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Biomedical subjects

Jennifer Taylor

Publications and source records attributed to Jennifer Taylor.

35 records · Page 2Linked to original sources
PubMed2006

Schwannoma of the true vocal fold: a rare diagnosis.

Schwannomas of the larynx are rare, benign, slowly growing tumors. When they do occur, they are most often isolated in the aryepiglottic folds or false vocal folds. When a tumor originates in the larynx, it typically causes hoarseness and a globus sensation. As the tumor expands, it may cause dyspnea, stridor, and possibly asphyxiation as a result of the mass effect. In this article, we report an unusual case of a schwannoma of the true vocal fold in a young woman.

Adult↗
PubMed2005

Prehabilitation and rehabilitation for attenuating hindlimb unweighting effects on skeletal muscle and gait in adult and old rats.

OBJECTIVE: To compare the effectiveness of no exercise with prehabilitation (exercise before hindlimb unweighting [HLU]) versus rehabilitation (exercise given after HLU) on gait function and skeletal muscle mass and force. DESIGN: Randomized controlled trial. SETTING: Animal laboratory. ANIMALS: Male-specific, pathogen-free Fisher344/Brown Norway rats (N=149). Groups consisted of adult and old controls, HLU, prehabilitation, rehabilitation, natural cage recovery (reloading), and exercise without HLU. INTERVENTIONS: Ten days of general conditioning exercise were given to 6-month-old adult and 30-month-old old rats before or after a week of HLU. MAIN OUTCOME MEASURES: Gait stride length and width; soleus, plantaris, extensor digitorum longus, and peroneus longus mass and peak contractile force; whole gastrocnemius mass; and total protein concentration for the soleus and gastrocnemius. RESULTS: Muscle mass (approximately 30%) and force (24%-36%) declined with age in all muscles studied. In adult rats declines in muscle mass occurred with HLU in the soleus, plantaris, and gastrocnemius. Prehabilitation did not prevent the loss of muscle mass in adult rats. Rehabilitation and natural recovery effectively restored soleus and gastrocnemius muscle mass in adult rats but not soleus peak force. Old rats had a significant 23% HLU effect only on gastrocnemius mass (control, 1670+/-129 mg; HLU, 1274+/-184 mg). Prehabilitation did not prevent the decline in gastrocnemius mass. Rehabilitation in old rats restored gastrocnemius mass to within 13% of control levels. Prehabilitation was effective for preventing and rehabilitation was effective for restoring soleus contractile force in old rats (control, 114+/-9 mg; HLU, 67+/-22 mg; prehabilitation, 106+/-31 mg; rehabilitation, 120+/-26 mg) compared with recovery without exercise (86+/-29 g). A significant reduction in stride length was observed with aging (136+/-18 mm vs 98+/-10 mm), which decreased further with HLU (78+/-14 mm). Prehabilitation attenuated HLU-related reductions in stride length, and rehabilitation was effective for stride length restoration in old rats. CONCLUSIONS: Exercise, particularly rehabilitation, was more effective for old than young rats. Prehabilitation and rehabilitation diminished some of the detrimental effects of HLU on skeletal muscle mass and force and gait function in old rats.

Age Factors↗
PubMed2004

Microarray expression profiling in melanoma reveals a BRAF mutation signature.

We have used microarray gene expression profiling and machine learning to predict the presence of BRAF mutations in a panel of 61 melanoma cell lines. The BRAF gene was found to be mutated in 42 samples (69%) and intragenic mutations of the NRAS gene were detected in seven samples (11%). No cell line carried mutations of both genes. Using support vector machines, we have built a classifier that differentiates between melanoma cell lines based on BRAF mutation status. As few as 83 genes are able to discriminate between BRAF mutant and BRAF wild-type samples with clear separation observed using hierarchical clustering. Multidimensional scaling was used to visualize the relationship between a BRAF mutation signature and that of a generalized mitogen-activated protein kinase (MAPK) activation (either BRAF or NRAS mutation) in the context of the discriminating gene list. We observed that samples carrying NRAS mutations lie somewhere between those with or without BRAF mutations. These observations suggest that there are gene-specific mutation signals in addition to a common MAPK activation that result from the pleiotropic effects of either BRAF or NRAS on other signaling pathways, leading to measurably different transcriptional changes.

Amino Acid Substitution↗
PubMed2004

Clinical features of children with screening-identified evidence of celiac disease.

OBJECTIVE: At-risk groups commonly undergo screening for autoantibodies associated with celiac disease (CD). However, the clinical significance of a positive test remains uncertain. The objective of this study was to evaluate growth and clinical features of children who test positive for an autoantibody associated with CD. METHODS: A case-control study of Denver area healthy infants and young children with and without CD autoantibodies was conducted. A cohort of HLA-characterized children were followed prospectively since birth for the development of immunoglobulin A antitissue transglutaminase autoantibodies (TG). Clinical evaluation, questionnaire, blood draw, and small bowel biopsy were performed. Growth and nutrition and frequency of positive responses were measured. RESULTS: Compared with 100 age- and gender-matched TG-negative controls, 18 TG-positive children, 5.5 +/- 0.5 years of age, had a greater number of symptoms and lower z scores for weight-for-height and for body mass index. Responses that were independently associated with TG-positive status were irritability/lethargy, abdominal distention/gas, and difficulty with weight gain. CONCLUSIONS: Screening-identified TG-positive children demonstrate mild alterations in growth and nutrition and report more symptoms than control subjects. Additional study is needed on the benefit and risk of identifying CD in at-risk groups.

Autoantibodies↗
PubMed2003

Akt2 negatively regulates assembly of the POSH-MLK-JNK signaling complex.

We demonstrate that POSH, a scaffold for the JNK signaling pathway, binds to Akt2. A POSH mutant that is unable to bind Akt2 (POSH W489A) exhibits enhanced-binding to MLK3, and this increase in binding is accompanied by increased activation of the JNK signaling pathway. In addition, we show that the association of MLK3 with POSH is increased upon inhibition of the endogenous phosphatidylinositol 3-kinase/Akt signaling pathway. Thus, the assembly of an active JNK signaling complex by POSH is negatively regulated by Akt2. Further, the level of Akt-phosphorylated MLK3 is reduced in cells expressing the Akt2 binding domain of POSH, which acts as a dominant interfering protein. Taken together, our results support a model in which Akt2 binds to a POSH-MLK-MKK-JNK complex and phosphorylates MLK3; phosphorylation of MLK3 by Akt2 results in the disassembly of the JNK complex bound to POSH and down-regulation of the JNK signaling pathway.

Adaptor Proteins, Signal Transducing↗
PubMed2003

Antisense oligonucleotide inhibition of Bcl-xL and Bid expression in liver regulates responses in a mouse model of Fas-induced fulminant hepatitis.

Activation of the cell-surface receptor Fas can lead to apoptosis in parenchymal cells in the liver, and if severe enough, result in fulminant hepatic failure and animal death. In the present study, we have examined the roles played by the Bcl-2 family members Bcl-xL and Bid in regulating this response. To do this, we have developed chemically modified 2'-O-(2-methoxy) ethyl antisense inhibitors of both Bid and Bcl-xL expression. In Balb/c mice, dosing with these antisense oligonucleotides reduced expression of the targeted mRNA by greater than 80% in the liver. This reduction was highly dependent upon oligonucleotide sequence and oligonucleotide dose. Reduction of Bcl-xL expression resulted in a potentiation of Fas-mediated apoptosis in liver and significant increase of the lethality of Fas-mediated fulminant hepatitis (p < 0.0001). In contrast, reduction of Bid expression protected the animals against Fas-mediated fulminant hepatitis and death (p < 0.0001). Simultaneous dosing of mice with Bcl-xL and Bid-targeting antisense oligonucleotides resulted in an inhibition of expression of both targeted proteins and protection of the animals from Fas-mediated apoptosis. These results demonstrate, for the first time, the role of Bcl-xL in regulating responses to proapoptotic Fas signaling in mouse liver. In addition, this is the first reported example demonstrating the ability of antisense inhibitors to reduce expression of multiple proteins in animals by simultaneous dosing.

Animals↗
PubMed2003

Simultaneous inhibition of GSK3alpha and GSK3beta using hairpin siRNA expression vectors.

Short interfering RNAs (siRNAs) can mediate sequence-specific inhibition of gene expression in mammalian cells. We and others have recently developed expression vector-based systems for synthesizing siRNAs or hairpin siRNAs in mammalian cells. Expression vector-based RNA interference (RNAi) effectively suppresses expression of target genes and is likely to be a powerful tool for analysis of gene function. Here we compare inhibition by vectors expressing hairpin siRNA designs either with different loop sequences connecting the two siRNA strands, or with duplex regions of different lengths. Our results suggest that lengthening the 19-nucleotide duplex region of a relatively ineffective hairpin siRNA can increase inhibition, but increasing the length of an effective 19-nt hairpin siRNA does not increase inhibition. We also demonstrate that hairpin siRNA vectors can be used to inhibit two target genes simultaneously. We have targeted glycogen synthase kinase-3alpha (GSK-3alpha) and GSK-3beta, two related kinases involved in the regulation of a variety of cellular processes and also implicated in the pathogenesis of several human diseases. Inhibition of either GSK-3alpha or GSK-3beta by transfection of hairpin siRNA vectors leads to elevated expression of the GSK-3 target beta-catenin, whereas inhibition of both kinases further increases beta-catenin expression. Our results suggest that vector-based siRNA inhibition may be useful for dissecting the functional roles of GSK-3alpha and GSK-3beta in somatic cells. The ability to inhibit two or more genes simultaneously with hairpin siRNA expression vectors should facilitate studies of gene function in mammalian cells.

Animals↗
PubMed2003

Differential effectiveness of low-intensity exercise in young and old rats.

Low-intensity exercise increases strength and function in old adults, but it is unclear if change occurs secondary to "neural adaptation" or to intrinsic muscle adaptation. Whether function and strength change concomitantly is also unclear. We examined effects of a modest intensity, 10-session exercise program on muscle mass, contractile force, and function (gait) in 6-month-old and 30-month-old rats. Animals underwent 45 minutes of activity (e.g., ramp walking, balancing) 5 days/week. In old animals, a significant increase in muscle mass and peak contractile force occurred with exercise in soleus, plantaris, extensor digitorum longus, and peroneus longus compared with controls, but did not restore values to those for young controls. The increase in muscle force in old rats was accompanied by a significant lengthening of stride (90 +/- 9 to 103 +/- 15 mm), which was still 23% less than stride values for young rats. Changes in muscle function and gait with exercise were not apparent in young rats. Results suggest that (a). rapid and significant changes in muscle mass and strength in an aged organism can occur with a modest activity program, (b). the threshold for muscle adaptation may differ in young versus old rats, and (c). changes in strength and function in old rats may occur concomitantly.

Aging↗
PubMed2003

Akt regulates basic helix-loop-helix transcription factor-coactivator complex formation and activity during neuronal differentiation.

Neural basic helix-loop-helix (bHLH) transcription factors regulate neurogenesis in vertebrates. Signaling by peptide growth factors also plays critical roles in regulating neuronal differentiation and survival. Many peptide growth factors activate phosphatidylinositol 3-kinase (PI3K) and subsequently the Akt kinases, raising the possibility that Akt may impact bHLH protein function during neurogenesis. Here we demonstrate that reducing expression of endogenous Akt1 and Akt2 by RNA interference (RNAi) reduces neuron generation in P19 cells transfected with a neural bHLH expression vector. The reduction in neuron generation from decreased Akt expression is not solely due to decreased cell survival, since addition of the caspase inhibitor z-VAD-FMK rescues cell death associated with loss of Akt function but does not restore neuron formation. This result indicates that Akt1 and Akt2 have additional functions during neuronal differentiation that are separable from neuronal survival. We show that activated Akt1 enhances complex formation between bHLH proteins and the transcriptional coactivator p300. Activated Akt1 also significantly augments the transcriptional activity of the bHLH protein neurogenin 3 in complex with the coactivators p300 or CBP. In addition, inhibition of endogenous Akt activity by the PI3K/Akt inhibitor LY294002 abolishes transcriptional cooperativity between the bHLH proteins and p300. We propose that Akt regulates the assembly and activity of bHLH-coactivator complexes to promote neuronal differentiation.

Amino Acid Chloromethyl Ketones↗
PubMedDate not supplied

High flyers.

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Air Ambulances↗
PubMedDate not supplied

Shifting priorities.

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Adaptation, Psychological↗
PubMedDate not supplied

Question time.

Choosing to train as a nurse is a major decision, rife with different emotions and considerations. Regardless of what point you have reached in your studies, whether you are studying towards a degree or diploma, whatever your age and whether you are from the UK or overseas, you face common challenges. These include surviving financially, juggling study and clinical placements, learning new information and addressing patients' needs. While the profession certainly offers exciting opportunities, nursing students in 2006 face a range of uncertainties. There have been cuts and freezes to existing and vacant posts across NHS trusts, while students from overseas face the additional problem that band 5 and 6 nursing posts have been removed from the Home Office's shortage occupation list. Will there be enough mentors to teach students? Will there be jobs when they qualify? How can students survive financially? Will overseas students be able to stay once qualified? NT put students' key questions to a panel of experts and influential figures.

Attitude of Health Personnel↗
PubMedDate not supplied

Transforming lives.

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Fecal Incontinence↗