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J Gheuens

Publications and source records attributed to J Gheuens.

51 records · Page 3Linked to original sources

A multivalent antibody radioimmunoassay (MARIA) for screening specific antibody secretion by lymphocyte hybridoma cultures.

A new radioimmunoassay which is suitable for screening lymphocyte hybridoma cultures for monoclonal antibody production is described. Solid-phase antigen is first incubated with the sample, and secondly with soluble 125I-labeled antigen. When the sample contains multivalent specific antibody, the labeled antigen will be bound to the solid-phase antigen. Because no anti-immunoglobulin reagent is used as a second reagent, this type of radioimmunoassay offers several advantages, in particular for the production of monoclonal anti-idiotypic antibodies.

Animals↗

Idiotypes and biological activity of murine monoclonal antibodies against the hemagglutinin of measles virus.

Three hybridomas, designated C2, V17, and B2, were produced from BALB/c mice after immunization with measles virus. All three were directed against the virus hemagglutinin (HA). The HA is a structural peptide of the virus and constitutes a major target for the host immune response during measles infection. The monoclonal anti-HA antibodies have biological functions such as (i) measles virus neutralization in vitro, (ii) binding to acutely and persistently infected cells, and (iii) inhibition of HA-mediated Rhesus monkey erythrocyte agglutination. Different idiotypes, designated HAMM-1, HAMM-2, and HAMM-3, were defined on C2, V17, and B2, respectively, by syngeneic anti-idiotype sera against those three monoclonal antibodies. A limited cross-reactivity with the HAMM-1 idiotype was detected in sera from some BALB/c mice immunized with measles virus. The anti-idiotype sera could significantly inhibit the biological functions of the HAMM-1 and HAMM-3 idiotypes bearing monoclonal anti-HA-antibodies. This suggests a possible role for auto-anti-idiotypes in the immune response after infection with measles virus.

Animals↗

Immunochemical determination and immunocytological localization of brain-specific protein alpha-albumin (GFA) in isolated astrocytes.

Astrocyte- and neuron-enriched fractions were isolated by preparative centrifugatin from rat brain and human brain, obtained at autopsy. The brain-specific protein alpha-albumin (GFA) was studied in these fractions by quantitative immunoradiochemical and by immunocytological methods. It is concluded that morphologically intact astrocytes can be isolated not only from rat, but also from human brain. In the rat, alpha-albumin (GFA) is only found in the astrocyte-enriched fractions; this shows that detemination of alpha-albumin (GFA) is useful for the evaluation of cell separation methods for the brain. From the astrocyte-enriched fractions, four times more alpha-albumin (GFA) can be extracted when detergent (0.1% SDS) is used, than when an aqueous extract is made. About +/- 0.15 X 10(-6) particles were extracted in 1 ml of either PBS or SDS/PBS. This suggests that alpha-albumin (GFA) exists in at least two forms, one hydrosoluble, and one detergent soluble, possibly structurally bound, form.

Albumins↗

A two-site immunoradiometric assay for the determination of alpha-albumin.

A two-site immunoradiometric assay for a brain specific protein (alpha-albumin or glial fibrillary acidic protein) is described which may be applied to other proteins. The assay variables studied are immunoadsorbent dilution, temperature, incubation times, reactivity of the labelled antibodies and effect of the washing. Each of these factors is optimalised, resulting in a sensitive, specific, reliable assay. The working range is 5--5000 ng/ml, the within-assay variance is 5%. No high dose hook effect is seen in this range. The method is applied for the measurement of alpha-albumin present in cerebrospinal fluid, nervous tissue extracts and cell cultures.

Albumins↗

Improved sensitivity of MRI in multiple sclerosis by use of extensive standardized procedures.

The relative value of two different MRI procedures for the assessment of infratentorial extension in multiple sclerosis (MS) was studied. Multislice spin-echo techniques were used overall. Procedure A consisted of parasagittal T1-weighted images (500/30) and axial T2-weighted images (2500/30, 2500/120). Procedure B consisted of parasagittal T2-weighted images (1600/35, 1600/90). In the parasagittal T2-weighted images clear visualization of MS lesions is achieved because signal intensities of CSF and normal nervous tissue are nearly identical. All images were performed with a 0.5 Tesla MR system. Data were obtained in 98 patients with definite (N = 30) or probable MS (N = 68). Areas with abnormal signal intensity in the infratentorial regions (brainstem, cerebellum, and/or cervical spinal cord) were identified in 44% of the patients with procedure A and in 64% with procedure B. The standard application of the combination of both procedures improves the sensitivity of the MR examination for the diagnosis of MS, the delineation of infratentorial lesions and the correlation between clinical and MR data without excessively increasing imaging time.

Adolescent↗

Safety and pharmacokinetics of the neuroprotective drug lubeluzole in patients with ischemic stroke.

A total of 22 patients with acute ischemic stroke participated in two randomized, single-masked, placebo-controlled studies that evaluated the safety and pharmacokinetics of single escalating intravenous doses of lubeluzole. The first dose of study medication in all patients was given within 6 hours of the first sign of stroke onset. In the first study, 6 patients received a single 1-hour intravenous infusion of 5 mg of lubeluzole; 4 of these patients received an additional 10-mg dose 3 to 4 days later. Two additional patients received placebo. In the second study, 4 patients received a single 1-hour infusion of 10 mg of lubeluzole, and 2 patients received placebo. After a safety evaluation of the second study, 6 additional patients received 15 mg of lubeluzole, and 2 other patients received placebo. Lubeluzole had no clinically relevant effects on any cardiovascular variable compared with placebo. The majority of adverse experiences were mild to moderate and resolved during treatment. No unexpected electroencephalogram abnormalities were observed, and no evidence of epileptiform discharges was found in any of the patients. At the end of the infusion, plasma lubeluzole concentrations decayed biphasically, with mean distribution half-lives of 46.3 to 101.0 minutes and mean terminal half-lives of 20.8 to 27.7 hours. Comparisons of the dose-normalized value of the individual plasma concentrations at the end of the infusion and the total area under the curve from time 0 to infinity suggested that lubeluzole exhibited linear kinetics over the dose range evaluated in patients with ischemic stroke. In the small number of patients studied, lubeluzole's favorable safety profile was demonstrated by the lack of clinically relevant effects on cardiovascular variables and by neurologic examination and clinical laboratory findings.

Aged↗

Failure of familial Alzheimer's disease to segregate with the A4-amyloid gene in several European families.

The gene coding for the amyloid protein, a component of neuritic plaques found in brain tissue from patients with Alzheimer's disease, has been localized to chromosome 21, and neighbouring polymorphic DNA markers segregate with Alzheimer's disease in several large families. These data, and the association of Alzheimer's disease with Down's syndrome, suggest that overproduction of the amyloid protein, or production of an abnormal variant of the protein, may be the underlying pathological change causing Alzheimer's disease. We have identified a restriction fragment length polymorphism of the A4-amyloid gene, and find recombinants in two Alzheimer's disease families between Alzheimer's disease and the A4-amyloid locus. This demonstrates that the gene for plaque core A4-amyloid cannot be the locus of a defect causing Alzheimer's disease in these families. These data indicate that alterations in the plaque core amyloid gene cannot explain the molecular pathology for all cases of Alzheimer's disease.

Adult↗

Gadolinium-DOTA enhanced MR imaging of intracranial lesions.

Gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid (Gd-DOTA) is the first of a new class of macrocyclic paramagnetic magnetic resonance (MR) contrast agents (gadolinium cryptelates) to be used in clinical practice. Gadolinium-DOTA possesses relaxation properties similar to those of gadolinium diethylene triamine pentaacetic acid (Gd-DTPA). We report our initial clinical experience in 38 patients with intracranial lesions studied with MR before and after injection of Gd-DOTA. Diseases included primary and metastatic brain tumor, cerebral infarct, vascular malformation, meningioma, hemangiopericytoma, schwannoma, and pituitary macroadenoma. Gadolinium-DOTA was administered intravenously in a dosage of 0.1 mmol/kg body weight. All studies were performed on a superconductive 0.5 T system. As compared to noncontrast T1- and T2-weighted images (WI), Gd-DOTA enhanced T1 WI were useful in defining the anatomy of malignant intraaxial tumors (high-grade glioma, metastasis) and in tumor versus edema differentiation. Low-grade gliomas did not enhance; in these cases the precontrast T2-weighted sequence was found to be more informative. In post-operative patients, Gd-DOTA allowed us to demonstrate residual tumor or tumor recurrence. Extraaxial tumors (meningioma, hemangiopericytoma, neuroma) enhanced markedly, presumably reflecting tumor vascularity. In our experience, the use of Gd-DOTA improves the anatomic definition of cerebral lesions and in some cases increases both MR sensitivity and specificity. We found Gd-DOTA to be a well tolerated and effective paramagnetic contrast agent. Gadolinium-DOTA can be considered as an alternative water-soluble MR contrast agent to Gd-DTPA.

Adult↗

Comparison of the brain specific protein alpha-albumin and GFA (glial fibrillary acidic protein).

In this study, the brain specific proteins alpha-albumin and glial fibrillary acidic protein (GFA) are compared by several biochemical and immunological methods. It is concluded that alpha-albumin and GFA are immunologically identical and biochemically narrowly related. The existence of two forms of this protein, a water soluble and a water insoluble, under physiological conditions is discussed by comparing the results of quantitative determinations and histoimmunological localizations.

Albumins↗

Autoantibodies to brain specific proteins in human serum from normal and several pathological conditions.

Autoantibodies to three nervous tissue specific proteins [alpha Albumin (GFA, Eng et al., 1971), S100 (Moore et al., 1968) and MBP (Eylar et al., 1969)] were determined in sera from 270 neurological patients. Control values were established in sera from 21 blood donors. Differences between the control group and several pathological conditions were found, positive results were obtained in sera of patients affected with MS, polyneuropathy and astroglial tumors.

Astrocytoma↗