Biomedical subjects
Publications and source records attributed to A Hornby.
Long after a new language has been learned and forgotten, relearning a few words seems to trigger the recall of other words. Neural-network models indicate that this form of spontaneous recovery may result from the storage of distributed representations, which are thought to mediate human memory. Here we use a psychomotor learning task to show that a corresponding effect of spontaneous memory recovery occurs in human subjects.
The prominent 'desmoplastic' or stromal reaction seen in many invasive breast carcinomas lead to early speculation that stromal cells play a role in breast cancer pathogenesis. Experimental evidence now supports this hypothesis and interactions between stromal cells and epithelial cells appear to be important for both normal mammary development and neoplasia. The identification of genes that are selectively expressed in the stroma of malignant breast lesions has recently provided new insights into the molecular basis of stromal-epithelial interactions. Stromally expressed genes include growth factors, proteases and extracellular matrix proteins, all biological activities with potential roles in malignant progression. Investigations discussed here concern the nature of the paracrine signals provided by malignant epithelial cells that activate changes in stromal gene expression, the effect that the stromally derived factors have on the behavior of malignant epithelial cells and the identification of novel factors and receptors in either stroma or epithelia that contribute to their mutual interactions. These questions will be addressed in the context of this laboratory's studies on insulin-like growth factors, as these molecules show marked differences in stromal expression between benign and malignant breast tissue and thus provide a useful paradigm for investigations into the paracrine environment of an evolving breast tumor.
Normal bone marrow and peripheral blood committed progenitor cells were found to be significantly more resistant to treatment with the photosensitizer benzoporphyrin derivative (BPD) and white fluorescent light (11 J/cm2) than were clonogenic cells from two cell lines (K562 and EM2) derived from nonremission patients with myelogenous leukemias. Bone marrow and peripheral blood committed progenitor cells from normal donors were also found to be more resistant to this treatment than were equivalent cells from patients with chronic myelogenous leukemia (CML). Normal bone marrow mononuclear cells grown in long-term marrow culture (LTMC) following treatment with BPD and light showed that no differences in stem cell productivity existed between control and treated samples. When bone marrow from CML patients was treated in the same manner, the numbers of progenitors detected in the nonadherent population during culture were greatly reduced compared to control material. Two rounds of PCR using nested primers to detect BCR-ABL mRNA showed that while this treatment significantly decreased the numbers of stem cells bearing the Philadelphia chromosome, it did not eliminate them.
Benzoporphyrin derivative (BPD) and light is a potent photosensitizer. We investigated this modality as a means to selectively eliminate clonogenic Ph(+) chronic myeloid leukemia (CML) cells. BPD at 10 ng/ml and 10.8 J/cm2 broad spectrum light eliminates from 5 to 6 logs of Ph(+) EM-2 cells. Long-term marrow culture studies of treated mixtures of normal and CML cells indicate that multipotent progenitor cell viability is retained while cells transcribing BCR-ABL are not detected. We conclude that BPD and light may offer a means of providing CML autografts potentially free of Ph(+) clonogenic cells.
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