Search PubMed⌕ Search

Biomedical subjects

J Freudenberg

Publications and source records attributed to J Freudenberg.

At least 19 recordsLinked to original sources

Variation of the serotonin transporter gene SLC6A4 in the susceptibility to migraine with aura.

To replicate a reported association between migraine with aura (MA) and a promoter polymorphism in the serotonin transporter gene (SLC6A4), we performed a case-control study in a large German sample comprising 472 patients with MA and 506 controls. Neither this polymorphism nor a systematic analysis with single nucleotide polymorphisms capturing the main haplotype diversity of the SLC6A4 locus provided evidence for a contribution of SLC6A4 to the predisposition of complex inherited MA.

Adult↗

Systematic investigation of genetic variability in 111 human genes-implications for studying variable drug response.

In order to identify single-nucleotide polymorphisms (SNPs) and analyze their characteristics in a set of 111 genes, we resequenced exons and flanking regions in an average of 170 chromosomes from individuals of European origin. Genetic variability was decreased in noncoding regions highly conserved between human and rodents, indicating functional relevance of these regions. Furthermore, diversity of coding nonsynonymous SNPs was found lower in regions encoding a known protein sequence motif. SNPs predicted to be of functional significance were more common amongst rare variants. Despite the significant recent growth of SNP numbers in public SNP databases, only a small fraction of these rare variants is represented. This may be relevant in the investigation of the genetic causes of severe side effects, for which rare variants are plausible candidates. Estimation of htSNPs reduces the genotyping effort required in capturing common haplotypes, for certain genes, however, this accounts for only a small fraction of haplotype diversity.

Alleles↗

Examination of G72 and D-amino-acid oxidase as genetic risk factors for schizophrenia and bipolar affective disorder.

A recent study has suggested that the brain-expressed genes for G72 and D-amino-acid oxidase (DAAO) exert an influence on susceptibility to schizophrenia. Our aim was to replicate this finding in German schizophrenic patients and to assess whether G72 and DAAO might also contribute to the development of bipolar affective disorder. We genotyped seven single-nucleotide polymorphisms (SNPs) in the G72 gene and three in the DAAO gene in 599 patients (299 schizophrenic, 300 bipolar) and 300 controls. At G72, individual SNPs and a four-marker haplotype were associated with schizophrenia. The most significant SNP as well as the haplotype were also associated with bipolar affective disorder (BPAD). DAAO was associated with schizophrenia, but not with BPAD. The association of variation at G72 with schizophrenia as well as BPAD provides molecular support for the hypothesis that these two major psychiatric disorders share some of their etiologic background.

Adult↗

Comparison of preprocessing procedures for oligo-nucleotide micro-arrays by parametric bootstrap simulation of spike-in experiments.

OBJECTIVE: Due to scarcity of calibration data for microarray experiments, simulation methods are employed to assess preprocessing procedures. Here we analyze several procedures' robustness against increasing numbers of differentially expressed genes and varying proportions of up-regulation. METHODS: Raw probe data from oligo-nucleotide microarrays are assumed to be approximately multivariate normally distributed on the log scale. Chips can be simulated from a multivariate normal distribution with mean and variance-covariance matrix estimated from a real raw data set. A chip effect induces strong positive correlations. In reverse, sampling from a normal distribution with strong correlation variance-covariance matrix generates data exhibiting a chip effect. No explicit model of chip-effect is needed. Differences can be artificially spiked-in according to a given distribution of effect sizes. Thirty preprocessing procedures combining background correction, normalization, perfect match correction and summarization methods available from the BioConductor project were compared. RESULTS: In the symmetrical setting "50% differentially expressed genes, 50% of which up-regulated" background correction reduces bias, but inflates low intensity probe variance as well as the mean squared error of the estimates. Any normalization reduces variance and increases sensitivity with no clear winner. Asymmetry between up and down regulation causes bias in the effect-size estimate of non-differentially expressed genes. This markedly inflates the false positive discovery rates. Variance stabilizing normalization (VSN) behaved best. CONCLUSION: A simple parametric bootstrap was used to simulate oligo-nucleotide micro-array raw data. Current normalization methods inflate the false positive rate when many genes show an effect in the same direction.

Computer Simulation↗

A similarity-based method for genome-wide prediction of disease-relevant human genes.

MOTIVATION: A method for prediction of disease relevant human genes from the phenotypic appearance of a query disease is presented. Diseases of known genetic origin are clustered according to their phenotypic similarity. Each cluster entry consists of a disease and its underlying disease gene. Potential disease genes from the human genome are scored by their functional similarity to known disease genes in these clusters, which are phenotypically similar to the query disease. RESULTS: For assessment of the approach, a leave-one-out cross-validation of 878 diseases from the OMIM database, using 10672 candidate genes from the human genome, is performed. Depending on the applied parameters, in roughly one-third of cases the true solution is contained within the top scoring 3% of predictions and in two-third of cases the true solution is contained within the top scoring 15% of predictions. The prediction results can either be used to identify target genes, when searching for a mutation in monogenic diseases or for selection of loci in genotyping experiments in genetically complex diseases.

Algorithms↗

Simulation of cardiac excitation patterns in a three-dimensional anatomical heart atlas.

Computerized anatomical atlas systems enable interactive investigation of digital body models. Here we present a three-dimensional atlas of the human heart, based on image data provided in the Visible Human Project. This heart atlas consists of multiple kinds of cardiac tissues and offers unlimited possibilities for its visual exploration. A temporal dimension is added to the underlying heart model by simulation of cardiac excitation spreading. For this purpose a second generation cellular automata algorithm is adapted to the excitation kinetics of cardiac tissue. The presented system is shown as a successful method for the visualization-based investigation of cardiac excitation.

Algorithms↗

A contactless surface acoustic wave biosensor.

Surface acoustic wave sensors operating in liquid generally cause problems resulting from wire bonding. The authors present an approach for a biosensor where the need for bonding wires is eliminated by utilizing inductive coupling of the sensor device to the RF circuitry. Protection of the electrodes from the liquid is achieved by coating the device surface with a SiO2 layer, resulting in a simplified handling of the devices. The first measurements with a sensor operating at 420 MHz are presented, demonstrating the potential of this operating principle for biosensing.

Acoustics↗

Platelet-activating factor mediates monocyte chemoattractant protein-1 expression in glomerular immune injury.

These studies were designed to determine the possible role of platelet-activating factor (PAF) in the production of monocyte chemoattractant protein-1 (MCP-1) in glomerular immune injury. The glomerular lesion was induced in isolated perfused rat kidneys by a rabbit anti-rat-thymocyte serum (ATS) and rat serum (RS) as a complement source. Perfusion of kidneys with ATS and RS results in the selective binding of the antiserum to the glomerular mesangium with consecutive intraglomerular activation of complement. Antibody binding and complement activation induced a significant increase in glomerular MCP-1 mRNA levels when assessed by Northern blotting or RT-PCR. Decomplemented RS or non antibody rabbit IgG had only moderate effects on glomerular MCP-1 mRNA levels. The PAF receptor antagonist WEB 2170 almost completely blocked the ATS and RS induced MCP-1 mRNA levels. Perfusion of control kidneys with PAF increased MCP-1 mRNA expression, an effect which was blocked by WEB 2170. Glomerular MCP-1 protein formation, assessed by Western blotting, was stimulated following ATS and RS and PAF, respectively, was blocked by WEB 2170. These data show that PAF, derived from glomerular resident cells following antibody and complement induced injury, stimulates MCP-1 expression. In addition to the direct effects on leukocyte adhesion and activation PAF may mediate inflammatory cell influx in glomerular injuries due to the release of MCP-1.

Animals↗

[Malignant hyperthermia and sevoflurane--a case report].

The authors report on a course of malignant hyperthermia (MH) in an almost 5-years old boy. In the past, he had been anaesthetized two times with halothane without complications. The causative triggering agent was sevoflurane, a new user-friendly substance for paediatric anaesthesia. Forty five minutes after induction of anaesthesia he developed symptoms of a MH-crisis with increase in endexspiratory CO2 up 87 mmHg and followed by an increase in heart rate up to 160 beats/minute. The blood gas analysis showed a respiratory and metabolic acidosis. The timely administration of dantrolene rapidly reversed the life-threatening signs and prevent progression of the disease. It is apparent that monitoring of endtidal carbon dioxide by means of capnometry is of crucial importance in detecting MH at an early stage, and appropriate treatment is being instituted more promptly. By such early recognition, and treatment with dantrolene, we can reasonably except a further decrease in mortality and morbidity of this enigmatic disorder.

Anesthetics, Inhalation↗

Prostaglandin E1 reduces the glomerular mRNA expression of monocyte-chemoattractant protein 1 in anti-thymocyte antibody-induced glomerular injury.

To study whether prostaglandins (PG) can regulate the mRNA expression of monocyte-chemoattractant protein 1 (MCP-1) in glomerular immune injury, MCP-1 mRNA levels were evaluated in anti-thymocyte antibody (ATS) -induced glomerular injury by Northern blotting and reverse transcription-polymerase chain reaction. Immune injury was induced in vivo by the intravenous application of ATS to male Wistar rats and in vitro by the perfusion of isolated rat kidneys with ATS and rat serum. In vivo 3 h and 5 days after antibody application, glomerular mRNA expression of MCP-1 was markedly enhanced compared with controls. In the isolated perfused kidney, antibody and complement also induced an increase in MCP-1 expression at 10 min and 60 min after antibody perfusion. When the rats were treated with PGE (250 micrograms, twice daily), the increase in MCP-1 expression was reduced. This was associated with a reduction of intraglomerular recruitment of monocytes/macrophages. In the isolated perfused kidneys, PGE1 (1 mg/L) prevented the antibody- and rat serum-stimulated increase in glomerular MCP-1 mRNA expression. These data demonstrate that PGE1 reduces glomerular MCP-1 mRNA expression in glomerulonephritis and in the isolated perfused rat kidney after induction of immune injury with antibody and complement. The data suggest that prostaglandins might mediate MCP-1 effects in glomerular immune injuries.

Alprostadil↗

[Pituitary crisis and acute renal failure--a case report].

Based on a case report, the combined occurrence of a hypopituitary crisis and acute renal failure (ARF) is discussed. Aetiologically, the patient's disease dates back to an operation on the pituitary gland 40 years previously followed by a panhypopituitarism. The course of the disease presented initial symptoms which did not suggest a hypopituitary crisis to the first physician. The patient was hospitalized primarily on the tentative diagnosis of encephalitis. Subsequently, both laboratory findings and sonography of the abdomen pointed to chronic renal failure. The severity of the clinical course led to the transfer of the patient to our hospital for haemodialysis. Examination of the soporous patient revealed in addition to symptoms of ARF based on ambilateral pyelonephritic nephrocirrhosis typical cardinal symptoms of an endocrine insufficiency. Sopor, serious exsiccosis, pale, cool, pigmentless skin, deficiency of axillary and pubic hair, gonadal atrophy, hypotonia, hypothermia, bradypnoea and bradycardia as well as anamnesis of the patient substantiated the tentative diagnosis of a hypophysical coma based on hypopituitarism, clinically dominated by hypothyroidism. Following an immediately launched hormone substitution in combination with haemodialysis the state of the patient improved. However, during the fifth haemodialysis cardiac arrest occurred, the cause of which was put down to a dysequilibrium syndrome. The cause, however, must be seen in a continuing stress situation, inadequate hormone substitution and in sedation with diazepam. After reanimation the patient was transferred to the ICU.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗

Comparison of plateletpheresis with two different cell separators using 100 identical donors.

Plateletpheresis with the cell separator COBE Spectra and Fenwal CS 3000 was compared in 100 identical donors. The Spectra was significantly superior with regard to collection efficiency (53% vs. 42%, p less than .001) and leukocyte contamination of the platelet products (.1 x 10(8) vs. 1.4 x 10(8), p less than .001). Additionally, it offers a selectable volume of the concentrate and a better control of the ACD infusion. The Spectra standard procedure needs more ACD, resulting in more citrate dependent donor reactions (5% vs. 1%). In conclusion, the Spectra system shows a more efficient and pure platelet separation compared with the CS 3000.

Adolescent↗

[Blood donor selection in providing anticytomegalovirus-negative blood components].

Sera of 1731 blood donors of the Ulm blood bank were screened for cytomegalovirus (CMV) antibodies. Prevalence of these antibodies was 37%. The seroconversion rate among 1090 anti-CMV-negative blood donors was 13 per thousand per year for the whole donor population over a period of 27 months and depended on age. It was 16 per thousand per year for donors aged 18-40 years, but only 7 per thousand for those over 41 years old. Seropositivity was higher in women than men. To provide anti-CMV-negative blood requires a prescreened anti-CMV-negative donor group and the rescreening of each further donated blood component.

Adolescent↗

HLA antigen frequencies in patients with Huntington's chorea and their relatives.

Twenty patients with Hungtington's chorea and 30 family members were typed for 30 antigens of the HLA-A, B, and C series. There was an increased frequency of HLA-BW 16, significant at the 1%-level. After correcting for multiple inferences, the association of HLA-BW 16 with Huntington's chorea was no longer statistically significant. There was also no reliable indication of coupling between HLA antigens and Huntington's chorea in the family studies.

Adult↗

[HLA antigen frequencies in patients with progressive systemic sclerosis and morphea (author's transl)].

Forty three patients with progressive systemic sclerosis and 24 patients with morphea are typed for 30 antigens of the HLA-A and B series. There is an increase of the frequency of HLA-B8 in patients with progressive systemic sclerosis (37% vs. 20% in controls: P less than 0.001, Pcorr. = n.s.). The increase of the HLA-B8 frequency seems to be most pronounced in patients with a diffuse form of progressive systemic sclerosis. 4 out of 5 patients are HLA-B8 positive (P = 0.00672). In patients with acrosclerosis is HLA-B8 only slightly increased (32%), but the increase is greater in male patients (44%) and in patients with an early onset of the disease (36%). With the exception of HLA-A1 there is no deviation of the frequencies of any other HLA antigen tested, especially not of HLA-Aw24. The number of patients with morphea is to small for statistical evaluation.

Adult↗