Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.3.5.1 (succinate dehydrogenase)
 8,177 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A number of phenotypic abnormalities of the colorectal mucosa which appears normal have been described to be biomarkers of cancer development. To improve their sensitivity and specificity, we simultaneously determined 10 morphological and histochemical parameters in biopsies from the colonoscopically normal mucosa of the descending colon, sigmoid, and rectum. The results were analysed by multivariate statistical methods. We tested the discriminating power of proliferative, morphometric, enzyme and mucin histochemical parameters from 80 patients either at average risk (controls), with an increased risk for colorectal carcinoma (high-risk), or with a manifest carcinoma. The following parameters were investigated: number of mitotic figures per crypt, crypt length, apical, medial and basal crypt diameter, crypt surface, activity of succinate dehydrogenase (EC 1.3.99.1), activity of acid beta-galactosidase (EC 3.2.1.23), sulpho- and sialomucin contents. Univariate statistical analyses revealed that crypt length, crypt diameter and crypt surface were significantly increased in the high-risk group, the carcinoma carriers having intermediate values between average-risk and high-risk patients. In a two-group discriminant analysis, high-risk or carcinoma patients could be separated from average-risk patients with a sensitivity of 92.9% and a specificity of 100%. When the analysis was repeated for three groups (carcinoma carriers separated from high-risk patients), sensitivity and specificity were 100% for each group. We conclude that identification of patients at risk for colorectal carcinoma is possible from the normal-appearing left colonic and rectal mucosa by morphometric and cytochemical analysis of biopsies.
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PMID:Identification of patients at high risk for colorectal carcinoma from biopsy studies of the apparently normal colorectal mucosa. A multivariate analysis. 190 33

Preneoplastic mucosal changes were studied at six different time-points during dimethylhydrazine (DMH)-induced colorectal carcinogenesis in the rat. After 40 weeks of treatment, seven of 10 animals were bearing a total of 11 colorectal adenocarcinomas. The crypt cell production rate in the normal mucosa of DMH-treated animals was greatly increased in the left colon and rectum and further rose with the duration of the experiment. Focal disturbances of the mucosal architecture could be detected as early as 4 weeks after the initiation of DMH-treatment using a stereomicroscope. Their incidence was greatest in the left colon and rectum and increased strongly with the duration of carcinogen exposure. Characterization of these mucosal alterations, by means of conventional histology, morphometry after microdissection, cell kinetics, mucin histochemistry and quantitative enzyme histochemistry performed with serial sections, revealed mild epithelial dysplasia, a considerable elongation and dilatation of the crypts and a marked increase of the crypt cell production, including a shift of the main proliferative compartment from the basal to the medial crypt segment as well as the occurrence of mitotic figures in the luminal epithelium. In affected crypts, the goblet cells completely lacked sulphomucins and exclusively contained sialomucins. The activities of the enzymes diaminopeptidase IV (brush-border), succinate dehydrogenase (mitochondria) and acid beta-galactosidase (lysosomes) were markedly reduced. We conclude that these early mucosal alterations are indeed preneoplastic lesions and indicate the existence of the adenoma-carcinoma sequence in this animal model.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of stereomicroscopically identified preneoplastic lesions during dimethylhydrazine-induced colonic carcinogenesis. 314 93

An investigation was undertaken to study the distribution of enzymes associated with submandibular gland salivary calculi. Ten calculi were freeze-sectioned and incubated for acid and alkaline phosphatases and for lactate, succinate and maleate dehydrogenases. All calculi were partly covered by a 50-210 micrometers wide zone of organic material consisting of connective tissue and metaplastic squamous epithelium facing the mineralized calculus, or of a structureless substance attached to the mineralized calculus. The epithelium showed an intense staining reaction for acid phosphatase and lactate dehydrogenase and a moderate reaction for succinate dehydrogenase throughout all levels of the epithelium. The structureless peripheral zone exhibited a moderate activity of acid phosphatase and succinate dehydrogenase located to an area close to the mineralized matrix. Also alkaline phosphatase and lactate dehydrogenase were found in a special pattern in the structureless zone. Sodium fluoride and sodium vanadate added to the incubation medium inhibited acid phosphatase activity whereas cupric chloride only lowered the staining reaction. Enzyme activity was found only within the peripheral zone of organic material with one exception. The results suggest that the calcification process of salivary calculi is not a passive calcification of necrotic material or mucin but rather an active process promoted by enzymes in the surrounding organic substances.
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PMID:An enzyme histochemical study of human salivary duct calculi. 641 30

Loops of rat jejunum were exposed in vivo to different concentrations of deoxycholic acid (DOC; 0, 2.5, 5, 10 and 20 mM). Following a 30 min exposure period, DOC was washed out of the loops and the intestines were allowed to recover for 15 or 150 min. Frozen tissue for enzyme histochemistry was collected during exposure and following the recovery periods. As shown previously, exposure to DOC caused a dose-dependent loss of epithelial cells at the villous tips and denudation of the lamina propria. Flattened epithelial cells bordering the denuded areas were, however, responsible for a rapid restoration of epithelial continuity, which was completed within 15 min. In the present study, these flattened cells showed normal reactivity for non-specific esterase and succinate dehydrogenase. In contrast, following a prolonged recovery period (150 min), a subpopulation of enterocytes at the villous tips that otherwise appeared normal showed decreased reactivity for brush border enzymes and non-specific esterase, and a positive reaction for mucin. A shutdown in the synthesis of cytoplasmic enzymes and redistribution of cell surface enzymes could be responsible for these late occurring enzyme changes, that were consistently observed after 150 min of recovery from DOC at 20 mM. Alternatively, retention of goblet cells and/or a modification in enzyme synthesis may explain the presence of mucin that was demonstrated in the epithelial cells which had low enzyme reactivity.
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PMID:Enzyme changes in remodelling epithelial cells: a histochemical study of the rat jejunum in vivo during and following exposure to deoxycholic acid. 832 98

Selected antibodies that have become available in recent years and have applications in diagnostic pathology are discussed. They include antibodies that are organ-related, provide information on cellular differentiation or histogenetic type, have predictive value in tumors, and highlight infective agents. PAX8 (paired box gene 8) is a marker expressed in the lower female genital tract, thyroid, and kidney and their tumors. Napsin A is expressed in the lung and kidney and is an alternative marker for pulmonary adenocarcinoma. Arginase A is a sensitive and specific marker for liver tumors. ERG (Ets-related gene) is an excellent marker for endothelium and vascular tumors as well as prostatic cancer (about 50% of cases). SOX10 (SRY-related HMG box) is expressed predominantly in melanocytic and Schwann cells and the corresponding tumors. DOG1 (discovered on GIST 1) is an excellent marker for gastrointestinal stromal tumor (GIST) and acinic cell carcinoma. OCT3/4 is a pan-germ cell tumor marker, except yolk sac tumor. SALL4 is positive in various types of germ cell tumors, including yolk sac tumor. MUC4 (mucin-related antigen 4) is a sensitive and specific marker for low-grade fibromyxoid sarcoma. Langerin is a specific marker for Langerhans cells and their tumors. SOX11 is a sensitive marker for mantle cell lymphoma. New generation antibodies against anaplastic lymphoma kinase (ALK) are required to reliably demonstrate ALK gene translocation in pulmonary carcinomas. Lack of expression of succinate dehydrogenase B is seen in paragangliomas of the hereditary form and in the pediatric type of GIST. Antibodies against Trepenoma pallidum can facilitate the diagnosis of syphilis, whereas those against SV40 (simian virus 40) are helpful for diagnosis of BK virus infection and progressive multifocal leukoencephalopathy.
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PMID:Newly available antibodies with practical applications in surgical pathology. 2422 78

Regulated secretion is a conserved process occurring across diverse cells and tissues. Current models suggest that the conserved cargo receptor Tango1 mediates the packaging of collagen into large coat protein complex II (COPII) vesicles that move from the endoplasmic reticulum (ER) to the Golgi apparatus. However, how Tango1 regulates the formation of COPII carriers and influences the secretion of other cargo remains unknown. Here, through high-resolution imaging of Tango1, COPII, Golgi, and secretory cargo (mucins) in Drosophila larval salivary glands, we found that Tango1 forms ring-like structures that mediate the formation of COPII rings rather than vesicles. These COPII rings act as docking sites for the cis-Golgi. Moreover, we observed nascent secretory mucins emerging from the Golgi side of these Tango1-COPII-Golgi complexes, suggesting that these structures represent functional docking sites/fusion points between the ER exit sites and the Golgi. Loss of Tango1 disrupted the formation of COPII rings, the association of COPII with the cis-Golgi, mucin O-glycosylation, and secretory granule biosynthesis. Additionally, we identified a Tango1 self-association domain that is essential for formation of this structure. Our results provide evidence that Tango1 organizes an interaction site where secretory cargo is efficiently transferred from the ER to Golgi and then to secretory vesicles. These findings may explain how the loss of Tango1 can influence Golgi/ER morphology and affect the secretion of diverse proteins across many tissues.
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PMID:Tango1 coordinates the formation of endoplasmic reticulum/Golgi docking sites to mediate secretory granule formation. 3169 Jun 24