Summary 1. The most primitive type of epiphysial mechanism known is found in bony fishes, and from this type all others are easily derivable. The cartilaginous epiphyses contain a mass of undifferentiated cells, a growth zone of flattened cells, and a zone of hyper‐trophied cells derived from them. Endochondral bone and marrow are well developed. Temporary cessation of growth may occur with loss of differentiation in the growth zone and the formation of a closing plate of endochondral bone shutting off the marrow from the epiphysial cartilage. 2. In some modern fishes, Chondrostei and Dipnoi, endochondral bone and marrow have been lost, in others a secondary centre of calcification may be found in the epiphysis, but these changes are peculiar specializations. 3. In primitive tetrapods, including all typical early fossil forms and the living Crocodilia and Chelonia, the cells of the growth zone are arranged more or less regularly in columns, and the endochondral bone, guided by these columns, again has a regular arrangement. 4. Of the modern amphibians the Urodela have lost the regular arrangement of the cells of the growth cartilage, and have reduced the amount of their endochondral bone, while the Anura have developed a peculiar match‐head type of epiphysis with a calcified secondary centre. 5. In Sphenodon a large calcified secondary centre is developed between the articular cartilage and the growth cartilage. By separating these cartilages it allows each to adopt the most advantageous position, the one for the formation of the joint surface, and the other for directing the arrangement of the trabeculae of the endochondral bone. 6. All other groups are specialized in one direction or another. Bony secondary centres which strengthen the epiphyses are found in typical Lacertilia except in some small forms which have lost them, in the tibia of Aves and in Mammalia. Cartilage canals, developed primarily for the nutrition of the cartilaginous epiphyses, are found in Varanidae, Aves and Eutheria, and possibly in Anura, while the Monotremata have a very peculiar cartilage canal system whose development is not yet understood. These features are the result of very detailed parallelisms in evolution. 7. Intratendinous centres of ossification, formed by ossification of tendons where these are inserted into epiphysial cartilage, are distinguished structurally from typical epiphysial centres.

Introduction: The tumour microenvironment is hypoglycaemic, hypoxic and acidotic. This activates a stress signalling pathway: the unfolded protein response (UPR). The UPR is cytoprotective if the stressor is mild, but may initiate apoptosis if severe. Activation of the UPR in breast carcinoma is induced by microenvironmental stress such as glucose and oxygen deprivation, but may also be linked to oestrogen stimulation. It may be clinically significant as it may alter chemosensitivity to doxorubicin. Methods: 395 human breast adenocarcinomas were immunohistochemically stained for UPR activation markers (glucose-regulated protein (GRP-78 and XBP-1). A model of UPR activation in vitro by glucose deprivation of T47D breast cancer cells was developed to determine how the UPR affects cellular sensitivity to doxorubicin and 5-fluorouracil. Cytotoxicity was assessed using a colorimetric cytotoxicity assay (MTT). The effect of oestrogen stimulation and tamoxifen exposure on UPR activation by T47D cells was determined by western blotting measurement of the key UPR protein, GRP-78. Results: Expression of GRP78 and XBP-1 was demonstrated in 76% and 90% of the breast cancers, respectively, and correlated with oestrogen receptor positivity ( P =0.045 and 0.017, respectively). In vitro UPR activation induced resistance to both doxorubicin and 5-flurouracil, ( P <0.05). Oestrogen stimulation induced GRP78 and XBP1 over-expression on western blotting. Tamoxifen did not block this response and may induce UPR activation in its own right. Conclusions: The UPR is activated in the majority of breast cancers and confers resistance to chemotherapy. In vitro oestrogen stimulates UPR induction. UPR activation may contribute to breast cancer chemoresistance and interact with oestrogen response elements.

1. The anatomy of the forefoot in hallux valgus is compared with the normal, with a review of the literature and descriptions of anatomical preparations, observations at operation and radiographs. 2. The early and essential lesions are stretching of the ligaments on the medial side of the metatarso-phalangeal joint that attach the medial sesamoid and basal phalanx to the metatarsal, and erosion of the ridge that separates the grooves for the sesamoids on the metatarsal head. 3. In established hallux valgus a sagittal groove, formed where the cartilage is free from pressure by either the phalanx or the ligaments, cuts off a medial eminence, which articulates with the stretched ligaments, from a restricted area for the phalanx. 4. Apart from osteophytic lipping which squares off the outline of the eminence as it is seen in radiographs and a small amount of lipping of the ridge on the metatarsal there is no evidence of new bone growth. In chronic cases the eminence may degenerate or disappear. 5. The articular surfaces at the cuneo-metatarsal joint become adapted to the changed positions of the metatarsal without gross pathological change. 6. The four deep transverse ligaments that bind together the five plantar pads of the metatarso-phalangeal joints are not unduly stretched, so that as the metatarsals spread it is the ligaments that bind the pads to the heads of the metatarsals that give way. 7. The plantar metatarsal artery to the first space pursues a tortuous course between the two heads of the flexor hallucis brevis. In hallux valgus the course becomes still more tortuous and part of the pain experienced may be due to ischaemic effects.

No abstract

Seedlings of Nymphaea coerulea, N . lotus and Nuphar luteum were examined for monocotyledonous and dicotyledonous characters. The cotyledonary formation could be interpreted either as a single bilobed structure or as two separate cotyledons. However, the presence of an operculum and the recognition of a coleoptile and mesocotyl similar to those of grasses and sedges gave grounds for including Nymphaeaceae in the monocotyledons The form of the hypocotyl and radicle and the leaf-type supported a position, as a specialized family, in or close to the Helobiae.