The role of 1,25-dihydroxycholecalciferol and prostaglandin E2 in the regulation of human osteoclastic bone resorption in vitro.

Prostaglandins increase human osteoclast generation in vivo whereas they have been shown to exert the opposite effect in vitro: the latter results are based on enumeration of osteoclast-like cells, whose nature is controversial. We have generated human osteoclasts in vitro as assessed by bone resorption, a function unique to the osteoclast, and analysed the role of prostaglandin E2 (PGE2) in osteoclast activity. Human bone marrow cells were cultured to form a mature stroma and then sedimented onto bone slices with or without a recharge of non-adherent bone marrow cells. Bone resorption was increased by 1,25-dihydroxycholecalciferol (1,25(OH)2D3) and PGE2 and inhibited by indomethacin: this inhibition was reversed by addition of PGE2. Our work supports the observation that PGE2 increases bone resorption in vivo and demonstrates the value of assessing osteoclast generation and activity in vitro using bone resorption.

Oral idarubicin in the treatment of acute myelogenous leukaemia and the blast phase of chronic myeloid leukaemia.

Fourteen patients with poor-risk acute myelogenous leukaemia (AML) and five patients with accelerated phase/blast crisis chronic myeloid leukaemia (CML) were treated with 3 days of oral idarubicin (25 mg/m2/day). No complete remissions or return to chronic phase CML were observed. A fall in the peripheral blast count was seen in all patients with the first cycle of treatment, and with subsequent cycles in CML patients, but all responses were transient, with eventual reemergence of peripheral blasts. In some patients, there was a clear cut improvement in symptoms such as bone and splenic pain. Five of the AML patients and all of the CML patients were treated as out-patients. In this group of patients oral idarubicin was found to be a useful drug for palliative treatment.

Cracks and pores: a closer look.

Most pores and some cracks in several rocks, as directly viewed with a new technique, have a shape that suggests an origin early in the history of these rocks. Thus, behavior in the laboratory may be a reliable indication of behavior in the earth's crust, for electrical resistivity, permeability, or other properties that depend on microporosity.

California earthquakes: why only shallow focus?

Frictional sliding on sawcuts and faults in laboratory samples of granite and gabbro is markedly temperature-dependent. At pressures from 1 to 5 kilobars, stick-slip gave way to stable sliding as temperature was increased from 200 to 500 degrees Celsius. Increased temperature with depth could thus cause the abrupt disappearance of earthquakes noted at shallow depths in California.

High-pressure mechanical instability in rocks.

At a confining pressure of a few kilobars, deformation of many sedimentary rocks, altered mafic rocks, porous volcanic rocks, and sand is ductile, in that instabilities leading to audible elastic shocks are absent. At pressures of 7 to 10 kilobars, however, unstable faulting and stick-slip in certain of these rocks was observed. This high pressure-low temperature instability might be responsible for earthquakes in deeply buried sedimentary or volcanic sequences.

Electrical Resistivity Changes in Saturated Rock under Stress.

Electrical resistivity of water-saturated crystalline rock such as granite, diabase, dunite, or quartzite changes by an order of magnitude prior to fracture of the rock in compression. The effect observed even under high confining pressure is due to formation of open cracks which first appear at one-third to two-thirds the fracture stress.

Stick-slip as a mechanism for earthquakes.

Stick-slip often accompanies frictional sliding in laboratory experi ments with geologic materials. Shallow focus earthquakes may represent stick slip during sliding along old or newly formed faults in the earth In such a situation, observed stress drops repre sent release of a small fraction of the stress supported by the rock surround ing the earthquake focus.