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T McDevitt

Publications and source records attributed to T McDevitt.

8 recordsLinked to original sources

Predictive testing for BRCA1 and 2 mutations: a male contribution.

BACKGROUND: Management strategies for women carrying BRCA1 and 2 mutations are becoming clearer and predictive testing for a known family mutation is commonly undertaken. Implications for men are not as clear and they participate less frequently. PATIENTS AND METHODS: Twenty-six men from 10 extended families underwent predictive testing. Their motivation, reaction and outcome were studied. Subjects had appropriate pre- and post-test counselling. Informed consent was obtained before predictive testing for known deleterious mutations. DNA analysis followed standard procedures. RESULTS: Eighteen tested positive and eight negative. Four had adverse psychological reactions and three reneged on their commitments to impart results. The spouse of another man had an adverse psychological reaction to the disclosure of his positive result. Two, already suffering from prostate cancer, were phenocopies and paternal lineage transmission was unexpectedly determined in another. Risk was removed from 33 offspring and confirmed for 56. CONCLUSIONS: Complex themes associated with genetic testing are confirmed and the spectrum extended. Men appear to understand the importance of participating in this process. Methods of avoiding adverse reactions merit further study along with other aspects of the process.

Adult↗

Merocyanine 540 solubilized as an ion pair with cationic surfactant in nonpolar solvents: spectral and photochemical properties.

Merocyanine 540 (MC) is an anionic dye that is used to photopurge the bone marrow of leukemia cells. Under these conditions it is localized mostly in cell membranes, which may affect its photochemical reactivity. We investigated the photochemistry of MC dissolved as a hydrophobic ion pair with a hexadecyltrioctadecylammonium cation in cyclohexane, trimethylpentane and toluene as well as in propylene carbonate, CH3CN, C2H5OH and D2O. In organic solvents, the absorption and fluorescence spectra of MC were strongly red-shifted compared with aqueous solutions. The fluorescence was also more intense despite aggregation that occurred in some solvents. Aggregation strongly affects the spectral and photochemical properties of MC, especially in aliphatic hydrocarbons in which distinctive H-type aggregates are formed. Hydrophobic MC is a moderate photosensitizer of singlet molecular oxygen (1O2). The following values for 1O2 quantum yields were calculated based on 1O2 phosphorescence relative to 1O2 generation by Rose Bengal: approximately 0.12 in trimethylpenthane, approximately 0.13 in cyclohexane, 0.045 in EtOH, 0.039 in toluene, 0.007 in CH3CN and approximately 3 x 10(-4) in D2O. The H-aggregates of MC in cyclohexane and trimethylpentane are better 1O2 producers than monomeric MC. The above 1O2 quantum yields are corrected for self-quenching because MC is an efficient 1O2 quencher (17 x 10(7) M-1 s-1 in CH3CN, 6.8 x 10(7) M-1 s-1 in D2O, 5.2 x 10(7) M-1 s-1 in EtOH, and 1.4 x 10(7) M-1 s-1 in toluene). Merocyanine undergoes photodegradation, a solvent-dependent process that proceeds faster when the dye is aggregated. The initial photodegradation rate is much slower in organic solvents than in water, but photodegradation products accumulated during longer irradiation may increase the rate in most solvents. Higher photostability and better photosensitization by MC in hydrophobic nonpolar solvents suggest that the killing of leukemia cells via a photodynamic mechanism may operate mostly in cell membranes. In contrast, any cytotoxic products from photodecomposition may be important in hydrophilic cell compartments. Our data show the spectral and photochemical properties of MC in a pure hydrophobic environment.

Humans↗

Characterization of a cancer cachectic factor.

Cancer cachexia is a syndrome of progressive wasting which has been suggested to be mediated by tumour-necrosis factor-alpha, interleukins 1 and 6, interferon-gamma and leukaemia-inhibitory factor. It has proved difficult to correlate levels of tumour-necrosis factor-alpha and interleukin-6 with cancer cachexia, and the weight loss induced by leukaemia-inhibitory factor may be due to toxicity. In the murine adenocarcinoma MAC16, cachexia is mediated by circulatory catabolic factors, which we have now isolated using an antibody cloned from splenocytes of mice transplanted with the MAC16 tumour, with a delayed cachexia. The material is a proteoglycan of relative molecular mass 24K which produces cachexia in vivo by inducing catabolism of skeletal muscle. The 24K material was also present in urine of cachectic cancer patients, but was absent from normal subjects, patients with weight loss due to trauma, and cancer patients with little or no weight loss. This suggests that cachexia in mice and humans may be produced by the same material.

Adenocarcinoma↗

Reactions to AIDS and other illnesses: reported interactions in the workplace.

Previous research on the public's response to AIDS has been concerned with attitudes and knowledge in relation to the disease itself. The present study investigated American students' willingness to interact in the workplace with AIDS patients and compared this with their reactions to cancer and hepatitis patients. The effects of perceived control over the cause of the disease were also examined. Exposure to the diseases was manipulated with written scenarios. Results demonstrated that the type of illness affected a willingness to interact with individuals--AIDS patients were reacted to least positively, followed by hepatitis, and cancer patients. Perceived control over the cause of the disease did not affect reactions.

Acquired Immunodeficiency Syndrome↗

The effects of monensin on the abundance of mRNA(alpha) and of sodium pumps in human cultured cells.

HeLa or MRC5-VI cells were grown for up to 1 day in media containing monensin at concentrations up to 10 microM. We measured the sodium pump density of the plasma membrane with [3H]ouabain and the mRNA for the alpha-subunit of the pump by hybridization to a cDNA probe. The sodium and potassium concentrations were measured under similar conditions, and in some experiments the rate of internalization of the sodium pumps estimated by using [3H]ouabain uptake into the cell. We found that the relationship between sodium pump density and [Na+]i was well described by Michaelis-Menten kinetics with a Km of 12 mM-[Na+]i and a Vmax twice the normal value. There was no obvious relationship between cell potassium and pump density. The relationship between sodium pump density and [Na+]i was the same as that found by growing the cells in low-potassium medium, so we conclude that the manner of raising [Na+]i is not important, merely the final value. In conditions of raised intracellular sodium there was an increase in the mRNA for the alpha-subunit of the pump, but there was no slowing of the rate of internalization of the pumps from the plasma membrane. We conclude that the increased density of pumps is due to an increased synthesis rather than a decreased internalization rate of pumps, suggesting that the cell can control the method of upregulation.

Cell Membrane↗