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  • 1
    ISSN: 1432-0428
    Keywords: Keywords NOD mice ; class II MHC ; I-Ag7 ; T cells ; peptide therapy ; tolerance ; GAD-65.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. Major histocompatibility complex class II molecules present antigenic peptides to T-cells and have an important role in T-cell thymic education. The mechanism by which major histocompatibility complex alleles confer a high genetic risk for autoimmune diabetes is not known. One hypothesis is that during positive thymic selection, the peripheral T-cell repertoire is modelled by major histocompatibility complex-restricted presentation of self major histocompatibility complex molecule-derived peptides, some of which mimic tissue autoantigens. The sequence similarity between a known T-cell epitope of glutamic acid decarboxylase-65, 509:VPPSLRTLED and the non-obese diabetic mouse class II major histocompatibility complex molecule I-Ag7 86:VPTSLRRLEQ is consistent with this. Methods. We measured spontaneous proliferation of peripheral T-cells from non-obese diabetic mice and other, non-diabetes-prone strains, to the I-Ag7 86–101 and glutamic acid decarboxylase-65509–524 peptides, binding of these peptides to intact I-Ag7 and assessed the effect of tolerance induction on diabetes development, by injecting young non-obese diabetic mice with high doses of peptide. Results. T-cells from non-obese diabetic, but not other mice strains, spontaneously proliferate to the I-Ag7 86–101 and glutamic acid decarboxylase-65509–524 peptides, but not control peptides. Both test peptides bind I-Ag7. Tolerance induction prolongs diabetes-free survival in non-obese diabetic mice when either the I-Ag7 86–101 or glutamic acid decarboxylase-65509–524 peptide, but not control peptide, is used. Conclusion/interpretation. A peptide from the unique class II major histocompatibility complex, diabetes-susceptibility molecule, I-Ag7, presented by I-Ag7 is a target of T-cell responses in diabetes-prone non- obese diabetic mice and tolerance induction against the peptide offers appreciable protection against the development of diabetes. [Diabetologia (1999) 42: 560–565]
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1106
    Keywords: Key words Central pain ; Endogenous opioids ; Naloxone ; Neuropathic pain ; Spinal cord ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We have previously reported that ischemic spinal cord injury in rats leads to chronic pain-related behaviors. Thus, rats exhibited aversive reactions to innocuous mechanical stimuli (mechanical allodynia) applied to a body area at or rostral to the dermatomes innervated by the injured spinal segments. The responses of the rats to cold are also markedly enhanced (cold allodynia). Interestingly, more than 50% of spinally injured rats did not develop these abnormal pain-related behaviors after spinal cord injury. In the present study, we showed that the extent of injury is similar between allodynic and nonallodynic rats. Furthermore, intrathecal (i.t.) naloxone, a broad-spectrum opioid receptor antagonist, reversibly provoked mechanical and cold allodynia-like responses in spinally injured rats that did not develop such behaviors spontaneously. However, naloxone did not elicit such reactions in normal rats and did not alter the tail-flick latency in normal or spinally injured rats. Furthermore, i.t. d-Phe-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) or naltridole, selective antagonists of μ and δ opioid receptors, respectively, also triggered pain-related behaviors similarly to naloxone. Although norbinaltorphimine (nor-BIN), a selective κ-receptor antagonist, also elicited such responses, the time course of the effect makes it unlikely that spinal κ-receptors were involved. These results suggested that the expression of abnormal pain-related behaviors in some spinally injured rats is tonically suppressed by the spinal opioidergic system. Interindividual differences that lead to lack or dysfunction of such inhibition may underly the appearence of pain-related behavior in some, but not all, spinally injured rats. It is suggested that such inhibition is exerted through spinal μ and δ, but not κ, opioid receptors. The endogenous opioidergic control appears to be only active against abnormal pain-related behaviors in spinally injured rats. Our results are relevant for the clinical observation that only a subgroup of patients with nerve injury suffers from neuropathic pain.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The interaction of intrathecally (i.t.) applied galanin (GAL) with substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), somatostatin (SOM) and C-fibre conditioning stimulation (CS) with regard to their effects on the spinal nociceptive flexor reflex was studied in decerebrate, spinalized, unanaesthetized rats with intact or sectioned sciatic nerves. SP, CGRP, VIP and SOM applied onto the surface of lumbar spinal cord or a brief CS train (1 Hz, 20 s) to the sural nerve facilitated the flexor reflex for several minutes in animals with intact or sectioned nerves. Pretreatment with GAL, which by itself had a biphasic effect on the flexor reflex in a dose-dependent manner, antagonized the reflex facilitation induced by sural CS before and after sciatic nerve section. SP-induced facilitation of the flexor reflex was antagonized by GAL in rats with intact sciatic nerves, but not after nerve section. In contrast, VIP-induced reflex facilitation was antagonized by GAL only after sectioning of the sciatic nerve. GAL was effective in antagonizing the facilitatory effect of CGRP under both situations, but had no effect on SOM-induced facilitation. A parallel immunohistochemical study revealed that after sciatic nerve section GAL-like immunoreactivity (LI) and VIP-LI are increased in the dorsal root ganglia and that these two peptides coexist in many cells. The present results indicate that GAL antagonizes the excitatory effect of some neuropeptides which exist in the spinal cord. This antagonism could explain the inhibitory effect of GAL on C-fibre CS-induced facilitation of the flexor reflex, which is presumably due to the release of some of these neuropeptides from the terminals of primary afferents. Furthermore, the interaction between GAL and other neuropeptides is altered by sciatic nerve section, paralleling changes in the levels of these neuropeptides in primary afferents and their pattern of coexistence after nerve section. It is proposed that SP and CGRP are important mediators of the spinal flexor reflex in intact rats. However, after axotomy VIP may replace SP in this capacity, paralleling the decrease in SP and marked increase in VIP levels. In general the study provides further support for involvement of peptides in sensory function.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford BSL : Blackwell Science Ltd
    Clinical & experimental allergy 28 (1998), S. 0 
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Aberrant expression of CD23 (low affinity IgE receptor) on cells of the monocyte/macrophage series in peripheral blood and lesional skin of patients with atopic eczema has been demonstrated. It is not known whether this abnormality results from a fundamental systemic problem of the monocytes of these patients or reflects local changes to cell populations within the skin tissues.〈section xml:id="abs1-2"〉〈title type="main"〉ObjectivesThis study was designed to determine whether this aberrant expression was caused by local cutaneous influences on mature cells or fundamental changes in monocyte differentiation. The possible relationship between these aberrations and clinical severity was also investigated by repeating these immunopathological studies after a course of efficacious treatment with Chinese herbal therapy (CHT).〈section xml:id="abs1-3"〉〈title type="main"〉MethodsPeripheral blood mononuclear cells were obtained from patients with atopic eczema before, and after 8 weeks of treatment. Efficacy of CHT was quantified on clinical grounds. Monocytes were isolated by adherence to plastic and cultured for up to 7 days. Samples were harvested at 2, 5 and 7 days of culture and cytospins prepared. Immunocytochemical staining to identify phenotypic subsets was performed on the monocytes at time 0 and on maturing cells from culture. This immunocytology was quantified using computerized image analysis equipment to determine the emergence of macrophage subsets and their level of CD23 expression. Biopsies were taken from lesional skin before and after treatment and immunohistology was performed on cryostat sections to determine the number of antigen presenting cells expressing CD23 as well as the level of expression of these molecules.〈section xml:id="abs1-4"〉〈title type="main"〉ResultsThe results showed that increased numbers of monocytes from patients with atopic eczema express CD23 at day 0 and that cultured monocytes from these patients differentiate faster during the 7 day culture period as compared to normal controls. Efficacious treatment did not affect the number of peripheral blood monocytes expressing CD23. However, treatment did lead to a significant decrease in the number of CD23+ mature macrophages in the skin as well as a reduction in the level of expression of this moiety. These results demonstrate that changes in clinical severity are more closely related to the expression of CD23 on mature antigen presenting cells in lesional skin rather than to differentiating peripheral blood monocyte CD23 expression.〈section xml:id="abs1-5"〉〈title type="main"〉ConclusionsThese results suggests that local factors within lesional skin govern the accumulation and the expression of CD23 on mature macrophages and that these factors may be more relevant to the pathogenesis of the disease than aberrations in CD23 expression that may occur systemically.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    British journal of dermatology 136 (1997), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Ten patients with atopic eczema (AE) received treatment with Chinese herbal therapy (CHT; Zemaphyte) for 2 months. The severity ot the eczema was recorded and skin biopsies were taken from lesional (L) and non-lesional (NL) skin before and after treatment. The skin biopsies were stained to detect T-cell subsets (CD4, CDH, CD45Ro and CD25), macrophage subsets (RFD7), dendritic cells (RFD1). Langerhans cells (CD1), HLA-DR, low-affinity IgE receptors (CD23) and high-affinity IgE receptors (15A5, 22E7). A quantitative assessment of the numbers of positively stained cells was made. Monoclonal antibody binding specifically to CD23(FcɛRII) was used, in combination with cell subset monoclonal antibodies to quantify the cellular distribution of CD23 antigen in the skin. Following 2 months of treatment with CHT, erythema was reduced by 53%. There was also a significant reduction in HLA-DR expression. The numbers of RFD1+CD23+, RFD7+CD23+, CD1+CD23+ and CD25+ cells in lesional skin decreased significantly after treatment (RFD1+CD23+ from 0.39 to 0·21, RFD7+CD23+ from 0.29 to 0·16· CD1+CD23 + from 0·24 to 0·09, CD25+ from 0·84 to 0·31 in epidermis and from 1·62 to 0·94 in dermis (mean cells numbers per unit area). No significant change in cell numbers in NL skin or expression of FcERI in either L or NL samples was observed after treatment. This study confirms that CHT is clinically efficacious and that clinical improvement is associated with a significant reduction in antigenpresenting cells expressing CD23.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 0022-328X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 0167-0115
    Keywords: Neuropeptide ; Nociception ; Primary afferent ; Spinal cord ; Substance P antagonist
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 0167-0115
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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