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B Schütz

Publications and source records attributed to B Schütz.

18 recordsLinked to original sources
PubMed2001

Independent patterns of transcription for the products of the rat cholinergic gene locus.

The cholinergic phenotype requires the expression of the vesicular acetylcholine transporter and choline acetyltransferase proteins. Both genes are encoded at one chromosomal location called the cholinergic gene locus. We have identified by in situ hybridization histochemistry distinct patterns of transcription from the cholinergic gene locus in the subdivisions of the rat cholinergic nervous system. The vesicular acetylcholine transporter and choline acetyltransferase are co-expressed in cholinergic neurons at all developmental stages in all major types of cholinergic neurons. The relative levels of vesicular acetylcholine transporter and choline acetyltransferase transcripts, however, change substantially during development in the CNS. They also differ dramatically in distinct subdivisions of the mature cholinergic nervous system, with vesicular acetylcholine transporter mRNA expressed at high levels relative to choline acetyltransferase mRNA in the peripheral nervous system, but at equivalent levels in the CNS. Expression of the R-exon, the presumptive first non-coding exon common to both the vesicular acetylcholine transporter and choline acetyltransferase, was not detectable at any developmental stage in any of the cholinergic neuronal subtypes in the rat nervous system. Thus, in contrast to less complex metazoan organisms, production of the vesicular acetylcholine transporter and choline acetyltransferase via a common differentially spliced transcript does not seem to occur to a significant extent in the rat. We suggest that separate transcriptional start sites within the cholinergic gene locus control vesicular acetylcholine transporter and choline acetyltransferase transcription, while additional elements are responsible for the specific transcriptional control of the entire locus in cholinergic versus non-cholinergic neurons. Independent transcription of the vesicular acetylcholine transporter and choline acetyltransferase genes provides a mechanism for regulating the relative expression of these two proteins to fine-tune acetylcholine quantal size in different types of cholinergic neurons, both centrally and peripherally.

Acetylcholine↗
PubMed2000

Somatomotor neuron-specific expression of the human cholinergic gene locus in transgenic mice.

We examined the expression pattern of the vesicular acetylcholine transporter in the mouse nervous system, using rodent-specific riboprobes and antibodies, prior to comparing it with the distribution of vesicular acetylcholine transporter expressed from a human transgene in the mouse, using riboprobes and antibodies specific for human. Endogenous vesicular acetylcholine transporter expression was high in spinal and brainstem somatomotor neurons, vagal visceromotor neurons, and postganglionic parasympathetic neurons, moderate in basal forebrain and brainstem projection neurons and striatal interneurons, and low in intestinal intrinsic neurons. Vesicular acetylcholine transporter expression in intrinsic cortical neurons was restricted to the entorhinal cortex. The sequence of the mouse cholinergic gene locus to 5.1kb upstream of the start of transcription of the vesicular acetylcholine transporter gene was determined and compared with the corresponding region of the human gene. Cis-regulatory domains implicated previously in human or rat cholinergic gene regulation are highly conserved in mouse, indicating their probable relevance to the regulation of the mammalian cholinergic gene locus in vivo. Mouse lines were established containing a human transgene that included the vesicular acetylcholine transporter gene and sequences spanning 5kb upstream and 1.8kb downstream of the vesicular acetylcholine transporter open reading frame. In this transgene, the intact human vesicular acetylcholine transporter was able to act as its own reporter. This allowed elements within the vesicular acetylcholine transporter open reading frame itself, shown previously to affect transcription in vitro, to be assessed in vivo with antibodies and riboprobes that reliably distinguished between human and mouse vesicular acetylcholine transporters and their messenger RNAs. Expression of the human vesicular acetylcholine transporter was restricted to mouse cholinergic somatomotor neurons in the spinal cord and brainstem, but absent from other central and peripheral cholinergic neurons. The mouse appears to be an appropriate model for the study of the genetic regulation of the cholinergic gene locus, and the physiology and neurochemistry of the mammalian cholinergic nervous system, although differences exist in the distribution of cortical cholinergic neurons between the mouse and other mammals. The somatomotor neuron-specific expression pattern of the transgenic human vesicular acetylcholine transporter suggests a mosaic model for cholinergic gene locus regulation in separate subdivisions of the mammalian cholinergic nervous system.

Acetylcholine↗
PubMed1999

Candida albicans clinical isolates inactivated by formalin with different adherence to buccal epithelial cells induce proinflammatory and regulatory cytokines in human peripheral blood mononuclear cells.

Besides the activation of phagocytes, the release of cytokines is the most important immunological defence mechanism of an organism against infection with Candida albicans. On the other hand cytokines induced in the organism by the yeast itself are able to modulate the immune responses of the host. We investigated whether eight clinically isolated strains of C. albicans inactivated by formalin as well as a laboratory strain were able to induce proinflammatory and regulatory cytokines in peripheral blood mononuclear cells (PBMC) of four different donors. Under our assay conditions the yeast strains induced the cytokines interleukin-1 beta (IL-1 beta), interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) in PBMC to varying extents, but not the cytokine interleukin-4 (IL-4). We observed a difference in the reaction of the individual donors to the stimulus C. albicans but on the other hand the extent of the cytokine signal seemed to be dependent on the yeast strain as well. No correlation was found between the ability of the individual C. albicans strains to induce cytokines in PBMC and their ability to adhere to buccal epithelial cells. Determination of the cytokine induction potential of C. albicans strains possibly may contribute to the detection of new virulence factors of this yeast.

Candida albicans↗
PubMed1998

Vesicular amine transporter expression and isoform selection in developing brain, peripheral nervous system and gut.

The vesicular monoamine transporters VMAT1 and VMAT2 are essential components of monoaminergic neurons and endocrine cells whose expression in development may provide insight into lineage pathways for chemical coding in the diffuse neuroendocrine system. Thus, the brain is a compartment in which only monoaminergic neurons are generated, the gut epithelium generates only endocrine monoamine-containing cells, and the neural crest produces both autonomic monoaminergic neurons and endocrine/paracrine monoaminergic cells. Selection of either the VMAT1 or VMAT2 isoform was examined in these three compartments during development. In the central nervous system VMAT2, but not VMAT1, was expressed in neuroepithelial cells by embryonic day 12 (E12), and all major monoaminergic cell groups by E14. Thalamocortical and hypothalamic neurons that do not express VMAT2 in adulthood were transiently VMAT2-positive from E16 to postnatal day 6 (P6). EC cells of the gut expressed exclusively VMAT1 from E19 on, while histamine-containing enterochromaffin-like (ECL) cells of the stomach expressed only VMAT2 by E19 and throughout postnatal development. VMAT2 and the vesicular acetylcholine transporter VAChT were co-expressed in early development of the primary sympathetic chain as well as in the cranial parasympathetic ganglia. VAChT was progressively restricted to a small population of VMAT2-negative post-ganglionic neurons in the adult sympathetic chain, while VMAT2 expression persisted in sympathetic principal ganglion and SIF cells but was eventually extinguished in cranial parasympathetic ganglia. VMAT1 was co-expressed with VAChT and VMAT2 mRNA in the primary sympathetic chain on E12, but progressively restricted to small intensely fluorescent (SIF) and chromaffin cells thereafter. Thus, expression of the vesicular amine transporters appropriate for chemical coding of brain neurons and gut endocrine cells are pre-determined developmentally. In contrast, the neural crest-derived sympathoadrenal and neural crest-derived parasympathetic cell groups examined here initially co-express two or more vesicular amine transporters, followed by extinction of the inappropriate transporter(s) later in development. Some neural crest-derived neuroendocrine cell populations continue to express both isoforms of VMAT even in adulthood. Lineage distinctions in ontogeny of vesicular amine transporter expression in brain, gut and autonomic nervous system make it likely that the same genes are regulated differently in the autonomic nervous system compared to brain and gut.

Animals↗
PubMed1998

Dammarane Triterpenes from the Leaves of Securinega melanthesoides

Two new dammarane triterpenoids, trans-securinegin [(20S)-24-methylidenedammarane-3alpha-yl(2E)-3-(4-hydroxyphenyl)-2-propenate (1)] and cis-securinegin [(20S)-24-methylidenedammarane-3alpha-yl(2Z)-3-(4-hydroxyphenyl)-2-propenate (2)], were isolated from the leaves of Securinega melanthesoides, along with the known compound bergenin. The structures of 1 and 2 were elucidated using spectroscopic methods, mainly 2D NMR techniques.

Journal Article↗
PubMed1997

Target-independent cholinergic differentiation in the rat sympathetic nervous system.

Chemical coding in the sympathetic nervous system involves both noradrenergic and, for a minority of neurons, cholinergic neurotransmission. The expression of the cholinergic phenotype in the developing sympathetic nervous system was examined to determine if coding for cholinergic transmission occurs before or after innervation of peripheral target organs. The vesicular acetylcholine transporter (VAChT) and choline acetyltransferase, the products of the "cholinergic gene locus" determining the cholinergic phenotype, were expressed in principal cells of the paravertebral, but only rarely in prevertebral, sympathetic chains as early as embryonic day 14. A subpopulation of VAChT- and choline acetyltransferase-positive sympathetic ganglion cells persisted throughout development of the stellate and more caudal paravertebral ganglia into anatomically distinct cell groups, and into adulthood. The forepaw eccrine sweat glands, innervated exclusively by the stellate ganglion, received VAChT-positive nerve terminals at least as early as postembryonic day 4, coincident with the development of the sweat glands themselves. These terminals, like the VAChT-positive cell bodies of the developing stellate ganglion, have some noradrenergic traits including expression of tyrosine hydroxylase, but did not express the vesicular monoamine transporter, and are therefore not functionally noradrenergic. Development of the cholinergic phenotype in principal cells of the sympathetic paravertebral ganglia apparently occurs via receipt of instructive cues, or selection, within the sympathetic chain itself or perhaps even during migration of the cells of the neural crest from which the paravertebral ganglia arise.

Animals↗
PubMed1995

Comparative genomic hybridization in the investigation of myeloid leukemias.

Comparative genomic hybridization (CGH) was used for the examination of ten cases of myeloid leukemia (eight acute myeloid leukemias and two myelodysplastic syndromes). In five cases, genomic gains or losses were identified, which mapped to chromosomal regions known to be involved in this group of malignancies. In comparison to the results obtained by banding analysis, discrepancies were found in three of the ten cases; in two cases, chromosomal imbalances were not identified by CGH because they were present only in small subclones. In the other case, there were no evaluable metaphase cells for banding analysis; CGH revealed an overrepresentation of chromosome 8, which was confirmed by interphase cytogenetics with a chromosome 8-specific alphoid probe. All abnormalities revealed by CGH were confirmed by G-banding or subsequent interphase cytogenetic analysis, which demonstrates the high specificity of the method. Furthermore, in all cases, CGH identified the chromosomal imbalances present in the major clone as detected by banding analysis. The good correlation between CGH and chromosome banding results in myeloid leukemias makes this tumor a good model for the assessment of tools that are developed for automated and quantitative CGH analysis.

Aneuploidy↗
PubMed1994

Cloning and structure of a chicken zinc finger cDNA: restricted expression in developing neural crest cells.

The cloning, DNA sequence analysis and expression pattern of a chicken cDNA, cKr2, is described. cKr2 is a 4492-bp cDNA that encodes a 1173-amino-acid (aa) protein with two domains: the N-terminal portion contains 16 zinc fingers (Zf) of the 2Cys + 2His class, while the C-terminal domain contains a stretch of 181 aa which consists of seven consecutive sequence repeats each being 24 aa in length. The aa sequence repeats harbor a putative DNA-binding helix-turn-helix motif. Northern and Western blotting experiments indicate cKr2 expression from days 2 to 12 of development. In situ hybridization and immunohistochemical analyses using an anti-cKr2 antibody and the HNK-1 antibody, a marker of neural crest cells, revealed cKr2 activity in cephalic and trunk neural crest-derived cells. cKr2 is expressed predominantly in differentiating Schwann cells lining the nerves which innervate the branchial arches and limb buds, in cells of the sympathetic ganglia and aortic plexus, and in putative neuroblasts of dorsal root ganglia. The nuclear localization of the cKr2-encoded protein is consistent with its presumed role as a transcription factor.

Amino Acid Sequence↗
PubMed1992

Risks of alternative nutrition in infancy: a case report of severe iodine and carnitine deficiency.

A 7.5-month-old infant with failure to thrive, developmental delay, muscular hypotonia, a visible goitre and severe osteopenia is described. Laboratory examination revealed a markedly increased serum TSH with low free T4, severe iodine and carnitine deficiency. The infant was breastfed until the age of 2.5 months and was then given a mixture of almond extract in water. The mother is a strict vegan and the father a lactovegetarian. The nutritional intake of the child was severely depleted in calories (-46%), calcium (-73%) and iodine (-88%). The restrictive alternative nutrition was responsible for the various deficiency disorders.

Carnitine↗
PubMed1991

Reassessment of the v-fms sequence: threonine phosphorylation of the COOH-terminal domain.

The v-fms oncogene product of the McDonough strain of feline sarcoma virus is a member of the receptor tyrosine kinase family. Its cellular counterpart, the c-fms product, is the receptor for colony-stimulating factor 1 (CSF-1) of macrophages. We have reanalyzed the v-fms gene by direct sequencing of a biologically active clone. An additional A nucleotide was detected in position 2810 of the published v-fms sequence. The frameshift changed the COOH-terminal sequence of the v-fms protein from -R-937-G-P-P-L-COOH to -Q-937-R-T-P-P-V-A-R-COOH. Antibodies against a synthetic peptide representing this new sequence precipitated the v-fms proteins from transformed NRK cells as well as from feline sarcoma virus (McDonough)-infected feline fibroblasts. We show by tryptic peptide mapping that threonine 939 present in the new sequence is phosphorylated by a yet unknown serine/threonine kinase in vivo. In chicken fibroblasts expressing the v-fms gene, this phosphorylation clearly depended on the addition of exogenous CSF-1. Furthermore, addition of CSF-1 appeared to activate the serine/threonine kinase, as judged by phosphorylation of the synthetic peptide QRTPPVAR.

Amino Acid Sequence↗
PubMed1991

Transforming mechanism of the feline sarcoma virus encoded v-fms oncogene product.

The v-fms oncogene product encoded by the McDonough strain of feline sarcoma virus (SM-FeSV) is a transmembrane glycoprotein which belongs to the tyrosine kinase receptor family. The cellular counterpart, the c-fms product, is the receptor for macrophage colony stimulating factor (M-CSF or CSF-1). The v-fms and the c-fms product differ structurally only in seven point mutations and in their C-terminal domains. We have corrected the published sequence of the v-fms product and found that the new C-terminal end contains a threonine phosphorylation site (Thr939). This site is phosphorylated in vivo leading to an enhancement of the v-fms-specific tyrosine kinase activity. The extracellular domain of the v-fms product contains 11 N-glycosylation sites. Glycosylation and transport of the v-fms molecules to the plasma membrane are prerequisites for the transforming potential of the virus. Phosphorylation of the v-fms molecules in tyrosine, serine and threonine residues takes place only at the plasma membrane. Coexpression showed that the overexpression of M-CSF and c-fms in fibroblasts leads to cell transformation by an autocrine loop mechanism. This interaction between M-CSF and the c-fms protein also takes place at the plasma membrane. To study the v-fms transforming mechanisms, we have expressed the v-fms oncogene in chicken fibroblasts which are free of the cross-reactive M-CSF. The expression of the v-fms oncogene alone did not cause transformation. However, upon addition of M-CSF, these cells became completely transformed.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1989

Immune-mediated agranulocytosis related to drugs and their metabolites: mode of sensitization and heterogeneity of antibodies.

Two major unresolved problems in drug-related immune agranulocytosis are understanding the mechanism by which sensitization takes place in vivo, and verification of the diagnosis. Using a sensitive, competitive enzyme-linked immunoassay (ELISA) we were able to characterize the causative antibodies in 13 patients with drug-related agranulocytosis [metamizole (n = 5), penicillin (n = 5), dimethylaminophenazone (n = 1), propyphenazone (n = 1) and diclofenac (n = 1)]. Irrespective of the causative drug, the majority of patients appear to have developed autoantibodies (aab) in addition to drug-dependent antibodies (ddab) of the IgG and/or IgM classes. In all cases related to metamizole, and in the single case related to diclofenac, the ddab appeared to recognize only metabolites of the drug since they were reactive in the presence of ex vivo antigens (urine from individuals receiving therapeutic levels of the drugs), but not the native drugs. Only a few ddab were reactive with granulocytes pretreated with the drug (cell-drug complexes); the majority of ddab could not be detected unless the drug or ex vivo antigen was added to the incubation mixture as well as the solution used for subsequent washes. Our results indicate that drugs and/or their metabolites interact with target cells and thereby directly function as immunogenic haptens, even when the drugs do not bind tightly to the cells.

Adolescent↗
PubMed1988

[Disease course in 20 patients with an early diagnosis of phenylketonuria and hyperphenylalaninemia].

Twenty patients with PKU or hyperphenylalaninemia at ages 0.1 to 15.6 years (median age 6.2 years) were studied prospectively. In all children the condition had been diagnosed when they were neonates on the basis of an abnormal Guthrie test. To maintain plasma phenylalanine levels between 0.2-0.5 mM, dietary restriction of phenylalanine to 20-80 mg/kg daily (median 40 mg/kg) was necessary in 14 children. In children above 8 years, however, these plasma levels were frequently exceeded. In 6 children plasma phenylalanine levels were higher than normal diet. Height, weight and head circumference were within normal range in all patients at all ages. Determinations of DQ/IQ were done at 2, 4, 6 and 8 years of age and revealed values between 90-120 with a median of 102 in the 14 patients who were tested. Only 1 patient had IQ levels between 75-85 and attended special school. Nine other patients were in grade school performing averagely or above. This study confirms that early treatment and long-term follow-up of patients with PKU yield good results. Unsolved problems include duration of dietary treatment and the management of pregnancy in women with PKU.

Adolescent↗
PubMed1986

[Pancreas divisum as a possible cause of misinterpretation in ERCP, computed tomography, sonography and MDP].

In 488 patients endoscopic retrograde pancreatography (ERP) revealed a pancreas divisum in 21 (4.3%): in 17/21 patients we found a complete, in 4/21 an incomplete separation of the pancreatic ducts. The pancreas divisum is caused by a malfusion of the ductal system. On examination by ultrasound, computed tomography or hypotonic duodenography this variant can suggest an inflammation or tumour of the head of the pancreas. A definite diagnosis is possible by ERP only. Since the small ventral duct can be confused with an alteration caused by inflammation or by a tumour, to much of contrast medium can be injected. Pancreas divisum is often associated with a chronic pancreatitis which can be demonstrated via ERP of the dorsal duct through the accessory papilla.

Cholangiopancreatography, Endoscopic Retrograde↗
PubMedDate not supplied

From the cholinergic gene locus to the cholinergic neuron.

The cholinergic gene locus (CGL) was first identified in 1994 as the site (human chromosome 10q11.2) at which choline acetyltransferase and a functional vesicular acetylcholine transporter are co-localized. Here, we present recent neuroanatomical, developmental, and evolutionary insights into the chemical coding of cholinergic neurotransmission that have been gleaned from the study of the CGL, and its protein products VAChT and ChAT, which comprise a synthesis-sequestration pathway that functionally defines the cholinergic phenotype.

Animals↗