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  • 1
    Electronic Resource
    Electronic Resource
    Islet amyloid polypeptide: demonstration of mRNA in human pancreatic islets by in situ hybridization in islets with and without amyloid deposits (1993)
    Springer
    Diabetologia 36 (1993), S. 323-328 
    Details
    ISSN: 1432-0428
    Keywords: Islet amyloid polypeptide ; deposits ; fibrils ; in situ hybridization ; expression ; immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Islet amyloid polypeptide which is normally coexpressed with insulin in beta cells, forms amyloid deposits especially in islets of Type 2 (non-insulin-dependent) diabetic subjects. Occurrence of islet amyloid is paradoxically associated with loss of islet amyloid polypeptide immunoreactivity in beta cells. The present study was undertaken to examine whether the islet amyloid polypeptide gene is expressed in islets with decreased islet amyloid polypeptide immunoreactivity. Pancreatic tissue from 14 patients, 7 with Type 2 diabetes and 7 non-diabetic, were obtained at autopsy or surgery and studied for islet amyloid polypeptide expression by in situ hybridization and for presence of insulin and islet amyloid polypeptide by immunohistochemistry. Six of the specimens from the diabetic and three of those from the non-diabetic patients had varying degrees of islet amyloid polypeptide-derived islet amyloid. Amyloid deposits were associated with decreased numbers of beta cells with islet amyloid polypeptide immunoreactivity despite an apparent normal frequency of insulin-containing cells. This discrepancy might reflect an alteration in islet amyloid polypeptide production or processing at a transcriptional or post-transcriptional level. In contrast to the varying immunohistochemical patterns, islets of all categories showed strong labelling using an islet amyloid polypeptide probe for in situ hybridization. It is concluded that islet amyloid polypeptide production is not altered at the transcriptional level. The following possibilities remain: (1) islet amyloid polypeptide production may be altered at a post-transcriptional level or (2) that islet amyloid polypeptide production is normal but the reduced immunoreactivity of the cells reflects a reduced storage of IAPP in secretory granules. We favour the second possibility since islet amyloid deposition is incompatible with reduced islet amyloid polypeptide synthesis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400235
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  • 2
    Electronic Resource
    Electronic Resource
    Immunohistochemical measurements of nerves and neuropeptides in diabetic skin: relationship to tests of neurological function (1992)
    Springer
    Diabetologia 35 (1992), S. 889-897 
    Details
    ISSN: 1432-0428
    Keywords: Diabetic neuropathy ; small-fibre studies ; neuropeptides ; immunohistochemistry ; neurophysiology ; sudomotor function
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Image-analysis was used to measure nerves immunoreactive to the general neuronal marker protein gene product 9.5 (PGP 9.5-IR) and the neuropeptides calcitonin gene-related peptide and vasoactive intestinal polypeptide in standardised leg skin biopsies of three age-matched groups of young subjects: non-diabetic (n=14), diabetic patients with normal small fibre function (“non-neuropathic”, (n=11) and diabetic patients with abnormal small fibre function (“neuropathic”, n=11). Depletion of nerves and neuropeptides was most marked in the epidermis, where calcitonin gene-related peptide-immunoreactivity was more frequently absent than PGP 9.5-IR in diabetic patients. Epidermal PGP 9.5-IR nerve area and counts were reduced in neuropathic compared with normal subjects (p〈0.001), as were epidermal calcitonin gene-related peptide nerve counts (p=0.003). Sweat gland PGP 9.5 and vasoactive intestinal polypeptide, which may be involved in sweat production, showed no diminution in diabetic patients (area: p=0.160, p=0.372 by ANOVA). Two diabetic patients showed elevated sweat gland PGP 9.5-IR and three had increased sweat gland vasoactive intestinal polypeptide; this may represent nerve proliferation. In local sweat tests, acetylcholine-stimulated sweat output was associated with increased immunoreactivity, while the sympathetic skin response showed inverse correlations with immunoreactivity. There were no consistent changes with other commonly-used neurophysiological tests. HbA1 correlated negatively with immunohistochemical measurements. Neuropeptide changes were seen in the absence of macro- and microvascular disease, and epidermal nerve depletion occurred in patients with normal thermal thresholds and cardiac autonomic function. Immunohistochemical measurement of cutaneous nerves in skin biopsies is a practical method for assessing peripheral small fibres in diabetes, and one which could be repeated in longitudinal studies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00399938
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  • 3
    Electronic Resource
    Electronic Resource
    Elevated levels of vasoactive intestinal peptide in the eye and urinary bladder of diabetic and prediabetic Chinese hamsters (1985)
    Springer
    Diabetologia 28 (1985), S. 302-307 
    Details
    ISSN: 1432-0428
    Keywords: VIP ; radioimmunoassay ; immunocytochemistry ; eyes ; urinary bladder ; prediabetes ; diabetic Chinese hamsters
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The eyes and urinary bladder of non-diabetic, prediabetic and diabetic Chinese hamsters were evaluated by radioimmunoassay and immunocytochemistry to determine the content and distribution of vasoactive intestinal peptide (VIP). The average concentration of VIP was increased in the eyes of all diabetic (pmol/g = 68%, pmol/organ = 50%) and prediabetic (pmol/g = 152%, pmol/organ = 115%) hamsters compared with age-matched non-diabetic animals. Immunocytochemistry showed that the elevation of VIP was primarily related to greater intensity of fluorescence of the nerve fibres in the vasculature of the choroid. The average content of VIP in the urinary bladder was greater in diabetic animals only on the basis of pmol/organ (135%) and in prediabetics on the basis of pmol/g (87%) compared with non-diabetic animals. Qualitative immunocytochemistry suggested that the elevated level of VIP was related to a larger distribution of nerve fibres in the urinary bladder of diabetic hamsters. The high level of VIP in the eyes and urinary bladder of diabetic and prediabetic hamsters is an interesting observation which should receive further study to determine whether it is an aetiological agent underlying the pathogenesis of ophthalmic complications and neurogenic bladder or the result of some pathological process which affects these organs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00271690
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  • 4
    Electronic Resource
    Electronic Resource
    Differential effects of NT-3 on reinnervation of the fast extensor digitorum longus (EDL) and the slow soleus muscle of rat (2000)
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 12 (2000), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Previous studies of gastrocnemius muscle reinnervation showed specific normalization of the proportion and diameter of fast type 2b muscle fibres following NT-3 delivery to the proximal stump of the cut sciatic nerve. Here, we investigate if normalization was related to greater improvement of muscle reinnervation of fast (extensor digitorum longus; EDL) than slow (soleus) motor units. NT-3-impregnated (NT-3 group) or plain fibronectin (FN group) mats were inserted into a sciatic nerve gap. Neuromuscular junctions (NMJs) labelled with TRITC-α-bungarotoxin were colabelled with calcitonin gene-related peptide (CGRP) or 4E2 antisera and imaged using confocal microscopy. CGRP and 4E2 were used as markers for newly reinnervated and structurally mature NMJs, respectively. At 40 days postsurgery, denervated NMJs in EDL and soleus muscles of both groups presented a 50% decrease of surface area due to decreased width. At day 80 in EDL, more NMJs were reinnervated by CGRP-immunoreactive terminals in the NT-3 (7.1%) than in the FN group (4.2%); there was no difference between groups for soleus. At 120 days, 4E2-immunoreactive NMJs were more numerous in EDL of the NT-3 (40.0%) than in the FN group (7.3%), unlike in soleus (NT-3, 1.6%; FN, 1.8%), and presented a partial size recovery. These results indicate that NT-3 preferentially improves reinnervation of fast muscles over slow muscle, although the mechanism of this improvement is still unclear.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1460-9568.2000.00975.x
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  • 5
    Electronic Resource
    Electronic Resource
    Neurotrophin-3 Delivered Locally via Fibronectin Mats Enhances Peripheral Nerve Regeneration (1997)
    Oxford, UK : Blackwell Publishing Ltd
    European journal of neuroscience 9 (1997), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: A better understanding of the mechanisms of nerve regeneration could improve the outcome of surgical nerve repair. We have previously shown that axonal regeneration is increased by nerve growth factor. Neurotrophin-3 (NT-3) belongs to the same family as nerve growth factor but acts on a distinct neuron subpopulation. As little is known about its role following nerve injury, we have investigated the effect of NT-3 delivered via fibronectin mats, previously shown to support nerve regeneration comparable to nerve grafts. NT-3 stimulation (0.1–1000 ng/ml) of neurite extension from embryonic chick dorsal root ganglia in vitro has shown that fibronectin can bind and release bioactive NT-3. Fibronectin mats impregnated with NT-3 (500 ng/ml) were grafted into 1 cm sciatic nerve defects in adult Lewis rats. Plain mats were used as controls. Computerized quantification of penetration distance, volume of axonal regeneration and myelinated fibre counts was undertaken using immunostaining for axonal markers (growth-associated protein 43, calcitonin gene-related peptide, substance P, vasoactive intestinal peptide and neuropeptide tyrosine), or S100 orthionine blue staining up to 8 months postoperatively. The maximal effect of NT-3 occurred at day 15, when for GAP43-immunostained axons both penetration distance (NT-3, 6.10 ± 0.42 mm; control, 4.11 ± 0.41 mm; P 〈0.01) and staining area (NT-3, 0.137 ± 0.012 mm2; control, 0.077 ± 0.018 mm2; P 〈 0.05) were significantly increased. Similar results were found for each neuronal subpopulation investigated. By 8 months after repair, the NT-3 group supported a significantly greater number of myelinated axons (NT-3, 7003 ± 402; control, 4932 ± 725; P 〈 0.05) of similar diameter and g-ratio to controls. These results demonstrate the contribution of NT-3 to the increase of nerve regeneration promoted by growth factors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1460-9568.1997.tb01493.x
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  • 6
    Electronic Resource
    Electronic Resource
    Bndothelin-l expression is not altered in necrobiosis lipoidica and granuloma annulare (1994)
    Oxford, UK : Blackwell Publishing Ltd
    British journal of dermatology 130 (1994), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2133.1994.tb03426.x
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  • 7
    Electronic Resource
    Electronic Resource
    Regeneration pattern of blood vessels and nerves in cultured keratinocyte grafts assessed by confocal laser scanning microscopy (1995)
    Oxford, UK : Blackwell Publishing Ltd
    British journal of dermatology 132 (1995), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The aim of this study was to investigate the pattern of both neovascularization and reinnervation, and the relationship between the two processes, in keratodermal grafts, using confocal laser scanning microscopy, at different time points during the healing process. Keratodermal grafts were prepared in pigs by combining autologous dermis with cultured autologous keratinocytes. Immunohistochemistry was carried out on thick cryostat sections (100-150 μm), using antisera to the endothelial marker von Willebrand factor (vWf) and the pan-neuronal marker protein gene product 9–5 (PGP9-5). The results suggest that the neovascularization and reinnervation in the cultured keratodermal graft is almost complete at 6 weeks. Neovascularization precedes innervation, reaching the surface covered by the keratinocytes at 2 weeks, initially with a linear vascular pattern. From 3 weeks, there is a gradual arborization of the vessels to form a typical vascular plexus. The process of reinnervation is similar in pattern to that of neovascularization, although slower in developing a full network of fibres. In conclusion, the use of confocal microscopy allows the precise definition of complex patterns of neovascularization and nerve growth, which are not fully apparent when using conventional microscopy. Because angiogenesis occurs first, it probably plays a leading role in the survival of keratodermal grafts during wound healing. Indeed, new blood vessels form a pathway for the subsequent innervation process, and quickly reach the epidermal layer which, in turn, may play a key role in the tropism of both blood vessels and nerves.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2133.1995.tb08670.x
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  • 8
    Electronic Resource
    Electronic Resource
    Increased sensory neuropeptides in nodular prurigo: a quantitative immunohistochemical analysis (1992)
    Oxford, UK : Blackwell Publishing Ltd
    British journal of dermatology 127 (1992), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary Seven patients with nodular prurigo, five patients with lichenified eczema and seven control volunteers were studied immunohistochemically using antisera to the pan-neuronal marker protein gene product 9.5 (PGP), and the neuropeptides calcitonin gene-related peptide (CGRP), substance P (SP), tyrosine hydroxylase (TH), vasoactive intestinal polypeptide (VIP) and the C-flanking region of neuropeptide Y (C-PON), PGP-, CGRP- and SP-immunoreactivities were also evaluated using image analysis quantification, and the data compared by statistical analysis. No significant changes were noted in the lichenified skin of patients with chronic eczema, compared with the control groups. In contrast, a significant increase in PGP immunoreactive nerve fibres was seen in lesional skin of all nodular prurigo cases studied, when compared with non-lesional skin from the same patient or from control subjects (P〈0.001). In one case massive neural hyperplasia was also identified. Staining for CGRP and SP showed a large increase of immunoreactive nerves in lesional skin of nodular prurigo patients, which closely paralleled that of PGP. Staining with VIP, C-PON and TH was similar in both lesional and non-lesional skin. These results indicate that neural changes in nodular prurigo are associated with an increase of sensory neuropeptides, which could be related to the intense pruritus which accompanies nodular prurigo. The absence of significant changes in lichenified skin suggests that the increase in CGRP- and SP-immunoreactive nerve fibres is a characteristic feature of nodular prurigo and may be important in its pathogenesis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2133.1992.tb00452.x
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  • 9
    Electronic Resource
    Electronic Resource
    Expression of the SmN Splicing Protein Is Developmentally Regulated in the Rodent Brain but Not in the Rodent Heart
    Amsterdam : Elsevier
    Developmental Biology 156 (1993), S. 319-323 
    Details
    ISSN: 0012-1606
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1006/dbio.1993.1080
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  • 10
    Electronic Resource
    Electronic Resource
    Depleted cutaneous innervation in familial amyloid (1996)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental dermatology 21 (1996), S. 0 
    Details
    ISSN: 1365-2230
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: A patient with familial amyloid polyneuropathy is reported who presented with peripheral neuropathy, pruritus and xerosis, and in whom immunohistochemistry showed reduced neurotransmitters around sweat and sebaceous glands.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2230.1996.tb00154.x
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