Toward earlier diagnosis of amyotrophic lateral sclerosis: revised criteria. rhCNTF ALS Study Group

We modified the World Federation of Neurology (WFN) diagnostic criteria for ALS to facilitate early diagnosis and used these criteria for enrollment of ALS patients in a clinical trial. The criteria developed required lower motor neuron (LMN) involvement in at least two limbs and upper motor neuron involvement in at least one region (bulbar, cervical, or lumbosacral). The EMG finding of fibrillation potentials was required for evidence of LMN involvement. Electrodiagnostic studies, neuroimaging, and laboratory studies were also used to exclude disorders that might mimic ALS. Using these criteria, the diagnosis of ALS was made at a mean time of 9.7 months from onset of symptoms, which compares favorably with the 12-month period cited in the literature. Using clinical assessment at completion of the trial, the diagnosis of ALS was believed to be accurate in those patients entered in the trial. However, pathologic confirmation of the diagnosis of ALS was not obtained. Based on our preliminary experience, we propose that these ALS diagnostic criteria will facilitate early diagnosis of ALS. Future studies should prospectively compare these criteria with the WFN criteria currently in use.     

Vowel Duration Affects Visual Word Identification: Evidence That the Mediating Phonology Is Phonetically Informed.

What form is the lexical phonology that gives rise to phonological effects in visual lexical decision? The authors explored the hypothesis that beyond phonological contrasts the physical phonetic details of words are included. Three experiments using lexical decision and 1 using naming compared processing times for printed words (e.g., plead and pleat) that differ, when spoken, in vowel length and overall duration. Latencies were longer for long-vowel words than for short-vowel words in lexical decision but not in naming. Further, lexical decision on long-vowel words benefited more from identity priming than lexical decision on short-vowel words, suggesting that representations of long-vowel words achieve activation thresholds more slowly. The discussion focused on phonetically informed phonologies, particularly gestural phonology and its potential for understanding reading acquisition and performance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Theoretical antideuteron-nucleus absorptive cross sections

Antideuteron-nucleus absorptive cross sections for intermediate to high energies are calculated using an ion-ion optical model. Good agreement with experiment (within 15 percent) is obtained in this same model for mean p-nucleus cross sections at laboratory energies up to 15 GeV. We describe a technique for estimating antinucleus-nucleus cross sections from N mean N data and suggest that further cosmic ray studies to search for antideuterons and other antinuclei be undertaken.     

Sex differences in human motor activity level.

Examined sex differences in activity level (AL) by quantitatively integrating results from 90 citations encompassing 127 independent sex-difference studies. A variety of developmental, situational, measurement, and investigator factors thought to be related to the AL sex-difference magnitude was assessed. Sample sizes ranged from 7 to 25,000; chronological ages ranged from 2 mo before birth to 30 yrs. A scale-independent index of effect size (d) was used to summarize the results of a between-sexes comparison, and ds across investigations were aggregated with measures of AL. Findings indicate that males were generally more active than females, although the magnitude of the difference was associated with other features of the research investigation, such as participant age and situational characteristics. This AL result was judged to be a large effect within the context of established behavioral sex differences. Data are consistent with the view that social influences enlarge AL sex differences. A list of citations used in the study is appended. (32 ref) (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Self-reactive B cells in nonautoimmune and autoimmune mice

The defining feature of autoimmune disease is the presence of specific autoreactive lymphocytes. Systemic lupus erythematosus (SLE), for example, is characterized by a discrete set of antibodies directed to nuclear antigens; these include autoantibodies to DNA and snRNPs that are diagnostic for SLE. The murine model of SLE, the MRL-lpr/lpr mouse, likewise, has a similar autoantibody profile. To understand how SLE-associated autoantibodies are regulated in healthy individuals and to identify mechanisms underlying their expression in autoimmunity, we have developed a transgenic (tg) model system using multiple sets of tgs. The development of B cells bearing these tgs has been studied in BALB/c and MRL-lpr/lpr autoimmune backgrounds, and the relative fates of anti-ssDNA and anti-dsDNA tg B cells when they are a part of a diverse as well as monoclonal B cell repertoire have been evaluated.     

Direct measurement of the energy expenditure of physical activity in preterm infants

The energy cost of physical activity (EEA) has been estimated to account for 5-17% of total energy expenditure (TEE) in neonates. To directly measure EEA, a force plate was developed and validated to measure work outputs ranging from 0.3 to 40 kcal . kg-1 . day-1. By use of this force plate plus indirect calorimetry, TEE and EEA were measured and correlated with five activity states in 24 infants with gestational age of 31.6 +/- 0.5 (SE) wk and postnatal age of 24.8 +/- 3.7 days. TEE and EEA were 69.2 +/- 1.5 and 2.4 +/- 0.2 kcal . kg-1 . day-1, respectively. EEA per state was 0.5 +/- 0.0 (quiet sleep), 2.4 +/- 0.2 (active sleep), 2.8 +/- 0.4 (quiet awake), 7.5 +/- 0.8 (active awake), and 15.1 +/- 2.3 (crying) kcal . kg-1 . day-1. This provides the first direct measurement of the contribution of physical activity to TEE in preterm infants and will enable measurement of caloric expenditure from muscle activity in various disease conditions and development of nursing strategies to minimize unnecessary energy losses.     

Cervical assessment by magnetic resonance imaging--its relationship to gestational age and interval to delivery

The aim of this cross-sectional study was to assess the uterine cervix in late pregnancy, using MRI, and to study its relationship to the gestational age and the time interval to delivery. 91 women with a singleton cephalic presenting fetus had MRI of the pelvis between 35 and 41 weeks. All had had one prior lower segment Caesarean section and no history of prior vaginal delivery. The cervical length, internal and external os diameter, cervical signal intensity and the angulation of the cervix with the cephalocaudal axis were measured on sagittal T2 weighted images and correlated with the gestational age and the interval from the MRI examination to delivery. It was found that the signal intensity of the cervical stroma increased with the gestational age. A higher signal intensity in the cervical stroma was associated with a shorter time interval to delivery. Deliveries after 40 weeks tended to occur more commonly in those with lower signal intensity in the cervical stroma and also in those with a smaller external os diameter. It is concluded that cervical softening as assessed on MRI correlated with gestational age and the time interval to delivery.     

Prolonged discordant xenograft survival and delayed xenograft rejection in a pig-to-baboon orthotopic cardiac xenograft model

OBJECTIVE: Our objectives were to study delayed xenograft rejection and the effectiveness of pretransplantation total lymphoid irradiation combined with immunosuppression on rejection in a pig-to-baboon cardiac xenograft model. METHODS: Baboons were treated with pretransplantation total lymphoid irradiation, cyclosporine A (INN: ciclosporin), and methotrexate. Orthotopic pig-to-baboon cardiac transplantations were performed after depletion of circulating xenoreactive natural antibody by pretransplantation donor organ hemoperfusion. Tissue samples were collected for immunologic and immunopathologic evaluation. RESULTS: Pig cardiac xenografts survived more than 18 and 19 days without evidence of hyperacute rejection. Immunologic analysis of serum samples demonstrated that circulating xenoreactive natural antibody levels did not return to pretransplantation levels. The production of xenoreactive natural antibodies from the recipient's splenocytes was inhibited completely. Histologic examination of xenografts showed the feature of acute vascular rejection. Immunohistochemical studies demonstrated infiltration of cardiac xenografts by large numbers of macrophages, small numbers of natural killer cells, and a few T cells. The infiltrating macrophages also showed expression of interleukin-1 and tumor necrosis factor. Diffuse deposition of immunoglobulin G, C1Q, C3, and fibrin on xenograft vasculature was observed. Interleukin-2 expression was not found in rejected cardiac xenografts. Xenograft endothelial cells also showed evidence of activation (expression of cytokines interleukin-1 and tumor necrosis factor). CONCLUSIONS: This study demonstrates prolonged discordant cardiac xenograft survival and delayed xenograft rejection in a pig-to-baboon model. The delayed xenograft rejection is mediated by both humoral and cellular mechanisms. Pretransplantation total lymphoid irradiation combined with cyclosporine A and methotrexate can inhibit xenoreactive natural antibody production but not elicited antipig antibody production and the xenoreactivity of macrophages.     

Involvement of IL-16 in the induction of airway hyper-responsiveness and up-regulation of IgE in a murine model of allergic asthma

Experiments were designed to investigate the role of IL-16 in a mouse model of allergic asthma. OVA-sensitized mice were repeatedly exposed to OVA or saline aerosols. Bronchoalveolar lavage fluid (BALF) was collected after the last aerosol, and the presence of IL-16 was evaluated using a migration assay with human lymphocytes. Migration of lymphocytes was significantly increased in the presence of cell-free BALF from OVA-challenged mice compared with BALF from saline-challenged controls. This response was significantly inhibited after addition of antibodies to IL-16, demonstrating the presence of IL-16 in BALF of OVA-challenged animals. Immunohistochemistry was performed and revealed IL-16 immunoreactivity particularly in airway epithelial cells but also in cellular infiltrates in OVA-challenged mice. IL-16 immunoreactivity was absent in nonsensitized animals; however, some reactivity was detected in epithelial cells of sensitized but saline-challenged mice, suggesting that sensitization induced IL-16 expression in airway epithelium. Treatment of mice with antibodies to IL-16 during the challenge period significantly suppressed up-regulation of OVA-specific IgE in OVA-challenged animals. Furthermore, antibodies to IL-16 significantly inhibited the development of airway hyper-responsiveness after repeated OVA inhalations, whereas the number of eosinophils in bronchoalveolar lavage or airway tissue was not affected. In conclusion, IL-16 immunoreactivity is present in the airways after sensitization. After repeated OVA inhalation, IL-16 immunoreactivity is markedly increased and IL-16 is detectable in BALF. Furthermore, IL-16 plays an important role in airway hyper-responsiveness and up-regulation of IgE but is not important for eosinophil accumulation in a mouse model of allergic asthma.