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Alternative excitotoxic hypotheses
Abstract
It is known that asthma is a heterogeneous entity whose manifestations vary with age. Our objective was to examine changes in the manifestation of asthma and asthma-related traits in childhood by defining empirically derived childhood asthma phenotypes and examining their transitions over time. To define the phenotypes we used data on respiratory symptoms, healthcare utilisation, medications, spirometry, airway hyperresponsiveness (AHR), exhaled nitric oxide concentration and atopy from a birth cohort recruited on the basis of having a first-degree relative with asthma. Data were acquired at ages 1.5–11.5 years and analysed using latent transition analysis. In a study population of 370 participants, we classified subjects into four phenotypes: 1) nonatopic, few symptoms (prevalence range from 1.5 to 5 years: 52–60%), 2) atopic, few symptoms (3–21%), 3) nonatopic, asthma and rhinitis symptoms (13–35%), and 4) atopic, asthma and rhinitis symptoms (2–14%) in early childhood; and 1) nonatopic, no respiratory disease (prevalence range from 8 to 11.5 years: 41–46%), 2) atopic, no respiratory disease (23–33%), 3) nonatopic, asthma symptoms, no AHR or airway inflammation (8–12%) and 4) atopic asthma (19%) in mid-childhood. Transitioning between phenotypes was common in early childhood, but less common in later childhood. This analysis represents the first attempt to incorporate longitudinal patterns of several manifestations of asthma into a single model to simultaneously define phenotypes and examine their transitions over time. It provides quantitative support for the view that asthma is a heterogeneous entity, and that some children with wheeze and other respiratory symptoms in early life progress to asthma in mid-childhood, while others become asymptomatic.
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“Damage to glutamatergic neurons, in particular cell bodies and neurites in layers III and IV of the neocortex, together with damage to glutamatergically-innervated cortical and hippocampal neurons, are particularly evident in AD brain (Albin and Greenamyre 1992).”
From Alzheimer’s disease: Targeting the glutamatergic system (2020) · cites this paper as Albin and Greenamyre 1992
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“s) which are already in a low energy state. Due to disinhibition and energy deficiency, SNc somas might become overactive, which leads to calcium build-up, resulting in excitotoxic loss of SNc somas (Albin and Greenamyre, 1992; Muddapu et al., 2019). When higher concentrations of extracellular LDOPA were available, th…”
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Metadata
- Authors
- Albin, R. L., & Greenamyre, J. T.
- Affiliations
- University of Michigan (US)
- University of Rochester (US)
- Venue
- Neurology
- Published
- 1992-04
- Volume
- 42
- Issue
- 4
- Pages
- 733-733
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W2058176457
- Cited by
- 574
- References
- 0
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 6 · 2023: 3 · 2022: 18 · 2021: 4 · 2020: 12 · 2019: 3 · 2018: 6 · 2017: 7 · 2016: 5 · 2015: 4 · 2014: 10 · 2013: 12 · 2012: 16
- FWCI
- 14.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5k08ns001300-03, 5k08ns001487-03)
- National Institute of Neurological Disorders and Stroke (NS01300, NS 01487)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Asthma and respiratory diseases
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Occupational exposure and asthma
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Respiratory and Cough-Related Research
- Keywords
- asthma phenotypes, childhood asthma, asthma heterogeneity, phenotype transition, atopy, rhinitis, airway hyperresponsiveness, exhaled nitric oxide, wheezing, latent transition analysis, birth cohort
- MeSH terms
- Acute Disease, Amino Acids, Chronic Disease, Humans, Models, Neurological, Nerve Degeneration, Nervous System Diseases, Neurology, Neurotoxins, Receptors, Cell Surface, Receptors, Amino Acid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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