Native and a synthetic analogue of the malignancy-associated parathyroid hormone-like protein have in vitro transforming growth factor-like properties.

A human parathyroid-like protein (PLP) has recently been isolated and cloned from human tumors associated with the paraneoplastic syndrome, humoral hypercalcemia of malignancy. PLP shares NH2-terminal amino acid sequence similarity with PTH but has a unique primary structure thereafter. Studies reported to date have indicated that both native and synthetic amino-terminal PLP polypeptides display actions in vivo and in vitro that are similar to those of PTH. We report here that purified native PLP and synthetic 36Tyr(1-36)amide human PLP induce epidermal growth factor-dependent transformation of NRK 49F cells in soft agar. Further, the synthetic peptide induces a significant increase in the biosynthesis of fibronectin by human dermal fibroblasts. (1-34)PTH does not display either of these biological activities. These data indicate that there are qualitative differences between PTH and the recently identified PLP. The latter hormone appears to possess transforming growth factor-like properties that may be relevant to its physiological actions.

Human keratinocytes catabolize thymidine.

Human neonatal foreskin keratinocytes incorporate exogenous thymidine into DNA and proliferate in vitro even after reaching confluence. Keratinocytes also catabolize thymidine, as reported for the first time below. Stratified cultures of keratinocytes reduced the amount of thymidine in the medium by more than 90% within 2 to 4 h. Consequently, the rate of incorporation of thymidine (0.2 microM, 4 microCi/ml) into DNA was linear for no more than 2 h. Linear incorporation of thymidine into DNA for at least 12 h could be achieved by continual addition of fresh radioactive thymidine to the culture medium. Different tissues have widely differing abilities to catabolize thymidine. Cutaneous catabolism of thymidine shows striking species differences. Soluble extracts from human neonatal foreskin and adult skin, as well as from cultivated human keratinocytes, actively catabolize thymidine. Soluble extracts of skin from mouse, rabbit, or guinea pig do not catabolize thymidine. Extracts from cultivated human fibroblasts and melanocytes have little or no ability to catabolize thymidine. Catabolism of thymidine by keratinocytes has important implications for the use of [3H]thymidine in studies of keratinocyte proliferation and for the use of thymidine analogs in therapy of cutaneous disease.

Skin-derived fibroblasts respond to human parathyroid hormone-like adenylate cyclase-stimulating proteins.

Human tumors and keratinocyte-conditioned medium contain PTH-like adenylate cyclase-stimulating proteins. Human dermal fibroblasts have receptors that recognize PTH and a factor associated with humoral hypercalcemia of malignancy in rats. We examined 10 human dermal fibroblast lines for an adenylate cyclase response to PTH. Six of 10 lines tested displayed a definite response (2.4- to 3.8-fold over basal) to 10(-6) M bovine PTH-(1-34). This response was inhibited by the PTH analog and antagonist Nle8,18,Tyr34-bPTH-(3-34). We also examined whether human dermal fibroblasts are capable of responding to either a human PTH-like tumor-derived factor or the PTH-like factor contained in human keratinocyte-conditioned medium. Both human humoral hypercalcemia of malignancy-associated tumor extract (2.5 X 10(-10) M) and keratinocyte-conditioned medium (8 X 10(-10) M) stimulated human dermal fibroblast adenylate cyclase. These concentrations are markedly lower than those required for PTH-induced adenylate cyclase stimulation. This activity was also inhibited by the PTH analog. The high prevalence of PTH-responsive adenylate cyclase in dermal fibroblast lines and the apparent potency of tumor-derived and keratinocyte-derived PTH-like factors in dermal fibroblasts suggest that these factors may play a role in normal dermal physiology.

Personnel selection: looking toward the future--remembering the past.

This chapter reviews personnel selection research from 1995 through 1999. Areas covered are job analysis; performance criteria; cognitive ability and personality predictors; interview, assessment center, and biodata assessment methods; measurement issues; meta-analysis and validity generalization; evaluation of selection systems in terms of differential prediction, adverse impact, utility, and applicant reactions; emerging topics on team selection and cross-cultural issues; and finally professional, legal, and ethical standards. Three major themes are revealed: (a) Better taxonomies produce better selection decisions; (b) The nature and analyses of work behavior are changing, influencing personnel selection practices; (c) The field of personality research is healthy, as new measurement methods, personality constructs, and compound constructs of well-known traits are being researched and applied to personnel selection.