The role of complement receptors CD21/CD35 in positive selection of B-1 cells.
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Biomedical subjects
Publications and source records attributed to R R Reid.
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While the significance of natural Ab is not entirely clear, one proposed role is clearance of bacterial Ags. To determine whether natural Ab was involved in clearance of endotoxin, we have examined novel strains of mice with either a total or selective deficiency in Ig. Recombinase-activating gene-2 (RAG-2(-/-))-deficient mice, which have no serum Ig due to arrested development of B cells at the pro-B stage, demonstrate increased sensitivity to endotoxin that correlates with an impaired clearance. When RAG-2(-/-) mice are reconstituted with pooled sera from normal mice, both survival and clearance of circulating endotoxin are enhanced. To further define the nature of the protective Ab, Bruton's tyrosine kinase (Btk)-deficient mice were characterized in the high dose LPS model. Like RAG-2(-/-) mice, they are highly sensitive to endotoxin and have an impaired clearance of LPS. Reconstitution of Btk(-/-) mice, which have reduced levels of IgG3 and IgM, with purified normal mouse IgM dramatically enhances their ability to clear endotoxin compared with mock (saline)-reconstituted littermates. The cellular source of natural anti-LPS IgM was identified as the peritoneal-residing B-1 cell by enzyme-linked immunospot (ELISPOT) assay. Taken together, these studies demonstrate the important role of natural Ab and complement in the clearance of pathogenic substances from the circulation.
Endotoxin shock is a life-threatening syndrome associated with a Gram-negative infection and mediated by a systemic inflammatory response. As a major effector of inflammation, the complement system has been implicated in both the pathogenesis and the protection from endotoxin shock. To clarify the role of complement in endotoxin shock, we have used mice totally deficient in either complement component C3 or C4. We found that both the C3- and C4-deficient mice were significantly more sensitive to endotoxin than wild-type controls. The endotoxin-challenged complement-deficient mice failed to clear endotoxin efficiently from the circulation and this led to excess consumption of C1 inhibitor protein (C1 INH), a major regulator of both complement and the contact system of blood coagulation. Replacement of C1 INH rescued the endotoxin-challenged complement-deficient mice from shock and death. These findings suggest a novel therapy for treatment of endotoxemia with C1 INH protein.
Within the new field of performing arts medicine is an active group of researchers and clinicians who are dedicated to advancing our understanding of musculoskeletal problems of performers. Among these problems are those of the upper extremity in instrumental musicians such as overuse syndrome, entrapment neuropathies, focal dystonia, osteoarthritis, and problems related to joint hypermobility. The epidemiology of these problems is presented as well as results of recent studies investigating their etiology as they relate to musicians. A brief discussion of the treatment of injured musicians also is included.
We administered pulsatile low doses of gonadotropin-releasing hormone (GnRH) (1 to 5 micrograms) to patients whose anovulation was caused by relative and absolute deficiency of endogenous GnRH. Eight such patients, including one with previous pituitary stalk transection, were treated during a total of 23 cycles; pulses of GnRH were administered via a portable pump every 96 or 120 minutes. Activation of pituitary-ovarian function with orderly development of a single dominant follicle, a luteinizing hormone surge, and ovulation occurred in 20 of the 23 cycles. The other three cycles were anovulatory. All patients responded, and five (62%) of the eight conceived, for a total of seven pregnancies and four full-term deliveries of normal infants. This study demonstrates that small pulsatile doses of GnRH can activate cyclic pituitary-ovarian function in hypogonadotropin-acyclic women and induce ovulation resulting in pregnancy and live birth.
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