Cytomechanics of axonal development

Mechanical tension is a robust regulator of axonal development of cultured neurons. We review work from our laboratory, using calibrated glass needles to measure or apply tension to chick sensory neurons, chick forebrain neurons, and rat PC12 cells. We survey direct evidence for two different regimes of tension effects on neurons, a fluid-like growth regime, and a nongrowth, elastic regime. Above a minimum tension threshold, we observe growth effects of tension regulating four phases of axonal development: 1. Initiation of process outgrowth from the cell body; 2. Growth cone-mediated elongation of the axon; 3. Elongation of the axon after synaptogenesis, which normally accommodates the skeletal growth of vertebrates; and 4. Axonal elimination by retraction. Significantly, the quantitative relationship between the force and the growth response is surprisingly similar to the simple relationship characteristic of Newtonian fluid mechanical elements: elongation rate is directly proportional to tension (above the threshold), and this robust linear relationship extends from physiological growth rates to far-above-physiological rates. Thus, tension apparently integrates the complex biochemistry of axonal elongation, including cytoskeletal and membrane dynamics, to produce a simple "force input/growth output" relationship. In addition to this fluid-like growth response, peripheral neurons show elastic behaviors at low tensions (below the threshold tension for growth), as do most cell types. Thus, neurites could exert small static forces without diminution for long periods. In addition, axons of peripheral neurons can actively generate modest tensions, presumably similar to muscle contraction, at tensions near zero. The elastic and force-generating capability of neural axons has recently been proposed to play a major role in the morphogenesis of the brain.     

Log-linear allometry of fetal craniofacial growth in Down's syndrome

Trisomy 21 develops as a result of nondisjunction of two homologous chromosomes during either the first or second meiotic division. One of the more important consequences of these genetic alterations is the predictable, although variable disturbance in the architecture of the craniofacial region [1]. Postnatal craniofacial morphology has been extensively studied in Down's syndrome (DS). However, little information is available on human prenatal development of the head and face in such patients. The time at which changes in craniofacial phenotype first emerge in Down's syndrome fetuses and at which physical growth begins to diverge from normal is unknown. To explore these questions, we compared prenatal craniofacial growth in 50 Down's syndrome fetuses with that of 555 fetuses judged to be "typical for body weight and age" using the method of log-linear allometry [2].     

Lobectomy combined with volume reduction for patients with lung cancer and advanced emphysema

Methanol-induced conformational transitions of hen egg white lysozyme were investigated with a combined use of far- and near-UV CD and NMR spectroscopies, ANS binding and small-angle X-ray scattering. Addition of methanol induced no global change in the native conformation itself, but induced a transition from the native state to the denatured state which was highly cooperative, as shown by the coincidence of transition curves monitored by the far- and near-UV CD spectroscopy, by isodichroic points in the far- and near-UV CD spectra and by the concomitant disappearance of individual 1H NMR signals of the native state. The ANS binding experiments could detect no intermediate conformer similar to the molten globule state in the process of the methanol denaturation. However, at high concentration of methanol, e.g., 60% (v/v) methanol/water, a highly helical state (H) was realized. The H state had a helical content much higher than the native state, monitored by far-UV CD spectroscopy, and had no specific tertiary structure, monitored both by near-UV CD and NMR spectroscopy. The radius of gyration in the H state, 24.9 angstroms, was significantly larger than that in the native state (15.7 angstroms). The Kratky plot for the H state did not show a clear peak and was quite similar to that for the urea-denatured state, indicating a complete lack of globularity. Thus we conclude that the H state has a considerably expanded, flexible broken rod-like conformation which is clearly distinguishable from the "molten globule" state. The stability of both N and H states depends on pH and methanol concentration. Thus a phase diagram involving N and H was constructed.     

Refining the level for anticipated hepatotoxicity in acetaminophen poisoning

Treatment of an acetaminophen overdose with N-acetyl cysteine usually is based on the position of the 4-h acetaminophen (APAP) level on the Rumack-Matthew nomogram; however, there is disagreement on the level at which clinically relevant hepatotoxicity occurs. A retrospective review of all acute adult formulation APAP exposures reported to our poison center between 1986 and 1993 was performed and cases corresponding to the "possible risk or toxicity" range on the nomogram were identified. Our current poison center protocol for APAP poisoning does not recommend treatment with N-acetylcysteine (NAC) in low-risk patients if the 4-h serum APAP level or the extrapolated equivalent falls within the possible toxicity range on the nomogram. Seventeen cases met the inclusion criteria for the study and received no NAC; six additional patients met inclusion criteria but received one or two doses of NAC before therapy was discontinued. No patients in either group demonstrated clinical evidence of hepatotoxicity. This pilot study suggests that patients with no risk factors and APAP levels in the "possible risk" range may not require NAC therapy.     

HLA-DRB1 genes and disease severity in rheumatoid arthritis. The MIRA Trial Group. Minocycline in Rheumatoid Arthritis

OBJECTIVE: To examine the effect of alleles encoding the "shared"/"rheumatoid" epitope on rheumatoid arthritis (RA) disease severity in patients who participated in the minocycline in RA (MIRA) trial. METHODS: Of 205 patients with a week-48 visit, blood was available for typing of HLA-DRB1 and HLA-DQB1 in 174 (85%) and successfully completed in 169 (82%). Baseline erosions were used to assess disease severity and new erosions at the last visit served as a proxy for progression. RESULTS: At baseline, there was no association between the presence of erosive disease or rheumatoid factor status and the dose of rheumatoid epitope (homozygous, heterozygous, none) or the specific alleles identified. At the final visit, a gradient was observed for the 3 allelic subgroups (and their gene doses) in the occurrence of new erosions among the Caucasian placebo-treated, but not the minocycline-treated, patients. A treatment group/HLA-DR4 epitope interaction was demonstrated in multivariate analyses. Approximately two-thirds of African-American patients did not have the rheumatoid epitope. CONCLUSION: HLA-DRB1 oligotyping may be useful in predicting the progression of disease in some Caucasian patients. Our study corroborates the infrequency of the epitope among African-American patients with RA.     

A test of the fail-safe N for self-help programs.

A meta-analysis of published studies on the clinical efficacy of selected self-help programs (F. Scogin et al; see record 1990-15222-001) indicated that such conditions were more effective than no-treatment controls. Calculation of a fail-safe N showed that 53 nonsignificant studies would have to exist to render the conclusions of the meta-analysis invalid. Results indicate that unpublished research is unlikely to threaten the validity of the original meta-analysis. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Perinuclear antineutrophil cytoplasmic antibodies in patients with Crohn's disease define a clinical subgroup

BACKGROUND & AIMS: Antineutrophil cytoplasmic antibodies (ANCA) have been consistently detected in a subgroup of patients with Crohn's disease (CD). This study was designed to determine whether serum ANCA expression in patients with CD characterizes an identifiable clinical subgroup. METHODS: The study population consisted of 69 consecutive patients with an established diagnosis of CD as determined by a combination of characteristic clinical, radiographic, endoscopic, and histopathologic criteria. Sera from the patients were analyzed for the presence of ANCAs using the fixed neutrophil enzyme-linked immunosorbent assay (ELISA) assay. Perinuclear ANCA (pANCA)-positive and cytoplasmic ANCA (cANCA)-positive results by ELISA were confirmed by indirect immunofluorescence staining. Clinical profiles of the ANCA-positive patients with CD were compared with those of patients with CD not expressing ANCA (ANCA-negative). RESULTS: pANCA-positive patients with CD have endoscopically and/or histopathologically documented left-sided colitis and symptoms of left-sided colonic inflammation, clinically reflected by rectal bleeding and mucus discharge, urgency, and treatment with topical agents. One hundred percent of patients with CD expressing pANCA had "UC-like" features. CONCLUSIONS: In patients with CD, serum pANCA expression characterizes a UC-like clinical phenotype. Stratification of CD by serum pANCA provides evidence of heterogeneity within CD and suggests a common intestinal mucosal inflammatory process among a definable subgroup of patients with CD and UC expressing this marker.     

Remote sensing of photosynthetic light-use efficiency across two forested biomes: Spatial scaling

Eddy covariance (EC) measurements have greatly advanced our knowledge of carbon exchange in terrestrial ecosystems. However, appropriate techniques are required to upscale these spatially discrete findings globally. Satellite remote sensing provides unique opportunities in this respect, but remote sensing of the photosynthetic light-use efficiency (ε), one of the key components of Gross Primary Production, is challenging. Some progress has been made in recent years using the photochemical reflectance index, a narrow waveband index centered at 531 and 570 nm. The high sensitivity of this index to various extraneous effects such as canopy structure, and the view observer geometry has so far prevented its use at landscape and global scales. One critical aspect of upscaling PRI is the development of generic algorithms to account for structural differences in vegetation. Building on previous work, this study compares the differences in the PRI: ? relationship between a coastal Douglas-fir forest located on Vancouver Island, British Columbia, and a mature Aspen stand located in central Saskatchewan, Canada. Using continuous, tower-based observations acquired from an automated multi-angular spectro-radiometer (AMSPEC II) installed at each site, we demonstrate that PRI can be used to measure ? throughout the vegetation season at the DF-49 stand (r² = 0.91, p < 0.00) as well as the deciduous site (r² = 0.88, p < 0.00). It is further shown that this PRI signal can be also observed from space at both sites using daily observations from the Moderate Resolution Imaging Spectro-radiometer (MODIS) and a multi-angular implementation of atmospheric correction (MAIAC) (r² = 0.54 DF-49; r² = 0.63 SOA; p < 0.00). By implementing a simple hillshade model derived from airborne light detection and ranging (LiDAR) to approximate canopy shadow fractions (α_s), it is further demonstrated that the differences observed in the relationship between PRI and ε at DF-49 and SOA can be attributed largely to differences in α_s. The findings of this study suggest that algorithms used to separate physiological from extraneous effects in PRI reflectance may be more broadly applicable and portable across these two climatically and structurally different biome types, when the differences in canopy structure are known.     

An assessment of photosynthetic light use efficiency from space: Modeling the atmospheric and directional impacts on PRI reflectance

Estimation of photosynthetic light use efficiency (ε) from satellite observations is an important component of climate change research. The photochemical reflectance index, a narrow waveband index based on the reflectance at 531 and 570 nm, allows sampling of the photosynthetic activity of leaves; upscaling of these measurements to landscape and global scales, however, remains challenging. Only a few studies have used spaceborne observations of PRI so far, and research has largely focused on the MODIS sensor. Its daily global coverage and the capacity to detect a narrow reflectance band at 531 nm make it the best available choice for sensing ε from space. Previous results however, have identified a number of key issues with MODIS-based observations of PRI. First, the differences between the footprint of eddy covariance (EC) measurements and the MODIS footprint, which is determined by the sensor's observation geometry make a direct comparison between both data sources challenging and second, the PRI reflectance bands are affected by atmospheric scattering effects confounding the existing physiological signal. In this study we introduce a new approach for upscaling EC based ε measurements to MODIS. First, EC-measured ε values were “translated” into a tower-level optical PRI signal using AMSPEC, an automated multi-angular, tower-based spectroradiometer instrument. AMSPEC enabled us to adjust tower-measured PRI values to the individual viewing geometry of each MODIS overpass. Second, MODIS data were atmospherically corrected using a Multi-Angle Implementation of Atmospheric Correction (MAIAC) algorithm, which uses a time series approach and an image-based rather than pixel-based processing for simultaneous retrievals of atmospheric aerosol and surface bidirectional reflectance (BRDF). Using this approach, we found a strong relationship between tower-based and spaceborne reflectance measurements (r² = 0.74, p < 0.01) throughout the vegetation period of 2006. Swath (non-gridded) observations yielded stronger correlations than gridded data (r² = 0.58, p < 0.01) both of which included forward and backscatter observations. Spaceborne PRI values were strongly related to canopy shadow fractions and varied with different levels of ε. We conclude that MAIAC-corrected MODIS observations were able to track the site-level physiological changes from space throughout the observation period.