25-Hydroxyvitamin D3 metabolism in a human leukemia cell line

Summary 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) is a potent inducer of monocytic differentiation of the human promyelocytic leukemia cell line, HL-60. We have noted that 25-hydroxyvitamin D₃ (25(OH)D₃) in high doses is also capable of promoting monocytic differentiation of this cell line. To test the possibility that the latter activity is due to conversion of 25OHD₃ to 1,25(OH)₂D₃ by HL-60, we exposed HL-60 cells to 25OHD₃ and analyzed the products by HPLC and radioreceptor assay. When chromatographed in the traditional solvent system (isopropanol-hexane), a new peak appears which migrates with authentic 1,25(OH)₂D₃. However, in a solvent system containing dichloromethane, 90% of the peak migrates with another metabolite, 19-Nor-10-Keto-25OHD₃ (19-Nor-25OHD₃). Production of this metabolite is enhanced by living cells and is synthesized by both virgin HL-60 and those which have undergone differentiation. We next determined if authentic 19-Nor-25OHD₃ also promotes differentiation of this cell. As assessed by appearance of the monocyte-specific surface antigen (63D3) and macrophage-specific esterase activity, we find that this metabolite does, in fact, induce monocytic differentiation of HL-60 with a potency of approximately 1/200 that of 1,25(OH)₂D₃ and similar to that of 25OHD₃. In agreement with the effect upon cell maturation, 19-Nor-25OHD₃ displaces³H-1,25(OH)₂D₃ from its HL-60 receptor with an efficiency comparable to 25OHD₃. Hence, HL-60 cells convert 25OHD₃ to 19-Nor-25OHD₃, and 19-Nor-25OHD₃ induces monocytic differentiation of HL-60 with comparable efficiency to its precursor, 25OHD₃.     

A stereotactic approach to deep-seated central nervous system neoplasms using the carbon dioxide laser

This report describes a technique in which deep-seated CNS neoplasms, the volume and shape of which had been determined and stereotactically localized by computer reconstruction of CT data, were vaporized with a carbon dioxide laser attached to a stereotactic frame. The clinical results with 6 patients treated by this technique are presented.     

Isolated angiitis of the central nervous system: involvement of penetrating vessels at the base of the brain

Summary Isolated angiitis of the central nervous system (IAC) was diagnosed in a 40-year-old Caucasian male by histological examination of a leptomeningeal biopsy specimen, and the exclusion of systemic inflammatory or infective disease. Therapy with prednisone 30 mg/day and cyclophosphamide 100 mg/day resulted in clinical and radiological improvement, which have been maintained for an 8-month follow-up period. Magnetic resonance imaging (MRI) showed lesions implicating involvement of specific penetrating vessels at the base of the brain, an unusual complication of IAC, and allowed an accurate MRI-clinical correlation.     

Eight year study of viral isolates from cot deaths in Glasgow

Over an eight year period 21 different viral strains excluding polioviruses were isolated in 44 (19%) of 237 cot deaths. The percentage of viral positive cases was significantly greater in over 16 week age groups and in cultures obtained less than 24 hours after death.