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540 results on '"Appenzeller, O."'

4. Altered iPSC-derived neurons’ sodium channel properties in subjects with Monge’s disease

Author

Zhao, HW, Gu, XQ, Chailangkarn, T, Perkins, G, Callacondo, D, Appenzeller, O, Poulsen, O, Zhou, D, Muotri, AR, and Haddad, GG

Subjects
Biomedical and Clinical Sciences, Neurosciences, Stem Cell Research - Induced Pluripotent Stem Cell - Human, Stem Cell Research - Induced Pluripotent Stem Cell, Clinical Research, Stem Cell Research, Brain Disorders, 2.1 Biological and endogenous factors, Neurological, Good Health and Well Being, Action Potentials, Adult, Altitude Sickness, Cell Culture Techniques, Cells, Cultured, Chronic Disease, Fibroblasts, Humans, Immunohistochemistry, Induced Pluripotent Stem Cells, Male, Neural Stem Cells, Neurogenesis, Neurons, Patch-Clamp Techniques, Peru, Sodium Channels, Young Adult, chronic mountain sickness, induced pluripotent stem cells, neurons, Na+ channel, Na(+) channel, Psychology, Cognitive Sciences, Neurology & Neurosurgery, Biological psychology
Abstract

Monge's disease, also known as chronic mountain sickness (CMS), is a disease that potentially threatens more than 140 million highlanders during extended time living at high altitudes (over 2500m). The prevalence of CMS in Andeans is about 15-20%, suggesting that the majority of highlanders (non-CMS) are rather healthy at high altitudes; however, CMS subjects experience severe hypoxemia, erythrocytosis and many neurologic manifestations including migraine, headache, mental fatigue, confusion, and memory loss. The underlying mechanisms of CMS neuropathology are not well understood and no ideal treatment is available to prevent or cure CMS, except for phlebotomy. In the current study, we reprogrammed fibroblast cells from both CMS and non-CMS subjects' skin biopsies into the induced pluripotent stem cells (iPSCs), then differentiated into neurons and compared their neuronal properties. We discovered that CMS neurons were much less excitable (higher rheobase) than non-CMS neurons. This decreased excitability was not caused by differences in passive neuronal properties, but instead by a significantly lowered Na(+) channel current density and by a shift of the voltage-conductance curve in the depolarization direction. Our findings provide, for the first time, evidence of a neuronal abnormality in CMS subjects as compared to non-CMS subjects, hoping that such studies can pave the way to a better understanding of the neuropathology in CMS.

Published
2015

9. Neurology then and Now Letter

Author

Appenzeller O

Subjects
Pharmacology (medical)
Abstract

I review the changes in the teaching and practice of neurology as they occurred over two generations of neurologists assuming a generation to be approximately 30 years. I illustrate the highlights and mention some of the leading figures who have contributed to altitude medicine and clinical neurology as it is taught and practiced today.

Published
2019

35. Heart rate and respiratory rhythm dynamics on ascent to high altitude

Author

Lipsitz, L. A, Hashimoto, F, Lubowsky, L. P, Mietus, J, Moody, G. B, Appenzeller, O, and Goldberger, A. L

Subjects
Aerospace Medicine
Abstract

OBJECTIVE--To investigate the alterations in autonomic control of heart rate at high altitude and to test the hypothesis that hypoxaemic stress during exposure to high altitude induces non-linear, periodic heart rate oscillations, similar to those seen in heart failure and the sleep apnoea syndrome. SUBJECTS--11 healthy subjects aged 24-64. MAIN OUTCOME MEASURES--24 hour ambulatory electrocardiogram records obtained at baseline (1524 m) and at 4700 m. Simultaneous heart rate and respiratory dynamics during 2.5 hours of sleep by fast Fourier transform analysis of beat to beat heart rate and of an electrocardiographically derived respiration signal. RESULTS--All subjects had resting hypoxaemia at high altitude, with an average oxyhaemoglobin saturation of 81% (5%). There was no significant change in mean heart rate, but low frequency (0.01-0.05 Hz) spectral power was increased (P < 0.01) at high altitude. Time series analysis showed a complex range of non-linear sinus rhythm dynamics. Striking low frequency (0.04-0.06 Hz) heart rate oscillations were observed during sleep in eight subjects at high altitude. Analysis of the electrocardiographically derived respiration signal indicated that these heart rate oscillations correlated with low frequency respiratory oscillations. CONCLUSIONS--These data suggest (a) that increased low frequency power during high altitude exposure is not simply attributable to increased sympathetic modulation of heart rate, but relates to distinctive cardiopulmonary oscillations at approximately 0.05 Hz and (b) that the emergence of periodic heart rate oscillations at high altitude is consistent with an unstable cardiopulmonary control system that may develop on acute exposure to hypoxaemic stress.

Published
1995

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