Evidence of key role of Cdk2 overexpression in pemphigus vulgaris

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. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc

Increased myocardial apoptosis in patients with unfavorable left ventricular remodeling and early symptomatic post-infarction heart failure

AbstractObjectivesThe purpose of this study was to evaluate a potential correlation between apoptotic rate (AR), post-infarction left ventricular (LV) remodeling, and clinical characteristics in subjects who died late (≥10 days) after an acute myocardial infarction (AMI) with evidence of persistent occlusion of the infarct-related artery at autopsy.BackgroundApoptosis contributes to myocardiocyte loss in cardiac disease and may have a pathophysiologic role in post-infarction LV remodeling.MethodsThe AR was calculated at the site of infarction and in remote unaffected LV regions, using co-localization of in situ end labeling for deoxyribonucleic acid fragmentation and immunohistochemistry for caspase-3, in 14 subjects who died within two months after AMI. Correlation between AR and clinical characteristics such as age, site of AMI, transmural extension, multivessel coronary disease, and signs and/or symptoms of heart failure (HF), at the time of initial hospitalization for AMI or subsequently before death, was assessed using non-parametric statistical tests. Parameters of LV remodeling including diameters, free wall thickness, diameter-to-wall-thickness ratio, and mass were measured at gross examination at autopsy. Values are expressed as median (interquartile range).ResultsAmong clinical variables, early symptomatic post-infarction HF (9 cases, 64%) was associated with nearly fourfold increased AR at the site of infarction (26.2% [24.5% to 28.8%] vs. 6.4% [1.9% to 13.3%], p = 0.001). Moreover, AR both at the site of infarction and in unaffected regions was significantly correlated with parameters of progressive LV remodeling (p < 0.05).ConclusionsOur data show that in patients dying ≥10 days after AMI, myocardial apoptosis is strongly associated with and may be a major determinant of unfavorable LV remodeling and early symptomatic post-infarction HF

Clinical Practice: Giant Cell Tumour of the Jaw Mimicking Bone Malignancy on Three-Dimensional Computed Tomography (3D CT) Reconstruction

A wide range of diseases may present with radiographic features of osteolysis. Periapical inflammation, cysts and benign tumours, bone malignancies, all of these conditions may show bone resorption on radiograph. Features of the surrounding bone, margins of the lesion, and biological behaviour including tendency to infiltration and root resorption, may represent important criteria for distinguishing benign tumours from their malign counterpart, although the radiographic aspect of the lesion is not always predictive. Therefore a critical differential diagnosis has to be reached to choose the best management. Here, we report a case of giant cell tumour (GCT) whose radiological features by computed tomography (CT) suggested the presence of bone malignancy, whereas the evaluation of a routine OPT scan comforted us about the benign nature of the lesion. A brief review of the literature on such a benign but locally aggressive neoplasm is also provided

Clinical Practice: Giant Cell Tumour of the Jaw Mimicking Bone Malignancy on Three-Dimensional Computed Tomography (3D CT) Reconstruction

A wide range of diseases may present with radiographic features of osteolysis. Periapical inflammation, cysts and benign tumours, bone malignancies, all of these conditions may show bone resorption on radiograph. Features of the surrounding bone, margins of the lesion, and biological behaviour including tendency to infiltration and root resorption, may represent important criteria for distinguishing benign tumours from their malign counterpart, although the radiographic aspect of the lesion is not always predictive. Therefore a critical differential diagnosis has to be reached to choose the best management. Here, we report a case of giant cell tumour (GCT) whose radiological features by computed tomography (CT) suggested the presence of bone malignancy, whereas the evaluation of a routine OPT scan comforted us about the benign nature of the lesion. A brief review of the literature on such a benign but locally aggressive neoplasm is also provided

BILATERAL PELVIC GANGLIONEUROMA: CLINICO-PATHOLOGICAL FINDINGS: A CASE REPORT

Ganglioneuroma is a rare benign neurogenic tumor originating from the autonomic nervous system, and is considered the benign counterpart of neuroblastoma, lacking the immature neuroblastic cells. A case of pelvic ganglioneuroma with bilateral pelvic spread is described

Melanoacanthoma Simulating Pigmented Spitz Nevus: an Unusual Dermoscopy Pitfall

The starburst pattern is the dermoscopic hallmark of pigmented Spitz nevus, although it has been rarely observed in melanoma as well

Giant basal cell carcinoma

A 72-year-old white man presented with a large cutaneous tumor on his back. The patient said the lesion, mostly asymptomatic, had increased in size for about 7 years. Physical examination revealed a vegetating mass (Figure 1), partially ulcerated, measuring 30 x 20 cm, which easily dripped serum and blood, with small necrotic areas and a sclerotic border. Perilesional skin appeared edematous, probably owing to inflammation and impaired lymphatic flow. Clinically, there was no evidence of lymph node involvement. His family history was noncontributory. Hematologic examination revealed hypochromic microcytic anemia. Laboratory test results showed hyperuricemia and hypercholesterolemia. The patient's history revealed mild hypertension, ischemic cardiopathy treated with percutaneous transluminal coronary angioplasty and anticoagulant drugs, and moderate chronic renal insufficiency. Histologic examination of a biopsy specimen taken from the margin of the lesion displayed a superficial area of ulceration and invasion of the deeper dermis and subcutaneous tissue (Figure 2A and Figure 2B). The tumor mostly showed an adenoid pattern: gland-like structures and cystic spaces sometimes containing amorphous or granular material, surrounded by strands of basaloid cells devoid of any peripheral palisading (Figure 2C). In some areas, the adenoid pattern coexisted with infiltrated areas characterized by thin and elongated strands or cords of basaloid cells with irregular and jagged peripheral contours within a fibrous or edematous stroma (Figure 2D). Basaloid cells often revealed nuclear atypia, marked pleomorphism and hyperchromatism (Figure 2C and Figure 2D). Therefore, a diagnosis of basal cell carcinoma, adenoid subtype, was made. Magnetic resonance imaging showed a 10-cm wide thickening of the subcutaneous layer on the lumbar region, with a partial neoplastic infiltration of the muscle fascia. No evidence of metastases was found with a total body computed tomography scan. Because the patient was taking anticoagulant drugs and had unstable renal and cardiac function, surgical treatment was at least temporarily excluded, and the patient was referred for radiation therapy

Melanoma simulating seborrheic keratosis: A major dermoscopy pitfall

Dermoscopy is a noninvasive diagnostic technique that improves the diagnostic accuracy of pigmented skin lesions. It permits to differentiate melanoma from seborrheic keratosis by detecting the presence of specific dermoscopic features, eg, atypical pigment network and blue-white veil in melanoma, and comedolike openings and milialike cysts in seborrheic keratosis, to name but a few differential diagnostic criteria. We report the dermoscopic-pathologic correlations of a melanoma in situ simulating a seborrheic keratosis on clinical and dermoscopic examinations

Antimitotic effects of usnic acid on different biological systems

Usnic acid is a biosynthesis product characteristic of several epiphytic lichens such as Evernia, Cladonia and Parmelia. Usnic acid has several interesting biological properties. It is an antibiotic and it also seems to exert an antimitotic action. It has even been postulated that usnic acid can play a role as an environmental indicator, since its concentration varies according to the presence of toxic agents. A series of tests have been run on different biological systems such as fungi, yeasts, plant cells and neoplastic human cell cultures in order to make a general evaluation of the properties of usnic acid and to highlight any analogy between its effects on phylogenetically distant organisms. The results obtained confirm some of the already known properties of usnic acid and identify concentration ranges that are active against cells from different organisms. Furthermore, at low concentrations, the acid displays a capacity to stimulate cell metabolism in some of the biological systems tested