Search PubMed⌕ Search

Biomedical subjects

M Herold

Publications and source records attributed to M Herold.

At least 91 records · Page 5Linked to original sources
PubMed1996

Pulmonary sarcoidosis: patterns of cytokine release in vitro.

This study was designed to investigate the ability of bronchoalveolar and blood mononuclear cells to produce inflammatory mediators in vitro in pulmonary sarcoidosis. Seventeen patients with pulmonary sarcoidosis (stage I n = 8; stage II/III n = 9) and 10 normal controls were investigated. Bronchoalveolar and peripheral blood mononuclear cells were cultured in serum-free medium, without stimulant, for 24 h, and the supernatants analysed for concentrations of interleukin (IL)-1 beta (IL-1 beta), IL-2, IL-6, tumour necrosis factor-alpha (TNF-alpha), granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-gamma (IFN-gamma) and neopterin. Bronchoalveolar lavage cells (BALC) of sarcoid patients released significantly higher amounts of TNF-alpha, IL-6, IFN-gamma and neopterin in comparison to normal controls. When smokers were excluded, there was also an increased release of IL-1 beta and GM-CSF. In the sarcoid group, the levels of IL-1 beta, IL-6, TNF-alpha and GM-CSF showed highly significant correlations between each other, but not with IL-2, IFN-gamma or neopterin. Sarcoid patients whose BALC released more TNF-alpha or GM-CSF had higher percentage counts of alveolar macrophages but fewer lavage lymphocytes. In sarcoid patients, peripheral blood mononuclear cells (PBMNC) also released higher amounts of IL-1 beta, TNF-alpha, IL-6 and GM-CSF but less neopterin than normal controls. Patients whose PBMNC produced more IL-1 beta, IL-6 and GM-CSF had higher absolute and relative lavage neutrophil counts. No relationships were observed between cytokine release and radiographic or physiological markers of disease severity. We conclude from this study that sarcoid inflammation is associated with an increased and concerted release of monocyte/macrophage-derived cytokines not only in the lung but also in the peripheral blood. We speculate that the lymphokines, IFN-gamma and IL-2, are not the primary triggers.

Adult↗
PubMed1996

Serum neopterin, interleukin-4, and interleukin-6 concentrations in cerebral malaria patients and the effect of iron chelation therapy.

To determine if iron chelation therapy alters immune responses in children with cerebral malaria, we retrospectively measured mean serum levels of neopterin, interleukin-4 (IL-4), and IL-6 in children who received desferrioxamine B or placebo for three days in addition to quinine-based therapy. Mean levels of neopterin, IL-4, and IL-6 were elevated above the expected normal range on admission. Neopterin correlated significantly with the degree of anemia, IL-4 with the duration of fever prior to admission, and IL-6 with parasite density. Serial measurements of cytokines and neopterin were performed over four days in 39 children, 21 randomized to receive desferrioxamine B and 18 to receive placebo. Mean concentrations of neopterin did not change significantly in either group while levels of IL-4 increased significantly in the placebo group (P = 0.04) but remained unchanged in the desferrioxamine B group. Interleukin-6 concentrations decreased markedly in both groups (P < 0.025). Stable IL-4 levels in children given desferrioxamine B may represent an inhibition of the T helper lymphocyte-2 (TH-2) response resulting from a strengthened TH-1 response associated with iron chelation therapy. Any effect of iron chelation on immunity in the setting of severe malaria will have to be confirmed in future prospective investigations.

Biopterins↗
PubMed1996

Assessment of endothelial preservation in human cell cultures.

BACKGROUND: Impairment of microcirculation due to endothelial cell damage must be considered a limiting factor in organ preservation. The present study aims at a quantitative assessment of preservation-induced injury in cultured human endothelial cells. METHODS: Monolayer cultures of human umbilical vein endothelial cells were exposed to cold (40 degrees C) hypoxic storage in University of Wisconsin solution, histidine-tryptophane-ketoglutarate solution, Euro-Collins solution, and saline solution. Cellular integrity was evaluated by viable cell count, ultrastructural analysis, and prostacyclin release after 24, 48, and 72 hours of storage and subsequent 6 hours of reincubation in culture medium at 37 degrees C. Expression of intercellular adhesion molecule-1 was investigated after 6, 12, and 24 hours of cold preservation and after 6 hours of rewarming. RESULTS: Cellular viability was best maintained with University of Wisconsin and histidine-tryptophane-ketoglutarate solutions with no significant reduction of cell count up to 72 hours; Euro-Collins solution and saline solution caused a significant decline in cell numbers after 24 hours (p < 0.05). Morphology was best preserved by University of Wisconsin solution. Prostacyclin values were elevated after 24 hours in Euro-Collins solution and saline solution, after 48 hours in histidine-tryptophane-ketoglutarate, Euro-Collins, and saline solutions, and after 72 hours in Euro-Collins solution (p < 0.05, compared with University of Wisconsin solution). ICAM expression was weak after cold storage (24 hours) in University of Wisconsin solution, moderate after incubation in histidine-tryptophane-ketoglutarate and Euro-Collins solutions and intensive after storage in saline solution. In contrast, rewarming caused intensive expression of intercellular adhesion molecule-1 in all experimental groups as compared with controls, which showed baseline expression at any time. CONCLUSIONS: From our results we conclude that in this model cellular integrity is best protected by University of Wisconsin solution, increased prostacyclin release is consistent with morphologic alterations and intercellular adhesion molecule-1 expression is clearly up-regulated in endothelial cells under reperfusion conditions after cold hypoxic storage.

Adenosine↗
PubMed1996

In vitro stimulation of erythropoiesis by stem cell factor alone in myelodysplastic syndrome patients with elevated endogenous erythropoietin serum levels.

Anemia remains a therapeutic problem in patients with myelodysplastic syndrome (MDS). In view of the recently reported potential of stem cell factor (SCF) in restoring erythropoiesis in combination with erythropoietin (Epo), we first aimed to define a correlation between SCF serum levels and anemia in MDS. Endogenous SCF levels in 50 MDS patients were determined by using a quantitative sandwich enzyme immunoassay. Broad interindividual variations were observed, but SCF serum levels were in the normal range with no correlation to peripheral blood count. A soft agar culture system was used to further define the role of SCF for stimulation of erythroid growth. Bone marrow mononucleated cells of 20 MDS patients (4 refractory anemia, 5 refractory anemia with excess of blasts, 7 refractory anemia with excess of blasts in transition, and 4 chronic myelomonocytic leukemia) were investigated, and SCF plus Epo was able to stimulate burst-forming unit-erythroid significantly more than SCF or Epo alone independent of French-American-British group. When mononucleated cells from six MDS patients (two refractory anemia, two refractory anemia with excess of blasts, and 2 refractory anemia with excess of blasts in transition) with elevated serum Epo levels were incubated in the presence of SCF and autologous serum, a significant dose-dependent stimulation of burst-forming unit-erythroid number and cells per colony was detected. Erythroid differentiation was further enhanced by adding serum with high colony-stimulating activity obtained from patients with severe aplastic anemia. Our data suggest that in MDS patients with high endogenous Epo serum levels SCF alone might be effective in stimulating erythropoiesis in vivo.

Adult↗
PubMed1995

Nitric oxide formation as predictive parameter for acute graft-versus-host disease after human allogeneic bone marrow transplantation.

Due to the accumulation of evidence concerning a putative role of nitric oxide (NO) in graft-versus-host disease (GVHD), we performed follow-up measurements of the stable end-products of NO, nitrite/nitrate (NO2-/NO3-) in plasma of patients undergoing allogeneic (n = 16) and autologous (n = 6, as a control) bone marrow transplantation. NO2-/NO3- concentrations were set in relation to the clinical course and to serum levels of soluble tumor necrosis factor receptor 75 (sT-NFrec 75) and neopterin, both of which are known to be sensitive indicators of cellular immune activation phenomena involving macrophages in vivo, and endogenous interleukin (IL)-10, a major T helper cell type 2 (TH-2)-derived cytokine and potent inhibitor of macrophage activation and NO formation. A significant rise of NO2-/NO3- levels was observed in patients with GVHD and preceded the onset of clinical symptoms by up to 3 days. In contrast to indicators of macrophage activation, i.e., neopterin and sT-NFrec75, NO2-/NO3- concentrations were not significantly altered from baseline levels during infectious complications, as NO2-/NO3- concentrations did not fluctuate in patients after autologous engraftment. During episodes of acute GVHD, NO2-/NO3- concentrations showed a strong positive correlation with levels of plasma neopterin and sTNFrec 75, but were also significantly related to IL-10. In non-GVHD patients, a negative correlation between IL-10 and NO2-/NO3- concentrations was evident. Therefore, NO2-/NO3- determination may be a valuable early indicator of the initiation of human GVHD. Our results provide some further insights concerning cytokine-related metabolic changes in the course of human GVHD in vivo which may prove useful in the development of new therapeutic approaches for this disease.

Acute Disease↗
PubMed1995

Impaired nocturnal secretion of melatonin in coronary heart disease.

Patients with coronary heart disease have increased nocturnal urinary noradrenaline. Because melatonin suppresses sympathetic activity, we measured serum melatonin concentrations at night (0200 h) in 15 patients with coronary heart disease. Melatonin was significantly lower in the patients than in 10 healthy controls (median 7.8 [interquartile range 6.5-11.8] vs 36.2 [32.2-42.5] pg/mL, p < 0.0001). Thus, impaired nocturnal secretion of melatonin is associated with coronary heart disease.

Circadian Rhythm↗
PubMed1995

IL-6 secretion by human peritoneal mesothelial and ovarian cancer cells.

Malignant ascites of epithelial ovarian cancer patients contains high levels of interleukin 6 (IL-6). The present study was conducted to compare the secretion of IL-6 by seven different human ovarian cancer cell lines (OVCA) and cultured human peritoneal mesothelial cells (HPMC) and to examine the regulation of its production by other cytokines. IL-6 was detected in supernatant medium of all mesothelial cell cultures (8/8) and 6/7 ovarian cancer cell lines. Levels of IL-6 secreted by HPMC (median 27,100 pg/1 x 10(5) cells; range 3870-168,200) were 590-fold higher (P < 0.01) than those secreted by OVCA (median 46 pg/1 x 10(5) cells; range 0-16,450). Treatment with TNF-alpha or IL-1 beta (both 10 ng/ml) for both types of cells and both cytokines resulted in a significant (P < 0.05) elevation of IL-6 production. In OVCA IL-6 secretion was increased 7- and 39-fold and in HPMC 6- and 8-fold, respectively. Under TNF-alpha treatment IL-6-levels secreted by HPMC were 149-fold higher (P < 0.01) than those generated by OVCA. Similarly, IL-1 beta-induced IL-6 levels were 102-fold higher in HPMC (median 288,800 pg/1 x 10(5) cells; range 93,125-552,800) than in OVCA. IFN-gamma (10 ng/ml) increased IL-6 generation in OVCA (6-fold) but not HPMC. The proliferation of both cell types however, was significantly (P < 0.05) inhibited by IFN-gamma. Our results suggest that peritoneal mesothelial cells may be a prominent source of IL-6 in ovarian cancer-related ascites.

Ascites↗
PubMed1995

Interleukin-1 receptor antagonist in differential diagnosis of inflammatory bowel diseases.

BACKGROUND: Immunoregulatory properties of cytokines may mediate disordered inflammatory events in inflammatory bowel diseases (IBDs). On the basis of data obtained in experimental colitis, the hypothesis has been advanced that in IBD the balance between interleukin-1 (IL-1) and the naturally occurring IL-1 receptor antagonist (IL-1ra) might influence disease expression. OBJECTIVE: We studied the profiles of IL-1ra and acute phase proteins produced by activated macrophages to determine whether the level of IL-1ra in peripheral blood is a marker of disease activity in IBD and a possible differential diagnostic marker. PATIENTS AND METHODS: Levels of IL-1ra, serum neopterin, urinary neopterin, alpha 1-glycoprotein and C-reactive protein (CRP) were measured in 80 patients with ulcerative colitis, Crohn's disease or infectious colitis. RESULTS: Levels of IL-1ra were markedly increased in patients with active ulcerative colitis or active Crohn's disease compared with those in patients with infectious colitis. Patients with active Crohn's disease had significantly higher serum IL-1ra levels than patients with active ulcerative colitis. Moreover, a positive correlation was found between levels of C-reactive protein, alpha 1-glycoprotein, and serum neopterin and the level of IL-1ra in active Crohn's disease but not in active ulcerative colitis, strongly suggesting that the pathogenesis of the two conditions differs. CONCLUSION: Levels of IL-1ra in the peripheral blood of patients with IBD are of clinical relevance, representing a potent marker of disease activity and a possible differential diagnostic marker.

Acute-Phase Proteins↗
PubMed1995

Serum neopterin concentrations in chronic liver disease.

Neopterin is produced by macrophages after stimulation with interferon gamma or lipopolysaccharide. Its production is increased in many infectious, autoimmune, and malignant diseases. The aim of this study was to examine whether, on the basis of neopterin as a marker, liver diseases could be classified according to aetiology and stage of disease. A cohort of 264 patients with chronic liver diseases (viral, metabolic, autoimmune, toxic) and 150 normal controls were studied; 136 of the patients had cirrhosis. Increased serum neopterin concentrations were found in 41% of all patients (controls 6.0 (2.2) nmol/l), with patients in the cirrhotic stage of disease showing higher neopterin values (mean (SD) 15.7 (23.6) nmol/ml) than those in the non-cirrhotic stage (9.9 (5.5)). There were no statistically significant differences in the serum neopterin concentrations that could be considered characteristic for different stages of disease classified according to the Child criteria. Such differences in concentrations of neopterin that were found in patients with liver diseases grouped according to underlying causes were only marginal. Serum neopterin concentrations were found to be significantly lower than in any other disease group only in patients with Wilson's disease. The results suggest that activated macrophages participate in the development of chronic liver disease. Measurement of serum neopterin does not offer a reliable method for differentiating between various aetiologies of chronic liver diseases and does not help to predict severity of cirrhosis.

Biopterins↗
PubMed1995

Growth-inhibitory effect of 2-CdA on myeloid CFU-GM progenitors in normal human long-term bone marrow cultures and its compensation by G-CSF or IL-3.

As neutropenia is a common side effect of treatment with 2-chlorodeoxyadenosine (2-CdA), we investigated the myelosuppressive action of 2-CdA in Dexter-type human long-term bone marrow cultures (LTBMCs). LTBMCs were incubated with varying doses of 2-CdA (5 to 20 nM/L) during the first week. At 20 and 10 nM/L 2-CdA, we found a marked reduction in colony-forming unit-granulocyte/macrophage (CFU-GM) production throughout the culture period of 7 weeks (maximum reduction to 3.5% of untreated control cultures with 20 nM/L and to 27.2% with 10 nM/L, respectively). Even the lowest 2-CdA dose tested (5 nM/L) strongly reduced the number of CFU-GM progenitors during the first 3 weeks (maximum reduction to 52.4% of untreated controls), but this effect was transient, and values had recovered to normal within in 5 weeks. 2-CdA was also shown to cause a dose-dependent decrease in long-term culture-initiating cell (LTCIC) detections after 5 weeks in culture (49.6% of control cultures with 10 nM/L 2-CdA and 14% with 20 nM/L 2-CdA, respectively). When 2-CdA was added to LTBMCs initiated on preformed irradiated stromal feeder layers, similar results on CFU-GM production were obtained, indicating that the effects observed were not secondary to effects on the formation of a supportive layer. In addition, IL-6-concentrations in the supernatant of LTBMCs measured at various intervals after the addition of fresh medium with or without 2-CdA showed no significant decrease in cultures treated with 2-CdA. As neutropenia has been shown to be associated with a small but significant risk of fatal infection, we subsequently investigated the reversal potential of the 2-CdA effect by addition of recombinant human granulocyte colony-stimulating factor (rhG-CSF) or rh interleukin-3 (rhIL-3). The weekly addition of 100 ng/mL rhG-CSF counteracted the 2-CdA-mediated decrease in CFU-GM numbers during the entire period of 7 weeks, reaching statistical significance from weeks 3 to 7 (p < 0.05). Addition of rhIL-3 (100 ng/mL) showed an enhancement of CFU-GM output in 2-CdA-treated cultures that resulted in their numbers exceeding those in control cultures (without 2-CdA) from weeks 1 to 5 (p < 0.05) with a maximum increase of 5.1-fold over the parallel control value at week 3.(ABSTRACT TRUNCATED AT 400 WORDS)

2-Chloroadenosine↗
PubMed1995

[Captopril in the treatment of heart failure].

The inhibitor of angiotensin converting enzyme played in recent years a significant role in the treatment of cardiac failure. Captopril administration to patients after myocardial infarction prevents enlargement of the left ventricle and its dysfunction. This leads to a reduced mortality and fewer relapses of infarction even in patients with asymptomatic left ventricular dysfunction.

Captopril↗
PubMed1994

Serum concentrations of circulating endogenous granulocyte-macrophage colony-stimulating factor in HIV-1-seropositive injecting drug users.

OBJECTIVES: We compared serum concentrations cytokines in seronegative and seropositive HIV-I intravenous drug abusers. METHODS: The cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and the immune activation markers soluble interleukin-2 receptor (sIL-2R) and neopterin were determined in sera of HIV-1-seropositive and HIV-1-seronegative injecting drug users (IDUs). RESULTS: HIV-1-seropositive IDUs showed significantly lower serum concentrations of GM-CSF (p = 0.0064) and significantly higher concentrations of neopterin (p = 0.0005) than HIV-1-seronegative IDUs. All HIV-1-seropositive IDUs had neopterin levels above the normal range. Levels of TNF-alpha in HIV-1-seronegative IDUs did not differ from HIV-1-seropositive IDUs. Increased levels of IL-1 beta were found in 83.3% HIV-1-seronegative and in 94.4% HIV-1-seropositive IDUs with no significant difference between the two groups. An increase of serum levels of sIL-2R was found in 60% HIV-1-seronegative and in 63.6% HIV-1-seropositive IDUs. Again, no difference was found between the two groups. Neopterin concentrations correlated with TNF-alpha in HIV-1-seropositive as well as in HIV-1-seronegative IDUs, neopterin concentrations correlated with sIL-2R only in the HIV-1-seropositive IDUs. No correlations were found for GM-CSF. CONCLUSIONS: An impaired production of GM-CSF may contribute to the loss of the myelopoetic progenitor cells and to the functional abnormalities of leukocytes associated with HIV-1 infection. Injecting drug use contributes to the levels of immune activation markers, therefore their use in HIV-1 infection may be limited in IDUs. However, neopterin remains a useful marker for HIV-1 infected IDUs.

Adult↗
PubMed1994

Serum levels of interleukin 6, interleukin 8, and C-reactive protein after human allogeneic bone marrow transplantation.

Serum levels of interleukin 6 (IL-6) and C-reactive protein (CRP) were measured every second day from day -6 to day +86 in 24 patients undergoing allogeneic (n = 23) and syngeneic (n = 1) bone marrow transplantation (BMT). Endogenous serum levels of IL-6, IL-8, and CRP were further analyzed during complications after BMT, such as fever of unknown origin (FUO), severe infectious complications and acute graft-versus-host disease (GVHD). In addition, CRP levels were measured in 10 patients with interstitial pneumonitis of various origins (CMV, idiopathic). In all 24 patients IL-6 and CRP levels showed a characteristic monophasic pattern. After a slight decrease in the first days after BMT, a significant increase was observed, starting on day +3/+5 (P < 0.05) and reaching peak levels on day +9/+11 (P < 0.01). CRP had a similar pattern, with an increase in serum levels on day +3/+5 and maximum levels one to three days after the IL-6 peak was reached. The magnitude of the peak was related to the development of complications in the further course of BMT and was high in patients with and low in patients without complications. Serum levels of both molecules returned to baseline after day 14 posttransplant. Increased IL-6 and CRP levels were observed in the further course of BMT during severe infections or FUO either on the day of clinical onset (IL-6) or three days later (CRP), but not during acute GVHD grade III/IV. CMV interstitial pneumonitis (CMV-IP) was accompanied by an increase in CRP levels, while no such elevations were observed in patients with idiopathic interstitial pneumonitis (IIP). Elevated IL-8 serum levels occurred during bacterial infections, but to a lesser amount also during GVHD and CMV-IP. In conclusion, a characteristic pattern of IL-6 and CRP was observed after allogeneic BMT and a further increase associated with infectious complications. Since no significant elevations were seen in patients with GVHD, we conclude that both molecules are not involved in the induction of GVHD and might be useful diagnostic tools for the prediction and diagnosis of infectious complications after BMT. In contrast, assessment of IL-8 serum values does not permit clinical complications to be specified.

Adolescent↗
PubMed1994

Genetically determined target organ susceptibility in the pathogenesis of spontaneous autoimmune thyroiditis: aberrant expression of MHC-class II antigens and the possible role of virus.

Considerable controversy exists concerning the role of aberrant MHC-class II antigen expression in the pathogenesis of organ-specific auto-immune disease. Since Obese strain (OS) chickens are afflicted with a spontaneously occurring autoimmune thyroiditis (SAT), we have readdressed this pivotal question by investigating the chronical appearance of MHC-class II antigens on thyroid epithelial cells (TEC) of OS and normal healthy CB chickens before onset of overt clinical symptoms in the former. Among the candidates as potent inducers of aberrant MHC-class II antigen expression, interest in our studies focussed on the potential role of viruses in the development of SAT. Since aberrant MHC-class II antigen expression could prove to be an epiphenomenon of virally afflicted TEC, we determined 2,5-oligoadenylate synthetase and 2,5-oligoadenylatepolymer cytosol levels in both chicken lines. Our results indicate that the presence of infiltrating lymphocytes does not necessarily represent a prerequisite for the aberrant expression of MHC-class II antigens but coincides in most cases. However, the phenomenon seems to play a perpetuating rather than a causative role. Moreover, in support of a possible viral involvement, elevated levels of the 2,5-oligoadenylate synthetase and 2,5-oligomers could be demonstrated in TEC cytosol of OS chickens.

2',5'-Oligoadenylate Synthetase↗
PubMed1994

Protective effects of various preservation solutions on cultured endothelial cells.

Vascular endothelium represents the first target in organ preservation and plays an important role in reperfusion injury. Bovine aortic endothelial cells were cultivated and the most commonly used preservation solutions, such as University of Wisconsin HTK (Brettschneider's histidine-tryptophane-ketoglutarate), and Euro-Collins solutions were tested on the endothelial monolayer. In addition, one group of cultivated cells was preserved with cold saline solution, and endothelial monolayers grown in culture medium were used as controls. The quality of preservation was assessed after 24, 48, and 72 hours of cold storage. Reperfusion was simulated and its effects were observed by reincubation in culture medium at 37 degrees C for 6 hours. The total number of cells, cell viability (determined using trypan blue exclusion), and morphologic alterations were determined. Prostacyclin release was evaluated as a biochemical marker. University of Wisconsin solution maintains more than 99% cell viability after rewarming after both 24 and 48 hours of cold storage. After 72 hours, 86.7% of cells were still viable. Preservation with HTK and Euro-Collins solution allowed cell survival for only 24 hours (96.7%, HTK; 49.9%, Euro-Collins), with no viable cells seen after 48 hours. The cold saline-preserved sample showed 57.8% viable cells after 24 hours and 29.7% after 48 hours. No viable cells were detectable after 72 hours. Light microscopy revealed several patterns of both structural damage and intracellular change (nucleus and cytoplasm) in the endothelial monolayer after preservation with HTK, Euro-Collins solution, and cold saline solution. No morphologic alterations were seen in the University of Wisconsin solution group for as long as 72 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗