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S Aitken

Publications and source records attributed to S Aitken.

29 records · Page 2Linked to original sources
PubMed1987

Assay of mitogen-induced effects on cellular incorporation of precursors for scavenger, de novo, and net DNA synthesis.

In summary we have presented data on [3H]dThd incorporation into DNA for a positive and negative growth modulator. These data clearly do not correspond to those based on net DNA synthesis (ortho[32P]phosphate incorporation into purified DNA) and previous knowledge of the effects of these hormones on cell number and cellular DNA accumulation. The paradox was resolved by directly analyzing effects of hormones on de novo pyrimidine biosynthesis. E2 stimulated both de novo and scavenger pathways in the first wave of DNA synthesis and only de novo in the second (and subsequent) waves. In contrast, tam progressively inhibited de novo pyrimidine biosynthesis. These hormonal effects on intracellulr pyrimidine pool sizes rendered [3H]dThd incorporation data by itself uninterpretable. [3H]dThd is a useful measure of DNA synthesis only if verified by independent measures of net DNA synthesis for the same time course and treatment conditions. In addition it may prove beneficial in various experimental systems to develop direct assays of de novo pyrimidine biosynthesis to assess mitogen effects. The experiments presented may also prove to be useful in evaluating the effects of mitogens and antimitogens on cells synchronized in the cell cycle by any of a variety of means.

Acetates↗
PubMed1986

Poor prognosis metastatic gestational trophoblastic disease: experience with moderate dose methotrexate plus folinic acid rescue as initial therapy.

From 1971 to 1981, twenty patients with poor-prognosis metastatic gestational trophoblastic neoplasia (GTN) were treated with moderate-dose methotrexate (1 g) and folinic-acid rescue (MD-MTX-FAR) as initial therapy. Seven (35%) were cured with MD-MTX-FAR, and salvage chemotherapy was successful in an additional seven, for a total cure rate of 70%. The ultimate outcome is similar to that reported for MAC triple therapy during this era. Hematologic and mucosal toxicity were negligible and no serious complications were encountered. We now use combination chemotherapy in patients with poor-prognosis GTN as first-line treatment. However, these results suggest that there may be advantages to the incorporation of MD-MTX-FAR in combination regimens in place of low-dose methotrexate, because of reduced toxicity and potential benefits for the prophylaxis and treatment of cerebral metastases.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

Influence of cell proliferation and cell cycle phase on expression of estrogen receptor in MCF-7 breast cancer cells.

In the present study, the effects of cell cycle phase and proliferation rate on the expression of specific estrogen binding activity were explored in hormone-dependent human breast cancer cells. A technique was developed to alter the proliferative rate of MCF-7 cells by plating at different densities. The doubling time ranged from 20 to 48 hr, showing a negative relation to the number of plated cells. Slowly proliferating cells had accumulated more than twice as much estrogen receptor (ER) activity as did fast-proliferating cells. Exposure of exponentially growing cells to isoleucine-deficient medium resulted in decreased thymidine incorporation and disappearance of detectable cellular ER activity. Overall protein synthesis was reduced by only 30% in cells growing in isoleucine-free medium. At 24 hr after release from isoleucine deprivation, ER levels are fully restored, although thymidine incorporation does not resume for an additional 6 to 8 hr, and increases in cell number are not seen for 24 hr. Exposure of exponentially growing cells to 2 mM thymidine for 24 hr produced partially synchronized MCF-7 cells (approximately 70%). Six hr after release from excess thymidine, cells reached S phase; after 9 hr, G2; and after 18 hr, G1. ER levels immediately and, 6 hr after release, remained unchanged, showed a slight increase at 9 hr, and showed an increase of about 50 to 60% at 18 hr. These data suggest that: (a) ER binding activity and DNA synthesis can be dissociated; (b) ongoing protein synthesis is necessary for maintenance of cellular ER activity; and (c) ER is apparently synthesized throughout the cell cycle, with some evidence that this is predominantly in G1 and G2.

Breast Neoplasms↗
PubMed1983

Developmental aspects of sensory substitution.

Research involving the provision of an artificial intersensory substitute--the SonicguideTM--is reported. Subjects were congenitally blind infants and young children. In a search task requiring distally appropriate responses, results indicated that younger subjects showed a more rapid sensitivity to the spatial information provided by the device. The implications of these developmental differences for intersensory substitutability are discussed.

Aging↗
PubMed1981

Purification and properties of estrogen-responsive cytoplasmic thymidine kinase from human breast cancer.

The effect of 17 beta-estradiol on cytoplasmic thymidine kinase activity was studied in MCF-7, a human breast cancer cell line in culture which responds to estrogens with an increase in the rate of growth. Levels of 17 beta-estradiol which maximally stimulate [3H]thymidine incorporation into DNA also maximally stimulate thymidine kinase activity. The Vmax for thymidine increased while the Km was not affected by estrogen stimulation when performed on nonpurified enzyme. Tamoxifen, an antiestrogen, decreased the specific activity of the enzyme. To further study its hormonal regulation, cytoplasmic thymidine kinase was purified greater than 2000-fold by affinity column chromatography. The purified preparation migrated in one band to a pI of 8.5 on an isoelectric focusing gel. The purified thymidine kinase was further characterized by examining its molecular weight, pH optimum, heat stability, utilization of phosphate donors, inhibition by nucleotides, and the effect of pyrimidine nucleoside analogs.

Breast Neoplasms↗
PubMed1975

Immune status of children with and without severe infection during remission of malignant disease.

The immune status of children with malignant disease in remission was assessed usingvarious immune function tests. Children with infections had significantlymore neutropenia, hypogammaglobulinaemia, and impaired cell-mediated immune responses than those without. These two groups combined had much more absolute lymphopenia and impairment of both cell-mediated immunity and antibody-producing capacity thancontrol children with non-malignant conditions. Regular immunological evaluation isrecommended for children with malignant disease when new intensive treatment schedules are under trial and for individual patients particularly prone to develop infections during treatment.

Antibody Formation↗
PubMedDate not supplied

Deception and lies.

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Adaptation, Psychological↗