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Biomedical subjects

A Manning

Publications and source records attributed to A Manning.

At least 19 recordsLinked to original sources
PubMed2006

Epidemiological profile and clinical associations of human bocavirus and other human parvoviruses.

BACKGROUND: Human bocavirus (HBoV) and PARV4 are newly discovered human parvoviruses. HBoV, which was first detected in respiratory samples, has a potential role in the development of human respiratory disease. The present study compared the frequencies, epidemiological profiles, and clinical backgrounds of HBoV and PARV4 infections with those of other respiratory virus infections, by evaluating diagnostic samples referred to the Specialist Virology Laboratory (SVL) at the Royal Infirmary of Edinburgh (Edinburgh, United Kingdom). METHODS: Anonymized samples and study subject information were obtained from the respiratory sample archive of the SVL. Samples were screened for HBoV, PARV4, B19, respiratory syncytial virus (RSV), adenoviruses, influenza viruses, and parainfluenza viruses by use of nested polymerase chain reaction. RESULTS: HBoV infection was detected in 47 (8.2%) of 574 study subjects, ranking third in prevalence behind RSV infection (15.7%) and adenovirus infection (10.3%). Peak incidences of HBoV were noted among infants and young children (age, 6-24 months) during the midwinter months (December and January) and were specifically associated with lower respiratory tract infections. HBoV infections were frequently accompanied by other respiratory viruses (frequency, 43%), and they were more prevalent among individuals infected with other respiratory viruses (17%), frequently adenovirus or RSV. All respiratory samples were negative for PARV4. CONCLUSIONS: In the present study, HBoV was a frequently detected, potential respiratory pathogen, with a prevalence and an epidemiological profile comparable to those of RSV. Identification of HBoV infections may be clinically important in the future.

Female↗
PubMed2006

Song of the dunes as a self-synchronized instrument.

Since Marco Polo it has been known that some sand dunes have the peculiar ability to emit a loud sound with a well-defined frequency, sometimes for several minutes. The origin of this sustained sound has remained mysterious, partly because of its rarity in nature. It has been recognized that the sound is not due to the air flow around the dunes but to the motion of an avalanche, and not to an acoustic excitation of the grains but to their relative motion. By comparing singing dunes around the world and two controlled experiments, in the laboratory and the field, we prove that the frequency of the sound is the frequency of the relative motion of the sand grains. Sound is produced because moving grains synchronize their motions. The laboratory experiment shows that the dune is not needed for sound emission. A velocity threshold for sound emission is found in both experiments, and an interpretation is proposed.

Colloids↗
PubMed2004

Can the confidence in long range atmospheric transport models be increased? The pan-european experience of ensemble.

Is atmospheric dispersion forecasting an important asset of the early-phase nuclear emergency response management? Is there a 'perfect atmospheric dispersion model'? Is there a way to make the results of dispersion models more reliable and trustworthy? While seeking to answer these questions the multi-model ensemble dispersion forecast system ENSEMBLE will be presented.

Air Movements↗
PubMed2001

NF-kappa B regulation by I kappa B kinase-2 in rheumatoid arthritis synoviocytes.

IkappaB kinase-1 and IkappaB kinase-2 (IKK1 and IKK2; also called IKKalpha and IKKbeta, respectively) are part of the signal complex that regulates NF-kappaB activity in many cell types, including fibroblast-like synoviocytes (FLS). We determined which of these two kinases is responsible for cytokine-induced NF-kappaB activation in synoviocytes and assessed the functional consequences of IKK1 or IKK2 overexpression and inhibition. FLS were infected with adenovirus constructs encoding either wild-type (wt) IKK1 or IKK2, the dominant negative (dn) mutant of both kinases, or a control construct encoding green fluorescence protein. Analysis of the NF-kappaB pathway revealed that cytokine-induced IKK activation, IkappaB degradation, and NF-kappaB activation was prevented in cells expressing the IKK2 dn mutant, whereas baseline NF-kappaB activity was increased by IKK2 wt. In addition, synthesis of IL-6 and IL-8, as well as expression of ICAM-1 and collagenase, was only increased by IKK2 wt, and their cytokine-induced production was abrogated by IKK2 dn mutant. However, the IKK1 dn mutant did not inhibit cytokine-mediated activation of NF-kappaB or any of the functional assays. These data indicate that IKK2 is the key convergence pathway for cytokine-induced NF-kappaB activation. Furthermore, IKK2 regulates adhesion molecule, matrix metalloproteinase, and cytokine production in FLS.

Adenoviridae↗
PubMed2001

Ganglioneurocytoma mimicking a malignant tumor: case report with a literature review of the MRI appearance of neurocytomas and gangliogliomas.

A 14-year-old girl presented with symptoms of increased intracranial pressure after her head was squeezed at a party. MRI demonstrated a mass that was hypointense to brain on T1WI and heterogeneous in signal on PD and T2WI; compression of the ventricle, midline shift, and mild ventriculomegaly also were present. Contrast enhancement was extensive and heterogeneous, mimicking a malignant tumor. Neuropathology revealed a ganglioneurocytoma.

Adolescent↗
PubMed2001

Mutation analysis of a Mauritian hereditary breast cancer family reveals the BRCA2 6503deITT mutation previously found to recur in different ethnic populations.

Mauritius, a small island some 855 km off the east coast of Madagascar, has a multiethnic population of about 1.2 million with a high population density of about 611 per km(2). The recent industrialization of the island seems to have been accompanied, in less than 10 years, by an increase of at least 30% in breast cancer incidence. We have detected the BRCA2 6503delTT mutation in two sisters of the same family of Indian origin but living in Mauritius for at least five generations. This mutation has been found to recur in geographically diverse populations and haplotype analysis has shown a common ancestry. The haplotype of the mutation found in the Mauritian family differs from that found in other populations harbouring the same mutation, suggesting that the BRCA2 6503delTT mutation most likely arose independently.

BRCA2 Protein↗
PubMed1999

Immunohistochemical analysis of the activation of NF-kappaB and expression of associated cytokines and adhesion molecules in human models of allergic inflammation.

To investigate the role of NF-kappaB in regulating allergic inflammation, a monoclonal antibody directed to the activated form of NF-kappaB has been developed and immunohistochemistry has been employed to study the pro-inflammatory transcriptive function of NF-kappaB and the adhesion molecules and cytokines that it regulates. Human umbilical vein endothelial cells (HUVECs) exposed to physiological levels of TNFalpha demonstrated dose- and time-dependent cytoplasmic and nuclear activation of NF-kappaB, followed by up-regulation of ICAM-1. This was suppressed by the selective inhibitors of NF-kappaB activation, calpain and gliotoxin. Using monoclonal antibodies directed to NF-kappaB and associated cytokines and adhesion molecules, immunohistochemistry was applied to bronchial explants stimulated ex vivo with TNFalpha, and to nasal polyp tissue, embedded in glycol methacrylate. Stimulation of the bronchial explants increased expression of NF-kappaB, IL-8, and GM-CSF in the epithelium and endothelium and ICAM-1 in the endothelium. In nasal polyp, expression of NF-kappaB was in the epithelium, the endothelium and in submucosal mast cells, eosinophils, T and B lymphocytes, and macrophages. Thus, immunohistochemistry can be used to determine the cellular provenance of NF-kappaB and its activation status in single cell and complex tissue systems, in parallel with appropriate inflammatory markers.

Animals↗
PubMed1999

Tourette syndrome associated with unilateral cystic changes in the gyrus rectus.

Brain magnetic resonance imaging of an 11-year-old male with Tourette syndrome demonstrated multicystic changes predominately in the gyrus rectus of the left frontal lobe. Other brain regions, including the basal ganglia, were normal. He did not have any symptoms of the comorbid conditions associated with Tourette syndrome, such as attention-deficit disorder or obsessive-compulsive disorder. The possible neurobiologic connection between Tourette syndrome and the gyrus rectus and its interconnecting pathways is discussed.

Child↗
PubMed1998

Effect of aspirin on protein binding and tissue disposition of oligonucleotide phosphorothioate in rats.

Pharmacokinetic studies of phosphorothioate oligodeoxynucleotides (PS-oligonucleotides) in animals show that following intravenous administration, PS-oligonucleotide clears out rapidly from the plasma and is distributed to majority of the organs. PS-oligonucleotides are bound to plasma proteins extensively. This study was aimed to determine the effect of aspirin, a commonly used drug, on pharmacokinetics of PS-oligonucleotides. In the present study, PS-oligonucleotide was administered to rats that had received aspirin by gavage. Pharmacokinetic study shows that if PS-oligonucleotide was administered following aspirin administration in rats, a) plasma pharmacokinetic parameters (t1/2alpha?, t1/2beta, AUC, etc.) had lower values, b) tissue disposition was different, and c) rate and route of elimination was affected in animals compared to rats receiving PS-oligonucleotide alone. This finding suggests that pharmacokinetics of PS-oligonucleotides can be affected with certain class of drugs, which may have direct impact on biological activity and safety.

Animals↗
PubMed1997

IKK-1 and IKK-2: cytokine-activated IkappaB kinases essential for NF-kappaB activation.

Activation of the transcription factor nuclear factor kappa B (NF-kappaB) is controlled by sequential phosphorylation, ubiquitination, and degradation of its inhibitory subunit IkappaB. A large multiprotein complex, the IkappaB kinase (IKK) signalsome, was purified from HeLa cells and found to contain a cytokine-inducible IkappaB kinase activity that phosphorylates IkappaB-alpha and IkappaB-beta. Two components of the IKK signalsome, IKK-1 and IKK-2, were identified as closely related protein serine kinases containing leucine zipper and helix-loop-helix protein interaction motifs. Mutant versions of IKK-2 had pronounced effects on RelA nuclear translocation and NF-kappaB-dependent reporter activity, consistent with a critical role for the IKK kinases in the NF-kappaB signaling pathway.

Cell Cycle Proteins↗
PubMed1997

Mixed backbone antisense oligonucleotides: design, biochemical and biological properties of oligonucleotides containing 2'-5'-ribo- and 3'-5'-deoxyribonucleotide segments.

We have designed and synthesized mixed backbone oligonucleotides (MBOs) containing 2'-5'-ribo- and 3'-5'-deoxyribonucleotide segments. Thermal melting studies of the phosphodiester MBOs (three 2'-5'linkages at each end) with the complementary 3'-5'-DNA and -RNA target strands suggest that 2'-5'-ribonucleoside incorporation into 3'-5'-oligodeoxyribonucleotides reduces binding to the target strands compared with an all 3'-5'-oligodeoxyribonucleotide of the same sequence and length. Increasing the number of 2'-5'linkages (from six to nine) further reduces binding to the DNA target strand more than the RNA target strand [Kandimalla,E.R. and Agrawal,S. (1996)Nucleic Acids Symp. Ser., 35, 125-126]. Phosphorothioate (PS) analogs of MBOs destabilize the duplex with the DNA target strand more than the duplex with the RNA target strand. Circular dichroism studies indicate that the duplexes of MBOs with the DNA and RNA target strands have spectral characteristics of both A- and B-type conformations. Compared with the control oligonucleotide, MBOs exhibit moderately higher stability against snake venom phosphodiesterase, S1 nuclease and in fetal calf serum. Although 2'-5'modification does not evoke RNase H activity, this modification does not effect the RNase H activation property of the 3'-5'-deoxyribonucleotide segment adjacent to the modification. In vitro studies with MBOs suggest that they have lesser effects on cell proliferation, clotting prolongation and hemolytic complement lysis than do control PS oligodeoxyribonucleotides. PS analogs of MBOs show HIV-1 inhibition comparable with that of a control PS oligodeoxyribonucleotide with all 3'-5'linkages. The current results suggest that a limited number of 2'-5'linkages could be used in conjunction with PS oligonucleotides to further modulate the properties of antisense oligonucleotides as therapeutic agents.

Animals↗
PubMed1996

Single stand targeted triplex formation: physicochemical and biochemical properties of foldback triplexes.

Oligodeoxyribonucleotides containing both Watson-Crick and Hoogsteen hydrogen bonding domains joined by a nucleotide loop (FTFOs) are studied for their binding affinity and specificity to the DNA and RNA single-stranded targets. Thermal denaturation studies reveal that FTFOs have high binding affinity for their targets than do antisense (duplex forming) and antigene (triplex forming) oligonucleotides, because of involvement of both the Watson-Crick and Hoogsteen domains in the interaction. Studies with FTFOs containing different sizes and sequences of loops show that 4-6 bases long loops are optimum for binding; loop sequence does not have a dramatic effect on binding. The FTFOs have greater sequence specificity than do antisense and antigene oligonucleotides because they read the target sequence twice. SI-, PI- and mung bean nuclease protection assays show that the DNA FTFO forms a stable triplex with the DNA target strand, but a weak or no triplex with the RNA target strand. Gel mobility shift assay is used to determine binding of FTFOs to DNA and RNA targets. The circular dichroism (CD) spectrum of the foldback triplex formed with the DNA target strand resembles the B-DNA spectrum, suggesting that the triplex has a B-type of conformation.

Binding Sites↗
PubMed1996

E-selectin in focal cerebral ischemia and reperfusion in the rat.

The selectin family of glycoproteins facilitates the early phase of polymorphonuclear leukocyte adhesion to the endothelial cell and, thus, may promote ischemic cell damage. To evaluate E-selectin in the pathogenesis of focal cerebral ischemia and reperfusion injury, we cloned rat E-selectin cDNA and measured the temporal profiles E-selectin mRNA (Northern blot) and protein (immunohistochemistry) during (1 h of ischemia) and after (up to 1 week) transient (2 h) middle cerebral artery (MCA) occlusion in the male Wistar rat. We also tested the effect on these rats of administration of CY-1503, an analog of sialyl Lewis(x) (SLe(x)), on ischemia cell damage. mRNA for E-selectin was first detected in the ischemic hemisphere at 2 h of reperfusion and persisted to 46 h of reperfusion. E-selectin (protein) was localized to microvessels within the ischemic lesion at 0 h of reperfusion and persisted to 70 h of reperfusion. Treatment of the ischemic animals with CY-1503 (50 mg/kg) (n = 8) significantly reduced infarct volume by 42% (p < 0.05) and significantly reduced myeloperoxidase immunoreactive cells in the ischemic lesion by 60% (p < 0.05). These findings provide the first direct evidence for the involvement of E-selectin in transient MCA occlusion in rats and suggest that the E-selectin may facilitate neutrophil adhesion and subsequent cerebral ischemic cell damage.

Amino Acid Sequence↗
PubMed1995

Design, biochemical, biophysical and biological properties of cooperative antisense oligonucleotides.

Short oligonucleotides that can bind to adjacent sites on target mRNA sequences are designed and evaluated for their binding affinity and biological activity. Sequence-specific binding of short tandem oligonucleotides is compared with a full-length single oligonucleotide (21mer) that binds to the same target sequence. Two short oligonucleotides that bind without a base separation between their binding sites on the target bind cooperatively, while oligonucleotides that have a one or two base separation between the binding oligonucleotides do not. The binding affinity of the tandem oligonucleotides is improved by extending the ends of the two oligonucleotides with complementary sequences. These extended sequences form a duplex stem when both oligonucleotides bind to the target, resulting in a stable ternary complex. RNase H studies reveal that the cooperative oligonucleotides bind to the target RNA with sequence specificity. A short oligonucleotide (9mer) with one or two mismatches does not bind at the intended site, while longer oligonucleotides (21mers) with one or two mismatches still bind to the same site, as does a perfectly matched 21mer, and evoke RNase H activity. HIV-1 inhibition studies reveal an increase in activity of the cooperative oligonucleotide combinations as the length of the dimerization domain increases.

Antiviral Agents↗
PubMed1995

Effects of irbesartan (SR47436/BMS-186295) on angiotensin II-induced pressor responses in the pithed rat: potential mechanisms of action.

The effects of two new non-peptide angiotensin receptor antagonists, irbesartan (SR 47436/BMS-186295, (2-n-butyl-4-spirocyclopentane-1-[((2'-tetrazol-5-yl)bipheny l-4-yl)methyl]2 - imidazolin-5-one) and SR 47155A (2-n-butyl-4-spirocyclopentane-1-[((2'-carboxy)biphenyl-4-yl)methy l]2- imidazolin-5-one, trifluoroacetate), on angiotensin II-induced pressor responses were studied in the pithed rat in comparison to losartan, EXP 3174 and [Sar1,Val5,Ala8]angiotensin II. SR 47155A (1-10 mg/kg i.v.) and losartan (1-10 mg/kg i.v.) shifted dose dependently the dose-response curve of angiotensin II to the right without affecting the maximal response. SR 47436 (0.3-10 mg/kg i.v.), EXP 3174 (0.03-1 mg/kg i.v.) and [Sar1,Val5,Ala8]angiotensin II (0.03-1 mg/kg i.v.) induced, at least at high doses, a non-parallel shift to the right of the angiotensin II dose-response curve and this was associated with a reduction of the maximal response. During a 70 min period, the effect of [Sar1,Val5,Ala8]angiotensin II (1 mg/kg i.v.) on the angiotensin II (0.3 microgram/kg i.v.)-induced pressor response was shown to be reversible, the effect of SR 47155A (10 mg/kg i.v.) was partially reversible and the effect of SR 47436 (3 mg/kg i.v.), EXP 3174 (1 mg/kg i.v.) or losartan (6 mg/kg i.v.) was not reversed at the end of this 70 min period. Administration of SR 47155A (10 mg/kg i.v.) before SR 47436 (1-10 mg/kg i.v.) reversed the reduced angiotensin II-maximal response induced by SR 47436. Administration of SR 47436 (10 mg/kg i.v.) before SR 47155A (1-10 mg/kg i.v.) prevented the full development of the pressor response as observed in the absence of SR 47436. In the pithed rat, SR 47436 (30 mg/kg i.v.) and losartan (30 mg/kg i.v.) reduced the change in diastolic blood pressure induced by electrical stimulation of the spinal cord only at low stimulation rates. Taken together these results indicate that SR 47436, under in vivo conditions, is a potent non-peptide angiotensin receptor antagonist. The type of antagonism (partially insurmountable but selective) can be explained by different theoretical models which are discussed.

Angiotensin II↗