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H P Tony

Publications and source records attributed to H P Tony.

At least 19 recordsLinked to original sources
PubMed2006

[NSAIDs and COX-2-inhibitors: current status].

NSAIDs (non steroidal anti-inflammatory drugs) are a crucial component for the therapy of pain induced by inflammatory and degenerative joint diseases. Nevertheless their known therapeutic efficacy is contrasted by significant side effects. The recently developed selective COX-2-inhibitors appear to have a better gastrointestinal safety profile, especially relevant to patients with an increased risk for gastrointestinal ulcers and bleeding. However, this effect may similarly be reached by the combination of NSAIDs with proton pump inhibitors. Recent data relate to an elevated myocardial infarction rate in patients using COX-2-inhibitors. This risk may also occur in conventional NSAIDs. Therefore an individual risk calculation is necessary before COX-2-inhibitors or NSAIDs are used. Treatment should be performed with the lowest dosage for the shortest time possible. Combination therapy with salicylic acid seems to abolish the protective effect of COX-2-inhibitors in the GI-tract. Definite risk factors for the treatment with NSAIDs and COX-2-inhibitors have to be defined in further studies providing the best treatment schedule for an individual patient.

Aged↗
PubMed2006

[Systemic sclerosis].

Systemic sclerosis (SSc; syn. systemic scleroderma) is a rare autoimmune disorder with characteristic cutaneous manifestations. Prevalence in women is fivefold higher than in men. The course of the disease is slowly progressive with a variable degree of internal organ involvement due to fibrosis and obliteration of small vessels. The diffuse form shows more frequent and severe organ manifestations compared to the limited form. Increased mortality is particularly related to a cardiopulmonary involvement leading to a 5-year survival of around 75%. Treatment indications are dependent on the severity of the disease. In the acute state, immunosuppressive agents are needed in case of significant organ involvement. Vasodilative drugs are often used for the symptomatic treatment of Raynaud's phenomenon.

Autoantibodies↗
PubMed2004

Improvement of refractory rheumatoid arthritis after depletion of B cells.

OBJECTIVE: B cells are involved in the pathogenesis of rheumatoid arthritis (RA). To evaluate the effect of therapeutic B-cell depletion for treatment of RA, an open label study has been performed using the B-cell depleting anti-CD20 antibody rituximab. METHODS: Five patients with refractory RA were treated weekly with four infusions of rituximab (375 mg/m2) alone, or in combination with ongoing methotrexate (MTX). Patients were followed for at least 44 weeks and monitored for safety and tolerability of treatment. RESULTS: Treatment could be performed without serious side effects and resulted in peripheral B-cell depletion lasting between 36 weeks up to > 1 year. The follow-up revealed no significant treatment-associated side effects. At 22 weeks, 4/5 patients showed a significant improvement (> 1.2) of the Disease Activity Score (DAS28). The mean DAS28 of all patients declined from 6.2 to 4.1. At 44 weeks there was one drop-out, another patient still had a sustained response, and three patients showed slowly increasing disease activity (mean DAS28 of the remaining four patients: Week 0: 6.0; Week 22: 3.85; Week 44: 5.6). Despite relatively constant immunoglobulin levels, rheumatoid factor levels decreased parallel to disease activity. CONCLUSION: In patients with refractory RA, B-cell depletion with rituximab is safe and well tolerated. A reduction of disease activity could be observed, which eventually deteriorated after B-cell repopulation. The findings give more evidence for B-cell targeted therapies in RA.

Adult↗
PubMed2002

[Spondyloarthritis].

Explore the source record for details and available documents.

Cross-Sectional Studies↗
PubMed2000

Stimulation of gammadelta T cells by aminobisphosphonates and induction of antiplasma cell activity in multiple myeloma.

Bisphosphonates are well-known inhibitors of osteoclastic bone resorption, but recent clinical reports support the possibility of direct or indirect antitumor effects by these compounds. Because bisphosphonates share structural homologies with recently identified gamma delta T-cell ligands, we examined the stimulatory capacity of bisphosphonates to gamma delta T cells and determined whether gamma delta T-cell stimulation by bisphosphonates could be exploited to generate antiplasma cell activity in multiple myeloma (MM). All tested aminobisphosphonates (alendronate, ibandronate, and pamidronate) induced significant expansion of gamma delta T cells (V gamma 9V delta 2++ subset) in peripheral blood mononuclear cell cultures of healthy donors at clinically relevant concentrations (half-maximal activity, 0.9-4 mcmol/L). The proliferative response of gamma delta T cells to aminobisphosphonates was IL-2 dependent, whereas activation of gamma delta T cells (up-regulation of CD25 and CD69) occurred in the absence of exogenous cytokines. Pamidronate-activated gamma delta T cells produced cytokines (ie, interferon [IFN]-gamma) and exhibited specific cytotoxicity against lymphoma (Daudi) and myeloma cell lines (RPMI 8226, U266). Pamidronate-treated bone marrow (BM) cultures of 24 patients with MM showed significantly reduced plasma cell survival compared with untreated cultures, especially in cultures in which activation of BM-gamma delta T cells was evident (14 of 24 patients with MM). gamma delta T-cell depletion from BM cultures completely abrogated the cytoreductive effect on myeloma cells in 2 of 3 tested patients with MM. These results show that aminobisphosphonates stimulating gamma delta T cells have pronounced effects on the immune system, which might contribute to the antitumor effects of these drugs. (Blood. 2000;96:384-392)

Alendronate↗
PubMed2000

Persistent polyclonal B-cell lymphocytosis--an important differential diagnosis of B-cell chronic lymphocytic leukemia.

Over the last 17 years, 83 cases of polyclonal B-cell lymphocytosis (PPBL) have been published. This rare hematological disorder of unknown etiology is characterized by morphologically atypical lymphocytes, polyclonal immunoglobulin M production in association with smoking, female gender, and HLA-DR7 phenotype. We studied another male patient with PPBL. In contrast to normal B-cells, PPBL cells showed no response to interleukin-4 with regard to CD23 and human leukocyte antigen-DR expression. F2mu antibodies failed to co-stimulate interleukin-4-mediated CD23 expression. Crosslinking membrane immunoglobulin M receptors by F2mu resulted in elevated human leukocyte antigen-DR expression but did not induce in vitro proliferation of PPBL cells. This indicates a different activation and differentiation status than normal B-cells.

Adult↗
PubMed2000

STAT6 and the regulation of CD23 expression in B-chronic lymphocytic leukemia.

High CD23 expression is a hallmark of B-CLL cells. It is lost during in vitro culture and can be reinduced by IL-4, albeit to a lower extent than in normal B cells. To elucidate the events controlling CD23 expression in B-CLL cells, the IL-4 mediated induction of STAT6 was investigated. Western-blot analysis demonstrated that B-CLL cells contain comparable amounts of STAT6. Electrophoretic mobility shift assays (EMSA) showed no constitutive nuclear translocation of STAT6. IL-4 induced the translocation of STAT6 in B-CLL cells from all 22 patients investigated. The increase was transient, dose and time dependent without a distinct difference between B-CLL cells and non-malignant B cells. However, in contrast to normal B lymphocytes no strict correlation between CD23 expression and STAT6 activation was detected in B-CLL. Therefore further signalling pathways and transcription factors in addition to STAT6 have to be activated to explain the high expression of CD23 in B-CLL cells. For example, STAT1 which is induced by IFN-gamma and binds to the classical STAT6 site. It might be involved in the strong induction of CD23 on B-CLL cells after cotreatment with IL-4 and IFN-gamma, while in non-malignant B lymphocytes IFN-gamma leads to a reduction of IL-4 mediated CD23 expression.

Biological Transport↗
PubMed2000

Assessment of microvascular changes in Raynaud's phenomenon and connective tissue disease using colour doppler ultrasound.

OBJECTIVE: We used colour Doppler ultrasound (CDU) to differentiate primary from secondary Raynaud's phenomenon (pRP and sRP, respectively) and to assess digital vascular damage in patients with connective tissue disease (CTD). METHODS: Vascularity in the nailbeds of 15 healthy controls and 35 patients with CTD (systemic sclerosis or systemic lupus erythematosus) was quantified using a multi-D array transducer before and after cold and warm challenge, respectively. The results were compared with the clinically evaluated initial skin lesions. Vascularity was compared similarly between 10 pRP and 22 sRP patients. RESULTS: Vascularity at ambient temperature differed between healthy subjects and sRP patients as well as between healthy subjects and CTD patients without initial skin lesions. Patients with pRP had normal vascularity at ambient temperature but differed from healthy controls in response to a dynamic temperature challenge. CDU confirmed the clinical evaluation in 89.4% of the patients with RP and in 78.0% of the skin lesions. CONCLUSION: The novel CDU technique presented here makes it possible to discriminate between pRP and sRP and to quantify vascular changes in CTD patients.

Adult↗
PubMed1999

Evaluation of pannus and vascularization of the metacarpophalangeal and proximal interphalangeal joints in rheumatoid arthritis by high-resolution ultrasound (multidimensional linear array).

OBJECTIVE: To evaluate the extent of intraarticular vascularization and pannus formation in metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of patients with rheumatoid arthritis (RA) by high-resolution ultrasound (US). METHODS: A newly developed, high-resolution multidimensional linear array US was utilized to obtain longitudinal and transverse scans of joints with active RA (n = 21), moderately active RA (n = 39), or inactive RA (n = 93), and of joints from healthy controls (n = 120). RESULTS: Healthy joints had no detectable pannus, whereas pannus could be detected in 52% of the joints with active RA, 82% of the joints with moderately active RA, and 67% of the joints with inactive RA. There was a significant difference in vascularization in the joints of all subgroups of RA patients and those of healthy subjects (P < 0.001). Moreover, vascularization differed significantly among the RA subgroups: inactive versus moderately active RA (P < 0.02) and inactive versus active RA (P < 0.05). Both pannus and vascularization appeared to be localized preferentially on the radial side of the joints. CONCLUSION: Evaluation of pannus and the extent of vascularization within the joints of patients with RA by high-resolution US might be helpful in the assessment of disease activity, and thus influence therapeutic strategies.

Adult↗
PubMed1999

Inhibition of T cell/B cell interaction by B-CLL cells.

The course of disease in patients suffering from chronic lymphocytic leukemia (CLL) is determined by a profound dysregulation of the immune system. The resulting immune suppression is the main cause of death in those patients. In the present study we addressed the question of whether leukemic B cells (B-CLL) are able to suppress regular T cell/B cell interaction. Activated CD4+ T cell clones induce expression of the early activation antigen CD23 on B lymphocytes in vitro. Under conditions used, this B cell activation event was dependent upon direct T cell contact. Addition of certain bystander B-CLL cells or normal B lymphocytes resulted in a cell number-dependent inhibition of B cell induction. This seems to reflect the competition of B-CLL cells for a cell contact-mediated T cell helper signal. By using CD40 ligand transfected fibroblasts as a substitute for T cell help, we show that the same B-CLL cells also suppress CD40 ligand-mediated B cell activation. B-CLL cells differ in their ability to inhibit CD40 ligand-mediated B cell activation. Some B-CLL cases (eight out of 14) are unable to compete for the T cell or CD40 ligand-mediated signal, even though they can functionally interact with CD40 ligand and thereby get activated themselves. In addition, these results indicate that the observed inhibition is not a result of cell crowding by merely reducing the chance of specific B cell/T cell interactions. Collectively, these data indicate that B-CLL cells are able to inhibit the interaction of activated T lymphocytes with normal B lymphocytes in vitro. Perturbed T cell/B cell interaction may represent an important mechanism underlying the various defects of the specific immune system observed in patients suffering from B-CLL.

Antigens, CD↗
PubMed1999

Vgamma9/Vdelta2 T cell activation induced by bacterial low molecular mass compounds depends on the 1-deoxy-D-xylulose 5-phosphate pathway of isoprenoid biosynthesis.

Isopentenyl diphosphate (IPP), an important precursor of isoprenoid biosynthesis in prokaryotic and eukaryotic organisms, has been shown to activate Vgamma9/Vdelta2 T cells, the major subset of human gammadelta T cells. The biosynthesis of IPP has been first described as the acetate/mevalonate pathway. Recently, 1-deoxy-D-xylulose 5-phosphate (DOXP) and 2-C-methyl-D-erythritol 4-phosphate have been shown to be key metabolites in the DOXP pathway also leading to the formation of IPP in some eubacteria such as Escherichia coli. Here we report that the low molecular mass fraction of extracts from bacteria using the DOXP pathway induces Vgamma9/Vdelta2 T cell activation, while analogous preparations from bacteria using the classical mevalonate pathway fail to do so. Addition of 1-deoxy-D-xylulose potentiates the ability of E. coli extracts to activate Vgamma9/Vdelta2 T cells. As the amounts of IPP present in the bacterial preparations are not sufficient to induce significant Vgamma9/Vdelta2 T cell activation, our data suggest that compounds other than IPP associated with the DOXP pathway are responsible for Vgamma9/Vdelta2 T cell activation.

Chemical Fractionation↗
PubMed1999

Atrial ejection force in systemic autoimmune diseases.

Systemic autoimmune disorders may affect several organs, including the heart. We analyzed two-dimensional and pulsed Doppler echocardiograms of patients (n = 37) with systemic lupus erythematosus (SLE, n = 24) or rheumatoid arthritis (RA, n = 13) to determine whether atrial ejection force (AEF) could represent a suitable parameter for detecting left ventricular filling abnormalities in SLE and RA. In both patient subgroups, AEF was significantly higher than in healthy controls (n = 40) matched for gender and age (14.0 +/- 5.4 vs. 11.0 +/- 3.5 kdyn, p < 0.01). Because conventional echocardiographic parameters of left ventricular function failed to detect such a difference, AEF might serve as an additional sensitive parameter for detecting left ventricular diastolic filling abnormalities early in the course of a systemic autoimmune disease.

Adolescent↗
PubMed1997

Host cell factor CD59 restricts complement lysis of Plasmodium falciparum-infected erythrocytes.

Here we demonstrate that components of the entire complement cascade are fixed on the surface of erythrocytes infected with the human malarial parasite Plasmodium falciparum. Despite the activation of lytic complement factors, no complement-mediated lysis of P. falciparum-infected erythrocytes occurred only in the absence of functional intrinsic CD59. These data suggest that the restriction of the complement attack of P. falciparum-infected erythrocytes is principally mediated by intrinsic host cell factors, in particular CD59.

Animals↗
PubMed1997

Endothelial cells are the major source of sICAM-1 in rheumatoid synovial tissue.

The objective of this research was to investigate the cellular source of soluble ICAM-1 (siCAM-1) from rheumatoid synovial tissue (RS) and its relation to sICAM-1 in synovial fluid (SF) and serum, and to study the expression of ICAM-1 in isolated cells of RS. sICAM-1 was determined by using the enzyme-linked immunosorbent assay (ELISA) and Western blot analysis in supernatants from RS cultured for short periods (n = 19), in SF (n = 7) and in serum (n = 19). ICAM-1 expression, vascularization and inflammatory infiltration (CD3, CD68, CD22) were characterized immunohistochemically in cytospin preparations (n = 18), cryosections (n = 18) and in conventionally stained paraffin sections (n = 19) of RS. The degree of RS vascularization was analysed morphometrically in immunohistochemically stained cryosections (factor VIII related antigen). We found 90-kD sICAM-1 in supernatants of cultured cells, in SF and in sera. sICAM-1 in cellular supernatant correlated significantly (P < 0.01) with SF sICAM-1. The amount of sICAM in cellular supernatants showed no correlation to the score of inflammatory infiltration, but correlated significantly (P < 0.001) with the vascularization index of RS. The percentage of ICAM-1-expressing cells correlated significantly (P < 0.001) with the percentage of CD68-positive macrophages, but not with CD3- and CD22-positive lymphocytes. Macrophages, multinucleated giant cells and endothelial cells exhibited a higher expression of ICAM-1 as compared to lymphocytes and fibroblasts. The differential expression of ICAM-1 on infiltrating leucocytes and resident cells of RS indicates a functional role of ICAM-1 in the local inflammatory process. SF sICAM-1 originated in RS, but serum sICAM-1 did not. Shedding of sICAM-1 by RS was independent of inflammatory infiltration, but depended on the degree of vascularization, indicating that endothelial cells are the major source of sICAM-1 in RS.

Adult↗