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Biomedical subjects

G Richter

Publications and source records attributed to G Richter.

At least 109 records · Page 6Linked to original sources

[Rapeseed and rapeseed meal as components in diets of laying hens].

In an experiment with 405 Hisex white hens rations with 5-20% low glucosinolate rapeseed (RS) or rapeseed meal (RSM) of 00 quality were used. Feed intake, egg production, individual egg weight and live weight gain were reduced in hens fed 5-20% RS and 10-20% RSM. There was a positive correlation between the RS proportion in the ration and the thyroid weight as well as the iodine content of the thyroid. The relation between the iodine content related to one gram of thyroid and the RS proportion was not significant. There were not any significant differences between the RSM groups and the iodine content of the thyroid. The T3 and T4 concentrations in the blood plasma was independent of the RS- or RSM-proportion in the diet. The outward egg quality was not influenced by feeding. The Haugh units were lower when RS or RSM were offered. The fatty acid pattern of the yolk was changed by RS or RSM feeding, particularly the proportion of oleic acid increased. We concluded from the results, RS cannot be recommended for feeding white hens and only a maximum of 5% RSM should be administered.

Animal Feed↗

Treatment of old mice with IL-2 corrects dysregulated IL-2 and IL-4 production.

Splenic T cells from old BALB/c mice, activated in vitro with antibody to CD3epsilon, secrete more IL-4 but less IL-2 than splenic T cells from young mice. The age-associated increase in IL-4 secretion is associated with a significantly increased concentration of intracellular IL-4 and its mRNA, although there is no increase in the number of activated T cells with intracellular IL-4. In contrast, the age-associated decrease in IL-2 secretion is associated with a significant decrease in the number of activated T cells with intracellular IL-2. In vivo there is a similar age-associated change in the number of activated T cells with detectable cytokine. The number of activated T cells with intracellular IL-4 is comparable in old and young mice, while the number of activated T cells with intracellular IL-2 is significantly decreased in old compared with young mice. Of great interest is the fact that old mice continuously exposed to IL-2 in vivo following the transplantation of J558 cells expressing the transfected IL-2 gene product have an increased number of splenic T cells with intracellular IL-2 that equals the level of such cells observed in young mice. Most important, the effect of continuous IL-2 administration in vivo was stable as spleen cells from old, IL-2-treated mice when stimulated in vitro with anti-CD3epsilon had a young-like pattern of both intracellular IL-2 and IL-4 expression as well as IL-2 and IL-4 secretion following in vitro activation. Thus, it appears that exposure of old mice to exogenous IL-2 can redress the age-associated imbalance in cytokine expression in vivo and cytokine secretion in vitro.

Age Factors↗

The highly acidic C-terminal region of the yeast initiation factor subunit 2 alpha (eIF-2 alpha) contains casein kinase phosphorylation sites and is essential for maintaining normal regulation of GCN4.

Regulation of the effective activity of eukaryotic initiation factor 2 (eIF-2) in protein synthesis is known to involve phosphorylation of its alpha subunit. Two mammalian enzymes, the haem-controlled repressor (HCR) and the double-stranded RNA-activated inhibitor (dsI), phosphorylate Ser-51 of the alpha subunit, thereby inhibiting the exchange of bound nucleotides on, and thus the recycling of, eIF-2. In Saccharomyces cerevisiae, the equivalent serine seems to be phosphorylated by the GCN2 protein kinase, which is activated by amino acid starvation. However, in the present paper we show that this is not the only site of phosphorylation in yeast eIF-2 alpha. We report the preparation of recombinant yeast eIF-2 alpha from Escherichia coli and its use in in vitro phosphorylation studies. Mammalian HCR and dsI are shown to phosphorylate specifically Ser-51 of yeast eIF-2 alpha, whereas extracts from yeast cells do not. Instead, at least one of three serine residue in the acidic C-terminal region of this protein is phosphorylated by fractions of yeast possessing casein kinase activities 1 and 2. A triple Ser-->Ala mutant form of yeast eIF-2 alpha was found to be no longer phosphorylated by either of the yeast (or mammalian) casein kinase activities in vitro. Isoelectric focusing of yeast extracts confirmed that the mutated sites normally act as sites of phosphorylation in vivo. The same mutant was used to show that the three sites have no essential function under normal physiological conditions in yeast. In contrast, deletion of the 13 amino acid long C-terminal region of eIF-2 alpha, including the three phosphorylation sites, led to derepression of GCN4 in vivo. Thus removal of the short, highly acidic C-terminal region of eIF-2 alpha has the same regulatory effect on translational (re)initiation as phosphorylation of the Ser-51 residue of the wild-type protein. This result provides new insight into the role of eIF-2 alpha activity in the regulation of translational (re-) initiation.

Amino Acid Sequence↗

The rat interleukin 4 receptor: coevolution of ligand and receptor.

A rat interleukin 4 receptor (IL-4R) cDNA was cloned by polymerase chain reaction (PCR) using RNA of Con A activated T cells and primers deduced from mouse and human IL-4R sequences. Sequence analysis revealed an open reading frame for a putative membrane protein of 800 amino acids in length. It comprises an overall identity of 52 and 78% to its human and mouse homologues, respectively. The extracellular part of the rat IL-4R contains a number of residues including cysteines and a WSXWS motif typical for the cytokine receptor superfamily. Analysis of amino acid exchanges between rat and mouse IL-4 receptors deciphered for replacement (R) or silent (S) mutations suggested different types of selective pressure acting on the extracellular and intracellular domains. A high R/S value that indicates selective pressure for amino acid exchanges was found for the extracellular domain and a low R/S value for the intracellular part of the IL-4R. Since we previously found a similar high R/S value in the rat IL-4 gene encoding the ligand for the IL-4R, the high amino acid exchange rate can best be explained by coevolution between IL-4 and the ligand binding domain of the IL-4R to improve or retain affinity.

Amino Acid Sequence↗

The blue light-responsive AthH2 gene of Arabidopsis thaliana is primarily expressed in expanding as well as in differentiating cells and encodes a putative channel protein of the plasmalemma.

According to our previous studies the Arabidopsis gene AthH2 which is inducible by blue light and phytohormones codes for an intrinsic membrane protein. It bears a resemblance to several distinct channel proteins of plant and animal species classified as the MIP/NOD-26/GlpF family. In the present study biochemical analyses and electron microscopic immunochemistry were used to elucidate the subcellular location of the AthH2 protein. The results clearly demonstrate that it is an exclusive constituent of the plasmalemma. Furthermore, the expression of the AthH2 gene in transgenic Arabidopsis plants containing the promoter region of AthH2 fused to the beta-glucuronidase (gus) reporter gene was studied. The in situ localization of gus activity revealed that the specific promoter is temporally activated by light in expanding and/or differentiating cells comprising newly formed tissues and organs: root elongation zone, guard cells of stomata, vascular bundle sheaths, filaments of stamen and young siliques. Several sites of gus expression coincide spatially with those of in situ hybridization and the immunocytochemical reaction, respectively, suggesting that the AthH2 promoter had correctly responded to light as an important exogenous factor with relevance to the complex pattern of differentiation. Studies with protoplasts from plants transformed with an antisense construct revealed a water transport capacity of the AthH2 protein.

Arabidopsis↗

[Incorporation and mobilization of vitamin A in laying hens].

216 laying hybrids were given diets with 1500, 3000 or 6000 IU vitamin A kg-1 between their 21st and 64th week of age. The ration did not contain any vitamin A between the 5th and 16th as well as the 25th and 28th week. The control animals were fed a diet with 6000 IU kg-1. Feed consumption, laying performance, egg weight, feed efficiency, mortality and the vitamin A content in egg yolk and liver depend on the vitamin A supply. 4-week depletion took an adverse effect on feed intake and laying performance. It was not possible to detect vitamin A in the egg yolk after 4 weeks and in the liver after 16 weeks of depletion.

Aging↗

Glucagon-like peptide-1 and glucose-dependent insulin-releasing polypeptide plasma levels in response to nutrients.

The nutrient-dependent glucagon-like peptide-1 (7-36) amide (GLP-1) release was studied in comparison to the glucose-dependent insulin-releasing polypeptide (GIP) response in 10 healthy volunteers each undergoing various protocols. Plasma samples were saved up to 120 min after challenges by oral, intravenous or intraduodenal administration of nutrients. Basal plasma-GLP-1 concentrations ranged between 0.4 and 1.4 pM, maximal postprandial GLP-1 levels peaked between 10 and 12 pM. Intravenous glucose (25 g i.v.) did not change basal GLP-1 levels. Oral administration of glucose (50 g) induced a biphasic GLP-1 release peaking at 30-60 min and a biphasic GIP release peaking at 5 and 45 min. This increase paralleled the secretion of insulin. Oral galactose (100 g) and amino acids (25 g) also induced a rapid plasma GLP-1 response. After fat (67 g corn oil) a strong and long-lasting (> 120 min) increase of GLP-1 plasma levels occurred. When a mixed liquid meal was given (6 g soybean oil, 5 g casein, 13 g glucose) immunoreactive (IR)-GLP-1 rapidly increased and peaked after 5 min with declining levels after 30 min. In response to an intraduodenal infusion of a small glucose load (5.34 g within 120 min) a rapid, short-lasting GLP-1 response occurred whereas plasma GIP and insulin levels remained unaltered. Luminal perfusion of an isolated vascularly perfused rat ileum with a polydiet induced a rapid rise of portally released IR-GLP-1 which was followed by a sustained release. Glucose evoked sodium-dependently a sharp increase of IR-GLP-1 levels followed by a plateau release. The intraluminal infusion of a mixture of amino acids or fat was without any effect on IR-GLP-1. We hypothesize that in contrast to GIP the GLP-1 release from L cells is triggered by nervous reflexes, by putative humoral factor(s) being released from the upper small intestine in addition to nutrient stimuli acting at the luminal surface of the gut.

Adult↗

[Do proton pump inhibitors after endoscopic control of acute ulcer hemorrhage have an advantage over H2 receptor antagonists?].

During a two year period (1992-1993) we investigated whether or not, after endoscopic therapy of bleeding ulcers, the suppression of gastric acid secretion with an administration of a proton pump blocker (Omeprazol) is more effective than the administration of H2-receptor antagonist (Ranitidin) with respect to prevention of recurrent bleeding episodes, frequency of surgical intervention and mortality. 106 patients (64 men, 42 women) were treated with the proton pump blocker and 126 patients (82 men, 44 women) received the H2-receptor antagonist. Patients were treated either with an initial dose of 80 mg Omeprazol followed by 3 x 40 mg Omeprazol i.v. or with a daily dose of 3 mg/kg body weight Ranitidin i.v. No significant differences could be detected between the two treatment regimes with respect to the parameters mentioned above. Rebleeding which could be controlled by endoscopic hemostasis occurred in 19.8% vs. 17.5% (Omeprazol/Ranitidin) of patients. Surgical intervention because of rebleeding was necessary on 8.5% vs. 8.7% of the patients. Mortality due to hemorrhage was 5.7% vs. 4.0%. From these results we conclude that, following endoscopic hemostasis of bleeding ulcers, Omeprazol has no advantage over Ranitidin using our dosage regimes.

Adult↗

The measurement of beta-phenylethylamine in human plasma and rat brain.

A sensitive and specific analytical method has been developed for the measurement of beta-phenylethylamine (PEA) in human plasma and rat brain extracts. The method involves solvent extraction of PEA with cyclohexane in the presence of amphetamine or phenylpropylamine (PPA) as internal standards. Automated precolumn derivatization with o-phthalaldehyde and 2-mercaptoethanol followed by reverse-phase HPLC separated PEA and PPA from endogenous interferences. Detection and quantification were carried out by amperometric detection at +0.75 V relative to a Ag/AgCl reference electrode or by coulometric detection with analytical cell potentials set at +0.29 and +0.50 V. The limit of detection for PEA was 10 pg and the limit of quantification in plasma was 60 pg/ml. The within-day and day-to-day coefficients of variation were 16.1% (n = 3) and 40.6% (n = 8), respectively, at a plasma concentration of 154 pg/ml and 15.2% (n = 5) and 28% (n = 10) at a brain extract concentration of 110 pg/ml. Basal endogenous plasma PEA concentrations of 335 +/- 255 pg/ml (n = 12, range 127-1002 pg/ml) were found for normal volunteers and single, daily doses of 24 mg but not 12 mg of the MAO-B inhibitor, mofegiline, were shown to increase plasma PEA significantly. Basal whole brain and striatal concentrations were 0.584 +/- 0.243 ng/g wet wt (n = 3) and 2.89 +/- 1.03 ng/g wet wt (n = 4), respectively. Statistically significant increases (5.7-fold) in rat whole brain PEA concentrations were seen 3 and 6 h following the administration of a single dose of 0.3 mg/kg mofegiline to rats.

Adult↗

The lumazine synthase/riboflavin synthase complex of Bacillus subtilis. X-ray structure analysis of hollow reconstituted beta-subunit capsids.

The lumazine synthase/riboflavin synthase complex of Bacillus subtilis consists of an icosahedral capsid of 60 beta subunits enclosing a triplet of alpha subunits. An X-ray structure of 0.32 nm resolution has been obtained for the icosahedral capsid of the native alpha 3 beta 60 complex [Ladenstein, R., Schneider, M., Huber, R., Bartunik, H. D., Wilson, K., Schott, K. & Bacher, A. (1988) J. Mol. Biol. 203, 1045-1070]. beta subunits were isolated after denaturation of the alpha 3 beta 60 complex and were subsequently reconstituted in a ligand-driven reaction yielding artifactual, hollow beta 60 capsids with icosahedral symmetry. Hexagonal crystals (space group P6(3)22) of the reconstituted capsids diffracted X-rays to a resolution of 0.32 nm. Crystallographic intensity data were obtained using synchrotron radiation. Freeze-etched electron-microscopic images and rotation function calculations showed that the hexagonal crystal forms of the artifactual beta 60 capsids and the native alpha 3 beta 60 complex are isomorphous. Orientation and translation parameters of the beta-subunit model were refined by XPLOR rigid-body refinement. The electron-density map was improved by cyclic icosahedral averaging and phase extension from 0.5-0.32 nm resolution. The beta-subunit structure was partially refined by energy minimization and crystallographic refinement (XPLOR) assuming strict icosahedral symmetry (final R factor 30.9% for data at 0.8-0.32 nm resolution). The topology and chain folding of the beta subunits in the artifactual beta 60 capsid are similar to the native alpha 3 beta 60 enzyme. Structural features of the substrate-binding site and the binding of the substrate-analogous ligand 5-nitro-6-ribitylamino-2,4(1H,3H)-pyrimidinedione are discussed. Ligand binding occurs at the pentamer interfaces and includes van der Waals' interactions and hydrogen bonding. The binding pocket shows a hydrophobic region which accomodates the pyrimidinedione ring and a hydrophilic region to which the ribityl side chain binds. Most amino acid residues involved in the active site are conserved as shown by sequence comparisons with the putative lumazine-synthase genes of Escherichia coli and Photobacterium leiognathi. In the final electron-density map, a residual density feature was tentatively assigned to a bound phosphate ion which mimics the binding of the second substrate, 3,4-dihydroxy-2-butanone 4-phosphate. This putative phosphate-binding site involves a highly conserved amino acid sequence containing three basic residues.

Bacillus subtilis↗

Changes in external and internal lead load in different working areas of a starter battery production plant in the period 1982 to 1991.

Our investigation was based on routine ambient and biological monitoring data in a starter battery production plant from 1982 to 1991. This retrospective longitudinal study included 134 blue collar workers in seven main production areas (casting, lead oxide production, bunker, pasting, formation, plate stacking, assembly). Over the whole period a statistically significant decrease in blood lead concentration in the whole sample, from 48.92 micrograms/dl (1982) to 22.99 micrograms/dl (1991), could be ascertained. This positive trend could also be proven for the most important production areas. The highest internal lead load was present in employees from the formation and adjoining production areas, followed by pasting, casting and assembly. In comparison to other battery factories our results are in the lower range. Furthermore, we carried out a data linkage between air and blood lead concentrations. We were able to demonstrate a decrease in external lead load in most of the production areas, but this reduction was not so distinct as that in the blood lead concentration. These results indicate the efficiency of preventive efforts in technical work protection and especially in intensive medical supervision of the exposed workers. Influencing personal hygienic behaviour and intervention at blood lead levels of 50 micrograms/dl promises the best success in worker protection.

Air Pollutants, Occupational↗

Molecular cloning of a cDNA encoding for the GLP-1 receptor expressed in rat lung.

Recent data revealed the existence, localization and possible function of specific receptors for glucagon-like peptide 1 (7-36) amide (GLP-1) in rat lung. This receptor has different biochemical features than the GLP-1 receptor in endocrine pancreas. Therefore, we aimed to clone the lung receptor cDNA in order to analyze whether biochemical and functional diversity of the GLP-1 receptors in lung and pancreas is based upon genetic differences. A cDNA library from rat lung in a lambda gt11 vector was screened with a cDNA probe coding for the rat pancreas GLP-1 receptor. Thereby, we found a lung GLP-1 receptor cDNA which shows nearly complete homology to the pancreatic beta-cell receptor cDNA. Only one base exchange occurred at base 1 of a codon at position 977 resulting in a change of valine residue for isoleucine at position 323 of the amino acid sequence within the fifth transmembrane region. Northern blot hybridization identified transcripts at 2.7, 3.4, and 3.6 Kb. Expression of the recombinant lung GLP-1 receptor cDNA in CHO cells displayed a pharmacological profile similar to that seen with cells expressing the beta-cell derived cDNA. Therefore, we conclude that tissue-specificity for GLP-1 receptors is based upon posttranslational modifications of the receptor protein (for example glycosilation) or alternative splicing of primary transcripts and not on variations within the coding sequence of the receptor gene.

Amino Acid Sequence↗

[Effect of enzyme mixtures in broiler diets of barley, rye or wheat].

In three trials with a total of 4120 male and female broilers, kept on floor or in cages maize has been partly replaced by barley, rye or triticale and different combinations of enzymes were fed. The supplementation of cellulases with mainly glucanase in barley based diets has had no significant influence on growth performance. In case of diets with 20% rye the addition of cellulases with mainly hemicellulases resulted in 5% higher live weight gains and a better feed efficiency (5%) on average of two trials. The negative influence of rye feeding on excrement constitution was lowered and the dry matter content of excrements increased by 1.3%. In diets based on triticale the growth performance of broilers was insignificantly better. The addition of enzymes did not influence the proportion of different body fractions as well as the crude nutrient content of edible carcass.

Animal Feed↗

Intestinal effects of alpha-glucosidase inhibitors: absorption of nutrients and enterohormonal changes.

The present paper addresses the question how alpha-glucosidase inhibitors affect glucose homeostasis. To facilitate this already established data on the effects of induced malabsorption on gut hormones such as gastric inhibitory polypeptide (GIP) in connection with preliminary findings which deal with the new incretin hormone glucagon-like peptide 1 (7-36) amide (GLP-1) are discussed. To emphasize the possibly important impact of a regulated GLP-1 release in response to glucosidase inhibitor treatment we evaluate the recently introduced concept of 'glucose competence' of pancreatic beta-cells. The slowing of nutrient (i.e. glucose) absorption by therapeutic means (for example, acarbose) could supplement a new approach in the treatment of type 2 diabetics which would utilize the well-preserved insulinotropic activity of GLP-1 in these patients, its glucagon-lowering effect, and its possible inhibition of gastric emptying rates, the latter helping to reduce the requirement for rapid insulin secretory responses as is intended while using alpha-glucosidase inhibitor treatment.

Animals↗

[Arterial embolization as a therapeutic possibility of tumors of the skeletal system].

Arterial embolization is an approved method in treating bleeding tumors of the urogenital tract. In orthopedic patients it has been applied for hypervascularized skeletal metastases of the pelvic, spine and long bones. Intraoperative blood loss with its known risks can be markedly reduced. Reduction of pain has also been reported. The good results in our series of 9 patients together with the low incidence of side effects suggest that arterial embolization is indicated on a large scale.

Adult↗

[Liver transplantation after surgical shunt or transjugular intrahepatic portasystemic shunt].

The goal of this study was to assess the influence of prior treatment of bleeding esophageal varices on liver transplantation. After sclerotherapy the results of liver transplantation were identical to those achieved in patients without previous variceal hemorrhage (74% 1-year survival). The results of liver transplantation to patients who already had surgical shunts were dismal. Four of nine patients with portocaval or Warren shunts were long-term survivors. In comparison, the intraoperative course in five patients with transjugular intrahepatic portosystemic stent shunts (TIPSS) was uneventful and four of these were long-term survivors. This has led us to adopt TIPSS as the treatment modality of choice for patients with bleeding varices awaiting liver transplantation.

Adult↗