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Biomedical subjects

E Schuller

Publications and source records attributed to E Schuller.

At least 19 recordsLinked to original sources

Characterisation of a tryptic peptide from human placental ribonuclease inhibitor which inhibits ribonuclease activity.

Affinity-purified human placental ribonuclease inhibitor (PRI) was digested by trypsin. Subsequent fractionation of the hydrolysate by HPLC yielded 44 fractions, 3 of which retained the ability to inhibit ribonuclease. One of these, the most active, was a 15 amino acid peptide which had an amino acid composition corresponding to a tryptic fragment of PRI. This peptide was synthesised, and preliminary experiments were carried out on its interactions with ribonuclease. These experiments suggested that the behaviour of the peptide in terms of effect of pH, and effect of salt concentration were similar to the protein from which it was derived. These studies together with the strategic positioning of the peptide in the sequence of the ribonuclease inhibitor, suggest that this segment of PRI has an important role in the inhibitory activity of the intact protein.

Amino Acid Sequence

Intrathecal synthesis of proteins: from immunoglobulins to prealbumin.

The assessment of proteins intrathecal synthesis (ITS) is an essential step in the CSF analysis. It can be established qualitatively by different ratios and quantitatively by empirical formulae. Schuller and Sagar's formula was proposed 10 years ago for the calculation of IgG ITS. From this calculation, the antibody specific activity of intrathecal immunoglobulins may be also evaluated. The same principle may be used for complement components and for different other CSF proteins. Two examples (concerning Fibronectin and prealbumin ITS) demonstrate the usefulness of this approach, which can be programmed by a computer.

Acquired Immunodeficiency Syndrome

Fibronectin in plasma and CSF: evidence for its intrathecal synthesis.

A new methodology, using electroimmunodiffusion, has been described for the determination of fibronectin (Fn) in plasma and CSF. Fn was determined in the plasma of 35 normal subjects, and in the plasma and the CSF of 86 patients: 10 controls, 17 definite MS, 15 other inflammatory processes, 11 degenerative diseases, 13 peripheral neuropathies and 20 other neurological diseases. The normal mean was 354 +/- 53 micrograms/ml in plasma, not influenced by sex or age, and in the CSF 2.3 +/- 0.85 micrograms/ml. A significant increase of plasma Fn was observed in each of the patients-group. In the CSF an increase of Fn was observed predominantly in inflammatory processes but not in MS. An intrathecal synthesis of Fn was established in 24/76 patients, most often in inflammatory (9/15) processes but rarely (3/17) in MS. The intrathecal synthesis was suspected from the CSF Fn/CSF Albumin ratio and calculated using a formula derived from the principles previously described for IgG intrathecal synthesis. It represents the principal source of Fn increase in the CSF. In all inflammatory processes (including MS) the eventual influence of corticoids, immunosuppressive or anti-inflammatory drugs has not been established. The significance of the CSF Fn level in MS is discussed with regard to the recent demonstration of its presence within MS lesions and on macrophages in plaques.

Adult

Intrathecal synthesis of IgG subclasses in multiple sclerosis and in acquired immunodeficiency syndrome (AIDS).

Serum and cerebrospinal fluid (CSF) of 50 neurological patients (24 multiple sclerosis (MS), ten acquired immunodeficiency syndrome (AIDS) and 16 other neurological diseases (OND)) and ten controls were analyzed by enzyme-linked immunosorbent assay (ELISA) for IgG subclass quantification and for the calculation of intrathecal synthesis (ITS). Total IgG was determined by two methods: electroimmunodiffusion (EID) and ELISA. A highly significant correlation was established between both methods. The existence of ITS was proved by the IgG/albumin ratio, the IgG index, Tourtellotte's formula, and Schuller's formula. In AIDS patients all IgG subclasses showed an increase in the CSF, whereas in sera only the IgG1 was significantly increased. CSF of MS patients showed a predominant increase of IgG1 whereas no significant modification of IgG subclasses was observed in sera. In most of the AIDS patients there was an ITS of IgG1, IgG3 and IgG4, but rarely (3/10) IgG2. In contrast, a polyclonal ITS of IgG was exceptional (1/24) in MS patients. No significant correlation could be established between clinical data and IgG subclass ITS in MS. The variations of each IgG subclass in serum and in ITS were not significantly correlated. Measurement of each IgG subclass and calculation of ITS seems essential in order to analyze any subclass antibody repertory inside the central nervous system.

Acquired Immunodeficiency Syndrome

Virological markers in the cerebrospinal fluid from HIV-1-infected individuals.

We analysed 127 specimens of cerebrospinal fluid (CSF) from 118 HIV-1-infected individuals at different stages of infection. Intrathecal antibody synthesis was evident in 23 samples tested and was more frequently directed against HIV than against rubella virus, herpes simplex virus, varicella zoster virus or cytomegalovirus. HIV was isolated from only 14% of the 127 CSF specimens, but from 82% of CSF-paired blood samples. HIV antigen was detected in 12% of CSF specimens and 44% of paired plasma samples. Twenty specimens analysed using the polymerase chain reaction (PCR) detected proviral DNA in 75% of CSF specimens. The low rate of virus recovery from CSF was caused by neither the freezing of specimens prior to culture nor therapy. In contrast, virus isolation from CSF was significantly associated with CSF cell count. Virus isolation and antigen detection in CSF were not correlated with either the Centers for Disease Control disease stage or the peripheral CD4+ lymphocyte count, whereas viraemia was significantly associated with a low CD4+ lymphocyte count. Moreover, virus isolation and antigen detection in CSF were not associated with symptoms of subacute HIV encephalitis, suggesting that these markers are not of potential value in the diagnosis of HIV-specific neurologic complications. The value of PCR in this field merits further investigation.

AIDS Dementia Complex

Peripheral facial nerve palsy related to HIV infection: relationship with the immunological status and the HIV staging in Central Africa.

Twelve cases of infranuclear facial nerve palsy associated with infection by the human immunodeficiency virus in the heterosexual African are reported with clinical and immunological studies. Eight cases were healthy HIV carriers, three patients manifested AIDS-related complex and one case fulfilled the CDC criteria for AIDS. Nine patients had a typical Bell's palsy, two presented cephalic Herpes zoster infection with Ramsay Hunt syndrome and one, who suffered from progressive facial weakness, could be considered as having a cephalic form of Guillain-Barré syndrome.

Adult

Immunoglobulins and complement components in 37 patients infected by HIV-1 virus: comparison of general (systemic) and intrathecal immunity.

Intrathecal (IT) immunity was assessed by simultaneous analysis of paired cerebrospinal fluid (CSF) and sera of 37 patients infected by human immunodeficiency virus-1 (HIV-1). Only 8 of these 37 patients had no neurological or neuropsychiatric symptoms. There were 3 prominent abnormalities observed: (1) IT IgA production occurred in 15 patients, IT IgM production in 14 patients, and IT IgG production in 34 patients. (2) IT Anti-HIV-1 antibody specific activity (ASA) was higher than in serum in 33 of the 37 patients indicating that IT synthesis of antibody specific for HIV-1 occurs even in asymptomatic patients; IT anti-HIV-1 antibody synthesis was not correlated with clinical severity or neurological involvement. IT anti-herpes simplex ASA was also higher than serum ASA in 6 patients indicating a possible associated herpes simplex virus infection. (3) IT production of the complement component C4 was found frequently and was highly correlated with increased serum C4. IT C3 levels were decreased in 21 of 37 patients indicating that complement activation is a frequent accompaniment of the IT immune response in HIV-1-positive patients. These results indicate a unique and localized IT immune response which is different from the pattern observed in the systemic immune compartment in HIV-1-seropositive individuals and from the pattern common to the other CNS infectious diseases.

Acquired Immunodeficiency Syndrome

[Sex determination at the DNA level. Are inter-individual differences in male sex specific quotients to be expected?].

A determination of sex was performed for 23 male individuals using sex-specific DNA-probe (Y) (pJA 1143) and total human DNA as DNA-probes (A). The DNA-probes were P32 marked. Applying dot-blot-hybridisation black spots are obtained, the intensity of which may be quantified by a densimeter. The ratio (A/Y) of the intensity of the spots related to total human DNA (A) and to the sex-specific DNA-probe (Y) was calculated. DNA-dilutions of one male individual were prepared in order to determine the ratio (A/Y) for different DNA-concentrations. It was evident that the deviations for the sex-specific quotients of the DNA-dilutions amounts so large-scaled as compared to the quotients of the 23 male individuals, that the method of dot-blot-hybridisation appears not to be applicable to detect an individual component of a particular spot.

Base Sequence

[Analysis of intrathecal immunity].

The occurrence of an intrathecal immune reaction, specific to the central nervous system, may reflect either a contemporary systemic immune reaction or a local process directly related to the disease observed. Analysis of this reaction proceeds in 3 stages: the intrathecal production of immunoglobulins is assessed; the specific antibody activity of the intrathecal immunoglobulins is compared with that observed in serum; possible variations in components of complement are investigated. These different data are derived from the examination of serum and cerebrospinal fluid samples obtained simultaneously. The results of the analysis help in determining the cause of the disease, enable the severity and potential prognostic value of the immune reaction to be assessed and provide precise information on the influence of treatment on the course of the reaction. Several examples (syphilis, AIDS, measles panencephalitis, multiple sclerosis) illustrate these results.

Acquired Immunodeficiency Syndrome

Feeding frequency for lactating cows: diurnal patterns of hormones and metabolites in peripheral blood in relation to milk-fat concentration.

1. The present paper reports the effects of dietary modifications on the diurnal pattern of concentrations of certain metabolites and hormones in the peripheral blood of lactating dairy cows. The cows were given fixed rations of hay and high-cereal concentrates in the proportions of 30:70 or 10:90 (w/w). The concentrates were given in either two or six equal meals daily; the hay was given twice daily. 2. Previous reports of the same experiment had shown that milk-fat yield and concentration were reduced by increasing the proportion of concentrates in the diet and increased by more frequent feeding of the concentrates. These changes could be explained in part by changes in rumen volatile fatty acid (VFA) proportions and mean daily concentrations of VFA, particularly propionic acid, and insulin in the peripheral blood, but these factors failed to explain all the increase in milk-fat concentration caused by more frequent feeding. 3. Analysis of blood samples taken at hourly intervals for 24 h at two stages of lactation showed that, in the cows fed six times daily, the concentrations of metabolites and hormones remained relatively constant over the day. In the cows fed twice daily, the concentrations of VFA, 3-hydroxybutyric acid and insulin all increased after both meals whereas the concentrations of glucose and growth hormone tended to fall. The concentration of non-esterified fatty acids tended to increase overnight and fall rapidly after the morning feed. The concentrations of glucagon, thyroxine and prolactin showed no clear pattern in relation to meals. The postprandial responses of propionate, insulin and growth hormone were greater with the higher concentrate diet. 4. The maximum concentration and the diurnal range of concentrations were reduced by more frequent feeding of both diets in the case of propionic acid and of the higher concentrate diet in the case of insulin, but the effects on insulin concentrations of more frequent feeding of the lower concentrate diet were smaller and not significant. The maximum concentration and the diurnal range of concentrations of growth hormone were unaffected by meal frequency. 5. It is concluded that the severity of milk-fat depression in cows fed twice daily is increased by the rapid rise in propionic acid concentration in the peripheral blood after a meal, which in turn increases insulin secretion and may be accompanied by a suppression of growth hormone release. This causes lipogenesis to be diverted towards adipose tissue at the expense of the mammary gland.(ABSTRACT TRUNCATED AT 400 WORDS)

3-Hydroxybutyric Acid

Association of Guillain-Barré syndrome and Henoch-Schönlein purpura: is immunoglobulin a responsible for the neurologic syndrome?

Guillain-Barré syndrome and Henoch-Schönlein purpura (HSP) appeared simultaneously in a 35-year-old woman. During the course of the Guillain-Barré syndrome, the presence of IgA aggregates and a decrease in complement components were noted in the cerebrospinal fluid. These abnormalities disappeared when the neurologic syndrome remitted. This suggests the responsibility of IgA immune complexes, characteristic of HSP, in the occurrence of the associated Guillain-Barré syndrome.

Adult

[Cerebrospinal fluid proteins form the colloidal benzoin reaction to the present: a study of intrathecal immunity].

The benzoin reaction, described by Guillain, Laroche and Lechelle (1920) was probably the first test evaluating local (intrathecal) immunity in inflammatory diseases of the nervous system. Significant advances have taken place during the past 25 years: 1) Exact and precise determination of cerebrospinal fluid total protein by Lowry's method, and separation of gamma-globulins by precipitation or electrophoresis with identification of the oligoclonal aspect, the picture of intrathecal IgG synthesis. 2) Immunochemical determination of immunoglobulins and complement components by electro-immunodiffusion and detection of intrathecal anti-nucleic acid antibody synthesis. Different empirical formulae have been proposed to evaluate the intrathecal immunity. This evaluation allows: 1) a neuro-immunological classification of cerebrospinal fluid patterns. 2) a better appreciation of evolutivity in some neuro-immunological diseases (e.g. multiple sclerosis). 3) an evaluation of the antibody specific activity (ASA) and a comparison between this ASA in plasmatic and in intrathecally synthesized IgG. The study of complement components, also, can give some informations on the evolutivity of the immunological processus, suggesting, in some patients, an intrathecal formation of immune-complexes.

Benzoin