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Biomedical subjects

A Mullen

Publications and source records attributed to A Mullen.

14 recordsLinked to original sources
PubMed2005

Effect of dietary supplementation with conjugated linoleic acid on markers of calcium and bone metabolism in healthy adult men.

INTRODUCTION: Conjugated linoleic acid (CLA) has been shown to positively influence calcium and bone metabolism in experimental animals and cells in culture, but there are limited human data available. OBJECTIVE: To investigate the effect of CLA supplementation on biomarkers of calcium and bone metabolism in healthy adult males. DESIGN: The study consisted of a double-blind, placebo-controlled trial in which 60 healthy adult males (aged 39-64 y) were randomly assigned to receive daily either 3.0 g CLA isomer blend (50:50% cis-9,trans-11:trans-10,cis-12 isomers) or a palm/bean oil blend (placebo) for 8 weeks. Urine and blood samples were collected at weeks 0 and 8 and were analysed for biomarkers of calcium and bone metabolism. RESULTS: Supplementation with CLA or placebo for 8 weeks had no significant effects on markers of bone formation (serum osteocalcin and bone-specific alkaline phosphatase) or bone resorption (serum C-telopeptide-related fraction of type 1 collagen degradation products, urinary N-telopeptide-related fraction of type 1 collagen degradation products, urinary pyridinoline and deoxypyridinoline), or on serum or urinary calcium levels. Baseline levels of these biochemical parameters were similar in both groups of subjects. While the placebo had no effect, CLA supplementation resulted in a three-fold increase (P<0.00001) in cis-9,trans-11 CLA isomer in total plasma lipids. CONCLUSION: Under the conditions tested in this double-blind, placebo-controlled trial in adult men, a CLA supplement of mixed isomers did not affect markers of calcium or bone metabolism. Further investigation of the effects of CLA on calcium and bone metabolism in other gender- and age-groups is warranted.

Adult↗
PubMed2001

Fibroblast growth factor 2 activation of stromal cell vascular endothelial growth factor expression and angiogenesis.

Angiogenesis is a key component of human cancer progression and metastasis. In an effort to recapitulate early events in tumor-induced angiogenesis, we have employed a subcutaneous Matrigel implant model using immunodeficient mice as hosts. Matrigel-containing fibroblast growth factor 2 (FGF-2; 1.2 microg/ml) induced stromal cell infiltration into the Matrigel/skin interface within 4 days and maximal neovascularization at 7 days. Cells staining positive for the endothelial cell marker, platelet-endothelial cell adhesion molecule 1 (PECAM-1), were present in neovessels and in isolated cells within the Matrigel matrix. Immunohistochemical analysis revealed high levels of vascular endothelial growth factor (VEGF) deposited in the stromal interface present only in the FGF-2-containing but not in control Matrigel implants. VEGF expression was confirmed with in situ hybridization. High VEGF mRNA levels were observed in the infiltrating stromal cells but not in endothelial or endothelial precursors as defined by PECAM-1 staining. In vitro analysis of FGF-2-treated embryonic fibroblasts, Balb/c 3T3 cells, showed an induction of VEGF transcription, mRNA synthesis, and protein secretion as defined by transcriptional reporter, Northern blot, and ELISA assays. The FGF-2-induced VEGF expression was not dependent on select matrix adherence or signaling components because VEGF mRNA expression induced by FGF-2 was equally activated on serum, basement membrane, and fibronectin matrix substrates. Systemic application of anti-VEGF antibodies significantly repressed FGF-2-induced angiogenesis over control antibody by 88% (p < 0.001). These data support an FGF-2 angiogenic model that is dependent on endothelial cell activation, stromal cell infiltration, and VEGF expression by the infiltrating stromal cell population.

3T3 Cells↗
PubMed1999

Role of protein kinase C isoforms in phorbol ester-induced vascular endothelial growth factor expression in human glioblastoma cells.

Aberrant expression of the potent angiogenic cytokine, vascular endothelial growth factor (VEGF), has been demonstrated to be associated with most human solid tumors. Both transcriptional and post-transcriptional mechanisms have been shown to modulate VEGF expression in a multitude of cell types. Here we report that when protein kinase C (PKC) pathways were activated in human glioblastoma U373 cells by phorbol 12-myristate 13-acetate (PMA), VEGF mRNA expression was up-regulated via a post-transcriptional mRNA stabilization mechanism. PMA treatment exhibited no increase in VEGF-specific transcriptional activation as determined by run-off transcription assays and VEGF promoter-luciferase reporter assays. However, PMA increased VEGF mRNA half-life from 0.8 to 3.6 h which was blocked by PKC inhibitors but not by protein kinase A or cyclic nucleotide-dependent protein kinase inhibitors. When U373 cells were transfected with antisense oligonucleotide sequences to the translation start sites of PKC-alpha, -beta, -gamma, -delta, -epsilon, or -zeta isoforms, both PKC-alpha and -zeta antisense oligonucleotides showed substantial inhibition of PMA-induced VEGF mRNA. In addition, overexpression of PKC-zeta resulted in a strong constitutive up-regulation of VEGF mRNA expression. This study demonstrates for the first time that specific PKC isoforms regulate VEGF mRNA expression through post-transcriptional mechanisms.

Endothelial Growth Factors↗
PubMed1999

AIDS diagnosis and depression in the Multicenter AIDS Cohort Study: the ameliorating impact of pet ownership.

The impact of pet ownership on depression was tested among a sample of gay and bisexual men (n = 1,872). Multivariate analyses, controlling for demographics and baseline depressive symptomatology, showed that neither pet ownership nor the presence of HIV infection was associated with depression. Depression was influenced by the presence of AIDS and by having relatively few confidants. Analyses among HIV-infected men only showed that persons with AIDS who owned pets reported less depression than persons with AIDS who did not own pets. This beneficial effect of pet ownership occurred principally among persons who reported fewer confidants. These results suggest that by enhancing companionship for some HIV-infected persons, pets may buffer the stressful impact of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Ramipril prevents basal arterial constriction and enhanced myogenic tone in the femoral artery in mildly uraemic normotensive rats.

Some aspects of vascular reactivity are altered in mild experimental uraemia, as shown by increased myogenic tone and a reduced lumen diameter in the femoral artery. This study was conducted to investigate the prevention of these uraemia-induced vascular abnormalities by the angiotensin-converting enzyme inhibitor (ACE-I) Ramipril. Ten male Wistar rats were rendered uraemic (U) by 5/6th nephrectomy, and 10 control (C) rats were concurrently sham-operated. After 4 weeks, both groups were given daily subcutaneous injections of 3 microg of Ramipril for a further 4 weeks. Tail-cuff systolic blood pressure was then recorded and the rat was killed. Isolated femoral arteries were mounted on a pressure myograph and pressurized at 40 mmHg for baseline measurements of the lumen internal diameter. Myogenic tone was then assessed over a range of intravascular pressures from 40 to 160 mmHg. Biochemically, serum urea and creatinine were significantly higher in the uraemic (U) group [urea: U, 23+/-3 mmol/l; C, 6+/-1 mmol/l (P<0.001); creatinine: U, 147+/-17 mmol/l, C, 72+/-11 mmol/l (P<0.01)]. Systolic blood pressure was the same in both groups (U, 127+/-7 mmHg; C, 127+/-3 mmHg). The mean baseline internal diameter was the same in both groups (U, 756+/-22 microm; C, 721+/-34 microm, not significant), as was mean myogenic tone (U, 4.7+/-1%; C, 3.4+/-1%). In conclusion, there were no differences in baseline lumen diameter or myogenic tone in uraemic compared with control femoral arteries of rats treated with Ramipril, which suggests that Ramipril may prevent the development of elevated myogenic tone and decreased lumen diameter previously observed in this model of uraemia. These results suggest that these specific vascular abnormalities in uraemia may be mediated by renin or bradykinin, or by the direct action of angiotensin II on vascular smooth muscle.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Identification of a human VPF/VEGF 3' untranslated region mediating hypoxia-induced mRNA stability.

Hypoxia is a prominent feature of malignant tumors that are characterized by angiogenesis and vascular hyperpermeability. Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) has been shown to be up-regulated in the vicinity of necrotic tumor areas, and hypoxia potently induces VPF/VEGF expression in several tumor cell lines in vitro. Here we report that hypoxia-induced VPF/VEGF expression is mediated by increased transcription and mRNA stability in human M21 melanoma cells. RNA-binding/electrophoretic mobility shift assays identified a single 125-bp AU-rich element in the 3' untranslated region that formed hypoxia-inducible RNA-protein complexes. Hypoxia-induced expression of chimeric luciferase reporter constructs containing this 125-bp AU-rich hypoxia stability region were significantly higher than constructs containing an adjacent 3' untranslated region element without RNA-binding activity. Using UV-cross-linking studies, we have identified a series of hypoxia-induced proteins of 90/88 kDa, 72 kDa, 60 kDa, 56 kDa, and 46 kDa that bound to the hypoxia stability region element. The 90/88-kDa and 60-kDa species were specifically competed by excess hypoxia stability region RNA. Thus, increased VPF/VEGF mRNA stability induced by hypoxia is mediated, at least in part, by specific interactions between a defined mRNA stability sequence in the 3' untranslated region and distinct mRNA-binding proteins in human tumor cells.

Base Sequence↗
PubMed1998

Multinational pharmaceutical companies gather in Berlin.

The 39th Annual General Meeting of the Pharma Documentation Ring (PDR) was held in Berlin, Germany, on September 26, 1997. Common themes reported on included the impact and widespread use of intranet technology; expansion in end-user searching; experience with electronic journals; and programs for the development of electronic archiving and document management systems. Other sessions discussed aspects of chemistry systems; copyright; drug information systems on development products; information management, in-house management of databases; Intranet/Internet activities; and patents. The core topic presented at the meeting involved an overview on document delivery/electronic journals. There is considerable activity in this area by primary and secondary publishers with real momentum seen in the area of electronic document delivery services on the Internet. The 40th anniversary of the PDR will be celebrated at the upcoming AGM, to be held in Montpellier, France, September 30 October 2, 1998.

Journal Article↗
PubMed1989

[Online patent searching--rapid responses to critical questions].

Online searching in publically available patent files opens up interesting possibilities to provide a rapid response to critical questions. A computerized analysis of all patents of leading German pharmaceutical companies over the last decade in important indication areas is described. Supported by subsequent manual processing of individual patents it is shown that duplicate experiments on animals practically never occur.

Chemical Phenomena↗
PubMed1977

Dreaming, fenfluramine, and vitamin C.

The effect of increasing doses of fenfluramine on dream patterns was studied in 20 patients receiving a reducing diet with or without a controlled dietary intake of vitamin C daily. The dream pattern was unchanged in six patients and dreams disappeared in another who normally dreamed often. In 13 patients dreams increased in frequency and intensity, and in five the dreams assumed frightening proportions. There was a significant straight-line relation between response and the size of the dose. When placebo tablets were given to four patients their dreams disappeared or assumed their pretreatment normal pattern. Absence of vitamin C from the diet did not significantly affect the dream pattern. That fenfluramine has dose-related cerebral effects should be remembered in patients with a history of mental illness.

Ascorbic Acid↗