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21.
Nadine?AME?van der BeekEmail author Juna?M?de Vries Marloes?LC?Hagemans Wim?CJ?Hop Marian?A?Kroos John?HJ?Wokke Marianne?de Visser Baziel?GM?van Engelen Jan?BM?Kuks Anneke?J?van der Kooi Nicolette?C?Notermans Karin?G?Faber Jan?JGM?Verschuuren Arnold?JJ?Reuser Ans?T?van der Ploeg Pieter?A?van Doorn 《Orphanet journal of rare diseases》2012,7(1):88
Background
Due partly to physicians’ unawareness, many adults with Pompe disease are diagnosed with great delay. Besides, it is not well known which factors influence the rate of disease progression, and thus disease outcome. We delineated the specific clinical features of Pompe disease in adults, and mapped out the distribution and severity of muscle weakness, and the sequence of involvement of the individual muscle groups. Furthermore, we defined the natural disease course and identified prognostic factors for disease progression.Methods
We conducted a single-center, prospective, observational study. Muscle strength (manual muscle testing, and hand-held dynamometry), muscle function (quick motor function test), and pulmonary function (forced vital capacity in sitting and supine positions) were assessed every 3–6 months and analyzed using repeated-measures ANOVA.Results
Between October 2004 and August 2009, 94 patients aged between 25 and 75 years were included in the study. Although skeletal muscle weakness was typically distributed in a limb-girdle pattern, many patients had unfamiliar features such as ptosis (23%), bulbar weakness (28%), and scapular winging (33%). During follow-up (average 1.6 years, range 0.5-4.2 years), skeletal muscle strength deteriorated significantly (mean declines of ?1.3% point/year for manual muscle testing and of ?2.6% points/year for hand-held dynamometry; both p<0.001). Longer disease duration (>15 years) and pulmonary involvement (forced vital capacity in sitting position <80%) at study entry predicted faster decline. On average, forced vital capacity in supine position deteriorated by 1.3% points per year (p=0.02). Decline in pulmonary function was consistent across subgroups. Ten percent of patients declined unexpectedly fast.Conclusions
Recognizing patterns of common and less familiar characteristics in adults with Pompe disease facilitates timely diagnosis. Longer disease duration and reduced pulmonary function stand out as predictors of rapid disease progression, and aid in deciding whether to initiate enzyme replacement therapy, or when.22.
Visinoni S Fam BC Blair A Rantzau C Lamont BJ Bouwman R Watt MJ Proietto J Favaloro JM Andrikopoulos S 《American journal of physiology. Endocrinology and metabolism》2008,295(5):E1132-E1141
Increased endogenous glucose production (EGP) predominantly from the liver is a characteristic feature of type 2 diabetes, which positively correlates with fasting hyperglycemia. Gluconeogenesis is the biochemical pathway shown to significantly contribute to increased EGP in diabetes. Fructose-1,6-bisphosphatase (FBPase) is a regulated enzyme in gluconeogenesis that is increased in animal models of obesity and insulin resistance. However, whether a specific increase in liver FBPase can result in increased EGP has not been shown. The objective of this study was to determine the role of upregulated liver FBPase in glucose homeostasis. To achieve this goal, we generated human liver FBPase transgenic mice under the control of the transthyretin promoter, using insulator sequences to flank the transgene and protect it from site-of-integration effects. This resulted in a liver-specific model, as transgene expression was not detected in other tissues. Mice were studied under the following conditions: 1) at two ages (24 wk and 1 yr old), 2) after a 60% high-fat diet, and 3) when bred to homozygosity. Hemizygous transgenic mice had an approximately threefold increase in total liver FBPase mRNA with concomitant increases in FBPase protein and enzyme activity levels. After high-fat feeding, hemizygous transgenics were glucose intolerant compared with negative littermates (P < 0.02). Furthermore, when bred to homozygosity, chow-fed transgenic mice showed a 5.5-fold increase in liver FBPase levels and were glucose intolerant compared with negative littermates, with a significantly higher rate of EGP (P < 0.006). This is the first study to show that FBPase regulates EGP and whole body glucose homeostasis in a liver-specific transgenic model. Our homozygous transgenic model may be useful for testing human FBPase inhibitor compounds with the potential to treat patients with type 2 diabetes. 相似文献
23.
The consequences of uncertainties in land use, climate and vegetation responses on the terrestrial carbon 总被引:1,自引:0,他引:1
The IPCC SRES narratives were implemented in IMAGE 2.2 to evaluate thefuture condition of the climate system (including the biosphere). A series of scenario experiments was used to assess possible ranges in emissions and concentrations of greenhouse gases, climate change and impacts. These experiments focussed on the role of the terrestrial carbon cycle. The experiments show that the SRES narratives dominate human emissions and not natural processes. In contrary, atmospheric CO2 concentration strongly differs between the experiments. Atmospheric CO2 concentrations range for A1B from 714 to 1009 ppmv CO2 in 2100. The spread of this range is comparable with the full SRES range as implemented in IMAGE 2.2 (515-895 μmol/mol CO2). The most important negative and positive feedback processes in IMAGE 2.2 on the build-up of CO2 concentrations are CO2 fertilisation and soil respiration respectively. Indirect effects of these processes furtherchange land-use patterns, deforestation rates and alter the natural C fluxes. The cumulative effects of these changes have a pronounced influence on the final CO2 concentrations. Our scenario experiments highlight the importance of a proper parameterisation of feedback processes, C-cycle and land use in determining the future states of the climate system. 相似文献
24.
S. M. Redpath B. E. Arroyo B. Etheridge F. Leckie K. Bouwman S. J. Thirgood 《Ecography》2002,25(5):533-540
Climate is an important factor limiting demography and distribution patterns in many organisms. For species with a broad geographical distribution, the mechanism by which climate influences demography is likely to vary dramatically from one end of the range to the other. In this paper we first assess, in a Scottish population of hen harriers Circus cyaneus , how temperature and rainfall influence adult behaviour and chick mortality patterns at the nest. We then test for associations between harrier productivity and weather across Scotland, towards the northern edge of the range, and Spain, towards the southern edge of the range. We show that during the nestling period, female brooding time increased in cold weather. Male provisioning rate was negatively related to temperature and rainfall. Chick mortality increased in cold temperatures and was most likely to occur at nests where male prey delivery rates were low relative to temperature. Annual values of harrier fledged brood size across Scotland were positively related to summer temperature suggesting that the patterns seen in one population held at a national scale. In Spain, however, the opposite patterns were observed with fledged brood size being negatively related to temperature. This shows that whilst the impact of weather on productivity may be equally strong at two ends of a geographical range, the mechanisms vary dramatically. Large-scale predictive models need to take such patterns into account. 相似文献
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Erika van Wyk Henk Bouwman Herman van der Bank Gerhard H Verdoorn Dieter Hofmann 《Comparative biochemistry and physiology. Toxicology & pharmacology : CBP》2001,129(3):243-264
Gaschromatography was used to establish the presence of quantifiable residues of 14 persistent chlorinated hydrocarbon pollutants in whole blood, clotted blood, heart, kidney, liver and muscle samples obtained from individual African whitebacked (Pseudogyps africanus), Cape griffon (Gyps coprotheres) and Lappetfaced (Torgos tracheliotos) vultures from different localities in South Africa. The levels of pesticides measured in whole blood samples of live specimens were compared between nestlings from two natural breeding colonies, adults from a wildlife area and birds held in captivity. Statistically significant (P<0.05) differences between populations were detected in geometric means calculated for γ-BHC (lindane), α(cis)-chlordane and α-endosulfan. Five of the organochlorine contaminants displayed significant variations between concentrations detected in the clotted blood, organs and muscles excised from vulture carcasses. This includes residues of γ-BHC, α-chlordane, dieldrin, β-endosulfan and heptachlor epoxide. Values of the respective biocides measured in vulture samples were generally low in comparison to results documented for a number of avian species. Although no threat is posed by any of the organochloride pesticides, continual monitoring of especially breeding colonies is recommended. Furthermore, the suitability of African whitebacked vulture nestlings as basic bioindicators is highly advocated. 相似文献
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