BACKGROUND:The smaller airways, < 2 mm in diameter, offer little resistance in normal lungs, but become the major site of obstruction in chronic obstructive pulmonary disease (COPD).OBJECTIVE:To examine bronchiolar remodeling and alveolar destruction in COPD using micro-computed tomography (micro-CT).METHODS:Micro-CT was used to measure the number and cross-sectional lumen area of terminal bronchioles (TB) and alveolar mean linear intercept (Lm) in 4 lungs removed from patients with very severe (GOLD-4) COPD and 4 unused donor lungs that served as controls. These lungs were inflated with air to a transpulmonary pressure (P(L)) of 30 cm H(2)O and held at P(L) 10 cm H(2)O while they were frozen solid in liquid nitrogen vapor. A high resolution CT scan was performed on the frozen specimen prior to cutting it into 2-cm thick transverse slices. Representative core samples of lung tissue 2 cm long and 1 cm in diameter cut from each slice were fixed at -80 degrees C in a 1% solution of gluteraldehyde in pure acetone, post-fixed in osmium, critically point dried, and examined by micro-CT.RESULTS:A 10-fold reduction in terminal bronchiolar number and a 100-fold reduction in their minimal cross-sectional lumen area were measured in both emphysematous and non-emphysematous regions of the COPD lungs.CONCLUSIONS:The centrilobular emphysematous phenotype of COPD is associated with narrowing and obliteration of the terminal bronchioles that begins prior to the onset of emphysematous destruction.

Q-space imaging (QSI), a diffusion MRI technique, can provide quantitative tissue architecture information at cellular dimensions not amenable by conventional diffusion MRI. By exploiting regularities in molecular diffusion barriers, QSI can estimate the average barrier spacing such as the mean axon diameter in white matter (WM). In this work, we performed ex vivo QSI on cervical spinal cord sections from healthy C57BL/6 mice at 400 MHz using a custom-designed uniaxial 50T/m gradient probe delivering a 0.6 microm displacement resolution capable of measuring axon diameters on the scale of 1 microm. After generating QSI-derived axon diameter maps, diameters were calculated using histology from seven WM tracts (dorsal corticospinal, gracilis, cuneatus, rubrospinal, spinothalamic, reticulospinal, and vestibulospinal tracts) each with different axon diameters. We found QSI-derived diameters from regions drawn in the seven WM tracts (1.1 to 2.1 microm) to be highly correlated (r(2)=0.95) with those calculated from histology (0.8 to 1.8 microm). The QSI-derived values overestimated those obtained by histology by approximately 20%, which is likely due to the presence of extra-cellular signal. Finally, simulations on images of synthetic circular axons and axons from histology suggest that QSI-derived diameters are informative despite diameter and axon shape variation and the presence of intra-cellular and extra-cellular signal. QSI may be able to quantify nondestructively changes in WM axon architecture due to pathology or injury at the cellular level.

To determine in vivo function for Notch signaling in vascular smooth muscle cells (VSMCs), mice were genetically engineered to express dominant-negative mastermind-like 1 (DNMAML1) peptide, an inhibitor of canonical Notch signaling, under the transcriptional regulation of the smooth muscle promoter, SM22α. These mice lack gross developmental abnormalities, but display striking phenotypes when subjected to vascular stress. Unilateral carotid artery ligation results in ipsilateral cerebral insufficiency manifest by severe motor deficit and death. Cerebral vasculature exhibits an unusual complex branching network with involvement of the Circle of Willis. Furthermore, ligation of the femoral artery results in distal limb ischemia and partial paralysis, suggesting insufficient collateral blood flow. Ongoing studies are further defining the precise anatomic and functional mechanisms underlying this stress-induced vascular phenotype. Moreover, these results strongly suggest that Notch has an important role in maintenance of adult vasculature and preservation of normal arterial patterning through signaling in VSMCs. As such, the mouse model described herein should provide new mechanistic insights into human vascular syndromes linked to mutations in Notch signaling components. This research is supported by NIH funds.

Stroke is the third leading cause of death and a significant contributor of morbidity in the United States. In humans, suboptimal cerebral collateral circulation within the circle of Willis (CW) predisposes to ischemia and stroke risk in the setting of occlusive carotid artery disease. Unique genes or developmental pathways responsible for proper CW formation are unknown. Herein we characterize a mouse model lacking Notch signaling in vascular smooth muscle cells (vSMCs), in which the animals are intolerant to reduced cerebral blood flow. Remarkably, unilateral carotid artery ligation results in profound neurological sequelae and death. After carotid ligation, perfusion of the ipsilateral cerebral hemisphere was markedly diminished, suggesting an anastomotic deficiency within the CW. High-resolution microcomputed tomographic (μ-CT) imaging revealed profound defects in cerebrovascular patterning, including interruption of the CW and anatomic deformity of the cerebral arteries. These data identify a vSMC-autonomous function for Notch signaling in patterning and collateral formation within the cerebral arterial circulation. The data further implicate genetic or functional deficiencies in Notch signaling in the pathogenesis of anatomic derangements underlying cerebrovascular accidents.

We hypothesize that high-resolution magnetic resonance imaging (MRI) in vivo can accurately quantify carotid plaque volume and differentiate carotid plaque elements that are related to ischemic events. A randomized, placebo-controlled pilot study in patients with clinically stable carotid atherosclerosis (n = 60) is currently underway using quantitative micro-MRI techniques to determine the effect of aggressive low-density lipoprotein (LDL) lowering (simvastatin 80 mg), moderate LDL lowering (simvastatin 10 mg), and LDL lowering with high-density lipoprotein elevation (simvastatin 20 mg and Niaspan [extended-release niacin; Kos Pharmaceuticals, Inc., Miami, FL] 2,000 mg) on MRI plaque characteristics over 12 months. MRI (1.5 T) consisted of 3D time-of-flight magnetic resonance angiography of the carotid bifurcation, axial T1-weighted spin echo, axial proton density fast spin echo (FSE), and axial T2-weighted FSE at the level of the bifurcation (approximately ± 1.6 cm). Total plaque volume was estimated from computer-assisted measurement of plaque cross-sectional area plaque area × slice thickness × number of slices (typically 2.0 mm × 16 slices). The intraclass correlation coefficient for plaque volume from repeat baseline scans (n = 8) was 0.95 using fat-suppressed proton density FSE images. In these patients, plaque volume was estimated at 1.34 ± 0.38 cm3 (mean ± SD). Plaque calcification, fibrous tissue content, lipid content, and hemorrhage are currently being estimated using the multiparametric imaging data. The effect of treatment on MRI indices will be correlated with changes in lipoproteins, serum inflammatory markers and urinary isoprostanes, indices of oxidant stress in vivo. Noninvasive micro-MRI techniques applied to carotid atherosclerosis in humans in vivo offers the potential to assess the longitudinal effect of therapies on quantitative indices of plaque morphology.

Background/aims:Characterization of skin phosphometabol‐ism in vivo by non‐invasive magnetic resonance spectroscopy (MRS) might allow assessment of ischemic or irradiative damage.Methods:Based on a study of 17 healthy volunteers, we present statistical analyses for intra‐ and inter‐tissue metabolite concentration ratios, as well as for pH and [Mg2+].Results:Results contrasted steady‐state energy metabolism in skin and muscle, showing lower phosphocreatine/ATP, higher percentage of inorganic phosphate, phosphodiesters and phos‐phomonoesters, and higher pH and [Mg2+] in skin than in muscle.Conclusion:Results were consistent with known skin physiology and structure and suggested an inverse relationship between skin phosphodiester levels and melanin.

The effect of disease in two cultivars of barley, sown at different times in two seasons, on the relative importance of stored carbohydrate reserves and current photosynthesis for grain filling was assessed. Three methods of measuring stem reserve contributions to grain filling are reviewed and compared. Disease reduced stem dry weight and the amount of stored carbohydrate in most situations. In contrast, the total amount of stored carbohydrates used for grain filling was often increased by disease. The magnitude of these effects varied with the method used for estimation, and was also different in the crops sown at different times and in different seasons. The estimates of stem reserve contributions to grain filling ranged up to a maximum of 50% in some cases. At least 10 t/ha of reserve material was retranslocated in the healthy 1984 crop studied using 14C pulse feeding, and up to 0.3 t/ha more was utilized in a diseased crop. The effect of disease on the storage and utilization of stem reserves depended on the time of epidemic development, its duration, and the yield potential of the crop. This suggests that crops could be characterized as those which are very sensitive to disease during grain filling, with low stem reserves or high yield potential, and those with lower sensitivity, with more stem reserves or lower yield potential. Such interacting factors could be incorporated in future plant and yield‐loss mechanistic models.

The effect of disease on growth and yield of two barley cultivars sown at different times and in different years was investigated in New Zealand. The data were used to develop yield-loss models based on both disease severity (measured as green leaf area) and yield target (estimated by duration of crop growth). Disease influenced yield differently in Triumph and Sonya barley (spring and winter types, respectively), and yield components were affected to different degrees. Empirical yield-loss models for individual cultivars, sowing dates and seasons had different slope values, and the best models were based on measurements of disease at different growth stages. Combined models were less significant and explained less variation in yield than the individual models. Models which included the duration of crop growth as an estimate of yield target improved the fit to the data. Empirical models were specific to cultivar, sowing date and season, suggesting that they were not applicable in the varying conditions tested. The inclusion of estimated yield target improved the general applicability of models, and provided a method of using models in crops sown at different times and in different seasons, without measuring yield target directly.

Anomalous ‘bent’ microtwins lying in a 〈111〉 direction and containing high concentrations of Ga and As have been observed in ZnSe epitaxial layers grown on (100)-oriented GaAs substrates by molecular beam epitaxy at 410°C. The bend radius R meas of 0·928 × 10−5 m compares favourably with a theoretical value based on the use of expressions applicable to a bimetallic strip comprised of GaAs and ZnSe.

Neutron diffraction techniques have been employed to Investigate the structure of PbO-PbCl, glasses as a functlon of composltlon In the nomlnal range PbO-PbCh to 9Pb0.PbC12.It Is concluded that, whereas the flrst Pb-0 distance is well defined.the distrlbutlon of Pb-Cl distances Is much broader.In agreement with a previous EXAFS study.

Journal Article Phaeochromocytoma as a cause of gastro-intestinal distension Get access A Bernstein, BA, MB (Dubl), A Bernstein, BA, MB (Dubl) Senior House Officer Hope Hospital, Salford 6 Search for other works by this author on: Oxford Academic Google Scholar A C Wright, MB, ChB, A C Wright, MB, ChB Medical Registrar Hope Hospital, Salford 6 Search for other works by this author on: Oxford Academic Google Scholar D Spencer, MB, ChB D Spencer, MB, ChB Registrar in Pathology Hope Hospital, Salford 6 Search for other works by this author on: Oxford Academic Google Scholar Postgraduate Medical Journal, Volume 43, Issue 497, March 1967, Pages 180–183, https://doi.org/10.1136/pgmj.43.497.180 Published: 01 March 1967