Biomedical subjects

A Löw

Publications and source records attributed to A Löw.

11 recordsLinked to original sources

PubMed2000

Event-related potentials in a working-memory task in schizophrenics and controls.

Event-related potentials (ERPs) were recorded from 65 channels in 12 schizophrenics and 12 age- and sex-matched controls during a delayed matching-to-sample design with variation of working-memory (WM) challenge: following a 500 ms visual sample stimulus (called S1, two diamonds varying in size, rotation angle and vertical position), the same pattern was either presented throughout a 6s retention interval (no challenge) or a diamond pattern differing from the first one in at least one dimension was presented during this interval (WM challenge). The 500 ms matching stimulus (called S2) comprised one diamond, which had to be matched for identity to either the left or the right diamond of the sample stimulus. The topographical distribution of ERPs during an interval of 500 ms after S1-onset, 5s of the retention interval, a 500 ms-interval preceding the S2, and a 1s postimperative interval were evaluated. No WM challenge during the retention interval induced a right-posterior accentuation of the slow negative potentials in either group, while WM challenge evoked a tendency for left-hemispheric negativity in controls, but not in patients. Patients exhibited a postimperative negative variation (PINV) with left-anterior focus irrespective of the preceding WM challenge, while in controls, the left-anterior PINV was found only following WM challenge. In schizophrenic patients the lack of a left-anterior accentuation of negative ERPs under WM challenge might be related to WM dysfunction, and the condition-independent PINV might be considered either the consequence of this dysfunction or indication of processes related more to the diagnoses than to WM-challenge and -dysfunction.

Adult↗

PubMed1999

Determining working memory from ERP topography.

Event-related potentials were recorded during a delayed matching-to-sample design from 17 volunteers (5 f) using high-resolution (65 channels) EEG-recordings. In the two-stimulus paradigm, the 500-ms stimulus S1 comprised a visual pattern of two diamonds differing in size, angular rotation and location; in the delay period, Working Memory (WM) load was varied in the following way: a stimulus-free interval of 1 s was followed by a 6-s presentation either of a pattern identical to the S1 (low WM load) or of a pattern differing from S1 (high WM load). The 500-ms stimulus S2 comprised one diamond; the subject's task was to indicate by left- or right-hand (respectively) button press, whether the S2 matched the (a) left- or (b) right-positioned S1-diamond, or (c) did not match at all (NoGo). The topographical distribution of activity in the time intervals (a) following S1-offset, (b) during the WM manipulation interval and (c) prior to S2 were evaluated in the signal (scalp potential) and source (Minimum Norm) space. Following S1-offset the ERP pattern was characterised by negativity over posterior areas, slightly more so over the right hemisphere. In the subsequent 6-s interval high WM load elicited a larger negative slow ERP than low WM load, the negativity increase due to high WM load being larger over frontal than central areas. Source modelling indicated activity in anterior areas under high, and posterior activity under low WM load. Asymmetry of activity, although indicating a shift to left-hemispheric activity under high compared to low WM load, varied considerably between subjects. Results suggest that high-resolution ERP recordings allow to examine cortical activity during WM challenge.

Adolescent↗

PubMed1994

Cyclic hexapeptide NK-2 antagonists.

The synthesis of 11 cyclic hexapeptides, some of which contain a carbohydrate side chain moiety, is described in this paper. A glycosylamine was coupled without hydroxyl protecting groups either directly or via a butyric acid spacer to the side chain of glutamic acid, leading to beta-N-glycosylated peptides. All peptides described are selective NK-2 antagonists. The binding affinity to the NK-2-receptor ranges from 7 x 10(-7) to 1 x 10(-8) M, whereas at the NK-1 receptor the IC50 was > 10(-5) M with the exception of cyclo(-Lys(Boc)-Trp-Phe-Gly-Leu-D-Leu-) (I), which shows low affinity to the NK-1 receptor (IC50 = 9 x 10(-6) M). The antagonist activity is determined in the hamster trachea assay. pA2-Values range from 7.1 to 7.8. The results demonstrate the broad range of side chains which can be accommodated at the glutamine position without a major drop in activity. The different charges of the lysine and the glutamic acid peptides indicate that the interaction with the receptor at this position is not determined by ionic forces. Rather, we expect that conformational flexibility allows differently charged amino acid residues to be accommodated by the receptor.

Amino Acid Sequence↗

PubMed1993

[Carbohydrate building blocks for the construction of tumor-associated antigens. Synthesis of Lewis Y determinants].

The synthesis of the ethoxycarbonyloctanyl glycoside of the Lewis-Y (Ley) tetrasaccharide, a part of complex glycosphingolipids, was based on the trichloroacetimidate method for glycoside synthesis. The regioselective introduction of protective groups and the high yield of epimers of the azidonitration reaction applied to O-[2,3,4-tri-O-acetyl-6-O-[dimethyl-(2,3-dimethyl-2-butyl)silyl]-beta-D- galactopyranosyl]-(1-->4)-3-O-acetyl-1,5-anhydro-6-O-[dimet hyl-(2,3- dimethyl-2-butyl)silyl]-D-arabino-hex-1-enitol led to a lactosamine acceptor molecule. The double specific introduction of an alpha-L-fucosyl group in high yield gave a protected Ley-tetrasaccharide. After activation to give the alpha-trichloroacetimidate, specific beta-glycosylation with 8-ethoxycarbonyl octanol under SN 2 condition, followed by cleavage of all protective groups led to the tetrasaccharide, alpha-L-Fucp-(1-->2)-beta-D-galp-(1-->4)-[alpha-L-fucp-(1--> 3)]-beta-D- GlcpNAcO(CH2)8CO2Et in high yield.

Antigens, Neoplasm↗

PubMed1993

Affinity labeling of c-H-ras p21 consensus elements with periodate-oxidized GDP and GTP.

The amino acid sequence motifs of human c-H-ras p21 involved in the interaction with guanosine nucleotides were cross-linked to in situ periodate-oxidized [alpha-32P]GDP or [alpha-32P]GTP. Site-specific reaction was achieved by cross-linking conserved lysine residues close to the G-nucleotide binding site of p21 with the 2',3'-dialdehyde derivatives of GDP or GTP under kinetically controlled conditions. After endoproteinase Asp-N digestion, HPLC separation of 32P-labeled peptides and N-terminal microsequence analysis, two single lysine residues, namely, K117 and K147, which are parts of the N-K-X-D and S-A-K/L consensus elements of ras proteins, respectively, were identified. No significant divergences in the position and extent of covalent modification could be detected between p21.GDP and p21.GTP. This is in contrast to Thermus thermophilus EF-Tu.GDP and EF-Tu.GTP, which were investigated with the same technique [Peter, M. E., Wittmann-Liebold, B. & Sprinzl, M. (1988) Biochemistry 27, 9132-9139] and which exhibited considerable differences in cross-linking efficiency in the GTP form as compared to the GDP form of the protein. The described affinity labeling technique of cross-linking [alpha-32P]GTP with GTP-binding proteins can be used as a general analytical method for the detection and identification of consensus elements in GTPases from different organisms.

Affinity Labels↗

PubMed1993

Nucleotide binding and GTP hydrolysis by the 21-kDa product of the c-H-ras gene as monitored by proton-NMR spectroscopy.

Proton-NMR signals in the downfield region (below approximately 10 ppm) have been shown to provide a useful spectroscopic window to monitor the binding of guanine nucleotides to the active site of GTP/GDP-binding proteins via H-bonds, as specified here by the 21-kDa product of the c-H-ras gene (p21). The time course of the intensity change of certain peaks upon addition of GTP to nucleotide-free p21 corresponds to the GTP hydrolysis rate as determined by HPLC. Though there are fewer potential H-bond acceptors in the GDP-bound protein than in the GTP complex, more downfield peaks are found in the former complex, suggesting tighter binding of GDP. Moreover, inspection of the downfield proton-NMR spectra permits rapid detection of subtle changes of the active site induced by complexation with slowly hydrolyzing GTP analogues resulting from mutations of the amino acid sequence, especially in the phosphate binding loop. Our studies strongly suggest that no major conformational change of the phosphate-binding region occurs upon nucleotide complexation that precedes the catalytic step. Besides, it is suspected that the Ser17 hydroxyl group is involved in nucleotide binding and GTP hydrolysis.

Binding Sites↗

PubMed1992

Affinity labeling of GTP-binding proteins in cellular extracts.

GTP-binding proteins in cellular extracts from Escherichia coli, Thermus thermophilus, yeast, wheat germ or calf thymus were identified using in situ periodate-oxidized [alpha-32P]GTP as affinity label. Site-specific reaction of individual GTP-binding proteins was achieved by cross-linking the protein-bound 2',3'-dialdehyde derivative of GTP with the single lysine residue of the conserved NKXD sequence through Schiff's base formation and subsequent cyanoborohydride reduction. Labeled GTP-binding proteins from prokaryotic or eukaryotic cell homogenates were separated by polyacrylamide gel electrophoresis and visualized by autoradiography. In addition cross-linking of [alpha-32P]GTP with GTP-binding proteins was demonstrated in model systems using different purified GTPases, human c-H-ras p21, transducin from bovine retina, polypeptide elongation factor Tu (EF-Tu) from T. thermophilus and initiation factor 2 (IF2) from T. thermophilus. The described affinity labeling technique can serve as an analytical method for the identification of GTPases belonging to the classes of ras-proteins, elongation and initiation factors, and heterotrimeric signal transducing G-proteins.

Affinity Labels↗

PubMed1988

Molecular consequences of truncations of the first exon for in vitro splicing of yeast actin pre-mRNA.

A defined minimum length of the first exon is required for the generation of spliced products from a synthetic yeast actin mRNA-precursor in vitro. If the first exon is 1, 2, 3 or 5 nucleotides long, only the first step of the splicing reaction can take place. A transcript starting with the first nucleotide of the intron does not get converted into any of the normally obtained splicing products or intermediates. On the other hand, spliceosome assembly does not depend on the presence of a first exon.

Actins↗

PubMed1985

The nonspecific clearance function of the reticuloendothelial system in patients with immune complex mediated diseases before and after therapeutic plasmapheresis.

The nonspecific clearance function of the reticuloendothelial system (RES) in six patients with immune complex mediated systemic vasculitis was determined by the evaluation of the disappearance rate of technetium 99m labelled microaggregated human serum albumin colloid (MHAC) injected IV before and after therapeutic plasma exchange. Three patients with systemic lupus erythematosus (SLE) and one patient with immune complex vasculitis (ICV) exhibited a significant clinical improvement after plasmapheresis which was paralleled by an accelerated MHAC elimination rate following plasma exchange therapy. One patient with ICV and unresponsive to plasma exchange showed delayed MHAC elimination. In one patient with myasthenia gravis (MG), the elimination rate was not altered by plasmapheresis. The data obtained indicate that nonspecific clearance of the RES may be one effect of plasma exchange therapy in patients with immune complex mediated diseases.

Adolescent↗

PubMed1984

[Combined bone marrow and skeletal scintigraphy in osseous and myelogenous diseases].

In 87 patients with proved diagnosis and a normal or pathologic bone scan (BS) in addition a bone marrow scan (BMS) was performed using a 99mtechnetium-labelled microcolloid. The analysis of scintigraphic findings included those obtained by other investigations shows that in these selected patients a false normal or false positive interpretation would have been resulted in 18% performing the BS only. Both methods BS and BMS were capable of diagnosing the correct stage of disease in all patients. The results indicate an augmentation of diagnostic facilities by the BMS in diseases affecting bone or bone marrow.

Adult↗

PubMed1983

Increased serum concentration of free L-triiodothyronine in patients treated with L-thyroxine.

This study demonstrates that in spite of measured normal concentrations of carrier proteins one cannot deduce in all cases a normal fT3 from a normal level of TT3 when l-thyroxine given for diagnostic or therapeutic purposes is present in excess. The displacement of l-triiodothyronine from its binding sites is shown in 35 patients with non-toxic goitre who received an oral dose of 200 micrograms l-thyroxine/die for two weeks. Apart from a significant increase of TT4 (from 7.85 to 14.21 micrograms/dl equal + 81%) and of fT4 (from 1.58 to 3.7 ng/dl equal + 134%) there is only a slight increase in TT3 from 148 to 158 ng/dl (equal + 10%) after 14 days of treatment. By contrast fT3 rises clearly from 4.97 to 8.07 pg/ml equal + 63% (normal range: 2.8-5.6 pg/ml). Compared with the increase of TT3 (+ 10%) the free T3 rises by a factor of 6.3 (63%/10%). On account of higher affinity of l-thyroxine to binding proteins the free T4 is influenced to a lesser degree. Compared with the increase of TT4 (+ 81%) free T4 rises by a factor of 1.6 (134%/81%). It is supposed that the serum concentration of free T3 can be increased despite a normal concentration of TT3 when l-thyroxine is present in excess. Therefore, for laboratory work fT3 should be assigned a higher validity than TT3 when patients are treated with comparatively high doses of l-thyroxine.

Adult↗