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Biomedical subjects

O R Hommes

Publications and source records attributed to O R Hommes.

At least 73 records · Page 4Linked to original sources
PubMed1984

A study on post-synthetic modifications in alfa-alfa enolase (EC 4.2.1.11) brought about by a human serum protein.

Human alfa-alfa enolase is modified in the blood circulation by a serum protein for which the name 'modifying protein' is proposed. The protein occurs in every human serum tested and appears to be the same protein that is responsible for the post-synthetic modification in the M subunit of creatine kinase. Three alfa-alfa enolase forms, the original one plus two modified forms can be found in serum both in vivo and after in vitro incubation. The original alfa-alfa enolase is modified completely within a few hours in vitro in a pH-controlled human serum matrix at 37 degrees C. As the modification also takes place in vivo it is theoretically possible to acquire information about the activity of a disease process by doing one single determination of the amount of circulating alfa-alfa 3 enolase. A mechanism is proposed for the modification, where at first one of the two alfa chains is modified resulting in the alfa-alfa 2 form. Ultimately the second alfa chain is also modified. The alfa-alfa 1 form seems to be the completely modified alfa-alfa form. The three enolase forms differ in their isoelectric points but have similar Michaelis-Menten constants.

Blood Proteins↗
PubMed1984

Lymphocyte subpopulations in multiple sclerosis: spontaneous and mitogen-induced activity.

Lymphocytes of chronic progressive multiple sclerosis (MS) patients and healthy persons were isolated by nylon-wool column filtration followed by density centrifugation. Incubating part of these lymphocytes with 2- aminoethyliso thiouronium bromide hydrobromide-treated sheep erythrocytes resulted in two other subfractions, the rosette-forming (E+) lymphocytes and the nonrosette -forming (E-) lymphocytes. Increased spontaneous activity was observed with the nonfractionated lymphocyte populations and with the E+- and E- -cell fractions of MS patients compared to the corresponding cell populations of controls following a culture period of one or several days. Phytohemagglutinin- and pokeweed mitogen-induced stimulation of these different lymphocyte fractions was the same in MS patients and controls. No influence of disease activity could be found on the immune parameters. Characterization of the different lymphocyte populations with monoclonal anti-human T-cell antibodies demonstrated a prevalence for helper T cells in forming rosettes.

Adult↗
PubMed1984

T-cell subsets in spinal fluid of multiple sclerosis patients.

CSF T-cells and T-cell subsets were characterized by monoclonal antibodies in 15 untreated multiple sclerosis (MS) patients, 17 immunosuppressed chronic progressive MS patients and 9 patients with other neurological diseases. A negative correlation was found between total cell numbers and T suppressor cell percentages in untreated and treated MS patients. A negative correlation (r = -0.71) was found between intrathecal IgG levels and T suppressor cell percentages in untreated MS patients. In peripheral blood, no correlation between T-cells and T-cell subsets with IgG levels was found. It is discussed that T-cell subsets and intrathecal IgG levels may be indicators of the activity of the inflammatory process in the brains of chronic progressive MS patients.

Antibodies, Monoclonal↗
PubMed1984

SSEP chronotopography in patients with multiple sclerosis.

In 10 patients with definite MS, an SSEP chronotopogram was constructed of 7 different, well-defined components: N20, P25, P45, P100, N140, P200 and P300. Chronotopographical maps were constructed on the basis of the localization of maximal amplitudes of the different components and their dipolar counterparts (when present). Most patients showed a delay of different specific as well as aspecific components. The chronotopogram was not much different from normal except for P45. Most generators therefore seem to stay stable. One of the P45 dipole generators vanished, probably due to a slight change in its direction, or more probably as a consequence of loss of association fibres in the cortical white matter. Spatio-temporal mapping provides new, clinically relevant information. The development of automatic methods for this mapping is justified for routine clinical use in neurology.

Adult↗
PubMed1984

The effect of cyclophosphamide on T lymphocytes and T lymphocyte subsets in patients with chronic progressive multiple sclerosis.

The lymphocytes in peripheral blood and cerebrospinal fluid of patients with chronic progressive multiple sclerosis (MS) were characterized with monoclonal antibodies to surface antigens of T cells, helper/inducer T cells and suppressor/cytotoxic T cells. The influence of cyclophosphamide treatment on these immune parameters was investigated. Compared to healthy persons, the mononuclear cell fraction of the peripheral blood of patients with chronic progressive MS consisted of normal %s of T cells and helper/inducer T cells, but decreased %s of suppressor/cytotoxic T lymphocytes. Intensive as well as chronic treatment of MS patients with cyclophosphamide resulted in a decline in the %s of T cells and helper/inducer T cells, whereas the %s of suppressor/cytotoxic T cells returned to normal. In cerebrospinal fluid, cyclophosphamide also induced a relative decrease in the % of helper/inducer T cells and an increase in the % of suppressor/cytotoxic T cells compared to untreated MS patients. Intensive as well as chronic therapy with cyclophosphamide both led to a significant decrease in the absolute number of T cells and T cell subsets in the blood of the patients.

Adult↗
PubMed1983

A bioluminescent assay for enolase (EC 4.2.1.11) activity in human serum and cerebrospinal fluid.

A simple method is described for the measurement of enolase enzyme activity in human serum and in unconcentrated cerebrospinal fluid. The enzyme is measured by a bioluminescent assay, making use of the luciferine/luciferase system. The method is very suitable for use in clinical chemical laboratories. The Michaelis-Menten constants of three enolase isozyme forms have been measured. Data concerning the in vitro stability at 37 degrees C of alfa-alfa, alfa-gamma and gamma-gamma enolase in cerebrospinal fluid are presented. The gamma-gamma form is the most stable enolase form under these conditions. Preliminary data from a clinical study about the diagnostic significance of the enzyme indicate that evident elevations in cerebrospinal fluid enolase levels can be seen in patients from neurological wards. There is a poor correlation between total creatine kinase and enolase cerebrospinal fluid levels.

Electrophoresis, Agar Gel↗
PubMed1983

Inhibition of rat brain monoamine oxidase type A by 2-aminotetralin and tetrahydroisoquinoline analogues of dopamine.

The in vitro inhibition of rat brain monoamine oxidase type A (MAO-A) by various dopamine analogues is reported and compared to some established inhibitors of the enzyme. The estimated IC50's were found to be in the range 10(-5)-10(-3) mol/l. This makes these compounds more than 10 000 times less potent than the selective MAO-A inhibitor harmaline and more than 10 times less potent than the selective MAO-B inhibitors pargyline and deprenyl. When the brain concentrations that are reached after peripheral administration of these drugs are taken into account it is unlikely that inhibition of MAO is relevant to their effects as has been suggested. Also the endogenous brain concentrations of some tetrahydroisoquinolines are probably too low to produce an inhibition of the enzyme.

Animals↗
PubMed1983

Cyclophosphamide levels in serum and spinal fluid of multiple sclerosis patients treated with immunosuppression.

The cyclophosphamide content of urine, serum and spinal fluid of immuno-suppressed multiple sclerosis patients was determined using a newly developed off-line combination of high pressure liquid chromatography and field desorption mass spectrometry. Although urinary excretion of the drug varied considerably between patients, the levels in serum and spinal fluid were in the same range, a relationship that may facilitate control of the dosage.

Adult↗
PubMed1983

T-cell subpopulations in blood and cerebrospinal fluid of multiple sclerosis patients: effect of cyclophosphamide.

Monoclonal antibodies to various lymphocyte surface antigens were used for characterization of cerebrospinal fluid (CSF) and peripheral blood (PB) cells of patients with chronic progressive multiple sclerosis (MS) and of patients with other neurological diseases (OND). The effect of cyclophosphamide on these T-lymphocyte subpopulations in both compartments was studied. In the CSF of all patients 90 +/- 9% of the cells were T lymphocytes. T-helper/inducer (Th) lymphocytes comprised 70 +/- 9% and T-suppressor/cytotoxic (Ts) lymphocytes 31 +/- 10%. No significant differences in the percentages of T-lymphocyte subpopulations in CSF were observed between MS patients and patients with OND. The results obtained with monoclonal antibodies to Ia antigens suggested the presence of activated T cells in CSF of MS as well as OND patients. The mononuclear cell population isolated from PB of all patients contained 64 +/- 13% T lymphocytes, 44 +/- 11% Th cells, and 21 +/- 7% Ts cells. No significant difference in the ratio Th/Ts cells was observed between CSF and PB. The mononuclear cells isolated from the PB of untreated chronic progressive MS patients contained lower percentages of Ts cells (17 +/- 5%) and increased ratios of Th/Ts cells (3.1 +/- 1.6) compared to neurological controls (23 +/- 8% and 1.9 +/- 0.7) and healthy persons (23 +/- 6% and 1.9 +/- 0.5). In both PB and CSF, compared to untreated patients, cyclophosphamide-treated MS patients showed lower percentages of Th lymphocytes, whereas Ts-cell percentages were higher, leading to a normal ratio of Th/Ts cells in both compartments. The percentage of total T lymphocytes in PB was reduced by this treatment.

Antibodies, Monoclonal↗
PubMed1983

Influence of cerebroside and ganglioside on the encephalitogenic activity of myelin basic protein in guinea pigs.

The effect of 2 central nervous system glycolipids (cerebroside and ganglioside) on the encephalitogenic activity of bovine myelin basic protein (MBP) was studied in guinea pigs. Mixing each of these glycolipids with MBP and injection of these mixtures in Freund's incomplete adjuvant (FIA) abrogated the resistance to encephalomyelitis upon challenge with MBP in Freund's complete adjuvant (FCA). Primary injection of these glycolipid-MBP mixtures in FCA diminished the clinical signs of experimental allergic encephalomyelitis (EAE) as compared to primary injection of MBP in FCA. Considering the amount of ganglioside needed to optimally induce these effects, this phenomenon seemed to be aspecific. However, with cerebroside, only minor quantities were sufficient, suggesting specific interaction with the basic protein. In several aspects, close correlation was found between cellular immune activity to MBP as measured by skin reactivity and the development of EAE.

Animals↗
PubMed1982

Cell-mediated immunity in multiple sclerosis as determined by sensitivity of different lymphocyte populations to various brain tissue antigens.

Peripheral blood lymphocytes from patients with multiple sclerosis (MS) or other neurological diseases and from healthy individuals were separated by density gradient sedimentation into several subfractions. Individual cell populations were cultured in the presence of several human brain tissue antigens. In comparison to controls, mononuclear cells with a density of less than 1.077 gm/cm3 from MS patients displayed a significantly increased sensitivity after incubation with purified human myelin basic protein (MBP) but not with other brain tissue antigens. In particular, the lymphocytes of patients suffering from MS for more than four years reacted positively with MBP, suggesting that the reaction dependent. No difference between MS patients and controls in sensitivity to any brain tissue antigen could be detected with cells of lower density (i.e., 1.073 to 1.069 gm/cm3 or less than 1.069 gm/cm3). Comparable lymphocyte activity was found to antigens isolated from both MS and control brain tissue. These results suggest that patients with chromic progressive MS have a secondary immune activity to MBP.

Adult↗
PubMed1982

In vitro studies of 5, 10-methylenetetrahydrofolate reductase: inhibition by folate derivatives, folate antagonists, and monoamine derivatives.

Folate monoglutamates and folate antagonists have an inhibitory action on the activity of 5,10-methylenetetrahydrofolate reductase in rat brain. The type of inhibition was studied for dihydrofolic acid using the Lineweaver--Burk transformation. Some of the monoamine alkaloids, the in vitro products of 5,10-methylenetetrahydrofolate reductase, have either a stimulatory or inhibitory effect on the enzyme activity.

Animals↗
PubMed1982

Spontaneous and mitogen-induced activity of lymphocytes of different density in multiple sclerosis.

Some immunological parameters of patients with multiple sclerosis (MS), of patients with other neurological diseases and of healthy volunteers were compared. No significant differences between these groups of persons were found in the number of leukocytes, granulocytes or lymphocytes per milliliter of peripheral blood. A density distribution profile of the peripheral blood mononuclear cells revealed a relatively increased number of low density cells (less than or greater than 1.069 g/cm3) and a relatively decreased number of cells with higher density (1.069-1.073 g/cm3) in MS patients as compared to healthy controls. The spontaneous activity and the pokeweed mitogen-induced activity of the different cell subfractions, separated according to density, appeared to be normal in MS patients. The results suggest a continuous stimulation of the immune system of MS patients resulting in a shift of cells towards lower density. This change was not related to disease duration or severity.

Adult↗
PubMed1981

The preselection value of the Doppler LP test for shunt-therapy in patients with normal pressure hydrocephalus.

The results of this study confirm the hypothesis that the simple innocuous Doppler LP test may be useful in obtaining information about CSFP-CBF (cerebrospinal fluid pressure-cerebral blood flow) relationships. The value of this test in predicting the clinical outcome of CSF shunting in patients with normal pressure hydrocephalus (NPH) was studied. Fourteen patients with NPH were examined; eight patients showed a positive and six patients a negative Doppler LP test. Seven of the eight patients with a positive test improved following the shunting procedure, but none of the six patients improved after operation. This study suggests that the Doppler LP test is a useful preoperative selection test in patients with NPH. In addition this study supports the hypothesis that CBF autoregulation may be impaired with NPH.

Adolescent↗
PubMed1981

Relation between EEG and disability scores in multiple sclerosis.

A disability-scoring and an EEG-spectral analysis was performed in patients suffering from clinically and biochemically (oligoclonal aspect in cerebro-spinal fluid) proven multiple sclerosis at two stages of their illness, that are before and after a short intensive immuno suppressive therapy. In both stages a relationship is found between the degree of disability and the amount of beta activity in the fronto-central area and the amount of the theta activity in the temporal area. Significant improvement in the clinical state of the patient and a marked increase of the mean alpha frequency in the parietooccipital region could be demonstrated after short intensive immunosuppressive therapy.

Adult↗
PubMed1980

Determination of cyclophosphamide in urine, serum and cerebrospinal fluid of multiple sclerosis patients by field desorption mass spectrometry.

The levels of cyclophosphamide in samples of urine, serum and cerebrospinal fluid of multiple sclerosis patients, who had received the drug orally (4 x 100 mg/day) have been determined by field desorption mass spectrometry using the principle of stable isotope dilution. After thorough preparation of the samples, concentrations of cyclophosphamide of 10 to 60 micrograms/ml in urine and 200 to 400 ng/ml in serum and cerebrospinal fluid have been determined from 0.6-3 ml samples. The first quantitative data for cyclophosphamide in cerebrospinal fluid of multiple sclerosis patients could be established without the use of radioactive material. The relatively high level of the parent drug found in the fluid at the end of a 3-weeks treatment may shed some light on the mechanism of action of this drug in the treatment of the disease.

Cyclophosphamide↗