Biomedical subjects

S L Godwin

Publications and source records attributed to S L Godwin.

6 recordsLinked to original sources

PubMed2002

Calcium-sensing receptor-mediated activation of phospholipase C-gamma1 is downstream of phospholipase C-beta and protein kinase C in MC3T3-E1 osteoblasts.

Elevated extracellular calcium (Ca(e)) stimulates both chemotaxis and mitogenesis of MC3T3-E1 osteoblasts via a calcium-sensing receptor (CasR). Ca(e)-mediated chemotaxis of these bone-forming cells is dependent on phospholipase C (PLC) and blocked by the Gi-protein inhibitor pertussis toxin. In this study, we examine the signaling mechanisms by which the CasR stimulates PLC activity in MC3T3-E1 osteoblasts. We found that elevated Ca(e) stimulated PLC-gamma1 tyrosine phosphorylation in a time-dependent and Ca(e)-concentration-dependent manner. The maximal increase in PLC-gamma1 tyrosine phosphorylation was observed 3-5 min after increasing Ca(e) by 3.2 mmol/L from 1.8 mmol/L. Elevated Ca(e) also promoted a rapid increase in both inositol 1,4,5-trisphosphate [Ins(1,4,5)P3], a second messenger formed by PLC-mediated hydrolysis of phosphatidylinositol 4,5-bisphosphate, and cytosolic free calcium ([Ca+2]i). The kinetics of the CasR-mediated increases in Ins(1,4,5)P3 and [Ca+2]i and the sensitivity of the Ca(e)-stimulated elevation in [Ca+2]i to U73122 (a PLC inhibitor) together suggest that the osteoblast CasR is coupled via Gq to PLC-beta. U73122 blocked the Ca(e)-promoted, but not PDGF-promoted, PLC-gamma1 tyrosine phosphorylation, suggesting that the activation of PLC-beta is upstream of PLC-gamma1 activation. Inhibition of protein kinase C (PKC) disrupted Ca(e)-stimulated tyrosine phosphorylation of PLC-gamma1. In addition, exposure to pertussis toxin or exogenous activation of protein kinase A (PKA) inhibited PLC-gamma1 tyrosine phosphorylation in response to Ca(e). The results indicate that: (a) the osteoblast CasR activates PLC-gamma1 downstream of PLC-beta in a PKC-dependent manner; (b) PKA is a negative regulator of Ca(e)-promoted PLC-gamma1 phosphorylation; and (c) Gq and Gi are both involved in the CasR-mediated phosphorylation of PLC-gamma1.

Animals↗

PubMed2000

Cognitive strategies for reporting portion sizes using dietary recall procedures.

OBJECTIVES: To examine recall strategies used by interview respondents when making judgments about portion size and to better understand how respondents use various portion-size aids. DESIGN: Study participants were separated into groups, each using a different set of portion-size estimation aids: (a) 2-dimensional paper aids presented in stacks, (b) 2-dimensional aids, cut out and presented on rings, (c) household-type aids, and (d) a combination of 2- and 3-dimensional aids, many of which are used in national government surveys. Respondents gave a "quick list" of foods consumed the previous day and practiced cognitive thinking skills. Then the interviewer selected at least 2 solid, 2 liquid, and 2 amorphous foods for probing. Respondents were asked to think aloud as they reported how much they ate of each food. Types and frequencies of cognitive strategies used for portion-size estimation were determined. SUBJECTS: Interviews of 1 to 1 1/2 hours were conducted with 76 adults aged 18 to 65 years. Participants were recruited to obtain a mix of races, ages, educational levels, and genders. RESULTS: The most frequently used strategy was visualization and comparison to aids. Others strategies were known amounts, estimations based on known amounts, visualization of volume or a container, and actions such as pouring or moving hands to the mouth. Respondents preferred aids that were similar in size and shape to actual portions consumed for liquid or amorphous food and preferred the ruler for solid foods. APPLICATIONS: To obtain the best data from dietary recalls, expect answers that are possible for respondents to give, supply respondents with aids that help them recall amounts consumed, and guide respondents to appropriate aids that help them formulate focused responses.

Adolescent↗

PubMed1999

Multiple roles for Src in a PDGF-stimulated cell.

The observation that platelet-derived growth factor (PDGF) increases the catalytic activity of Src family members (Src) suggests that they contribute to PDGF-dependent responses. The role of Src in PDGF-dependent cell cycle progression, phosphorylation of proteins, and chemotaxis has been tested by investigators using a variety of cell types and approaches, and it appears that the contribution of Src is highly variable. This idea is perhaps best illustrated by the finding that Src plays radically different roles downstream of the PDGF alpha- and beta-receptor subunits. Hence, Src is a versatile signal relay enzyme, whose contribution to a signaling cascade depends on variables such as the nature of the receptor via which the cell is activated, as well as the cell type itself.

Cell Cycle↗

PubMed1997

Extracellular calcium and platelet-derived growth factor promote receptor-mediated chemotaxis in osteoblasts through different signaling pathways.

The discovery of a calcium receptor has stimulated interest in the signaling events underlying extracellular calcium ([Ca2+]o)-induced cell-specific responses. In osteoblasts, elevated levels of extracellular calcium mediate both mitogenesis and chemotaxis. Here we provide evidence that [Ca2+]o-stimulated chemotaxis of MC3T3-E1 osteoblast-like cells involves a G-protein-linked calcium-sensing receptor. [Ca2+]o promotes chemotaxis in a concentration-dependent manner. Pertussis toxin blocked almost all of [Ca2+]o-stimulated chemotaxis but had only a small effect on platelet-derived growth factor (PDGF)-stimulated chemotaxis. Consistent with the signaling model for PDGF-mediated chemotaxis, activation of phospholipase C played a critical role in [Ca2+]o-initiated chemotaxis: U-73122, an inhibitor of the activation of phospholipase C, blocked approximately 50% of PDGF-stimulated chemotaxis but blocked nearly all of the [Ca2+]o-stimulated chemotaxis. Down-regulation of protein kinase C also blocked about 50% of PDGF-stimulated chemotaxis but did not block [Ca2+]o-stimulated chemotaxis. Thus, unlike PDGF-mediated chemotaxis, chemotaxis stimulated by [Ca2+]o does not appear to require protein kinase C activation. This finding suggests events downstream of inositol 1,4,5-trisphosphate production rather than diacylglycerol production are critical to [Ca2+]o-promoted chemotaxis of MC3T3-E1 cells. The signal transduction mechanism underlying PDGF-induced chemotaxis involves the activation of phosphoinositide 3-kinase, as judged by the in vivo production of phosphatidylinositol 3,4-diphosphate and 3,4,5-trisphosphate and the partial sensitivity of chemotaxis to wortmannin, an inhibitor of phosphoinositide 3-kinase. In contrast, [Ca2+]o-stimulated chemotaxis was not blocked by wortmannin and elevations in [Ca2+]o did not increase the production of lipid products of phosphoinositide 3-kinase. Overall, [Ca2+]o-promoted chemotaxis of osteoblasts appears to utilize a unique signaling mechanism via a calcium-sensing receptor.

Animals↗

PubMed1996

The concept of the sagittal orbital-globe relationship in craniofacial surgery.

Euophthalmos, the normal relationship of the orbital rims to the eyes, is critical to planning and to surgical correction of craniofacial deformities. The four most easily localized anthropometric (soft tissue) landmarks for the sagittal orbital-globe relationship are orbitale superius (os), orbitale inferius (oi), orbitale laterale (ol), and nasion (n), all referenced to apex corneae (acor). The normal adult values for os, oi, ol, and n were extracted from the literature. Age-specific anthropometric landmarks were computed from age-specific Bolton cephalometric templates. A vernier caliper was used to measure preoperatively the surface orbital landmarks in patients with various syndromic and nonsyndromic craniosynostotic disorders. Preoperative measurements were compared with the derived normative data to determine the necessary sagittal orbital translocation for frontal advancement (n=19) and frontal-midfacial advancement (n=2). Postoperative orbital anthropometry documented the degree of normalization of the sagittal orbital-globe relationship. The problems with current instrumentation for orbital anthropometry are discussed.

Adolescent↗

PubMed1989

Interference reflection microscopic study of sites of association between gliding bacteria and glass substrata.

Sites of close contact between gliding Cytophaga sp. strain U67 cells and glass were examined by interference reflection microscopy. Site patterns changed during translocation and moved relative to the substratum, in contrast to previous interference reflection microscopy observations of fibroblast and amoeboid motility. Sinistral rotation around the long axis of the cell was coupled with gliding, except when curved cells traversed curvilinear pathways. Close contact was temporary, since cells flipped up off the substratum on one pole, pivoted, or were displaced laterally in collisions. Other members of the order Cytophagales and Myxococcus sp. demonstrated similar patterns of close association with substrata.

Bacterial Adhesion↗