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Biomedical subjects

A Ceccarelli

Publications and source records attributed to A Ceccarelli.

At least 19 recordsLinked to original sources
PubMed2002

Course and prognosis in early-onset MS: comparison with adult-onset forms.

OBJECTIVES: To establish the prognostic role of clinical and demographic factors in a hospital-based cohort of MS patients categorized by age at clinical onset and clinical course. METHODS: Eighty-three patients with MS had a clinical onset of the disease in childhood (age <16 years; early-onset MS [EOMS]) and 710 in adult age (between 16 and 65 years; adult-onset MS [AOMS]). Patients were followed for a mean period of observation of 5 years. Univariate and multivariate analyses of clinical and demographic predictors for rapid progression and disability were performed using a stepwise Cox regression model with time-dependent covariates. RESULTS: In EOMS, the Expanded Disability Status Scale (EDSS) evaluated at last clinical examination was lower than in AOMS, despite a longer disease duration. The probability to reach growth disability and progression was significantly lower in EOMS than in AOMS. Median times to reach EDSS score of 4 and secondary progression were longer in EOMS than in AOMS, but the age at both endpoints was significantly lower in EOMS. In EOMS and AOMS, an irreversible disability was related to a secondary progressive course, a sphincteric system involvement at onset, and an older age at onset (in EOMS only for the group >14 years); in AOMS, other unfavorable factors were a pyramidal involvement at onset and a high relapse frequency in the first 2 years. The risk of entering secondary progression was significantly influenced by a high number of relapses in EOMS and by a higher age at onset and a short interattack interval in AOMS. CONCLUSION: A slower rate of progression of disease characterized EOMS patients, suggesting more plasticity to recover in developing CNS, but the early clinical manifestation cannot be considered a positive prognostic factor.

Adolescent↗
PubMed2002

Psychological and emotional development, intellectual capabilities, and body image in short normal children.

It is well established that children with short stature frequently have problems in cognitive development, personality, self-esteem and social relations. This is partly due to the fact that many parents view them as more vulnerable than other children of normal stature and do not allow them to face the normal experiences that correspond to their actual age. The aim of the present study was to assess, through the administration of appropriate psychological tools, a series of psychological and cognitive characteristics [i.e. anxiety, depression, good adjustment, social functioning, feeling of guilt, interpersonal relationship, intelligence quotient (IQ)], as well as variables linked to development of body image, in a group of children suffering from normal growth variants [familial short stature (FSS), no. 10, 4 males/6 females; with constitutional growth delay (CGD), no. 4,4 males; height standard deviation score (HSDS) ranging between -2.4 and -1.9] and in a control group children of normal stature (HSDS between -0.1 and +0.1). Children with short stature significantly differed from normal statured controls as far as Colored Progressive Matrices (CPMs, centiles), IQ (IQ, obtained using the Goodenough test), "Good Adjustment" (Draw-a-Person index, DAP), "Feelings of Guilt" (DAP index), "Height" (as emerges from drawings of the body) are concerned. Significant relationships were found between the height of the subjects (in centiles) and cognitive skills, measured both using CPMs (r=0.408; p=0.017) and Draw-a-Man (DAM) (r=0.359; p=0.037) and between height and feelings of guilt (r=0.325; p=0.027), measured using DAP. CPM scores correlated positively with the "Good Adjustment" index of DAP (r=0.354; p=0.05) and negatively with Children's Depression Inventory (CDI) (r=-0.609; p=0.01), "School Anxiety" index (r=-0.427; p=0.05) and "Total Anxiety" index (r=-0.436; p=0.05) of the Anxiety Scale Questionnaire for the Age of Development, and with 2 indices of DAP, namely, "Feelings of Guilt" (r=-0.461; p=0.01) and "Interpersonal Relationships (Difficulty in Establishing)" (r=-0.455; p=0.01). A significant positive correlation was found between the height of the subject and both the measurement of the "Body of Drawing 3" (r=0.450, p=0.01) and the measurement of the "Body of Drawing 4" (r=0.461, p=0.01), as well as the with the "Total Height of Drawing 4" (r=0.464, p=0.01). Higher indices for anxiety, depression, feelings of guilt and difficulty in establishing interpersonal relationships and lower indices for good adjustment were found in children with CGD as compared to subjects with FSS or normal statured children. Although further additional studies on larger samples are needed to confirm these preliminary observations, the present study underlines the importance of psychological support also during the growth and development in short normal children.

Adaptation, Psychological↗
PubMed2001

Inhibition of neutrophil elastase prevents cathelicidin activation and impairs clearance of bacteria from wounds.

The host defense roles of neutrophil elastase in a porcine skin wound chamber model were explored. Analysis of wound fluid by acid-urea polyacrylamide gel electrophoresis, Western blot, and bacterial overlay confirmed that the neutrophil-derived protegrins constituted the major stable antimicrobial polypeptide in the wound fluid. The application to the wound of 0.10 and 0.25 mM N-methoxysuccinyl-alanine-alanine-proline-valine (AAPV) chloromethyl ketone, a specific neutrophil elastase inhibitor (NEI), blocked the proteolytic activation of protegrins and diminished the associated antimicrobial activity as detected by radial diffusion assay against Staphylococcus epidermidis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans or by bacterial gel overlay against S epidermidis and E coli. The application of the related cathepsin G inhibitor (CGI), benzyloxycarbonyl-glycine-leucine-phenylalanine (ZGLF) chloromethyl ketone, had no effect. In wound chambers that received 10(6) colony-forming unit (CFU)/mL of S epidermidis, the presence of NEI significantly decreased the 24-hour clearance of bacteria from the wound compared to wounds treated with CGI or solvent only. Neither inhibitor, at 0.10 or 0.25 mM concentration, affected leukocyte accumulation or degranulation in the wound chambers. The in vitro microbicidal decrement due to NEI was restored by an amount of the specific protegrin (PG-1), which was equivalent to the measured difference of protegrin between control and inhibited chambers. Administration of 1 microg/mL exogenous PG-1 4 hours after chamber preparation was sufficient to normalize in vivo antimicrobial activity. Although pharmacologic NEIs are promising candidates as anti-inflammatory drugs, they may impair host defense in part by inhibiting the activation of cathelicidins by neutrophil elastase.

Animals↗
PubMed2000

Early onset multiple sclerosis.

Multiple sclerosis (MS) onset is usually in adult life (age 20-40 years). Discordant data have been reported concerning the frequency of early onset MS (EOMS) that ranges from 2.7% to 5%, whereas there is a general agreement on prevalence of female sex, particularly after puberty. The initial symptoms in EOMS are frequently characterized by visual loss whereas the other functional systems are involved with a variable frequency. Literature data show that EOMS tends to have a relapsing-remitting course, a high rate of recovery from the initial attack, a long time interval between the first and second attacks and a slow progression rate. A poor prognosis is reported in a few cases of EOMS and seems to be related to number of relapses and to the delay between the first and second attacks.

Adolescent↗
PubMed2000

Characterisation of a DNA sequence element that directs Dictyostelium stalk cell-specific gene expression.

The ecmB gene of Dictyostelium is expressed at culmination both in the prestalk cells that enter the stalk tube and in ancillary stalk cell structures such as the basal disc. Stalk tube-specific expression is regulated by sequence elements within the cap-site proximal part of the promoter, the stalk tube (ST) promoter region. Dd-STATa, a member of the STAT transcription factor family, binds to elements present in the ST promoter-region and represses transcription prior to entry into the stalk tube. We have characterised an activatory DNA sequence element, that lies distal to the repressor elements and that is both necessary and sufficient for expression within the stalk tube. We have mapped this activator to a 28 nucleotide region (the 28-mer) within which we have identified a GA-containing sequence element that is required for efficient gene transcription. The Dd-STATa protein binds to the 28-mer in an in vitro binding assay, and binding is dependent upon the GA-containing sequence. However, the ecmB gene is expressed in a Dd-STATa null mutant, therefore Dd-STATa cannot be responsible for activating the 28-mer in vivo. Instead, we identified a distinct 28-mer binding activity in nuclear extracts from the Dd-STATa null mutant, the activity of this GA binding activity being largely masked in wild type extracts by the high affinity binding of the Dd-STATa protein. We suggest, that in addition to the long range repression exerted by binding to the two known repressor sites, Dd-STATa inhibits transcription by direct competition with this putative activator for binding to the GA sequence.

Animals↗
PubMed2000

Cell-cell signaling and adhesion in phagocytosis and early development of Dictyostelium.

Cell-cell signaling and adhesion regulate transition from the unicellular to the multicellular stage of development in the cellular slime mold Dictyostelium. Essential gene networks involved in these processes have been identified and their interplay dissected. Heterotrimeric G protein-linked signal transduction plays a key role in regulating expression of genes mediating chemotaxis or cell adhesion, as well as coordinating actin-based cell motility during phagocytosis and chemotaxis. Two classes of cell adhesion molecules, one cadherin-like and the second belonging to the IgG superfamily, contribute to the strength of adhesion in Dictyostelium aggregates. The developmental role of genes involved in motility and adhesion, and their degree of redundancy, have been re-assessed by using novel developmental assay conditions which are closer to development in nature.

Animals↗
PubMed1999

Evidence that the Dictyostelium Dd-STATa protein is a repressor that regulates commitment to stalk cell differentiation and is also required for efficient chemotaxis.

Dd-STATa is a structural and functional homologue of the metazoan STAT (Signal Transducer and Activator of Transcription) proteins. We show that Dd-STATa null cells exhibit several distinct developmental phenotypes. The aggregation of Dd-STATa null cells is delayed and they chemotax slowly to a cyclic AMP source, suggesting a role for Dd-STATa in these early processes. In Dd-STATa null strains, slug-like structures are formed but they have an aberrant pattern of gene expression. In such slugs, ecmB/lacZ, a marker that is normally specific for cells on the stalk cell differentiation pathway, is expressed throughout the prestalk region. Stalk cell differentiation in Dictyostelium has been proposed to be under negative control, mediated by repressor elements present in the promoters of stalk cell-specific genes. Dd-STATa binds these repressor elements in vitro and the ectopic expression of ecmB/lacZ in the null strain provides in vivo evidence that Dd-STATa is the repressor protein that regulates commitment to stalk cell differentiation. Dd-STATa null cells display aberrant behavior in a monolayer assay wherein stalk cell differentiation is induced using the stalk cell morphogen DIF. The ecmB gene, a general marker for stalk cell differentiation, is greatly overinduced by DIF in Dd-STATa null cells. Also, Dd-STATa null cells are hypersensitive to DIF for expression of ST/lacZ, a marker for the earliest stages in the differentiation of one of the stalk cell sub-types. We suggest that both these manifestations of DIF hypersensitivity in the null strain result from the balance between activation and repression of the promoter elements being tipped in favor of activation when the repressor is absent. Paradoxically, although Dd-STATa null cells are hypersensitive to the inducing effects of DIF and readily form stalk cells in monolayer assay, the Dd-STATa null cells show little or no terminal stalk cell differentiation within the slug. Dd-STATa null slugs remain developmentally arrested for several days before forming very small spore masses supported by a column of apparently undifferentiated cells. Thus, complete stalk cell differentiation appears to require at least two events: a commitment step, whereby the repression exerted by Dd-STATa is lifted, and a second step that is blocked in a Dd-STATa null organism. This latter step may involve extracellular cAMP, a known repressor of stalk cell differentiation, because Dd-STATa null cells are abnormally sensitive to the inhibitory effects of extracellular cyclic AMP.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1998

UGUS, a reporter for use with destabilizing N-termini.

Due to constraints in vector construction, reporter polypeptides often carry N-terminal sequences of extraneous origin. Since protein half-life can be influenced by small determinants in the N-terminus, such foreign sequences can destabilize proteins and compromise results of reporter-based studies. We provide a real-life example of this problem (destabilizing sequences derived from a ribosomal protein) and show that it can be solved with the ubiquitin fusion technique, in which ubiquitin sequences are placed upstream of the reporter, in our case beta-glucuronidase. Post-translational processing by characterized pathways removes the ubiquitin together with destabilizing sequences, generating a stable reporter whose N-terminus is constant.

Animals↗
PubMed1996

Characterisation and reactivity of a glycidic antigenic component in Toxoplasma gondii.

Toxoplasma gondii is composed of a complex antigenic mosaic and some antigenic fractions are of major diagnostic interest. We studied an antigenic fraction with molecular weight < 17 kda, identified by SDS-PAGE 15% and immunoblotting. This fraction could be easily extracted from the whole antigen with phenol/CH-Cl3 and its analysis showed a mainly carbohydrate composition. With immunoblotting this fraction showed strong reactivity with specific IgM and IgG in early-acute infection; IgM reactivity disappears or is much less marked in chronic acquired infection. Extraction with phenol/CHCl3 allows this fraction to be used as an antigen in other diagnostic methods.

Animals↗
PubMed1993

Double-blind study of nimesulide in divers with inflammatory disorders of the ear, nose and throat.

200 divers of either sex, aged 18 to 54 years, entered a double-blind study to compare the efficacy and tolerability of nimesulide 200 mg/day with those of seaprose S 60 mg/day in the treatment of nonbacterial inflammatory disorders of the ear, nose, and throat. At the end of the 1-week treatment period, both drugs were judged to be effective, with improvements and, in most cases, complete remission of all symptoms observed. Nimesulide showed greater clinical efficacy, and both drugs were well tolerated.

Adult↗
PubMed1992

A G-rich sequence element common to Dictyostelium genes which differ radically in their patterns of expression.

Removal of a G-rich element from the DIF-inducible, prestalk-, and stalk-specific ecmB gene reduces expression but cell-type specificity is retained. The ecmB element will functionally substitute for a homologous sequence upstream of CP2, a cAMP-inducible gene and is bound by GBF, the factor which interacts with the CP2 G box. These results suggest that the G box may play a similar stimulatory role in these two independently regulated genes where it presumably interacts with different ancillary promoter elements.

Animals↗
PubMed1991

Selective induction of gene expression and second-messenger accumulation in Dictyostelium discoideum by the partial chemotactic antagonist 8-p-chlorophenylthioadenosine 3',5'-cyclic monophosphate.

During development of the cellular slime mold Dictyostelium discoideum, cAMP induces chemotaxis and expression of different classes of genes by means of interaction with surface cAMP receptors. We describe a cAMP derivative, 8-p-chlorophenylthioadenosine 3',5'-cyclic monophosphate (8-CPT-cAMP), which inhibits cAMP-induced chemotaxis at low concentrations but induces chemotaxis at supersaturating concentrations. This compound, moreover, selectively activates expression of aggregative genes but not of postaggregative genes. 8-CPT-cAMP induces normal cGMP and cAMP accumulation but in contrast to cAMP, which increases inositol 1,4,5-trisphosphate levels, 8-CPT-cAMP decreases inositol 1,4,5-trisphosphate levels. The derivative induces reduced activation of guanine nucleotide regulatory proteins, which may cause its defective activation of inositol 1,4,5-trisphosphate production. Our data suggest that disruption of inositolphospholipid signaling impairs chemotaxis and expression of a subclass of cAMP-regulated genes.

Journal Article↗
PubMed1991

Positively and negatively acting signals regulating stalk cell and anterior-like cell differentiation in Dictyostelium.

The Dictyostelium ecmB gene encodes an extracellular matrix protein and is inducible by the stalk cell morphogen DIF. It is expressed in a subset of prestalk (pstB) cells in the slug and surrounding pstA cells first express it at culmination. A region of the ecmB promoter can direct transcription in all anterior prestalk cells, but a separate, downstream region acts to prevent its expression in pstA cells prior to culmination. This may be the site of interaction of a repressor, regulated by an extracellular antagonist to DIF. At culmination, expression of the ecmB gene also becomes greatly elevated in anterior-like cells as they move to surround the spore mass. A distal region of the ecmB promoter directs increased expression in those anterior-like cells that surmount the spore head. This divergence in gene expression suggests that anterior-like cells and anterior prestalk cells experience different inductive conditions at culmination.

Base Sequence↗
PubMed1991

Comparative evaluation of specific vaccines and immuno-modulators in disease control of beef cattle.

Two field trials were undertaken to evaluate specific vaccines and Biological Response Modifiers (B.R.M.) with regard to disease control of beef cattle. Clinical data and laboratory results strongly suggested a genetically determined resistance to transportation stress of some cattle breeds, with possible important consequences on the occurrence of multi-factor diseases. Plenty of calves showed detectable levels of serum interferon and a remarkable activation of at least some lymphocyte populations in the first days after arrival. In general, B.R.M.-treated cattle could better react against environmental pathogens, as evidenced by both clinical and laboratory findings. Several data emerged that even the efficacy of specific vaccines could be largely accounted for by a positive modulation of non-specific immunity; this latter feature can be mainly referred to adjuvants and/or some bacterial antigens.

Animals↗
PubMed1989

Complementation of a Dictyostelium discoideum thymidylate synthase mutation with the mouse gene provides a new selectable marker for transformation.

A cDNA encoding mouse thymidylate synthase has been inserted 3' to the Dictyostelium discoideum actin 15 promoter in an E. coli-D.discoideum shuttle vector. When this construct was introduced into a D.discoideum thymidylate synthase mutant strain HPS400, stable transformants were obtained at high frequency. These transformants grew in standard axenic medium without requiring exogenous thymidine. This construct provides a second selectable marker for use in transformation of D.discoideum.

Animals↗
PubMed1989

Characterization of some parameters of non-specific immunity in dairy cattle (I).

The concentrations of serum protein and immunoglobulin, complement, lysozyme, serum bactericidal activity and blast transformation of peripheral blood lymphocytes were assessed in dairy cattle in different herds and age groups. The study aimed at defining fundamental aspects of non-specific defence under the field conditions, related to age/season/management influences. The observed differences in the expression of these parameters are discussed, with regard to their role in the immune defence of calves and their relation to colostrum uptake. The possible use of these parameters in the control of animal welfare is stressed and the possibility is put forward of predicting possible unfavourable interactions with environmental pathogens.

Animals↗
PubMed1989

Analysis of specific mRNA destabilization during Dictyostelium development.

A number of specific mRNAs are destabilized upon disaggregation of developing Dictyostelium discoideum cells. Analysis of a family of cloned genes indicates that only prespore-enriched mRNAs are affected; constitutive mRNAs that are expressed throughout development and mRNAs that accumulate preferentially in prestalk cells are stable under these conditions. The decay of sensitive prespore mRNAs can be halted by allowing the cells to reaggregate, indicating that destabilization occurs by the progressive selection of individual molecules rather than on all members of an mRNA subpopulation at the time of disaggregation. Individual molecules of the sensitive mRNA species remain engaged in protein synthesis in the disaggregated cells until selected. Destabilization of sensitive mRNAs is induced by cell dissociation even in the presence of concentrations of nogalamycin that inhibit RNA synthesis. The reported prevention of disaggregation-induced mRNA decay by actinomycin D and daunomycin is therefore probably a secondary effect unrelated to the inhibition of transcription.

Dictyostelium↗