[Show abstract][Hide abstract] ABSTRACT: A novel explanation of pemphigus vulgaris (PV) pathogenesis suggests that serum autoantibodies may affect desmoglein 3 (Dsg3)-mediated adhesion by triggering depletion of Dsg3 from desmosomes. Furthermore, abrogation of Dsg3 from the cell seems to depend on anti-Dsg3 pemphigus IgG. In this study we sought to gain more insights into the role of PV IgG recognizing non-conformational epitopes of Dsg3 (anti-Dsg3-L IgG) by semi-quantitative living cell immunofluorescence (LCIF) microscopy, in-cell ELISA and morphometric analysis of acantholysis. Our data demonstrate that PV serum and PV IgG can induce acantholysis and reduce the total amount of Dsg3 in cultured keratinocytes, whereas anti-Dsg3-L IgG fail to do so when administered at concentrations comparable to those present in pathogenic PV sera. However, the Dsg3-depleting activity of such polyclonal anti-Dsg3 IgG was acquired when used at 1 microg/ml. Interestingly, both PV sera and IgG, including anti-Dsg3-L IgG, caused early depletion of surface Dsg3 while slightly affecting the total cell content of Dsg3 until late acantholysis. This raises a possibility that depletion of Dsg3 from cell membrane and reduction of the total cellular levels of Dsg3 represent distinct phenomena in PV acantholysis. Taken together, our data demonstrate that anti-Dsg3 PV IgG against linear epitopes of Dsg3 can induce acantholytic changes of keratinocytes in a dose- and time-dependent manner. Specifically, both morphological and biochemical changes suggestive of acantholysis are seen only at high IgG concentrations. We conclude that anti-Dsg3L IgG play a minor role in experimental PV under physiologic conditions.
Full-text · Article · Oct 2010 · International journal of immunopathology and pharmacology
[Show abstract][Hide abstract] ABSTRACT: Recurrent aphthous stomatitis (RAS) is characterized by recurrent painful oral ulcers whose etiology remains largely unknown. Numerous therapeutic protocols have been tried so far, but effectiveness remains an issue.
To test a new drug for patients with recurrent oral aphthae nonresponsive to local corticosteroid therapy, we compared the therapeutic effectiveness and adverse effects of systemic prednisone and systemic montelukast in a placebo-controlled trial.
Sixty patients suffering from minor RAS for > or =6 months were studied and randomly assigned to 3 groups of 20 each in a double-blind study. Patients of group A took 25 mg prednisone orally daily for 15 days, 12.5 mg daily for 15 days, 6.25 mg daily for 15 days, then 6.25 mg on alternate days for 15 days. Patients of group B took 10 mg montelukast orally every evening and then on alternate days for the second month. Patients of group C took 100 mg cellulose (placebo) by mouth daily for the first month and on alternate days for the second month. Outcomes assessed were days til pain cessation, days to ulcer healing, and number of aphthae occurring during the follow-up period.
Both prednisone and montelukast were effective in reducing the number of lesions and improving pain relief and ulcer healing when compared with placebo. Prednisone was more effective than montelukast in pain cessation (P < .0001) and in accelerating ulcer healing (P < .0001). However, adverse drug reactions recorded during the entire trial were more common in the prednisone group compared with montelukast (10%) and placebo (10%).
These data suggest that the effectiveness of systemic montelukast is similar to that of systemic prednisone in patients with RAS. The lack of serious side effects makes montelukast a candidate drug to use in cases of RAS where pharmacologic therapy for long periods is needed.
Full-text · Article · Nov 2009 · Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology
[Show abstract][Hide abstract] ABSTRACT: Pemphigus vulgaris (PV) is an autoimmune blistering disease affecting primarily oral mucosa and skin. Among the drugs used for the therapy of pemphigus, both methylprednisolone (MP) and pyridostigmine bromide (PBr) can prevent acantholysis in vitro. However, their putative therapeutic properties in regenerating PV-like lesions and promoting the healing process still remain to be demonstrated. To address this issue, here we have developed a model for studying the process of epithelial cleft regeneration in PV by artificially wounding keratinocyte monolayers.
The experimental model was established by scratching confluent monolayers to simulate the epithelial cleft; then, wound regeneration in the presence of submaximal concentrations of PV sera was studied by time-lapse microscopy, with or without the addition of MP and PBr in the culture medium.
Pemphigus vulgaris serum inhibited epithelial cleft repair of wounded monolayers. Indeed, in the presence of 10% (v/v) PV serum, keratinocytes reached only 2% confluence within 72 h vs an almost complete healing of controls. When administered together with PV sera, MP significantly (P < 0.01) enhanced wound fill by 30% after 72 h. PV-associated wound repair was significantly (P < 0.05) ameliorated by PBr by 24 h and keratinocytes reached 20% confluence after 72 h. Interestingly, neither MP nor PBr could accelerate wound healing when compared with untreated control monolayers.
In PV, MP and PBr exert their curative effects in part by enhancing the regeneration properties of keratinocytes. Indeed, our data suggest that both drugs can specifically counterbalance the detrimental effects of PV serum on keratinocyte wound healing. These findings provide an explanation for the efficacy of MP and PBr in the treatment of PV lesions in human skin and oral mucosa.
[Show abstract][Hide abstract] ABSTRACT: We have previously demonstrated that serum autoantibodies of patients with pemphigus vulgaris (PV) may affect desmoglein 3 (Dsg3)-mediated adhesion by decreasing its half-life and inducing Dsg3 cleavage. Here we sought to gain more insights into the role of Dsg3-targetting IgG in acantholysis. To do so, alterations of keratinocyte morphology and cell-cell adhesion strength were investigated in the presence of PV serum, PV IgG, and IgG purified from PV patients' sera against linear epitopes of Dsg3 (anti-Dsg3-L IgG). Changes in Dsg3 protein levels were assessed by Western blotting. Results showed that both PV serum and PV IgG were able to induce acantholysis and decrease the total amount of Dsg3 in cell lysates. Polyclonal anti-Dsg3-L IgG displayed Dsg3-depleting activity solely when used at 1 microg/ml, i.e. under non-physiologic conditions. Furthermore, cell-cell detachment induced by PV IgG and anti-Dsg3-L IgG seemed to precede the loss of Dsg3 from keratinocytes, suggesting that depletion/degradation of Dsg3 represents a late event in acantholysis. Collectively, the data presented here demonstrate that PV IgG recognizing non-conformational epitopes of Dsg3 are pathogenic when administered on doses largely exceeding those found in PV sera.
Full-text · Article · Mar 2009 · Immunology letters
[Show abstract][Hide abstract] ABSTRACT: The aim of this research was to evaluate the effect of the Delaire surgical technique on the midfacial morphology in a group of subjects with a congenital unilateral cleft of lip and palate (UCLP), prior to orthodontic treatment. Thirty-five UCLP (15 left and 20 right) patients (16 males and 19 females, mean age 7.03+/-0.9 years; age range 8.7-5.0 years), treated for the correction of congenital malformation, were retrospectively selected. Analysis of midfacial growth was undertaken on lateral cephalograms, and the data were compared with reference values (Ricketts analysis). A Mann-Whitney ranked sum test was used to detect significant differences between the findings and reference values. P <or= 0.05 was considered as significant. The results demonstrated a retropositioning of both the maxilla and mandible (SNA and SNB P<0.01) and increased mandibular development (Go-Me distance). Vertically, there was a trend to a posterior rotation of the mandible (P<0.01), resulting in a hyperdivergent profile. This trend was confirmed by the increase in SpA-SpP/Go-Me (P<0.05). In agreement with previous studies, the effects of surgical closure of a cleft lip might be responsible for excessive maxillary retropositioning with a downward rotation.
Preview · Article · Dec 2008 · The European Journal of Orthodontics
[Show abstract][Hide abstract] ABSTRACT: We have previously demonstrated that serum of patients with pemphigus vulgaris induces reduction of desmoglein 3 (Dsg3) half-life in keratinocytes (FEBS Lett 2006: 580: 3276). This phenomenon seems to occur as a consequence of the progressive depletion of Dsg3 from desmosomes. Here we reported that reduction of full-length Dsg3 may be due to its progressive cleavage, leading to the formation of two fragmentation products with apparent molecular masses of about 60 kDa (fragment 1) and 70 kDa (fragment 2), as revealed by Western blotting. Unexpectedly, analysis of fragmentation pattern suggested cleavage to occur intracellularly. Consistently, fragment 1 was shed and localized within the cytosol, as shown by living cell immunofluorescence microscopy. Total amounts of full-length plakoglobin and Dsg1 were apparently unchanged. Taken together, our findings provide evidence that proteolytic processing of Dsg3 can lead to depletion of Dsg3 from the cell.
Full-text · Article · Oct 2008 · Experimental Dermatology
[Show abstract][Hide abstract] ABSTRACT: Burning mouth disorder (BMD) is a burning or stinging sensation affecting the oral mucosa, lips, and/or tongue, in the absence of clinically visible mucosal lesions. There is a strong female predilection, with the age of onset being approximately 50 years. The causes of BMD are multifactorial and remain poorly understood. Often BMD patients report, in association, change in taste. In this regards, it is relevant that in central nervous system connections exist between taste and oral pain and that taste normally inhibits oral pain.
The working hypothesis of this study considers a possible relationship between burning mouth disorders and alterations of taste. Several conditions or pathologies can be responsible of taste disturbances that might be the cause of oral pain in BMD patients.
We have analyzed, retrospectively, 142 cases of BMD with associated taste disturbance. Possible causes that could be responsible for alterations of taste were investigated.
Sixty-one subjects revealed the habitual use of drugs having a documented interference with taste perception. Thirty-five subjects, among the 81 patients who had no associated pathology or habitual use of drugs, noticed in their clinical history conditions, pathologies or use of drugs that are known to affect the gustatory system. Therefore, we propose that BMD may represent an oral phantom pain induced in susceptible individuals by alteration of taste.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Alpha-lipoic acid (ALA), is a potent antioxidant mitochondrial coenzyme, the trometamol salt of thioctic acid that has been shown in clinical studies to be neuroprotective. This study examined the effect of ALA on the symptomatology of Burning mouth syndrome (BMS).SUBJECTS AND METHODS: Forty-two patients with BMS and no clinical or laboratory evidence of organic oral disease were divided into two groups (Test and Control) each of 21 subjects, matched for age and sex. The Test group were given ALA (thioctic acid; Tiobec) for 30 days, as 600 mg per day orally for 20 days followed by 200 mg per day for 10 days. The Control group were given cellulose starch 100 mg per day as placebo for 30 days. All BMS patients were reviewed at 10-day intervals and scored for changes in symptomatology.RESULTS: Significant improvements were shown in the symptomatology of BMS in up to two-thirds of patients with BMS receiving alpha-lipoic acid, in about 15% of those using placebo and also in up to two-thirds of those who, having tried placebo, were switched to ALA.
[Show abstract][Hide abstract] ABSTRACT: Aphthous ulcers are the most common oral mucosal lesions in the general population. Several precipitating factors for aphthous ulcers are suggested to operate on subjects with genetic predisposition. Sometimes aphthous ulcers can be the sign of systemic diseases. Therefore, it is essential to establish a correct diagnosis to determine suitable therapy. There are several diseases potentially responsible for oral ulcers. Sometimes appearance of periodic oral ulcers coincides with periodic fever and other symptoms leading to the diagnosis of a rare childhood disease: PFAPA (periodic fever, aphthous stomatitis, pharyngitis and adenopathy) syndrome. PFAPA or Marshall's syndrome is characterized by abrupt onset of periodic episodes of high fever accompanied by aphthous stomatitis, pharyngitis and cervical adenitis, often associated with headache and / or abdominal or joint pain. Owing to the periodic onset of oral symptoms, often an oral physician or pediatric dentist may be the first healthcare worker to evaluate a child with clinical signs compatible with PFAPA syndrome. Children diagnosed with this condition require systematic oral follow-up to monitor for signs of ulceration.
Full-text · Article · Aug 2008 · Journal of Oral Pathology and Medicine
[Show abstract][Hide abstract] ABSTRACT: Aphthous ulcers are the most common oral mucosal lesions in the general population. Several precipitating factors for aphthous ulcers are suggested to operate on subjects with genetic predisposition. Sometimes aphthous ulcers can be the sign of systemic diseases. Therefore, it is essential to establish a correct diagnosis to determine suitable therapy. There are several diseases potentially responsible for oral ulcers. Sometimes appearance of periodic oral ulcers coincides with periodic fever and other symptoms leading to the diagnosis of a rare childhood disease: PFAPA (periodic fever, aphthous stomatitis, pharyngitis and adenopathy) syndrome. PFAPA or Marshall’s syndrome is characterized by abrupt onset of periodic episodes of high fever accompanied by aphthous stomatitis, pharyngitis and cervical adenitis, often associated with headache and / or abdominal or joint pain. Owing to the periodic onset of oral symptoms, often an oral physician or pediatric dentist may be the first healthcare worker to evaluate a child with clinical signs compatible with PFAPA syndrome. Children diagnosed with this condition require systematic oral follow-up to monitor for signs of ulceration.
Full-text · Article · Jul 2008 · Journal of Oral Pathology and Medicine
[Show abstract][Hide abstract] ABSTRACT: Adverse drug reactions are noxious and unintended responses to a medicinal product. Many drugs have the potential to induce adverse reactions in the mouth. The extent of such reactions is unknown; however, because a lot of them are asymptomatic, many are believed to go unnoticed. Adverse oral drug reactions are responsible for oral lesions and manifestations that can mime local or systemic disease. Their pathogenesis, especially of the mucosal reactions, is largely unknown and appears to involve complex interactions between the drug in question, other medications, the patient's underlying disease, genetics and lifestyle factors.
In this study, we have listed the principal signs and symptoms of oral and perioral adverse drug reactions and the responsible drugs. Diagnosis for adverse drug reaction is not easy given also the limited utility of laboratory tests. The association between a drug and an adverse drug reaction is mostly based on the disappearance of the reactions following discontinuance of the offending drug. Sometimes, it is useful to perform rechallenge tests reintroducing the drug to establish cause and effect.
Knowledge of adverse drug-induced oral effects helps health professionals to better diagnose oral disease, administer drugs and improve patient compliance during drug therapy and may foster a more rational use of drugs.
Full-text · Article · Jul 2008 · Journal of the European Academy of Dermatology and Venereology
[Show abstract][Hide abstract] ABSTRACT: The pathogenesis of pemphigus vulgaris (PV) is still poorly understood. Autoantibodies present in PV patients can promote detrimental effects by triggering altered transduction of signals, which results in a final acantholysis. To investigate mechanisms involved in PV, cultured keratinocytes were treated with PV serum. PV sera were able to promote the cell cycle progression, inducing the accumulation of cyclin-dependent kinase 2 (Cdk2). Microarray analysis on keratinocytes detected that PV serum induced important changes in genes coding for one and the same proteins with known biological functions involved in PV disease (560 differentially expressed genes were identified). Then, we used two different approaches to investigate the role of Cdk2. First, small interfering RNA depletion of Cdk2 prevented cell-cell detachment induced by PV sera. Second, pharmacological inhibition of Cdk2 activity through roscovitine prevented blister formation and acantholysis in the mouse model of the disease. In vivo PV serum was found to alter multiple different pathways by microarray analysis (1463 differentially expressed genes were identified). Major changes in gene expression induced by roscovitine were studied through comparison of effects of PV serum alone and in association with roscovitine. The most significantly enriched pathways were cell communication, gap junction, focal adhesion, adherens junction, and tight junction. Our data indicate that major Cdk2-dependent multiple gene regulatory events are present in PV. This alteration may influence the evolution of PV and its therapy.
[Show abstract][Hide abstract] ABSTRACT: Primary oral melanoma (POM) is an uncommon malignant tumor that originates from the proliferation of melanocytes. Such tumors can be present at any location in the oral cavity; however, it affects more frequently the hard palate and the maxillary alveolar mucosa. POM is usually asymptomatic in the early stages and it presents normally as a pigmented patch or as a mass with a rapid growth rate. In the advanced stages, it can show ulceration, swelling, bleeding, rapid enlargement and loosening of teeth. Melanoma of the mouth is rare, most commonly occurring in the upper jaw of patients more than 65 years. Because of a frequent delay in diagnosis, the tumors are often diagnosed when they are deeper than the average cutaneous melanoma. The prognosis is extremely poor, especially in advanced stages. Therefore, pigmented lesions of undetermined origin should be routinely subjected to a biopsy examination. In this study, we aimed to present a review on primary malignancy.
Full-text · Article · Mar 2008 · Journal of Oral Pathology and Medicine
[Show abstract][Hide abstract] ABSTRACT: Within the last decade, a number of theories on the pathogenesis of pemphigus vulgaris (PV) have followed one another. Of these, plesminogen activation and desmoglein compensation hypotheses have been substantiated by a conspicuous body of evidence. A significant change of this scenario occurred with the discovery that autoimmunity in PV can target acetylcholine receptors and that PV serum elicits a pletora of intracellular signals. Since then, a myriad of explanations accounting for PV acantholysis have appeared in the literature. However, as revolutionary as they can be, the majority of organic theories seemed to be highly speculative. We have recently obtained evidence for a proteolytic cleavage of desmoglein 3 in an in vitro model of PV; furthermore, our previous findings suggested the possible involvement of proteases such as matrix metalloproteinase (MMP) 9 in PV acantholysis both in vitro and in vivo. Hence, in formulating the "specific proteolysis theory" we have kept the rationale and the well-established evidence of both plasminogen activation and desmoglein compensation hypotheses. However, the specific proteolysis theory proposed by us is not just a return to the past. On the basis of the current knowledge on MMP substrate specificity we propose that Dsg1 and Dsg3, along with other important cadherins which are likely to be proteolytically targeted in PV, could be cleaved by either ADAM or typical MMPs, respectively. Whether this view was confirmed by further investigations, these enzymes could be specifically targeted by selective drugs which would permit more rational approaches to the treatment of pemphigus.
Full-text · Article · Feb 2008 · Medical Hypotheses
[Show abstract][Hide abstract] ABSTRACT: Burning mouth syndrome (BMS) is a common disorder frequently affecting women past the 5th decade of age. It is characterized by oral burning, mainly involving the tongue, lip, and anterior palate, but without oral lesions or alteration showing in blood tests and/or instrumental findings.
We proposed to exclude alterations due to thyroid function and echographic abnormality in formulating BMS diagnosis. The aim of this study was to propose a blood and instrumental protocol including thyroid function and echography to obtain a correct BMS diagnosis. In the absence of such an assessment, a number of patients with oral burning and hypothyroidism may erroneously be considered BMS patients.
For this study, a group of 123 patients initially diagnosed with BMS was selected, following use of the current preliminary diagnostic protocol for BMS (study group). A further 123 patients with dental problems and without oral burning were selected as a control group. All patients were submitted to further protocol based on a study of their thyroid function and echography.
Thirteen control patients showed some thyroid alteration compared with 85 patients of the study group. In relation to these further examinations, a therapeutic protocol based on use of thyroxine, lipoic acid, or clonazepam was applied for patients belonging to the study group. Fifty-eight patients (47%) showed hypothyroidism and were treated with thyroxine, and 37 (64%) of these showed a positive response (VAS 1 and 0). Twenty-seven patients (22%) evinced euthyroidism with an inhomogeneous parenchyma thyroid echographic pattern. These were treated with lipoic acid, and 23 (85%) of them responded positively (VAS 1 and 0). Thirty-eight patients (31%) showed euthyroidism and no echographic alteration. Only these were considered to be true BMS patients and were treated with lipoic acid. Only 10 (26%) of these patients responded positively (VAS 1 and 0).
This study reveals that subjects with thyroid alterations are often considered to be BMS patients and that hypothyroidism could be responsible for oral burning and/or dysgeusia in some supertaster subjects. For these reasons, we propose that the study of thyroid function be inserted in the diagnostic process for BMS patients.
Full-text · Article · Feb 2008 · Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology
[Show abstract][Hide abstract] ABSTRACT: Apoptotic cells are known to regulate the ordered dismantling of intercellular contacts through caspase activity. Despite the important role of desmoglein (Dsg) 2 in epithelial cell-cell adhesion, the fate of this widespread desmosomal cadherin during apoptosis is yet poorly understood. Here, by means of pharmacological approaches, we investigated whether Dsg2 was targeted by caspases in HaCaT and HT-29 cell lines undergoing staurosporine (STS)-induced apoptosis. Results showed that STS induced a caspase-dependent form of cell-death in both keratinocytes (HaCaT) and enterocytes (HT-29), that associated with progressive depletion of Dsg2 from cell lysates. The proteolytic processing of full-length Dsg2 resulted in the appearance of a 70-kDa fragment which was released into the cytosol. Consistently, immunofluorescence studies revealed that Dsg2 staining was abolished from cell surface whereas the cytoplasmic region of Dsg2 did localize intracellularly. Plakoglobin (Pg) also underwent cleavage and detached from Dsg2. Apoptotic changes paralleled with progressive loss of intercellular adhesion strength. All these biochemical, morphological, and functional changes were regulated by caspase 3. Indeed, in the presence of the caspase 3-inhibitor z-DEVD-fmk, full-length Dsg2 protein levels were preserved, whereas the amount of the 70-kDa fragment was maintained on control levels. Furthermore, cells pretreated with z-DEVD-fmk retained the membrane labeling of Dsg2. Taken together, our data demonstrate that the apoptotic processing of Dsg2 is mediated by caspase 3 in epithelial cells.
Full-text · Article · Feb 2008 · Journal of Cellular Biochemistry
[Show abstract][Hide abstract] ABSTRACT: Patients with pemphigus vulgaris (PV) who have both antidesmoglein (Dsg)1 and anti-Dsg3 antibodies usually develop flaccid blisters on skin and mucous membranes. We report a case of PV with crusting skin lesions resembling pemphigus erythematosus, the localized variant of pemphigus foliaceus (PF). Notably, the patient had high titres of anti-Dsg1 IgG, as assessed by ELISA. We then established an in vitro model of pemphigus, and found that patient's serum was able to induce suprabasilar acantholysis in mouse skin culture. However, epidermal splitting also occurred within the granular layer, suggesting that the pathogenic potential of such a high-titre anti-Dsg1 serum was intermediate between PV and PF. Thus, the levels of anti-Dsg1 antibodies could play a role in determining the clinical phenotype of pemphigus.
No preview · Article · Feb 2008 · Clinical and Experimental Dermatology
[Show abstract][Hide abstract] ABSTRACT: Vascular lesions of the oral cavity represent a diagnostic challenge for clinicians. Beyond the need to separate hemangioma and other tumors from malformations, it is evident that over the years the term hemangioma was overapplied without regard to etiology or clinical behaviour (reviewed in ref. 1). The misunderstanding on the nosologic distinction between oral haemangiomas and vascular malformations still leads to diagnostic mistakes. Despite the International Society for the Study of Vascular Anomalies (ISSVA) adopted a biology-based classification system, the term haemangioma continues to be o verused by clinicians. By presenting a case of multiple oral vascular tumescence of uncertain origin, here we sought to briefly address this controversy. Case Presentation A 36-year-old male was referred to the surgery service of the Second University of Naples complaining difficulties in eating. On clinical examination, he exhibited a swelling in left parotid region (Fig.1). It was present since childhood but was increased in volume in the last 15 years. This lesion was completely asymptomatic and covered by apparently uninflamed skin without any discoloration. The tumescence was dislocable from underlying layers, fluctuating and reducible. No internal pulsations were detectable. Head and neck lymph nodes were painless, not palpable, and there was no clinically detectable lymphadenopathy. Patient didn't refer any subjective symptomatology. However, he reported an increase of the swelling both in the morning after awakening and in supine position. The enlarged tumescence paralleled with changes in its consistency, probably due to t he augmented blood afflux to the vascular channels composing the tumour. Intraoral examination revealed the p resence of three vascular lesions situated on both left margin and ventral side of the tongue (Fig.2). The lesion located in the third posterior of the tongue on its left margin (Fig.2a, 2b) appeared ten years ago as a little prominence which underwent a slow but progressive growth. At present the tumour measured about 1.5 cm in diameter. Within the subsequent six years two more tumescence appeared. One was on the left margin of the tongue (Fig. 2c) and the second one on its ventral side (Fig. 2d). Both had i ncreased in volume in the last ten years. These tongue vascular anomalies presented many similar clinical features: they were exophytic and irregularly spherical in shape, painless, variable in diameter (1 cm to 2 cm), covered by red to r ed-blue-violet mucosa. The patient referred trouble in chewing and eating, along with pain and bleeding during mastication. Color doppler imaging was suggestive of mixed arteriovenous vascular lesions (not shown). A clinical diagnosis of vascular tumour was established, which was compatible with both vascular malformation and vascular neoplasm (haemangioma). The patient was operated in total anaesthesia and electroscalpel was preferred to prevent bleeding. Suture was made in absorbable material for muscular tissues and silk for superficial tissues.
[Show abstract][Hide abstract] ABSTRACT: Intercellular adhesion among keratinocytes is guaranteed by desmosomes. Disruption of desmosomal integrity leads to cell-cell detachment or acantholysis, as it classically occurs in pemphigus vulgaris (PV), an autoimmune blistering disease of skin and mucous membranes. While purified PV IgG seems to trigger intracellular signaling that crucially involves p38 MAPK, keratinocyte acantholysis induced by whole PV serum may recruit a number of additional signals. In this study, the Pro-Q Diamond Phosphoprotein Assay was used to investigate the overall changes in protein phosphorylation levels in an in vitro model of PV. We showed that keratinocytes exposed to whole PV sera underwent at least three early and transient phosphorylation events. Two bands with apparent molecular masses of 35 and 45 kDa were found to be phosphorylated within 1 min after incubation with PV sera. A third band of about 80 kDa reached the peak of phosphorylation level after 3 hours. Morphologic evidence of cell shrinkage and acantholysis were late events and did not correlate temporally with kinase activation, suggesting that cytoskeleton reorganization is a downstream phenomenon. Interestingly, pharmacological abrogation of PV-specific protein phosphorylation was able to inhibit the cell-cell detachment, rounding up, and redistribution of Dsg3 in keratinocytes. Thus, at least three phosphorylation events are pathogenically involved in pemphigus acantholysis.
No preview · Article · Jan 2008 · International journal of immunopathology and pharmacology