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Biomedical subjects

H Link

Publications and source records attributed to H Link.

568 records · Page 32Linked to original sources
PubMedDate not supplied

Effect of monoamine reuptake inhibiting antidepressants on major histocompatibility complex expression on macrophages in normal rats and rats with experimental allergic neuritis (EAN).

This study examined the modulation of IFN-gamma induced MHC class I and II expression on normal Lewis rats and rats with EAN peritoneal macrophages cultured in the absence or presence of 10(-4)-10(-8) M of the 5-HT reuptake inhibiting antidepressants zimeldine, and its metabolites norzimeldine and cpp200 oxalate as well as the antidepressants clomipramine and imipramine, in addition amitriptyline, nortriptyline and maprotiline in EAN rats. In normal rats, MHC class I expression was suppressed by the antidepressants zimeldine, norzimeldine and cpp200 oxalate at concentrations up to 10(-5) M. At concentrations between 10(-6) to 10(-8) M, the same drugs significantly enhanced MHC class expression. Clomipramine at 10(-8) M and imipramine at 10(-6)-10(-7) M enhanced MHC class I expression, while the MHC class II expression was not significantly influenced by concentrations < or = 10(-5) M of these two drugs. In EAN rats, MHC class I expression was enhanced by zimeldine, cpp200, imipramine, and nortriptyline at 10(-5)-10(-8) M, amitriptyline at 10(-5)-10(-7) M as well as by norzimeldine and clomipramine at 10(-6) M-10(-8) M. However, maprotiline at 10(-4)-10(-6) M suppressed class I expression in the presence of 0.5 U/ml and 1.0 U/ml of IFN-gamma. MHC class II expression was suppressed by cpp200 and clomipramine at 10(-4)-10(-5) M in presence of 0.5 U/ml of IFN-gamma. At concentrations < 10(-5) M most tested drugs significantly enhanced IFN-gamma induced MHC class II expression. Compared to the results in normal rats, drug effects on EAN macrophages were more pronounced and reached higher levels of significance. The 5-HT reuptake inhibiting antidepressants also exerted a modulatory effect on MHC class I and II in EAN rat macrophages even in the absence of IFN-gamma. The modulatory effect of antidepressant drugs on IFN-gamma induced MHC class I and II expression may contribute to their influence on demyelinating autoimmune diseases, and may have implications for their clinical use.

Amitriptyline↗
PubMedDate not supplied

Demonstration in children of oligoclonal IgG bands in unconcentrated CSF using agarose isoelectric focusing and immunolabeling.

Agarose isoelectric focusing, followed by protein transfer to cellulose nitrate membrane and double-antibody avidin-biotin peroxidase staining (avidin-biotin agarose isoelectric focusing), was used to demonstrate oligoclonal IgG bands in unconcentrated cerebrospinal fluid (CSF) and serum; 161 consecutive pediatric patients, ages 6 months to 16 years with a variety of mainly neurologic disorders, were studied. The procedure was standardized for agarose isoelectric focusing (AIF) using 5 microliter specimens containing 125 ng of IgG. Oligoclonal bands were found in the CSF of 12% of the patients; bands were found simultaneously in the CSF and serum of 10% of the patients, mostly those with nervous system infections, but also those with central nervous system tumors, seizures, or migraine. In about 50% of positive cases, oligoclonal bands constituted the only CSF abnormality, reflecting an abnormal humoral immune response within the CSF-central nervous system compartment. Avidin-biotin AIF can be recommended as an integrated part of routine CSF examinations in children.

Adolescent↗
PubMedDate not supplied

T-cell depletion of allogeneic peripheral blood stem cells.

The high content of immunocompetent T-cells in apheresis products may expose recipients of allogeneic peripheral blood stem cells (PBSC) to an elevated risk of acute and chronic graft-versus-host disease (GvHD). Thus, the use of an appropriate T-cell reduction or depletion technique might reduce this risk. The hazards of rejection and of a higher relapse rate should be avoided by maintaining a portion of the T-cells in the graft or by increasing the number of transplanted stem cells. The positive selection of CD34+ cells from peripheral blood preparations simultaneously provides an approximately 1,000-fold reduction of T-cells. Purified CD34+ cells containing committed and pluripotent stem cells are suitable for allogeneic transplantation. In transplantation from HLA-mismatched or three HLA-loci different family donors the amount of stem cells can be increased for reducing the incidence of rejection without increasing the T-cell number. In cases of poor marrow graft function a 'boost' with stem cells from the same family donor can be given. The risk of GvHD in transplantation from volunteer-matched unrelated donors might be reduced by T-cell depletion. If T-cells are used for enhancing the graft-versus-leukaemia effect, CD34+ enriched cells can be given for haematopoietic engraftment.

Antigens, CD34↗
PubMedDate not supplied

Prognosis in patients with infarction and TIA in carotid territory during and after anticoagulant therapy.

One hundred seventeen patients, 31 with TIA and 86 with cerebral infarction, had angiographically verified atherosclerosis within the relevant carotid artery territory and normal CSF. They were treated with anticoagulants for a mean of 11.1 months. No TIA but 1 cerebral infarction, appearing during inadequate anticoagulant therapy, was registered. Seventy-six of the patients, 20 with TIA and 56 with infarction, were followed for a mean of 4.4 months after cessation of anticoagulants or during inadequate antinecessitating re-institution of anticoagulant therapy. Long-term, anticoagulant treatment can be recommended in carefully selected patients with TIA, and also with infarction in the carotid territory.

Adult↗
PubMedDate not supplied

[Clinical usefulness of oligoclonal bands].

The presence of oligoclonal bands (OCB) of immunoglobulin G (IgG) is in our days the most useful finding in the study of the CSF for the diagnosis of multiple sclerosis (MS). The most sensitive method for the detection of OCB is the isoelectric focusing followed by immunoblotting. The prevalence of OCB changes in different populations with a rank of results from 60 to 95 97%. We have determined the prevalence of OCB in our population and the sensitivity and the specificity of the technique used in our laboratory. We have included 391 patients in whom we analysed the presence of OCB, subdivided in; Group 0: Diagnosed of MS, group 1: First episode of demyelinating process, group 2: Neurological disorders considered noninflammatory or nonautoimmune (NINA),group 3: Neurological disorders considered inflammatory, infectious or autoimmune (IIA). The presence of OCB was searched in CSF and serum simultaneously using isoelectric focusing and immunoblotting. In order to standardize the technique we achieved and internal and external validation. Internal validation: sensitivity and specificity (using as a control group first the group NINA and after the group IA). External validation: we choose 10 pairs of CSF/serum from patients with different diagnostics and sent to a reference laboratory ( Karolinska Institute Medical School) that was blind of our results and of the diagnostics. The prevalence of OCB in each group has been: group 0 (MS): 87.7%, group 1: 54.8%, group 2 (NINA): 17.5%, group 3(IIA): 52.7%. Sensitivity: 97.7%, specificity using group NINA as control 82.5% and using group IIA 45.7%. Concordance with the reference laboratory in 9/10 determinations. We conclude that in our population the prevalence of OCB, in patients with MS, is lower than in Northern Europe. The OCB appear in may inflammatory, autoimmune diseases, their specificity for the diagnostic of MS is low.

Autoimmune Diseases↗
PubMedDate not supplied

[Musculoskeletal manifestations in patients after bone marrow transplantation. Initial clinical rheumatologic observations].

From January 1986 through January 1989 69 adult patients received bone marrow transplants--20 with autologous, and 49 with allogeneic bone marrow. Ten patients after autologous and 33 patients after allogeneic transplantation (TX) could be examined for rheumatological complaints. None of the patients after autologous TX displayed rheumatological manifestations; 8/33 patients after allogeneic TX developed bone necrosis and they had to be treated for several months with high daily doses of prednisolon (mean: 55 mg/day). In 18/33 patients an oligoarthropathy of large joints could be observed after a significant reduction of prednisolon dosage over a period of 5 months. In addition 15/18 of these patients later developed a chronic g-v-h-disease. The TX arthropathy may be induced by cortico-steroid therapy (resp. reduction), but most important, it is a clinical sign for an imminent chronic g-v-h-disease.

Adult↗
PubMedDate not supplied

HLA-DR expression and neopterin levels as activity markers in multiple sclerosis.

We adopted a new double-immunofluorescence labelling assay on prefixed isolated cerebrospinal fluid (CSF) and peripheral blood mononuclear cells from patients with multiple sclerosis (MS) for class II expression (HLA-DR) on T cells. No accumulation of such cells was demonstrated in MS CSF. In contrast, patients with acute aseptic meningo-encephalitis (AM) displayed accumulation in CSF of activated, DR positive T cells as a marker of actively involved cellular immunity within the CNS. Thus, enumeration of DR expressing T cells in CSF can not currently be used as reflection of disease activity in MS. In contrast, determination of neopterin levels in CSF may be a useful marker of disease activity in this disease. Levels of neopterin, a factor known to be released from macrophages and monocytes at increased rates in cellular immune reactions, were higher in CSF in 10 of 12 patients with MS during clinical exacerbations in comparison with remissions. This significant elevation in CSF was not reflected in serum. We have also reported high neopterin levels in CSF in a majority of patients during acute phase of AM followed by normalization after clinical recovery. It is concluded that neopterin in CSF is a valuable marker of acute cellular immune response, and should represent an objective way to monitor disease activity in MS, e.g. in relation to effects of putative therapeutic agent.

Adolescent↗
PubMedDate not supplied

The value of cerebrospinal fluid immunoglobulin analysis in clincial neurology.

The IgG index (formula: see text) corrects for the influence of serum protein abnormalities as well as a bloodbrain barrier damage and is, therefore, a better measure for the presence of an IgG elevation in CSF due to IgG synthesis, when compared with other IgG quotients commonly used. Agar gel electrophoresis of CSF for demonstration of oligoclonal IgG is probably superior to the determination of the IgG index when a diagnosis of MS is suspected. Determination of kappa and lambda light chain antigenic determinants in CSF, and calculation of the kappa/lambda ratio may also be used to demonstrate the occurrence of oligoclonal CSF immunoglobulins. An abnormal ratio can, however, be demonstrated only in 50% of MS patients and has, therefore, at present no place as a routine diagnostic method when MS is suspected.

Humans↗
PubMedDate not supplied

The phosphodiesterase i.v. inhibitor rolipram in vitro reduces the numbers of MBP-reactive IFN-gamma and TNF-alpha mRNA expressing blood mononuclear cells in patients with multiple sclerosis.

The inflammatory nature of multiple sclerosis (MS) implicates the participation of cytokines as immune response mediators. Targeting the cytokine balance by downregulating proinflammatory cytokines and/or upregulating immunosuppressive cytokines could benefit patients with MS. This article reports on the in vitro effects of the phosphodiesterase i.v. inhibitor Rolipram on the production of pro- and anti-inflammatory cytokines in MS and, for reference, in myasthenia gravis (MG). Blood mononuclear cells (MNC) were cultured in the presence of the organ-specific autoantigens myelin basic protein (MBP) or acetylcholine receptor (AChR), and in the absence of antigens, with and without Rolipram. In situ hybridization with synthetic oligonucleotide probes was used to detect and enumerate blood MNC expressing IFN-gamma, TNF-alpha, LT, TGF-beta, IL-4, and IL-10 mRNA. Numbers of MNC-secreting IFN-gamma and IL-4 in blood blood were examined by ELISPOT assays. Rolipram reduced the numbers of MBP-reactive IFN-gamma- and TNF-alpha mRNA-expressing blood MNC in MS, and numbers of AChR-reactive IFN-gamma-, TNF-alpha-, and LT mRNA-positive cells in MG. In contrast, expression of the Th2 cell related IL-4 and the anti-inflammatory IL-10, and TGF-beta was not affected. These data support a role for Rolipram in the treatment of diseases such as MS.

3',5'-Cyclic-AMP Phosphodiesterases↗