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D C Jackson

Publications and source records attributed to D C Jackson.

At least 37 records · Page 2Linked to original sources

Bone and shell contribution to lactic acid buffering of submerged turtles Chrysemys picta bellii at 3 degrees C.

To evaluate shell and bone buffering of lactic acid during acidosis at 3 degrees C, turtles were submerged in anoxic or aerated water and tested at intervals for blood acid-base status and plasma ions and for bone and shell percent water, percent ash, and concentrations of lactate, Ca(2+), Mg(2+), P(i), Na(+), and K(+). After 125 days, plasma lactate concentration rose from 1.6 +/- 0.2 mM (mean +/- SE) to 155.2 +/- 10.8 mM in the anoxic group but only to 25.2 +/- 6.4 mM in the aerated group. The acid-base state of the normoxic animals was stable after 25 days of submergence. Plasma calcium concentration (¿Ca(2+)) rose during anoxia from 3.2 +/- 0.2 to 46.0 +/- 0.6 mM and ¿Mg(2+) from 2.7 +/- 0.2 to 12.2 +/- 0.6 mM. Both shell and bone accumulated lactate to concentrations of 135.6 +/- 35.2 and 163.6 +/- 5.1 mmol/kg wet wt, respectively, after 125 days anoxia. Shell and bone ¿Na(+) both fell during anoxia but the fate of this Na(+) is uncertain because plasma ¿Na(+) also fell. No other shell ions changed significantly in concentration, although the concentrations of both bone calcium and bone potassium changed significantly. Control shell water (27.8 +/- 0.6%) was less than bone water (33.6 +/- 1.1%), but neither changed during submergence. Shell ash (44.7 +/- 0.8%) remained unchanged, but bone ash (41.0 +/- 1.0%) fell significantly. We conclude that bone, as well as shell, accumulate lactate when plasma lactate is elevated, and that both export sodium carbonate, as well as calcium and magnesium carbonates, to supplement ECF buffering.

Acid-Base Equilibrium↗

Suppression and enhancement of emotional responses to unpleasant pictures.

Despite the prominence of emotional dysfunction in psychopathology, relatively few experiments have explicitly studied emotion regulation in adults. The present study examined one type of emotion regulation: voluntary regulation of short-term emotional responses to unpleasant visual stimuli. In a sample of 48 college students, both eyeblink startle magnitude and corrugator activity were sensitive to experimental manipulation. Instructions to suppress negative emotion led to both smaller startle eyeblinks and decreased corrugator activity. Instructions to enhance negative emotion led to larger startle eyeblinks and increased corrugator activity. Several advantages of this experimental manipulation are discussed, including the use of both a suppress and an enhance emotion condition, independent measurement of initial emotion elicitation and subsequent regulation of that emotion, the use of a completely within-subjects design, and the use of naturalistic emotion regulation strategies.

Adult↗

The antigenic and immunogenic properties of synthetic peptide immunocontraceptive vaccine candidates based on gamete antigens.

In this study we have investigated the immunogenicity and antigenicity of synthetic immunocontraceptive vaccine candidates containing T- and B-cell epitopes arranged in different geometries. Two epitopes were selected, a B-cell epitope from fox sperm lactate dehydrogenase C(4) and a B-cell epitope from murine zona pellucida protein 3. Both were immunogenic in BALB/c mice when coupled to defined T helper cell determinants, eliciting antibodies which bound to the corresponding B-cell epitope and also to the recombinant protein. Because each of these proteins represent important components in the fertilisation process the results encourage further investigation of synthetic immunocontraceptive vaccines.

Amino Acid Sequence↗

Synthetic peptide antigens induce antibodies to Taenia ovis oncospheres.

Sheep immunised with the Taenia ovis recombinant 45W antigen are protected from infection with the parasite. Two peptides were synthesised corresponding to putative host-protective regions at the N- and C-termini of 45W. Sera from sheep immunised with 45W or related recombinant proteins reacted strongly with the N-terminal peptide. Approximately 40% of the antibody directed against 45WB/X, a truncated form of 45W, was found to be directed against the N-terminal peptide sequence. Sheep were immunised with the N- and C-terminal peptides alone or conjugated to a carrier protein. The N-terminal peptide was found to be highly immunogenic whereas the C-terminal peptide required conjugation to a carrier protein to be immunogenic. Antibodies raised against each of these immunogens crossreacted with the parent protein, 45WB/X, however, only antibodies specific for the N-terminal peptide were found to bind to antigens from the T. ovis oncosphere.

Amino Acid Sequence↗

The physiology of diving in a north-temperate and three tropical turtle species.

We examined changes in blood gases, plasma ions, and acid-base status during prolonged submergence (6 h) of four aquatic turtle species in aerated water at 20 degrees C. Our objective was to determine whether the temperate species, Chrysemys picta bellii, exhibits greater tolerance to submergence apnea than the tropical species, Pelomedusa subrufa, Elseya novaeguineae, and Emydura subglobosa. Blood was sampled from indwelling arterial catheters for measurements of blood PO2, PCO2, pH, and hematocrit and for plasma concentrations of lactate, glucose, Na+, K+, Cl-, total Ca, and total Mg. The pattern of change was similar in all species: a combined respiratory and metabolic acidosis associated with a marked decrease of blood PO2. The severity of the acidosis developed in the temperate species, however, was significantly less than that of the tropical turtles. Lactate rose significantly and HCO3- fell proportionately in all turtles; changes in other plasma ion concentrations were small but were generally in the directions consistent with compensatory exchanges with other body compartments; i.e., cations (K+, Ca, and Mg increased) and anions (Cl- decreased). The results indicate that hypoxia tolerance is a conserved trait in turtles, even in those that do not experience enforced winter submergence, and that the temperate species may be superior in this capacity because of reduced metabolic rate.

Acid-Base Equilibrium↗

Preparation and properties of totally synthetic immunogens.

Although the induction of antibodies and T cells by synthetic peptides representing defined antigenic determinants is a routine laboratory procedure, their use as vaccines has not yet been generally realised. There are a number of reasons for this and paramount is the limitation of valency which affects not only immunogenicity, but also the coverage of the antigenic universe. This paper is a review of our own work in which we have assembled synthetic peptides into multivalent artificial proteins and then examined their immunological properties.

Amino Acid Sequence↗

Different effects of simple anoxic lactic acidosis and simulated in vivo anoxic acidosis on turtle heart.

We compared responses of turtle heart at 20 degrees C to an anoxic lactic acidosis solution (LA) containing 35 mM lactic acid in an otherwise normal turtle Ringers equilibrated with 3% CO2/97% N2 at pH 7.0) to a solution simulating in vivo anoxic acidosis (VA), with elevated concentrations of lactate, Ca2+, Mg2+, and K+, and decreased Cl-, equilibrated with 10.8% CO2/89.2% N2 at pH 7.0. We examined mechanical properties on cardiac muscle strips and determined intracellular pH (pHi) and high energy phosphates on perfused hearts using 31P-NMR. Maximum active force (Fmax) and the maximum rate of force development (dF/dtmax) of muscle strips were significantly higher during VA than during LA superfusion. An elevation of Ca2+ alone (to 6 mM) in LA significantly increased both Fmax and dF/dtmax but the effects diminished toward the end of the exposure; however, hypercapnic anoxic lactic acidosis (addition of 20 mM HCO3- to LA, equilibrated with 10.8% CO2/89.2% N2, pH 7.0) did not significantly affect Fmax or dF/dtmax. During VA perfusion, pHi (6.73 +/- 0.01) was significantly higher than that during LA perfusion (pHi 6.69 +/- 0.013), but the difference is probably too small to have physiological significance. ATP, creatine phosphate, and inorganic phosphate were not significantly different in the two anoxic solutions. We conclude that the reduction of cardiac mechanical function in vivo is minimized by the integrated effects of changes of ionic concentrations, but the observed changes in Ca2+ and pHi cannot fully explain the effect.

Acidosis, Lactic↗

Functional analysis of IgA antibodies specific for a conserved epitope within the M protein of group A streptococci from Australian Aboriginal endemic communities.

The mucosa is one of the initial sites of group A streptococcal (GAS) infection and salivary IgA (sIgA) is thought to be critical to immunity. However, the target epitopes of sIgA and the function of sIgA in GAS immunity, in particular the role of accessory cells and complement, is largely unknown. We studied the aquisition and the function of sIgA specific for a conserved region epitope, p145 (sequence: LRRDLDASREAKKQVEKALE) of the M protein. Peptide 145-specific sIgA is highly prevalent within an Aboriginal population living in an area endemic for GAS and acquisition of p145-specific sIgA increases with age, consistent with a role for such antibodies in immunity to GAS. Human sIgA and IgG specific for p145 were affinity purified and shown to opsonize M5 GAS in vitro. Opsonization could be specifically inhibited by the addition of free p145 to the antibodies during assay. Opsonization of GAS was totally dependent on the presence of both complement and polymorphonuclear leukocytes, and, moreover, affinity-purified p145-specific sIgA was shown to fix complement in the presence of M5 GAS. These data show that mucosal IgA to this conserved region peptide within the M protein has an important role in human immunity against GAS and may be useful in a broad-based cross-protective anti-streptococcal vaccine.

Adolescent↗

Antigenic and immunogenic properties of totally synthetic peptide-based anti-fertility vaccines.

In this study we describe the results of experiments in which a variety of totally synthetic luteinizing hormone releasing hormone (LHRH) vaccines were assembled and examined for their abilities to elicit antibody responses and induce sterility in mice. It is shown that totally synthetic vaccines consisting of a 15 residue-defined T cell epitope and the 10 residue LHRH epitope not only induced high titers of antibody but also induced sterility. This effect did not appear to correlate with antibody titer, antibody isotype or comparative antibody affinity, but may be related to the length of time for which antibodies are present to exert their influence.

Amino Acid Sequence↗

Mice lacking the transcription factor subunit Rel can clear an influenza infection and have functional anti-viral cytotoxic T cells but do not develop an optimal antibody response.

Rel, a haemopoietic cell-restricted member of the NF-kappaB/Rel family of transcription factors, has recently been shown to be important in the function of B and T lymphocytes. In an attempt to understand the role of this protein in the immune response, we examined the ability of Rel(-/-) mice to counter an influenza virus infection. Normal levels of virus-specific cytotoxic T cells induced in Rel(-/-) mice were able to clear virus from the lungs, albeit with somewhat delayed kinetics compared to normal mice. Rel(-/-) mice did, however, display a markedly reduced T cell proliferative response to the virus, and exhibited impaired local and systemic influenza virus-specific antibody responses. This defect was sufficient to result in an inability of vaccinated mice, but not of previously infected mice, to acquire antibody-dependent protective immunity to reinfection with the same virus. These findings establish that during the response to influenza virus, Rel function allows optimal development of humoral immunity, a role that apparently cannot be fulfilled by other NF-kappaB/Rel proteins.

Animals↗

Avoidance of self-reactivity results in skewed CTL responses to rare components of synthetic immunogens.

In studying the CTL recognition of peptide determinants derived from the nuclear Ag La (SS-B), we observed significant skewing of the response toward rare components present within the immunogen. Thus, priming of naive mouse lymphocytes in vitro with a synthetic H-2Kb-binding peptide comprising human La (hLa) residues 51-58 resulted in class I-restricted cytotoxic T cells that failed to recognize naturally presented hLa 51-58 peptide. Instead, the majority of T hybrids recognized a low abundance (< or = 1%) contaminant present at picomolar concentrations in the original synthesis and identified as a peptide adduct containing N,4-t-butyl asparagine at position 6 of the hLa 51-58 sequence. The preferred T cell recognition of the butyl adduct was not due to increased affinity of this peptide for the H-2Kb molecule or to the antagonism of CTL recognizing the unmodified determinant. Rather, the bias in the immune response appeared to be the result of partial self-tolerance to the homologous mouse La 51-58 determinant, which differs from its human counterpart by only a single amino acid at position 1 (T-->I). Accordingly, the CTL response appeared to be focused on "non-self" ligands present within the synthesis, even though they were present at very low concentrations. These observations have significant implications for the use of synthetic peptide vaccines, especially those designed to manipulate responses to self peptides such as tumor Ags in which self-tolerance may result in unexpected reactivity.

Amino Acid Substitution↗

Immunopotentiation of humoral and cellular responses to inactivated influenza vaccines by two different adjuvants with potential for human use.

Two quite different adjuvants, currently under development for use in humans, have been examined for their effects on the magnitude and type of immunity elicited in response to inactivated influenza vaccine. Immunostimulating complexes (ISCOM adjuvant) contain the saponin ISCOPREP 703, and SPT is an oil-in-water emulsion of squalane, non-ionic block copolymer (L121) and Tween 80. Influenza virus vaccines formulated in either adjuvant were far superior to the non-adjuvanted aqueous vaccine in eliciting antibody and T-cell responses in mice, particularly at lower doses of antigen. In addition, the vaccines containing adjuvant were superior in eliciting protective immunity. One of the shortcomings of the unadjuvanted inactivated influenza vaccine was its inability to elicit a primary proliferative T-cell response. However, after one dose of either adjuvanted vaccine, strong proliferative responses were achieved. We also show that subcutaneous vaccination with inactivated vaccines is capable of modulating the isotype profile of antibody secreting cells generated in the lungs of mice in response to intranasal challenge with live virus. In this system, the isotype of antibody elicited after challenge of mice that had received ISCOM vaccine more closely mimicked that of animals vaccinated with live virus.

Adjuvants, Immunologic↗

Relations between PET-derived measures of thalamic glucose metabolism and EEG alpha power.

Electroencephalogram (EEG) alpha power has been demonstrated to be inversely related to mental activity and has subsequently been used as an indirect measure of brain activation. The thalamus has been proposed as an important site for modulation of rhythmic alpha activity. Studies in animals have suggested that cortical alpha rhythms are correlated with alpha rhythms in the thalamus. However, little empirical evidence exists for this relation in humans. In the current study, resting EEG and a fluorodeoxyglucose positron emission tomography scan were measured during the same experimental session. Over a 30-min period, average EEG alpha power across 28 electrodes from 27 participants was robustly inversely correlated with glucose metabolic activity in the thalamus. These data provide the first evidence for a relation between alpha EEG power and thalamic activity in humans.

Adult↗

Free radical induced polymerization of synthetic peptides into polymeric immunogens.

Free radical induced polymerization of vinyl monomers such as the acryloyl peptides described here is a facile and rapid reaction used routinely, for example, in the polymerization of acrylamide and bisacrylamide for the assembly of polyacrylamide gels. The technology allows the incorporation of many of the same or different peptide determinants into a single polymer chain. In this study large polymers containing multiple copies of peptides representing T- and B-cell determinants of influenza haemagglutinin were constructed. The determinants retained antigenicity after the polymerization procedure and the polymers were highly immunogenic; the levels of antibody obtained after a single dose of polymeric immunogen were at least as great as those achieved only after repeated doses of the equivalent monomeric peptide. The technology has a wide range of potential applications, not the least significant of which is the construction of designer immunogens for third generation vaccine candidates.

Amino Acid Sequence↗

Mechanisms of pHi recovery from NH4Cl-induced acidosis in anoxic isolated turtle heart: a 31P-NMR study.

Mechanisms of intracellular pH (pHi) recovery from NH4Cl-induced acidosis were investigated on isolated perfused hearts of the turtle, Chrysemys picta bellii, using 31P nuclear magnetic resonance (NMR) spectroscopy at 20 degrees C. A major goal was to assess the activity of these mechanisms under anoxic conditions. Based on calculated buffer capacity and a pHi recovery range at 20 degrees C of 6.75-6.95 (normal pHi 7.2-7.4), mean H' efflux rate during perfusion with CO2-free N-tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid (TES)-buffered Ringer was only 15% (normoxia) and 25% (anoxia) of that with HCO3-buffered Ringer. With HCO3 solution, anoxic H1 efflux rate was approximately 50% of normoxia (0.333 vs. 0.645 mmol.l-1.min-1), but in TES solution, H1 efflux rate was unaffected by anoxia. To further characterize the transporters, we used blockers [the Na(+)-H+ antiport inhibitor 5-(N-ethyl-N-isopropyl)-amiloride (EIPA) and the anion exchanger inhibitor 4,4'diisothiocyanostilbene-2, 2'-disulfonic acid (DIDS)], ion substitution, and temperature change. EIPA (10 microM) inhibited H+ efflux rate by 40% in anoxic TES solution; DIDS (0.5 mM) blocked H+ efflux rate by 85% in anoxic HCO3 solution. No pHi recovery was observed in either normoxic or anoxic Na(+)-free solutions, but normal recovery was observed in the absence of extracellular Cl-. Recovery of pHi occurred 2-3 times faster at 30 degrees C than at 20 degrees C. ATP was unaffected by any manipulation in this study, whereas creatine phosphate (CP) fell during anoxia, and both CP and mechanical performance changed in parallel to pHi. We conclude that pHi regulation functions during anoxia, although at a reduced rate, and that recovery from acidosis is dominated, during both normoxia and anoxia, by a DIDS-sensitive Na+ and HCO3(-)-dependent mechanism, whereas EIPA-sensitive Na(+)-H+ antiport plays a less important role.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Effects of anoxia, acidosis and temperature on the contractile properties of turtle cardiac muscle strips.

The responses to anoxia and acidosis of cardiac ventricular muscle strips from the anoxia-tolerant turtle Chrysemys picta bellii were investigated at 10 degrees C and 20 degrees C. Force-velocity curves were determined by quick isotonic releases at 85% of the time to peak isometric force under control, anoxia, lactate acidosis and anoxic lactate acidosis conditions. The isotonic forces during quick releases spanned 5-95% of the measured isometric force at each conditions. Superfusion solution pH was 7.8 and 7.95 for non-acidosis experiments, and 7.0 and 7.15 for acidosis experiments, at 20 degrees C and 10 degrees C, respectively. After normalizing force data to control isometric force, the values of maximum isometric force (P0), maximum velocity of shortening (Vmax) and maximal power output (Powermax) were evaluated by fitting the curves using the hyperbolic Hill equation. The maximum rate of force development (dF/dtmax), time-to-peak force (TPF) and half-relaxation time (T1/2) were also determined. At 20 degrees C, during acidosis, anoxia and anoxic acidosis, P0 decreased significantly to 81%, 40% and 24% of control values, dF/dtmax decreased significantly to 67%, 53% and 23% of control values, and Powermax decreased significantly to 75%, 40% and 14% of control values, respectively. Vmax, however, was not significantly affected by acidosis, anoxia or even anoxia acidosis. TPF was significantly shortened by anoxia, but prolonged by acidosis. The effects were similar at 10 degrees C, Temperature did not affect P0, but Vmax decreased by a factor of 1.6-1.8 at all corresponding conditions when temperature was reduced from 20 degrees C to 10 degrees C. We conclude that acidosis and anoxia inhibit isometric force production and Powermax of turtle cardiac muscle, but have no effect on Vmax, and the insensitivity of Vmax indicates that the rate of cross-bridge cycling is not affected by these conditions. Our observations indicate that the reduced power outputs of the hearts of submerged anoxic turtles at low temperature are due in part to inhibition of force production by anoxia and acidosis, and to a reduction of contraction velocity at low temperature.

Acidosis, Lactic↗

Hierarchical self-tolerance to T cell determinants within the ubiquitous nuclear self-antigen La (SS-B) permits induction of systemic autoimmunity in normal mice.

Systemic autoimmune diseases are frequently associated with clustering of high titer autoantibody responses towards nuclear self-antigens. Little is known, however, about the extent of immune tolerance to the target nuclear antigens or the events leading to the complex autoantibody responses that are characteristic of systemic autoimmunity. To address these issues, we have examined the mouse immune response to La autoantigen (mLa) and the homologous human La antigen (hLa), which are components of the La(SS-B)/Ro(SS-A) ribonucleoprotein (RNP) complex targeted in systemic lupus erythematosus and primary Sjögren's syndrome. The findings reveal the presence of hierarchical T cell tolerance involving multiple autodeterminants within the La autoantigen expressed by normal H-2k and H-2a mice. At one end of this spectrum, there was no detectable T or B cell autoimmunity observed in mice that were immunized with the immunodominant mLa287-301 determinant, which differed by a single residue in its core sequence from the homologous but highly immunogenic human La288-302 determinant. Interestingly, the mLa287-301 peptide acted as an altered peptide ligand that specifically antagonized the activation of an hLa288-302-specific T cell hybridoma. In contrast to the tolerogenic mLa287-301 determinant, a range of autoimmune potential was identified among poorly tolerizing, subdominant self-peptides present within mouse La autoantigen. Notably, immunization of normal mice with the autologous subdominant La25-44 and La106-129 determinants resulted in limited or no detectable autoantibody response. In contrast, immunization with the subdominant mouse La13-30 determinant induced a proliferative T cell response associated with the appearance of specific autoantibodies recognizing multiple intrastructural (La) and intermolecular components (Ro) of the murine La/Ro RNP. The findings suggest how diversified autoimmunity might follow initiation of immunity to simple peptide mimics of poorly tolerogenic determinants that are present within ubiquitous self-antigens.

Amino Acid Sequence↗

CTL recognition of an altered peptide associated with asparagine bond rearrangement. Implications for immunity and vaccine design.

The extent to which peptides containing chemically and post-translationally modified amino acid side chains are recognized by primed CTL has not been clearly defined. We report on the CTL recognition of a MHC class I-restricted peptide containing a cyclized asparagine (succinimide) residue. This modification of the asparagine side chain is a common intermediate structure during deamidation, isomerization, and bond rearrangements of amide-containing amino acids and also occurs as a side reaction in peptide synthesis. The CTL specifically recognized the succinimide-containing peptide showing only weak cross-reactivity at high concentrations of the parent peptide containing unmodified asparagine. Similarly, CTL raised against the parent peptide did not recognize the succinimide derivative of this peptide. Naturally processed forms of these structures are likely to occur given the importance and frequency of deamidation both in vitro and in vivo. Moreover, since succinimide intermediates of deamidated peptides can occasionally be very stable, these peptides have the potential to act as altered self-Ags with significant implications for autoimmunity. In addition, unwanted and potentially hazardous specificities may be elicited when using synthetic peptides in subunit vaccines in which succinimide residues may form spontaneously during storage or chemical synthesis.

Amino Acid Sequence↗