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  • Springer  (12)
  • 2000-2004  (11)
  • 1940-1944  (1)
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  • 1
    ISSN: 1573-7373
    Keywords: Angiogenesis ; brain tumor ; glioma ; clinical trials
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The use of angiogenesis inhibitors may offer novel strategies in brain tumor therapy. In contrast to traditional cancer treatments that attack tumor cells directly, angiogenesis inhibitors target at the formation of tumor-feeding blood vessels that provide continuous supply of nutrients and oxygen. With respect to brain tumor therapy, inhibitors of angiogenesis display unique features that are unknown to conventional chemotherapeutic agents. The most important features are independence of the blood–brain barrier, cell type specificity, and reduced resistance. Malignant brain tumors, especially malignant gliomas, are among the most vascularized tumors known. Despite multimodal therapeutic approaches, the prognosis remains dismal. Thus, angiogenesis inhibitors may be highly effective drugs against these tumors. In a clinical setting, they could be applied in the treatment of multiple tumors or postsurgically as an adjuvant therapy to prevent recurrence. This article provides an overview of current anti-angiogenic treatment strategies with emphasis on substances already in clinical trials or candidate substances for clinical trials. The cellular and molecular basis of these substances is reviewed.
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  • 2
    ISSN: 1573-7373
    Keywords: Angiogenesis ; brain tumor ; glioma ; clinical trials
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Angiogenesis and the development of metastases are intrinsically connected. Experimental data suggest that establishment and growth of metastases are influenced by soluble factors secreted from the originating solid tumor. Among these factors are so-called endogenous inhibitors of angiogenesis which keep metastasis in a non-proliferating quiescent state. For a number of tumors it has been shown that this dormant state is mediated through inhibition of angiogenesis. This dormant state is characterized by normal proliferation, increased apoptosis, and insufficient neovascularization. Removal of inhibiting anti-angiogenic factors led to growth of dormant metastases. A number of endogenous inhibitors have been identified and have shown success in experimental therapeutic trials. This might be of special interest for the treatment of cerebral metastases which are the most common type of malignant brain tumors. Similar to the spread of metastases, it is known that single glioma cells can be found in distant parts of the brain. While local recurrence is a common phenomenon in glioma, formation of clinical apparent distant metastasis occurs rarely. Several lines of evidence suggest that growth inhibition of remote glioma cells may be mediated by an endogenous inhibitory mechanism.
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  • 3
    ISSN: 1424-0661
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics , Physics
    Notes: Abstract. We consider the three-dimensional Schrödinger operator with constant magnetic field and bounded random electric potential. We investigate the asymptotic behaviour of the integrated density of states for this operator as the norm of the magnetic field tends to infinity.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Mathematische Zeitschrift 235 (2000), S. 421-433 
    ISSN: 0025-5874
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Abstract. In this paper we consider the Anderson model with decaying randomness $a_nq_{\omega}(n)$ , $a_n 〉 0, n \in {\mathbb Z}^{\nu}$ and $q_{\omega}(n)$ , i.i.d. random variables with an absolutely continuous distribution $\mu$ . For a class of $\mu$ we show the following results on a set $\omega$ of full measure. (i) If $|a_n| \rightarrow 0$ as $|n| \rightarrow \infty$ , then $\sigma_c(H_{\omega})\subseteq [-2\nu, 2\nu]$ (ii) $\sigma(H_{\omega}) ={\mathbb R}$ . (iii) If $|a_n| \leq (|n|^{-1-\epsilon})$ for large $|n|$ and $\nu \geq 3$ , the mobility edges are the two points $\{-2\nu, 2\nu\}$ .
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Microchimica acta 30 (1942), S. 269-272 
    ISSN: 1436-5073
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
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  • 6
    ISSN: 1619-7089
    Keywords: Single-photon emission tomography Iodine-123-labelled amino acids Amino acid transport Cerebral glioma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. In developing iodine-123-labelled amino acid derivatives for imaging cerebral gliomas by single-photon emission tomography (SPET), we compared p-[123I]iodo-l-phenylalanine (IPA), l-[123I]iodo-1,2,3,4-tetrahydro-7-hydroxyisoquinoline-3-carboxylic acid (ITIC) and l-3-[123I]iodo-α-methyltyrosine (IMT) with regard to their uptake in human glioblastoma T99 and T3868 cells, and thereafter studied the mechanisms promoting the cellular uptake. The potential of the 123I-iodinated agents for use as SPET radiopharmaceuticals was evaluated in healthy experimental rats as well as in rats with stereotactically implanted C6 gliomas. The radiopharmaceutical uptake into glioblastoma cells was rapid, temperature and pH dependent, and linear during the first 5 min. Equilibrium was reached after 15–20 min, except in the case of ITIC, the initial uptake of which gradually decreased from 15 min onwards. The radioactivity concentration in glioma cells following 30-min incubation at 37°C (pH 7.4) varied from 11% to 35% of the total activity per million cells (ITIC 〈 IMT ≤ IPA). Competitive inhibition experiments using α-(methylamino)-isobutyric acid and 2-amino-2-norbornane-carboxylic acid, known as specific substrates for systems A and L, respectively, as well as representative amino acids preferentially transported by system ASC, indicated that IPA, like IMT, is predominantly mediated by the L and ASC transport systems, while no significant involvement of the A transport system could be demonstrated. By contrast, none of the three principal neutral amino acid transport systems (A, L and ASC) appear to be substantially involved in the uptake of ITIC into glioblastoma cells. Analysis of uptake under conditions that change the cell membrane potential, i.e. in high K+ medium, showed that the membrane potential plays an important role in ITIC uptake. Alteration of the mitochondrial activity by means of valinomycin or nigericin induces a slight increase or decrease in the radiopharmaceutical uptake, suggesting a minor contribution of the mitochondria in the uptake. IPA, IMT and ITIC passed the blood-brain barrier, and thereafter showed efflux from the brain. The radioactivity concentration in healthy rat brain 15 min following intravenous injection varied from 0.07% (ITIC) to 0.27% ID/g (IPA). In comparison, the brain uptake in the stereotactically implanted C6 glioma rats was substantially higher (up to 1.10% ID/g 15 min p.i.), with tumour-to-background ratios greater than 4. These data indicate that IPA and ITIC, like IMT, exhibit interesting biological characteristics which hold promise for in vivo brain tumour investigations by SPET.
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  • 7
    ISSN: 1432-0827
    Keywords: Key words: Thyroid cartilage — Mineralization — Matrix vesicles — Annexin — Collagen.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract. Mineralization and ossification of human thyroid cartilage first starts after the end of adolescence when the previously cartilaginous human skeleton has become ossified and the epiphyseal discs are in the process of closing. However, the mechanisms involved in mineralization and ossification of human thyroid cartilage are not well understood. Ultrastructural analysis of human thyroid cartilage revealed that mineralization started close to cartilage canals in a matrix containing gigantic collagen fibers (asbestoid fibers). Matrix vesicles were detected in mineralized areas and were often associated with needle-like crystals. For the first time we were able to isolate matrix vesicles from human thyroid cartilage by mild enzymatic digestions and ultracentrifugation. These particles were oval and varied in size; some were heavily calcified. They were enriched in alkaline phosphatase, calcium, and inorganic phosphate, suggesting that the particles contain Ca2+-Pi complexes. Immunoblot analysis of these vesicles revealed the presence of annexins II, V, and VI, membrane-associated, channel-forming proteins, which allow influx of Ca2+ into the vesicles and intralumenal crystal growth. In addition, the vesicles were associated with types II and X collagen, suggesting that this association not only anchors the vesicles to the extracellular matrix, but, as shown previously, also stimulates Ca2+ influx into these particles. In conclusion, matrix vesicles isolated from human thyroid cartilage contain all the components, enabling them to initiate and mediate the mineralization process in human thyroid cartilage.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Der Nervenarzt 71 (2000), S. 44-49 
    ISSN: 1433-0407
    Keywords: Schlüsselwörter Frontotemporale Demenz ; Pick-Krankheit ; präsenile Demenz ; Zerebrale Bildgebung ; Key words Frontotemporal dementia ; Pick's disease ; Presenile Dementia ; Neuroimaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The term frontotemporal dementia is used to describe a primary degenerative form of dementia, which is characterized by typical clinical, neuropsychological, radiological and neuropathological features. Its onset is usually before the age of 65 years; manifestations before the age of 30 years have rarely been described. We report the case of a 22-year old man, who showed symptoms of behavioural disorder such as social retreat, lack of initiative, mental rigidity, progressive reduction of speech, and stereotyped behaviour. The neuropsychological examination revealed disorders of the executive functions. The cerebral MRI investigations showed bifrontal atrophies corresponding with hypoperfusion areas on the SPECT. Other investigations including EEG, evoked potentials, duplex ultrasonography, cerebral angiography, laboratory tests and cerebrospinal fluid were normal. In the present case report we discuss the clinical presentation of frontotemporal dementia with early onset.
    Notes: Zusammenfassung Als frontotemporale Demenz (FTD) wird in der Literatur eine primär degenerative Demenzform bezeichnet, die durch charakteristische klinische, neuropsychologische, radiologische und neuropathologische Befunde gekennzeichnet ist. Die Krankheit manifestiert sich überwiegend vor dem 65. Lebensjahr; ein Beginn vor dem 30. Lebensjahr ist bisher äußerst selten beschrieben worden. Wir stellen einen bei Krankheitsbeginn 22-jährigen Mann vor, der klinisch durch sozialen Rückzug, reduzierten Eigenantrieb, geistige Starrheit, Sprachverarmung und Stereotypien auffiel. Neuropsychologisch imponierten Störungen der Exekutivfunktionen. In MRT-Verlaufsuntersuchungen war eine bilaterale, frontal und temporal-anterior betonte Hirnsubstanzminderung nachweisbar. Damit korrespondierten im Hirn-SPECT ausgeprägte Minderperfusionen. Die übrige Diagnostik (EEG, evozierte Potentiale, Duplexsonographie hirnversorgender Gefäße, zerebrale Angiographie, Serologie, Liquor, Humangenetik) erbrachte unauffällige Befunde. Vor dem Hintergrund dieser Kasuistik diskutieren wir das klinische Bild der frontotemporalen Demenz.
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  • 9
    ISSN: 1433-0385
    Keywords: Keywords: Pathogenesis – Varicose veins – Vein wall – Elastic properties – Extracellular matrix. ; Schlüsselwörter: Pathogenese – Varicen – Venenwand – Elastizität – extracelluläre Matrix.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung. Die Frage nach der Pathogenese der Varicen führte zu Untersuchungen varicöser V. saphena magna im Vergleich mit klinisch noch gesunder Vene und klinisch und histologisch gesunder Vene. Untersucht wurde das mechanische Verhalten und die extracelluläre Matrix. Es zeigte sich, daß die Varicenwand rigider war als die Wand normaler Venen, davon war auch die Venenwand unterhalb einer noch intakten Venenklappe betroffen. Die Veränderung der Vene und damit die Ursache für die Änderung der Zugfestigkeit lag in der Venenwand und hier insbesondere an den Bestandteilen der extracellulären Matrix. Die Matrixproteine lagen vermehrt vor, die elastischen Fasern waren reduziert und fragmentiert. In der Zusammenschau der mechanischen Versuche und der immunhistochemischen Ergebnisse läßt sich die Theorie der primären Klappenzerstörung und der anschließenden varicösen Umbildung der Vene nicht bestätigen, viel eher kommt es zunächst zu einer Veränderung der Venenwand und damit auch zu einer Klappeninsuffizienz.
    Notes: Abstract. The aetiology of varicosis is still unclear. Investigation of changes in normal veins which result in the formation of varicosis led to examination of elastic properties and histomorphological alterations in the region of the extracellular matrix in the vessel wall of the long saphenous vein in normal and varicose veins. The rigidity of varicose veins was higher than that of normal veins; there was no difference between the varicose vein above a competent valve and the „normal“ vein below this competent valve. The matrix proteins demonstrated an increase in total fibres, whereas the elastic fibres were reduced and fragmented, explained the rigidity of varices. These results suggest that the role of the venous valves in the development of varicose veins is secondary to changes of the vein wall.
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  • 10
    ISSN: 1432-1920
    Keywords: Key words Spine ; Subdural haematoma ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We present MRI findings in three patients with acute spontaneous subdural haematomas of the spine. Acute haematomas (1–3 days) were isointense or gave slightly high signal on T1- and heterogeneous signal on T2-weighted images. MRI precisely defined the level and extent of the haematoma preoperatively. The MRI was prospectively correctly interpreted as acute subdural haematomas in all patients. As a specific, noninvasive modality, MRI is the preferred imaging technique in this rare clinical entity.
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