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Biomedical subjects

A Sauer

Publications and source records attributed to A Sauer.

At least 19 recordsLinked to original sources
PubMed2004

Androgenic and estrogenic effects of the synthetic androgen 17alpha-methyltestosterone on sexual development and reproductive performance in the fathead minnow (Pimephales promelas) determined using the gonadal recrudescence assay.

The effects of the androgen, 17alpha-methyltestosterone were assessed on sexual development and reproductive performance in the fathead minnow (Pimephales promelas) using a gonadal recrudescence assay. In this assay, mature male and female fathead minnow, previously kept under simulated winter conditions (15 degrees C; 8:16 h light:dark regime) were transferred to simulated summer conditions (25 degrees C water temperature; 16:8 h light:dark regime) to induce gonadal recrudescence. To assess sexual development fish were exposed to nominal concentrations of 0, 0.1, 1, 5 and 50 microg/L 17alpha-methyltestosterone. After 3 weeks of chemical exposure, effects on condition (condition factor, CF), plasma vitellogenin (VTG), secondary sex characteristics, gonad growth (gonadosomatic index; GSI) and gonad histology were investigated. Reproductive performance, including reproductive output (egg production), spawning behaviour, and fertilisation rate were measured over a subsequent 3-week-period in breeding adults maintained in clean water. 17alpha-Methyltestosterone had no effects on the condition of fish at any of the doses tested. 17alpha-Methyltestosterone induced both androgenic and estrogenic effects with females generally more affected by 17alpha-methyltestosterone than males: atretic follicles and male-specific sex characteristics (androgenic effect) were induced in females at > or = 0.1 and > or = 1 microg/L 17alpha-methyltestosterone, respectively. An inhibitory effect on ovary growth occurred at an exposure concentration of 50 microg/L 17alpha-methyltestosterone. In males 1 microg/L 17alpha-methyltestosterone induced a concentration-response induction of plasma vitellogenin (estrogenic effect) likely due to its conversion into 17alpha-methylestradiol, rather to the competition with endogenous steroids and their cross reactivity with the estrogen receptor. In the fish breeding studies, concentration-dependent reductions in egg number, fertilisation rate and increases in abnormal sexual behaviour in females were observed. All of these effects occurred at exposure concentrations of > or = 5 microg/L 17alpha-methyltestosterone. Thus, it could be assumed that the observed estrogenic effects in male fathead minnow were likely to the conversion of 17alpha-methyltestosterone into the estrogen 17alpha-methylestradiol, rather to the acting of 17alpha-methyltestosterone itself. In conclusion to this, showing hormonally activity of 17alpha-methyltestosterone in fish down to 100 ng/L, indicates that its potency was close to the range of several naturally occurring estrogens.

Analysis of Variance↗
PubMed2002

[The tracheostomy-sphincter procedure - case report of a modified tracheostomy].

BACKGROUND: For an adequate speech production after tracheostomy patients are dependant on a temporary closure of the stoma. This closure can either be done manually or by the use of various tracheostoma valves. The tracheostomy-sphincter procedure, which is introduced in this case, allows the voluntary constriction of the stoma. METHODS: This case describes the treatment of a paediatric patient with laryngeal stenosis. During tracheostomy formation, an artificial muscle-sphincter was created, using the sternohyoid muscle (strap muscle). RESULTS: Postoperative contractile movements were possible, which were improved by special exercises. After 3 months the complete closure of the tracheostoma was achieved. CONCLUSIONS: The establishment of a tracheostomy-sphincter can be carried out during tracheostomy and allows the patient to speak without the use of a device. Tracheobronchial secretions can be cleared via the pharynx by coughing.

Adolescent↗
PubMed2000

Ultrastructure and molecular histology of rabbit hind-limb collateral artery growth (arteriogenesis).

Previous studies in the canine heart had shown that the growth of collateral arteries occurs via proliferative enlargement of pre-existing arteriolar connections (arteriogenesis). In the present study, we investigated the ultrastructure and molecular histology of growing and remodeling collateral arteries that develop after femoral artery occlusion in rabbits as a function of time from 2 h to 240 days after occlusion. Pre-existent arteriolar collaterals had a diameter of about 50 microm. They consisted of one to two layers of smooth muscle cells (SMCs) and were morphologically indistinguishable from normal arterioles. The stages of arteriogenesis consisted of arteriolar thinning, followed by transformation of SMCs from the contractile- into the proliferative- and synthetic phenotype. Endothelial cells (ECs) and SMCs proliferated, and SMCs migrated and formed a neo-intima. Intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1) showed early upregulation in ECs, which was accompanied by accumulation of blood-derived macrophages. Mitosis of ECs and SMCs started about 24 h after occlusion, whereas adhesion molecule expression and monocyte adhesion occurred as early as 12 h after occlusion, suggesting a role of monocytes in vascular cell proliferation. Treatment of rabbits with the pro-inflammatory cytokine MCP-1 increased monocyte adhesion and accelerated vascular remodeling. In vitro shear-stress experiments in cultured ECs revealed an increased phosphorylation of the focal contacts after 30 min and induction of ICAM-1 and VCAM-1 expression between 2 h and 6 h after shear onset, suggesting that shear stress may be the initiating event. We conclude that the process of arteriogenesis, which leads to the positive remodeling of an arteriole into an artery up to 12 times its original size, can be modified by modulators of inflammation.

Animals↗
PubMed1998

Characterization of yeast protein Deg1 as pseudouridine synthase (Pus3) catalyzing the formation of psi 38 and psi 39 in tRNA anticodon loop.

The enzymatic activity of yeast gene product Deg1 was identified using both disrupted yeast strain and cloned recombinant protein expressed in yeast and in Escherichia coli. The results show that the DEG1-disrupted yeast strain lacks synthase activity for the formation of pseudouridines psi 38 and psi 39 in tRNA whereas the other activities, specific for psi formation at positions 13, 27, 28, 32, 34, 35, 36, and 55 in tRNA, remain unaffected. Also, the His6-tagged recombinant yeast Deg1p expressed in E. coli as well as a protein fusion with protein A in yeast display the enzymatic activity only toward psi 38 and psi 39 formation in different tRNA substrates. Therefore, Deg1p is the third tRNA:pseudouridine synthase (Pus3p) characterized so far in yeast. Disruption of the DEG1 gene is not lethal but reduces considerably the yeast growth rate, especially at an elevated temperature (37 degrees C). Deg1p localizes both in the nucleus and in the cytoplasm, as shown by immunofluorescence microscopy. Identification of the pseudouridine residues present (or absent) in selected naturally occurring cytoplasmic and mitochondrial tRNAs from DEG1-disrupted strain points out a common origin of psi 38- and psi 39-synthesizing activity in both of these two cellular compartments. The sensitivity of Pus3p (Deg1p) activity to overall three-dimensional tRNA architecture and to a few individual mutations in tRNA was also studied. The results indicate the existence of subtle differences in the tRNA recognition by yeast Pus3p and by its homologous tRNA:pseudouridine synthase truA from E. coli (initially called hisT or PSU-I gene product).

Amino Acid Sequence↗
PubMed1998

A conserved domain within Arc1p delivers tRNA to aminoacyl-tRNA synthetases.

Two yeast enzymes that catalyze aminoacylation of tRNAs, MetRS and GluRS, form a complex with the protein Arc1p. We show here that association of Arc1p with MetRS and GluRS is required in vivo for effective recruitment of the corresponding cognate tRNAs within this complex. Arc1p is linked to MetRS and GluRS through its amino-terminal domain, while its middle and carboxy-terminal parts comprise a novel tRNA-binding domain. This results in high affinity binding of cognate tRNAs and increased aminoacylation efficiency. These findings suggest that Arc1p operates as a mobile, trans-acting tRNA-binding synthetase domain and provide new insight into the role of eukaryotic multimeric synthetase complexes.

Amino Acyl-tRNA Synthetases↗
PubMed1997

Overactivation of the immune system by translocated bacteria and bacterial products.

Gut-derived bacteria and their constituents, namely endotoxins, contribute to the pathogenesis of septic multi-organ failure. Ischemia, trauma, chronic inflammation, immunosuppression or reduced blood flow in the gut are conditions that enhance bacterial translocation, which in turn activates the non-specific immune system, i.e. macrophages and granulocytes to release mediators of inflammation such as cytokines, eicosanoids and degranulation products. Besides blood leukocytes, the liver macrophage population (Kupffer cells), the majority of macrophages in the organism, is a central part of the defense. When overactivated this system can turn against the host, resulting in inflammatory organ damage such as liver injury. A variety of cell and animal models was used to characterize the response of blood and liver leukocytes stimulated by bacteria and bacterial wall preparations. Inflammatory hepatocytotoxicity was studied in vivo as well as in a coculture model of Kupffer cells and hepatocytes. A combination of tumor necrosis factor-mediated apoptosis and interleukin-1-mediated necrosis was identified as a crucial mechanism of endotoxin-inducible hepatocytotoxicity in vitro. Lactulose is believed to reduce bacterial translocation and could thus limit the adverse overactivation of the non-specific immune system. In addition, lactulose at high concentrations inhibited Kupffer cell release of inflammatory mediators and protected hepatocytes against macrophage toxicity. The clinical significance of this observation deserves further investigation.

Animals↗
PubMed1997

Melatonin cycle in the fiddler crab Uca pugilator and influence of melatonin on limb regeneration.

Melatonin was measured over 24 hr in the eyestalks of Uca pugilator by means of radioimmunoassay; crabs were acclimatized either to a LD 12:12 photoperiod or constant darkness. A significant peak occurred at 13.00 hr in the LD 12:12 crabs. A photophase peak in melatonin has only been reported in one other species, also a crustacean. In constant darkness, two melatonin peaks occurred, one at 16.00 hr and the other 12 hr later; these results suggest that the melatonin cycle is a true circadian rhythm. HPLC with ultraviolet-visible detection was used to confirm the identity of melatonin immunoactivity. The influence of melatonin on regeneration of the walking legs was also examined: eyestalks were either removed or left intact, and limb bud length was measured every other day for at least 17 days in control and melatonin-treated crabs (60 microg ml(-1) seawater). Melatonin significantly increased the rate of limb regeneration in both eyestalk-intact and eyestalk-removed groups; this is contrary to results of regeneration studies in other phyla, in which similar melatonin concentrations inhibited regeneration.

Animals↗
PubMed1996

Endotoxin-inducible granulocyte-mediated hepatocytotoxicity requires adhesion and serine protease release.

In primary cultures of Kupffer cells and hepatocytes, human granulocytes potentiated toxicity of endotoxin about 1000-fold. Granulocyte elastase activity was found to correlate with toxicity. The serine protease inhibitors alpha1-antitrypsin, eglin C, and aprotinin protected against toxicity. Tumor necrosis factor-alpha (TNF-alpha) induced cytotoxicity and elastase release, whereas neutralization of TNF-alpha blocked both events. We conclude that TNF-alpha formed by Kupffer cells activates granulocytes. Experiments in cultures where cells were separated by membranes permeable to mediators indicated that cell contact is needed for toxicity. Scanning electron microscopy showed granulocytes adhering to and interdigitating with hepatocytes. Using liver cells from ICAM-1-deficient mice had no effect on toxicity. However, neutralizing CD31 inhibited toxicity and elastase release but not granulocyte adhesion. Our findings demonstrate that adhesion of granulocytes is a necessary but not sufficient condition for the synergistic interaction of endotoxin-stimulated liver macrophages and granulocytes in the proteolytic killing of hepatocytes.

Androstadienes↗
PubMed1996

Control of fecal peritoneal infection in mice by colony-stimulating factors.

Granulocyte colony-stimulating factor (G-CSF) recruits and primes neutrophilic granulocytes. The role of endogenous and exogenous G-CSF was examined in a murine fecal peritoneal infection model characterized by rapid production of high levels of circulating G-CSF. Pretreatment with anti-murine G-CSF for 5 days reduced neutrophil counts by 50% and sensitized mice to sublethal peritonitis. There were more aerobic bacteria in livers of antiserum-pretreated animals but fewer neutrophils in peritoneal cavities. Pretreatment with 100 micrograms/kg recombinant murine G-CSF intravenously for 2 days raised neutrophil counts 5-fold and significantly protected animals against lethal peritonitis. A similar prophylactic administration of murine granulocyte-macrophage (GM)-CSF neither augmented leukocyte numbers nor protected infected mice. These results show a dissociation between the pharmacologic properties of GM-CSF and G-CSF and demonstrate the crucial role of endogenous G-CSF in controlling neutrophil-dependent defense against bacterial invasion in infection.

Animals↗
PubMed1996

Testing of immunomodulatory properties in vitro.

The immune response of different species to a given stimulus varies considerably. The in vitro evaluation of immunomodulatory properties of test compounds therefore prompts the use of human cells. We have conducted experiments on human whole blood incubations which offer the advantages of few preparation artefacts, natural cell environment and easy performance. Ten different immune stimuli were used to initiate leukocyte mediator release. Out of > 20 factors as readout, each and every stimulus released a unique set of factors with different kinetics and concentration dependences. We also used liver macrophages as an alternative cellular model. In this model, over-activation of the macrophages by endotoxin released a toxic combination of factors which killed co-cultured hepatocytes. Co-culture experiments were carried out with primary rat as well as with human liver cells to check for common mechanisms. Furthermore, we added human neutrophil granulocytes to these co-cultures which synergized with the macrophages in killing hepatocytes. Since a similar cellular interaction exists in vivo, this extended cell system bears additional characteristics of the in vivo situation. Therefore, these in vitro models of basic mechanisms of inflammation might be suitable for the evaluation of pro- and anti-inflammatory properties of test compounds.

Adjuvants, Immunologic↗
PubMed1995

Enzymatic analysis of cell surface lactosaminyl glycans by flow cytometry.

Cell surface expressed lactosaminyl glycans were determined on live cells by flow cytometry using a sialyltransferase mediated labeling procedure. Fluorescent CMP-sialic acid and Gal beta 1,4GlcNAc alpha 2,6-sialyltransferase were applied to probe expression of acceptor glycans on untreated or sialidase pretreated erythrocytes. After enzymatic fluorescence labeling, erythrocytes were treated with endo-beta-galactosidase or trypsin to distinguish polylactosaminyl- and complex-type glycans. The expression of lactosaminyl sequences on cord- was 20% lower than on adult cells. After sialidase treatment fluorescence incorporation on both cell types increased twofold compared to untreated cells indicating a low sialylation extent. A recombinant alpha 2,3-sialyltransferase was preferentially labeling polylactosaminyl glycans. Taking advantage of the different fine specificity as determined here, alpha 2,6- and alpha 2,3-sialyltransferase can be applied to distinguish certain types of lactosaminyl glycans.

Adult↗
PubMed1995

Effect of granulocyte colony-stimulating factor treatment on ex vivo blood cytokine response in human volunteers.

We explored the ex vivo alteration in the cytokine release of stimulated blood taken from healthy volunteers treated subcutaneously with 480 micrograms granulocyte colony-stimulating factor (G-CSF). In a double-blind, controlled, randomized study with 21 volunteers who received G-CSF once or twice 24 hours apart, we measured lipopolysaccharide (LPS)-inducible release of various cytokines and soluble receptors at different times after treatment. At day 1 after a single dose of G-CSF, mediator release was also initiated with muramyl dipeptide, Staphylococcus aureus enterotoxin A, lipoteichoic acid, streptolysin O, complement factor C5a, phytohemagglutinin, or phorbol myristate acetate. In blood from G-CSF-treated subjects, our major findings were (1) a maximal 12-fold increase in interleukin-1 receptor antagonist (IL-1ra) release and an increase of both the p55 and p75 soluble tumor necrosis factor (TNF) receptors; (2) a reduction in TNF release when using all the various stimuli described except LPS; (3) an increase in G-CSF and, to lesser extent, in IL-6, IL-8, and IL-10 release; and (4) an attenuation of interferon-gamma (IFN-gamma) and granulocyte-macrophage (GM)-CSF release. Our findings demonstrate that the major effect of G-CSF treatment is a change in the responsiveness of blood towards a variety of stimuli, which we interpret as a shift toward an antiinflammatory cytokine response.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1995

Isolation and characterization of rat primary lung cells.

Lung cell culture may be useful as an in vitro alternative to study the susceptibility of the lung to various toxic agents. Lungs from female Wistar rats were enzymatically digested by recirculating perfusion through the pulmonary artery with a sequence of solutions containing deoxyribonuclease, chymopapain, pronase, collagenase, and elastase. Lung tissue was microdissected and resuspended and the cells obtained were washed by centrifugation. By this isolation method, 2 x 10(8) cells per rat lung were obtained with an average viability of 97%. Lung cells cultured in medium containing antibiotics and serum maintained a viability of > 70% for 5 d. Rat primary lung cells were exposed to various toxic agents and their viability was assessed by formazan production capacity after 18 h of incubation. Compared to rat and mouse hepatocyte cultures (EC50 = 5.8 mM), rat primary lung cells were much more susceptible to hydrogen peroxide (EC50 = 0.6 mM). All cell types were equally sensitive to the more potent toxicant tert-butylhydroperoxide (EC50 = 0.1 mM). Paraquat was more toxic to lung cells (EC50 = 0.03 mM) than to rat (EC50 = 2.8 mM) and mouse (EC50 = 0.2 mM) hepatocytes. In contrast, rat lung cells were less sensitive to sodium nitroprusside (EC50 = 2.6 mM) compared to rat (EC50 = 0.2 mM) and mouse (EC50 = 0.03 mM) hepatocytes. Nitrofurantoin and menadione (at EC50 = 0.04 mM and 0.006 mM, respectively) were more toxic to rat lung and liver cells than to murine hepatocytes (EC50 = 0.2 mM and 0.04 mM, respectively). Our findings demonstrate the applicability of this rat primary lung cell culture for studying the effects of lung toxicants.

Animals↗
PubMed1994

Susceptibility to scrapie in mice is dependent on PrPC.

Mice devoid of functional PrP genes (Prn-p(o/o) mice) showed normal development and behaviour. When inoculated with mouse scrapie prions they remained free of scrapie symptoms for at least 18 months whereas wild-type controls all died within 6 months. No propagation of infectivity could be detected in the PrP null mice. Surprisingly, heterozygous Prn-p(o/+) mice also showed enhanced resistance to scrapie. After introduction of Syrian hamster PrP transgenes, Prn-p(o/o) mice became highly susceptible to hamster but not to mouse prions. These experiments show that PrPC, possibly at close to normal levels, is required for the usual susceptibility to scrapie and that lack of homology between incoming prions and the host's PrP genes retards disease.

Animals↗
PubMed1992

Developmental patterns of ganglioside sialosylation coincident with neuritogenesis in cultured embryonic chick brain neurons.

Chick brain precursor neurons were observed to introduce sialic acid biosynthetically into only three specific gangliosides: monosialosyl lactosyl ceramide (GM3), disialosyl lactosyl ceramide (GD3), and disialosyl gangliotrihexosyl ceramide (GD2), when sialic acid was labeled metabolically by its obligate precursor, [3H] ManNAc. Sialosyl donor CMP-[3H]NeuAc supplied in the culture medium gave rise uniquely to surface-labeled GD3. Thus sialosyl transferase/GD3 synthase activity is expressed both intraneuronally and in the neuronal exofacial surface. Upon epidermal growth factor-induced onset of neurite outgrowth, labeled complex sialosyl gangliotetrahexosyl ceramide species of gangliosides began to appear in the embryonic neuronal plasma membrane. However, intraneuronal and exofacial sialosyl transferase/GD3 synthase activities remained constant, with or without neurite outgrowth. Moreover, simpler species of gangliosides maintained a steady quantitative sialosyl level (1.6 +/- 0.2 micrograms of sialic acid/mg of protein), whereas more complex species completely absent before neurite outgrowth accrued and reached 4.8 +/- 0.9 micrograms of sialic acid/mg of protein with full neurite development. This analysis of developmental patterns of ganglioside sialosylation has provided evidence that stable neurite outgrowth depends upon generation by the neuron of special plasma membrane with a massive content of complex higher species of gangliosides.

Animals↗
PubMed1992

Effects of a high-cholesterol diet on arterial wall thickness and vascular reactivity in young rabbits.

Cholesterol enrichment of arteries may induce biochemical and structural abnormalities in vascular smooth muscle resulting in increased arterial contractile sensitivity. We studied the effects of a high-cholesterol diet on arterial structural properties and vascular reactivity in young rabbits. In vivo measurements of aortic intimal-plus-medial thickness using high resolution ultrasound imaging were obtained before and after 3 weeks of a high-cholesterol diet in 12 rabbits (group 2) and compared to data from 12 animals a cholesterol-free diet fed (group 1). Six rabbits (group 3) were studied before and after a 3-week, high-cholesterol diet and after a subsequent 13-week, cholesterol-free recovery diet. Blood pressure responsiveness to noradrenaline was evaluated before and at the end of each diet period. In groups 2 and 3, high dietary cholesterol caused an increase in intimal-plus-medial thickness from 0.31 mm and 0.33 mm to 0.88 mm and 0.89 mm, respectively (p less than 0.001). Plasma cholesterol concentration rose from 0.9 +/- 0.26 mmol/l to 36.7 +/- 8.56 mmol/l. There was no change in group 1. In group 3, intimal-plus-medial thickness remained increased (1.01 mm) following the cholesterol-free recovery diet despite normal plasma cholesterol. Blood pressure responsiveness to noradrenaline was markedly increased after the high-cholesterol diet (p less than 0.001) in groups 2 and 3 and after the cholesterol-free recovery diet in group 3 (p less than 0.001), and was directly related to intimal-plus-medial thickness (r = 0.84; p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Kinetics of hemolysis of normal and abnormal red blood cells in glycerol-containing media.

The kinetics of hemolysis of erythrocytes in glycerol-containing media was studied spectrophotometrically. The hemolytic process starts by a rapid process, obeying a first order rate law, which is followed by a slow change in absorbance. The kinetics of hemolysis may be described by (a) the maximum absorption, Emax, due to cellular expansion, (b) the rate constant, k, of the fast process and (c) the final absorption at its end, Einf and the ratio Einf/Emax. At pH 6.85 in normal human cells, k = 0.72 min-1 while in hereditary spherocytosis cells, k = 1.06 min-1, iron deficiency k = 0.52 and beta-thalassemia minor k = 0.36 min-1. The percentages of Einf/Emax were 35.3 in control cells, while they were 9.8, 50.0 and 88.3 in spherocytosis, iron deficiency and thalassemia, respectively. Thus these kinetic parameters may help to distinguish and understand the above mentioned erythrocyte disorders. At physiological pH (7.4-7.2), no hemolysis was detected in the medium used. When the pH decreased, hemolysis occurred, its rate increasing gradually until pH 6.3. On further acidosis, the hemolytic rate slowed down again. Addition of DIDS to the whole blood prior to the test inhibits hemolysis. Similar effect of DIDS was noted in washed cells; this effect was partially reversed by albumin. These results suggest that a process involving band 3 affects the rate and degree of glycerol-induced hemolysis of normal red blood cells.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗