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Robert A Brown

Publications and source records attributed to Robert A Brown.

At least 19 recordsLinked to original sources
PubMed2006

Computation of the nonhomogeneous equilibrium states of a rigid-rod solution.

The nonhomogeneous equilibrium phase behavior of a solution of rigid rods is analyzed for a periodic one-dimensional system. Stable and unstable equilibrium solutions for the distribution function are computed as extrema of the free energy of the system expressed by the nonhomogeneous generalization of Onsager's [Ann. N.Y. Acad. Sci. 51, 627 (1949)] theory, which models interaction between rods on the scale of a single rod length. Biaxial equilibrium solutions are computed in a periodic system by discretizing the Euler-Lagrange nonlinear integral equation by the finite-element method and using Newton's method to solve the resulting set of nonlinear equations. Stable states for isotropic-nematic coexistence are computed in a periodic system rather than the semi-infinite system used in previous calculations. The density and order parameter profiles evolve monotically from the isotropic phase to the nematic phase. Unstable, nonhomogeneous, equilibrium states are also computed for concentrations of rods that exceed the value for spinodal decomposition. These nonhomogeneous states are characterized by combinations of bend, twist, and splay distortions in physical space and correspond to unstable attractors in the dynamic process of isotropic-nematic spinodal decomposition. For large systems, the nonhomogeneous states develop wide, bulklike nematic regions separated by thin regions with sharp gradients in orientation. The free energy formulation was also used to compute the accurate neutral stability curve; this curve shows the limits of applicability of the low-wave-number approximations frequently used in the study of spinodal decomposition.

Journal Article↗
PubMed2006

Parvovirus B19 infection after transplantation: a review of 98 cases.

BACKGROUND: Infections with parvovirus B19 (PVB19) can cause significant morbidity in transplant recipients. METHODS: To characterize the epidemiology and clinical spectrum of posttransplant PVB19 infection, we reviewed all cases at our institution during a 16-year period, summarized the data from 91 cases published in the medical literature, and performed longitudinal molecular surveillance for PVB19 DNAemia among 47 solid organ and hematopoietic stem cell transplant recipients. RESULTS: The median time to onset of PVB19 disease was 7 weeks after transplantation. Anemia, leukopenia, and thrombocytopenia were present in 98.8%, 37.5%, and 21.0% of patients, respectively. Hepatitis, myocarditis, and pneumonitis were also reported in association with PVB19 disease. Allograft tissue loss or dysfunction was observed at the time of PVB19 disease in 10% of cases. At the onset of disease, PVB19 IgM serological test results were negative in 29% of cases. Almost all patients (96%) with anti-PVB19 IgM had a positive PVB19 polymerase chain reaction assay result. Intravenous immunoglobulin was the most commonly used treatment modality. Three of 98 patients died of myocarditis and cardiogenic shock associated with PVB19 disease. Molecular surveillance throughout the first year after transplantation did not reveal PVB19 DNAemia in 47 anemic solid organ and hematopoietic stem cell transplant patients. CONCLUSIONS: PVB19 is a rare but clinically significant infection that manifests as refractory anemia during the posttransplantation period. The use of polymerase chain reaction for diagnosis is particularly helpful in immunosuppressed transplant patients who may fail to mount antibodies against PVB19 during active infection.

Adult↗
PubMed2006

Characterization of a "blanch-blush" mechano-response in palmar skin.

Palmar finger skin reacts to extension under mechanical load -- blanching over proximal (intercrease skin, ICS) and middle phalanges, while blushing in crease skin (CS), which we have called the Blanch-Blush Reaction (BBR). The idea that the BBR is a result of surface capillary blood flow changes that relate to predictable deformation of aligned collagen matrices under applied uniaxial loads was tested. Nondestructive techniques, digital image analysis (DIA), laser Doppler scanning, and elastic scatter spectroscopy (ESS) were used to measure color and blood flow changes in healthy fingers when at rest and extended. Skin strain increased directly with applied load and DIA identified blanching (loss of redness) in the ICS, reflected by a decrease in hemoglobin (by ESS). Laser Doppler flowmetry identified an increase in blood flow in the CS zone on extension, with a minor increase in blood flow in the ICS zone, apparently due to diversion of flow to deeper vessels, when monitored by this technique. These changes correlated with the BBR, owing to altered capillary flow in the ICS and CS. The histology of orientation of collagen fibers and vessels in the two zones was consistent with this mechanism. This study demonstrates the interdependence between matrix orientation, applied load, and flow. It represents an elegant demonstration of collagenous tissue function through an everyday tissue reaction, which has not been described previously.

Adult↗
PubMed2006

In situ monitoring of tendon structural changes by elastic scattering spectroscopy: correlation with changes in collagen fibril diameter and crimp.

The aim of this study was to monitor structural changes in loaded rabbit digital flexor tendons in situ and ex situ via elastic scattering spectroscopy (ESS). The optical setup consisted of a xenon white light source (lambda = 320-860 nm), connected to a fiber optic probe (with a source-detector separation of approximately 350 microm) and a spectrometer, controlled by a personal computer (PC). Cadaveric rabbit tendons were studied in situ under 3 tensional regimens: unloaded (no extrinsic tension applied), stretched, and 1-kg loaded and compared with excised tendons (i.e., no tension). Four times more light was detected in in situ unloaded tendons perpendicular to the tendon long axis than parallel to it. Backscatter anisotropy was expressed as the anisotropy factor (AF600nm: ratio of greatest to least backscatter intensity, measured with orthogonal probe positions). Differences in backscatter anisotropy between tendons from different digits were not significant. AF600nm had the smallest value (2.72 +/- 0.38) for the least aligned tendon preparations (excised tendons), and increased to 7.17 +/- 0.54 (1-kg loaded) as in situ loads were applied. Electron microscopy revealed that the distribution of collagen fibril diameters changed as loads were applied, with the diameter of larger fibrils decreasing approximately 33% for 1-kg loaded compared with excised tendons. Polarized light microscopy showed a characteristic crimp pattern in excised tendons, but this was hardly detectable in unloaded tendons and not detectable in tendons fixed in situ under a 1-kg load. We propose that the increase in optical anisotropy is a function of collagen fibril straightening and reducing fibril diameter as the tendon undergoes progressive loading. These findings are important for monitoring structure in vivo and in bioreactors for tissue engineers.

Animals↗
PubMed2005

The origins and regulation of tissue tension: identification of collagen tension-fixation process in vitro.

The absence of a controllable in vitro model of soft tissue remodeling is a major impediment, limiting our understanding of collagen pathologies, tissue repair and engineering. Using 3D fibroblast-collagen lattice model, we have quantified changes in matrix tension and material properties following remodeling by blockade of cell-generated tension with cytochalasin D. This demonstrated a time-dependent shortening of the collagen network, progressively stabilized into a built-in tension within the matrix. This was differentially enhanced by TGFB1 and mechanical loading to give subtle control of the new, remodeled matrix material properties. Through this model, we have been able to identify the 'tension remodeling' process, by which cells control material properties in response to environmental factors.

Animals↗
PubMed2005

Herpesvirus infections in solid organ transplant patients at high risk of primary cytomegalovirus disease.

The epidemiology of infections with 5 human herpesviruses (HHVs) (HHV-6, HHV-7, HHV-8, varicella zoster virus [VZV], and Epstein-Barr virus [EBV]) was investigated during the first year after solid organ transplantation in 263 patients who received oral ganciclovir or valganciclovir prophylaxis. HHV-6B DNAemia was uncommon, HHV-6A DNAemia was not observed, and HHV-7 DNAemia was prevalent. HHV-6 and HHV-7 DNAemia were not significantly associated with cytomegalovirus (CMV) disease, although a trend toward higher incidence of CMV disease was observed in HHV-6 DNAemic patients. VZV and HHV-8 DNAemia were not detected. EBV infection was common, although incidence of high-level EBV DNAemia was low, especially in patients who received valganciclovir prophylaxis. EBV-related posttransplant lymphoproliferative disease was not observed up to 12 months after transplantation. Compared with historic data, data from the present study suggest that antiviral prophylaxis may lower the incidence, prevalence, or level of DNAemia for infection with HHV-6, HHV-8, VZV, and EBV but not for infection with HHV-7.

Antiviral Agents↗
PubMed2005

A longitudinal molecular surveillance study of human polyomavirus viremia in heart, kidney, liver, and pancreas transplant patients.

In this study of 263 heart, kidney, liver, and pancreas transplant patients, BK virus (BKV) and JC virus (JCV) DNAemia were observed most commonly in kidney and/or pancreas transplant patients (26%), although they were also observed, to a lesser extent, in heart (7%) and liver (4%) transplant patients. The majority of episodes of polyomavirus DNAemia were subclinical, although, in some cases, BKV DNAemia was associated with kidney rejection, and JCV DNAemia was accompanied by nonspecific symptoms. Hence, BKV and JCV DNAemia are not uncommon during the first year after kidney, heart, liver, and pancreas transplantation, and they could be associated with certain clinical syndromes in transplant patients.

Heart↗
PubMed2005

Development of an RNA isolation procedure for the characterisation of human endothelial cell interactions with polyurethane cardiovascular bypass grafts.

To date no reliable method has been developed for the isolation of RNA from cells seeded onto cylindrical vascular grafts. This study was performed in order to develop a reliable methodology for isolating RNA from cylindrical conduits made from poly(carbonate-urea)urethane (PU). Human umbilical vein EC were seeded onto PU vascular grafts and an Alamar blue assay performed to assess cell viability. Cells were prepared for RNA extraction by trypsinisation, cell scraping and direct application of cell lysis buffer. In all cases RNA was extracted using a "Qiagen RNeasy" kit. Alamar blue showed viable cells were present on all of the seeded PU vascular grafts. Levels of RNA extracted from the cells removed from the graft by the trypsinisation yielded 0.130 microg/microl, by scraping 0.078 microg/microl and by direct lysing 0.093 microg/microl of RNA, respectively. RTPCR was conducted successfully for GAPDH and TGF-beta1. Trypsinisation prior to RNA extraction provided the highest RNA yield and attained near complete cell removal ensuring that gene expression obtained was representative.

Biocompatible Materials↗
PubMed2005

A novel method to derive separate gray and white matter cerebral blood flow measures from MR imaging of acute ischemic stroke patients.

Perfusion-weighted imaging (PWI) measures can predict tissue outcome in acute ischemic stroke. Accuracy might be improved if differential tissue susceptibility to ischemia is considered. We present a novel voxel-by-voxel analysis to characterize cerebral blood flow (CBF) separately in gray (GM) and white matter (WM). Ten patients were scanned with inversion-recovery spin-echo EPI (IRSEPI), diffusion-weighted imaging (DWI), PWI<6 h from onset and fluid attenuated inversion-recovery (FLAIR) at 30 days. Image processing included coregistration to PWI, automatic segmentation of IRSEPI into GM, WM and CSF and semiautomatic segmentation of DWI/FLAIR to derive the acute and 30-day lesions. Five tissue compartments were defined: (1) 'Core' (abnormal acutely and at 30 days), (2) 'Growth' (or 'infarcted penumbra', abnormal only at 30 days), (3) 'Reversed' (abnormal acutely but normal at 30 days), (4) 'MTT-Delayed ' (tissue with delayed mean transit time but not part of the acute or 30-day lesion), and (5) 'Normal' brain. Cerebral blood flow in GM and WM of each compartment was obtained from quantitative maps. Gray matter and WM mean CBF in the growth region differed by 5.5 mL/100 g min (P=0.015). Mean CBF also differed significantly within normal and MTT-Delayed compartments. The difference in the reversed region approached statistical significance. In core, GM and WM CBF did not differ. The results suggest separate ischemic thresholds for GM and WM in stroke penumbra.

Aged↗
PubMed2005

MR perfusion and diffusion in acute ischemic stroke: human gray and white matter have different thresholds for infarction.

It is thought that gray and white matter (GM and WM) have different perfusion and diffusion thresholds for cerebral infarction in humans. We sought to determine these thresholds with voxel-by-voxel, tissue-specific analysis of co-registered acute and follow-up magnetic resonance (MR) perfusion- and diffusion-weighted imaging. Quantitative cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and apparent diffusion coefficient (ADC) maps were analyzed from nine acute stroke patients (imaging acquired within 6 h of onset). The average values of each measure were calculated for GM and WM in normally perfused tissue, the region of recovered tissue and in the final infarct. Perfusion and diffusion thresholds for infarction were determined on a patient-by-patient basis in GM and WM separately by selecting thresholds with equal sensitivities and specificities. Gray matter has higher thresholds for infarction than WM (P<0.009) for CBF (20.0 mL/100 g min in GM and 12.3 mL/100 g min in WM), CBV (2.4 mL/100 g in GM and 1.7 mL/100 g in WM), and ADC (786 x 10(-6) mm(2)/s in GM and 708 x 10(-6) mm(2)/s in WM). The MTT threshold for infarction in GM is lower (P=0.014) than for WM (6.8 secs in GM and 7.1 secs in WM). A single common threshold applied to both tissues overestimates tissue at risk in WM and underestimates tissue at risk in GM. This study suggests that tissue-specific analysis of perfusion and diffusion imaging is required to accurately predict tissue at risk of infarction in acute ischemic stroke.

Aged↗
PubMed2005

Distributed vector processing of a new local multiscale Fourier transform for medical imaging applications.

The recently developed S-transform (ST) combines features of the Fourier and Wavelet transforms; it reveals frequency variation over both space and time. It is a potentially powerful tool that can be applied to medical image processing including texture analysis and noise filtering. However, calculation of the ST is computationally intensive, making conventional implementations too slow for many medical applications. This problem was addressed by combining parallel and vector computations to provide a 25-fold reduction in computation time. This approach could help accelerate many medical image processing algorithms.

Algorithms↗
PubMed2004

Mechanical functioning of peripheral nerves: linkage with the "mushrooming" effect.

Biomechanical properties of nerve have been studied extensively. All neural matrix tissues have been suggested to be the main load-bearing component. Based on the ultrastructure it has been proposed that the architecture of the epineurium allows some degree of extensibility of the nerve. A role of the perineurium could be to withstand the positive endoneurial pressure. The hypothesis is that the mechanical behaviour of nerves is dependent on an interaction between the core swelling pressure and restraint by the outer sheath. Loss of this balance will alter that behaviour. To test this, rat sciatic nerves were subjected to mechanical loading at in vivo and ex vivo tension. Retraction of nerve segments was measured after excision and after incubation at 37 degrees C or freezing. Swelling properties of the nerve were measured by immersion in water or PBS (phosphate buffer solution) with intact or opened epineurium. Results showed a significant decrease in strength and stiffness with an increase in strain of the nerve after excision, compared to in vivo. Retraction was on average 11%. Freezing or incubation at 37 degrees C did not alter retraction. The swelling properties of the nerve demonstrated a significant difference between intact and opened epineurium and similar results for water and PBS, indicating that epineurium is a constraint and that the nerves are underhydrated. The proposed model for the intact nerve is a continuous connective tissue tube surrounding and constraining an inner swelling pressure of the neural core. Loss of integrity of the nerve has detrimental effects on its biomechanical properties.

Animals↗
PubMed2004

A large population of 'Lyman-break' galaxies in a protocluster at redshift z approximately 4.1.

The most massive galaxies and the richest clusters are believed to have emerged from regions with the largest enhancements of mass density relative to the surrounding space. Distant radio galaxies may pinpoint the locations of the ancestors of rich clusters, because they are massive systems associated with 'overdensities' of galaxies that are bright in the Lyman-alpha line of hydrogen. A powerful technique for detecting high-redshift galaxies is to search for the characteristic 'Lyman break' feature in the galaxy colour, at wavelengths just shortwards of Lyalpha, which is due to absorption of radiation from the galaxy by the intervening intergalactic medium. Here we report multicolour imaging of the most distant candidate protocluster, TN J1338-1942 at a redshift z approximately 4.1. We find a large number of objects with the characteristic colours of galaxies at that redshift, and we show that this excess is concentrated around the targeted dominant radio galaxy. Our data therefore indicate that TN J1338-1942 is indeed the most distant cluster progenitor of a rich local cluster, and that galaxy clusters began forming when the Universe was only ten per cent of its present age.

Journal Article↗
PubMed2004

Removal of phase artifacts from fMRI data using a Stockwell transform filter improves brain activity detection.

A novel and automated technique is described for removing fMRI image artifacts resulting from motion outside of the imaging field of view. The technique is based on the Stockwell transform (ST), a mathematical operation that provides the frequency content at each time point within a time-varying signal. Using this technique, 1D Fourier transforms (FTs) are performed on raw image data to obtain phase profiles. The time series of phase magnitude for each and every point in the phase profile is then subjected to the ST to obtain a time-frequency spectrum. The temporal location of an artifact is identified based on the magnitude of a frequency component relative to the median magnitude of that frequency's occurrence over all time points. After each artifact frequency is removed by replacing its magnitude with the median magnitude, an inverse ST is applied to regain the MR signal. Brain activity detection within fMRI datasets is improved by significantly reducing image artifacts that overlap anatomical regions of interest. The major advantage of ST-filtering is that artifact frequencies may be removed within a narrow time-window, while preserving the frequency information at all other time points.

Artifacts↗
PubMed2004

Fluid shear in viscous fibronectin gels allows aggregation of fibrous materials for CNS tissue engineering.

Fibronectin (Fn) materials prepared from human plasma have been used in various forms as substrates for tissue engineering. Such purposes require that the soluble protein aggregates into insoluble fibrous structures which encourage the attachment and migration of cells. The method of aggregation due to mechanical shear was investigated by applying fluid shear forces directly to a viscous solution of Fn. Structural analysis revealed that mechanical shear resulted in the formation of an orientated fibrous protein material that was less soluble than its non-sheared counterpart. The suitability of this shear aggregated Fn material for CNS repair purposes was assessed in vitro where it supported the growth of fibroblasts, S100 immunoreactive Schwann cells and GFAP immunoreactive astrocytes. Implantation of the shear aggregated Fn material into a rat model of spinal cord injury provided a permissive environment for axonal growth. This was extended using an impermeable coating to improve orientation and straightness of axonal growth.

Animals↗
PubMed2004

Stabilisation of cables of fibronectin with micromolar concentrations of copper: in vitro cell substrate properties.

We have previously described the production of large cables of fibronectin, a large extracellular matrix cell adhesion glycoprotein, which has a potential application in tissue engineering. Here we have stabilised these cables for longer survival and looked at their ultrastructural cell-substrate behaviour in vitro. Dissolution experiments showed that low concentrations of copper not only caused significant material stabilisation but left pores which could promote cell ingrowth, as we have previously reported with Fn-mats. Indeed, the greatest amount of cell ingrowth was observed for copper treated cables. Immunostaining showed S-100(+) multi-layers of cells around the edge of cables while ultrastructural analysis confirmed the presence of a mixture of fibroblasts and bipolar cells associated with fragments of basal lamina, which is a Schwann cell phenotype. Interestingly, the outermost layers of cells consisted of S-100(-) cells, presumed fibroblasts, apparently 'capping' the Schwann cells. Toxicity tests revealed that Schwann cells were only able to grow at the lowest concentration of copper used (1microM) while fibroblasts grew at all concentrations tested. These results could be used to design biomaterials with optimum properties for promoting cellular ingrowth and survival in tissue engineered grafts which may be used to improve peripheral nerve repair.

Animals↗