Full chirality transfer in the synthesis of hindered tertiary boronic esters under in situ lithiation-borylation conditions.

Hindered tertiary neopentyl glycol boronic esters can be prepared by using in situ lithiation-borylation of enantiopure secondary benzylic carbamates at -20 °C with full chirality transfer.

Effect of anticardiolipin/beta2-glycoprotein I complexes on production of thromboxane A2 by platelets from patients with the antiphospholipid syndrome.

OBJECTIVE: Antiphospholipid antibodies (aPL) reactive with anionic phospholipids and beta2-glycoprotein I (beta2-GPI) are found in the sera of patients with autoimmune diseases. Clinically, aPL/beta2-GPI complexes are associated with arterial and venous thrombosis, fetal loss, and thrombocytopenia, i.e., the antiphospholipid syndrome (APS). The mechanism of thrombosis is not known. We hypothesized that aPL/beta2-GPI complexes could perturb the platelet membrane and increase production of thromboxane A2 (TXA2, a proaggregatory prostanoid). METHODS: We isolated an IgG fraction containing anticardiolipin antibody (aCL) and the plasma cofactor, beta2-GPI, from a patient with a high titer of aCL and thrombotic cerebrovascular disease. We then examined the effect of aCL, beta2-GPI, and the aCL/beta2-GPI complex on platelet TXB2 (a stable metabolite of TXA2) biosynthesis in vitro from 7 healthy controls. We also measured in vitro platelet TXB2 biosynthesis in 7 patients with APS and in 8 controls. RESULTS: We found: (1) significantly increased in vitro TXB2 production by platelets from controls after incubation with aCL/beta2-GPI complexes; (2) moderately increased TXB2 production by aCL alone; (3) no increase in TXB2 production by beta2-GPI alone; and (4) significantly increased 11-dehydro-TXB2, a metabolite of TXB2 production in vivo, in the urine of patients with APS compared with controls. CONCLUSION: These data suggest that aCL/beta2-GPI complexes play a role in activating platelets to produce TXA2, which could contribute to the prothrombotic state found in patients with APS.

Writing a job description/contract for a dental hygienist in dental practice.

THE JOB DESCRIPTION: Describes how the dentist wants to use that person in the practice, adapted by communication and the resourcefulness of the employee. A hygienist is trained with a particular philosophy. The practice philosophy is generally something that has developed without the help of the hygienist's philosophy, but none the less both need active manipulation and respect. The job description described here has changed rapidly and will continue to evolve as we communicate, educate and change to try to improve our overall service and delivery. THE CONTRACT: Now that an understanding has been reached as to both hygienist's's and dentist expectations, a contract for employment is required. The Employment Act in New Zealand has determined that this is essential. It is difficult to determine a contract without the job description. A contract should have a time-frame and be concise. It should be firm and binding whereas the job description should be flexible. The contract should have a clause which takes account of the flexibility and developing nature of the job description. The job description can be a baseline not only for the hygienist, but for the communication necessary to develop and improve team systems and programmes. The contract and its renewal is just one of those systems. The changes to a contract can only occur on renewal, but this doesn't mean to say you can't both tear it up and start again. The rapid changes that occur in modern dentistry cannot all be accounted for and there will always be the missing clauses. Your teamwork and communication will reduce these, and help promote a more satisfactory, comfortable and less stressful work environment.

Isolation and purification of anticardiolipin antibody from plasma of a patient with antiphospholipid syndrome: induced generation of platelet thromboxane A2 synthesis.

Antiphospholipid antibodies, particularly anticardiolipin antibodies (aCL) are autoantibodies frequently detected in the serum of patients with systemic lupus erythematosus (SLE) and the primary antiphospholipid antibody syndrome (PAPS). These patients commonly suffer from thrombosis, recurrent fetal loss and thrombocytopenia. Since platelet aggregation is pivotal in the genesis of thrombosis, we tested the hypothesis that perturbation of platelet membrane by aCL/beta 2-glycoprotein (aCL/beta 2GP) complex could trigger the biosynthesis of TXA2, a proaggregatory metabolite of AA. The preincubation of 14C-arachidonic acid (14C-AA)-labeled platelet pellets (14C-PP) from normal individuals with aCL alone followed by incubation with thrombin, resulted in a moderate increase in platelet thromboxane B2 (14C-TXB2) biosynthesis when compared to controls (without aCL). Similar incubations with beta 2GP-I alone resulted in negligible 14C-TXB2 biosynthesis. In contrast, the preincubations of normal 14C-PP with aCL/beta 2GP-I complex resulted in marked thrombin-induced TXB2 biosynthesis, underscoring the requirement of beta 2GP-I in aCL-induced platelet TXB2 biosynthesis. Taken together, these results are consistent with the view that aCL/beta 2GP-I platelet interactions do play a role, at least in part, in platelet hyperactivity and thrombosis in antiphospholipid antibody syndrome.

Immunologic mechanisms in common rheumatologic diseases.

Rheumatoid arthritis and seronegative spondyloarthropathies are rheumatologic diseases that likely are caused by inflammatory reactions occurring in genetically predisposed individuals mounting an immune response to the antigen. Understanding the immunopathology of these diseases provides insight into their etiology, pathogenesis, and a rationale for therapies targeting immune component interactions. Although the antigen in rheumatoid arthritis is not known, several bacterial antigens have been associated with seronegative spondyloarthropathies. These antigens result in an interaction between the human leukocyte antigen-B27 restricted CD8 positive T lymphocytes and the antigen presenting cell, producing an inflammatory response. Rheumatoid factors are autoantibodies directed against the fragment crystallizable portion of the immunoglobulin G. Rheumatoid factor immunoglobulin G immune complexes contribute to the inflammatory events in the rheumatoid joint, and may play an important role in antigen presentation. A novel antigen capture enzyme linked immunosorbent assay was developed that mimicked B cell surface expressed rheumatoid factor. Conversely, a direct binding enzyme linked immunosorbent assay mimicked secreted rheumatoid factor. Comparison of rheumatoid binding enzyme linked immunosorbent assays showed that the physical state of rheumatoid factor can affect binding characteristics. The state of glycosylation of immunoglobulin G may contribute to its antigenic structure. These physical characteristics may be important in rheumatoid factor's pathogenic role in rheumatoid arthritis.

Rheumatoid arthritis: new science, new treatment.

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease that occurs two to four times as often in women as in men and increases in incidence with advancing age. It affects synovial-lined joints and can also affect the pulmonary, cardiac, nervous, integumentary, and reticuloendothelial systems. RA is manifested clinically by malaise and fatigue, followed by a symmetric pattern of joint inflammation characterized by pain and stiffness. RA most likely occurs in the setting of a genetically predisposed individual, triggered by infectious agents or endogenous antigens. Many of the newer treatments being studied involve blocking cytokine-mediated interactions between cells of the synovium.