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Biomedical subjects

A Rodger

Publications and source records attributed to A Rodger.

At least 55 records · Page 3Linked to original sources
PubMed1995

Multiple DNA binding modes of anthracene-9-carbonyl-N1-spermine.

The poly(dAdT)2 complex of anthracene-9-carbonyl-N1-spermine, a spermine derivative terminally substituted with an anthracene moiety, has been studied using fluorescence, linear dichroism, circular dichroism, normal absorption spectroscopy (as a function of temperature) and computer modelling. For comparison, some data are also provided for the same ligand with poly(dGdC)2 and calf thymus DNA. Following detailed fluorescence and CD spectroscopic studies, we propose that anthracene-9-carbonyl-N1-spermine intercalates in at least two different binding orientations with poly(dAdT)2. Based on computer simulation data, we deduce that the ligand can intercalate from both the minor groove and the major groove. In contrast, intercalation with poly(dGdC)2 probably occurs only from the major groove. At high ligand concentrations, the CD spectra suggest anthracene-anthracene interactions, whilst the LD data point towards a groove-bound anthracene. Again from computer simulations, we propose binding modes consistent with these observations. Other data from the LD spectra suggest a sequential nature to the binding of the ligand to calf thymus DNA, with GC-rich sites being occupied first. At low ligand concentrations, anthracene-9-carbonyl-N1-spermine is able to stabilize poly(dAdT)2 against thermal decomposition, but not as effectively as spermine. The reverse is found to be true with calf thymus DNA. Both the anthracene-9-carbonyl-N1-spermine and spermine complexes of poly(dAdT)2 show pre-melt transitions in their melting curves. The anthracene-9-carbonyl-N1-spermine complex with poly(dAdT)2 also shows a post-melt transition.

Antineoplastic Agents↗
PubMed1995

Adjuvant therapy with 5-fluorouracil for breast cancer of likely poor prognosis: 15-year results of a randomized trial.

In a trial conducted in southeast Scotland between April 1974 and December 1979, 332 women with invasive breast cancer of Stage I and II with histological evidence of node involvement, or who had operable or inoperable Stage III disease, were randomized, after primary local therapy (mastectomy, node biopsy and radiotherapy for all except the inoperable disease patients who underwent radiotherapy alone) to receive 12 4-weekly intravenous injections of 5-fluorouracil (5-FU), 700 mg/m2 or no systemic therapy. After a median follow-up of 15 years from randomization, no difference is shown between the two groups in terms of distant relapse (hazard ratio (HR) = 1.02; 95% CI 0.78-1.32), event free survival (HR = 1.23; 95% CI 0.97-1.56), or total survival (HR = 1.19; 95% CI 0.93-1.52). Locoregional relapse is significantly reduced by 5-FU administration (HR = 1.88; 95% CI 1.20-2.96). The results are similar for the trial as a whole or when mastectomy patients are considered alone. Toxicity was minimal with marrow suppression in only 19 of 147 patients receiving more than one injection; only five patients discontinued therapy due to nausea and vomiting. However, retrosternal pain occurred in 16 patients, nine of whom had their treatment curtailed as a result. Seventy-seven per cent of patients have died, the majority from breast cancer. Only 1.2% of deaths are considered attributable to cardiac causes of 5-FU is not associated with excess cardiac deaths in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

DNA binding of a spermine derivative: spectroscopic study of anthracene-9-carbonyl-N1-spermine with poly[d(G-C).(d(G-C)] and poly[d(A-T).d(A-T)].

The binding of polyamines, including spermidine (1) and spermine (2), to poly[d(G-C).d(G-C)] was probed using spectroscopic studies of anthracene-9-carbonyl-N1-spermine (3); data from normal absorption, linear dichroism (LD), and circular dichroism (CD) are reported. Ligand LD and CD for transitions located in the DNA region of the spectrum were used. The data show that 3 binds to DNA in a manner characteristic of both its amine and polycyclic aromatic parts. With poly[(dG-dC).(dG-dC)], binding modes are occupied sequentially and different modes correspond to different structural perturbations of the DNA. The most stable binding mode for 3 with poly[d(G-C).d(G-C)] has a site size of 6 +/- 1 bases, and an equilibrium binding constant of (2.2 +/- 1.1) x 10(7) M-1 with the anthracene moiety intercalated. It dominates the spectra from mixing ratios of approximately 133:1 until 6:1 DNA phosphate: 3 is reached. The analogous data for poly[d(A-T).d(A-T)] between mixing ratios 36:1 and 7:1 indicates a site size of 8.3 +/- 1.1 bases and an equilibrium binding constant of (6.6 +/- 3.3) x 10(5) M-1. Thus, 3 binds preferentially to poly[d(G-C).d(G-C)] at these concentrations.

Circular Dichroism↗
PubMed1994

The effect of pulmonary function of local and loco-regional irradiation for breast cancer.

Eighty-five patients treated with loco-regional radiotherapy to the breast/chest wall and cervico-axillary nodes, and 16 patients treated with local radiotherapy to the breast/chest wall alone for breast cancer were enrolled in a prospective study to measure the effects of treatment on pulmonary function during the acute phase (10 weeks after completing irradiation) and during the late phase (12 months after completing irradiation). Baseline pulmonary function values were obtained from all patients immediately prior to commencing radiotherapy. Twenty-two patients (25.8%) treated with loco-regional radiotherapy developed transient chest symptoms compared with two patients (12.5%) treated with local radiotherapy (P = 0.11). Patients undergoing loco-regional radiotherapy showed a reduction of mean vital capacity of 0.13 litres (4.2%) (P < 0.0001) during the acute phase and at 1 year a further decrease occurred (P = 0.02) so that mean vital capacity was reduced by 0.18 litres (5.8%) (P < 0.0001) compared to pretreatment values. Mean transfer factor for carbon monoxide (TLCO) was reduced by 0.85 mmol.kPa-1.min-1 [11.9%] (P < 0.0001) during the acute phase and remained unchanged at 1 year. Patients undergoing local radiotherapy to the breast/chest wall alone did not show any significant loss of vital capacity but mean TLCO was reduced during the acute phase by 0.65 mmol.kPa-1.min-1 (8.3%) (P < 0.002) which remained unchanged at 1 year. No significant association was found between impairment of ventilation or gas transfer and respiratory history, smoking history, concurrent respiratory symptoms, age, side treated or physiological pulmonary function in either the acute or late phase. This study has quantified some of the physiological sequelae following local and loco-regional radiotherapy for breast cancer. There is no evidence to suggest that any of the above factors are relevant to deciding which patients should, or should not, be offered local or loco-regional radiotherapy for breast cancer.

Breast Neoplasms↗
PubMed1994

Impaired renin stimulation in pre-eclampsia.

1. Pre-eclampsia is characterized by reduced plasma active renin concentration and renal prostacyclin production. The aim of this study was to determine whether the plasma active renin concentration could be stimulated in women with pre-eclampsia by intravenous frusemide, which stimulates renin acutely through a prostacyclin-mediated mechanism. 2. Plasma active renin concentration, plasma aldosterone concentration, haematocrit and urinary sodium, creatinine and 6-keto-prostaglandin F1 alpha were measured before (0) and 15, 30 and 60 min after intravenous frusemide in 10 non-pregnant women, 10 normal pregnant women and nine women with pre-eclampsia. Six normal pregnant and six non-pregnant women underwent the same measurements after injection of 2ml of saline to control for effects of time and posture. 3. Baseline plasma active renin concentration (but not plasma aldosterone concentration) was lower in pre-eclamptic women [4.0 (1.7-6.2) pmol of angiotensin I h-1 ml-1; median (interquartile range)] than in normal pregnant women [6.7 (5.3-12.2) pmol of angiotensin I h-1 ml-1] (P < 0.05). Baseline urinary 6-keto-prostaglandin F1 alpha/creatinine ratio, urinary sodium excretion and fractional sodium excretion did not differ between normal pregnant and pre-eclamptic women. 4. After frusemide, plasma active renin concentration rose significantly in non-pregnant (P = 0.002) and normal pregnant (P = 0.008) women, but not in women with pre-eclampsia. Individual results showed stimulation in all non-pregnant and normal pregnant women but in only six out of nine pre-eclamptic women, significantly fewer than in normal pregnancy (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1994

Comments on the use of a dichromophoric circular dichroism assay for the identification of beta-turns in peptides.

Use of the dichromophoric CD assay for beta-turn formation in peptide sequences has been investigated. The assay involves the observation of Cotton effects in CD spectra, originating from the approach of N- and C-terminal aromatic chromophores in tetrapeptides. The approach of the chromophores was believed to be brought about by a beta-turn in the peptide structure. Our investigations were paralleled by NMR studies which revealed the presence of a previously unreported hydrogen bond in the beta-turn conformers, which appears to play a role in the generation of the observed Cotton effects. This suggests caution in the use of the CD technique alone as an assay for beta-turn conformers in peptides.

Amino Acid Sequence↗
PubMed1993

Multiple primary tumours in patients treated with radiotherapy for breast cancer.

Between January 1954 and March 1964, 3926 patients with primary breast cancer were referred to The Department of Clinical Oncology, Edinburgh. One hundred and eighty patients developed 195 malignancies subsequent to the treatment of their initial breast cancer. Overall, the total number of second tumours was not significantly in excess of the expected incidence in the general population. However, statistical analysis revealed a significant increase in the incidence of rectal, skin and bone tumours. The excess of bone tumours was likely due to radiation exposure. There was not an overall excess of tumours within the irradiated or scattered radiation volume.

Breast Neoplasms↗