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Biomedical subjects

A Campbell

Publications and source records attributed to A Campbell.

At least 55 records · Page 3Linked to original sources

Use of Pyrene Spectroscopic Probes in the Study of Colloidal Systems.

The interfacial behavior of polyethylene oxide (PEO) end-labeled with the often-used fluorescent probe pyrene was monitored to asess the effect of use of such hydrophobic probes on system behavior. Mixtures of labeled and unlabeled PEO were adsorbed on silica and the resulting suspension properties noted. The suspension behavior was found to be markedly different, depending on the ratio of labeled-to-unlabeled PEO employed. While it was "safe" to use pyrene probes in amounts of 3% or less for spectroscopic investigation of PEO effects, it was found that ratios equal to, or greater than, 1 : 3 produced anomalous behavior of the silica suspensions. This was manifested in the form of decreased suspension stability, as evidenced by significantly higher settling rates. Similar experiments using free pyrene revealed that these effects could be attributed to the chemical attachment of the pyrene probe to the polyethylene oxide chain. Fluorescence spectroscopy was used to simultaneously monitor the behavior of the adsorbed polyethylene oxide molecules. These results were used to explain the observed suspension behavior as a function of the labeled-to-unlabeled polymer mixing ratio. Bridging effects facilitated by hydrophobic interaction between pyrene end groups is proposed as the reason for the observed phenomena. Copyright 2000 Academic Press.

Journal Article↗

Simplified purification of human basophils.

Studies of human basophils have been limited by the low number present in peripheral blood and the difficulties of purification to homogeneity with reasonable yield and functional status. Reproducible purification of human basophils to 96.5+/-0.5% with a yield of 40.8+/-5.3% was obtained by negative selection using immunomagnetic beads following initial separation by density gradient centrifugation. Isolated cells demonstrated complete viability by vital dye exclusion and spontaneous histamine release following incubation of <5%. Stimulation with anti-IgE or calcium ionophore A23187 caused histamine release and leukotriene C(4) production. Basophils demonstrated dose-dependent chemotaxis to monocyte chemotactic protein-3. This simplified methodology results in fully functional basophils in very high purity and good yield.

Antibodies, Anti-Idiotypic↗

Translocation of SAPK/JNK to mitochondria and interaction with Bcl-x(L) in response to DNA damage.

Activation of the stress-activated protein kinase (SAPK/JNK) by genotoxic agents is necessary for induction of apoptosis. We report here that ionizing radiation ionizing radiation exposure induces translocation of SAPK to mitochondria and association of SAPK with the anti-apoptotic Bcl-x(L) protein. SAPK phosphorylates Bcl-x(L) on threonine 47 (Thr-47) and threonine 115 (Thr-115) in vitro and in vivo. In contrast to wild-type Bcl-x(L), a mutant Bcl-x(L) with the two threonines substituted by alanines (Ala-47, Ala-115) is a more potent inhibitor of ionizing radiation-induced apoptosis. These findings indicate that translocation of SAPK to mitochondria is functionally important for interactions with Bcl-x(L) in the apoptotic response to genotoxic stress.

Apoptosis↗

GABA(B) receptors: altered coupling to G-proteins in rats sensitized to amphetamine.

Modified dopamine and glutamate neurotransmission in discrete brain regions is implicated in stimulant-induced behavioral sensitization. Release of both neurotransmitters is influenced by GABA(B) metabotropic receptors for the principal inhibitory neurotransmitter GABA. Accordingly, GABA(B) receptors were examined in rats sensitized to amphetamine by measuring receptor density and coupling to G-proteins indicated as [(3)H]baclofen binding and baclofen-mediated [(35)S]GTP gamma S binding. Repeated treatment with (+)-amphetamine (5mg/kg per day, i.p., for five days) sensitized the rats to amphetamine challenge (1mg/kg) at 14 days, but not one day, later. GABA(B) receptor density was not altered at either time. Baclofen-mediated [(35)S]GTP gamma S binding, however, was selectively augmented in the prefrontal cortex and attenuated in the nucleus accumbens at 14 days, but not one day, after amphetamine treatment. Changes in GABA(B) receptor coupling to G-proteins in rats sensitized to amphetamine, but not in similarly treated but unsensitized rats, lead us to suggest that altered GABA(B) receptor functioning may contribute to the expression of amphetamine-induced behavioral sensitization.

Amphetamine↗

Performance of the radiometer OSM3 and ABL505 blood gas analysers for determination of sodium, potassium and haemoglobin concentrations.

We have compared results obtained from two widely used ward-based blood gas analysers, the Radiometer OSM3 and ABL505, with standard laboratory analysers, for haemoglobin, sodium and potassium measurement in critically ill adult patients. During the study, paired samples for analysis were obtained from 81 patients for haemoglobin, 115 patients for sodium and 95 patients for potassium. There was good agreement between the ward and the laboratory analysers in terms of the mean results for each test. However, the limits of agreement for the ward-based analysers were wide, suggesting that their results should be used with caution.

Adult↗

Aluminum increases levels of beta-amyloid and ubiquitin in neuroblastoma but not in glioma cells.

Several epidemiological studies suggest the involvement of aluminum (Al) in the pathogenesis of Alzheimer's disease (AD). There is an increase in the levels of Abeta and ubiquitin in the pathological lesions of AD. Therefore, we have investigated whether aluminum (Al) treatment alters the levels of Abeta and ubiquitin in murine neuroblastoma (NBP2) and rat glioma (C-6) cell cultures. At a low concentration (10 microM), aluminum sulfate stimulated the level of immunoreactive Abeta and ubiquitin in NBP2 cells without changing the levels of the amyloid precursor protein (APP). However, at higher concentrations (100 and 500 microM), aluminum failed to elicit any significant effect on beta-amyloid, whereas ubiquitin levels continued to increase. No changes in the Abeta and ubiquitin content were found in the C-6 glioma cells following treatment with Al at any of the concentrations tested. Exposure of cells to aluminum salts did not alter the rate of proliferation in either of the two cell lines. These data suggest that one of the mechanisms by which Al may play a role in AD is by promoting the formation of Abeta and ubiquitin in neurons.

Alum Compounds↗

Provision and quality assurance for head and neck cancer care.

In 1998, the British Association of Head and Neck Oncologists (BAHNO) published a report entitled 'Provision and quality assurance for head and neck cancer care in the United Kingdom. A nationally co-ordinated multidisciplinary approach'. This document considered, amongst other issues, operational policies for patient care. We audited three aspects of the care of 73 patients with head and neck cancer from initial referral to definitive treatment against standards set out in this report.Fifty-nine patients (81%) were seen within two weeks of initial referral, the maximum interval proposed by the BAHNO report. In 41 patients (56%), the diagnosis was confirmed and their treatment plan determined within the further two-week period suggested in the report. Of the 25 patients who required adjuvant radiotherapy, only 11 (44%) began treatment within six weeks of their surgical phase; this represented the greatest variance from the BAHNO recommendations. These findings highlight the need for units active in the treatment of specific diseases to audit their activity against available minimum standards in an attempt to improve the quality of patient care.

Adult↗

Should ICSI be the treatment of choice for all cases of in-vitro conception?

The objective of this study was to examine different clinical scenarios of in-vitro conception, viz. fertilization with conventional IVF, IVF with high insemination concentration (HIC) and intracytoplasmic sperm injection (ICSI), and assess on a sibling oocyte comparison the hypothesis that ICSI should be performed in all cases requiring in-vitro conception. ICSI with husband's spermatozoa had a higher incidence of fertilization as compared with IVF or IVF with HIC with donor spermatozoa (if previous failure of fertilization had occurred) for unexplained infertility. Similarly, ICSI with husband's spermatozoa had as high an incidence of fertilization as IVF with donor spermatozoa for patients with severe oligozoospermia, asthenozoospermia and/or teratozoospermia, even when the spermatozoa were not selected for their morphology. Two studies were performed to assess ICSI in potential oocyte-related failure of IVF, viz. when fertilization occurred in >50% of oocytes for one group of patients, and in <50% of oocytes in a second group. In both of these studies a significant proportion of the oocytes that failed to fertilize with conventional IVF eventually fertilized after ICSI. The overall conclusion was that ICSI as a first option offers a higher incidence of fertilization, maximizes the number of embryos and minimizes the risk of complete failure of fertilization for all cases requiring in-vitro conception. However, among other concerns, current knowledge of ICSI as an outcome procedure does not provide the confidence to use this process in all cases of IVF for the time being.

Female↗

Configuration of thiols dictates their ability to promote iron-induced reactive oxygen species generation.

Iron catalyzes the production of reactive oxygen species (ROS) through the Fenton reaction. The modification of this phenomenon in the presence of various thiol compounds that are nominally reducing agents has been studied. Using the synaptosomal/mitochondrial (P2) fraction of rat cerebral cortex as a biological source of reactive oxygen species (ROS) production, we studied the influence of four compounds, glutathione (GSH), cysteine, N-acetyl-cysteine (NAC), and homocysteine on iron-induced ROS production. None of the thiol compounds alone, at the concentrations used, affected the basal rate of ROS production in the P2 fraction. GSH, homocysteine and NAC did not alter Fe-induced ROS generation, while cysteine greatly potentiated ROS formation. Measurement of the rate of ROS production in the presence of varying concentrations of cysteine together with 20 microM ferrous iron revealed a dose-response relationship. The mechanism whereby free cysteine, but not the cysteine-containing peptide GSH, homocysteine or NAC with a blocked amino group, exacerbates the pro-oxidant properties of ferrous iron probably involves formation of a complex between iron, a sulfhydryl and a free carboxyl residue located at a critical distance from the -SH group. Cysteine-iron interactions may, in part, account for the excessive toxicity of free cysteine in contrast to GSH and NAC.

Acetylcysteine↗

Aluminum induced oxidative events and its relation to inflammation: a role for the metal in Alzheimer's disease.

Aluminum (Al) is a simple trivalent cation incapable of redox changes. The toxicity of the metal has been the subject of much controversy in the past few decades. Although it has been generally believed that the metal is innocuous to human health, a causal role for Al has been established in dialysis dementia (Alfrey et al., 1976), osteomalacia (Bushinsky et al., 1995) and microcytic anemia without iron deficiency (Touam et al., 1983). Aluminum has also been implicated in Alzheimer's disease (AD) although a direct causal role has not been determined. The exact mechanism of Al toxicity is not known. However, there are several lines of evidence that show the metal's capacity to exacerbate oxidative events. The present review is intended to propose a coherent pathway linking Al-induced oxidative events to Alzheimer's disease. The preliminary segment is an introduction to reactive oxygen species and their potential involvement in the pathogenesis of AD and the generation of an inflammatory response. Evidence on the relation between AD and inflammatory processes is also presented. The epidemiological and clinical evidence of Al neurotoxicity is summarized in the second section of the review. Finally, a hypothesis indicating that aluminum can exacerbate AD by activating ROS generation and initiation of an inflammatory cascade is presented.

Aluminum↗

Genome signature comparisons among prokaryote, plasmid, and mitochondrial DNA.

Our basic observation is that each genome has a characteristic "signature" defined as the ratios between the observed dinucleotide frequencies and the frequencies expected if neighbors were chosen at random (dinucleotide relative abundances). The remarkable fact is that the signature is relatively constant throughout the genome; i.e. , the patterns and levels of dinucleotide relative abundances of every 50-kb segment of the genome are about the same. Comparison of the signatures of different genomes provides a measure of similarity which has the advantage that it looks at all the DNA of an organism and does not depend on the ability to align homologous sequences of specific genes. Genome signature comparisons show that plasmids, both specialized and broad-range, and their hosts have substantially compatible (similar) genome signatures. Mammalian mitochondrial (Mt) genomes are very similar, and animal and fungal Mt are generally moderately similar, but they diverge significantly from plant and protist Mt sets. Moreover, Mt genome signature differences between species parallel the corresponding nuclear genome signature differences, despite large differences between Mt and host nuclear signatures. In signature terms, we find that the archaea are not a coherent clade. For example, Sulfolobus and Halobacterium are extremely divergent. There is no consistent pattern of signature differences among thermophiles. More generally, grouping prokaryotes by environmental criteria (e.g., habitat propensities, osmolarity tolerance, chemical conditions) reveals no correlations in genome signature.

Animals↗

Aluminum-induced oxidative events in cell lines: glioma are more responsive than neuroblastoma.

Aluminum, a trivalent cation unable to undergo redox reactions, has been linked to many diseases such as dialysis dementia and microcytic anemia without iron deficiency. It has also been implicated in Alzheimer's disease although this is controversial. Because cell death due to oxidative injury is suspected to be a contributory factor in many neurological diseases and aluminum neurotoxicity, glioma (C-6) and neuroblastoma (NBP2) cells were utilized to assess early changes in oxidative parameters consequent to a 48-h exposure to aluminum sulfate. A 500-microM concentration of this salt produced a significant increase in reactive oxygen species (ROS) production and a significant decrease in glutathione (GSH) content in glioma cells. However, the same concentration of the aluminum salt did not lead to any significant changes in the neuroblastoma cells. Mitochondrial respiratory activity in glioma cells was also found to be significantly higher in the aluminum treated cells. As judged by morin-metal complex formation, aluminum can enter glioma cells much more readily than neuroblastoma cells. Thus, it is possible that the cerebral target following an acute exposure to aluminum may be glial rather than neuronal.

Alum Compounds↗

The origins of classical homoeopathy?

Writers on homoeopathy frequently refer to classical homoeopathy, usually with the implication that this is the most complete and authoritative version of Hahnemann's views. However, such claims do not correspond with the historical facts. Homoeopathy arrived in the USA early in the 19th century and there underwent considerable modifications at the hands of its most influential adherents, who were deeply influenced by the ideas of Emanuel Swedenborg. J.T. Kent is particularly important in this respect and he also introduced ideas from other sources. The 'extremist' character of Kentian homoeopathy goes far to explain the gulf that has separated homoeopathy from orthodox medicine until comparatively recently. Kentian views were brought to Britain by Margaret Tyler early in the 20th century and became dominant after the First World War, to give rise to what is called classical homoeopathy today. This is not only a considerable modification of Hahnemann's teaching, but it fails to take account of Hahnemann's late ideas which he developed in his Paris years and incorporated in the sixth edition of 'The Organon', published posthumously in 1920. Whatever one's opinion of the value of classical homoeopathy, it cannot be legitimately represented as a purely Hahnemannian teaching.

History, 20th Century↗