic stimuli. The understanding that the lethal actions of numerous antineoplastic agents are, in many instances, antagonized by cytoprotective signaling systems has been an important stimulus for the development of novel antineoplastic strategies. In this regard, inhibition of PKC, which has been shown to initiate apoptosis in a variety of malignant cell types, has recently been the focus of intense interest. Furthermore, there is accumulating evidence that selective targeting of PKC may prove useful in improving the therapeutic efficacy of established antineoplastic agents. Such chemosensitizing strategies can involve either (a) direct inhibition of PKC (e.g., following acute treatment with relatively specific inhibitors such as the synthetic sphingoid base analog safingol, or the novel staurosporine derivatives UCN-01 and CGP-41251) or (b) down-regulation (e.g., following chronic treatment with the non-tumor-promoting PKC activator bryostatin 1). In preclinical model systems, suppression of the cytoprotective function(s) of PKC potentiates the activity of cytotoxic agents (e.g., cytarabine) as well as ionizing radiation, and efforts to translate these findings into the clinical arena in humans are currently underway. Although the PKC-driven cytoprotective signaling systems affected by these treatments have not been definitively characterized, interference with PKC activity has been associated with loss of the mitogen-activated protein kinase (MAPK) response. Accordingly, recent pre-clinical studies have demonstrated that pharmacological disruption of the primary MEK-ERK module can mimic the chemopotentiating and radiopotentiating actions of PKC inhibition and/or down-regulation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006328303451
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  • 175
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    Activation-Induced Apoptosis of Peripheral Lymphocytes Treated with 7-Hydroxystaurosporine, UCN-01 (1999)
    Springer
    Investigational new drugs 17 (1999), S. 335-341 
    Details
    ISSN: 1573-0646
    Keywords: UCN-01 ; IL-2 receptor ; Fas ; Fas-ligand ; apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract 7-hydroxystaurosporine (UCN-01) is a new anticancer agentwhich exerts an inhibitory effect on cell cycle check points andis currently under phase I clinical trials in US and Japan.Preliminary clinical data indicated that UCN-01 remained inplasma at high concentrations for long periods of time. Thisunavoidable high plasma drug exposure is likely to lead tohematological toxicities in patients. In the present study,cultured human peripheral blood lymphocytes (PBLs) were used toevaluate the possible hematological toxicities of UCN-01treatment. UCN-01 induces apoptosis, and the induction ofapoptosis-related surface markers were also examined toinvestigate the involvement of these molecules in UCN-01-inducedapoptosis in PBLs. in vitroviability of PBLs wasdecreased by high dose of UCN-01 (25 μM, 3-day exposure). Thiseffect of UCN-01 was significantly suppressed by the presence ofhuman serum, suggesting that some specific inhibitory factor(s)in human serum may antagonize the lympholytic effect of UCN-01.The percentage of annexin V-positive PI-negative cells increasedwith exposure to UCN-01 in a time- and dose-dependent manner; byup to 30.3% after exposure to 25 μM UCN-01 for 3 days.At the same time, the expression of both interleukin-2 receptor(IL-2R, CD25) and Fas (CD95), analyzed by flow cytometry, wasinduced. Con A-stimulated PBLs were more sensitive toUCN-01-induced apoptosis than non-stimulated lymphocytes andUCN-01 increased the sFas-L released into culture medium from conA-stimulated PBLs. Therefore, lymphocyte depletion mediated byactivation-induced apoptosis is likely to occur in patientstreated with UCN-01 at high doses.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006374118879
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  • 176
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    Influence of bcl-2 on antibody productivity in high cell density perfusion cultures of hybridoma (1999)
    Springer
    Cytotechnology 30 (1999), S. 95-106 
    Details
    ISSN: 1573-0778
    Keywords: apoptosis ; Bcl-2 ; fixed-bed ; hollow fibre ; hybridoma ; perfusion ; protein-free medium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract Apoptosis is an active, genetically determined death mechanism which can be induced by a wide range of physiological factors and by mild stress. It is the predominant form of cell death during the production of antibodies from murine hybridoma cell lines. A number of studies have now demonstrated that the suppression of this death pathway, by means of over-expression of survival genes such as bcl-2, results in improved cellular robustness and antibody productivity during batch culture. In the present study, the influence of bcl-2 expression on hybridoma productivity in two high density perfusion bioreactor systems was investigated. In the first system, a fixed-bed reactor, the DNA content in the spent medium was 25% higher in the control (TB/C3-pEF) culture than that found in the bcl-2 transfected (TB/C3-bcl2) cultures at all perfusion rates. This is indicative of a higher level of cell death in the control cell line. The average antibody concentration for the TB/C3-pEF cell line was 14.9 mg L-1 at perfusion rates of 2.6 and 5.2 d-1. However, for the TB/C3-bcl2 cell line it was 33 mg L-1 at dilution rates of 2 and 4 d-1. A substantial increase in antibody concentration was also found in the Integra Tecnomouse hollow fibre reactor. The antibody titre in the TB/C3-bcl2 cassette was nearly 100% higher than that in the TB/C3-pEF cassette during the cultivation period which lasted 6 weeks. Clearly, these results demonstrate the positive impact of bcl-2 over-expression on production of antibody in hybridoma perfusion cultures.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008055702079
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  • 177
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    Co-expression of bcl-2 and bag-1, apoptosis suppressing genes, prolonged viable culture period of hybridoma and enhanced antibody production (1999)
    Springer
    Cytotechnology 31 (1999), S. 143-151 
    Details
    ISSN: 1573-0778
    Keywords: antibody productivity ; apoptosis ; BAG-1 ; Bcl-2 ; cell survival ; hybridoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract Human bcl-2 and bag-1 DNA were introduced into mouse hybridoma 2E3- O cells and expressed. The expression of bcl-2 in BCMGneo-bcl2 transfectants was confirmed by ELISA and that of bag-1 in pZeo-bag1 was confirmed by western blotting. In batch cultures, the over-expression of bcl-2 prolonged the culture period by 2 days and co-expression of bcl-2 and bag-1 prolonged the culture period by 3 days. The delayed increase in the dead cell number in culture of the bcl-2 and bag-1 cotransfectant indicated the additional antiapoptosis effect of bcl-2 and bag-1 cotransfection in comparison with the bcl-2 only transfection. The bcl-2 transfectants (2E3O-Bcl2) produced antibody twofold per batch culture in comparison with 2E3-O cells transfected with BCMGSneo (2E3O-Mock). Enhancement of this MoAb production was due to the improved survival of the cells and was not due to stimulation of antibody production rate per cell by Bcl-2 expression. And the bcl-2 and bag-1 co-transfectant (2E3O-Bcl2-BAG1) produced antibody approximately fourfold of 2E3O-Mock per batch culture. Enhancement of this MoAb production was due to the improved survival of the cells and was partly due to stimulation of MoAb production rate per cell in the non-growing phase by the cotransfection. The method to engineer hybridoma cells genetically with bcl-2 and bag-1 for increasing viability and productivity would be widely applied for improving antibody productivity of hybridoma cultures.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008080407581
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  • 178
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    A novel 96-well scintillation proximity assay for the measurement of apoptosis (1999)
    Springer
    Cytotechnology 31 (1999), S. 271-282 
    Details
    ISSN: 1573-0778
    Keywords: annexin V ; Apo-2 ligand ; apoptosis ; Cytostar-T® scintillating microplates ; flow cytometry ; lymphotoxin (LT)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract The translocation of phospholipids across the plasma membrane has been widely documented as one of the earliest measurable biochemical events of apoptosis. Using fluorescently labelled annexin V, which preferentially binds phosphatidylserine (PS) in the presence of Ca2+, the externalization of PS can be measured and apoptosis quantified using flow cytometry. Conventional detection methods utilizing annexin V, while faster than in situ DNA end-labelling or DNA laddering, require extensive sample preparation which may compromise samples and makes rapid, high volume screening prohibitive. This paper describes a novel assay for the measurement of apoptosis based upon binding of radiolabelled annexin V to apoptotic cells attached to the growth surface of a 96-well scintillating microplate (Cytostar-T®). We compared measurements of apoptosis made by flow cytometry to those obtained with the scintillating microplate in three model systems, treatment of: mouse connective tissue (L-M) cells with lymphotoxin (LT), human lung carcinoma (H460) cells with Apo-2 ligand and human umbilical vein endothelial (HUVE) cells with staurosporine. In this assay, we compare both direct and indirect labelling methods by utilizing either iodinated annexin V or biotinylated annexin V/[35S] streptavidin to radiolabel apoptotic cells. The signal detected is a direct consequence of the binding of annexin V to externalized PS on apoptotic cells and the proximity of the label to the base of the plate. Using this method, separation of bound and unbound radiolabel signal occurs directly within the well resulting in a sensitive assay that requires minimal manipulation and can accomodate a large number of samples.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008053320396
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  • 179
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    Apoptosis in Cardiac Diseases—New Opportunities for Novel Therapeutics for Heart Diseases (1999)
    Springer
    Cardiovascular drugs and therapy 13 (1999), S. 289-294 
    Details
    ISSN: 1573-7241
    Keywords: heart failure ; apoptosis ; protein kinases ; caspases ; DNA damage ; cardiomyocytes ; β-blocks
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Apoptosis as defined by contemporary science describes a form of cell death that involves discrete genetic and molecular programs, de novo protein expression and unique cellular phenotype. Evidence for the existence of apoptosis in the human heart has been reported in various cardiac diseases, including ischemic and non-ischemic heart failure, myocardial infarction and arrhythmias. Among the most potent stimuli that elicit cardiomyocyte apoptosis are: oxygen radicals (including NO), cytokines, (FAS/TNFα family of cytokines) and growth factors/energy deprivation. Several complex signal transduction pathways have been implicated in execution of cardiomyocyte apoptosis, including: Fas/TNFα receptors signaling, stress or mitogen activated protein kinases (SAPK/MAPK), sphingolipids metabolites (ceramide), G-protein coupled receptor (GPCR) signaling (Gαi, Gαq) and NFkB activation. Apoptosis of cardiac myocytes may contribute to progressive pump-failure, arrhythmias and cardiac remodeling. The recognition of numerous molecular targets associated with cardiomyocyte apoptosis that are amenable for pharmacologic manipulation, may provide novel therapeutic strategies for diverse cardiac ailments, as recently suggested by pharmacologic studies in experimental animals.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007735413477
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  • 180
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    Control of Proliferation and Survival of C6 Glioma Cells with Modification of the Nerve Growth Factor Autocrine System (1999)
    Springer
    Journal of neuro-oncology 41 (1999), S. 121-128 
    Details
    ISSN: 1573-7373
    Keywords: apoptosis ; cell death ; C6 glioma ; nerve growth factor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Nerve growth factor (NGF) plays an important physiological role in differentiation and survival of various types of neurons. Glial cells and glial tumor cells synthesize multiple neurotrophic factors including NGF and secrete them into the surrounding environment; however, the mechanisms of NGF and the significance of NGF receptors have not been studied in detail. The C6 glioma cell line can synthesize NGF, respond to exogenous application of NGF and stimulate the expression of NGF receptor in an autocrine manner. In order to determine the significance of such an NGF autocrine system, the effects of exposure to exogenous NGF and deprivation of endogenous NGF were examined in a C6 glioma cell line in vitro. Exogenous NGF significantly inhibited maintenance of the cell number and thymidine incorporation. Morphological changes, including the formation of growth cones, outgrowth of processes and cellular hypertrophy, were observed, concurrently, indicating that exogenous NGF stimulated differentiation and thereby inhibited proliferation of the cells. Deprivation of endogenous NGF with anti-NGF antibody elicited a rapid decrease in cell number and thymidine incorporation, and led almost all of the cells to death within 8 days. The protein synthesis inhibitor, cycloheximide, strongly inhibited the death of NGF-deprived cells, suggesting the involvement of an active process requiring synthesis of suicide proteins. These findings imply that the NGF autocrine system plays a significant role in regulating the differentiation and survival of C6 glioma cells, similarly to neuronal cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006127624487
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  • 181
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    Participation of Bcl-2/Bax-α in Glutamate-induced Apoptosis of Human Glioblastoma Cells (1999)
    Springer
    Journal of neuro-oncology 44 (1999), S. 109-117 
    Details
    ISSN: 1573-7373
    Keywords: glutamate ; glioblastoma ; apoptosis ; Bcl-2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Glutamate has been shown to function as a toxic agent in neuronal and glial cells, as well as an excitatory neurotransmitter throughout the central nervous system. In the present study, we examined the effect of increasing glutamate concentration on the induction of apoptosis in the two human glioblastoma cell lines GB-4 and GB-12. Glutamate exposure caused cell death of GB-4 and GB-12 in a dose-dependent manner. The cells were found to die via apoptosis in response to glutamate based on the following criteria: propidium iodide (PI) staining, H–E staining, electron microscopic analysis, and the TdT-mediated dUTP-biotin nick end labeling (TUNEL) method. The glutamate-induced apoptosis appears to involve the modulation of Bcl-2 family gene products such as Bcl-2, Bcl-xL, and Bax-α. Both Bcl-2 and Bcl-xL were down-regulated by glutamate at 24 h and further at 48 h. The apoptosis-promoting product p21 Bax-α was also down-regulated in GB-12 but slightly up-regulated in GB-4, accompanied by generation of variant form of p18 Bax-α in both cell lines. These findings suggest that glutamate toxicity results in cellular death via an apoptotic mechanism which appears to involve the Bcl-2/Bax-α molecular complex.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006310815374
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  • 182
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    Targeted Disruption of the bcl-2 Gene in Mice Exacerbates Focal Ischemic Brain Injury (1999)
    Springer
    Metabolic brain disease 14 (1999), S. 117-124 
    Details
    ISSN: 1573-7365
    Keywords: Cerebral ischemia ; focal ischemia ; mutant mice ; bcl-2 ; apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Neuronal death after brain ischemia is mainly due to necrosis but there is also evidence for involvement of apoptosis. To test the importance of apoptosis, we investigated the effect of targeted disruption of the apoptosis-suppressive gene bcl-2 on the severity of ischemic brain injury. Transient focal ischemia for 1 hour was induced by occlusion of the middle cerebral artery in homozygous (n=7) and heterozygous (n = 6) bcl-2 knockout mice as well as in their wildtype littermates (n=5). Bcl-2 ablation did not influence cerebral blood flow but it significantly increased infarct size and neurological deficit score at 1 day after reperfusion in a gene-dose dependent manner. The exacerbation of tissue damage in the absence of Bcl-2 underscores the importance of apoptotic pathways for the manifestation of ischemic injury after transient vascular occlusion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1020709814456
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  • 183
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    Analysis of Proliferation and Apoptosis in Brain Gliomas: Prognostic and Clinical Value (1999)
    Springer
    Journal of neuro-oncology 44 (1999), S. 255-266 
    Details
    ISSN: 1573-7373
    Keywords: glioma ; immunohistochemistry ; MIB-1 ; apoptosis ; TUNEL
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract With the introduction of new (immuno-)histochemical techniques it is now possible to assess rates of proliferation and apoptosis in brain gliomas using archival paraffin embedded material. As proliferation and apoptosis are related to tumour growth rate quantification of these processes has prognostic value and is related to tumour grading. In this study we assessed the proliferation rate by measuring the Ki-67 labelling index using the MIB-1 antibody (MIB-LI) and the apoptotic rate using the in situ labelling of DNA strand breaks with TUNEL (TUNEL-LI) in 315 supratentorial gliomas. MIB-LI and TUNEL-LI in astrocytomas (A) where significantly lower compared to anaplastic astrocytomas (AA), glioblastomas (GBM) and oligodendroglial tumours [oligodendrogliomas (O) and anaplastic oligodendrogliomas (AO)]. MIB-LI and TUNEL-LI were significantly lower in AA compared to GBM. In astrocytic tumours MIB-LI and TUNEL-LI appeared to be correlated. As the distinction between A and AA is of clinical value but can be difficult histomorphologically we analysed the prognostic value of MIB-LI and TUNEL-LI in gliomas with particular emphasis on A and AA. MIB-LI below 10% was of prognostic value in A and AA, O and AO but not in GBM on univariate survival analysis. TUNEL-LI was of no prognostic value. With multivariate survival analysis MIB-LI lost prognostic significance in O and AO. Astrocytomas with a gemistocytic component (AG) are similar to A with respect to survival and MIB-LI and TUNEL-LI. MIB-LI is of independent prognostic value in A and AA. Assessment of MIB-LI in A and AA can be used as an aid in distinguishing A and AA.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006398613605
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  • 184
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    Protein Kinase C Inhibition by UCN-01 Induces Apoptosis in Human Glioma Cells in a Time-dependent Fashion (1999)
    Springer
    Journal of neuro-oncology 41 (1999), S. 9-20 
    Details
    ISSN: 1573-7373
    Keywords: apoptosis ; astrocytoma ; glioma ; growth inhibition ; protein kinase C ; signal transduction ; UCN-01
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Recent studies in our laboratory have shown that UCN-01 (7-hydroxystaurosporine), which is a derivative of the non-selective protein kinase inhibitor staurosporine that exhibits relative selectivity for protein kinase C (PKC), is a potent inhibitor of glioma growth in in vitro and in vivo models. This agent exhibits both cytotoxic and cytostatic effects, depending on the time period of drug exposure. In the present study, we examined whether UCN-01-induced cytotoxicity correlated with the induction of apoptosis, and characterized further the time course of this process as a prelude to application of UCN-01 in clinical trials. We first demonstrated that the cytotoxic effects of UCN-01 were associated with the induction of morphological features of apoptosis. Secondly. we identified electrophoretic features of apoptosis semiquantitatively at a series of time points using field inversion gel electrophoresis. These studies showed a peak in the induction of high-molecular-weight DNA fragmentation after 3–6 days of drug treatment. Thirdly, we measured the percentage of cells undergoing apoptosis at various time points using a terminal transferase-catalyzed in situ end-labeling technique, which confirmed a time- and concentration-dependent increase in apoptotic cell numbers. This correlated with a progressive decrease in the percentage of cells that were viable as assessed by trypan blue exclusion. Cell killing peaked within 2–4 days after beginning UCN-01 treatment, but continued at a lower level in the ensuing days. Taken together, these studies demonstrated that extended periods of exposure to UCN-01 are needed for optimal manifestation of cytotoxic effects against glioma cells, a factor that must be taken into consideration in the design of future clinical trials with this agent for malignant gliomas.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006047025425
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  • 185
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    Spontaneous Regression of a Residual Pineal Tumor after Resection of a Cerebellar Vermian Germinoma (1999)
    Springer
    Journal of neuro-oncology 41 (1999), S. 65-70 
    Details
    ISSN: 1573-7373
    Keywords: germinoma ; spontaneous regression ; multiple intracranial ; germ cell tumor ; immunological mechanism ; apoptosis ; MIB-1 index
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A case of multiple intracranial germ cell tumor in which a pineal tumor regressed spontaneously after resection of the cerebellar mass is reported. Immunohistochemical staining of the cerebellar mass showed that most of the infiltrating lymphocytes were positive for CD3 and CD8. The anti-Ki-67 monoclonal antibody MIB-1 staining of the resected tumor revealed a high MIB-1 positivity ratio (36.1%) among the large tumor cells, and TUNEL staining demonstrated that positivity in up to 6% of the tumor cells. Possible mechanisms responsible for this spontaneous regression including immunological responses and apoptosis induced by T lymphocytes are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006155120191
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  • 186
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    Soluble Factors, Including TNFα, Secreted by Human T Cells are Both Cytotoxic and Cytostatic for Medulloblastoma Cells (1999)
    Springer
    Journal of neuro-oncology 43 (1999), S. 115-126 
    Details
    ISSN: 1573-7373
    Keywords: apoptosis ; cell cycle ; cell death ; medulloblastoma ; T cells ; tumour necrosis factor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We studied the effect of the treatment of a medulloblastoma cell line by human T cells derived soluble factors. Medulloblastoma is one of the more common aggressive solid neoplasms in children for which there is no adequate therapy. Cell lines established from such tumours may be helpful to test the effect of various molecules on cell proliferation. Previous studies have suggested that T cell-derived factors may be toxic for the medulloblastoma cell line Dev. Cytokines were thought to mediate this effect. In this paper, we described changes in morphology, survival and cell cycle induced in Dev cells cocultured with human T cell lines chronically infected with a retrovirus (HTLV-I) and known to secrete high level of cytokines TNFα, IL1α and IL6. Such cocultures resulted in the death of a part of Dev cells and in decreased proliferation of surviving cells, associated with morphological changes and increase in vimentin expression. Treatment with conditioned medium from infected Dev cells, containing virus induced cytokines, triggered the same effect. Reduction of these effects by TNFα deprivation of conditioned medium suggested that this cytokine may be implicated. Direct treatment of Dev cells with recombinant cytokines indicated that TNFα, but not IL1 or IL6, is associated with Dev cell alterations. TNFα was shown to induce the death of Dev cells by an apoptotic pathway. Furthermore, TNFα had a bimodal effect on the cell cycle of surviving Dev cells. These differential effects of such cytokines on medulloblastoma cells could be therefore of interest for immunotherapy of these tumours.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006273514906
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  • 187
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    Adenovirus-mediated Wild-type p53 Expression Induces Apoptosis and Suppresses Tumorigenesis of Experimental Intracranial Human Malignant Glioma (1999)
    Springer
    Journal of neuro-oncology 43 (1999), S. 99-108 
    Details
    ISSN: 1573-7373
    Keywords: adenoviral gene transfer ; p53 ; apoptosis ; experimental malignant gliomas
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Adenoviral-mediated gene transfer for the treatment of experimental intrinsic malignant brain neoplasms holds promise. The role, however, of intracellular, adenoviral-mediated p53 expression to inhibit growth of experimental human intracranial malignant gliomas remains largely unexplored. Using the AdCMV.p53 vector we measured the in vitro expression of p53 and the resultant effect upon U251 human malignant glioma cellular proliferation. We further measured the survival of nude mice after intracranial injection of the infected vs. control U251 cells. The growth of the infected U251 cells was inhibited when compared to both the uninfected cells and cells infected with the control vector (AdCMV.Null). Agarose gel electrophoresis confirmed the AdCMV.p53-dependent cellular apoptosis. Nude mice having intracranial injections of the U251 cells infected with the control (AdCMV.Null) vector showed diminished survival. In contrast, mice having intracranial injections of the cells infected with the AdCMV.p53 vector showed 100% survivorship measured 100 days after treatment. Gene therapy via the AdCMV.p53 viral vector holds promise for the clinical treatment of human malignant gliomas.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006289505801
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  • 188
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    Neuroblastoma as a Neurobiological Disease (1999)
    Springer
    Journal of neuro-oncology 41 (1999), S. 159-166 
    Details
    ISSN: 1573-7373
    Keywords: neuroblastoma ; chemotherapy ; apoptosis ; dopamine receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract While neuroscientists are often involved in the assessment and care of patients with central nervous system tumors, they are only rarely involved in the case of peripheral nervous system neoplasia. Neuroblastoma is a childhood tumor of the primitive sympathetic nervous system. It is at once one of the most common and one of the most deadly tumors of childhood. The prognosis for children with this tumor has not changed in the past two decades. Clearly, a fresh approach to neuroblastoma is needed. The neuroscientist has much to add to our understanding and treatment of neuroblastoma and its sequelae. Conversely, neuroblastoma has much to teach us regarding the normal development of the neural crest and the aberrant loss of neurons in this lineage. A neuroscientist's approach to neuroblastoma, its biology and clinical features, is presented herein.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006171406740
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  • 189
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    Lovastatin-induced Apoptosis of Human Medulloblastoma Cell Lines in vitro (1999)
    Springer
    Journal of neuro-oncology 42 (1999), S. 1-11 
    Details
    ISSN: 1573-7373
    Keywords: apoptosis ; chemotherapy ; human cell lines ; lovastatin ; medulloblastoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Medulloblastoma is a malignant paediatric central nervous system tumor with a poor prognosis, stimulating the evaluation of improved treatment strategies. Lovastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, is currently used to treat patients with hypercholesterolemia. This compound also inhibits the production of non-steroidal mevalonate derivatives that are implicated in the control of cellular proliferation, and can induce cell-cycle arrest in vitro. We recently showed that lovastatin inhibited growth and promoted apoptosis of neuroblastoma, the peripheral nervous system ‘cousin’ of medulloblastoma. Therefore the potential of lovastatin as a possible anticancer drug against medulloblastoma was evaluated in vitro. Four medulloblastoma cell lines, Daoy, UW228, D341 Med and D283 Med, were treated with 1–40 µM of lovastatin in vitro. Analysis of cell morphologic changes, cell viability, DNA fragmentation and flow cytometry in all four cell lines showed growth inhibition and induction of apoptosis with lovastatin treatment. As little as 10 µM of lovastatin was sufficient to cause a marked reduction in cell numbers, and more than 20 µM of lovastatin induced 〉90% cells to undergo apoptosis, after intervals ranging between 36 and 96 h, depending on the cell line. Lovastatin induced apoptosis in these cell lines was concomitant with cell cycle arrest in G1. The attached cell lines UW228 and Daoy were more sensitive to lovastatin than D283 Med and D341 Med. Daoy cells which survived several cycles of lovastatin treatment could still be induced to undergo apoptosis after longer treatment times. The efficient induction of apoptosis by lovastatin favours this drug as a potential new avenue of therapeutic intervention for medulloablastoma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006164406202
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  • 190
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    Glucocorticoid Treatment of Primary CNS Lymphoma (1999)
    Springer
    Journal of neuro-oncology 43 (1999), S. 237-239 
    Details
    ISSN: 1573-7373
    Keywords: primary CNS lymphoma ; glucocorticoids ; cerebral edema ; apoptosis ; bcl-2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Glucocorticoid therapy may result in the rapid resolution of cerebral mass lesions in patients with primary CNS lymphoma. Since glucocorticoids will obscure the histological diagnosis of primary CNS lymphoma upon biopsy, steroids should be withheld if primary CNS lymphoma is a likely diagnosis by neuroradiological criteria. The lympholytic effect of glucocorticoids is mediated by cytoplasmic steroid receptors which are translocated to the nucleus and signal apoptosis. Glucocorticoid-induced apoptosis of lymphoid cells does not require wild-type p53 activity, seems not to depend on caspase activation, but is attenuated by the bcl-2 protooncogene product. Long-term glucocorticoid therapy of primary CNS lymphoma is not recommended because relapse is probably inevitable and because of the prominent side effects of long-term glucocorticoid treatment. Further, long-term glucocorticoid treatment is contraindicated in immunocompromised patients with primary CNS lymphoma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006254518848
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  • 191
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    Cellular uptake of the prion protein fragment PrP106-126 in vitro (1999)
    Springer
    Journal of neurocytology 28 (1999), S. 149-159 
    Details
    ISSN: 1573-7381
    Keywords: prion disease ; transmissible spongiform encephalopathy ; cell culture ; toxicity ; apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aetiological agent of prion disease is proposed to be an aberrant isoform of the cell surface glycoprotein known as the prion protein (PrPc). This pathological isoform (PrPSc) is abnormally deposited in the extracellular space of diseased CNS. Neurodegeneration in these disease has been shown to be associated with accumulation of PrPSc in affected tissue. To investigate the possible uptake mechanisms that may be required for PrPSc-induced neurodegeneration we studied the cellular trafficking of the neurotoxic fragment, PrP106-126. We were able to detect, by fluorescence microscopy, PrP106-126 inclusions in murine neurones, astrocytes and microglia in vitro. These inclusions were abundant after 24 hour exposure and still present 48h post-exposure. Shorter exposure times yielded only occasional cells with inclusions. Large extracellular aggregates of PrP106-126 could also be detected, which appeared in a time dependent manner. The appearance of inclusions or aggregates was not dependent on PrPc expression as determined by exposure of peptides from PrP-null mice. Using transmission electron microscopy and gold particle detection, positively labelled osmiophilic inclusions of peptide could be detected in the cytoplasm of exposed cells. These results demonstrate that cultured cells are capable of sequestering PrP106-126 and may indicate uptake pathways for PrPSc in various cell types. Toxicity of PrP106-126 may thus be mediated via a sequestration pathway that is not effective for this peptide in PrP-null cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007028323666
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  • 192
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    Verotoxin/Globotriaosyl Ceramide Recognition: Angiopathy, Angiogenesis and Antineoplasia (1999)
    Springer
    Bioscience reports 19 (1999), S. 345-354 
    Details
    ISSN: 1573-4935
    Keywords: Glycolipid ; apoptosis ; intracellular traffic ; multidrug resistance ; ovarian carcinoma ; astrocytoma ; post transplant lymphoproliferative disease ; bone marrow purging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Verotoxin (VT) is involved in the etiology of both hemorrhagic colitis and the hemolytic uremic syndrome which are microvasculopathies of the colon and pediatric renal glomerulus respectively. Thus, VT can be considered a vasotoxin. Cell sensitivity in vitro varies according to the receptor glycolipid (globotriaosyl ceramide-Gb3) expression and also to intracellular trafficking of the receptor/toxin complex, such that in highly sensitive cells, the toxin is targeted to the endoplasmic reticulum and nuclear envelope. Such cells include tumor cells which have become drug resistant. Thus Gb3 is upregulated in certain tumors and when such tumor cells become drug resistant, their sensitivity to verotoxin increases. This may be due to a direct role of the MDR1 drug efflux pump in glycolipid biosynthesis. In addition to the tumor tissue, the toxin receptor may also be expressed in the tumor neovasculature suggesting that activated endothelial cells may be verotoxin sensitive. Thus VT may have both a direct and indirect antineoplastic potential. VT has proved highly effective in a xenograft cancer model and the possible therapeutic use of VT is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1020299819637
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  • 193
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    Ceramide Glycanase Activities in Human Cancer Cells (1999)
    Springer
    Bioscience reports 19 (1999), S. 449-460 
    Details
    ISSN: 1573-4935
    Keywords: ceramide glycanase ; cancer cells ; glycosphingolipid ; sphingosine ; ceramide ; apoptosis ; PPMP ; PDMP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Ceramide glycanase (CGase) activities have been detected in different human tumor cells (colon, carcinoma Colo-205; neuroblastoma, IMR-32; breast cancer lines, SKBr3 and MCF7). However, the level of enzymatic activity is lower in these cells compared to that present in other mammalian tissues reported before (Basu, M., Kelly, P., Girzadas, M. A., Li, Z., and Basu, S. Methods Enzymol. (in press)). The majority of CGase activity was found in the 100,000g soluble supernatant fraction isolated from all these cell lines and tissues. Using the soluble enzyme, the requirement for optimum CGase activity was found to be consistent with previous observations found for rat and rabbit tissues (Basu, M., Dastgheib, S., Girzadas, M. A., O'Donnell, P. H., Westervelt, C. W., Li, Z., Inokuchi, J. I., and Basu, S. (1998) Acta Pol. Biochim. 42:327). The CGase activities from both Colo-205 and IMR-32 cells are optimum at a protein to detergent ratio of one. All the mammalian CGases, including human cancer cells, show an optimum pH between 5.5 and 5.8 in sodium acetate buffer. The CGase activities from cancer cells are found to be cation-independent; however, mercury, zinc, and copper ions seem to inhibit the enzyme activity substantially in both tumor cells lines. The mercury ion inhibition of CGase activities from all different sources indicates a possible structural homology in the CGase proteins. Radiolabeled substrates, labeled at the sphingosine double bond or at the 3-position of sphingosine without modifying double bond of sphingosine were used in this investigation. Both were active substrates with all enzyme preparations isolated from different cancer cells (apparent Km, 500 μM for nLcOse5[3H-DT]Cer and 350 μM for GgOse4[sph-3-3H]Cer with Colo-205 enzyme). Structural analogues of ceramide and sphingosine (L-PPMP, L-PDMP, alkylamines, and Tamoxifen) inhibited cancer cell CGase activities in vitro.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1020220524180
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  • 194
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    Immunocytochemical Accumulation of p53 in Corticotroph Adenomas: Relationship with Heat Shock Proteins and Apoptosis (1999)
    Springer
    Pituitary 1 (1999), S. 207-212 
    Details
    ISSN: 1573-7403
    Keywords: apoptosis ; corticotroph adenomas ; heat shock proteins ; p53
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The pathogenesis of corticotroph adenomas is unknown. In a recent study accumulation of p53 protein was detected by immunohistochemistry in a substantial proportion of pituitary corticotroph adenomas, and it has been suggested that it may be causally related to their development. However, other immunohistochemical studies have not confirmed the high incidence of p53 accumulation in this tumor type. Therefore, in the present study, p53 protein accumulation was re-examined in a series of 31 cases of corticotroph adenomas, using different sets of well validated anti-p53 antibodies. Furthermore, in view of the known association of p53 protein with apoptosis, and the known property of p53 to form complexes with heat shock proteins (HSPs), the relationship of p53 accumulation in corticotroph adenomas with apoptosis and HSP-70 was also investigated. Tumor samples staining positively for ACTH from patients with Cushing's disease or Nelson's syndrome were studied. Accumulation of p53 protein was tested by the standard ABC method using two different sets of clone Pab1801 and DO-7 monoclonal antibodies, applied after incubation of sections in a microwave oven. Using the DO-7 antibody, nuclear accumulation of p53 protein was detected in a total of 15 cases, with cytoplasmic staining observed in only 3 tumors. In contrast, using the Pab1801 antibody nuclear staining was observed in only 5 adenomas, with 11 adenomas demonstrating focal cytoplasmic immunoreactivity. Parallel sections of all corticotroph tumors demonstrating cytoplasmic accumulation of p53 protein were tested for the immunohistochemical presence of heat shock protein HSP-70. A striking similar distribution pattern of these two proteins was observed. Apoptosis, identified by the in situ end labeling technique, was detected in a total of 15 out of 28 corticotroph adenomas tested. Calculation of the apoptotic labeling index (ALI) by image analysis showed a significantly lower ALI in those corticotroph adenomas demonstrating nuclear p53 accumulation compared to those with no nuclear p53 immunostaining (p〈0.05). There was no significant difference in the ALI between cytoplasmic p53 positive and negative tumors. It is concluded that depending on the antibody used there is a significant variation of p53 protein detection in corticotroph adenomas. Overall, a significant proportion of corticotroph adenomas studied expressed the p53 protein, which depending on the antibody used, was located either in the nucleus and/or the cytoplasm of tumorous corticotroph cells. Cytoplasmic accumulation of p53, as shown by our colocalization studies with HSP-70, may be due to p53/HSP-70 complex formation. Although such a complex-mediated cytoplasmic exclusion of p53 has no significant effect on apoptosis, nuclear accumulation of p53 protein is associated with a significantly lower apoptotic index indicating a failure of p53 protein to exert its apoptotic action in at least a subset of this tumor type.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009929704018
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  • 195
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    Adenosine-induced cell death: evidence for receptor-mediated signalling (1999)
    Springer
    Apoptosis 4 (1999), S. 197-211 
    Details
    ISSN: 1573-675X
    Keywords: Adenosine ; apoptosis ; necrosis ; physiopathological implications.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Adenosine modulates the proliferation, survival and apoptosis of many different cell types, ranging from epithelial, endothelial and smooth muscle cells, to cells of the immune and neural lineages. In this review, we critically discuss the available in vitro and in vivo data which support a role for adenosine in both development-associated apoptosis, and in diseases characterized by either pathologically increased cell death (e.g., ischemia, trauma and aging-associated neurodegeneration) or abnormally reduced spontaneous apoptosis (e.g., cancer). Particular emphasis is given to the possible role of extracellular adenosine receptors, since these may represent novel and attractive molecular targets for the pharmacological modulation of apoptosis. In some instances, adenosine-induced cell death has been demonstrated to require entry of the nucleoside inside cells; however, in many other cases, activation of specific adenosine extracellular receptors has been demonstrated. Of the four G protein-coupled adenosine receptors so far identified, the A2A and the A3 receptors have been specifically implicated in modulation of cell death. For the A3 receptor, results obtained by exposing both cardiomyocytes and brain astrocytes to graded concentrations of selective agonists suggest induction of both cell protection and cell death. Such opposite effects, which likely depend on the degree of receptor activation, may have important therapeutic implications in the pharmacological modulation of cardiac and brain ischemia. For the A2A receptor, recent intriguing data suggest a specific role in immune cell death and immunosuppression, which may be relevant to both adenosine-deaminase-immunodeficiency syndrome (a pathology characterized by accumulation of adenosine to toxic levels) and in tumors where induction of apoptosis via activation of specific extracellular receptors may be desirable. Finally, preliminary data suggest that, in a similar way to the adenosine-deaminase-immunodeficiency syndrome, the abnormal accumulation of adenosine in degenerative muscular diseases may contribute to muscle cell death. Although the role of adenosine receptors in this effect still remains to be determined, these data suggest that adenosine-induced apoptosis may also represent a novel pathogenic pathway in muscular dystrophies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009666707307
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  • 196
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    Apoptin®-induced apoptosis: a review (1999)
    Springer
    Apoptosis 4 (1999), S. 317-319 
    Details
    ISSN: 1573-675X
    Keywords: Anti-tumor therapy ; Apoptin® ; apoptosis ; Bcl-2 ; p53.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Apoptin, a protein encoded by an avian virus, induces apoptosis in various cultured human tumorigenic and/ or transformed cell lines, e.g. derived from breast and lung tumor, leukemia, lymphoma, osteosarcoma melanoma, cholangiocarcinoma, and hepatoma. In such cells, Apoptin induces p53-independent apoptosis, and the proto-oncogene Bcl-2 can accelerate this effect. The latter is surprising for, in general, Bcl-2 is known to inhibit e.g., p53-induced apoptosis. On the other hand, in normal non-transformed human cells, Apoptin is unable to induce apoptosis, even when Bcl-2 is over-expressed. In animal models Apoptin-induced apoptosis appears to be a safe and efficient anti-tumor agent. These data, in continuation with the observations that Apoptin is specifically stimulated by Bcl-2 in tumor cells, does not need p53, and is not inhibited by Bcr-Abl in these cells, imply that Apoptin is a potential anti-tumor therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009687019221
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  • 197
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    Apoptosis in ventricular myocytes: the role of tumor suppressor proteins (1999)
    Springer
    Apoptosis 4 (1999), S. 229-234 
    Details
    ISSN: 1573-675X
    Keywords: Adenovirus ; apoptosis ; Bcl-2 ; p53 ; Rb ; ventricular myocytes.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Apoptosis or programmed cell death is an important physiologic event crucial for the selective removal of damaged or unwanted cells from body tissues. In the cardiovascular system, apoptosis has been observed in the vasculature and myocardium. Untimely or inappropriate myocardial cell loss through an apoptotic process may contribute to ventricular remodeling and the ultimate demise of ventricular function following injury. Therapeutic interventions designed to modulate or prevent myocardial apoptotic cell loss may therefore prove beneficial in maintaining cardiac function. Incite into the molecular mechanisms that govern apoptosis in mammalian cells has led to the identification of several key factors that promote or prevent the apoptotic process. In this report, we discuss putative regulators of cardiac cell apoptosis with specific reference to the tumor suppressor proteins, p53 and Rb. The interplay between these factors, as well as the anti-apoptotic molecules related to the Bcl-2 the family are discussed in the context of the heart under normal and disease conditions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009640124029
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  • 198
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    Tau protein is involved in the apoptotic process induced by anti-microtubule agents on neuroblastoma cells (1999)
    Springer
    Apoptosis 4 (1999), S. 47-58 
    Details
    ISSN: 1573-675X
    Keywords: Anti-microtubule agents ; apoptosis ; doxorubicin ; neuroblastoma ; tau ; taxoid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Paclitaxel and docetaxel are potent anti-microtubule and antimitotic agents that induce apoptosis in bone marrow-derived cells and epithelial cells. This study examined apoptosis induced by anti-microtubule agents in the neuroblastoma SK-N-SH cell line with a special focus on tau protein which is one of the main Microtubule-Associated- Proteins (MAPs) in neuronal cells. In time, treatment with 1 μM paclitaxel successively induced formation of bundles, then pseudo-asters concomitantly with mitotic block and phosphorylation of bcl-2 (48 h), then phosphorylation of tau and externalization of phosphatidylserine at the early phase of apoptosis (72 h) and finally DNA fragmentation (96 h). Similar results were obtained with 0.5 μM vinorelbine. Paclitaxel induced a lower increase in tau phosphorylation in differentiated SK-N-SH/RA+ cells which are less sensitive to apoptosis. Moreover, doxorubicin whose mechanism of action is independent of microtubules also induced immunostaining of tau at 72 h treatment. In conclusion, our results on neuroblastoma cells show that overexpression of hyperphosphorylated tau is involved in the apoptotic process induced by anti-microtubule agents and may be extended to others cytostatic drugs. Thus, tau protein may play a role in the cellular events observed in neuroblastoma cells undergoing apoptosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009682116158
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  • 199
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    IL-3 induces apoptosis in a ras-transformed myeloid cell line (1999)
    Springer
    Apoptosis 4 (1999), S. 71-80 
    Details
    ISSN: 1573-675X
    Keywords: abl ; apoptosis ; interleukin-3 ; oncogenes ; ras.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Growth factors promote cell survival and proliferation. Homeostasis is maintained by programmed cell death which occurs when the growth stimulus is withdrawn, in response to negative growth regulators such as interferons, TNF-α and CD95 ligand, or following differentiation. Although acutely-transforming oncogenes often overcome the need for growth factors, growth regulatory cytokines can influence proliferative responses of transformed cells. In this study we investigated the effects of IL-3 on the proliferative responses of parental bone marrow-derived 32D cells and cells transformed with ras and abl oncogenes. We show that treatment of ras-transformed 32D cells with IL-3 reduced proliferative responses and decreased colony-forming ability. These effects were exacerbated in the absence of serum and associated with inhibition of tyrosine kinase activity, down-regulation of RAS and MYC expression, and induction of apoptosis as indicated by DNA fragmentation. In contrast, treatment of parental 32D cells with IL-3, which is obligatory for cell survival and proliferation, increased tyrosine kinase activity, upregulated MYC and RAS expression and maintained DNA integrity. With abl-transformed cells, proliferation and colony-forming ability were also inhibited by IL-3. Tyrosine kinase activity and MYC expression were reduced, but early apoptosis was not evident. Calcium uptake however, was stimulated by IL-3 in both parental and oncogene-transformed cells. These results suggest that threshold levels of tyrosine kinase activity are necessary for cell survival and proliferation and that with ras-transformed cells, IL-3 treatment may result in this threshold being breached. We conclude that in some situations, growth-promoting cytokines can inhibit proliferation of transformed cells and induce cell death by apoptosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009686220607
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    Electronic Resource
    Electronic Resource
    Ameloblast apoptosis and IGF-1 receptor expression in the continuously erupting rat incisor model (1999)
    Springer
    Apoptosis 4 (1999), S. 441-447 
    Details
    ISSN: 1573-675X
    Keywords: ameloblasts ; amelogenesis ; apoptosis ; insulin-like growth factor.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Enamel-producing cells (ameloblasts) pass through several phenotypic and functional stages during enamel formation. In the transition between secretory and maturation stages, about one quarter of the ameloblasts suddenly undergo apoptosis. We have studied this phenomenon using the continuously erupting rat incisor model. A special feature of this model is that all stages of ameloblast differentiation are presented within a single longitudinal section of the developing tooth. This permits investigation of the temporal sequence of gene and growth factor receptor expression during ameloblast differentiation and apoptosis. We describe the light and electron microscopic morphology of ameloblast apoptosis and the pattern of insulin-like growth factor-1 receptor expression by ameloblasts in the continuously erupting rat incisor model. In the developing rat incisor, ameloblast apoptosis is associated with downregulated expression of the insulin-like growth factor-1 receptor. These data are consistent with the hypothesis that ameloblasts are “hard wired” for apoptosis and that insulin-like growth factor-1 receptor expression is required to block the default apoptotic pathway. Possible mechanisms of insulin-like growth factor-1 inhibition of ameloblast apoptosis are presented. The rat incisor model may be useful in studies of physiological apoptosis as it presents apoptosis in a predictable pattern in adult tissues.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009600409421
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