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Biomedical subjects

M Fusco

Publications and source records attributed to M Fusco.

At least 19 recordsLinked to original sources

Grown-up coeliac children: the effects of only a few years on a gluten-free diet in childhood.

AIM: To evaluate clinical and psychological status of adults with childhood diagnosis of coeliac disease who were re-exposed to gluten after only a few years and now on a gluten-containing diet, compared with adults with recent diagnosis of coeliac disease, and adults who remained on gluten-free diet after childhood diagnosis. METHODS: A total of 195 adults with a biopsy suggestive of coeliac disease in childhood, who either had adhered to a gluten-free diet for at least 1 year after diagnosis and now are either on gluten-free diet (n = 110) or on gluten-containing diet (n = 85), and adults with newly diagnosed coeliac disease (n = 165) underwent a medical check-up. RESULTS: Body mass index and main laboratory indices were statistically different among groups (lowest in never on gluten-free diet, highest in gluten-free diet). The lowest average levels of bone mineral density were found among never on gluten-free diet patients. Prevalence of autoimmune disorders was increased in never on gluten-free diet when compared with the transient gluten-free diet and gluten-free diet groups. Histology revealed villous subatrophy in all patients of never on gluten-free diet group, in 39 of 110 patients of gluten-free diet and in 84 of 85 of transient gluten-free diet groups. Herpetiform dermatitis was found in three patients of gluten-free diet, three of transient gluten-free diet and three of never on gluten-free diet. Dental enamel defects were found in 15 patients of transient gluten-free diet, 43 of never on gluten-free diet and in zero of the gluten-free diet group. Pregnancy outcome was not significantly different between the two groups, but neonatal weight was lower and breast feeding was shorter in the never on gluten-free diet group. Sexual habits, alcohol intake and cigarette smoking were significantly different in the never on gluten-free diet group when compared with the other two groups. CONCLUSION: Gluten withdrawal in childhood partly protects coeliac adults from clinical and behavioural effects of gluten sensitivity.

Adolescent↗

Rapid differential diagnosis of Mycoplasma agalactiae and Mycoplasma bovis based on a multiplex-PCR and a PCR-RFLP.

The membrane-protein 81 gene (mb-mp81) of Mycoplasma bovis was cloned, sequenced and compared to membrane-protein 81 gene (ma-mp81) of Mycoplasma agalactiae. After alignment of both sequences, specific primers pairs were designed from variable or unchanging nucleotide segments. In this study, we describe the development and optimization of a multiplex-PCR (MPCR) for the rapid detection of M. agalactiae and M. bovis strains. In addition, a simple and rapid PCR-restriction fragment length polymorphism (RFLP) assay, using the restriction enzymes AluI, DraI, RsaI and XbaI, is described to distinguish between both species. The results suggest that MPCR and PCR-RFLP assays could be used as an alternative method in routine diagnosis for rapid and specific simultaneous detection of M. agalactiae and M. bovis.

Bacterial Proteins↗

Infection with human herpes virus type 8 in an area at high prevalence for hepatitis C virus infection in southern Italy.

The Campania Region is a geographical area of southern Italy characterized by high incidence rates of hepatocellular carcinoma and of classic Kaposi's sarcoma. Epidemiological investigations carried out among different population groups in this region have found high prevalence rates of both hepatitis C virus (HCV) and human herpesvirus type 8 (HHV-8). To assess co-infection rates of HCV and HHV-8, we carried out a cross-sectional seroepidemiological study prevalence in Pomigliano d'Arco, a Health District of Campania located 20 km away from Naples. The overall rate of HCV/HHV-8 co-infection was 3.1%, 3.5% among men and 2.7% among women. No difference emerged in the HCV/HHV-8 co-infection rates according to seropositivity for HCV infection, either overall (Mantel Haenszel odds ratio = 1.2, 95% CI: 0.6-2.6) or when the analysis was stratified by gender. These findings support the hypothesis that in Campania common routes of transmission are rarely shared by HCV and HHV-8 infections. Local factors may result in different epidemiological patterns for these two viral infections. However, our findings have important public health implications, especially in Mediterranean countries where HCV and HHV-8 infections are endemic.

Adult↗

Neurogenic inflammation in primary headaches.

The headache in migraine is thought to result from neuronal nociceptive activity in the trigeminovascular system, that is, the meninges. In addition, trigeminal axons projecting to the meninges contain vasoactive neuropeptides, such as substance P, calcitonin gene-related peptide and neurokinin A, that may promote, when released, plasma protein leakage and vasodilation within dura mater, characteristic of neurogenic inflammation. Thus, it has been hypothesized that a sterile neurogenic inflammation in the meninges may be involved in generating or sustaining, via occurrence of a vicious cycle, the pain accompanying the migraine attacks. We here review the evidence in support of this hypothesis as well as its potential significance in better tailoring therapies in migraine or other types of primary headaches.

Animals↗

Thoracic intradural extramedullary lipomas. Report of three cases and review of the literature.

BACKGROUND: Indication for surgery and the surgical strategy for treatment of spinal intradural lipomas are still discussed controversially. Among spinal lipomas the cervicothoracic region is rarely affected. We report on our experience with spinal decompression for the treatment of three intradural thoracic lipomas. FINDINGS: Three adult patients with extramedullary intradural lipomas of the thoracic spinal cord demonstrated progressive neurological symptoms and signs without evidence of growth of the lipoma. All patients underwent surgery with decompression of the affected spinal levels. No attempt was made to reduce the size of the lipomas. Postoperatively, each patient demonstrated significant clinical improvement. Interpretation. Attempts to remove lipomas are associated with significant risks of surgical morbidity. Lipomas are hamartomas which change their size according to alterations of body fat. Therefore, decompression of the affected spinal levels is sufficient to achieve significant neurological improvement.

Adult↗

Recruitment of mononuclear leucocytes to osteoarthritic human synovial xenografts in the ears of SCID mice.

A system has been established to assess the recruitment of 99mTc-hexamethylpropylene amine oxamine (99mTc-HMPAO)-labelled PBMC and [125I]iododeoxyuridine-labelled Con A stimulated lymphoblasts to allogeneic human synovial xenografts in the ears of SCID mice. Successful engraftment of osteoarthritic synovium was achieved in approximately 90% of cases and a connection between the human microvasculature of the xenograft and the circulation of the mouse was shown. Cells were delivered to the xenograft by a system of regional vascular perfusion, thus avoiding the major murine vascular beds. The accumulation of 99mTc-HMPAO-labelled PBMC in mouse ears was monitored in real time. Direct injection of xenograft-bearing ears with recombinant human TNF-alpha, 7 h prior to perfusion, increased the accumulation of both PBMC and lymphoblasts in cytokine-injected ears compared to contralateral control-injected ears. Autoradiography revealed the presence of [125I]iododeoxyuridine-labelled lymphoblasts associated with human microvasculature within the xenograft. However, the increased accumulation of lymphoblasts in cytokine-injected ears occurred in the tissues surrounding the xenograft, where lymphoblasts were associated more often with murine than human vessels. Although the system described offers advantages over similar models, the propensity for mouse endothelium to interact with human leucocytes is likely to be a generic disadvantage for models of human leucocyte recruitment to xenografts in immunodeficient mice.

Animals↗

Endoscopic endonasal transsphenoidal surgery in recurrent and residual pituitary adenomas: technical note.

Despite a good cure rate after surgery, the recurrence rate in pituitary adenomas is globally high. The decision making in such cases can be problematic for the nature of the lesion, for the anatomic structures involved, for the different pharmacological, surgical, radiotherapeutic and radiosurgical options nowadays available. In the perspective of an improvement and refinement of the surgical procedure an endoscopic endonasal transsphenoidal approach to the pituitary was recently adopted in the Neurosurgical Department of the University of Naples. Its minimal invasiveness and its wider and direct anatomic control of the operative field has allowed a faster, greater and safer potential of tumour excision, with respect of the sphenoid, sellar and parasellar structures. The authors have examined the advantages provided by this technique in 12 patients with recurrent pituitary adenomas and in 2 craniopharyngiomas already treated via a transnasal transsphenoidal approach (TTA), where the anatomy of surgical field had been distorted by the first operation or the radiation therapy. They conclude that the endoscopic transsphenoidal re-operation might be considered the procedure of choice in case of recurrences and its easiness in such conditions could favour its larger use, before other more aggressive therapeutic solutions.

Adenoma↗

Accessible xenografts of human synovium in the subcutaneous tissues of the ears of SCID mice.

This work was undertaken to examine whether human synovium could be engrafted into subcutaneous pouches in the ears of severe combined immunodeficient (SCID) mice. Synovium was transplanted into surgically constructed ear pouches. The grafts were examined by histological and immunohistochemical methods after varying periods after engraftment, or after percutaneous injection of TNF-alpha. Normal, osteo-arthritic and rheumatoid synovium was engrafted successfully in subcutaneous ear pouches. The general morphology and cellular compositions of xenografts were retained including human endothelial cells. In rheumatoid xenografts, macrophages, fibroblasts and lymphocytes persisted for at least 4 weeks. Vascular expression of intercellular adhesion molecule-1 (ICAM-1) was maintained but expression of vascular adhesion molecule-1 (VCAM-1), E-selectin and MHC class II diminished with time. Percutaneous injection of TNF-alpha induced up-regulation of VCAM-1. Human synovium can be engrafted into subcutaneous ear pouches in SCID mice. The xenografts are accessible and respond to injection of a pro-inflammatory cytokine.

Adult↗

Anomalous meningeal branches of the ophthalmic artery feeding meningiomas of the brain convexity.

Many anomalies may involve the ophthalmic and middle meningeal arteries, because of the close relationship of their development. The system of the ophthalmic artery may supply the dural convexity by the middle meningeal artery of ophthalmic origin, the anterior branch of the middle meningeal artery or an accessory meningeal artery. The development and the anatomic arrangement of these anomalous vessels are discussed. Three cases of meningiomas of the brain convexity supplied by anomalous meningeal arteries arising from the ophthalmic artery are described. In one case internal carotid angiography showed an anomalous anterior branch of the middle meningeal artery arising from the ophthalmic artery, whereas the maxillary artery provided only the posterior branch of the middle meningeal artery. In two cases the middle meningeal artery system was normal, but the ophthalmic artery provided an accessory meningeal artery supplying the meningioma. Whereas an ophthalmic origin of the middle meningeal artery is rather common, the angiographic finding of an accessory meningeal artery or an anterior branch of the middle meningeal artery arising from the ophthalmic arterial system is exceptional. The preoperative embolization of dural lesions supplied by anomalous meningeal vessels of ophthalmic origin is dangerous because of the risk of embolization into the ophthalmic circle.

Adult↗

The antigen receptor complex on cord B lymphocytes.

The neonatal immune system responds to a restricted range of antigens, producing largely IgM antibody of low affinity. Comparison of the components of the B-cell antigen receptor complex shows significantly elevated membrane levels of IgM in neonatal B cells, compared with adult cells. CD79, which acts as the signal transducer for membrane immunoglobulin, is elevated in parallel with IgM, while IgD is elevated to a lesser degree. CD19, CD21, CD22 and CD81, which are all involved in transmitting activation signals when immunoglobulin is engaged, are not elevated. CD32, which is involved in negative regulation of activation, is present at reduced levels on cord B cells. The elevation of B-cell membrane IgM persists during infancy. Neonatal B cells respond in vitro to interleukin-4 (IL-4) by further elevation of membrane IgM levels. The elevated level of membrane IgM may make neonatal B cells easier to trigger by low concentrations of antigen, but in vitro activation and immunoglobulin modulation experiments did not show significant differences between cord and adult B-cell responses to anti-IgM.

Adult↗

The Fas antigen (CD95) on human lymphoid cells: epitope analysis with ten antibodies.

The expression of CD95 antigen was examined on adult and cord blood lymphocytes using a highly sensitive immunofluorescence/flow cytometric procedure. CD95 was expressed by the majority of circulating blood T cells in adults, and by a smaller proportion of CD4+ and CD8+ T cells in cord blood. The majority of circulating B cells did not react with seven CD95 antibodies, but three antibodies did stain B cells. In tonsil sections, CD95 was expressed throughout the tissue but germinal centres showed generally stronger staining than the surrounding follicular mantle and interfollicular areas. This was confirmed by flow cytometry, which showed expression preferentially on B cells with a germinal centre phenotype. Because different antibodies stained different proportions of B cells, CD95 epitopes were examined by inhibition, additive binding and protease susceptibility studies using a panel of ten CD95 antibodies. B cells apparently reacting selectively with CD95 antibodies were sorted and CD95 mRNA was reverse transcribed to cDNA and analyzed, in order to confirm the presence of CD95 in cells which reacted selectively and to explore the possible existence of CD95 isoforms. The major cDNA band was identical in the two populations. Inhibition of N-glycosylation suggested that the epitopes detected differentially could not be accounted for by differential N-glycosylation.

Adult↗

Reduced expression of the interleukin-2-receptor gamma chain on cord blood lymphocytes: relationship to functional immaturity of the neonatal immune response.

Mutation of the interleukin-2 (IL-2) receptor gamma chain, which also serves as a component of the receptor complexes for IL-4, 7, 9 and 15, results in severe immune deficiency. We hypothesized that the immunological immaturity of healthy neonates might be associated with low levels of expression of this receptor molecule. Using monoclonal antibody and a highly sensitive immunofluorescence method, we showed that IL-2 receptor gamma chain is expressed at significantly lower levels on cord blood cells compared with adult cells. IL-2-dependent T-cell activation in vitro was reduced in cord blood cells compared with adult cells, but B-cell responses to IL-4 were not obviously impaired. The lower level of expression of the gamma chain and some other cytokine receptor chains may contribute to the immunological immaturity of the newborn, by selectively depressing particular immunological mechanisms.

Adult↗

IgE+ cells in the peripheral blood of atopic, nonatopic, and bee venom-hypersensitive individuals exhibit the phenotype of highly differentiated B cells.

We have analyzed IgE+ cells in peripheral blood of atopic donors, donors hypersensitive to bee venom, and nonatopic control donors with two- and three-color flow cytometry. Although the percentage of IgE+ cells varied among these groups, the overall phenotypic patterns were similar. Most IgE+ cells do not display typical B-cell markers, such as CD19, CD20, and CD21. A significant proportion of these cells stain for CD38, indicating that they are more differentiated. IgE+ cells express Fc gamma RII and CD45RO, an isoform associated with an advanced level of differentiation. The majority of IgE+ cells do not coexpress other surface immunoglobulin isotypes. In the case of bee venom-hypersensitive donors, we have been able to identify a small population of IgE+ cells with a specificity for phospholipase A2, a major immunogenic component of bee venom. The phospholipase A2+ cells display a phenotype similar to that of the IgE+ cells.

Antibodies, Monoclonal↗

Cytokine receptor expression in human lymphoid tissue: analysis by fluorescence microscopy.

A highly-sensitive flourescence method, capable of detecting cytokine receptors present at low concentrations (around 100 molecules per cell) by flow cytometry, was adapted for use on tissue sections. This method was used to examine the expression of several cytokine receptors in lymphoid tissues. IL-2 receptors were distributed broadly, with higher concentrations in T cell areas. IL-1 receptor Type 1 was detected in T cell areas and in the follicular mantle, and was strongly expressed on vascular endothelium. IL-6 receptor was found at very low concentration, both within and outside germinal centres. The gp 130 molecule, which is involved in the functional receptor complex for IL-6 and several other cytokines, was present at higher concentrations, particularly in the germinal centre. Analysis of receptor expression in secondary lymphoid tissue provides evidence bearing on the physiological roles of cytokines, as these tissues contain cells at various stages of physiological activation located in well-defined functional zones.

Antibodies, Monoclonal↗

Expression of cytokine receptors by human cord blood lymphocytes: comparison with adult blood lymphocytes.

The expression of receptors for several cytokines (IL 2, IL-4, IL-6, IL-7, tumor necrosis factor, and interferon-gamma) was examined in human cord blood cells in comparison with adult blood cells. A previously described high sensitivity immunofluorescence procedure was used to render the low levels of receptor measurable. Cord blood lymphocytes expressed measurable levels of most cytokine receptors, but expression tended to be lower than in adult blood cells. Examination of different lymphocyte subpopulations revealed a complex pattern with some cell types expressing particular receptors equivalent to adult levels. Cord and adult blood monocytes expressed similar cytokine receptor profiles. Receptor expression in cord lymphocytes could be regulated by activation. The results provide indications as to the relative activities of different cytokines in the development of the immune system in the neonate.

Adult↗

Pharmacokinetics of nerve growth factor (NGF) following different routes of administration to adult rats.

The suggested potential for therapeutic use of nerve growth factor (NGF) in the treatment of toxic and degenerative disorders of the nervous system indicates a need to determine its pharmacokinetics. To this end, murine NGF was administered to adult rats and multiple blood samples were withdrawn at intervals. NGF levels, determined in plasma samples by a two-site enzyme immunoassay, were used to determine the pharmacokinetics of NGF. These studies demonstrate that murine NGF has a distribution half-life of about 5.4 min and an elimination half-life of 2.3 h following intravenous injection. When administered by subcutaneous (sc) injection, the elimination half-life is prolonged to 4.5 h. Administration of NGF by sc continuous infusion, using mini-osmotic pumps, provides stable, dose-related levels of circulating NGF within few days from pump implantation. Upon removal of the pump, NGF levels show a rapid decay (t1/2 about 1.5 h) followed by a slow elimination phase (t1/2 about 150 h). These pharmacokinetic parameters might serve for selection of an appropriate administration route and dose regimen that would optimize schedule-dependent expression of NGF therapeutic activity.

Animals↗

Intracerebroventricular administration of nerve growth factor affects muscarinic cholinergic receptors in the cerebral cortex of neonatal rats.

The repeated intracerebroventricular administration of nerve growth factor (5 micrograms/2.5 microliters) to neonatal rats induced the activation of choline acetyltransferase in forebrain cholinergic neurons that was paralleled by a concomitant change in the density of muscarinic cholinergic receptors in the cerebral cortex. The administration of nerve growth factor altered muscarinic binding sites in a biphasic fashion during postnatal development. A significant stimulation of the developmental increase in the density of muscarinic binding sites occurred in nerve growth factor-treated animals at days 2 and 3 after birth. Conversely, nerve growth factor induced a significant decrease in the receptor number at postnatal days 8 and 14. Muscarinic receptor number returned to control values after treatment, suggesting that nerve growth factor-induced changes to muscarinic cholinergic receptors are reversible. Nerve growth factor administration did not affect muscarinic cholinergic receptor density in striatal membranes and did not alter the relative content of cortical messenger RNAs encoding m1 and m3 muscarinic cholinergic receptor subtypes at postnatal day 14, as determined by reverse transcriptase-polymerase chain reaction. The up- and down-regulation of muscarinic cholinergic receptors induced by nerve growth factor during postnatal development may be temporally related events associated with concomitant changes in the activity of choline acetyltransferase.

Animals↗