Search PubMed⌕ Search

Biomedical subjects

K Felgenhauer

Publications and source records attributed to K Felgenhauer.

At least 109 records · Page 6Linked to original sources

Cerebrospinal fluid virus antibodies. A diagnostic indicator for multiple sclerosis?

Specific antibody activities (antibody per weight unit IgG) of serum and CSF against a broad variety of viruses were compared in multiple sclerosis and certain inflammatory diseases of the central nervous system, e.g. neurosyphilis, as well as herpes simplex and zoster encephalitis. No "unspecific" antiviral activities within the CSF compartment were found in the non-MS diseases. The most frequent antibodies locally produced were directed against measles, rubella and zoster antigens. A diagnostic test with these three viruses would give positive results in about 80% of patients with MS. This finding is not as frequent as the oligoclonal pattern of the CSF gamma-globulins but would have a considerably greater diagnostic significance.

Antibodies, Viral↗

[Immunoglobulin G synthesizing lymphocytes in the cerebrospinal fluid in multiple sclerosis and non-inflammatory diseases of the nervous system].

In 208 patients, the IgG-synthesizing lymphocytes of the CSF were demonstrated with immunocytochemical methods. These cells were found in 59 of 111 patients with multiple sclerosis. Their frequency of appearance was dependent on the duration of the disease and its clinical severity. A comparative laser-nephelometric examination of serum and CSF, together with CSF cell diagnosis, demonstrated that IgG-synthesizing lymphocytes were present in 12% of the patients without simultaneous local IgG production within the CNS. These cases showed mostly very short clinical courses. IgG-synthesizing lymphocytes were absent from the CSF of 97 patients with non-inflammatory diseases of the nervous system.

Adolescent↗

OKT8-binding lymphocytes in diseases of the nervous system.

OKT8-binding lymphocytes, which consist mainly of suppressor-cytotoxic T cells, were demonstrated in blood and CSF by an immunochemical method. In patients with non-inflammatory diseases, the mean value was 18% in blood and 19% in CSF. In acute viral infections of the CNS, on the other hand, the percentage was significantly lower in the initial days of the disease but then increased up to the 5th week. Eleven patients suffering from multiple sclerosis had similar percentages of OKT8-binding cells, whether or not they had acute symptoms.

Central Nervous System Diseases↗

Development of the blood-CSF barrier.

The development of the blood-CSF barrier was investigated by establishing total protein, individual protein levels and cell-counts in the CSF and serum of 185 healthy children, with an age range from 27 fetal weeks to 16 years. Albumin, alpha 2-macroglobulin and immunoglobulin G were found in all CSF specimens. With the exception of IgG, their concentrations decreased continuously until the end of the first year of life. IgM was not present in the CSF and IgA was found in only a few cases. Serum:CSF ratios of individual proteins increased continuously from the fetal period to the first year and there was a decline in barrier selectivity during the same period. Maturation of the barrier was maximal during the third month of life, decreasing quickly thereafter. The barrier condition of preterm infants was closely related to conceptional age, but not to the time of birth.

Albumins↗

Low molecular solutes and the blood cerebrospinal fluid barrier.

An attempt is made to evaluate those portions of low molecular hydrophilic solutes that obey apparent passive transfer principles at the blood cerebrospinal fluid (CSF) barrier under steady state conditions. Twenty-four electrolytes, metabolites, and amino acids are determined in serum and CSF obtained simultaneously. The correlation found between the serum/CSF concentration ratios and the molecular radii of most compounds is indicative of the prevalence of passive transfer processes in CSF formation, as has been already demonstrated for proteins. The level of some constituents in the primary filtrate may be secondarily increased by influx from the adjacent extracellular space, e.g. glutamine and creatinine, or decreased by specific uptake from the CSF compartment, e.g. glycine. The CSF levels of all compounds are dependent upon the actual state of the blood CSF barrier as evaluated by the serum/CSF concentration ratios of albumin and alpha 2-macroglobulin. The results do not support the assumption that CSF may be used to test the permeability state of the blood brain barrier propery.

Blood-Brain Barrier↗

[Low-symptom herpes simplex encephalitis (author's transl)].

A 39-year-old man had acoustic hallucinations for about one year due to chronic alcoholism. He suddenly lost consciousness after suffering from headaches for about four weeks. EEG and CT scan were indicative of a brain tumour but lumbar puncture revealed slight pleocytosis and an immunoglobulin G fraction synthesized within the central nervous system. This secretory fraction contained major portions of locally produced herpes simplex antibodies detectable with a complement fixation test and a recently developed enzyme immunoassay. The patient remained in hospital for only a few days and went back to work after six weeks. To our knowledge this is the first case reported surviving herpes simplex encephalitis outside hospital without impairment of consciousness, confusion or substantial neurologic symptoms. The question remains open, whether the generally severe course of this disease had been modified by the chronic alcoholism. It is obvious that the correct diagnosis would have been missed without lumbar puncture.

Adult↗

[Zoster encephalitis without rash: report of two cases (author's transl)].

Two previously healthy men, aged 54 and 41 years, fell ill with headaches and increased fatiguability, one also with vomiting, the other with fever, transitory visual disturbances and slight weakness of the left hand. Both of them had a stiff neck and clouded consciousness. The EEG had moderate to severe dysrhythmia, predominantly over the temporal area, CSF showed an increased cell count of 1000/3, predominantly lymphocytes, and increased protein. The younger patient also had global aphasia and the computed tomography indicated an area of decreased density in the left temporal region. In the CSF there were locally produced IgG. The clinical findings were similar to those of herpes encephalitis, but were milder and regressed more quickly. Severe months later only a few minor organic behavioural changes were present. Antibody findings in CSF and serum suggest varicella-zoster virus as the causative agent, although in both instances no rash was observed throughout the entire period of observation.

Adult↗

Differentiation of the humoral immune response in inflammatory diseases of the central nervous system.

The three main immunoglobulin classes obey the basic principles of passive protein transfer at the blood-CSF barrier and the serum-derived portions could therefore be quantified with the help of the permeability marker albumin. The Ig fractions secreted into the CSF by sessile plasma cell clones have been determined in various inflammatory diseases of the central nervous system. The humoral immune response in multiple sclerosis and chronic encephalitis of unknown cause was dominated by IgG antibodies. In most other inflammatory diseases IgA and IgM were concomitantly synthesized, e.g. in neurosyphilis and meningoencephalitis caused by viruses of the herpes group. In tick-borne meningopolyneuritis Bannwarth, only IgM and in bacterial meningitis only IgA may be produced locally. The detection of a secretory immunoglobulin fraction in the CSF may be the sole laboratory parameter in chronic inflammatory processes of the nervous system.

Adult↗

The demonstration of locally synthesized herpes simplex IgG antibodies in CSF by a Sepharose 4B linked enzyme immunoassay.

A newly developed peroxidase-linked immunoassay is described which is sensitive enough to quantify herpes simplex antibodies in serum and cerebrospinal fluid diluted to an IgG level of 1 mg/dl. Thus, a comparison of photometric signals allows the direct detection of specific antibodies which have been secreted by activated tissue B lymphocytes into the CSF compartment during the humoral immune phase of herpes simplex encephalitis. The technique utilizes urea-Triton-dissolved virus antigens covalently bound to Sepharose 4B pearls. A highly specific sandwich antibody was purified by immune absorption column chromatography and labelled in its protected state. In the majority of cases the antibody level increased around the 10th day, to reach its maximum a few days after. In some cases however the serum levels gradually rose over a period of several weeks. The antibody levels in the CSF increase uniformly at the same time, irrespective of the general immune response and soared up to higher than serum levels within a few days. Local antibody production may persist for years so that late diagnosis of herpes encephalitis becomes possible with a single side by side test of serum and CSF from the patient.

Acute Disease↗

Late elevation of CSF proteins in three cases of mumps meningoencephalitis.

Three children suffered from mumps meningoencephalitis and pneumonia. The clinical course was uneventful. After 2 weeks antibiotic therapy for pneumonia a repeat lumbar puncture showed a massive increase of CSF protein levels. This phenomenon was transitory. It is explained by an obstruction in CSF pathway in the course of mumps meningoencephalitis.

Cerebrospinal Fluid Proteins↗

Two-dimensional separation of human body fluid proteins.

High resolution protein patterns of various human body fluids are compared. They were obtained by non-restrictive agarose electrophoresis in the first and exclusion electrophoresis on polyacrylamide pore gradients in the second dimension. The majority of serum proteins above 10 mg/dl have been identified and the heterogeneities of high density lipoproteins, immunoglobulins and haptoglobins become visible within the charge/size grid of the two-dimensional pattern. Since secretory and serum-derived components can be differentiated, the contribution of protein synthesis and filtration to the formation of the finally released fluid can be assessed. The technique may be used to screen complex soluble protein mixtures for pathological components. There is a wide range of variations in composition from the secretory fluids (e.g. tears, colostrum, milk, seminal fluid) to virtually "pure" filtrates (pleural effusions, osteoarthritic synovial fluid, cyst puncture fluid, and amniotic fluid). It is evident that the composition of the serum-derived fraction depends primarily upon the selectivity of the respective blood/body fluid barriers. The resolution capacity of the technique is compared with that obtained by two-dimensional gel-focusing/SDS electrophoresis of the constituent serum protein subunits.

Blood Proteins↗

The detection of activated cerebrospinal fluid B lymphocytes by peroxidase conjugated antibodies.

A method for the preparation of a potent and specific peroxidase-labelled antihuman IgG antibody is described. CSF cells from patients with various neurological diseases were stained. Only in cases of inflammatory diseases was IgG detectable. The stained cells were so-called lymphoid cells. As the demonstrable IgG can be regarded as a product of intracellular synthesis, it is justified to call these cells activated B lymphocytes. The relative portion of activated B cells tends to be high in the first half of the mononuclear phase and depends upon the type of disease. It is low in most cases of bacterial and benign viral meningitis whereas high B cell numbers were found in Bannwarth meningopolyneuritis, mumps meningitis and herpes simplex encephalitis. Albeit there exists a time lag between the maximal number of activated B lymphocytes and the demonstration of the secretory immunoglobulin fraction, quantitative correlation between these two inflammation parameters were demonstrated in cases of acute meningoencephalitis. These correlations were not seen in chronic inflammatory diseases.

B-Lymphocytes↗

The process dynamics of viral and bacterial diseases of the central nervous system.

Several patients with herpes simplex encephalitis developed a prolonged humoral immune reaction within the central nervous system, which was evaluated by the measurement of locally synthesized immunoglobulin fractions in cerebrospinal fluid. Such phasic immune responses seem to occur predominantly in CNS infections with herpes and myxo/paramyxo viruses. In many cases the B-cell response follows a primary neutrophilic and a secondary mononuclear phase. Most benign viral encephalomeningitis cases lack this type of strong local B-cell activity. This is also true in most cases of bacterial meningitis, that recover after a strong neutrophilic attack and a minor mononuclear reaction. The initial phase of a purulent meningitis is characterized by a complete breakdown of the blood-CSF barrier. This occurs also in some cases of "apurulent bacterial meningitis", that are characterized by very low CSF-cell counts in spite of a totally broken barrier. The "compartmental leucopenia" is interpreted as an imbalance between the supply from the blood and an intense phagocytic consumption within the CSF space. The influence of the hydrodynamic size of viruses on the mode of entry into the central nervous system and on the dynamics of the inflammatory reactions is discussed.

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↗