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Heinrich Brinkmeier

Publications and source records attributed to Heinrich Brinkmeier.

8 recordsLinked to original sources
PubMed2006

Glatiramer acetate-specific human CD8(+) T cells: increased IL-4 production in multiple sclerosis is reduced by glatiramer acetate treatment.

Glatiramer acetate (GA) is an approved drug for therapy of relapsing remitting MS that acts as a T cell antigen. Here, we report the cloning of HLA restricted, GA-specific human CD8(+) T cells. In addition, we analyzed the cytokine profile of GA-reactive CD8(+) T cell lines. Unexpectedly, IL-4 was increased in untreated MS patients as compared to healthy individuals (p<0.001). In GA-treated patients, however, IL-4 (p<0.001), IL-10 (p<0.001) and TNF-alpha (p<0.001) were decreased. Thus, while GA is known to induce a TH2 bias in CD4(+) T cells, we detected a distinct pattern in GA-reactive CD8(+) T cells.

Adult↗
PubMed2006

Tissue-specific expression of TRP channel genes in the mouse and its variation in three different mouse strains.

BACKGROUND: The purpose of this work was to study the gene expression of transient receptor potential (TRP) channels in the mouse. The application of a standardized and quantitative technique, TaqMan RT-PCR, should give information about the pattern and relative importance of TRP channels for murine tissues and cell types. To verify data sets with an independent method, we studied the occurrence of some of the transcripts by in situ hybridization. RESULTS: We have characterized the mRNA expression of 22 TRP channels in the mouse with a focus on nerve and muscle tissues. This is the first study to describe the expression profiles of all channel isoforms of the four related Group 1 subfamilies (TRPC, TRPV, TRPM and TRPA) with a standardized and quantitative technique. Comparisons of transcript abundance showed a consistent dominance of TRPM7 and TRPC3 in most tissues. We further observed characteristic patterns and differences in gene expression of individual channels ranging over three orders of magnitude. The overall level of TRP channel mRNAs was highest in brain areas followed by kidney, lung, reproductive organs and muscle. In brain TRPM3 and TRPM7 dominated and 19 other isoforms were detected. In lung and kidney TRPV4, TRPV5 and TRPM7 were found in highest levels. TRPM7, TRPC3, TRPC6 and TRPM3 mRNAs were characteristically present in all tested muscle tissues. Most data obtained with the C57Bl/10 mouse strain were confirmed with Balb/c and NOD mice. However, TRPC3, C6, TRPM7, M3, TRPV2 and V4 expression showed marked differences in the three tested mouse strains. In situ hybridization revealed co-expression of transcripts on the cellular level and widely confirmed the data obtained with RT-PCR. CONCLUSION: Transcripts coding for members of the TRPC, TRPV, TRPM and TRPA subfamilies of TRP cation channels are present in a broad spectrum of murine tissues. Several channel isoforms often coexist in a specific tissue or cell type. TRP channel expression does not show typical tissue specific dominance of individual members as is known from other ion channel families. Mouse strain specific variations of TRP channel expression indicate that genetic background or physiological requirements considerably influence expression levels.

Animals↗
PubMed2003

Serum and glucocorticoid inducible kinases in the regulation of the cardiac sodium channel SCN5A.

The serum and glucocorticoid inducible kinase SGK1 and its isoform SGK3 are both expressed in cardiac tissue. One of the functions of SGK1 is the phosphorylation and inactivation of the ubiquitin ligase Nedd4-2, which in turn could be shown to downregulate the voltage-gated Na+ channel SCN5A (hH1). The present study has been performed to test for a role of SGK1 and SGK3 in the regulation of SCN5A. To this end cRNA encoding the human Na+ channel SCN5A was injected into Xenopus laevis oocytes with or without cRNA encoding the wild-type kinases SGK1, the constitutively active kinase (S422D)SGK1, the inactive form K127NSGK1 or the wild-type SGK3. SCN5A currents were activated by coexpression of either wild-type SGK1 or SGK3 or the constitutively active S422DSGK1. In contrast, the inactive mutant K127NSGK1 significantly decreased the currents. Moreover, coexpression of SGK3 significantly altered SCN5A gating, i.e. it hyperpolarized the activation threshold and depolarized the prepotential required for 50% availability of the channel. Opposite shifts of gating properties were elicited by mutation of serine to alanine (S483ASCN5A and S663ASCN5A) in the SGK consensus sequences of SCN5A. The present observations disclose a role of the kinases SGK1 and SGK3 in the regulation of cardiac Na+ channels. As SGK1 is upregulated by glucocorticoids, mineralocorticoids and a variety of inflammatory mediators and both kinases are activated by insulin and IGF1, the kinases could mediate effects of those hormones and mediators on cardiac function.

Animals↗
PubMed2003

Defective integrin switch and matrix composition at alpha 7-deficient myotendinous junctions precede the onset of muscular dystrophy in mice.

Force transmission at the myotendinous junction requires a strong link between the muscle cytoskeleton and the extracellular matrix. At the adult junction, two splice variants of the laminin-binding integrins, alpha7Abeta1D and alpha7Bbeta1D, are highly enriched. The alpha7 subunits are critical for the integrity of the junctional sarcolemma because integrin alpha7-deficient mice develop muscular dystrophy, primarily affecting this site of the muscle. Here, we report that beta1D integrin coimmunoprecipitates and colocalizes with the alpha5 subunit at alpha7-deficient junctions, but does not associate with alpha3, alpha6 or alphav integrins. By immunogold labelling we show that the basement membranes of integrin alpha7-deficient muscles recruit abnormally high levels of fibronectin, the ligand of alpha5beta1D. Finally, we demonstrate that alpha5beta1D is down-regulated at the normal postnatal junction and is displaced by alpha7beta1D. These results suggest that the alpha7 subunit is implicated in the down-regulation of alpha5beta1D and in the removal of fibronectin from the maturing myotendinous junction, thus providing an alpha7beta1D-based link to laminin. We propose that the persistence of alpha5beta1D in alpha7-deficient mice is not compatible with normal muscle function and leads to muscle wasting.

Animals↗
PubMed2003

[CSF Filtration as Experimental Therapy in Therapyresistant Psychoses in Borna Disease Virus-Seropositive Patients]

According to previous investigations, mild Borna disease virus encephalitis may underlie a subgroup of affective or schizophrenic type psychoses. And virus-induced immune pathology may underlie even a larger subgroup of psychoses. We treated BDV seropositive patients suffering from therapy resistant schizophrenic or affective spectrum psychoses by cerebrospinal fluid filtration (CSFF) in an experimental add-on treatment. CSFF was shown previously to be an effective immune modulatory treatment in autoimmune neurological disease, Guillain-Barré syndrome. CSFF appears to be an effective treatment in therapy resistant psychosis also, but only 4 patients were treated yet.

Journal Article↗
PubMed2003

[Cerebrospinal fluid filtration as experimental therapy in therapy refractory psychoses in Borna disease virus seropositive patients. Therapeutic effects, findings].

According to previous investigations, mild Borna disease virus encephalitis may underlie a subgroup of affective or schizophrenic type psychoses. And virus-induced immune pathology may underlie even a larger subgroup of psychoses. We treated BDV seropositive patients suffering from therapy resistant schizophrenic or affective spectrum psychoses by cerebrospinal fluid filtration (CSFF) in an experimental add-on treatment. CSFF was shown previously to be an effective immune modulatory treatment in autoimmune neurological disease, Guillain-Barré syndrome. CSFF appears to be an effective treatment in therapy resistant psychosis also, but only 4 patients were treated yet.

Antibodies, Viral↗
PubMed2002

The endogenous pentapeptide QYNAD induces acute conduction block in the isolated rat sciatic nerve.

Reversible block of sodium channels by endogenous substances was claimed to account for the fast relapses and remissions seen in demyelinating autoimmune disorders. The pentapeptide QYNAD, isolated from the cerebrospinal fluid from patients with multiple sclerosis (MS), blocked Na+ channels in various types of cultured cells. We show that 100 microM QYNAD bath-applied to isolated rat sciatic nerve causes the amplitude and area of the compound nerve action potential to decrease by 30-40%, while the latency increases. Wash-out reverses the changes in part. This suggests that QYNAD may indeed contribute to the fast symptom changes in MS and related diseases.

Action Potentials↗