Biomedical subjects

M Kreis

Publications and source records attributed to M Kreis.

At least 19 recordsLinked to original sources

PubMed2005

Lipopolysaccharide-induced changes in mesenteric afferent sensitivity of rat jejunum in vitro: role of prostaglandins.

Bacterial translocation across the intestinal mucosal barrier leads to a macrophage-mediated inflammatory response, visceral hyperalgesia, and ileus. Our aim was to examine how mediators released into mesenteric lymph following LPS treatment influence intestinal afferent sensitivity and the role played by prostanoids in any sensitization. Intestinal lymph was collected from awake rats following treatment with either saline or LPS (5 mg/kg ip). Extracellular multiunit afferent recordings were made from paravascular mesenteric nerve bundles supplying the rat jejunum in vitro following arterial administration of control lymph, LPS lymph, and LPS. Mesenteric afferent discharge increased significantly after LPS lymph compared with control lymph. Peak discharge occurred within 2 min and remained elevated for 5 to 8 min. This response was attenuated by pretreatment with naproxen (10 microM), and restored upon addition of prostaglandin E(2) (5 microM) in the presence of naproxen, but AH6809 (5 microM), an EP(1)/EP(2) receptor(s) antagonist, failed to decrease the magnitude of LPS lymph-induced response. LPS itself also stimulated mesenteric afferent discharge but was unaffected by naproxen. TNF-alpha was significantly increased in LPS lymph compared with control lymph (1,583 +/- 197 vs. 169 +/- 38 pg/ml, P < 0.01) but exogenous TNF-alpha failed to evoke any afferent nerve discharge. We concluded that inflammatory mediators released from the gut into mesenteric lymph during endotoxemia have a profound effect on afferent discharge. These mediators influence afferent firing via the release of local prostaglandins.

Animals↗

PubMed2005

The clinical utility of structural neuroimaging with MRI for diagnosis and differential diagnosis of dementia: a memory clinic study.

OBJECTIVES: The individual contribution to the final comprehensive clinical diagnosis of neuropsychology (NP) and magnetic resonance imaging (MRI), respectively, was quantified in a specialized tertiary care setting to investigate the added clinical value of routine MRI. METHODS: In 106 patients referred to a university memory clinic for the work-up of cognitive disturbances the primary care diagnosis, the initial clinical neuropsychiatric diagnosis, the neuropsychological and MRI diagnoses, and the final comprehensive clinical diagnosis were documented. The neuropsychological investigation was performed using the CERAD test battery. MRI was performed using T1, double echo and FLAIR sequences without contrast medium. The change of the final comprehensive clinical diagnosis in relation to the initial neuropsychiatric diagnosis was used to determine the diagnostic contribution of both, MRI and NP. RESULTS: NP and MRI led to a significant change of the final comprehensive diagnosis in 26% of patients (CI: 0.26 +/- 0.09; p < 0.05). In addition, three cases of secondary dementias, and six cases of vascular encephalopathy without dementia were recognized by MRI. Sensitivity, specificity, and the positive predictive value were higher for NP and MRI, respectively, than for the initial clinical diagnosis alone. CONCLUSION: MRI as well as neuropsychological testing improves early detection and differential diagnosis of dementia and additionally supplies clinically relevant findings. MRI carries added clinical value in the investigation of dementias.

Aged↗

PubMed2005

[Reliability of quantifying vascular white matter brain lesions -- a contribution to reproducible quantitative diagnosis].

PURPOSE: Microangiopathic lesions of the brain tissue correlate with the clinical diagnosis of vascular subcortical dementia. The "experience-based" evaluation is insufficient. Rating scales may contribute to reproducible quantification. MATERIALS AND METHODS: In MRI studies of 10 patients, 9 neuroradiologists quantified vascular white matter lesions (WMLs) at two different points in time for 12 anatomically defined regions with respect to number, size and localization (score). For 9 observers and 10 studies, 90 intra-observer differences were obtained for each of the 12 WML scores. To calculate the inter-observer reliability, rating pairs were formed. Furthermore, 360 differences were computed for each score and rating for 12 anatomically defined WML scores, and the intraclass correlation (ICC) was calculated as a measure of agreement (reliability). RESULTS: As to the intra-observer reliability, the median of the differences was 1.5 for the entire brain as opposed to 0 for defined brain regions. The corresponding values for the inter-observer reliability were 3 and 1, respectively. The mean intra-class correlation coefficient for the 10 studies was 0.88, whereas the mean interclass correlation concerning the inter-observer reliability was 0.70, with the first and second rating being averaged. The rating of each study took about 6 minutes. CONCLUSION: The rating scale with high intra- and inter-observer reliability can dependably quantify WMLs and correlates with the clinical diagnosis of vascular dementia. Using a reliable rating scale, the diagnostic distinction of age-associated physiological vs. pathological size of the WML can make a contribution to the reproducible quantifiable diagnostic evaluation of vascular brain tissue lesions within the framework of dementia diagnostics.

Aged↗

PubMed2005

[Quantification of microangiopathic lesions in brain parenchyma and age-adjusted mean scores for the diagnostic separation of normal from pathological values in senile dementia].

PURPOSE: To quantify microangiopathic lesions in the cerebral white matter and to develop age-corrected cut-off values for separating normal from dementia-related pathological lesions. MATERIALS AND METHODS: In a memory clinic, 338 patients were investigated neuropsychiatrically by a psychological test battery and by MRI. Using a FLAIR sequence and a newly developed rating scale, white matter lesions (WMLs) were quantified with respect to localization, number and intensity, and these ratings were condensed into a score. The WML scores were correlated with the mini-mental state examination (MMSE) and clinical dementia rating (CDR) score in dementia patients. A non-linear smoothing procedure was used to calculate age-related mean values and confidence intervals, separate for cognitively intact subjects and dementia patients. RESULTS: The WML scores correlated highly significantly with age in cognitively intact subjects and with psychometric scores in dementia patients. Age-adjusted WML scores of cognitively intact subjects were significantly different from those of dementia patients with respect to the whole brain as well as to the frontal lobe. Mean value and confidence intervals adjusted for age significantly separated dementia patients from cognitively intact subjects over an age range of 54 through 84 years. CONCLUSION: A rating scale for the quantification of WML was validated and age-adjusted mean values with their confidence intervals for a diagnostically relevant age range were developed. This allows an easy to handle, fast and reliable diagnosis of the vascular component in senile dementia.

Age Factors↗

PubMed2004

Polymorphisms in glutathione S-transferase omega-1 and AD, vascular dementia, and stroke.

BACKGROUND: Glutathione S-transferase omega-1 (GSTO1) protects from oxidative stress, a risk factor for Alzheimer disease (AD), vascular dementia (VaD), and stroke. Polymorphisms in GSTO1 might influence the function of the protein and thus the risk of AD, VaD, and stroke. METHODS: The GSTO1 gene was screened for variations. The effect of the detected polymorphisms on the risk of AD, VaD, and stroke was evaluated. CSF levels of cholesterol and plasma homocysteine levels were compared according to the GSTO1 genotype. RESULTS: Two missense polymorphisms in exon 4 of GSTO1 (Ala140Asp and Glu155DeltaGlu) were detected and tested for their association with AD, VaD, and stroke. The Asp/Asp and Ala/Asp genotypes increased the risk of stroke (p = 0.003, OR = 2.1), and the Asp/Asp genotype increased the risk of VaD (p = 0.02, OR = 2.2). GSTO1 polymorphisms did not influence the risk of AD, but the Asp allele influenced the age at onset (p = 0.05). In nondemented probands CSF levels of cholesterol were increased in carriers of the Asp/Asp genotype (p = 0.004); however, in patients with manifest dementia the authors found decreased CSF levels of cholesterol in carriers of the Asp/Asp genotype (p = 0.028). Serum homocysteine levels in stroke patients were higher in carriers of at least one Asp allele (p = 0.011). CONCLUSION: The GSTO1 Asp allele may be a genetic risk factor for cerebrovascular diseases, and might influence the course of Alzheimer disease, even though effects vary in different studies.

Adult↗

PubMed2004

ACE I/D polymorphism is a risk factor of Alzheimer's disease but not of vascular dementia.

Different studies have investigated the effect of the angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism on the risk of Alzheimer dementia (AD). However, results on the association of the ACE-I allele with AD have been inconclusive. A recent meta-analysis reported an association of the I-allele with the risk of AD. A few small studies also investigated the effect of ACE polymorphism on the risk of vascular dementia (VD). We have investigated the effect of ACE I/D polymorphism in 351 AD and 155 VD patients and 348 healthy controls. We found the I/I genotype to be associated with an increased risk of AD, but not with the risk of VD. Cell-specific effects of ACE polymorphism are suggested, additional studies on neuronal cells might help to understand the role of this polymorphism in AD.

Aged↗

PubMed2004

Arabidopsis kinome: after the casting.

Arabidopsis thaliana is used as a favourite experimental organism for many aspects of plant biology. We capitalized on the recently available Arabidopsis genome sequence and predicted proteome, to draw up a genome-scale protein serine/threonine kinase (PSTK) inventory. The PSTKs represent about 4% of the A. thaliana proteome. In this study, we provide a description of the content and diversity of the non-receptor PSTKs. These kinases have crucial functions in sensing, mediating and coordinating cellular responses to an extensive range of stimuli. A total of 369 predicted non receptor PSTKs were detailed: the Raf superfamily, the CMGC, CaMK, AGC and STE families, as well as a few small clades and orphan sequences. An extensive relationship analysis of these kinases allows us to classify the proteins in superfamilies, families, sub-families and groups. The classification provides a better knowledge of the characteristics shared by the different clades. We focused on the MAP kinase module elements, with particular attention to their docking sites for protein-protein interaction and their biological function. The large number of A. thaliana genes encoding kinases might have been achieved through successive rounds of gene and genome duplications. The evolution towards an increasing gene number suggests that functional redundancy plays an important role in plant genetic robustness.

Arabidopsis↗

PubMed2004

[Effects of extended clinical diagnostics on the diagnostic spectrum of an outpatient memory clinic].

OBJECTIVES: In an outpatient memory clinic, the methods of extended clinical diagnostics pertaining to imaging and neuropsychology were changed but the modus of assignment to the clinic remained unchanged at different times. Expected changes in the diagnostic spectrum can be attributed to the changed diagnostics. Consistent with reports from the literature regarding the consequences of such changes, the associated costs have to be taken into consideration as well. METHODS: The clinical final diagnoses of 174 patients referred in 2000/2001 for the diagnostics and differential diagnostics of dementia ("current population") were compared with those of 169 patients who visited the same outpatient clinic in 1998/1999 ("former population"). The diagnostic spectra of the two populations were compared. The diagnoses were differentiated in "no dementia" (XD), "neurodegenerative dementia" (ND), "vascular dementia" (VD), and "dementia of the mixed type" (MIXD). For all patients, the same clinical diagnostic criteria (ICD-10) and laboratory tests were implemented. Only the neuroradiological and neuropsychological methods changed from 1998/1999 to 2000/2001: The current population was examined with MRI instead of CT and underwent an expanded neuropsychological test battery with additional power and speed tests. RESULTS: The diagnoses of the two populations differed significantly in their frequency distribution. A dementia was excluded in 51.1% of the "current" patients vs 19.5% of the "former" patients. The frequencies of the dementia diagnoses were significantly different for the diagnoses ND (29.9 vs 47.9%) and MIXD (1.1 vs 7.7%), but not for VD (13.2 vs 12.4%). Beside other independent modalities, the improvement of imaging with MRI is discussed as recording atrophy size and vascular lesions better than CT. The improvement of the neuropsychological test battery containing additional speed tests is discussed as being able to differentiate even minimal cognitive disturbances. CONCLUSION: Using optimized imaging and neuropsychological methods, the diagnostic spectrum of an outpatient memory clinic changed. The clinical diagnosis was improved by the more sensitive, extended clinical diagnostics. Through optimized differential diagnostic allocation and the exclusion of dementia, expenses can be reduced by early and indication-related medication and by the resulting delay of institutionalized care.

Aged↗

PubMed2004

[Does magnetization transfer ratio (MTR) contribute to the diagnosis and differential diagnosis of the dementias?].

PURPOSE: The magnetization transfer ratio (MTR) is a MR-based neuroimaging procedure aiming at the quantification of the structural integrity of brain tissue. Its contribution to the differential diagnosis of dementias was examined and discussed in relation to the pathogenesis of age-related dementias. MATERIALS AND METHODS: Sixty-one patients from a memory clinic were diagnosed by general physical and neuropsychiatric examination, and underwent neuropsychologic testing and neuroimaging using MRI. Their clinical diagnoses were based on standard operational research criteria. Additionally, the MTR in 10 defined regions of interest (ROI) was determined. This investigation was performed using a T1-weighted SE sequence. Average MTR values were determined in the individual ROI and their combinations and correlated with the age, gender, cognitive impairment and clinical diagnosis. Sensitivity, specificity, positive and negative predictive value were determined, as well as the rate of correct classifications. RESULTS: For cognitive healthy subjects, the MRT values correlate only mildly, though significantly, with age in the hippocampus and with gender in the dorsal corpus callosum. In contrast, the MTR in the frontal white matter correlates strongly and highly significantly with cognitive impairment in patients with dementia. The differential diagnostic assignment of Alzheimer's disease versus vascular dementia by MTR provides a correct classification of approximately 50 % to 70 %. PPV for no dementia vs. vascular dementia or the NPV for vascular vs. Alzheimer's disease are considerably higher exceeding 80 %. For no dementia vs. Alzheimer's disease, the NPV was over 90 %. CONCLUSION: MTR values indicate functional changes in the brain tissue between cognitive healthy and demented patients, and correlate with the cognitive loss, but not with age and gender. In principle, the MTR is suitable for the diagnosis of age-related dementias, but does not contribute substantially to the differential diagnosis of vascular dementia vs. Alzheimer's disease. The present results support the assumption of a synergy between vascular and degenerative components of age-related dementias.

Age Factors↗

PubMed2003

[Microangiopathic lesions of white matter. Quantitation of cerebral MRI findings and correlation with psychological tests].

AIM: The importance of vascular lesions in the white matter of the brain (WML) is viewed differently. Diagnostic evaluation is determined by experience and age-associated normal values are not available. MATERIAL AND METHODS: One hundred fifty-two patients aged 68.8 years (range 50-89) were examined at a memory clinic using a magnetic resonance FLAIR sequence,which is sensitive for WML. The WMLs were entered with respect to size, localization, laterality, and density. The WML scores of 76 clinically and psychologically normal subjects with microangiopathic lesions and 27 patients with vascular dementia were correlated with psychological test results. The contribution of local WML scores to the differentiation between age-associated microangiopathy and vascular dementia was calculated using logistic regression analysis. Nonparametric monotonic regression was used to analyse the age-associated WML scores of both groups, taking individual age into account. RESULTS: The WML scores correlated linearly with the age of psychologically normal subjects but with degree of dementia for those with vascular dementia, and it allowed differentiation between these two groups with an accuracy of up to 88% and specificity of approximately 95% with reference to the right frontal region. The odds ratios of the general and frontal WML scores were significantly different (1,102 and 1,400, respectively). Statistical significance of the age-associated WML scores varied for different age ranges. CONCLUSION: It is possible to differentiate psychologically normal subjects with microangiopathic brain lesions from patients with vascular dementia on MRI when referring to frontal WML scores.

Aged↗

PubMed2003

[Is there a referral bias in the diagnoses of patients of a memory clinic?].

In a recent study addressing the contribution of neuropsychology and neuroradiology to the improvement of the dementia diagnoses of a memory clinic more than 45% of the patients (45 out of 101) did not meet the criteria for dementia. This finding was unexpected because all patients had been referred for the diagnosis and differential diagnosis of dementia. The aim of the present study was to examine whether the proportion of nondemented patients varies with the "modus of referral". This was not found to be true. The frequency of the diagnosis "no dementia" was not significantly different for the two patient groups "general practitioner" vs. "neuropsychiatrist" referred patients (p=0.859). In conclusion, there is no difference between the two groups of physicians in the reliability judging whether a "cognitive complainer" needs to be referred to a specialized memory clinic.

Age Factors↗

PubMed2003

[Evaluation of the contribution of the importance of neuroimaging for the diagnostics of dementias--comparison to the psychological diagnostics].

OBJECTIVE: While psychology is accepted as a necessary component of the dementia diagnostics, the extended clinical diagnostics with neuroimaging is differently estimated. The goal of the study is the quantification of the individual contribution of the two different methods. METHODS: Of 100 patients the diagnosis of entrance, the neurological, the psychological, and the final clinical diagnosis were documented. For both imaging and psychology the sensitivity, specificity, and the positive predictive value were computed. The diagnostic of each method was determined from the change of the final in relation to the initial clinical diagnosis. The neuroradiological investigation took place with MRI, the psychological examination used both usual power and special speed tests. RESULTS: The extended clinical diagnostics led for 26 % of the patients to the change of the clinical diagnosis. Imaging and psychology supplied different own but supplementing contributions. In the case of annihilation imaging contributed with 73.3 %, psychology with 54.1 % to the diagnosis of a neurodegenerative dementia, whereas the contributions to the diagnosis of a vascular dementia were 83.3 % and 70.8 %, respectively. However psychology diagnosed and quantified the dementia. The contribution of neuroimaging consisted in the differential diagnosis of the dementias. Organic causes of symptomatic dementias and vascular encephalopathy without dementia but with consequences for a secondary prophylaxis were additional information also. CONCLUSION: Psychology improves the diagnostic accuracy of dementias. Neuroimaging improves the differential diagnosis of dementias and supplies additional clinically relevant findings. In the qualified diagnostics and differential diagnostics of the dementias both methods are indispensable.

Aged↗

PubMed2002

AtSKtheta, a plant homologue of SGG/GSK-3 marks developing tissues in Arabidopsis thaliana.

The Arabidopsis thaliana AtSK sub-family of serine threonine protein kinases groups 10 homologues of SHAGGY/GSK-3. Previous results obtained with different plant members of the SHAGGY/GSK-3 family strongly suggest that these proteins are involved in cell differentiation and stress responses. In order to gain further insight into the biological functions of this family in A. thaliana, polyclonal antibodies were raised against specific domains of the AtSKtheta protein. The antibodies were purified and used in immunolocalization studies in various tissues of A. thaliana. Our results show that the protein is located in the cell nuclei of various developing organs. Differential protein localization profiles were found in some of the observed tissues, notably during gametophyte and embryo development. Based on this protein location pattern, and on what is known about the mammalian members of the GSK-3 family, we suggest that AtSKtheta may have a role in the regulation of transcription factors.

Amino Acid Sequence↗

PubMed2001

The protein kinases AtMAP3Kepsilon1 and BnMAP3Kepsilon1 are functional homologues of S. pombe cdc7p and may be involved in cell division.

We identified an Arabidopsis thaliana gene, AtMAP3Kepsilon1, and a Brassica napus cDNA, BnMAP3Kepsilon1, encoding functional protein serine/threonine kinases closely related to cdc7p and Cdc15p from Schizosaccharomyces pombe and Saccharomyces cerevisiae, respectively. This is the first report of cdc7-related genes in non-fungal eukaryotes; no such genes have as yet been identified in Metazoans. The B. napus protein is able to partially complement a cdc7 loss of function mutation in S. pombe. RT-PCR and in situ hybridisation revealed that the A. thaliana and B. napus genes are expressed in both the sporophytic and the gametophytic tissues of the respective plant species and revealed further that expression is highest in dividing cells. Moreover, AtMAP3Kepsilon1 gene expression is cell cycle-regulated, with higher expression in G2-M phases. Our results strongly suggest that the plant cdc7p-related protein kinases are involved in a signal transduction pathway similar to the SIN pathway, which positively regulates cytokinesis in S. pombe.

Amino Acid Sequence↗

PubMed2001

Evolution of intron/exon structure of DEAD helicase family genes in Arabidopsis, Caenorhabditis, and Drosophila.

The DEAD box RNA helicase (RH) proteins are homologs involved in diverse cellular functions in all of the organisms from prokaryotes to eukaryotes. Nevertheless, there is a lack of conservation in the splicing pattern in the 53 Arabidopsis thaliana (AtRHs), the 32 Caenorhabditis elegans (CeRHs) and the 29 Drosophila melanogaster (DmRHs) genes. Of the 153 different observed intron positions, 4 are conserved between AtRHs, CeRHs, and DmRHs, and one position is also found in RHs from yeast and human. Of the 27 different AtRH structures with introns, 20 have at least one predicted ancient intron in the regions coding for the catalytic domain. In all of the organisms examined, we found at least one gene with most of its intron predicted to be ancient. In A. thaliana, the large diversity in RH structures suggests that duplications of the ancestral RH were followed by a high number of intron deletions and additions. The very high bias toward phase 0 introns is in favor of intron addition, preferentially in phase 0. Results from this comparative study of the same gene family in a plant and in two animals are discussed in terms of the general mechanisms of gene family evolution.

Animals↗

PubMed2000

Progress in Arabidopsis genome sequencing and functional genomics.

Arabidopsis thaliana has a relatively small genome of approximately 130 Mb containing about 10% repetitive DNA. Genome sequencing studies reveal a gene-rich genome, predicted to contain approximately 25000 genes spaced on average every 4.5 kb. Between 10 to 20% of the predicted genes occur as clusters of related genes, indicating that local sequence duplication and subsequent divergence generates a significant proportion of gene families. In addition to gene families, repetitive sequences comprise individual and small clusters of two to three retroelements and other classes of smaller repeats. The clustering of highly repetitive elements is a striking feature of the A. thaliana genome emerging from sequence and other analyses.

Agriculture↗

PubMed2000

In Arabidopsis thaliana, 1% of the genome codes for a novel protein family unique to plants.

In the sequences released by the Arabidopsis Genome Initiative (AGI), we discovered a new and unexpectedly large family of orphan genes (127 genes by 01.08.99), named AtPCMP. The distribution of the AtPCMP genes on the five chromosomes suggests that the genome of Arabidopsis thaliana contains more than 200 genes of this family (1% of the whole genome). The deduced AtPCMP proteins are characterized by a surprising combinatorial organization of sequence motifs. The amino-terminal domain is made of a succession of three conserved motifs which generate an important diversity. These proteins are classified into three subfamilies based on the length and nature of their carboxy-terminal domain constituted by 1-6 motifs. All the motifs characterized have an important level of conservation in both sequence and spacing. A specific signature of this large family is defined. The presence of ESTs in databases and the detection of clones in A. thaliana cDNA libraries indicate that most of the genes of this family are expressed. The absence of similar sequences outside the plant kingdom strongly suggests that this unusually large orphan family is unique to plants. Features, the genesis, the potential function and the evolution of this plant combinatorial and modular protein family are discussed.

Algorithms↗

PubMed2000

Organization and structural evolution of four multigene families in Arabidopsis thaliana: AtLCAD, AtLGT, AtMYST and AtHD-GL2.

The Arabidopsis Genome Initiative has released up to now more than 80% of the genome sequence of Arabidopsis thaliana. About 70% of the identified genes have at least one paralogue. In order to understand the biological function of individual genes, it is essential to study the structure, expression and organization of the entire multigene family. A systematic analysis of multigene families, made possible by the amount of genomic sequence data available, provides important clues for the understanding of genome evolution and plasticity. In this paper, four multigene families of A. thaliana are characterized, namely LCAD, HD-GL2, LGT and MYST. Members of HD-GL2 and LCAD have already been reported in plants. The LGT genes specify proteins containing motifs of glycosyl transferase. No plant genes similar to the LGT genes have been reported to date. The novel MYST family, most likely plant-specific, encodes proteins with no identified function. Sequencing and in silico analysis led to the characterization of 29 novel genes belonging to these four gene families. The organization, structure and evolution of all the members of the four families are discussed, as well as their chromosome location. Expression data of some of the paralogues of each family are also presented.

Alcohol Oxidoreductases↗