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Biomedical subjects

A Spreafico

Publications and source records attributed to A Spreafico.

At least 19 recordsLinked to original sources
PubMed2006

Calcaneus ultrasonometry and dual-energy X-ray absorptiometry for the evaluation of vertebral fracture risk.

The aim of this retrospective, cross-sectional, controlled, non-population-based study was to evaluate the specificity and sensitivity of quantitative ultrasonometry (QUS) of the heel and of dual-energy X-ray absorptiometry (DXA) in the prediction of morphometric vertebral fracture in postmenopausal women and to establish whether the combination of the two devices could improve the capacity to identify the presence of vertebral fracture. Also, we tried to identify the best T-score threshold for high risk of vertebral fracture for both QUS and DXA, highlighting the discrepancies between the two methodologies and between the various sites examined with DXA. From 6,300 patients examined by DXA (total body, lumbar spine, total femur, femoral neck), QUS and DXA vertebral morphometry (MXA), we selected 764 postmenopausal women with nontraumatic vertebral fractures; 770 postmenopausal women with normal morphometry were chosen as a control group. Logistic regression analysis yielded odds ratios (ORs) for bone mineral density (BMD) measurements and QUS that were comparable: BMD-total body 4.16, BMD-lumbar spine 4.80, BMD-total femur 3.77, BMD-femoral neck 3.86, and QUS 4.41, without statistical differences even after correction for different confounding variables (menopausal years, weight, height, body mass index, and age). The ORs obtained from different combinations of QUS and DXA results did not show statistically significant differences compared to those from a single method alone. The sensitivity and specificity of all measurements were determined by area using the receiver operating characteristic curve; these were 0.94 for total body, 0.95 for lumbar spine, 0.86 for total femur, 0.89 for femoral neck, and 0.93 for QUS, without statistical difference. The areas under the curve obtained from the combination of QUS and DXA were higher but without statistical significance compared to QUS alone. In conclusion, both QUS and DXA were able to discriminate women with fracture from women without fracture and independently contributed to determining the association with fracture. The combination of QUS and BMD did not improve the diagnostic ability of either individual technique. We found different diagnostic thresholds for QUS and DXA.

Absorptiometry, Photon↗
PubMed2004

Efficacy and tolerability of gefitinib in pretreated elderly patients with advanced non-small-cell lung cancer (NSCLC).

The activity and toxicity profile of gefitinib in non-small cell lung cancer (NSCLC) patients aged 70 years or older has been only partially evaluated. The aim of this study was to evaluate the response rate and safety of gefitinib in elderly NSCLC patients. Elderly NSCLC patients pretreated with chemotherapy and with at least one measurable lesion received gefitinib at the daily dose of 250 mg until disease progression, unacceptable toxicity or refusal. From August 2001 to May 2003, 40 consecutive elderly patients have been enrolled onto the study in three Italian institutions. We observed one complete (2.5%) and one partial response (2.5%), 18 disease stabilisations (NC: 45%) lasting at least 2 months, including six patients (15%) who had disease stabilisation of 6 months or longer, for an overall disease control rate of 50% (95% CI: 34.5-65.5%). The median duration of response was 4.4 months (range 1.7-9.2). The side effects were generally mild and consisted of diarrhoea and skin toxicity. Grade 1-2 diarrhoea occurred in 23.6%, and one patient experienced grade 4 diarrhoea, requiring hospitalisation. Grade 1-2 skin toxicity, including rash, pruritus, dry skin, and acne, occurred in 20 patients (52.6%). Gefitinib is safe and well tolerated in elderly pretreated NSCLC patients. The disease-control rate achieved suggests that this drug could represent a valid option in the management of this unfavourable subgroup of patients.

Aged↗
PubMed2001

Mimicking the nicotinic receptor binding site by a single chain Fv selected by competitive panning from a synthetic phage library.

We have developed a novel competitive method to select from a phage display library a single chain Fv which is able to mimic the alpha-bungarotoxin binding site of the muscle nicotinic receptor. The single chain Fv was selected from a large synthetic library using alpha-bungarotoxin-coated magnetic beads. Toxin-bound phages were then eluted by competition with affinity purified nicotinic receptor. Recognition of the toxin by the anti-alpha-bungarotoxin single chain Fv was very similar to that of the receptor, such as indicated by the epitope mapping of alpha-bungarotoxin through overlapping synthetic peptides. Moreover, several positively charged residues located in the toxin second loop and in the C-terminal region were found to be critical, to a similar extent, for toxin recognition by the single chain Fv and the receptor. However, although the anti-alpha-bungarotoxin single chain Fv seems to mimic the toxin binding site of the nicotinic receptor, it does not bind other nicotinic agonists or antagonists. Our results suggest that competitive selection of anti-ligand antibody phages can allow the production of receptor-mimicking molecules directly and exclusively targeted at one specific ligand. Since physiologically and pharmacologically different ligands can produce opposite effects on receptor functions, such selective ligand decoys can have important therapeutic applications.

Animals↗
PubMed1998

Rabbit monoclonal Fab derived from a phage display library.

Rabbit monoclonal antibodies (RmAb) are not routinely obtained by eukaryotic cell fusion techniques. Therefore, we have applied phage display technology to produce a recombinant rabbit Fab molecule directed against the KLH model antigen. The Fab fragments selected from the rabbit phage display library were subcloned in an expression vector to permit the production of a fusion protein comprising a dimer of bacterial alkaline phosphatase (phoA). This fusion protein was directly produced into the periplasmic space of Escherichia coli. We show that a crude extract containing these conjugates can be used in a direct enzyme immunoassay, as exemplified in the case of the KLH antigen.

Alkaline Phosphatase↗
PubMed1997

Molecular mimicry between the rabies virus glycoprotein and human immunodeficiency virus-1 GP120: cross-reacting antibodies induced by rabies vaccination.

The 160-170 sequence of human immunodeficiency virus (HIV)-1 gp120 mimics a nicotinic receptor-binding motif of rabies virus glycoprotein and snake neurotoxins. This sequence has been proposed to be involved in the binding of HIV-1 gp120 to the acetylcholine binding sites of nicotinic receptors. By using biomolecular interaction analysis (BIA) technology we have found that HIV-1 gp120 can bind to detergent-extracted nicotinic receptor from fetal calf muscle. The binding is inhibited by nicotine and by a synthetic peptide reproducing the gp120 160-170 sequence. The molecular mimicry between gp120 and rabies virus glycoprotein is confirmed by cross-reacting antibodies. We have found that vaccination against rabies can induce the production of anti-HIV-1 gp120 antibodies in humans. The cross-reacting antibodies are directed to the gp120 sequence involved in the mimicry with the rabies virus glycoprotein. The cross-reactivity between the rabies virus and HIV-1 has important implications in transfusion medicine. Moreover, the presence of cross-reacting antibodies between the nicotinic receptor binding site of rabies virus glycoprotein and a fragment of HIV-1 gp120 strengthens the hypothesis about the possible role of nicotinic receptors as potential receptors for HIV-1 in the central nervous system.

Antibodies, Viral↗
PubMed1997

Hierarchical affinity maturation of a phage library derived antibody for the selective removal of cytomegalovirus from plasma.

Recombinant antibody fragments can be produced in large quantities using bacterial expression systems and could potentially be useful for the generation of biofilters for the selective removal of viral particles from fluids. A human single chain-Fv antibody library, derived from synthetic repertoires of germ line VH-gene segments rearranged in vitro and paired to a single light chain (Nissim et al., 1994, EMBO J., 13, 692-698), has recently been used to isolate hundreds of different binding specificities by panning with antigen. Antibodies from this library typically have affinities in the 10(6)-10(7) M-1 range. Occasionally, better binders are isolated but at other times the affinities recovered are poor. In the latter situation binding cannot be detected with soluble antibodies, but only by high-avidity display of multiple copies of antibodies on phage. By panning with human cytomegalovirus (HCMV)-coated immunotubes, we have isolated a number of antibody clones from this library that bound to the antigen only if displayed on the filamentous phage, but not in soluble form. One of these clones was selected for an affinity maturation procedure, achieved by combinatorial mutagenesis of the complementarity determining region 3 (CDR3) of the antibody light chain, followed by selection of the resulting library for HCMV binding. By this means, we were able to isolate a number of binders, some of which exhibited specific HCMV binding in soluble form. The clone that gave the strongest ELISA signal was expressed in bacteria, purified in solution, characterised using a novel capture methodology with surface plasmon resonance detection on a BIAcore instrument and used for the production of an immunofilter for the removal of HCMV form human serum. The filter removed more than 99% of applied HCMV in 10 min circulation time, while the amount of HCMV retained non-specifically in a cartridge derivatised with a non-specific antibody was less than 10% under similar conditions.

Antibodies, Viral↗
PubMed1993

A model of the rabies virus glycoprotein active site.

The glycoprotein from the neurotropic rabies virus shows a significant homology with the alpha neurotoxin that binds to the nicotinic acetylcholine receptor. The crystal structure of the alpha neurotoxins suggests that the Arg 37 guanidinium group and the Asp 31 side-chain carboxylate of the erabutoxin have stereochemical features resembling those of acetylcholine. Conformational studies on the Asn194-Ser195-Arg196-Gly197 tetrapeptide, an essential part of the binding site of the rabies virus glycoprotein, indicate that the side chains of Asn and Arg could also mimic the acetylcholine structure. This observation is consistent with the recently proposed mechanism of the viral infection.

Amino Acid Sequence↗
PubMed1989

A monoclonal antibody to a synthetic fragment of rabies virus glycoprotein binds ligands of the nicotinic cholinergic receptor.

Rabies virus glycoprotein and snake venom curaremimetic neurotoxins share a region of high homology (30-45 for neurotoxins and 190-203 for the glycoprotein) in the regions that are believed to be responsible for binding the nicotinic acetylcholine receptor. Monoclonal antibodies raised to the 190-203 synthetic fragment of rabies virus glycoprotein were immobilized on a high performance affinity chromatography column and were able to bind neurotoxins. Toxins were displaced from the affinity column by elution at acidic pH and by affinity competition with acetylcholine at neutral pH. Furthermore, the affinity column proved to be useful for the purification of cholinergic ligands. Overall, these results indicate that the paratope of our monoclonal antibodies could behave as an 'internal image' of the nicotinic cholinergic receptor acetylcholine binding site.

Amino Acid Sequence↗
PubMed1987

[Postoperative treatment of medial meniscectomy with an elastic bandage of the Van Unen type].

On the basis of a clinical review of a consecutive series of 27 medial meniscectomies of the knee, the authors report the results obtained by the systematic use of the Van Unen elastic bandage ii the post-operative period. The use of this technique would appear to be advantageous both as a means of speeding up functional recovery of the joint operated on and as a means of preventing complications of an arthrosynovitic type which are often secondary to early rehabilitation treatments.

Humans↗
PubMed1986

The postcoital IUD as an effective continuing contraceptive method.

A two-year controlled clinical study of the effectiveness of postcoital IUD as a continuing contraceptive method in 98 women requesting a postcoital contraception is presented. The control group was selected from women requesting an IUD as contraceptive choice. The rates of accidental pregnancy, expulsion and removal for medical reasons did not differ between the two groups. Removal for personal reasons was the only termination event that showed a significant difference at one year. Moreover, the removal for personal reasons of interceptive IUD users mainly occurred in the early months after insertion. Postcoital IUD has proved to be an effective continuing contraceptive method. Special attention and sympathetic counseling should be given to postcoital IUD users before insertion and during the three months following insertion.

Adolescent↗
PubMed1983

[Hypothyroid neuropathy. Description 2 cases].

Although neurological complications of hypothyroidism are well recognized, scanty data, to the best of our knowledge, are available about peripheral neuropathies in this condition. The electrographic studies so far performed are nearly all devoted to the well known association myxoedema-carpal tunnel syndrome. Our data concern two patients affected by neuropathy in hypothyroidism, presenting diffuse anomalies of electrographic parameters (motor and sensitive nerve conduction velocity, F-wave, H-reflex, H-index); and, in one of these cases, a marked segmental demyelination and axonal degenerations were disclosed by pathological examination of sural nerve (according to Dyck and Lambert, 1970; Shirabe and coll., 1975).

Aged↗
PubMed1978

[Diaphragmatic paralysis in amyotrophic lateral sclerosis (author's transl)].

One clinical case of neurogenic diaphragmatic paralysis secondary to amyophic lateral sclerosis as a prominent presenting symptom is described. The condition is a very rare one, only eight cases being reported till now in literature. The Authors lay stress one some diagnostic criteria for the individuation of neurogenic diaphragmatic paralysis due to motor neuron disease.

Acid-Base Equilibrium↗
PubMedDate not supplied

[Anabolic effects and inhibition of interleukin 6 production induced by neridronate on human osteoblasts].

UNLABELLED: Bisphosphonates (BPs) are pharmacological compounds widely used in the treatment of a variety of bone-related diseases, particularly where the bone-turnover is skewed in favour of osteolysis. The mechanisms by which BPs reduce bone-resorption directly acting on osteoclasts (OCs) are now largely clarified even at molecular level. The researches concerning the BPs effects on osteoblasts (OBs) have instead shown variable results. OBJECTIVES: We have investigated the efficacy of neridronate (NER), an amino-BP, as anabolic agent on human OBs. Moreover, we have tried to verify if NER is able to negatively modulate the production of IL-6 on OBs stimulated or not by the pro-inflammatory cytokine IL-1beta. METHODS: We have tested if different concentrations of NER (from 10-11 M to 10-3 M), added to primary human OB cultures, could affect the cells number, the endogenous cellular alkaline phosphatase (ALP) activity, the collagen I (COL-I) synthesis, the formation of mineralized nodules and the IL-6 production. Our experimental approach was performed testing a wide range of NER concentrations because, under physiological conditions, OBs seems to be exposed to variable and transient levels of the drug. RESULTS: Our results show that NER doesn't negatively affect in vitro the viability, proliferation and cellular activity of human OBs, even after 20 days of exposure to concentrations < or =10-5 M (therapeutic dose). In addition, NER seems to enhance the differentiation of cultured OBs in mature bone-forming cells. A maximum increase of COL-I synthesis (+25% after 4 days; p < 0.05), ALP activity (+50% after 10 days; p < 0.01) and mineralized nodules (+48% after 20 days; p < 0.05) was observed in cultures treated with NER 10-8 M. A maximal reduction of IL-6 secretion (-24% on IL-1beta stimulated cultures and -29% on unstimulated cultures) was observed for NER 10-9 M. CONCLUSIONS: These results encourage the use of neridronate in therapy of demineralizing metabolic bone disorders.

Aged↗
PubMedDate not supplied

Clinical determinants of bone mass and bone ultrasonometry in patients with systemic sclerosis.

OBJECTIVE: The aim of this study was to evaluate bone mass and bone ultrasonometry in patients affected with systemic sclerosis (SSc). METHODS: Fifty-five patients (mean age 54.1 +/- 14.1 years; 25 premenopausal, and 30 postmenopausal women) affected with SSc (in a limited, intermediate or diffused form) and 60 age-matched healthy controls (30 premenopausal, and 30 postmenopausal women) were studied for Bone Mineral Density (BMD) measured by fan-beam x-ray densitometry, Stiffness Index (SI) measured by ultrasonometry of the heel, inflammation indices (erithrocyte sedimentation rate, C-reactive protein), and autoantibodies (ANA, ENA). Examinations were also carried out in order to determine any internal organ involvement. None of the patients had previously received steroid treatment. RESULTS: BMD was significantly lower in the SSc group than in the control group, whether it was expressed in g/cm2 (lumbar spine: 0.980 vs 1.241, p < 0.01; femoral neck: 0.832 vs 0.955, p < 0.05; total body 1.050 vs 1.168, p < 0.01) or by T- and Z-score (lumbar spine: T = -2.48; Z = -1.10; femoral neck: T = -1.69; Z = -0.55; total body: T = -1.11; Z = -0.48). SI was also altered (75.8 vs 96.2, p < 0.01; T = -2.10, Z = -1.12). BMD and SI were lower in women with the diffuse form of skin involvement. BMD and SI were lower in women in whom one or more internal organs were involved. CONCLUSION: SSc patients had reduced BMD and SI that was more marked in the diffuse form and in those with internal organ involvement and that became more marked with age and estrogen deficiency. This demineralisation was not related to the inflammation indices, disease duration, or to the immunological pattern.

Absorptiometry, Photon↗