MKP-1 antagonizes C/EBPß activity and lowers the apoptotic threshold after ischemic injury.

The dual specificity phosphatase MAPK phosphatase-1 (MKP-1) feeds back on MAP kinase signaling to regulate metabolic, inflammatory and survival responses. MKP-1 is widely expressed in the central nervous system (CNS) and induced after ischemic stress, although its function in these contexts remains unclear. Here we report that MKP-1 activated several cell death factors, including BCL2 and adenovirus E1B 19 kDa interacting protein 3, and caspases 3 and 12 culminating in apoptotic cell death in vitro. MKP-1 also exerted inhibitory effects on the bZIP transcription factor CCAAT/enhancer-binding protein (C/EBPß), previously shown to have neuroprotective properties. These effects included reduced expression of the full-length C/EBPß variant and hypo-phosphorylation at the MEK-ERK1/2-sensitive Thr(188) site. Notably, enforced expression C/EBPß rescued cells from MKP-1-induced toxicity. Studies performed in knock-out mice indicate that the MKP-1 activity is required to exclude C/EBPß from the nucleus basally, and that MKP-1 antagonizes C/EBPß expression after global forebrain ischemia, particularly within the vulnerable CA1 sector of the hippocampus. Overall, MKP-1 appears to lower the cellular apoptotic threshold by inhibiting C/EBPß and enhancing both BH3 protein expression and cellular caspase activity. Thus, although manipulation of the MKP-1-C/EBPß axis could have therapeutic value in ischemic disorders, our observations using MKP-1 catalytic mutants suggest that approaches geared towards inhibiting MKP-1's phosphatase activity alone may be ineffective.

Effects of feeding silage and grain from glyphosate-tolerant or insect-protected corn hybrids on feed intake, ruminal digestion, and milk production in dairy cattle.

Lactating dairy cows were used to determine effects of feeding glyphosate-tolerant or insect-protected corn hybrids on feed intake, milk production, milk composition, and ruminal digestibility. Corn resistant to European corn borer (Ostrinia nubilalis) infestation (Bt-MON810), or its nontransgenic control (Bt-CON), were planted in alternating fields during two successive years. One-half of each strip was harvested for whole plant corn silage and the remainder was allowed to mature and harvested as grain. Effects of feeding diets containing either Bt-MON810 or Bt-CON grain and silage were determined in two experiments (1 and 2) conducted during successive years. In experiment 3, glyphosate-tolerant Roundup Ready corn (RR-GA21) or its nontransgenic control (RR-CON) corn were grown in alternating fields during one cropping season. Diets contained 42 to 60% corn silage and 20 to 34% corn grain from Bt-MON810, RR-GA21, or the appropriate nontransgenic counterpart; treatments were applied using a switchback design. Cows were fed ad libitum and milked twice daily. There were no differences for nutrient composition between silage sources or between grain sources within an experiment. Data for experiments 1 and 2 indicated similar dry matter intake (DMI), 4% fat-corrected milk (FCM) production, and milk composition between Bt-MON810 and Bt-CON diets. There were no differences for DMI, 4% FCM production, and milk composition between RR-GA21 and RR-CON diets. There was no difference in ruminal degradability, determined separately for corn silage and corn grain, for RR-GA21 or Bt-MON810-hybrids compared with their respective controls. These data demonstrate equivalence of nutritional value and production efficiency for corn containing Bt-MON810 compared with its control and for RR-GA21 corn compared with its control.

Primary care outcomes in patients treated by nurse practitioners or physicians: a randomized trial.

CONTEXT: Studies have suggested that the quality of primary care delivered by nurse practitioners is equal to that of physicians. However, these studies did not measure nurse practitioner practices that had the same degree of independence as the comparison physician practices, nor did previous studies provide direct comparison of outcomes for patients with nurse practitioner or physician providers. OBJECTIVE: To compare outcomes for patients randomly assigned to nurse practitioners or physicians for primary care follow-up and ongoing care after an emergency department or urgent care visit. DESIGN: Randomized trial conducted between August 1995 and October 1997, with patient interviews at 6 months after initial appointment and health services utilization data recorded at 6 months and 1 year after initial appointment. SETTING: Four community-based primary care clinics (17 physicians) and 1 primary care clinic (7 nurse practitioners) at an urban academic medical center. PATIENTS: Of 3397 adults originally screened, 1316 patients (mean age, 45.9 years; 76.8% female; 90.3% Hispanic) who had no regular source of care and kept their initial primary care appointment were enrolled and randomized with either a nurse practitioner (n = 806) or physician (n = 510). MAIN OUTCOME MEASURES: Patient satisfaction after initial appointment (based on 15-item questionnaire); health status (Medical Outcomes Study Short-Form 36), satisfaction, and physiologic test results 6 months later; and service utilization (obtained from computer records) for 1 year after initial appointment, compared by type of provider. RESULTS: No significant differences were found in patients' health status (nurse practitioners vs physicians) at 6 months (P = .92). Physiologic test results for patients with diabetes (P = .82) or asthma (P = .77) were not different. For patients with hypertension, the diastolic value was statistically significantly lower for nurse practitioner patients (82 vs 85 mm Hg; P = .04). No significant differences were found in health services utilization after either 6 months or 1 year. There were no differences in satisfaction ratings following the initial appointment (P = .88 for overall satisfaction). Satisfaction ratings at 6 months differed for 1 of 4 dimensions measured (provider attributes), with physicians rated higher (4.2 vs 4.1 on a scale where 5 = excellent; P = .05). CONCLUSIONS: In an ambulatory care situation in which patients were randomly assigned to either nurse practitioners or physicians, and where nurse practitioners had the same authority, responsibilities, productivity and administrative requirements, and patient population as primary care physicians, patients' outcomes were comparable.

Differentiated primary care and evidence-based practice: the Columbia nursing experiment.

Changes in our health care system and the growth of managed care have turned the spotlight on primary care and are driving sweeping reforms in health professions education, patient care, and research. The Columbia University School of Nursing has responded to this challenge by establishing a community primary care clinic managed by nurse practitioners. This article describes this clinic, an evaluation study of this practice, and their relevance to pending policy discussions on primary care provider designation and payment and the regulation of scope of professional practice.