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Biomedical subjects

M Hermann

Publications and source records attributed to M Hermann.

At least 19 recordsLinked to original sources

Lactoferrin specifically inhibits endocytosis of chylomicron remnants but not alpha-macroglobulin.

Our recently found nonlipoprotein inhibitor of chylomicron remnant uptake, lactoferrin, has been investigated in vivo and in vitro. Lipoprotein lipase extracted triglycerides from chylomicrons, doubly labeled with [3H]retinol/[14C]oleate, in the presence of lactoferrin normally. The subsequent uptake of remnants into liver was retarded considerably. In the intact rat, chylomicron remnants (CRs), predominantly labeled in the apoB48 moiety by 125I, were excluded from the hepatic endosomal compartment in the presence of lactoferrin as shown in subcellular fractionation studies of rat livers. In tissue culture, internalization of [125I]chylomicron remnants was inhibited in the presence of 14 pM lactoferrin by 70%. Upon removal of lactoferrin, internalization was rapidly restored. Protease digestion eliminated the inhibitory effect completely. Modification of arginine residues with cyclohexanedione reversibly removed the inhibitory potency of lactoferrin. We located by molecular modeling an alpha-helical segment in lactoferrin on the exposed surface of the molecule containing the sequence Arg-X-X-Arg-Lys-X-Arg, which resembles the receptor recognition structure in apolipoprotein E (apoE). This firmly established ligand correspondence with apoE, the candidate ligand for CR recognition by the receptor. Finally, the postulated second function of low density lipoprotein receptor-related protein, uptake of alpha-2-macroglobulin (alpha 2M) was found to be distinct from lipoprotein binding, since lactoferrin inhibited CR but not alpha 2M internalization. In addition, CR uptake was not affected by alpha 2M. We conclude that if a bifunctional receptor were to operate, its diverse functions were exerted by independently operating substructures. The results of our in vivo and cell culture experiments are, however, entirely compatible with the existence of two receptors as well.

Adenosine Triphosphatases

Creatinine and N-methylhydantoin degradation in two newly isolated Clostridium species.

With N-methylhydantoin (NMH) as the main organic substrate, two strictly anaerobic spore forming Gram-positive bacterial strains were isolated from sewage sludge. These strains, named Clostridium sp. FS23 and Clostridium sp. FS41, totally degraded NMH, via N-carbamoylsarcosine (CS) and sarcosine as intermediates. Strain FS23 grew also with creatinine, which was converted to NMH by creatinine iminohydrolase (EC 3.5.4.21). This enzyme was formed at high rates with all substrates tested. Cytosine and 5-fluorocytosine were not utilized as substrates by creatinine iminohydrolase preparations purified to a homogeneity of 98%. NMH amidohydrolase (NMHase) and N-carbamoylsarcosine amidohydrolase (CSHase) turned out to be inducible in both strains. Other than in aerobic organisms, NMHase from these two isolated did not require ATP for enzymatic activity. SH-group protecting agents were not necessary for stability.

Adenosine Triphosphate

[Color-coded Doppler sonography of the thyroid: an advance in carcinoma diagnosis?].

There are several papers suggesting that colour-coded Doppler sonography is a useful diagnostic tool for the differentiation of malignant and benign lesions of the thyroid gland. This hypothesis (hypervascularization of malignant nodules) is reconsidered by preoperative examination of 65 patients by using colour-coded Doppler sonography and scintigraphy. Among these patients 21 carcinomas and 2 malignant lymphomas of the thyroid gland were found histologically. Colour-coded Doppler sonography was true positive in 10 cases, true negative in 28 cases, false positive in 14 cases and false negative in 13 cases. Our conclusion is that colour-coded Doppler sonography cannot be used unconditionally for the detection of carcinoma of the thyroid gland.

Adult

Altered susceptibility to in vitro oxidation of LDL in LDL complexes and LDL aggregates.

Low density lipoprotein (LDL) is known to form complexes with polysulfated compounds, like heparin, dextran sulfate (DS), and chondroitin sulfate. In particular, chondroitin 6-sulfate (C6S)-rich proteoglycans of the arterial intima can associate with LDL, resulting in accumulation of LDL in atherosclerotic lesions. Besides LDL complex formation, LDL self-aggregation has been recently suggested to play a role in atherogenesis. Oxidative modification of LDL has also been implicated as a factor in the generation of the atherosclerotic plaque. Assuming that LDL self-aggregation may alter the molecule's susceptibility to oxidative modification, we have studied the sensitivity of LDL in LDL a aggregates as well as in insoluble and soluble LDL-C6S, LDL-heparin, and LDL-DS complexes to in vitro oxidation by cooper ions. Complexing the LDL with C6S and heparin resulted in an increased susceptibility of LDL to in vitro oxidation, whereas the oxidation of LDL complexed with DS was unaffected. In great contrast to the oxidation of LDL in LDL complexes, the in vitro oxidation of LDL in LDL aggregates (self-aggregation by denaturation) was strongly reduced. The results suggest that complex or aggregate formation may alter the susceptibility of the lipoprotein to oxidative modification and finally its metabolic fate or biological activity.

Chondroitin Sulfates

Suramin affects differentiated and undifferentiated human thyroid epithelial cells in vitro.

In the last decade, suramin has become known for its antiproliferative, differentiation-inducing effects on cells and has been successfully used in the therapy of cancer patients. The present study was undertaken to investigate the effects of suramin on normal human thyroid cells in primary monolayer culture and to analyse whether it also affected cells from thyroid carcinomas. The results show that suramin, at concentrations similar to serum levels obtainable during therapy, inhibited the proliferation of thyroid cells as well as the secretion of thyroglobulin. It suppressed the activation of adenylyl cyclase in thyroid membranes and decreased the immunogenicity of the cells by reducing their surface expression of HLA-DR and ICAM-1. Although the morphology of differentiated thyroid cells remained unaffected by suramin, morphological changes compatible with differentiation were observed in cells from undifferentiated thyroid carcinomas when suramin was added to the culture medium. In conclusion, the data demonstrate that suramin has pronounced in-vitro effects on normal and neoplastic thyroid cells. It may, therefore, also be effective in patients with thyroid cancer, for whom no other form of treatment is available.

Adenylyl Cyclases

Gi alpha-1 expression in the human thyroid is regulated by TSH: loss of regulation in thyroid autonomous adenoma.

The molecular mechanisms underlying the development of endocrine active thyroid tumors are poorly understood. These tumors produce excess thyroid hormone, which then suppresses TSH (thyroid stimulating hormone) production. In the present report, we show that the expression of Gi alpha-1 is under control of TSH in the normal human thyroid. In contrast Gi alpha-1 escapes TSH control in autonomous adenoma and thus is constitutively expressed. Since receptor-mediated activation of Gi controlled pathways is known to elicit a proliferative response in several cell types, we propose that in thyroid adenomas the unregulated constitutive expression of Gi alpha-1 is causally related to the autonomous growth.

Adenoma

Kinetics of hydroxyethyl starch in horses.

In a controlled study, the distribution and elimination kinetics of hydroxyethyl starch as well as clinically relevant parameters were determined in horses. The half-life of the first phase was 5.59 hours, that of the second phase 122.22 hours. During the first phase, hydroxyethyl starch persisted almost exclusively intravascularly. The results of this study are largely in agreement with those in human beings. Thus, routes of elimination, duration of plasma-expanding action, distribution volume and redistribution kinetics in horses and human beings are very similar. However, the elimination kinetics of the second phase and the behavior of serum amylase appear to be equine-specific. Coagulation is barley influenced by the administration of hydroxyethyl starch. The results of this study confirm that hydroxyethyl starch is very suitable for use as a plasma-expander in horses.

Amylases

[Clinico-chemical blood parameters in foals in the first two months of life].

Eighteen healthy foals were studied from birth until 2 months of age. Blood samples were obtained at the following times: presuckle, 30 hours, 1, 3, 5, 7 and 9 weeks of age. Changes in serum P, Mg, Ca, Na, K, Cl, iron, AP, ASAT, ALAT, GGT, GLDH, CK, lipase, urea, creatinine, cholesterol, triglyceride, uric acid, protein and fibrinogen and in plasma total solids were examined and the values compared to reference values of adult horses. There were characteristic age related changes in several parameters. Single measurements should be interpreted cautiously to allow for individual variations.

Aging

[Multivisceral and extended resection in tumor surgery--esophageal cancer].

Extended resections are strategies in the surgical treatment of cancer which provide large oncological safety margins: these are of particular relevance in the neck in view of the close anatomical relation of the major cervical organs. In the region of the distal esophagus, extended resections may be a reasonable alternative to conservative approaches even when only intended as a palliative treatment. The removal of metastases does not influence the outcome in patients with esophageal carcinoma, in contrast to simultaneous surgery of other malignancies.

Esophageal Neoplasms

RP 49356: inhibitory effects of ionic and secretory events in rat pancreatic islets.

Rp 49356, a 'K+ channel opener', inhibited 86Rb outflow, 45Ca outflow and insulin release from glucose-stimulated islets perifused in the presence of Ca2+. The drug lost its capacity to reduce 86Rb outflow in islets exposed to glucose-free or Ca(2+)-free medium. These observations suggest that RP 49356 might exhibit antagonistic actions on B-cell Ca2+ channels. This will, in turn, reduce glucose-stimulated insulin output and Ca(2+)-dependent 86Rb outflow.

Animals

Ionic and secretory response of pancreatic islet cells to minoxidil sulfate.

Minoxidil sulfate is an antihypertensive agent belonging to the new class of vasodilators, the "K+ channel openers." The present study was undertaken to characterize the effects of minoxidil sulfate on ionic and secretory events in rat pancreatic islets. The drug unexpectedly provoked a concentration-dependent decrease in 86Rb outflow. This inhibitory effect was reduced in a concentration-dependent manner by glucose and tolbutamide. Minoxidil sulfate did not affect 45Ca outflow from islets perfused in the presence of extracellular Ca++ and absence or presence of glucose. However, in islets exposed to a medium deprived of extracellular Ca++, the drug provoked a rise in 45Ca outflow. Whether in the absence or presence of extracellular Ca++, minoxidil sulfate increased the cytosolic free Ca++ concentration of islet cells. Lastly, minoxidil sulfate increased the release of insulin from glucose-stimulated pancreatic islets. These results suggest that minoxidil sulfate reduces the activity of the ATP-sensitive K+ channels and promotes an intracellular translocation of Ca++. The latter change might account for the effect of the drug on the insulin-releasing process. However, the secretory response to minoxidil sulfate could also be mediated, at least in part, by a modest Ca++ entry.

Animals

Expression of procoagulant activity by equine lung macrophages: stimulation by blood lymphocytes.

Increases in procoagulant activities (PCA) in equine lung macrophages were induced by non-adherent blood lymphocytes which were prestimulated with phytohaemagglutinin for 48 to 72 hours or by supernatants harvested from prestimulated blood lymphocyte cultures. However, prestimulated lymphocyte suspensions themselves expressed PCA which was most probably derived from contaminating monocytes. Because non-adherent cells from lymphocyte suspensions may have attached to adherent macrophages, cells within lymphocyte suspensions might have contributed to the PCAs expressed by lymphocyte-stimulated lung macrophages. Stimulation of lung macrophages for 24 hours by supernatants of phytohaemagglutinin-prestimulated blood lymphocytes induced a significantly greater PCA increase than stimulation by phytohaemagglutin alone. Thus, cytokines from lymphocyte cultures might have triggered or enhanced PCA induction. Direct stimulation of lung cell preparations with phytohaemagglutinin for 48 hours resulted in a progressive increase of PCA in only two of five specimens tested. The failure to induce PCA in three specimens could be due to the absence of sufficient numbers of T cells within the adherent lung cell preparations. In conclusion, PCA response of equine lung macrophages might be lymphocyte-stimulated in which case PCA might be a useful tool for monitoring the processes of cell-mediated immunity in horses.

Animals

Spontaneous and lipopolysaccharide-induced expression of procoagulant activity by equine lung macrophages in comparison with blood monocytes and blood neutrophils.

The procoagulant activity (PCA) associated with equine bronchoalveolar lavage cells was determined and compared with that expressed by peripheral blood mononuclear cells and neutrophils. Lung cell preparations from horses affected with chronic pulmonary disease were included in all experiments and there was no difference in the qualitative type of response compared with lung cells which were obtained from healthy horses. Significant amounts of PCA were expressed by cells freshly procured from bronchoalveolar lavages of healthy and diseased horses. When adherent lung cells were kept in culture for some time, cell-associated PCA slightly decreased within 4 h, reached its lowest point after approximately 24 h and rose again during the second week of culture. In contrast, freshly isolated blood mononuclear cells or neutrophils expressed little PCA. Following culture for 24 h, mononuclear cells began to express increased PCA levels. Both cultivated lung cells (comprised mainly on alveolar macrophages) and blood mononuclear cells responded to LPS by dramatically increased PCA expression, whereas neutrophils showed a small augmentation of PCA on LPS stimulation. Fresh mononuclear cells and cultivated lung cells differed in their PCA response to LPS in several respects. Blood mononuclear cells were more sensitive to LPS than lung macrophages and responded to a 100-fold lower LPS concentration than the latter. Mononuclear cell-associated PCA peaked 4 h after stimulation whereas that of cultured macrophages continued to increase up to 24 h after stimulation. Lung macrophages cultured in adherence responded to LPS stimulation with a much higher PCA increase than macrophages cultured in suspension, in teflon containers. However, the culture vessel did not influence the PCA expressed by unstimulated cells. PCA expression depended to a large extent on transcription and translation, as evidenced by a 60-85% reduction of PCA in cycloheximide- or actinomycin D-treated, LPS-stimulated lung macrophages. PCA was largely cell-associated; only a small proportion of cell-associated PCA was shed into the medium. The PCA associated with mononuclear cells and with lung macrophages was tissue factor because of its dependence on clotting factor VII and its independence from clotting factor VIII. The expression of PCA by freshly isolated cells, the lower sensitivity to LPS, and the loss of PCA in the first 24 h of cultivation are indicative of in vivo activation of lung macrophages.

Animals

Neutrophil migration induced by equine respiratory secretions, bronchoalveolar lavage fluids and culture supernatants of pulmonary lavage cells.

Supernatants of equine respiratory secretions enhanced the migration of equine neutrophils into the lower compartments of Boyden chambers. Checkerboard analysis revealed that the neutrophil migration promoting activity (NMPA) of secretion specimens was in great part caused by chemokinesis, irrespective of the neutrophil score of the specimen. The NMPA of respiratory secretions was correlated neither with the neutrophil score of the secretion specimen nor with the severity of the chronic pulmonary disease. Respiratory secretions collected while horses were kept under low dust or under dusty housing conditions induced migration of neutrophils in the same order of magnitude. The number of migrated neutrophils and the procoagulant activity (PCA) within respiratory secretion specimens was positively correlated; however, the meaning of this finding is not yet clear. None of the nine cell-free supernatants of bronchoalveolar lavage fluid, which were assayed undiluted, induced significant neutrophil migration, although some samples contained up to 4.0 x 10(5) neutrophils/ml. In vitro culture of lung lavage cells, which mainly comprised macrophages and lymphocytes, without stimulation or with the addition of low doses of phytohemagglutinin (PHA) resulted in the secretion of NMPA which was in great part chemotactic. However, culture supernatants of lung cell preparations which were stimulated by lipopolysaccharide (LPS) or by PHA-prestimulated lymphocytes reduced the migration of neutrophils compared with the supernatants of control cells. NMPA within culture supernatants had a highly significant negative correlation with the PCA of macrophages within the lung cell preparations. Our results imply that a complicated and sophisticated regulation underlies neutrophil accumulation within the airways of horses affected with chronic pulmonary disease. Future experiments are required to assess the biological significance of the factors modulating neutrophil migration which are present in the respiratory secretions and in the culture supernatants of equine lung lavage cells.

Animals

An investigation of the incidence of chronic obstructive pulmonary disease (COPD) in random populations of Swiss horses.

The incidence of Chronic Obstructive Pulmonary Disease (COPD) in Switzerland was determined in three groups of horses selected at random. Group A (97 horses) and Group B (93 horses) had no history of respiratory disease, but Group C (113 horses) had a history of lower respiratory tract disease. All horses were examined by auscultation of the respiratory tract under forced breathing, endoscopic examination of the upper and lower respiratory tract, arterial blood gas analysis at rest and cytological examination of respiratory secretions (RS). Fifty-four per cent of the horses in Group A and 54.8 per cent of Group B were diagnosed as suffering clinical COPD and only 12.4 per cent of horses in Group A and 8.6 per cent in Group B had no detectable abnormalities in their lower respiratory tracts. In Group B, 19.4 per cent were considered to be suffering from parasitic pulmonary disease indicated by elevated numbers of eosinophils in their RS. Pharyngeal lymphoid hyperplasia was exhibited in 70.1 per cent of Group A and 74.2 per cent of Group B. Cytological examination of RS was useful to determine if the secretions found in the trachea originated from the upper or lower respiratory tract. Arterial blood gas analysis revealed no significant differences between healthy horses and those with subclinical or mild COPD.

Animals

[Risk factors in recurrent nerve paralysis: a statistical analysis of 7566 cases of struma surgery].

Between 1979-1988, 7566 operations for benign diseases of the thyroid gland were performed. The frequency of the paresis of the recurrent nerve examined between the third and fifth postoperative day was 5.2% for patients and 3.2% for resected lobes. The incidence was correlated to performed operative procedure (enucleation, subtotal resection, lobectomy) to size (weight of specimen) and to the expansion of the goiter (substernal, intrathoracic, retrotracheal) as well as to sex. These factors influence the risk of injury with high statistic significance. The side of resection and the ligature of the thyroid inferior artery also influenced the rate of recurrent nerve pareses. Age of patient and morphology of the thyroid disease did not cause an increasing risk of nerve injury.

Adenoma

Comparison of bronchoalveolar lavage and respiratory secretion cytology in horses with histologically diagnosed pulmonary disease.

Equine bronchoalveolar lavage (BAL) fluid collected from 70 horses and respiratory secretions (RS) obtained from 61 of these horses were evaluated cytologically and grouped according to the histological diagnosis of the lungs from which they were obtained. The histological categories included: normal lung (8 horses); pulmonary eosinophilic infiltration (9 horses); interstitial pneumonia (5 horses); pulmonary hemorrhage (5 horses); and mild (12 horses), moderate (7 horses) and severe (24 horses) chronic small airway disease. In horses with pulmonary disease, all BAL samples and all but one RS sample differed cytologically to those obtained from normal horses; however, the type and severity of the pulmonary disease could not always be determined using either BAL or RS cytology. There was a positive association between the percentage of neutrophils in BAL and the neutrophil scores in RS specimens; there was no positive association between other cell types.

Animals

[Malignant lymphomas of the thyroid gland].

In the period from 1957-1989 43 malignant lymphomas of the thyroid gland were treated in the surgical department of Kaiser Elisabeth hospital. 42 were classified as non-Hodgkin lymphomas and one as a Hodgkin lymphoma. The sex distribution was 32 women (mean age 70) to 11 men (mean age 72). The patients were divided into two groups according to postoperative management. First group (1957-1978): conventional irradiation. N = 24 patients, mean survival time 5 months (0-37 months). Second group (1979-1989): high voltage irradiation and/or chemotherapy. N = 19 patients, mean survival time 39 months (1-128 months). All patients in the first group died, whilst in the second group only 9 have died to date. Moreover, 9 of the 10 patients who are still alive are in full remission. Over the past 10 years we have achieved a clear improvement in survival time; this is a result of extended radicality of the surgical procedures, haematological staging and an improvement in the chemotherapy and irradiation regimens.

Adult