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Biomedical subjects

N A Jones

Publications and source records attributed to N A Jones.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

Cisplatin, camptothecin, and taxol sensitivities of cells with p53-associated multidrug resistance.

With the use of clonogenic survival assays, we show that wild-type p53-expressing A2780 human ovarian cell lines transfected with a dominant negative mutant p53 gene (codon 143, valine to alanine) acquired cross-resistance to ionizing radiation, cisplatin, doxorubicin, and 1-beta-D-arabinofuranosylcytosine. However, these mutant p53-transfected cell lines retained sensitivity to taxol and camptothecin. We also show that immature thymocytes from mice with the p53 gene genetically inactivated showed reduced ability to undergo apoptosis after treatment with ionizing radiation and cisplatin compared with wild-type mice. However, taxol-induced apoptosis in thymocytes does not seem to be dependent on p53 status. Camptothecin also induced apoptosis in a p53-independent manner in thymocytes at low doses but in a p53-dependent manner at high doses. These data suggest that taxoids and camptothecin analogs could have activity in tumors that have aberrant p53 function and provide a rationale for the clinical observations of responsiveness of refractory ovarian cancer to these drugs.

Animals↗

Down-regulation but not phosphorylation of stathmin is associated with induction of HL60 cell growth arrest and differentiation by physiological agents.

Stathmin is a cytosolic phosphoprotein that has an important but, as yet, undefined role in cell proliferation and differentiation. Induction of growth arrest and differentiation of HL60 cells to monocytes by phorbol 12-myristate 13-acetate is associated with rapid phosphorylation of the protein. Stathmin phosphorylation was not seen when HL60 cells were induced to differentiate to monocytes, by 1 alpha, 25-dihydroxyvitamin D3, and to neutrophils, by all-trans retinoic acid and granulocyte colony stimulating factor. In all the above instances, stathmin expression was down-regulated. Thus, increased stathmin phosphorylation is not required for cell growth arrest or differentiation or down-regulation of stathmin expression.

Blotting, Western↗

Stathmin is expressed by the proliferating hepatocytes during liver regeneration.

Aim-To determine the liver cell populations that express the phylogenetically conserved cytosolic protein stathmin during liver regeneration.Methods-Double immunostaining for stathmin and the Ki67 antigen was performed on sections of formaldehyde fixed, paraffin wax embedded tissues from 31 liver specimens. These included a variety of disease conditions characterised by some degree of hepatocyte regeneration. Quantitative western blot analysis was performed on 22 of these specimens.Results-Variable amounts of stathmin protein were detected by western blotting in all of the specimens examined. Stathmin was not detected in three cases of histologically normal liver. On immunostaining, stathmin was demonstrated in a proportion of hepatocytes as well as lymphoid inflammatory cells and other tissue elements. In all cases most of these stathmin positive cells showed nuclear positivity for the Ki67 antigen.Conclusions-Stathmin is expressed by proliferating hepatocytes but not by resting hepatocytes. Thus, it is likely that the protein has a function important to cell proliferation as opposed to cell differentiation.

Journal Article↗

Stathmin expression is a feature of proliferating cells of most, if not all, cell lineages.

BACKGROUND: Stathmin is a phylogenetically conserved protein which was identified initially as a prominent cytosolic protein in hemopoietic cells, endocrine cells, brain, and testis. In these tissues, it has been suggested that the level of stathmin expression is important in development and cell proliferation. Furthermore, stathmin phosphorylation appears to be involved in the regulation of cell growth arrest, terminal differentiation, and hormone secretion. Elevated levels of expression of stathmin have been described in leukemia and lymphoma cells. The aim of this study was to characterize the distribution of cells that express the stathmin protein in a wide variety of normal human and rodent tissues. EXPERIMENTAL DESIGN: First, antisera against a synthetic stathmin peptide have been raised in rabbits and the specificity of these antisera confirmed by their reactivity with stathmin on 1-dimensional and 2-dimensional Western blots. Second, the most appropriate means of fixing tissues in order to stain stathmin has been investigated. Finally, using the optimized conditions of tissue fixation, the antisera have been used to immunostain sections taken from a wide variety of tissues. RESULTS: Immunopositivity was found in cells of all the lineages studied, with the stained cells present within the proliferating compartment of tissues. Conversely, most nonproliferating mature cells did not stain with the antisera to stathmin. The only nonproliferating cells that appeared to express stathmin were a subpopulation of glial cells, neurons, and anterior pituitary cells. CONCLUSIONS: It is proposed that stathmin is necessary for cell proliferation in most, or all, cell lineages and that its primary function relates to some aspect of cell division.

Animals↗

Eye protection for the vascular surgeon.

Contamination occurring during vascular surgery was studied prospectively using a surgical mask incorporating a Splashguard visor. Over a 16-week period 78 vascular procedures were included; 44 were of < 2 h duration and 34 were of > or = 2 h. Contamination on both mask and visor from blood spots was recorded at the end of each procedure. Overall, 51 per cent of principal surgeons' visors were contaminated, with contamination of the mask itself in 32 per cent. When two surgeons were operating the contamination rate for the second was also high: 36 per cent for the visor and 42 per cent for the mask. Assistants had a contamination rate of 36 per cent for the visor and 13 per cent for the mask. The lowest rate of contamination occurred for the visor and mask of the scrub nurse, 10 and 4 per cent respectively. For emergency procedures the duration of operation had no influence on the frequency of contamination. However, for the principal surgeon elective operations of < 2 h duration were less likely to involve contamination than those of > or = 2 h (P < 0.035). Blood contamination of visors and masks is common in vascular surgery but rarely appreciated by the surgeon. Routine eye protection should be considered in vascular surgery, in particular for emergency and prolonged elective procedures.

Blood-Borne Pathogens↗