PubMed HealthSearch

Biomedical subjects

K Felgenhauer

Publications and source records attributed to K Felgenhauer.

11 recordsLinked to original sources

The diagnostic significance of antibody specificity indices in multiple sclerosis and herpes virus induced diseases of the nervous system.

The antibody specificity index (ASI) indicates the cerebrospinal fluid (CSF)/serum difference of antibody amounts per weight unit IgG (normal less than 1.5). It has proven to be the most sensitive inflammation parameter in CSF analysis so far, more sensitive than the Western blot, the "oligoclonal" response, and the empirical differentiation of CSF immunoglobulins. By this diagnostic criterion, several benign viral meningitis cases were found to be caused by the varicella/zoster virus. The diagnostic relevance of local zoster antibody synthesis was greatest in ganglionitis cases, e.g., in zoster oticus sine herpete (facial paresis) and acute radicular syndromes of the elderly. The diagnostic significance of the local immune response against measles, rubella, and zoster antigens (MRZ response) was ascertained further. Together with oligoclonal gamma-globulin fractionation, there is now only 1 out of 100 multiple sclerosis (MS) patients left who has been found to have a normal CSF.

Adult

Characterization of native multicomponent protein mixtures by one- and two-dimensional gradient electrophoresis.

An arrangement of one- and two-dimensional polyacrylamide gradients has been applied to the analysis of multicomponent mixtures of soluble proteins: (1) two-dimensional 3-25% slabs; (2) 3-40% cylinders; and (3) 20-50% cylinders. The run in the first dimension is performed in non-restrictive agarose gel to ascertain a "pure" charge abscissa. Gradient electrophoresis is performed over prolonged periods in order to reach or closely approach the exclusion (pore) limit, which is taken as an operational parameter for the hydrodynamic size of globular molecules irrespective of their frictional ratios. For each of the three gradients one to four reference mixtures were formulated that allow size evaluations of non-denatured proteins. Human serum again proved its usefulness as a universal reference mixture for newly developed techniques. The number of stainable components is in accordance with expectation based on the broad knowledge of serum proteins. Two-dimensional agarose/gradient electrophoresis seems to fulfil the one band-one protein strategy of high-resolution techniques.

Animals

[Blood-cerebrospinal fluid barrier and the local immune response in the course of meningitis in childhood].

The condition of the blood-CSF barrier can be evaluated by the simultaneous quantitation of marker proteins in serum and cerebrospinal fluid. The concentration ratios of albumin and alpha 2-macroglobulin, plotted versus the hydrodynamic radii are used as permeability parameter. There are wide ranging barrier disturbances during the early stages of meningitis. In mumps meningitis only slight disturbances were found, meanwhile in bacterial meningitis the barrier permeability was strongly increased. In both disease groups one may detect secretory fractions of both immunglobulins G and A. In some cases of mumps meningitis a prolonged humoral immune reaction was found.

Age Factors

Serum-CSF protein gradients, the blood-CSF barrier and the local immune response

For the majority of proteins there is a steady state equilbrium between the serum and the CSF compartment which depends upon the hydrodynamic radii of the passively transferred molecules. For clinical purposes the serum-CSF concentration ratios of albumin (Aalb) and alpha2-macroglobulin (Qalpha2 M) have proven to be a reliable barrier parameter, which is more sensitive than the total protein level in certain diseases, e.g. disk protrusions, degenerative processes and metabolic disorders. The immunoglobulins G and A cope with the passive transfer mechanism in both normal conditions and all degrees of pure barrier impairments but deviate in cases with local immunoglobulin production. The method described produces a quantitative differentiation between the locally synthesized and the serum-derived immunoglobulin fractions. A humoral immune response within the central nervous system was found in certain stages of acute infectious diseases and with chronic inflammatory processes such as subacute sclerosing panencephalitis, neurolues and multiple sclerosis.

Blood-Brain Barrier

Rapid determination of proteins in serum and cerebrospinal fluid by laser-nephelometry.

The Laser-nephelometric technique is characterized by its easy handling, accuracy, good reproducibility and especially by the short time in which reliable results are available. A very good correlation was found between the results obtained by the electroimmunoassay and those obtained by Laser-nephelometry. In both techniques alpha2-macroglobulin is the largest serum protein that can be determined in normal unconcentrated cerebrospinal fluid (CSF). This is of diagnostic significance, since the serum/CSF ratios of both albumin and alpha2-macroglobulin are used as a parameter for the blood-CSF barrier condition.

Albumins

Hydrodynamic radii versus molecular weights in clearance studies of urine and cerebrospinal fluid.

The protein permeabilities of the blood-cerebrospinal-fluid barrier and the blood-urine barrier are compared. In both instances the permeation rates of proteins can be better correlated to hydrodynamic radii than to molecular weights. The decreasing clearance rates of ceruloplasmin, IgG, and IgA reflect the hydrodynamic heterogeneity of these proteins, which have similar weights. The IgM clearance rate appears too high, possibly owing to monomer IgM, other IgM fragments, selective transport, or active immunity, so its inclusion is not recommended in clearance studies.

Ceruloplasmin

Evaluation of the blood-CSF barrier by protein gradients and the humoral immune response within the central nervous system.

A linear correlation was found between the serum/cerebrospinal fluid (CSF) concentration ratios of albumin, caeruloplasmin and alpha2-macroglobulin and their hydrodynamic radii in a semilogarithmic plot. This protein gradient is used as a parameter to evaluate the blood-CSF barrier under normal and pathological conditions. Irrespective of vastly different transfer rates, the ratio/size permeation curves of proteins at the blood-CSF barrier and the blood-lymph barrier have comparable characteristics. Therefore the protein gradients found in various disease states are interpreted by means of Renkin's general law of lymph formation. Declined gradients are caused either by an increased permeability of the barrier sites or by a decreased turnover rate of the CSF within the compartment punctured. The concentration ratios of immunoglobulins are related to the gradient that is constructed with the ratios of the barrier-indicative marker proteins. As judged by comparative disc electrophoresis of serum and CSF, those disease states that are dominated by barrier impairment are used to establish the range of concentration ratios, compatible with a passive immunoglobulin transfer in any condition in which the barrier is disordered. A mathematical approach is described, which allows the quantitative evaluation of the minimal immunoglobulin portion that is synthesized within the central nervous system.

Adult

The development of the blood-CSF barrier after birth.

The serum/CSF concentration ratio of alpha-2-macroglobulin is used as parameter to follow the development of the blood-CSF barrier throughout childhood. The decline of the protein permeability within the first year of life has all characteristics of a maturation process. The tightening of the barrier is thought to be the last stage of a continuous developmental process of capillaries. It is accompanied by a compositional shift in favour of small molecular serum proteins.

Adolescent