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  • 1
    Electronic Resource
    Electronic Resource
    Modeling of a periodic instability in paired helical filaments reveals an axial repeat (2000)
    Springer
    Acta neuropathologica 99 (2000), S. 534-538 
    Details
    ISSN: 1432-0533
    Keywords: Key words Paired helical filaments ; Electron ¶microscopy ; Tau ; Neurofibrillary tangles ; Mathematical modeling
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Ultrastructural studies of paired helical filaments (PHF) have been facilitated by the ability to isolate enriched fractions of detergent-insoluble forms of PHF. These fractions are composed of a relatively homogeneous population of short (usually 〈 400 nm) highly fragmented PHF. A small proportion of isolated PHF have highly stereotyped angled profiles that represent deformations due to structural instability. These distorted PHF can be characterized quantitatively using a simple numerical procedure that reveals that the axial instabilities occur with predictable regularity over the length of the PHF. Using a structural model of PHF, it is shown that the periodicity of the axial instability can be correlated to an axially repeated subunit of uniform size. The upper limit for the axial extent of the repeated segment was calculated to be 80 nm, similar to the size of a single one-half twist in the PHF ribbon. It is proposed that this segment may represent one type of particle in the hierarchy of structural subunits in the PHF ribbon, or an oligomeric intermediate species in PHF assembly.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004010051157
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  • 2
    Electronic Resource
    Electronic Resource
    Absence of protease-resistant prion protein in dementia characterized by neuronal loss and status spongiosus (1993)
    Springer
    Acta neuropathologica 86 (1993), S. 515-517 
    Details
    ISSN: 1432-0533
    Keywords: Dementia ; Prion ; Pick's disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Dementia characterized by neuronal loss and status spongiosus (DNLS) is a non-Alzheimer degenerative process which is characterized by Pick-like lobar atrophy with neuronal depletion and gliosis of the cerebral cortex, corpus striatum, medial thalamus, and substantia nigra and the absence of neuronal inclusions. To further investigate the cause and pathogenesis of DNLS, we probed cerebral homogenates from three cases of DNLS for protease-resistant prion protein to determine if DNLS could be a variant of a human prion disease. Limited proteolysis of prion proteins and guanidine thiocyanate treatment of cortical homogenates was used to enrich potential abnormal prion protein immunoreactivity. Although protease-resistant prion protein was detected in a case of sporadic Creutzfeldt-Jakob disease no abnormal prion protein was found in the cases of DNLS. We conclude that DNLS is not a human prion disease and remains an important dementia of uncertain eitology.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00228588
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  • 3
    Electronic Resource
    Electronic Resource
    Hereditary diabetes insipidus: an immunohistochemical study of the hypothalamus and pituitary gland (1991)
    Springer
    Acta neuropathologica 81 (1991), S. 345-348 
    Details
    ISSN: 1432-0533
    Keywords: Hereditary diabetes insipidus ; Vasopressin ; Neurohypophysis ; Hypothalamus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We report the histological findings in a case of hereditary diabetes insipidus (HDI) using vasopressin (VP) immunohistochemistry. The hypothalamus displayed a marked loss of magnocellular VP neurons, with preservation of the smaller cells. The neurohypophysis was severely atrophic with scanty immunoreactivity. Our results support the hypothesis that HDI results from a selective degeneration of VP neurons affecting chiefly the magnocellular elements projecting to the neurohypophysis. The sparing of the parvocellular component may reflect the projection of these neurons to non-pituitary targets.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00305879
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  • 4
    Electronic Resource
    Electronic Resource
    Characterization of a shared epitope in cortical Lewy body fibrils and Alzheimer paired helical filaments (1994)
    Springer
    Acta neuropathologica 88 (1994), S. 1-6 
    Details
    ISSN: 1432-0533
    Keywords: Lewy body ; Neurofilament ; Alzheimer's disease ; Paired helical filaments ; Diffuse Lewy body disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The straight fibrils of the Lewy body contain an epitope related to phosphorylation of the KSPV motif common to the C termini of the 200- and 170-kDa neurofilament subunits and τ. To further characterize this phosphorylated neurofilament/τ epitope in Lewy bodies and to analyze the constituents of isolated Lewy bodies we used a combined biochemical and immunochemical approach. In formalin-fixed paraffin-embedded tissue cortical Lewy bodies were labelled by monoclonal antibodies directed to phosphorylation-dependent KSPV epitopes in the sequences of neurofilament and phosphorylation-independent epitopes. Immunoblotting of solubilized Lewy body fibrils with the same antibodies which stained Lewy bodies in tissue sections revealed that the immunoreactive Lewy body proteins were phosphorylated neurofilament subunits. An antibody to the 68-kDa neurofilament subunit labelled Lewy bodies and Lewy body protein at 50–68 kDa. We conclude that the shared phosphorylated epitope in Lewy body fibrils and paired helical filaments is related to the common KSPV sequence in neurofilament and τ, and that all three neurofilament subunits are present in the Lewy body. This result indicates that although Lewy bodies and neurofibrillary tangles share epitopes they are comprised of distinct structural subunits.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00294352
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  • 5
    Electronic Resource
    Electronic Resource
    Induction chemotherapy followed by allogeneic bone marrow transplantation or aggressive consolidation chemotherapy in childhood acute myeloblastic leukemia: A prospective study from the French Society of Pediatric Hematology and Immunology (SHIP) (1997)
    Springer
    Hematology and cell therapy 38 (1997), S. 169-176 
    Details
    ISSN: 1279-8509
    Keywords: Acute myeloblastic leukemia ; Child ; Bone marrow transplantation ; Chemotherapy ; Cytarabine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the LAME89/91 protocol, children with acute myeloid leukemia (AML) who achieved complete remission (CR) after induction chemotherapy, were treated either with allogeneic bone marrow transplantation (BMT) if they had an HLA-compatible related donor or with chemotherapy including high-dose cytarabine. The objectives of this study were to describe the overall results of this strategy and to compare the two post-remission arms. Two hundred and thirty-one children were enrolled in the protocol. Induction chemotherapy consisted of a combination of cytarabine and mitoxantrone. A CR was achieved in 204 children (88%). Fifty-one of them had an HLA-identical sibling donor and were eligible for BMT. These 51 patients, as well as two additional children who had a one antigen HLA-mismatched father, received BMT during first CR. Consequently, 53 patients were analysed in the BMT group and 151 in the chemotherapy group. With a mean follow up duration in the study of 38 ± 2 months, overall event-free survival (EFS) was 47 ± 7% at 4 years for the 231 patients entered into the protocol. The 4-year disease-free survival (DFS) was 53 ± 8% for the 204 patients who achieved complete remission after induction therapy. The 4-year probability of relapse was 28 ± 14% in the BMT group and 47 ± 9% in the chemotherapy group (p = 0.02). The risk of therapy-related death was 6.2% for BMT and 8.1% for chemotherapy. DFS was 68 ± 14% in the BMT group and 48 ± 9% in the chemotherapy group (p = 0.02). We conclude that allogeneic BMT from a matched sibling donor is the treatment of choice for reducing the relapse risk and for increasing DFS in children with AML in first CR.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s00282-996-0169-7
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  • 6
    Electronic Resource
    Electronic Resource
    Regulation of procollagen I (α1) by interleukin-4 in human bronchial fibroblasts: a possible role in airway remodelling in asthma (2003)
    Oxford, UK : Blackwell Science Ltd
    Clinical & experimental allergy 33 (2003), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background In bronchial mucosa, T cells are in close association with fibroblasts. This cell contact raises the possibility of cross-talk between the two cell types through cytokines, such as interleukin-4 (IL-4).Objective We postulated that IL-4 may modulate collagen synthesis and degradation in the fibroblasts of asthmatics.Methods Bronchial fibroblasts from asthmatics (BAF) and normal controls (BNF) were stimulated with IL-4. Procollagen I gene expression and protein production were measured by real-time PCR, RT-PCR, and radioimmunoassay. The effect of IL-4 on the regulation of procollagen I (α1) promoter was studied through transient cell transfections. The implication of Sp1 and AP-1 in regulating IL-4-induced procollagen I (α1) production was determined. The effect of IL-4 on metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) production and gene expression was evaluated.Results Following IL-4 stimulation, there was a significant increase in the expression of mRNA of procollagen I (α1) by human bronchial fibroblasts of asthmatics and controls. IL-4 has a dose–response effect on mRNA, with a maximal effect at 5 ng/mL, as determined by real-time PCR. The maximal increase in procollagen I (α1) was observed at 6 h after IL-4 stimulation in both BNF and BAF. BAFs have a greater increase in the procollagen I (α1)/β2 microglobulin ratio after 6 h of IL-4 stimulation (4.1×10−2±0.03 to 20.8×10−2±0.1) compared with BNF (2.9×10−2±0.006 to 9.2×10−2±0.08) (P=0.001). In transient transfection experiments, IL-4 increased promoter activity by threefold in BAF and BNF. Sp1 was up-regulated after IL-4 stimulation and AP-1 was down-regulated as shown by electrophoretic mobility shift assay. IL-4 decreased MMP-2 protein and mRNA levels, and did not alter TIMP-2 production.Conclusions IL-4 positively regulates procollagen I (α1) transcription by direct promoter activation and increases the TIMP-2/MMP-2 ratio, thereby supporting the profibrotic effect of this cytokine. Thus, this study emphasizes that IL-4 may be considered as a link between inflammation and collagen deposition observed in asthmatic airways.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2222.2003.01785.x
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  • 7
    Electronic Resource
    Electronic Resource
    Retiform Sertoli–Leydig cell tumours: clinical, morphological and immunohistochemical findings (2002)
    Oxford, UK : Blackwell Science Ltd
    Histopathology 41 (2002), S. 0 
    Details
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Retiform Sertoli–Leydig cell tumours: clinical, morphological and immunohistochemical findingsAims:  To determine the morphological and immunohistochemical profile of retiform Sertoli–Leydig cell tumours and to compare the observed profile with that of adult rete ovarii.Methods and results:  Nineteen retiform Sertoli–Leydig cell tumours were studied, eight by immunohistochemistry, and five examples of rete ovarii from adult females were also evaluated immunohistochemically. The patients ranged in age from 3 to 74 years with a mean age of 31 years. Four patients were virilized and had an abdominal mass; two were virilized with amenorrhoea and two had amenorrhoea alone. Eight presented with an abdominal mass and one patient was pregnant. Two tumours were incidental findings. Information on stage was available in 16 patients: 14 tumours were stage 1, one was stage 2, and one was stage 3. Fifteen tumours were of intermediate differentiation and four were poorly differentiated. Papillary structures were evident grossly in four cases. Microscopically, all cases had a retiform pattern in addition to varying quantities of sex cord, gonadal stromal and heterologous elements. Heterologous elements were present in 13 cases andconsisted of hepatocytes (n = 7), mucinous epithelium (n = 7) and skeletal muscle (n = 2). Immunohistochemical evaluation of eight tumours showed a more intense positivity for keratin in the retiform areas, whereas the gonadal stromal component had a more intense expression of inhibin. Inhibin stains Leydig cells strongly and hepatocytes moderately. Rete ovarii epithelium was positive for keratin and vimentin in the five cases studied, and for inhibin in one case. Follow-up was available on 13 patients. Three tumours behaved in a malignant fashion: one each was stage 1, 2, and 3 at diagnosis.Conclusions:  Immunohistochemistry is useful in distinguishing retiform Sertoli–Leydig cell tumours from other tumours that they may resemble. Inclusion of inhibin is essential in a panel of antibodies to evaluate these tumours. The clinical behaviour of these neoplasms cannot always be predicted from their morphology or clinical stage.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2559.2002.01426.x
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  • 8
    Electronic Resource
    Electronic Resource
    Alzheimer paired helical filaments: a comparison with the twisted ribbon model (1995)
    Springer
    Acta neuropathologica 90 (1995), S. 194-197 
    Details
    ISSN: 1432-0533
    Keywords: Alzheimer's disease ; Paired helical filaments ; Electron microscopy ; Tau
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To investigate if Alzheimer paired helical filaments (PHF) closely resemble twisted ribbons, as indicated by recent high-resolution ultrastructural studies, we compared physical models of twisted ribbons with electron microscopic images of PHF. Uranyl-acetate-stained, isolated PHF with one or two helical turns were compared with scale models of twisted ribbons with one and two helical turns rotated at different angles. The various rotations of the twisted ribbon model corresponded well with the different orientations of randomly dispersed PHF. The electron-dense regions of individual PHF turns previously thought to represent a cross-over site of paired filaments corresponded to the edge of the twisted ribbon when the ribbon was oriented perpendicular to the filament axis. These data indicate that the overall configuration of PHF is a twisted ribbon but does not exclude possible configuration restrictions due to an ordered arrangement of subunits.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00294320
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  • 9
    Electronic Resource
    Electronic Resource
    Membranous nephropathy and orbital malignant tumor (2000)
    Springer
    Pediatric nephrology 14 (2000), S. 53-55 
    Details
    ISSN: 1432-198X
    Keywords: Key words Membranous nephropathy ; Malignancy ; Nephrotic syndrome ; Paraneoplastic syndrome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A 7-year-old girl with membranous nephropathy is reported who suffered 16 months later from an orbital rhabdomyosarcoma. Proteinuria disappeared at the time of the remission of the tumor. Membranous nephropathy as paraneoplastic syndrome is exceptional in children, since only two other cases associated with a solid tumor have been reported in the literature.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004670050013
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  • 10
    Electronic Resource
    Electronic Resource
    Alzheimer paired helical filaments: a comparison with the twisted ribbon model (1995)
    Springer
    Acta neuropathologica 90 (1995), S. 194-197 
    Details
    ISSN: 1432-0533
    Keywords: Key words Alzheimer's disease ; Paired helical ; filaments ; Electron microscopy ; Tau
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To investigate if Alzheimer paired helical filaments (PHF) closely resemble twisted ribbons, as indicated by recent high-resolution ultrastructural studies, we compared physical models of twisted ribbons with electron microscopic images of PHF. Uranyl-acetate-stained, isolated PHF with one or two helical turns were compared with scale models of twisted ribbons with one and two helical turns rotated at different angles. The various rotations of the twisted ribbon model corresponded well with the different orientations of randomly dispersed PHF. The electron-dense regions of individual PHF turns previously thought to represent a cross-over site of paired filaments corresponded to the edge of the twisted ribbon when the ribbon was oriented perpendicular to the filament axis. These data indicate that the overall configuration of PHF is a twisted ribbon but does not exclude possible configuration restrictions due to an ordered arrangement of subunits.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004010050318
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