Search PubMed⌕ Search

Biomedical subjects

G Heine

Publications and source records attributed to G Heine.

At least 19 recordsLinked to original sources
PubMed2006

Type-IV sensitization profile of individuals with atopic eczema: results from the Information Network of Departments of Dermatology (IVDK) and the German Contact Dermatitis Research Group (DKG).

UNLABELLED: The role of atopic eczema (AE) as risk factor for the development of allergic contact dermatitis is discussed controversially, as well as its influence on patch test results due to increased irritability. In this study, we analysed the pattern of positive patch test results to most frequent contact allergens in patients with AE (n = 9020) and age matched nonatopic (n = 15,263) individuals. The pattern and the frequencies of the observed sensitizations did not differ greatly from nonatopic individuals. Bufexamac is an exception: in AE patients sensitization is observed three times more often. For the other substances tested only minor differences were detected. Moreover, the frequencies of single, double or polyvalent sensitizations were nearly identical between the two groups. The analysis of the anatomical sites of dermatitis shows differences between the groups: in AE patients, the face (7.2%) and hand dermatitis (6.6%) was more common, and leg dermatitis (4.0%) less common. Analysis of occupation, suspected allergen source, and accompanying factors revealed no major differences between the both groups. CONCLUSION: The chronic and long-term exposure to external drugs and emollients presumably carries a risk for sensitization against specific contact allergens in AE patients. However, the sensitization of contact allergens differs surprisingly little between patients with or without AE.

Allergens↗
PubMed2005

Brain injury and proteomics/peptidomics: is it relevant? an overview.

Proteomics and peptidomics are different and supplemental to genomics, since in contrast to the basically constant genome - the proteome and peptidome are dynamic, constantly changing, and complex networks. Proteomics is traditionally linked to 2D-gel electrophoresis techniques. Concerning peptidomics, three different approaches are currently available, all using mass spectrometry as a key element. The use of proteomics or peptidomics in traumatic brain injury (TBI) research is demanding. From the technical point of view there are high-level requirements concerning the preanalytical phase, specific machinery, sophisticated software and skilled manpower/intellectual input. There are currently no bedside techniques and most methods are suitable for experimental TBI research in specialized laboratories. In screening experiments of CSF following controlled cortical impact in rats we identified several peptides, which, although previously known, were so far not reported in the TBI context or in CSF. Peptidomics and proteomics, as highly complex screening technologies, thus seem to carry a large potential to lead TBI science. Newly "discovered" peptide targets have to be validated with different methodology to establish a real diagnostic or therapeutic value.

Animals↗
PubMed2005

Retinoic acid inhibits CD40 plus IL-4 mediated IgE production through alterations of sCD23, sCD54 and IL-6 production.

BACKGROUND: All-trans retinoic acid (ATRA) inhibits IgE synthesis from anti-CD40 plus IL-4 stimulated human B lymphocytes. OBJECTIVE: To study the underlying mechanisms, we examined here molecules which are known to have an impact on IgE production, namely CD23, CD54 and IL-6. METHODS: Human anti-CD40 plus IL-4 stimulated B cells were cultured in the absence and presence of ATRA (10(-6)-10(-10) M). ELISAs were performed to determine soluble (s) CD23 and sCD54, IL-6 and IgE-levels. CD23 and CD54 surface expression were determined by flow cytometric analysis. Semiquantitative-RT-PCR was employed to analyse IL-6, CD23 and CD54 mRNA expression. RESULTS: ATRA induced a dose-dependent increase of percent CD23 (3.4 fold) or CD54 (1.6 fold) positive B cells. At the mRNA level, this was reflected by a modest increase of CD54 mRNA (46.5 +/- 15.8%) only. By contrast, levels of sCD54 were decreased dose-dependently in the presence of ATRA (56.6 +/- 7.6%). Cytokine analysis showed that IL-6 secretion was significantly inhibited by ATRA (53.6 +/- 0.6%) and also IL-6 mRNA synthesis was reduced (66.3 +/- 11.6%). The observed inhibition of IgE production mediated by ATRA was significantly reversed to 90.5 +/- 12% by the addition of 100 pg/mL recombinant IL-6. CONCLUSIONS: ATRA interferes through several pathways with the anti-CD40 plus IL-4 mediated B cell activation, namely IL-6, CD23 and CD54.

Antigens, Differentiation, B-Lymphocyte↗
PubMed2003

Allergen-mediated modulation of CD23 expression is interferon-gamma and interleukin-10 dependent in allergic and non-allergic individuals.

BACKGROUND: CD23 plays an important role in IgE regulation. The modulation of CD23 expression during specific immunotherapy (SIT) has been described previously. In the present study, we investigated in detail the effects of complete birch pollen allergen extract (BPA) on CD23 expression of peripheral blood mononuclear cells (PBMCs) in vitro. METHODS: PBMCs from 14 birch pollen-allergic (bp-allergic) patients and eight non-bp-allergic controls were stimulated with IL-4 and increasing doses of BPA. CD23 expression on monocytes and B cells was measured by flow cytometry; sCD23 release and the levels of IFN-gamma and IL-10 secretion were determined by ELISA. To analyse the mechanisms on CD23 expression in more detail, neutralizing anti-IFN-gamma and anti-IL-10 antibodies were added to IL-4 and BPA-stimulated cultures. RESULTS: IL-4 induced CD23 expression on B cells and on monocytes and sCD23 release in the bp-allergic and non-bp-allergic groups. The addition of BPA to IL-4-stimulated PBMC decreased CD23 expression significantly and dose-dependently on B cells in both groups. CD23 expression on monocytes was also decreased in both groups after the addition of BPA, but higher doses were required in the non-bp-allergic population. IL-4-induced sCD23 release was also significantly decreased after the addition of BPA. IFN-gamma and IL-10 were induced by BPA in both the bp-allergic and non-bp-allergic groups. The addition of neutralizing anti-IFN-gamma antibodies increased CD23 expression on B cells, which were stimulated with IL-4 and BPA, but had no effect on monocytes, whereas the addition of anti-IL-10 antibodies increased CD23 expression on monocytes but not on B cells. CONCLUSION: These data indicate that early immunological effects like down-regulation of CD23 on B cells and monocytes, which are observed during SIT are dose dependent, mediated by IFN-gamma and IL-10 and seem not to depend per se on the sensitization state of an individual.

Adult↗
PubMed2001

Levels of virus-specific CD4 T cells correlate with cytomegalovirus control and predict virus-induced disease after renal transplantation.

BACKGROUND: Immunosuppressive treatment in transplant patients frequently causes infectious complications with cytomegalovirus (CMV). The extent of CMV replication can be followed by a number of diagnostic methods. There is, however, no simple diagnostic tool to assess the quality of the cellular antiviral immune response of an individual patient. This would be of particular importance for therapy decisions, as patients with detectable virus load do not necessarily develop CMV-related disease. Using a rapid whole blood assay, the frequencies of CMV-reactive CD4 and CD8 T cells were followed after renal transplantation to characterize their relative contribution in the containment of CMV infection. METHODS: T cells from transplant patients ands healthy control persons were stimulated with CMV antigen in vitro. Based on specific cellular activation and induction of intracellular cytokines, the frequency of CMV-reactive CD4 and CD8 T cells was determined using flow cytometry. Viral load quantified using the "hybrid-capture" assay. RESULTS: The absence of CMV complications in long-term transplant recipients is reflected by stable virus-specific T-cell frequencies, which do not differ from healthy CMV-positive controls. In contrast, during the first months after transplantation, clinical symptoms are preceded by a decrease in CMV-reactive CD4 T-cell frequencies and an increase in CMV load. CONCLUSIONS: The individual immune response and CMV replication are critically balanced and can be characterized by assesing both viral load and antiviral T cells. Our experimental design allows the identification of patients with sufficient, insufficient, or absent T-cell activity and can serve as diagnostic tool to facilitate decisions on antiviral therapy.

Adult↗
PubMed2001

Painful regional anaesthesia induces an immunological stress reaction: the model of retrobulbar anaesthesia.

BACKGROUND AND OBJECTIVE: Laboratory stress studies found that acute psychological stresses may elicit changes in leukocyte numbers similar to those occurring in physical stresses. Both types of stress evoke - mainly by release of catecholamines - leukocytosis resulting from a release of natural killer cells (NK-cells), of CD8+ T-cells, of monocytes and of neutrophils. However, there is little proof that laboratory stress models can be applied to daily clinical routines. As a likely inductor of an immunological stress response the setting of retrobulbar anaesthesia prior to intraocular surgery permits the study of a short-term painful anaesthetic procedure under highly standardized conditions. This was examined in 16 female patients. METHODS: Counts of leukocyte subsets, serum cortisol and cardiovascular variables were measured 30 min and 1 min prior to retrobulbar anaesthesia as well as 2, 15 and 45 min afterwards. RESULTS: The setting of retrobulbar anaesthesia induced an increase in total leukocytes [+380 cells microL-1; P < 0.01 (means; significance level)] mainly due to rising counts of neutrophils (+241 cells microL-1, P < 0.01). Of all lymphocyte subpopulations, natural killer cells increased most markedly (+64 cells microL-1; P < 0.01). Furthermore, the retrobulbar block induced an increase in systolic arterial pressure (+15.2 mmHg; P < 0.01). CONCLUSION: These changes in immunological and cardiovascular variables are considered to be elements of a sympatho-adrenal stress reaction; catecholamines are considered to induce a demargination of leukocytes by binding to beta2-adrenoceptors and by modifying the avidity state of adhesion molecules.

Aged↗
PubMed2001

Strong depletion of CD14(+)CD16(+) monocytes during haemodialysis treatment.

BACKGROUND: The immune defect in haemodialysis (HD) patients is associated with a monocytic dysfunction, including an increased production of proinflammatory cytokines. Monocytes fall into subpopulations comprising CD14(++)CD16(-) and CD14(+)CD16(+) cells. Circulating numbers of the latter can rapidly increase during infectious episodes and inflammation. METHODS: We determined the amount of CD14(+)CD16(+) monocytes in HD patients and characterized their fate during HD treatment. In 34 HD patients and 17 healthy controls, the distinct cell populations were determined by differential blood counts and flow cytometry. Cells from 14 HD patients were analysed at the start, 10, 30 and 120 min thereafter, and at the end of HD treatment. RESULTS: Before HD, patients show a monocytosis with a strongly increased CD14(+)CD16(+) subpopulation. Early during HD treatment, circulating leukocyte numbers decrease, with monocytes being most profoundly influenced. Interestingly, among them, sequestration is most pronounced in the CD14(+) CD16(+) subpopulation. After 30 min, approximately 83+/-9% of CD14(+)CD16(+) cells are removed from circulation. This sequestration does not differ between patients treated with polyamide or haemophan membranes. The sequestration is a short-lived temporary effect and cell numbers are replenished within 120 min of treatment for the entire monocyte population. Beyond that time point, cellular activation by the dialyser membrane becomes visible. Reappearence kinetics of CD14(+)CD16(+) monocytes is slower; however, initial numbers are reached by the end of treatment. CONCLUSION: Haemodiaysis leads to temporary removal of monocytes from the bloodstream followed by the reappearance of activated cells. This might contribute to the state of chronic microinflammation, which is reflected by high levels of CD14(+)CD16(+) monocytes.

Antigens, CD↗
PubMed2001

Peptidomics: the comprehensive analysis of peptides in complex biological mixtures.

Progress in the sequencing of genomes has resulted in an increasing demand for a functional analysis of gene products in order to understand the underlying physiology. Proteomics has established itself as a highly valuable technology for producing functionally related data in an unparalleled fashion, but is methodologically restricted to the analysis of proteins with higher molecular masses (>10 kDa). The development of a technology which covers peptides with low molecular weight and small proteins (0.5 to 15 kDa) was necessary, since peptides, amongst them families of hormones, cytokines and growth factors, play a central role in many biological processes. To summarise the technologies used for this approach the term "peptidomics" is introduced. In this article, we present the rationale and first results of a novel, universal peptide display approach for the analysis and visualisation of peptides and small proteins from biological samples. Special attention is given to samples derived from extracellular fluids such as blood plasma and cerebrospinal fluid. Additionally, a high throughput identification procedure for the analysis of peptides in their native and processed molecular form is outlined.

Combinatorial Chemistry Techniques↗
PubMed2000

[Tolerance of early oral feeding after operations of the lower gastrointestinal tract].

INTRODUCTION: Oral feeding is usually offered following surgery of the lower gastrointestinal tract when clinical signs of normal intestinal motility are present. However, some studies have shown that early oral feeding is well tolerated with low morbidity. METHODS: A prospective cohort study was performed to evaluate whether early oral feeding according to a standardized schedule is tolerated under normal clinical circumstances. One hundred consecutive patients following small- or large-bowel resection with anastomosis were offered fluids on post-operative day 1, soup on post-operative day 2, mashed food on post-operative day 3 and a regular diet on post-operative day 4. Parenteral nutrition was only given if necessary. Tolerance of oral feeding and the amount of food were checked twice a day. End points of the study were nausea (VAS score 1-100), vomiting (> 200 ml), reinsertion of a nasogastric tube, level of food intake, parenteral nutrition (ml), appetite and well-being. RESULTS: Loop ileostomies were done in 21 patients, colonic resections above the sigmoid in 32, and sigmoid and rectal resections in 47. The average age was 63 +/- 13 years. The frequency of nausea was less than 30% and of vomiting less than 10%. Only in two cases was a nasogastric tube inserted. Forty-three percent of all patients tolerated feeding very well according to the schedule. On post-operative day 3 more than 60% tolerated oral intake, on post-operative day 4, 74% and on post-operative day 5, 88%. Only 22% of the patients needed parenteral fluids on post-operative day 4. The first bowel movement was noted after 2.8 +/- 1.1 days. Surgical complications were documented in 18 patients and general complications in 6 patients. CONCLUSION: Most patients tolerated early oral feeding very well according to the schedule with low morbidity. Therefore, early feeding is now a substantial component of the postoperative treatment following small- or large-bowel resections.

Aged↗
PubMed1999

Liquid chromatography and electrospray mass spectrometric mapping of peptides from human plasma filtrate.

We present a multidimensional approach to map the composition of complex peptide mixtures obtained as crude extract from biological liquids by (1) cation exchange chromatography and (2) subsequent microbore reversed-phase liquid chromatography and electrospray mass spectrometry coupling (LC-MS). Human hemofiltrate is an equivalent to blood and is used to obtain peptide material in large quantities from patients with chronic renal failure. The upper exclusion limit of the filtration membranes used results in a protein-free filtrate containing peptides in a range up to 20 ku. Using this unique peptide source, several thousand peptides were detected and an LC-MS data base of circulating human peptides was created. The search for known peptides by their molecular mass is a reliable method to guide peptide purification.

Chromatography, Ion Exchange↗
PubMed1999

Structural and phylogenetic characterization of human SLURP-1, the first secreted mammalian member of the Ly-6/uPAR protein superfamily.

Members of the Ly-6/uPAR protein family share one or several repeat units of the Ly-6/uPAR domain that is defined by a distinct disulfide bonding pattern between 8 or 10 cysteine residues. The Ly-6/uPAR protein family can be divided into two subfamilies. One comprises GPI-anchored glycoprotein receptors with 10 cysteine residues. The other subfamily includes the secreted single-domain snake and frog cytotoxins, and differs significantly in that its members generally possess only eight cysteines and no GPI-anchoring signal sequence. We report the purification and structural characterization of human SLURP-1 (secreted mammalian Ly-6/uPAR related protein 1) from blood and urine peptide libraries. SLURP-1 is encoded by the ARS (component B)-81/s locus, and appears to be the first mammalian member of the Ly-6/uPAR family lacking a GPI-anchoring signal sequence. A phylogenetic analysis based on the SLURP-1 primary protein structure revealed a closer relationship to the subfamily of cytotoxins. Since the SLURP-1 gene maps to the same chromosomal region as several members of the Ly-6/uPAR subfamily of glycoprotein receptors, it is suggested that both biologically distinct subfamilies might have co-evolved from local chromosomal duplication events.

Animals↗
PubMed1999

Exercise and atherogenesis: where is the missing link?

Cardiovascular disease is the principal cause of death in Europe, the United States, and much of Asia. If sedentary people begin exercising on a regular basis, there is epidemiologal evidence of approximately 50% reduction in their risk of developing coronary heart disease. This article is an overview about epidemiology and pathogenesis of atherosclerotic lesions. It is intended to put forth the hypothesis that exercise modulates monocytes and T-lymphocytes and that this modulation is capable of guarding against atherosclerosis or inducing regression of atherosclerotic lesions. The literature does not provide sufficient data for drawing conclusions, but this article introduces a new direction of exercise immunological research. Prevention of atherosclerosis or regression of reversible forms of atherosclerotic lesions such as fatty streaks is the principal goal of preventive efforts. Sports medicine and exercise immunology may contribute significantly to the knowledge base if the cellular and molecular responses of regular exercise for atherogenesis are discovered.

Arteriosclerosis↗
PubMed1998

Sequential increases in capillarization and mitochondrial enzymes in low-frequency-stimulated rabbit muscle.

To investigate temporal changes in capillarization and increases in mitochondrial enzyme activity, rabbit tibialis anterior muscles underwent chronic low-frequency stimulation for up to 50 days. Capillary density (CD), capillary-to-fiber ratio (C/F), intercapillary distance (ICD), and mean capillary area (MCA), as well as several other parameters of capillarization, were examined. In addition, tissue levels of mRNA specific to vascular endothelial growth factor (VEGF) were assessed by reverse transcriptase-polymerase chain reaction. Citrate synthase (CS) activity, a marker of aerobic-oxidative metabolic potential, was measured in the same muscles. Significant increases in CD and C/F, respectively, and decreases in ICD and MCA were observed after 2 days. These changes reached stable maxima by 14 days. The increases in capillarization occurred in a fiber-type-specific manner, affecting type IId fibers before types IIda and IIa. VEGF mRNA levels increased in a bimodal time pattern with a first elevation (2.5-fold) after 1 day and a second (9-fold) after 6-8 days. Increases in CS were first noted after 8 days. Obviously, increases in capillarization as induced by enhanced contractile activity precede increases in the aerobic-oxidative potential of energy metabolism.

Aerobiosis↗
PubMed1997

Mapping of peptides and protein fragments in human urine using liquid chromatography-mass spectrometry.

A method for the mapping of peptide mixtures, heterogeneous with respect to the concentration and the size of individual peptides, was established with the aim of obtaining a comprehensive analysis of human urine peptides. Peptide extraction and fractionation were optimized to achieve a two-step analysis, using reversed-phase and ion-exchange chromatography. Highly sensitive detection of peptides was performed by coupling microbore HPLC with electrospray mass spectrometry (ESI-MS). Peptides such as urodilatin, angiotensin and fragments of psoriasin, granulin and uromodulin were isolated and sequenced. The procedure presented here is a tool for the analysis of complex peptide mixtures from human urine.

Amino Acid Sequence↗
PubMed1997

Isolation and characterization of the bioactive circulating human parathyroid hormone, hPTH-1-37.

The occurrence of hPTH-1-37 as the native bioactive circulating form of PTH-1-84 has now been obtained using a specific purification procedure for circulating parathyroid hormone, which involves a newly developed immunoenzymetric assay for N-terminally intact hPTH. In combination with two different methods of mass spectrometry, the molecular weight of the isolated immunoreactive peptide was shown to be 4401 Da, which corresponds to hPTH-1-37. Synthetic hPTH-1-37 material was tested in the chick bioassay and produced a clearcut increase in serum calcium concentration. We conclude that hPTH-1-37 is the native bioactive fragment of hPTH-1-84 in circulation.

Animals↗
PubMed1997

Time-dependent increase of succinate dehydrogenase activity in low-frequency stimulated rabbit muscle: a comparison between microphotometric and biochemical methods.

We present an improved method for microphotometric measurement of enzyme activity in muscle fibres by determining maximum reaction rates using computer-assisted image analysis. The method was used to determine absolute and relative activities of succinate dehydrogenase (SDH) in 4801 whole-fibre cross-sections of rabbit tibialis anterior muscles stimulated at low frequency (10 Hz) for different time periods of up to 50 days. Measurements were performed on cross-sections of composite blocks from stimulated and contralateral control muscles. The validity of the method was checked by determining SDH activity in homogenates of the same muscles using a standard photometric assay. Both methods yielded similar results for the time-dependent increases of SDH activity in response to chronic low-frequency stimulation. Significant increases in catalytic activity were detected by the two methods only in muscles stimulated for longer than 8 days. According to homogenate measurements, overall SDH activity was 7.4-fold elevated in 50-day-stimulated total muscles. Depending on whether or not measurements were corrected for the so-called nothing-dehydrogenase activity, the average increase in microphotometrically determined SDH activity amounted to approximately 8-fold or 10-fold, respectively. Microphotometry revealed pronounced scattering of SDH activities within the fibre populations of both normal and stimulated muscles. The heterogeneity of the fibre population with regard to SDH activity increased in long-term stimulated muscles ranging between 5-fold and 15-fold elevations.

Animals↗