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Biomedical subjects

H Link

Publications and source records attributed to H Link.

At least 505 records · Page 28Linked to original sources

Observations on the effect of injection of lymphocytes from multiple sclerosis and Guillain-Barré syndrome in the rabbit eye model.

The effect of 10 X 10(5) peripheral blood lymphocytes (PBL) obtained from patients with multiple sclerosis (MS), Guillain-Barré syndrome (GBS) and healthy controls was studied after injection into the rabbit eye. Infiltration of inflammatory cells, strikingly localized to myelinated strips, was obtained with PBL from some of the MS patients and controls, indicating the non-specificity of the phenomenon. PBL from 2 GBS patients gave the strongest infiltration. No effect was obtained with 10 X 10(4) PBL or CSF lymphocytes from MS patients, indicating that the number of lymphocytes is an essential factor in the induction of lesions.

Adult↗

Studies on the humoral and cell-mediated immune response in a patient with Mollaret's meningitis.

A patient with Mollaret's meningitis with protracted course and a strong immune response within the central nervous system is described. The findings of IgG bands in agarose gel electrophoresis of CSF together with elevated CSF IgG index values are in accordance with intrathecal synthesis of IgG, possibly against an antigen persistent in the CNS. Subgrouping of CSF lymphocytes morphologically (B/T, active T cells) and functionally (stimulation with mitogens) showed that these cells differed from peripheral blood lymphocytes. A defect in the regulatory function of T cells may be responsible for the continuing pathologic process in Mollaret's meningitis.

Antibodies, Viral↗

Reduced in vitro response of CSF lymphocytes to mitogen stimulation in multiple sclerosis.

By means of a microculture technique and calculation of incorporation of 14C-thymidine, cerebrospinal fluid (CSF) lymphocytes from multiple sclerosis (MS) patients showed low or absent proliferation when stimulated with phytohaemagglutinin, concanavalin A, or pokeweed mitogen, in contrast to peripheral blood lymphocytes (PBL) obtained simultaneously and investigated in parallel. A lower proliferation of CSF lymphocytes compared with PBL was also found in acute aseptic meningitis, although it has been reported that CSF lymphocytes show greater proliferation than PBL when specifically stimulated. The low proliferation of MS CSF lymphocytes on mitogen stimulation may be a consequence of prolonged sensitization to an as yet unidentified antigen. The proliferation of MS CSF lymphocytes was not improved by adding irradiated PBL, making helper cell insufficiency less likely. MS CSF had no inhibitory effect on proliferation of PBL, arguing against an inhibitory effect of soluble factors in the CSF as an explanation for the depressed response of CSF lymphocytes.

Cells, Cultured↗

Measles-adherent lymphocyte phenomenon of Levy in multiple sclerosis: normal reactivity of blood lymphocytes.

The measles-adherent phenomenon described by Levy in multiple sclerosis was investigated by studying the rosetting effect of blood lymphocytes from multiple sclerosis patients and healthy controls on chronically measles infected heteroploid Hela cells (Lu 106). No significant difference in rosetting was observed, irrespective if a lymphocyte/virus infected Lu cell ratio of 10/1 or 50/1 was used. Therefore, the test is not discriminative for multiple sclerosis.

Adult↗

Genetic basis of multiple sclerosis: HLA antigens, disease progression, and oligoclonal IgG in CSF.

The HLA antigens B7 and Dw2 occurred at elevated frequencies in 105 multiple sclerosis (MS) patients (49 and 47%, respectively), compared to healthy controls (29 and 30%), especially in MS patients with oligoclonal CSF-IgG (51 and 50%), in cases with CSF-IgG index values above 1.5 (64 and 64%), and in those with the most malignant course of the disease (47 and 59%). Normal or only slightly elevated frequencies of B7 and Dw2 were found in MS patients without oligoclonal CSF IgG (35 and 29%), normal CSF-IgG index (43 and 39%), and the most benign course (42 and 37%). No correlation was found between the HLA type and measles virus antibody titers in serum or a measles virus antibody response within the CNS.

Adult↗

Pleocytosis and immunoglobulin changes in cerebrospinal fluid and herpesvirus serology in patients with Guillain-Barré syndrome.

In a follow-up study of 24 patients with Guillain-Barré syndrome, 55% developed a cerebrospinal fluid (CSF) mononuclear pleocytosis, which persisted for 4 months or more. Raised index values of CSF-immunoglobulin G (IgG), CSF-IgA, and CSF-IgM, indicating synthesis of the immunoglobulin in question in the central nervous system, were found in 63, 35, and 25%, respectively. Agarose gel eletrophoresis revealed oligoclonal immunoglobulin in CSF in 21% and in both CSF and serum in another 21% of the patients. Twenty-five percent had abnormally low kappa/lambda ratios of CSF and/or serum, indicating synthesis of oligoclonal immunoglobulin, mainly of the lambda light-chain type. The inflammatory reaction in the central nervous system, as reflected by pleocytosis, immunoglobulin synthesis, and oligoclonal immunoglobulin, was not correlated to the severity or course of Guillain-Barré syndrome. A raised CSF-IgM index and oligoclonal immunoglobulin were found more often in the Guillain-Barré syndrome patients who displayed pleocytosis. All patients had or developed antibodies to Epstein-Barr virus. Three patients had serology indicating a primary infection, 11 patients had antibody changes indicating a reactivated infection, and 10 had serology indicating previous exposure. Two patients showed serological evidence for a primary cytomegalovirus infection, 2 had serology indicative of a reactivated infection, 12 had titers as caused by previous exposure, and 8 remained seronegative. Virus-specific IgM was measurable in all cases of primary infection. Neither primary or reactivated Epstein-Barr virus nor cytomegalovirus infections were obviously related to CSF pleocytosis.

Adult↗

Characterisation of the mobility on isoelectric focusing of individual proteins in CSF and serum by immunofixation.

The mobility of 17 different proteins in CSF and serum on isoelectric focusing was investigated by subsequent immunofixation using monospecific antisera. Individual proteins yielded identical, often complex band patterns in normal CSF and serum, except transferrin which gave one to two additional bands between pH 5.8-6.4, and the low molecular wieght beta-trace protein and gamma-trace protein, which gave three bands at pH 7.4, 8.0, and 8.4, and a single band at pH 9.5, respectively, on investigation of CSF but not serum. Polyclonal IgC migrated as multiple bands between pH 4.7-8.6. Oligoclonal IgG in CSF in multiple sclerosis and neurosyphilis migrated between pH 8.6-9.5 and was easily discriminated from other proteins.

Blood Proteins↗

Normal functional capacity of blood lymphocytes in multiple sclerosis measured by stimulation with mitogens.

The effect of phytohemagglutinin (PHA) and pokeweed mitogen (PWM) on blood lymphocytes was studied in multiple sclerosis, patients with acute CNS infections, and healthy controls. No significant differences in lymphocyte proliferation were registered between the group of MS patients and the two other groups, irrespective of mitogen used. The ratio between the PWM and PHA responses did not differ significantly from the ratios in the two other groups. The lymphocyte proliferation with PWM was significantly lower in the group with acute CNS infections compared with controls. The results indicate that alterations in cell-mediated immunity, if present in MS, are not confined to lymphocytes outside the CNS.

Adult↗

No association between oligoclonal immunoglobulins in cerebrospinal fluid and HLA antigens in acute aseptic meningitis.

The frequencies of the HLA antigens A3, B7, and Dw2, previously related with multiple sclerosis, were investigated in 26 patients with acute aseptic meningitis and oligoclonal immunoglobulins in cerebrospinal fluid (CSF), but not in serum when investigated by agarose gel electrophoresis. HLA antigen frequencies were similar in patients with aseptic meningitis and controls. The oligoclonal immune response within the central nervous system in aseptic meningitis is not associated with the same HLA antigens found in patients with multiple sclerosis.

Acute Disease↗

Myelinotoxic activity on tadpole optic nerve of cerebrospinal fluid from patients with optic neuritis.

The myelinotoxic activity of unconcentrated cerebrospinal fluid (CSF) from eight optic neuritis (ON) and five multiple sclerosis (MS) patients with oligoclonal IgG, and from five ON patients without oligoclonal IgG, was tested in the tadpole optic nerve system. CSF from ON or MS patients with oligoclonal CSF IgG gave a significantly greater number of myelinotoxic lesions than did CSF from ON patients without oligoclonal CSF IgG, CSF from control patients, or physiologic saline. Induction of myelinotoxic lesions may be coupled with the presence of oligoclonal IgG. The findings support the hypothesis that there are two different forms of ON, of which one, characterized by oligoclonal IgG in the CSF, is more closely related to MS.

Adult↗

[Incidence of toxic liver lesions due to Gravistat].

In 200 women who on the average 5.6 years took ovosiston and/or non-ovlon, and in 40 women who during the last three months had not taken an oral contraceptive we determined the GOT, the GPT, and LP-X and the cholesterol in the serum before and after a three weeks intake of gravistat. After a three weeks intake of gravistat of the two groups ca. one fourth showed pathological transaminases. 30 women with pathological transaminases and/or positive LP-X were hepatologically investigated including liver biopsy after an on an average 7.3 weeks exposition of gravistat. In ca. one third of the cases histologically provable changes of the liver (toxic hepatosis, fatty liver, infectious hepatitis) and in ca. two thirds of the cases the picture of the metabolic activation were found. Morphologically no signs of an intrahepatic cholostasis could be proved, so that it does not seem to be the leading parameter of the toxic liver damage.

Chemical and Drug Induced Liver Injury↗

The immune response in human demyelinating diseases.

Lymphocytes present in the brain, meninges and cerebrospinal fluid (CSF) in multiple sclerosis (MS) are capable of synthesizing IgG. The CSF in MS contains more T-lymphocytes and fewer B-lymphocytes compared to blood. The reactivity of CSF lymphocytes in MS to T-cell mitogens and probably also to a combined B-and T-cell mitogen is absent or heavily reduced. This unresponsiveness of CSF lymphocytes may be a consequence of their previous activation. The blood lymphocytes in MS are not altered regarding distribution of B-and T-cells, nor regarding responsiveness to mitogens, when compared with healthy controls. An asynchronous synthesis of heavy and light immunoglobulin chains occurs within the CNS in many MS patients, giving rise to oligoclonal band patterns on electrophoresis and abnormal kappa/lambda light chain ratios of CSF. The synthesized immunoglobulins are most probably antibodies which may play a role in the pathogenesis and course of human demyelinating diseases. The brain must be regarded, from an immunological point of view, as a privileged site with its own immune system and its characteristic immune reactions, and future research concerning demyelinating diseases should, if possible, include investigations of these reactions.

Antibodies, Viral↗

Hereditary optic atrophy with probable association with a specific HLA haplotype.

A family with hereditary optic atrophy in 4 members of 3 generations is described. The clinical findings differ from those previously observed in hereditary optic atrophy and in Leber's disease, indicating that the hereditary optic atrophy described in this report represents a new disease entity, which is inherited in an autosomal, dominant way with incomplete penetrance. Analyses of the cerebrospinal fluid and serum did not reveal signs of immunoglobulin synthesis within the central nervous system, i.e. findings encountered in a considerable proportion of patients with optic neuritis. An association was found between the family members affected by the disease and the major histocompatibility system haplotype A2 B8. A linkage thus occurred between the disease and the HLA region on human chromosome No. 6.

Adolescent↗

Demonstration of cerebrospinal fluid lymphocytes sensitized against virus antigens in mumps meningitis.

Virus-induced proliferation of cerebrospinal fluid (CSF) lymphocytes and blood lymphocytes was studied in patients with mump meningitis and in patients with aseptic meningitis of other etiology. In four out of five patients with mump meningitis the proliferation of CSF lymphocytes after mumps virus stimulation was higher than obtained with the corresponding number of blood lymphocytes. No proliferation was registered when lymphocytes from patients with other aseptic meningitis were stimulated with mumps virus. These data indicate the occurrence in CSF of lymphocytes specifically sensitized against mumps virus in patients with mumps meningitis.

Adolescent↗

B and T lymphocytes in cerebrospinal fluid and blood in multiple sclerosis, optic neuritis and mumps meningitis.

B and T cells were defined in cerebrospinal fluid (CSF) and blood of 18 multiple sclerosis (MS), five optic neuritis, and 17 mumps meningitis patients by counting immunoglobulin-bearing lymphocytes for B cells, and the capacity of rosette formation with sheep erythrocytes of T-cell determination. Patients with MS and mumps meningitis had significantly higher T-cell values in CSF compared to blood, while the B cell value was significantly lower in CSF in mumps meningitis only. MS patients also displayed significantly lower B-cell values in blood compared to mumps meningitis patients and blood donors. No significant differences were observed between MS patients in exacerbation and in remission.

Adolescent↗

Localization of the immunoglobulins G, A and M, beta-trace protein and gamma-trace protein on isoelectric focusing of serum and cerebrospinal fluid by immunofixation.

The mobility of the immunoglobulins G, A and M, beta-trace protein and gramma-trace protein on isoleectric focusing of serum and CSF was determined by immunofixation using specific antisera. Polyclonal IgG migrated as multiple bands between pH 4.7--8.6, polyclonal IgA as multiple bands between pH 4.9--6.1 in CSF and serum. IgM could not be identified in normal CSF or serum. beta-trace protein gave three bands at pH 8.0, 8.4 and 7.4--7.5, respectively, while gamma-trace protein gave one single band at pH 9.5--greater than 9.5. Oligoclonal IgG in CSF in multiple sclerosis and neurosyphilis migrated between pH 8.6--greater than 9.5 and was easily discriminated from other proteins.

Cerebrospinal Fluid Proteins↗