Crystal structure of inhibitor-bound human 5-lipoxygenase-activating protein

Leukotrienes are proinflammatory products of arachidonic acid oxidation by 5-lipoxygenase that have been shown to be involved in respiratory and cardiovascular diseases. The integral membrane protein FLAP is essential for leukotriene biosynthesis. We describe the x-ray crystal structures of human FLAP in complex with two leukotriene biosynthesis inhibitors at 4.0 and 4.2 angstrom resolution, respectively. The structures show that inhibitors bind in membrane-embedded pockets of FLAP, which suggests how these inhibitors prevent arachidonic acid from binding to FLAP and subsequently being transferred to 5-lipoxygenase, thereby preventing leukotriene biosynthesis. This structural information provides a platform for the development of therapeutics for respiratory and cardiovascular diseases.     

Type III hyperlipoproteinemia associated with apolipoprotein E deficiency

Subjects with type III hyperlipoproteinemia develop premature atherosclerosis and have hyperlipidemia due to an increase in cholesterol-rich very low density lipoproteins (VLDL) of abnormal electrophoretic mobility. Apolipoprotein E is a major protein constituent of VLDL and appears to be important for the hepatic uptake of triglyceride-rich lipoproteins. A new kindred of patients with type III hyperlipoproteinemia is described in which no plasma apolipoprotein E could be detected, consistent with the concept that type III hyperlipoproteinemia may be due to an absence or striking deficiency of apolipoprotein E.     

Vibriolytic antibody-forming cells: a new application of the Pfeiffer phenomenon

Complement-mediated immune lysis was first described by Pfeiffer after observing an immune reaction against Vibrio cholerae. Application of this reaction in agar gel, with viable vibro organisms, gave results which were unique compared to the red blood cell or enterobacterial systems. Among these was the lack of a detectable "background," a lengthened latent period and differentiable results among the three major cell wall antigens characteristic of this bacterial groups.     

Excitation of orbital angular momentum resonances in helically twisted photonic crystal fiber

Spiral twisting offers additional opportunities for controlling the loss, dispersion, and polarization state of light in optical fibers with noncircular guiding cores. Here, we report an effect that appears in continuously twisted photonic crystal fiber. Guided by the helical lattice of hollow channels, cladding light is forced to follow a spiral path. This diverts a fraction of the axial momentum flow into the azimuthal direction, leading to the formation of discrete orbital angular momentum states at wavelengths that scale linearly with the twist rate. Core-guided light phase-matches topologically to these leaky states, causing a series of dips in the transmitted spectrum. Twisted photonic crystal fiber has potential applications in, for example, band-rejection filters and dispersion control.     

Human beta-adrenoceptors: relation of myocardial and lymphocyte beta-adrenoceptor density

In human right atria obtained from 21 patients during open-heart surgery, beta-adrenoceptor density [assessed by iodine-125-labeled (-)-cyanopindolol binding] and responsiveness (positive inotropic responses to isoprenaline) were linearly related to the beta-adrenoceptor density in the corresponding circulating lymphocytes. This direct relation of human myocardial and lymphocyte beta-adrenoceptor alterations, therefore, makes it possible to monitor drug- or disease-induced beta-adrenoceptor changes in tissues not easily accessible in humans.     

Deleted HTLV-I provirus in blood and cutaneous lesions of patients with mycosis fungoides.

Mycosis fungoides, a rare form of cutaneous T cell leukemia/lymphoma, is suspected of having a viral etiology on the basis of certain similarities to adult T cell leukemia, which is associated with human T cell leukemia/lymphoma virus type I (HTLV-I) infection. Cell lines were established from peripheral blood mononuclear cells (PBMC) of an HTLV-I-seronegative patient with mycosis fungoides. DNA hybridization analysis revealed the presence of HTLV-I-related sequences with unusual restriction endonuclease sites. Sequence analysis of subcloned fragments demonstrated the presence of a monoclonally integrated provirus with a 5.5-kilobase deletion involving large regions of gag and env and all of pol. Additional evidence for the presence of deleted proviruses was found by polymerase chain reaction (PCR) amplification of DNA from cutaneous lesions of five other HTLV-I-seronegative patients. The findings suggest that HTLV-I infection may be involved in the etiology of at least certain cases of mycosis fungoides.