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Protein Gene Product (protein + gene_product)
Selected AbstractsExpression of PGP 9.5 in granular cell nerve sheath tumors: an immunohistochemical study of six casesJOURNAL OF CUTANEOUS PATHOLOGY, Issue 6 2001Meera Mahalingam Background: Protein gene product 9.5 (PGP 9.5) is expressed in brain at 20 to 50 times the levels detected in other organs. Immunohistochemical studies reveal this protein is localized to both central and peripheral neurons. Recently, PGP 9.5 is reported to be a useful marker for cellular neurothekeomas. Herein we test whether PGP 9.5 is a new marker for granular cell nerve sheath tumors. Material and Methods: An immunohistochemical analysis for PGP 9.5 expression was carried out on all cases with the diagnosis of granular cell nerve sheath tumor seen over a 2-year period. In addition, we compared expression of PGP 9.5 with other accepted markers for neuroectodermal tumors including anti-S-100 protein and NKI/C3 monoclonal antibodies. Results: Six granular cell nerve sheath tumors were diagnosed in over 80,000 dermatopathology specimens in the two-year period. These cases were all positive for PGP 9.5 as well as for S-100 protein and NK1/C3. Conclusion: These findings identify PGP 9.5 as a new immunohistochemical marker for use in the diagnosis of granular cell tumors. They also strengthen the histogenetic relationship between granular cell nerve sheath tumors and tumors of Schwann cell or perineurial origin. [source] Pulpal status of human primary teeth with physiological root resorptionINTERNATIONAL JOURNAL OF PAEDIATRIC DENTISTRY, Issue 1 2009JOANA MONTEIRO Objective., The overall aim of this study was to determine whether any changes occur in the pulpal structure of human primary teeth in association with physiological root resorption. Methods., The experimental material comprised 64 sound primary molars, obtained from children requiring routine dental extractions under general anaesthesia. Pulp sections were processed for indirect immunofluorescence using combinations of: (i) protein gene product 9.5 (a general neuronal marker); (ii) leucocyte common antigen CD45 (a general immune cell marker); and (iii) Ulex europaeus I lectin (a marker of vascular endothelium). Image analysis was then used to determine the percentage area of staining for each label within both the pulp horn and mid-coronal region. Following measurement of the greatest degree of root resorption in each sample, teeth were subdivided into three groups: those with physiological resorption involving less than one-third, one-third to two-thirds, and more than two-thirds of their root length. Results., Wide variation was evident between different tooth samples with some resorbed teeth showing marked changes in pulpal histology. Decreased innervation density, increased immune cell accumulation, and increased vascularity were evident in some teeth with advanced root resorption. Analysis of pooled data, however, did not reveal any significant differences in mean percentage area of staining for any of these variables according to the three root resorption subgroups (P > 0.05, analysis of variance on transformed data). Conclusions., This investigation has revealed some changes in pulpal status of human primary teeth with physiological root resorption. These were not, however, as profound as one may have anticipated. It is therefore speculated that teeth could retain the potential for sensation, healing, and repair until advanced stages of root resorption. [source] Immunocytochemical investigation of immune cells within human primary and permanent tooth pulpINTERNATIONAL JOURNAL OF PAEDIATRIC DENTISTRY, Issue 1 2006H. D. RODD Summary. Aim., The aim of this study was to determine whether there are any differences in the number and distribution of immune cells within human primary and permanent tooth pulp, both in health and disease. Design., The research took the form of a quantitative immunocytochemical study. One hundred and twenty-four mandibular first permanent molars and second primary molars were obtained from children requiring dental extractions under general anaesthesia. Following exodontia, 10-µm-thick frozen pulp sections were processed for indirect immunofluorescence. Triple-labelling regimes were employed using combinations of the following: (1) protein gene product 9·5, a general neuronal marker; (2) leucocyte common antigen (LCA); and (3) Ulex europaeus I lectin, a marker of vascular endothelium. Image analysis was then used to determine the percentage area of immunostaining for LCA. Results., Leucocytes were significantly more abundant in the pulp horn and mid-coronal region of intact and carious primary teeth, as compared to permanent teeth (P < 0·05, anova). Both dentitions demonstrated the presence of well-localized inflammatory cell infiltrates and marked aborization of pulpal nerves in areas of dense leucocyte accumulation. Conclusions., Primary and permanent tooth pulps appear to have a similar potential to mount inflammatory responses to gross caries The management of the compromised primary tooth pulp needs to be reappraised in the light of these findings. [source] Immunohistochemical and electron microscopic study of extrinsic hepatic reinnervation following orthotopic liver transplantation in ratsLIVER INTERNATIONAL, Issue 5 2001Tsuyoshi Takahashi Abstract:Background/Aims: Because little has been known about the morphological and functional consequences of liver transplantation on hepatic autonomic nerves, we examined the time-course of extrinsic hepatic innervation at the level of the porta hepatis of liver allografts. Methods: Orthotopic liver transplantation was performed using male Lewis rats. Crosscut tissue specimens were obtained postoperatively for up to 6 months from the porta hepatis of transplanted livers, and processed for immunohistochemical staining for protein gene product 9.5 (PGP 9.5) and growth-associated protein 43 (GAP-43), and for transmission electron microscopy (TEM). Results: Extrinsic nerve fibers at the porta hepatis stained positively for PGP 9.5 throughout the entire study period. In contrast, the immunoreactivity of GAP-43 was negative at postoperative day (POD) 1 and 2. GAP-43-positive nerves were first observed to appear in the porta hepatis at POD 3. The immunoreactivity of GAP-43 remained positive thereafter until 3 months post-OLT, and became negative in all the specimens at 4 months post-OLT. Transmission electron microscopy demonstrated a small number of regenerating axons existing among many degenerating axons at POD 3. At 3 months post-OLT, most regenerating axons had been fully ensheathed by the cytoplasm of Schwann cells, although their density remained at a lower level compared with normal. Conclusion: The results of this study suggest that liver allografts become extrinsically reinnervated, with the regenerating axons reaching the hepatic hilus 3 days after transplantation. The process of extrinsic hepatic reinnervation is considered to almost terminate 4 months after transplantation in rats. [source] Post inflammatory damage to the enteric nervous system in diverticular disease and its relationship to symptomsNEUROGASTROENTEROLOGY & MOTILITY, Issue 8 2009J. Simpson Abstract:, Some patients with colonic diverticula suffer recurrent abdominal pain and exhibit visceral hypersensitivity, though the mechanism is unclear. Prior diverticulitis increases the risk of being symptomatic while experimental colitis in animals increases expression of neuropeptides within the enteric nervous system (ENS) which may mediate visceral hypersensitivity. Our aim was to determine the expression of neuropeptides within the ENS in diverticulitis (study 1) and in patients with symptomatic disease (study 2). Study 1 , Nerves in colonic resection specimens with either acute diverticulitis (AD, n = 16) or chronic diverticulitis (CD, n = 16) were assessed for neuropeptide expression recording % area staining with protein gene product (PGP9.5), substance P (SP), neuropeptide K (NPK), pituitary adenylate cyclase activating polypeptide (PACAP), vasoactive intestinal polypeptide (VIP) and galanin. Study 2 , Seventeen symptomatic and 15 asymptomatic patients with colonic diverticula underwent flexible sigmoidoscopy and multiple peridiverticular mucosal biopsies. Study 1, Neural tissue, as assessed by PGP staining was increased to a similar degree in circular muscle in both AD and CD. The CD specimens showed significant increases in the immunoreactivity of SP, NPK and galanin in both mucosal and circular muscle layer compared with controls. Study 2 , Mucosal histology was normal and PGP9.5 staining was similar between groups however patients with symptomatic diverticular disease demonstrated significantly higher levels of SP, NPK, VIP, PACAP and galanin within the mucosal plexus. Patients with symptomatic diverticular disease exhibit increased neuropeptides in mucosal biopsies which may reflect resolved prior inflammation, as it parallels the changes seen in acute and chronic diverticulitis. [source] Effect of age on the enteric nervous system of the human colonNEUROGASTROENTEROLOGY & MOTILITY, Issue 7 2009C. E. Bernard Abstract, The effect of age on the anatomy and function of the human colon is incompletely understood. The prevalence of disorders in adults such as constipation increase with age but it is unclear if this is due to confounding factors or age-related structural defects. The aim of this study was to determine number and subtypes of enteric neurons and neuronal volumes in the human colon of different ages. Normal colon (descending and sigmoid) from 16 patients (nine male) was studied; ages 33,99. Antibodies to HuC/D, choline acetyltransferase (ChAT), neuronal nitric oxide synthase (nNOS), and protein gene product 9.5 were used. Effect of age was determined by testing for linear trends using regression analysis. In the myenteric plexus, number of Hu-positive neurons declined with age (slope = ,1.3 neurons/mm/10 years, P = 0.03). The number of ChAT-positive neurons also declined with age (slope = ,1.1 neurons/mm/10 years of age, P = 0.02). The number of nNOS-positive neurons did not decline with age. As a result, the ratio of nNOS to Hu increased (slope = 0.03 per 10 years of age, P = 0.01). In the submucosal plexus, the number of neurons did not decline with age (slope = ,0.3 neurons/mm/10 years, P = 0.09). Volume of nerve fibres in the circular muscle and volume of neuronal structures in the myenteric plexus did not change with age. In conclusion, the number of neurons in the human colon declines with age with sparing of nNOS-positive neurons. This change was not accompanied by changes in total volume of neuronal structures suggesting compensatory changes in the remaining neurons. [source] Ubiquitin C-terminal hydrolase-L1 (PGP9.5) expression in human neural cell lines following induction of neuronal differentiation and exposure to cytokines, neurotrophic factors or heat stressNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 2 2001J.-I. Satoh Dysfunction of the ubiquitin-dependent proteolytic pathway contributes to progressive accumulation of ubiquitinated protein inclusions in neurodegenerative disorders, such as Parkinson's disease (PD). Ubiquitin C-terminal hydrolase-L1 (UCH-L1), alternatively designated protein gene product 9.5 (PGP9.5), is a neural deubiquitinating enzyme which is identified as a principal constituent of Lewy bodies. To clarify the regulatory mechanism of UCH-L1 expression in human neural cells, we studied the constitutive, cytokine/neurotrophic factor-regulated, and heat stress-induced expression of UCH-L1 in cultured human neural cell lines by Western blot analysis. The constitutive expression of UCH-L1 was identified in SK-N-SH neuroblastoma cells, IMR-32 neuroblastoma cells, U-373MG astrocytoma cells, and NTera2 teratocarcinoma-derived differentiated neurones (NTera2-N). The levels of UCH-L1 expression were unaltered in these cell lines following treatment with TNF-,, IL-1,, BDNF, GDNF, dibutyryl cyclic AMP, or phorbol 12-myristate 13-acetate, and remained unchanged by exposure to heat stress. In contrast, its levels were elevated substantially in NTera2 teratocarcinoma cells following retinoic acid-induced neuronal differentiation, accompanied with an increased expression of ,-synuclein and synaptophysin. These results indicate that UCH-L1 is expressed constitutively in human neual cell lines, where it is upregulated following induction of neuronal differentiation, but unaffected by exposure to heat stress, cytokines, or growth/differentiation factors which are supposed to be invloved in the nigral neuronal death and survival in PD. [source] Nestin expression as a new marker in malignant peripheral nerve sheath tumorsPATHOLOGY INTERNATIONAL, Issue 2 2007Satoko Shimada Malignant peripheral nerve sheath tumor (MPNST) can be difficult to diagnose because it lacks specific immunohistochemical markers. S-100, which is a useful marker of MPNST, has limited diagnostic utility. Recent studies suggest that nestin, which is an intermediate filament protein, is expressed in neuroectodermal stem cells. The diagnostic utility of immunostains for nestin and three other neural markers (S-100, CD56 and protein gene product 9.5 (PGP 9.5)) were evaluated in 35 cases of MPNST and in other spindle cell tumors. All MPNST cases were strongly positive for nestin and had cytoplasmic staining. Stains for S-100, CD56, and PGP 9.5 were positive in fewer cases (17/35, 11/35, and 29/35 cases, respectively), and had less extensive staining. Nestin was negative in 10/10 leiomyomas, and weak nestin expression was seen in 10/10 schwannomas, 3/10 neurofibromas, 2/8 synovial sarcomas, 2/10 liposarcomas, 4/7 carcinosarcomas and 3/7 malignant fibrous histiocytomas. In contrast, strong nestin positivity was seen in 10/10 rhabdomyosarcomas, 15/19 leiomyosarcomas, and 9/9 desmoplastic melanomas. Nestin is more sensitive for MPNST than other neural markers and immunostains for nestin in combination with other markers could be useful in the diagnosis of MPNST. [source] New Insights into the Neuromuscular Anatomy of the Ileocecal ValveTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 2 2009Tamas Cserni Abstract The neuroanatomy of the ileocecal valve (ICV) is poorly understood. A better understanding of this important functional component of the gastrointestinal tract would enable surgeons to reconstruct an effective valve following surgical resection of the ICV. ICVs were examined in young pigs (N = 5) using frontal and transverse paraffin embedded and frozen sections. Hematoxylin+Eosin (H+E) staining, acetylcholinesterase (AchE), and NADPH-diaphorase (NADPH-d) histochemistry and protein gene product 9.5 (PGP 9.5) and C-kit immunohistochemistry were performed. The H+E staining revealed that the ICV consists of three muscle layers: an external circular muscle layer continuous with that of the ileal circular muscle layer, an inner circular muscle layer continuous with that of the cecal circular muscle layer, and a single longitudinal muscle layer, which appears to be secondary to a fusion of the ileal and cecal longitudinal muscle layers. The AchE, NADPH-d, and PGP 9.5 staining revealed two distinct coaxial myenteric plexuses, together with superficial and deep submucosal plexuses. The C-kit immunostaining showed a continuous myenteric ICC network within the ICV. The structure of the neuromuscular components within the ICV suggests that the valve is a result of a simple intussusception of the terminal ileum into the cecum. This knowledge may help surgeons in their future attempts at reconstructing more anatomically and functionally suitable ICVs following surgical resection of native ICVs. Anat Rec 2009. © 2008 Wiley-Liss, Inc. [source] Increased Nerve Fiber Expression of Sensory Sodium Channels Nav1.7, Nav1.8, and Nav1.9 in Rhinitis,,THE LARYNGOSCOPE, Issue 4 2008Siew M. Keh MRCS Abstract Introduction: Voltage-gated sodium channels Nav1.7, Nav1.8, and Nav1.9 are involved in nerve action potentials and have been proposed to underlie neuronal hypersensitivity. We have therefore studied their levels in allergic and nonallergic rhinitis. Materials and Methods: Inferior turbinate biopsies from 50 patients (n = 18 controls, n = 20 allergic, and n = 12 nonallergic rhinitis) were studied by immunohistology using antibodies to Nav1.7, Nav1.8, and Nav1.9, the structural nerve marker (protein gene product [PGP]9.5), nerve growth factor (NGF), mast cells (c-kit), macrophages (CD68), and T cells (CD3). Sodium channel-positive nerve fibers were counted per millimeter length of subepithelium, and immunoreactivity for inflammatory cell markers PGP9.5 and NGF were image analyzed. Results: All three sodium channel-immunoreactive nerve fiber numbers were significantly increased in allergic (Nav1.7, P = .0004; Nav1.8, P = .028; Nav1.9, P = .02) and nonallergic (Nav1.7, P = .006; Nav1.8, P = .019; Nav1.9, P = .0037) rhinitis. There was a significant increase of subepithelial innervation (PGP9.5, P = .01) and epithelial NGF immunoreactivity (P = .03) in nonallergic rhinitis, comparable with our previous report in allergic rhinitis. Inflammatory cell markers were significantly increased in allergic (mast cells, P = .06; macrophages, P = .044; T cells, P = .007) but not nonallergic rhinitis. Conclusion: The increased levels of sensory sodium channels in allergic and nonallergic rhinitis may contribute to the hypersensitive state, irrespective of the degree of active inflammation. Selective blockers of these sodium channels, administered topically, may have therapeutic potential in rhinitis. [source] Small nerve fiber involvement in systemic lupus erythematosus: A controlled studyARTHRITIS & RHEUMATISM, Issue 5 2002Roald Omdal Objective To determine if patients with systemic lupus erythematosus (SLE) may have a peripheral neuropathy involving unmyelinated and small, myelinated nerve fibers, by immunostaining epidermal nerve fibers (ENF) in skin biopsy samples for the panaxonal marker, protein gene product 9.5 (PGP 9.5). Methods Fifteen consecutive and nonselected SLE patients and 15 age- and sex-matched controls were included in the study. The age of the patients ranged from 25 years to 65 years, with a mean ± SD age of 47.3 ± 10.2 years and a disease duration of 2,28 years (mean ± SD 14.8 ± 8.6 years). Two 3-mm skin biopsy samples were obtained with a punch needle ,10 cm superior to the lateral malleolus of the right leg and immunostained with 0.1% rabbit polyclonal antibodies to human PGP 9.5. The number of ENF per millimeter was counted and recorded as the mean ± SD of counts in six 50-,m sections, 3 from each of the 2 biopsy samples. Results The mean number of ENF per mm in patients with SLE was 8.0 ± 1.5 (range 5.0,9.9), while the matched controls had 12.2 ± 3.8 ENF per mm (range 6.8,18.6) (P = 0.0006). Conclusion This study indicates that a small fiber involvement in patients with SLE may be responsible for the prevalent neuropathic symptoms and impaired warm sense that is observed in such patients. [source] Unexpected diminished innervation of epidermis and dermoepidermal junction in lichen amyloidosusBRITISH JOURNAL OF DERMATOLOGY, Issue 2 2008B. Maddison Summary Background, Lichen amyloidosus is a localized, chronic, pruritic skin disease characterized by deposition of amyloid in the papillary dermis. The pathogenesis of the pruritus of lichen amyloidosus is largely unknown. Objectives, To determine any change in the nerve fibre density in lichen amyloidosus lesions as an explanation for itch. Methods, Using an antibody to protein gene product (PGP) 9.5, the immunohistochemical analysis of the skin biopsies of 30 Hispanic patients with clinicopathologically proven lichen amyloidosus and of 11 healthy Hispanic controls matched for age, sex and site was performed. Results, Unexpectedly, the mean amount of PGP9.5 stain, a measure for nerve fibre amount, for the healthy controls was higher than the lichen amyloidosus group both in the epidermis (P < 0·0019) and dermoepidermal junction (P < 0·0064). No change was observed in the papillary dermis. Furthermore, the proportion of area covered by PGP9.5 showed a significant decrease in the epidermis (P < 0·0024) and dermoepidermal junction (P < 0·0075) in lichen amyloidosus compared with healthy controls. Age, gender and body site were found not to be influencing factors in nerve fibre amounts in lichen amyloidosus samples. Conclusions, We speculate that the severe pruritus observed in lichen amyloidosus might be the result of the hypersensitivity of the remaining nerve fibres as a response to an unexplained neurodegeneration of the absent nerve fibres. [source] Expression of protein gene product 9·5 (PGP9·5)/ubiquitin-C-terminal hydrolase 1 (UCHL-1) in human myeloma cellsBRITISH JOURNAL OF HAEMATOLOGY, Issue 3 2004T. Otsuki Summary The neuron cytoplasmic protein gene product 9·5 (PGP9·5)/ubiquitin-C-terminal hydrolase 1 (UCHL-1) protein is a thiol protease that recognizes and hydrolyzes a peptide bond at the C-terminal of ubiquitin, and is involved in the processing of ubiquitin precursors and ubiquinated proteins. Although this molecule is known as a specific tissue marker for the neuroendocrine system, many reports have indicated that PGP9·5 is a marker for certain tumour types, such as cancer of the lung, colon, and pancreas. The expression of PGP9·5 in myeloma cells was examined. PGP9·5 seemed to be expressed specifically in myeloma cells as compared with other haematological malignant cells. In addition, in myeloma cells subjected to growth-factor starvation, the upregulation of PGP9·5 was observed in association with that of p27Kip1, a cyclin-dependent-kinase inhibitor, although the upregulation caused by irradiation was milder. In contrast, the hypoxic culture of myeloma cells induced down-regulation of PGP9·5. These results suggested that PGP9·5 may be a good marker for myeloma among haematological malignancies. In addition, it may indicate certain cellular features of myeloma cells, such as sensitivity to proteasome inhibitors. [source] Mesenteric transection decreases expression of interstitial cells of Cajal in an experimental modelBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 4 2007M. Nishimura Background: After anterior resection for rectal carcinoma patients often complain of defaecatory dysfunction. The aim of this study was to examine the number of interstitial cells of Cajal (ICCs) and ganglion cells in the distal colon partially denervated by mesenteric transection in a rat model. Methods: Four groups of rats were operated on, a control group and three experimental groups, with increasing degree of mesenteric transection to denervate the distal colon. Animals were killed after 3 months, and the denervated colon was investigated using immunohistochemistry with Kit and protein gene product 9.5 antibodies to detect ICCs and ganglion cells respectively. Reverse transcriptase,polymerase chain reaction for c-kit and histomorphometry of muscular thickness were performed. Results: The total number of ICCs was significantly lower in the three operated models than in the control, particularly in the histological layers of the myenteric plexus and submucosal border. There was no difference in the number of ganglion cells or changes in muscular thickness between the models. Conclusion: The number of ICCs in rat distal colon denervated by mesenteric transection is decreased at 3 months after surgery. Copyright © 2007 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] | |||||||||||||||||||