Biomedical subjects

P Fredman

Publications and source records attributed to P Fredman.

150 records · Page 9Linked to original sources

PubMedDate not supplied

Altered expression of ganglioside phenotypes of human gliomas in vivo and in vitro.

A library of epitope-defined antiganglioside monoclonal antibodies has been used to analyze the ganglioside phenotype of human glioma cell lines, rodent xenografts derived from them, and a separate panel of human glioma biopsies by multiple quantitative and qualitative assays. We have shown that the ganglioside phenotypes of cultured cell lines differ from the ganglioside phenotypes in the xenografts grown from the parent lines. The lacto series gangliosides 3'-isoLM1 and 3',6'-isoLD1 are expressed in the majority of primary human central nervous system neoplasms and xenografts derived from glioma cell lines, whereas glioma cell lines themselves express 3'-isoLM1 and 3',6'-isoLD1 in only 2/15 and 0/15 cases, respectively. Examination of the ganglioside profiles of serially passaged xenografts established from the glioma cell line D-54 MG, which does not express the lacto series, revealed the appearance of these gangliosides within one to two passages in vivo. The presence of these defined gangliosides in the majority of human gliomas and their absence in normal brain supports their application in compartmental therapy of primary central nervous system tumors.

Animals↗

PubMedDate not supplied

Cerebrospinal fluid antibodies directed against neuron-associated gangliosides in HIV-1 infection.

BACKGROUND: Loss of synapses and neurons is a common finding in HIV-1 infection. Since the in vivo infection of neurons by HIV-1 is limited, indirect factors are likely to contribute to the pathogenesis. PATIENTS AND METHODS: We have analyzed cerebrospinal fluid (CSF) and serum samples from 25 HIV-1-infected individuals (nine with and 16 without CNS complications) and 19 HIV-negative controls with aseptic meningitis or viral encephalitis, for the presence of antibodies directed against the neuron-associated gangliosides GM1, GD1a and GD1b. RESULTS: Positive antibody titers to > or =1 of the gangliosides were found in 13/25 HIV-1-infected patients in CSF and in 17/25 in serum. Significant correlations were found between the presence and titers of CSF antibodies against GM1, GD1a, and GD1b. Six out of nine patients with, and 3/16 without neurological complications (p < 0.05) had positive CSF titers of > or = 1 of the ganglioside antibodies combined with negative serum titers, indicating intrathecal antibody production. In contrast, only 1/19 controls had detectable anti-ganglioside antibodies in the CSF. CONCLUSION: The results should be interpreted with caution and CSF anti-ganglioside antibody production might be a part of a non-specific intrathecal polyclonal immunoactivation. Nevertheless, autoantibodies directed against neuron-associated gangliosides might be involved in the neuropathogenesis in HIV-1 disease.

Adult↗

PubMedDate not supplied

Intracerebroventricular administration of GM1 ganglioside to presenile Alzheimer patients.

We have conducted a preliminary study of the optimum conditions for a therapeutic effect of ganglioside GM1 in Alzheimer's disease. Five patients with the early onset form of Alzheimer's disease (AD type I) received the ganglioside by intracerebroventricular administration for 12 months. Bilateral stereotactic punction of the frontal horns of the ventricular system was performed, and shunt catheters were implanted and connected to a programmable pump. The optimum GM1 dose varied between 20 and 30 mg/24 h. Neurological neuropsychological, psychiatric and neurochemical examinations were performed 7 days before surgery and on days 30, 90, 180 and 360. No patient found the surgery difficult and no patient or relative regretted that they participated in the study. The patients became more active and safer in relation to others and to performance of various activities from day 90. The cerebrospinal fluid level of the monoamine metabolites homovanillic acid and 5-hydroxyindoleacetic acid and the neuropeptide somatostatin increased.

Aged↗

PubMedDate not supplied

Gangliosides and sulfatide in cerebrospinal fluid in leukoaraiosis.

The aim of the study was to evaluate gangliosides and sulfatide in cerebrospinal fluid (CSF) as markers for neuronal degeneration, gliosis, and demyelination in leukoaraiosis (LA). Lumbar CSF samples were taken from 37 elderly subjects with LA on computed tomography (CT). Patients with other pathology than LA or infarction on CT were excluded. In addition, CSF samples were collected from 16 elderly reference subjects without any neurological disease. Gangliosides GM1, GD1a, GD1b, GT1b, GD3, and sulfatide were determined. This concentration of the individual gangliosides and sulfatide showed no correlation with age. Gangliosides GD1b, GT1b, and GD3 were elevated in patients with mild LA compared to controls and patients with moderate or severe LA. GD1a was elevated in patients with mild LA compared to those with moderate LA. The concentration of sulfatide did not differ between the groups. When the patients were grouped in accordance to whether they had had cerebral infarction or not, differences between the groups were not found in the concentrations of any gangliosides and sulfatide. In conclusion, the analysis of CSF markers suggests that neuronal degeneration and gliosis predominate in the early stage of LA.

Aged↗

PubMedDate not supplied

Apolipoprotein E in cerebrospinal fluid from patients with Alzheimer's disease and other forms of dementia is reduced but without any correlation to the apoE4 isoform.

Apolipoprotein E (apoE) has been suggested to play a role in regenerative processes in the brain after trauma, and also in the pathogenesis of Alzheimer's disease (AD). We examined cerebrospinal fluid (CSF) apoE in a material consisting of 23 patients with early-onset AD (EAD), 31 with late-onset AD (LAD), 16 with frontal-lobe dementia (FLD), 25 with vascular dementia (VAD) and 25 controls. CSF-apoE was decreased in all of EAD (1.8 +/- 1.1 mg/l; p < 0.0005), LAD (2.5 +/- 0.9 mg/l; p < 0.0005), VAD (2.3 +/- 1.4 mg/l; P < 0.0005) and FLD (3.0 +/- 1.3 mg/l; p < 0.05) compared to the control group (5.7 +/- 4.0 mg/l). Since apoE4 has been found to bind to beta/A4-amyloid, and AD patients homozygous for apoE4 to have higher number of senile plaques than apoE3 homozygotes, we also examined the relation between CSF-apoE and apoE alleles. However, CSF-apoE did not significantly differ between patients with different apoE isoforms. Our findings support that apoE is involved in the pathogenesis of dementia disorders, both degenerative and vascular, but the CSF-apoE level is not influenced by the apoE isoforms. CSF-apoE may be used as an unspecific marker for neurodegenerative disorders, but not in purpose of differential diagnostics between different dementia disorders.

Age of Onset↗

PubMedDate not supplied

Application of a panel of antiganglioside monoclonal antibodies to cytologic specimens.

The cytologic evaluation of poorly differentiated tumors frequently poses a diagnostic dilemma as to the tissue of origin. To assess the diagnostic utility of monoclonal antibodies (MAbs) in these situations, we applied a panel of three highly purified MAbs specific for tumor-associated ganglioside epitopes to a diverse series of cytologic specimens. The panel was composed of DMAb-3, reactive with the epitope GalNAc beta 1-4 (NeuAc alpha 2-3)Gal- of GM2; DMAb-7, reactive with the epitope (NeuAc alpha 2-8NeuAc alpha 2-3)Gal beta 1-4(Glc or GlcNAc)- of GD3 and 3'8'-LD1; and DMAb-20, reactive with the epitope GalNAc beta 1-4(NeuAc alpha 2-8NeuAc alpha 2-3)Gal- of GD2. The cytologic material consisted of air-dried Cytospin preparations prepared predominantly from fine needle aspirates and stained with the ABC immunohistochemical method. Positive reactivity was recognized when greater than 5% of tumor cells stained with the antibody; lesser reactivity was called negative. DMAb-3 stained 9/14 (64%) glial tumors, 4/13 (31%) nonglial central nervous system tumors, 1/21 (5%) melanomas, 7/38 (18%) non-small cell carcinomas (NSCC), 1/15 (7%) small cell carcinomas (SCC), 0/9 (0%) lymphomas/leukemias, 2/10 (20%) sarcomas, 1/7 (14%) miscellaneous tumors and 2/2 (100%) reactive fluids. DMAb-7 recognized 14/14 (100%) glial tumors, 9/13 (69%) non-glial central nervous system tumors, 19/22 (86%) melanomas, 19/43 (44%) NSCC, 5/15 (33%) SCC, 2/9 (22%) lymphomas/leukemias, 6/10 (60%) sarcomas, 1/7 (14%) miscellaneous tumors and 4/4 (100%) reactive fluids. DMAb-20 stained 6/14 (43%) glial tumors, 2/13 (15%) nonglial central nervous system tumors, 1/21 (5%) melanomas, 4/38 (10%) NSCC, 0/15 (0%) SCC, 0/9 (0%) lymphomas/leukemias, 1/10 (10%) sarcomas, 1/7 (14%) miscellaneous tumors and 1/3 (33%) reactive fluids. The GD3-reactive DMAb-7 recognized a large portion of many tumor types and thus is not diagnostically useful alone. DMAb-3 and DMAb-20 were more selective and showed the strongest reactivity for glial tumors and minimal reactivity for melanomas, small cell carcinomas, and lymphomas or leukemias. DMAb-3 and DMAb-20 may be useful as components of a larger panel of MAbs in distinguishing between poorly differentiated tumors in samples derived from the central nervous system.

Antibodies, Monoclonal↗