Hans-Rudolf Wiedemann: an appreciation.
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Biomedical subjects
Publications and source records attributed to P Mullen.
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To clarify the mechanism by which the luteinising hormone-releasing hormone agonist, buserelin, may have direct effects on breast cancer cells, factors potentially influencing its action have been studied in the MCF-7 breast cancer cell line. Oestradiol and epidermal growth factor (EGF), which stimulate the growth of MCF-7 cells in culture, reversed, at least in part, the inhibitory effects of buserelin. Insulin also abolished growth inhibition. Quantitative effects of buserelin differed according to the batch of fetal calf serum used as media supplement. These data suggest that the direct inhibitory effects of buserelin on breast cancer cells are mediated at least in part by an antagonism of growth-promoting factors.
Controversy exists as to whether interferons usefully influence the growth of epithelial carcinomas. A small cell lung carcinoma (SCLC) cell line, WX322, has been derived which is greater than 1000-fold more sensitive to alpha-interferon (IFN) when grown in agar than other reported SCLC cell lines. The WX322 line has been characterised to prove its epithelial origin and its chemosensitivity compared with that of the NCI-H69 small cell line. The WX322 cell line expresses neuroendocrine and epithelial markers and possesses a morphology consistent with SCLC origin. A concentration of 5 IU ml-1 of IFN produced 50% inhibition of colony formation in agar in the WX322 line, whereas a concentration of greater than 10(5) IU ml-1 was required to produce a comparable effect with the NCI-H69 cell line. In contrast, WX322, possessed similar sensitivity to NCI-H69 cells when exposed to a range of cytotoxic agents. Analysis of the cell cycle indicated that IFN increased the percentage of cells in the G0/G1 phase for the WX322 cell line but increased the percentage in S phase for the NCI-H69 line. Growth of the xenograft, from which the cell line was derived, was also inhibited by IFN at doses greater than 10(5) IU/mouse/day. The WX322 cell line whether grown in agar or as a xenograft shows an unusually high sensitivity to IFN and provides an interesting model for studying mechanisms of IFN cytotoxicity to epithelial cells.
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The present study was carried out to determine the variation in DNA content between multiple fine needle aspirates (FNA) of the same tumour from patients with breast cancer. Analysis of different aliquots of the same FNA showed good reproducibility in terms of cell cycle distribution and DNA index. Duplicate FNAs taken from different sites in nine of 11 excised tumours showed similar reproducibility. However, two of the aneuploid tumours displayed substantial variations in the distribution of cell populations between the duplicate samples. Sequential FNAs with no intervening therapy were obtained from the same tumour in 17 patients; one at the time of diagnosis and the other at biopsy 1-3 weeks later. Only five cases showed no variation between the sequential FNAs; the remaining 12 displayed different DNA profiles. A further 13 patients were studied before and during systemic therapy. While there was no variation between sequential FNAs in four patients, marked differences in the DNA profile were observed in the remaining nine patients undergoing treatment, the changes not necessarily being associated with clinical response to therapy. It is concluded that the monitoring of cellular changes by DNA analysis of sequential FNAs may be complex and subject to problems associated with heterogenecity.
This investigation uses an electrical stimulation model of ocular herpes simplex virus (HSV) reactivation to elucidate the relationship between neuronal protein synthesis, axonal transport and electrical stimulation. In this study, healthy adult albino rabbits were implanted with electrodes over the trigeminal ganglion (TG) and stimulated chronically twice a week for 28-34 days (previously shown to induce HSV reactivation in infected rabbits). The TG was visualized surgically and injected with 3H-proline to label newly synthesized protein. After various times, the TG, corneas and ophthalmic nerve were analyzed for labeled proteins. In nonimplanted and implanted rabbits (whether stimulated or not), the rate of fast anterograde axonal transport in the ophthalmic nerve was 347 mm/day and 326 mm/day, respectively. A lag period of 45 min occurred between initiation of protein labeling and onset of axonal transport. Only a small percentage of newly synthesized neuronal proteins were transported in the ophthalmic nerve (1-4% in the proximal 10 mm) or deposited in the cornea (less than 0.5%) after 24 hr. Neither the rate of protein synthesis in the TG nor the rate of axonal transport was changed by electrical stimulation. However, the amount of radioactively labeled proteins undergoing axonal transport in the stimulated group was five times that of the sham control group. Thus, the routing and loading of TG proteins for axonal transport is enhanced in the electrical stimulation model.
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Cellular DNA was analysed by flow cytometry in fine needles aspirates (FNA) from both benign and malignant breast lesions in order to determine the feasibility of flow cytometric analysis. In 22 of 26 (84%) benign and 69 of 74 (93%) malignant aspirates, sufficient cells were present to produce good quality DNA histograms. DNA in all 22 benign lesions was diploid. In contrast, of the 69 cancers with sufficient cells for analysis, 40.6% had a diploid DNA content alone, whilst 59.4% had an additional DNA aneuploid line. These results indicate that the majority of FNAs provide sufficient material for flow cytometric analysis of DNA profiles. Such aspirates taken in a sequential manner may also prove to be an ideal method of studying tumour response to therapy.
Fungal mural endocarditis is a rare entity in which the antemortem diagnosis is seldom made. This case presentation describes a patient in whom the clinical diagnosis of Aspergillus mural endocarditis was made by echocardiography and by biopsy of a peripheral embolic lesion. This led to a combined medical and surgical approach to therapy.
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