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)

The toxicity due to interleukin-2 (IL-2) strongly resembles the clinical picture seen during septic shock. In septic shock activation of polymorphonuclear neutrophils (PMN) and the complement system contribute significantly to the pathophysiology of the condition. We therefore investigated whether similar events contributed to the toxicity observed with IL-2. Four patients received seven cycles of escalating dose IL-2 (18.0 to 72.0 X 10(6) IU m-2 day-1) and 16 were treated with 20 cycles of fixed dose IL-2 (12.0 or 18.0 X 10(6) IU m-2 day-1). Toxicity, as judged by hypotension (P = less than 0.005) and capillary leakage (fall in serum albumin 18.2 vs 4.0 gm l-1; P = less than 0.0005 and weight gain 4.0 vs 1.2 kg; P = less than 0.025) were worse with the esc. dose protocol. PMN became activated following IL-2 with mean peak elastase/alpha 1-antitrypsin (E alpha 1 A) and lactoferrin values of 212 (SEM = 37) and 534 (SEM = 92) ng ml-1 respectively occurring 6 h after the IL-2. Peak values for the esc. dose IL-2 group being generally higher than 500 ng ml-1. Activation of the complement cascade was evidenced by a dose dependent elevation of peak C3a values (fixed dose 9.1 (SEM = 0.6); esc. dose 25.7 (SEM = 6.33); P = less than 0.005) on day 5 of IL-2. There was a significant correlation between C3a levels and the degree of hypotention during the first 24 h after IL-2 (r = 0.91) and parameters of capillary leakage such as weight gain and fall in serum albumin (r = 0.71). These data suggest that activation of PMN initiates endothelial cell damage which subsequently leads to activation of the complement cascade. This latter system then contributes to the haemodynamic changes and capillary leakage seen in IL-2 treated patients.
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PMID:The activation of polymorphonuclear neutrophils and the complement system during immunotherapy with recombinant interleukin-2. 173 48

The interaction of lactoferrin (Lf) with Aeromonas hydrophila (n = 28) was tested in a 125I-labeled protein-binding assay. The mean per cent binding values for human Lf (HLf) and bovine Lf (BLf) were 13.4 +/- 2.0 (SEM), and 17.5 +/- 2.7 (SEM), respectively. The Lf binding was characterized in type strain A. hydrophila subsp. hydrophila CCUG 14551. The HLf and BLf binding reached a complete saturation within 2 h. Unlabeled HLf and BLf displaced 125I-HLf binding in a dose-dependent manner, and more effectively by the heterologous (1 microgram for 50% inhibition) than the homologous (10 micrograms for 50% inhibition) ligand. Apo- and holo-forms of HLf and BLf both inhibited more than 80%, while mucin caused approx. 50% inhibition of the HLf binding. Various other proteins (including transferrin) or carbohydrates did not block the binding. Two HLf-binding proteins with an estimated molecular masses of 40 kDa and 30 kDa were identified in a boiled-cell-envelope preparation, while the unboiled cell envelope demonstrated a short-ladder pattern at the top of the separating gel and a second band at approx. 60 kDa position. These data establish a specific interaction of Lf and the Lf-binding proteins seem to be porins in A. hydrophila.
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PMID:Specific binding of lactoferrin to Aeromonas hydrophila. 177 17

Lactoferrin (LF) was isolated from human milk by serial procedures of 45% ammonium sulfate precipitation, CM Sephadex C-50 ion-exchange chromatography, Sephadex G-100 gel filtration, and Cu-affinity chromatography, in which 59Fe lactoferrin was used as the tracer. The recovery of LF from human milk was 3.3%. LF from human milk was a single component having a molecular weight of 78k on SDS-PAGE, and showed pI 8.02 by isoelectric focusing on slab gel. The LF concentration was measured by rocket immunoelectrophoretic assay using anti-human LF antiserum in human colostrum and milk, from 1 to 60 days after parturition (125 samples). The LF concentrations in colostrum (1-3 days of puerperium, n = 35), the transitional milk (4-7 days, n = 60), and mature milk (20-60 days, n = 30) were 6.7 +/- 0.7, 3.7 +/- 0.1, and 2.6 +/- 0.4 (mean +/- SEM) g/liter, respectively. Both the LF and total protein (TP) concentrations showed significantly inverse correlations with the days after parturition (p less than 0.001). The lactoferrin/total protein ratio (LF/TP) in the mature milk (16.1 +/- 1.4%) was significantly less than that in the colostrum (20.4 +/- 1.2%, p less than 0.05) and the transitional milk (21.4 +/- 0.9%, p less than 0.05). Furthermore, iron concentration (Fe) in human milk was also measured by the internal standard technique of the spiked method on atomic absorption, and the lactoferrin iron saturation (LS%) was calculated. Neither Fe nor LS% had significant difference among these three stages of the lactation. The means (n = 125) of Fe and LS% were 60.6 +/- 5.4 micrograms/100 ml and 11.8 +/- 1.1%, respectively. However, significant correlation was observed between LF and Fe (p less than 0.005) or between LF/TP and both of Fe (p less than 0.05) and TP (p less than 0.001) in the mature milk. These results suggest that the mechanism stimulating the synthesis and secretion of LF is different from those of other proteins and LF can play variable roles in iron nutrition of babies at the different stages of lactation.
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PMID:Concentrations of lactoferrin and iron in human milk at different stages of lactation. 209 25

Iron absorption from human milk and infant formula has received much attention, but experimental design problems have been common. In our study, iron retention from human milk, milk-based infant formula (IF) with and without supplemental ferrous sulfate, and IF supplemented with either human or bovine lactoferrin (Lf) was evaluated in infant rhesus monkeys. The exchange of 59Fe (III) Cl3 between the whey, casein, and fat fractions required up to 72 h to reach the same distribution as intrinsic iron, depending on the type of diet. Infant monkeys were intubated with labeled human milk or IF and counted in a whole body counter. Each infant received all five diets and was also intubated with a reference dose of 55Fe (II) ascorbate. There was no significant difference in iron retention (mean +/- SEM) from the experimental diets: human milk 32.5 +/- 5.1%; IF 32.1 +/- 8.0%; IF + Fe 23.0 +/- 3.9%; IF + human Lf 23.5 +/- 3.3%; IF + bovine Lf 22.7 +/- 4.9%. Therefore, infant monkeys absorb and retain iron similarly from human milk and infant formula. Supplementation of infant formula with human or bovine Lf resulted in similar iron retention to that of ferrous sulfate-supplemented infant formula.
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PMID:Iron retention from lactoferrin-supplemented formulas in infant rhesus monkeys. 231 47

Gastrin-releasing peptide (GRP), the 27 amino acid mammalian form of bombesin, was studied in human inferior turbinate nasal mucosa. The GRP content of the mucosa measured by radioimmunoassay was 0.60 +/- 0.25 pmol/g tissue (n = 9 patients; mean +/- SEM). GRP-immunoreactive nerves detected by the immunogold method of indirect immunohistochemistry were found predominantly in small muscular arteries, arterioles, venous sinusoids, and between submucosal gland acini. 125I-GRP binding sites determined by autoradiography were exclusively and specifically localized to nasal epithelium and submucosal glands. There was no binding to vessels. The effects of GRP on submucosal gland product release were studied in short-term explant culture. GRP (10 microM) significantly stimulated the release of the serous cell-specific product lactoferrin, and [3H]glucosamine-labeled glycoconjugates which are products of epithelial goblet cells and submucosal gland cells. These observations indicate that GRP released from nerve fibers probably acts on glandular GRP receptors to induce glycoconjugate release from submucosal glands and epithelium and lactoferrin release from serous cells, but that GRP would probably not affect vascular permeability.
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PMID:Gastrin-releasing peptide in human nasal mucosa. 231 84

Previous studies with neutrophils from newborn infants compared to neutrophils from healthy adults have documented increased respiratory burst activity including enhanced superoxide anion (O2-) production, nitroblue tetrazolium dye reduction, and hexose monophosphate shunt activity. To investigate the biochemical basis for these observations, we examined oxidative metabolism in membrane-rich fractions of neutrophils. Neutrophils from cord blood of vaginally delivered term infants or healthy adults were disrupted by nitrogen cavitation and subcellular fractions collected on discontinuous sucrose density gradients. Subcellular fractions of newborn neutrophils separated in a fashion identical with samples from healthy adults. Activity of alkaline phosphatase, a plasma membrane marker, was increased 4- to 5-fold in disrupted cells free from nuclei (postnuclear supernatant) as well as plasma membrane fractions from newborn samples compared to those from healthy adults. Content of lactoferrin, a specific granule marker, was decreased in postnuclear supernatants but equivalent in specific granule fractions of newborn cells compared to those from adults. No differences were noted in myeloperoxidase content of postnuclear supernatants or any other subcellular fraction. Plasma membrane fractions from phorbol myristate acetate-stimulated cord blood neutrophils made significantly more O2- than samples from adults (newborn 32.9 +/- 8.1 nmol O2-/min/mg protein mean +/- SEM, n = 3 versus adult 10.8 +/- 4.2, n = 3; p less than 0.05). Plasma membrane-rich fractions were also collected by the technique of differential centrifugation and kinetic parameters of the NADPH-dependent oxidase enzyme(s) were measured for vaginally delivered newborn and adult samples.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increased activity of the respiratory burst in cord blood neutrophils: kinetics of the NADPH oxidase enzyme system in subcellular fractions. 302 58

Cell-associated lactoferrin (Lf) was analyzed using a new method involving cell permeabilization, indirect immunofluorescence staining, and flow cytometry. Statistical techniques to evaluate the results for percentage of positive cells, relative fluorescence and homogeneity of Lf distribution were also devised. Most normal adult neutrophils (97.1 +/- 0.3% (SEM), range 92.7-99.6%, n = 41) had brilliant fluorescence homogeneously distributed among the cells. There was significantly greater homogeneity of neutrophil Lf distribution in post-menopausal than pre-menopausal females. In chronic myelogenous leukemia (n = 13) and cord blood (n = 7), fractions of Lf-positive neutrophils were decreased (77.3 +/- 7.5%, range 13.3-96.3%; 71.4 +/- 9.3, range 32.0-95.6%, respectively). Normal monocyte-rich isolates had moderate fluorescence (28.7 +/- 3.6%, range 9.3-76.8%, n = 22). Among blood lymphocyte-rich preparations, 13.1 +/- 1.3% of cells had weak positivity (range 4.9-26.6%, n = 19); monoclonal B and T lymphocytes had similar parameters. No other cells had detectable Lf. Our results were significantly correlated with those obtained manually (r = 0.98, P less than 0.001), and are consistent with Lf quantity and distribution determined using other methods.
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PMID:Assessment of total immunoreactive lactoferrin in hematopoietic cells using flow cytometry. 328 Jun 85

Generation of oxygen metabolites is an important component of the neutrophil's armamentarium against microbes. Production of superoxide anion (O2-) and generation of hydroxyl radical (OH) were measured in neutrophils from cord blood of 12 vaginally delivered, term newborn infants and 12 adults after stimulation with phorbol myristate acetate (PMA) and opsonized zymosan. With either stimulus, generation of OH was relatively less than production of O2- for all infants studied. This discrepancy might be related to abnormal release or diminished cell content of a cofactor necessary for production of OH from O2-. Since both lactoferrin (LF) found in specific granules and myeloperoxidase (MPO) found in azurophilic granules have been shown to enhance OH generation, we compared degranulation of both granule types in response to PMA and opsonized zymosan and total neutrophil content of MPO, LF, and lysozyme in cord blood and adult neutrophils. Degranulation, even after pretreatment with cytochalasin B, was the same for newborn and adult neutrophils. Content of MPO was identical (adult, 204 +/- 24 A units, mean +/- SEM, n = 9; newborn, 201 +/- 21, n = 9) but lysozyme was mildly diminished (adults, 111 +/- 10 A units; newborn, 89 +/- 6, n = 9, p less than 0.05), and lactoferrin was moderately decreased (adult, 89.0 +/- 7.3 micrograms/mg cell protein, n = 11; newborn, 43.2 +/- 7.0, n = 11, p less than 0.005). Generation of OH in response to PMA and LF content were measured in seven cord blood-adult control pairs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oxidative metabolism of cord blood neutrophils: relationship to content and degranulation of cytoplasmic granules. 609 99

Complement (C) activation, neutropenia, and mild pulmonary dysfunction attend hemodialysis (HD) with cellophane [for example, cuprophan (Cu)] membranes. While usually asymptomatic, these phenomena may cause distress in patients with cardiopulmonary disease, and "start-up" symptoms of HD might be mediated by C-stimulated granulocytes (PMNs). Cellulose acetate (CA) hemodialysis membranes have been devised and claimed more blood compatible than Cu. In a blinded series of HD patients, pruritus, fatigue, and sense of well-being were each scored statistically more favorably by the patients during HD with CA than during HD with Cu (P less than 0.05). Postulating that less C activation might underlie the benefit, we showed that neutropenia was less severe with CA (nadir 77.6% of initial count, +/- 4 SEM) than with Cu (38.3% +/- 2.9; P less than 0.01). In vitro, incubation of CA membranes with plasma led to less C3 conversion (20% vs. 40%), less PMN aggregating activity (5.9 ZAP units vs. 36.3) and less decrement in CH50 (6.5% vs. 22%) than like incubations of Cu. C activation was also less potent in vivo: During HD plasma C3a rose from a mean 401 ng/ml to a peak 6,325 in patients on Cu dialyzers, but from 426 to only 3,637 in patients on CA devices (P less than 0.05). Time-course studies suggested CA was initially as potent an activator as Cu but rapidly lost ability to activate C, possibly because of saturation of C3b binding sites. As an index of PMN activation, we also assayed plasma lactoferrin and found levels significantly higher during Cu than CA dialysis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Symptoms and activation of granulocytes and complement with two dialysis membranes. 660 68

Lactoferrin and pancreatic stone protein (PSP) are thought to be closely related to pancreatic stone formation in chronic pancreatitis. However, the results reported so far have not been conclusive. To reevaluate the pathological importance of PSP in chronic pancreatitis, compared to lactoferrin, levels of PSP were determined by applying an immunoassay specific to PSP to pure pancreatic juice taken from a total of 52 patients. The patients consisted of 16 controls, 19 chronic pancreatitis patients (13 noncalcified and 6 calcified), and 17 probable cases of pancreatitis. The monoclonal antibody PSP antagonist used in the study recognizes both forms of the protein, PSP S1 and S2-5, with equal effectiveness. No significant reduction of PSP was observed in either calcified (mean +/- SEM, 111 +/- 30 micrograms/mg and 24 +/- 3 micrograms/mg protein) or noncalcified (305 +/- 133 and 97 +/- 47) chronic pancreatitis patients compared with controls (85 +/- 23 and 34 +/- 16). PSP levels did not decrease, at least not in the complete forms of the protein found in chronic pancreatitis. PSP antibody and assay results indicated that a reduction of PSP S2-5 alone could not be ruled out in chronic pancreatitis either.
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PMID:Pancreatic stone protein and lactoferrin in human pancreatic juice in chronic pancreatitis. 771 37


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