Difficulties in the Mutation Analysis of Plasminogen Gene: A Study in Two Patients with Ligneous Conjunctivitis

The absence or very low levels of plasminogen cause a rare disabling disease called ligneous conjunctivitis, characterized by the growth of fibrin-rich pseudomembranes in the conjunctiva and on other mucosal surfaces. Several mutations have been detected in the plasminogen gene of patients affected with ligneous conjunctivitis. The human plasminogen gene, located on chromosome 6, has a marked homology with the genes belonging to the plasminogenapo(a) family, and with a number of pseudogenes and plasminogen-like genes located on chromosome 2. This work describes a series of nucleotide variations related to genes other than the plasminogen one, found during the genetic characterization of plasminogen defect in two unrelated patients with ligneous conjunctivitis. The results of automated sequences of each exon and intron-exon boundaries were compared with those of the human plasminogen gene from the NCBI gene bank. In particular, a co-amplified gene on chromosome 2 mimicking a 14 bp deletion in exon 5 of the plasminogen gene was identified by sequencing two different bands obtained from a long run of the PCR exon 5 product in NuSieve agarose gel, and by PstI restriction enzyme analysis of the same amplicons. Moreover, 21 single nucleotide exchanges due to plasminogen-like genes co-amplification were observed, namely one in exon 1, two in exon 4, three in exons 3, 5 and 16, four in exon 13, and five in exon 17. In conclusion, these data confirm the difficulty of plasminogen genetic analysis and may help researchers to better identify the true plasminogen gene mutations causing molecular defects

GENERALIZED AND SPECIFIC EMOTION IMPAIRMENTS AS POTENTIAL MARKERS OF SEVERITY IN OBSESSIVECOMPULSIVE DISORDER: A PRELIMINARY STUDY USING FACIAL ACTION CODING SYSTEM (FACS)

Background: The role of emotional deficits in the poor outcomes of patients with Obsessive-Compulsive Disorder (OCD) has been emphasized. Generalized and specific emotional abnormalities have been reported, often related to OCD severity and functional disabilities. The objective of the present study was to assess the abilities of experiencing and displaying emotions in OCD patients in response to specific stimuli in relation with the severity of their clinical condition. Subjects and methods: Thirty-six individuals participated in the study: 10 OCD patients with severe symptoms, 11 with mildmoderate symptoms, and 15 healthy controls. All participants watched emotion-eliciting video clips while their facial activity was videotaped. The congruent/incongruent feeling of emotions and the facial expression in reaction to emotions were evaluated. Results: The two subgroups of OCD patients presented similarly incongruent emotive feelings and facial expressions (significantly worse than healthy participants). Moreover, OCD patients with severe symptoms expressed the emotion of happiness and disgust significantly less appropriately than OCD patients with mild-moderate symptoms. Conclusions: The present data support the hypothesis that impaired emotional processing may: (i) represent a potential contributor to poor outcome in OCD; (ii) constitute a warning sign for clinicians to establish a more comprehensive protocol for more severe cases; (iii) influence therapeutic strategies used to treat this disorder

E-cadherin, N-cadherin expression and histologic characterization of canine choroid plexus tumors

Choroid plexus tumors (CPTs) are reported with an increasing incidence in dogs, and they call for a reexamination of histologic features and criteria of classification corresponding to their biological behavior. In this study, the human World Health Organization classification was applied to 16 canine CPTs, and the expression of molecules involved in neoplastic cell adhesion (E-cadherin, N-cadherin), invasion (doublecortin), and proliferation (Ki-67) was investigated. Mitotic index was found to be the main criterion for grading CPTs. Cell density and multilayering of papillae were also statistically associated with histologic grade. Intraventricular spread and parenchymal invasion was observed for tumors showing histologic benign features. E-cadherin was expressed in all CPT grades, independent of tumor invasion. N-cadherin immunolabeling was more expressed in grade I than high-grade CPTs, whereas doublecortin expression was not detected in CPTs. An increasing proliferative activity was observed in relation with histologic grade

Plasma fibrinolytic capacity in renal transplant recipients: Effect of steroid-free immunosuppression therapy.

Background. Cardiovascular disease is the most common cause of death among renal transplant recipients (RTRs). Impaired fibrinolytic capacity caused by an increase in plasminogen activator inhibitor type 1 (PAI-1) levels is involved in the onset of atherosclerosis and thrombotic complications. Long-term steroid treatment may induce arterial hypertension and metabolic and prothrombotic changes (including up-regulation of PAI-1 synthesis), which increase the cardiovascular risk. We evaluated plasma fibrinolytic behavior in two groups of RTRs treated with different immunosuppressive regimens. Methods. Twenty-seven RTRs were randomized to receive long-term (17 patients) or perioperative short-term (10 patients) steroids in addition to immunosuppression with cyclosporine A plus everolimus (Certican; Novartis, Basel, Switzerland) (7 patients) or FK506 plus mycophenolate mofetil (20 patients). In each patient, fibrinolytic capacity was studied with the 20-min venous occlusion test 1 and 6 months after transplantation. The following were assayed: euglobulin lysis time, tissue-type plasminogen activator antigen, and PAI-1 antigen and activity. Results. One month after transplantation, a severe impairment of fibrinolytic capacity, mainly caused by an increase in PAI-1 antigen and activity levels, was seen in patients with and without steroid treatment. Six months after transplantation, an improvement in fibrinolytic potential as the result of a decrease in PAI-1 levels was observed only in patients without steroid therapy. None of the steroid-treated patients demonstrated PAI-1 values correlating with body mass index, blood pressure, and metabolic parameters, thus confirming the effect of exogenous factors on PAI-1 expression. Moreover, all patients revealed a slight impairment of stimulated endothelial tissue-type plasminogen activator release, regardless of any steroid treatment, which was probably attributable to calcineurin inhibitor-induced endothelial dysfunction. Conclusions. Our study suggests that steroid-free immunosuppression is associated with a better fibrinolytic capacity in RTRs. This finding may contribute toward reducing the risk of cardiovascular events

Role of fibrinolytic and clotting parameters in the diagnosis of liver veno-occlusive disease after hematopoietic stem cell transplantation in a pediatric population

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