Evidence for a Second Receptor Binding Site on Human Prolactin

in Journal of Biological Chemistry (1994), 269(51), 32598-606

The existence of a second receptor binding site on human prolactin (hPRL) was investigated by site-directed mutagenesis. First, 12 residues of helices 1 and 3 were mutated to alanine. Since none of the ... [more ▼]

The existence of a second receptor binding site on human prolactin (hPRL) was investigated by site-directed mutagenesis. First, 12 residues of helices 1 and 3 were mutated to alanine. Since none of the resulting mutants exhibit reduced bioactivity in the Nb2 cell proliferation bioassay, the mutated residues do not appear to be functionally necessary. Next, small residues surrounding the helix 1-helix 3 interface were replaced with Arg and/or Trp, the aim being to sterically hinder the second binding site. Several of these mutants exhibit only weak agonistic properties, supporting our hypothesis that the channel between helices 1 and 3 is involved in a second receptor binding site. We then analyzed the antagonistic and self-antagonistic properties of native hPRL and of several hPRLs analogs altered at binding site 1 or 2. Even at high concentrations (approximately 10 microM), no self-inhibition was observed with native hPRL; site 2 hPRL mutants self-antagonized while site 1 mutants did not. From these data, we propose a model of hPRL-PRL receptor interaction which slightly differs from that proposed earlier for the homologous human growth hormone (hGH) (Fuh, G., Cunningham, B. C., Fukunaga, R., Nagata, S., and Goeddel, D. V., and Well, J. A. (1992) Science 256, 1677-1680). Like hGH, hPRL would bind sequentially to two receptor molecules, first through site 1, then through site 2, but we would expect the two sites of hPRL to display, unlike the two binding sites of hGH, about the same binding affinity, thus preventing self-antagonism at high concentrations. [less ▲]

A conserved 5' to 3' exonuclease activity in yeast and human nucleotide excision repair protein RAD2 and XPG

in Journal of Biological Chemistry (1994), 269(50), 31342-5

Traitement de l'ostéoporose: données actuelles et perspectives

in Revue du Rhumatisme (1994), 61(10, Pt 2), 155-164

Postmenopausal osteoporosis is characterized not only by a reduction in bone mass but also by bone microarchitecture alterations, which result in greater bone frailty and in an increased fracture risk ... [more ▼]

Postmenopausal osteoporosis is characterized not only by a reduction in bone mass but also by bone microarchitecture alterations, which result in greater bone frailty and in an increased fracture risk. Many drugs have been studied to determine whether they prevent bone loss or reduce the incidence of additional fractures in patients with established osteoporosis. Primary prevention of osteoporosis rests on regular exercising and adequate intake of dietary calcium. For secondary prevention in women undergoing menopause, replacement estrogen therapy given for at least ten years is associated with substantial reductions in fractures of the radius, hip, and spine. Other drugs capable of arresting postmenopausal bone loss include parenteral, nasal or rectal calcitonin and diphosphonates. However, the long-term safety of the latter requires further evaluation. Current studies are evaluating new molecules with potential preventive efficacy, such as ipriflavone. There is no general consensus about the efficacy of treatments for established osteoporosis with fractures. To date, no controlled studies have demonstrated a reduction in the incidence of further fractures in patients given calcium alone. Studies of hydroxylated vitamin D derivatives have been disappointing, although daily administration of vitamin D3 in combination with calcium significantly reduced the incidence of nonvertebral fractures in a population of elderly institutionalized subjects. Plausible explanations for this effect include increased vitamin D levels and reduced parathyroid levels in the bloodstream. Parenteral or nasal calcitonin stabilizes or increases bone mineral content in both cancellous and cortical bone. This effect is especially marked in high-turn-over patients. Several lines of evidence suggest that calcitonin therapy has a protective effect against vertebral and hip fractures. In patients with osteoporosis, oral or intravenous diphosphonates are associated with a significant increase in cancellous bone mass with no loss of cortical bone. Etidronate may be especially beneficial in severe osteoporosis with marked loss of bone and multiple vertebral crush fractures. Fluoride stimulates the growth and synthetic activity of osteoblasts. Accurate information is needed on the optimal dosage of fluoride, on the effects of fluoride on the appendicular skeleton, and, above all, on the biomechanical properties of the bone produced under fluoride therapy. In addition to these commercially available drugs, several other agents are at various stages of the development process.(ABSTRACT TRUNCATED AT 400 WORDS) [less ▲]

Pyridothiadiazines inhibit glucose-induced insulin release by activating ATP-sensitive K+ channels

Conference (1994, December 10)

Tumeur à cellules géantes du rachis lombaire : traitement chirurgical par vertébrectomie complète en deux temps, y compris la reconstruction

Conference (1994, December 05)

Epidémiologie des facteurs de risque cardiovasculaire : dyslipidémies et hypertension artérielle.

Conference (1994, December 03)

VHRS: the Very High Resolution Spectrograph for the VLT.

in Future VLT Instruments: Scientific Drivers and Concept Definitions (1994, December 01)

Not Available

(Erratum) Further observational evidence that MG J0414+0534 is a gravitational mirage.

in Astronomy and Astrophysics (1994), 292

In Sect. 3.3, the identifications of components A1 and A2 for the optical data were inadvertently inverted. This does not change substantially the discussion; just read A1 for A2 and vice versa. In ... [more ▼]

In Sect. 3.3, the identifications of components A1 and A2 for the optical data were inadvertently inverted. This does not change substantially the discussion; just read A1 for A2 and vice versa. In particular, the ratio A2/A1 = 0.3 cannot be made compatible with the radio value without one or several of the mechanisms we suggested. We apologize for the error and thank Dr S. Mao for bringing it to our attention. Erratum to Astron. Astrophys. 281, 388-394 (1994) [less ▲]

Nomenclature stellaire et catalogues astronomiques - II.

Article for general public (1994)

Not Available

Simulated growth front of 123-(RE)BCO near 211 particles

in Physica C: Superconductivity (1994), 235(Part 1), 427-428

The microstructural features observed on some DyBa2Cu3O7-x, samples show that kinetic considerations are as important as thermodynamic ones. In order to compute and characterize the kinetic growth front ... [more ▼]

The microstructural features observed on some DyBa2Cu3O7-x, samples show that kinetic considerations are as important as thermodynamic ones. In order to compute and characterize the kinetic growth front of 123-(RE)BCO compounds, we have introduced an anisotropic growth direction into a simple two-dimensional growth model: the Eden model defined on a square lattice. The presence of 211 particles has been also considered. The simulated patterns in the ab and ac planes agree with observations and contribute to a more comprehensive model of the kinetic of the growth front near 211 particles. [less ▲]