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Biomedical subjects

W Kiefer

Publications and source records attributed to W Kiefer.

At least 55 records · Page 3Linked to original sources
PubMed1997

Synthesis and evaluation of a novel series of pyrrolizine derivatives as dual cyclooxygenase-1 and 5-lipoxygenase inhibitors.

The aim of our study was to investigate structure activity relationship following the replacement of the 6-phenyl substituent at the 6,7-diaryl-2,3-dihydropyrrolizine template by various heteroaromatic residues. In this context we developed a new, efficient, and highly sensitive test method for the screening of dual cyclooxygenase-1 (COX-1) and 5-lipoxygenase (5-LOX) inhibitors. We used human platelets as a source of COX-1 and human PMNLs as a source of 5-LOX. Both cell types were isolated from the same volume of blood. PGE2 and LTB4 respectively were determined by highly selective and sensitive ELISA kits, using monoclonal antibodies. For a single determination at most 0.5 mL whole blood is needed.

Arachidonate 5-Lipoxygenase↗
PubMed1997

Photochemical and photobiological studies with acridine and phenanthridine hydroperoxides in cell-free DNA.

The acridine and phenanthridine hydroperoxides 3 and 7 were synthesized as photochemical hydroxyl radical sources for oxidative DNA damage studies. The generation of hydroxyl radicals upon UVA irradiation (lambda = 350 nm) was verified by trapping experiments with 5,5-dimethyl-1-pyrroline N-oxide and benzene. The enzymatic assays of the damage in cell-free DNA from bacteriophage PM2 caused by the acridine and phenanthridine hydroperoxides 3 and 7 under near-UVA irradiation revealed a wide range of DNA modifications. Particularly, extensive single-strand break formation and DNA base modifications sensitive to formamidopyrimidine DNA glycosylase (Fpg protein) were observed. In the photooxidation of calf thymus DNA, up to 0.69 +/- 0.03% 8-oxo-7,8-dihydroguanine was formed by the hydroperoxides 3 and 7 on irradiation, whose yield was reduced up to 40% in the presence of the hydroxyl radical scavengers mannitol and tert-butanol. The acridine and phenanthridine hydroperoxides 3 and 7 also induce DNA damage through the type I photooxidation process, for which photoinduced electron transfer from 2'-deoxyguanosine to the singlet states of 3 and 7 was estimated by the Rehm-Weller equation to possess a negative Gibb's free energy of ca -5 kcal/ mol. Control experiments with the sensitizers acridine 1 and the acridine alcohol 4 in calf thymus and PM2 DNA confirmed the photosensitizing propensity of the UVA-absorbing chromophores. The present study emphasizes that for the development of selective and efficient photochemical hydroxyl radical sources, chromophores with low photosensitizing ability must be chosen to avoid type I and type II photooxidation processes.

Cell-Free System↗
PubMed1996

Applications of the optical trapping technique to analyze chemical reactions in single emulsion particles.

The applicability of the single beam gradient force optical trap and the optical levitation technique to investigate dynamic processes in microparticles is examined. The device allows to follow chemical reactions, like the emulsion polymerization and the ester hydrolysis reaction, in single emulsion droplets. Furthermore the usability of optical traps to investigate living cells is demonstrated.

Journal Article↗
PubMed1996

Matrix-isolation Raman spectroscopy and photochemistry of carbonyl-metal-silyl complexes.

To study the photochemistry of metal-silyl complexes the compounds Cp(CO)(2)Fe-SiH(2)(CH(3)) (Cp = eta(5)-C(5)H(5)) and Cp*(CO)(2)((CH(3))(3)P)Mo-SiH(3) (Cp* = eta(5)-C(5)(CH(3))(5)) have been isolated in krypton or nitrogen matrices and subsequently detected by Raman spectroscopy. Vibrational assignments for the two compounds are given. Furthermore, differences in the Raman spectra induced by UV irradiation are discussed.

Journal Article↗
PubMed1996

Chemical composition and reaction analysis of single aerosol particles.

In situ measurements of gas-liquid surface reactions of single aerosol microdroplets are presented. By means of optical levitation in combination with elastic (Mie) and inelastic (Raman) light scattering it is possible to get information on the chemistry of e.g. acid/base reactions as well as the physical behavior of single microparticles.

Journal Article↗
PubMed1995

Non-steroidal anti-inflammatory agents, Part 19. E-2-pyrrolizin-5-yl acrylic acids as potent dual or selective inhibitors of bovine cyclooxygenase and 5-lipoxygenase.

The pyrrolizinyl substituted acrylic acid derivatives represent another class of dual and selective inhibitors of cyclooxygenase and 5-lipoxygenase. By modifying their substitution pattern at the phenyl moiety of C-6 the balance between the activity against cyclooxygenase and against 5-lipoxygenase can be shifted. Structure-activity relationships are discussed. Compound 6k is the most potent and well-balanced dual inhibitor of both enzymes, while the highest selectivity of lipoxygenase inhibition was found for 6j. The activity and selectivity of compounds with an additional sulfur moiety depend on the oxidation status of this atom, giving an indication of the discussed coupling between peroxidase and cyclooxygenase. The inhibition of cyclooxygenase was determined in a bovine thrombocyte intact cell assay and that of 5-lipoxygenase using intact bovine PMNLs.

Acrylates↗
PubMed1994

(6,7-Diaryldihydropyrrolizin-5-yl)acetic acids, a novel class of potent dual inhibitors of both cyclooxygenase and 5-lipoxygenase.

A novel class of nonantioxidant dual inhibitors of both CO and 5-LO is described. The balance between the activity against CO and 5-LO can be shifted by modifying the substitution pattern of the phenyl moiety at the 6-position of the pyrrolizine ring. Structure-activity relationships are discussed. Compound 3e with a 4-Cl substituent (IC50 = 0.21 microM (CO); 0.18 microM (5-LO)) and 3n with a 4-OCH3 substituent (IC50 = 0.1 microM (CO); 0.24 microM (5-LO)) are the most potent and well-balanced dual inhibitors of both enzymes. The inhibition of CO was determined in a bovine thrombocyte intact cell assay and that of 5-LO using intact bovine PMNL. Compound 3e was also investigated in human cells.

Acetates↗
PubMed1994

Nonsteroidal antiinflammatory agents, XVIII: C-5 functionalized 6,7-diphenyl-2,3-dihydro-1H-pyrrolizines as inhibitors of bovine cyclooxygenase and 5-lipoxygenase.

6-(4-Chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizines with functional groups at position 5 of the heterocyclic moiety were synthesized and tested. To determine their antiinflammatory activity bovine blood was used as enzyme source for the cyclooxygenase and 5-lipoxygenase, respectively. The iminoxy acetic acid derivative and the iminotetrazole selectively inhibit the 5-lipoxygenase, all the other compounds show medium or low affinity to the active sites of cyclooxygenase and 5-lipoxygenase. In general all compounds inhibit 5-lipoxygenase more effectively than cyclooxygenase. Concerning the inhibition of 5-lipoxygenase the most active compounds found are equipotent to the corresponding propionic acid compounds, but they aren't well balanced dual inhibitors as shown for the carboxylic derivatives. A structure activity relationship and the enzyme selectivity are discussed.

Animals↗
PubMed1993

The role of the lateral suprasylvian visual cortex of the cat in object-background interactions: permanent deficits following lesions.

The contribution of the lateral suprasylvian cortex to pattern recognition was studied by behavioural detection experiments in combination with bilateral lesions of different parts of the lateral suprasylvian areas (LSA) and area 7 in seven cats. In a two-alternatives forced choice task the cats had to discriminate simple outline patterns which were additively superimposed on a structured visual background made up of broadband Gaussian noise. For various stimulus conditions (moving or stationary patterns and/or background) the detection probability (PD) of the cats was measured as a function of the signal-to-noise ratio (S/N). Each cat was tested before and after the lesion. Four different types of lesion could be distinguished depending on their extent: (1) lesion of parts of the (LSA); (2) lesion of parts of the LSA with undercutting of areas 17, 18 and 19; (3) lesion of area 7; (4) lesion of area 7 and parts of the LSA. 1. We found that a large bilateral lesion of the LSA led to significant deficits in all test situations which were dependent on the existence of relative velocity of moving patterns against a structured background. The ability of the cats to discriminate simple outline patterns which were kept stationary was not reduced. On the contrary, when they were tested with stationary and moving patterns on unfocused (empty) backgrounds, we found, to our great surprise, that the performance of the lesioned cats was significantly improved compared with intact animals. As these lesioned cats had no deficits with moving patterns on a uniformly grey background, we conclude that the deficits with the moving patterns must have been caused by interactions between patterns and background, and not by movement of a pattern per se. 2. As soon as the lesion of the LSA was extended by a bilateral undercutting of areas 17, 18 and 19 we found very severe deficits in all test situations, regardless of whether the patterns were moving or kept stationary, or whether they were superimposed on a background or not. The most substantial deficits occurred when the patterns were moving on a stationary background. In these situations the cats were no longer able to reach the 84% correct criterion. Again, the cats were able to reach criterion with moving patterns on a uniformly grey background indicating that this deficit is probably caused by the interaction of patterns and background and not by motion of the patterns per se.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Lesion of the suprasylvian cortex impairs depth perception of cats.

Using a 2-alternative-forced-choice-procedure on a jumping stand, four adult cats were trained to make simple depth discriminations. They were tested binocularly and monocularly before and after bilateral lesions of different parts of the lateral suprasylvian cortex. Our results give support to a functional segregation between the lateral suprasylvian visual areas (LSA) and area 7. Lesion of any of these areas impairs the ability to use binocular depth cues. However, lesion of LSA more severely impairs the ability to use monocular depth cues whereas binocular ones can still be used. After lesion of area 7, binocular depth cues can no longer be used. Additional undercutting of areas 17/18/19 leads to a performance similar to that of area 17/18 lesioned cats.

Animals↗
PubMed1989

Considerable deficits in the detection performance of the cat after lesion of the suprasylvian visual cortex.

The ability of two cats to discriminate between two geometrical outline patterns in the presence of superimposed structured background was tested before and after bilateral removal of the lateral suprasylvian visual areas (PMLS, PLLS, AMLS, ALLS, part of area 7). There were mild deficits when patterns and background were kept stationary; these deficits may be due to a partial undercutting of areas 17, 18 and 19. However, there was a severe impairment in performance when the patterns were moving on a stationary background which may be due to loss of the suprasylvian visual areas. Movement of the background relative to the figure resulted in an intermediate detection deficit.

Animals↗
PubMed1989

Melatonin administered systemically alters the properties of visual cortex cells in cat: further evidence for a role in visual information processing.

The effects of melatonin given systemically at night-time were investigated in the visual system of cats by means of electrophysiological recordings from single cells in the striate cortex (area 17). Following intravenous injection of melatonin, the spontaneous discharge rate (SDR) was found to decrease in the majority of units when compared to control situations. In addition, the amplitude of responses to photic stimulation (moved light bars on a dark background) was augmented. These results reveal that, following application of melatonin, an improved signal-to-noise ratio is found in response to visual stimuli. The physiological source and putative action sites of melatonin are discussed with regard to its physiological role as a neuromodulating substance. The present data, in addition to previous work, suggest that melatonin is involved in visual information processing such as object detection and dark adaptation.

Action Potentials↗
PubMed1988

Lesion of areas 17/18/19: effects on the cat's performance in a binary detection task.

The ability of two cats to discriminate between two geometrical outline patterns in the presence of superimposed Gaussian visual noise-i.e. in a binary detection task--was tested before and after bilateral removal of cortical areas 17, 18 and 19. The detection probability PD was measured as a function of the signal-to-noise ratio. After a lesion of areas 17, 18 and 19 both cats were unable to carry out the discrimination tasks. Their detection performance dropped to chance level, but after an extensive phase of retraining (3 months) they regained the ability to discriminate visual patterns. It was thus possible to obtain detection curves and to determine a measure of a performance which is predominantly bound to be mediated by extra-geniculo-cortical systems. The detection capacity was abnormally low with both large and small patterns. However, the detection of stationary small patterns was similar to the performance of cats with 17/18 lesions; the detection of stationary large patterns was only slightly better than the detection of small patterns and much worse than the comparable performance of cats with 17/18 lesions. Furthermore the cats with lesions of areas 17/18/19 were unable to discriminate moving patterns, their performances being at chance level, whereas for the cats with 17/18 lesions the detection of moving and stationary patterns was equal.

Animals↗
PubMed1976

Genetic transfer of Salmonella O antigens to Escherichia coli O8.

His+ hybrids from a cross between a Salmonella typhimurium donor and an Escherichia coli O8 recipient expressed E. coli O8 specificity and in addition Salmonella O4,12-specificity. This indicated that the recipients had received the his-linked donor rfb cluster determining the synthesis of S. typhimurium O-specific repeat units and that the rfb genes of both mating partners are functional in these hybrids. Chemical analyses showed that the hybrids contained an E. coli O8 lipopolysaccharide (O antigen) and a S. typhimurium specific lipopolysaccharide with only one O-specific repeat unit (SR antigen). O8-negative mutants selected from the O8-positive hybrids retained the Salmonella O-specificity and represent semi-rough (SR) forms, because the rfc gene(s) determining the polymerization of repeat units has not been transferred. Attempts to introduce the S. typhimurium rfc locus into E. coli O8 remained unsuccessful. Crosses between a S. typhi donor and E. coli O8 gave rise to smooth (S) and SR His+ recombinants exhibiting only S. typhi O-specificity. The smooth recombinants are assumed to have obtained the his-linked rfb cluster and in addition the rfc gene(s) of the donor. The exchange of the rfb region of such smooth recombinants by that of a S. typhimurium donor led to smooth hybrids with O4,(5), 12-specificity. The phenotypically smooth recombinants exhibited concomitantly S- and SR-lipopolysaccharides of S. typhi and S. typhimurium O-specificity, respectively.

Antigens, Bacterial↗