Modulation of immune responses to allergens of house dust mite.
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Allergens↗
Biomedical subjects
L Guida
Publications and source records attributed to L Guida.
Carotid diameter and blood flow velocities in cerebral circulation in hypertensive patients.
BACKGROUND AND PURPOSE: The recent development of noninvasive techniques for the evaluation of the carotid arteries has focused attention on the study of arterial wall thickness to identify early lesions of vessels in patients at high risk for atherosclerosis, such as those with hypercholesterolemia, diabetes mellitus, and hypertension. METHODS: In a sample of 70 hypertensive patients without clinical evidence of target organ damage, we showed a thickening of the intimal plus medial layers compared with age- and sex-matched normotensive control subjects. In this sample we also studied the diameter of the carotid arteries by ultrasound imaging, and we studied flow velocities in common carotid, internal carotid, and middle cerebral arteries by Doppler technique. Pulsatility and resistance indexes were calculated. RESULTS: Absolute values of the carotid diameter were similar in the two groups (6.3 +/- 0.7 versus 6.0 +/- 0.8 mm); however, the ratio of diameter to blood pressure was significantly reduced in hypertensive compared with normotensive subjects (5.3 +/- 0.7 versus 6.5 +/- 0.8; P < .001 for mean blood pressure). Parietal stress was increased in the hypertensive subgroup and significantly correlated with arterial diameter in the normotensive group but not in the hypertensive group. No significant differences between the two groups were observed in blood flow velocities, with the exception of a slight significant increase of mean velocity in the internal carotid artery in hypertensive patients (37.5 +/- 9.1 versus 32.7 +/- 3.0 cm/s; P < .02). CONCLUSIONS: These results indicate that in addition to the degenerative changes of the common carotid wall, the diameter of the carotid artery and the relation to parietal stress show an early impairment in patients with uncomplicated hypertension.
Blood Flow Velocity↗
Synergy between dexamethasone and interleukin-5 for the induction of major histocompatibility complex class II expression by human peripheral blood eosinophils.
The hematopoietic growth factors interleukin-3 (IL-3), IL-5, and granulocyte-macrophage colony-stimulating factor (GM-CSF) regulate the survival, maturation, and activation of eosinophils. Corticosteroids in contrast have a negative effect both on the hematopoietic process and the function of eosinophils. We have unexpectedly observed synergy between IL-5 and glucocorticoids such as dexamethasone and hydrocortisone for induction of the MHC class II antigens HLA-DR and HLA-DP on eosinophils isolated from human blood. Similarly glucocorticoids enhanced GM-CSF and IL-3, but not interferon gamma (IFN gamma), induced expression of these antigens. Expression of a third MHC class II molecule, HLA-DQ, was not induced on eosinophils by any of the cytokines alone, but in one of three donors tested, IL-3 plus dexamethasone induced high levels of expression. Although cytokine-induced expression of the accessory molecule intercellular adhesion molecule 1 (ICAM-1) was partially inhibited by glucocorticoids, cytokine- and dexamethasone-treated eosinophils presented antigen more efficiently to a hemagglutinin peptide-specific T-cell clone than eosinophils treated with cytokine alone. These results highlight a potential new role for endogenous or exogenous glucocorticoid hormones in enhancing MHC class II expression by eosinophils.
Cells, Cultured↗
Self-aggregation of the transmembrane glycoprotein CD38 purified from human erythrocytes.
The 46 kDa human transmembrane glycoprotein CD38 is a multicatalytic enzyme exhibiting ADPribosyl cyclase, cyclic ADPribose hydrolase and NAD(+)-glycohydrolase activities at its extracellular domain. When CD38, purified to homogeneity from human erythrocyte membranes, was incubated with NAD+ or beta-mercaptoethanol, extensive aggregation took place. Addition of both compounds to CD38 led to the formation of still larger aggregates (over 300 nm), which were resistant to TCA precipitation. Extensive and stable CD38 self-aggregation was shown by, i) SDS-PAGE and autoradiography of the [32P]NAD(+)-incubated CD38, ii) SDS-PAGE followed by immunochemical detection of CD38 on the transblots, iii) direct electron microscopy on negatively stained CD38 samples. Self-aggregation of CD38 might be correlated with its putative function as a transducer of activation and proliferation signals in a number of hematopoietic cells.
ADP-ribosyl Cyclase↗
Dexamethasone up-regulates granulocyte-macrophage colony-stimulating factor receptor expression on human monocytes.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) are weak inducers of major histocompatibility complex (MHC) class II expression on purified human blood monocytes. The glucocorticoid dexamethasone synergizes with GM-CSF or IL-3 for the upregulation of HLA-DR, -DP and -DQ antigen mRNA and cell-surface expression by these cells. The purpose of the present study was to address the mechanism of dexamethasone action. We demonstrate that the capacity of dexamethasone to up-regulate GM-CSF-induced MHC class II expression correlates with the capacity to up-regulate GM-CSF receptor, but not the interferon-gamma (IFN-gamma) receptor, in a highly dose-dependent manner on monocytes. Although dexamethasone induces GM-CSF receptor expression, it does not confer responsiveness to IL-5, a cytokine that shares a common chain of its heterodimeric cytokine receptor signalling molecule with IL-3 and GM-CSF. Three other steroid hormones, beta-oestradiol, vitamin D3 and dehydroepiandosterone (DHEA), were also tested for their capacity to up-regulate MHC class II expression. All three mediators failed to enhance MHC class II expression or GM-CSF receptor expression on the surface of human monocytes. These experiments suggest that dexamethasone may act to up-regulate GM-CSF-induced MHC class II antigen expression on monocytes by up-regulating cytokine receptor expression.
Adult↗
A single protein immunologically identified as CD38 displays NAD+ glycohydrolase, ADP-ribosyl cyclase and cyclic ADP-ribose hydrolase activities at the outer surface of human erythrocytes.
The three ectoenzyme activities, NAD+ glycohydrolase, ADP-ribosyl cyclase and cyclic ADP-ribose hydrolase were purified to homogeneity from solubilized human erythrocyte membranes. The purification procedure involved three sequential chromatography steps on hydroxylapatite, immobilized Cu++ and immobilized anti-CD38 monoclonal antibody resins. The final step yielded a single 46 kDa protein displaying all three enzymatic activities. Since the protein bound specifically to the anti-CD38 resin, it was immunologically identified as CD38, a 46 kDa surface antigen involved in activation and proliferation of lymphocyte populations.
ADP-ribosyl Cyclase↗
Free ADP-ribose in human erythrocytes: pathways of intra-erythrocytic conversion and non-enzymic binding to membrane proteins.
We have previously identified free ADP-ribose (ADPR) as a normal metabolite in mature human erythrocytes. In this study the metabolic transformations of ADPR were investigated in both supernatants from erythrocyte lysates and intact erythrocytes, loaded with ADPR by means of a procedure involving hypotonic haemolysis and isotonic resealing. In both experimental systems, the main pathway was a dinucleotide pyrophosphatase-catalysed hydrolysis to yield AMP, which was readily converted into the adenylic and inosinic nucleotide pools. To a lesser extent, ADPR underwent conversion into a compound that was identified as ADP-ribulose (ADPRu), on the basis of m.s., n.m.r. spectroscopy and enzymic analysis. ADPRu was also susceptible to degradation by the dinucleotide pyrophosphatase, which was partially purified from erythrocyte lysates and characterized with respect to its substrate specificity. Isomerization of ADPR to ADPRu was markedly enhanced by ATP. Incubation of unsealed haemoglobin-free erythrocyte membranes with labelled ADPR did not cause any transformation of this nucleotide and resulted in its trichloroacetic acid- and formic acid-resistant binding to a number of membrane cytoskeletal proteins. These proteins include spectrin, glyceraldehyde 3-phosphate dehydrogenase (Ga3PDH), three proteins of molecular masses 98, 79 and 72 kDa, which apparently comigrate with bands 3, 4.1 and 4.2 respectively, and two additional proteins of molecular masses 58 and 41 kDa. Acid-resistant binding of ADPR, as well as of NAD+, to Ga3PDH was confirmed for the enzyme purified from human erythrocytes.
Adenine Nucleotides↗
Production and hydrolysis of cyclic ADP-ribose at the outer surface of human erythrocytes.
Hemoglobin-free membranes from human erythrocytes are able to convert beta-NAD+ to cyclic ADP-ribose, a calcium mobilizer as potent as inositol 1,4,5-trisphosphate. Identification of cyclic ADP-ribose was based on HPLC analyses and its Ca(2+)-mobilizing activity on sea urchin egg microsomes. Erythrocyte membranes also hydrolyze cyclic ADP-ribose to ADP-ribose. By comparing the cyclic ADP-ribose-synthesizing and -hydrolyzing activities on unsealed and right-side-out resealed ghosts, it can be concluded that both are localized at the extracellular side of the membrane. This is confirmed by the demonstration of both enzyme activities on the surface of intact human red cells. Identification of the two enzymes involved in cyclic ADP-ribose metabolism might suggest some physiological role of this nucleotide in red cells.
ADP-ribosyl Cyclase↗
Adenosine diphosphate ribulose in human erythrocytes: a new metabolite with membrane binding properties.
Incubation of ADPribose with yeast phosphoriboisomerase resulted in the formation of an adenylic nucleotide that was identified with ADPribulose by mass spectrometry. Synthesis of [32P]ADPribulose from [32P]NAD+ by the combined activities of commercial NAD+ glycohydrolase and phosphoriboisomerase allowed us to use it as a labeled internal standard throughout the procedure of purification from trichloroacetic acid extracts of human red blood cells. ADPribulose was purified by means of three sequential reverse phase HPLC separations and its concentration in human erythrocytes was estimated to be 0.11 +/- 0.1 microM. Unsealed erythrocyte ghosts did not transform ADPribulose, which bound to specific membrane proteins with a trichloroacetic and formic acid-resistant binding. The labeled proteins were identified as spectrin, bands 3, 4.1, 4.2 and Glyceraldehyde 3-phosphate dehydrogenase on the basis of their relative mobilities on SDS-PAGE.
Adenosine Diphosphate Ribose↗
3 alpha-Hydroxylated bile acid profiles in clinically normal cats, cats with severe hepatic lipidosis, and cats with complete extrahepatic bile duct occlusion.
Concentrations of 3 alpha-hydroxylated bile acids were measured in serum and urine of clinically normal (healthy) cats (n = 6), cats with severe hepatic lipidosis (n = 9), and cats with complete bile duct occlusion (n = 4). Bile acid concentrations were measured by use of a gradient flow high-performance liquid chromatography procedure with an acetonitrile and ammonium phosphate mobile phase and an in-line postanalytic column containing 3 alpha-hydroxy-steroid dehydrogenase and a fluorescence detector. Specific identification of all bile acid peaks was not completed; unidentified moieties were represented in terms of their elution time (in minutes). Significant differences in serum and urine bile acid concentrations, quantitative and proportional, were determined among groups of cats. Cats with hepatic lipidosis and bile duct occlusion had significantly (P > or = 0.05) greater total serum and urine bile acids concentrations than did healthy cats. The proportion of hydrophobic bile acids in serum, those eluting at > or = 400 minutes, was 1.9% for healthy cats, 3.3% for cats with lipidosis, and 5.4% for bile duct-obstructed cats. Both groups of ill cats had a broader spectrum of unidentified late-eluting serum bile acids than did healthy cats; the largest spectrum developed in bile duct-occluded cats.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Ultrastructural hepatocellular features associated with severe hepatic lipidosis in cats.
In this study, we compared hepatic ultrastructure in healthy cats, in cats with severe hepatic lipidosis, and in cats with experimentally induced, chronic, extrahepatic bile duct occlusion. Ultrastructural features unique to the lipidosis syndrome included an apparent reduction in number of peroxisomes and alteration in their morphologic features. The quantity of endoplasmic reticulum, Golgi complexes, and lysosomes was subjectively reduced, and paucity of cytosolic glycogen was observed. Bile canaliculi appeared collapsed because of cytosolic distention with lipid. Mitochondria were reduced in number and were markedly pleomorphic. Cristae assumed a variety of shapes, lengths, and orientations. Ultrastructural features of bile duct occlusion were similar to those described in other species and differed from those in cats with hepatic lipidosis.
Animals↗
Engineered erythrocytes as carriers and bioreactors.
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Animals↗
Presence and turnover of adenosine diphosphate ribose in human erythrocytes.
ADP-ribose was detected in human red blood cells (RBC) at 0.45 +/- 0.1 microM concentrations. These levels could be estimated after purification of ADP-ribose by means of three sequential HPLC fractionations of RBC extracts. Extraction was performed by sonication of RBC either in trichloroacetic acid, followed by centrifugation, or in carbonate-bicarbonate buffer, pH 10.0, followed by rapid ultrafiltration. Neither procedure of extraction caused artefactual formation of ADP-ribose. Prolonged incubation of intact RBC in isotonic buffer containing labeled orthophosphate resulted in the slow incorporation of radioactivity into ADP-ribose. Identification of the labeled ADP-ribose was confirmed upon incubation of the purified metabolite with nucleotide pyrophosphatase, yielding radioactive 5'-AMP and ribose 5-phosphate, while its exposure to a nonspecific deaminase resulted in the quantitative formation of labeled inosine diphosphate ribose.
Adenosine Diphosphate↗
The human squamous cervical carcinoma cell line, HOG-1, is responsive to steroid hormones.
Growth of the human squamous cervical carcinoma cell line, HOG-I, was stimulated in response to oestradiol in serum-containing and chemically defined medium. The oestradiol-stimulated growth could be inhibited by 4-OH tamoxifen, progesterone and medroxyprogesterone acetate; the last 2 compounds also inhibited basal cell growth in serum-containing and chemically defined media. The data are consistent with the sensitivity of human squamous cervical cancer to sex-steroid hormones and suggest that endocrine therapies may be of benefit in this disease.
Adult↗
Use of glutaraldehyde treated autologous human erythrocytes for hepatic targeting of doxorubicin.
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Colorectal Neoplasms↗
Mechanisms of perturbation of erythrocyte calcium homeostasis in favism.
Favism is an acute hemolytic anemia triggered by ingestion of fava beans in genetically susceptible subjects with severe deficiency of glucose-6-phosphate dehydrogenase (G6PD) activity. Erythrocytes from 10 favic patients had constantly and markedly increased calcium levels, as compared with values detected in 4 asymptomatic G6PD-deficient controls. Correspondingly, the calcium permeability of erythrocytes, estimated as the fraction of intracellular calcium exchangeable with externally added 45Ca2+, was invariably enhanced in favism and returned to normal patterns after several months from the acute hemolytic crisis. In favic patients, the levels of erythrocyte calcium ATPase activities showed wide variability, ranging from 2.0-12.9 mumol Pi/ml RBC/h, while control values in asymptomatic G6PD-deficient subjects were 10.62 +/- 2.03 mumol Pi/ml RBC/h. Analysis of the calcium ATPase in situ in erythrocyte membranes from favic patients showed the same molecular mass of 134 kD as observed in the control subjects. Exposure of G6PD-deficient erythrocytes in vitro to autoxidizing divicine, a pyrimidine aglycone strongly implicated in the pathogenesis of favism which leads to late accumulation of intracellular calcium, caused: (i) a marked inactivation of calcium ATPase, without changes in the molecular mass of 134 kD; and (ii) the concomitant loss of spectrin, band 3 and band 4.1, all known substrates of the calcium activated procalpain-calpain proteolytic system. Thus, the increased intraerythrocytic calcium apparently results in the degradation of calcium ATPase observed in some favic patients. It is proposed that both enhanced calcium permeability and a calcium-stimulated degradation of the calcium pump are the mechanisms responsible for the perturbation of erythrocyte calcium homeostasis in favism.
Calcimycin↗
Aluminium toxicity and binding to Escherichia coli.
The toxicity and binding of aluminium to Escherichia coli has been studied. Inhibition of growth by aluminium nitrate was markedly dependent on pH; growth in medium buffered to pH 5.4 was more sensitive to 0.9 mM or 2.25 mM aluminium than was growth at pH 6.6-6.8. In medium buffered with 2-(N-morpholino)ethanesulphonic acid (MES), aluminium toxicity was enhanced by omission of iron from the medium or by use of exponential phase starter cultures. Analysis of bound aluminium by atomic absorption spectroscopy showed that aluminium was bound intracellularly at one type of site with a Km of 0.4 mM and a capacity of 0.13 mol (g dry wt)-1. In contrast, binding of aluminium at the cell surface occurred at two or more sites with evidence of cooperativity. Addition of aluminium nitrate to a weakly buffered cell suspension caused acidification of the medium attributable to displacement of protons from cell surfaces by metal cations. It is concluded that aluminium toxicity is related to pH-dependent speciation [with Al(H2O)6(3+) probably being the active species] and chelation of aluminium in the medium. Aluminium transport to intracellular binding sites may involve Fe(III) transport pathways.
Aluminum↗
Liver targeting of autologous erythrocytes loaded with doxorubicin.
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Doxorubicin↗