Anti-HIV-1 ADCC: clinical and therapeutic implications.

The predominant antienvelope cell-mediated cytotoxicity in HIV-1-infected patients is a direct form of antibody-dependent cellular cytotoxicity (ADCC) in which circulating NK/K cells armed with cytophilic antibodies comprise a cytolytic effector cell complex capable of destroying HIV-1-expressing targets. This non-MHC-restricted form of virus-specific cytotoxicity is present in most infected patients, with maximum activity in early disease, gradually declining with disease progression. This endogenous cytotoxicity provides a focal point in the design of interventive strategies involving immune-based therapies. In the first such attempts, the lymphokine interleukin-2 has been employed in an effort to augment these potentially beneficial cytolytic reactivities. The focus of this article is to present the rationale, early clinical results, and future direction of such therapeutic approaches and, in doing so, to illustrate how careful basic research findings can be applied to the design of rational therapeutic strategies.     

Artemia monica cyst production and recruitment in Mono Lake,California, USA

Annual egg production was determined for Artemia monica in Mono Lake, California, from 1983 to 1987. Annual oviparous (overwintering cyst) production was 3 and 7 million cysts m^–2 yr^–1 in 1986 and 1987, respectively, as measured by in situ sediment traps. Cyst production for the entire five year period was calculated using Artemia census data and inter-brood duration derived from mixolimnetic temperature. These estimates ranged from 2 to 5 million cysts m^–2 yr^–1. This method underestimated annual production by 30%, when compared to estimates using sediment traps. Cyst production was similar during 1983–1986 and showed a significant increase in 1987, which was due primarily to a larger reproductive population later in the year. Recruitment into the adult populations of the following spring ranged between 1.4 to 3.2%. Overall abundance of this generation reflected the patterns in annual cyst production. Compensatory effects must operate on the second generation of each year, since summer populations were similar in all years despite differences in cyst production.     

Structure of tendon organs in fishes of the genus Polymixia

Summary Modified branchiostegal rays 1 through 3 support the proximal end of the paired hyoid barbels in the beardfish (Beryciformes: Polymixiidae). The polymixiid barbel is unusual in that it has an unique intrinsic muscular system. Using silver impregnation and electron microscopic techniques, unencapsulated, free nerve endings were located within the tendon of the third modified branchiostegal ray. Branchiostegal rays 1 and 2 do not have any free nerve endings associated with their tendons, however. It is suggested that the free nerve endings are proprioceptors acting as stretch-sensitive mechanoreceptors, and that branchiostegal ray 3 acts as part of a sensory apparatus for monitoring the positional state of the barbel. Branchiostegal rays 1 and 2 merely provide support for the barbel.Abbreviations used in Figures BA barbel - br r 3 branchiostegal ray 3 - IM intermandibularis - IOP interoperculum - LIM interoperculomandibular ligament - MD mandible - MX maxilla - OP operculum - PM premaxilla - POP preoperculum - SOP suboperculum     

Transposition of the kanamycin-resistance transposon Tn903

Summary The insertion of the kanamycin-resistance transposon, Tn903, into the Escherichia coli chromosome was studied. Tn903 is similar in structure to the well known transposons Tn5 and Tn10 in that it has a unique central sequence flanked by inverted repeat sequences extending more than a thousand base pairs. However, the central region of Tn903 has enough single-frame coding capacity only for the drug modifying enzyme, whereas Tn5 and Tn10 carry multigenic unique sequences. In this paper we demonstrate that two different classes of insertion event occur: (1) the first class is a complex event in which all or part of the genome of the bacteriophage lambda vector is co-inserted near the purE locus on the E. coli chromosome (11.7 min); (2) the second class appears to be a simple transposition event in which the transposon alone is inserted at relatively nonspecific sites in the chromosome, as has been described for Tn5 and Tn10. Furthermore both classes show dependency on homology-requiring recombination systems. We suggest that Tn903 transposes infrequently because it must utilize a recA-controlled host function, whereas Tn5 and Tn10 are recA-independent and encode similar but more active functions on the transposon DNA.     

Lectin induction of lymphokines in cultured murine leukocytes

Antigens induce sensitized lymphocytes to undergo mitosis and to secrete soluble products, termed lymphokines, which modulate the immune response. Plant lectins are known to act as polyclonal lymphocyte mitogens and, in some cases, stimulate lymphocytes to produce lymphokines. In an effort to explore the relationship of specific cell surface glycoconjugates to the induction of mitosis and the production of lymphokine activities we have examined the ability of the mitogenic lectins, concanavalin A and Wistaria floribunda mitogen, and the nonmitogenic hemagglutinin from Wistaria floribunda seeds to stimulate the production of macrophage migration inhibition factor (MIF), macrophage chemotactic factor (CF), and lymphotoxin (LT). Concanavalin A causes lymphocytes to produce MIF and LT but no detectable CF activities. W. floribunda mitogen induces lymphocytes to produce soluble substances which exhibit all three lymphokine activities. The nonmitogenic W. floribunda agglutinin causes lymphocytes to produce MIF and CF but no observable LT activity. Within the sensitivity of the assays employed, the results indicate that mitogenesis is not a corequisite of the expression of either macrophage migration inhibition factor or lymphocyte-derived chemotactic factor but it may be associated with the induction of lymphotoxin. It is also apparent that the expression of each lymphokine activity is independent of the expression of the other lymphokines studied.     

Systematic studies of Pinus balfouriana based on volatile terpenoids from wood and needles and on seed morphology

Essential oil from wood and from needles of Pinus balfouriana, growing in six geographically well-separated locations in California, was analysed by GLC. Several monoterpenoid components, in particular -pinene from needles, were found to be usable for distinguishing between trees from the northern and southern parts of the geographic range. Similarity coefficients were calculated and dendrograms constructed. These demonstrated the distinct separation of the northern from the southern populations, and thus substantiated the proposal by Mastrogiuseppe to regard the southern populations as a subspecies. While the northern populations exhibited a tendency to produce larger seeds with longer wings, the difference was of only moderate diagnostic value.     

Evaluation of three E-rosette assays in melanoma patients

Summary The percentage of E-rosette-forming cells (E-RFC) was determined repeatedly in the peripheral blood of 43 patients with malignant melanoma. Three methods of E-rosette assaying were used: total E-rosette test, active E-rosette test, and 29° C E-rosette assay.Depressed E-RFC values were found in fewer assays than normal values. The mean values of E-RFC and the proportion of depressed E-RFC in patients in stage I did not differ from the values in healthy control persons whatever method of assay was used.The frequency of depressed E-RFC values was higher in advanced stages. Significant differences were demonstrated between stage I and stages II and III combined in the values for total and for active E-rosettes (P<0.01).The active E-rosette test and the 29° C E-rosette assay gave no more positive results (i.e., depressed E-RFC values) than the total E-rosette test in melanoma patients.     

Adjacent repeating units of xenopus laevis 5S DNA can be heterogeneous in length

The distribution of length heterogeneity in adjacent repeating units of X. laevis 5S DNA has been examined by “cloning” 5S DNA in bacteria. Fragments of 5S DNA produced by partial digestion with Hind III and containing 1, 4, and 5 repeating units have been inserted at the single Hind III site of the tetracycline-resistance plasmid, pSC101, and the hybrid plasmids cloned in E. coli. Adjacent 5S DNA repeats in the cloned multi-repeat fragments can differ in length. This finding rules out some mechanisms which have been proposed to account for the parallel evolution of tandem repeated DNAs. The results are consistent with an unequal crossing-over mechanism and place some constraints on the molecular processes in this recombinatory event.     

Permeability of sarcoplasmic reticulum membrane. The effect of changed ionic environments on Ca2+ release

Summary Permeability properties and the effects of a changed membrane potential on Ca²⁺ release of sarcoplasmic reticulum vesicles of rabbit skeletal muscle were investigated by Millipore filtration. The relative permeability of sarcoplasmic reticulum to solutes determined under conditions of isotope exchange at equilibrium and/or under conditions of net flow of solute and water into the vesicles was as follows: sucrose, Ca²⁺, Mn²⁺–, choline⁺, Tris⁺–+, Na⁺, Li⁺, Cl^–. Transient membrane potentials were induced by rapidly changing the ionic environment of the vesicles. Knowledge of the relative permeation rates of the above ions allowed prediction of the direction and extent of membrane polarization. Osmotic effects in the polarization measurements due to the rapid influx of solute and water into the vesicles were minimized by using media containing a fast (K⁺ or Cl^–) and a relatively slow (gluconate^– or choline⁺) penetrating ion.⁴⁵Ca²⁺ efflux from vesicles derived from different parts of the sarcoplasmic reticulum structure was not appreciably changed when vesicles were made more positive inside (choline chloride potassium gluconate) or more negative inside (potassium gluconate choline chloride). These studies suggest that part or all of the ion-induced changes in sarcoplasmic reticulum membrane permeability, previously interpreted to indicate depolarization-induced Ca²⁺ release, may be due to osmotic effects.     

Water in normal muscle and muscle with a tumor

The total water content, the amount of non-freezable water, and the Na⁺ and K⁺ contents in the gastrocnemius muscle of albino mice with and without a solid tumor were determined. The spin-lattice relaxation time (T₁) for the water protons in the two kinds of muscle were measured at six resonance frequencies ranging from 4.5 to 60 MHz over the temperature range +37 to −65°C. Quantitatively calculated T₁ values are given. The difference in T₁ for the two types of muscle at temperatures above −5°C is attributed to the difference in the distribution ratio of water between hydration and free states, and bears no direct relation to the concentration of Na⁺.