Cancer screening in otorhinolaryngology.
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France↗
Biomedical subjects
L Calabrese
Publications and source records attributed to L Calabrese.
Detecting alcohol use disorders in the severely mentally ill.
The frequent co-occurrence of alcoholism with serious mental illnesses ("dual diagnosis") necessitates that clinicians are able to recognize its presence in people with disabling mental illnesses. This study demonstrates that professionals often miss the diagnosis, but that their ability to detect alcoholism can be greatly enhanced by the use of a simple screening tool. Members of an urban psychosocial rehabilitation program who received psychiatric treatment in an affiliated outpatient clinic were interviewed after their clinic therapists and rehabilitation counselors had been asked questions pertaining to their general health and substance use. The members were interviewed with two screening tests, the CAGE and the SMAST, and a clinical DSM-III-R diagnosis of alcohol use disorder was established. Both the SMAST and CAGE had good sensitivity and the addition of a screener enhanced the clinicians' ability to detect alcohol use disorders.
Adult↗
Investigation of the integration process of dental implants by means of a numerical analysis of dynamic response.
OBJECTIVES: The aim of this work was to present a preliminary numerical analysis of the integration process of dental implants using a finite element simulation of the dynamic response following impulse excitation. Assessment of the osseointegration process has been previously examined using a numerical approach by calculating the natural frequency of a cantilever attached to the implant. The methodology adopted in this work allows a direct measurement of the implant response following impulse loading and avoids the addition of a bulky cantilever set-up. METHODS: The geometric configuration was obtained by averaging the coordinate data from tomographic scans of 14 mandibles. The materials properties were approximated from experimental analysis performed on trabecular and cortical bone tissue. A load was applied to the top of the implant in one direction resulting in an initial displacement. The implant was then freed and allowed to vibrate over approximately 10 cycles. Three fixity conditions were assumed by changing the properties of the surrounding bone ranging from full integration to a poorly integrated implant typical of the situation during bone healing following surgery. The results of the three fixity conditions were compared by calculating the fundamental displacement amplitudes and frequencies of the vibrating impact. RESULTS: The calculated results indicated that the implant vibrated at a predominant frequency when partially integrated with a displacement principally in the direction of the applied impulse. However, when the implant was fully integrated a more complex vibration pattern ensued, suggesting the superposition of two or more fundamentals. SIGNIFICANCE: Attention has been paid to the formulation of the numerical model for validation purposes as well as a reliable reference for the optimum interpretation of the experimental data. In this way it was possible to establish a simulation procedure to investigate the response of the tissues surrounding the implant and their properties at different stages of healing. It should be pointed out that the numerical procedures represented a valid preliminary approach to the problem and were capable of indicating a guide to the optimum design of the experimental apparatus for measurement of displacement and frequency in vivo.
Alveolar Process↗
Characterization of Cu,Zn superoxide dismutase from the bathophile fish, Lampanyctus crocodilus.
Cu,Zn SOD from the bathophile teleost Lampanyctus crocodilus (LSOD) shows a high degree of homology with the sequence of the enzymes from other teleostean fish species. The catalytic properties of LSOD are very similar to those of the bovine enzyme, albeit with higher sensitivity to thermal denaturation. The apparent molecular mass of LSOD (37.6 KDa) is higher than the other Cu,Zn SOD variants studied. The aminoacid sequence of LSOD reveals interesting substitutions compared to the bovine enzyme. These are discussed in view of the particular environmental conditions to which L. crocodilus is adapted.
Amino Acid Sequence↗
Oral leukoplakias: to treat or not?
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Chemoprevention↗
Ceruloplasmin impairs endothelium-dependent relaxation of rabbit aorta.
This study evaluated the effects of ceruloplasmin, the copper-containing blue oxidase of vertebrate plasma, on the relaxation of rabbit aortic rings after endothelial release of nitric oxide (NO). Ceruloplasmin at physiological, i.e., micromolar, concentrations inhibited relaxation of rabbit aorta induced by endothelium-dependent agonists like acetylcholine or ADP, whereas it was ineffective toward vasodilation due to direct stimulation of smooth muscle cells by nitroglycerin. The effect was reversible and specific for native, fully metalated ceruloplasmin, since relaxation was not impaired by the heat-treated or metal-depleted derivatives. A trapping mechanism, involving a direct interaction of NO or other NO-containing species (like nitrosothiols and iron-dinitrosyls) with the copper sites and/or with the free thiol of ceruloplasmin, could be safely excluded on the basis of spectroscopic and chemical analyses of the protein exposed to authentic NO, nitrosothiols, or iron-dinitrosyls. The data presented in this paper constitute the first evidence of impairment of the endothelium-dependent vasodilatation by a plasma protein and may shed some light on the still uncertain physiological role of ceruloplasmin.
Acetylcholine↗
[Endometriosis of the abdominal wall. Clinical case and review of literature].
The authors report a clinical case of endometriosis the abdomen rectum muscle, in woman 28 years old, after a cesarean section delivery. On the basis of literature on the topic, the following are taken into consideration, the incidence, the pathogenesis, the clinical characteristics of this kind of pathology and the aspects which might facilitate the diagnostic approach and correct therapeutic to be given or follow. Parietal endometriosis is an extremely rare disease with incidence in feminine population of 0.03-1%. The pathogenesis is still ill-known. Lack of the classical symptoms and the unusual site can make diagnosis difficult. Pathognomonics but not always present are the presence of tumescence palpable of the abdominal wall near or proximity of preceding surgical scar, the cyclic character of painful symptomatology, the augmentation of volume and the bleeding in period menstrual or premenstrual. The ultrasonography, the computerized axial tomography, the nuclear magnetic resonance can facilitate the preoperative diagnosis but they do not always furnish reports of certainty. The aspirate-needle in ultrasonography control can furnish one of orientation diagnosis. The diagnosis of certainty is founded on the histologic examination after biopsy or excision. The treatment of the abdominal wall endometriosis is surgically essential. The excision of tumescence, easy usually, it is the only means to obtain the definitive recovery. The medical therapy postoperative is adjuvant in the treatment of unrecognized pelvic centres of endometriosis.
Adult↗
Amino acid sequence of chicken Cu, Zn-containing superoxide dismutase and identification of glutathionyl adducts at exposed cysteine residues.
The copper, zinc-containing superoxide dismutase electromorphs from chicken erythrocytes have been isolated, their complete amino acid sequence determined and the identity of the protein moieties established. All electromorphs are constituted by a polypeptide chain made of 153 amino acid residues, corresponding to a molecular mass of 15,598 Da. Accurate molecular mass determination by electrospray mass spectrometry of the separated electromorphs unequivocally proved that, in the chicken superoxide dismutase, either one or two cysteine residues/subunit are involved in a mixed disulfide with glutathione. The same post-translational modification has been proven to occur in human superoxide dismutase. A different rate of S-thiolation by endogenous glutathione was also demonstrated to be responsible for charge heterogeneity in cells. Effect of this modification on the catalytic and molecular properties of superoxide dismutases, and possible mechanisms for the S-thiolation process, were also investigated and discussed.
Amino Acid Sequence↗
Reconstitution of ceruloplasmin by the Cu(I)-glutathione complex. Evidence for a role of Mg2+ and ATP.
The copper-glutathione complex (Cu(I)-GSH) efficiently acted in vitro as the source of Cu(I) in the reconstitution of apoceruloplasmin. Copper was found to reinstate in the various sites in a multistep process, with metal entry into the protein in a first phase, and a second step involving conformational changes of the protein leading to the recovery of the native structural and functional properties. This latter phase was found to be strongly facilitated by Mg2+ or Ca2+ and by ATP. Both Mg2+ and ATP had to be present for optimal reconstitution. These results may shed some light on the mechanisms governing the biosynthesis of ceruloplasmin in vivo. Cu(I)-GSH was the only complex able to reconstitute ceruloplasmin at neutral pH. Glutathione may thus function to shuttle the metal from the membrane copper pump, as the Wilson disease ATPase, and ceruloplasmin in the secretory compartments of the cell. The finding that ceruloplasmin acquires the native conformation after metal entry through a complex pathway triggered by Mg2+ and ATP suggests that they may act as physiological modulators of this process in vivo.
Adenosine Triphosphate↗
Divalent cation binding to ceruloplasmin.
Binding of calcium to human and sheep ceruloplasmin was investigated by metal substitution with manganese and competitive displacement of bound manganese by calcium monitored by electron paramagnetic resonance spectroscopy. The Kd for calcium was found to be 1.4 mM. Magnesium also bound to ceruloplasmin, with Kd = 0.3 and 0.7 mM for the human and sheep protein, respectively. The thermal stability of ceruloplasmin, as studied by differential scanning calorimetry, was affected by calcium but not by magnesium. A considerable increase of the Tm value, from 73.8 to 83.1 degrees C, was observed for sheep ceruloplasmin in the presence of calcium. The Tm value of the human protein was only slightly altered by calcium (from 85.1 to 87 degrees C). The interaction of ceruloplasmin with the chromatographic material used for its isolation, Sepharose 4B derivatized with chloroethylamine, was weakened by calcium. This allowed us to set up a novel purification scheme that made it possible to efficiently isolate ceruloplasmin and prothrombin from plasma with the same single-step chromatography.
Animals↗
Direct bone formation on sand-blasted titanium implants: an experimental study.
Surface modifications of an implant have been demonstrated to be important in influencing the tissue reactions around the implant. Recently, osteoblasts have been shown to be capable of laying down a mineralized matrix in direct contact with the titanium surface. The aim of the present study was to analyse the early bone responses to titanium implants with an aluminium dioxide sand-blasted surface. Microscopical analysis showed that in the first week it was possible to observe the presence of mineralized bone in direct contact with the metal surface, while in other portions of the interface, osteoblasts were seen at the implant surface. These results were confirmed in the 2 and 4 wk observations. Our results could help to explain the increased removal torque forces reported in the literature concerning sand-blasted implants.
Animals↗
The discharge mechanism of acontial nematocytes involves the release of nitric oxide
The events which trigger the activation of nematocytes are still poorly understood, and no evidence has been presented so far on either the nature of the activatory signal for the nematocyte or the transduction mechanism. In this paper, we present evidence for a role of NO in the discharge of acontial nematocytes. A citrulline-forming enzymatic activity, significantly decreased by the NO synthase inhibitor Nomega-nitro-l-arginine (l-NNA) and by the Ca2+-chelating agent EGTA, was found in the acontial tissue of Aiptasia diaphana. Staining for NADPH diaphorase suggested that NO synthase is localized in supporting cells surrounding the nematocytes. The ability of K+ to induce the discharge of nematocytes in situ could be abolished by preincubation of acontia with l-NNA and restored by addition of excess l-arginine. Direct measurements on K+-induced discharging nematocytes in situ confirmed that NO was released by stimulated acontia. Both in situ and isolated acontial nematocytes promptly discharged when perfused with an aqueous solution of NO. The responsiveness to NO of isolated nematocytes was not abolished in Ca2+-free medium or by treatment with La3+, a well-known Ca2+ channel inhibitor. Since the discharge of in situ nematocytes is known to be Ca2+-dependent, it is proposed that activation of in situ acontial nematocytes is triggered by a Ca2+-dependent release of NO from supporting and/or sensory cells.
Journal Article↗
Effect of ceruloplasmin on 6-hydroxydopamine oxidation.
The effects of ceruloplasmin, a blu copper-containing serum glycoprotein, on the oxidation of the neurotoxin 6-hydroxydopamine in several chemical environments were studied. The spontaneous autoxidation of 6-hydroxydopamine proceeded by a free radical chain reaction involving O2-. and produced the corresponding chromogen 6-hydroxydopaminequinone and hydrogen peroxide. The process was accelerated in the presence of horse plasma ceruloplasmin. Yields of hydrogen peroxide in the presence of ceruloplasmin were significantly less than those measured in its absence. This is the first evidence of oxidase activity of ceruloplasmin toward a natural substrate, the 6-hydroxydopamine.
Animals↗
Double-blind, placebo-controlled multicenter trial using chimeric monoclonal anti-CD4 antibody, cM-T412, in rheumatoid arthritis patients receiving concomitant methotrexate.
OBJECTIVE: To evaluate the clinical response to and safety of single and repeat doses of a chimeric anti-CD4 monoclonal antibody, cM-T412, in patients with rheumatoid arthritis (RA) concomitantly treated with a stable regimen of low-dose methotrexate. METHODS: Sixty-four patients with refractory RA, who were already receiving stable doses of methotrexate, were randomized into a multicenter, double-blind, placebo-controlled trial to receive 3 monthly treatments with either a placebo, or 5, 10, or 50 mg cM-T412, given intravenously. RESULTS: Using > or = 50% improvement in swollen joint counts as a criterion for clinical response, 13%, 13%, 18%, and 13% of patients receiving 50, 10, or 5 mg cM-T412, or the placebo, respectively, exhibited a clinical response at 3 months of therapy. Using > or = 50% improvement in tender joint counts as a measure of clinical efficacy at 3 months, 19%, 13%, 12%, and 6% of patients receiving 50, 10, or 5 mg cM-T412, or the placebo, respectively, exhibited a clinical response. "Flu-like" symptoms (fever, chills, rigor) within 24 hours of the infusion occurred more frequently in the groups receiving 50-mg (29%) and 10-mg (31%) doses of cM-T412 than those receiving 5 mg cM-T412 (12%) or the placebo (13%). Significant CD4+ T cell depletion occurred in the 50-mg group (mean of 353 CD4+ T cells/mm3 at 6 months versus 856 CD4+ T cells/mm3 at baseline). All patients were followed up for 12 months after the final treatment; no opportunistic infectious complications occurred. CONCLUSION: Treatment with cM-T412 in this cohort of RA patients who were also taking methotrexate was not associated with clinical efficacy or enhanced toxicity from infectious complications, despite significant peripheral CD4+ T cell depletion.
Adult↗
Modulation of the redox state of the copper sites of human ceruloplasmin by chloride.
Incubation of human ceruloplasmin with physiological concentrations of chloride at neutral pH invariably caused dramatic changes of both the spectroscopic and the functional properties of the protein. The optical intensity at 610 nm increased up to 60%, with a concomitant decrease at 330 nm and the appearance of new bands between 410 and 500 nm. Signals previously undetectable appeared in the EPR spectrum. On the basis of computer simulations, they were interpreted as stemming from an oxidized type 1 copper site and from a half-reduced type 3 copper pair. Removal of chloride completely restored the original optical and EPR lineshapes. Hydrogen peroxide, added to ceruloplasmin in the presence of chloride, was able to capture the electron of the half-reduced type 3 site and to yield a protein insensitive to subsequent removal and readdition of the anion. As a whole, the spectroscopic data indicate that a blue site is partially reduced in the resting protein and that, upon binding of chloride, human ceruloplasmin undergoes a structural change leading to displacement of an electron from the reduced type 1 site to the type 3 site pair. Chloride dramatically affected the catalytic efficiency of human ceruloplasmin. At neutral pH, the anion was an activator of the oxidase activity, being able to enhance up to tenfold the catalytic rate. At pH < 6, in line with all previous reports, chloride strongly inhibited the activity. At intermediate pH values, i.e., around 6, the effect was composite, with an activating effect at low concentration and an inhibitory effect at higher concentration. Since chloride is present at very high concentrations in the plasma, these results suggest that human ceruloplasmin is, in the plasma, under control of this anion.
Binding Sites↗
Comparative study of ELISA and indirect immunofluorescence for the detection of anti-neutrophil cytoplasmic antibodies. Evaluation of the SCIMEDX/EURO Diagnostica ELISA assay in a clinical setting.
This study evaluates the performance of a commercial ELISA assay for detection of anti-neutrophil cytoplasmic antibodies (ANCA). Anti-proteinase 3 (anti-PR3) and anti-myeloperoxidase (anti-MPO) ELISA by (SCIMEDX/EURO Diagnostica, Denville, NJ) were compared with the indirect immunofluorescence (IIF) method using ethanol-fixed neutrophils. Three hundred sixty serum samples were examined. There was complete correlation of results in 357 (99.2%) cases between cANCA pattern and anti-PR3 results, and in 356 (98.9%) cases between pANCA pattern and anti-MPO ELISA results. The specificity of ELISA for detection of vasculitis was 95.7% and sensitivity was 60%, whereas for IIF, they were 95.7% and 65%, respectively. The ELISA showed good reproducibility with interassay variation (CV), ranging from 7.1% to 13.2%. Our results show that SCIMEDX/EURO Diagnostica ELISA for ANCA is a reliable and reproducible method that is as good as IIF for detection of ANCA.
Antibodies, Antineutrophil Cytoplasmic↗
Molecular modeling and electrostatic potential calculations on chemically modified Cu,Zn superoxide dismutases from Bos taurus and shark Prionace glauca: role of Lys134 in electrostatically steering the substrate to the active site.
The three-dimensional structure of Cu,Zn superoxide dismutase (SOD) from the shark Prionace glauca was homology modeled on the structure of the bovine enzyme used as a template. Shark SOD displays the conservative substitution of one of the residues involved in the electrostatic guidance of superoxide toward the active site of the enzyme, i.e., Lys134, which is replaced by arginine. The association rate, calculated by brownian dynamics simulations incorporating electrostatic terms, and the enzyme reaction rate, measured by the pulse radiolysis method, were found to be identical for both bovine and shark SODs. In order to quantify the role of Lys134 in electrostatically steering the superoxide to the active site, chemical modification of the lysine residues by carbamoylation was carried out on both bovine and shark SODs. Experimental determination of the enzymatic reaction rate indicated that the charge located on the residue 134 gives 19% contribution to the guidance of superoxide anion at low ionic strength. This value matches the association rates predicted by brownian dynamics.
Amino Acid Sequence↗
Age-related changes in human ceruloplasmin. Evidence for oxidative modifications.
Human plasma or serum from donors of age comprised between 15 and 95 years was analyzed for paramagnetic and total copper content, as well as for immunoreactive ceruloplasmin content and oxidase activity. All parameters were essentially unaltered, except the paramagnetic copper content, which increased 2-fold upon aging. A dramatic change of the electron paramagnetic resonance spectrum due to ceruloplasmin occurred in individuals over 65 years old and was associated with both an increase of the type 1 copper signal intensity and the appearance of new resonances of a type 2 copper species. Ceruloplasmin was isolated from either young or old donors. Spectroscopic analyses of the isolated proteins confirmed the tendency of type 1 copper to stay reduced in the "young" and oxidized in the "old" protein. The type 2 copper signal observed in most young ceruloplasmin samples was different from the species invariably present in the old protein. The magnetic parameters of the latter species were more consistent with a partially reduced trinuclear copper site. In vitro limited proteolysis resulted in identical fragmentation patterns and kinetics in both proteins. However, changes of the net electric charge were detected in the fragments of the protein isolated from aged individuals, which exhibited a carbonyl content of 0.6 mol of carbonyl/mol of protein. The same pattern of modifications, including a higher carbonyl content (0.65 versus 0.2 mol of carbonyl/mol of protein), could be reproduced by exposure of the young protein to the metal-catalyzed oxidation system iron/ascorbate. These results suggest that during aging ceruloplasmin is subjected to oxidative modifications which are likely to be the source of conformational changes around the copper sites leading to an intramolecular electron rearrangement among the various copper sites.
Adolescent↗