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Biomedical subjects

E M Walker

Publications and source records attributed to E M Walker.

At least 19 recordsLinked to original sources
PubMed2006

Surgeons' views on multi-disciplinary breast meetings.

The aim of this study was to assess surgeons' views and their current commitments to multi-disciplinary breast meetings (MDMs). Two hundred and fifty questionnaires were sent out to registered members of the British Association of Surgical Oncology. Hundred and fifty-three were returned (reply rate 61.2%), of which 136 were suitable for analysis. All those who replied were involved in MDMs. 80.9% held MDMs once a week. Only 28% of MDMs were held during a protected session. Over 95% of surgeons and breast care nurses were present for the whole meeting. Radiologists and pathologists were present for the whole meeting in 90-95% of cases. In contrast, clinical oncologists were present for the whole MDM in 70% of cases and medical oncologists attended the whole meeting in only 44.1% of cases. There was variability in which patients were discussed in MDMs, and in many centres not all patients with cancer were discussed before surgery. Suggestions for improvement of MDMs included more time on protected sessions (72.8% in favour), time to prepare for meetings (29% in favour), allocation of a designated co-ordinator (30.9% in favour) and attendance of oncologists for the whole meeting (over 35% in favour). The majority of Breast MDMs were held at breakfast, lunch or the evening. There was variable attendance with a significant percentage of both clinical and medical oncologists not being present for the whole meeting. A quarter of units did not discuss patients with breast cancer before operation. This study shows that there is a need to improve provision for MDMs and to produce guidelines for these meetings.

Attitude of Health Personnel↗
PubMed2006

Aging influences multiple incidices of oxidative stress in the aortic media of the Fischer 344/NNiaxBrown Norway/BiNia rat.

Here, we determine the influence of aging on multiple markers of oxidative stress in the aorta of adult (6-month), aged (30-month) and very aged (36-month) Fischer 344/NNiaHSdxBrown Norway/BiNia (F344/NxBN) rats. Compared to adults, increases in as determined by oxidation of hydroethidine (HE) to ethidium (Et) were increased 79.7+/-7.0% in 36-month aortae and this finding was highly correlated with increases in medal thickness (r=0.773, p<0.01) and total protein nitration (r=0.706, p<0.01) but not Ki67, a marker for cell proliferation. Regression analysis showed that increases in aortic superoxide anion (O.-2) with aging were significantly correlated with changes in the expression and/or regulation of proteins involved in metabolic (AMPK-alpha), signaling (mitogen activated protein kinases (MAPKs) along with c-Src), apoptotic (Bax, Bcl-2, Traf-2) and transcriptional (NF-kappaB) activities. These results suggest that the aging F344/NxBN aorta may be highly suited for unraveling the molecular events that lead to age-associated alterations in aortic oxidative stress.

AMP-Activated Protein Kinases↗
PubMed2001

Role of protein kinase Calpha in signaling from the histamine H(1) receptor to the nucleus.

Stimulation of histamine H(1) receptors produced a marked activation of inositol phospholipid hydrolysis, intracellular calcium mobilization, and stimulation of the c-fos promoter in CHO-H1 cells expressing the H(1) receptor at a level of 3 pmol/mg protein. The latter response was determined using a luciferase-based reporter gene (pGL3). This response to histamine was not sensitive to inhibition by pertussis toxin but could be completely attenuated by the protein kinase C (PKC) inhibitor Ro-31-8220, or by 24-h pretreatment with the phorbol esters phorbol 12,13-dibutyrate or phorbol-12-myristate-13-acetate. Several isoforms of PKC can be detected in CHO-H1 cells (alpha, delta, epsilon, mu, iota, zeta) but only PKCalpha and PKCdelta were down-regulated by prolonged treatment with phorbol esters. Of the two isoforms that were down-regulated, only protein kinase Calpha was translocated to CHO-H1 cell membranes after stimulation with either histamine or phorbol esters. The PKC inhibitor Gö 6976, which inhibits PKCalpha but not PKCdelta, was also able to significantly attenuate the c-fos-luciferase response to histamine. The mitogen-activated protein kinase kinase inhibitor PD 98059 markedly inhibited the response to histamine, suggesting that the likely major target for PKCalpha was the mitogen-activated protein kinase pathway. These data suggest that the histamine H(1) receptor can signal to the nucleus via PKCalpha after activation of phospholipase Cbeta.

Animals↗
PubMed2000

Effects of iron overload on the immune system.

Iron and its binding proteins have immunoregulatory properties, and shifting of immunoregulatory balances by iron excess or deficiency may produce severe, deleterious physiological effects. Effects of iron overload include decreased antibody-mediated and mitogen-stimulated phagocytosis by monocytes and macrophages, alterations in T-lymphocyte subsets, and modification of lymphocyte distribution in different compartments of the immune system. The importance of iron in regulating the expression of T-lymphocyte cell surface markers, influencing the expansion of different T-cell subsets, and affecting immune cell functions can be demonstrated in vitro and in vivo. The poor ability of lymphocytes to sequester excess iron in ferritin may help to explain the immune system abnormalities in iron-overloaded patients. Iron overload as seen in hereditary hemochromatosis patients enhances suppressor T-cell (CD8) numbers and activity, decreases the proliferative capacity, numbers, and activity of helper T cells (CD4) with increases in CD8/CD4 ratios, impairs the generation of cytotoxic T cells, and alters immunoglobulin secretion when compared to treated hereditary hemochromatosis patients or controls. A correlation has recently been found between low CD8+ lymphocyte numbers, liver damage associated with HCV positivity, and severity of iron overload in beta-thalassemia major patients. Iron overload, with its associated increases of serum iron levels and transferrin saturation, may cause a poor response to interferon therapy. Iron overload with hyperferremia is associated with suppressed functions of the complement system (classic or alternative types). High plasma ferritin content in patients with chronic, diffuse diseases of the liver (cirrhosis, chronic hepatitis), beta-thalassemia major, dyserythropoiesis, and hereditary hemochromatosis may induce the development of anti-ferritin antibodies with the production of circulating immune complexes. Increased body stores of iron in various clinical situations may tip the immunoregulatory balance unfavorably to allow increased growth rates of cancer cells and infectious organisms, and complicate the clinical management of preexisting acute and chronic diseases.

B-Lymphocytes↗
PubMed1998

Nonselective effects of the putative phospholipase C inhibitor, U73122, on adenosine A1 receptor-mediated signal transduction events in Chinese hamster ovary cells.

Adenosine A1 receptors can signal, through Gi/o proteins, to inhibit adenylyl cyclase activity and also to stimulate phosphoinositide hydrolysis and the subsequent release of intracellular Ca2+ stores. The aminosteroid U73122 (1-[6-1[17beta-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1 H-pyrrole-2,5-dione) has been widely used as an inhibitor of phospholipase C, the enzyme mediating phosphoinositide hydrolysis. Using U73122, we sought to selectively block signalling through the phospholipase C pathway, in Chinese hamster ovary (CHO-K1) cells heterologously expressing human adenosine A1 receptors. U73122 inhibited A1 receptor-mediated phosphoinositide hydrolysis, as measured by total inositol phosphate accumulation, over the concentration range 1-15 microM. However, over the same concentration range, it also appeared to inhibit A1 receptor-mediated inhibition of forskolin-stimulated cyclic AMP accumulation, A1 receptor agonist-promoted [35S]GTP-gammaS binding, and at the higher concentrations (10-15 microM) produced marked morphological changes, leading to cytolysis. The structural analogue of U73122, U73343 (1-[6-[[17beta-3-methoxyestra-1,3,5(10-trien-17-yl]amino]hexyl]-2, 5-pyrrolidone-dione), typically used as an inactive control compound, had little effect on these events. The data suggest that U73122 is not a selective inhibitor of phospholipase C activity, interfering with adenosine A1 receptor signalling generally, either at the pre-effector level involving Gi/o proteins, or as a consequence of the morphological changes it induces.

Animals↗
PubMed1996

Vitamin A status affects the development of diabetes and insulitis in BB rats.

BB/Wor rats develop autoimmune diabetes mellitus with many features in common with human insulin-dependent diabetes mellitus. Since retinoids are known to have effects on insulin secretion and immune function, these studies were designed to investigate the effects of retinoid deficiency on diabetes in BB/Wor rats and to identify a role for retinoid status in the pathogenesis of autoimmune diabetes mellitus. Litters of diabetes-prone (DP) and diabetes-resistant (DR) BB/Wor rats were divided at weaning and fed a diet either (1) devoid of retinoids and leading to clinical deficiency at approximately 60 days of age (A-def diet)-following 10 days of clinical deficiency, rats on the A-def diet were changed to a diet containing 2 microg/g retinoic (A-def/RA diet); (2) containing 2 microg/g retinoic acid but deficient in retinol (RA diet); or (3) replete in retinol with 4 microg/g retinyl palmitate (RP diet). Rats receiving RP or RA diets were pair-fed to rats on the A-def/RA diet. Diabetes by 120 days of age was greatly reduced (P < .01) in DP rats that received the A-def/RA diet (four of 27) or RA diet (four of 29) versus the RP diet (13 of 31). Insulitis progressed with age in nondiabetic DP rats receiving the RP diet (P < .02) or RA diet (P < .05), but not the A-def/RA diet (P > .22). Insulin secretion was measured in perfused pancreas of nondiabetic rats after age 120 days and correlated negatively with insulitis (P < .05). DP rats receiving the RP diet had reduced insulin secretion as compared with other DP and DR rats (P < .05). In DR rats, retinoid status had no effects on insulitis through 120 days of age or on insulin secretion after 120 days of age. In conclusion, retinol deficiency reduces diabetes and insulitis in DP BB/Wor rats, and retinoic acid can at least partly substitute for retinol in the development of insulitis.

Animals↗
PubMed1996

Cadmium mobilization by nitrogen donor chelating agents.

The relative abilities of a series of acyclic polyamine chelating agents containing only nitrogen donors (N-donors) to induce the urinary excretion of cadmium has been examined in the rat. The compounds examined include triethylenetetramine dihydrochloride (TRIEN), tris(2-aminoethyl)amine trihydrochloride (TREN), tetraethylenepentamine pentahydrochloride (TETRAEN), and pentaethylenehexamine hexahydrochloride (PENTAEN). Sodium N-methyl-D-glucamine-N-carbodithioate (NaG) was used as a positive control compound. The polyamines induced a significant increase in the urinary excretion of cadmium in rats that had been loaded with cadmium at least 4 d prior to the polyamine treatments. A comparison of these with similar data on macrocylic nitrogen donor systems, which form much more stable complexes with cadmium but are also ineffective in enhancing the excretion of cadmium from such aged deposits, suggests that the factors responsible for the relative inefficiency of these compounds may involve either a difficulty in penetrating cellular membranes or a slow rate of reaction with biologically bound cadmium. The occurrence of oliguria and anuria following the administration of the several of the polyamines indicates that their use is accompanied by significant renal damage in cadmium-exposed rats.

Animals↗
PubMed1996

A survey of knowledge, attitudes, and perceptions (KAPs) of lymphatic filariasis, elephantiasis, and hydrocele among residents in an endemic area in Haiti.

To assess knowledge, attitudes, and perceptions about bancroftian filariasis, 104 residents of an endemic area in Haiti were interviewed. Questions focused on 1) whether people understood the relationship between infection and disease, 2) recognition of the role that mosquitoes play in transmission, 3) perceived importance of hydrocele and elephantiasis in relation to other recognized diseases, and 4) the willingness of the community to participate in a control program. Fewer than 50% of residents had heard of filariasis and only 6% of those surveyed knew that it was transmitted by mosquitoes. In contrast, all persons knew of the clinical conditions of hydrocele and elephantiasis. Hydrocele was thought to be caused by trauma (60%) or trapped gas (30%); elephantiasis by walking bare foot on soil or water (37%) or by use of ceremonial powder that had been sprinkled on the ground (23%). Of 76 respondents, 53% and 38% thought that hydrocele could be treated through surgery or a drug, respectively, whereas 86 respondents, 85% and 15% believed that either surgery or a drug could be used to treat elephantiasis. In this context, persons were not referring to a specific drug; rather, they believed a drug existed (possibly in some other country) that could cure these conditions. Hydrocele and elephantiasis ranked second to acquired immunodeficiency syndrome as perceived health problems, most likely because residents believed treatment for conditions such as malaria, intestinal worms, anemia, and diarrhea was easily obtained. Responses were influenced by age, sex, and symptoms, but none of these effects were statistically significant except that persons with hydrocele or elephantiasis were more likely to have sought treatment than persons without these conditions (P = 0.0006). The survey results indicate that awareness of the causes of disease, the relationship between infection and disease, and goals of treatment must be heightened through community-based education campaigns to increase the possibility of acceptance and support of control programs.

Adolescent↗
PubMed1996

Intrahepatic larval nematode infection in the northern spring peeper, Pseudacris crucifer crucifer (Anura: Hylidae), in West Virginia.

Larval stages of an unknown nematode were observed encapsulated in the livers of spring peepers, Pseudacris crucifer crucifer (Weid-Neuweid), collected from a marsh in western West Virginia (USA) during the spring breeding seasons of 1993 and 1994. Prevalence and mean intensity of infection were 37% (30 of 82 animals) and 2.03 parasites per infected host, respectively. Capsules with white or darkly pigmented walls were observed in infected livers; the former containing viable larvae, and the latter enveloping larvae in various stages of degeneration.

Animals↗
PubMed1995

Onchocerca volvulus: parasitologic and serologic responses in experimentally infected chimpanzees and mangabey monkeys.

Six chimpanzees (Pan troglodytes) and six mangabey monkeys (Cercocebus atys) were inoculated with Onchocerca volvulus third-stage larvae (L3) of West African origin. Two chimpanzees each received 200, 300, or 400 L3, while three mangabeys each received either 50 or 250 L3. All six chimpanzees became microfilaria positive between 11 and 25 months postinoculation (PI), while two of the six mangabeys were skin-snip positive at 24 and 37 months PI, respectively. All chimpanzees developed antibodies to two native antigens of 14 and 22 kDa and to the recombinant antigens OV16, OC3.6, and OC9.3. Marked antibody responses were observed in the mangabey monkeys, and in general, the responses were similar to those observed in the chimpanzees. However, in the mangabeys, these responses did not generally manifest themselves until later in the infection. The results of this study suggest that in chimpanzees, the smallest inoculum used, 200 L3, was sufficient to initiate consistent infections that had parasitologic and immunologic parameters equivalent to animals inoculated with larger numbers of larvae. Similarly, inoculation of mangabey monkeys with small numbers of larvae appeared to be as likely to establish infection and induce immunologic responses as did inoculation of larger numbers of larvae. Microfilaria-positive chimpanzees and mangabey monkeys were examined by three conventional imaging techniques (X ray, ultrasound, and magnetic resonance imaging (MRI)), but no adult worms or nodules could be identified in any animal.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Does catheter traction reduce post-transurethral resection of the prostate blood loss?

OBJECTIVE: To determine if traction on a catheter after transurethral resection of the prostate (TURP) reduces post-operative bleeding. PATIENTS AND METHODS: This prospective trial included 115 consecutive patients undergoing TURP. After resection patients were randomly selected to have either traction (57) or no traction (58) on the catheter for 30 min. Blood loss was measured during and for 2 h after the operation. A simple method for applying constant traction is described. RESULTS: Catheter traction reduced post-operative bleeding while applied, but had no further effect after the removal of traction. CONCLUSION: Catheter traction is a useful technique to aid the control of post-TURP bleeding.

Aged↗
PubMed1995

Physical map of the genome of Treponema pallidum subsp. pallidum (Nichols).

A physical map of the chromosome of Treponema pallidum subsp. pallidum (Nichols), the causative agent of syphilis, was constructed from restriction fragments produced by NotI, SfiI, and SrfI. These rare-cutting restriction endonucleases cleaved the T. pallidum genome into 16, 8, and 15 fragments, respectively. Summation of the physical lengths of the fragments indicates that the chromosome of T. pallidum subsp. pallidum is approximately 1,030 to 1,080 kbp in size. The physical map was constructed by hybridizing a variety of probes to Southern blots of single and double digests of T. pallidum genomic DNA separated by contour-clamped homogeneous electric field electrophoresis. Probes included cosmid clones constructed from T. pallidum subsp. pallidum genomic DNA, restriction fragments excised from gels, and selected genes. Physical mapping confirmed that the chromosome of T. pallidum subsp. pallidum is circular, as the SfiI and SrfI maps formed complete circles. A total of 13 genes, including those encoding five membrane lipoproteins (tpn47, tpn41, tpn29-35, tpn17, and tpn15), a putative outer membrane porin (tpn50), the flagellar sheath and hook proteins (flaA and flgE), the cytoplasmic filament protein (cfpA), 16S rRNA (rrnA), a major sigma factor (rpoD), and a homolog of cysteinyl-tRNA synthetase (cysS), have been localized in the physical map as a first step toward studying the genetic organization of this noncultivable pathogen.

Chromosome Mapping↗
PubMed1995

Survival and infectivity of Babesia in blood maintained at 25 C and 2-4 C.

Babesia microti-infected blood was stored at room temperature (approximately 25 C) or refrigerated (4 C) for 30 days. To assess viability of the parasites after storage at these 2 temperatures, a 0.25-ml aliquot was inoculated into each of 2 hamsters in 2 separate experiments at days 3, 7, 10, 14, 17, 21, 25, and 30. Blood films were prepared and examined weekly for the presence of parasites from all hamsters. Of hamsters inoculated with blood held at room temperature, only those inoculated at day 3 became positive, whereas 4/4 hamsters inoculated with refrigerated blood on day 17 became parasitemic and 1/4 hamsters inoculated with blood held for 21 days became parasitemic. These results indicate that under blood banking conditions, this intracellular protozoan parasite can remain infective and transfusion-acquired infection with this parasite could occur throughout most of the time that blood is normally stored.

Animals↗
PubMed1994

Mobilization of iron by chiral and achiral anionic 3-hydroxypyrid-4-ones.

In the search for 3-hydroxypyrid-4-ones with enhanced iron-mobilizing ability, seven chiral, anionic amino acid derivatives of maltol (3-hydroxy-2-methyl-4-pyrone) have been synthesized, utilizing L-methionine, L-serine, L-leucine, L-phenylalanine, L-glutamic acid, and the D- and L-isomers of alanine. Two achiral, aromatic compounds were also synthesized and compared with the phenylalanine derivative. The biliary iron excretion following iv injection and the urinary iron excretion following po administration were measured using female Sprague-Dawley rats and compared to that of the standard, 1,2-dimethyl-3-hydroxypyrid-4-one (L1). While none of the compounds was as effective as L1 in enhancing the urinary excretion of iron, all monoanionic chelators increased excretion relative to the controls. All monoanionic compounds were at least equivalent to L1 in enhancing the biliary excretion of iron, with the methionine, leucine, and benzoate derivatives surpassing the standard and the other aromatic compounds also showing strong activity. The dianionic glutamate derivative showed low activity relative to the controls for both urinary and biliary iron excretion. No significant difference in iron excretion was observed due to variation in chirality; molecular weight and the number of negative charges appeared to have the greatest influence on the ability of the various derivatives to enhance iron excretion. In order to evaluate the relative purity of the stereoisomers, the alanine derivatives were analyzed by circular dichroism. Further characterization was provided by UV/vis spectroscopy for all compounds and X-ray crystallography for the novel dianionic derivative.

Animals↗
PubMed1994

A set of ninety-seven overlapping yeast artificial chromosome clones spanning the human Y chromosome euchromatin.

Contiguous arrays of yeast artificial chromosomes (YACs) extending from proximal heterochromatic Yq into the pseudoautosomal portion of the Y chromosome and separated by a small interval at the centromere have been constructed. A total of 97 YACs have been aligned along the Y chromosome by STS content analysis using 222 sequence tagged sites (STSs) that detect 263 loci. Forty-five of the STSs used are novel. Their inclusion provides a significant improvement over previously available maps on the density of STS coverage along the Y chromosome, reducing the average spacing to 120 kb assuming a length of 30 Mb for the euchromatin. The average size of 61 YACs determined by pulsed-field gel electrophoresis analysis was at least 0.9 Mb. Minor differences noted between the ordering of STSs on this map compared with those previously reported may be attributed to inherent polymorphism between the Y chromosomes used to construct the YAC libraries.

Base Sequence↗
PubMed1994

Inhibition of cisplatin toxicity without decreasing antitumor efficacy. Use of a dithiocarbamate.

OBJECTIVE: To demonstrate whether a dithiocarbamate derivative, N-methyl-D-glucaminedithiocarbamate, could prevent anorexia and weight loss and enhance survival without decreasing the antitumor efficacy of high-dose cisplatin therapy. DESIGN: One hundred forty-two mice were randomized into groups receiving cisplatin, 5 mg/kg per day, 7.5 mg/kg per day, or 10 mg/kg per day for three days with or without N-methyl-D-glucaminedithiocarbamate, 1000 mg/kg per day. Weight loss and morbidity were examined between groups. Antitumor efficacy of cisplatin combined with N-methyl-D-glucaminedithiocarbamate was examined using a subcutaneous melanoma model. SETTING: Institutional laboratory. MAIN OUTCOME MEASURES: N-methyl-D-glucaminedithiocarbamate intervention would decrease morbidity, weight loss, and increase survival without decreasing the antitumor efficacy of cisplatin. RESULTS: Weight loss and morbidity were significantly reduced when N-methyl-D-glucaminedithiocarbamate was coadministered with cisplatin (P < .05) at all doses of cisplatin. The antitumor efficacy of high-dose cisplatin therapy (7.5 mg/kg per day and 10 mg/kg per day) was not significantly decreased (P > .05) at all doses of cisplatin. CONCLUSION: As N-methyl-D-glucaminedithiocarbamate seems to limit morbidity and mortality of high-dose cisplatin administration without decreasing its antitumor efficacy, this drug deserves further investigation in the treatment of cancer.

Animals↗