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PubMed1989

Measurement and characterization of postischemic free radical generation in the isolated perfused heart.

Electron paramagnetic resonance spectroscopy has been applied to measure radical generation in the postischemic heart; however, there is controversy regarding the methods used and the conclusion as to whether radicals are generated. In order to resolve this controversy, direct and spin trapping measurements of the time course and mechanisms of radical generation were performed in isolated perfused rabbit hearts. In reperfused tissue, 3 prominent radical signals are observed: A, isotropic g = 2.004 suggestive of a semiquinone; B, anisotropic g parallel = 2.033 and g perpendicular = 2.005 suggestive of ROO.; and C, a triplet g = 2.000 and aN = 24 G suggestive of a nitrogen centered radical. B and C, however, are highly labile and disappear at temperatures probably encountered in some previous studies. In normally perfused hearts, A is observed with only small amounts of B and C. During ischemia, B and C increase reaching a maximum after 45 min while A decreases. On reflow with oxygenated perfusate all 3 signals increase. With varying duration of ischemia and reflow, peak signal intensities occurred after 15 s of reflow following 30 min of ischemia. Reperfusion with superoxide dismutase, deferoxamine, or mannitol abolished the reperfusion increase of B. Measurements performed with the spin trap 5,5'-dimethyl-1-pyrroline-N-oxide (DMPO) demonstrated a similar time course of radical generation with prominent DMPO-OH and DMPO-R signals peaking between 10 and 20 s of reflow. Superoxide dismutase and deferoxamine also quenched these signals. Thus, .O2- derived .OH, R., and ROO. radicals are generated in postischemic myocardium. While the experimental techniques used can result in loss of intrinsic radicals and generation of extraneous radicals, with proper care and controls valid measurements of free radicals in biological tissues can be performed.

Animals↗
PubMed1985

Suppression of alloimmune cytotoxic T lymphocyte (CTL) generation by depletion of NK cells and restoration by interferon and/or interleukin 2.

By using rabbit antiserum to a glycolipid, ganglio-n-tetraosylceramide (ASGM1), the accessory effect of natural killer (NK) cells on the generation of alloimmune CTL in mice was investigated. When normal C3H/He mice were immunized with C57BL/6 or BALB/c spleen cells, they generated alloimmune CTL with a surface marker phenotype of Thy-1+ Lyt-1-2+ ASGM1-, preceded by early augmentation of cytotoxic activity of NK cells with a Thy-1-Lyt-1-2-ASGM1+ phenotype. Administration of anti-ASGM1 (10 microliters) in mice resulted in a complete depletion of NK activity and ASGM1+ cells in the spleen even 1 day after injection, but no changes in the proportions of T (Thy-1+) cells and their Lyt-1 and Lyt-2 subsets as revealed by an immunofluorescence analyzer (FACS) and phagocytic cells. When these anti-ASGM1-treated mice were immunized with allogeneic cells, they showed neither augmented NK activity nor generation of alloimmune CTL, and spleen cells isolated from these anti-ASGM1-treated mice produced no CTL response to alloimmunization in vitro. Normal spleen cells treated with the antiserum and complement in vitro also showed a complete NK depletion without any deterioration of T cells and their Lyt-1 and Lyt-2 subsets, and when stimulated with allogeneic cells they generated no CTL. Spleen NK (ASGM1+) cells were purified by Percoll-gradient centrifugations followed by complement-dependent killing of T cells with the use of anti-Thy-1 monoclonal antibody, and were further purified by panning methods with anti-ASGM1, giving a preparation consisting of greater than 90% ASGM1+, Ly-5+ cells, and less than 0.5% of Thy-1+, Lyt-1+, and Lyt-2+ cells. These purified ASGM1+ Thy-1- cells alone generated no alloimmune CTL in response to alloantigens, suggesting that ASGM1+ NK cells contained no precursors of alloimmune CTL. When added into NK-depleted spleen cells, they restored the normal alloimmune CTL response of the spleen cells, indicating that ASGM1+ fractions contained cells to provide an accessory function for CTL generation. Lyt-1+ cells purified by panning methods did not restore the CTL response of NK-depleted spleen cells. These results indicate that ASGM1+ NK cells, but not Lyt-1+ helper T cells contaminating ASGM1+ fractions at undetectable levels, are responsible for the accessory function. When these purified ASGM1+ Thy-1- cells were stimulated with allogeneic cells, they produced IL 2 and IFN.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Antiresorptive dose-response relationships across three generations of bisphosphonates.

The first generation of bisphosphonates was discovered in the late 1960s and is characterized by short alkyl or halide side-chains. Well known representatives of this class are 1-hydroxyethane-1,1-bisphosphonate (etidronate) and dichloromethane bisphosphonate (clodronate). The antiresorptive activity of these and other analogues was measured in an assay in which a drug was administered for 7 days to growing rats, followed by a morphological assessment of bone volume. In this model, the first generation analogues have antiresorptive activity at dose levels from 0.1 to 10 mg P/kg. Some first generation analogues are now used to treat metabolic bone disease but, when given orally, their efficacy in aggressive resorptive disease may be limited because of low potency. A second generation of bisphosphonates, characterized by an amino terminal group and a higher antiresorptive potency, includes 3-amino-1-hydroxypropane-1,1-bisphosphonate (pamidronate) and 4-amino-1-hydroxybutane-1,1-bisphosphonate. Their antiresorptive activity in growing rats ranges from 0.01 to 1 mg P/kg. In the 1980s a third generation of bisphosphonates, characterized by a cyclic chain, was synthesized. It includes series of pyridinyl ethane bisphosphonates, pyridinyl aminomethane bisphosphonates, indan bisphosphonates, cyclopentane bisphosphonates, piperidyl ethane bisphosphonates, pyridinyl and piperidyl hydroxyethane bisphosphonates, piperidinylidene aminomethane bisphosphonates, and pyridinyl oxa- and thiomethane bisphosphonates. Several of these show antiresorptive activity in growing rats as low as 0.001 mg P/kg. Many of the first-, second- and third-generation bisphosphonates have been tested in a model of retinoid-induced bone resorption, and in this model the rank ordering of potency is similar, though somewhat larger doses of bisphosphonate are required to block the resorption induced by the retinoid.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Effects of first and second generation sulphonylureas on cardiotoxicity of strophanthidin in rabbits.

The effects of the first generation sulphonylurea compound gliclazide and the second generation sulphonylurea compound glipizide on strophanthidin toxicity was investigated in rabbits. The sulphonylurea pretreated animals were intravenously infused with 23 mumol/kg strophanthidin until the appearance of the first ventricular ectopic beat and continued thereafter until the appearance of ventricular fibrillation. The first generation sulphonylurea gliclazide increased, while the second generation sulphonylurea glipizide decreased the strophanthidin toxicity in a dose dependent manner. It was concluded that instead of first generation sulphonylureas, second generation sulphonylureas must be preferred in cardiac glycoside treated diabetics, when sulphonylurea treatment is necessary.

Animals↗
PubMed1989

Generation of oxidants in the near-UV photooxidation of human lens alpha-crystallin.

In this study we report on the generation of superoxide anion (O2-) and hydrogen peroxide in the near-UV irradiation of human lens alpha-crystallin by monochromatic light at 300 nm. Photolysis of human lens alpha-crystallin at 300 nm, at irradiances similar to those encountered in sunlight causes an alteration of protein tertiary structure, a loss of tryptophan fluorescence and increase of nontryptophan fluorescence. The nontryptophan fluorescence is likely to be due to the photooxidation of tryptophan to N-formylkynurenine (N-FK or related species), which is a good photodynamic sensitizer, has significant absorption at 300 nm, and can thus react via its triplet state with O2 to generate 1O2 or with reducing substrates (amino acids of the protein) to generate free radicals. The latter, in the presence of O2 can lead to the generation of O2- and H2O2. These species have been directly assayed in this study in photolyzed solutions of fetal, young and old human lens alpha-crystallin. The addition of superoxide dismutase (SOD) to the protein solution prior to photolysis increased the amount of H2O2 generated by 3- to 4-fold. This observation not only provides definitive evidence for the photogeneration of O2-, but also indicates that only a fraction of this species is transformed into H2O2 in the absence of SOD. Significant amounts of O2- and H2O2 were formed by 340 nm irradiation of old human lens alpha-crystallin, in which the basal level of N-FK is high. The role of 1O2 in these photoreactions has been studied by investigating the quenching effect of azide and the enhancing effects of D2O on the rate of loss of tryptophan fluorescence yield and the effect of azide on the rate of H2O2 generation.

Adult↗
PubMed1989

Generation and characterization of purified adherent lymphokine-activated killer cells in mice.

During the incubation of murine spleen, lymph node, or bone marrow cells with IL-2 (1000 U/ml) a small percentage of cells became adherent to the surface of plastic tissue culture flasks. After removal of the non-adherent lymphoid cells, plastic adherent lymphokine-activated killer (LAK) cells could be efficiently expanded in the presence of IL-2. Plastic adherent-derived A-LAK cells were characterized by high rates of proliferation and their cytotoxic activity was more than 10 fold higher than LAK cells generated in the bulk (unfractionated) spleen cell cultures. A-LAK cells could be continuously generated from the non-adherent cell population. Using multiple transfers (every 1 to 2 days) of non-adherent LAK cells into new flasks, new rounds of plastic adherent cells were generated with high expansion capability and high levels of cytotoxic activity. Morphologically, A-LAK cells were large granular lymphocyte and phenotypically expressed markers characteristic of NK cells (asialo GM1+, NK1.1+, Qa5+, Ly-6.2+, Thy-1.2+, but negative for Lyt-2.2 and L3T4). A-LAK cells generated from mice of different strains expressing low and high levels of NK cell activity were equally highly cytotoxic. However, A-LAK cells obtained from nude or beige mice had relatively lower levels of cytotoxicity. Stimulation of NK cell activity by poly I:C or inhibition by in vivo or in vitro treatment with anti-asialo GM1 serum did not affect the generation of A-LAK cells. A-LAK cells derived from spleen or bone marrow of C57BL/6 or nude mice treated with anti-asialo GM1 serum were found to be asialo GM1+ suggesting that A-LAK cell could be generated from the asialo GM1- precursor cells. Expansion of plastic adherent A-LAK cells in the presence of IL-2 could provide large numbers of highly purified cytotoxic A-LAK cells suitable for cancer immunotherapy.

Animals↗
PubMed1988

Superoxide generation by the electrogenic NADPH oxidase of human neutrophils is limited by the movement of a compensating charge.

The ability of the NADPH oxidase of human neutrophil-derived cytoplasts to generate O2.-anions on the addition of phorbol 12-myristate 13-acetate is severely reduced in the presence of valinomycin and Zn2+ ions. The addition of NH4Cl or carbonyl cyanide m-chlorophenylhydrazone (K+ medium only) to these cytoplasts results in a restoration of O2.- generation. At an elevated pHo CCCP restores a greater rate of O2.- generation. Increasing the concentration of Zn2+ ions reduces the extent of the generation of O2.- on the addition of PMA. The restoration of O2.- generation by NH4Cl or CCCP requires the presence of valinomycin. The restoration of O2.- generation appears to be dependent on the movement of NH4+ ions or the anionic form of the uncoupler across the plasma membrane. The activity of the electrogenic NADPH oxidase of cytoplasts is limited by the movement of an ion to act as a compensator. The NADPH oxidase therefore exhibits respiratory control.

Ammonium Chloride↗
PubMed1988

Two-generation study of neuroleptic isofloxythepin in rats.

The neuroleptic isofloxythepin was tested in a two-generation study in rats in oral doses of 0.1 mg base/kg and 1 mg base/kg. The substance was administered to male and female rats of each generation daily from the weaning onward till the conclusion of the study. The pups of two consecutive generations F0 and F1 were surveilled always in two litters. There were assessed the numbers and body weights of the pups from birth till the weaning, the postnatal developmental milestones, and the results of neuromuscular and locomotor activity tests. In the parents the fertility parameters were followed. --Isofloxythepin at higher dosage, 1 mg/kg, influenced the estrous cycles in the females, prolonging the diestrus stage, but exerted no significant effects upon their fertility and pregnancy. The growth of the offspring of parents treated with isofloxythepin in both generations was slightly retarded. In the F0 generation the pup's mortality increased in the perinatal period. The sedative effect of the neuroleptic manifested itself by a lowering of the locomotor activity. The proved effects of isofloxythepin in the higher dose are mostly connected with the drug's neuroleptic properties. Analogous effects of other substances of this type have been reported in the literature, too. In the course of the study the effects of isofloxythepin did not intensify from the first to the second generation.

Animals↗
PubMed1986

Generation of Na+ electrochemical potential by the Na+-motive NADH oxidase and Na+/H+ antiport system of a moderately halophilic Vibrio costicola.

Cells of Vibrio costicola at pH 8.5 generate both membrane potential (inside negative) and delta pH (inside acidic) in the presence of a proton conductor, carbonyl cyanide m-chlorophenylhydrazone (CCCP). The generation of CCCP-resistant membrane potential was inhibited by 2-heptyl-4-hydroxyquinoline-N-oxide that is known to inhibit the Na+-motive NADH oxidase of Vibrio alginolyticus. NADH oxidase, but not lactate oxidase, of inverted membrane vesicles prepared from V. costicola required Na+ for a maximum activity and was inhibited by 2-heptyl-4-hydroxyquinoline-N-oxide. By the oxidation of NADH, inverted membrane vesicles generated concentration gradients of Na+ across the membrane, whose magnitude was always larger than that of delta pH by about 50 mV. In contrast, magnitudes of delta pH and Na+ concentration gradients generated by the oxidation of lactate were similar. Na+ translocation in the presence of lactate was inhibited by CCCP but little affected by valinomycin. On the other hand, Na+ translocation in the presence of NADH was resistant to CCCP and stimulated by valinomycin. Amiloride, an inhibitor for a eucaryotic Na+/H+ antiport system, inhibited the lactate-dependent Na+ translocation but had little effect on the NADH-dependent Na+ translocation. These results indicate that a primary event of lactate oxidation is the translocation of H+, which then causes the generation of Na+ concentration gradients via the secondary Na+/H+ antiport system. We conclude that the NADH oxidase of V. costicola translocates Na+ as an immediate result of respiration, leading to the generation of Na+ electrochemical potential.

Amiloride↗
PubMed1986

Enhancement by monokines of leukotriene generation by human eosinophils and neutrophils stimulated with calcium ionophore A23187.

Human blood eosinophils and neutrophils that had been incubated with the supernatants of cultures of lipopolysaccharide (LPS)-stimulated blood mononuclear cells demonstrated respective enhanced abilities to produce immunoreactive leukotriene C4 (LTC4) and immunoreactive leukotriene B4 (LTB4) after activation by the calcium ionophore A23187. Under optimal conditions, the enhancing effect was observed with the eosinophils (n = 21) and the neutrophils (n = 14) from all but one donor of each type of granulocyte. Enhancement was maximum when granulocytes were preincubated with a 1/3 dilution of LPS-stimulated mononuclear cell culture supernatants for 1 to 2.5 min and were then stimulated with 2.5 microM ionophore for 1 to 2 min (neutrophils) or 15 min (eosinophils). Maximal enhancement ranged from 20 to 4500% for LTC4 generation by eosinophils (geometric mean, 87%) and from 30 to 1600% for LTB4 generation by neutrophils (geometric mean, 105%). There was no enhancement of leukotriene biosynthesis when the LPS-stimulated mononuclear cell culture supernatants and ionophore were added simultaneously to the granulocytes. The enhancing activity for LTC4 generation by eosinophils was removed by washing the cells after the addition of the LPS-stimulated mononuclear cell culture supernatants and before the introduction of ionophore. This enhancing activity was produced by Ig-, Leu-1- adherent blood mononuclear cells, which are presumed to be monocytes; supernatants of adherent cells augmented A23187-induced LTC4 generation by eosinophils from 21 to 2300% (geometric mean, 402%) in 11 experiments and LTB4 generation by neutrophils from 7 to 200% (geometric mean, 60%) in 10 experiments. There was an inverse correlation between the percent enhancement and the LTC4 levels produced by stimulated eosinophils in the absence of the monokine(s) (r = -0.79, p less than 0.01), but not between percent enhancement and the LTB4 levels generated by ionophore-activated neutrophils in the control buffer. The activity of the monocyte-derived enhancing material on each type of granulocyte was relatively heat stable. Enhancement of eosinophil production of LTC4 was associated with an acidic group of monocyte-derived molecules having isoelectric points of 4.2 to 4.3, 4.5 to 4.6, and 4.9, and exhibiting marked heterogeneity in size.(ABSTRACT TRUNCATED AT 400 WORDS)

Arachidonic Acid↗
PubMed1986

Generation of reactive oxygen radicals through bioactivation of mitomycin antibiotics.

Mitomycin C (MC) is a naturally occurring anticancer agent which has been shown to be more cytotoxic to hypoxic tumor cells than to their aerobic counterparts. The mechanism of action of this agent is thought to involve biological reductive activation, to a species that alkylates DNA. A comparison of the cytotoxicity of MC to EMT6 tumor cells with that of the structural analogues porfiromycin (PM), N-(N',N'-dimethylaminomethylene)amine analogue of mitomycin C (BMY-25282), and N-(N',N'-dimethylaminomethylene)amine analogue of porfiromycin (BL-6783) has demonstrated that PM is considerably less cytotoxic to aerobic EMT6 cells than MC, whereas BMY-25282 and BL-6783 are significantly more toxic. The relative abilities of each of these compounds to generate oxygen free radicals following biological activation were measured. Tumor cell sonicates, reduced nicotinamide adenine dinucleotide phosphate-cytochrome c reductase, xanthine oxidase, and mitochondria were used as the biological reducing systems. All four mitomycin antibiotics produced oxygen radicals following biological reduction, a process that may account for the aerobic cytotoxicity of agents of this class. The generation of relative amounts of superoxide and hydroxyl radical were also measured in EMT6 cell sonicates. BMY-25282 and BL-6783 produced significantly greater quantities of oxygen free radicals with the EMT6 cell sonicate, reduced nicotinamide adenine dinucleotide phosphate-cytochrome c reductase, and mitochondria than did MC and PM. In contrast, BMY-25282 and BL-6783 did not generate detectable levels of free radicals in the presence of xanthine oxidase, whereas this enzyme was capable of generating free radicals with MC and PM as substrates. MC consistently produced greater amounts of free radicals than PM with all of the reducing systems. BMY-25282, BL-6783, and MC all generated hydroxyl radicals, while PM did not appear to form these radicals. The findings indicate that a correlation exists between the ability of the mitomycin antibiotics to generate oxygen radicals and their cytotoxicity to aerobic EMT6 tumor cells.

Animals↗
PubMed1988

The comparative study of reactive oxygen species generated by polymorphonuclear leukocytes as alpha 1-proteinase inhibitor inactivators-possible application for antioxidant prevention of emphysema.

The oxidative inactivation of alpha 1-proteinase (alpha 1AP) inhibitor is a one of mechanisms that may lead to the pulmonary emphysema. This process is caused by oxidants derived from atmosphere and released from lung phagocytes. These cells produce various oxidants hydrogen peroxide (H2O2), hypochlorous acid (HClO), hydroxyl (OH.) and superoxide (O2-) radicals after inflammatory stimulation. In this study I have investigated the effects of H2O2 (1.5 x 10(-5) to 1.5 x 10(-2) M) alone or with addition of FeCl2 (50 microM) in order to generate OH., chloramine-T (1.5 x 10(-5) to 1.5 x 10(-3) M) which generates HClO, glucose 10 mg/ml-glucose oxidase (12.5 to 80 mU/ml)-H2O2 generating system, xanthine 0.2 mM-xanthine oxidase (12.5 to 80 mU/ml)-O2-2 generating system on the elastase inhibitory activity of alpha 1AP in vitro. H2O2 was weak in alpha 1AP inactivation--only concentration of H2O2 1.5 x 10(-2) caused severe loss of its activity to 23 +/- 8% inhibition of elastase. Addition of FeCl2 to H2O2 and following OH. generation did not enhance its alpha 1AP inactivation. O2-2 generating system inhibited moderately alpha 1AP. The % inhibition of elastase at concentration of xanthine oxidase 80 mU/ml was 65 +/- 7. HClO was most effective as an alpha 1AP inactivator. All used chloramine-T concentrations completely suppressed alpha 1AP activity. The obtained results and in vivo consumption of H2O2 by polymorphonuclear leukocyte myeloperoxidase for HClO production suggest that scavenging of these reactive oxygen species may be useful in prevention of emphysema.

Antioxidants↗
PubMed1986

The role of I-region associated antigen (Ia)-bearing accessory cells in the generation of cytotoxic T cells in a subpopulation of thymocytes.

The roles of killer-helper factor (KHF) and accessory cells bearing I-region associated antigen (Ia) in the generation of cytotoxic T lymphocytes (CTL) were analyzed. Peanut agglutinin-binding (PNA+) thymocytes from C3H/HeN mice generated efficient CTL responses against 2,4,6-trinitrophenyl (TNP)-modified syngeneic spleen cells in the presence of cell-free supernatant (CFS) derived from purified protein derivatives (PPD)-stimulated Mycobacterium tuberculosis-primed BALB/c spleen cell culture (PPD-CFS). The KHF which is present in PPD-CFS devoid of the activities of IL-1 or IL-2 was required in conjunction with IL-2 for generation of CTL in PNA+ thymocytes. In contrast, PNA- thymocytes as well as spleen cells could generate CTL in the absence of helper factors. However, a significant CTL response against Ia-negative syngeneic tumor cells was not induced from either PNA+, PNA- thymocytes or spleen cells in the absence of Ia-positive accessory cells. Moreover, the treatment of spleen cells with relevant anti-Ia antiserum plus complement before TNP-modification abrogated the stimulatory capacity of TNP-spleen cells. In both cases, the addition of Ia-positive accessory cells restored the impaired capacity of TNP-modified stimulator cells. The addition of IL-1 to the culture of PNA- thymocytes or spleen cells stimulated with TNP-X5563 cells in the absence of accessory cells restored the CTL generation. In contrast, the addition of IL-1 to the culture of PNA+ thymocytes was ineffective. The role of Ia-positive accessory cells in the generation of CTL in a subpopulation of thymocytes is discussed.

Animals↗
PubMed1988

[A mathematical model of the activity of spinal generators of rhythmic movements].

Different organization schemes concerning locomotor and scratching rhythmicity generators are analyzed by means of the mathematical simulation model. A functional group of neurons (half-centre constructed on the stochastically organized neuronal network) is the basis for generator. Some organization schemes concerning locomotor and scratching rhythmicity generators are considered, such as: two half-centres with reciprocal inhibitory connections and tonic excitatory influences on these half-centres: two half-centres with inhibitory-excitatory connections and tonic excitatory influences on one half-centre; ring structures consisting of more than two functional groups of neurons with excitatory and inhibitory connections between them. In all the schemes considered generation of rhythmic activity is possible with time characteristics similar to those of the locomotor and scratching rhythmicity. It is shown that transition from locomotor to scratching rhythmicity can be realized through simply organized actions on generator neurons. Possible principles of construction of spinal generators for locomotor and scratching movements are discussed.

Animals↗
PubMed1988

Age-related changes in the capability of the bone marrow to generate B cells.

The capability of the bone marrow (BM) to generate new B cells in aging was studied in vitro. BM cells from old (26 to 30 mo) or young (3 mo) BALB/c and (C3H/eB x C57BL/6)F1 mice were depleted of mature B cells and these surface Ig (sIg) BM cells were incubated in culture for 3 days. The frequency of newly generated B cells in these cultures was determined by assessing the frequency of slg+ cells and of B cells forming colonies in agar and by assaying the proliferative capacity of these newly generated B cells after stimulation by LPS. We found that BM cells from aged mice are significantly inferior to young ones in their capability to generate new B cells in culture. By mixing old and young slg- BM cells, we found that, in general, this reduction was not caused by a suppressive effect of T cells or of any other cells, but rather to lack of some sort of supportive cell or factor in the aged BM. In addition, we found that the frequency of cells expressing the B220 surface molecule, a B lineage-specific marker, is significantly reduced in aged BM. These results indicate that a quantitative decrease in B cell progenitors combined with changes in cell populations that are important in supporting B cell generation contribute to the age-related decrease in the capacity to generate B cells.

Aging↗
PubMed1988

Fractionated extract of Astragalus membranaceus, a Chinese medicinal herb, potentiates LAK cell cytotoxicity generated by a low dose of recombinant interleukin-2.

Success with rIL-2 immunotherapy of human cancer appears to depend on the administration of high doses which are frequently associated with excessive toxicity. Future use of rIL-2 will require certain modifications based on the use of lower doses of rIL-2 without significant loss of antitumor efficacy. We tested in vitro the possibility of potentiating the activity of rIL-2 in terms of LAK cell generation. We hypothesized that co-incubation of LAK cell precursors with a Chinese herbal extract (F3) of Astragalus membranaceus, (an immune modulator currently under study in our laboratory), along with a low concentration of rIL-2, would generate levels of LAK cell activity equivalent to those generated by high concentrations of rIL-2 alone. We found (1) a 10-fold potentiation of rIL-2 activity manifested by tumor cell-killing activity of 80% resulting from LAK cell generation with F3 plus 100 u/ml of rIL-2 versus 76% generated by 1,000 u/ml of rIL-2 alone; (2) a significant reduction in the number of effector LAK cells required for equicytotoxic reaction following LAK cell generation with F3 plus rIL-2 compared to rIL-2 alone. We conclude that potentiation of antitumor activity mediated by rIL-2 in low concentrations is possible by the concomitant use of another immune modulator such as Astragalus membranaceus.

Adjuvants, Immunologic↗
PubMed1988

Tibial torque generation in a flexed weight-bearing stance.

Internal and external torque generated about the long axis of the lower extremity was measured in 18 male subjects who were instructed to twist with maximal effort against a fixed footplate containing an instrumented torque cell. Mean torque values ranged from 30 to 71 newton meters (Nm) depending upon the test conditions. Torques recorded during the flexed single-leg stance were 19% to 49% higher than those measured while seated. Values at 45 degrees of knee flexion were 11% to 16% greater than those at 20 degrees. Torques generated while wearing a ski boot were 8% to 11% greater than those recorded in an athletic shoe. When movement of the pelvis and upper torso was allowed, torque values were 17% to 49% higher than those recorded when the hips and shoulders were restrained which allowed only lower leg musculature to act in an isolated fashion. There were no differences between internal versus external generated torques when the hips and torso were restrained. When the hips and shoulders were unrestrained, internal torque was 12% greater than external torque. There were no strong correlations between generated torque and body weight or height. These generated torque values suggest that if ski bindings are set to American Society for Testing and Materials (ASTM) standards for twist-release torque, then upper torso and pelvic movement in conjunction with tensed knee musculature (i.e., a "locked knee") may be necessary to accomplish binding release. Use of the lower leg musculature alone (i.e., ankle twist) may not generate sufficient torque for release.

Adult↗
PubMed1987

Application of the three-channel lissajous trajectory of auditory brainstem-evoked potentials to the question of generators.

In studies of generators of auditory brainstem-evoked potentials (ABEP), depth recordings and clinical correlates may not reflect all the activity involved. Although the 'inverse problem' is mathematically ill-posed, a synthesis of physico-anatomical data with a three-channel Lissajous trajectory (3CLT) may indicate the actual number and identity of generators. A 3CLT of ABEP in three-dimensional voltage space, is isomorphic with the vector tip representing the momentary centrally located dipole in a uniform, spherical volume conductor. This isomorphism enables approximations of ABEP dipole equivalents to be made. 3CLT summarizes the surface activity in a single plot. It accentuates correlations within the orthogonal records, such as planarity of segments, allowing segmentation of the analysis epoch into components. These properties of 3CLT simplify the analysis of parametric effects on the surface distribution of ABEP components. The results of applying this technique indicate the experimental conditions under which the assumptions for the approximation of generators are closest to being fulfilled. Of all the points along the trajectory, apices (points with maximum absolute amplitude and curvature) have the most unique generators. The 3CLT to low-intensity and high-rate clicks, indicate more unique generators than the customarily used high-intensity slow-rate clicks, in which considerable temporal overlap of generator activity exists.

Brain Stem↗