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Biomedical subjects

Fernando Gombos

Publications and source records attributed to Fernando Gombos.

17 recordsLinked to original sources
PubMed2007

Changes in desmoglein 1 expression and subcellular localization in cultured keratinocytes subjected to anti-desmoglein 1 pemphigus autoimmunity.

The complexity of pemphigus acantholysis together with the weak expression of desmoglein 1 (Dsg1) in cultured keratinocytes have made the study on the pathogenic action of anti-Dsg1 antibodies quite difficult. The pathophysiology of the acantholytic phenomenon could depend on the reduction of Dsg1 adhesion function occurring after its massive internalization or decrease of its synthesis. Here, we have investigated this hypothesis by using sera of patients having antibodies against Dsg1 or monoclonal anti-Dsg1 antibodies to simulate pemphigus autoimmunity in Dsg1-rich keratinocytes. Similar to pemphigus foliaceus (PF) and vulgaris (PV) sera, monoclonal anti-Dsg1 antibodies induced transient internalization of Dsg1 and reduced the adhesion strength among keratinocytes. However, binding of IgG to Dsg1 did not determine its early depletion from the adhesion complexes but reduced the amount of Dsg1 found in the Triton X-100 soluble pool of proteins. Taken together, our results represent the first demonstration that anti-Dsg1 antibodies induce similar alterations on the subcellular distribution of Dsg1 irrespective of the disease where they come from. Furthermore, the present study provides insight into the mechanisms underlying epithelial blistering observed in the skin type of pemphigus.

Acantholysis↗
PubMed2006

TGFbeta3 expression in non-syndromic orofacial clefts.

BACKGROUND: Genetic studies have demonstrated that non-syndromic cleft is composed of two separate entities - cleft palate only (CPO) and cleft of lip, alveolus with or without cleft palate (CL+/-P) -, both have a heterogeneous genetic background and environmental factors contribute to the onset of these malformations. Previous studies have shown that TGFbeta3 could be involved in these diseases, but no conclusive results have been reached. PURPOSE: In order to detect if TGFbeta3 has a role in cleft diseases, a series of non-syndromic cleft patients and controls are analyzed for TGFbeta3 protein expression. MATERIAL AND METHODS: Forty-three non-syndromic cleft patients and 21 unaffected subjects were involved in this study. Paraffin-embedded specimens were matched with the TGFbeta3 antibody and then scanned with a computerized image analyzer. TGFbeta3 was found to be absent (less than 10%), moderate (from 10% to 30%) and highly expressed (higher than 30%) in epithelium (EP), minor palatal salivary gland (GL) and fibres of elevator palati muscle (MU). Data was statistically analyzed with a Kruskal-Wallis test. RESULTS: Only GL and EP have a statistically significant lower expression in non-syndromic cleft compared to unaffected subjects. A subsequent comparison between CL+/-P and CPO groups demonstrates a statistically significant difference only for GL, with a lower expression in GL of CPO patients. CONCLUSIONS: TGFbeta3 is decreasingly expressed in GL of unaffected CL+/-P and CPO patients and thus further strength is given to a pathogenetic role of TGFbeta3 in the onset of clefts.

Case-Control Studies↗
PubMed2006

Physical training and metabolic supplementation reduce spontaneous atherosclerotic plaque rupture and prolong survival in hypercholesterolemic mice.

Moderate physical exercise (PE) combined with metabolic treatment (MT) (antioxidants and l-arginine) are well known to reduce atherosclerotic lesion formation in hypercholesterolemic mice. However, the long-term beneficial effects on unstable atheroma remain poorly understood. We started early PE training in large groups of 6-week-old hypercholesterolemic mice (by graduated swimming) alone or in combination with nutritional supplementation (1.0% vitamin E added to the chow and 0.05% vitamin C and 6% l-arginine added to the drinking water). Inactive controls did not receive PE. The spontaneous development of atherosclerotic plaque rupture (associated with advanced atherosclerosis) and survival rates were evaluated. Moderate PE elicited an increase in plasma levels of nitric oxide. Early combined treatment with PE and MT in the hypercholesterolemic mice significantly reduced lesions (also detected noninvasively at 10 months) and spontaneous atherosclerotic plaque rupture and prolonged survival more effectively than each intervention alone. Thus, early concerted actions of MT and PE improve the natural history of atherosclerotic lesions and reduce the plaque instability in hypercholesterolemic mice.

Animals↗
PubMed2006

Serum from pemphigus vulgaris reduces desmoglein 3 half-life and perturbs its de novo assembly to desmosomal sites in cultured keratinocytes.

Defects of cell-cell adhesion underlie disruption of epithelial integrity observed in patients with pemphigus vulgaris (PV), an autoimmune disease characterized by severe mucosal erosions and skin blisters. Pathogenic PV autoantibodies found in patients' sera target desmoglein 3 (Dsg3), a major component of the desmosome, but how does this phenomenon affect Dsg-dependent adhesion and lead to acantholysis still remains controversial. Here, we show that PV serum determines a reduction of Dsg3 half-life in HaCaT keratinocytes, although the total amount of Dsg3 remains unchanged. Immunofluorescence studies suggest that PV IgG exert their effect prevalently by binding non-desmosomal Dsg3 without causing its massive internalization. Furthermore, PV IgG targeting desmosome-assembled Dsg3 do not induce depletion of Dsg3 from the adhesion sites. Conversely, incorporation of PV IgG-Dsg3 complexes into new forming desmosomes appears perturbed. With our study, the basic biochemical changes of Dsg3 in an in vitro model of PV have been defined.

Autoantibodies↗
PubMed2006

In vitro bone production using stem cells derived from human dental pulp.

To harvest bone for autologous grafting is a daily problem encountered by craniofacial and oral surgeons. Stem cells derived from human dental pulp are able to differentiate in osteoblasts and are a potential source of autologous bone produced in vitro. The authors describe their preliminary results in this new field with its potential application in craniomaxillofacial surgery. Dental pulp was gently extracted from 34 human permanent teeth (all third molars) of patients 19 to 37 years of age. After they were digested, the cells were selected using a cytometer for c-kit, STRO-1, CD34, CD45, and then for CD44 and RUNX-2. This study, made on a considerable number of cases, provided evidence that dental pulp is extremely rich in stem cells, which were c-kit+/CD34+/STRO-1+/CD45-, capable of differentiation toward several stromal-derived differentiated cells and mainly osteoblasts. These findings, supported by the large number of cases, are of great interest for tissue regeneration, tissue-based clinical therapies, and transplantation.

Adolescent↗
PubMed2006

How does acantholysis occur in pemphigus vulgaris: a critical review.

BACKGROUND: Pemphigus vulgaris is a life-threatening autoimmune blistering disease targeting skin and mucous membranes, characterized by disruption of keratinocytes' adhesion termed acantholysis. Today multiple classes of targets are considered to play a role in the genesis of the acantholysis; of these, the classical pemphigus antigens, desmosomal cadherins (desmoglein 1 and 3) are the best characterized and considered as the most important. Additional antigens include the novel epithelial acetylcholine receptors (alpha9 and pemphaxin). Thus, acantholysis in pemphigus seems to result from a cooperative action of antibodies to different keratinocyte self-antigens, but the mechanisms by which epithelial cleft occurs are not yet clearly understood. In fact, the binding of the autoantibodies to these targets generates a plethora of biological effects due, on one hand, to their direct interference with adhesive function and, on the other, to more complex events involving intracellular pathways that modify proteases activity or calcium metabolism, leading to loss of cell-cell adhesion.

Acantholysis↗
PubMed2005

Delaire's cheilorhinoplasty: unilateral cleft aesthetic outcome scored according to the EUROCLEFT guidelines.

OBJECTIVE: The aim of our study is to evaluate, in accordance with EUROCLEFT guidelines, the aesthetics of nasolabial area in a sample of complete unilateral cleft of lip and palate patients (UCLP), after surgical correction with Delaire' technique. METHODS: Twenty-two UCLP patients (16 males and 6 females, 9 right and 13 left side clefts) were enrolled in this retrospective study. Patients were operated at 7 (mean value) months of age by a single surgeon. Frontal and sub-mental photos for each baby were recorded at 8.5 (mean value) years of age, and evaluated twice, by three independent maxillofacial surgeons. A five-point scale (EUROCLEFT guidelines) was used. Nonparametric analysis (Kruskal-Wallis test) was applied to detect differences in medians obtained in studied groups. RESULTS: Kruskal-Wallis test showed no statistical significant differences among evaluations of three surgeons and between the first and the second evaluation of the same surgeon. The global appearance of the upper lip and nose was scored with a mean value of 2 (i.e. good). The sample was then divided into two subgroups, according with patient' age; the aesthetics and the symmetry of the nose resulted better in elder patients (i.e. subgroup A, mean period of observation=10.2 years), whereas upper lip achieved better results in younger patients (i.e. subgroup B, mean period of observation=4.9 years). CONCLUSIONS: EUROCLEFT guidelines are a useful method to evaluate--aesthetically and over time--cleft lip and palate patients, treated with a single surgical procedure. We hypothesize that Delaire technique could progressively improve aesthetics and symmetry of the nose, throughout the growth of the patient.

Child↗
PubMed2005

Study of folate receptor genes in nonsyndromic familial and sporadic cleft lip with or without cleft palate cases.

Folate receptor family members (FOLRs) mediate the delivery of 5-methyltetrahydrofolate to the interior of, out of within, or between cells in a process known as potocytosis. Three FOLRs and a pseudogene map to 11q13.4. The aim of this study was to verify whether FOLRs could be responsible for the onset of nonsyndromic cleft lip with or without cleft palate (CL/P). Linkage and linkage disequilibrium between genetic markers and disorder were analyzed. Patients and their mothers from 71 familial CL/P pedigrees and 75 sporadic cases from Italian population were investigated by PCR-SSCP analysis. Data from mutation scanning allowed us to find only a silent mutation in FOLR1 present in a mother and her child. Our findings do not support FOLR1 and FOLR2 genes in the onset of CL/P.

Carrier Proteins↗
PubMed2005

Non-syndromic orofacial clefts in Southern Italy: pattern analysis according to gender, history of maternal smoking, folic acid intake and familial diabetes.

BACKGROUND: Genetic studies have demonstrated that non-syndromic clefts of the lip, alveolus and palate have an heterogeneous genetic background, and that environmental factors contribute to the onset of this malformation. Therefore studies on different and homogeneous populations can be useful in detecting potentially related environmental and genetic factors. PURPOSE: The aim of the present study was to evaluate whether gender, folic acid intake, family history of diabetes and/or smoking during pregnancy were associated with a specific type of cleft in a group of patients affected by non-syndromic clefts, collected from Southern Italy. MATERIAL AND METHODS: Data from one hundred and twenty-six patients were evaluated retrospectively. Each cleft was described as composed by separate antomical entities such as lip, alveolus, primary and secondary palate. None had an isolated alveolar cleft and this was used as internal control. Pattern analysis was used to detect differences in the frequencies of any possible combination of 7 types of clefting stratified according to the studied variables. Data were analysed by comparing observed proportions. RESULTS: Isolated cleft palate as well as right-sided clefts of lip, alveolus and palate were more frequent in females (p = 0.0014 and 0.0281, respectively), while left sided clefts were more frequent in males (p = 0.0359). A lack of consumption of folic acid was associated with an higher incidence of clefts of the left lip (p = 0.018), while familial diabetes was associated more often with isolated cleft palate (p = 0.0014). CONCLUSIONS: Gender-related results were comparable with those found in Northern Italy and other countries. Environmentally related results disclosed specific subclasses of clefting associated with lack of folic acid consumption and familial diabetes.

Cleft Lip↗
PubMed2005

Pemphigus mimicking aphthous stomatitis.

BACKGROUND: The aim of this report is to highlight the case that pemphigus vulgaris (PV) may mimic aphthous stomatitis. Pemphigus classically causes persistent oral ulceration. METHODS AND RESULTS: We report five patients from southern Europe, who presented with recurrent oral ulceration mimicking aphthous stomatitis, but who proved by histology, immunostaining and antibodies against epithelial intercellular substance to have PV. CONCLUSION: It is advisable to assay antibodies against desmoglein 3 in patients who appear to suffer recurrent aphthous stomatitis (RAS) with atypical ulceration for location and in adulthood.

Adult↗
PubMed2003

Oral erosive/ulcerative lichen planus: preliminary findings in an open trial of sulodexide compared with cyclosporine (ciclosporin) therapy.

OBJECTIVE: To study the effect of the heparinoid sulodexide systemically, compared with topical cyclosporine (ciclosporin), on chronic oral erosive/ulcerative lichen planus. STUDY DESIGN: An open nonrandomized trial was conducted in two groups of 10 Italian patients with lichen planus, with subjective assessment of pain and assessment of ulceration amelioration by nonblinded clinicians. RESULTS: Comparable pain relief and amelioration of erosions/ulcers were seen in patients on sulodexide and in those on ciclosporin, but with faster healing in those on sulodexide. CONCLUSIONS: Sulodexide appears to be as effective, and perhaps more effective, than topical ciclosporin in the therapy of oral lichen planus, and is less expensive, but full double-blind placebo-controlled studies are required.

Adult↗
PubMed2003

Recurrent aphthous stomatitis unresponsive to topical corticosteroids: a study of the comparative therapeutic effects of systemic prednisone and systemic sulodexide.

BACKGROUND: Recurrent aphthous stomatitis (RAS) is a common oral condition, the etiology of which remains largely unclear. Numerous therapeutic protocols have been tried. Apart from immunomodulators, no therapy is unequivocally effective, and many systemic therapies have potential adverse effects. OBJECTIVE: To compare, in patients with frequent RAS unresponsive to conventional therapies, the therapeutic effectiveness of systemic prednisone with that of systemic sulodexide, a low-molecular-weight heparin with immunosuppressive activity but few adverse effects. METHODS: The study involved a group of 30 patients suffering from frequent minor RAS over >or= 4 months unresponsive to topical corticosteroids. Patients were randomly assigned to one of three study groups: blind therapy with systemic sulodexide or systemic prednisone and control (no treatment). The outcomes were assessed blind on the basis of the days to recovery from pain and days to recovery from ulceration (epithelialization) during the first month of therapy; the number of aphthae appearing during the second month of therapy; and the number of aphthae appearing in the 2 months after the end of the 2-month treatment cycle. RESULTS AND CONCLUSIONS: The effectiveness of systemic sulodexide was almost comparable with that of systemic prednisone in patients with frequent RAS, without significant adverse effects.

Administration, Topical↗
PubMed2003

Linear IgA dermatosis induced by a new angiotensin-converting enzyme inhibitor.

A 68-year-old female patient treated with benazepril for arterial hypertension developed oral and cutaneous blistering. Biopsy of the oral and cutaneous lesions showed neutrophilic microabscesses in the mesenchymal papillae, with epitheliomesenchymal separation. Direct immunofluorescence revealed linear immunoglobulin deposits at the epithelial basement membrane zone, consisting predominantly of IgA. The histologic results supported the clinical diagnosis of drug-induced linear IgA disease. The substitution of benazepril with a beta blocker resulted in complete resolution of all mucocutaneous lesions.

Aged↗
PubMed2003

Sweet's syndrome: recurrent oral ulceration, pyrexia, thrombophlebitis, and cutaneous lesions.

We report a case of Sweet's syndrome with recurrent oral ulceration, pyrexia, skin lesions, and migratory thrombophlebitis, with no detectable systemic cause, during a 2-year follow-up. Biopsy examination both of oral lesions and the skin eruption showed a characteristic dense, perivascular, neutrophilic infiltrate in the lamina propria. Laboratory investigations confirmed an inflammatory syndrome with an increased erythrocyte sedimentation rate, but no underlying cause was found. Sweet's syndrome is a rare immunologically mediated condition that belongs to the group of neutrophilic dermatoses that must be differentiated particularly from Behcet's disease. It is characterized by red-brown plaques and nodules that are frequently painful and occur primarily on the head, neck, and upper extremities. Often the patients also have neutrophilia and fever and may have oral ulceration. In approximately 10% of patients with Sweet's syndrome, there is an associated malignancy--most commonly acute myelogenous leukemia--but some cases, as here, are unassociated with detectable malignant or other disease, although the syndrome may precede the onset of definable systemic disease.

Adult↗
PubMed2003

Recent developments in orofacial cleft genetics.

Nonsyndromic cleft of the lip and/or palate (CLP or orofacial cleft) derives from an embryopathy with consequent failure of the nasal process and/or palatal shelves fusion. This severe birth defect is one of the most common malformations among live births. Nonsyndromic CLP is composed of two separate entities: cleft lip and palate (CL+/-P) and cleft palate only (CPO). Both have a genetic background, and environmental factors probably disclose these malformations. In CL+/-P, several loci have been identified, and, in one case, a specific gene has also been found. In CPO, one gene has been identified, but many more are probably involved. Because of the complexity of the genetics of nonsyndromic CLP as a result of the difference between CL+/-P and CPO, heterogeneity of each group caused by the number of involved genes, type of inheritance, and interaction with environmental factors, we discuss the more sound results obtained with different approaches: epidemiological studies, animal models, human genetic studies, and in vitro studies.

Animals↗
PubMedDate not supplied

Burning Mouth Syndrome: open trial of psychotherapy alone, medication with alpha-lipoic acid (thioctic acid), and combination therapy.

OBJECTIVE AND STUDY DESIGN: This open study of 192 otherwise healthy persons with burning mouth syndrome, examined the efficacy on control of symptoms of psychotherapy alone with two hour sessions weekly for two months; alpha lipoic acid (ALA, tioctic acid; Tiobec) 600 mg/day alone for two months; or combination therapy of psychoanalysis and 600 mg/day ALA for two months. Controls received placebo alone. RESULTS: Most benefit was obtained with combination therapy. Combination therapy of psychoanalysis and alpha lipoic acid (ALA, tioctic acid; Tiobec. 600 mg/day) for two months gave most benefit and significantly more than psychoanalysis alone for two 1 hour sessions weekly for two months (p<0.0005), or ALA 600 mg/day alone for two months (p<0.0005). CONCLUSION: The present results suggest that alpha lipoic acid may complement psychotherapy and can be an acceptable alternative to psychoactive agents, but trials to compare the two approaches are now warranted.

Adult↗