Hyperspectral and multispectral bioluminescence optical tomography for small animal imaging

For bioluminescence imaging studies in small animals, it is important to be able to accurately localize the three-dimensional (3D) distribution of the underlying bioluminescent source. The spectrum of light produced by the source that escapes the subject varies with the depth of the emission source because of the wavelength-dependence of the optical properties of tissue. Consequently, multispectral or hyperspectral data acquisition should help in the 3D localization of deep sources. In this paper, we describe a framework for fully 3D bioluminescence tomographic image acquisition and reconstruction that exploits spectral information. We describe regularized tomographic reconstruction techniques that use semi-infinite slab or FEM-based diffusion approximations of photon transport through turbid media. Singular value decomposition analysis was used for data dimensionality reduction and to illustrate the advantage of using hyperspectral rather than achromatic data. Simulation studies in an atlas-mouse geometry indicated that sub-millimeter resolution may be attainable given accurate knowledge of the optical properties of the animal. A fixed arrangement of mirrors and a single CCD camera were used for simultaneous acquisition of multispectral imaging data over most of the surface of the animal. Phantom studies conducted using this system demonstrated our ability to accurately localize deep point-like sources and show that a resolution of 1.5 to 2.2 mm for depths up to 6 mm can be achieved. We also include an in vivo study of a mouse with a brain tumour expressing firefly luciferase. Co-registration of the reconstructed 3D bioluminescent image with magnetic resonance images indicated good anatomical localization of the tumour.     

Evaluation of a microsphere-based flow cytometric assay for diagnosis of celiac disease

The multiplexed particle-based flow cytometric technology proposes a new approach for the diagnosis of autoimmune diseases combining the advantages of conventional methods with the ability to quantitatively determine multiple autoantibodies in the same sample, simultaneously and rapidly. Recently, a commercial kit (FIDIS Celiac, Biomedical Diagnostics, Mane la Vallé, France) was introduced for the simultaneous detection of IgA anti-tissue transglutaminase (anti-tTG), IgG, and IgA anti-gliadin antibodies (AGA). This study was undertaken to evaluate and compare the FIDIS Celiac kit with standardized commercial ELISAs (QUANTA Lite, INOVA Diagnostics Inc., San Diego, CA). A disease group consisted of 21 samples from untreated patients with biopsy confirmed celiac disease (CD), and two control groups of historical sera (207 from regular blood donors and 181 from chronically infected hepatitis patients) were studied. All control sera were negative for IgA anti-endomysial antibodies (EmA) and had an IgA concentration above the lower normal limit. Concerning the reproducibility, intra- and inter-assay coefficients of variation (CVs) ranging between 2% and 12%, and between 3% and 21%, respectively, were observed. Regarding the diagnostic quality, each assay was compared to the disease diagnosis using the McNemar test and the kappa (K) parameter, while ROC analysis was applied. Generally, the performance of FIDIS assay was proved almost equally adequate to that of ELISA in the detection of IgA anti-tTG antibodies, IgA and IgG AGA. However, the performance of FIDIS assay was found surmounting that of ELISA among hepatitis patients, possibly due to the avoidance of debris and unbound cross contaminants and, hence, the "noise" of such materials in samples under analysis. Taking our results together with the simplicity and the high throughput of FIDIS assay, its overall performance in the diagnosis of CD seems better than that of ELISA.     

Pathobiology of familial hypercholesterolemic atherosclerosis

Many factors play a role in the development of atherosclerotic lesions. One of the leading risk factors for development of atherosclerosis is familial hypercholesterolemia (FH). FH is a genetic disease characterized by a deficiency, and/or mutation, of receptors for low density lipoprotein (LDL) on the plasmalemma of endothelial cells (EC), a high level of low density lipoprotein in the plasma, and early, spontaneous development of atherosclerosis and skin xanthoma. In this review we describe Watanabe heritable hyperlipidemic (WHHL) rabbits, which represent such an animal model for human FH. This strain of the rabbits is characterized by a genetic deficiency or mutation of functional LDL receptors and develops severe atherosclerosis, which is pathologically similar to familial homozygous hyperlipidemic patients. The most completely characterized animal model is the Watanabe rabbit, a model of homozygous and heterozygous type IIa hypercholesterolemia related to an LDL receptor deficiency. Additional manipulation such as aortic injury in this rabbit model induces the development of atherosclerotic lesions that are structurally similar to those found in humans. Thus, this model of hypercholesterolemia fulfils the above criteria set, i.e. it is able to provide new insights for a better understanding of the pathogenesis of atherosclerosis and for testing new treatment strategies.     

Cortisol and testosterone concentrations in wheelchair athletes during submaximal wheelchair ergometry

It is yet unknown how upper body exercise combined with high ambient temperatures affects plasma testosterone and cortisol concentrations and furthermore, how these hormones respond to exercise in people suffering spinal cord injuries. The purpose of this study was to characterize plasma testosterone and cortisol responses to upper body exercise in wheelchair athletes (WA) compared to able-bodied individuals (AB) at two ambient temperatures. Four WA [mean age 36 (SEM 13) years, mean body mass 66.9 (SEM 11.8) kg, injury level T₇–T₁₁], matched with five AB [mean age 33.4 (SEM 8.9) years, mean body mass 72.5 (SEM 13.1) kg] exercised (cross-over design) for 20 min on a wheelchair ergometer (0.03 kg resistance · kg⁻¹ body mass) at 25 °C and 32 °C. Blood samples were obtained before (PRE), at min 10 (MID), and min 20 (END) of exercise. No differences were found between results obtained at 25 °C and 32 °C for any physiological variable studied and therefore these data were combined. Pre-exercise testosterone concentration was lower (P < 0.05) in WA [18.3 (SEM 0.9) nmol · l⁻¹] compared to AB [21.9 (SEM 3.6) nmol · l⁻¹], and increased PRE to END only in WA. Cortisol concentrations were similar between groups before and during exercise, despite higher rectal temperatures in WA compared to AB, at MID [37.21 (SEM  0.14) and 37.02 (SEM  0.08)°C, respectively] and END [37.36 (SEM 0.16) and 37.19 (SEM 0.10)°C, respectively]. Plasma norepinephrine responses were similar between groups. In conclusion, there were no differences in plasma cortisol concentrations, which may have been due to the low relative exercise intensities employed. The greater exercise response in WA for plasma testosterone should be confirmed on a larger population. It could have been the result of the lower plasma testosterone concentrations at rest in our group. Accepted: 4 September 2000     

Anatomic study of the tricuspid valve in children

We performed an anatomic study of the right atrioventricular valve in children under one year of age using a conservative method of dissection of the heart valve. The main aspects studied were the number of cusps and their morphometric characteristics, such as the width of the base and the depth of the cusps. Other parameters studied were the number of papillary muscles, number of tendinous cords, and diameter of the fibrous ring and the last one were divided in three regions, anterior, posterior and septal for localization of cusps. Our results showed that the number of cusps varied from two to four. Three cusps was the commonest finding and the fourth cusp, if present, was classified as anterolateral in location. The anterior and septal cusps had bases bigger than those of the posterior and anterolateral cusps; the septal cusp was deeper than the others; and the number of tendinous cords was greater for the anterior and septal cusps than for the posterior and anterolateral cusps. In addition, the posterior region showed great variability: in 35.7% it was occupied by undeveloped valve tissue and the posterior valve in these cases was located anteriorly.     

APOE is a potential modifier gene in an autosomal dominant form of frontotemporal dementia (IBMPFD).

PURPOSE: Inclusion-body myopathy, Paget's disease of bone and frontotemporal dementia is an adult-onset autosomal dominant illness (IBMPFD) caused by mutations in the valosin-containing protein (VCP) on chromosome 9p21.1-p12. The penetrance of the gene is 82% for myopathy, 49% for Paget's disease, but may be as low as 30% for frontotemporal dementia. Modifier genes could account for decreased frontotemporal dementia penetrance. In this study apolipoprotein-E (APOE) was evaluated for this role in IBMPFD families based on its known modifier effect in Alzheimer's disease. METHODS: From a database of 231 members of 15 families, 174 had APOE genotype available for analysis. Logistic regressions on APOE genotype and frontotemporal dementia were performed, using appropriate covariates. RESULTS AND CONCLUSION: FTD was associated with APOE 4 genotype (P=0.0002), myopathy (P=0.0006), and age (P=0.01), but not microtubule associated protein tau (MAPT) H2 haplotype (P=0.5) or gender (0.09) after adjustment for membership in pedigrees with at least one APOE 4 genotype. These data suggest a potential link between APOE 4 genotype and the specific form of frontotemporal dementia found in IBMPFD. The molecular basis of this link bears further investigation. We did not observe an association of frontotemporal dementia and H2 MAPT haplotype.