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N Davis

Publications and source records attributed to N Davis.

At least 19 recordsLinked to original sources
PubMed1997

Genistein inhibits Na+/Ca2+ exchange activity in primary rat cortical neuron culture.

We have examined the possible regulatory effect of tyrosine kinase activity on Ca2+ transport observed in the cultured rat cortical neurons. Na+/Ca2+ exchange was studied using cells cultured for various time periods. A nearly two fold increase in Ca2+ uptake was seen when comparing 3 day and 9 day cultures. Western blot analysis also showed a two fold increase in Na+/Ca2+ exchanger (NCX1) protein levels as cells matured in culture. To study the effect of genistein (a specific tyrosine kinase inhibitor) cells were incubated with 100 microM genistein (in 1% DMSO) for 1 hour before the assay of Na+/Ca2+ exchange activity. There was a significant decrease of Ca2+ uptake in genistein treated neurons (control: 4.596+/-0.205 nmol/mg protein/15 min, n=12; genistein: 1.420+/-0.131 nmol/mg protein/15 min, n=12, mean+/-S.E. P<0.001). Daidzein, an inactive analog of genistein and phorbol myristate acetate (PMA), a PKC activator were without effect. The results suggest that as cells mature in culture, Na+/Ca2+ exchange capacity increases, as a result of greater protein expression. Exposure to genistein inhibited Ca2+ uptake suggesting that the exchanger may be modulated by tyrosine phosphorylation.

Animals↗
PubMed1997

Core biopsy for microcalcifications in the breast.

BACKGROUND: The conventional method of dealing with clustered mammographic microcalcification in the breast when it is of uncertain aetiology is to undertake either a short-term mammographic review or to surgically excise the abnormal area and submit it for histological examination. Stereotactic wide-bore needle biopsy (core biopsy) of microcalcifications is a suitable alternative to surgical biopsy and experience with this technique forms the basis of the present study. METHODS: Percutaneous core biopsy has been used at the Wesley Breast Clinic as a means of assessing clustered calcification in 297 cases from November 1992 to October 1995. The procedure is done under local anaesthesia as an outpatient procedure using a stereotactic attachment to a standard mammography unit. RESULTS: A diagnosis of frank malignancy was made on core samples in 22 cases (7.4%), and in all of these malignancy was confirmed at open surgical biopsy. In a further six women in whom the core biopsy was reported as 'suspicious of malignancy', open surgical biopsy confirmed malignancy in three women, lobular in situ carcinoma was found in two women, and atypical ductal hyperplasia in one woman. In two instances the core sample was reported as showing atypical ductal hyperplasia and in those cases, this was confirmed at open surgical biopsy. In 265 cases (89%) the histology of the core revealed appearances of benign breast tissue. Open surgical biopsy has been undertaken in only six of these cases, but in all instances the histology has confirmed a benign process. In the two remaining cases, the procedure was considered to be technically unsatisfactory, and open surgical biopsy was recommended because of doubt about the appearance of the microcalcification. In both instances, malignancy was demonstrated. CONCLUSIONS: Core biopsy of clustered mammographic microcalcification of uncertain aetiology is recommended as a satisfactory and reliable alternative to open surgical biopsy. It is less expensive, can be done quickly, produces few complications, and does not produce subsequent mammographic distortion.

Ambulatory Surgical Procedures↗
PubMed1996

Aging does not affect steady-state expression of the Na+/Ca2+ exchanger in rat brain.

1. Steady-state protein and mRNA levels of the Na+/Ca2+ exchanger were studied in old (24-month) and young (3-month) brains of male Fischer 344 rats by Western and Northern analysis. 2. Northern analysis with a cDNA proble for the Na+/Ca2+ exchanger amplified from human brain RNA indicated the presence of two transcripts for the Na+/Ca2+ exchanger (6 and 16 kb). Both transcripts were present in similar abundance in the cerebrum and hippocampus. In the cerebellum the 6-kb transcript predominated. The cerebellum had the highest overall level of expression. There were no significant age-related effects seen on the level of expression of either transcript in each of the brain areas tested. 3. Western analysis of plasma membrane vesicles purified from cerebral cortex identified a single protein of 116 kDa. Consistent with the Northern analysis, no age-related effect on protein levels was seen. 4. The mechanisms underlying altered Na+/Ca2+ exchange activity in aging rat brain (Michaelis, 1989) most likely do not involve changes in gene expression and are therefore more likely to represent posttranslation modifications of the protein.

Aging↗
PubMed1995

Post-transcriptional regulation of the Na+/Ca2+ exchanger in aging rat heart.

Altered calcium homeostasis in the senescent heart appears to be the result, at least in part, of decreased Na+/Ca2+ exchange activity. To further investigate the basis of the decrease in Na+/Ca2+ exchange activity, Na+/Ca2+ exchanger gene expression in the heart was compared in 3 and 24 month old male Fischer 344 rats. Sarcolemmal vesicles prepared from left ventricle and septum showed reduced Na(+)-dependent Ca2+ uptake in 24 month old animals when compared to 3 month old animals (0.156 +/- 0.005 and 0.135 +/- 0.008 nmol Ca2+/mg/10 s; mean +/- S.E. for 3 month and 24 month old animals, respectively). Western analysis showed immunodetectable Na+/Ca2+ exchanger protein levels were decreased by 19% in 24 month old animals when compared to 3 month old animals. Poly(A+) RNA was purified from left and right ventricle and left and right atria and subjected to Northern analysis using digoxin labeled cDNA probes for the Na+/Ca2+ exchanger and actin. The Na+/Ca2+ exchanger probe labeled a 7 kb message in both ventricle and atria, while the actin probe labeled both beta-actin (2.2 kb) and alpha-actin (1.4 kb). The steady state level of expression of Na+/Ca2+ exchanger Poly(A+) RNA when normalized to beta-actin, was similar when ventricle and atria were compared. There were no observable differences in Na+/Ca2+ exchanger or alpha-actin Poly(A+) RNA steady state levels when comparing 3 and 24 month old animals. The results suggest that reduced Na+/Ca2+ exchange activity in the left ventricle of 24 month old animals was most likely the result of post-transcriptional modification of the protein that was detectable by Western analysis.

Aging↗
PubMed1994

Studies of the mechanism underlying increased Na+/Ca2+ exchange activity in Alzheimer's disease brain.

The Na+/Ca2+ exchanger was characterized in plasma membrane vesicles derived from frozen human postmortem tissues. The frontal cortex, temporal cortex and cerebellum of control and Alzheimer's disease (AD) tissues were compared. Na+/Ca2+ exchange activity was defined as the change in vesicular Ca2+ content seen after Na+ loaded vesicles were diluted into choline buffer. The time course of changes in Ca2+ content after dilution was similar in all three regions of control brain. In AD brain, both frontal and temporal cortex vesicles showed elevated Ca2+ content, most evident as an increased peak Ca2+ content at 2 min. The AD cerebellar cortex time course was similar to control and did not show an elevated peak at 2 min. No differences were seen in the passive permeability to Ca2+ when comparing plasma membrane vesicles prepared from control and AD brain. Vesicles from the frontal and temporal cortex of AD brain showed increases in the Vmax of the initial velocity of Ca2+ uptake when compared to control brain, whereas, the cerebellum did not. There were no significant effects of AD on the Km for Ca2+ activation of the initial velocity. Ca2+ influx measured during the rise in vesicular Ca2+ content was elevated in vesicles from AD temporal cortex when compared to control. Two known inhibitors (exchange inhibitory peptide and dichlorobenzamil) of the cardiac Na+/Ca2+ exchanger inhibited the human brain exchanger equally well in control and AD vesicles. Increased Na+/Ca2+ exchange activity was not due to astrocytic gliosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Alzheimer Disease↗
PubMed1994

The NSABP trials.

Explore the source record for details and available documents.

Breast Neoplasms↗
PubMed1994

Evaluating a patient satisfaction survey for maximum benefit.

BACKGROUND: Patient satisfaction surveys are now in use in some form at most hospitals and health care systems. Yet, it is unclear how well information collected meets the needs of all groups who might benefit from patient feedback. An evaluation was conducted at the Center for Outcomes Research, Sisters of Providence Health System (Portland, Ore), to determine the extent to which the survey, then almost three years in use, was satisfying its internal consumers and to guide redesign of the entire survey process. METHOD: The evaluation of the survey process was designed to address several questions: who uses the results (consumers); what are their objectives (goals); what results are useful (product); and what is done with the results (intervention utility). Techniques such as interviews, literature reviews, and supplemental data collection, were used to explore the needs of each consumer group. CONCLUSION: The evaluation has led to a number of changes in the patient satisfaction survey process. Large-scale patient satisfaction surveys result in large-scale costs and therefore must be beneficial to multiple users in multiple ways.

Adult↗
PubMed1994

Effects of a job-simulated exercise programme on employees performing manual handling operations.

This study investigated the effects of physical training on employees performing manual handling operations in three manufacturing plants. Employees from two plants were trained using progressive resistance exercise (PRE) while employees in the third plant were trained using PRE and trunk flexibility exercises (TFE). The results were: (1) a combined TFE and PRE programme significantly improved muscular endurance (124%), dynamic (86%) and static (back: 59%; arm: 25%; shoulder: 23%) muscular strength, and trunk flexibility (low back flexibility: 11%; total trunk rotation: 48%); (2) a dynamic PRE programme did not improve static strength (arm: 3%; shoulder: 8%; back: 14%; composite: 7%) as much as dynamic strength (71%); (3) endurance time at a fixed workload increased without changing job demand perception, but daily operations were performed more easily.

Adult↗
PubMed1994

Outcome of deliberate self-poisoning. An examination of risk factors for repetition.

BACKGROUND: One of the most important outcomes following an episode of non-fatal deliberate self-poisoning is its repetition. METHOD: In a prospective follow-up study the subjects were 992 people responsible for 1096 consecutive episodes of deliberate self-poisoning recorded at a teaching hospital accident and emergency department. Risk factors examined were socio-demographic variables, psychiatric and self-harm history, aspects of the self-poisoning episode, and appearance and behaviour at accident and emergency; the frequency of each was compared between those patients who repeated within one year (n = 116) and those who did not (n = 876). RESULTS: Those who repeated were more likely to have ingested more than one drug, to report a previous episode of self-poisoning, to be aged 25-54, and to have experienced previous psychiatric care or psychiatric admission. They were less likely to be in paid employment, or to have expressed a threat to another person or written a note. The best predictor--previous psychiatric contact--only had a positive predictive value of 21% (95% confidence interval 16-25%). CONCLUSIONS: Risk factors for repetition of self-poisoning should be kept up-to-date despite modest predictive power. More attention might be paid to clinical rather than socio-demographic aspects of self-harm.

Adult↗
PubMed1993

Evidence for functional dissociation of dependence and tolerance in guinea-pig isolated ileal segments following 20 hour exposure to morphine in vitro.

1. In the present study we have examined the relationship between tolerance and dependence in isolated ileal segments from the guinea-pig under three different conditions: fresh preparations not previously exposed to morphine (fresh/morphine naive); preparations stored overnight at 4 degrees C in modified Krebs-Henseleit saline (overnight-stored/morphine-naive); preparations stored overnight at 4 degrees C in Krebs-Henseleit saline containing 10 microM morphine and extensively washed with modified Krebs-Henseleit saline to remove residual morphine (overnight-stored/morphine-exposed). 2. Morphine produced a concentration-dependent inhibition of the response of ileal segment to 0.1 Hz, 1 ms and 10 V transmural field stimulation in fresh/morphine-naive, overnight-stored/morphine-naive and overnight-stored/morphine-exposed preparations. The maximum effect observed was similar in all three preparations-approximately 80% inhibition. Although, morphine was significantly more potent in the fresh/morphine-naive preparations (pD2 6.72 +/- 0.05, n = 8) than either the overnight-stored/morphine-native (pD2 6.42 +/- 0.11, n = 8) or the overnight-stored/morphine-exposed (pD2 6.44 +/- 0.14, n = 8), there was no significant difference between the overnight exposure to ileal segments to 10 microM morphine at 4 degrees C failed to induce tolerance to morphine. 3. The mu opiate receptor antagonist, naloxone (10 microM), produced contractions in both fresh/morphine-naive and overnight-stored/morphine-naive ileal segments following acute exposure to 10 microM morphine. Naloxone (10 microM) also produced contractions in 2/9 fresh/morphine-naive, 1/9 overnight-stored/morphine-naive and 7/9 overnight-stored/morphine-exposed preparations in the absence of morphine. The greater incidence of naloxone-induced contractions in overnight-stored/morphine-exposed preparations,suggests that dependence in this model is the product of adaptive changes that outlive the presence of morphine.4. The selective alpha2-adrenoceptor agonists, clonidine (0.3 microM) and 5-bromo-6-[2-imidazolin-2-ylamino]-quinoxaline bitartrate (UK-14304, 1 microM), inhibited naloxone-induced contractions in overnight-stored/morphine-exposed preparations of ileal segments (n = 4 preparations for each agonist), suggesting that the response is due to transmitter release from the myenteric plexus.5. The findings in the present study indicate that tolerance and dependence to morphine in ileal segments of the guinea-pig can be functionally dissociated by overnight exposure to morphine at 4 degrees C.The development of tolerance to morphine, unlike dependence, appears to be a temperature-dependent process. This also raises the possibility that naloxone possesses intrinsic negative agonism at morphine sensitive receptors, which is manifested as a functional response only after adaptive changes in the myenteric plexus following exposure to morphine.

Animals↗
PubMed1993

Modified polyvinyl alcohol-benzoporphyrin derivative conjugates as phototoxic agents.

Photosensitizing and biodistribution characteristics of a photosensitizer (benzoporphyrin derivative, monoacid ring A; BPD) conjugated to a macromolecule (modified polyvinyl alcohol; M-PVA, molecular weight = 10,000) were tested in vitro and in vivo. Modified PVA was loaded with BPD at molar ratios 1:12, 1:25, 1:50, 1:75 and 1:100. Most of the work was carried out with a conjugate having a 1:25 molar ratio. In vitro photosensitization was tested using A549 (human lung carcinoma), A432 (human epidermoid carcinoma) and P815 (mastocytoma of DBA/2 mice) cell lines. Photosensitization of M1 (rhabdomyosarcoma of DBA/2 mice) tumors was tested in an in vivo/in vitro assay, in which tumor-bearing mice were injected intravenously with free or conjugated 3H-BPD and 3 h later light activation of tumor cells was carried out in vitro. Biodistribution studies were carried out using M1 tumor-bearing DBA/2 mice and 3H-BPD either free or conjugated to M-PVA. The results of these studies showed that the conjugation of BPD to M-PVA resulted in the formation of a macromolecular photosensitizer that retained full photosensitizing activity of the photosensitizer molecules and at the same time gained new characteristics, advantageous for photodynamic treatment, especially in vivo. In vitro M-PVA-BPD conjugates were at least as efficient in photosensitization of tumor cells as an equivalent number of free BPD molecules, both in the presence and in the absence of serum. Although the biodistribution was in general comparable to free BPD, the conjugate (1:25) reached slightly higher levels in the blood, kidney, lung and spleen, and lower levels in the liver, brain, skin and muscle in comparison with free BPD.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Direct association of pp40/I kappa B beta with rel/NF-kappa B transcription factors: role of ankyrin repeats in the inhibition of DNA binding activity.

To understand the mechanism by which pp40/I kappa B beta inhibits DNA binding activity of the rel/NF-kappa B family of transcription factors, we have investigated the role of ankyrin repeats on the biological function of pp40 by deleting or mutating conserved residues. We show that (i) ankyrin repeats alone are not sufficient to manifest biological activity but require the C-terminal region of the pp40 protein; (ii) four out of the five ankyrin repeats are essential for inhibiting the DNA binding activity; (iii) pp40 mutants that do not inhibit DNA binding of rel protein also do not associate with rel; (iv) although pp40 can associate with the p65 and p50 subunits of NF-kappa B, pp40 inhibits the DNA binding activity of only the p50-p65 heterodimer and the p65 homodimer; and (v) pp40 inhibits the transcription of genes linked to kappa B site; however, mutants that do not affect DNA binding have no effect. We propose that the ankyrin repeats and the C-terminal region of pp40 form a structure that associates with the rel homology domain to inhibit DNA binding activity.

Amino Acid Sequence↗
PubMed1992

Role of frozen section and clinical parameters in distinguishing benign from malignant follicular neoplasms of the thyroid.

The determination of malignancy preoperatively or intraoperatively is difficult in patients with follicular neoplasms of the thyroid. This study reviews a series of 395 patients treated for follicular neoplasms at the Vancouver General Hospital and the British Columbia Cancer Agency between the years of 1955 and 1988, 198 of whom had frozen section at the time of surgery. Frozen section was 79% accurate in differentiating follicular adenomas from carcinomas, with a sensitivity of 52% and a specificity of 100%. The positive predictive value of a frozen section showing carcinoma was 100%, and the negative predictive value was 73%. An incorrect diagnosis of a benign lesion was made in 21% of patients in whom the final diagnosis by fixed section was carcinoma. These same statistics were calculated for patients aged greater than 50 years, tumor size greater than 3 cm, and patients with a history of previous neck irradiation, three clinical factors shown in a previous study to be strong prognostic indicators of malignancy. The results were compared with those found by frozen section. The implications of these results in terms of patient management are discussed.

Adenocarcinoma↗
PubMed1991

Rel-associated pp40: an inhibitor of the rel family of transcription factors.

The Rel-associated protein pp40 is functionally related to I kappa B, an inhibitor of the transcription factor NF-kappa B. Purified pp40 inhibits the DNA binding activity of the NF-kappa B protein complex (p50:p65 heterodimers), p50:c-Rel heteromers, and c-Rel homodimers. The sequence of the complementary DNA encoding pp40 revealed similarity to the gene encoding MAD-3, a protein with mammalian I kappa B-like activity. Protein sequencing of I kappa B purified from rabbit lung confirmed that MAD-3 encodes a protein similar to I kappa B. The sequence similarity between MAD-3 and pp40 includes a casein kinase II and consensus tyrosine phosphorylation site, as well as five repeats of a sequence found in the human erythrocyte protein ankyrin. These results suggest that rel-related transcription factors, which are capable of cytosolic to nuclear translocation, may be held in the cytosol by interaction with related cytoplasmic anchor molecules.

Amino Acid Sequence↗
PubMed1991

The rel-associated pp40 protein prevents DNA binding of Rel and NF-kappa B: relationship with I kappa B beta and regulation by phosphorylation.

The product of proto-oncogene Rel associates with a number of cellular proteins. We have studied the effect of one of them, a phosphoprotein of 40 kD (pp40), on the DNA-binding activity of the Rel protein. We demonstrate that purified pp40 not only inhibits the binding of Rel, but also NF-kappa B (p50-p65) heterocomplex to DNA. Additionally, I kappa B beta, but not I kappa B alpha, also prevented the binding of Rel to the kappa B site. I kappa B beta and pp40 are related proteins because (1) they share a number of common tryptic peptides, (2) their inhibitory effect on DNA binding can be abolished by preincubation with pp40-specific antiserum, and (3) labeled I kappa B beta can be immunoprecipitated with pp40 antibodies. pp40 is part of the Rel complex present in the cytoplasm and nuclear extracts of WEHI-231 cells. The activity of pp40 to inhibit the DNA binding of Rel and NF-kappa B is modulated by phosphorylation.

Animals↗
PubMed1991

Is the non-pharmacological treatment of hypertension neglected?

Non-pharmacological techniques in the management of hypertension have been shown to be beneficial. This pilot study was set up to examine how often routine advice was given with respect to weight reduction and/or lifestyle adjustments, and whether it was needed. Three-quarters of the 69 patients in the study smoked or were overweight but only half of the smokers recalled advice to stop. One-fifth of the patients were apparently not told to lose weight. Only one-third recalled being told to reduce alcohol intake. Lifestyle counselling and the management of hypertension in this small study appeared to be not completely effective for various reasons. It is likely to be cheaper and more satisfactory than medication alone or as an adjunct and its application deserves further study.

Body Weight↗