Glucose-induced alterations of intracellular ionized magnesium in human lymphocytes

The intracellular ionic content of human erythrocytes may be altered by hyperglycaemia. Despite this, very little is known about the cellular mechanisms linking glucose and cellular magnesium homeostasis. We measured intracellular ionized magnesium in human lymphocytes, by means of a fluorimetric technique, total intracellular magnesium by means of atomic absorption spectrophotometry and intracellular ATP by means of HPLC. The incubation of lymphocytes with D-glucose in the absence of insulin was followed by a significant decrease in intracellular ionized magnesium; this effect did not occur when the cells were incubated with L-glucose. The effect of glucose on intracellular ionized magnesium was blocked by amphotericin B and the EC(50) of the effect of glucose on intracellular ionized magnesium was about 5 mmol/l of glucose. The increase of intracellular ionized magnesium in cells incubated in the absence of glucose was followed by a decrease in intracellular ATP. In a Na(+)-free medium the decrease of intracellular ionized magnesium in the presence of glucose was still present and the incubation of lymphocytes with glucose did not modify total intralymphocyte magnesium. By selective permeabilization of cell membranes, we established that glucose could not increase compartmentalized intracellular ionized magnesium. Our data supports the hypothesis that glucose per se induces a substantial decrease in intracellular ionized magnesium, which is probably due to an augmented binding of intracellular ionized magnesium to cellular ATP.     

Pemphigus vulgaris IgG-induced desmoglein-3 endocytosis and desmosomal disassembly are mediated by a clathrin- and dynamin-independent mechanism

Pemphigus vulgaris (PV) is a life-threatening autoimmune disease characterized by oral mucosal erosions and epidermal blistering. The autoantibodies generated target the desmosomal cadherin desmoglein-3 (Dsg3). Previous studies demonstrate that upon PV IgG binding, Dsg3 is internalized and enters an endo-lysosomal pathway where it is degraded. To define the endocytic machinery involved in PV IgG-induced Dsg3 internalization, human keratinocytes were incubated with PV IgG, and various tools were used to perturb distinct endocytic pathways. The PV IgG.Dsg3 complex failed to colocalize with clathrin, and inhibitors of clathrin- and dynamin-dependent pathways had little or no effect on Dsg3 internalization. In contrast, cholesterol binding agents such as filipin and nystatin and the tyrosine kinase inhibitor genistein dramatically inhibited Dsg3 internalization. Furthermore, the Dsg3 cytoplasmic tail specified sensitivity to these inhibitors. Moreover, inhibition of Dsg3 endocytosis with genistein prevented disruption of desmosomes and loss of adhesion in the presence of PV IgG. Altogether, these results suggest that PV IgG-induced Dsg3 internalization is mediated through a clathrin- and dynamin-independent pathway and that Dsg3 endocytosis is tightly coupled to the pathogenic activity of PV IgG.     

Hemoglobin E: report of the first 2 cases in French subjects

Hemoglobin E has been discovered casually in the blood of two French donors: one coming from the Alsace region, the other one coming from the Champagne region. In the two cases, the hemoglobin E is in an heterozygote state and takes the place of 33 per cent of the total haemoglobin in the first and 24 per cent in the second. We investigated in their families and found that other members of these families had hemoglobin E. Each time, it was associated with a microcytosis and polycythaemia without anemy or iron deficiency. The red cells morphology shows many microspherocytes and target-cells. There is no relationship between these two families and the research of an asiatic antecedent proved negative. These two observations give a supplementary proof that the geographic repartition of the hemoglobin E is larger than what we read in the first publications and shows the interest to study the hemoglobin of unexplained polycythaemia with microcytes in the blood of blood donors.     

Digital glomus tumors: a 29-year experience with a lateral subperiosteal approach

The excision of distal digital glomus tumors has traditionally been performed directly over the involved nail bed. This can lead to nail deformities that are often unacceptable for the surgeon and the patient. The authors describe their experience with successful excision of digital glomus tumors using a lateral subperiosteal approach, which creates a dorsal flap. In 29 years, 19 patients were diagnosed with digital glomus tumors. All patients underwent excision using the lateral subperiosteal approach. The mean tumor size was 0.52 cm. The tumors were located on the pulp of the distal phalanx in two patients (10.5 percent) and subungually in 17 patients (89.5 percent). In all patients, preoperative clinical diagnosis was confirmed postoperatively with the biopsy result. Complications occurred in only two patients and included one paronychia and one temporary nail loss. The overall recurrence rate was 15.7 percent. All patients remained asymptomatic after surgery and regained full active and passive range of motion. There were no nail deformities by this approach. This technique represents a safe and effective approach to excising digital glomus tumors.     

Primary Localization and Tumor Thickness as Prognostic Factors of Survival in Patients with Mucosal Melanoma

Background

Data on survival with mucosal melanoma and on prognostic factors of are scarce. It is still unclear if the disease course allows for mucosal melanoma to be treated as primary cutaneous melanoma or if differences in overall survival patterns require adapted therapeutic approaches. Furthermore, this investigation is the first to present 10-year survival rates for mucosal melanomas of different anatomical localizations.

Methodology

116 cases from Sep 10 1984 until Feb 15 2011 retrieved from the Comprehensive Cancer Center and of the Central Register of the German Dermatologic Society databases in Tübingen were included in our analysis. We recorded anatomical location and tumor thickness, and estimated overall survival at 2, 5 and 10 years and the mean overall survival time. Survival times were analyzed with the Kaplan-Meier method. The log-rank test was used to compare survival times by localizations and by T-stages.

Principal Findings

We found a median overall survival time of 80.9 months, with an overall 2-year survival of 71.7%, 5-year survival of 55.8% and 10-year survival of 38.3%. The 10-year survival rates for patients with T₁, T₂, T₃ or T₄ stage tumors were 100.0%, 77.9%, 66.3% and 10.6% respectively. 10-year survival of patients with melanomas of the vulva was 64.5% in comparison to 22.3% of patients with non-vulva mucosal melanomas.

Conclusion

Survival times differed significantly between patients with melanomas of the vulva compared to the rest (p = 0.0006). It also depends on T-stage at the time of diagnosis (p<0.0001).