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H Reiber

Publications and source records attributed to H Reiber.

At least 55 records · Page 3Linked to original sources

Protein transfer at the blood cerebrospinal fluid barrier and the quantitation of the humoral immune response within the central nervous system.

The cerebrospinal fluid (CSF)/serum concentration quotients of albumin and the immunoglobulins G, A and M have been determined for 396 patients with a normal blood CSF barrier function or a pure barrier impairment without a humoral immune response within the central nervous system. The ratios between the concentration quotients of the three immunoglobulins and that of albumin increase in a nonlinear fashion with progressive impairments of the blood CSF barrier, i.e. the molecular size dependent discrimination of the protein transfer ('selectivity') decreases. The upper reference values of the concentration quotients for the whole range of passive transfer comply with the hyperbolic function: Q(IgX) = a/b square root Q(Alb)2 + b2 - c with different constants a/b, b2, c for IgG (0.8, 15 X 10(-6), 1.8 X 10(-3), IgA (0.72, 80 X 10(-6), 5.1 X 10(-3) and IgM (0.65, 150 X 10(-6), 7.5 X 10(-3). With these discriminatory functions the locally synthesized fractions IgX(loc) of IgG, IgA and IgM in CSF can be calculated by the general formula: IgX(loc) = [Q(IgX) - a/b square root Q(Alb)2 + b2 + c] X IgX(Ser).

Albumins↗

Sensitive quantitation of carcinoembryonic antigen in cerebrospinal fluid and its barrier-dependent differentiation.

Modification of an enzyme immunoassay using beads as solid phase allows the detection of 3 pg/ml carcinoembryonic antigen (CEA). The beads are shown to be advantageous for the extraction of proteins in highly diluted antigen solutions thus replacing a need for concentration of the sample. The mean concentration of CEA in pooled cerebrospinal fluid (CSF) from 120 control persons was shown to be 2.7 pg/ml. The mean of the CSF/serum concentration quotients of CEA was 0.0015 for normal blood CSF barrier function with a corresponding mean albumin CSF/serum quotient of 0.0048. From the ratio of these two quotients (QCEA/QA = 0.31) and the corresponding biological variation we constructed the normal range of an evaluation graph. In the range of a blood CSF barrier dysfunction, the discrimination line between values with or without a local CEA synthesis in brain was determined to be QCEA = 0.7 QA. Twenty-five out of 383 control persons and 29 out of 45 patients with a tumor metastasis had evaluable quotients. The evaluation graph had a high significance with respect to the identification of tumor metastasis: from a group of patients with a confirmed leptomeningeal metastasis 13 out of 13 and from a group of patients with intraparenchymatous tumor metastasis 10 out of 16 could be identified by CSF analysis. The CEA CSF/serum concentration quotient fits well in the concept of a molecular size-dependent filter function of the blood CSF barrier.

Blood-Brain Barrier↗

The clinical relevance of locally produced carcinoembryonic antigen in cerebrospinal fluid.

Sixteen out of eighteen meningeal carcinomas (89%) secreted carcinoembryonic antigen (CEA) into the cerebrospinal fluid, where it could be quantified separately from the portion originating from the circulating blood. The discrimination of both fractions was performed according to an empirical approach analogous to the immunoglobulins. Only 47% of the intraparenchymal carcinomas released CEA into the CSF compartment and it is possible that the extra-cellular space of these tumour sites does not communicate with the free CSF space. Extradural metastases may cause an impairment of the blood-CSF barrier via restrictions of the CSF fluid turnover, but the dura remains impermeable for the tumour marker. Seven out of 54 primary brain tumours (13%) released carcinoembryonic antigen into the cerebrospinal fluid.

Blood-Brain Barrier↗

Cyclosporin-A treatment of experimental allergic encephalomyelitis: changes in immunological regulation and blood-CSF barrier function.

Strain 13 guinea pigs at 18-21 days of age were sensitised with spinal cord and Freund's complete adjuvant to induce experimental allergic encephalomyelitis (EAE). Treatment with cyclosporin-A (CS-A) from one day before sensitisation until from 12 to 39 days after sensitisation resulted in a suppression of the disease. Suppression was indicated by an absence or reduction in severity of clinical signs together with a lack of increase in blood-cerebrospinal fluid (CSF) barrier permeability to proteins and a lower white cell count in the CSF from treated animals. When CS-A treatment was withdrawn, clinical disease reappeared but changes in IgG concentration in the CSF indicated that intrathecal synthesis of IgG had occurred, which was not the case in the untreated disease. Modification by CS-A of the immunoregulatory processes involved in the development of EAE, provides a model to study the special conditions which operate in neuroimmunological disorders.

Albumins↗

Chronic relapsing experimental allergic encephalomyelitis: cyclosporin-A treatment of relapsing and remitting disease.

Adult strain 13 guinea pigs in the relapsing-remitting phase of chronic relapsing experimental allergic encephalomyelitis were treated with cyclosporin-A (CS-A) at an oral dose of 35 mg kg-1 body wt. for periods of 17-32 days. Of the animals treated in relapse or remission the majority (6/11) showed a deterioration in clinical condition during treatment with the remaining 5 showing no change and 6/8 developed more severe clinical signs after treatment had ceased. In contrast, a similar group of untreated or vehicle-only treated relapsing-remitting animals developed a worse or better clinical condition in similar numbers when assessed over a similar time period with the majority (22/33) showing no change in clinical signs. Blood white cell counts and plasma IgG values remained constant throughout treatment and no clinical signs of drug toxicity were evident. Cerebrospinal fluid (CSF) mononuclear cell counts rose initially only in CS-A treated animals but fell to levels below those of controls by the end of treatment. These results are discussed in the context of the effectiveness of CS-A therapy in autoimmune diseases of the central nervous system.

Albumins↗

Amino acid transport across the human blood-CSF barrier. An evaluation graph for amino acid concentrations in cerebrospinal fluid.

The correlation of cerebrospinal fluid (CSF)/serum concentration quotients was used as a method for identification of amino acids which are transported by a common carrier system across the blood-CSF barrier. Isoleucine, leucine, valine, phenylalanine, tyrosine and lysine were found to compete for the same carrier system. This group of amino acids in man was found to be different from the system described as a neutral amino acid carrier at the blood-brain barrier in rats. In man, methionine and tryptophan do not compete with the other neutral amino acids for the same carrier system. In contrast, lysine as a basic amino acid is found to be correlated with the same transport system as the five neutral amino acids. A graph for the evaluation of pathological amino acid concentrations in CSF is presented. Patients with a blood-CSF barrier dysfunction for proteins showed partly normal, partly increased, CSF/serum concentration quotients for the amino acids. Hydroxyproline could be identified as a constituent of the amino acid pool in CSF. For proline and hydroxyproline a special control system has to be suggested because of their smaller biological variance in CSF than in blood. Contrary to the other amino acids proline and hydroxyproline have a smaller biological variation in CSF than in serum.

Adolescent↗

The effect of Freund's adjuvants on blood-cerebrospinal fluid barrier permeability.

In guinea pigs with experimental allergic encephalomyelitis induced by spinal cord homogenate--complete Freund's adjuvant (CFA) emulsions an increase in the albumin permeability of the blood--cerebrospinal fluid barrier occurred from day 10 post-inoculation (p.i.) onward. In animals inoculated with CFA alone an increased albumin permeability was also demonstrated but only between days 5 and 10 after inoculation; by day 14-16 p.i. the barrier permeability had returned to control values. A similar change was seen in animals inoculated with incomplete Freund's adjuvant (IFA) only. However, both CFA and CFA-cord induced a strong humoral immune response which was not seen in animals inoculated with IFA alone. These results may have important consequences for the understanding of the development of inflammatory diseases of the central nervous system.

Animals↗

Cerebrospinal fluid sampling from guineapigs: sample volume--related changes in protein concentration in control animals and animals in the relapsing phase of chronic relapsing experimental allergic encephalomyelitis.

Cerebrospinal fluid (CSF) was removed from guineapigs by puncture of the cisterna magna and the total sample volume of 200-360 microl divided into 40 microl aliquots. After determination of albumin and IgG in these CSF aliquots it was found that successive samples gave different results. In general, up to 100 microl CSF could be removed before the protein concentration began to increase. In animals with chronic relapsing experimental allergic encephalomyelitis (CR-EAE) the rise in albumin concentration was accompanied by a corresponding fall in the number of white cells in later samples.

Albumins↗

Kinetics of protein agglomeration. A nephelometric method for the determination of total protein in biological samples.

The kinetics of agglomeration of proteins precipitating in a viscous solution was measured by light scattering. The resulting transitory maximum was linearly proportional to the mass of protein over three orders of magnitude. The change in scattering intensity is described as a change in scattering symmetry due to a continuous increase in particle size. This method is both fast (minutes) and sensitive (30 ng protein) and is independent of the chemical composition of the different protein species and is barely influenced by size and shape of the proteins. By solubilising the protein samples in an alkaline dodecyl sulfate solution this method can be applied to all types of biological samples (e.g. tissue homogenates, membrane proteins) and also to all types of biological preparations containing detergents as well as urea, sucrose, salts and lipids.

Animals↗

Chronic relapsing experimental allergic encephalomyelitis. Immunological and blood--cerebrospinal fluid barrier-dependent changes in the cerebrospinal fluid.

Cerebrospinal fluid (CSF) and plasma were taken from strain 13 guinea pigs in various stages of chronic relapsing experimental allergic encephalomyelitis using techniques which allowed repeated sampling from the same animal. Samples were assayed for albumin and IgG and the corresponding CSF/plasma quotients evaluated graphically using a method which could discriminate between blood-CSF barrier dysfunction and local IgG synthesis in the central nervous system (CNS). During the disease a 2-3-fold increase in plasma IgG concentration developed and an increase in blood-CSF permeability was noted. Isoelectric focusing revealed an oligoclonal IgG pattern identical in both plasma and CSF. The results provided no evidence for a local production of IgG in the CNS like that which is known to occur in multiple sclerosis.

Albumins↗

Suboccipital puncture of guinea pigs.

Cisternal cerebrospinal fluid (CSF) was tapped from anaesthetized guinea pigs by an improved technique. This method allowed repeated weekly punctures of the same animal without any cellular or neurochemical changes in CSF or changes in behaviour. About 60% of the punctures produced enough CSF (30-330 microliters) with no or a sufficiently low blood contamination for neurochemical analysis. The CSF space in the spinal canal, cisterna magna and basal cisterns was demonstrated by myelography.

Animals↗

Species-dependent variables in blood cerebrospinal fluid barrier for proteins.

Cerebrospinal fluid/plasma concentration quotients for immunoglobulin G (I) and albumin (A) were determined in guinea pigs. Age and sex-dependent influences on these quotients (I/A) were analyzed and compared with the values for human lumbar, cisternal and ventricular cerebrospinal fluid. The ratio I/A, which characterizes the molecular size-dependent selectivity of the blood cerebrospinal fluid barrier function for proteins, was found to be a constant in a single species, but showed marked interspecies differences.

Aging↗

The discrimination between different blood-CSF barrier dysfunctions and inflammatory reactions of the CNS by a recent evaluation graph for the protein profile of cerebrospinal fluid.

A graph for the evaluation of the CSF-protein profile is presented as a basic program for the clinical-neurochemical laboratory. The graph has the following advantages: Simultaneous information on the functional state of the blood-CSF barrier and the inflammatory response of the CNS; maximal sensitivity for the determination of a pathological local IgG production in CNS--with the possibility of calculating the IgG fraction in CSF originating from the CNS; minimal number of protein assays necessary (albumin and IgG in serum and CSF); suitable for the demonstration of the course of the disease in a single patient as well as for demonstration of a group of cases for statistical purposes. Complementary chemical investigations and the correspondence with the clinical diagnosis are discussed for a number of typical cases. Two different types of blood-CSF barrier dysfunctions are discriminated by a proportional and a dis-proportionate increase of the CSF/serum protein concentration gradients.

Albumins↗