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Biomedical subjects

P Riddle

Publications and source records attributed to P Riddle.

13 recordsLinked to original sources
PubMed1992

Phenotypic responses of mouse mammary tumours and normal mammary epithelium cultured in collagen gels: correlation with tumour type and progression.

Mammary tumours in female BR6/Icrf mice and the corresponding contralateral normal mammary glands were disaggregated with collagenase and the epithelial structures released ('organoids') separated from other cellular components by filtration. The organoids were established in primary culture in a collagen matrix and the outgrowths obtained were studied by light microscopy and time-lapse cinemicroscopy. The pattern of three-dimensional outgrowths produced was found to be specific to the original tissue. Organoids from normal tissue formed a characteristic outgrowth designated Pattern A. Normal tissue from pregnant mice formed an additional characteristic outgrowth (Pattern A') which has not been described previously. Pregnancy-dependent tumours produced a distinctive phenotypic outgrowth designated Pattern D, whereas pregnancy-independent tumours gave a different distinctive Pattern B as well as a unique specific outgrowth designated Pattern C. Outgrowths of Pattern D from a pregnancy-dependent tumour were removed from culture and implanted into a syngeneic female mouse. Tumours arising in the host were found to be pregnancy-independent and showed phenotypic outgrowths in subsequent culture of pregnancy-independent Patterns B and C. The results show that the type of outgrowths in these cultures correlates with the biology of the tissue in vivo and that changes in tumour progression in vivo are accompanied by alterations in phenotypic outgrowths in culture.

Animals↗
PubMed1991

Gene mapping by microdissection and enzymatic amplification: heterogeneity in leukaemia associated breakpoints on chromosome 11.

A new strategy for mapping chromosome translocation breakpoints in relation to known genes has been developed. This approach is based on the amplification by the polymerase chain reaction (PCR) of specific target sequences from small numbers of microdissected chromosome fragments. This method has been applied to leukaemia-associated translocations affecting the q23 region of chromosome 11. In two independent leukaemias, the t(6;11) translocation was distinguished from the t(9;11) and t(4;11) translocations by demonstrating that the former breakpoint on chromosome 11 lay proximal to the CD3D gene while the latter breakpoints lay distal to CD3D. All three translocation breakpoints were found to lie proximal to ETSI and THYI. The data suggest that although these leukaemia-associated breakpoints on chromosome 11 are cytogenetically identical they may involve disruption of different genes. This approach offers a rapid alternative to mapping by hybridisation of probes either in situ to chromosomes or to somatic cell hybrids containing the appropriate derivative chromosomes.

Base Sequence↗
PubMed1991

Operative factors & tumor membrane antigen changes in escape from immune surveillance of bladder cancer.

1. Survival of skin allografts in mice is increased in proportion to the duration of anaesthesia to a degree that is equivalent to that achievable with a major immunosuppressive agent such as azothiaprine or antilymphocyte serum. 2. Immune cytochemical studies have demonstrated that bladder tumors which metastases express beta HCG and show variable degrees of loss of HLA class I antigens--features which mimic the behaviour of human trophoblast in protecting the foetus from maternal rejection. It is concluded that there may be a case for using such prognostic factors to define a sub group of patients in whom reconstruction of the bladder following cystectomy should be deferred until the patient has survived without metastases for a prolonged period.

Animals↗
PubMed1990

Lysosomal sorting mutants of coronavirus E1 protein, a Golgi membrane protein.

As a model for the intracellular sorting of Golgi membrane proteins, we are studying the E1 protein of the coronavirus Mouse Hepatitis Virus A59. The wild-type protein, when expressed from synthetic RNA, is localised in the Golgi complex. When the second and third of the three predicted membrane-spanning sequences were deleted from the protein, the resulting mutant was retained in the endoplasmic reticulum. In contrast, removal of the first and second membrane-spanning sequences allowed the protein to pass through the Golgi complex and reach the lysosomes. Likewise, when 40 amino acids were deleted from the C-terminal cytoplasmic part of E1, the truncated protein was transported to the lysosomes. We discuss the implications of these results for the structure of the E1 protein and the mechanism by which it is localised in the cell.

Amino Acid Sequence↗
PubMed1990

Narrow linear strips of adhesive substratum are powerful inducers of both growth and total focal contact area.

The stimulus to growth that occurs when cells attach to the substratum can be studied with small adhesive islands. Large numbers of these islands can be grouped together into arrays made up of various sizes, and the response of cells to incubation on these arrays allows the anchorage stimulus to be measured. Past work has shown that single isolated cells can be stimulated to proliferate under these circumstances quite as freely as they do in ordinary cultures, and that the maximum response is given by islands whose size is less than 5000 microns 2. This anchorage stimulus might be mediated by the cytoskeleton, which assembles rapidly around the points of attachment to the substratum. One possible approach to testing this hypothesis is to expose cells to islands of different shapes, and to search for common factors among the different arrangements of the cytoskeleton that these different islands cause. Circular islands induced a relatively disordered arrangement of actin fibres. The fibres were attached at one end to foci of vinculin, which sometimes became arranged in a ring around the margin of the island. Triangular islands showed a more orderly arrangement of actin, in three bands parallel to the sides. In this case, the vinculin accumulated at the apices. Long islands only 3 microns wide could also provide effective attachment for the cells. In this shape the actin accumulated in two bands 2 microns or more apart and up to 5 microns high, and the vinculin similarly collected in parallel interrupted bands along the margins of the island. The number of vinculin foci differed on these three different island shapes, and the total area of vinculin was more than three times greater on long islands than on circles or triangles of the same size. Despite these differences, all three different shapes of island were capable of inducing up to 100 microns 2 of vinculin foci in each cell. Round and triangular islands induced this maximum amount of vinculin when their size was 5000 microns 2. Linear islands induced the same amount when they were only 1000 microns 2. The effect of different shapes on total vinculin focal area was paralleled by their effects on growth. All three shapes could support a similar amount of proliferation. Round and triangular islands induced the maximum amount of proliferation when they were 5000 microns 2 in area, and linear islands when they were only 1000 microns 2.(ABSTRACT TRUNCATED AT 400 WORDS)

Actins↗
PubMed1988

Platelet-derived growth factor promotes division and motility and inhibits premature differentiation of the oligodendrocyte/type-2 astrocyte progenitor cell.

The mitogens which modulate cell-cell interactions during development of the central nervous system are unknown. One of the few interactions sufficiently well understood to allow identification of such molecules involves the two glial lineages which make up the rat optic nerve. One population of glial cells in this tissue, the type-1 astrocytes, secrete a soluble factor(s) which promotes division of a second population of bipotential oligodendrocyte/type-2 astrocyte (O-2A) progenitor cells; these progenitors give rise to oligodendrocytes, which myelinate large axons in the CNS, and type-2 astrocytes, which enwrap bare axons at nodes of Ranvier. Type-1 astrocytes also promote progenitor motility, and inhibit the premature differentiation of progenitors into oligodendrocytes which occur when these cells are grown in the absence of type-1 astrocytes. We have now found that platelet-derived growth factor mimics the effects of type-1 astrocytes on O-2A progenitor cells, and antibodies to PDGF block the effects of type-1 astrocytes.

Animals↗
PubMed1987

Intravesical chemotherapy: combination with Tween 80 increases cytotoxicity in vitro.

Tween 80 was shown to enhance significantly the cytotoxic activities of the four drugs (adriamycin, epodyl, mitomycin-c, thiotepa) most frequently administered intravesically to treat superficial bladder cancer. The colony forming ability of a human bladder cancer cell line, RT112, was measured following a 1 h exposure to each of the four drugs both alone and in combination with 0.1% and 0.3% Tween 80. Cell survival was not reduced by 0.1% Tween 80 alone. We conclude that the combination of Tween 80 with these drugs might increase the therapeutic index of intravesical chemotherapy.

Administration, Intravesical↗
PubMed1985

Stimulating the proliferation of quiescent 3T3 fibroblasts by peptide growth factors or by agents which elevate cellular cyclic AMP level has opposite effects on motility.

The effects of some chemically defined growth factors on the locomotion of quiescent Swiss 3T3 fibroblasts have been studied. A computer digitiser has been used to facilitate recording the paths followed by cells in time-lapse films; this method allows 500 cell-hours to be recorded in 1 h of real time. Individual cells in the same culture vary widely in speed. This variation is not associated with the positions of the cells in the cell cycle; a small deceleration which seems to occur in G2 cannot account for any significant part of the variation seen. Nor is it related to the time elapsing before the cell divides, although this is equally variable; the speed and age at division of particular cells appear to be entirely independent of one another. Nevertheless, good reproducibility is seen between the mean speeds of large numbers of cells from the same type of culture. The mean speed of quiescent cells is less than 2 microns/h. A mixture of epidermal growth factor (EGF) and vasopressin, in the presence of insulin, is known to be a potent promoter of proliferation in this system. We have found it to increase speed to 30 microns/h. Agents which stimulate the cellular level of cAMP are also known to be potent promoters of proliferation in the presence of insulin. We have found these agents to be inhibitors of locomotion; several cycles of cell division take place while the cells move at a speed no greater than that seen in the presence of cytochalasin B (CB) or colchicine. These findings therefore give further support to the idea that there may be two different classes of growth-promoting factors, with major differences in their mode of action. They show that some members of these two different classes have opposite effects on motility.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗
PubMed1978

Movement of human mammary tumour cells in culture: exclusion of fibroblasts by epithelial territories.

Time-lapse cinematography was used to investigate the movement of confronting populations of human mammary epithelium and stromal cells (fibroblasts). Epithelial cell islands from fibroadenomas and from normal lacteal secretions completely excluded the fibroblasts, and individual cell territories were maintained even in dense cultures. Electron microscopy of the boundary between epithelium and fibroblasts showed that the two cell types made contact. In contrast, epithelial islands from two carcinomas did not retain territorial integrity and allowed penetration of mammary fibroblasts. Confronting homologous eptihelial islands from benign tumours merged, but this was shown to be due to interdigitation rather than free mixing of cell. Epithelial cells moved actively but unlike fibroblasts they retained their neighbour relationships.

Adenofibroma↗
PubMed1971

Vasectomy.

Explore the source record for details and available documents.

Adult↗
PubMedDate not supplied

Evidence for migration of oligodendrocyte--type-2 astrocyte progenitor cells into the developing rat optic nerve.

Formation of myelinated tracts in central nervous system (CNS) regions such as the optic nerve seems to depend on two glial cell types, both of which derive from a common progenitor cell. This oligodendrocyte--type-2 astrocyte (O-2A) progenitor cell gives rise to oligodendrocytes, which produce internodal myelin sheaths, and to type-2 astrocytes, which extend fine processes in the region of the nodal axolemma. The optic nerve also contains a third glial cell, the type-1 astrocyte, which derives from a separate precursor. These three glial cells develop in a fixed sequence over a two-week period: type-1 astrocytes appear at embryonic day 16 (E16), oligodendrocytes at the day of birth (E21 or postnatal day P0), and type-2 astrocytes between P8 and P10. Type-1 astrocytes secrete a potent mitogen which causes expansion of the O-2A progenitor cell population in vitro. Here, we report that dividing O-2A progenitor cells are highly motile and seem to migrate from the brain into the optic nerve, beginning at its chiasmal end. Our results indicate that long-distance migration along the neural axis is characteristic only of progenitors of the O-2A lineage and may serve to distribute these cells to regions of the CNS that will become myelinated. These results also suggest that the intrinsic neuroepithelial cells of the optic stalk may be even more restricted than previously thought, giving rise only to type-1 astrocytes.

Aging↗