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H Heine

Publications and source records attributed to H Heine.

At least 37 records · Page 2Linked to original sources
PubMed1997

Actin: a target of lipopolysaccharide-induced phosphorylation in human monocytes.

We have previously reported that lipopolysaccharide (LPS) causes altered phosphate labelling of cytosolic proteins of 36 kDa and 38 kDa (p36/38) and that inhibition of phosphorylation is accompanied by a loss of cytokine production. Here we have purified the two phosphorylated proteins via two-dimensional polyacrylamide gel electrophoresis. P 36 was found to consist of two proteins p36a and p36b. The proteins were analysed by matrix-assisted laser desorption ionization (MALDI) mass spectrometry and p36b was identified as gamma-actin, p36a as beta/gamma-actin. The ability of LPS to cause altered phosphate labelling of beta/gamma-actin suggests a participation of the microfilament network in LPS-induced monocyte activation.

Actins↗
PubMed1997

Collagen crosslinks in fibromyalgia.

OBJECTIVE: To determine if abnormal collagen metabolism is a characteristic of fibromyalgia. METHODS: The diagnosis of fibromyalgia was made according to the American College of Rheumatology criteria. Skin biopsy samples were obtained from the trapezius region of 8 patients with fibromyalgia. Urine was collected under standardized conditions from 55 control subjects and 39 patients with fibromyalgia, and serum was obtained from 17 controls and 22 patients with fibromyalgia. Pyridinoline (Pyd), an indicator of connective tissue disease, and deoxypyridinoline (Dpyd), an indicator of bone degradation, both of which represent products of lysyl oxidase-mediated crosslinking in collagen, were analyzed by ion-paired and gradient high-performance liquid chromatography (HPLC) methods with fluorescence detection. Levels of hydroxyproline (Hyp), a collagen turnover marker, were also measured. The findings were related to creatinine levels, and the Pyd:Dpyd ratio was determined. RESULTS: Highly ordered cuffs of collagen were observed around the terminal nerve fibers by electron microscopic examination of biopsy tissue from all 8 patients with fibromyalgia, but were not observed in any of the control skin samples. The Pyd:Dpyd ratios in the urine and serum and the Hyp levels in the urine were significantly lower in patients with fibromyalgia than in healthy controls. CONCLUSION: Decreased levels of collagen crosslinking in fibromyalgia may contribute to remodeling of the extracellular matrix and collagen deposition around the nerve fibers, and may contribute to the lower pain threshold at the tender points. Analysis of altered collagen metabolism either by histologic examination on biopsy, or preferably, by HPLC analysis of collagen metabolites in urine or serum may aid in understanding more about the pathogenesis of fibromyalgia.

Amino Acids↗
PubMed1997

Role of ADP-ribosylation in activated monocytes/macrophages.

Stimulating monocytes/macrophages with bacterial lipopolysaccharide (LPS) results in TNF-alpha, IL-1, IL-6 and nitrite (NO2-) formation. Inhibitors of poly(ADP-ribose)polymerase inhibit release of these mediators by preventing mRNA expression indicating that ADP-ribosylation plays a crucial role in the synthesis of these mediators. Furthermore we present evidence that ADP-ribosylation is involved in modifying cellular proteins. In murine macrophages a 33 kDa cytosolic protein could be identified that in response to LPS changed its state of ADP-ribosylation, and in human monocytes we showed that the inhibitor nicotinamide prevents LPS induced phosphorylation of two cytosolic proteins of 36 kDa and 38 kDa (p36/38) LPS. Taken together these data indicate that protein modification by ADP-ribosylation may control cellular processes involved in distinct steps of monocyte/macrophage activation.

Adenosine Diphosphate Ribose↗
PubMed1995

Lipopolysaccharide-induced change of phosphorylation of two cytosolic proteins in human monocytes is prevented by inhibitors of ADP-ribosylation.

Interaction of LPS with human monocytes causes altered phosphate labeling of cytosolic proteins of 36 kDa and 38 kDa (p36/38). This property, determined by in vitro studies, is shared by other monocyte activators. Phosphorylated p36/38 are distinct from p38, 42-kDa, and 44-kDa isoforms of mitogen-activated protein kinases expressed in monocytes. Occupation of LPS binding sites by a LPS antagonist, the synthetic tetraacylated bisphosphate precursor of Escherichia coli lipid A (also known as compound 406, lipid IVa, or precursor Ia), prevents LPS-induced changes in the phosphate labeling of the two proteins. Abs against CD14 inhibit protein phosphorylation induced by low concentrations of LPS (10 ng/ml), whereas at high concentrations (1 microgram/ml), the Abs fail to prevent phosphorylation. In addition to phosphorylation, ADP-ribosylation of proteins has been implicated in a number of biologic processes. Here we show that inhibitors of ADP-ribosylation, namely meta-iodobenzylguanidine and nicotinamide, inhibit LPS-initiated altered phosphorylation of p36/38. This loss of phosphate labeling of p36/38 is accompanied by an inhibition of TNF-alpha and Il-6 mRNA and protein production. The synthesis of IL-1 is not affected. This suggests that the inhibitors interfere with specific steps in IL-6 and TNF-alpha production, which are not required for IL-1 synthesis. Taken together, the data indicate that ADP-ribosylation may be involved in LPS-induced alteration of the phosphorylation state of two cytosolic proteins (p36/38) and that these proteins modulate cellular processes leading to TNF-alpha and IL-6 release.

3-Iodobenzylguanidine↗
PubMed1995

Molecular mechanisms of endotoxin activity.

Endotoxin (lipopolysaccharide, LPS), a constituent of the outer membrane of the cell wall of gram-negative bacteria, exerts a wide variety of biological effects in humans. This review focuses on the molecular mechanisms underlying these activities and discusses structure-function relationships of the endotoxin molecule, its interaction with humoral and cellular receptors involved in cell activation, and transmembrane and intracellular signal transduction pathways.

Animals↗
PubMed1994

Dixyrazine premedication for cataract surgery. A comparison with diazepam.

Peroral dixyrazine (15-30 mg, n = 50) and diazepam (4-10 mg, n = 50) were used as premedicants for geriatric patients having cataract surgery under regional block. Compared to the diazepam patients, a larger number of the dixyrazine medicated patients appeared anxious, and there was a statistically significant difference between the groups, when summing up changes in anxiety throughout the study period. The dixyrazine patients needed more frequent supplementation with intravenous sedative drugs, compared with their diazepam counterparts. Peroral dixyrazine is an applicable choice for calm patients, when only slight sedation, or avoidance of somnolence are required.

Administration, Oral↗
PubMed1994

Efficacy of Contractubex gel in the treatment of fresh scars after thoracic surgery in children and adolescents.

Scar development was investigated in 45 young patients who had undergone thoracic surgery. Patients were randomly assigned either to a group which was treated topically with Contractubex gel (Merz + Co., D-Frankfurt/Main), containing 10% onion extract, 50/U of sodium heparin per one g of gel and 1% allantoin, or to a group receiving no treatment. The treatment began on average 26 days after the operation and was continued for one year. The scars of all treated and untreated patients were evaluated at monthly intervals. The appearance of the scar, including scar type and scar size as well as scar colour, was assessed by the physician. A reduction of the increase of scar width was seen in the Contractubex-treated group as compared with the untreated group. Further, physiological scars and skin-coloured scars were more frequent in the treated group than in the untreated group. Hypertrophic or keloidal scars were less frequent in the treated group. No differences in scar length and scar height were seen. At the end of the observation period, the clinical course of scar development was rated as "very good" or "good" in more than 90% of the treated patients, "good" in less than 40% and "moderate" or "bad" in more than 60% of the untreated cases. The tolerability of the drug was "good" or "very good" in all cases. In conclusion, Contractubex gel is useful in scar treatment after thoracic surgery.

Administration, Topical↗
PubMed1992

Modulation of endotoxin-induced monokine release in human monocytes by lipid A partial structures that inhibit binding of 125I-lipopolysaccharide.

We have previously shown that the synthetic tetraacyl precursor Ia (compound 406, LA-14-PP, or lipid IVa) was not able to induce the production of tumor necrosis factor, interleukin-1, and interleukin-6 in human monocytes but strongly antagonized lipopolysaccharide (LPS)-induced formation of these monokines. This inhibition was detectable at the level of mRNA production. To achieve a better understanding of molecular basis of this inhibition, we investigated whether lipid A precursor Ia (LA-14-PP), Escherichia coli-type lipid A (LA-15-PP), Chromobacterium violaceum-type lipid A (LA-22-PP), and synthetic lipid A partial structures and analogs (LA-23-PP, LA-24-PP, and PE-4) were able to influence the binding of 125I-LPS to human monocytes and compared this inhibitory activity with the agonistic and antagonistic action in the induction of monokines in human monocytes. 125I-LPS (20 ng per well) was added to human monocytes in the presence or absence of unlabeled rough Re mutant-derived LPS (Re-LPS) or lipid A compounds, and specific LPS binding was determined after 7 h. This binding was found to be dependent on CD14 as shown by the use of an anti-CD14 monoclonal antibody. Compound LA-14-PP was found to inhibit the binding of 125I-LPS to the cells in a similar dose-response to that of unlabeled LPS. This shows that the inhibitory capacity on LPS binding does not correlate with the monokine-inducing capacity because Re-LPS is active in inducing tumor necrosis factor, interleukin-1, and interleukin-6, while LA-14-PP is not. The strong capacity of LA-14-PP to inhibit 125I-LPS binding, however, correlates with the strong inhibitory capacity of this compound on LPS-induced monokine production. Compounds LA-15-PP, LA-23-PP, and LA-24-PP were active in the inhibition of 125I-LPS binding but were 5- to 10-fold weaker than Re-LPS and LA-14-PP. Of all lipid A structures tested, compound LA-22-PP expressed the weakest inhibitory capacity on LPS binding. These compounds showed again that the activity of binding inhibition does not correlate with the monokine-inducing capacity. We assume that the inhibitory effects of lipid A partial structures on LPS-induced monokine production have their origin in a competitive inhibition between LPS and the lipid A partial structures for the same binding site on the cell membrane.

Antigens, CD↗
PubMed1992

Biological activity of synthetic phosphonooxyethyl analogs of lipid A and lipid A partial structures.

We investigated the biological activity of four new synthetic analogs of lipid A, termed PE-1, PE-2, PE-3, and PE-4. All compounds contain an alpha-oxyethyl-linked (-O-CH2-CH2-) phosphoryl group in position 1 of the reducing glucosaminyl residue (GlcN I) of lipid A. PE-1 is a hexaacylated analog of Escherichia coli lipid A (compound 506). PE-2 differs from PE-1 in carrying two myristic acid residues at GlcN I. PE-3 has the same acylation pattern as PE-2, but GlcN I is present in the beta anomeric form. Finally, PE-4 represents an analog of tetraacyl precursor Ia (compound 406). Structure-activity relationships of these compounds were determined by measuring their capacity to induce tumor necrosis factor alpha, interleukin 1, and interleukin 6 release by human mononuclear cells and to cause mitogenicity of murine spleen cells. The results show that replacement of the glycosidic phosphoryl residue by a phosphonooxyethyl group had no substantial effect on the biological activity of compounds. However, the anomeric configuration of GlcN I was found to be of great biological relevance, as, in general, the alpha anomer (PE-2) expressed high activity, and the beta anomer (PE-3) expressed low mediator-inducing and mitogenic activity. The absence of the 3-hydroxyl groups within the acyl residues at GlcN I in PE-2 was found to only slightly affect the induction of monokines in human mononuclear cells compared with that of PE-1 or lipid A (506). These stable 1-phosphonooxyethyl analogs of lipid A may be candidates in the development of immunomodulators for the treatment of systemic endotoxicosis.

Animals↗
PubMed1990

[15N tracer technical studies of protein metabolism in arteriosclerosis patients].

The incorporation of the stable isotope 15N in plasma proteins and blood cells after oral application of 3 g 15NH4Cl (95 At% 15N) per 70 kg body weight was followed up in 11 patients with ischemic heart disease or peripheral arteriosclerosis and in 7 healthy control subjects. Preliminary results indicate that the turnover of plasma protein, especially fibrin, is elevated in patients with arteriosclerosis. Investigations of platelets intimate a decreased turnover of platelet protein in patients with arteriosclerosis as compared to control subjects. Possible reasons for these alterations are discussed.

Arteriosclerosis↗
PubMed1990

[Assessment of prognosis in acute myocardial infarct after reaching the maximum enzyme activity].

A new method is described for estimation of the prognosis of acute myocardial infarction progress due to temporary decrease in the isoenzymes, i.e. malic dehydrogenase (MDH), aspartate aminotransferase (ASAT), lactic dehydrogenase (LDH), and the decrease in the creatine kinase (CK). It is shown that the time of enzymatic activity is an essential factor. If 120 hours of decrease in enzymatic activity of MDH, LDH, and CK are exceeded, the prognosis of the myocardial infarction deteriorates dramatically.

Aged↗
PubMed1990

Extreme decrease of linoleic acid in renal medulla from rats after a diet supplemented with cod liver oil.

Spontaneously hypertensive (SHR) and normotensive rats were fed a diet supplemented with linseed oil or cod liver oil for 22 weeks. The most remarkable finding was an extreme fall of linoleic acid in lipids from renal medulla after cod liver oil supplementation. In free fatty acids (FFA) eicosatrienoic acid (C2): 3n-9) appeared increased as a sign of essential fatty acid (EFA) deficiency.

Animals↗
PubMed1990

Combined Doppler and M-mode analysis of diastolic filling behaviour in arterial hypertension with and without left ventricular hypertrophy.

The authors analysed Doppler and M-mode derived diastolic parameters of left ventricular filling in patients with arterial hypertension with and without left ventricular hypertrophy (LVH) and with hypertrophic nonobstructive cardiomyopathy (HNCM). In hypertrophied hearts they demonstrated that the transmitral flow during rapid filling phase was significantly reduced. The lower early diastolic flow is compensated by an augmentation of atrial systole. Diastolic filling anomalies are the consequence of an impaired ventricular relaxation due to LVH as could been proved by the M-mode derived retraction constant Te. Diastolic filling anomalies significantly depend on the extent of left ventricular hypertrophy. Impaired diastolic function was found in hypertensive patients without LVH. In this case, diastolic disorders indicate an early involvement of the heart in the hypertensive process.

Adult↗
PubMed1990

[Prognosis assessment of acute myocardial infarction on the basis of temporal changes of isoenzyme activities].

A new method is described for determining the prognosis of acute myocardial infarction (AMI) progress due to temporal increase in the isoenzyme, i.e. malic dehydrogenase (MDH), aspartate aminotransferase (ASAT), lactic dehydrogenase (LDH), and the increase in the creatine kinase (CK). It is shown that the time of enzymatic activity is an essential factor. If 25 hours of increase in enzymatic activity of MDH and CK are exceeded, AMI deteriorates dramatically.

Adult↗
PubMed1989

[Anticoagulants and inhibitors of thrombocyte function in the long-term treatment of arteriosclerosis].

Oral anticoagulants are suitable for the delay of progression of arteriosclerosis. The therapeutic effect is bound to the stability of the hypocoagulation with values of the thromboplastin time between 15 to 20%. There is a high risk of thrombosis after discontinuation of the therapy. Of the inhibitors of thrombocyte function acetyl salicylic acid preparations are antithrombotically effective. The controversies of dosage high (= 1,500 mg/d) or low (= 20-30 mg/d) are opposed by the concept of the individual dosage via the ASA-test.

Adult↗