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Biomedical subjects

Henrik Jönsson

Publications and source records attributed to Henrik Jönsson.

15 recordsLinked to original sources
PubMed2006

Modelling meristem development in plants.

Meristems continually supply new cells for post-embryonic plant development and coordinate the initiation of new organs, such as leaves and flowers. Meristem function is regulated by a large and interconnected dynamic system that includes transcription networks, intercellular protein signalling, polarized transport of hormones and a constantly changing cellular topology. Mathematical modelling, in which the dynamics of a system are simulated using explicitly defined interactions, can serve as a powerful tool for examining the expected behaviour of such a system given our present knowledge and assumptions. Modelling can also help to investigate new hypotheses in silico both to validate ideas and to obtain inspiration for new experiments. Several recent studies have used new molecular data together with modelling and computational techniques to investigate meristem function.

Indoleacetic Acids↗
PubMed2006

A rate equation approach to elucidate the kinetics and robustness of the TGF-beta pathway.

We present a rate equation model for the TGF-beta pathway in endothelial cells together with novel measurements. This pathway plays a prominent role in inter- and intracellular communication and subversion can lead to cancer, fibrosis vascular disorders, and immune diseases. The model successfully describes the kinetics of experimental data and also correctly predicts the behavior in experiments where the system is perturbed. A novel method in this context, simulated tempering, is used to fit the model parameters to the data. It provides an ensemble of high quality solutions, which are analyzed with clustering methods and display a hierarchical structure highlighting distinct parameter subspaces with biological interpretations. This analysis discriminates between different biological mechanisms to achieve a transient signal from a sustained TGF-beta input, where one mechanism is to use a negative feedback to turn the signal off. Further analysis in terms of parameter sensitivity reveals that this negative feedback loop in TGF-beta signaling renders the system global robustness. This sheds light upon the role of the Smad7 protein in this system.

Computer Simulation↗
PubMed2006

An auxin-driven polarized transport model for phyllotaxis.

Recent studies show that plant organ positioning may be mediated by localized concentrations of the plant hormone auxin. Auxin patterning in the shoot apical meristem is in turn brought about by the subcellular polar distribution of the putative auxin efflux mediator, PIN1. However, the question of what signals determine PIN1 polarization and how this gives rise to regular patterns of auxin concentration remains unknown. Here we address these questions by using mathematical modeling combined with confocal imaging. We propose a model that is based on the assumption that auxin influences the polarization of its own efflux within the meristem epidermis. We show that such a model is sufficient to create regular spatial patterns of auxin concentration on systems with static and dynamic cellular connectivities, the latter governed by a mechanical model. We also optimize parameter values for the PIN1 dynamics by using a detailed auxin transport model, for which parameter values are taken from experimental estimates, together with a template consisting of cell and wall compartments as well as PIN1 concentrations quantitatively extracted from confocal data. The model shows how polarized transport can drive the formation of regular patterns.

Arabidopsis↗
PubMed2006

Differential distribution of lipid microemboli after cardiac surgery.

BACKGROUND: Lipid microemboli found in shed blood during cardiac surgery have been shown to block capillaries of the brain postoperatively. In this study, the distribution of lipid microemboli in different regions of the brain and other organs was examined. A novel porcine model using radioactive lipid particles was used. METHODS: Ten animals (2 controls and 8 cases) were anesthetized and put on cardiopulmonary bypass. A shed-blood phantom was produced from arterial blood, saline, and tritium-labeled triolein. The phantom was infused into the cardiopulmonary bypass circuit. Tissue samples were taken postmortem from examined organs and prepared for scintillation counting. Levels of radioactivity were used as a measure of the uptake of lipid microemboli. RESULTS: High levels of radioactivity were found in kidney and spleen (5 to 10 times higher than in the other organs investigated). In the brain, radioactivity was found in all regions examined. The gray matter of cerebrum showed the highest level of the regions examined. CONCLUSIONS: This study shows that embolization of lipids is not a phenomenon restricted to the brain, but affected all the organs examined. The high levels found in the kidneys, and the relatively high levels in the gray matter of the cerebrum further legitimize the debate on the impact lipid microemboli has on postoperative kidney and cognitive dysfunction.

Animals↗
PubMed2005

Carrier medium exchange through ultrasonic particle switching in microfluidic channels.

This paper describes a method, utilizing acoustic force manipulation of suspended particles, in which particles in a laminar flow microchannel are continuously translated from one medium to another with virtually no mixing of the two media. During the study, 5-microm polyamide spheres suspended in distilled water, spiked (contaminated) with Evans blue, were switched over to clean distilled water. More than 95% of the polyamide spheres could be collected in the clean medium while removing up to 95% of the contaminant. Preliminary experiments to use this method to wash blood were performed. Red blood cells were switched from blood, spiked with Evans blue, to clean blood plasma. At least 95% of the red blood cells (bovine blood) could be collected in clean blood plasma while up to 98% of the contaminant was removed. The obtained results indicate that the presented method can be used as a generic method for particle washing and, more specifically, be applied for both intraoperative and postoperative blood washing.

Journal Article↗
PubMed2005

Modeling the organization of the WUSCHEL expression domain in the shoot apical meristem.

MOTIVATION: The above-ground tissues of higher plants are generated from a small region of cells situated at the plant apex called the shoot apical meristem. An important genetic control circuit modulating the size of the Arabidopsis thaliana meristem is a feed-back network between the CLAVATA3 and WUSCHEL genes. Although the expression patterns for these genes do not overlap, WUSCHEL activity is both necessary and sufficient (when expressed ectopically) for the induction of CLAVATA3 expression. However, upregulation of CLAVATA3 in conjunction with the receptor kinase CLAVATA1 results in the downregulation of WUSCHEL. Despite much work, experimental data for this network are incomplete and additional hypotheses are needed to explain the spatial locations and dynamics of these expression domains. Predictive mathematical models describing the system should provide a useful tool for investigating and discriminating among possible hypotheses, by determining which hypotheses best explain observed gene expression dynamics. RESULTS: We are developing a method using in vivo live confocal microscopy to capture quantitative gene expression data and create templates for computational models. We present two models accounting for the organization of the WUSCHEL expression domain. Our preferred model uses a reaction-diffusion mechanism in which an activator induces WUSCHEL expression. This model is able to organize the WUSCHEL expression domain. In addition, the model predicts the dynamical reorganization seen in experiments where cells, including the WUSCHEL domain, are ablated, and it also predicts the spatial expansion of the WUSCHEL domain resulting from removal of the CLAVATA3 signal. AVAILABILITY: An extended description of the model framework and image processing algorithms can be found at http://www.computableplant.org, together with additional results and simulation movies. SUPPLEMENTARY INFORMATION: http://www.computableplant.org/ and alternatively for a direct link to the page, http://computableplant.ics.uci.edu/bti1036 can be accessed.

Arabidopsis↗
PubMed2005

Particle separation using ultrasound can be used with human shed mediastinal blood.

BACKGROUND: Shed mediastinal blood collected by cardiotomy suction has been shown to be a large contributor to lipid microemboli ending up in different organs. The aim of this study was to test the separation efficiency on human shed blood of a new separation method developed to meet this demand. METHODS: Shed mediastinal blood collected from the pericardial cavity of 13 patients undergoing cardiac surgery with cardiopulmonary bypass was collected. The blood was processed in an eight-channel parallel PARSUS separator, and separation efficiency was determined. RESULTS: Erythrocyte recovery, in terms of a separation ratio, varied between 68% and 91%. Minor electrolyte changes took place, where levels of sodium increased and levels of potassium and calcium decreased. CONCLUSION: This study demonstrates that PARSUS technology can be used on human shed mediastinal blood with good separation efficiency. The technology is, thereby, suggested to have future clinical relevance.

Blood Transfusion, Autologous↗
PubMed2004

Controversial significance of early S100B levels after cardiac surgery.

BACKGROUND: The brain-derived protein S100B has been shown to be a useful marker of brain injury of different etiologies. Cognitive dysfunction after cardiac surgery using cardiopulmonary bypass has been reported to occur in up to 70% of patients. In this study we tried to evaluate S100B as a marker for cognitive dysfunction after coronary bypass surgery with cardiopulmonary bypass in a model where the inflow of S100B from shed mediastinal blood was corrected for. METHODS: 56 patients scheduled for coronary artery bypass grafting underwent prospective neuropsychological testing. The test scores were standardized and an impairment index was constructed. S100B was sampled at the end of surgery, hourly for the first 6 hours, and then 8, 10, 15, 24 and 48 hours after surgery. None of the patients received autotransfusion. RESULTS: In simple linear analysis, no significant relation was found between S100B levels and neuropsychological outcome. In a backwards stepwise regression analysis the three variables, S100B levels at the end of cardiopulmonary bypass, S100B levels 1 hour later and the age of the patients were found to explain part of the neuropsychological deterioration (r = 0.49, p < 0.005). CONCLUSIONS: In this study we found that S100B levels 1 hour after surgery seem to be the most informative. Our attempt to control the increased levels of S100B caused by contamination from the surgical field did not yield different results. We conclude that the clinical value of S100B as a predictive measurement of postoperative cognitive dysfunction after cardiac surgery is limited.

Age Factors↗
PubMed2004

Acoustic control of suspended particles in micro fluidic chips.

A method to separate suspended particles from their medium in a continuous mode at microchip level is described. The method combines an ultrasonic standing wave field with the extreme laminar flow properties obtained in a silicon micro channel. The channel was 750 microm wide and 250 microm deep with vertical side walls defined by anisotropic wet etching. The suspension comprised "Orgasol 5 microm" polyamide spheres and distilled water. The channel was perfused by applying an under pressure (suction) to the outlets. The channel was ultrasonically actuated from the back side of the chip by a piezoceramic plate. When operating the acoustic separator at the fundamental resonance frequency the acoustic forces were not strong enough to focus the particles into a well defined single band in the centre of the channel. The frequency was therefore changed to about 2 MHz, the first harmonic with two pressure nodes in the standing wave, and consequently two lines of particles were formed which were collected via the side outlets. Two different microchip separator designs were investigated with exit channels branching off from the separation channel at angles of 90 degrees and 45 degrees respectively. The 45 degrees separator displayed the most optimal fluid dynamic properties and 90% of the particles were gathered in 2/3 of the original fluid volume.

Acoustics↗
PubMed2004

Particle separation using ultrasound can radically reduce embolic load to brain after cardiac surgery.

BACKGROUND: Microembolism during cardiopulmonary bypass has been suggested as being the predominant cause of neurocognitive disorders after cardiac surgery. Shed blood, normally retransfused into the patient during cardiopulmonary bypass, is a major source of lipid microemboli in the brain capillaries. A newly developed technique based on acoustic standing-wave separation of particles in fluid in microchannels, with the capacity to remove lipid particles in blood, is presented. METHODS: A separator consisting of eight parallel, high-fidelity microfabricated channels was actuated with an ultrasound field to create a standing wave. Three different concentrations of lipid particles (diameter, 0.3 microm) were added to blood samples with increasing hematocrits and introduced into the separator channels to separate lipid particles and erythrocytes. RESULTS: The mean separation rates for lipid particles were 81.9% +/- 7.6% and for erythrocytes 79.8% +/- 9.9%, and both were related to the hematocrit level of the incoming blood sample. The procedure was atraumatic and did not cause hemolysis. CONCLUSIONS: Particle separation by means of an acoustic standing-wave technique can be used for atraumatic and effective removal of lipid particles from blood, with the possible clinical implication of reducing neurocognitive complications after cardiopulmonary bypass.

Animals↗
PubMed2003

Increased S100B in blood after cardiac surgery is a powerful predictor of late mortality.

BACKGROUND: Long-term outcome in patients who suffered stroke after undergoing a cardiac operation has been investigated sparingly, but increased long-term mortality has been reported. S100B is a biochemical marker of brain cell ischemia and blood-brain barrier dysfunction. The aim of this investigation was to record the long-term mortality in consecutive patients undergoing cardiac operations and to explore whether increased concentrations of S100B in blood had a predictive value for mortality. METHODS: Prospectively collected clinical variables, including S100B, in 767 patients who survived more than 30 days after a cardiac operation, were analyzed with actuarial survival analysis and 678 patients were analyzed with Cox multiple regression analysis. RESULTS: Forty-nine patients (6.4%) were dead at follow-up (range, 18 to 42 months); 11.5% (88 of 767 patients) had elevated S100B 2 days after operation (range, 38 to 42 hours). The probability for death at follow-up was 0.239 if the S100B level was more than 0.3 microg/L, and 0.041 if it was less than 0.3 microg/L. The clinical variables independently associated with mortality were preoperative renal failure, preoperative low left ventricular ejection fraction, emergency operation, severe postoperative central nervous system complication, and elevated S100B values, which turned out to be the most powerful predictor. CONCLUSIONS: Even slightly elevated S100B values in blood 2 days after cardiac operation imply a bad prognosis for outcome, and especially so in combination with any central nervous system complication.

Actuarial Analysis↗
PubMed2003

An approximate maximum likelihood approach, applied to phylogenetic trees.

A novel type of approximation scheme to the maximum likelihood (ML) approach is presented and discussed in the context of phylogenetic tree reconstruction from aligned DNA sequences. It is based on a parameterized approximation to the conditional distribution of hidden variables (related, e.g., to the sequences of unobserved branch point ancestors) given the observed data. A modified likelihood, based on the extended data, is then maximized with respect to the parameters of the model as well as to those involved in the approximation. With a suitable form of the approximation, the proposed method allows for simpler updating of the parameters, at the cost of an increased parameter count and a slight decrease in performance. The method is tested on phylogenetic tree reconstruction from artificially generated sequences, and its performance is compared to that of ML, showing that the approach is competitive for reasonably similar sequences. The method is also applied to real DNA sequences from primates, yielding a result consistent with those obtained by other standard algorithms.

Animals↗
PubMed2003

S100B and cardiac surgery: possibilities and limitations.

Serum determinations of the glial protein S100B has been found to correlate with brain damage after cardiac surgery. Forty-eight hours and later after surgery, increased S100B levels correlates with the presence of brain infarction, and the extent of infracted brain tissue. S100B at this time-point has been shown to predict long-term outcome, higher S100B levels correlated with decreased survival. Early levels (2-8 hours after surgery) of S100B have shown disparate results when trying to correlate it with postoperative cognitive decline. One reason for the lack of strong correlation could be the contamination of S100B from shed blood the first hours after surgery.

Animals↗
PubMed2002

In the eye of both patient and spouse: memory is poor 1 to 2 years after coronary bypass and angioplasty.

BACKGROUND: The study aimed to investigate patient and spouse perception of cognitive functioning 1 to 2 years after coronary artery bypass grafting. METHODS: Seventy-six married patients who had undergone coronary artery bypass grafting were selected and sex- and age-matched with 75 concurrent married patients who had undergone percutaneous transluminal coronary angioplasty. Couples received a letter of explanation and then completed telephone interviews. Forty-seven questions assessed memory, concentration, general health, social functioning, and emotional state. Response choices were: improved, unchanged, or deteriorated function after coronary artery bypass grafting/percutaneous transluminal coronary angioplasty. RESULTS: Patients who had undergone coronary artery bypass grafting did not differ in subjective ratings on any measure from patients who had undergone percutaneous transluminal coronary angioplasty. There were no differences between spouses in the respective groups; spouse ratings also did not differ from patient ratings. Only in memory function did patients and spouses report a postprocedural decline. CONCLUSIONS: No subjective differences were found in patients who had undergone either coronary artery bypass grafting or percutaneous transluminal coronary angioplasty. Spouse ratings agreed with each other and with patient ratings. Positive correlations were found between the questionnaire factors, suggesting that perceived health and well-being are associated with subjective cognition.

Activities of Daily Living↗