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- Aldskogius, Håkan
(författare)
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Mechanisms and consequences of microglial responses to peripheral axotomy
- 2011
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Ingår i: Frontiers in Bioscience. - : IMR Press. - 1093-9946 .- 1093-4715 .- 1945-0516 .- 1945-0524. ; 3, s. 857-868
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Tidskriftsartikel (refereegranskat)abstract
- Microglia respond rapidly to injury of peripheral nerve axons (axotomy). This response is integrated into the responses of the injured neurons, i.e. processes for neuron survival, axon regeneration and restoration of target contact. The microglial response is also integrated in changes in presynaptic terminals on axotomized motor or autonomic neurons and in changes in the central terminals of peripherally axotomized sensory neurons. Microglia also has an established role in interacting with astrocytes to shape their response to peripheral axotomy. Axotomy models in mice have demonstrated a role for microglia in regulating the entry of lymphocytes into motor nuclei or sensory areas following peripheral axotomy. Whether this is a universal component of peripheral nerve injury remains to be determined. Under certain circumstances, microglia activated by axotomy are major contributors to CNS pathology, e.g. in models of neuropathic pain. However, the general roles played by microglia after peripheral nerve injury are still incompletely understood. Early proposals that the microglial reaction to peripheral nerve injury is preparatory for the eventuality of neuron degeneration may still have relevance.
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| 4. |
- Wennmalm, Stefan, 1970-, et al.
(författare)
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Inverse-fluorescence correlation spectroscopy: more information and less labeling
- 2011
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Ingår i: Frontiers in Bioscience. - : Frontiers in Bioscience. - 1093-9946 .- 1093-4715 .- 1945-0516 .- 1945-0524. ; s3, s. 385-392
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Tidskriftsartikel (refereegranskat)abstract
- Inverse-Fluorescence Correlation Spectroscopy(iFCS) is a recently developed modification of standardFCS that allows analysis of particles and biomoleculeswithout labeling. The particles generate no signal; insteadthe signal is generated by a surrounding medium. Particlesdiffusing through the FCS-detection volume displace afraction of the surrounding medium, causing transient dipsin the detected signal. These give information about themobility and concentration of the analyzed particles. Alsolabeled particles can be analyzed, whereby their signal iscross-correlated with that from the surrounding medium(iFCCS). This can give information about the volume of thelabeled particles, or alternatively about the size of thedetection volume. Also the interaction of unlabeledparticles with small, labeled ligands can be analyzed withiFCCS. This allows using cross-correlation as a sensitiveindication of binding, even though only one binding-partneris labeled. This review describes the principles of iFCS andiFCCS and measurements of microspheres dissolved in asurrounding medium containing alexa 488. We also discusspractical considerations, and future possibilities foranalyses of biomolecules.
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| 5. |
- Singh, Kalpana, et al.
(författare)
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A Role for TLRs in Moraxella-superantigen induced polyclonal B cell activation.
- 2012
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Ingår i: Frontiers in bioscience (Scholar edition). - 1945-0524. ; 4, s. 1031-1043
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Tidskriftsartikel (refereegranskat)abstract
- A number of microorganisms are capable of binding immunoglobulins (Igs) in a manner, which excludes binding to conventional antigen binding sites. Interaction of such bacterial proteins with surface immunoglobulins leads to polyclonal activation of B-lymphocytes. A recent example is Moraxella catarrhalis that binds to B lymphocytes in an IgD-dependent manner and induces proliferation and differentiation of B lymphocytes leading to the production of unspecific Igs. The activation is mediated by Moraxella IgD binding protein (MID), which specifically binds to both soluble IgD and the IgD B cell receptor (BCR). Besides cross-linking the BCR, whole Moraxella and outer membrane vesicles (OMVs) engage Toll like receptors (TLRs) to further increase the response. TLR activation leads to initiation of signaling pathways, which evoke a proinflammatory response against the invading microbes. Polyclonal B cell activation has in general been implicated in various phenomenons that are detrimental for the host but beneficial for pathogens, for example, autoimmune manifestations and redirection of the immune system.
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| 6. |
- Tjust, Anton E, et al.
(författare)
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Unaffected motor endplate occupancy in eye muscles of ALS G93A mouse model
- 2012
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Ingår i: Frontiers in bioscience (Scholar edition). - : Frontiers in Bioscience. - 1945-0524. ; 4, s. 1547-1555
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Tidskriftsartikel (refereegranskat)abstract
- Amyotrophic lateral sclerosis (ALS) is a progressive, lethal neurodegenerative disorder characterised by selective loss of motor neurons with accompanying muscle paralysis and respiratory failure. Despite progressive paralysis in trunk and extremity muscles, disturbed eye motility is not a hallmark of ALS. Extraocular muscles (EOMs) of terminal ALS patients show far less morphological signs of disease than their limb muscles. One of the earliest signs of the disease in the transgenic G93A SOD1 mouse model of ALS is loss of motor neuron contact at the neuromuscular junctions (NMJ) in limb muscles. We used immunohistochemistry to identify NMJs and evaluate innervation in EOMs and limb muscles of G93A mice. In G93A limb muscles, loss of axonal contact was seen in 6-82 percent of the NMJs. On the contrary, the degree of endplate occupancy in the EOMs did not differ between transgenic mice and wild-type controls. We propose that EOM-specific properties make these muscles more resistant to the underlying pathophysiological process of ALS and that the EOMs are a useful model to advance our understanding of ALS.
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| 7. |
- Zhou, Dapeng, et al.
(författare)
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Immunologic mapping of glycomes: implications for cancer diagnosis and therapy.
- 2011
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Ingår i: Frontiers in bioscience (Scholar edition). - 1945-0524. ; 3, s. 1520-32
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Tidskriftsartikel (refereegranskat)abstract
- Cancer associated glycoconjugates are important biomarkers, as exemplified by globo-H, CA125, CA15.3 and CA27.29. However, the exact chemical structures of many such biomarkers remain unknown because of technological limitations. In this article, we propose the "immunologic mapping" of cancer glycomes based on specific immune recognition of glycan structures, which can be hypothesized theoretically, produced chemically, and examined biologically by immuno-assays. Immunologic mapping of glycans not only provides a unique perspective on cancer glycomes, but also may lead to the invention of powerful reagents for diagnosis and therapy.
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| 8. |
- Filipsson, Helena, 1966, et al.
(författare)
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The impact of glucocorticoid replacement regimens on metabolic outcome and comorbidity in hypopituitary patients.
- 2006
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 91:10, s. 3954-61
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Hypopituitary patients with untreated GH deficiency and patients on inappropriately high doses of glucocorticoid (GC) share certain clinical features. OBJECTIVE: The aim of the study was to examine the influence of GC substitution on clinical characteristics in hypopituitary patients before and after GH replacement therapy. METHOD: A total of 2424 hypopituitary patients within the KIMS (Pfizer International Metabolic Database) were grouped according to ACTH status. Comparisons were performed between subjects on hydrocortisone (HC) (n = 1186), cortisone acetate (CA) (n = 487), and prednisolone/dexamethasone (n = 52), and ACTH-sufficient patients (AS) (n = 717) before and after 1 yr of GH treatment in terms of body mass index, waist and hip circumference, blood pressure, glucose, glycosylated hemoglobin (HbA1c), serum lipids, IGF-I, and comorbidity. Hydrocortisone equivalent (HCeq) doses were calculated, and measurements were adjusted for sex and age. RESULTS: At baseline, the HC group had increased total cholesterol, triglycerides, waist circumference, and HbA1c, and the prednisolone/dexamethasone group had increased waist/hip ratio as compared with AS. After HCeq dose adjustment, the HC group retained higher HbA1c than the CA group. GC-treated patients showed a dose-related increase in serum IGF-I, body mass index, triglycerides, low-density lipoprotein cholesterol and total cholesterol levels. Subjects with HCeq doses less than 20 mg/d (n = 328) at baseline did not differ from AS in metabolic endpoints. The 1-yr metabolic response to GH was similar in all GC groups and dose categories. All new cases of diabetes (n = 12), stroke (n = 8), and myocardial infarction (n = 3) during GH treatment occurred in GC-treated subjects. CONCLUSION: HCeq doses of at least 20 mg/d in adults with hypopituitarism are associated with an unfavorable metabolic profile. CA replacement may have metabolic advantages compared with other GCs.
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