3 research outputs found
ChemInform Abstract: Cascade Rearrangements. Part 21. Mono- and Bicyclic Cyclopentenes by Rearrangement of 1-Methylcyclobutylmethanols: Synthesis of (.+-.)-Cuparene and Formal Syntheses of (.+-.)-Laurene and (.+-.)-Herbertene.
Cascade rearrangements, part 24. Synthesis and rearrangement of [1,1 '-bicyclobutyl]-1-ols and spiro[3.4]octan-5-ols: a general access to bicyclo[3.3.0]octenes (hexahydropentalenes)
Several new Grignard reagents based on substituted cyclobutanes have been generated and added to cyclobutanones to yield mono- to trimethylated [1,1'-bicyclobutyl]-1-ols. Mono- to trimethylated spiro[3.4]octan-5-ols have been prepared from the parent ketone via alkylation and/or addition reactions. Upon treatment with acid, all [1,1'-bicyclobutyl]- 1 -ols and spiro[3.4]octan-5-ols rearrange to yield a single bicyclo[3.3.0]octene. (C) 2004 Elsevier Ltd. All rights reserved
The regulation of haemopoietic stem cell and progenitor cell proliferation by humoral factors
The mechanisms which regulate the growth fraction of the
haemopoietic stem cell (CFU-S) and granulocyte macrophage
progenitor cell (GM-CFC) have been investigated. In normal murine
bone marrow (NMBM) a small proportion of the CFU-S are synthesising
DNA (-10%). In contrast, in the bone marrow from mice regenerating
after treatment with cytotoxic drugs and in developing haemopoietic
tissues such as murine fetal liver a large proportion of the CFU-S
(-40%) are synthesising DNA. Medium conditioned by normal murine
and human bone marrow cells inhibited the proliferation of rapidly
cycling CFU-S from regenerating bone marrow. This inhibitor was
contained in a 50-100K daltons ultrafiltration fraction. In
contra-distinction medium conditioned by human fetal liver cells
stimulated the proliferation of CFU-S from NMBM. The stimulator
was produced by adherent cells and was contained in a 30-50K
daltons ultrafiltration fraction.
An alternative assay for the humoral regulators of CFU-S
proliferation was developed. Different numbers of haemopoietic
cells were injected into lethally irradiated mice. Five days later
they were injected with 2iCi of
125IUdR
and sacrificed 2 hours
later. There was a linear relationship between the log 125IUdR
uptake into the spleen and femur and the log cell dose injected.
Pre-treatment of haemopoietic cells with an S-phase specific
cytotoxic drug resulted in a reduction in the
125IUdR
incorporation
into the spleen. This enabled the kinetic properties of a
haemopoietic stem cell population to be assessed and the humoral
111
factors which modulate the growth fraction of these cells to be
investigated.
At early stages of gestation (11-14 weeks) in human fetal
liver few GM-CFC are synthesising DNA, whereas later in gestation
(>14 weeks) a large proportion of GM-CFC are in S-phase, Moore and
Williams (1973b). Incubation of NMBM GM-CFC (approx 40% in DNA
synthesis) with a supernatant from an early human fetal liver
(11-14 weeks) reduced the proportion synthesising DNA to <5%. In
contrast, the proportion of murine GM-CFC synthesising DNA was not
affected by incubation with a supernatant from a late human fetal
liver (>14 weeks). GM-CFC that had been switched out of cycle by
incubation with a supernatant from an early gestation human fetal
liver were switched back into cycle following incubation with a
late human fetal liver supernatant. The inhibitor and stimulator
of GM-CFC proliferation were both produced by non-adherent cells
and were contained in >100K and 30-50K daltons ultrafiltration
fractions repectively. It is likely that changes in the relative
levels of a proliferation inhibitor and stimulator throughout
gestation might control the proportion of GM-CFC in cycle
