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Biomedical subjects

S Woodward

Publications and source records attributed to S Woodward.

At least 19 recordsLinked to original sources

Expression of the zinc finger gene EVI-1 in ovarian and other cancers.

The EVI-1 gene was originally detected as an ectopic viral insertion site and encodes a nuclear zinc finger DNA-binding protein. Previous studies showed restricted EVI-1 RNA or protein expression during ontogeny; in a kidney and an endometrial carcinoma cell line; and in normal murine oocytes and kidney cells. EVI-1 expression was also detected in a subset of acute myeloid leukaemias (AMLs) and myelodysplasia. Because EVI-1 is expressed in the urogenital tract during development, we examined ovarian cancers and normal ovaries for EVI-1 RNA expression using reverse transcription polymerase chain reaction (RT-PCR) and RNAase protection. Chromosome abnormalities were examined using karyotypes and whole chromosome 3 and 3q26 fluorescence in situ hybridisation (FISH). RNA from six primary ovarian tumours, five normal ovaries and 47 tumour cell lines (25 ovarian, seven melanoma, three prostate, seven breast and one each of bladder, endometrial, lung, epidermoid and histiocytic lymphoma) was studied. Five of six primary ovarian tumours, three of five normal ovaries and 22 of 25 ovarian cell lines expressed EVI-1 RNA. A variety of other non-haematological cancers also expressed EVI-1 RNA. Immunostaining of ovarian cancer cell lines revealed nuclear EVI-1 protein. In contrast, normal ovary stained primarily within oocytes and faintly in stroma. Primary ovarian tumours showed nuclear and intense, diffuse cytoplasmic staining. Quantitation of EVI-1 RNA, performed using RNAase protection, showed ovarian carcinoma cells expressed 0 to 40 times the EVI-1 RNA in normal ovary, and 0-6 times the levels in leukaemia cell lines. Southern analyses of ovarian carcinoma cell lines showed no amplification or rearrangements involving EVI-1. In some acute leukaemias, activation of EVI-1 transcription is associated with translocations involving 3q26, the site of the EVI-1 gene. Ovarian carcinoma karyotypes showed one line with quadruplication 3(q24q27), but no other clonal structural rearrangements involving 3q26. However, whole chromsome 3 and 3q26 FISH performed on lines with high EVI-1 expression showed translocations involving chromosome 3q26. EVI-1 is overexpressed in ovarian cancer compared with normal ovaries, suggesting a role for EVI-1 in solid tumour carcinogenesis or progression. Mechanisms underlying EVI-1 overexpression remain unclear, but may include rearrangements involving chromosome 3q26.

Blotting, Southern

Nutritional support for head-injured patients.

Brain-injured patients require increased nutritional support in order to prevent complications of inadequate nutrition. Nurses are in a strong position to influence the nutritional support provided to such patients.

Craniocerebral Trauma

Core body temperature during menopausal hot flushes.

OBJECTIVE: To measure core body temperature by ingested radiotelemetry pill and rectal temperature during menopausal hot flushes under controlled laboratory conditions. DESIGN: Patients were recorded during sleep using both methods in a sound-proofed, temperature and humidity-controlled laboratory room. SETTING: University medical center. PATIENTS: Eight postmenopausal women who were amenorrheic for > or = 1 year and reported frequent hot flushes. RESULTS: Thirty-seven hot flushes were detected by criterion increases in sternal skin conductance level. Significant increases in telemetered but not rectal temperature occurred before 24 of the hot flushes. CONCLUSIONS: Core body temperature elevations precede a majority of menopausal hot flushes and serve as one trigger of this heat-loss phenomenon.

Body Temperature

Core body temperature and circadian rhythm of hot flashes in menopausal women.

Postmenopausal hot flashes are characterized by sweating and peripheral vasodilation and occur more frequently during increased heat loads. The circadian rhythm of core body temperature (TC) is well known and suggests that hot flashes will be most frequent when core temperature is highest. This hypothesis has not been tested previously. Ten symptomatic and six asymptomatic postmenopausal women were recruited from advertisements and screened. Each received 24-h ambulatory monitoring of sternal skin conductance levels to detect hot flashes, ambient temperature, skin temperature, and TC. The last measure was recorded using an ingested radiotelemetry pill. Cosinor analysis demonstrated a circadian rhythm (P < 0.02) of hot flashes with a peak at about 1825 h. TC values of the symptomatic women were lower than those of the asymptomatic women (P < .05) from 0000-0400 h and at 1500 and 2200 h. The majority of hot flashes were preceded by elevations in TC. Thus, elevated TC may serve as one trigger of menopausal hot flashes.

Body Temperature

Nurse and patient perceptions of pain.

Patient pain is a problem frequently encountered by nurses, who are often directly responsible for its management. Accurate pain assessment is vital for appropriate management. The nurse's role in pain control should evolve to one of empowering patients to determine the management of their own pain where possible.

Attitude of Health Personnel

Expression of EVI1 in myelodysplastic syndromes and other hematologic malignancies without 3q26 translocations.

The EVI1 gene encodes a zinc-finger, DNA-binding protein originally described as the transforming gene associated with a common ecotropic viral insertion site in myeloid leukemias. Previous studies demonstrated EVI1 expression in human leukemias in cases with 3q26 translocations, but not in normal blood or bone marrow. These studies also suggested an association between EVI1 expression and chromosome 7 deletion (del). Because of this association, we examined expression of EVI1 using RNA polymerase chain reaction (PCR) in patients with myelodysplastic syndromes (MDS) and acute leukemia with and without 3q26 translocations. EVI1 RNA was expressed in 29% of 34 (95% confidence interval, 20% to 50%) patients with the MDS subtypes refractory anemia (RA), refractory anemia with excess blasts (RAEB), or refractory anemia with excess blasts in transformation (RAEB-T). The vast majority of these cases occurred in patients with RAEB and RAEB-T. EVI1 expression was not detected in patients with chronic myelomonocytic leukemia (CMML), normal bone marrow or cord blood, or a variety of other hematologic malignancies. EVI1 RNA was detected in three of 18 patients with acute myelogenous leukemia (AML) and in two of four patients with acute promyelocytic leukemia (APL). Karyotypes showed that only one AML patient had karyotype 3q26 abnormalities, indicating that EVI1 expression is associated with cases that do not have structural abnormalities involving chromosome 3q26. These studies document for the first time the abnormal expression of EVI1 RNA by patients with MDS, and suggest an important role for EVI1 in the pathogenesis or progression of some myeloid malignancies.

Adult

The thermoregulatory effects of menopausal hot flashes on sleep.

Menopausal hot flashes are thought to be a disorder of thermoregulation initiated centrally within the medial preoptic area of the hypothalamus. These heat-loss mechanisms appear to be activated in the presence of normal core body temperature. Previous studies have demonstrated that thermal stimuli have the potential to alter sleep stages. We performed 24-hour ambulatory recordings of hot flashes and all-night sleep parameters on 12 postmenopausal women with hot flashes and seven postmenopausal women without flashes to determine whether the presence of hot flashes prior to sleep or during sleep itself would result in alterations in sleep pattern. The results show that hot flashes are associated with increased Stage 4 sleep and a shortened first rapid eye movement period. Hot flashes occurring in the 2 hours prior to sleep onset were positively correlated with the amount of slow-wave sleep. The central thermoregulatory mechanism underlying hot flashes may affect hypnogenic pathways inducing sleep and heat loss in the absence of a thermal load.

Body Temperature Regulation

Effects of publicity and a warning letter on illegal cigarette sales to minors.

The study aimed to assess rates of illegal cigarette sales to children and the impact on these rates of publicity and a warning letter threatening prosecution. Children aged 12 and 13 made two repeat purchasing attempts, three months apart, at 255 randomly selected tobacco retail outlets in Sydney. A randomly selected 50 per cent of retail outlets which sold cigarettes illegally at the first attempt were sent warning letters threatening prosecution. Publicity about the undercover buying operation was organised between the attempts. At the first attempts, 39 per cent of shops sold cigarettes to the children and 32 per cent sold them at the second attempt. Shops which sold on the first occasion and received warning letters reduced selling by 69 per cent compared to the 40 per cent reduction in shops which sold cigarettes on the first attempt and were not sent warning letters, a net reduction of 29 per cent seemingly attributable to the warning letters (95 per cent confidence interval 8 per cent to 50 per cent). It is extremely easy for children as young as 12 to buy cigarettes. The combined effects of publicity about undercover buying operations and warning letters threatening prosecution seem capable of reducing selling by about 29 per cent. Because of inconsistencies in selling or refusals, future attempts to measure selling rates to children should use repeat purchasing attempts and classify outlets as 'selling', 'not selling' or 'sometimes selling'.

Adolescent

Nonneural mediation of digital vasodilation during menopausal hot flushes.

Menopausal hot flushes are accompanied by profuse sweating, decreased skin resistance, modest tachycardia and cutaneous vasodilation. With the exception of the last effect, these events are consistent with an abrupt increase in sympathetic outflow. Blood flow in the human finger is controlled through sympathetic vasoconstricting nerves, and increased sympathetic activation results in digital vasoconstriction. We therefore sought to determine if digital vasodilation during hot flushes was mediated through efferent sympathetic nerves. Bilateral finger temperature and blood flow were recorded after the digital nerves on one hand had been blocked with a local injection of lidocaine. The effectiveness of the nerve blocks was verified by a reflex vasoconstriction test. Hot flushes were objectively defined using skin conductance responses recorded from the sternum. Fifteen hot flushes occurred in 8 women. Significant elevations in finger temperature and blood flow occurred during the flushes, in nerve-blocked and intact fingers. These findings suggest that digital vasodilation during hot flushes is due to a circulating vasodilating substance.

Adult

Heterobasidion annosum 5.8s ribosomal DNA and internal transcribed spacer sequence: rapid identification of European intersterility groups by ribosomal DNA restriction polymorphism.

Using conserved fungal ribosomal gene sequences the internal transcribed spacer (ITS) regions one and two (ITS1, ITS2) and the 5.8s ribosomal RNA gene (rRNA) of Heterobasidion annosum were amplified by the polymerase chain reaction (PCR). The nucleotide sequence was determined in three European intersterility groups (ISG-S, -F and -P). Three sequence variants of the ITS were found in ISG-S isolates. The sequence of the ITS of ISG-F differed by two residues from the major ISG-S sequence variant. The ISG-P sequence differed from ISG-S and ISG-F at 15-16 and 16 residues, respectively. Amplified intergenic spacer elements were informative for ISG fingerprinting following digestion with various 4-cutter restriction endonucleases. All differences in the restriction fragments between the ISGs were because of sequence differences in the ITS regions. The fingerprint patterns of isolates from the same intersterility group but from different European localities were identical. These results show that ribosomal DNA fingerprinting is a rapid technique to identify ISGs in Heterobasidion annosum.

Base Sequence

Fostering a change in policy. HIV, AIDS and the neuroscience nurse.

As new treatments and drug therapies enable the control of opportunistic diseases associated with Aids, its neurological manifestations are becoming more prevalent. This poses new challenges to neuroscience nurses, who must reassess their attitude to and understanding of the disease.

AIDS Dementia Complex

A molecular model for membrane fusion based on solution studies of an amphiphilic peptide from HIV gp41.

The mechanism of protein-mediated membrane fusion and lysis has been investigated by solution-state studies of the effects of peptides on liposomes. A peptide (SI) corresponding to a highly amphiphilic C-terminal segment from the envelope protein (gp41) of the human immunodeficiency virus (HIV) was synthesized and tested for its ability to cause lipid membranes to fuse together (fusion) or to break open (lysis). These effects were compared to those produced by the lytic and fusogenic peptide from bee venom, melittin. Other properties studied included the changes in visible absorbance and mean particle size, and the secondary structure of peptides as judged by CD spectroscopy. Taken together, the observations suggest that protein-mediated membrane fusion is dependent not only on hydrophobic and electrostatic forces but also on the spatial arrangement of the amino acid residues to form an amphiphilic structure that promotes the mixing of the lipids between membranes. A speculative molecular model is proposed for membrane fusion by alpha-helical peptides, and its relationship to the forces involved in protein-membrane interactions is discussed.

Amino Acid Sequence

Behavioral treatment of menopausal hot flushes: evaluation by ambulatory monitoring.

OBJECTIVES: We attempted to develop an effective behavioral treatment for menopausal hot flushes and to determine the active behavioral components of this procedure. STUDY DESIGN: Thirty-three women with frequent menopausal hot flushes were randomly assigned to receive eight sessions of training in paced respiration, muscle relaxation, or alpha-wave electroencephalographic biofeedback (placebo control). Hot flushes were objectively measured by means of 24-hour ambulatory monitoring of the sternal skin conductance level. RESULTS: Subjects undergoing paced respiration had significant reductions in hot flush frequency and respiration rate, as well as increases in tidal volume. CONCLUSION: Paced respiration training may be a useful treatment alternative for the reduction of hot flushes in women who cannot tolerate hormone replacement therapy.

Ambulatory Care

Use of suppressor analysis to identify DNA polymerase mutations in herpes simplex virus which affect deoxynucleoside triphosphate substrate specificity.

Herpes simplex virus DNA polymerase mutations which map in the N-terminal part of the protein and appear to alter deoxynucleoside triphosphate (dNTP) substrate specificity are described. These mutations suppress a drug hypersensitivity associated with the downstream mutation, Aphr10. We suggest that the mutant residues form part of the dNTP-binding site, a site previously thought to be confined to the C terminus.

Aphidicolin