Isolation of short-wavelength-sensitive cone photoreceptors in 4-6-week-old human infants

Spectral sensitivity was measured for nine infants, 4-6 weeks of age, and three adults under conditions of chromatic adaptation chosen to reveal the presence of short-wavelength-sensitive cones. Monochromatic test stimuli (400-550 nm) were presented at 2 Hz superimposed on a broadband, yellow background. Following 4 min of adaptation to the background, test stimuli were presented while recording the steady-state, visually-evoked cortical potential (VECP). Response averages were obtained for several radiance levels at each test wavelength, and the amplitude of the fundamental frequency was extracted from the digitized response with a fast-Fourier transform. These data were used to construct response vs intensity functions for each wavelength. A fixed criterion response was chosen from the latter family of functions to generate individual spectral sensitivity curves. These VECP spectral sensitivity functions matched the psychophysically-determined functions of adults, measured by the method of adjustment and with the same stimulus configuration. Peak sensitivity for infants and adults under these conditions occurred at about 440 nm, and the main lobe of the curve (400-500 nm) was well fitted by the Vos-Walraven short-wavelength cone fundamental. The only major difference between the infant and adult data was in the relative sensitivity of the secondary mode of the curves (above 500 nm). These results demonstrate the presence of short-wavelength-sensitive cones and a functional pathway to the visual cortex by 4-6 weeks of age.     

Development and proliferation of lymphocytes in mice deficient for both interleukins-2 and -4

Interleukin (IL)-2 and IL-4 are considered as important regulators of growth and differentiation of lymphocytes. We report that in mice made deficient for both IL-2 and IL-4 by gene targeting all major T cell subsets and B cells were normal, indicating that IL-2 and IL-4 are not essential for development of the immune system. Paradoxically, proliferation of T cells was increased in both IL-2- and IL-4-deficient homozygous mice.     

Testing the effectiveness of the exercise plus program in older women post-hip fracture

Background: Exercise is an important strategy with potential to improve recovery in older adults following a hip fracture.Purpose: The purpose of this study was to test the impact of a self-efficacy based intervention, the Exercise Plus Program, and the different components of the intervention, on self-efficacy, outcome expectations, and exercise behavior among older women post-hip fracture.Methods: Participants were randomized to one of four groups: exercise plus, exercise only, plus only (i.e., motivation), or routine care. Data collection was done at baseline (within 22 days of fracture), 2, 6, and 12 months post-hip fracture.Results: A total of 209 women were recruited with an average age of 81.0 years (SD=6.9). The majority was White (97.1%), was widowed (57.2%), and had a high school education (66.7%). Generalized Estimating Equations were used to perform repeated measures analyses. No differences in trajectories of recovery were observed for self-efficacy or outcome expectations. A statistically significant difference in the overall trajectory of time in exercise was seen (p<.001), with more time spent exercising in all three treatment groups.Conclusions: The study demonstrated that it was possible to engage these women in a home-based exercise program and that the plus only, exercise only, and the exercise plus groups all increased exercise. Support for this project was provided by National Institute on Aging grants R37 AG09901, R01-AG18668, R01 AG17082, and the Claude D. Pepper Older Americans Independence Center P60-AG12583.     

Role of DAT‐SPECT in the diagnostic work up of Parkinsonism

The diagnosis of idiopathic Parkinson's disease (PD) can be achieved with high degrees of accuracy in cases with full expression of classical clinical features. However, diagnostic uncertainty remains in early disease with subtle or ambiguous signs. Functional imaging has been suggested to increase the diagnostic yield in parkinsonian syndromes with uncertain clinical classification. Loss of striatal dopamine nerve terminal function, a hallmark of neurodegenerative Parkinsonism, is strongly related to decreases of dopamine transporter (DAT) density, which can be measured by single photon emission computed tomography (SPECT). The use of DAT‐SPECT facilitates the differential diagnosis in patients with isolated tremor symptoms not fulfilling PD or essential tremor criteria, drug‐induced, psychogenic and vascular Parkinsonism as well as dementia when associated with Parkinsonism. This review addresses the value of DAT‐SPECT in early differential diagnosis, and its potential as a screening tool for subjects at risk of developing PD as well as issues around the assessment of disease progression. © 2007 Movement Disorder Society     

High-risk children in young adulthood: a longitudinal study from birth to 32 years

The developmental courses of high-risk and resilient children were analyzed in a follow-up study of members of a 1955 birth cohort on the island of Kauai, Hawaii. Relative impact of risk and protective factors changed at various life phases, with males displaying greater vulnerability than females in their first decade and less during their second; another shift appears under way at the beginning of their fourth decade. Certain protective factors seem to have a more general effect on adaptation than do specific risk factors.     

Meeting the regulatory requirements for pharmaceutical production of recombinant DNA derived products

Genetic engineering provides the opportunity for the synthesis of human proteins and derivatives thereof which are of significant value for replacement therapy. However, in addition to genetic engineering an extensive process development has to be carried out in order to establish an economic production process and to guarantee consistently high product quality from batch to batch. This includes the characterization of the production host cell vector construct, the validation of the fermentation and the protein purification process as well as the lyophilization and the reconstitution of the final product. A number of in-process and final product controls have to be established and limits for the specification have to be elaborated to provide consistent product quality. Real time stability data have to be supplied because data from accelerated conditions do not allow extrapolation of the shelf life of proteins. Data obtained from process development and validation of the production process contributes to the preparation of the chemical pharmaceutical dossier and the expert report to be submitted to the regulatory authorities.     

Stimulated elastase release from human leukocytes: Influence of anti-asthmatic,anti-inflammatory and calcium antagonist drugsin vitro

In the present study the effects of drugs, with different modes of action, on FMLP-stimulated release of elastase from human leukocytes were investigatedin vitro. Anti-asthmatic and anti-allergic drugs were compared to well-known anti-inflammatory and anti-histamine agents. The anti-asthmatic/anti-allergic compounds azelastine, astemizole and oxatomide, and the 5-lipoxygenase inhibitor NDGA, were able to suppress the release of elastase from human leukocytes in concentrations between 10 and 100 μM. NSAIDs such as indomethacin, diclofenac and piroxicam and the glucocorticoids dexamethasone and hydrocortisone showed little or no activity. The histamine H1 antagonists mepyramine and ketotifen and the calcium antagonists verapamil, nifedipine and TMB-8 were also ineffective in suppressing FMLP-induced elastase release. Reduction in elastase release by azelastine, that accumulates in lung tissue during long-term treatment in animals, may contribute to its anti-inflammatory and anti-allergic effects which are thought to be central to its use in asthma therapy.