Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two-dimensional gel electrophoresis of acidic and basic [35S]methionine-labeled polypeptides derived from primary cultures of human retinal-pigment epithelial cells revealed about 850 proteins. By co-electrophoresis with highly purified, evolutionally conserved proteins, alpha-actinin, calmodulin, cytosol retinal-binding protein, alpha- and beta-tubulin, and vinculin (mass: 130 000 Da) were tentatively identified in the fluorograms. Quantification of greater than 100 of the excised radioactive spots by liquid scintillation counting revealed an estimated overall gel/gel and donor/donor variation of 40% (SEM, 21%), the latter for data on three to four donors 57 to 81 years old. Therefore, for a difference from normal to be significant (p less than or equal to 0.01), it would, on average, have to exceed 88% of the control mean for that protein. Putative glycoproteins were independently radiolabeled, with tritiated sugars as precursors. Glucosamine was incorporated most rapidly and with the highest specific activity. It labeled about 170 polypeptides. Fucose and N-acetylmannosamine, respectively, labeled 74 and 27 polypeptides. The glycoprotein label was maximal in about 16 very acidic proteins with apparent molecular masses between 50 000 and 150 000 Da. Parallel use of both a sugar and an amino acid label facilitates identification of proteins in two-dimensional gels.
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PMID:Two-dimensional electrophoresis of proteins from cultured human retinal-pigment epithelial cells: internal references, cataloging, and glycoproteins. 649 66

In a study of early neonatal infection, 278 babies had a blood culture and an alpha 1-acid glycoprotein (alpha 1-AGP) determination. There were significant differences between the mean (+/- SEM) levels of alpha 1-AGP in infants who were noninfected (26 +/- 1.3 mg/dl, n = 244), infected (81 +/- 11 mg/dl, n = 12) and proved to have sepsis (66 +/- 10 mg/dl, n = 22). In the 'noninfected' group, alpha 1-AGP levels increased with postnatal age. Increasing levels were seen on the 1st day with both increasing gestational age (15-34 mg/dl from less than 30 to greater than or equal to 38 weeks) and birth weight (17-42 mg/dl from less than 1,000 to greater than or equal to 4,000 g), irrespective of the infant's sex. Among the sepsis group, infants who died had lower levels than those who survived (19 mg/dl vs. 90 mg/dl).
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PMID:Alpha 1-acid glycoprotein in the neonate with and without infection. 686 Jul 14

The retina cognin (a glycoprotein isolated from the surface membrane of neural retina cells of chick embryos and postulated to mediate self-recognition and histogenetic association of retina cells) has been visualized by SEM on the surface of embryonic retina cells in vitro following immunolabeling of the cells with antibodies to the purified cognin and with polystyrene latex microbeads. Trypsin dissociation of retina tissue into separated cells resulted in cognin depletion from the cell surface; following incubation at 37 degrees C the cells regenerated the cognin. Regeneration was fastest and most abundant on cells from the youngest retinas examined; it declined markedly with the embryonic age of the cells, suggesting an age-dependent decrease in cell capacity for cognin formation. Evidence is discussed that the rate and amount of cognin regeneration on the cell surface are temporally-causally correlated with the capacity of the cells to reaggregate into retinotypic tissue. The results support the suggested role of the cognin in the mechanism of self-affinity and morphogenetic association of embryonic neural retinal cells.
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PMID:Age-dependent differences in cognin regeneration on embryonic retina cells: immunolabeling and SEM studies. 699 94

The protein binding of doxepin (DOX) and desmethyldoxepin (DDOX) were studied in serum and plasma samples from healthy volunteers and psychiatric patients. Binding was measured by equilibrium dialysis (16 hrs at 37 degrees) and drug concentrations by radioimmunoassay. In addition, albumin and alpha 1-acid glycoprotein concentrations of the samples were measured by radial immunodiffusion. The mean +/- SEM percentages of unbound DOX were: 20.4 +/- 1.2 and 15.9 +/- 1.2 in healthy subjects (n = 16) and patients (n = 15) respectively, and those of DDOX: 21.4 +/- 0.9 and 19.0 +/- 1.4 for healthy subjects and patients, respectively. There was a significant negative correlation between serum alpha 1-acid glycoprotein concentration and free fraction of DOX in both groups. In healthy subjects a significant negative correlation was also found between albumin concentrations and free fraction of both DOX and DDOX. Binding experiments with isolated protein fractions revealed that all of the total binding in plasma could be explained by binding to albumin and alpha 1-acid glycoprotein. The observed 2--4-fold interindividual variability in the free fractions of these drugs is probably less important than the much larger variability in the total serum concentrations.
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PMID:Protein binding of doxepin and desmethyldoxepin. 711 22

We have recently described an assay system for human peripheral blood megakaryocyte colony-forming unit cells (CFU-M) using an anti-platelet glycoprotein antiserum probe to define megakaryocyte colonies grown in vitro. This system was applied to study the nature and regulation of human bone marrow CFU-M. In the absence of a specific megakaryocyte growth-promoting factor, 12.4 +/- 3.0 (means +/- SEM) megakaryocyte colonies were cloned per 5 X 10(5) cells cultured. Colonies were present after 6 d of incubation reaching peak numbers between days 10 and 14 and slowly decreasing thereafter. Erythropoietin in concentrations of up to 4 U/ml failed to augment colony numbers. Also failing to enhance megakaryocyte colony plating efficiency were media containing burst-promoting activity and colony-stimulating activity. A medium conditioned by human embryonic kidney cells, which has been previously demonstrated to contain thrombopoietin, also had no effect on megakaryocyte colony numbers. In contrast, sera from three patients with severe aplastic anemia produced significant enhancement of CFU-M-derived colony formation in vitro. Both the number of megakaryocyte colonies present and the number of megakaryocytes per colony were increased in proportion to the final concentration of aplastic anemia serum. In the presence of 10% aplastic anemia serum, cultured megakaryocyte colony numbers were linear with respect to the number of bone marrow mononuclear cells plated suggesting a clonal origin of each of the colonies. This in vitro assay for bone marrow CFU-M is a reliable means by which to study the regulation of human megakaryocytopoiesis. Initial data suggest that megakaryocyte production is stimulated by a factor detectable in aplastic anemia serum that may be distinct from other known hematopoietic stem cell regulators.
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PMID:Regulation of human megakaryocytopoiesis. An in vito analysis. 727 69

The IFNs, alpha and gamma, have been shown to enhance the tumor-associated glycoprotein (TAG-72) on adenocarcinoma cells in vitro and in mice with human breast cancer xenografts, resulting in improved targeting of monoclonal antibody CC49. To determine the effect of IFN-alpha on biodistribution and tumor uptake of 131I-labeled CC49, patients with metastatic breast cancer were randomized to either receive or not receive IFN-alpha (3 million units daily for 14 days) by s.c. injection. Three days after beginning IFN-alpha, all patients received 10-20 mCi of 131I-CC49 (specific activity, 16.7 mCi/mg) i.v. Total-body Anger camera scans, along with total-body blood and plasma pharmacokinetics, were performed. Tumor biopsies were taken in all patients before and 48 h after IFN-alpha treatment. There were no significant differences in number of metastases imaged or whole-body, blood and plasma pharmacokinetics between IFN-alpha-treated and untreated patients. Quantitative immunohistochemistry on biopsy specimens from IFN-alpha-treated patients demonstrated a significant increase in mean +/- SEM TAG-72 expression (45.7 +/- 19.4%) compared to patients that were not given IFN-alpha (1.3 +/- 0.95%; P < 0.05). Although slight increases in the percent injected dose of 131I-CC49 in tumor occurred after IFN-alpha-treatment, the changes were not significant at the P < 0.05 level. These data suggest that IFN-alpha may be useful in enhancing TAG-72 antigen expression in vivo in humans, despite modest improvement in tumor uptake of CC49, possibly because of limited tumor access or other unknown factors.
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PMID:Enhanced TAG-72 expression and tumor uptake of radiolabeled monoclonal antibody CC49 in metastatic breast cancer patients following alpha-interferon treatment. 749 72

Glycoprotein hormone alpha-subunit (alpha SU) is a recognized product of clinically non-functioning, glycoprotein hormone-secreting and somatotroph adenomas but has not been studied systematically in corticotroph tumours. We have performed immunohistochemistry for alpha SU in a consecutive series of four corticotroph tumours causing Nelson's syndrome, three corticotroph macroadenomas, 12 corticotroph microadenomas and one adrenocorticotrophin-secreting bronchial carcinoid tumour. In addition we have assessed alpha SU secretion in vitro in corticotroph adenomas from two subjects with Cushing's disease and two subjects with Nelson's syndrome. Immunohistochemistry, performed after microwave treatment of sections to enhance antigen retrieval, demonstrated alpha SU positivity in 3/4 Nelson's tumours, 2/3 corticotroph macroadenomas, 7/12 microadenomas and one bronchial carcinoid. Eight of the 13 tumours positive for alpha SU were also immunostained after microwave pretreatment of sections for thyrotrophin (six positive), follicle-stimulating hormone (four positive), luteinizing hormone (three positive), beta-chorionic gonadotrophin (five positive), growth hormone (three positive) and prolactin (two positive) immunoreactivity. In vitro cell cultures of all four tumours studied secreted adrenocorticotrophin and three secreted alpha SU, with the variable presence of luteinizing hormone, follicle-stimulating hormone, thyrotrophin, growth hormone and prolactin, in basal culture. The alpha SU secretion was augmented by phorbol ester (160 +/- 15%, SEM, n = 3 wells; p < 0.01) and 8-bromo-cAMP (138 +/- 8%; p < 0.05) in one tumour. These data indicate that plurihormonality and, in particular, alpha SU elaboration and secretion by corticotroph tumours is more common than hitherto recognized. Possible mechanisms include abnormal or deregulated gene expression, autocrine or paracrine effects or a stem cell origin of tumour.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glycoprotein hormone alpha-subunit production and plurihormonality in human corticotroph tumours--an in vitro and immunohistochemical study. 754 79

Cardiovascular surgery for valve replacement led to a significant (p < 0.001) increase of plasma von Willebrand factor antigen level from 227% +/- 30.9 (x +/- SEM) recorded before surgery, to 397% +/- 40.7 at the end of the surgical procedure and the levels of this endothelia-derived glycoprotein remained high (427% +/- 38.9) 48 hours later. On the other hand plasma antithrombin III activity decreased from 85.4% +/- 8 before surgery, to 67.0% +/- 6 at the end of the surgical intervention and rose to 81.3% +/- 7, two days later. Lethal outcome occurred in a patient with initial low antithrombin III level (62%). These observations stress the importance of a thorough investigation of hemostatic variables in patients submitted to cardiovascular surgery.
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PMID:Plasma von Willebrand factor and antithrombin III in patients submitted to open heart surgery. 761 97

The hypothesis that the colonic epithelium is diffusely abnormal in ulcerative colitis was examined by comparing disease related responses in expression of markers of differentiation by colonic crypt cells to culture with and without butyrate. Cells were isolated from patients with normal colon (15), cancer (24), ulcerative colitis (19), or Crohn's disease (16). Alkaline phosphatase activities were measured in cell homogenates and the rate of glycoprotein synthesis assessed at the end of 24 hours of culture and expressed relative to the rate of protein synthesis as the G:P ratio. Alkaline phosphatase activities, but not G:P ratios, differed across the groups before and after 24 hour culture (p < 0.05), activities being lowest in the cancer group and highest in inflammatory bowel disease groups. Butyrate (1 mM) suppressed alkaline phosphatase activities in the cancer group by mean (SEM) of 17 (4) (p = 0.006) compared with no change in the other groups. Butyrate suppressed G:P ratios only in the cancer (6 (3)%, p = 0.03) and ulcerative colitis groups (5 (3)%, p = 0.04) and the changes in both were different (p < 0.05) from those in normal cells (increase of 10 (7)%). Changes in ulcerative colitis were different from those in Crohn's disease (p = 0.029). Responses were independent of the presence or absence of mucosal inflammation. These data confirm the diffuse nature of epithelial abnormalities in colorectal cancer. In ulcerative colitis, a different pattern of abnormality occurs, supporting the notion that the epithelium is also diffusely abnormal independent of mucosal inflammation.
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PMID:Colonic epithelium is diffusely abnormal in ulcerative colitis and colorectal cancer. 761 74

The effects of human recombinant insulin-like growth factor 1 (IGF-1) on the secretion, viability, and proliferation of dispersed human anterior pituitary adenomas secreting FSH, LH, and alpha-subunit (alpha-su) were examined in vitro over 4 h and 4 days. The acute effect of IGF-1 on secretion over 4 h was examined in four tumors secreting FSH, LH, and alpha-su. IGF-1 (100 nmol/L) reduced LH compared to control (100%) in one tumor (61%, P < 0.01), and three tumors remained unaffected. FSH and alpha-su secretion were insufficient to measure over 4 h. Nine tumors were studied over 4 days; relative to control, IGF-1 (100 nmol/L) increased FSH secretion in all seven tumors secreting FSH (28-266%, P < 0.05) and increased alpha-su secretion in all four tumors studied (36%, 63%, 91%, and 121%, P < 0.05). IGF-1 reduced LH secretion in four/nine tumors (13%, 23%, 32%, and 50%, P < 0.05). Dose response curves (1-100 nmol/L IGF-1) were performed on three tumors cosecreting FSH and LH. Stimulation of FSH was achieved with either 1 or 10 nmol/L IGF-1, a single tumor in which alpha-su was measured showed maximal stimulation at 10 nmol/L IGF-1, and one of three tumors showed LH inhibition with 100 nmol/L IGF-1. In situ viability of attached cells was assessed with fluorescein and propidium iodide in seven tumors. After 4 days' exposure to 100 nmol/L IGF-1, in situ viability was increased in five tumors (range 12-19%, 15 +/- 1.3% SEM, P < 0.05). The effects of IGF-1 on the adenoma cell proliferative S-phase fraction was determined in six tumors after 4 days of treatment using double immunostaining with bromodeoxyuridine incorporation for 1 h. In four/six adenomas that stained positive for bromodeoxyuridine in the controls (1-5.6%), the S-phase fraction was increased by 100 nmol/L IGF-1 [(range 2.1-10.6%, increase 90-220%) (P < 0.05)]. These results show that IGF-1 has differential effects on gonadotropins from human pituitary adenomas, stimulating intact FSH and alpha-su, inhibiting or being without effect on intact LH in vitro, and increasing both viability and number of tumorous glycoprotein-secreting cells entering into the S-phase of proliferation.
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PMID:Differential effects of insulin-like growth factor 1 on the hormonal product and proliferation of glycoprotein-secreting human pituitary adenomas. 769 62


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