Suppression of proline-directed protein kinase F(A) systemically inhibits the growth of human acute leukemia cells

Initial studies revealed that proline-directed protein kinase F(A) (PDPK F(A)) was overexpressed in various cancerous tissues relative to normal controls. However, the functional role of overexpressed PDPK F(A) in cancer remains to be established. In this report, we explore the potential role of PDPK F(A) in leukemia cell growth by investigating the effects of partial inhibition of this kinase on human acute promyelocytic leukemia (HL-60) and acute lymphoblastic leukemia (Jurkat) cells. Cloning of PDPK F(A) cDNA and its recombinant antisense expression vector and antibody were successfully developed. Several stable antisense clones of HL-60 and Jurkat cells were subcloned, which expressed a low level of PDPK F(A) when compared with the control-transfected clone in immunoblot analysis. Moreover, these antisense clones potently inhibited cell growth, clonogenic growth in soft agar and serum-independent growth. The results taken together demonstrate that suppression of PDPK F(A) is able to interfere with the growth of HL-60 and Jurkat cells, suggesting an essential role of this PDPK in human acute leukemia cell growth.     

Bilateral anomalous origins of the posterior meningeal artery from the ascending pharyngeal arteries

We present a rare case of angiographically confirmed dural arteriovenous fistula supplied mainly by the posterior meningeal artery with bilateral anomalous origins from the bilateral ascending pharyngeal arteries. The bilaterality of the origins of the posterior meningeal artery is important in the angiographic diagnosis and management of a dural vascular malformation in the posterior fossa or the posterior part of the falx cerebri.     

Temporal patterns of disruptive vocalization in elderly nursing home residents

This study used computer-assisted real-time data collection procedures to study temporal patterns of disruptive vocalization (DV) in demented nursing home residents. Residents (N = 68) were observed from 8 a.m. to 8 p.m. and total mean duration of DV within hourly blocks was calculated. Analysis of the temporal distribution of DV exhibited by the group of 68 residents indicated a significant cubic trend. Exploratory cluster analysis uncovered three distinct temporal patterns of DV; although two of the patterns are generally supportive of sundowning. Cluster 1 showed a relatively constant pattern of low rate DV. Clusters 2 and 3 showed cyclic trends. Peaks in DV were observed during noontime and in the evening for Cluster 2. Cluster 3 showed peaks in DV in the early morning hours and late afternoon. MANOVA was employed to examine any differences among clusters in age, cognitive status, and ADL status. Univariate analyses indicated that cognitive status was the only factor that differed significantly among clusters, with members of Cluster 1 (constant low rate DV) manifesting higher cognitive status scores than Clusters 2 and 3. A step-wise discriminant function analysis also showed cognitive status to be the only statistically significant predictor of cluster membership. The authors' note that the scientific literature on agitation is fraught with contradictory findings and assert that inconsistencies may be due to differences across studies in problem definition, method of measurement, and sample size. The results are discussed in relation to these methodological issues and clinical implications of the findings.     

Beard dermatitis due to para-phenylenediamine use in Arabic men

The most common active ingredient in hair coloring is para-phenylenediamine (PPDA), which can produce contact dermatitis, particularly in persons who dye their scalp hair and in hairdressers. We have identified another group of patients also at risk, namely men from Arab countries, who commonly grow beards and dye them. We searched the computerized patient database at the Mayo Clinic for patients with beard dermatitis associated with dye use. Eight Arabic men presented to the Mayo Clinic between 1994 and 1999 with beard dermatitis and a positive patch test to PPDA. The lesions were described as pruritic, erythematous, papular eruptions that developed in the jaw area after each application of beard dye. The symptoms subsided after the patients discontinued use of the PPDA-containing dye and received treatment with topical corticosteroids. Allergic contact dermatitis in the beard area due to PPDA occurs in Arabic men as a result of their propensity to dye their beards.     

Reduced neuritic outgrowth and cell adhesion in neuronal cells transfected with human alpha-synuclein

Since recent reports have suggested that alpha-synuclein might play a role in neuronal plasticity, the main objective of this study was to determine the effects of alpha-synuclein on neuritic outgrowth. We stably transfected either human (h) alpha- or beta-synuclein cDNA in B103 rat neuronal cells. Expression of h(alpha)-synuclein resulted in reduced neurite extension and weak adhesion compared to vector-transfected and h(beta)-synuclein expressing cells. To investigate the potential pathways involved, we studied the effects of reagents known to modulate B103 proliferation and differentiation. Neither phorbol 12-myristate 13-acetate nor forskolin or antioxidants (catalase, superoxide dismutase, or vitamin E) were able to restore the reduced length of neurites in h(alpha)-synuclein-expressing cells. These results suggest that reduced neuritic activity in the h(alpha)-synuclein-expressing cells might be due, in part, to alterations in cell adhesion capacity. This might be attributed to alpha-synuclein affecting a signal transduction pathway distinct from protein kinase C and protein kinase A.     

Growth of endothelial cells on different concentrations of Gly-Arg-Gly-Asp photochemically grafted in polyethylene glycol modified polyurethane

To improve endothelial cell adhesion and growth on the surface of polyethylene glycol modified polyurethane (PU-PEG), cell adhesive peptide Gly-Arg-Gly-Asp (GRGD) was photochemically grafted to the surface. The surface grafted GRGD-N-Succinimidyl-6-[4'-azido-2'-nitrophenylamino]hexanoate (SANPAH) on a PU-PEG surface was performed by adsorption and subsequent ultraviolet irradiation. Fourier transform infrared spectra (FTIR) and electron spectroscopy for chemical analysis (ESCA) confirmed the GRGD grafted to form a PU-PEG-GRGD surface. The composition fraction of nitrogen calculated from ESCA analysis for the PU-PEG-GRGD surface was well correlated with the concentration of GRGD to be immobilized. Human umbilical vein endothelial cells (ECs) were well adhered and growing on the PU-PEG-GRGD surface. Moreover, the viability of ECs growing on PU-PEG-GRGD surfaces, analyzed by MTT test, was also well correlated with the GRGD concentrations immobilized on the surface. With photochemical techniques, we could manipulate different contents of GRGD to form multiple regions of PU-PEG-GRGD surface that could enhance the growth of ECs on the surface, and the enhancement efficiency was well correlated with GRGD contents.     

Middle cerebral artery Doppler velocimetric deceleration angle as a predictor of fetal anemia in Rh-alloimmunized fetuses without hydrops

OBJECTIVE: The purpose of this study was to evaluate the screening performance of a new middle cerebral artery Doppler velocimetric index for the prediction of fetal anemia. STUDY DESIGN: Doppler velocimetry of the middle cerebral artery was performed before cordocentesis in 24 Rh-alloimmunized fetuses without hydrops on 52 occasions. The angle between the line describing the average slope during the diastolic phase of the cardiac cycle and the vertical, the middle cerebral artery standardized deceleration angle, was measured. The deceleration angle values were expressed in multiples of the median for gestational age. The screening performances of deceleration angle for the prediction of anemia (difference between expected mean hemoglobin level and measured value >/=2 g/dL) and severe anemia (hemoglobin deficit >/=5 g/dL) were determined. RESULTS: The mean (+/-SD) gestational age at cordocentesis was 28.6 +/- 5.7 weeks' gestation. The risk of fetal anemia increased with decreasing deceleration angle values. The sensitivity and false-positive rate for the detection of anemia in cases with no previous transfusions (one measurement per patient) were 72.0% and 13.3%, respectively; among those with one previous transfusion the values were 90.0% and 0.0%, respectively. For severe anemia the corresponding values were 100% and 0%, respectively, among those with no previous transfusions and 100.0% and 16.7%, respectively, among those with one previous transfusion. There was no risk of severe anemia when the angle was >0.9 multiples of the median. The risk of anemia was significantly reduced with an angle greater than the median for gestational age (deceleration angle >1.0 multiples of the median; relative risk, 0.09; 95% confidence interval, 0.02-0.37). The risk was significantly increased with an angle less than the median for gestational age (deceleration angle <1.0 multiples of the median; relative risk, 30.0; 95% confidence interval, 5.9-158.4). CONCLUSION: The risk of fetal hydrops is remote in the absence of severe anemia. With a new Doppler velocimetric index in the middle cerebral artery the risk of severe anemia was found to be low when the deceleration angle was >0.9 multiples of the median. Anemia can also be predicted with this index. The high sensitivities and acceptable false-positive rates support the potential clinical applicability of the method to reduce the reliance on cordocentesis in Rh alloimmunization. Our findings appear to validate the utility of the deceleration angle for the prediction of fetal anemia.