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Biomedical subjects

R Coleman

Publications and source records attributed to R Coleman.

At least 73 records · Page 4Linked to original sources
PubMed2001

Pomegranate juice supplementation to atherosclerotic mice reduces macrophage lipid peroxidation, cellular cholesterol accumulation and development of atherosclerosis.

Inhibition of lipid peroxidation contributes to the attenuation of macrophage cholesterol accumulation, foam-cell formation and atherosclerosis. Evidence suggests that nutritional antioxidants such as pomegranate juice (PJ) can contribute to the reduction of oxidative stress and atherogenesis. The goals of the present study were to determine whether such beneficial effects of PJ exist when supplemented to apolipoprotein E-deficient (E(0)) mice with advanced atherosclerosis and to analyze the antiatherosclerotic activity of a tannin-fraction isolated from PJ. Mice (4-mo-old) were supplemented with PJ in their drinking water for 2 mo and compared with age-matched placebo-treated mice, as well as to young (4-mo-old) control mice, for their mouse peritoneal macrophage (MPM) oxidative state, cholesterol flux and mice atherosclerotic lesion size. PJ supplementation reduced each of the proatherogenic variables determined in the present study compared with age-matched placebo-treated mice. It significantly induced serum paraoxonase activity and reduced MPM lipid peroxide content compared with placebo-treated mice and control mice. PJ administration to E(0) mice significantly reduced the oxidized (Ox)-LDL MPM uptake by 31% and MPM cholesterol esterification and increased macrophage cholesterol efflux by 39% compared with age-matched, placebo-treated mice. PJ consumption reduced macrophage Ox-LDL uptake and cholesterol esterification to levels lower than those in 4-mo-old, unsupplemented controls. PJ supplementation to E(0) mice with advanced atherosclerosis reduced the lesion size by 17% compared with placebo-treated mice. In a separate study, supplementation of young (2-mo-old) E(0) mice for 2 mo with a tannin fraction isolated from PJ reduced their atherosclerotic lesion size, paralleled by reduced plasma lipid peroxidation and decreased Ox-LDL MPM uptake. PJ supplementation to mice with advanced atherosclerosis reduced their macrophage oxidative stress, their macrophage cholesterol flux and even attenuated the development of atherosclerosis. Moreover, a tannin-fraction isolated from PJ had a significant antiatherosclerotic activity.

Animals↗
PubMed2001

Inhibition of hematopoietic progenitor cell proliferation by ethanol in human immunodeficiency virus type 1 tat-expressing transgenic mice.

BACKGROUND: A number of hematological abnormalities are associated with both human immunodeficiency virus type 1 (HIV-1) infection and alcohol abuse. There is little information on how alcohol abuse might further influence the survival and growth of hematopoietic progenitors in HIV-infected individuals in the presence of immune system abnormalities and anti-HIV drugs. Because there is evidence that viral transactivator Tat itself can induce hematopoietic suppression, in this study we examined the role of ethanol as a cofactor in transgenic mice that expressed HIV-1 Tat protein. METHODS: Tat transgenic mice and nontransgenic littermates were given ethanol (20% v/v) and the anti-HIV drug 3'-azido-3'-deoxythymidine (AZT; 1 mg/ml) in drinking water. Immunosuppression in mice was induced by weekly intraperitoneal injections of anti-CD4 antibody. Hematopoiesis was examined by erythroid colony forming unit (CFU-E) and granulocyte/macrophage colony-forming unit (CFU-GM) assays of the bone marrow progenitor cells. RESULTS: Administration of ethanol for 7 weeks resulted in a 50% decrease in the proliferative capacity of CFU-E- and CFU-GM-derived progenitors from transgenic mice compared with that of ethanol-treated nontransgenic controls. Similar decreases also were observed in transgenic mice treated with AZT or a combination of AZT and ethanol. Furthermore, ethanol and AZT were significantly more toxic to the granulopoietic progenitors (40-50% inhibition) than to the erythropoietic progenitors (10-20% inhibition) in Tat transgenic mice. Although a 10 day exposure of Tat transgenic and nontransgenic mice to a combination of ethanol and AZT had no suppressive effect on the erythropoietic and granulopoietic progenitor cells, there was a marked decrease (40-60%) in CFU-GM in mice made immunodeficient by CD4+ T-lymphocyte depletion. The ethanol-treated Tat transgenic mice but not the nontransgenic litter-mates also showed a significant decrease (25%) in CFU-GM. CONCLUSION: Our in vivo study strongly suggests that ethanol ingestion in HIV-1-infected individuals, particularly those on antiretroviral drugs, might increase bone marrow toxicity and contribute to HIV-1-associated hematopoietic impairment.

Animals↗
PubMed2001

Odour emission rates from manure treatment/storage systems.

The effects of agitation, liquid-only manure, depth and time on odour emission rates were investigated. Manure storage tanks were filled to incremental depths every two weeks. At each depth odour samples were collected twice. The second sample was collected seven days after the first. Odour concentration was measured with an olfactometer. Three different pig-manure treatments were investigated. In one treatment, slurry manure in a storage tank was agitated before and during odour sampling. In a second treatment, the settlable solids in manure were removed gravimetrically over 24 hours and liquid manure was pumped to a storage tank. In the third treatment (control), odour samples were collected from unseparated and undisturbed slurry manure. Overall, the odour emission rates in the agitated manure treatment ranged between 0.39 and 1.02 ou s(-1) m(-2), increased with depth and decreased with time, i.e. after seven days at each depth. In the liquid-only manure treatment, the emission rates ranged between 0.09 and 0.69 ou s(-1) m(-2), increased with depth but the effect of time was not evident. In the control treatment, the emission rates ranged between 0.20 and 0.66 ou s(-1) m(-2) and increased with depth on the first odour sampling day but decreased with depth on the second sampling day.

Agriculture↗
PubMed2000

Search for the decay K(L) --> pi(0)&mgr;(+)&mgr;(-)

We report on a search for the decay K(L)-->pi(0)&mgr;(+)&mgr;(-) carried out as a part of the KTeV experiment at Fermilab. This decay is expected to have a significant CP violating contribution and a direct measurement will either support the Cabibbo-Kobayashi-Maskawa mechanism for CP violation or point to new physics. Two events were observed in the 1997 data with an expected background of 0.87+/-0.15 events, and we set an upper limit B(K(L)-->pi(0)&mgr;(+)&mgr;(-))<3. 8x10(-10) at the 90% confidence level.

Journal Article↗
PubMed2000

Human Kaposi's sarcoma cell-mediated tumorigenesis in human immunodeficiency type 1 tat-expressing transgenic mice.

BACKGROUND: The human immunodeficiency virus type 1 (HIV-1) transactivator (Tat) protein has been linked to the development and course of Kaposi's sarcoma (KS) associated with acquired immunodeficiency disease syndrome (AIDS-KS). Tat is an 86-101 amino-acid protein encoded by two exons. To evaluate the growth-promoting effects of Tat in AIDS-KS in vivo, we developed transgenic mice expressing the one-exon-encoded 72 amino-acid protein (Tat(72)) and the two-exon-encoded 86 amino-acid protein (Tat(86)). METHODS: Human KS SLK cells were injected subcutaneously into CD4(+) T-cell-depleted male mice, and the tumors that formed after 3-4 weeks were recovered and analyzed for the expression of Tat protein(s), different cytokine messenger RNAs (mRNAs), and matrix metalloproteinases (MMPs). All statistical tests were two-sided. RESULTS: The average tumor weight was maximum in Tat(86) mice ( approximately 600 mg) compared with Tat(72) ( approximately 200 mg) and nontransgenic ( approximately 100 mg) mice (P<.005). Histologic examination of tumors showed spindle-shaped SLK cells with prominent infiltrates of inflammatory cells. All of the tumors from Tat mice expressed abundant Tat mRNA, suggesting that the infiltrating mouse cells actively expressed Tat. A comparison of the growth-promoting cytokines in the tumors from Tat(86)-transgenic and nontransgenic mice showed that the expression of the following cytokines was substantially increased in the tumors of the Tat(86) mice: tumor necrosis factor-alpha, interleukin 6, interleukin 8, granulocyte-macrophage colony-stimulating factor, and basic fibroblast growth factor. Furthermore, these tumors showed abundant expression of a 105-kd MMP activity associated with infiltrates of host leukocytes in the lesions. CONCLUSION: Our in vivo data clearly suggest that extracellular Tat can contribute to the growth and tumorigenesis of human KS cells.

Animals↗
PubMed2000

Search for the weak decay of a lightly bound H0 dibaryon

We present results of a search for a new form of hadronic matter, a six-quark, dibaryon state called the H0, a state predicted to exist in several theoretical models. Analyzing data collected by experiment E799-II at Fermilab, we searched for the decay H0-->Lambdappi(-) and found no candidate events. We place an upper limit on [B(H0-->Lambdappi(-))dsigma(H)/dOmega]/(dsigma(Xi)/dOmega) and, in the context of published models, exclude the region of lightly bound mass states just below the LambdaLambda mass threshold, 2.194<M(H)<2.231 GeV/c(2), with lifetimes from approximately 5x10(-10) sec to approximately 1x10(-3) sec.

Journal Article↗
PubMed2000

Efficacy of artesunate plus pyrimethamine-sulphadoxine for uncomplicated malaria in Gambian children: a double-blind, randomised, controlled trial.

BACKGROUND: Resistance to cheap effective antimalarial drugs, especially to pyrimethaminesulphadoxine (Fansidar), is likely to have a striking impact on childhood mortality in sub-Sharan Africa. The use of artesunate (artesunic acid) [corrected] in combination with pyrimethamine-sulphadoxine may delay or prevent resistance. We investigated the efficacy, safety, and tolerability of this combined treatment. METHODS: We did a double-blind, randomised, placebo-controlled trial in The Gambia. 600 children with acute uncomplicated Plasmodium falciparum malaria, aged 6 months to 10 years, at five health centres were randomly assigned pyrimethaminesulphadoxine (25 mg/500 mg) with placebo; pyrimethamine-sulphadoxine plus one dose of artesunate (4mg/kg bodyweight); or pyrimethamine-sulphadoxine plus one dose 4 mg/kg bodyweight artesunate daily for 3 days. Children were visited at home each day after the start of treatment until parasitaemia had cleared. FINDINGS: The combined treatment was well tolerated. No adverse reactions attributable to treatment were recorded. By day 1, only 178 (47%) of 381 children treated with artesunate were still parasitaemic, compared with 157 (81%) of 195 children in the pyrimethamine-sulphadoxine alone group (relative risk 1.7 [95% CI 1.5-2.0], p<0.001). Treatment-failure rates at day 14 were 3.1% in the pyrimethamine sulphadoxine alone group, and 3.7% in the one-dose artesunate group (risk difference -0.6% [-4.2 to 3.0]) and 1.6% in the three-dose group (1.5 [1.5-4.5], p=0.048). Symptoms resolved faster in children who received artesunate, but there was no additional benefit for three doses of artesunate over one dose. Children given artesunate were less likely to be gametocytaemic after treatment. INTERPRETATION: The combined treatment was safe, well tolerated, and effective. The addition of artesunate to malaria treatment regimens in Africa results in lower gametocyte rates and may lower transmission rates.

Animals↗
PubMed2000

Observation of CP violation in K(L)-->pi(+)pi(-)e(+)e(-) decays

We report the first observation of a manifestly CP violating effect in the K(L)-->pi(+)pi(-)e(+)e(-) decay mode. A large asymmetry was observed in the distribution of these decays in the CP-odd and T-odd angle straight phi between the decay planes of the e(+)e(-) and pi(+)pi(-) pairs in the K(L) center of mass system. After acceptance corrections, the overall asymmetry is found to be [13.6+/-2. 5(stat)+/-1.2(syst)]%. This is the largest CP-violating effect yet observed when integrating over the entire phase space of a mode and the first such effect observed in an angular variable.

Journal Article↗
PubMed2000

Guidelines for the stratification of patients recruited to trials of therapy for low-risk gestational trophoblastic tumor.

OBJECTIVE: The aim of the study was to initiate a search for factors which might independently predict the need for salvage therapy in patients with low-risk gestational trophoblastic tumor. METHODS: The independent effect of six factors on the need for salvage chemotherapy was assessed in patients with low-risk gestational trophoblastic tumor who were treated with low-dose methotrexate and folinic acid. The accuracies of World Health Organization and Charing Cross Hospital scores were also compared. RESULTS: Age, pretreatment beta hCG, antecedent pregnancy-treatment interval, and the presence of chest metastases detected on chest X ray were not significantly predictive. The size of tumor (P = 0.001) and the presence of chest metastases on chest computerized tomography (P = 0. 00028) had independent, statistically significant predictive power, and a simple prognostic index was derived from these variables. The World Health Organization score was found to be significantly better than the Charing Cross Hospital score. The accuracy of the simple prognostic index was slightly greater than that of the World Health Organization score, although this was not statistically significant. CONCLUSIONS: These results confirm that patients entered into studies of different therapies for low-risk gestational trophoblastic tumor should be stratified and that a simple score, derived from the results of tumor size and chest computerized tomography, is potentially as good as the World Health Organization score for predicting the need for salvage therapy.

Adolescent↗
PubMed2000

9:30-9:45. Preliminary Evaluation of F-18 Fluorocholine (FCH) as a PET Tumor Imaging Agent.

The purpose of this study was to develop and evaluate an F-18 labeled choline tumor imaging agent.FCH was synthesized through the intermediate F-18 fluorobromomethane that was used to alkylate dimethylethanolamine. The isolated FCH was evaluated in PC-3 human prostate cancer cells, PC-3 human prostate cancer xenograft studies, and human prostate and brain tumor patients.FCH was accumulated at a slightly lower rate than FDG in the cultures of PC-3 cells. Inhibition of choline transport and phosphorylation by hemicholinium-3 resulted in a 90% decrease in FCH uptake without altering FDG uptake. FCH had a similar biodistribution as C-14 choline in mice, with the liver and kidneys being the primary sites of uptake. Tumor uptake of FCH and FDG were comparable at 45-60 mins after injections. The tumor:blood ratio was higher for FCH (5.3 +/- 2.4) than for FDG (3.2 +/- 0.3). Brain uptake of FCH was 10% that of FDG. FCH-PET studies were compared to FDG-PET studies. In the prostate cancer patients, more lesions have been seen on the FCH studies than on the FDG studies, and the standardized uptake values (SUV) have been higher with the FCH. Decreases in FCH-PET SUV have been noted in patients treated by androgen deprivation. Patients with suspected recurrent brain tumors have had more clearly defined abnormal accumulation on the FCH-PET scans than on the FDG-PET scans. The FCH is not accumulated by normal cortex.FCH is a promising imaging agent for the evaluation of metastatic prostate cancer and recurrent brain tumor.

Journal Article↗
PubMed2000

27. PET Image Interpretation. Attenuation-Corrected (ATN) Vs Non-Attenuation Corrected (NATN) Images.

Purpose: The purpose of this study was to evaluate the difference, if any, in lesion detection in ATN and NATN images.Methods: Sixty-one consecutive patients having clinical whole body FDG PET scans for oncologic indications were included. The patients were administered 10-20 mCi FDG intravenously, and imaging on the Advance (GE Medical Systems) was started 45 min-1 h after injection. The emission images were acquired for 4 min and the transmission images for 3 min per bed position. The images were reviewed on the vendor-provided workstation. Four of the interpreting physicians read the ATN images first, and the other read the NATN images first. The interpreting physicians were asked to determine if any lesions were seen on only the ATN or NATN images (discordant findings) and to describe differences in the images not affecting overall interpretation.Results: In the 61 patients, 3 discordant findings with abnormalities on the ATN images but not on the NATN images included the following: lung nodule, AP window node, and small para-aortic node. Observations that did not affect overall interpretation include the following: transmission scan helped localize lesion to be below instead of above the diaphragm; AT-N image better demonstrated liver metastasis; benign lung lesion seen only on ATN image (3 cases); pretracheal node seen better on NATN images; and low grade hilar activity on NATN not seen on ATN images.Conclusion: These results demonstrate that the ATN images detect more lesions than the NATN images, and that reviewing NATN images may not be necessary. A different method for performing this evaluation is now being undertaken.

Journal Article↗
PubMed2000

EORTC 10941: A phase II study of liarozole in postmenopausal patients with 'chemotherapy-resistant' or 'potentially hormone sensitive' metastatic breast cancer.

Liarozole is an imidazole compound that inhibits enzymes involved in steroid hormone aromatisation and retinoid metabolism. The IDBBC branch of the EORTC has performed a series of phase II studies of the agent in four groups of postmenopausal women with metastatic breast cancer. This paper reports the results of the first two groups: 'Chemotherapy Resistant' (unrestricted ER status, 1 or 2 prior chemotherapy regimens, 0-2 prior hormonal therapies) and 'Potentially Hormone Sensitive' (ER positive or unknown, 1 or 2 prior hormonal therapies with a substantial disease free interval or progression free survival, and no history of chemotherapy for metastatic disease). Liarozole was administered at 150-300 mg orally bid. The objective response rate was 12% in the 'Chemotherapy Resistant' group (n = 34), and 22% in the 'Potentially Hormone Sensitive' group (n = 37), with median response durations of 9 and 14 months, respectively. Median time to treatment failure was only 2 months in both groups, due largely to the significant percentage (24%) of patients who ceased treatment following excessive mucocutaneous and gastrointestinal toxicity. This adverse event profile will limit its use in breast cancer. Results of the 'ER negative' and 'Tamoxifen Refractory' groups will be reported in a future paper.

Adult↗
PubMed2000

Absorption of iron in rats with experimental enteritis.

Inflammatory conditions of the gastrointestinal tract and iron-deficiency anemia are very common in humans. Acute intestinal inflammation was pathologically established in rats by intraluminal administration of acetic acid into the duodenum and the proximal jejunum. The study included two control groups of intact (untreated) rats and sham-operated (saline-treated) rats for each intestinal segment. A third group of rats received acetic acid. The acetic acid-induced inflammatory process was established histopathologically and biochemically. Two days after treatment, iron absorption was measured using ligated 10-cm loops of proximal jejunum or ligated duodenum in which 59Fe was injected intraluminally (n = 6 in each group). In another four control groups (intact and sham-operated for each intestinal segment) and two acetic acid-treated groups, serosal-luminal secretion of 59Fe was measured after intravenous injection (n = 5 in each group). 59Fe transfer from the lumens of the duodenum and jejunum to the portal system was significantly lower in those rats in whom inflammation was induced by acetic acid. There was no apparent serosal-luminal secretion of intravenously injected 59Fe in any of the studied groups. We conclude that acetic acid-induced intestinal inflammation significantly reduces iron absorption by the duodenum and the proximal jejunum.

Acetic Acid↗
PubMed2000

Hepatocyte couplets.

Hepatocyte couplets, by retaining functional and morphological polarity similar to that of hepatocytes in situ, are a valuable in vitro model to study mechanisms of bile secretion, cholestasis and hepatocellular injury. They have been useful in studies of the hormonal control of bile formation and are suitable for morphological studies. The availability of periportal- and perivenous-enriched couplet populations now allows a zonal perspective. Their contribution to our understanding of regulatory aspects of hepatobiliary dysfunction due to toxicological or cholestatic insult, as well as its reversion by using hepatoprotective agents, is still at an early stage. The next few years should see further exiting contributions to our understanding of hepatobiliary function and dysfunction.

Animals↗
PubMed2000

Control by signaling modulators of the sorting of canalicular transporters in rat hepatocyte couplets: role of the cytoskeleton.

Hormonal control of the restoration of hepatocanalicular polarity in short-term cultured hepatocyte couplets was analyzed. One hour following isolation, couplets were unable to accumulate the fluorescent bile acid analogue, cholyl-lysyl-fluorescein (CLF), and showed a nonpolarized distribution of F-actin and mrp2 over the cell body. A progressive, time-dependent restoration of couplet-polarized function and morphology was reached after 4 hours of culture. Both dibutyryl cyclic adenosine monophosphate (DBcAMP) and the Ca(2+)-elevating compound, thapsigargin, accelerated restoration of normal couplet morphology and function. The DBcAMP-mediated stimulus was inhibited by the Ca(2+) chelator, 1, 2-bis-(o-aminophenoxy)-ethene-N,N,N',N'-tetra-acetate tetra-(acetomethyl)ester (BAPTA/AM), but not by the protein kinase A (PKA) inhibitors, KT5720 or H89, suggesting that Ca(2+) elevation rather than PKA activation is involved. N-(6-aminohexyl-5-chloro-1-napththalenesulfonamide (W-7), a calmodulin inhibitor, and the protein kinase C (PKC) activator, phorbol dibutyrate, inhibited both the basal and the DBcAMP-stimulated recovery of functional polarity, whereas staurosporine and Gö 6976, 2 PKC inhibitors, accelerated the basal recovery of polarized function. Disruption of the microtubule cytoskeleton by colchicine induced only minor changes under basal, but not under DBcAMP-stimulated, conditions. The Golgi complex disruptor, brefeldin A, significantly delayed, and the microfilament-disrupting agent, cytochalasin D, fully blocked, both processes. However, DBcAMP stimulated trafficking of vesicles containing CLF to the pericanalicular region under the last condition. Our results indicate that restoration of couplet polarity following isolation occurs via a Ca(2+)-calmodulin-mediated mechanism, which depends on microfilament, but not on microtubule integrity. A second pathway is activated by DBcAMP activation via Ca(2+)-calmodulin formation, whose requirements with respect to cytoskeletal components are opposite. PKC has a negative regulatory role in both pathways.

Actins↗
PubMed2000

The impact of histochemistry--a historical perspective.

Histochemistry has a remarkable long-term impact on cell and tissue biology, embryology, and pathology and remains at the forefront of research in these disciplines. Histochemical techniques, and particularly immunohistochemical and in situ hybridization techniques, are now more widely used than ever and, in conjunction with new developments in microscopical imaging and analysis, will continue to have an important position in the life sciences and medicine. However, histochemistry is often mistakenly perceived as an archaic discipline, and its contributions to cell and molecular biology are not always given the credit it deserves.

Histocytochemistry↗
PubMed2000

'You'll never walk alone': CCTV surveillance, order and neo-liberal rule in Liverpool city centre.

This paper is concerned to chart the establishment and uses of CCTV within the location of Liverpool city centre. In doing this the paper seeks to contextualize CCTV within contemporary 'partnership' approaches to regeneration which are reshaping the material and discursive form of the city. Thus CCTV schemes along with other security initiatives are understood as social ordering strategies emanating from within locally powerful networks which are seeking to define and enact orderly regeneration projects. In focusing on the normative aspects of CCTV, the paper raises questions concerning the efficacy of understanding contemporary forms of 'social ordering practices' primarily in terms of technical rationalities while neglecting other, more material and ideological processes involved in the construction of social order.

Authoritarianism↗