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M Holman

Publications and source records attributed to M Holman.

46 records · Page 3Linked to original sources
PubMed1986

Activation and proliferation signals in mouse B cells. VIII. Induction of DNA synthesis in B cells by a combination of calcium ionophores and phorbol myristate acetate.

Mouse B cells cultured with either phorbol myristate acetate (PMA), or with Ca2+ ionophores enter a transitional activated state, between quiescence (G0) and G1, but do not synthesize DNA. It is shown here that the combination of PMA plus the ionophore ionomycin induces resting B cells to synthesize DNA, but not to secrete antibody. B cells from CBA/N mice carrying the xid defect, and those from the lipopolysaccharide-unresponsive C3H/HeJ strain also respond to this combination. Suboptimal doses of the two stimuli synergize with B cell-stimulating factor 1 in promoting proliferation of resting B cells, but the co-mitogen does not substitute for type II B cell growth factor in the BCL1 lymphoma. Furthermore, (as predicted) the combination of these two agents does not induce the breakdown of inositol phospholipids in B cells. These data are consistent with the hypothesis that elevation of intracellular Ca2+ (by the ionophore), plus activation of protein kinase C (by PMA) leads to DNA synthesis in B cells. The combination of Ca2+ ionophore and PMA thus appears to essentially mimic the biochemical effects of ligation of surface immunoglobulin receptors on B cells, by providing the two second messengers normally emanating from the receptor-mediated breakdown of polyphosphoinositides.

Animals↗
PubMed1986

Interleukin 4 (B-cell growth factor II/eosinophil differentiation factor) is a mitogen and differentiation factor for preactivated murine B lymphocytes.

Recently we described a murine T-cell hybrid that produces activities that promote the differentiation of eosinophils (eosinophil differentiation factor) and cause proliferation of the BCL1 B-cell lymphoma (B-cell growth factor II activity). Both activities appear to be associated with the same molecule, which has therefore been termed interleukin 4. The hybrid does not produce any other known lymphokines. We now find that purified interleukin 4 has no effects on small resting B cells but induces naturally occurring large B cells (which have presumably been preactivated in vivo) to synthesize DNA and to secrete IgM and low levels of IgG. B cells activated by anti-Ig antibodies apparently only become responsive to the factor once they have reached late G1 stage. All bioactivities of interleukin 4 are associated with a protein of Mr 44,000 (by NaDodSO4/PAGE). Therefore these results demonstrate that this lymphokine alone is sufficient to induce clonal expansion and maturation of activated B cells.

Animals↗
PubMed1985

Activation and proliferation signals in mouse B cells. VII. Calcium ionophores are non-mitogenic polyclonal B-cell activators.

Calcium ionophores cause polyclonal proliferation of lymphocytes from man, rabbit and pig, but are not mitogenic for mouse T or B lymphocytes. We show here that two Ca2+ ionophores (A23187 and ionomycin) nonetheless activate a substantial proportion of mouse B lymphocytes at concentrations which effectively inhibit DNA synthesis induced by conventional mitogens, such as anti-immunoglobulin antibodies. Activation of B cells was detected by (i) increased expression of Ia antigen after 24 hr culture with ionophores, and (ii) the accelerated onset of DNA synthesis in B cells primed with ionophores for 24 hr, washed and then rechallenged with anti-Ig. Unlike anti-Ig, the ionophores did not induce either the breakdown of inositol phospholipids, or RNA synthesis in B cells. Finally, activation of B cells by ionophores is highly susceptible to inhibition by cyclosporine. These results therefore suggest that elevation of intracellular Ca2+ induced by these ionophores is sufficient to cause B cells to leave Go, but not to enter the G1 phase of the cell cycle. Clearly, additional signals are required for B cells to progress further into cycle and eventually become committed to DNA synthesis.

Animals↗
PubMed1984

Activation and proliferation signals in mouse B cells. III. Intact (IGG) anti-immunoglobulin antibodies activate B cells but inhibit induction of DNA synthesis.

Intact (IgG) rabbit anti-immunoglobulin antibodies are generally not mitogenic for mouse B cells but, on the contrary, inhibit proliferation induced by either F(ab')2 anti-Ig or by lipopolysaccharide. We show here, however, that IgG anti-Ig activates mouse B cells, since it causes B cells to depolarize, to enlarge and to express increased levels of Ia antigens. In the continuing presence of IgG anti-Ig, B cells do not synthesise DNA. However, if cells cultured with IgG antibody are then washed, they start to proliferate earlier in response to F(ab')2 anti-Ig, i.e. they have become primed. We therefore conclude that IgG anti-Ig is an example of a 'step-one activator' for mouse B cells, which drives resting B cells out of Go, but actively prevents the cells from progressing into S. The latter effect appears to result from cross-linking of surface Ig and Fc receptors on B cells, although the mechanism is, as yet, unknown.

Animals↗
PubMed1966

Transmission from intramural inhibitory nerves to the smooth muscle of the guinea-pig taenia coli.

1. Membrane potential changes of smooth muscle cells were recorded during stimulation of the intramural inhibitory nerves to the taenia coli.2. Stimulation across the taenia coli with single pulses of 200 musec duration excites the intramural nerves and not the muscle directly.3. The membrane potential changes due to stimulation of the intramural inhibitory nerves were different from those produced by perivascular inhibitory nerve stimulation in the following ways: hyperpolarizations (i.j.p.'s) of up to 25 mV were produced in response to single pulses; the latency, i.e. the time taken for the membrane to hyperpolarize after a stimulus of maximal strength, was as short as 80 msec; when the nerves were stimulated repetitively the membrane was hyperpolarized by up to 35 mV and all spontaneous activity was abolished; the mean hyperpolarization due to repetitive stimulation increased with the frequency of stimulation up to 10 pulses/sec and then remained constant; the hyperpolarization due to stimulation at frequencies greater than 5 pulses/sec was not maintained but decreased after 3-5 sec of stimulation; and finally when stimulation had ceased action potentials commenced firing at frequencies greater than normal.4. The amplitude and rate of hyperpolarization of the i.j.p. increased with increasing strength of stimulation until a maximum amplitude and rate of hyperpolarization was reached. The recovery or depolarizing phase of the i.j.p. was exponential with a time constant which varied from about 250 msec to 500 msec and could not therefore be due to the discharge of the membrane capacitance. In some cases there was an inflexion on this depolarizing phase and in these cases recovery led directly into an action potential.5. Spontaneous hyperpolarizations of the membrane were seen in some cells, and these hyperpolarizations were similar to those recorded on submaximal stimulation of the intramural nerves.6. There were no changes in the characteristics of the i.j.p. in the presence of guanethidine or bretylium.

Animals↗
PubMedDate not supplied

Nosocomial sepsis in neonates with single lumen vascular catheters.

Catheter-related sepsis is commonly encountered in the neonatal intensive care unit. We retrospectively studied infants with vascular catheters at 2 NICUs. Data were obtained from the computerised admission records available at both the hospitals. Our aims were to describe the clinical and microbial profile of nosocomial sepsis in infants with vascular catheters [umbilical artery (UA), umbilical venous (UV), central venous Broviac (CV), percutaneously placed central venous (PC), peripheral artery (PA)], and to determine the association between catheter type, duration and sepsis in a subset of the population. Nosocomial sepsis (positive blood culture after the 3rd postnatal day) occurred in 217 of 2091 (10.4%) infants. Infected infants, in contrast to non-infected, had a significantly (P < 0.001) greater number of multiple catheters (2.3 vs 1.4) had lower birth weights (1.2 vs 2.1 kg), were younger (28 vs 33 weeks) and had lower 1 and 5 minute Apgar scores (4.3 and 6.7 vs 5.5 and 7.4). The most common organism was coagulase negative Staphylococcus. In a subset population as analyses revealed, longer duration of UA use was associated with higher infection rates [13.6% with UA use for > or = 8 days vs 1.3% for < or = 7 days (P < 0.0001)]. PC use had a lower rate of sepsis than CV use (5.1% vs 15.2%; P < 0.05). Use of intravascular catheters should be balanced between the need for vascular access and the risk of sepsis.

Catheterization↗