Biomedical subjects
T C Holme
Publications and source records attributed to T C Holme.
Haemopneumothorax after fine needle aspiration of the breast.
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Sigmoido-appendiceal fistula due to diverticulitis.
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Cholesterol granuloma of the breast presenting as an intracystic papilloma.
Cholesterol granuloma of the breast is a rare benign condition. It is often clinically and radiologically indistinguishable from breast carcinoma. A case of cholesterol granuloma which manifested as an intracystic papilloma on ultrasound is described. This unusual ultrasonographic appearance has not previously been reported.
Monoclonal antibodies to cytoskeletal proteins: an immunohistochemical investigation of human colon cancer.
Monoclonal antibodies raised to a number of microfilament-associated proteins were shown to recognize the appropriate proteins in extracts from human colon tissue. They were then used in an immunohistochemical study of normal colonic mucosa, adenomas, and adenocarcinomas. A strong reaction was seen in stromal cells within the tumours (both adenomas and adenocarcinomas) when frozen sections were stained with antibodies to filamin and caldesmon. In addition, a similar reaction was seen in the adenocarcinomas when stained with antibodies to talin and gelsolin. We believe that immunohistochemical staining with these antibodies reveals a tumour-induced process in the surrounding cells, possibly related to a host response to tumours.
Is mammographic microcalcification of biological significance?
Mammographic microcalcification is a feature of a proportion of breast cancers. Its occurrence does not appear to be significantly associated with age or primary tumour size. Lymph node involvement by tumour is present in 50% of patients with mammographic microcalcification in relation to the primary tumour, but only 24% of patients without microcalcification. A significantly larger number of lymph nodes (61 of 241 nodes) are involved with tumour in patients with, in comparison to those without (59 of 476 nodes) microcalcification (P < 0.001, chi 2 test). These differences suggest a biologically significant role for the deposition of calcium in microcalcifications, which may relate to the process of tumour cell metastasis. This may be of importance in the assessment of patients with cancers which demonstrate microcalcification on mammography.
Cancer cell structure: actin changes in tumour cells--possible mechanisms for malignant tumour formation.
Improvement in treatment of solid tumours is likely to depend on a better knowledge of the biological mechanisms of malignant tumour formation. Over the past few years a great deal of progress has occurred in our understanding of cell biology, and one of the main areas of development has been the cell cytoskeleton. The cytoskeleton contributes to maintenance of cell structure and to a variety of other cell functions. Several studies have implicated one of the elements of the cytoskeleton, the microfilaments, in malignant change, and these microfilaments are directly affected by the activity of some 'oncogenes'. Changes in the control of filament polymerization and organization have been demonstrated in response to the activity of the src oncogene. The protease trypsin has been shown to affect the actin cytoskeleton grossly and illustrates that proteases released in the vicinity of tumours may have a biologically significant effect on the internal structure and stability of the cell. Further investigation of the microfilament system may reveal important clues for future manipulation of the cancer cell and the treatment of the patient with advanced cancer.
Actin in B16 melanoma cells of differing metastatic potential. Effects of trypsin and serum.
Actin is present in cells in monomeric and polymeric (filamentous) forms. Filamentous actin is distributed in Triton-soluble (cytosolic) and Triton-insoluble (cytoskeletal core) fractions. We have used the DNase 1 inhibition assay and immunofluorescence to investigate the distribution of actin in monomeric and polymeric forms in cloned B16 murine melanoma cell lines of low and high metastatic capacity. The protease trypsin caused rounding up and detachment of both cell lines within 5 min. This was associated with almost complete depolymerization of cytosolic actin filaments but the Triton-insoluble cytoskeleton was not quantitatively affected by trypsin treatment. There were quantitative differences between the clones in their response to incubation in the presence or absence of 10% serum. The highly metastatic cell line contained 35% more actin when incubated in the presence of 10% serum, almost completely distributed to the Triton-insoluble cytoskeleton, an effect not seen in the low metastatic cells.
Membrane and cytoskeletal changes in cells after transformation by Rous sarcoma virus.
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Effect of transformation by Rous sarcoma virus on the character and distribution of actin in Rat-1 fibroblasts: a biochemical and microscopical study.
Actin has been measured in subcellular fractions from Rat-1 fibroblasts and in Rous sarcoma virus-transformed Rat-1 cells (VIT), using the DNase 1 inhibition assay. The transformed cells showed a significant shift in the actin monomer (G)in equilibrium with polymer (F) equilibrium within the cell cytosol, and a significant increase in actin in the Triton-insoluble cytoskeletal core in comparison with untransformed cells. This incorporation of actin into the cytoskeletal core fraction is associated with a change in filamentous actin assemblies from 'stress fibre' patterns to punctate filament aggregates. These differences have been correlated with changes in morphology, in actin, vinculin and alpha-actinin distribution, in adhesion plaque formation and with the production of pp60v-src-associated protein kinase activity in the transformed cells. Changes in actin distribution and its polymerization in response to src-gene expression may play an important role in the determination of the transformed cell characteristics.
Oncogenes and human cancer--a surgeon's perspective.
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Interaction of tumour promoters with epithelial cells in culture. An immunofluorescence study.
12-O-tetradecanoyl phorbol-13-acetate (TPA) has a profound and rapid influence on the cytoskeleton of Madin-Darby Canine Kidney (MDCK) cells. Within 10 min, TPA induces a rapid change in morphology, from a flat, cuboidal state to a rounded or elongated morphology in which the cell membranes become convoluted. Concomitant with this morphological change is a rapid dissolution of stress fibres and a redistribution of F-actin from microfilament bundles to a membrane or sub-membranous location. The rearrangement of actin is paralleled by a rearrangement of alpha-actinin and a reduction in the number of vinculin-containing adhesion plaques. Unusual F-actin configurations are often found emanating from a perinuclear location, usually containing alpha-actinin and terminating in a vinculin-containing adhesion plaque. The cytoskeletal rearrangements occur in the presence of inhibitors of protein synthesis or oxidative phosphorylation, but do not occur if glycolysis is also inhibited. The rearrangements are partly abrogated by the presence of cytochalasin B (CB). Despite these dramatic changes in microfilaments the polymerization state of actin remained unaltered after TPA treatment. Furthermore, although changes in the movement of membrane lipids have been reported, no obvious differences in the ability of glycoproteins to redistribute in the plane of the membrane were found as judged by FITC-concanavalin A (conA) induced patching. The rapidity of the morphological response of MDCK cells to TPA indicates that the cytoskeleton is one of the primary targets of TPA, but that tumour promoters differ from RNA tumour viruses in their effect on the state of actin polymerization.
Elective splenectomy. Indications and complications in 102 patients.
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