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J Braun

Publications and source records attributed to J Braun.

At least 163 records · Page 9Linked to original sources
PubMed2001

Intracellular cytokine repertoire in different T cell subsets from patients with sarcoidosis.

BACKGROUND: Pulmonary sarcoidosis is characterised by a mononuclear alveolitis with a predominance of CD4+ T cells and macrophages. We determined the intracellular expression of interferon (IFN)gamma, interleukin (IL)-2, tumour necrosis factor (TNF)alpha, IL-4, IL-5 and IL-10 in CD4+ and CD8+, naive and memory lymphocytes from blood and bronchoalveolar lavage (BAL) fluid using three colour flow cytometry. METHODS: Eighteen untreated patients with pulmonary sarcoidosis were evaluated and stratified according to whether they had acute or chronic disease. RESULTS: Significantly more T cells expressed Th1 than Th2 type cytokines in both BAL fluid and peripheral blood samples, regardless of clinical presentation. Significantly greater proportions of T cells secreted Th1 type cytokines in BAL fluid than in peripheral blood. Th1 type cytokines were more frequently expressed by peripheral and alveolar T cells in acute disease than in chronic disease. There were no significant differences between CD4+ and CD8+ T cells. Concerning naive and memory lymphocytes, significantly higher CD45RO:CD45RA ratios were found in BAL fluid than in blood, and increased expression of Th2 type cytokines was found in peripheral compared with alveolar memory T cells. CONCLUSIONS: Our data support the immunopathogenetic concept of Th1/Th2 imbalance and compartmentalisation in pulmonary sarcoidosis and suggest that the cytokine patterns change during the course of disease. Expression of Th2 type cytokines in memory lymphocytes is decreased in the alveolar compartment compared with peripheral blood.

Acute Disease↗
PubMed2001

Scattered brain infarct pattern on diffusion-weighted magnetic resonance imaging in patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: Infarct patterns on brain imaging contribute to the etiologic classification of ischemic stroke. However, the association of specific subtypes of infarcts and etiologic mechanisms is often weak, and acute lesions are frequently missed on initial computed tomography (CT). Diffusion-weighted imaging (DWI) is superior in visualizing acute ischemic lesions as compared to CT and conventional magnetic resonance imaging (MRI). In our prospective study, we addressed the question whether a distinct pattern of infarction on DWI is associated with infarct etiology and clinical outcome. METHODS: Sixty-two patients with clinical signs of acute ischemic stroke and negative acute CT upon admission underwent DWI within 10 days after the ictus. Neurological status was documented using the NIH stroke scale. A scattered lesion pattern was defined by at least 2 separate hyperintense DWI lesions within the territory of one of the major cerebral arteries. Ischemic lesions were defined as acute if the region was demarcated strongly hyperintense in all DW images, and if the apparent diffusion coefficient was below normal. RESULTS: In 32 patients, DWI revealed a scattered lesion pattern, while in 30 patients a single acute lesion was detected. In patients with scattered lesions, potential arterial or cardiac embolic sources were detected in 26 patients (81.3%), as compared to 5 patients (16.6%) in the group with single lesions (chi(2) test, p < 0.0001). The neurological status of patients with scattered lesions improved significantly more than among patients with single lesions (Mann-Whitney test, p < 0.0003). CONCLUSION: A scattered lesion pattern on DWI in patients with acute brain infarction and negative initial CT scan is associated with an embolic etiology and may indicate a favorable clinical outcome.

Adult↗
PubMed2001

The codon 17 polymorphism of the CTLA4 gene in type 2 diabetes mellitus.

Several studies have demonstrated an association of CTLA4 (IDDM12) alanine-17 with type 1 diabetes, but CTLA4 variants have not yet been investigated in type 2 diabetes. The CTLA4 exon 1 polymorphism (49 A/G) was analyzed in 300 Caucasian patients with type 2 diabetes and 466 healthy controls. All patients were negative for glutamate decarboxylase and islet cell antibodies. CTLA4 alleles were defined by PCR, single-strand conformational polymorphism, and restriction length fragment polymorphism analysis using BBV:I. The distribution of alleles as well as the genotypic and phenotypic frequencies were similar among patients and controls [AA, 42 vs. 39%; AG, 47 vs. 46%; GG, 11 vs. 15%, P = not significant (n.s.); A/G, 65/35% vs. 62/38%, P = n.s.; alanine/threonine 92/58% vs. 85/61%, P = n.s.]. However, detailed analysis of clinical and biochemical parameters revealed a tendency of GG (alanine/alanine) toward younger age at disease manifestation (46.8 +/- 0.8 vs. 49.5 +/- 0.8 yr, mean +/- SEM), lower body mass index (21.4 +/- 0.5 vs. 24.4 +/- 0.5 kg/m(2), P = 0.042), and basal C-peptide level (0.33 +/- 0.07 vs. 0.53 +/- 0.07nmol/L), as well as earlier start of insulin treatment (5.8 +/- 1.2 vs. 8.7 +/- 0.6 yr) and higher portion of patients on insulin (71 vs. 61%). Patients with the AA genotype were significantly less likely to develop microangiopathic lesions (P < 0.0005). No differences were found for hypertension or family history of type 2 diabetes. In conclusion, CTLA4 alanine-17 does not represent a major risk factor for type 2 diabetes. Additional studies on larger groups and different ethnic groups are warranted to clarify the association of the GG genotype with faster ss-cell failure and the lower rate of microvascular complications in AA carriers.

Abatacept↗
PubMed2001

Treatment of the peg lateral incisor: a case study.

If guidelines are properly followed, porcelain laminate veneers can offer enviable and predictable results. Advantages of veneers include a highly esthetic outcome, durability and stability, all accomplished with a reasonably conservative approach. This case study illustrates the use of veneers to restore a peg lateral incisor of a young patient.

Adolescent↗
PubMed2000

Design, synthesis, and discovery of 3-piperazinyl-3,4-dihydro-2(1H)-quinolinone derivatives: a novel series of mixed dopamine D2/D4 receptor antagonists.

3-Piperazinyl-3,4-dihydro-2(1H)-quinolinone derivatives (delta-lactams) were designed, synthesized, and identified as a new series of mixed dopamine D2/D4 receptor antagonists. To further the structure-activity relationship (SAR) study, 3-piperazinylindolin-2-ones (gamma-lactams) and 3-piperazinyl-3H,4H,5H-benzo[f]azepin-2-ones (epsilon-lactams) were also prepared and examined.

Antipsychotic Agents↗
PubMed2000

Viral and cellular cytokines in AIDS-related malignant lymphomatous effusions.

Kaposi sarcoma-associated herpesvirus encodes viral IL-6 (vIL-6). To investigate the potential role of vIL-6 in the pathogenesis of human immunodeficiency virus (HIV)- related primary effusion lymphomas (PEL), a sensitive enzyme-linked immunosorbent assay was developed for vIL-6 and applied to the study of PEL. Whereas vIL-6 was detectable in 6 of 8 PEL effusions (range, 1390-66 630 pg/mL), it was not detectable in any of the control effusions. As expected, all PEL effusions contained human IL-6 (range, 957-37 494 pg/mL), and 7 of 8 contained detectable human IL-10 (range, 66-2,521,297 pg/mL). Human and vIL-6 have previously been shown to induce vascular endothelial growth factor, which in turn can increase vascular permeability. The results of the current study suggest that these cytokines play a central role in the pathogenesis and manifestations of PEL. (Blood. 2000;96:1599-1601)

Body Fluids↗
PubMed2000

Gender differences in the functional organization of the brain for working memory.

Gender differences in brain activation during working memory tasks were examined with fMRI. Seventeen right-handed subjects (nine males, eight females) were studied with four different verbal working memory tasks of varying difficulty using whole brain echo-planar fMRI. Consistent with prior studies, we observed activation of the lateral prefrontal cortices (LPFC), the parietal cortices (PC), and additionally, caudate activation in both sexes. The volume of activated brain tissue increased with increasing task difficulty. For all four tasks, the male subjects showed bilateral activation or right-sided dominance (LPFC, PC and caudate), whereas females showed activation predominantly in the left hemisphere. The task performance data demonstrated higher accuracy and slightly slower reaction times for the female subjects. Our results show a highly significant (p < 0.001) gender differences in the functional organization of the brain for working memory. These gender-specific differences in functional organization of the brain may be due to gender-differences in problem solving strategies or the neurodevelopment. Therefore, gender matching or stratification is required for studies of brain function using imaging techniques.

Adult↗
PubMed2000

Overexpression of murine fizzy-related (fzr) increases natural killer cell-mediated cell death and suppresses tumor growth.

Fizzy-related (fzr) is a recently identified 7WD domain family member implicated in cell cycle regulation of Drosophila and yeast. In this study, the murine homologue of fzr was isolated by suppression subtractive hybridization as a gene with decreased expression during malignant progression of a murine B-lymphoma cell line. Retroviral overexpression of fzr in B-lymphoma cells reduced tumor formation. Those tumors that did arise had diminished or extinguished retroviral Fzr. Surprisingly, fzr overexpression dramatically increased B-lymphoma cell susceptibility to natural killer cell (NK) cytotoxicity, a host-resistant mechanism for tumor formation in this model system. These findings implicate fzr as a new category of genes suppressing B-cell tumorigenesis and suggest a novel role for fzr in the target cell interaction with NK cells.

Animals↗
PubMed2000

Multispecific CD4+ T cell response to a single 12-mer epitope of the immunodominant heat-shock protein 60 of Yersinia enterocolitica in Yersinia-triggered reactive arthritis: overlap with the B27-restricted CD8 epitope, functional properties, and epitope presentation by multiple DR alleles.

Yersinia heat-shock protein 60 (Ye-hsp60) has recently been found to be a dominant CD4 and CD8 T cell Ag in Yersinia-triggered reactive arthritis. The nature of this response with respect to the epitopes recognized and functional characteristics of the T cells is largely unknown. CD4+ T cell clones specific for Ye-hsp60 were raised from synovial fluid mononuclear cells from a patient with Yersinia-triggered reactive arthritis. and their specificity was determined using three recombinant Ye-hsp60 fragments, overlapping 18-mer synthetic peptides as well as truncated peptides. Functional characteristics were assessed by cytokine secretion analysis in culture supernatants after specific antigenic stimulation. Amino acid positions relevant for T cell activation were detected by single alanine substitutions within the epitopes. Fragment II comprising amino acid sequence 182-371 was recognized by the majority of clones. All these clones were specific for peptide 319-342. Th1 clones and IL-10-secreting clones occurred in parallel, sometimes with the same fine specificity. The 12-mer core epitope 322-333 is a degenerate MHC binder and is presented to some T cell clones in a "promiscuous" manner. This epitope is almost identical with a B27-restricted CTL epitope of Ye-hsp60. Cross-reactivity of Ye-hsp60-specific T cell clones with self-hsp60 was not observed. In conclusion, an interesting Ye-hsp60 T cell epitope has been identified and characterized. It remains to be determined whether this epitope is also relevant in other reactive arthritis patients.

Adolescent↗
PubMed2000

Histogram-based characterization of healthy and ischemic brain tissues using multiparametric MR imaging including apparent diffusion coefficient maps and relaxometry.

Decreased, renormalized, or increased values of the calculated apparent diffusion coefficient (ADC) are observed in stroke models. A quantitative description of corresponding tissue states using ADC values may be extended to include true relaxation times. A histogram-based segmentation is well suited for characterizing tissues according to specific parameter combinations irrespective of the heterogeneity found for human healthy and ischemic brain tissues. In a new approach, navigated diffusion-weighted images and ADC maps were incorporated into voxel-based parameter sets of relaxation times (T1, T2), and T1- or T2-weighted images, followed by a supervised histogram-based analysis. Healthy tissues were segmented by incorporating T1 relaxation into the data set, ischemic regions by combining T2- or diffusion-weighted images with ADC maps. Mean values of healthy and pathologic tissues were determined, spatial distributions of the parameter vectors were visualized using color-encoded overlays. One to six days after stroke, ischemic regions exhibited reduced relative mean ADC values.

Adult↗
PubMed2000

Report on the Fourth International Workshop on Reactive Arthritis.

There are large differences in the antigenicity and biology of the ReA-associated bacteria. For induction of arthritis, the relevance seems to be only that antigenic material reaches the joint, alive or dead. If there is a common antigen, it has to be a highly conserved one. Bacterial hsp60 seems to be an immunodominant T cell antigen in ReA, but there must be other relevant antigens shared by these different bacteria. An ineffective immune response (for example, low production of TNFalpha) seems to contribute to the manifestations and course of ReA. Although arthritis can also occur in its absence, HLA-B27 plays an important role in the pathogenesis of ReA and the other SpA. Current data suggest that B27 probably acts as an antigen-presenting molecule for a still-unknown arthritogenic molecule. Comparison of ReA with IBD-associated arthritis suggests that there might indeed be a common antigen shared by ReA-associated bacteria and bacteria of the gut flora. CD8+ T cells seem to be important in ReA and other SpA. In some parts of the world, such as in Mexico, ReA could be a major predisposing cause of the development of AS. Antibiotic treatment is not effective, probably because the triggering bacteria are already dead or in a partly latent state at the time arthritis occurs. Based on this knowledge and on new technologies, it should be possible in future years to derive answers to the questions about ReA and the other SpA and, as a consequence, to find a cure.

Arthritis↗
PubMed2000

Successful treatment of active ankylosing spondylitis with the anti-tumor necrosis factor alpha monoclonal antibody infliximab.

OBJECTIVE: Tumor necrosis factor alpha (TNFalpha) has been detected in sacroiliac joint biopsy specimens from patients with spondylarthropathy. The present open pilot study was undertaken to test the efficacy of the anti-TNFalpha monoclonal antibody infliximab in the treatment of active ankylosing spondylitis (AS). METHODS: Eleven patients with AS of short duration (median 5 years, range 0.5-13 years) that had been active for at least 3 months (range 3-72 months) were treated with 3 infusions of infliximab (at weeks 0, 2, and 6), in a dosage of 5 mg/kg. Ten of the 11 patients had elevated C-reactive protein (CRP) levels (>6 mg/liter) before treatment; these elevations were known to have had persisted > 1 year in at least 3 patients. The Bath AS Disease Activity Index (BASDAI), the Bath AS Functional Index (BASFI), pain as measured on a visual analog scale, and the Bath AS Metrology Index (BASMI) were assessed. Quality of life was assessed using the Short Form 36 instrument. Laboratory markers of disease activity, including interleukin-6 (IL-6) levels, were determined. Dynamic magnetic resonance imaging (MRI) of the spine was performed in 5 patients. RESULTS: One patient withdrew from the study due to the occurrence of urticarial xanthoma 8 days after the first infusion. At study enrollment, 3 of 5 patients had evidence of spinal inflammation (spondylitis and spondylodiscitis) as detected by MRI; followup MRI 2-6 weeks after the third infusion revealed improvement in 2. Improvement of > or = 50% in activity, function, and pain scores was documented in 9 of 10 patients; the median improvement in the BASDAI after 4 weeks was 70% (range 41-94%). This clear-cut benefit lasted for 6 weeks after the third infusion in 8 of 10 patients. The median CRP level decreased from 15.5 mg/liter (range <6-90.8) to normal, and the median IL-6 level from 12.4 mg/liter (range 0-28.4) to normal (<5). There was improvement in all 9 SF-36 concepts; the improvement was significant for 6 concepts. CONCLUSION: These data suggest that anti-TNFalpha therapy is very effective for several weeks in AS. Whether this therapy, in addition to its antiinflammatory effect, prevents ankylosis remains to be determined.

Adult↗
PubMed2000

Analysis of the antigen-specific T cell response in reactive arthritis by flow cytometry.

OBJECTIVE: In reactive arthritis (ReA) a bacteria-specific T cell response to the triggering microbe is detected in synovial fluid (SF), and an impaired Th1 cytokine response has been described. The recent identification of immunodominant bacterial proteins/peptides and new technologies make a more detailed analysis of the immune response possible. The aim of the present study was to use these new techniques to determine the antigen-specific T cell frequency and the cytokine secretion pattern on stimulation with bacteria-derived recombinant proteins in the peripheral blood (PB) and SF from patients with ReA. METHODS: In 3 patients with Chlamydia-induced ReA and 2 patients with Yersinia-induced ReA, the SF T cell response was investigated after stimulation with the Chlamydia-derived proteins major outer membrane protein (MOMP) and heat-shock protein 60 (Hsp60) and the Yersinia-derived proteins 19-kd protein and Hsp60. In 3 of these patients, the PB T cell response was investigated in parallel. T cells were stimulated in whole blood or whole SF with antigen plus anti-CD28 for 6 hours, brefeldin A was added after 2 hours, and cells were fixed and stained with antibodies against the surface markers CD4 and CD69 and against the cytokines interferon-gamma (IFNgamma), tumor necrosis factor alpha, interleukin-10 (IL-10), and IL-4. Positive cells were quantified by flow cytometry. RESULTS: In the 3 patients with Chlamydia-induced ReA, the antigen-specific T cell frequency (percentage of IFNgamma CD69 double-positive CD4+ T cells) in response to MOMP (mean +/- SD 1.2 +/- 1.38%) and to Hsp60 (1.21 +/- 1.45%) in SF was about the same. In the 2 patients with Yersinia-induced ReA, the mean +/- SD frequency was 0.66 +/- 0.36% in response to the Hsp60 and 03% +/- 0.22 in response to the 19-kd protein. In the 3 patients whose PB was evaluated, the corresponding T cell response was > or =10 times lower. In 2 patients with Chlamydia-induced ReA, antigen-specific IL-10-positive CD4+ T cells were detected in 0.10-0.23% of the CD4+ T cell subpopulation. CONCLUSION: The frequency of antigen-specific T cells to Chlamydia- and Yersinia-derived antigens in the SF of ReA patients is between 1:200 and 1:50. Both the chlamydial Hsp60 and MOMP are dominant T cell antigens in Chlamydia-induced ReA. In patients with Chlamydia-induced ReA, we detected antigen-specific IL-10 secretion, which might mediate an inhibition of effective bacterial clearance.

Adult↗
PubMed2000

Mast cell and neuroendocrine cytoplasmic autoantigen(s) detected by monoclonal pANCA antibodies.

pANCA is a marker antibody expressed in most patients with ulcerative colitis, and its cognate antigen is potentially an immunologic target in this disease. This study evaluates whether pANCA detects an autoantigen that is expressed in the colonic mucosa. Immunohistochemistry of colon specimens with human pANCA monoclonal antibodies (Fab 5-2 and 5-3) revealed a minor population of immunoreactive mucosal cells bearing a cytoplasmic vesicle antigen. By distribution, morphology, and tryptase expression, these were identified as mast cells. Immunofluorescent analysis revealed similar immunoreactivity of mouse mast cell lines and human KU812. Western analysis of mouse mast cell lines revealed immunoreactive proteins, and these were distinct from previously proposed pANCA antigens (histone H1, HMG 1 and 2, and neutrophil vesicle antigens). Cognate antigen for Fab 5-2 and 5-3 was also expressed in other tissue mast cells, cerebellar neurons, and pancreatic islet cells. These findings identify a novel cytoplasmic autoantigen(s) associated with UC by its presence in colonic mucosa and recognition by a disease-associated marker antibody.

Animals↗
PubMed2000

Identification of histone H1 as a cognate antigen of the ulcerative colitis-associated marker antibody pANCA.

Perinuclear anti-neutrophil cytoplasmic antibody (pANCA)(4)is a predominant serum marker of ulcerative colitis (UC), and a familial trait associated with disease susceptibility and disease associated MHC haplotypes. This study characterizes the pANCA antigen defined by representative UC-pANCA human monoclonal antibodies, Fab 5-3 and 5-2. Western blot analysis probed with Fab 5-3 revealed specific binding to a nuclear protein doublet (apparent MW=32-33 kDa) expressed in several cell types. Purification and tryptic peptide sequencing identified the protein as histone H1, and this specificity was confirmed by Fab 5-3 binding to purified H1. Rabbit anti-histone H1 immunostaining and Western blot analysis confirmed that the pANCA epitope is preferentially immunoaccessible in polymorphonuclear neutrophils (PMN). The epitope was localized to the COOH-terminal region by site-specific proteolysis, and recombinant deletants further localized binding activity for both Fab 5-2 and 5-3 to two non-overlapping segments (AA 69-171 and 172-226) associated with a recurring PKKAK motif. Serum IgG binding was detectable to these segments, but was not significantly correlated with pANCA titer or disease status. These findings indicate that histone H1 bears a recurring COOH-terminal epitope recognized by monoclonal ulcerative colitis-associated pANCA marker antibodies, but this epitope is not a predominant specificity of serum pANCA.

Amino Acid Sequence↗