Guillain-Barré syndrome (GBS) is an inflammatory disorder that may implicate proinflammatory cytokines such as TNF-α in its pathogenesis. We determined serum levels of TNF-α and the specific ...antagonists sTNF-Rs p55 and p75 in 24 patients with GBS at days 1, 15 and 30 of hospitalization. Patients were in the progression phase of the disease at day 1, and in the recovery phase at day 30. They were classified as able to walk (stage A), confined to bed (B), or under assisted ventilation (C). All patients underwent plasma exchange within day 1–12. At day 1, TNF-α levels were elevated in
15
24
patients, and sTNF-Rs were elevated in
21
23
. TNF-α levels had not decreased at day 15, and dropped at day 30 (
p < 0.04), whereas sTNF-R p55 remained elevated at day 15 and day 30. The TNF-α/sTNF-Rs ratio, estimating active TNF-α unbound to sTNF-Rs, decreased from day 1 to day 30 (
p < 0.05). A positive correlation was found between disease severity and sTNF-Rs serum levels (
p < 0.01). In conclusion, elevated circulating sTNF-Rs assesses activation of the TNF-α system in almost all patients with GBS and correlates positively with disease severity. Drop of TNF-α contrasting with sustained elevation of sTNF-R p55 during recovery suggests that sTNF-R p55 may be important in the fading of the neural inflammatory effect of TNF-α in GBS.
Climatic changes are altering Earth's hydrological cycle, resulting in altered precipitation amounts, increased interannual variability of precipitation, and more frequent extreme precipitation ...events. These trends will likely continue into the future, having substantial impacts on net primary productivity (NPP) and associated ecosystem services such as food production and carbon sequestration. Frequently, experimental manipulations of precipitation have linked altered precipitation regimes to changes in NPP. Yet, findings have been diverse and substantial uncertainty still surrounds generalities describing patterns of ecosystem sensitivity to altered precipitation. Additionally, we do not know whether previously observed correlations between NPP and precipitation remain accurate when precipitation changes become extreme. We synthesized results from 83 case studies of experimental precipitation manipulations in grasslands worldwide. We used meta‐analytical techniques to search for generalities and asymmetries of aboveground NPP (ANPP) and belowground NPP (BNPP) responses to both the direction and magnitude of precipitation change. Sensitivity (i.e., productivity response standardized by the amount of precipitation change) of BNPP was similar under precipitation additions and reductions, but ANPP was more sensitive to precipitation additions than reductions; this was especially evident in drier ecosystems. Additionally, overall relationships between the magnitude of productivity responses and the magnitude of precipitation change were saturating in form. The saturating form of this relationship was likely driven by ANPP responses to very extreme precipitation increases, although there were limited studies imposing extreme precipitation change, and there was considerable variation among experiments. This highlights the importance of incorporating gradients of manipulations, ranging from extreme drought to extreme precipitation increases into future climate change experiments. Additionally, policy and land management decisions related to global change scenarios should consider how ANPP and BNPP responses may differ, and that ecosystem responses to extreme events might not be predicted from relationships found under moderate environmental changes.
Future changes in precipitation will strongly impact ecosystem functioning and services through changes in plant growth. Here, we synthesize 83 precipitation experiments to look at responses of above and belowground plant growth (ANPP and BNPP) across climatic gradients and levels of precipitation change extremity. Overall, we found that (1) ANPP was more responsive to precipitation increases than decreases, and this was especially evident in dry ecosystems; (2) BNPP responses were similar under precipitation increases vs. decreases; (3) under extreme wet conditions, NPP responses leveled off, creating a saturating function of NPP response vs. the magnitude of precipitation change. Based on these findings, we suggest that future research focus on BNPP and plant responses to extreme precipitation change.
The muscle changes related to pelvic floor disorders are poorly understood. We conducted an anatomical and histological study of the perineum of the normal mouse and of a transgenic mouse strain ...deficient in urokinase‐type plasminogen activator (uPA−/−) that was previously reported to develop a high incidence of rectal prolapse. We could clearly identify the iliococcygeus (ILC) and pubococcygeus (PC) muscles and anal (SPA) and urethral (SPU) sphincters in male and female mice. The bulbocavernosus (BC), ischiocavernosus (ISC) and levator ani (LA) muscles could be found only in male mice. Histochemical analysis of the pelvic floor muscles revealed a majority of type IIA fibres. Rectal prolapses were observed only in male uPA−/− mice. The most obvious finding was an irreducible evagination of the rectal mucosa and a swelling of the entire perineal region corresponding to an irreducible hernia of the seminal vesicles through the pelvic outlet. The hernia caused stretching and thinning of the ISC, BC and LA. Myopathic damage, with degenerated and centronucleated myofibres, were observed in these muscles. The PC, ILC, SPA and SPU were not affected. This study provides an original description of a model of pelvic floor disorder and illustrates the differences existing between the perineum of humans and that of a quadruped species. In spite of these differences, the histopathologic changes observed in the pelvic floor muscles of uPA−/− mice with rectal prolapse suggest that prolonged muscular stretching causes a primary myopathic injury. This should be taken into account in the evaluation of pelvic floor disorders.
Soil stores approximately twice as much carbon as the atmosphere and fluctuations in the size of the soil carbon pool directly influence climate conditions. We used the Nutrient Network global change ...experiment to examine how anthropogenic nutrient enrichment might influence grassland soil carbon storage at a global scale. In isolation, enrichment of nitrogen and phosphorous had minimal impacts on soil carbon storage. However, when these nutrients were added in combination with potassium and micronutrients, soil carbon stocks changed considerably, with an average increase of 0.04 KgCm−2 year−1 (standard deviation 0.18 KgCm−2 year−1). These effects did not correlate with changes in primary productivity, suggesting that soil carbon decomposition may have been restricted. Although nutrient enrichment caused soil carbon gains most dry, sandy regions, considerable absolute losses of soil carbon may occur in high‐latitude regions that store the majority of the world's soil carbon. These mechanistic insights into the sensitivity of grassland carbon stocks to nutrient enrichment can facilitate biochemical modelling efforts to project carbon cycling under future climate scenarios.
C. Christov, H. Adle‐Biassette, C. Le Guerinel, S. Natchev and R. K. Gherardi (1998) Neuropathology and Applied Neurobiology24, 29–35
Immunohistochemical detection of vascular endothelial growth ...factor (VEGF) in the vasculature of oligodendrogliomas
Vascular endothelial growth factor (VEGF) appears to be implicated in tumour angiogenesis. In the present study immunohistochemical expression of VEGF was evaluated in 34 oligodendrogliomas (13 grade II, 21 grade III WHO). VEGF immunoreactivity was found in 31 of 34 cases. Expression of VEGF was observed in endothelial cells and some vascular smooth muscle cells, but not in neoplastic oligodendrocytes. Vessel counts, percentages of VEGF‐positive vessels and vessels with vascular endothelial proliferation were assessed. The degree of VEGF labelling and vascular‐endothelial proliferation in each vessel were evaluated using a 3 degree intensity score. Expression of VEGF was higher in grade III than in grade II oligodendrogliomas as assessed by percentage of VEGF positive vessels (55.8 ± 29.2% vs 17.0 ± 19.0% P < 0.001) and by VEGF immunostaining intensity (1.90 ± 0.60 vs 0.90 ± 0.40 P < 0.001). VEGF expression did not correlate with vessel density. Intensity of VEGF expression correlated positively with that of vascular‐endothelial proliferation in grade III tumours (r=+0.47 P < 0.05). The percentage of VEGF positive vessels showed some degree of positive correlation with the percentage of vessels showing vascular‐endothelial proliferation (r=+408 P < 0.10). Within individual grade III tumours 67.5 ± 29.6% of all vessels with vascular‐endothelial proliferation were VEGF‐positive and 31.0 ± 20.5% of all VEGF‐positive vessels showed no evidence of vascular‐endothelial proliferation. We conclude that (i) expression of VEGF is observed in the vasculature of oligodendrogliomas; (ii) marked expression of VEGF is observed in grade III oligodendrogliomas; (iii) VEGF may be one of the interrelated causative stimuli acting in concert to induce vascular‐endothelial proliferation.
To investigate the therapeutic potential of bone marrow transplantation in Duchenne muscular dystrophy, green fluorescent protein-positive (GFP
+) bone marrow cells were transplanted into irradiated ...wild-type and dystrophin-deficient
mdx
mice. Tibialis anterior muscles showed fivefold to sixfold more GFP
+ mononucleated cells and threefold to fourfold more GFP
+ myofibers in
mdx
than in wild-type mice. In contrast, dystrophin expression in
mdx
mice remained within the level of nontransplanted
mdx
mice, and co-expression with GFP was rare. Longitudinal sections of 5000 myofibers showed 160 GFP
+ fibers, including 9 that co-expressed dystrophin. GFP was always visualized as full-length sarcoplasmic fluorescence that exceeded the span of sample length (up to 1500 μm), whereas dystrophin expression was restricted to 11 to 28% of this length. Dystrophin expression span was much shorter in GFP
+ fibers (116 ± 46 μm) than in revertant fibers (654 ± 409 μm). These data suggest that soluble GFP diffuses far from the fusion site with a pre-existing dystrophin
− myofiber whereas dystrophin remains mainly expressed close to the site of fusion. Because restoration of dystrophin in whole muscle fiber length is required to expect functional improvement and clinical benefits for Duchenne muscular dystrophy, future applications of cell therapies to neuromuscular disorders could be more appropriately envisaged for replacement of defective soluble sarcoplasmic proteins.
To evaluate the possible role of cytokines in human immunodeficiency virus (HIV)-associated muscular disorders, we performed immunocytochemistry for interleukin-1 alpha, -1 beta, and -6 and tumor ...necrosis factor-alpha on frozen muscle biopsy specimens from HIV-infected patients with various myopathies (HIV polymyositis in 5, HIV-wasting syndrome in 5, zidovudine myopathy in 10) and from seronegative individuals (normal muscle in 2, mitochondrial cytopathies in 10). The HIV-infected patients showed positive reactivities in vessels (interleukin-1) and in inflammatory cells (mainly interleukin-1 and tumor necrosis factor-alpha), including perivascular hemosiderin-laden macrophages in 5 patients. In zidovudine myopathy, a majority of AZT fibers (i.e., ragged-red fibers with marked myofibrillar changes) showed mild to marked expression of interleukin-1. Expression of interleukin-1 in the other mitochondrial myopathies was much weaker. Interleukin-1 beta messenger RNA was demonstrated in muscle fibers by in situ hybridization, implying that interleukin-1 was produced in muscle cells. Immunoelectron microscopy showed that interleukin-1 alpha was mainly bound to mitochondrial membranes in AZT fibers. Proinflammatory and destructive effects of the studied cytokines might be responsible for several myopathological changes observed in HIV-infected patients, including inflammation and hemosiderin deposits in muscle tissue, and prominent myofibrillar breakdown in AZT fibers.
Cytokines and peripheral nerve disorders Créange, A; Barlovatz-Meimon, G; Gherardi, R K
European cytokine network (Montrouge),
06/1997, Letnik:
8, Številka:
2
Journal Article
Recenzirano
Peripheral nerve production of cytokines originates from resident and recruited macrophages, lymphocytes, mastocytes, Schwann cells, and probably neurons. Cytokines are involved in nerve lesions and ...repair. Tumor necrosis factor-alpha (TNF-alpha) injected into nerve induces Wallerian degeneration, whereas, interleukin-1 (IL-1) production promotes detersion by scavenger macrophages, and synthesis of neurotrophic factors (nerve growth factor-NGF- and leukemia inhibitory factor-LIF). After experimental axotomy, other neurotrophic factors, including IL-6, LIF and transforming growth factor-beta 1 (TGF-beta 1), are overexpressed in nerve and promote axonal growth until axon/Schwann cell contact. Proinflammatory cytokines are instrumental in the course of inflammatory demyelinating neuropathies. They increase vascular permeability and blood nerve barrier breakdown (TNF-alpha, vascular endothelial growth factor/ vascular permeability factor-VEGF/VPF), favor transmigration of leukocytes into nerve, induce activation and proliferation of lymphocytes (IL-1, IL-2) and macrophages (gamma-interferon-IFN-gamma), and have a direct myelinotoxic activity (TNF-alpha and TNF-beta). In addition, downregulation of the immunosuppressive cytokine TGF-beta 1 may favor the nerve inflammatory reactions.
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