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Biomedical subjects

C Kneitz

Publications and source records attributed to C Kneitz.

14 recordsLinked to original sources
PubMed2002

[Spondyloarthritis].

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Cross-Sectional Studies↗
PubMed2002

High resolution ultrasound detects a decrease in pannus vascularisation of small finger joints in patients with rheumatoid arthritis receiving treatment with soluble tumour necrosis factor alpha receptor (etanercept).

OBJECTIVE: High resolution ultrasound (HRUS) was used to investigate the effects of tumour necrosis factor alpha (TNFalpha) blockade on pannus formation and vascularisation of small finger joints in patients with active rheumatoid arthritis (RA). METHODS: Five patients with active RA were treated with etanercept, a soluble TNFalpha receptor protein, for one month. Before, during, and after treatment the patients were followed up by clinical rheumatological examination, determination of their subjective pain score, blood chemistry, and by HRUS of the second metacarpophalangeal (MCP) joint of the right hand. RESULTS: One month after treatment with etanercept, rheumatological examination showed a significant decrease in a modified single joint rheumatic disease activity index (from 2.9 (SD 0.2) to 1.2 (0.7); p<0.05) in all patients. Moreover, a significant decrease in the general pain score (from 4.7 (0.4) to 1.8 (0.6); p<0.05) and in C reactive protein (CRP) levels was seen (from 3.02 (0.9) to 0.24 (0.1); p<0.05). Concordantly, HRUS showed a significant reduction in pannus vascularisation of the MCPII joints (from 23,602 (5339) to 2907 (1609) colour signals/region of interest, CS/ROI; p<0.001). Pearson's correlation coefficient between the results obtained by HRUS and the clinical response was 0.85. CONCLUSION: HRUS is promising as an additional useful method in the assessment of RA activity, and probably also in monitoring therapeutic responses.

Aged↗
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↗
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↗
PubMed1996

Nuclear NF-ATp is a hallmark of unstimulated B cells from B-CLL patients.

B lymphocytes from the peripheral blood of patients with chronic lymphocytic leukaemia (CLL) were analysed for the nuclear presence and DNA binding of a panel of transcription factors which are involved in the gene control of lymphoid cells. The following transcription factors were studied: the Octamer factors Oct-1 and Oct-2, members of the AP-1 factor family, NF-AT factors, in particular NF-ATp, and members of the Rel/NF-kB family. We show that the constitutive nuclear translocation of NF-ATp, a member of the growing family of NF-AT factors, is a hallmark of nonstimulated B cells from CLL patients that distinguishes B-CLL cells from 'normal' B lymphocytes. Constitutive nuclear appearance was also observed for NF-kB2/p52. Constitutive binding of further factor proteins to DNA, such as JunD, c-Fos and FosB, was detected in several patients whereas the localisation and DNA binding of other factors such as c-Jun, RelA/p65 and c-Rel was unaltered. It is remarkable that in B-CLL cells the nuclear appearance and DNA binding of specific transcription factors is dramatically affected whereas other members of the same factor family remained unaltered in these leukemic cells. It remains to be shown which molecular events lead to the specific 'pre-activation', i.e. constitutive nuclear translocation and DNA binding, of these members of NF-AT, NF-kB and AP-1 factor families.

B-Lymphocytes↗
PubMed1995

[Sarcoidosis in monozygotic twins].

Identical (monozygotic) female twins both simultaneously developed acute sarcoidosis with unusual manifestations. Additional to pulmonary involvement they both also had hypercalcaemia with compensated renal failure. When seen at the age of 33 years, these findings were more marked in one of them (case 2) than in the other, and she also had granulomatous conjunctivitis, while in the other one (case 1) the dominant sign was widespread lymph node enlargement. Both were also found by magnetic resonance imaging to have multiple lesions in the white matter, interpreted as the morphological correlate of neurosarcoidosis. But they caused clinical symptoms (visual disorder, unsteady gait) in only one sister (case 1). Treatment with prednisolone largely normalized the lung functions in case 2, completely in case 1, and renal functions in both. But when the daily prednisolone dose was reduced to below 10 mg, the pulmonary symptoms recurred. These observations indicate that even in chronic sarcoidosis acute episodes may occur, with involvement of multiple organs and other rare complications. The manifestations of the underlying disease in identical twins and the similarities of its course in the two sisters underline the possible role of genetic factors in the pathogenesis of sarcoidosis.

Acute Disease↗
PubMed1993

Early phenotypic and functional alterations in lymphocytes from simian immunodeficiency virus infected macaques.

Phenotypic and functional changes in lymphocytes from rhesus monkeys (Macaca mulatta) were investigated during the first 6 months after infection with SIV mac 32H. Animals preimmunized with keyhole limpet hemocyanin (KLH) were sacrificed 1, 3, 6, 12, and 24 weeks post infection. Subset composition and function of lymphocytes from blood, spleen, lymph node and thymus were analysed. In addition to a rapid decline in CD4/CD8 ratios, a massive reduction in CD29+ CD4+ cells was seen in the periphery. Although depletion of this subset was observed throughout the course of this experiment, the loss of proliferative T cell responses was most pronounced very early after infection and partially recovered after Month 3. Polyclonal cytotoxic responses were only slightly affected. In the thymus, a gradual, but moderate loss of CD4+CD8+ immature thymocytes, and a relative increase in both CD4+ and CD8+ mature subsets was observed. Infectious virus was readily recovered from homogenates of lymph node and spleen, but not of thymus tissue. Interestingly, however, virus was detected in thymocytes from all infected animals by cocultivation with a simian immunodeficiency virus (SIV) susceptible cell line.

Animals↗
PubMed1993

Alterations of thymus cortical epithelium and interdigitating dendritic cells but no increase of thymocyte cell death in the early course of simian immunodeficiency virus infection.

The role of the thymus in the pathogenesis of simian acquired immunodeficiency syndrome was investigated in 18 juvenile rhesus monkeys (Macaca mulatta). The thymus was infected from the first week post-SIVmac inoculation, but the amount of virus-positive cells was very low (< 1 in 10(4) T cells) as demonstrated by polymerase chain reaction and in situ hybridization. First morphological alteration was a narrowing of the cortex at 12 and 24 wpi. Morphometry revealed no increase of pyknotic T cells but a decrease of the proliferation rate and flow cytometry showed a reduction of the immature CD4+/CD8+ double-positive T cells. Ultrastructural analysis revealed vacuolization, shrinkage, and finally cytolysis of the cortical epithelial cells and the interdigitating dendritic cells. Immunofluorescence staining exhibited a widespread loss of cortical epithelial cells. This damage to the thymic microenvironment could explain the breakdown of the intrathymic T cell proliferation. It preceded fully developed simian acquired immunodeficiency syndrome and is therefore considered to play a major role in its pathogenesis.

Animals↗
PubMed1992

Mechanism of MHC class I downregulation in HIV infected cells.

HIV infection of CD4+ peripheral blood lymphocytes leads to a loss of MHC class I molecules on the surface of the infected cells as detectable by monoclonal antibody staining and flow cytometry. Incubation of the infected cells at 26 degrees C or treatment at 37 degrees C with peptides leads to upregulation of MHC class I to levels equal to those found on uninfected cells cultured under the same conditions. The data suggest that, after HIV infection, the mechanisms responsible for peptide generation, peptide transport and thus stable association between peptides and MHC class I molecules are severely affected.

CD4-Positive T-Lymphocytes↗
PubMed1991

[Morphological alterations of lymph nodes and thymus during the early course of SIV infection of rhesus monkeys].

Rhesus monkeys (M. mulatta) were i.v. infected with SIV mac251. Three phases of lymph node changes were observed. 1: physiological follicular hyperplasia (3 and 6 weeks p.i.). 2: Alterations of germinal centers: loss of follicular mantle zone, fragmentation or sclerosis (12 and 24 weeks p.i.). 3: Partial depletion of T-lymphocytes, accumulation of plasma cells, increased numbers of syncytial giant cells, hemophgocytosis in the sinuses (about 1 year p.i.). The thymus of the juvenile animals showed first changes 12 and 24 weeks after infection with focal loss of immature (and Ki-67 positive) cortical thymocytes, leading to severe accidental involution of the thymuses one year after infection and reduced numbers of Hassalls corpuscles. These investigations show the value of this animal model for the study of morphology and pathogenesis of AIDS.

Animals↗