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Biomedical subjects

J Schumacher

Publications and source records attributed to J Schumacher.

At least 19 recordsLinked to original sources
PubMed2006

Interrelationship and familiality of dyslexia related quantitative measures.

Dyslexia is a complex gene-environment disorder with poorly understood etiology that affects about 5% of school-age children. Dyslexia occurs in all languages and is associated with a high level of social and psychological morbidity for the individual and their family; approximately 40-50% have persistent disability into adulthood. The core symptoms are word reading and spelling deficits, but several other cognitive components influence the core phenotype. A broad spectrum of dyslexia related phenotypes, including phonological decoding, phoneme awareness, orthographic processing, short-term memory, rapid naming and basic mathematical abilities, were investigated in large sample of 287 German dyslexia families. We explored the interrelationship between the component phenotypes using correlation and principal component analyses (PCA). In addition, we estimated familiality for phenotypes as well as for the factors suggested by PCA. The correlation between the component phenotypes varied between -0.1 and 0.7. The PCA resulted in three factors: a general dyslexia factor, a speed of processing factor and a mathematical abilities factor. The familiality estimates of single components and factors ranged between 0.25 and 0.63. Instead of analyzing single dyslexia-related components, multivariate analyses including factor analytic approaches may help in the identification of susceptibility genes.

Adolescent↗
PubMed2006

Genome-wide scan for genes involved in bipolar affective disorder in 70 European families ascertained through a bipolar type I early-onset proband: supportive evidence for linkage at 3p14.

Preliminary studies suggested that age at onset (AAO) may help to define homogeneous bipolar affective disorder (BPAD) subtypes. This candidate symptom approach might be useful to identify vulnerability genes. Thus, the probability of detecting major disease-causing genes might be increased by focusing on families with early-onset BPAD type I probands. This study was conducted as part of the European Collaborative Study of Early Onset BPAD (France, Germany, Ireland, Scotland, Switzerland, England, Slovenia). We performed a genome-wide search with 384 microsatellite markers using non-parametric linkage analysis in 87 sib-pairs ascertained through an early-onset BPAD type I proband (AAO of 21 years or below). Non-parametric multipoint analysis suggested eight regions of linkage with P-values<0.01 (2p21, 2q14.3, 3p14, 5q33, 7q36, 10q23, 16q23 and 20p12). The 3p14 region showed the most significant linkage (genome-wide P-value estimated over 10 000 simulated replicates of 0.015 [0.01-0.02]). After genome-wide search analysis, we performed additional linkage analyses with increased marker density using markers in four regions suggestive for linkage and having an information contents lower than 75% (3p14, 10q23, 16q23 and 20p12). For these regions, the information content improved by about 10%. In chromosome 3, the non-parametric linkage score increased from 3.51 to 3.83. This study is the first to use early-onset bipolar type I probands in an attempt to increase sample homogeneity. These preliminary findings require confirmation in independent panels of families.

Adolescent↗
PubMed2006

Effects of candesartan and enalaprilat on the organ-specific microvascular permeability during haemorrhagic shock in rats.

BACKGROUND: To counteract the contribution of angiotensin II to shock-induced ischaemic organ damage pharmacologic blockade of the renin-angiotensin-system (RAS) is currently under investigation. To evaluate potential side-effects of RAS blockade regarding capillary leak, we studied alterations in microvascular permeability in various organs during haemorrhagic shock (HS) in rats pretreated with candesartan (AT(1)-receptor antagonism) or enalaprilat (ACE-inhibition). METHODS: Thirty-eight instrumented and anaesthetized animals received either candesartan, enalaprilat or placebo. Within each of the three groups 6-7 animals were exposed to HS and 6 animals of each group served as normovolaemic controls. After 30 min of shock, 50 mg kg(-1) Evans blue (EB) was injected i.v. followed by a distribution period of 20 min. Exsanguination was performed with saline, before harvesting organs to quantify albumin-bound EB extravasation. RESULTS: To reduce cardiac output from 37.5 (1.3) to 20.4 (1.1) ml min(-1) [mean (SEM)] in the shock groups, withdrawal of 4.0 (0.25) ml [mean (SEM)] blood was necessary. Simultaneously mean arterial pressure decreased from 77.5 (3.2) to 36.1 (2) mm Hg. Serum lactate increased significantly from 1.3 (0.1) to 3.5 (0.24) mmol litre(-1). Treatment with candesartan increased EB extravasation in the kidney in normovolaemic controls. Specific AT(1) and ACE-blockade before acute non-resuscitated HS significantly increased EB extravasation in the rat ileum by 53 and 66%, respectively. CONCLUSION: This observation of increased microvascular albumin extravasation should be borne in mind for any interventional use of candesartan or enalaprilat during circulatory stress.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2006

A second paradigm for gene activation in bacteria.

Control of gene expression is key to development and adaptation. Using purified transcription components from bacteria, we employ structural and functional studies in an integrative manner to elaborate a detailed description of an obligatory step, the accessing of the DNA template, in gene expression. Our work focuses on a specialized molecular machinery that utilizes ATP hydrolysis to initiate DNA opening and permits a description of how the events triggered by ATP hydrolysis within a transcriptional activator can lead to DNA opening and transcription. The bacterial EBPs (enhancer binding proteins) that belong to the AAA(+) (ATPases associated with various cellular activities) protein family remodel the RNAP (RNA polymerase) holoenzyme containing the sigma(54) factor and convert the initial, transcriptionally silent promoter complex into a transcriptionally proficient open complex using transactions that reflect the use of ATP hydrolysis to establish different functional states of the EBP. A molecular switch within the model EBP we study [called PspF (phage shock protein F)] is evident, and functions to control the exposure of a solvent-accessible flexible loop that engages directly with the initial RNAP promoter complex. The sigma(54) factor then controls the conformational changes in the RNAP required to form the open promoter complex.

Bacteria↗
PubMed2006

Biomimetic evolutionary analysis: testing the adaptive value of vertebrate tail stiffness in autonomous swimming robots.

For early vertebrates, a long-standing hypothesis is that vertebrae evolved as a locomotor adaptation, stiffening the body axis and enhancing swimming performance. While supported by biomechanical data, this hypothesis has not been tested using an evolutionary approach. We did so by extending biomimetic evolutionary analysis (BEA), which builds physical simulations of extinct systems, to include use of autonomous robots as proxies of early vertebrates competing in a forage navigation task. Modeled after free-swimming larvae of sea squirts (Chordata, Urochordata), three robotic tadpoles (;Tadros'), each with a propulsive tail bearing a biomimetic notochord of variable spring stiffness, k (N m(-1)), searched for, oriented to, and orbited in two dimensions around a light source. Within each of ten generations, we selected for increased swimming speed, U (m s(-1)) and decreased time to the light source, t (s), average distance from the source, R (m) and wobble maneuvering, W (rad s(-2)). In software simulation, we coded two quantitative trait loci (QTL) that determine k: bending modulus, E (Nm(-2)) and length, L (m). Both QTL were mutated during replication, independently assorted during meiosis and, as haploid gametes, entered into the gene pool in proportion to parental fitness. After random mating created three new diploid genotypes, we fabricated three new offspring tails. In the presence of both selection and chance events (mutation, genetic drift), the phenotypic means of this small population evolved. The classic hypothesis was supported in that k was positively correlated (r(2)=0.40) with navigational prowess, NP, the dimensionless ratio of U to the product of R, t and W. However, the plausible adaptive scenario, even in this simplified system, is more complex, since the remaining variance in NP was correlated with the residuals of R and U taken with respect to k, suggesting that changes in k alone are insufficient to explain the evolution of NP.

Animals↗
PubMed2006

Hemangiopericytoma in the eyelid of a horse.

Hemangiopericytoma (HP) is a well-recognized neoplasm arising from vascular pericytes that has been reported only in the dog and man. In this study, we describe a 14-year-old female Arabian horse that was presented for surgical excision of a 2-cm-diameter expansile subcuticular mass in the right lower eyelid. Histologically, the mass consisted of loosely arranged interlacing streams and storiform bundles of spindle cells that often formed distinct whorls around a central capillary and bundles of collagen (Antoni A-like pattern). Immunohistochemical analysis revealed strong diffuse cytoplasmic immunoreactivity for vimentin and focal immunoreactivity for smooth muscle actin, whereas neoplastic cells did not stain for Factor VIII-related antigen, Glial fibrillary acidic protein (GFAP), or S100. On the basis of histomorphology and immunohistochemical reactivity, the present tumor was diagnosed as HP. To our knowledge, this is the first report describing a HP in a horse.

Animals↗
PubMed2005

Linkage analyses of chromosomal region 18p11-q12 in dyslexia.

Dyslexia is characterized as a significant impairment in reading and spelling ability that cannot be explained by low intelligence, low school attendance or deficits in sensory acuity. It is known to be a hereditary disorder that affects about 5% of school aged children, making it the most common of childhood learning disorders. Several susceptibility loci have been reported on chromosomes 1, 2, 3, 6, 15, and 18. The locus on chromosome 18 has been described as having the strongest influence on single word reading, phoneme awareness, and orthographic coding in the largest genome wide linkage study published to date (Fisher et al., 2002). Here we present data from 82 German families in order to investigate linkage of various dyslexia-related traits to the previously described region on chromosome 18p11-q12. Using two- and multipoint analyses, we did not find support for linkage of spelling, single word reading, phoneme awareness, orthographic coding and rapid naming to any of the 14 genotyped STR markers. Possible explanations for our non-replication include differences in study design, limited power of our study and overestimation of the effect of the chromosome 18 locus in the original study.

Adolescent↗
PubMed2005

Effects of surgery on the acute phase response in clinically normal and diseased horses.

The serum concentrations of serum amyloid A, haptoglobin and fibrinogen were measured in a group of horses before and at intervals after elective and non-elective surgery, and in a control group of normal horses. There was a significant, rapid and repeatable increase in the concentration of serum amyloid A in response to both elective and non-elective surgery. In the control horses its serum concentration was within the normal range, from 0 to 0.2 microg/ml. Twenty-four hours after elective surgery its mean peak concentration was 16.4 microg/ml, and after non-elective surgery it was 27.3 microg/ml. In contrast, the serum concentrations of haptoglobin and fibrinogen increased more slowly after surgery and had not decreased by 72 hours after surgery.

Acute-Phase Reaction↗
PubMed2005

An investigation of the ability of the glutaraldehyde test to distinguish between acute and chronic inflammatory disease in horses.

The glutaraldehyde test (GT), a rapid and inexpensive test, has been utilized empirically for many years in bovine practice for diagnosing inflammatory diseases. GT is used primarily to demonstrate increased serum concentrations of fibrinogen and globulin. Glutaraldehyde binds with free amino groups in fibrinogen and immunoglobulin to create a clot in a first degree chemical reaction. The clotting time of the GT estimates the content of proteins produced in response to inflammation. The applicability of GT for diagnosing inflammation in the horse has never been investigated. The objective of this study was to determine the ability of GT to distinguish between acute and chronic inflammatory disease in horses. Thirty-seven horses with suspected inflammatory diseases were evaluated using the GT, history, complete clinical examination and routine blood analysis. GT-times, laboratory results and clinical outcome were compared statistically. Horses that were determined to be acutely affected (based on history, clinical examination and routine blood analysis) tended to have a negative GT (75%). Results of the GT did not correlate with blood fibrinogen concentration. Positive GT also predicted a fatal outcome in 69% of the clinical cases. The results of this trial indicate that GT can be a useful screening test to distinguish between acute and chronic inflammatory disease in horses.

Acute Disease↗
PubMed2005

Concentration of methylprednisolone in the centrodistal joint after administration of methylprednisolone acetate in the tarsometatarsal joint.

REASONS FOR PERFORMING STUDY: The centrodistal (CD) and tarsometatarsal (TMT) joints are often injected individually with a corticosteroid to resolve lameness caused by osteoarthritis (OA). There are no data available regarding diffusion of methylprednisolone (MP) from the TMT joint to the CD joint. HYPOTHESIS: A therapeutic concentration of MP diffuses into the CD joint after methylprednisolone acetate (MPA) is administered into the TMT joint. OBJECTIVE: To measure the concentration of MP in the CD joint after MPA was administered into the TMT joint. METHODS: MPA was administered into a TMT joint of 16 horses. At different times, the ipsilateral CD joint of these horses was injected with a small amount of saline and recovered saline was measured for concentration of MP using high performance liquid chromatography. RESULTS: Six hours after administration of MPA into the TMT joint, a therapeutic concentration of MP was found in all 10 CD joints sampled at this time. CONCLUSIONS: Horses with pain arising from the distal 2 joints of the hock can be treated by administering MPA into the TMT joint alone. POTENTIAL RELEVANCE: Administering MPA into the TMT joint only, to treat OA of the distal 2 hock joints, reduces the difficulties and risks associated with centesis of the CD joint.

Animals↗
PubMed2005

[Pilot study of echocardiographic studies using color- and pulsed-wave spectral Doppler methods in blue-crowned amazons (Amazona ventralis) and blue-fronted amazons (Amazona a. aestiva)].

Colour-flow and pulsed-wave spectral Doppler echocardiography was performed on 6 healthy, adult Hispaniolan amazon parrots (Amazona ventralis) and 6 blue-fronted amazon parrots (Amazona a. aestiva) to establish normal reference values. Birds were anesthetized with isoflurane in oxygen and placed in dorsal recumbency. An electrocardiogram was recorded continuously and birds were imaged with a micro-phased-array scanner with a frequency of 7.0 MHz. After assessment of cardiac function in 2-D-echocardiography, blood flow across the left and the right atrioventricular valve and across the aortic valve was determined using color-flow and pulsed-wave spectral Doppler echocardiography. Diastolic inflow (mean value +/- standard deviation) into the left ventricle was 0.17 +/- 0.02 m/s (Hispaniolan amazons) and 0.18 +/- 0.03 m/s (Blue fronted amazons). Diastolic inflow into the right ventricle was 0.22 +/- 0.05 m/s (Hispaniolan amazons) and 0.22 +/- 0.04 m/s (Blue fronted amazons). Velocity across the aortic valve was 0.84 +/- 0.07 m/s (Hispaniolan amazons) and 0.83 +/- 0.08 m/s (Blue fronted amazons). Systolic pulmonary flow could not be detected in any of the birds in this study. No significant differences were evident between the two species examined. Results of this study indicate that Doppler echocardiography is a promising technique to determine blood flow in the avian heart. Further studies in other avian species are needed to establish reference values for assessment of cardiac function in diseased birds.

Amazona↗
PubMed2004

Nucleotide-dependent interactions between a fork junction-RNA polymerase complex and an AAA+ transcriptional activator protein.

Enhancer-dependent transcriptional activators that act upon the sigma54 bacterial RNA polymerase holoenzyme belong to the extensive AAA+ superfamily of mechanochemical ATPases. Formation and collapse of the transition state for ATP hydrolysis engenders direct interactions between AAA+ activators and the sigma54 factor, required for RNA polymerase isomerization. A DNA fork junction structure present within closed complexes serves as a nucleation point for the DNA melting seen in open promoter complexes and restricts spontaneous activator-independent RNA polymerase isomerization. We now provide physical evidence showing that the ADP.AlF(x) bound form of the AAA+ domain of the transcriptional activator protein PspF changes interactions between sigma54-RNA polymerase and a DNA fork junction structure present in the closed promoter complex. The results suggest that one functional state of the nucleotide-bound activator serves to alter DNA binding by sigma54 and sigma54-RNA polymerase and appears to drive events that precede DNA opening. Clear evidence for a DNA-interacting activity in the AAA+ domain of PspF was obtained, suggesting that PspF may make a direct contact to the DNA component of a basal promoter complex to promote changes in sigma54-RNA polymerase-DNA interactions that favour open complex formation. We also provide evidence for two distinct closed promoter complexes with differing stabilities.

Adenosine Diphosphate↗