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David Ingram

Publications and source records attributed to David Ingram.

15 recordsLinked to original sources
PubMed2006

Angiogenic cells can be rapidly mobilized and efficiently harvested from the blood following treatment with AMD3100.

Circulating endothelial progenitor cells (EPCs) are thought to contribute to angiogenesis following vascular injury, stimulating interest in their ability to mediate therapeutic angiogenesis. However, the number of EPCs in the blood is low, limiting endogenous repair, and a method to rapidly mobilize EPCs has not been reported. In this study, healthy donors were mobilized sequentially with the CXCR4 antagonist, AMD3100, and G-CSF. The number of EPCs and circulating angiogenic cells (CACs) in the blood and pheresis product was determined and the angiogenic capacity of each cell population assessed. Compared with baseline, treatment with AMD3100 or G-CSF increased the number of blood CACs 10.0-fold +/- 4.4-fold and 8.8-fold +/- 3.7-fold, respectively. The number of EPCs in the blood increased 10.2-fold +/- 3.3-fold and 21.8-fold +/- 5.4-fold, respectively. On a percell basis, CACs harvested from G-CSF-mobilized blood displayed increased in vivo angiogenic potential compared with AMD3100-mobilized CACs. Mobilized EPCs displayed a greater proliferative capacity than EPCs isolated from baseline blood. Both CACs and EPCs were efficiently harvested by leukapheresis. Cryopreserved CACs but not EPCs retained functional activity after thawing. These data show that AMD3100 is a potent and rapid mobilizer of angiogenic cells and demonstrate the feasibility of obtaining and storing large numbers of angiogenic cells by leukapheresis.

Animals↗
PubMed2006

Neurofibromin plays a critical role in modulating osteoblast differentiation of mesenchymal stem/progenitor cells.

Mutations in the NF1 tumor suppressor gene cause neurofibromatosis type 1, a pandemic autosomal dominant genetic disorder with an incidence of 1:3000. Individuals with NF1 have a variety of malignant and non-malignant manifestations, including skeletal manifestations, such as osteoporosis, scoliosis and short statures. However, the mechanism(s) underlying the osseous manifestations in NF1 are poorly understood. In the present study, utilizing Nf1 haploinsufficient (+/-) mice, we demonstrate that Nf1+/- mesenchymal stem/progenitor cells (MSPC) have increased proliferation and colony forming unit-fibroblast (CFU-F) capacity compared with wild-type (WT) MSPC. Nf1+/- MSPC also have fewer senescent cells and have a significantly higher telomerase activity compared with WT MSPC. Nf1+/- MSPC have impaired osteoblast differentiation as determined by alkaline phosphatase staining, and confirmed by single CFU-F replating assays. The impaired osteoblast differentiation in Nf1+/- MSPC is consistent with the reduced expression of osteoblast markers at the mRNA level, including osteocalcin and osteonectin. Importantly, re-expression of the full-length NF1 GTPase activating related domain (NF1 GAP-related domain) is sufficient to restore the impaired osteoblast differentiation in Nf1+/- MSPC. Taken together, our results suggest that neurofibromin plays a crucial role in modulating MSPC differentiation into osteoblasts, and the defect in osteoblast differentiation may contribute at least in part to the osseous abnormalities seen in individuals with NF1.

Animals↗
PubMed2006

Exercise training improves femoral artery blood flow responses to endothelium-dependent dilators in hypercholesterolemic pigs.

We tested two hypotheses: 1) that the effects of hypercholesterolemia on endothelial function in femoral arteries exceed those reported in brachial arteries and 2) that exercise (Ex) training enhances endothelium-dependent dilation and improves femoral artery blood flow (FABF) in hypercholesterolemic pigs. Adult male pigs were fed a normal fat (NF) or high-fat/cholesterol (HF) diet for 20 wk. Four weeks after the diet was initiated, pigs were Ex trained or remained sedentary (Sed) for 16 wk, thus yielding four groups: NF-Sed, NF-Ex, HF-Sed, and HF-Ex. Endothelium-dependent vasodilator responses were assessed in vivo by measuring changes in FABF after intra-arterial injections of ADP and bradykinin (BK). Endothelium-dependent and -independent relaxation was assessed in vitro by measuring relaxation responses to BK and sodium nitroprusside (SNP). FABF increased in response to ADP and BK in all groups. FABF responses to ADP and BK were not impaired by HF but were improved by Ex in HF pigs. BK- and SNP-induced relaxation of femoral artery rings was not altered by HF or Ex. To determine whether the mechanism(s) for vasorelaxation of femoral arteries was altered by HF or Ex, BK-induced relaxation was assessed in vitro in the absence or presence of N(G)-nitro-l-arginine methyl ester [l-NAME; to inhibit nitric oxide synthase (NOS)], indomethacin (Indo; to inhibit cyclooxygenase), or l-NAME + Indo. BK-induced relaxation was inhibited by l-NAME and l-NAME + Indo in all groups of femoral arteries. Ex increased the NOS-dependent component of endothelium-dependent relaxation in NF (not HF) arteries. Indo did not inhibit BK-induced relaxation. Collectively, these results indicate that hypercholesterolemia does not alter endothelial function in femoral arteries and that Ex training improves FABF responses to ADP and BK; however, the improvement cannot be attributed to enhanced endothelial function in HF femoral arteries. These data suggest that Ex-induced improvements in FABF in HF arteries are mediated by vascular adaptations in arteries/arterioles downstream from the femoral artery.

Animals↗
PubMed2006

On global-local artificial neural networks for function approximation.

We present a hybrid radial basis function (RBF) sigmoid neural network with a three-step training algorithm that utilizes both global search and gradient descent training. The algorithm used is intended to identify global features of an input-output relationship before adding local detail to the approximating function. It aims to achieve efficient function approximation through the separate identification of aspects of a relationship that are expressed universally from those that vary only within particular regions of the input space. We test the effectiveness of our method using five regression tasks; four use synthetic datasets while the last problem uses real-world data on the wave overtopping of seawalls. It is shown that the hybrid architecture is often superior to architectures containing neurons of a single type in several ways: lower mean square errors are often achievable using fewer hidden neurons and with less need for regularization. Our global-local artificial neural network (GL-ANN) is also seen to compare favorably with both perceptron radial basis net and regression tree derived RBFs. A number of issues concerning the training of GL-ANNs are discussed: the use of regularization, the inclusion of a gradient descent optimization step, the choice of RBF spreads, model selection, and the development of appropriate stopping criteria.

Algorithms↗
PubMed2005

A linkable identity privacy algorithm for HealthGrid.

The issues of confidentiality and privacy have become increasingly important as Grid technology is being adopted in public sectors such as healthcare. This paper discusses the importance of protecting the confidentiality and privacy of patient health/medical records, and the challenges exhibited in enforcing this protection in a Grid environment. It proposes a novel algorithm to allow traceable/linkable identity privacy in dealing with de-identified medical records. Using the algorithm, de-identified health records associated to the same patient but generated by different healthcare providers are given different pseudonyms. However, these pseudonymised records of the same patient can still be linked by a trusted entity such as the NHS trust or HealthGrid manager. The paper has also recommended a security architecture that integrates the proposed algorithm with other data security measures needed to achieve the desired security and privacy in the HealthGrid context.

Algorithms↗
PubMed2004

Connexin 32 promoter P2 mutations: a mechanism of peripheral nerve dysfunction.

We identified a large Charcot-Marie-Tooth disease family with a novel mutation in the Connexin 32 (Cx32) P2 promoter region at position -526bp. This mutation was in a highly conserved SOX10 binding site. Functional studies were conducted on the Cx32 promoter that showed that this mutation reduced the activity of the Cx32 promoter and the affinity for SOX10 binding. These data suggest that interaction between the Cx32 P2 promoter, SOX10, and EGR2 highlight a mechanism of peripheral nerve dysfunction.

Animals↗
PubMed2004

Digital data collection and analysis: application for clinical practice.

Technology for digital speech recording and speech analysis is now readily available for all clinicians who use a computer. This article discusses some advantages of moving from analog to digital recordings and outlines basic recording procedures. The purpose of this article is to familiarize speech-language pathologists with computerized audio files and the benefits of working with those sound files as opposed to using analog recordings. This article addresses transcription issues and offers practical examples of various functions, such as playback, editing sound files, using waveform displays, and extracting utterances. An appendix is provided that describes step-by-step how digital recording can be done. It also provides some editing examples and a list of useful computer programs for audio editing and speech analyses. In addition, this article includes suggestions for clinical uses in both the assessment and the treatment of various speech and language diorders.

Computers↗
PubMed2003

Genetic evidence for convergence of c-Kit- and alpha4 integrin-mediated signals on class IA PI-3kinase and the Rac pathway in regulating integrin-directed migration in mast cells.

Mast cells play a critical role in host defense against a number of pathogens. Increased mast cell infiltration has been described in allergic asthma, in rheumatoid arthritis, and during helminthes infection. Despite the importance of mast cells in allergic disease and defense against infection, little is known about the mechanisms by which mast cells migrate to various tissues under steady state conditions or during infection or inflammation. Here, we show that activation of c-Kit by its ligand, stem cell factor (SCF), cooperates with alpha4 integrin in inducing directed migration of mast cells on fibronectin. A reduction in migration and activation of a small G protein, Rac, was observed in mast cells derived from class IA phosphoinositide-3 kinase (PI-3kinase)-deficient mice in response to SCF stimulation and in mast cells expressing the dominant-negative Rac (RacN17), as well as in mast cells deficient in the hematopoietic-specific small G protein, Rac2. In addition, a PI-3kinase inhibitor inhibited alpha4- as well as SCF-induced migration in a dose-dependent fashion. In contrast, a mitogen-activated protein kinase (MAPK) inhibitor had little effect. Consistent with the pharmacologic results, abrogating the binding of the p85alpha subunit of class IA PI-3kinase to c-Kit also resulted in inhibition of SCF-induced migration on fibronectin. These genetic and biochemical data demonstrate that both c-Kit and alpha4 integrin signaling are linked to class IA PI-3kinase and Rac pathways and regulate integrin-directed (haptotactic) migration in mast cells.

Animals↗
PubMed2002

The measurement of whole-word productions.

Attempts to measure phonological acquisition have largely focused on segments, with less effort made to examine whole-word productions. This article proposes four measures designed to estimate a child's whole-word abilities: 1. the phonological mean length of utterance, a measure of whole-word complexity for both child and target words, 2. the proportion of whole-word proximity, a measure of the proximity between the child's word and its target form, 3. The Proportion of whole-word correctness, a measure of the number of words produced correctly relative to the sample size, and 4. the proportion of whole-word variability, a measure of how often a child produces words in distinct phonological shapes. The central measure is the Phonological Mean Length of Utterance, which can be used to identify a child's stage of acquisition, to assess proximity to target words, and to evaluate the complexity of words. The value of the new measures will be demonstrated through preliminary applications to a range of contexts; i.e. monolingual children acquiring English (five children, 0;11 to 1;5), Cantonese (one child, 1;7), and Spanish (5 children, 2;2 to 2;11), bilingual children acquiring Hungarian-English (one child, 2;0) and Spanish-English (3 children, 2;4 to 2;11), children with phonological impairment (eighteen children, 2;11 to 5;3), and children with cochlear implants (six children, 4;5 to 7;11).

Articulation Disorders↗
PubMed2002

Morehead & Ingram (1973) revisited.

The finding in Morehead and Ingram (1973) that children with a language impairment do better in the use of inflectional morphology than MLU-matched typically developing children has been in marked contrast to several subsequent studies that have found the opposite relationship (cf. review in Leonard, 1998). This research note presents a reanalysis of a subset of the original Morehead and Ingram data in an attempt to reconcile these contradictory findings. The reanalysis revealed that the advantage on inflectional morphology for children with language impairment was only on the progressive suffix, not on plural and possessive or on the verbal morphemes third-person present tense and past tense. The results of the reanalysis are in line with more recent research (e.g., Rice, Wexler, & Cleave, 1995). The resolution of these discrepant results highlights the critical roles that methodological issues play--specifically, how subjects are matched on MLU, how inflectional morphology is measured, and the selection of subjects with regard to age.

Child↗
PubMed2002

Serum levels of micronutrients, antioxidants and total antioxidant status predict risk of breast cancer in a case control study.

We performed a case control study to assess the association between serum micronutrient and antioxidant levels and the risk of breast cancer. Newly diagnosed breast cancer cases were recruited before any treatment and matched with controls randomly selected from the electoral roll. Blood samples were collected from 153 breast cancer cases and 151 controls. Serum samples were analyzed for retinol, alpha-tocopherol, lycopene, alpha- and beta-carotene by HPLC, and total antioxidant status by the Trolox-equivalent antioxidant assay. Serum albumin, bilirubin and uric acid levels were also determined. After adjustment for age at menarche, parity, dietary fat and alcohol intake, we observed the following reductions in odds ratios for breast cancer risk comparing the highest with the lowest quartiles: 0.47 [95% confidence interval (CI) 0.24, 0.91] for beta-carotene; 0.53 (CI 0.28, 1.01) for retinol; 0.50 (CI 0.26, 0.97) for bilirubin and 0.47 (CI 0.24, 0.94) for total antioxidant status. We conclude that increased serum levels of beta-carotene, retinol, bilirubin and total antioxidant status are associated with reductions in breast cancer risk.

Antioxidants↗
PubMedDate not supplied

Bridging the digital divide: aspects of computerized data collection and analysis for language professionals.

Recent technological developments have made inexpensive digital speech recording and analysis available to any researcher interested in using them. This paper explores the benefits of working with digital sound files, it provides the reader with system recommendations, explains how to digitize audio recordings, and includes suggestions for selected uses.

Biophysical Phenomena↗
PubMedDate not supplied

Exercise training produces nonuniform increases in arteriolar density of rat soleus and gastrocnemius muscle.

OBJECTIVE: Exercise training has been shown to increase regional blood flow capacity to muscle tissue containing fibers that experience increased activity during exercise. The purpose of this study was to test the hypothesis that the increased blood flow capacity is partially the result of increases in arteriolar density (number of arterioles/mm2 of tissue), specifically in skeletal muscle tissue, with the largest relative increase in muscle fiber activity during training bouts. METHODS: This hypothesis was tested by comparing and contrasting the effects of endurance exercise training (ET) and interval sprint training (IST) on arteriolar density in soleus muscle (S) red (Gr) and white (Gw) portions of gastrocnemius muscle of male Sprague Dawley rats. ET rats completed 10 weeks of treadmill training 30 m/min, 15% grade, 60 min/day, 5 days/week, while IST rats completed 10 weeks of IST consisting of six 2.5-min exercise bouts, with 4.5-min rest between bouts (60 m/min, 15% incline), 5 days/week. The hypothesis would be supported if ET increased arteriolar density in S and Gr and if IST increased arteriolar density in Gw. RESULTS: ET increased arteriolar density above values of sedentary rats (SED) in both the Gw (ET = 0.93 +/- 0.19 arterioles/microm2; SED = 0.44 +/- 0.09 arterioles/microm2) and Gr (ET = 0.97 +/- 0.1 arterioles/microm2; SED = 0.51 +/- 0.06 arterioles/microm2) muscles, but not in S (ET = 1.69 +/- 0.45 arterioles/microm2; SED = 1.51 +/- 0.34 arterioles/microm2) muscle. In contrast, IST did not alter arteriolar density in Gw or Gr muscle tissue. Although arterial wall thickness was greater in S (3.95 +/- 0.40 microm) and Gr (6.24 +/- 0.59 microm) than Gw (2.76 +/- 0.18 microm), neither ET or IST altered mean wall thickness in either muscle. CONCLUSION: Increases in blood flow capacity produced in Gr and Gw by ET appear to be due in part to increased arteriolar density. In contrast, increased arteriolar density does not contribute to increased blood flow capacity of Gw in IST rats.

Adaptation, Physiological↗