Inhibition of protein kinase C-dependent protein phosphorylation correlates with increased polarity and locomotion in Walker 256 carcinosarcoma cells

Signal transduction pathways controlling tumor cell locomotion are not yet well understood. We have studied the role of protein kinase C (PKC)-dependent protein phosphorylation associated with changes in cell shape and locomotor activity of Walker carcinosarcoma cells in culture. We show that the inhibitory effect of phorbol-12-myristate-13-acetate (PMA), an activator of PKC, on cell polarity and locomotion can be suppressed by the PKC-selective inhibitor Ro 31-8220. PMA induces increased phosphorylation of at least 2 proteins, of 65 and 80 kDa, in intact Walker carcinosarcoma cells. These bands are enriched in cytosolic fractions isolated from cells incubated with ³²PO₄. Pre-incubation with Ro 31-8220 inhibits the PMA-induced phosphorylation of both bands in a concentration-dependent manner. This effect is very likely not due to inhibition of translocation of PKC to the membrane as Ro 31-8220 enhances, rather than inhibits, PMA-induced transfer of PKC β₁₁ to the particulate fraction. We have carried out a quantitative analysis of phosphorylation of the 80-kDa band. Ro 31-8220 reverses both PMA-induced phosphorylation of this band and PMA-induced suppression of cell polarity in parallel. Increased phosphorylation of proteins via PKC may thus be a stop signal for locomoting Walker carcinosarcoma cells. © 1996 Wiley-Liss, Inc.     

Risk Factors for Dysphagia and the Impact on Outcome After Spontaneous Subarachnoid Hemorrhage

Neurocritical Care - Despite the tremendous impact of swallowing disorders on outcome following ischemic stroke, little is known about the incidence of dysphagia after subarachnoid hemorrhage (SAH)...     

The Impact of Inpatient Multimodal Treatment or Family-Based Treatment on Six-Month Weight Outcomes in Youth with Anorexia Nervosa: A Naturalistic,Cross-Continental Comparison

In the USA, family-based treatment (FBT) with inpatient medical stabilization as needed is the leading evidence-based treatment for youth with anorexia nervosa (AN). In continental Europe, typically inpatient multimodal treatment targeting weight recovery followed by outpatient care (IMT) is standard care, if prior outpatient treatment was not sufficient. Our aim was to compare weekly weight gain and hospital days over six months for adolescents receiving FBT (USA) versus IMT (Germany) using naturalistic treatment data. To yield similar subgroups of youth aged 12–18 years, inclusion criteria were a percent median BMI (%mBMI) between 70–85 and the restrictive AN subtype. Weight gain and hospital days were compared, adjusted further in a multiple linear regression analysis (MLRA) for baseline group differences. Samples differed on baseline %mBMI (FBT [n = 71], 90.5 ± 12.8; IMT [n = 29], 78.3 ± 9.1, p < 0.05). In subgroups with comparable baseline %mBMI, the weekly weight gain over 6 months was similar (FBT [n = 21]: 0.35 ± 0.18 kg/week; IMT [n = 20]: 0.30 ± 0.18, p = 0.390, p = 0.166 after MLRA), but achieved fewer hospital days in FBT (FBT [n = 7]: 4 ± 6 days, IMT [n = 20]: 121 ± 42 days, p < 0.0001 before and after MLRA). FBT may be effective for a subgroup of adolescents with AN currently receiving IMT, but head-to-head studies in the same healthcare system are needed.     

Effects of Vitamin D Supplementation on 24-Hour Blood Pressure in Patients with Low 25-Hydroxyvitamin D Levels: A Randomized Controlled Trial

Accumulating evidence suggests that potential cardiovascular benefits of vitamin D supplementation may be restricted to individuals with very low 25-hydroxyvitamin D (25(OH)D) concentrations; the effect of vitamin D on blood pressure (BP) remains unclear. We addressed this issue in a post hoc analysis of the double-blind, randomized, placebo-controlled Styrian Vitamin D Hypertension Trial (2011–2014) with 200 hypertensive patients with 25(OH)D levels <30 ng/mL. We evaluated whether 2800 IU of vitamin D3/day or placebo (1:1) for 8 weeks affects 24-hour systolic ambulatory BP in patients with 25(OH)D concentrations <20 ng/mL, <16 ng/mL, and <12 ng/mL and whether achieved 25(OH)D concentrations were associated with BP measures. Taking into account correction for multiple testing, p values < 0.0026 were considered significant. No significant treatment effects on 24-hour BP were observed when different baseline 25(OH)D thresholds were used (all p-values > 0.30). However, there was a marginally significant trend towards an inverse association between the achieved 25(OH)D level with 24-hour systolic BP (−0.196 per ng/mL 25(OH)D, 95% CI (−0.325 to −0.067); p = 0.003). In conclusion, we could not document the antihypertensive effects of vitamin D in vitamin D-deficient individuals, but the association between achieved 25(OH)D concentrations and BP warrants further investigations on cardiovascular benefits of vitamin D in severe vitamin D deficiency.