Role of a pertussis toxin sensitive G-protein in mediating the effects of phorbol esters on receptor activated cyclic AMP accumulation in Jurkat cells

Summary In the human T -cell line, Jurkat, the accumulation of cyclic AMP induced by adenosine is enhanced by tumor-promoting phorbol esters, whereas prostaglandin E₂ receptor-stimulated cAMP accumulation is antagonized (Nordstedt et al. 1989). In the present study we examine the involvement of pertussis toxin sensitive guanine nucleotide binding proteins (G-proteins) in producing the phorbol ester effects.Pertussis toxin pretreatment of the Jurkat cells invariably caused an ADP ribosylation of two G-proteins that inhibit adenylyl cyclase, tentatively identified as G_i2 and G_i3, using Western blots. Pertussis toxin treatment had little effect on basal cAMP accumulation, but sometimes inhibited, sometimes stimulated agonist and cholera toxin induced cAMP accumulation. The latter effect was not mimicked by the B-oligomer. Irrespective of whether pertussis toxin stimulated or inhibited NECA and cholera toxin-induced cAMP accumulation it could not block the effect of phorbol-12,13-dibutyrate (PDBu). The inhibitory effect of PDBu on prostaglandin E2-induced cAMP accumulation was, however, invariably eliminated by pertussis toxin treatment.In conclusion, activation of protein kinase C by phorbol esters reveals a G_i-mediated prostaglandin E receptor-induced inhibition of adenylate cyclase in addition to the prostaglandin E receptor-mediated stimulation of cAMP accumulation in Jurkat cells. The enhancement of adenosine A₂ receptor stimulated CAMP accumulation by PDBu, on the other hand, does not involve a PTX sensitive G_i-protein. Send offprint requests to I. van der Ploeg at the above address     

A reappraisal of the Ortolani examination in children with developmental dysplasia of the hip

The Ortolani maneuver is currently accepted as an accurate test to detect developmental dislocation of the hip. However, the clinical sign does not always correlate with the findings seen on ultrasound. The ultrasound-documented position of the femoral head was correlated with the result of the clinical Ortolani examination to better understand the value and validity of the Ortolani test. Two populations were compared: hips with a positive Ortolani sign and hips with a negative Ortolani sign but with an ultrasound-documented dislocated hip. In the Ortolani-positive group, there were 45 patients (53 affected hips), and in the Ortolani-negative group, there were 24 patients (25 dislocated hips). Position of the femoral head at rest, side of involvement, and sex showed no significant difference between the Ortolani-positive and -negative groups. Mean age of patients in the Ortolani-positive group was less (mean, 28 days) and was statistically different (P < 0.05) from those in the Ortolani-negative group (mean, 91 days). In conclusion, dislocated hips that show similar femoral head movement can produce an Ortolani-positive examination in a younger patient and an Ortolani-negative examination in an older patient. The classic clinical method described by Ortolani for detecting hip dislocation in which the thigh of the affected hip is abducted and the femoral head was thought to be reducing into the acetabulum can be erroneous. All Ortolani-positive hips were abnormal, as the sensation characteristic of a positive Ortolani examination may be felt without full reduction and, in some cases, with no reduction, as documented by ultrasound.     

Ginkgo biloba extract regulates differentially the cell death induced by hydrogen peroxide and simvastatin

Several human diseases have been associated with the overproduction of reactive oxygen species (ROS) and subsequently various antioxidants emerged as potential therapeutic agents that scavenge ROS. As an oxidative stress model of human disease, we used hydrogen peroxide (H2O2) to study effect of ROS on C6 glioma cells as a surrogate for astrocytes. H2O2 induced dose- and time-dependent apoptotic cell death which was preceded by growth arrest, and transiently activated the signalling proteins ATF-2, ERK1/2 and AKT in C6 glioma cells. While several antioxidants failed to block H2O2-induced apoptosis of these cells, Ginkgo biloba extract (EGb) totally prevented the cell death and growth inhibition induced by H2O2. Interestingly, EGb did not prevent the activation of ATF-2, ERK1/2 and AKT induced by H2O2 excluding the role of these factors in the pro-apoptotic effect of H2O2. We have previously shown that the lipid-lowering drug, simvastatin, causes apoptotic cell death in C6 glioma cells [Koyuturk M, Ersoz M, Altiok N. Simvastatin induces proliferation inhibition and apoptosis in C6 glioma cells via c-jun N-terminal kinase. Neurosci Lett 2004;370(2-3):212-7]. However, in parallel experiments with H2O2, EGb was unable to prevent cell death induced by simvastatin suggesting the involvement of separate signalling pathways between H2O2 and simvastatin. Thus, EGb and other plant flavonoids might have potential as protective agents against apoptosis through scavenging ROS upon cerebral or myocardial diseases associated with free radical generation.     

The histogenic origin of melanoma arising in respiratory epithelium of a teratomatous germ cell tumor of the mediastinum: an enigma unraveled from an unlikely source

Mixed germ cell tumors are rare neoplasms that are known to occur in the anterior mediastinum. Characterized by two or more types of germ cell components, these tumors comprise upwards of 25% of mediastinal germ cell tumors. Even rarer are those harboring somatic-type malignancies such as carcinoma, sarcoma, and hematopoietic malignancies. To date, however, there are no known cases of melanoma arising in a malignant mixed germ cell tumor of the anterior mediastinum. We describe the first case of malignant melanoma with spindle and epithelioid components arising from respiratory epithelium in a mediastinal malignant mixed germ cell tumor of a 32-year-old male. In addition, we also provide evidence supporting the theory of neuroendocrine cells as the origin of melanoma arising in the respiratory epithelium. This case emphasizes the need to carefully evaluate all germ cell tumors, not only for a myriad of benign embryological components, but also for malignancies arising in these components, as they might change the prognosis and patient’s course of treatment. This microscopic approach should bring to light the diversity of mixed germ cell tumors in addition to somatic malignancies with corresponding biologic potentials.     

Kyphectomy in Children with Myelomeningocele

Background  

Patients with myelomeningocele and rigid lumbar and thoracolumbar kyphosis face substantial functional difficulties with sitting and lying supine and are prone to skin breakdown over the gibbus and risk of infection. Kyphectomy, along with cordotomy and segmental spinal instrumentation down to the pelvis, is one alternative that can provide reliable correction of the deformity but also can maintain that correction over a period of time.     

Comparison of predicted and observed PM10 concentrations in several urban street canyons

This paper presents an evaluation of a street canyon model (Operational Street Pollution Model) in several urban streets having different configurations. The model was performed for the prediction of particulate matter (PM₁₀) concentrations from exhaust emissions of mobile sources in five street canyons in the city of Izmir, Turkey. Hourly concentrations of PM₁₀ were observed at the streets and the relevant hourly meteorological parameters were measured at the roof level. The hourly street level measurements by a mobile ambient air quality monitoring station and on-site automatic traffic counts were conducted for 1 week in each street during the period of November 2007 and March 2008. The urban background concentrations were also obtained from four stationary air quality monitoring stations in the city during the measurement campaigns and they were included in the modeling studies as the contribution of background air quality. Finally, statistical analyses were carried out to evaluate the model performance by comparing the predicted and observed time series of PM₁₀ concentrations using a correlation coefficient and an index of agreement (IA). The IA varied from 0.87 to 0.98 at the symmetric canyons and the correlation coefficient ranged from 0.68 to 0.92, indicating modeling performances ranging from acceptable to very good. The similar values were calculated between 0.74 and 0.76 for IA and between 0.34 and 0.41 for correlation coefficient at the asymmetric canyons. The best agreement between predicted and observed PM₁₀ concentrations (IA = 0.98, R ² = 0.92) was found for Cumhuriyet Avenue in this study. These values are found as the best agreement in overall studies in literature.