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Biomedical subjects

S Köhler

Publications and source records attributed to S Köhler.

At least 55 records · Page 3Linked to original sources
PubMed1998

Low-density lipoprotein receptor-related protein in atherosclerosis development: up-regulation of gene expression in patients with coronary obstruction.

The low-density lipoprotein receptor-related protein (LRP) is a multifunctional cell-surface receptor that binds and mediates the endocytosis of several structurally and functionally distinct ligands. Involved in a variety of biological processes, including the regulation of the coagulation-fibrinolysis balance, the lipoprotein metabolism, cellular migration, proliferative processes and degenerative diseases, it has very recently become an interesting candidate for functional studies of the development of atherosclerosis. We investigated the individual cellular LRP gene expressions in 100 patients with angiographically confirmed severe coronary obstructions (myocardial infarction, patients with coronary angioplasty and patients with coronary bypass). Using a competitive reverse transcriptase polymerase chain reaction analysis we measured the specific LRP mRNA levels in monocytes from venous blood. In comparison with 110 unselected controls (122.1 ag/cell) the patient group demonstrated significantly higher LRP message levels (171.92 ag/cell). We found the most evident increase in the coronary angioplasty group (+43.5%). Investigating the intraindividual range of expression in healthy controls over a period of 4 weeks, we found nearly constant individual levels. Our results demonstrate a significant correlation of increased LRP mRNA levels with atherosclerotic processes (P<0.001), suggest an important implication of the LRP in atherosclerotic vascular processes, and emphasize the inclusion of LRP investigations in risk constellation studies.

Adult↗
PubMed1998

Networks of domain-specific and general regions involved in episodic memory for spatial location and object identity.

Positron emission tomography (PET) was used to investigate human episodic memory for spatial location and object identity. We measured regional cerebral bloodflow (rCBF) while subjects engaged in perceptual matching of the location or the identity of line drawings of objects. Perceptual matching also involved incidental encoding of the presented information. Subsequently, rCBF was measured when subjects retrieved the location or the identity of these objects from memory. Using the multivariate partial least squares image analysis, we identified three patterns of activity across the brain that allowed us to distinguish structures that are differentially involved in processing spatial location and object identity from structures that are differentially involved in encoding and retrieval but operate across both domains. Domain-specificity was evident by increased rCBF during the processing of spatial location in the right middle occipital gyrus, supramarginal gyrus, and superior temporal sulcus, and by increased rCBF during the processing of object identity in portions of bilateral lingual and fusiform gyri. There was a nearly complete overlap between domain-specific dorsal and ventral extrastriate cortex activations during perceptual matching and memory retrieval. Evidence of domain-specificity was also found in the prefrontal cortex and the left hippocampus, but the effect interacted with encoding and retrieval. Domain-general structures included bilateral superior temporal cortex regions, which were preferentially activated during encoding, and portions of bilateral middle and inferior frontal gyri, which were preferentially activated during retrieval. Together, our data suggest that encoding and retrieval in episodic memory depend on the interplay between domain-specific structures, most of which are involved in memory as well as perception, and domain-general structures, some of which operate more at encoding and others more at retrieval.

Adult↗
PubMed1998

Memory impairments associated with hippocampal versus parahippocampal-gyrus atrophy: an MR volumetry study in Alzheimer's disease.

Delayed memory impairments and medial temporal-lobe atrophy are considered to be cardinal features of Alzheimer's disease (AD). The goal of the present magnetic resonance (MR) volumetry study was to investigate the relationship between both features. We determined MR-derived estimates of hippocampal and parahippocampal volume in a sample of 27 AD patients and in a group of 26 healthy control subjects (NCs) of comparable age and education. We examined the performance of the two groups on immediate and delayed recall trials of an auditory-verbal list-learning task (CVLT), a visual non-verbal memory task (Visual Reproduction of the WMS-R), and a screening procedure that provides an estimate of overall cognitive functioning (DRS). Volumes of the hippocampus and the parahippocampal gyrus were significantly smaller in AD patients than in NCs. AD patients were impaired in their overall level of cognitive functioning and showed memory deficits under immediate and delayed recall conditions. The association between medial temporal-lobe atrophy and cognitive impairments in AD was found to be highly specific: Hippocampal volume correlated positively with delayed but not immediate recall of the verbal auditory list learning task. In contrast, parahippocampal gyrus volume, specifically in the right hemisphere, was positively related to delayed but not immediate recall of the non-verbal visual memory task. In NCs, there was a trend towards a negative association between hippocampal volumes and delayed verbal recall. Our results suggest that hippocampal and parahippocampal gyrus atrophy in AD are related to distinct aspects of the patients' memory impairments. Our findings have implications for current discussions regarding contributions of the hippocampus and the parahippocampal gyrus to memory in the intact human brain.

Aged↗
PubMed1998

Remission of bone metastases after combined chemotherapy and radionuclide therapy with Re-186 HEDP.

A patient with disseminated osseous metastases due to breast cancer reported multifocal pain. Because of persisting pain after a first cycle of chemotherapy, 1,295 MBq Re-186 HEDP was administered intravenously. Excellent pain relief was observed. Subsequently, the patient received further combined chemotherapy and Re-186 HEDP therapy and remained pain free. Tc-99m MDP bone imaging showed a significant regression of osseous metastases. It may be speculated that the combination of Re-186 HEDP and chemotherapy results in significantly increased palliation of metastatic bone disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

A plastid of probable green algal origin in Apicomplexan parasites.

Protozoan parasites of the phylum Apicomplexa contain three genetic elements: the nuclear and mitochondrial genomes characteristic of virtually all eukaryotic cells and a 35-kilobase circular extrachromosomal DNA. In situ hybridization techniques were used to localize the 35-kilobase DNA of Toxoplasma gondii to a discrete organelle surrounded by four membranes. Phylogenetic analysis of the tufA gene encoded by the 35-kilobase genomes of coccidians T. gondii and Eimeria tenella and the malaria parasite Plasmodium falciparum grouped this organellar genome with cyanobacteria and plastids, showing consistent clustering with green algal plastids. Taken together, these observations indicate that the Apicomplexa acquired a plastid by secondary endosymbiosis, probably from a green alga.

Animals↗
PubMed1997

Immunological responses to the tumor-associated antigen CA125 in patients with advanced ovarian cancer induced by the murine monoclonal anti-idiotype vaccine ACA125.

We have generated an immunoglobulin G1 (IgG1) murine monoclonal anti-idiotype antibody (Ab2) designated ACA125, which mimics a specific epitope on the tumor-associated antigen CA125. This antigen is expressed by most of malignant ovarian tumors. Patients with CA125-positive tumors are immunologically tolerant to CA125. We used ACA125 as a surrogate for the tumor-associated antigen CA125 for vaccine therapy of 16 patients with advanced epithelial ovarian cancer or recurrences. Each of the patients received a minimum of 3 injections up to 19 injections of the complete anti-idiotype MAb ACA125 at a dosage of 2 mg per injection. Nine of 16 patients developed anti-anti-idiotypic (Ab3) responses to the ACA125. All 9 patients generated specific anti-CA125 antibody demonstrated by reactivity with purified CA125. Nine of 16 patients developed a CA125-specific cellular immune response by their peripheral blood lymphocytes (PBL) and 3 of 16 showed an increase in gamma-interferon concentrations accompanied by Ab3 responses. Toxicity was limited to abdominal pain in one case, which led to the withdrawal of further immunizations. The median progression free survival in those patients, who showed a specific immune response to the tumor-associated antigen CA125, was 11.0 +/- 5.6 months without any other therapy, in contrast to 8.0 +/- 4.2 months in the anti-anti-idiotype negative group. This is the first report of the induction of a specific active immunity to the tumor-associated antigen CA125 in patients with advanced ovarian cancer treated with an anti-idiotype antibody that "mimics" CA125. Patients showed the development of a specific humoral and cellular immune response to an otherwise nonimmunogenic tumor antigen. The immune responses in patients treated with this anti-idiotype vaccine, the low rate of side effects, and the improved time to progression after the induction of a specific immune response against the tumor-associated antigen CA125 justify follow-up clinical trials in advanced ovarian cancer patients with minimal residual disease in an adjuvant approach.

Animals↗
PubMed1997

Sequencing of HLA class I genes based on the conserved diversity of the noncoding regions: sequencing-based typing of the HLA-A gene.

We present a sequencing-based typing strategy for the HLA-A locus that is generally applicable to all HLA class I genes. Sequencing-based typing is the method of choice for matching in unrelated bone marrow transplantation on the allelic level. We determined the noncoding sequences of all serological antigens and most of their subtypes and discovered a remarkably conserved diversity characterized by polymorphic sequence motifs. In this study we took advantage of this diversity we uncovered in the 5' flanking region, 5' untranslated region and in the introns 1, 2 and 3, which was related to serological families. We established 12 primer mixes for setting up a PCR-based template preparation. Our strategy is based on the separate amplification of haplotypes and therefore defines the cis/trans linkage of polymorphic sequence motifs. This allowed individual sequencing of the haplotypes in all samples heterozygous for the broad antigens as well as the complete analysis of the polymorphic exons 2 and 3. All templates included the 2nd intron which was used as a priming site for the gene-specific 5' and 3' universal sequencing primers regardless of the amplified haplotypes. The independent sequencing of the haplotypes allows the application of the dye terminator cycle sequencing technique, which is less time-consuming and less-laborious than dye primer chemistry. The lack of heterozygous positions essentially facilitates on the one hand the data analysis and on the other hand the detection of new alleles. Sequencing is only required in one direction due to the absence of peak shift problems. The results will remain unambiguous regardless of a growing HLA sequence data bank since this sequencing technique defines the cis/trans linkage of sequence motifs in more than 95% of the cases.

Base Sequence↗
PubMed1996

Participation of the molecular chaperone DnaK in intracellular growth of Brucella suis within U937-derived phagocytes.

In the intracellular bacterium Brucella suis, the molecular chaperone DnaK was induced under heat-shock conditions and at low pH. Insertional inactivation of dnaK and dnaJ within the dnaK/J locus led to the conclusion that DnaK, but not DnaJ, was required for growth at 37 degrees C in vitro. Viability of the dnaK null mutant was also greatly affected at low pH. Under conditions allowing intracellular multiplication, the infection of U937-derived phagocytes resulted in long-lasting DnaK induction in the wild-type bacteria. In infection experiments performed with both mutants at the reduced temperature of 30 degrees C, the dnaK mutant of B. suis survived but failed to multiply within U937 cells, whereas the wild-type strain and the dnaJ mutant multiplied normally. Complementation of the dnaK mutant with the cloned dnaK gene restored growth at 37 degrees C, increased resistance to acid pH, and increased intracellular multiplication. This is the first report of the effects of dnaK inactivation in a pathogenic species, and of the temperature-independent contribution of DnaK to intracellular multiplication of the pathogen B. suis.

Bacterial Proteins↗
PubMed1996

Interactions between professional phagocytes and Brucella spp.

Induced pathogenicity in animals and humans differs considerably. This review is devoted to the relations between Brucella spp. and professional phagocytes, particularly macrophages and macrophagic cell lines in vitro. Although numerous studies have been reported, the type of ingestion by macrophages, the receptor involved, and the molecular mechanisms, are poorly understood. The ability of most Brucella species to actively inhibit their ingestion by neutrophils or macrophages has been proposed as an explanation for the poor rate of in vitro phagocytosis and in vivo alteration of the phagocytic cells. Oxidative burst plays a significant role in the antibacterial processes of phagocytic cells. The effects of whole or fractioned B. abortus on the ability of neutrophils to induce an oxidative burst in response to stimulation with opsonized zymosan particles were examined. Besides oxygen-based killing, the phagocytic cells have developed other types of defence, including hydrolytic enzymes and reactive halides. Inside the cell, the bacteria encounter new environmental conditions. Their survival is conditioned by an adaptation to this new situation. Pathogens that have acquired the ability to multiply within macrophages should synthesize products specifically interacting with the host cell defence system. Survival of intracellular pathogens is closely linked to the mechanisms of evasion from cellular defences. Brucellae stay in membrane bound vacuoles called phagosomes, but the exact nature and the maturation pathway of this compartment have not yet been understood. Macrophages play a central role in the evolution of brucellosis; this first interaction between the pathogens and the cell will determine the course of the disease. There are natural differences between brucellae species regarding macrophage response to the bacteria.

Animals↗
PubMed1996

Efficacy of a fixed peppermint oil/caraway oil combination in non-ulcer dyspepsia.

The efficacy and safety of the standardized herbal combination preparation of Enteroplant, consisting of peppermint oil (90 mg) and caraway (50 mg) in an enteric coated capsule, have been studied in a double-blind, placebo-controlled multicentre trial in patients with non-ulcer dyspepsia. A total of 45 patients were included in the trial after thorough physical and gastro-enterological examination. The primary outcome variables were the change in the intensity of pain and the global clinical impression (Clinical Global Impression [CGI], Item 2), which were evaluated for 39 patients (test preparation: 19, placebo: 20). After four weeks of treatment both target parameters were significantly improved for the group of patients treated with the peppermint oil/caraway oil combination compared to the placebo group (p = 0.015 and 0.008, respectively). Before the start of treatment all patients in the test preparation group reported moderate to severe pain, while by the end of the study 63.2% of these patients were free of pain. The pain symptoms had improved in a total of 89.5% of the patients in the active treatment group. After 4 weeks the Clinical Global Impressions were improved for 94.5% of the patients treated with the peppermint oil/caraway oil combination. The trial medication was also superior to placebo with respect to pain frequency, medical prognosis, the severity of the disorder and the efficacy index (CGI, Items 1 and 3), which were adopted as secondary end-points for evaluation of efficacy. There were similarly favourable findings for the herbal combination, compared with placebo, with respect to the reduction of other gastrointestinal symptoms. The combination preparation was found to be excellently tolerated. There was a total of 7 adverse events (test preparation: 4, placebo: 3), with a causal association with the treatment being ascribed in one case for the test preparation group and one case for the placebo group.

Adult↗
PubMed1995

Dissociation of pathways for object and spatial vision: a PET study in humans.

A positron emission tomography (PET) study was conducted to determine which brain regions are differentially involved in visual object identification and object localization. Subjects engaged in a spatial task in which they matched the location of common objects, and an object task in which they matched the identity of common objects. In both tasks the stimulus arrangements used were of the same kind. Regional cerebral blood flow data showed that a right-sided region in the inferior parietal lobule was more activated during spatial than during object matching. In contrast, bilateral occipitotemporal regions, with the left more predominant, were more activated during object than spatial matching. These results provide support for Ungerleider and Mishkin's dual pathway model of vision and indicate important patterns of lateralization in the human visual system.

Brain↗
PubMed1995

Distinct neural correlates of visual long-term memory for spatial location and object identity: a positron emission tomography study in humans.

The purpose of the present study was to investigate by using positron emission tomography (PET) whether the cortical pathways that are involved in visual perception of spatial location and object identity are also differentially implicated in retrieval of these types of information from episodic long-term memory. Subjects studied a set of displays consisting of three unique representational line drawings arranged in different spatial configurations. Later, while undergoing PET scanning, subjects' memory for spatial location and identity of the objects in the displays was tested and compared to a perceptual baseline task involving the same displays. In comparison to the baseline task, each of the memory tasks activated both the dorsal and the ventral pathways in the right hemisphere but not to an equal extent. There was also activation of the right prefrontal cortex. When PET scans of the memory tasks were compared to each other, areas of activation were very circumscribed and restricted to the right hemisphere: For retrieval of object identity, the area was in the inferior temporal cortex in the region of the fusiform gyrus (area 37), whereas for retrieval of spatial location, it was in the inferior parietal lobule in the region of the supramarginal gyrus (area 40). Thus, our study shows that distinct neural pathways are activated during retrieval of information about spatial location and object identity from long-term memory.

Adult↗
PubMed1994

Complementation of a DnaK-deficient Escherichia coli strain with the dnaK/dnaJ operon of Brucella ovis reduces the rate of initial intracellular killing within the monocytic cell line U937.

Facultatively intracellular bacteria express heat shock proteins after phagocytosis by macrophages. Using non-pathogenic Escherichia coli strains and the human monocytic cell line U937, we showed that deletion of the dnaK gene significantly increased the rate of initial intracellular killing of bacteria. Trans-complementation of the deletion mutant with the dnaK/dnaJ operon of Brucella ovis restored the pattern of intracellular elimination of the control strain expressing dnaK. These differences were not observed using antibody-opsonized bacteria and activated cells. In vitro, strains expressing dnaK resisted hydrogen peroxide better than the deletion mutant; in contrast, the mutant complemented by dnaK/dnaJ of B. ovis tolerated low pH and low H2O2 better than the wild-type strain and the deletion mutant. Our results suggested the participation of DnaK in protection of intracellular bacteria against antimicrobial macrophage factors.

Bacterial Proteins↗
PubMed1994

Differentiated U937 cells exhibit increased bactericidal activity upon LPS activation and discriminate between virulent and avirulent Listeria and Brucella species.

In the study of interactions between facultative intracellular pathogens and macrophages, monocytic cell lines have the advantages of showing defined states of activation and lacking genetic variation among donors, thus yielding reproducible results. Nonpathogenic Escherichia coli K12 were killed at similar rates in the U937 cell line differentiated into macrophage-like cells by phorbol myristate acetate (PMA) or by the combination of retinoic acid (RA) and vitamin D3 (VD). Complete elimination was reached only when cells were activated by lipopolysaccharide for 30 min prior to infection, and it was further enhanced when bacteria were opsonized by specific immunoglobulin G. Both types of differentiation led to intracellular multiplication of virulent Listeria monocytogenes and to elimination of the animal pathogen Listeria ivanovii. For both strains, conditions for intracellular survival were more favorable in PMA-differentiated U937. During infection, RA/VD-differentiated U937 could discriminate between the human pathogen Brucella suis S1, which strongly multiplied, and the animal pathogen Brucella canis, which survived without multiplication. U937 cells differentiated by RA and VD therefore represent a basic model in bacteria-human macrophage interactions.

Blood Bactericidal Activity↗
PubMed1994

Quantitative characterization of verbal learning deficits in patients with Alzheimer's disease.

The performance of patients with Alzheimer's Disease (AD) was compared to that of normal controls (NCs) on a free recall rote learning task involving a list of words (California Verbal Learning Test). Exponential learning functions were fitted to the observed data of the two groups. These learning functions provided estimates for the rate of learning and the theoretically expected upper limit of recall performance in each group. The rate constant of learning was higher in AD patients than in NCs, indicating less distributed learning across the given trials. The expected upper limit of recall performance was lower in AD patients than in NCs. Results suggest that AD patients benefit less from the repetition of information at the time of encoding.

Aged↗
PubMed1994

Synthetic peptides derived from the Listeria monocytogenes p60 protein as antigens for the generation of polyclonal antibodies specific for secreted cell-free L. monocytogenes p60 proteins.

All species of the genus Listeria secrete a major extracellular protein called p60. A comparison of the deduced amino acid sequences of all listerial p60 proteins previously indicated there were only a few regions which were unique to the pathogenic, food-borne species Listeria monocytogenes. Two of these p60 regions were chosen for the development of antibodies specific for the facultative intracellular species L. monocytogenes. Initially, these regions were characterized via epitope mapping, and this led to the development of two different synthetic peptides. Rabbits immunized with these synthetic peptides generated polyclonal antibodies that were then used in Western blot (immunoblot) analyses. Antiserum against peptide A (PepA) recognized the p60 protein in the supernatants collected from most L. monocytogenes serotypes except for several strains belonging to serotypes 4a and 4c. No p60-related protein was detected in the supernatants from other Listeria species with this anti-PepA antiserum. Antibodies raised against peptide D (PepD) reacted with p60 from all L. monocytogenes serotypes, including all 4a and 4c strains that were tested, and also showed no cross-reactivity with supernatant proteins from other Listeria species. Both antisera also detected p60 in supernatants of a large number of environmental isolates of L. monocytogenes. Besides Western blot analyses, these antisera to PepA and PepD reacted with secreted p60 in an enzyme-linked immunosorbent assay, indicating recognition of the native antigen in addition to the denatured form. These data suggest that synthetic peptides derived from the variable region of the L. monocytogenes p60 protein may be useful for the development of an immunological diagnostic assay.

Amino Acid Sequence↗