Proteolytic cleavage and activation of PAK2 during UV irradiation-induced apoptosis in A431 cells

Exposure of mammalian cells to ultraviolet (UV) light elicits a cellular response and can also lead to apoptotic cell death. In this report, we show that a 36-kDa myelin basic protein (MBP) kinase detected by an in-gel kinase assay can be dramatically activated during the early stages of UV irradiation-triggered apoptosis of A431 cells. Immunoblot analysis revealed that this 36-kDa MBP kinase could be recognized by an antibody against the C-terminal regions of a family of p21Cdc42/Rac-activated kinases (PAKs). By using this antibody and a PAK2-specific antibody against the N-terminal region of PAK2 as studying tools, we further demonstrated that UV irradiation caused cleavage of PAK2 to generate a 36-kDa C-terminal catalytic fragment and a 30-kDa N-terminal fragment in A431 cells. The appearance of the 36-kDa C-terminal catalytic fragment of PAK2 matched exactly with the activation of the 36-kDa MBP kinase in A431 cells upon UV irradiation. In addition, UV irradiation also led to activation of CPP32/caspase-3, but not ICH-1L/caspase-2 and ICE/caspase-1, in A431 cells and the kinetics of activation of CPP32/caspase-3 appeared to correlate well with that of DNA fragmentation and of cleavage/activation of PAK2, respectively. Moreover, blockage of activation of CPP32/caspase-3 by pretreating the cells with two specific tetrapeptidic inhibitors for caspases (Ac-DEVD-cho and Ac-YVAD-cmk) could significantly attenuate the extent of cleavage/activation of PAK2 induced by UV irradiation. Collectively, the results demonstrate that cleavage and activation of PAK2 can be induced during the early stages of UV irradiation-triggered apoptosis and indicate the involvement of CPP32/caspase-3 in this process.     

New protein genetic studies in six Amazonian Indian populations

A total of 732 individuals affiliated with six Amazonian Indian populations were variously studied in relation to 26 protein genetic systems. Eleven of them were found to be monomorphic in these groups, in accordance with previous investigations. Similarities and dissimilarities (the latter involving the Rh, Duffy, haptoglobin and transferrin systems) were observed in relation to earlier investigations in four of these populations (Galibi, Palikour, Mundurucu and Tenharim). A dimeric, cathodal variant of albumin was found among two Galibi subjects, and the fairly common occurrence of CP* ACAY among some South American Indian populations was confirmed. The results in the six populations were compared with those from 29 others. When relationships are searched for among tribes of the same linguistic group, the factor that seems to be most influential is geographical localization, an exception being the pattern observed among the Cayapo subgroups. The latter shows genetic differences of the same level of magnitude as those observed among Ge-speaking tribes.     

The effect of intravenous and oral fluconazole on the pharmacokinetics and pharmacodynamics of intravenous alfentanil

The growth-promoting activity of PDGF-BB was studied on the adult osteoclasts in the present study. The PDGF receptor beta was detected on the osteoclast membrane through immunohistochemistry (LSAB method) and immunomicroscopy. The PDGF-BB was exerted on the osteoclasts that adhered to the bone slice at concentrations of 0, 10, 20, 30, and 40 ng/ml. The volume of Howship's lacuna augmented significantly and the number of resorption pits also increased with its dose (p < 0.01). The activity of both total acid phosphatase (ACP) and tartrate-resistant acid phosphatase (TRAP) increased significantly. These results suggest that PDGF-BB promotes adult osteoclastic bone resorption directly through PDGF receptor beta and is believed to play important roles in the bone healing process and reconstruction.     

Ruthenium-106 brachytherapy for peripheral retinal capillary hemangioma

OBJECTIVE: This study aimed to evaluate the efficacy and safety of ruthenium-106 brachytherapy of large peripheral retinal capillary hemangiomas. DESIGN: A retrospective case series. PARTICIPANTS: In 25 eyes of 24 patients, peripheral capillary retinal hemangiomas were treated. INTERVENTION: Brachytherapy using 106-ruthenium/106-rhodium plaques was performed. MAIN OUTCOME MEASURES: Eyes were reviewed for hemangioma regression after brachytherapy, occurrence of retinal detachment, requirement of additional vitreoretinal surgery, final visual outcome, and final retinal status. RESULTS: Preoperative mean visual acuity of all eyes treated was 20/60, mean hemangioma diameter was 3.8 mm, corresponding to approximately 2 disc diameters. In 14 eyes, the retina was attached before surgery, 8 eyes showed an exudative detachment, and 3 eyes showed a traction detachment. Fifteen patients had definite von Hippel-Lindau syndrome. Twenty-three of 25 hemangiomas could be destroyed by single brachytherapy. In 16 eyes, a favorable outcome could be achieved. In nine eyes, outcome was unfavorable, characterized by a severe drop in visual acuity, a persisting exudative retinal detachment, or a recurrent traction detachment. In one eye requiring repeated brachytherapy, irradiation retinopathy occurred. Hemangiomas up to a size of approximately 5.0 mm without preoperative exudative detachment could be treated safely by brachytherapy, whereas a larger hemangioma size or a pre-existing exudative retinal detachment predisposed to an unfavorable outcome. CONCLUSION: Solitary peripheral retinal hemangioma can be ablated effectively by ruthenium-106 brachytherapy. A favorable outcome can be expected if the hemangioma diameter is 5.0 mm or smaller and if there is no preoperative exudative retinal detachment.     

Mixed endo-exo ultrastructural morphology of some beta cells in adult porcine pancreas

Life-threatening, recurrent ventricular tachycardia developed in a 54-year-old heart transplant candidate with ischemic cardiomyopathy. The episodes of ventricular tachycardia were refractory to aggressive medical management and implantable cardiac defibrillator placement. A Heartmate left ventricular assist device was implanted, in combination with isolated right coronary artery bypass grafting, which abolished any further episode of ventricular tachycardia. The patient successfully underwent cardiac transplantation 79 days later.     

Circulating lymphocyte phenotypic surface markers in anxiety disorder patients and normal volunteers

Assessment of clinical utility involves a series of steps based primarily on published peer-reviewed medical literature. Relevant publications usually use the scientific method, appropriate control groups, blinded reading, prospective design, and other study elements. Assessments are more credible when conducted by those who do not have a conflict of interest in the technique. A detailed assessment of digital and quantitative EEG was conducted recently by the American Academy of Neurology. The American Clinical Neurophysiology Society was a joint sponsor. This assessment concluded that digital EEG is an excellent substitute for paper EEG. It also found quantitative techniques helpful in epilepsy monitoring, seizure detections, and in operating room/intensive care unit trend monitors. Several other applications were considered promising, whereas some applications were considered not ready for clinical use. Substantial problems still plague the field, predisposing to false-positive results.