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G Schreiber

Publications and source records attributed to G Schreiber.

At least 19 recordsLinked to original sources
PubMed1992

Protein synthesis at the blood-brain barrier. The major protein secreted by amphibian choroid plexus is a lipocalin.

Among the proteins secreted by choroid plexus of vertebrates, one protein is much more abundant than all others. In mammals, birds, and reptiles this protein is transthyretin, a tetramer of identical 15-kDa subunits. In this study choroid plexus from frogs, tadpoles, and toads incubated in vitro were found to synthesize and secrete one predominant protein. However, this consisted of one single 20-kDa polypeptide chain. It was expressed throughout amphibian metamorphosis. Part of its amino acid sequence was determined and used for construction of oligonucleotides for polymerase chain reaction. The amplified DNA was used to screen a toad choroid plexus cDNA library. Full-length cDNA clones were isolated and sequenced. The derived amino acid sequence for the encoded protein was 183 amino acids long, including a 20-amino acid presegment. The calculated molecular weight of the mature protein was 18,500. Sequence comparison with other proteins showed that the protein belonged to the lipocalin superfamily. Its expression was highest in choroid plexus, much lower in other brain areas, and absent from liver. Since no transthyretin was detected in proteins secreted from amphibian choroid plexus, abundant synthesis and secretion of transthyretin in choroid plexus must have evolved only after the stage of the amphibians.

Amino Acid Sequence↗
PubMed1992

Ziskind-Somerfeld research Award. The involvement of guanine nucleotide binding proteins in the pathogenesis and treatment of affective disorders.

Guanine nucleotide binding (G) proteins play a pivotal role in postreceptor information transduction. An important characteristic of G proteins is their increased guanine nucleotide binding following agonist stimulation, which in turn leads to their activation. We have developed a method that enables the measurement of early events in signal transduction beyond receptors, through activated receptor-coupled guanine nucleotide exchange on G proteins. Using this method, lithium was recently demonstrated to inhibit the coupling of both muscarinic cholinergic and beta-adrenergic receptors to pertussis toxin-sensitive and cholera toxin-sensitive G proteins, respectively, thus suggesting alteration of the function of G protein by lithium, as the single site for both the antimanic and antidepressant effects of this drug. One of the most puzzling aspects of the ability of lithium to ameliorate the manic-depressive condition is its relatively selective action upon the central nervous system (CNS). It was previously shown that lithium selectively attenuated the function of Gs proteins in the CNS. In the present study, we show that inhibition by lithium of muscarinic receptor-coupled G protein function is also selective to the CNS. The clinical profile of lithium, carbamazepine, and electroconvulsive treatment (ECT), agents that are effective in the prevention and treatment of bipolar affective disorder, differs from that of purely antidepressant drugs. Antidepressant drugs are effective in the acute treatment and prevention of depression only, and can even precipitate hypomanic or manic "switches," or "rapid cycling" between mania and depression. We have investigated and compared the effects of chronic antibipolar and antidepressant treatments on receptor-coupled G protein function. Antibipolar treatments (lithium, carbamazepine, ECT) attenuate both receptor-coupled Gs and non-Gs (i.e., Gi, Go) proteins function; in contrast, only Gs protein function is inhibited by antidepressant drugs [either tricyclics or monoamine oxidase (MAO) inhibitors]. Moreover, an integral adrenergic neuronal system is required for antidepressant inhibition of Gs protein function, as pretreatment with the noradrenergic neurotoxin DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine) specifically abolishes the effects of antidepressant drugs on Gs protein, whereas antibipolar drug effects on G protein function are unaffected by DSP-4. Our results suggest that attenuation of beta-adrenergic receptor-coupled Gs protein function, which is common to both antidepressant and antibipolar treatments, may be the mechanism underlying their antidepressant therapeutic efficacy.(ABSTRACT TRUNCATED AT 400 WORDS)

Antidepressive Agents↗
PubMed1992

The structure and expression of the genes for T-kininogen in the rat.

T-kininogen plays an important role in the acute phase response to trauma in the rat as a possible source of kinins and as a cysteine proteinase inhibitor. Two T-kininogens are expressed by rat liver from two separate genes. T-kininogen expression in liver during the acute phase response is regulated at the level of transcription. The similarity in T- and K-kininogen gene structure suggests divergent evolution from a common gene ancestor.

Acute-Phase Reaction↗
PubMed1992

[Status of the development of electron spin resonance measurement for the detection of irradiated food].

Electron spin resonance spectroscopy can be used for the detection of irradiation of various groups of foodstuffs. The results of ESR-measurements on irradiated meat and fish and fresh fruit, as well as dried fruit, spices and nuts as performed by the food irradiation laboratory of the German Federal Health Office are summarized in this report. For the detection of irradiated meat and fish, we examined the bones. Using the results from 10 different animal bones, we were able to develop an official method according to the German law section 35 LMBG. A similar routine method for fish will be established in 1992 (at the moment, an intercomparison with German food control laboratories is in progress). Irradiated dried fruit can be identified easily, because unirradiated samples give no ESR-spectra, while irradiated fruit show a partially resolved spectrum, which is caused by radiation induced sugar radicals. Interestingly, the structure of the resulting spectra is not identical for all irradiated species of fruit. We found three different types of ESR-spectra for irradiated dried fruit. Irradiated nutshells show an ESR-spectrum which reveals two additional lines (from cellulose-radicals) beside the main signal, while unirradiated samples show only the main signal. An official method for identifying irradiated nuts will be proposed in 1992. Irradiation specific ESR-signals of the cellulose radical were not only found for nutshells but also for fresh fruit and some spices, while most of the irradiated spices and herbs could not be identified by ESR-measurements.

Animals↗
PubMed1992

Species specificity and developmental patterns of expression of the beta amyloid precursor protein (APP) gene in brain, liver and choroid plexus in birds.

1. Human APP cDNA hybridized to a 3.5 kb mRNA in liver and brain RNA from chickens, pigeons, quail and ducks as well as in RNA from choroid plexus of chicken and quail. In contrast to all other species hitherto examined a 1.6 kb mRNA hybridizing to APP cDNA was found in abundant amounts in RNA from chicken and quail livers. 2. In the chicken, before hatching, the levels of APP mRNA in total RNA from liver and choroid plexus were higher than those in RNA from liver and choroid plexus of adults. However, RNA from the rest of the brain of chicken embryos contained less APP mRNA than RNA from brain of adults. 3. In the chicken, between 10 and 40 days after hatching, APP mRNA levels in RNA from liver were higher than adult levels, APP mRNA levels in RNA from choroid plexus were similar to adult levels and APP mRNA levels in RNA from the rest of brain were below the adult levels.

Amyloid beta-Peptides↗
PubMed1992

Expression of retinol-binding protein mRNA in mammalian choroid plexus.

1. The expression of the gene for retinol-binding protein in choroid plexus from rats, mice, sheep and cattle is demonstrated by Northern analysis and reverse transcription coupled with polymerase chain reaction. 2. The content of retinol-binding protein mRNA in total RNA from choroid plexus of ruminants was higher than that for RNA from any other extrahepatic tissues of adult animals reported so far. 3. The ratios of retinol-binding protein mRNA levels in choroid plexus RNA to those in liver RNA varied greatly among rodents, ruminants and carnivores.

Animals↗
PubMed1992

Strong conservation of the expression of cystatin C gene in choroid plexus.

The expression of the cystatin C gene was studied by Northern analysis of RNA isolated from the choroid plexus, other brain tissues, and liver from 11 mammalian and 4 avian species. The probe used for hybridization was cystatin C cDNA isolated previously from a rat choroid plexus cDNA library. Strong conservation of the expression of the cystatin C gene in choroid plexus was suggested by the observation of substantial levels of cystatin C mRNA in choroid plexus RNA from all mammalian and avian species studied. In contrast, levels of cystatin C mRNA in total liver RNA varied widely for mammalian as well as for avian species. It was concluded that the synthesis of cystatin C in choroid plexus has probably been conserved since the stage of the stem reptiles, the common ancestors of mammals and birds. The cystatin C gene was also found to be expressed early in ontogeny, as indicated by the observation of similar cystatin C mRNA levels in choroid plexus RNA from newly hatched and adult chickens.

Animals↗
PubMed1992

Steady state concentrations and diurnal fluctuations of carbamazepine in patients after different slow release formulations.

The bioavailability and serum level fluctuations of three carbamazepine (CBZ, CAS 298-46-4) slow release preparations marketed in Germany were compared in patients with epilepsy. Ten patients who were on CBZ monotherapy and had reached a steady state with morning trough levels above 10 micrograms/ml received all 3 preparations in sequential 3-day periods. On the 3rd day of each period, a 24-h serum drug level profile was determined. Only minimal differences could be found. One preparation had a significantly higher AUC than one of the others (p less than 0.05), and this difference seemed to be correlated with higher fluctuations of serum levels and, especially, an increased Cmax. Although the group differences are minimal, more important differences could be observed individually. One patient had, with one of the three preparations, a reduction in seizure frequency but simultaneously developed important signs and symptoms of toxicity. It is concluded that all 3 preparations are equally suitable for chronic antiepileptic drug treatment. In a well-controlled patient, however, interchange between preparations is not advisable as their kinetics in individual patients can be sufficiently different to cause toxicity or seizure relapse.

Adolescent↗
PubMed1992

Cerebral expression of transthyretin: evolution, ontogeny and function.

This paper reviews studies on the synthesis and secretion of the thyroid hormone-binding protein, transthyretin by the choroid plexus. The secretion of transthyretin by the choroid plexus into the cerebrospinal fluid may have an important function in the transport of thyroxine from the blood to the brain. The transthyretin gene is expressed in the choroid plexus of most vertebrates and synthesis of this protein may have evolved in the brain before the liver.

Animals↗
PubMed1991

Isolation, characterization, cDNA cloning and gene expression of an avian transthyretin. Implications for the evolution of structure and function of transthyretin in vertebrates.

A chicken liver cDNA library was constructed in bacteriophage lambda gt10. A full-length transthyretin cDNA clone was identified by screening with rat transthyretin cDNA and was sequenced. A three-dimensional model of chicken transthyretin was obtained by computer-graphics-based prediction from the derived amino acid sequence for chicken transthyretin and from the structure of human transthyretin determined by X-ray diffraction analysis [Blake, C.C.F., Geisow, M.J., Oatley, S.J., Rérat, B. & Rérat, C. (1978) J. Mol. Biol. 121, 339-356]. The similarity of the amino acid sequences of chicken and human transthyretins was 75% overall and 100% for the central channel containing the thyroxine-binding site. Also, the organization of the transthyretin gene into exons and introns and the tissue specificity of expression of the transthyretin gene were similar in chicken and mammals, despite an evolutionary distance of about 3 x 10(8) years from their common ancestor, the Cotylosaurus. By far the highest levels of transthyretin mRNA were found in choroid plexus. The data suggest a fundamental role for the cerebral expression of transthyretin in all vertebrates. It has been proposed that this role is the transport of thyroxine from the bloodstream to the brain [Schreiber, G., Aldred, A.R., Jaworowski, A., Nilsson, C., Achen, M.G. & Segal, M.B. (1990) Am. J. Physiol. 258, R338-R345].

Amino Acid Sequence↗
PubMed1991

The distribution of cerebral expression of the transferrin gene is species specific.

Various plasma proteins, for example, transferrin, are synthesized not only in the liver, but also in the brain. The proportion of transferrin mRNA in total RNA from different regions of brains from various mammalian species was studied by Northern blot analysis. Absolute amounts of transferrin mRNA were determined in brain, choroid plexus, and liver from rats, sheep, and pigs by hybridization in solution followed by ribonuclease protection assay. Corrections for differences in yields of RNA were made using internal RNA standards. Large proportions of transferrin mRNA in total RNA and high absolute levels of transferrin mRNA in choroid plexus were found only in rats. Small proportions of transferrin mRNA were observed in RNA from choroid plexus from mice, dogs, and rabbits, while no transferrin mRNA at all was detected in choroid plexus from humans, sheep, pigs, cows, and guinea pigs. In further analysis of sheep and pigs, various amounts of transferrin mRNA were found in many parts of the brain, in contrast to the absence of transferrin mRNA from choroid plexus. In conclusion, a striking species specificity was observed for the pattern of cerebral expression of the transferrin gene.

Amino Acid Sequence↗
PubMed1991

Transcriptional activity of the phosphoenolpyruvate carboxykinase gene decreases in regenerating rat liver.

Rat cytosolic phosphoenolpyruvate carboxykinase (PEPCK) gene expression and enzyme activity in liver were studied in rats fasted for 12 hours before and after partial hepatectomy, sham operation or no operation. Transcriptional activity and mRNA levels decreased in regenerating liver compared to sham-operated and unoperated controls. In contrast, PEPCK enzyme activity in regenerating liver was similar to that in the livers of sham-operated and unoperated controls. Since all the animals were fasted the decrease in transcription is probably caused by some factor other than insulin, the known repressor of PEPCK gene expression.

Animals↗
PubMed1991

Overexpression of the relA gene in Escherichia coli.

Intracellular levels of guanosine 3',5'-bispyrophosphate (ppGpp) governed by the relA gene are normally regulated by aminoacyl-tRNA availability for protein synthesis. An experimental system is described in which cellular levels of ppGpp are controlled instead by induction of plasmid pKK223-3 derivatives with the relA structural gene, or portions thereof, under control of the Ptac promoter. In amino acid-rich media, isopropyl-1-thio-beta-D-galactopyranoside induction of transcription of the wild type relA gene in pSM10 yields about a 100-fold overexpression of a metabolically stable, full length (743 amino acid) RelA protein to levels approximating the number of cellular ribosomes. This overexpression is accompanied by a roughly parallel and relC-dependent elevation of ppGpp levels. Induction of a relA gene deletion mutant in pSM11 containing 455 amino-terminal amino acids results in much lower levels of expression of a metabolically unstable 55-kDa protein and elevated ppGpp levels that are almost equivalent to induced pSM10 and are relC-independent. Induction of a larger deletion in pSM12 containing 331 amino-terminal amino acids does not provoke ppGpp accumulation. We are able to elicit high levels of ppGpp without changing nutritional abundance and without massive overexpression of the RelA protein by inducing the metabolically unstable, truncated RelA protein. We find the effects of elevated ppGpp levels to include a slowing of growth, an inhibition of stable RNA accumulation, an inhibition of cellular rrn P1 promoter activities as measured by primer extension, and changes in the pattern of gene expression viewed by two-dimensional electrophoresis of cellular proteins.

Base Sequence↗
PubMed1991

Hyperfunctional G proteins in mononuclear leukocytes of patients with mania.

In a recent study, we found that lithium inhibits the function of guanine nucleotide-binding proteins, implicating G proteins as the common site for both the antimanic and antidepressant therapeutic effects of lithium. These findings may also suggest that an altered G protein function is of pathophysiological importance in bipolar affective disorder. In the present study, the coupling of both muscarinic-cholinergic receptors and beta-adrenergic receptors to pertussis toxin-sensitive G proteins or cholera toxin-sensitive G proteins was compared among untreated manic patients, lithium-treated euthymic bipolar patients, and healthy volunteers using mononuclear leukocyte (MNL) membrane preparations. Hyperactive function of G proteins was detected in untreated manic patients. Both isoproterenol-induced and carbamylcholine-induced increases in Gpp(NH)p binding capacity were twofold to threefold higher than the increases observed in healthy volunteers. On the other hand, lithium-treated euthymic bipolar patients showed G protein responses to agonist activation that were no different from the healthy volunteers. Altered G protein function may be of pathophysiological importance in bipolar affective disorder.

Adenosine Diphosphate↗