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Biomedical subjects

M Reunanen

Publications and source records attributed to M Reunanen.

At least 55 records · Page 3Linked to original sources

HLA-Dw1 and BfF as protective markers in multiple sclerosis.

The frequencies of Properdin factor B allotypes were studied in 54 multiple sclerosis patients and 58 healthy control subjects, and the association of various phenotypes with HLA-Dw1 and Dw2 antigens (found with decreased and increased frequency in MS patients, respectively) was further studied. SS genotype was found in 76% of MS patients and 63% of control subjects (n.s.) F types (FS + FF) were found to be strongly associated with HLA-Dw1 in control subjects (P less than 0.0014), whereas neither SS nor F containing types were associated with Dw2. The findings support the concept of a hypothetical MS resistance factor in the HLA gene area.

Alleles↗

Lymphocyte blast transformation responses to mitogens and specific antigens in different clinical phases of multiple sclerosis: a follow-up study.

28 MS patients were studied at least 5 times for lymphocyte blast transformation responses to several mitogens (PHA, Con, PWM) and specific antigens (PPD, herpes simplex, measles, mumps, rubella), the mean duration of the follow-up being 15.3 months. Comparison of responses during remissions, exacerbations and ACTH treatment revealed no straight-forward association between the strength of response and clinical disease activity. Mitogen responses did not differ among various disease phases, but the PPD response was significantly lower during exacerbations than during remissions and still lower during ACTH treatment (P less than 0.05, Wilcoxon paired test). In responses to viral antigens, there was the same trend as in the PPD response. However, there were great individual differences in the behaviour of all antigen and mitogen induced lymphocyte responses. As a group, MS patients also showed more changes in their PHA mitogen responses during the follow-up than 8 control subjects followed similarly (P less than 0.005, F-test). The variation coefficient of the PHA response was also correlated with the maximal difference in the Fog neurologic deficit scale during the follow-up time (r = 0.460, P less than 0.05). However, patients with greatest clinical changes most often also received ACTH treatment, which may affect the results. The follow-up results of individual patients revealed that some had quite regular patterns of decreasing responses during disease relapses, whereas others had more irregular wide fluctuations of responses.

Adrenocorticotropic Hormone↗

Intrathecal antibody synthesis to virus antigens in multiple sclerosis.

Intrathecal antibody synthesis against 17 common viruses and Mycoplasma pneumoniae lipid antigen was measured in 30 multiple sclerosis patients and 30 patients with other neurological diseases. Antibody synthesis was found against all of the antigens in at least a few of the MS patients. The highest number of patients had intrathecal synthesis of antibodies to measles, rubella and paramyxo type viruses and the lowest frequency was against M. pneumoniae, herpes simplex virus, adenovirus and cytomegalovirus antigens. Simultaneous antibody synthesis occurred against 1-11 different antigens in these patients. When the summation of different antibody specificities synthesized intrathecally was compared to the CSF-IgG Index, which measures the intrathecal immunoglobulin G synthesis, a fairly close correlation was found. The control patients had occasional antibody synthesis but generally only against one single virus antigen. The intrathecal antibody synthesis against viruses did not correlate to the disability of the MS patients. The intrathecal antibody synthesis was not different in younger and older patients or patients with shorter or longer disease duration, suggesting that events leading to intrathecal antibody synthesis may occur relatively early in life in these patients. When presence of Dw2 antigen was compared to different specificities of intrathecally synthesized immunoglobulins, only measles virus antibody synthesis showed correlation.

Antibodies, Bacterial↗

PPD-, PWM-, and PHA-induced interferon in stable multiple sclerosis: association with HLA-Dw2 antigen and clinical variables.

Interferon production after stimulation of lymphocytes with purified protein derivative, pokeweed mitogen, and phytohemagglutinin was studied in 39 patients with stable multiple sclerosis (MS) and 39 age- and sex-matched controls. Stable MS patients produced less interferon, and the number of subjects producing undetectable amounts of interferon was higher in the MS group (11/39) than in the control group (2/39). A tendency toward an association between low interferon production and HLA-Dw2 antigen was found in MS patients. There was no clear-cut correlation between interferon production and the duration of disease or disability of the patients. Although there was no systematic correlation of age with interferon production, patients older than 55 years tended to be very poor interferon producers.

Female↗

Defective production of interferon-alpha associated with HLA-DW2 antigen in stable multiple sclerosis.

Interferon (IFN) production by peripheral blood mononuclear cells after induction with one purified and three crude viral antigens was studied in 29 patients with stable multiple sclerosis (MS) and 29 healthy controls. Antiviral substance produced was characterized as interferon-alpha. MS patients produced significantly less IFN-alpha after induction with mumps and purified measles virus antigens and the same tendency was seen after induction with rubella virus antigen. However, when herpes simplex virus antigen was used as the stimulating agent, no difference was seen between MS patients and controls. The decreased ability to produce IFN-alpha was associated with the histocompatibility antigen Dw2. Control subjects positive for Dw2 also produced less IFN-alpha than Dw2-negative controls. In conclusion, we suggest that the observed impaired interferon-alpha production in MS is at least partially due to a high prevalence of Dw2 antigen in this disease.

Antibodies↗

Circulating immune complexes in patients with multiple sclerosis. A longitudinal study of serum and CSF by C1q and platelet binding tests.

Two hundred and twenty-eight paired serum and CSF samples collected from 31 patients with MS during a 2-3-year follow-up were analyzed for the presence of immune complexes (IC) by C1q RIA and PIPA (platelet [125I]protein A) techniques. One hundred and forty-four sera from 11 healthy individuals were analyzed as controls. In almost all patients (29/31) IC were detectable during some period of the disease, as tested by either of the techniques. The results obtained by C1q RIA and PIPA correlated positively with each other in MS when mean serum values of each patient were compared. The mean CSF IC levels detected by C1q RIA appeared to correlate to the mean IgG indexes, an indicator of the intrathecal rate of IgG synthesis. The amount of IC in serum and CSF fluctuated independently in MS. The results of the PIPA test for MS serum IC correlated significantly to the duration of the disease. The PIPA test results also showed that patients in stable or chronic phases of MS displayed IC in serum and CSF more often than patients with a relapsing/remitting course of disease but there was no clear correlation between fluctuations in IC levels in individual patients measured by C1q RIA or PIPA techniques and the disease course. Because of the lack of a clear correlation between the presence, quantity and fluctuation of IC and the clinical picture we suggest that those IC detected in the present study are probably not a precipitating factor in the pathogenesis of multiple sclerosis.

Antigen-Antibody Complex↗

Desaminocysteine-D-arginine vasopressin test inthe evaluation and postoperative followup of obstructed kidneys in infancy and childhood.

Maximal renal concentrating capacity was determined with the aid of intranasal desaminocysteine-D-arginine vasopressin, a derivative of natural vasopressin, in 9 infants and 2 children with congenital or acquired pelvioureteral or vesicoureteral stenosis. Urinary tract infection was present in some but not all cases. Immediately postoperatively all 13 renal units displayed rather subnormal maximal renal concentration capacity (355 plus or minus 81 mosm. per kg. or mean plus or minus 1 standard deviation), which was corrected to some extent at the time of removal of the ureteral splint 5 to 10 days later (455 plus or minus 129 mosm. per kg.). Between 5 and 15 months postoperatively all but 1 renal unit displayed further significant increment in maximal renal concentration capacity. This single unit, operated on initially for vesicoureteral reflux secondary to neurogenic bladder, was found to be stenotic at the level of the ureterovesical junction. Routine determination of maximal renal concentration capacity at the time of operation could enable one to judge the kidney drainage postoperatively.

Arginine Vasopressin↗

Determination of volatile halocarbons in raw and drinking water, human serum, and urine by electron capture GC.

A method for quantitative determination of volatile halocarbons in raw and drinking water, human serum, and urine is presented. Samples of water, serum, or urine were extracted in a single step with petroleum ether, and the extracts are, without further purification, analysed by high resolution gas chromatography (GC) with electron capture detection (ECD). Both external and internal calibrations were used to standardize the analytical system. External calibration is done with pure halocarbons in purified well water. Internal calibration is accomplished by spiking serum and urine samples with reference halocarbons between each of two successive extractions and GC runs. 1-iodobutane is used as internal standard, both in calibrations and actual determinations.

Chromatography, Gas↗

Intrathecal immune responses in mumps meningitis patients.

The in vitro 3H-thymidine incorporation of peripheral blood (PB) and cerebrospinal fluid (CSF) lymphocytes from 11 mumps meningitis patients was studied after stimulation with non-specific mitogens and microbial antigens. Although corresponding viral antibodies were always found in the CSF of seropositive patients by a sensitive radioimmunoassay, their intrathecal synthesis was directed mainly against mumps virus. Most of the patients had PB lymphocytes that reacted on stimulation with phytohaemagglutinin (PHA) or pokeweed mitogen (PWM), but a smaller number of them had reactive CSF cells. Only four patients showed stronger responses to PHA in the CSF than in PB. Most patients had mumps-reactive lymphocytes in PB but only two of them in the CSF. In contrast, these patients more often had increased CSF cell reactivity when tested with purified protein derivative, measles, and herpes simplex virus antigens. The results could not be explained by a damaged blood-brain barrier alone but may reflect the immunological status of the brain compartment in these patients.

Adolescent↗

Immune complexes in serum and cerebrospinal fluid of multiple sclerosis patients and patients with other neurological diseases.

Paired serum and cerebrospinal fluid (CSF) specimens from 30 multiple sclerosis (MS) patients and 30 patients with other neurological diseases (ONDs) were analyzed for the presence of immune complexes (ICs). With each of the 4 tests used, ICs were found more frequently in sera from both MS and OND patients than in sera from healthy blood donors. IC-positivity for MS and OND patient CSF varied from 10-33% and from 10-17% in different tests. The number of IC-positive sera or CSF in MS patients did not differ significantly from those in OND patients. For both MS and OND patients, the positivity pattern for serum and CSF specimens in each IC test was essentially unique. Furthermore, because several CSF IC-positive and serum IC-negative paired specimens were found, intrathecal IC formation may be independent of IC formation in peripheral blood. The presence of ICs in serum or CSF did not correlate with the clinical status of or laboratory data on the MS patients, nor was a correlation found with the diagnosis of the OND patients. In total, these results suggest that the presence or absence of ICs in MS or OND patients may simply reflect changes in the immunological regulation of individual patients.

Adult↗

Intrathecal synthesis of virus antibodies in multiple sclerosis patients.

A follow-up study on the intrathecal synthesis of viral antibodies in multiple sclerosis patients was made on 28 patients over a period of about 2 years. Serial serum and cerebrospinal fluid specimens were assayed for antibodies against measles, rubella, parainfluenza type 2, respiratory syncytial, mumps, influenza A, influenza B, adeno, and herpes simplex viruses by employing a solid-phase enzyme immunoassay technique. All patients had local antibody synthesis against one or more of the antigens studied. Rubella and measles virus antibodies were found with the highest frequency and were synthesized at the highest rate. Simultaneous intrathecal antibody synthesis against the greater number of the viruses studied was associated with higher local immunoglobulin G synthesis. A good overall correspondence in the fluctuations of the different viral antibodies synthesized intrathecally was usually found. Sometimes the changes in intrathecal antibody levels correlated well with the changes in immunoglobulin G index and sometimes not. These fluctuations could not be correlated with the clinical course of the disease. The results of this study suggest that the viral antibodies studied are not relevant to the etiology or the pathogenesis of multiple sclerosis.

Adenoviridae↗

Antibodies to coronaviruses OC43 and 229E in multiple sclerosis patients.

Multiple sclerosis (MS) and matched control sera had similar antibody titers to coronaviruses OC43 and 229E when tested by a radioimmunoassay method. In contrast, cerebrospinal fluid from MS patients contained coronavirus antibodies more frequently and in higher titers than matched controls. Intrathecal antibody synthesis to OC43 and 229E viruses was detected in 41% (9/22) and 26% (7/27) of MS patients, respectively, but was not found in any of the neurologic control patients. This intrathecal antibody synthesis may mean that coronaviruses play an etiologic or pathogenic role in MS. Alternatively, intrathecal synthesis of coronavirus antibodies may be but part of a generalized and variable intrathecal antibody synthesis that is typical for MS patients.

Antibodies, Viral↗

IgM-class rheumatoid factor in serum and cerebrospinal fluid of multiple sclerosis and matched neurological control patients.

Paired serum and cerebrospinal fluid (CSF) specimens from 30 multiple sclerosis (MS) patients and 30 matched neurological control (NC) patients were quantitatively tested for IgM-class rheumatoid factor (RF). Significantly elevated RF levels were found in serum from 6 MS patients and 12 NC patients. Seven of the latter 12 patients had a diagnosis of recurrent head pain. RF was detected in CSF from 2 MS patients and 2 NC patients. In 3 of the 4 cases, this could be explained by blood-brain barrier damage or normal diffusion of RF into CSF. Intrathecal RF synthesis was found in the remaining MS patient. These results suggest that RF production may be related to underlying pathological mechanisms in at least some MS and NC patients. They also confirm that RF must be carefully accounted for in etiological studies designed to demonstrate pathogen-specific IgM antibodies in, for example, MS patients.

Blood-Brain Barrier↗

Lymphocyte blast transformation responses and viral antibodies in relation to HLA antigens in multiple sclerosis.

Fifty four clinically stable multiple sclerosis (MS) patients and 54 age- and sex-matched control subjects were HLA-typed, and their responses to herpes simplex, measles, mumps and rubella antigens were examined by the lymphocyte blast transformation test and by serum antibody titrations. Blast transformation response to purified tuberculin (PPD), mitogen phytohaemagglutinin (PHA), pokeweed mitogen (PWN) and concanavalin A (Con A) and spontaneous proliferation of lymphocytes were also studied. MS patients differed from controls by higher antibody levels to measles and rubella viruses and by lower specific blast transformation responses to rubella and measles antigens. When the relative strength of transformation responses was measured, mumps and herpes simplex responses were also lower in MS patients than in controls. In addition, spontaneous lymphocyte proliferation of MS patients in 6-day cultures was lower than that of control lymphocytes. In mitogen stimulations there were no differences between whole groups, but the oldest patients had lower responses to PHA and Con A than their matched controls. The frequency of HLA-Dw2 was 56.6% in MS patients and 32.1% in controls. The patients with and without Dw2 differed from each other only by a lower specific response to PPD in the Dw2-positive group. The immunological response of Dw2-positive controls resembled that of MS patients: low transformation response to viral antigens, low spontaneous proliferation and elevated measles antibodies. This finding supports the function of a genetically determined type of immune responsiveness with low cell-mediated immunity and high levels of certain viral antibodies as one susceptibility factor in multiple sclerosis.

Adult↗

Intrathecal synthesis of antibodies to diphtheria and tetanus toxoids in multiple sclerosis patients.

Antibodies to diphtheria and tetanus toxoids were measured in 30 multiple sclerosis (MS) patients and 30 neurological control patients by enzyme-immunoassays. The frequency of antibody-positive patients and the titer distribution were similar in both groups. In spite of this, some MS patients had intrathecal antibody synthesis to these toxoids. The histories of these patents did not reveal any diseases caused by diphtheria of tetanus bacteria but they had been vaccinated 2-24 years before the first clinical symptoms of MS. The findings suggest that lymphocytes earlier committed to specific antibody synthesis outside the brain compartment could enter the brain before or after the clinical onset of MS.

Antibodies, Bacterial↗