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1.
F. A. Ferrone 《Cellular and molecular life sciences : CMLS》1993,49(2):110-117
The polymerization of sickle hemoglobin occurs by the same mechanisms in solutions and in cells, and involves the formation of 14 stranded fibers from hemoglobin molecules which have assumed a deoxy quaternary structure. The fibers form via two types of highly concentration-dependent nucleation processes: homogeneous nucleation in solutions with hemoglobin activity above a critical activity, and heterogeneous nucleation in similarly supersaturated solutions which also contain hemoglobin polymers. The latter pathway is dominant, and creates polymer arrays called domains. The individual polymers bend, but also cross-link, and the resulting mass behaves as a solid. The concentration of polymerized hemoglobin increases exponentially unless clamped by rate limiting effects such as oxygen delivery. 相似文献
2.
S. Charache 《Cellular and molecular life sciences : CMLS》1993,49(2):126-132
The most studied pharmacological intervention in sickle cell anemia aiming at elevating HbF expression is the use of hydroxyurea. At the present time the experience has been that after 1 year of treatment with maximum tolerated doses (MTD) all patients showed increases of percent HbF, with a mean of 15% HbF, without apparent side effects besides the reversible ones observed during the process of attaining the MTD. The question of efficacy is presently being investigated by a multicenter placebo controlled double blind clinical trial that involves more than 20 sites. The goal of the study is to determine if hydroxyurea can decrease the incidence of painful crises by 50%. Results of this study are not expected before the end of 1993. 相似文献
3.
M. H. Ravindranath S. M. Brazeau D. L. Morton 《Cellular and molecular life sciences : CMLS》1994,50(7):648-653
Murine B16 melanoma expresses the ganglioside. GM3. GM3 shed from tumor cells is immunosuppressive and promotes tumor growth1. Reduction or elimination of the shed GM3 could be therapeutic, and the anti-GM3 antibodies may reduce and clear the shed ganglioside. To test this hypothesis, mice were challenged with tumor cells, with or without inducing anti-GM3 antibody response. Since gangliosides are poor immunogens and T-cell independent antigens, an adjuvant (monophosphoryl lipid A (MPL), a non-toxic lipid A ofSalmonella), directed against B-cells, was employed. MPL was incorporated onto liposomes and into the surface membrane of B16 mouse melanoma cells; both are rich in GM3. C57BL/6J mice immunized with MPL-liposomes or MPL-B16 cells responded with elevated levels of anti-GM3 IgM. Non-immunized mice or mice immunized with B16 cells alone or ganglioside GM3 alone (without MPL) elicited poor anti-GM3 IgM response, confirming the GM3's immunologic crypticity and MPL's immunopotentiating effect. MPL's immunopotentiating effect was improved by coupling it to melanoma cell membranes C57BL/6J mice were immunized with irradiated B16 alone or MPL alone or MPL-conjugated irradiated B16. After three weekly immunizations, each mouse received a challenge dose of viable syngeneic B16. Neither MPL alone nor B16 alone had a significant effect on tumor growth or host survival; however, administration of MPL-conjugated B16 cells significantly prevented tumor growth and prolonged survival. Our results indicate that MPL-incorporated B16 cells augment the anti-GM3 IgM response, which may reverse GM3-induced immunosuppression by eliminating tumor-derived GM3, and restore immunocompetence. 相似文献
4.
A population of uterine natural killer (NK) cells, commonly called granulated metrial gland (GMG) cells, differentiates in the mouse uterus during normal pregnancy. Little is known regarding the process of differentiation of GMG cells or of other NK cell subsets. It has been suggested that macrophage precursors, under the combined influences of the cytokine growth factors colony stimulating factor-1 (CSF-1) and interleukin-2, become NK-cell like in morphology, pattern of target cell lysis and surface antigen phenotype. Mice expressing the mutation osteopetrosis (op/op) are unable to produce the cytokine CSF-1. To determine whether CSF-1 is required for the successful differentiation of uterine NK cells, implantation sites in pregnant,op/op mice were studied histologically. GMG cell differentiation appeared to progress normally inop/op mice studied between days 7 and 14 of gestation. Thus, the growth factor CSF-1 is not required for differentiation of the uterine NK cell subset known as GMG cells and probably GMG cells do not differentiate from macrophage precursor cells which are deficient inop/op mice. 相似文献
5.
MurNAc etherases cleave the uniqued-lactyl ether bond of the bacterial cell wall sugar N-acetylmuramic acid (MurNAc). Members of this newly discovered family of enzymes are widely distributed among bacteria and
are required to utilize peptidoglycan fragments obtained either from the environment or from the endogenous cell wall (i.e.,
recycling). MurNAc etherases are strictly dependent on the substrate MurNAc possessing a free reducing end and a phosphoryl
group at C6. They carry a single conserved sugar phosphate isomerase/sugar phosphate- binding (SIS) domain to which MurNAc
6-phosphate is bound. Two subunits form an enzymatically active homodimer that structurally resembles the isomerase module
of the double-SIS domain protein GlmS, the glucosamine 6-phosphate synthase. Structural comparison provides insights into
the two-step lyase-type reaction mechanism of MurNAc etherases: β-elimination of the D-lactic acid substituent proceeds through
a 2,3-unsaturated sugar intermediate to which water is subsequently added.
Received 31 August 2007; received after revision 12 October 2007; accepted 1 November 2007 相似文献