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Biomedical subjects

K Schott

Publications and source records attributed to K Schott.

At least 19 recordsLinked to original sources
PubMed2005

Stage-dependent BDNF serum concentrations in Alzheimer's disease.

Alzheimer's disease (AD) is characterized by cognitive decline and loss of neurons in specific brain regions. Recent findings have suggested an involvement of brain-derived neurotrophic factor (BDNF) in the pathogenesis of AD. BDNF is an endogenous protein involved in the maintenance of neuronal function, synaptic plasticity and structural integrity in the adult brain. To our knowledge, the present pilot study assessed for the first time BDNF serum and CSF concentrations in 30 patients with different stages of AD in comparison to 10 age-matched non-demendet controls. AD patients were divided in two groups according to their MMSE score: Group 1 (n = 15) in early stages with MMSE scores >or=21 (mean of 25.5) and Group 2 (n = 15) with more severe stages of dementia with MMSE scores <21 (mean of 13.3). As main results, we found in patients with early stages of probable AD significantly increased BDNF serum concentrations as compared to more severe stages of AD (p < 0.0001) and age-matched healthy controls (p = 0.028). BDNF serum values in all AD patients correlated significantly with MMSE scores (r = 0.486; p < 0.0001). Levels of BDNF were below the detection limit of the assay in unconcentrated CSF samples of AD patients and non-demendet controls.In summary, BDNF serum values are increased in early stages of Alzheimer's disease, which may reflect a compensatory repair mechanism in early neurodegeneration and could also contribute to increased degradation of beta-amyloid (Abeta). During the course of the disease, BDNF is decreasing, which correlates with the severity of dementia. The decrease of BDNF may constitute a lack of trophic support with an increase of Abeta accumulation and thus contribute to progressive degeneration of specific regions in the AD-affected brain. BDNF should be further evaluated as a candidate marker for clinical diagnosis and therapeutic monitoring in Alzheimer's disease.

Aged↗
PubMed2005

Diminished production of proinflammatory cytokines in patients with Alzheimer's disease.

Cerebral inflammation as well as systemic immunological alterations have been reported in Alzheimer's disease (AD). We examined the production of the proinflammatory cytokines interleukin-6, interleukin-12, interferon-gamma, and tumor necrosis factor-alpha in whole blood cell cultures of AD patients and age-matched controls. The production of all measured cytokines after mitogen stimulation is significantly decreased in the AD group compared to controls. The results reflect an attenuated secretory activity of monocytes/macrophages, but also of T-helper cells. The data sustain the assumption that a systemic, possibly age-related alteration of immune mechanisms may play a pathogenetic role in the development of AD.

Aged↗
PubMed2002

Increased serum levels of CD95 in Alzheimer's disease.

There is growing evidence for a role of apoptosis in Alzheimer's disease (AD). Recent findings suggest an increased susceptibility of lymphocytes to apoptosis in AD. To prove the hypothesis of systemic alterations in the apoptotic balance in AD, serum and cerebrospinal fluid levels of soluble CD95, which is known to mediate apoptosis, were measured. In the serum, AD patients exhibited significantly higher levels of CD95 than the controls (p = 0.017), suggesting an involvement of peripheral markers in AD.

Aged↗
PubMed2001

A method for soluble overexpression of the alpha7 nicotinic acetylcholine receptor extracellular domain.

We describe the construction of a soluble protein carrying the N-terminal extracellular domain (ECD) of the alpha7 subunit of the nicotinic acetylcholine receptor. The approach was to fuse the alpha7 ECD at the C and N termini of several monomeric and pentameric soluble carrier proteins and to investigate the soluble expression of the product in Escherichia coli. An initial screening of six carrier proteins resulted in the selection of a fusion protein comprising, from the N to the C terminus, the maltose binding protein, a 17-aa linker containing an enterokinase binding site, and the alpha7 ECD. This protein is soluble upon expression in bacteria and is purified by affinity chromatography. It binds the competitive nicotinic antagonist alpha-bungarotoxin with 2.5 microM affinity and displays a CD spectrum corresponding to a folded protein. The method might be suitable to produce large quantities of protein for crystallization and immunochemical experiments.

ATP-Binding Cassette Transporters↗
PubMed1999

Oxaloacetate transport into plant mitochondria

The properties of oxaloacetate (OA) transport into mitochondria from potato (Solanum tuberosum) tuber and pea (Pisum sativum) leaves were studied by measuring the uptake of 14C-labeled OA into liposomes with incorporated mitochondrial membrane proteins preloaded with various dicarboxylates or citrate. OA was found to be transported in an obligatory counterexchange with malate, 2-oxoglutarate, succinate, citrate, or aspartate. Phtalonate inhibited all of these countertransports. OA-malate countertransport was inhibited by 4, 4'-dithiocyanostilbene-2,2'-disulfonate and pyridoxal phosphate, and also by p-chloromercuribenzene sulfonate and mersalyl, indicating that a lysine and a cysteine residue of the translocator protein are involved in the transport. From these and other inhibition studies, we concluded that plant mitochondria contain an OA translocator that differs from all other known mitochondrial translocators. Major functions of this translocator are the export of reducing equivalents from the mitochondria via the malate-OA shuttle and the export of citrate via the citrate-OA shuttle. In the cytosol, citrate can then be converted either into 2-oxoglutarate for use as a carbon skeleton for nitrate assimilation or into acetyl-coenzyme A for use as a precursor for fatty acid elongation or isoprenoid biosynthesis.

Journal Article↗
PubMed1998

Antibrain antibodies in mental disorder: no evidence for antibodies against synaptic membranes.

Antibody reactivity in serum to synaptic membranes from human was investigated in major depressive disorder (N = 20), paranoid schizophrenia (N = 20), schizoaffective psychosis (N = 20), and in controls (N = 20) using Western and Immunoblots and ELISA technique. None of the patients showed a significant immune response to synaptic membranes. There was a base-line activity in both controls and patients with antibodies directed to a double band of proteins at 66kD. These antibodies may represent natural autoantibodies. The authors conclude from this and other studies that there is at present no proof of antibrain antibodies in mental disorder.

Adult↗
PubMed1996

Autoantibody reactivity in serum of patients with Alzheimer's disease and other age-related dementias.

Serum antibodies against a series of antigens, including an organ-specific central nervous system (CNS) antigen and the neurotransmitter serotonin, were investigated in 22 patients with Alzheimer's Disease (n=15) and other age-related dementias (n=7) by indirect immunofluorescence assay and enzyme-linked immunosorbent assay. Patients with dementia showed an increase of antibody-positive sera against nuclear antigen, gastric parietal cells, CNS antigen, gangliosides (Gm1), laminin, and keratin. Alzheimer's Disease patients alone exhibited antibodies against CNS antigen. However, the results do not show sufficient specificity and sensitivity for use as a diagnostic indicator.

Aged↗
PubMed1996

Evidence for the expression of the triosephosphate translocator gene in green and non-green tissue of tomato and potato.

Western blot analysis revealed a cross reaction of an antibody against the spinach triosephosphate translocator with 29 kDa proteins from envelope membranes of plastids from green and red tomato fruits and also of potato tuber amyloplasts. Envelope membranes from potato tubers were isolated from a homogenate of total membranes by isopycnic sucrose density gradient centrifugation. We were able to demonstrate by reverse transcription and sequencing of the PCR product that the mRNA for the triosephosphate translocator in leaves is also present in green and red tomato fruits. The mature protein consists of 330 amino acid residues and is highly homologous to the triosephosphate translocator proteins from potato and tobacco. The PCR product obtained for potato tubers was partly sequenced. It corresponds entirely to the cDNA sequence encoding the potato leaf triosephosphate translocator protein. Evidence for the expression of the triosephosphate translocator gene in various photosynthetic active and inactive tomato tissues (leaf, green fruit, red fruit, root, petal, sepal) and potato tubers was further confirmed by northern blot analysis.

Amino Acid Sequence↗
PubMed1993

Induction of GTP-cyclohydrolase I mRNA expression by lectin activation and interferon-gamma treatment in human cells associated with the immune response.

The development of tetrahydrobiopterin synthesis during lectin stimulation of resting human T lymphocytes (Kerler et al. [1989] FEBS Lett., 250:622-624), the interferon-gamma induced neopterin production by human monocytes/macrophages (Huber et al. [1984] J. Exp. Med., 160:310-316), and the control of tetrahydrobiopterin synthesis in activated T cells by the synergistic action of interferon-gamma and interleukin 2 (Ziegler et al. [1990] J. Biol. Chem. 265:17026-17030) were previously explained by modulation of the apparent GTP-cyclohydrolase I activation. In this study we demonstrate that increases in GTP-cyclohydrolase I activity which occur after lectin induction and after cytokine treatment correlate with increased steady state mRNA levels specific for this enzyme. The enhancement of interferon-gamma induced enzyme activity in primed T cells by interleukin 2 also corresponds to further increases in mRNA expression. The steady state GTP-cyclohydrolase I mRNA levels in primed T cells, however, do not correlate with the steep decline which follows the culmination of enzyme activity 44 hours after treatment. This indicates that the down-regulation of apparent GTP-cyclohydrolase I activity is caused by posttranslational modification of the protein.

Biopterins↗
PubMed1993

Detection of a novel sepiapterin reductase mRNA: assay of mRNA in various cells and tissues of various species.

Fragments of cDNA coding for rat, murine, and human sepiapterin reductase (SR) were amplified by PCR via primer positioning close to the reported 3'-end of the coding region in the rat enzyme. They were sequenced and used as probes for mRNA detection. Northern blot analysis detected two mRNA species for SR. Their sizes were 1.3 and 2.1 kb for rat, 1.3 and 2.3 kb for mouse, and 1.6 and 2.1 kb for human cell lines. Comparison of rat cell lines and rat tissues indicated that in tissues only the 1.3-kb species is present. Washing of the Northern blots under different stringency conditions indicated a more stable interaction of the 1.3-kb mRNA species with the cDNA probe as compared to the 2.3-kb species. The 1.3-kb species corresponds to the reported 28.2-kDa molecular mass of rat SR monomer. SR mRNA expression is absent in the human NK-like cell line YT and in the murine erythroleukemia subclone B8/3, which both lack SR activity. Moreover, the relative mRNA expression correlates with the enzymatic activities of different cell lines within the same species. This indicates that SR activity is regulated by its steady state mRNA levels.

Alcohol Oxidoreductases↗
PubMed1992

Species and tissue specificity of mammalian GTP cyclohydrolase I messenger RNA.

Northern blot analysis of rat RNA from cell lines and isolated organs with a specific rat cDNA probe detected two GTP cyclohydrolase I mRNA species of approx. 1.4 and 3.6 kb. The ratio between these two species varies between 0.6 and 2.4 in different rat organs. Using primers derived from highly conserved regions in the rat and Escherichia coli cDNA sequences a human GTP cyclohydrolase I probe was obtained by means of reverse transcription and PCR (polymerase chain reaction). The human PCR product consisting of 555 bp was cloned and sequenced. It shows a 92% identity with the published sequence of the rat gene. The analysis of various human cell lines with this specific probe shows only one species of GTP cyclohydrolase I mRNA with an approximate size of 3.6 kb.

Amino Acid Sequence↗
PubMed1992

Control of cell-cycle-associated tetrahydrobiopterin synthesis in rat thymocytes.

The cell-cycle progression of rat thymocytes from G0 through G1 to DNA synthesis is associated with a transient synthesis of H4biopterin, the concentration of which reaches a maximum at the time of S-phase entry and then decreases. This synthesis of H4biopterin is controlled by the specific activity of GTP cyclohydrolase I, which peaks in G1/S cells. In contrast, the catalytic activity of sepiapterin reductase remains constant throughout the cell-cycle. At G0 the steady state mRNA levels specific for GTP cyclohydrolase I and sepiapterin reductase, respectively, are below the limits of detection. Both accumulate as the thymocytes progress through the cell-cycle but lack cyclic down regulation. The data indicate that the variations in H4biopterin synthesis during the cell-cycle are caused by growth regulated increase in GTP cyclohydrolase I mRNA expression, with subsequent post-translational inactivation. This latter is likely due to the degree of enzyme phosphorylation.

Alcohol Oxidoreductases↗
PubMed1992

[Results of electroconvulsive therapy in restrictive indications. A retrospective study of 15 years].

In Tübingen ECT is restricted to severely ill patients who do not respond to other somatic therapies; especially to patients with endogenous depression and pernicious catatonia. Between 1976 and 1990, 45 patients were treated with ECT, of whom 22 suffered from endogenous depression and 10 from pernicious catatonia. Thirteen patients with other diagnoses (schizophrenic and schizoaffective psychoses, borderline schizophrenia and obsessive-compulsive disorder) were treated with ECT for severe depressive states after failure of psychopharmacological therapy. A positive therapeutic response to ECT was observed in 46% of patients with endogenous depression and in all 10 with pernicious catatonia. In the patients with schizophrenia and schizoaffective psychosis, borderline schizophrenia and obsessive-compulsive disorder, an amelioration of the depressive or anxiety syndrome was observed only in individual cases. Side effects of ECT were transit syndromes (20%), reversible amnestic syndromes (20%) and cardiac arrhythmias (6%). According to our results, ECT is highly effective in therapy-resistant endogenous depression and pernicious catatonia, and therefore remains a necessary part of psychiatric therapy.

Adolescent↗
PubMed1991

Control of pteridine biosynthesis in the natural killer-like cell line YT.

The natural killer-like cell line YT constitutively expresses GTP-cyclohydrolase activity whereas 6-pyruvoyltetrahydropterin synthase and sepiapterin reductase are absent. The product, dihydroneopterin triphosphate, is dephosphorylated and oxidized causing neopterin to accumulate in the cells. The activities of the H4biopterin synthesizing enzymes are not controlled by IFN-gamma or the synergistic action of both IFN-gamma and IL-2 as has been shown for monocytes/macrophages (Huber C. et al. (1984) J. Exp. Med. 160, 310) and CD4+ T cells, respectively (Ziegler I. et al. (1990) J. Biol. Chem. 265, 17026). Sepiapterin reductase specifically is induced by incubation of the cells with sepiapterin, leaving GTP-cyclohydrolase, 6-pyruvoyltetrahydropterin synthase and other enzymes related to pteridine metabolism (dihydropteridine reductase, dihydrofolate reductase) unaffected. The data indicate that H4biopterin synthesis is individually regulated in the diverse cellular components of the immune system.

Alcohol Oxidoreductases↗