Biomedical subjects

M Paradisi

Publications and source records attributed to M Paradisi.

At least 19 recordsLinked to original sources

PubMed2005

[PTPN11 gene mutation in LEOPARD syndrome].

The multiple lentigines/LEOPARD syndrome (ML/LS) is a rare and complex genetic syndrome. It is an autosomal dominant disorder with a variable expressivity. The syndrome is mainly characterised by growth retardation, multiple lentigines, and congenital heart diseases with electrocardiographic anomalies, dysmorphia of the face and deafness. The incidence of this pathology is still unknown and a familial inheritance is present in 70% of cases. Some of the ML/LS clinical features are the same as those of the Noonan syndrome (NS), such as congenital cardiac abnormalities, dysmorphia and growth retardation. NS and ML/LS are caused by allele mutations of the PTPN11 gene. We report the case of a 3-year-old girl, who was observed for the presence of widespread lentigines, a 1/6-protosystolic murmur at the mesocardium and growth retardation. The diagnosis of ML/LS was made and thus a molecular analysis of the PTPN11 gene was carried out, directly sequencing the codifying region. The molecular analysis revealed a missense mutation (A836G) in hexone 7 (TYR279CYS) of the PTPNII gene. This mutation is has been observed, at present, in a few cases of ML/LS and Noonan syndrome.

Child, Preschool↗

PubMed2004

p75(NTR)-immunoreactivity in the subventricular zone of adult male rats: expression by cycling cells.

While the study of in vitro regulation of neural stem cell lineage from both embryonic and adult neurospheres is greatly advanced, much less is known about factors acting in situ for neural stem cell lineage in adult brain. We reported that neurotrophin low affinity receptor p75(NTR) is present in the subventricular zone (SVZ) in adult male rats. We then characterized co-distribution of markers associated with precursor cells (nestin and PSA-NCAM) with growth factor receptors (p75(NTR), trkA, EGFr) and proliferation-associated antigens (Ki67 and BrDU-uptake) in adult male rat by immunocytochemistry and confocal laser scan microscopy. Distribution of p75(NTR)-immunoreactivity (IR) was investigated using different mono- and polyclonal antisera. p75(NTR-) is not co-distributed with glial fibrillary acid protein. It was found to be co-distributed with a small number of nestin-IR cells, whereas no coexistence with PSA-NCAM-IR was observed. Conversely, p75(NTR)-IR was present in numerous dividing cells (Ki-67-positive) and co-distributed with EGFr. In order to verify the possible association between p75(NTR) and cell death, we investigated co-distribution of p75(NTR)-IR with nuclear condensation images as visualized by Hoechst 33258 staining. While few images indicating nuclear condensation were observed in the SVZ, no coexistence with p75(NTR) was found. TrkA- and trkB-IR was not found in the SVZ. We also investigated p75(NTR) immunostaining on post-natal day 1 and day 16, because of the dramatic reduction of proliferating cells in SVZ over this time-interval. p75(NTR)-IR was not increased in the early post-natal phase. Thus, p75(NTR) seems to be associated with cell cycle regulation in SVZ in adult rat brain.

Animals↗

PubMed2004

[Successful treatment of Norwegian scabies with ivermectin in a patient with recessive dystrophic epidermolysis bullosa].

A 14 year-old female born from consanguineous healthy parents was admitted to our institute for the presence of a generalized bullous eruption started at birth. The bullae were asymmetrically distributed all over the cutaneous surface and, over time, evolved into erosions that resolved with scarring areas. On the basis of the clinical picture and the ultrastructural and antigenic studies, a diagnosis of recessive dystrophic epidermolysis bullosa was made. In the following months, the patient began to complain a severe pruritus and the bullae and erosions were accompanied with diffuse erythematous patches and plaques covered by thick scale-crusts situated mostly on the arms. Microscopic examination of the scales revealed the presence of many mites and ova. Since the conventional topical therapies for scabies were uneffective, the patient was treated with a single dose (200 mcg/hg) of ivermectin. Although there was an initial improvement, scabies recurred within 2 months from discontinuation of the therapy. Finally, a further single administration of ivermectin at the same dosage led to the complete and permanent resolution of scabies. The association of recessive dystrophic epidermolysis bullosa and norwegian scabies has been already reported in literature. The case presented suggests that ivermectin represents an effective drug for severe forms of scabies occurring in patients affected by other dermatoses that prevent the use of topical treatments.

Adolescent↗

PubMed2003

Atrichia with papular lesions resulting from a novel homozygous missense mutation in the hairless gene.

Atrichia with papular lesions (APL) is a rare autosomal recessive disorder resulting in complete and irreversible hair loss shortly after birth. Affected individuals also develop papular lesions of keratin-filled follicular cysts over extensive areas of the body. Mutations in the hairless gene, a putative single zinc-finger transcription factor protein, have been implicated in the pathogenesis of APL. In this report, we describe a novel missense mutation, E583V, in the hairless gene in an Italian family affected with APL. The mutation resides between the LXXLL motif found in TRIPs (thyroid hormone receptor interacting proteins) in exon 5 and the six-cysteine zinc-finger motif in exon 6. The amino acid sequence neighbouring the LXXLL motif and zinc-finger domain is highly conserved in human, monkey, rat, and mouse hairless proteins. Our finding extends the body of evidence that supports the importance of the zinc-finger and LXXLL domains in the function of the hairless protein. Moreover, we continue to find small APL families without consanguinity from around the world.

Alopecia↗

PubMed2003

[Erythema nodosum induced by kerion celsi in a child with hypomelanosis of Ito].

A 3-year-old boy presented with an 8 week history of inflammatory nodular lesions on the scalp. Shortly afterwards painful subcutaneous nodules developed on the lower legs. Epidermophyton floccosum was isolated from the scalp lesions and a diagnosis of erythema nodosum induced by kerion celsi of the scalp was made. The patient was started on oral therapy with 250 mg/day griseolfuvin, associated with topical eosine and myconazol. Erythema nodosum represents a reaction pattern to a wide variety of inflammatory stimuli. The interest of this case lies in the unusual association of kerion celsi and erythema nodosum and in the identification of Epidermophyton floccosum in the lesions of the scalp.

Child, Preschool↗

PubMed2002

Circulating interleukin 16 (IL-16) in children with atopic/eczema dermatitis syndrome (AEDS): a novel serological marker of disease activity.

BACKGROUND: Chemokines play a central role in atopic eczema/dermatitis syndrome (AEDS). Interleukin 16 (IL-16) has been described as a main cytokine involved in CD4+ cell recruitment during inflammation. Recently the influx of CD4+ lymphocytes has been related to the up-regulation of IL-16 in AEDS skin lesions. Circulating beta-chemokines (Eotaxin and RANTES) and IL-16 were investigated in children with AEDS to correlate their presence with the severity of the disease. We also measured serum levels of soluble CD30 (sCD30), a marker of Th2 immune responses related to AEDS disease activity. METHODS: Serum levels of eotaxin, RANTES, IL-16 and sCD30 were measured by immunoenzymatic assay in paediatric patients with pure AEDS (pAEDS, n = 39); the severity of the disease was graded by SCORAD. Fifteen children with AEDS in presence of respiratory allergy (AEDS+A), 15 with allergic asthma (A) and 20 age-matched healthy donors were investigated as control groups. RESULTS: When compared to normals, high amounts of Eotaxin and IL-16 were detected in sera of pAEDS (P = 0.002; P < 0.0001), AEDS+A (P = 0.02; P = 0.01) and A patients (P = 0.004; P = 0.03) with respect to normals. Serum levels of RANTES were also elevated in pAEDS patients, significantly higher than normals (P = 0.009), whereas no statistically significant differences could be detected between pAEDS and AEDS+A or A groups. IL-16 was progressively increased in the different stages of pAEDS, with a positive correlation between IL-16 and both SCORAD and sCD30 (P < 0.0001). CONCLUSION: We suggest that IL-16 could serve as a useful marker of disease activity in childhood pAEDS.

Asthma↗

PubMed2001

Novel and recurrent mutations in the genes encoding keratins K6a, K16 and K17 in 13 cases of pachyonychia congenita.

Thirteen patients with pachyonychia congenita types 1 and 2 were studied, two of which had a family history of pachyonychia and 11 of which were sporadic cases. Heterozygous mis-sense or small in-frame insertion/deletion mutations were detected in the genes encoding keratins K6a, K16, and K17 in all cases. Three novel mutations, F174V, E472K, and L469R were found in the K6a gene. Two novel mutations, M121T and L128Q were detected in K16. Similarly, three novel mutations, L95P, S97del, and L99P were found in K17. In addition, we identified recurrent mutations N171del (three instances) and F174S in K6a and R94H in K17. Analysis of both phenotype and genotype data led to the following conclusions: (i) K6a or K16 mutations produce the pachyonychia congenita type 1 phenotype, whereas K17 (or K6b) mutations cause pachyonychia congenita type 2; (ii) the presence of pilosebaceous cysts following puberty is the best indicator of pachyonychia congenita type 2; (iii) prepubescent patients are more difficult to classify due to the lack of cysts; and (iv) natal teeth are indicative of pachyonychia congenita type 2, although their absence does not preclude the pachyonychia congenita type 2 phenotype. This study establishes useful diagnostic criteria for pachyonychia congenita types 1 and 2, which will help limit unnecessary DNA analysis in the diagnosis and management of this genetically heterogeneous group of genodermatoses.

DNA Mutational Analysis↗

PubMed2001

[Tinea faciei in a newborn].

Dermatophytosis in newborns and infants has been regarded as very unusual; a case recently observed of a 2-month-old child affected by tinea faciei is described. Twenty days before, localized erythematous infiltrated patches at the upper left eyelid and eyebrows with papules and pustules, were observed. Rarefaction of the eyebrows and partially loss of the eyelashes associated with scattered areas of erythematopapulous lesions on the face, were seen. Mycological examination was positive and trichophyton rubrum colonies grew. Tinea capitis is more common than tinea faciei in newborn and infants. Differential diagnosis includes: seborrheic dermatitis, atopic dermatitis with associated impetigo, candidiasis, bacterial folliculitis. The interhuman transmission by relatives is the most probable modality of trans-mission, as previously reported in the literature. A widespread of the dermatoses was due to previous application of topical corticosteroids. The lesions resolved completely after treatment with miconazole cream, applied twice daily for three weeks.

Age Factors↗

PubMed2001

[A Pediatric case of lupoid leishmaniasis diagnosed by PCR].

The purpose of this paper is to describe the clinical features of lupoid leishmaniasis in a child and to underline the use of PRC as a necessary and reliable tool in controversial diagnosis. Lupoid leishmaniasis, also known as chronic or relapsing leishmaniasis, is mainly widespread in the Middle East, where it represents up to 5% of all cutaneous Leishmaniasis. It strongly resembles Lupus Vulgaris, both clinically and histologically, and is therefore not usually diagnosed immediately but after a certain period of time. The amastigotic forms are rare or absent. The cutaneous nodules or plaques can slowly enlarge over the years. The case of an eleven-year-old albanian child living in Durazzo (Albania), suffering since three years with a plaque formed by apple-jelly nodules and scars on his right cheek, is presented. Using PCR, the presence of Leishmania infantum DNA led to a diagnosis of lupoid leishmaniasis. The therapeutic strategy of a combination of oral itraconazole and infiltration of metilglucamina antimoniate has been carried out, with good result, as checked through "telemedicine".

Administration, Oral↗

PubMed2001

Becker's nevus syndrome.

Becker's nevus (BN) is a unilateral hyperpigmented, often hairy, cutaneous hamartoma, with geographic borders. It is usually localized on the shoulder, anterior chest, scapula, or upper arm, but there have been reports of BN in other areas (eg, lower extremities, face). In most cases, the lesion appears in late childhood or adolescence, and both congenital and familial cases have been described.

Adolescent↗

PubMed2001

Infantile acute hemorrhagic edema of the skin.

Infantile acute hemorrhagic edema (AHE) of the skin is an uncommon form of cutaneous leukocytoclastic vasculitis that occurs in children younger than 3 years. We describe a 10-month-old boy with AHE, in whom the disease appeared after antibiotic treatment for an acute respiratory illness. AHE presented with fever, acral edema, and rosette-shaped purpuric plaques on the face and limbs. The causes of AHE are unclear, as is its nosologic position. Some authors consider the disease as a purely cutaneous form of Henoch-Schönlein purpura, and others believe that AHE should be regarded as a distinct clinicobiologic entity within the spectrum of leukocytoclastic vasculitis.

Acute Disease↗

PubMed2000

Localization of the Netherton syndrome gene to chromosome 5q32, by linkage analysis and homozygosity mapping.

Netherton syndrome (NS [MIM 256500]) is a rare and severe autosomal recessive disorder characterized by congenital ichthyosis, a specific hair-shaft defect (trichorrhexis invaginata), and atopic manifestations. Infants with this syndrome often fail to thrive; life-threatening complications result in high postnatal mortality. We report the assignment of the NS gene to chromosome 5q32, by linkage analysis and homozygosity mapping in 20 families affected with NS. Significant evidence for linkage (maximum multipoint LOD score 10.11) between markers D5S2017 and D5S413 was obtained, with no evidence for locus heterogeneity. Analysis of critical recombinants mapped the NS locus between markers D5S463 and D5S2013, within an <3.5-cM genetic interval. The NS locus is telomeric to the cytokine gene cluster in 5q31. The five known genes encoding casein kinase Ialpha, the alpha subunit of retinal rod cGMP phosphodiesterase, the regulator of mitotic-spindle assembly, adrenergic receptor beta2, and the diastrophic dysplasia sulfate-transporter gene, as well as the 38 expressed-sequence tags mapped within the critical region, are not obvious candidates. Our study is the first step toward the positional cloning of the NS gene. This finding promises a better understanding of the molecular mechanisms that control epidermal differentiation and immunity.

Adolescent↗

PubMed2000

Neonatal lupus erythematosus.

Neonatal lupus erythematosus (NLE) is a rare disease characterized by the transplacental passage from the mother to the fetus of autoantibodies, in particular anti-Ro(SS-A), anti-La(SS-B), or both. The majority of infants with NLE exhibit isolated congenital heart block, cutaneous lesions analogous to those of adult subacute cutaneous lupus erythematosus, or both. We report a case of NLE in a 3-month-old male infant, born to a clinically asymptomatic mother, presenting small, annular, erythematous plaques with sharp, hyperkeratotic borders and central clearing localized at the eyebrow region. Both the infant and the mother were positive for anti-Ro(SS-A).

Adult↗

PubMed1998

Compound heterozygosity for an out-of-frame deletion and a splice site mutation in the LAMB3 gene causes nonlethal junctional epidermolysis bullosa.

Laminin-5 is the major adhesion ligand of epithelial cells. Mutations in the genes encoding laminin-5 cause junctional epidermolysis bullosa (JEB), a clinically and genetically heterogeneous group of recessively inherited blistering disease of skin and mucous membranes. In this report, we describe a patient with a non-lethal variant of JEB who is a compound heterozygous for mutations affecting the LAMB3 gene. The paternally inherited mutation is a deletion of a single base (T) leading to a frameshift and premature termination codon. It results in mRNA decay. The maternally inherited mutation is a G-->A transition at the last base of exon 7 (628G-->A) which converts a codon for glutamic acid in a codon for lysine (E210K). The mutation 628G-->A alters the correct splicing of LAMB3 pre-mRNA giving rise to two aberrant mRNA, in addition to the RNA transcript carrying the G-->A substitution. This result is compatible with the reduced expression of mutated laminin 5 molecules with altered biological activity, and the mild JEB phenotype observed in the patient.

Base Sequence↗

PubMed1998

180-kDa bullous pemphigoid antigen defective generalized atrophic benign epidermolysis bullosa: report of four cases with an unusually mild phenotype.

Generalized atrophic benign epidermolysis bullosa (GABEB) is a rare variant of non-lethal junctional epidermolysis bullosa characterized by generalized skin blistering healing with atrophy and by atrophic alopecia with onset in childhood. Other features include mild mucosal blistering, dental abnormalities and nail dystrophy. We report four additional cases of GABEB from two families originating from the same isolated village. The patients shared an unusually mild clinical phenotype with cutaneous blisters strictly limited to trauma sites and rare occurrence of oral mucosal lesions. Scalp, eyelash and eyebrow alopecia was present in only two cases. Immunofluorescence studies showed a markedly reduced expression of the 180-kDa bullous pemphigoid antigen (BP180), and northern analysis of cultured keratinocytes indicated that the gene encoding for BP180 is affected in these GABEB patients.

Adult↗

PubMed1997

Neutrophilic figurate erythema of infancy.

We describe a transient figurate erythema in an 11-month-old female infant with a 2-month history of arcuate and annular erythematous lesions localized on the face, trunk, and limbs. Constitutional symptoms were absent. Previous medical history was unremarkable. Full blood examination, erythrocyte sedimentation rate, antistreptolysin-O titer, anti-Ro, and anti-La antibodies were within normal limits or negative. Histologic examination revealed a superficial and deep perivascular and interstitial dermatitis constituted mostly of neutrophils and abundant nuclear dust. The lesions resolved spontaneously within a few months without scarring or atrophy. Recurrence has not occurred. This case suggests that figurate erythemas in infants rarely may disclose a neutrophilic histologic pattern, which must be differentiated from that of other neutrophilic dermatoses.

Antibodies, Antinuclear↗

PubMed1997

Soluble CD30 in pediatric patients with atopic dermatitis.

Atopic dermatitis (AD) is a chronic, inflammatory skin disease in which a pathogenetic role of Th2 cells has been supposed. This study investigated the presence of soluble CD30 (sCD30), an activation marker of T-cell clones able to produce Th2-type cytokines, in sera from pediatric patients affected by AD (n = 25) with no symptoms of asthma or rhinitis. The severity of the disease was graded by both the SCORAD and Costa et al. clinical scoring systems. Serum levels of sCD30 were significantly higher in patients with AD in respect to both normal donors (n = 20) and urticaria patients (n = 10), and a positive correlation between serum sCD30 and clinical score was found (r = 0.508; P = 0.01) when AD patients were evaluated by Costa et al.'s method. Furthermore, a significant association (r = 0.443; P = 0.027) between sCD30 and serum levels of the soluble interleukin (IL)-2 receptor (sIL-2R) was observed in AD. The presence of high amounts of sCD30 in atopic patients seems to confirm the role of this molecule as an activation marker useful for in vivo evaluation of a Th2 immune response, and the correlation observed with both clinical score and sIL-2R levels indicates the role of sCD30 as an additional marker of disease activity in pediatric patients with AD.

Child↗

PubMed1997

[Ehlers-Danlos syndrome type I. Ultrastructural study].

Ehlers-Danlos syndrome comprises a very heterogeneous group of collagen diseases characterised in clinical terms by fragility and cutaneous hyperextensability, ligamentous hyperlaxity, ecchymosis, scarring, visceral and neurological manifestations. Having been described in detail by Ehlers in 1899 and Danlos in 1908, it was subsequently classified into various clinical types. At present at least 11 forms are recognised on the basis of their clinical characteristics, methods of transmission and biochemical defect; the first four types of the syndrome account for approximately 95% of cases. Almost all forms are transmitted with a dominant autosomic character. Specific genetic mutations have been ascertained whereas the biochemical defect has been identified in numerous types. Ehlers-Danlos type 1 syndrome is the most frequent and most severe form. The biochemical anomaly underlying the altered deposition of collagen fibre is still unknown and this is responsible for the "storiform" appearance of collagen fibre on ultrastructural examination. The authors have described a typical case of "Ehlers-Danlos type 1 syndrome" in which the diagnosis was confirmed by comparing clinical data and the results of ultrastructural tests which revealed the characteristic "pattern" of collagen fibres.

Adolescent↗