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B Jahn

Publications and source records attributed to B Jahn.

At least 37 records · Page 2Linked to original sources
PubMed1995

Susceptibility testing of Candida albicans and Aspergillus species by a simple microtiter menadione-augmented 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay.

We describe a simple microtiter method for determining the susceptibility of Candida albicans and hyphal forms of Aspergillus fumigatus against antifungal agents. The assay measures mitochondrial respiration by determining reduction of 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) to formazan, a process that is enhanced in the presence of menadione. C. albicans or conidial suspensions of A. fumigatus are seeded into microtiter plates. Hyphal outgrowth of Aspergillus spp. was achieved by a 12 to 14-h culture at 30 degrees C. Antifungal agents (amphotericin B, fluconazole, itraconazole) were added to the cultures for 24 h. Thereafter, incubations were continued for 3 h in the presence of MTT plus 0.1 mM menadione. Formazan formation was quantified photometrically after extraction of the formazan with acid isopropanol. Well-defined dose-response curves reflecting impairment of mitochondrial function by the antifungal agents were obtained. With C. albicans, the results correlated excellently with the MIC determinations performed according to the standard macrodilution procedure. In confirmation of a recent report, it was found that fluconazole was unable to exert its fungistatic action on a sensitive C. albicans strain in the presence of serum. The presented method can easily be integrated in the standard repertoire of a diagnostic microbiology laboratory and should prove useful as a means to assess the antifungal action of various agents on yeasts and filamentous fungi in the presence and absence of serum proteins or body fluids.

Amphotericin B↗
PubMed1994

In vivo regulation of transforming growth factor beta 1 transcription by immunotherapy: interleukin-2 impairs interferon-alpha-stimulated increase in steady-state mRNA levels of transforming growth factor beta 1.

Recombinant interleukin-2 (rIL-2) in combination with recombinant interferon alpha (rIFN alpha) has been shown to mediate significant antitumoral effects in some patients with advanced renal cell cancer or malignant melanoma. The therapeutic effects may be partially modulated by secondarily induced cytokines, especially with regard to in vivo lymphocyte activation. To investigate possible negative effects on lymphocyte activation during immunotherapy, we designed a study on transcription of transforming growth factor beta 1 (TGF beta 1), a known inhibitor of lymphocyte function, in patients undergoing treatment with daily alternating administration of rIFN alpha and rIL-2. Here we present data on gene expression of TGF beta 1. Kinetic mRNA studies revealed an increase of TGF beta 1 mRNA in peripheral mononuclear cells 12 h after subcutaneous injection of rIFN alpha. The following intravenous rIL-2 administration significantly decreased the amounts of TGF beta 1-specific mRNA. In contrast to the effect of the first dose, subsequent application of rIFN alpha did not enhance TGF beta gene expression during rIFN alpha/IL-2 therapy. The diminished TGF beta 1 gene expression returned to pretreatment levels 1-7 days after the last rIL-2 administration. When concomitant with a decrease in TGF beta 1 transcripts. Our results indicate a complex regulatory effect on secondarily induced cytokines such as TGF beta 1 by immunotherapeutic approaches. The rIL-2-mediated down-regulation of increased TGF beta 1 steady-state mRNA levels following rIFN alpha may represent a positive immune regulatory effect on cytotoxic cells. Furthermore this effect may modulate proliferation of neoplastic tissues.

Autoradiography↗
PubMed1993

Daily alternating administration of high-dose alpha-2b-interferon and interleukin-2 bolus infusion in metastatic renal cell cancer. A phase II study.

BACKGROUND: Both interleukin-2 (IL-2) and alpha-interferon (alpha-IFN) have some efficacy in renal cell cancer (RCC) as single agents. Additionally, there is some evidence for additive or synergistic antitumoral activity of IL-2 and alpha-IFN in vitro and possibly in vivo. Based on these data, the authors initiated a Phase II trial with a combination of recombinant IL-2 (rIL-2) and recombinant alpha-IFN (alpha-rIFN) in advanced RCC. METHODS: Thirty-six assessable patients with metastatic RCC were entered in this Phase II trial using a daily alternating schedule of alpha-rIFN and rIL-2. Over a period of 14 days, the patients received daily alternating treatment with 10 x 10(6) IU/m2 of recombinant alpha-2b-interferon subcutaneously and 18 x 10(6) IU/m2 of rIL-2 as a 1-hour intravenous infusion. This treatment schedule was repeated every sixth week up to a maximum of four cycles. After the second cycle, patients were examined for response. Patients with stable disease or better received two additional cycles of therapy. Patients with progressive disease were available for other strategies. RESULTS: Thirty-six patients entered the trial and were assessable for toxic effects. Thirty of 36 patients completed at least two cycles and were assessable for response. Nine patients achieved an objective response: 2 had complete responses (CR) and 7 had partial responses (PR). Three patients had a minor response. No effect was observed in patients with local relapse or bone metastases. A relapse-free survival length of 6 months or longer was seen in both patients with CR (12, 23 + months) and in four of seven patients with PR (6, 7, 12, 12 months). The toxicity was moderate and included fever and nausea in most patients, and hypotension, fatigue, skin rash, and arthralgia in a minority of the patients. No Grade 4 and only occasionally Grade 3 toxicity was observed. Fluid retention was negligible. The monitoring of immunologic parameters showed a significant rebound lymphocytosis including cytotoxic (CD56+) cells; in responders the peak of lymphocytosis occurred up to 1 week later than in nonresponders. Peripheral lymphocytes obtained after therapy showed only a slight increase of natural killer cell and lymphokine-activated killer cell activity. During therapy, there was a great release of secondary cytokines as tumor necrosis factor-alpha, gamma-interferon, and interleukin-6, with a peak level 2-4 hours after rIL-2 infusion. CONCLUSIONS: In conclusion, daily alternating administration of alpha-rIFN and rIL-2 is effective in RCC with less toxicity, and the response rate is comparable to those of other immunotherapeutic schedules, including adoptive immunotherapeutic schedules, including adoptive immunotherapy and combinations of high-dose IL-2 and alpha-IFN.

Aged↗
PubMed1993

Stimulation of mononuclear cells by contact with cuprophan membranes: further increase of beta 2-microglobulin synthesis by activated late complement components.

Contact of mononuclear cells (MNC) with cuprophan membranes in vitro causes an increase in beta 2-microglobulin (beta 2m) synthesis. Since in vivo the dialyzer membrane is rapidly coated with plasma proteins, contact activation of MNC was tested in the presence of normal human serum (NHS). After contact with cuprophan, deposition of C5b-9 on the cells was seen, followed by an increase in beta 2m synthesis and cytokine release, exceeding that seen after contact activation in the absence of serum. Inactivated serum or serum deficient in C8 did not increase beta 2m production, indicating that the additional activation was due to complement C5b-9. The results suggest that there are two cuprophan-related mechanisms of cell activation: one by contact of cells with the membrane, the other by the complement activation products. Both might synergistically contribute to an increased beta 2m synthesis in hemodialysis patients.

Blotting, Northern↗
PubMed1993

Immunosuppressive effects and clinical response of fludarabine in refractory chronic lymphocytic leukemia.

BACKGROUND: Fludarabine monophosphate is a new adenine nucleoside analogue with a promising efficacy in B-cell chronic lymphocytic leukemia (B-CLL) with response rates, including hematological complete remissions, of 50%-60% in previously treated and 75%-80% in previously untreated patients. PATIENTS AND METHODS: Here, the clinical experience with and side effects of fludarabine are reported in 19 patients with refractory CLL (17 B-CLL, 2 T-CLL). All patients were pretreated with one to four different regimens and had progressive disease. Fludarabine was administered at a dosage of 25 mg/m2 daily for 5 days as a 30-minute intravenous infusion. This course was repeated every fifth week. Dosage and time course were adapted to toxicity. RESULTS: 12/18 (67%) evaluable patients achieved partial remissions (PR), 1/18 (6%) had stable disease (SD) and 5/18 (28%) were progressive. The median duration of partial remission until relapse or death was 6 months. Most responses to fludarabine occurred within two treatment courses. Major toxic effects included infections in 11 patients and nausea in 8 (mainly grade 1). Meanwhile, three patients died of progressive disease and 8 of pneumonias or other infections. Two patients had pneumocystis carinii pneumonias and one an aspergillus pneumonia. The high infection rate may be due not only to hypogammaglobulinaemia or fludarabine-induced granulocytopenia but also to a remarkable decrease of CD4(+)-cells during fludarabine therapy. In one case a tumor lysis syndrome was observed. No CNS toxicity was noted. CONCLUSION: It is concluded that fludarabine is effective even in patients with advanced chronic lymphocytic leukemia refractory to multiple chemotherapy regimens. However, fludarabine has a remarkable suppressive effect on T-lymphocytes, predominantly CD4(+)-lymphocytes. Long-term antibiotic prophylaxis is recommended.

Adult↗
PubMed1993

Interaction of the terminal complement components C5b-9 with synovial fibroblasts: binding to the membrane surface leads to increased levels in collagenase-specific mRNA.

The late complement components, apart from their lytic function, are known to trigger the release of various proinflammatory substances from different types of nucleated cells. In the present study, the interaction of C5b-9 with synovial fibroblast cells (SFC) was examined. It was found that incubation of SFC with activated complement components resulted in binding of C5b-9 to the cell membrane; subsequently an increase in abundance of collagenase-specific mRNA was seen, as assessed by Northern blotting. When C8-deficient serum was used as source of complement neither binding of C5b-9 nor an increase in collagenase-specific mRNA could be detected. These findings suggest that C5b-9, which might be generated during rheumatoid inflammation, may contribute to chronic joint destruction by triggering collagenolytic activity.

Arthritis, Rheumatoid↗
PubMed1991

Enhancement of human immunodeficiency virus 1 replication in monocytes by 1,25-dihydroxycholecalciferol.

Human immunodeficiency virus (HIV) expression and replication are under tight regulatory control. We demonstrate that 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] enhances the replication of monocyte- and lymphocyte-tropic strains of HIV-1 up to 10,000-fold in monocyte cell lines, peripheral blood monocytes, and unfractionated peripheral blood mononuclear cells. 1,25(OH)2D3 is therefore one of the most potent regulators of HIV-1 replication described to date. Precursors of 1,25(OH)2D3 enhance HIV-1 replication in proportion to their affinity for the 1,25(OH)2D3 intracellular receptor, suggesting that 1,25(OH)2D3 influences HIV-1 replication by mechanisms involving this receptor. These studies may have important implications for the design of effective therapy of HIV-1 infection.

Antigens, CD↗
PubMed1991

Stimulation of beta 2-microglobulin synthesis in lymphocytes after exposure to Cuprophan dialyzer membranes.

We tested beta 2-microglobulin (beta 2m) synthesis by peripheral blood lymphocytes of non-uremic donors after contact with dialyzer membranes. Under serum-free conditions, lymphocytes were incubated with different dialyzer membranes for four hours. After subsequent culture in the absence of membranes to yield an overall culture time of 24 hours, RNA was extracted. Messenger RNA for beta 2m was quantitated by Northern blotting with specific probes. Increased beta 2m mRNA was seen after a minimum of one hour contact time with Cuprophan both in the presence and absence of cycloheximide. While no consistent stimulation was seen with polyacrylonitrile or polycarbonate-polyether membranes, respectively, the stimulation of beta 2m mRNA with Cuprophan was of the same order of magnitude as that obtained with interferon gamma. Stimulation of beta 2m mRNA by Cuprophan was stereospecifically diminished by 5 mM L-fucose. Apart from stimulated transcription of beta 2m we could also show increased surface expression of MHC class I molecules, using FACS technique. The results further prove complement-independent blood cell activation by Cuprophan membranes. It is uncertain whether the results are relevant for beta 2m amyloidosis.

Blood Proteins↗
PubMed1991

Antigenicity and accessory cell function of human articular chondrocytes.

It is postulated that chondrocytes may be actively involved in the pathogenesis of inflammatory joint diseases, presumably by providing tissue specific antigens that may initiate or sustain autoimmune reactions. To investigate whether chondrocytes may also function as accessory cells in ongoing immune processes, mixed leukocyte-chondrocyte cultures and antigen presentation assays were studied. Freshly isolated and short term cultured HLA class II antigen (Ia) negative as well as gamma-interferon treated Ia positive chondrocytes were weakly or not stimulatory to allogeneic or autologous resting lymphocytes derived from either normal donors or patients with rheumatoid arthritis. In an antigen presenting system using tetanus toxoid, the majority of chondrocyte preparations tested induced an antigen driven response in HLA matched allogeneic or autologous resting T cells which, however, was much less when compared to blood monocytes. In contrast, using activated T cells derived from tetanus toxoid specific T cell lines, an efficient antigen presenting capacity could be demonstrated in both Ia positive and initially Ia negative chondrocytes. Interestingly, the latter population had acquired Ia antigens upon incubation with the T cell line.

Antigen-Presenting Cells↗
PubMed1990

Oxygen radical generation in human platelets: dependence on 12-lipoxygenase activity and on the glutathione cycle.

Stimulation of the arachidonic acid metabolism in human platelets also induces chemiluminescence, which indicates the formation of highly reactive oxygen species. To analyze the pathway by which oxygen radicals are generated, we tested the dependence of O2- generation on the eicosanoid metabolism. We found that inhibition of lipoxygenase, but not of cyclooxygenase, prevented the O2- production. Moreover, depletion of cellular glutathione peroxidase resulted in reduced synthesis of the lipoxygenase product 12-hydroxyeicosatetraenoic acid, as well as in reduce O2- thus establishing a link between O2- generation, the lipoxygenase pathway and the glutathione cycle.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1989

Effect of the late complement components C5b-9 and of platelet-derived growth factor on the prostaglandin release of human synovial fibroblast-like cells.

We examined the prostaglandin E (PGE) synthesis of cultured adherent synovial fibroblast-like cells (SFC) from patients with osteoarthritis (OA) in the noninflammatory state as well as with rheumatoid arthritis (RA). In cells from RA patients the spontaneous PGE release was generally higher compared to that of OA patients, but decreased fast with time in culture. After cell passage, similar PGE baseline levels were seen in cells of the two patient groups. The cells could then be stimulated by the terminal complement components C5b-9 or C5b-8. PGE synthesis was also stimulated by the platelet-derived growth factor (PDGF), interleukin-1 (IL-1), or lipopolysaccharide (LPS). The amount of PGE synthesis after incubation with PDGF, LPS and IL-1 was comparable to that released after C5b-9. Thus, like other inflammatory mediators C5b-9 and PDGF trigger the increased PGE production by SFC and thus may participate in the development of synovial inflammation and contribute to the pathogenesis of RA.

Arthritis, Rheumatoid↗
PubMed1987

Peroxidative membrane damage in human erythrocytes induced by a concerted action of iodoacetate, vanadate and ferricyanide.

Human erythrocytes incubated without substrate in the presence of iodoacetate (0.2 mM), vanadate (0.5 mM) and ferricyanide (5 mM) form aqueous membrane leaks of equivalent radii of 0.5-0.8 nm leading to complete colloid-osmotic lysis within 180 min. All three components are indispensable for the effect. Inosine but not glucose markedly enhances the rate of hemolysis. These effects are due to oxidative damage, as indicated by concomitant destruction of polyunsaturated fatty acids and suppression of both effects by radical scavengers. Hemoglobin is not oxidized under these conditions. GSH and membrane SH levels remain almost normal, and no crosslinking or irreversible aggregation of membrane proteins is observed. In the absence of O2 no membrane damage can be observed. It is proposed that radical formation originates from reduction of O2 by NADPH, analogous to processes described in microsomal membranes. NADH seems not to be involved, since leak formation occurs in spite of the blockage of NADH formation by iodoacetate. Vanadate and ferricyanide are probably required to amplify the peroxidative reaction sufficiently to overcome the cellular antioxidative capacity.

Erythrocyte Membrane↗
PubMed1987

Changes in cell surface antigen expression on human articular chondrocytes induced by gamma-interferon. Induction of Ia antigens.

Ia antigens (class II HLA molecules) have been detected on cells eluted from affected human cartilage in certain disease states, but not on normal cartilage cells. Because the presence of Ia antigens on chondrocytes may play an important role in rheumatic diseases, we investigated the induction of these molecules by gamma-interferon (gamma-IFN), a potent Ia-inducing lymphokine. Human articular chondrocytes were incubated with recombinant gamma-IFN, and the expression of Ia antigens was studied by cell sorter analysis, using a panel of reagents that detect monomorphic and polymorphic specificities of the DR and DQ Ia antigen families. While the induction of DR antigens, including polymorphic DR specificities, was readily obtained with gamma-IFN (50-95% positive cells), DQ antigens were negative or were displayed only on a lower percentage of chondrocytes (5-60%). In addition, incubation with gamma-IFN led to an increased expression of HLA class I antigens. The expression of various other surface markers either remained unchanged (as in 4F2 and BA-2) or showed tendencies toward decreased percentages (as in 83c2) or increased percentages (as in M phi R-17). No apparent change in cell morphology or growth pattern was observed.

Antigens, Surface↗
PubMed1987

Functional and phenotypical characterization of activated T cells from intra-articular sites in inflammatory joint diseases. Possible modulation of the CD3 antigen.

The presence of activated T lymphocytes bearing interleukin 2 (IL-2) receptors and HLA class II (Ia) antigens accompanied by impaired T cell functions such as a decreased mitogenic responsiveness are characteristic findings, especially in intra-articular sites in chronic inflammatory joint diseases. The objective of the present study was to further characterize these in vivo activated T cells by the investigation of IL-2 production and a possible T cell receptor modulation. IL-2 receptors were found to be expressed primarily in the CD4+ subset. The Ia+ subset expressing both DR and DQ antigens showed a weaker mitogen-induced response as compared to the Ia- fraction. A decreased mitogen-induced IL-2 production and a lower response to anti-CD3 monoclonal antibodies was observed with synovial T lymphocytes as compared to peripheral blood T cells. The density of the CD3 molecule, known to be closely associated with the T cell receptor, was significantly lower in intra-articular sites, while other T cell-specific surface molecules were expressed to a similar extent in both compartments. The decreased synovial T cell mitogenesis was not restored by the addition of lymphokines (IL-1 and IL-2) or blood monocytes, nor by removing CD8+ T cells. These data present further evidence for a significant T cell activation in intra-articular sites in chronic inflammatory joint diseases. The decreased expression of the CD3 glycoprotein suggests a modulation by so far unidentified antigen(s), which could also be responsible for the weak T cell response elicited by polyclonal mitogens.

Antibodies, Monoclonal↗
PubMed1987

Differential expression of Ia antigens by rheumatoid synovial lining cells.

The differential expression of Ia antigens was studied in freshly isolated rheumatoid nonlymphoid synovial lining cells (SLC) and rheumatoid synovial fibroblast cell lines cultured in the presence of Interferon-gamma, using a large panel of anti-Ia reagents with monomorphic or polymorphic specificities. All the HLA-DR or -DQ specificities detectable on the corresponding peripheral blood B cells were also expressed in freshly isolated SLC. However, in all instances, the number of DR-positive SLC exceeded the percentage of cells expressing DQ antigens. In addition, the epitope expression of Ia antigens varied within the DR or DQ populations of Ia molecules as revealed by polymorphic reagents. Double-label experiments or using the ingestion of Latex particles as a marker demonstrated that the synovial macrophages (type I SLC) primarily bear the DR+DQ+ phenotype, while there is an additional population of nonphagocytic SLC (previously termed type II SLC) that has a DR+ and monocyte marker negative phenotype but did not have detectable levels of DQ antigens as analyzed by both fluorescence microscopy and cell sorter analysis. This latter population frequently had a morphology showing dendritic processes and rapidly lost the expression of Ia antigens upon culture. Cells with a similar, primarily DR+ phenotype were readily obtained in synovial fibroblast cultures after treatment with Interferon-gamma. These data suggest that there are two populations of Ia+ synovial lining cells: the synovial macrophages (type I cells) with the DR+DQ+ phenotype, and cells probably related to fibroblasts with a DR+ phenotype without detectable DQ antigens (type II cells). The fact that the latter phenotype could be induced by Interferon-gamma treatment of cultured synovial fibroblasts suggests that this mediator may have a similar role in vivo in the activation of certain synovial cell populations.

Arthritis, Rheumatoid↗
PubMed1986

Duration versus degree of hypotension as critical conditions of brain infarction in the albino rat.

In 41 anesthetized, spontaneously breathing male adult albino rats, cerebral hypotension of precisely defined duration and magnitude was induced by means of controlled arterial hemorrhage. One common carotid artery was occluded throughout the hypotensive period, and the target pressure was monitored in the ipsilateral internal carotid artery. Regional brain infarcts developed in all 16 animals with a target pressure of 14 mm Hg maintained for 90 minutes and in all five animals with a target pressure of 12 mm Hg maintained for 70 minutes. However, the brains of all 10 rats with a target pressure of 17 mm Hg maintained for 80 minutes remained intact. In two further groups of five animals each with target pressures of 15 mm Hg for 80 minutes and 16 mm Hg for 90 minutes the incidence of infarct was about 30%. There were no marked differences between the five groups of rats in body weight, body temperature, heart rate, respiratory rate, PaO2, PaCO2, arterial pH, or hematocrit. The data suggest that, in the rat, the clear-cut threshold for the induction of brain infarcts is a function of the severity and duration of arterial hypotension. Evidence is presented indicating that this function is distinctly species-dependent, due to species differences in the dilatory capacity of the arteries supplying the brain rather than species differences in brain vulnerability.

Animals↗
PubMed1986

Intraarticular T lymphocytes in monoarticular and oligoarticular inflammatory joint diseases. Normal subset distribution and less numbers of activated T cells indicate major differences as compared to rheumatoid arthritis.

T lymphocyte subpopulations and the expression of T cell activation antigens were determined in peripheral blood, synovial fluid and/or synovial tissues of patients with recurring monoarticular arthritis and patients with HLA-B27 associated oligoarthritis in comparison to patients with rheumatoid arthritis (RA). In individuals with monoarthritis or oligoarthritis, there was a normal T cell subset distribution, both in peripheral blood and in intraarticular sites, with only a small number of T cells bearing Ia antigens. This was in marked contrast to the patient group with RA that demonstrated a significantly decreased ratio of T helper/inducer to T suppressor/cytotoxic cells in addition to large numbers of Ia+ T cells in intraarticular sites. The expression of the Tac antigen was similar in all disease groups.

Adolescent↗