Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mammary small cell carcinoma (SmCC) is a very rare neoplasm with a poor prognosis compared with other invasive carcinomas. We studied the histological and immunohistochemical profiles of two cases of mammary SmCC, and compared them with those of five cases of carcinoma with endocrine features (CEF) and five cases of invasive ductal carcinoma (IDC), to elucidate the correct diagnosis of mammary SmCC. Immunohistochemical analysis was performed with antibodies against cytokeratins (CKAE1/AE3, CK34betaE12, CKCAM5.2, CK7, CK8, CK19, CK20), epithelial membrane antigen (EMA), vimentin, CD10, neural cell adhesion molecule (NCAM; CD56), neuron-specific enolase (NSE), chromogranin A, S-100 protein, carcino-embryonic antigen (CEA), E-cadherin, N-cadherin, thyroid transcription factor-1 (TTF-1), p53, estrogen (ER), progesterone (PR), HER2/neu, bcl-2, synaptophysin, calcitonin and Leu7. SmCCs were diffusely and strongly positive for NCAM in comparison with CEFs and IDCs. SmCCs were negative for vimentin, whereas CEFs and IDCs were positive. Neuro-endocrine carcinomas, including SmCCs and CEFs, were diffusely and strongly positive for NSE, compared with IDCs. Moreover, neuroendocrine carcinomas were negative for CK34betaE12, CK20 and CD10, whereas IDCs were positive. Our study suggests that NCAM and vimentin are useful markers for the diagnosis of mammary SmCC. CK34betaE12, NSE, CD10, CK20 and chromogranin A appear to be useful for differentiating neuroendocrine carcinoma from IDCs.
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PMID:Comparative study of primary mammary small cell carcinoma, carcinoma with endocrine features and invasive ductal carcinoma. 1501 Aug 80

Neuroendocrine cells (NEC) are abundant in fetal and neonatal lungs, but reduced in infants with hyaline membrane disease. Perinatal neuroendocrine cell hyperplasia (NCH) has been reported in the hypoplastic lung in diaphragmatic hernia, bronchopulmonary dysplasia, and Wilson-Mikity syndrome. Since we are unaware of any reports on NCH in fetal inflammatory conditions, this report addresses the NEC in fetuses with congenital pneumonia. Twenty-one fetuses/neonates with congenital pneumonia, autopsied between 1995 and 2001, were compared to 21 fetuses without a congenital infection matched for gestational age. Lung sections were immunostained for chromogranin, bombesin, calcitonin, and synaptophysin. Proportions of immunopositive cells lining 20 consecutive bronchioles calculated from digital images were significantly higher in the study than the control group for chromogranin (1.8 vs. 0.8%, P = 2.4 E-06), calcitonin (1.2 vs. 0.7%, P = 0.005), and bombesin (1.1 vs. 0.7%, P = 0.005). There was no difference in synaptophysin (11.7% vs. 12.6%, P = 0.07). The absence of significant differences in the synaptophysin ratio excludes simple NCH in the study group. The synchronous increase in three neurohormones is indicative of NEC hyperfunction, due to either altered enzymatic inactivation by neutral endopeptidase, known to be reduced in adult lung inflammation, or by an increase in expression of the neurohormone genes. These data indicate that NEC hyperfunction may be responsible for the deranged fetal/neonatal lung function and circulatory adaptation, and contribute to the lethality of the amniotic sac infection syndrome.
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PMID:Amniotic sac infection syndrome features fetal lung neuroendocrine cell hyperfunction. 1501 48

We assessed the metabolic degradation kinetics and cleavage patterns of some selected CPP (cell-penetrating peptides) after incubation with confluent epithelial models. Synthesis of N-terminal CF [5(6)-carboxyfluorescein]-labelled CPP, namely hCT (human calcitonin)-derived sequences, Tat(47-57) and penetratin(43-58), was through Fmoc (fluoren-9-ylmethoxycarbonyl) chemistry. Metabolic degradation kinetics of the tested CPP in contact with three cell-cultured epithelial models, MDCK (Madin-Darby canine kidney), Calu-3 and TR146, was evaluated by reversed-phase HPLC. Identification of the resulting metabolites of CF-hCT(9-32) was through reversed-phase HPLC fractionation and peak allocation by MALDI-TOF-MS (matrix-assisted laser-desorption ionization-time-of-flight mass spectrometry) or direct MALDI-TOF-MS of incubates. Levels of proteolytic activity varied highly between the investigated epithelial models and the CPP. The Calu-3 model exhibited the highest proteolytic activity. The patterns of metabolic cleavage of hCT(9-32) were similar in all three models. Initial cleavage of this peptide occurred at the N-terminal domain, possibly by endopeptidase activity yielding both the N- and the C-terminal counterparts. Further metabolic degradation was by aminopeptidase, endopeptidase and/or carboxypeptidase activities. In conclusion, when in contact with epithelial models, the studied CPP were subject to efficient metabolism, a prerequisite of cargo release on the one hand, but with potential for premature cleavage and loss of the cargo as well on the other. The results, particularly on hCT(9-32), may be used as a template to suggest structural modifications towards improved CPP performance.
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PMID:Metabolic cleavage of cell-penetrating peptides in contact with epithelial models: human calcitonin (hCT)-derived peptides, Tat(47-57) and penetratin(43-58). 1519 45

The neutral endopeptidase (NEP) is important for calcitonin gene related peptide (CGRP) degradation, while the role of angiotensin converting enzyme (ACE) remains unclear. By using dermal microdialysis we explored the effect of phosphoramidon (NEP blocker), captopril (ACE blocker) and a mixture of both drugs on the intensity of electrically-induced CGRP-mediated neurogenic flare. The results reveal that phosphoramidon elevated flare intensity, but that this was not further increased by adding captopril. In contrast, neurogenic flare was decreased when the drug mixture was applied in compared to NEP only. Electrically released CGRP levels could be measured directly in perfusates containing phosphoramidon and the mixture. Again, CGRP levels were elevated in phosphoramidon treated sites, and significantly reduced upon adding captopril. These findings suggest that NEP and ACE do not have additive effects regarding neuropeptide degradation. In contrast, inhibition of ACE seems to augment CGRP catabolism.
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PMID:Angiotensin converting enzyme has an inhibitory role in CGRP metabolism in human skin. 1640 41

When mice were scratched with brushes on their dorsal skins, they began to scratch themselves with their hind paws. Thus, self-scratching behaviour was induced in mice in response to skin-scratching stimulation. If the second skin-scratching stimulation was given within a few days, the induction of the second self-scratching behaviour was significantly suppressed compared with the first one. Thereafter, mice gradually recovered from this unresponsive state within a week. Thus, a transient unresponsive state of self-scratching behaviour is induced by skin-scratching stimulation. Pretreatment with a tachykinin receptor NK-1R antagonist L-703606 or capsaicin significantly suppressed self-scratching behaviour, while pretreatment with a neutral endopeptidase inhibitor phosphoramidon significantly enhanced it. Pretreatment with a calcitonin gene-related peptide (CGRP) receptor antagonist CGRP(8-37) did not affect the following self-scratching behaviour. From these results, it is suggested that substance P (SP) signalling through its receptor NK-1R at least in part mediates the induction of self-scratching behaviour. After skin-scratching stimulation, immunoreactivity of SP both in the peripheral nerve fibres and in the dorsal root ganglion (DRG) neurons was significantly decreased and was well-correlated with suppression of self-scratching behaviour. From these findings, it is suggested that the induction of unresponsive states of self-scratching behaviour may be at least in part caused by the depleted states of SP in peripheral nerve fibres and/or in DRG neurons. The induction of a transient unresponsive state after skin-scratching may possibly happen also in patients with pruritus. Thus, further studies to elucidate the precise mechanisms are required.
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PMID:A transient unresponsive state of self-scratching behaviour is induced in mice by skin-scratching stimulation. 1769 46

Tibia fracture in rats evokes nociceptive, vascular, and bone changes resembling complex regional pain syndrome (CRPS). Substance P (SP) signaling contributes to the hindpaw warmth, increased vascular permeability, and edema observed in this model, suggesting that neurogenic inflammatory responses could be enhanced after fracture. Four weeks after tibia fracture we measured SP and calcitonin gene-related peptide (CGRP) protein levels in the sciatic nerve and serum. Hindpaw skin extravasation responses and SP receptor (NK1), CGRP receptor (calcitonin receptor-like receptor, CRLR) and neutral endopeptidase (NEP) protein levels were also determined. Gene expression levels of these peptides, receptors, and peptidase were examined in the DRG and skin. Spontaneous and intravenous SP-evoked extravasation responses were increased ipsilateral, but not contralateral to the fracture. Fracture increased SP and CGRP gene expression in the ipsilateral L4,L5 DRG and neuropeptide protein levels in the sciatic nerve and in serum, but had no effect on electrically evoked SP and CGRP release. NK1 receptor expression was increased in the ipsilateral hindpaw skin keratinocytes and endothelial cells after injury, but CRLR and NEP expression were unchanged. Fracture also increased epidermal thickness, but had no effect on epidermal skin neurite counts. These results demonstrate that spontaneous and intravenous SP-evoked extravasation responses are enhanced in the ipsilateral hindlimb after fracture and that fracture chronically increases the expression of endothelial and keratinocyte NK1 receptors in the injured limb. We postulate that SP activation of these up-regulated NK1 receptors results in skin warmth, protein leakage, edema, and keratinocyte proliferation in the injured limb.
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PMID:Post-junctional facilitation of Substance P signaling in a tibia fracture rat model of complex regional pain syndrome type I. 1946 18

We report a case of a 56-year-old male with a primary large cell neuroendocrine renal carcinoma. Grossly, the left kidney was enlarged by a solid tumor that measured 145 x 125 x 100 mm. Histologically, the tumor consisted of large cells with a moderate to abundant amount of eosinophilic cytoplasm. The nuclei were irregular, some of them with finely or coarsely granular chromatin, others with vesicular chromatin and prominent nucleoli. The tumor cells showed multiple mitotic figures (up to 32 mitoses/10 HPF). In some areas, the tumor cells were arranged in solid sheets; however, the predominant pattern was solid-alveolar, trabecular and cribriform. Large areas of tumor necrosis were found. Immunohistochemically, the tumor cells were positive for synaptophysin, CD56 and CD57. Cytokeratin AE1/AE3, vimentin and CD10 were positive only focally. Chromogranin showed weak cytoplasmic positivity in rare tumor cells. Cytokeratin CAM5.2, cytokeratin 34betaE12, BerEP 4, EMA, TTF-1, cytokeratin 7, cytokeratin 20, calretinin, serotonin, somatostatin, gastrin, calcitonin, glukagon and insulin were negative. Primary large cell neuroendocrine carcinoma of the kidney is a rare tumor. To the best of our knowledge, only 3 cases of a tumor of this type have been reported to date.
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PMID:Primary large cell neuroendocrine carcinoma of the kidney. 1957 58

Complex regional pain syndrome (CRPS) is a condition that is characterized by severe pain and exaggerated neurogenic inflammation, which may develop after injury or surgery. Neurogenic inflammation is mediated by neuropeptides, such as calcitonin gene-related peptide (CGRP) and substance P (SP) that are released from nociceptors. Genetic factors may play a role in CRPS as was suggested by the occurrence of familial cases and several genetic association studies investigating mainly the human leukocyte antigen (HLA) system. Here we investigated the role of neutral endopeptidase (NEP), a key enzyme in neuropeptide catabolism. NEP dysfunction resulting in reduced inactivation of neuropeptides may be a possible pathomechanism in CRPS. To this end, we tested a GT-repeat polymorphism in the NEP promoter region as well as 18 tag-SNPs in six linkage disequilibrium (LD) blocks in the NEP gene region in 320 CRPS patients and 376 controls. No significant genetic association was observed. Thus, we conclude that the NEP gene does not seem to be a major risk factor for CRPS.
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PMID:Lack of genetic association of neutral endopeptidase (NEP) with complex regional pain syndrome (CRPS). 2010 52

Paragangliomas are relatively uncommon neoplasms that arise in adrenal and extra-adrenal paraganglia of the autonomic nervous system. Parasympathetic paraganglioma develop predominantly in the head and neck. It is exceedingly uncommon to develop a primary intraparathyroid paraganglioma. There is only a single case report in the English literature. The information from the single previous case report (Medline 1960-2009) was combined with this case report. Our patient was a 69 year old woman who presented with a thyroid gland mass, with extension into the substernal space. The patient had a history of renal cell carcinoma removed 18 months before. At surgery, a thyroid lobectomy and a parathyroidectomy were performed. The parathyroid tissue showed a very well defined zellballen arrangement of paraganglion cells within the parenchyma of the parathyroid gland. The cells had ample basophilic, granular cytoplasm. The nuclei were generally round to oval with 'salt-and-pepper' nuclear chromatin distribution. There was a richly vascularized stroma. Mitotic figures, necrosis, invasive growth, and profound nuclear pleomorphism were absent. The neoplastic cells were strongly and diffusely immunoreactive with chromogranin, synaptophysin, CD56, and focally with cyclin-D1. The paraganglioma showed a delicate S-100 protein positive supporting sustentacular framework. Keratin, CD10, PTH, calcitonin and RCC markers were negative. The patient showed no stigmata of Multiple Endocrine Neoplasia (MEN) and has no paraganglioma in any other anatomic site. She is alive without any additional findings 12 months after surgery. Isolated paraganglioma within the parathyroid is rare, and should be separated from parathyroid adenoma, hyperplasia or metastatic disease to assure appropriate management.
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PMID:Primary paraganglioma of the parathyroid: a case report and clinicopathologic review. 2023 87

The phenotypes of the human renal epithelial cell lines, SK-NEP-1 and G401 (Wilm's tumour lines) and ACHN, A498, A704, Caki-1 and Caki-2 (renal adenocarcinomas), were investigated in order to develop as toxicological model systems, human renal cell lines showing properties similar to those found in discrete renal tubular segments. All cell lines, except G401, demonstrated significant (P < 0.05) stimulation of adenyl cyclase activity by calcitonin. Alkaline phosphatase activity was not detectable in any cell line except for G401. None of the cell lines tested was capable of forming epithelial layers characteristic of 'tight' epithelia. The G401 cell line displayed several characteristics of the proximal nephron including a receptor for hPTH and detectable levels of the brush-border enzymes alkaline phosphatase (0.18 +/- 0.02 mU/mg protein), leucine aminopeptidase (14.0 +/- 5.1 mU/mg protein), glutathione transferase (8.61 +/- 2.53 mU/mg protein) and gamma-glutamyl transpeptidase (24.0 +/- 2.1 mU/mg protein). hPTH (0.01-1 mum) stimulated adenyl cyclase activity in homogenates of G401 cells in a dose-dependent manner, and this stimulation was reversed by 10 mum of the specific PTH antagonist Nle, Tyr-PTH 3-34 amide. The addition of 10 mum antagonist to unstimulated G401 cell homogenate reduced the basal activity of adenyl cyclase from 87.3 +/- 17.4 to 45.9 +/- 13.2 pmol cAMP/mg protein . 15 min. The effect of known nephrotoxic agents was tested on G401 cells by measuring basic mitochondrial enzyme function (MTT assay). The antibiotic gentamicin (5 mm), significantly (P < 0.001) inhibited MTT activity in a dose-dependent manner with a maximum inhibition to23.2 +/- 9.2% of untreated G401 cells. S- (1,1,2,2,tetrafluoroethyl)- l -glutathione (4 mm) and its cysteine conjugate (2.5 mm) reduced MTT activity to 44.0 +/- 10.9% and 33.3 +/- 2.6% of control untreated G401 cells, respectively. We suggest that the G401 cell line may be a useful model of the human proximal tubule in predictive toxicology.
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PMID:Established human renal cell lines: Phenotypic characteristics define suitability for use in in vitro models for predictive toxicology. 2073 80


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