Hematopoietic colony-forming cells derived from human embryonic stem cells.

Human embryonic stem (ES) cells are undifferentiated, pluripotent cells that can be maintained indefinitely in culture. Here we demonstrate that human ES cells differentiate to hematopoietic precursor cells when cocultured with the murine bone marrow cell line S17 or the yolk sac endothelial cell line C166. This hematopoietic differentiation requires fetal bovine serum, but no other exogenous cytokines. ES cell-derived hematopoietic precursor cells express the cell surface antigen CD34 and the hematopoietic transcription factors TAL-1, LMO-2, and GATA-2. When cultured on semisolid media with hematopoietic growth factors, these hematopoietic precursor cells form characteristic myeloid, erythroid, and megakaryocyte colonies. Selection for CD34(+) cells derived from human ES cells enriches for hematopoietic colony-forming cells, similar to CD34 selection of primary hematopoietic tissue (bone marrow, umbilical cord blood). More terminally differentiated hematopoietic cells derived from human ES cells under these conditions also express normal surface antigens: glycophorin A on erythroid cells, CD15 on myeloid cells, and CD41 on megakaryocytes. The in vitro differentiation of human ES cells provides an opportunity to better understand human hematopoiesis and could lead to a novel source of cells for transfusion and transplantation therapies.

Receptor-specific influence of endothelin-1 in the erectile response of the rat.

Specific receptor antagonists were used to examine the role of endothelin-1 (ET-1) in the erectile response of the rat. In these studies, intact rats were cannulated to permit the continuous recording of mean arterial pressure (MAP) and intracavernosal pressure (CCP). Erection was induced by electrical stimulation of the autonomic ganglion, which regulates blood flow to the penis. The animals were subjected to intracavernosal injection with vehicle only (Cont) or with an antagonist to the endothelin-A receptor (ET(A)) or to the endothelin-B receptor (ET(B)). Blockade of the ET(A) or the ET(B) had no effect on the erectile response (CCP/MAP) during maximal ganglionic stimulation. When ET-1 was injected into Cont rats, there was a marked vasoconstriction with a sharp rise in MAP and a decline in CCP as the cavernosal arterioles constricted and limited inflow. The injection of the ET(A) antagonist prevented the vasoconstriction after ET-1 injection into Cont rats, whereas blockade of the ET(B) had no effect on the vasoconstrictive effect to ET-1. Similar results were obtained during submaximal ganglionic stimulation. With minimal levels of ganglionic stimulation, ET-1 injection led to a moderated degree of vasodilation in the presence of the ET(A) antagonist. The ET(B) antagonist failed to alter the CCP response during minimal stimulation, but it did have a marked effect on the MAP response to ET-1 injection. The results of these studies confirm that cavernosal tissue of the rat penis is highly responsive to ET-1. However, the failure of the ET-1 antagonists to affect penile erection in response to ganglionic stimulation reflects a minimal role of ET-1 in the erectile response in the rat.

Falsifying serial and parallel parsing models: empirical conundrums and an overlooked paradigm.

When the human parser encounters a local structural ambiguity, are multiple structures pursued (parallel or breadth-first parsing), or just a single preferred structure (serial or depth-first parsing)? This note discusses four important classes of serial and parallel models: simple limited parallel, ranked limited parallel, deterministic serial with reanalysis, and probabilistic serial with reanalysis. It is argued that existing evidence is compatible only with probabilistic serial-reanalysis models, or ranked parallel models augmented with a reanalysis component. A new class of linguistic structures is introduced on which the behavior of serial and parallel parsers diverge the most radically: multiple local ambiguities are stacked to increase the number of viable alternatives in the ambiguous region from two to eight structures. This paradigm may provide the strongest test yet for parallel models.

Angiogenesis assays: problems and pitfalls.

Many studies of angiogenesis inducers and inhibitors rely on in vitro or in vivo models as indicators of efficacy. However, as valuable as these models are, there are limitations to each one of these. This overview describes some of the principal methods now in use and discusses the advantages and some of the limitations of these methods. It is suggested that multiple assays, involving both in vitro and in vivo assays, are at present the best way to minimize the problems inherent in any specific assay.

Serial amniotic fluid index in severe preeclampsia: a poor predictor of adverse outcome.

OBJECTIVE: The purpose of the study was to determine the relationship between low amniotic fluid index and intrauterine growth restriction and nonreassuring fetal testing in patients with severe preeclampsia. STUDY DESIGN: We reviewed the medical records of 136 women with severe preeclampsia managed conservatively for at least 48 hours. Patients were followed up with a daily nonstress test and amniotic fluid index. We evaluated amniotic fluid index < or = 5 cm and < or = 7 cm, measured on admission or just before delivery (i.e., final), and attempted to correlate these findings with the incidence of nonreassuring fetal testing necessitating cesarean section or the incidence of intrauterine growth restriction (birth weight < or = 10th percentile). RESULTS: One hundred seven patients had a cesarean section, but only 42 (39%) of these were for a nonreassuring fetal heart rate tracing or a persistent biophysical profile of < or = 4, and 38 (36%) of the pregnancies resulted in infants with intrauterine growth restriction. During expectant management, the amniotic fluid index worsened for 61 (45%) patients and improved or remained the same for 75 (55%). For those with an amniotic fluid index of < or = 5 cm both on admission and at delivery, there was a significantly higher incidence of intrauterine growth restriction compared with those with an amniotic fluid index > 5 cm (p = 0.007 and p = 0.029, respectively). However, there was no association between intrauterine growth restriction and an amniotic fluid index < or = 7 cm. Moreover, there was no difference in the frequency of nonreassuring fetal heart rate testing on the basis of amniotic fluid volume (p = 0.59) or intrauterine growth restriction (p = 0.4). CONCLUSIONS: For women with severe preeclampsia remote from term, an amniotic fluid index < or = 5 cm is predictive of intrauterine growth restriction but lacks sensitivity. There is no association between the amniotic fluid index status and frequency of cesarean section for fetal distress or nonreassuring fetal testing.

Interference in short-term memory: the magical number two (or three) in sentence processing.

Many theories have been proposed to explain difficulty with center embedded constructions, most attributing the problem to some kind of limited-capacity short-term memory. However, these theories have developed for the most part independently of more traditional memory research, which has focused on uncovering general principles such as chunking and interference. This article attempts to gain some unification with this research by suggesting that an interesting range of core sentence processing phenomena can be explained as interference effects in a sharply limited syntactic working memory. These include difficult and acceptable embeddings, as well as certain limitations on ambiguity resolution, length effects in garden path structures, and the requirement for locality in syntactic structure. The theory takes the form of an architecture for parsing that can index no more than two constituents under the same syntactic relation. A limitation of two or three items shows up in a variety of other verbal short-term memory tasks as well.

Emergency department quality assurance/improvement practices for the pediatric patient.

STUDY OBJECTIVE: To describe emergency department quality assurance (QA)/improvement (QI) practices for pediatric patients. DESIGN: Mail survey of a cohort of emergency physicians. PARTICIPANTS: Pediatric Section members of the American College of Emergency Physicians and a computer-generated random sample of general ACEP members. RESULTS: Pediatric Section and general ACEP physicians were mailed a 13-question QA survey. Of the 500 surveys distributed, 207 (41.4%) were returned. Three emergency care settings for pediatric patients seen in the ED were identified: (1) children's hospital ED (14%), (2) general ED with a separate area designated for the evaluation of pediatric patients (12%), and (3) general ED where pediatric and adult patients are evaluated in the same area (74%). Separate QA indicators were used to monitor care of the pediatric patients seen in the ED by 61% of the respondents; 39% used "adult" indicators only. High pediatric census was associated with pediatric representation on the ED QA/QI Committee, the use of separate pediatric indicators to monitor care of pediatric patients in the ED, the separation of pediatric and adult patient care areas and satisfaction with the respondent's ED QA/QI plan. CONCLUSION: The bulk of pediatric emergency patients are cared for in a general ED. Most ACEP members surveyed reported the use of separate QA indicators to monitor the care of pediatric patients seen in the ED. This survey provides the first description of QA/QI practices for pediatric patients by EDs nationwide.

Electroanalytical characteristics of the cardiotonics, enoximone and piroximone.

Enoximone and piroximone are cardiotonic agents for use in patients with congestive heart failure. Electroanalytical studies revealed that the dihydroimidazolone functionality was oxidizable and that this property can be analytically useful. The compounds undergo a two-electron, irreversible oxidation in neutral to acidic media, leading to two major products. Results in basic media show up to three electrons transferred per molecule and much higher oxidation potentials at the fresh carbon paste electrode than at identical electrodes preconditioned in supporting electrolyte at +1.2 V. Use of amperometric detection with HPLC provides excellent measurement sensitivity (less than 1 ng) and reproducibility. Carbon paste and glassy carbon electrodes surfaces are not obviously affected by the electrochemical reactants or products. Piroximone, in addition, contains a 4-pyridoyl function which is irreversibly reducible at a mercury electrode, with excellent response linearity, and measurement sensitivity to at least 10(-7) M by differential pulse polarography.