PubMed Health⌕ Search

Biomedical subjects

J Schulte

Publications and source records attributed to J Schulte.

At least 19 recordsLinked to original sources
PubMed2006

Heterogeneity in lipopolysaccharide responsiveness of endothelial cells identified by gene expression profiling: role of transcription factors.

Interindividual differences of endothelial cells in response to endotoxins might contribute to the diversity in clinical outcome among septic patients. The present study was conducted to test the hypothesis that endothelial cells (EC) with high and low proinflammatory potential exist and to dissect the molecular basis underlying this phenomenon. Thirty human umbilical vein endothelial cell (HUVEC) lines were stimulated for 24 h with lipopolysaccharide (LPS) and screened for interleukin (IL)-8 production. Based on IL-8 production five low and five high producers, tentatively called types I and II responders, respectively, were selected for genome-wide gene expression profiling. From the 74 genes that were modulated by LPS in all type II responders, 33 genes were not influenced in type I responders. Among the 41 genes that were increased in both responders, 17 were expressed significantly stronger in type II responders. Apart from IL-8, significant differences in the expression of proinflammatory related genes between types I and II responders were found for adhesion molecules [intercellular adhesion molecule (ICAM-1), E-selectin)], chemokines [monocyte chemoattractant protein (MCP-1), granulocyte chemotactic protein (GCP-2)], cytokines (IL-6) and the transcription factor CCAAT/enhancer binding protein-delta (C/EBP-delta). Type I responders also displayed a low response towards tumour necrosis factor (TNF)-alpha. In general, maximal activation of nuclear factor (NF)-kappaB was achieved in type I responders at higher concentrations of LPS compared to type II responders. In the present study we demonstrate that LPS-mediated gene expression differs quantitatively and qualitatively in types I and II responders. Our results suggest a pivotal role for common transcription factors as a low inflammatory response was also observed after TNF-alpha stimulation. Further studies are required to elucidate the relevance of these findings in terms of clinical outcome in septic patients.

Cells, Cultured↗
PubMed2006

Atorvastatin interferes with activation of human CD4(+) T cells via inhibition of small guanosine triphosphatase (GTPase) activity and caspase-independent apoptosis.

Although a beneficial effect of hydroxy-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, i.e. statins, on cell-mediated immunity has been suggested in vivo and in vitro, little is known about the molecular and biochemical events by which statins inhibit T cell proliferation. To address this question, we investigated the effects of atorvastatin (AT) on intracellular cytokine production, T cell activation markers, cell cycle progression and apoptosis in human CD4(+) T cells. AT did not influence intracellular cytokine production after short-term stimulation of whole blood with phorbol myristate acetate (PMA)/ionomycin or superantigen (SEB). In contrast, AT influenced CD45RA to RO switching dose-dependently, as well as CD25 expression, and caused cell cycle arrest in the G1 phase after long-term T cell stimulation. This occurred in conjunction with a reduced expression of cyclin-dependent kinases 2 and 4 and p21(wav1/cip1) and was paralleled by an increased protein expression of p27(kip1). In addition to G1 arrest, increased apoptosis was observed in AT-treated cells. In line with this, the expression of Bcl-xl and pBad were decreased by AT. Apoptosis was independent of caspases 3 and 9 activation. The inhibitory effect of AT on T cell proliferation could be overcome by addition of mevalonic acid or geranylgeranyl pyrophosphate, but not by farnesyl pyrophosphate or squalen, suggesting reduced protein prenylation. Activation of Rho, Rac and Ras were strongly reduced in AT-treated T cells, suggesting that impaired geranylation of these molecules might underlie the inhibitory effect of AT on T cell proliferation.

Apoptosis↗
PubMed2005

Subchronic alpha- and beta-adrenergic regulation of cardiac gap junction protein expression.

Gap junction channels are essential for intercellular electrical communication in the heart. The most important cardiac gap junction proteins are connexin43 (predominantly) (Cx43), connexin40 (Cx40), and in early developmental stages connexin45. Since catecholamines play an important role in cardiac (patho)physiology, we wanted to elucidate whether catecholamines may affect expression of Cx43 and Cx40. Cultured neonatal rat cardiomyocytes were exposed for 24 h to increasing concentrations of noradrenaline (1-10000 nM) (physiological agonist at alpha and beta-adrenoceptors), resulting in significantly increased Cx43-expression, while Cx40 was unaffected. In further experiments cells were incubated with either phenylephrine (alpha-adrenergic agonist) or isoproterenol (beta-adrenergic agonist) (0.1-1000 nM) for 24 h. Both catecholamines lead to a concentration-dependent increase in Cx43 protein and mRNA expression (EC50: 10-20 nM). Inhibition experiments showed that the phenylephrine effect was transduced via PKC, while the isoproterenol effect was mediated by PKA. Dual whole-cell voltage clamp demonstrated that increased Cx43-expression was accompanied by significant increases in gap junction current. In additional in vivo experiments, adult rats were subjected to 24-h infusion of isoproterenol or phenylephrine showing again significant increase in Cx43 but not Cx40. Adrenergic stimulation of cardiomyocytes can enhance Cx43 expression thereby increasing cellular coupling, indicating a possible role for catecholamines in the regulation of cardiac gap junction expression in cardiac disease.

Adrenergic alpha-Agonists↗
PubMed2005

Spike timing in CA3 pyramidal cells during behavior: implications for synaptic transmission.

Spike timing is thought to be an important mechanism for transmitting information in the CNS. Recent studies have emphasized millisecond precision in spike timing to allow temporal summation of rapid synaptic signals. However, spike timing over slower time scales could also be important, through mechanisms including activity-dependent synaptic plasticity or temporal summation of slow postsynaptic potentials (PSPs) such as those mediated by kainate receptors. To determine the extent to which these slower mechanisms contribute to information processing, it is first necessary to understand the properties of behaviorally relevant spike timing over this slow time scale. In this study, we examine the activity of CA3 pyramidal cells during the performance of a complex behavioral task in rats. Sustained firing rates vary over a wide range, and the firing rate of a cell is poorly correlated with the behavioral cues to which the cell responds. Nonrandom interactions between successive spikes can last for several seconds, but the nonrandom distribution of interspike intervals (ISIs) can account for the majority of nonrandom multi-spike patterns. During a stimulus, cellular responses are temporally complex, causing a shift in spike timing that favors intermediate ISIs over short and long ISIs. Response discrimination between related stimuli occurs through changes in both response time-course and response intensity. Precise synchrony between cells is limited, but loosely correlated firing between cells is common. This study indicates that spike timing is regulated over long time scales and suggests that slow synaptic mechanisms could play a substantial role in information processing in the CNS.

Action Potentials↗
PubMed2005

[Effects of dopamine on cellular and humoral immune responses in septic patients].

In vitro and in vivo studies have demonstrated that apart from its hemodynamic action dopamine can modulate immune responses. Dopamine reduces the synthesis of proinflammatory and induces the synthesis of anti-inflammatory mediators. Dopamine inhibits neurohormone synthesis, lymphocyte proliferation and platelet aggregation. It reduces the phagocytic activity of neutrophils and induces apoptosis. Particularly with regard to sepsis, where high serum dopamine levels are reached by enhanced endogenous production, exogenous application and impaired clearance, this immunomodulation may have a clinical impact. This review summarizes dopamine-mediated immunomodulating effects to advance the knowledge regarding dopamine as an immune regulator under septic conditions.

Animals↗
PubMed2005

Large-scale analysis of 73 329 physcomitrella plants transformed with different gene disruption libraries: production parameters and mutant phenotypes.

Gene targeting in the moss Physcomitrella patens has created a new platform for plant functional genomics. We produced a mutant collection of 73 329 Physcomitrella plants and evaluated the phenotype of each transformant in comparison to wild type Physcomitrella. Production parameters and morphological changes in 16 categories, such as plant structure, colour, coverage with gametophores, cell shape, etc., were listed and all data were compiled in a database (mossDB). Our mutant collection consists of at least 1804 auxotrophic mutants which showed growth defects on minimal Knop medium but were rescued on supplemented medium. 8129 haploid and 11 068 polyploid transformants had morphological alterations. 9 % of the haploid transformants had deviations in the leaf shape, 7 % developed less gametophores or had a different leaf cell shape. Other morphological deviations in plant structure, colour, and uniformity of leaves on a moss colony were less frequently observed. Preculture conditions of the plant material and the cDNA library (representing genes from either protonema, gametophore or sporophyte tissue) used to transform Physcomitrella had an effect on the number of transformants per transformation. We found correlations between ploidy level and plant morphology and growth rate on Knop medium. In haploid transformants correlations between the percentage of plants with specific phenotypes and the cDNA library used for transformation were detected. The number of different cDNAs present during transformation had no effect on the number of transformants per transformation, but it had an effect on the overall percentage of plants with phenotypic deviations. We conclude that by linking incoming molecular, proteome, and metabolome data of the transformants in the future, the database mossDB will be a valuable biological resource for systems biology.

Bryopsida↗
PubMed2005

Developmental outcome of the use of etamsylate for prevention of periventricular haemorrhage in a randomised controlled trial.

OBJECTIVE: To compare neurodevelopmental outcome of survivors of the multicentre trial of etamsylate (the iRNN for ethamsylate) for prevention of periventricular haemorrhage in very low birthweight infants. DESIGN: Double blind, single observer, prospective follow up of placebo controlled study. SETTING: Six neonatal intensive care units in the United Kingdom. Neurodevelopmental outcome was assessed in health premises or children's homes. SUBJECTS: 268 of 276 survivors of the original study were seen between 3.5 and 4.2 years of age. All were inborn and weighed 1500 g or less at birth. INTERVENTION: Etamsylate 12.5 mg/kg or placebo six hourly from within one hour of delivery for four days. MAIN OUTCOME MEASURES: McCarthy scales of children's abilities, standardised neurological examination, full physical examination, functional assessment, seven letter Stycar vision test, and audiometry. RESULTS: There was no difference between the groups in neuromotor outcome (cerebral palsy) or in the general cognitive index (GCI) of the McCarthy scales (mean GCI was 93.3 for the etamsylate group (n = 133) and 89.7 for the placebo group (n = 131); p = 0.10). There were more children with GCI < 70 (9 v 19; p = 0.047) or </= 50 (3 v 11; p = 0.03) in the placebo group. Fewer children in the etamsylate group had squints (17 v 30; p = 0.042) or required surgery for patent ductus arteriosus (1 v 8; p = 0.036). CONCLUSIONS: Etamsylate was not associated with a reduction in cerebral palsy. Severe cognitive impairment was reduced, but more children died and the improvement may be because fewer survived with low GCI.

Cerebral Hemorrhage↗
PubMed2004

Newborn screening for biotinidase deficiency in Brazil: biochemical and molecular characterizations.

Biotinidase deficiency is an inherited metabolic disorder characterized by neurological and cutaneous symptoms. Fortunately, it can be treated and the symptoms prevented by oral administration of the vitamin biotin. Using dried blood-soaked filter paper cards, biotinidase activity was determined in the sera of 225,136 newborns in Brazil. Mutation analysis performed on DNA from 21 babies with low serum biotinidase activity confirmed that 3 had profound biotinidase deficiency (less than 10% of mean normal sera biotinidase activity), 10 had partial biotinidase deficiency (10 to 30% of mean normal serum activity), 1 was homozygous for partial biotinidase deficiency, 4 were heterozygous for either profound or partial deficiency, and 3 were normal. Variability in serum enzyme activities and discrepancies with mutation analyses were probably due to inappropriate handling and storage of samples sent to the laboratory. Obtaining an appropriate control serum at the same time as that of the suspected child will undoubtedly decrease the false-positive rate (0.09%). Mutation analysis can be used to confirm the genotype of these children. The estimated incidence of biotinidase deficiency in Brazil is about 1 in 9,000, higher than in most other countries. Screening and treatment of biotinidase deficiency are effective and warranted. These results strongly suggest that biotinidase deficiency should be included in the newborn mass screening program of Brazil.

Biotinidase Deficiency↗
PubMed2003

Fractalkine is not a major chemoattractant for the migration of neutrophils across microvascular endothelium.

Inflammatory responses during sepsis are determined by leucocyte recruitment into inflamed tissues. Both chemokines and adhesion molecules are believed to be involved in this process. As fractalkine exists as transmembrane protein with cell adhesion properties and as soluble chemotactic factor, the present study was conducted to study the role of fractalkine, produced by microvascular and macrovascular endothelial cells, in neutrophil recruitment. Lung microvascular endothelial cells (LMVECs) stimulated with lipopolysaccharide, tumour necrosis factor-alpha or interleukin-1 (IL-1) produced much more fractalkine compared with the macrovascular human umbilical vein endothelial cells (HUVECs). No differences were found between microvascular endothelial cells of different organs. Chemotactic activity in supernatants was significantly stronger in stimulated LMVEC when compared with HUVEC. Although recombinant fractalkine induced migration of neutrophils, IL-8 and monocyte chemoattractant protein-1 were found to be more strictly required. In vivo fractalkine was strongly upregulated in septic lung and kidney. Our data suggest that fractalkine production per se does not explain the preference for inflammation in the lung of septic patients.

Chemokine CX3CL1↗
PubMed2002

Inhibition of LPS-induced chemokine production in human lung endothelial cells by lipid conjugates anchored to the membrane.

1. In acute respiratory distress syndrome (ARDS) induced by endotoxins, a high production of inflammatory mediators by microvascular lung endothelial cells (LMVEC) can be observed. Activation of cells by endotoxins may result in elevated secretion of phospholipase A(2) (sPLA(2)) which is thought to contribute to tissue damage. The present study was undertaken to investigate the role of sPLA(2) in chemokine production in human lung microvascular endothelial cells (LMVEC) stimulated with the endotoxins lipopolysaccharide (LPS) and lipoteichoic acid (LTA). In particular, we investigated the effects of sPLA(2) inhibitors, specifically, the extracellular PLA(2) inhibitors (ExPLIs), composed of N-derivatized phosphatidyl-ethanolamine linked to polymeric carriers, and LY311727, a specific inhibitor of non-pancreatic sPLA(2). 2. ExPLIs markedly inhibited LPS and LTA induced production and mRNA expression of the neutrophile attracting chemokines IL-8, Gro-alpha and ENA-78, as well as of the adhesion molecules ICAM-1 and E-selectin. Concomitantly, ExPLIs inhibited the LPS-induced activation of NF-kappaB by LPS but not its activation by TNF-alpha or IL-1. 3. Endotoxin mediated chemokine production in LMVEC seems not to involve PLA(2) activity, since LPS stimulation was not associated with activation of intracellular or secreted PLA(2). It therefore seems that the inhibitory effect of the ExPLIs was not due to their PLA(2) inhibiting capacity. This was supported by the finding that the LPS-induced chemokine production was not affected by the selective sPLA(2) inhibitor LY311727. 4. It is proposed that the ExPLIs may be considered a prototype of potent suppressors of specific endotoxin-induced inflammatory responses, with potential implications for the therapy of subsequent severe inflammation.

Cell Adhesion Molecules↗
PubMed2001

Peripheral glia direct axon guidance across the CNS/PNS transition zone.

CNS glia have integral roles in directing axon migration of both vertebrates and insects. In contrast, very little is known about the roles of PNS glia in axonal pathfinding. In vertebrates and Drosophila, anatomical evidence shows that peripheral glia prefigure the transition zones through which axons migrate into and out of the CNS. Therefore, peripheral glia could guide axons at the transition zone. We used the Drosophila model system to test this hypothesis by ablating peripheral glia early in embryonic neurodevelopment via targeted overexpression of cell death genes grim and ced-3. The effects of peripheral glial loss on sensory and motor neuron development were analyzed. Motor axons initially exit the CNS in abnormal patterns in the absence of peripheral glia. However, they must use other cues within the periphery to find their correct target muscles since early pathfinding errors are largely overcome. When peripheral glia are lost, sensory axons show disrupted migration as they travel centrally. This is not a result of motor neuron defects, as determined by motor/sensory double-labeling experiments. We conclude that peripheral glia prefigure the CNS/PNS transition zone and guide axons as they traverse this region.

Animals↗
PubMed2001

A new MFS-transporter gene next to the gibberellin biosynthesis gene cluster of Gibberella fujikuroi is not involved in gibberellin secretion.

The genes of the gibberellin (GA) biosynthesis pathway in Gibberella fujikuroi are organized in a gene cluster consisting of at least seven genes. Here we report the cloning and characterization of smt, a gene encoding a membrane transporter of the major facilitator super-family 1, which is located next to the GA gene cluster. Since pathway-specific transporters occur frequently in prokaryotic and fungal antibiotic and toxin clusters, smt was thought to be involved in GA secretion. The gene is expressed in mycelium grown under GA-production conditions, but not when the GA biosynthesis is repressed by high amounts of ammonium. To investigate the function of SMT, gene replacement experiments were performed. The smt-mutants did not show any reduction in the GA yield; and gibberellic acid or its precursors did not influence the gene expression. However, sugar alcohols, such as myo-inositol, sorbitol and mannitol, induced the expression of smt. The results demonstrate that the smt gene does not play an essential role in biosynthesis and secretion of GAs in G. fujikuroi, despite the location adjacent to the GA gene cluster.

DNA, Fungal↗
PubMed2001

Vocal development of 9-month-old babies with cleft palate.

This study compared the prelinguistic vocal development of 9-month-old babies with unrepaired cleft palate (n = 30) and age-matched peers (n = 15). Samples of the babies' spontaneous vocalizations were obtained while they interacted with their primary caregiver during play. The groups were compared on a number of variables including (a) canonical babbling ratios, (b) percentage of babies who reached the canonical babbling stage by 9 months, (c) syllable and segmental aspects of babbling, and (d) vocal frequency. Results indicated that the babies with cleft palate had smaller canonical babbling ratios than their age-matched peers, with just 57% of the babies with cleft palate reaching the canonical babbling stage by 9 months compared to 93% of the noncleft babies. Although syllable types and length were similar for the two groups, differences were noted for consonant characteristics. The babies with cleft palate had smaller consonant inventories, with fewer stops, glides, and velars noted. Glottals occurred more frequently in the vocalizations of the babies with cleft palate. Finally, no statistically significant difference was noted in the number of vocalizations produced by the two groups. Some possible explanations for why babies with cleft palate are delayed in babbling are explored.

Child Language↗
PubMed2001

Modulation of chemokine production in lung microvascular endothelial cells by dopamine is mediated via an oxidative mechanism.

Serum concentrations of catecholamines are high in patients with sepsis or acute respiratory distress syndrome (ARDS). Because chemokines mediate the recruitment of neutrophils into inflammatory sites, we addressed the question of whether dopamine (DA) is able to influence chemokine production in endothelial cells under basal and proinflammatory conditions. To this end, lung microvascular endothelial cells (LMVEC) were stimulated or not for 24 h with the bacterial toxins lipopolysaccharide (LPS) (1 microg/ml) or lipoteichonic acid (LTA) (10 microg/ml) in the presence or absence of various concentrations of DA (1-100 microg/ml). Whereas under basal and stimulatory conditions, the addition of DA to endothelial cells dose-dependently increased IL-8 production, the production of ENA-78 and Gro-alpha was significantly inhibited (P < 0.01). This effect could still be demonstrated when the cells were stimulated for up to 3 h with LPS before DA administration. Similar findings were detected for the mRNA expression of these chemokines. The influence of DA on chemokine production was not receptor mediated and could be prevented by antioxidants or radical scavengers. Moreover, addition of H(2)O(2) to endothelial cells gave results similar to those observed with DA stimulation, suggesting a pivotal role for reactive oxygen species in DA-mediated modulation of chemokine production in endothelial cells. Our data thus demonstrate that DA administration results in the induction of oxidative stress, with profound effects on endothelial chemokine production.

Cardiotonic Agents↗
PubMed2001

Inelastic scattering on spherical microparticles with inclusions.

The subject of the paper is scattering at spherical microparticles with inclusions. The inclusions are represented as dipoles for both elastic and inelastic scattering. For elastic scattering the dipoles are computed iteratively, and sequence transformations are used to accelerate this iteration. Mie theory is used to calculate the cross sections for scattering on spherical microparticles with inclusions as well as on agglomerates.

Journal Article↗
PubMed2001

Risk factors for latent tuberculosis infection among children in New York City.

OBJECTIVE: Although identification and appropriate treatment of children with latent tuberculosis (TB) infection (LTBI) is considered critical to the control and elimination of TB in the United States, there are limited data on risk factors for LTBI in pediatric populations. METHODS: To further improve targeted screening for LTBI, we performed a matched case-control study from September 1996 to December 1998. We actively surveyed 24 primary care clinics serving Northern Manhattan and Harlem twice monthly for case participants 1 to 5 years old with LTBI, defined as a child with a Mantoux tuberculin skin test (TST) >/=10 mm and a normal chest radiograph. Two age- and clinic-matched control participants with TSTs equal to 0 mm were enrolled per case. To determine risk factors for LTBI, a bilingual research worker reviewed the medical records of study participants and administered a questionnaire to the parents of participants. RESULTS: We enrolled 96 cases and 192 controls whom did not differ by age, gender, ethnicity, and race; overall, the mean age of participants was 2.9 years, 51% were male, 80% were Hispanic, and 9% black. Logistic regression analysis demonstrated that contact with an adult with active TB, foreign birth, foreign travel, and a relative with a positive TST were predictive of case status. In contrast, a history of a previous negative TST proved protective and BCG immunization was not an independent risk factor for a positive TST, suggesting that boosting was not important in this population. CONCLUSIONS: We identified several risk factors for LTBI in children that can be used to refine targeted surveillance for TB among Hispanic immigrant populations in the United States.

Case-Control Studies↗
PubMed2001

Prevalence of infectious diseases among internationally adopted children.

OBJECTIVE: Internationally adopted children are at increased risk of infections acquired in their country of origin. Ongoing surveillance of this unique population is needed to detect changing epidemiology and provide appropriate care. METHODS: We performed a retrospective cohort study of 504 children adopted from abroad and evaluated from 1997 to 1998 to determine the prevalence of and factors associated with various infectious diseases. RESULTS: The mean age of the study participants at medical evaluation was 1.6 years; 71% were girls, and they were adopted from 16 countries, including China (48%), Russia (31%), Southeast Asia (8%), Eastern Europe (8%), and Latin America (5%). Overall, 75 (19%) of 404 children tested had tuberculin skin tests >/=10 mm, but all had normal chest radiographs. BCG vaccination (odds ratio [OR]: 7.37; 95% confidence interval [CI]: 3.29, 17.16) and being Russian born (OR: 2.90; 95% CI: 1.68, 5.00) were risk factors for latent tuberculosis infection. Fourteen (2.8%) children had detectable hepatitis B surface antigen, but no child had active hepatitis C, human immunodeficiency virus, or syphilis. Giardia lamblia antigen was detected in 87 (19%) of 461 tested children, and such children were older (mean: 22 months vs 15.5 months) and more likely to have been born in Eastern Europe (OR: 2.82; 95% CI: 1.70, 4.68). CONCLUSIONS: We demonstrated increased rates of latent tuberculosis infection and G lamblia infection than previously reported. Thus, ongoing surveillance of internationally adopted children, international trends in infectious diseases, and appropriate screening will ensure the long-term health of adopted children as well as their families.

Adoption↗