p21WAF1/Cip1 is a negative transcriptional regulator of Wnt4 expression downstream of Notch1 activation.

In keratinocytes, the cyclin/CDK inhibitor p21(WAF1/Cip1) is a direct transcriptional target of Notch1 activation; loss of either the p21 or Notch1 genes expands stem cell populations and facilitates tumor development. The Notch1 tumor-suppressor function was associated with down-regulation of Wnt signaling. Here, we show that suppression of Wnt signaling by Notch1 activation is mediated, at least in part, by down-modulation of Wnts gene expression.

Wnt/beta-catenin signaling acts upstream of N-myc, BMP4, and FGF signaling to regulate proximal-distal patterning in the lung.

Branching morphogenesis in the lung serves as a model for the complex patterning that is reiterated in multiple organs throughout development. Beta-catenin and Wnt signaling mediate critical functions in cell fate specification and differentiation, but specific functions during branching morphogenesis have remained unclear. Here, we show that Wnt/beta-catenin signaling regulates proximal-distal differentiation of airway epithelium.

Pax3 functions at a nodal point in melanocyte stem cell differentiation.

Most stem cells are not totipotent. Instead, they are partially committed but remain undifferentiated. Upon appropriate stimulation they are capable of regenerating mature cell types.

Dural ectasia: a likely cause of inadequate spinal anaesthesia in two parturients with Marfan's syndrome.

We report two cases of Caesarean section in patients with Marfan's syndrome where continuous subarachnoid anaesthesia failed to provide an adequate surgical block. This was possibly because of dural ectasia, which was confirmed by a computed tomography scan in both cases.

A mutation in NFkB interacting protein 1 results in cardiomyopathy and abnormal skin development in wa3 mice.

We have identified waved 3 (wa3), a novel recessive mutation that causes abnormalities of the heart and skin. The cardiac defect results in a severe and rapidly progressive dilated cardiomyopathy. We identified the gene mutated in these mice, which we call NFkB interacting protein1 (Nkip1), using positional cloning.

Canonical WNT signaling promotes mammary placode development and is essential for initiation of mammary gland morphogenesis.

Mammary glands, like other skin appendages such as hair follicles and teeth, develop from the surface epithelium and underlying mesenchyme; however, the molecular controls of embryonic mammary development are largely unknown. We find that activation of the canonical WNT/beta-catenin signaling pathway in the embryonic mouse mammary region coincides with initiation of mammary morphogenesis, and that WNT pathway activity subsequently localizes to mammary placodes and buds. Several Wnt genes are broadly expressed in the surface epithelium at the time of mammary initiation, and expression of additional Wnt and WNT pathway genes localizes to the mammary lines and placodes as they develop.

Expression of Frizzled genes in developing and postnatal hair follicles.

Embryonic hair follicle development and postnatal hair growth rely on intercellular communication within the epithelium and between epithelial and mesenchymal cells. Several members of the WNT family of paracrine intercellular signaling molecules are expressed in specific subsets of cells in developing and mature mouse hair follicles, suggesting them as candidates for some of the intercellular signals that operate in these organs. As WNT ligands activate several different signaling pathways, they may play multiple and complex roles in developing and postnatal skin.

Anesthesia for cesarean section in a patient with spinal muscular atrophy.

We describe the anesthetic management for cesarean section and tubal ligation of a 23-year-old primipara with type II spinal muscular atrophy (benign Werdnig Hoffmann). She was wheelchair-bound, had severe restrictive lung disease, and severe kyphoscoliosis, with Harrington rods extending from the thoracic to the sacral spines. A general anesthetic was given.

Epithelial Bmpr1a regulates differentiation and proliferation in postnatal hair follicles and is essential for tooth development.

Bone morphogenetic protein (BMP) signaling is thought to perform multiple functions in the regulation of skin appendage morphogenesis and the postnatal growth of hair follicles. However, definitive genetic evidence for these roles has been lacking. Here, we show that Cre-mediated mutation of the gene encoding BMP receptor 1A in the surface epithelium and its derivatives causes arrest of tooth morphogenesis and lack of external hair.

External and body-centered frames of reference in spatial memory: evidence from touch.

The study reports independent effects of external and body-centered reference cues on spatial coding of an irregular sequence of haptic locations. The aim was to investigate the nature of spatial coding by using a modality that does not provide distal cues routinely. Our method isolates and combines body-centered and external spatial reference cues for irregularly placed locations, scanned along a raised-line route.

Spatial reference and scanning with the left and right hand.

Discrepant findings on performance by the two hands in spatial tasks make it difficult to infer spatial coding unambiguously. We tested the hypotheses (a) that the left hand is consistently better in haptic spatial tasks and (b) that adding spatial reference information produces more accurate coding in spatial tasks, independently task and hand effects. Instructions to use external cues from a surrounding frame as well as body-centred cues for reference produced highly significant increases in accuracy in haptic distance and location experiments.

Over- and ectopic expression of Wnt3 causes progressive loss of ameloblasts in postnatal mouse incisor teeth.

Intercellular signaling is essential for the development of teeth during embryogenesis and in maintenance of the continuously growing incisor teeth in postnatal rodents. WNT intercellular signaling molecules have been implicated in the regulation of tooth development, and the Wnt3 gene shows specific expression in the enamel knot at the cap stage. We demonstrate here that Wnt3 also is expressed in specific epithelial cell layers in postnatal incisor teeth.

Anesthetic management of a ventilator-dependent parturient with the King-Denborough syndrome.

Purpose: The King-Denborough syndrome (KDS) is a rare disorder that is associated with myopathy, susceptibility to malignant hyperthermia (MH) as well as congenital skeletal and facial anomalies. We report the anesthetic management of a parturient with KDS.

Clinical Features: We describe the management of a 24-yr-old primiparous woman with a diagnosis of KDS and a history of previous MH reaction (age two).

Patients' needs for nursing care: beyond staffing ratios.

The current focus on staffing ratios as a means to assure appropriate care for patients ignores the very real differences among patients in their needs for nursing care. Implementing a system that identifies these needs provides a more accurate indication of staffing requirements. In addition, storing the raw data from the system at their most basic level provides opportunities for more extensive analyses and informed, data-driven decision-making related to resource allocation, performance improvement, and productivity enhancement.

The Müller-Lyer illusion in touch and vision: implications for multisensory processes.

In six experiments, we used the Müller-Lyer illusion to investigate factors in the integration of touch, movement, and spatial cues in haptic shape perception, and in the similarity with the visual illusion. Latencies provided evidence against the hypothesis that scanning times explain the haptic illusion. Distinctive fin effects supported the hypothesis that cue distinctiveness contributes to the illusion, but showed also that it depends on modality-specific conditions, and is not the main factor.

WNT signals are required for the initiation of hair follicle development.

Hair follicle morphogenesis is initiated by a dermal signal that induces the development of placodes in the overlying epithelium. To determine whether WNT signals are required for initiation of follicular development, we ectopically expressed Dickkopf 1, a potent diffusible inhibitor of WNT action, in the skin of transgenic mice. This produced a complete failure of placode formation prior to morphological or molecular signs of differentiation, and blocked tooth and mammary gland development before the bud stage.

The WNT7b promoter is regulated by TTF-1, GATA6, and Foxa2 in lung epithelium.

In this study, we find that WNT7b is the only member of the WNT family of autocrine/paracrine signaling molecules whose expression in the lung is restricted to the airway epithelium during embryonic development. To study the transcriptional mechanisms that underlie this restricted pattern of WNT7b expression, we isolated the proximal 1.0-kb mouse WNT7b promoter and mapped the transcriptional start sites.

Molecular mechanisms regulating hair follicle development.

Clinical conditions causing hair loss, such as androgenetic alopecia, alopecia areata, and scarring alopecia, can be psychologically devastating to individuals and are the target of a multimillion dollar pharmaceutical industry. The importance of the hair follicle in skin biology, however, does not rest solely with its ability to produce hair. Hair follicles are self-renewing and contain reservoirs of multipotent stem cells that are capable of regenerating the epidermis and are thought to be utilized in wound healing.

A critical pathway for electronic medical record selection.

Electronic medical records (EMRs) are increasingly becoming a necessary tool in health care. Given their potential to influence every aspect of health care, there has been surprisingly little rigorous research applied to this important piece of emerging health technology. An initial phase of the COMPETE study, which is examining the impact of EMRs on efficiency, quality of care and privacy concerns, involved a rigorous "critical pathway" approach to EMR selection for the study.

Illusions in reading maps by touch: reducing distance errors.

The study reports systematic distance errors in reading raised-line maps by touch, and how they can be reduced. We show that T-shaped road junctions produce the typical error due to overestimating the length of the bisecting road compared to the bisected road. The error was not reduced when the target location was marked initially by a symbol.

Characterization of Wnt gene expression in developing and postnatal hair follicles and identification of Wnt5a as a target of Sonic hedgehog in hair follicle morphogenesis.

Mutations in WNT effector genes perturb hair follicle morphogenesis, suggesting key roles for WNT proteins in this process. We show that expression of Wnts 10b and 10a is upregulated in placodes at the onset of follicle morphogenesis and in postnatal hair follicles beginning a new cycle of hair growth. The expression of additional Wnt genes is observed in follicles at later stages of differentiation.

Cerebral hypoperfusion in immediate postoperative period following coronary artery bypass grafting, heart valve, and abdominal aortic surgery.

Perioperative levels of jugular bulb oxyhaemoglobin saturation (Sj(O(2))) and lactate concentration (Lj), and postoperative duration of Sj(O(2))<50% were compared between patients undergoing coronary artery bypass grafting (CABG) (n=86), heart valve (n=14) and abdominal aortic (n=16) surgery. Radial artery and jugular bulb blood samples were aspirated after induction of anaesthesia, during re-warming on cardiopulmonary bypass (CPB) (36 degrees C), on arrival in the intensive care unit (ICU) and, subsequently, at 1, 2 and 6 h after ICU admission. Most patients having heart surgery were hypocapnic at 36 degrees C on CPB.