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Biomedical subjects

N A Jones

Publications and source records attributed to N A Jones.

At least 19 recordsLinked to original sources
PubMed2001

Identification and quantification of phosphodiesterase 4 subtypes in CD4 and CD8 lymphocytes from healthy and asthmatic subjects.

In the present study, for the first time, PDE4 subtypes were identified and semi-quantified in both CD4 and CD8 lymphocytes from healthy and asthmatic individuals. CD4 and CD8 lymphocytes from healthy and mild asymptomatic asthmatic subjects (receiving beta-agonist therapy only) were isolated from peripheral venous blood using appropriate antibody coated paramagnetic beads. PDE4 subtypes and beta-actin were identified by digoxigenin (DIG)-labelling reverse transcriptase-polymerase chain reaction and semi-quantified by DIG-detection enzyme-linked immunosorbance assay. In CD4 and CD8 lymphocytes PDE4A, PDE4B and PDE4D were detected, with no significant differences observed between healthy and asthmatic groups. In CD8 lymphocytes, enzyme subtype expression was lower and showed more intersubject variability. In functional studies investigating the effects of various PDE inhibitors on PHA-induced proliferation of mononuclear cells from healthy and asthmatic subjects, CDP840 (0.03 - 10 microM), rolipram (0.1 - 10 microM) and theophylline (10 microM - 1 mM) inhibited PHA-induced proliferation of mononuclear cells from healthy and asthmatic subjects in a concentration-dependent manner, although no significant difference was observed between the groups investigated. In additional studies, total monocyte cyclic AMP PDE activity was investigated in cells isolated from asthmatic subjects both prior to and 24 h after allergen challenge. Total monocyte cyclic AMP PDE activity remained unaffected following challenge of asthmatic subjects with either house dust mite or cat dander and was inhibited in a concentration-dependent manner by rolipram (0.01 - 100 microM) both before and after allergen challenge.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2000

Polymer chemical structure is a key determinant of physicochemical and colloidal properties of polymer-DNA complexes for gene delivery.

Polyplexes are now emerging as potentially useful vectors for gene therapy. To improve our understanding of how the chemical structure of the polymer affects the properties of these systems, a series of structurally related polymers, the linear poly(amidoamine)s (PAAs), have been examined for their abilities to form complexes with DNA. Structure-dependent differences in DNA binding are shown by gel electrophoretic retardation of DNA and thermal transition analyses. Two PAAs, NG28 and NG30, stand out as having high affinity DNA binding characteristics, similar to the model homopolypeptide, poly-L-lysine. In addition, differences in complex formation, particle size and surface charge are displayed for the different polymer-DNA systems. Electron microscopy studies showed that the polymers condensed DNA into similar unit structures but only complexes with NG30 did not undergo agglomeration. This was attributed to an excess of complexed polymer forming a shell of uncomplexed polymer chain segments around a condensed DNA-polymer core. The transfection activities of these polymer complexes differ greatly, and some of these differences can be explained in a multifactorial way by the physicochemical and colloidal properties. It is concluded that polymer chemical structure dictates the apparent affinity of DNA binding, and also several of the important colloidal characteristics of the resulting complexes.

Chloroquine↗
PubMed2000

The regulation of AMP-activated protein kinase by phosphorylation.

The AMP-activated protein kinase (AMPK) cascade is activated by an increase in the AMP/ATP ratio within the cell. AMPK is regulated allosterically by AMP and by reversible phosphorylation. Threonine-172 within the catalytic subunit (alpha) of AMPK (Thr(172)) was identified as the major site phosphorylated by the AMP-activated protein kinase kinase (AMPKK) in vitro. We have used site-directed mutagenesis to study the role of phosphorylation of Thr(172) on AMPK activity. Mutation of Thr(172) to an aspartic acid residue (T172D) in either alpha1 or alpha2 resulted in a kinase complex with approx. 50% the activity of the corresponding wild-type complex. The activity of wild-type AMPK decreased by greater than 90% following treatment with protein phosphatases, whereas the activity of the T172D mutant complex fell by only 10-15%. Mutation of Thr(172) to an alanine residue (T172A) almost completely abolished kinase activity. These results indicate that phosphorylation of Thr(172) accounts for most of the activation by AMPKK, but that other sites are involved. In support of this we have shown that AMPKK phosphorylates at least two other sites on the alpha subunit and one site on the beta subunit. Furthermore, we provide evidence that phosphorylation of Thr(172) may be involved in the sensitivity of the AMPK complex to AMP.

AMP-Activated Protein Kinase Kinases↗
PubMed2000

Right frontal EEG asymmetry and lack of empathy in preschool children of depressed mothers.

EEG activity, empathic reactions to emotion-inducing stimuli, and the ability to complete a teaching task were examined in preschool children of depressed and non-depressed mothers. EEG activity from frontal and parietal regions was recorded. Repeated measures MANOVAs indicated that the children of depressed mothers had greater relative right frontal EEG asymmetry, a pattern that typically accompanies greater negative affect and showed less empathic responses to a crying infant as well as to their own mothers' simulated distress. Children of depressed mothers were slower in completing the teaching task (involving mutual cooperation with their mother) and they spent more time asking for help than children of non-depressed mothers. Further, the depressed mothers stated their approval less often and spent less time helping their child complete the task.

Analysis of Variance↗
PubMed1999

Cell damage-induced conformational changes of the pro-apoptotic protein Bak in vivo precede the onset of apoptosis.

Investigation of events committing cells to death revealed that a concealed NH2-terminal epitope of the pro-apoptotic protein Bak became exposed in vivo before apoptosis. This occurred after treatment of human Jurkat or CEM-C7A T-lymphoma cells with the mechanistically disparate agents staurosporine, etoposide or dexamethasone. The rapid, up to 10-fold increase in Bak-associated immunofluorescence was measured with epitope-specific monoclonal antibodies using flow cytometry and microscopy. In contrast, using a polyclonal antibody to Bak, immunofluorescence was detected both before and after treatment. There were no differences in Bak protein content nor in subcellular location before or after treatment. Immunofluorescence showed Bcl-xL and Bak were largely associated with mitochondria and in untreated cells they coimmunoprecipitated in the presence of nonioinic detergent. This association was significantly decreased after cell perturbation suggesting that Bcl-xL dissociation from Bak occurred on exposure of Bak's NH2 terminus. Multiple forms of Bak protein were observed by two dimensional electrophoresis but these were unchanged by inducers of apoptosis. This indicated that integration of cellular damage signals did not take place directly on the Bak protein. Release of proteins, including Bcl-xL, from Bak is suggested to be an important event in commitment to death.

Apoptosis↗
PubMed1999

One-year-old infants of intrusive and withdrawn depressed mothers.

This study examined behaviors of intrusive/depressed versus withdrawn/depressed mothers and their one-year-old infants during a structured teaching interaction. Group comparisons revealed that intrusive/depressed mothers showed more positive responses, more demonstrating toys, and more physical guidance, and their infants demonstrated less toy manipulation. Withdrawn/depressed mothers maintained infant play more frequently and showed more restricted affect, and their infants demonstrated less affective behavior, both positive and negative. These findings suggested that exposure to depressed mothers' nonoptimal interaction styles represents different types of risk to infants' cognitive and affective development.

Adolescent↗
PubMed1999

Massage and music therapies attenuate frontal EEG asymmetry in depressed adolescents.

EEG asymmetry, specifically greater relative right frontal activation, is associated with negative affect. Depressed adults show stable patterns of this asymmetry. The present study assessed the effects of massage therapy and music therapy on frontal EEG asymmetry in depressed adolescents. Thirty adolescents with greater relative right frontal EEG activation and symptoms of depression were given either massage therapy (n = 14) or music therapy (n = 16). EEG was recorded for three-minute periods before, during, and after therapy. Frontal EEG asymmetry was significantly attenuated during and after the massage and music sessions.

Adolescent↗
PubMed1998

The Drosophila Pax gene eye gone is required for embryonic salivary duct development.

What are the developmental mechanisms required for conversion of an undifferentiated, two-dimensional field of cells into a patterned, tubular organ? In this report, we describe the contribution of the Drosophila Pax gene eye gone to the development of the embryonic salivary glands and ducts. eye gone expression in salivary tissues is controlled by several known regulators of salivary fate. After the initial establishment of the salivary primordium by Sex combs reduced, fork head excludes eye gone expression from the pregland cells so that its salivary expression is restricted to the posterior preduct cells. trachealess, in contrast, activates eye gone expression in the posterior preduct cells. We have previously described the process by which fork head and the EGF receptor pathway define the border between the gland and duct primordia. Here we show that eye gone is required for the subdivision of the duct primordium itself into the posterior individual duct and the anterior common duct domains. In the absence of eye gone, individual ducts as well as the precursor of the adult salivary glands, the imaginal ring, are absent. We took advantage of this ductless phenotype to show that Drosophila larvae do not have an obligate requirement for salivary glands and ducts. In addition to its role in the salivary duct, eye gone is required in the embryo for the development of the eye-antennal imaginal disc and the chemosensory antennal organ.

Animals↗
PubMed1998

Aromatherapy positively affects mood, EEG patterns of alertness and math computations.

EEG activity, alertness, and mood were assessed in 40 adults given 3 minutes of aromatherapy using two aromas, lavender (considered a relaxing odor) or rosemary (considered a stimulating odor). Participants were also given simple math computations before and after the therapy. The lavender group showed increased beta power, suggesting increased drowsiness, they had less depressed mood (POMS) and reported feeling more relaxed and performed the math computations faster and more accurately following aromatherapy. The rosemary group, on the other hand, showed decreased frontal alpha and beta power, suggesting increased alertness. They also had lower state anxiety scores, reported feeling more relaxed and alert and they were only faster, not more accurate, at completing the math computations after the aromatherapy session.

Adult↗
PubMed1998

A randomized controlled trial of double-versus single-gloving in vascular surgery.

With the increasing incidence of hepatitis B and HIV, and the increasing awareness of the risk and prevalence of hepatitis C, it is becoming even more necessary to adopt stricter policies to safeguard personnel and to reduce the risk of transmission. Previous studies have shown a need for eye protection, protective clothing and the use of double-gloving during operative or interventional procedures. The risk of infection is much less with unbroken skin and conversely more likely when hollow needles are used. Arguments against the routine use of double-gloving include the loss of dexterity and the discomfort incurred, and the potential loss of dexterity that might theoretically result in more rather than fewer needle-stick injuries.

Gloves, Surgical↗
PubMed1998

Cisplatin- and paclitaxel-induced apoptosis of ovarian carcinoma cells and the relationship between bax and bak up-regulation and the functional status of p53.

We investigated the roles of p53 and Bcl-2 homologues in the induction of apoptosis by cisplatin and paclitaxel in wild-type p53-expressing human ovarian carcinoma cells and cisplatin-resistant derivatives that have lost p53 function. Cisplatin induced apoptosis in parental A2780 but not in cisplatin-resistant A2780/cp70 cells, whereas paclitaxel induced apoptosis in both cell lines. Immunoprecipitation of p53 using antibodies specific for p53 conformation (pAb 1620 and pAb 240) showed that there were no relative changes in p53 conformation before and after cisplatin treatment in either cell line. A2780/cp70 cells have lost p53 function, yet they have wild-type p53 gene sequence. However, A2780/cp70 cells constitutively express more p53 in a form detected by pAb 240, an antibody that also detects mutant conformations of p53 that are transcriptionally inactive. There were no changes in levels of Bcl-2, Bcl-XL, or 24-kDa Bax over 72 hr after exposure to cisplatin or paclitaxel, but each agent led to up-regulation of Bak and 21-kDa Bax in A2780 cells. Paclitaxel, but not cisplatin, increased Bak and 21-kDa Bax levels in A2780/cp70 cells. These data suggest that apoptosis in A2780 and A2780/cp70 is associated with an increased level of Bak and 21 kDa Bax after drug-induced damage and that functional p53 may be required for this effect after cisplatin but not after paclitaxel.

Antineoplastic Agents↗
PubMed1997

EEG activation in 1-month-old infants of depressed mothers.

Previous research has documented differences in the pattern of EEG activation between 3-month-old infants of depressed mothers and infants of nondepressed mothers. In the present study, EEG was recorded in even younger 1-month-old infants of depressed and nondepressed mothers. The infants of depressed mothers exhibited greater relative right frontal EEG asymmetry (due to reduced left frontal activation), and this pattern at 1 month was significantly related to 3-month EEG asymmetry. Right frontal EEG asymmetry was also related to more frequent negative facial expressions (sad and pre-cry faces) during the Brazelton exam. Finally, the infants of depressed mothers showed more indeterminate sleep, were less active, and cried less than infants of nondepressed mothers.

Adolescent↗
PubMed1997

EEG stability in infants/children of depressed mothers.

The stability of EEG was examined in infants of depressed (BDI > 16) and non-depressed mothers (BDI < 9) from 3 months to 3 years. Of the 32 infants seen at 3 months, 15 were seen again at 3 years of age. Seven of the eight children who had exhibited right frontal EEG asymmetry as infants still showed that EEG asymmetry pattern at the 3 year visit. Children with right frontal EEG asymmetry at 3 years were observed to be more inhibited during an exploratory play task, and children of depressed versus non-depressed mothers were less empathetic during simulated maternal distress.

Brain↗
PubMed1996

Comparison of lower limb arterial assessments using color-duplex ultrasound and ankle/brachial pressure index measurements.

The strength of agreement between two noninvasive methods of assessing lower limb arterial disease and their relationship to patient symptoms following exercise have been investigated. Color-duplex ultrasound (CDU) and ankle/brachial pressure index (ABPI) (before and afer exercise) measurements were obtained from 200 consecutive patients referred to a vascular investigations laboratory. From these patients, 290 limbs were available for study, comprising limbs without previous vascular surgery, from patients without diabetes and who could attempt a walking exercise test. The overall level of agreement between CDU and resting ABPI measurements was 83% (Kappa 0.66). The ABPI technique identified the more serious disease; a resting ABPI of less than 0.6 gave 100% agreement with CDU. With higher resting ABPIs the level of agreement became poorer: 83% (0.6 < or = ABPI <0.9) and 76% (normal ABPI > or = 0.9). The addition of postexercise ABPI measurements in determining significant arterial disease increased the strength of relationship between the two techniques by only 2% (85%, Kappa 0.69). The exercise test was generally limited by the most symptomatic limb in each patient, and the agreement between CDU and postexercise ABPI measurements in these limbs was higher at 93% (Kappa 0.81). In comparison, agreement for the least symptomatic group of limbs was found to be poor (69%, Kappa 0.37). Compared with symptoms after exercise, overall agreements with CDU and ABPI were both 67% (Kappa 0.27). The agreement was better (91%) when the resting ABPI was less than 0.6. The ABPI is biased toward the detection of more severe disease and is more consistent with CDU when the most symptomatic limbs are compared. The relationship between either test and symptoms after exercise is strong only for limbs with major disease.

Adult↗
PubMed1996

DNA-damaging agents induce both p53-dependent and p53-independent apoptosis in immature thymocytes.

Apoptosis in the immature thymus can be induced by both p53-dependent and -independent pathways, the former being activated by exposure to DNA-damaging agents and the latter being induced by glucocorticoids [Nature (Lond.) 362:847-849; Nature (Lond.) 362:849-852 (1993)]. We report that the DNA-damaging agents etoposide and gamma-radiation induced similar levels of apoptosis in both proliferatively enriched and quiescent immature rat thymocytes, as assessed by flow cytometry and the formation of both kilobase-pair and 180-bp integer fragments of DNA. However, a marked stabilization of p53 occurred exclusively in the proliferatively enriched population, which was also enriched for immature CD4- CD8- and mature CD4+ CD8-/CD4- CD8+ cells. In contrast, DNA damage-induced apoptosis in quiescent mature peripheral T cells was associated with an accumulation of p53. Our studies suggest that stabilization of p53 in thymocytes in response to DNA damage may be developmentally regulated. In immature thymocytes obtained from p53-null mice, DNA-damaging agents induced apoptosis at significantly lower levels and at later times than that seen in cells from p53 wild-type animals. These data support the hypothesis that DNA-damaging agents induce apoptosis primarily via a p53-dependent pathway in immature thymocytes as previously reported. We report here that DNA damage can also induce apoptosis by a p53-independent pathway in a particular subpopulation of immature thymocytes.

Amino Acid Sequence↗