Development of sensitivity to acetylcholine in cultured chick embryo sympathetic ganglion neurones

Dissociated sympathetic neurones from chick embryos of various ages were maintained in culture for several days and changes in sensitivity to iontophoretically applied acetylcholine (ACh) measured over 5 days in vitro. Neurones from 12-day embryos show a marked increase in ACh sensitivity, neurones from 14-day embryos a smaller change and those from 19-day embryos do not alter. These changes parallel those observed previously for binding of [Iα-bungarotoxin

Community-based exercise and wellness program for people diagnosed with Parkinson disease: Experiences from a 10-month trial

Objective: This study considered whether a therapy community could create an infrastructure for developing and maintaining a service delivery model grounded in a clinic-based physiotherapy model. A longitudinal clinical study was conducted to assess the abilities of participants with Parkinson disease in a 10-month community exercise program. Methods: Fifteen individuals averaging stage 3 on the Hoehn and Yahr scale, 6 years since Parkinson disease diagnosis, and 72 years old, participated. Results: Graphical analysis of ambulation endurance demonstrated the strongest improvement over time (11%). Walking speeds, balance, and mobility showed a maintenance effect over the 10 months. The total Unified Park inson Disease Rating Scale, Activities of Daily Living subscale, and Motor subscale remained statistically unchanged in the study. Scores on the Unified Parkinson Disease Rating Scale Mentation, Behavior, and Mood subscale improved by 38%. None of the scores met or exceeded the minimal detectable change, MDC95 but two scores demonstrated more than 10% change. Conclusion: This clinical study implemented previous shortterm research fi ndings into an ongoing community wellness program for individuals with Parkinson disease. No community-based studies have demonstrated an ability to maintain a group for an extended time frame. Group exercise including forward and backward treadmill training, designed and monitored by a physical therapist, may improve or maintain functional outcomes. Copyright © 2012 The Section on Geriatrics of the American Physical Therapy Association

Development of receptors for α-bungarotoxin in chick embryo sympathetic ganglion neurons in vitro

The development of receptors for α-bungarotoxin was examined in neurons in dissociated cultures of cells derived from chick embryo sympathetic ganglia. Neurons from 12 day embryos showed a marked increase in receptor numbers per cell over 3-4 days in culture. The increase was less marked in neurons from 14 day embryos and absent in 19 day embryos. The incidence of cholinergic synapses in cultures from 12 day and 19 day embryos was also examined. Evidence for synapse formation was found only in cultures from older embryos

Long-term exercise training for an individual with mixed corticobasal degeneration and progressive supranuclear palsy features: 10-year case report follow-up

Background and Purpose. This case report describes the effects of long-term (10-year) participation in a community exercise program for a client with mixed features of corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP). The effects of exercise participation on both functional status and brain volume are described. Case Description. A 60-year-old male dentist initially reported changes in gait and limb coordination. He received a diagnosis of atypical CBD at age 66 years; PSP was added at age 72 years. At age 70 years, the client began a therapist-led community group exercise program for people with Parkinson disease (PD). The program included trunk and lower extremity stretching and strengthening, upright balance and strengthening, and both forward and backward treadmill walking. The client participated twice weekly for 1 hour for 10 years and was reassessed in years 9 to 10. Outcomes. Falls (self-reported weekly over the 10-year period of the study by the client and his wife) decreased from 1.9 falls per month in year 1 to 0.3 falls per month in year 10. Balance, walking endurance, and general mobility declined slightly. Gait speed (both comfortable and fast) declined; the client was unable to vary gait speed. Quantitative brain measurements indicated a slow rate of whole brain volume loss and ventricular expansion compared with clients with autopsy-proven CBD or PSP. Discussion. This client has participated consistently in a regular group exercise program for 10 years. He has reduced fall frequency, maintained balance and endurance, and retained community ambulation using a walker. Combined with the slow rate of brain volume loss, this evidence supports the efficacy of a regular exercise program to prolong longevity and maintain function in people with CBD or PSP. © 2014 American Physical Therapy Association

Late-Glacial and Holocene Climatic Effects on Fire and Vegetation Dynamics at the Prairie–Forest Ecotone in South-Central Minnesota

1. Treeline ecotones, such as the prairie–forest boundary, represent climatically sensitive regions where the relative abundance of vegetation types is controlled by complex interactions between climate and local factors. Responses of vegetation and fire to climate change may be tightly linked as a result of strong feedbacks among fuel production, vegetation structure and fire frequency/severity, but the importance of these feedbacks for controlling the stability of this ecotone is unclear. 2. In this study, we examined the prairie–forest ecotone in south-central Minnesota using two lake sediment cores to reconstruct independent records of climate, vegetation and fire over the past 12 500 years. Using pollen, charcoal, sediment magnetic analyses and LOI properties, we investigated whether fires were controlled directly by climate or indirectly by fuel production. 3. Sediment magnetic and LOI data suggest four broad climatic periods occurring c. 11 350–8250 BP (cool/humid), c. 8250–4250 BP (warm/dry), c. 4250–2450 BP (warm/humid), and c. 2450–0 BP (cool/humid), indicating that, since the mid-Holocene, climate has shifted towards wetter conditions favouring greater in-lake production and fuel production on the landscape. 4. The area surrounding both lakes was characterized by boreal forest c. 12 500–10 000 BP, changing to an Ulmus-Ostrya forest c. 10 000–9000 BP, changing to a community dominated by prairie (Poaceae-Ambrosia-Artemisia) and deciduous forest taxa c. 8000–4250 BP, and finally shifting to a Quercus-dominated woodland/savanna beginning c. 4250–3000 BP. 5. Charcoal influx increased from an average of 0.11–0.62 mm2 cm−2 year−1 during the early Holocene forest period (c. 11 350–8250 BP) to 1.71–3.36 mm2 cm−2 year−1 during the period of prairie expansion (c. 8250–4250 BP) and again increased to 4.18–4.90 mm2 cm−2 year−1 at the start of the woodland/savanna period (c. 4250 BP). 6. As a result of the influence of climate on community composition and fuel productivity, changes in fire severity may be the result and not the cause of shifts in vegetation

Late-Glacial and Holocene Climatic Effects on Fire and Vegetation Dynamics at the Prairie–Forest Ecotone in South-Central Minnesota

1. Treeline ecotones, such as the prairie–forest boundary, represent climatically sensitive regions where the relative abundance of vegetation types is controlled by complex interactions between climate and local factors. Responses of vegetation and fire to climate change may be tightly linked as a result of strong feedbacks among fuel production, vegetation structure and fire frequency/severity, but the importance of these feedbacks for controlling the stability of this ecotone is unclear. 2. In this study, we examined the prairie–forest ecotone in south-central Minnesota using two lake sediment cores to reconstruct independent records of climate, vegetation and fire over the past 12 500 years. Using pollen, charcoal, sediment magnetic analyses and LOI properties, we investigated whether fires were controlled directly by climate or indirectly by fuel production. 3. Sediment magnetic and LOI data suggest four broad climatic periods occurring c. 11 350–8250 BP (cool/humid), c. 8250–4250 BP (warm/dry), c. 4250–2450 BP (warm/humid), and c. 2450–0 BP (cool/humid), indicating that, since the mid-Holocene, climate has shifted towards wetter conditions favouring greater in-lake production and fuel production on the landscape. 4. The area surrounding both lakes was characterized by boreal forest c. 12 500–10 000 BP, changing to an Ulmus-Ostrya forest c. 10 000–9000 BP, changing to a community dominated by prairie (Poaceae-Ambrosia-Artemisia) and deciduous forest taxa c. 8000–4250 BP, and finally shifting to a Quercus-dominated woodland/savanna beginning c. 4250–3000 BP. 5. Charcoal influx increased from an average of 0.11–0.62 mm2 cm−2 year−1 during the early Holocene forest period (c. 11 350–8250 BP) to 1.71–3.36 mm2 cm−2 year−1 during the period of prairie expansion (c. 8250–4250 BP) and again increased to 4.18–4.90 mm2 cm−2 year−1 at the start of the woodland/savanna period (c. 4250 BP). 6. As a result of the influence of climate on community composition and fuel productivity, changes in fire severity may be the result and not the cause of shifts in vegetation

In vitro and in vivo characterization of JNJ-31020028 (N-(4-{4-[2-(diethylamino)-2-oxo-1-phenylethyl]piperazin-1-yl}-3-fluorophenyl)-2-pyridin-3-ylbenzamide), a selective brain penetrant small molecule antagonist of the neuropeptide Y Y2 receptor

Rationale The lack of potent, selective, brain penetrant Y2 receptor antagonists has hampered in vivo functional studies of this receptor. Objective Here, we report the in vitro and in vivo characterization of JNJ-31020028 (N-(4-{4-[2-(diethylamino)-2-oxo-1-phenylethyl]piperazin-1-yl}-3-fluorophenyl)-2-pyridin-3-ylbenzamide), a novel Y2 receptor antagonist. Methods The affinity of JNJ-31020028 was determined by inhibition of the PYY binding to human Y2 receptors in KAN-Ts cells and rat Y2 receptors in rat hippocampus. The functional activity was determined by inhibition of PYY-stimulated calcium responses in KAN-Ts cells expressing a chimeric G protein Gqi5 and in the rat vas deferens (a prototypical Y2 bioassay). Ex vivo receptor occupancy was revealed by receptor autoradiography. JNJ-31020028 was tested in vivo with microdialysis, in anxiety models, and on corticosterone release. Results JNJ-31020028 bound with high affinity (pIC50 = 8.07 ± 0.05, human, and pIC50 = 8.22 ± 0.06, rat) and was >100-fold selective versus human Y1, Y4, and Y5 receptors. JNJ-31020028 was demonstrated to be an antagonist (pKB = 8.04 ± 0.13) in functional assays. JNJ-31020028 occupied Y2 receptor binding sites (~90% at 10 mg/kg) after subcutaneous administration in rats. JNJ-31020028 increased norepinephrine release in the hypothalamus, consistent with the colocalization of norepinephrine and neuropeptide Y. In a variety of anxiety models, JNJ-31020028 was found to be ineffective, although it did block stress-induced elevations in plasma corticosterone, without altering basal levels, and normalized food intake in stressed animals without affecting basal food intake. Conclusion These results suggest that Y2 receptors may not be critical for acute behaviors in rodents but may serve modulatory roles that can only be elucidated under specific situational conditions

Pulmonary fibrosis in dyskeratosis congenita: Report of 2 cases

Dyskeratosis congenita (DC) is a disorder of poor telomere maintenance and is related to 1 or more mutations that involve the vertebrate telomerase RNA component. Most affected patients develop mucocutaneous manifestations and cytopenias in the peripheral blood between 5 and 15 years of age. DC patients may also develop pulmonary complications including fibrotic interstitial lung disease and pulmonary vascular abnormalities. The radiologic and pathologic features of pulmonary fibrosis associated with DC are poorly defined. Herein, we report 2 new DC cases and suggest that the radiologic and histopathologic findings may resemble usual interstitial pneumonia but may not neatly fit into the current classification of interstitial lung disease