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Biomedical subjects

A M Sullivan

Publications and source records attributed to A M Sullivan.

29 records · Page 2Linked to original sources

Lack of permanent nigrostriatal dopamine deficit following 6-hydroxydopamine injection into the rat striatum. Short communication.

The lesion caused by a single 6-hydroxydopamine injection into rat striatum was evaluated. In vivo positron emission tomography using a dopamine reuptake tracer revealed no consistent reduction in striatal dopamine transporter. Amphetamine rotation test was negative up to 18 weeks. A 21% reduction in striatal dopamine seen at 11 weeks was not detectable at 18 weeks. Tyrosine hydroxylase-positive neurone counts showed no decline in substantia nigra. Our results suggest that this lesion may be subject to compensation and therefore should be used with caution in studies on neuroprotective treatments of Parkinson' disease.

Animals↗

Endothelins induce Fos expression in neurons and glia in organotypic cultures of rat cerebellum.

Endothelins (ETs) and their receptors are present in high levels in the brain and have been proposed to act as neuromodulators or neurotransmitters. However, neither their role nor their precise mechanism of action in the brain is understood. In this study, c-fos expression was used as a marker of neuronal activation in organotypic cultures of rat cerebellum. ETs induced Fos protein expression in both granule cells and glia but not in Purkinje cells. Granule cells and glia were both very sensitive to ETs, but different receptor subtypes appeared to be involved, because granule cells did not respond to ET-3. However, they did respond to the ETB-selective agonist BQ3020, suggesting the possible existence of a novel neuronal ETB-like receptor. The induction of Fos in granule cells was independent of extracellular calcium ion concentration, but the ryanodine receptor antagonist dantrolene significantly inhibited the response to ETs, suggesting that the mobilisation of calcium ions from intracellular stores is important. These data support previous evidence that ETs act directly on neurones and show that the intracellular pathways after ET receptor activation are complex. It appears likely that ETs play an important neuromodulatory role in the cerebellum.

Animals↗

Peripheral blood stem cell support does not accelerate haemopoietic recovery from miniBEAM chemotherapy.

Intermediate-dose salvage therapy is frequently given for relapsed and resistant lymphomas and is usually intensely myelosuppressive. In an attempt to reduce the haematological toxicity of miniBEAM, one of the commonly used salvage regimens, peripheral blood stem cell (PBSC) support was given to 21 consecutive patients who received miniBEAM chemotherapy. The outcome was compared with a non-randomised control group of consecutive patients who were similar to the supported group apart from the fact that it was not possible to collect PBSC before miniBEAM therapy. Apart from a small, marginally significant difference between the supported and unsupported groups in the number of days for which intravenous antibiotics were required, there were no other differences between the two groups in supportive care required and times to haematological recovery. In conclusion, PBSC support does not accelerate haematological recovery from miniBEAM therapy.

Adolescent↗

Preliminary crystallographic analysis of chloroperoxidase from Caldariomyces fumago.

Chloroperoxidase from the fungus Caldariomyces fumago has been crystallized in two space groups, C222(1) and P2(1)2(1)2(1) both of which are suitable for high-resolution X-ray studies. Parent data sets have been obtained to 2.16 A in space group C222(1) and 2.00 A in space group P2(1)2(1)2(1). Heavy-atom derivatives have been obtained with both forms and electron-density maps calculated. The heme has been located and continuous electron density between the heme and protein clearly indicates the location of the proximal ligand.

Journal Article↗

Accessory cells do not contribute to G-CSF or IL-6 production nor to rapid haematological recovery following peripheral blood stem cell transplantation.

Haemopoietic recovery is more rapid after peripheral blood stem cell (PBSC) transplantation than after autologous bone marrow transplantation, and the aim of this study was to assess the role of the large number of lymphocytes and monocytes (accessory cells) in a PBSC leukapheresis product in this rapid regeneration. Haematological recovery was therefore assessed in 10 PBSC recipients with lymphoma or myeloma in whom monocytes and T cells were depleted by a median of 2.3 and 3.3 logs by CD34+ cell selection using the CEPRATE SC stem cell concentration system and compared with recovery in 59 recipients who received whole PBSC. After allowing for the number of progenitor cells reinfused, there was no significant delay in engraftment induced by accessory cell depletion. Plasma levels of granulocyte-colony stimulating factor (G-CSF), granulocyte/monocyte-colony stimulating factor (GM-CSF), interleukin-6 (IL-6), stem cell factor (SCF) and macrophage-inhibition factor-alpha (MIP-1-alpha) during the transplant procedure were similar whether or not accessory cells were given. The G-CSF and IL-6 levels rose between days 5 and 14 post transplantation to approximately 1 ng/ml and 50 pg/ml respectively. This study indicates that accessory cells reinfused with PBSC collections are not responsible for the subsequent cytokine profile or rapid haematological recovery.

Adolescent↗

Resonance Raman spectroscopy of the catalytic intermediates and derivatives of chloroperoxidase from Caldariomyces fumago.

Near-ultraviolet resonance Raman spectra of chloroperoxidase derivatives and high valent intermediates show frequencies that can be systematically assigned. In accord with previous observations of low v4 frequencies for the ferric enzyme, and quite low v4 frequencies for the ferrous enzyme, low v4 frequencies are observed for ferryl compound II and several ferric derivatives. Resonance Raman spectra of chloroperoxidase compound I feature upshifted v2, v11, and v37 frequencies and other characteristics that argue for a 2A1u in preference to a 2A2u ground state for the porphyrin phi-cation radical. A moderately intense anomalously polarized band is observed at a frequency typical for octaethylporphyrin phi-cation radicals, which have been previously assigned as the 2A1u radical type. Similar resonance Raman spectral attributes are observed for horseradish peroxidase compound I, supporting a 2A1u symmetry state assignment for this species also. A 2A1u symmetry state assignment for chloroperoxidase and horseradish peroxidase compounds I is consistent with the beta-pyrrole substituent pattern of the protoporphyrin hemes found in these enzymes.

Catalysis↗

A third generation immunoassay for tumor necrosis factor alpha.

Tumor necrosis factor alpha (TNF alpha) is a polypeptide cytokine produced primarily by monocytes and macrophages. It is involved in a wide variety of immune reactions. Measurement of TNF alpha originally depended upon bioassays that are of varying reliability and reproducibility. Early immunoassays for TNF alpha required handling of radioisotopes and costly disposal of radioactive waste. Subsequent use of enzymes as reporter molecules in enzyme immunoassay (EIA) has eliminated the burden of radioisotope handling and its associated costs. However, EIA has presented new challenges. Use of thimerosal as a preservative in EIAs may require high disposal costs due to its mercury content. In addition, many EIAs lack the sensitivity achievable in radioimmunoassay (RIA). We have developed a simple microplate enzyme-linked immunosorbent assay (ELISA) for the detection of TNF alpha in serum, plasma and culture supernatants. Our high affinity capture antibody has enabled us to achieve a sensitivity of 1.5 pg/mL. The assay is calibrated to the World Health Organization (W.H.O.) first international standard for TNF alpha (87/650) and exhibits excellent precision and reproducibility. Tetramethylbenzidine is used to generate the colored end product of the reaction, and thimerosal has been removed from all components.

Enzyme-Linked Immunosorbent Assay↗

The mentally ill homeless: isolation and adaptation.

Project HELP was established in New York City in 1982 as a mobile outreach unit providing crisis medical and psychiatric services to impaired homeless persons. The authors describe the demographic characteristics of the population served, the disposition of patients accepting treatment or shelter services, and the adaptation of the homeless to weather extremes. They discuss the difficulties in providing services to a population whose members are distrustful of authority and are unwilling to provide information about themselves. They conclude that the more disaffiliated members of the homeless population, such as those served by Project HELP, need even more extensive services than the homeless who use some kind of existing sheltered care, and they suggest various kinds of services to meet their needs.

Adaptation, Psychological↗

A model career ladder approach to medical technology education.

The medical technology program at the University of Vermont was modified in 1972 to create a 2 + 2 integrated curriculum with specialty options progressing that associate degree to baccalaureate degree. This design allows the fundamentals acquired in the associate degree curriculum of the medical laboratory technician (MLT) to serve as a practical and theoretical foundation that can be expanded upon in the baccalaureate degree curriculum of the medical technologist (MT). Options in the baccalaureate degree curriculum are generalist, specialist in clinical chemistry, in hematology, and in clinical microbiology. The design of this program provides a response to the changing role of the clinical laboratory practitioner.

Curriculum↗