Search PubMed⌕ Search

Biomedical subjects

M Herold

Publications and source records attributed to M Herold.

At least 55 records · Page 3Linked to original sources
PubMed1999

Technical advance: transcriptional activator TGV mediates dexamethasone-inducible and tetracycline-inactivatable gene expression

A chemically regulated gene expression system that can be switched on with dexamethasone and switched off with tetracycline was constructed. It is based on a transcriptional activator (TGV) that consists of the Tn10 encoded Tet repressor, the rat glucocorticoid receptor hormone binding domain and the transcriptional activation domain of Herpes simplex virion protein VP16. When stably expressed in transgenic tobacco plants, it mediates dexamethasone-inducible transcription from a synthetic promoter (PTop10) consisting of seven tet operators upstream of a TATA-box. Tetracycline interferes with induction by negatively regulating the DNA-binding activity of the TetR moiety of TGV. The boundaries of the expression window of the TGV-driven PTop10 reach from undetectable levels of the reporter enzyme beta-glucuronidase in the absence of dexa- methasone to induced levels reaching 15-20% of the Cauliflower Mosaic Virus 35S promoter (PCaMV35S). By modifying the sequence of PTop10, we generated a new target promoter (PTax) that is stably expressed over several generations and that can be activated to levels comparable to PCaMV35S, while yielding only slightly elevated background activities.

Journal Article↗
PubMed1999

Associations between cellular immune effector function, iron metabolism, and disease activity in patients with chronic hepatitis C virus infection.

We studied the associations of macrophage activity, T-helper cell types 1 and 2 (Th-1/Th-2) responses, and iron status in 55 patients with hepatitis C virus (HCV)-related liver disease and 28 control patients with noninfectious liver disease. Serum concentrations of soluble tumor necrosis factor receptor type II (sTNFrec 75), a macrophage activation marker, were higher in cirrhotic than in noncirrhotic patients (P<.001) regardless of their HCV status, whereas levels of neopterin, interleukin (IL)-4 and IL-10 did not differ significantly. In HCV-positive patients, sTNFrec 75 levels and transferrin saturation (TfS) correlated positively with levels of aspartate transaminase (P<.001 for sTNFrec 75 and P=.028 for TfS) and alanine transaminase (P=.003 for sTNFrec 75 and P=.039 for TfS). Increased TfS correlated significantly with both advanced liver disease and a predominant Th-2 pattern in HCV patients. Our data suggest that an association exists between macrophage activation and hepatic dysfunction, and that iron status may affect the clinical course of HCV infection by modulating Th-1/Th-2 responses in vivo.

Antigens, CD↗
PubMed1999

Unconventional medicine in Central Europe: a misuse of public health insurance?

OBJECTIVE: To scrutinize the presumption maintained by critics that patients seeking medical treatment at a health resort may be more motivated by the prospect of a pleasant sojourn paid for by health insurance than by the impairment caused by a disease. DESIGN: Variables for mobility (occiput-to-wall distance, cervical rotation, chest expansion, thoracic flexion, lumbar flexion, and finger-to-floor distance) and C-reactive protein were determined in 181 patients (male 134, female 47; age 52.4 +/- SEM 0.8 years) with ankylosing spondylitis (AS) whose costs were covered by their health insurance (group A) and in 77 AS patients (male 66, female 11; age 51.6 +/- 1.2 years) who paid their own costs (group B). SUBJECTS: A group of 258 patients with AS presenting for 3- or 4-week speleotherapeutic radon treatment at the Gasteiner Heilstollen Hospital, a medical institution located at Badgastein in the Austrian Alps. RESULTS: After Bonferroni correction for multiple calculations no significant difference was seen between the two groups. CONCLUSIONS: The results suggest that patients presenting for medical treatment at a health resort suffer a like degree of disease impairment, whether they pay their own costs or not. There was no evidence that seeking treatment at a health resort may be an attempt by patients to misuse the health insurance for "sponsored" holidays.

C-Reactive Protein↗
PubMed1999

Heterologous expression of Arabidopsis phytochrome B in transgenic potato influences photosynthetic performance and tuber development.

Transgenic potato (Solanum tuberosum) plants expressing Arabidopsis phytochrome B were characterized morphologically and physiologically under white light in a greenhouse to explore their potential for improved photosynthesis and higher tuber yields. As expected, overexpression of functional phytochrome B caused pleiotropic effects such as semidwarfism, decreased apical dominance, a higher number of smaller but thicker leaves, and increased pigmentation. Because of increased numbers of chloroplasts in elongated palisade cells, photosynthesis per leaf area and in each individual plant increased. In addition, photosynthesis was less sensitive to photoinactivation under prolonged light stress. The beginning of senescence was not delayed, but deceleration of chlorophyll degradation extended the lifetime of photosynthetically active plants. Both the higher photosynthetic performance and the longer lifespan of the transgenic plants allowed greater biomass production, resulting in extended underground organs with increased tuber yields.

Arabidopsis↗
PubMed1999

[Changes of renal blood flow during organ-associated foot reflexology measured by color Doppler sonography].

Using colour Doppler sonography blood flow changes of the right kidney during foot reflexology were determined in a placebo-controlled, double-blind, randomised study. 32 healthy young adults (17 women, 15 men) were randomly assigned to the verum or placebo group. The verum group received foot reflexology at zones corresponding to the right kidney, the placebo group was treated on other foot zones. Before, during and after foot reflexology the blood flow of three vessels of the right kidney was measured using colour Doppler sonography. Systolic peak velocity and end diastolic peak velocity were measured in cm/s, and the resistive index, a parameter of the vascular resistance, was calculated. The resistive index in the verum group showed a highly significant decrease (p </= 0.001) during and an increase (p = 0.001) after foot reflexology. There was no difference between men and women and no difference between smokers and non-smokers. Verum and placebo group significantly differed concerning alterations of the resistive index both between the measuring points before versus during foot reflexology (p = 0.002) and those during versus after foot reflexology (p = 0.031). The significant decrease of the resistive index during foot reflexology in the verum group indicates a decrease of flow resistance in renal vessels and an increase of renal blood flow. These findings support the hypothesis that organ-associated foot reflexology is effective in changing renal blood flow during therapy.

Adult↗
PubMed1999

Cellular and humoral immune responses in patients with metastatic renal cell carcinoma after vaccination with antigen pulsed dendritic cells.

PURPOSE: Dendritic cells are the most potent stimulators of immune responses including antitumor responses. We performed a pilot study of cultured antigen loaded dendritic cells in patients with metastatic renal cell carcinoma. MATERIALS AND METHODS: Dendritic cells were obtained by culturing plastic adherent mononuclear cells from peripheral blood for 5 days in the presence of granulocyte-macrophage colony-stimulating factor and interleukin-4. Day 5 dendritic cells were loaded with cell lysate from cultured autologous tumor cells and with the immunogenic protein keyhole-limpet hemocyanin (KLH) which serves as a helper antigen and as a tracer molecule. During the antigen pulse dendritic cells were activated with a combination of tumor necrosis factor-alpha and prostaglandin E2. Dendritic cells were administered by 3 intravenous infusions at monthly intervals. Cellular and humoral immune responses to KLH and cell lysate were measured in vitro before and after the vaccinations. RESULTS: Preparation of 12 dendritic cell vaccines from patients with advanced renal cell carcinoma was successful. Treatment with fully activated CD83+ dendritic cells was well tolerated with moderate fever as the only side effect. Potent immunological responses to KLH and, most importantly, against cell lysate could be measured in vitro after the vaccinations. CONCLUSIONS: Our data demonstrate that a dendritic cell based vaccine can induce antigen specific immunity in patients with metastatic renal cell carcinoma. Dendritic cell based immunotherapy represents a feasible, well tolerated and promising new approach for the treatment of advanced renal cell carcinoma.

Aged↗
PubMed1998

Differential deactivation of human dendritic cells by endotoxin desensitization: role of tumor necrosis factor-alpha and prostaglandin E2.

The endotoxin (lipopolysaccharide)-induced cytokine response is followed by a state of unresponsiveness to lipopolysaccharide (LPS) referred to as LPS tolerance or endotoxin desensitization. LPS tolerance, which can be experimentally induced in vitro and in vivo, is also known to occur in septic disease. Here, we evaluated whether dendritic cells (DC), the most potent antigen-presenting cells, are also subject to this phenomenon. Single doses of LPS added at the initiation of DC culture inhibited in a dose-dependent fashion the production of tumor necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10), and IL-12, but not the production of IL-8, in response to a second LPS challenge in day-5 DC. In addition, the LPS-induced expression of the CD83 maturation antigen was inhibited in these cells. Moreover, the endocytic activity of DC generated in the presence of LPS was dramatically reduced. DC desensitized with LPS were potent stimulators of T-cell proliferation but poor inducers of interferon-gamma (IFN-gamma) production in the allogeneic mixed leukocyte reaction. TNF-alpha and prostaglandin E2, two major products of LPS stimulation, could replace LPS for the induction of tolerance to LPS. Moreover, treatment of desensitized DC with TNF-alpha plus prostaglandin E2 fully restored CD83 expression and partially restored IL-12 production as well as the IFN-gamma-inducing activity of DC in the mixed leukocyte reaction. Our data show that human DC are highly susceptible to the induction of LPS tolerance, which seems to be a state of differential deactivation in which some functions are impaired whereas others are retained. Tolerization at the level of the professional antigen-presenting cell by inflammatory mediators may play an important role in septic disease and in the origin of cancers associated with chronic inflammation.

Antigens, CD↗
PubMed1998

Induction of arachidonic acid metabolite release by human fibroblasts in proliferative vitreoretinopathy.

Proliferative vitreoretinopathy is a severe ocular disorder characterized by unwanted proliferation of cells and excessive production of fibrous tissue, which leads to the formation of cellular membranes on the surface of the retina and in the vitreous. Proliferative vitreoretinopathy is the most common cause of failure in retinal reattachment surgery, approximately occurring in one out of ten operated eyes. Proliferation of retinal pigment epithelial cells and fibroblasts is a cornerstone in the pathogenesis of proliferative vitreoretinopathy. An in vitro-proliferation assay showed previously that intraocular fluid from patients with proliferative vitreoretinopathy is potently effective in stimulating proliferation of human fibroblasts. Here we show that exposure of human fibroblasts to vitreous fluids from patients with proliferative vitreoretinopathy causes a rapid and sustained increase in arachidonic acid metabolite release as measured by competitive enzyme-immunoassay. The findings implicate prostaglandin E2 as a contributor to enhanced intraocular fibrosis in proliferative vitreoretinopathy. As prostaglandin E2 is a mediator of continuous aqueous-blood retinal barrier breakdown in this severe disease, cycclooxygenase inhibitors such as acetylsalicylic acid, which was successfully used in this study for blocking the effect of intraocular fluid, may be useful agents in targeting the progression of intraocular fibrosis.

Adult↗
PubMed1998

In ankylosing spondylitis serum interleukin-6 correlates with the degree of mobility restriction, but not with short-term changes in the variables for mobility.

The aim of this study was to evaluate whether the serum concentration of interleukin-6 (IL-6) reflects disease activity in ankylosing spondylitis (AS). A group of 271 AS patients were enrolled in the study, 261 of whom completed the entire protocol (201 males, 60 females, median age of 53 years). Serum IL-6 was measured three times (I, baseline; II, after 10-12 days; III, after 17-24 days) during a 3- or 4-week treatment at the health resort. At the same times, the variables for mobility were measured, and the patients were asked to assess their complaints (score) in a self-styled questionnaire. The serum concentration of IL-6 correlated with the measurements of occiput-to-wall distance, cervical rotation, finger-floor distance and Schober sign, and with morning pain at all three evaluations. Comparisons between changes in IL-6 and changes in the variables (measures of mobility, scores of the questionnaires) did not reveal significant correlations. Present data would suggest that in AS the serum concentration of IL-6 indicates the degree of mobility restriction resulting from previous disease progression, but is not a reliable marker of current disease activity.

Arthralgia↗
PubMed1998

Release of chemoattractants for human monocytes from endothelial cells by interaction with neutrophils.

OBJECTIVE: The release of monocyte chemoattractant protein-1 (MCP-1) in the vessel wall may lead to accumulation of monocytes in the subendothelial space. The role of neutrophils (PMNL) in the initiation of this process is unknown. We tested whether PMNL are able to induce the production and release of MCP-1 in endothelial cells. METHODS: PMNL were allowed to interact with human umbilical vein endothelial cell (HUVEC) monolayers in culture. Culture media were collected and assessed for chemotactic activity on mononuclear leukocytes (MNC) or purified monocytes in a modified Boyden chamber assay. Additionally, MCP-1 levels in supernatants were quantified by ELISA. RESULTS: Media from unstimulated HUVEC culture supernatants induced a slight increase (1.2-fold) of MNC and purified monocyte chemotaxis, which was significantly augmented by addition of PMNL for 1 h (1.4-fold; P < 0.05). The increase in chemotaxis was time- and dose-dependent and could be blocked by an anti-MCP-1 monoclonal antibody. Media obtained after coculture of PMNL and HUVEC for 1-5 h contained increased amounts of MCP-1 as measured by ELISA; addition of cycloheximide abolished this response. CONCLUSIONS: Interaction of PMNL with endothelium induces the release of functionally active MCP-1 suggesting that in the vascular wall, PMNL may play a role in the recruitment of MNC.

Arteriosclerosis↗
PubMed1998

About 8-hour variation of circulating human endothelin-1.

Plasma endothelin-1 (ET-1) and cortisol were measured around the clock at hourly intervals on 7 clinically healthy, diurnally active, nocturnally resting subjects 22-27 years of age. The circadian rhythm in cortisol is demonstrated for each subject (p < or = 0.020) as well as on a group basis (p = 0.002), peaking in the morning. By contrast, the circadian variation of ET-1 is statistically significant in only one of the subjects, and it is not detected for the group as a whole (p > 0.20). Instead, ET-1 is characterized by an about 8-h component (p < 0.001) that is not found for cortisol.

Adult↗
PubMed1998

Interleukin 1beta mediates the modulatory effects of monocytes on LNCaP human prostate cancer cells.

Proliferative and secretory responses in androgen-sensitive prostate cancer LNCaP cells are regulated by steroid and peptide hormones and by differentiation-promoting substances. In the present study, we evaluated whether peripheral blood monocytes that exhibit anti-tumour activity in haematopoietic and solid tumours influence growth and secretion in the LNCaP cell line. For this purpose, LNCaP cells were incubated with monocyte-conditioned medium (MCM), and proliferation as well as expression of androgen receptor (AR) and secretion of prostate-specific antigen (PSA) were assessed. Conditioned medium from monocytes reduced proliferation in a dose-dependent manner. Incubation with 40% MCM caused a 50% reduction in cell proliferation. AR protein decreased by 70% and PSA levels in supernatants from LNCaP cells were reduced by approximately 80% following treatment with MCM. We focused on the contribution of two major products of activated monocytes, prostaglandin E2 and interleukin 1beta (IL-1beta), to the MCM modulatory action. LNCaP cells treated with prostaglandin E2 showed neither a reduction in proliferation nor a down-regulation of AR and PSA levels. The effects of MCM on cellular proliferation, AR protein and PSA secretion were abolished by pretreatment of MCM with a neutralizing anti-IL-1beta antibody. In addition, recombinant IL-1beta was able to replace MCM for the inhibition of proliferation and down-regulation of AR and PSA proteins. LNCaP cells were shown to express the IL-1beta receptor type 1, which transduces IL-1beta signal. Our findings reveal that monocyte-derived IL-1beta inhibits the proliferation of androgen-responsive prostate tumour cells and reduces AR and PSA levels.

Cell Division↗
PubMed1998

Endogenous serum thrombopoietin concentrations in patients with myelodysplastic syndromes.

Prognosis in patients with myelodysplastic syndromes (MDS) is closely correlated with cytopenia. To date, no factor is available which is able to reliably stimulate megakaryopoiesis in vivo. Recently, the ligand of the mpl receptor was cloned and found to be thrombopoietin (TPO). We measured endogenous TPO serum levels in 69 patients suffering from MDS using an TPO receptor-based ELISA. Twenty-six of the patients suffered from refractory anemia (RA), 12 from RA with excess of blasts (RAEB), 25 from RAEB in transition (RAEBt), and six from chronic myelomonocytic leukemia (CMML). This assay uses a chimeric molecule consisting of the human TPO receptor fused to the Fc portion of human IgG as the capture reagent. Biotinylated antibody to TPO IgG was used for detection and the lower detection limit in serum was found to be 160 pg/ml. Samples obtained from healthy individuals with a normal platelet number were shown to be below detectable levels. In patients with RA, high endogenous serum TPO concentrations correlated with low platelet count and significantly elevated TPO concentrations were only found when megakaryopoiesis was absent or decreased in the bone marrow. This correlation was not detected in RAEB and RAEBt patients and no detectable TPO serum concentrations were found in six CMML patients whether they showed decreased or normal platelet count. Our data show that endogenous TPO production is upregulated by decreased circulating platelet count only in patients with refractory anemia. In the more advanced stages of MDS where the leukemic clone has further progressed, an inadequate TPO response occurs, possibly due to overexpression of the mpl receptor by the malignant clone.

Adult↗
PubMed1998

Interferon-gamma in the treatment of systemic sclerosis: a randomized controlled multicentre trial.

We report the results of a randomized controlled multicentre study on interferon-gamma (IFN-gamma) treatment of systemic sclerosis as determined by skin sclerosis, renal and other organ involvement, global assessment, subjective symptoms and quality of life. Forty-four patients were enrolled into the trial, 27 in the treatment group and 17 in the control group. All patients presented with type I or type II scleroderma. Twenty-nine patients (64%) finished the study. The mean duration of Raynaud's phenomenon and skin sclerosis was 15.3 and 10.8 years, respectively. The skin scores tended to improve in the treatment group (P > 0.05). Mouth aperture increased significantly from 38.5 to 47.7 mm in the treatment group (P < 0.001). Subanalysis of IFN-gamma treated patients with normalized skin sclerosis scores >/=1 showed significant improvement in both skin involvement and subjective symptoms (P < 0.05). Organ involvement improved in eight of 18 treatment patients and in three of 11 control patients. It worsened in three of 18 treatment patients and in four of 11 control patients. One control patient died due to cardiorespiratory failure during the study. No deterioration of renal function occurred during IFN-gamma treatment. There was a significant improvement in quality of life parameters in the control group but not in the treatment group. Plasma levels of neopterin increased significantly during IFN-gamma treatment but not in the control group, whereas N-terminal procollagen III peptide levels did not change in either group. There was a high frequency of mild to moderate influenza-like adverse events during IFN-gamma treatment. Only four of nine drop-out patients, however, experienced symptoms most probably associated with IFN-gamma treatment. We conclude that IFN-gamma therapy has mild beneficial effects on skin sclerosis and disease-associated symptoms in type I and II scleroderma. IFN-gamma treatment was associated with acceptable tolerability and did not induce major renal dysfunction in our patients.

Adolescent↗
PubMed1998

Modulation of alloimmune response in vitro by an IgM-enriched immunoglobulin preparation (Pentaglobin).

The mode of action of intravenous immunoglobulins (IVIG) in autoimmune and immunoregulatory disorders is still poorly understood. In vitro, direct effects of IVIG on cytokine release and on cytokine receptors have been described, as well as naturally occurring, neutralizing anticytokine antibodies. The aim of our study was to investigate whether the enrichment in IgM and IgA would have any impact on the in vitro immunomodilatory capacity of IVIG. The preparation tested (Pentaglobin) contains 76% IgG and 12% IgM and IgA, respectively. We could demonstrate a significant inhibition of alloantigen-induced proliferation in the mixed lymphocyte reaction (MLR) even at a Pentaglobin concentration of 1.0 mg/ml. About 10-fold higher concentrations of standard 7S IVIG containing only trace amounts of IgM and IgA were necessary to achieve equivalent suppression of the alloimmune response. Similarly, phytohaemagglutinin (PHA)-induced lymphocyte proliferation was more effectively inhibited by Pentaglobin than by standard 7S IVIG. Cytokine analyses in culture supernatants of MLR provide evidence that Pentaglobin not only modulates interleukin-2 (IL-2), which has already been observed with standard 7S IVIG, but, moreover, modulates interferon-gamma production with a subsequent impact on monocyte-derived tumour necrosis factor-alpha and IL-6 release. Based on these results we conclude that in vitro the IgM- and IgA-enriched Pentaglobin has a more potent immunomodulatory capacity than conventionally used standard 7S IVIG.

Cell Culture Techniques↗
PubMed1998

Urticaria pigmentosa: a clinical, hematopathologic, and serologic study of 30 adults.

Urticaria pigmentosa (UP) is the most common form of cutaneous mastocytosis and may be associated with systemic involvement, most often of the bone marrow. The incidence of systemic involvement is not yet well established, however. To address this question, we subjected a group of 30 adults with histologically proved UP to a retrospective study that included history, physical examination, laboratory tests including cytokine measurements, radiologic examinations, and bone marrow biopsies. The most frequently associated clinical symptoms were recurrent flush episodes in 16 of 30 patients, alcohol intolerance in 13, pruritus in 10, and gastrointestinal problems in 11 (recurrent diarrhea, 8 patients; gastritis, 2 patients; and history of peptic ulcer, 1 patient). Of the 30 patients, 18 (60%) had mast cell infiltrates of the bone marrow (nodular type, 10 patients; diffuse interstitial type, 8 patients). Bone marrow involvement was not correlated with massive cutaneous mast cell infiltration, clinically or histologically, or with the incidence of clinical symptoms and associated hematologic disorders. None of the patients had experienced progression of clinical symptoms, skin or organ involvement, or development of hematologic malignant neoplasms since UP was first diagnosed (10 years on average). Urticaria pigmentosa was found associated with mast cell infiltration of the bone marrow in 18 patients (60%). However, bone marrow involvement does not seem to predict adverse clinical course.

Adult↗