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Biomedical subjects

W Graninger

Publications and source records attributed to W Graninger.

At least 73 records · Page 4Linked to original sources
PubMed1999

Activation of Fas inhibits heat-induced activation of HSF1 and up-regulation of hsp70.

Activation of heat shock factor (HSF) 1-DNA binding and inducible heat shock protein (hsp) 70 (also called hsp72) expression enables cells to resist various forms of stress and survive. Fas, a membrane-bound protein, is a central proapoptotic factor; its activation leads to a cascade of events, resulting in programmed cell death. These two mechanisms with contradictory functions, promoting either cell survival or death, were examined for their potential to inhibit each other's activation. Induction of FAS-mediated signaling was followed by a rapid decrease in HSF1-DNA binding and inducible hsp70 expression. Inhibition of HSF1-DNA binding was demonstrated to be based on absent hyperphosphorylation of HSF1 during FAS signaling. These effects of FAS activation on the HSF1/hsp70 stress response were blocked by ICE (caspase 1) inhibitors, suggesting an ICE-mediated process. Furthermore, inhibition of HSF1/hsp70 was accompanied by an increase in apoptosis rates from 20% to 50% in response to heat stress. When analyzing the effects of HSF1/hsp70 activation on Fas-mediated apoptosis, protection from apoptosis was seen in cells with induced hsp70 protein levels, but not in cells that were just induced for HSF1-DNA binding. Thus, we conclude that inhibition of HSF1/hsp70 stress response during Fas-mediated apoptosis and vice versa may facilitate a cell to pass a previously chosen pathway, stress resistance or apoptosis, without the influence of inhibitory signals.

Apoptosis↗
PubMed1999

Expression of adhesion molecules on synovial fluid and peripheral blood monocytes in patients with inflammatory joint disease and osteoarthritis.

OBJECTIVE: To determine the presence of adhesion molecules on monocytes/macrophages (Mphi) from peripheral blood (PB) and synovial fluid (SF) in patients with osteoarthritis (OA) and inflammatory joint diseases (rheumatoid (RA) and reactive arthritis (ReA)) in order to improve our understanding of the possible mechanisms underlying the inflammatory process. METHODS: Whole blood and SF cells were stained with monoclonal antibodies against CD11a (LFA-1), CD15 s (sialyl-Lewis X), CD44, CD54, VLA-4, and HLA-DR counterstained with anti-CD14 antibodies as a Mphi marker for dual fluorescence analysis by flowcytometry. RESULTS: On PB-Mphi, CD15s was markedly increased in both RA as well as ReA compared with OA. Furthermore, in the PB LFA-1, CD44, and HLA-DR showed a higher surface density on Mphi in ReA than in OA. Comparison between SF and PB showed significantly higher CD44 and CD54 expression on SF-Mphi. These molecules play an important part in lymphocyte-Mphi interaction. CONCLUSION: In PB from patients with inflammatory joint diseases, Mphi are activated, allowing recruitment into the synovial compartment. These disorders, in contrast with OA seem to be "systemic" in nature. Within the SF, different adhesion molecules are expressed on CD14(+) Mphi as compared with PB.

Adult↗
PubMed1999

Increased frequency of Th2-type cytokine-producing T cells in microfilaremic loiasis.

The frequency of cytokine-producing peripheral blood mononuclear cells was assessed in 28 subjects with microfilaremic loiasis and in 14 amicrofilaremic individuals. In addition, a subgroup of seven microfilaremic individuals coinfected with Plasmodium malariae was evaluated. By using flow cytometry for the intracellular detection of cytokines, a more pronounced T helper (Th)2 cell-type response with the expansion of interleukin (IL)-4, IL-10, and IL-13 expressing CD4+ cells in the microfilaremic compared with the amicrofilaremic group was noted. Expression of IL-5 was equivalent in both groups as was the frequency of Th2-type cytokines expressing CD8+ cells and of Th1-type cytokines (interferon [IFN]-gamma, IL-2, IFN-gamma/IL-2) producing CD4+ and CD8+ cells. Th0-type cytokine-expressing cells, represented by IL-4/IFN-gamma, IL-10/IFN-gamma, and IL-13/IFN-gamma, were equally distributed within groups. Coinfection of P. malariae did not significantly alter the cytokine expression compared with microfilaremic individuals without P. malariae infections. By identifying a large panel of cytokine-producing T cell subpopulations, a Th2-driven immune response in microfilaremic Loa loa patients was noted.

Adult↗
PubMed1999

Frequency of cytokine-producing CD4-CD8- peripheral blood mononuclear cells in patients with Plasmodium falciparum malaria.

The frequency of cytokine-producing CD4-/CD8- mononuclear cells was assessed in patients of different age groups (29 infants, aged 1-5 years; 30 schoolchildren, aged 6-14 years, 26 adults, aged > 15 years) with acute Plasmodium falciparum malaria, from Gabon. Fifteen patients were followed up before antimalarial treatment (day 0), during parasite clearance (day 3) and after resolution of parasitemia (day 10). By using flow cytometry for intracellular detection of cytokines, a striking expansion of CD4-/CD8- cells producing the type 1 cytokines interleukin (IL)-2-/interferon (IFN)-gamma+, IL-2+/IFN-gamma+ and IL-2+/IFN-gamma- was observed in adults as compared with children. Type 2 cytokine expression (IL-4+/IFN-gamma-, IL-13+/IFN-gamma-) and type 0 cells (IL-4+/IFN-gamma+, IL-13+/IFN-gamma+) were not significantly different between the three age groups. Patients with severe malaria had a significantly increased frequency of type 2 cytokine-producing CD4-/CD8- cells. Drug-induced clearance of parasitemia was characterized by a decrease of IL-2+/IFN-gamma- and type 2 cytokine expressing CD4-/CD8- cells and by a gradual increase of IL-10+/IFN-gamma- expression. The type 1/type 2 dichotomy observed within the CD4-/CD8- cell population is likely to be of significance in the host response against P. falciparum malaria.

Adolescent↗
PubMed1999

Cytokines in sepsis due to Candida albicans and in bacterial sepsis.

Cytokines, such as tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and tumor necrosis factor-soluble receptor (TNF-sR), and adhesion molecules, e.g. vascular adhesion molecule-1 (VCAM-1) and E-selectin, play an important role in the pathogenesis of bacterial sepsis. Experimental data on cytokine expression during candidaemia are controversial. In this study, plasma concentrations of cytokines and adhesion molecules were compared between patients with sepsis due to Candida albicans and bacterial sepsis. Plasma levels of TNF-alpha, TNF-sR, IL-6, VCAM-1 and E-selectin, were determined in 20 patients with sepsis due to C. albicans, in 20 patients with bacterial sepsis, and in 20 controls on days 1, 7 and 14. On day 1, elevated plasma levels of TNF-alpha, TNF-sR and IL-6 were detected in both sepsis groups compared to controls. On day 1, VCAM-1 levels were higher, and E-selectin levels were lower in patients with Candida sepsis than in patients with bacterial sepsis (p < 0.05). At any time, VCAM-1 levels were significantly greater in patients with Candida sepsis than in patients with bacterial sepsis (p < 0.05). Non-survivors, regardless of the etiology of sepsis, had higher blood levels of IL-6, TNF-sR and E-selectin than survivors. The cytokines, TNF-alpha, IL-6 and TNF-sR, and the adhesion molecules, VCAM-1 and E-selectin, are involved in sepsis due to C. albicans as in bacterial sepsis.

Adolescent↗
PubMed1998

[New aspects in treatment of systemic mycoses].

The incidence of systemic fungal infection has been increasing during the last two decades. Candida and Aspergillus spp. are the classical opportunistic pathogens. Rare fungi, such as Mucor, Rhizopus, Fusarium, Trichosporon, Paecilomyces, Alternaria, Cladosporium and Pseudoallescheria, are emerging as cause of systemic fungal infection in the immunocompromised host. For more than 40 years Amphotericin B has been the gold standard of antifungal treatment because of its broad spectrum comprising yeasts, dimorphic fungi and moulds. Its nephrotoxicity has led to the development of lipid-associated preparations of amphotericin B: liposomal amphotericin B, amphotericin B colloidal dispersion and amphotericin B lipid complex. These preparations are less nephrotoxic, but higher doses than those of conventional amphotericin B are needed to achieve the same effect. The triazole fluconazole is the treatment of choice in infections caused by Candida albicans. New antifungal compounds are voriconazole and the candins, the pradimicin/benanomycin family, nikkomycin Z and a liposomal preparation of nystatin.

Amphotericin B↗
PubMed1998

[Malaria therapy in the era of chloroquine resistance].

Despite few efforts to develop new antimalarial compounds by the major pharmaceutical companies, some promising new therapeutics have been developed and tested clinically by small groups and companies throughout the world. Really new substances are scarce but combinations of known medicarnents have been shown to be a rational and effective approach to overcome problems with single compounds. Additionally, combination regimens are more easily authorized and accepted for treatment than completely new substances. Some examples in this respect are combinations of either atovaquone, doxycycline or clindamycin with a 'classical' antimalarial. Artemisinin, benflumetol and pyronaridine were originally developed in China and disperse currently to the rest of the world. First independent and international clinical trials gave promising results and one should bear in mind those substances for future applications. Especially artemisinin and its derivatives are of great interest because they represent, besides quinine, the only other therapeutic option for the treatment of multidrug-resistant severe malaria.

Antimalarials↗
PubMed1998

A case of visceral leishmaniasis in Austria.

We report a patient aged 41 years with fever of unknown origin. Notable aspects of his travel history were a trip to the Philippines and a sailing trip around Sicily. The patient presented with fever up to 40 degrees C since 4 weeks, weakness, headache, hepatosplenomegaly and night sweat. No specific cause could be found. Based on clinical findings tuberculosis was suspected and empirical tuberculostatic treatment was started. However, during the following 6 weeks the patient's condition deteriorated. A bone marrow biopsy performed to exclude a haematological malignancy revealed Leishmania sp. in macrophages. This histological diagnosis was confirmed retrospectively by re-examination of a previously performed liver biopsy and by an increased anti-leishmania serum antibody titer of 1:1280. The patient was treated with sodium stibogluconate (pentostam, 850 mg) for 30 days and recovered slowly.

Adult↗
PubMed1998

Influence of glycopeptide antibiotics on purine metabolism of endothelial cells.

We provide evidence that the commercially available preparations of glycopeptides for intravenous application are well tolerated by endothelial cells when applied in concentrations less than 5 mg/ml. Since the antibiotics tested are administered at maximal concentrations of 10 mg/ml, the dose range used in our in vitro experiments (5 and 10 mg/ml) mimics possible clinical concentrations at the site of infusion. Similar concentrations may be reached by retrograde intravenous pressure infusion techniques (10-12). We have demonstrated that these high concentrations lead to considerable endothelial cell damage. These findings may explain the common side effect associated with intravenously applied glycopeptides namely pain and phlebitis at the site of infusion (2, 13). Figure 1 shows that a detrimental effect measurable after 20 min occurs only using vancomycin solutions at concentrations of 10 mg/ml, whereas already a dilution to 5 mg/ml renders the solutions more compatible to HUVEC. These data are in line with the observation that slow intravenous application of glycopeptides into large veins can largely prevent the occurrence of local phlebitis. Alternatively, the occurrence of phlebitis should be avoidable by diluting the manufacturers' preparations at least to 2-5 mg/ml and not 10 mg/ml as recommended by the manufacturer of vancomycin. The same aspects need to be considered for use of glycopeptides for retrograde high pressure infusion. The tolerance of intravenously applied antibiotics has previously been tested in animal models (4). Our model of human venous endothelial cells for testing antibiotic solutions for intravenous compatibility provides a valuable alternate model. In conclusion our data show that the commercial preparation of teicoplanin is more compatible for HUVEC than those of vancomycin.

Adenosine Triphosphate↗
PubMed1998

Effects of parathyroid hormone and serum calcium on the phenotype and function of mononuclear cells in patients with primary hyperparathyroidism.

BACKGROUND: Several studies have demonstrated specific influence of parathyroid hormone (PTH) on immune parameters, especially on T- and B-cell function, migration of polymorphonuclear leucocytes (PMNLs) and antibody synthesis, in patients with secondary hyperparathyroidism and chronic renal failure and recently also in patients with primary hyperparathyroidism (pHPT). METHODS: We therefore examined 12 patients with pHPT before and 6 months after parathyroidectomy (PTX) and nine sex- and age-matched control subjects to determine the impact of PTH and serum calcium concentrations on several immune parameters, including (a) serum concentrations of immunoglobulins, (b) immunophenotype of peripheral blood lymphocytes, (c) phytohaemagglutinin (PHA)-induced lymphocyte proliferation and (d) monocytic surface marker expression. RESULTS: Serum concentrations of immunoglobulins (IgG, IgA, IgM) were unaffected by elevated serum PTH and calcium levels. T lymphocytes (CD3), B lymphocytes (CD19), NK cells (CD16/56) and monocytes (CD16) revealed a normal distribution and were not different before and after PTX in patients with pHPT when compared with the control group. CD4+ T-helper lymphocytes were significantly elevated pre- and post-operatively in patients with pHPT. The lymphocyte proliferation response to PHA in the highest concentration (12.5 micrograms L-1) tested was significantly suppressed in patients with pHPT preoperatively when compared with the patients post-operatively and the control group. In addition, both CD4+ and CD8+ lymphocytes showed a lower expression of activation markers, interleukin 2 (IL-2) receptor (CD25) and transferrin receptor (CD71), which could be partially restored 6 months after PTX, but did not reach normal values. CONCLUSION: In summary, in contrast to the findings in patients with secondary HPT, pHPT appears to be associated with less alterations of immune functions. Chronically elevated serum PTH and calcium concentrations in patients with pHPT induce a higher percentage of CD4+ helper T lymphocytes and a suppressed lymphocyte response to PHA as well as a reduced expression of activation markers on peripheral blood lymphocytes.

Adult↗
PubMed1998

Austrian national survey of prevalence of antimicrobial resistance among clinical isolates of Streptococcus pneumoniae 1994-96.

The antimicrobial susceptibilities of 1385 clinical isolates of Streptococcus pneumoniae obtained from 25 laboratories across Austria between December 1994 and January 1996 were tested. Minimal inhibitory concentration (MIC) values were determined in tests with penicillin, amoxycillin, amoxycillin/clavulanate, ceftriaxone, cefodizime, cefpirome, cefotaxime, cefpodoxime, cefadroxile, azithromycin, clarithromycin, josamycin and roxithromycin by the agar-dilution method. A total of 40 isolates (2.9%) demonstrated intermediate resistance (MIC 0.125-1 microg/ml) and 28 isolates (2.0%) had high-level resistance (MIC > or = 2 microg/ml) to penicillin. Excepting cefadroxil, with an MIC90 of 2 microg/ml, all other tested beta-lactams had MIC90s of 0.03-0.06 microg/ml. Penicillin-resistant strains were much more likely to be also resistant to the other beta-lactams. The macrolides proved to be very active compounds against pneumococci with MIC90s of 0.06 microg/ml (clarithromycin) and 0.25 microg/ml (all other macrolides). Regional differences within Austria with regard to antimicrobial resistance were not observed.

Anti-Bacterial Agents↗
PubMed1998

In-vitro selection of resistance to vancomycin and teicoplanin in Enterococcus faecium and Enterococcus faecalis compared with Staphylococcus epidermidis.

Clinical isolates of Enterococcus faecium, Enterococcus faecalis and Staphylococcus epidermidis were studied for their ability to develop resistance by two selection methods, one in broth and one on agar. The MICs for enterococci after exposure to vancomycin ranged from 0.5 mg/L to 4 mg/L, and those after exposure to teicoplanin ranged from 0.25 mg/L to 1 mg/L. No significant increases occurred for E. faecalis, whilst two isolates of E. faecium showed increases of up to eight-fold (from 0.125 mg/L to 1 mg/L). Vancomycin MICs ranged from 1 mg/L to 4 mg/L and teicoplanin MICs reached 32 mg/L for S. epidermidis. Pulsed-field gel electrophoresis analysis of SmaI-digested whole chromosomal DNA was performed to compare the genomic DNA of glycopeptide-exposed and wild-type strains. In-vitro exposure to vancomycin did not alter MICs significantly except in one S. epidermidis isolate for which the MIC reached 4 mg/L, whereas the teicoplanin-exposed cultures of S. epidermidis showed increases of up to 64 times the original MIC. Comparable results were achieved with the two selection methods.

Anti-Bacterial Agents↗
PubMed1998

Endothelial cell compatibility of glycopeptide antibiotics for intravenous use.

The use of human venous endothelial cells for testing antibiotic solutions for intravenous compatibility provides a valuable alternative to animal models. In order to evaluate the effect of vancomycin and teicoplanin on the viability of human umbilical venous endothelial cells, intracellular ATP levels were measured by a luciferin-luciferase assay. Prostacyclin (PGI2) and thromboxane A2 (TXA2) were determined by direct radioimmunoassay. Vancomycin at concentrations of 5 and 10 mg/mL reduced the intracellular ATP content by 18.7% and 69.9%, respectively, within 60 min. In contrast, cellular energy charge remained significantly higher after incubation with teicoplanin at 5 and 10 mg/mL (reduction 8.7% and 15.5%, respectively). Neither vancomycin nor teicoplanin at a concentration of 2 mg/mL led to significant ATP decline. However, endothelial cells incubated with vancomycin resulted in significantly lower release of PGI2 and TXA2 compared with teicoplanin. These results show that teicoplanin is more compatible with endothelial cells than vancomycin, and that both antibiotics are well tolerated if diluted to a final concentration of 2 mg/mL.

Adenosine Triphosphate↗
PubMed1998

Benefit of 6 months long-term physical training in polymyositis/dermatomyositis patients.

OBJECTIVE: The benefit of long-term physical training in patients with chronic polymyositis or dermatomyositis (PM/DM) was studied prospectively. METHODS: Eight patients with chronic PM/DM participated in a training programme for 6 months. A group of five PM/DM patients without any physical training was observed for control purposes. RESULTS: While there was no significant change in serum creatine phosphokinase (CPK) levels, the 'activities of daily living (ADL)' score improved significantly (P < 0.03), peak isometric torque (PIT) generated by muscle groups in the lower extremities rose significantly (P < 0.03) and there was a statistically highly significant increase in peak oxygen uptake (VO2max) relative to body weight (P < 0.02) due to the long-term training. The patients improved their aerobic capacity by 28%, which is clinically significant. In the untrained patients, no improvement in these target parameters was observed. CONCLUSION: In clinically stable DM/PM patients, long-term physical training can safely be performed and is recommended as part of a comprehensive rehabilitation management, particularly in view of the cardiopulmonary risk in these patients.

Activities of Daily Living↗
PubMed1998

Improvement of physical fitness and muscle strength in polymyositis/dermatomyositis patients by a training programme.

In the present investigation, the benefit of physical training in patients with inflammatory myopathy was studied. In this prospective, randomized, controlled study, 14 patients with polymyositis (PM) or dermatomyositis (DM) were investigated. The training, consisting of bicycle exercise and step aerobics, took place over a 6 week period. Baseline and endpoint measurements included an 'activities of daily living' (ADL) score, peak isometric torque (PIT) generated by muscle groups in the lower extremities, peak oxygen consumption (VO2max), and creatine phosphokinase (CPK) levels. There was no significant rise in disease activity in the training group in comparison to the controls. The ADL score for the treatment group, in comparison to the control group, improved (P < 0.02), PIT rose (P < 0.05) and there was a statistically significant increase in oxygen uptake relative to body weight (P < 0.05). No rise in inflammatory activity, but significant improvement in muscle strength, oxygen uptake and well-being, were found in patients with inflammatory myopathy as a result of physical training. Besides medication, a physical training programme consisting mainly of concentric muscle contractions should therefore be an integral part of therapy, particularly in view of the cardiopulmonary risk of these patients.

Adult↗
PubMed1998

Reciprocal regulation of Th1- and Th2-cytokine-producing T cells during clearance of parasitemia in Plasmodium falciparum malaria.

Flow cytometry for the intracellular detection of T-cell cytokines was performed for 15 Gabonese patients during acute uncomplicated Plasmodium falciparum malaria. A striking expansion of CD4(+) and CD8(+) T cells producing gamma interferon (IFN-gamma) was found during drug-induced clearance of parasitemia, paralleled by a decrease of interleukin-2 (IL-2) production. The frequency of IL-4- and IL-13-producing CD4(+) cells gradually decreased, whereas the frequency of T cells producing IL-2(+)-IFN-gamma+, IL-4(-)-IL-5(+), and IL-4(+)-IL-5(+) cytokines as well as IL-4(+)-IFN-gamma+ and IL-13(+)-IFN-gamma+ cytokines was not significantly altered. The capacity for IL-10 production within the CD4(+) subset increased due to an expansion of both IL-10(+)-IFN-gamma- and IL-10(+)-IFN-gamma+ cytokine-expressing cells. Thus, a more pronounced Th2-driven immune response during acute untreated P. falciparum infection with a shift towards Th1 responsiveness induced by parasite clearance is suggested.

Acute Disease↗