Characterization of the IgG-Fc receptor on human platelets

To determine quantitatively the number and avidity of receptors for the Fc portion of IgG on human platelets, we have measured the binding to platelets of human monomeric monoclonal IgG, and of small covalently crosslinked polymers of IgG1 labeled with 125I. The binding of labeled IgG1 monomers to platelets is too weak to permit quantitation. The binding of dimers or larger polymers of IgG1 is much more avid (greater at 4 degrees C than 37 degrees C), is readily reversible, and is saturable. The number of receptor sites ranges from 400 to 2000 per platelet and the mean equilibrium association constant (Ka) for the binding of dimers at 4 degrees C is 2.2 x 10(7) M-1 +/- 0.9 x 10(7) M- 1. The binding is specific for the Fc portion of IgG, and IgG1 and IgG3 bind to the receptors much more avidly than IgG2 or IgG4. Unlabeled IgG1 dimers are about 7--8-fold more potent in inhibiting binding than are IgG1 monomers, and larger polymers are even more potent than dimers. Thus, the Fc receptors on platelets bind human IgG1 with the same specificity and similar avidity as Fc receptors on polymorphonuclear leukocytes (PMNs), but PMNs have about 300-fold more receptors per unit of surface area than platelets.     

The variability of hemolysis in the cold agglutinin syndrome

The amount of lysis effected by cold agglutinins is directly related to the ability of the antibody to initiate complement activation. This ability is modified by the concentration of antibody, its thermal amplitude (the highest temperature at which the antibody will react with the cell), the degree to which antibody fixation is modified by the presence of complement components (particularly C3) on the membrane, and the degree to which antibody, once fixed, is able to fix the components of complement. In vitro measurement of these factors correlates with the rate of hemolysis in vivo.     

ELISA detection of IgM antibodies against phenolic glycolipid-I in the management of leprosy: a comparison between laboratories

IgM antibodies to the phenolic glycolipid-I (PGL-I) antigen of Mycobacterium leprae were detected by different ELISA techniques in three laboratories (in New York, Colorado, Seattle, U.S.A.). The agreement on seropositivity and overall correlation between techniques was excellent. A positive linear correlation between the bacterial index (BI) and anti-PGL-I IgM, previously reported by the New York laboratory, was detected by all techniques. The role of erythema nodosum leprosum in decreasing the relationship of BI versus anti-PGL-I IgM was seen by the New York laboratory with sera diluted 1:20 and ABTS substrate solution and by the Colorado laboratory but not by New York with sera at 1:300 and OPD substrate or by the Seattle laboratory.     

The biochemical and clinical consequences of 2'-deoxycoformycin in refractory lymphoproliferative malignancy

A deficiency of adenosine deaminase, an enzyme important in purine nucleoside catabolism, is associated with a severe combined immunodeficiency disease in children. Inhibition of this enzyme in vitro and in vivo results in an impairment in lymphoblast proliferation. We have investigated the pharmacologic inhibition of this enzyme by 2'-deoxycoformycin in 15 patients with hematologic malignancies. Biochemical consequences of the administration of this agent were closely monitored in erythrocytes, nucleated peripheral blood and bone marrow cells, serum, and urine. A marked rise in erythrocyte dATP was accompanied by a depletion of ATP in those patients exhibiting toxicity. Most patients excreted large amounts of deoxyadenosine but not adenosine in the urine. Serum deoxyadenosine rose in patients demonstrating a marked decrease in cell mass. The biochemical disturbances and clinical toxicity, including hepatic, renal, and conjunctival abnormalities, were usually reversible. Central nervous system toxicity, which potentially was the most serious consequence, was associated with high erythrocyte dATP/ATP ratios and high levels of cerebrospinal fluid deoxyadenosine. In patients with lymphoma and leukemia, objective responses were observed but were short- lived. Patients with chronic lymphocytic leukemia receiving weekly low doses of the drug demonstrated minimal toxicity and some efficacy. The chemotherapeutic potential o 2'-deoxycoformycin, as either a single agent or in combination with Ara-A, merits further exploration.     

HIV and STI Risk Behaviors, Knowledge, and Testing Among Female Adult Film Performers as Compared to Other California Women

A cross-sectional structured online survey was self-administered to a convenience sample of current female adult film performers via the Internet; bivariate analyses compared HIV and other STI risk behaviors, knowledge, and testing in female adult performers to California Women’s Health Survey respondents. 134 female adult film performers (mean age 27.8 years) were compared to the 1,773 female respondents (mean age 31.3 years) to the 2007 CWHS. Female performers initiated sex on average 3 years younger and had 6.8 more personal sexual partners in the prior year than other California women. The majority of performers reported HIV and Chlamydia testing (94 and 82%, respectively) in the prior 12 months. They more likely to use condoms consistently in their personal life than other California women (21 vs 17%), though this difference disappeared after controlling for other variables. Adult performers are routinely tested for HIV and Chlamydia, yet they have multiple sexual partners and use condoms inconsistently.     

Prostaglandins and angioplasty. An experimental study in canine arteries

To prevent platelet aggregation following percutaneous transluminal angioplasty (PTA), cyclooxygenase inhibitors such as acetylsalicylic acid (ASA) and indomethacin are recommended. However, ASA blocks both the proaggregating effects of thromboxane (TXA2) and the antiaggregating and vasodilating effects of prostacyclin (PGI2). The authors measured the contractile response of dilated canine carotid arteries in situ and in vitro using an isometric force transducer. Following PTA, contraction of the arterial wall was significantly reduced (p less than 0.01). By blocking cyclooxygenase with indomethacin (3 micrograms/ml), contraction was greatly improved (p less than 0.001). These results suggest that PTA may result in marked release of prostacyclin by the damaged arterial wall, which could account for the decreased responsiveness of the artery to exogenous norepinephrine.     

D-Arg[Hyp3-Thi5-D-Tic7-Tic8]-bradykinin, a potent antagonist of smooth muscle BK2 receptors and BK3 receptors.

D-Arg[Hyp3-Thi5-D-Tic7-Tic8]-bradykinin (NPC 16731) inhibited bradykinin (BK) binding and BK-induced contraction in guinea-pig ileum, being markedly more potent than D-Phe7-BK analogues as a BK2 receptor antagonist. In isolated trachea NPC 16731, unlike other BK2 antagonists, inhibited BK binding and BK-induced contraction, and 45Ca2+ efflux in tracheal smooth muscle cells. That NPC 16731 potently inhibits BK effects in trachea provides further evidence for the existence of the airway BK3 receptor.     

In vivo immunologic selection of class I major histocompatibility complex gene deletion variants from the B16-BL6 melanoma

The mechanism by which tumor allografts escape host immunologic attack was investigated. B16-BL6 cells (the bladder 6 subline of the B16 melanoma) (H-2b) were transfected with a gene (Dd) encoding an allogeneic class I major histocompatibility complex antigen. Clones that expressed Dd antigen were injected into the footpads of nonimmune syngeneic mice, syngeneic immune mice, and nude mice. Under conditions of immunologic selection a clone that contained multiple copies of the transfected gene formed variants that lacked the transfected gene. Primary tumors and pulmonary metastases of immunized mice and pulmonary metastases of nonimmunized mice had lost the Dd gene and, in most cases, all of the associated plasmid. In contrast, in immunodeficient nude mice, primary tumors and pulmonary metastases retained the Dd gene and the associated plasmid. Deletion of genes encoding cell surface antigens may be one of the mechanisms by which allogeneic tumors escape immunologic attack.