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R Hohlfeld

Publications and source records attributed to R Hohlfeld.

At least 91 records · Page 5Linked to original sources
PubMed1996

Differential expression of perforin in muscle-infiltrating T cells in polymyositis and dermatomyositis.

Polymyositis (PM) and dermatomyositis (DM) are the prototypical inflammatory diseases of skeletal muscle. In PM, CD8+ T cells invade and destroy muscle fibers, whereas humoral effector mechanisms prevail in DM. We studied the expression of the cytotoxic mediator perforin in inflammatory cells in PM and DM muscle by semiquantitative PCR, immunohistochemistry and confocal laser microscopy. Similar levels of perforin mRNA were expressed in PM and DM, and abundant perforin-expressing CD3+CD8+ and CD3+ CD4+ T cells were observed in both diseases. However, there was a striking difference in the intracellular localization of perforin. In DM, perforin was distributed randomly in the cytoplasm of the inflammatory T cells. In contrast, 43% of the CD8+ T cells that contacted a muscle fiber in PM showed perforin located vectorially towards the target muscle fiber. The results suggest (a) that the random distribution of perforin in the cytoplasm of muscle-infiltrating T cells observed in DM reflects nonspecific activation, and (b) that the vectorial orientation observed only in PM reflects the specific recognition via the T cell receptor of an antigen on the muscle fiber surface, pointing to a perforin- and secretion-dependent mechanism of muscle fiber injury.

Base Sequence↗
PubMed1996

BK virus encephalitis in an immunocompetent patient.

OBJECTIVES: To describe a previously healthy patient now suffering from monophasic encephalitis caused by a primary infection with BK virus and to discuss possible risk factors for developing BK virus encephalitis. DESIGN: Case report. SETTING: Referral hospital. PATIENT: The patient was examined on referral. MAIN OUTCOME MEASURES: The main diagnostic tests performed were serology, polymerase chain reaction on cerebrospinal fluid samples, and cranial magnetic resonance imaging. RESULTS: During the course of the patient's encephalitis, an IgM titer developed against polyomavirus, followed by anti-polyomavirus IgG. Wild-type BK virus was demonstrated in cerebrospinal fluid samples. Cranial magnetic resonance imaging showed diffuse reversible white matter changes most prominent on T2-weighted images. CONCLUSION: We conclude that diagnostic tests for BK, a human polyomavirus, should be included in the screening program for encephalitogenic pathogens.

Adult↗
PubMed1996

Multiple sclerosis: prospective analysis of TNF-alpha and 55 kDa TNF receptor in CSF and serum in correlation with clinical and MRI activity.

The possibility of antagonizing tumor necrosis factor-alpha (TNF-alpha) in vivo with antibodies or soluble TNF receptor has focused much interest on the role of this cytokine in the natural course of MS. We studied nine patients prospectively and serially for one year (14 time points, 131 observations). TNF-alpha and the 55 kDa soluble TNF receptor were measured every 4 weeks in the serum and at defined time points in the CSF. Each value was correlated to clinical symptoms and to MRI measurements obtained on the same day. All patients with relapsing-remitting disease showed periodic increases of TNF concentrations. Overall, the association between serum TNF-alpha levels and bursts of Gd-DTPA enhancement on cranial MRI was not sufficiently tight to reach statistical significance. However, serum TNF levels > 50 pg/ml and measurable CSF levels were always associated with Gd-DTPA enhancing MRI lesions. Isolated high serum TNF peaks were noted during episodes of infection, hay fever or psychic stress. After treatment with glucocorticoids, TNF levels were suppressed for several months, whereas new Gd-DTPA enhancing lesions continued to appear. The concentrations of the soluble 55 kDa TNF receptor did not show marked fluctuations. These results are consistent with an active role of TNF-alpha in MS during periods of disease activity and provide further support for the clinical evaluation of anti-TNF therapies.

Adult↗
PubMed1996

The use of intravenous immunoglobulins in the treatment of neuromuscular disorders.

Intravenous immunoglobulin is increasingly used in the treatment of neuromuscular disorders. Its efficacy has been proven in Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, and Lambert-Eaton myasthenic syndrome. In addition, there is increasing evidence that it has beneficial effects in other neuromuscular disorders.

Drug Administration Schedule↗
PubMed1996

Inhibitors of tumor necrosis factor-alpha: promising agents for the treatment of multiple sclerosis?

Tumor necrosis factor (TNF)-alpha is a critical inflammatory mediator of experimental autoimmune encephalomyelitis and multiple sclerosis, and may therefore be a useful target for immunotherapy. Therapeutic strategies aimed at TNF include pharmacological inhibitors of TNF synthesis and/or processing and biological inhibitors of TNF effects. Several anti-TNF agents are currently being tested in multiple sclerosis in pilot clinical trials.

Animals↗
PubMed1996

Reversible encephalopathy with cerebral vasospasm in a Guillain-Barré syndrome patient treated with intravenous immunoglobulin.

We report a patient with a reversible multifocal encephalopathy that developed 3 days after completion of treatment with intravenous immunoglobulin for Guillain-Barré syndrome. Magnetic resonance imaging showed reversible bioccipital white matter changes, and transcranial Doppler demonstrated transiently increased flow rates in all major cerebral arteries. We conclude that intravenous immunoglobulin therapy caused cerebral arterial vasospasm and a reversible encephalopathy.

Adult↗
PubMed1996

Thymoma-associated myasthenia gravis. Transplantation of thymoma and extrathymomal thymic tissue into SCID mice.

To study the possible role of thymomas and of extrathymomal thymic tissue in the development and maintenance of myasthenia gravis, we transplanted fragments of either tissue into SCID mice and monitored the production of anti-acetylcholine receptor antibodies in the recipients. Furthermore, the transplants were characterized by immunohistochemistry. Unlike after transplantation of thymus with lymphofollicular hyperplasia that induced high titers of anti-acetylcholine receptor antibodies, thymoma transplants never produced autoantibodies. Mice transplanted with extrathymomal thymic tissue also failed to produce anti-acetylcholine receptor antibodies except one group that received transplants containing hyperplastic extrathymomal tissue. These findings may explain the refractoriness of thymomatous myasthenia to thymectomy.

Adult↗
PubMed1996

[Therapy of multiple sclerosis with interferon-beta-1b. Educating the patient and managing side-effects].

Interferon beta-1b has been shown to reduce the frequency and severity of exacerbations in relapsing-remitting multiple sclerosis (MS). Unrealistic expectations of the patient and unexpected side effects may lead to discontinuation of the drug. Here we provide guidelines how to inform the patient adequately before therapy and discuss the most common side effects of interferon therapy.

Adjuvants, Immunologic↗
PubMed1995

T cell receptor repertoire in polymyositis: clonal expansion of autoaggressive CD8+ T cells.

In polymyositis (PM), CD8+ T cell receptor (TCR) alpha/beta + cells invade and destroy major histocompatibility complex class I-positive muscle fibers. We combined polymerase chain reaction (PCR) and double-fluorescence immunocytochemistry to analyze the T cell receptor (TCR) repertoire expressed in muscle of PM patients. In patient 1, inverse PCR revealed a preferential usage of TCR V alpha 33.1, V beta 13.1, and V beta 5.1. Six of six TCR V alpha 33.1+ clones and five of seven V beta 13.1+ clones had identical nucleotide sequences. In contrast, the V beta 5.1+ TCRs were more heterogeneous. Similar results were obtained with an independent PCR method using primers specific for TCR V alpha 33, V beta 13, or V beta 5. No TCR sequences could be amplified from noninflammatory control muscle. Furthermore, none of the TCR sequences found in PM muscle could be detected in blood from the same patient or from a normal control subject. Immunohistochemistry confirmed that V beta 5.1 and V beta 13.1 were overrepresented in the muscle lesions of this patient. 32% of all CD8+ T cells were V beta 13.1+, and 16% were V beta 5.1+. However, approximately 60% of the CD8+ T cells that invaded muscle fibers were V beta 13.1+, whereas 10% were V beta 5.1+. In patient 2, 50% of the T cells were V beta 5.1+, and as in patient 1, these T cells were mainly located in interstitial areas. In patient 3, > 75% of the autoinvasive T cells stained with an anti-V beta 3 mAb. Sequence analysis of 15 PCR clones amplified with a V beta 3-specific primer showed that 9 (60%) sequences were identical. The results suggest that (a) a strikingly limited TCR repertoire is expressed in PM muscle; (b) there is a dissociation between the TCR usage of autoinvasive and interstitial T cells; and (c) the autoinvasive T cells are clonally expanded.

Amino Acid Sequence↗
PubMed1995

Genetic control of multiple sclerosis: increased production of lymphotoxin and tumor necrosis factor-alpha by HLA-DR2+ T cells.

Lymphotoxin (LT) and tumor necrosis factor-alpha (TNF-alpha) play an important role in the pathogenesis of multiple sclerosis (MS). MS is associated with the HLA-DR2, Dw2, DQ6 HLA class II haplotype. Because both LT and TNF-alpha are encoded in the HLA region, the HLA association of MS may be related to the production of these cytokines. To test this hypothesis, we investigated the production of LT, TNF-alpha, and interferon-gamma (IFN-gamma) by CD4+ T-cell lines (TCLs) specific for myelin basic protein (MBP) or tetanus toxoid (TT) isolated from MS patients and normal controls. After stimulation with specific antigen but not mitogen, TCLs from HLA-DR2+ donors produced significantly more LT and TNF-alpha than TCLs from DR2- donors. In contrast, HLA-DR2+ and DR2- TCLs did not differ in the production of IFN-gamma, a cytokine also produced by T cells but not encoded in the HLA region. Increased secretion of LT and TNF-alpha was unrelated to the specificity (MBP vs TT), MHC restriction (HLA-DR2 vs other DR molecules), or source (MS vs normal) of the TCLs. There was no significant association of the cytokine production with individual LT or TNF-alpha alleles, indicating that the increased production of these cytokines may be linked to other polymorphic genes in this region. The results suggest that the association of MS with HLA-DR2 implies a genetically determined propensity of T cells to produce increased amounts of LT and TNF-alpha.

Animals↗
PubMed1995

The role of autoimmune T lymphocytes in the pathogenesis of multiple sclerosis.

Autoimmune T cells play a key role as regulators and effectors of autoimmune disease. In multiple sclerosis (MS), activated T cells specific for myelin components or other locally expressed autoantigens enter the CNS and recognize their antigen(s) on local antigen-presenting cells. After local stimulation, the T cells produce a plethora of cytokines and inflammatory mediators that have profound effects on the local cellular environment, induce and recruit additional inflammatory cells, and contribute to myelin damage. An increasingly detailed knowledge of these processes will greatly facilitate the development of new immunotherapies. This article focuses on the role of T cells in MS. We provide a brief overview of the principles of T-cell immunology, discuss the experimental techniques available for studying T cells, address the role of T cells in the pathogenesis of MS, and highlight modern concepts for immunotherapy.

Amino Acid Sequence↗