Long-term follow-up of health care workers with work-site exposure to human immunodeficiency virus.
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Adult↗
Biomedical subjects
S Pollack
Publications and source records attributed to S Pollack.
Stimulation of MAP-2 kinase activity in T lymphocytes by anti-CD3 or anti-Ti monoclonal antibody is partially dependent on protein kinase C.
Signaling via the alpha-beta T cell Ag receptor (Ti)-CD3 complex is a complicated event that implicates several protein kinases, most notably protein kinase C (PKC). We have recently identified a serine kinase in T lymphocytes with the following characteristics: molecular mass 43 kDa, in vitro substrate affinity for microtubule associated protein 2 (MAP-2) with a preference for Mn2+ during the catalytic reaction, and elution from DEAE resin over a salt range 100 to 200 mM NaCl. This kinase is activated in a rapidly reversible fashion during ligation of CD3/Ti by a process which involves prior phosphorylation; in vitro exposure of activated 43-kDa MAP-2 kinase (MAP-K) to an immobilized phosphatase abrogated its kinase activity. We now show that a MAP-2K response could also be obtained during treatment with mAb to Ti and the specific PKC agonist, PMA. Although the kinetics of the former response was rapidly reversible, PMA elicited a more prolonged response. The dose responsiveness for PMA was similar to the requirements for PKC activation in intact lymphocytes. Moreover, as with PKC, we found that the CD3-induced MAP-2K response could be further enhanced by using a second layer cross-linking antibody. The specificity of CD3/Ti in the Jurkat cell response is demonstrated by the fact that OKT-11(CD2) and anti-CD4 mAb did not stimulate a MAP-2K response. It was also not possible to elicit a response in a Jurkat cell mutant that lacks surface expression of CD3 and Ti. The specificity of PKC in these events was further explored with the cell permeant diacylglycerol, 1-oleoyl-2-acetylglycerol, and the nonagonist phorbol ester, 4 alpha-phorbol 12,13-didecanoate: whereas the former was an effective inducer of the MAP-2K response, the latter failed to yield any stimulation. Prior exposure of Jurkat cells to 100 mM PMA for 24 h eliminated greater than 60% of the MAP-2K response during anti-CD3 treatment. This response could also be inhibited in dose-dependent fashion by prior treatment of Jurkat cells with the potent PKC inhibitor 1-(5-isoquinolinesulfonyl) 2-methylpiperazine dihydrochloride. Although a Ca2(+)-ionophore failed to synergize with PMA at inducing a MAP-2K response, depletion of extracellular Ca2+ by EGTA abrogated anti-CD3 responsiveness. The events culminating in MAP-2K activation were slightly inhibited in the presence of cholera toxin but not pertussis toxin.(ABSTRACT TRUNCATED AT 400 WORDS)
Antibodies, Monoclonal↗
Mitochondria have Fe(III) receptors.
Recent work has provided new evidence that ATP is the major constituent of the low-Mr iron pool in the reticulocyte. The interaction of the iron complex of ATP with mitochondria was investigated in the present experiments. When ATP-Fe3+ was incubated with mitochondria, Fe3+, free of ATP, bound with high affinity to Fe3+ receptors on the mitochondria. The binding was saturable and reversible. Iron which was complexed to PPi, nitrilotriacetate, citrate, ADP and GTP also showed saturable binding to mitochondria; Fe3+ complexed to AMP bound non-specifically, as did Fe2+/ascorbate complexed to AMP bound non-specifically, as did Fe2+/ascorbate and Fe2+/dithionite.
Adenosine Triphosphate↗
Iron bound to low MW ligands: interactions with mitochondria and cytosolic proteins.
The iron in the low MW pool of the cell is the precursor of iron in haem and is bound primarily to ATP. This precursor-product relationship suggested that reticulocytes might accumulate ATP-iron if their haem synthesis were blocked. However reticulocytes, treated with succinylacetone or rotenone and taking up iron from transferrin, accumulated iron in nonhaem cytosolic proteins and in mitochondria and not in the low MW pool. This was demonstrated by NMR and also by disrupting the cell with shear stress, separating the cytosol and pellet and fractionating the cytosol with ammonium sulfate. This constancy of the low MW iron pool in the face of blocked haem synthesis could not be explained by saturation of cytosolic ATP or by sluggish exchange of the low MW pool with other compartments. Rather, nonhaem cytosolic proteins and mitochondria appeared to have a higher affinity for iron and to exchange it rapidly with that in the low MW pool.
Animals↗
Two pathways for iron uptake by guinea pig reticulocytes.
We have demonstrated that the intracellular processing of transferrin to effect iron removal involves two pathways, one sensitive to rotenone and the other not. We have also found that the effect of the rotenone is dependent on the transferrin concentration: iron uptake was suppressed with concentrations of transferrin in the micromolar range, and was not suppressed at physiologic concentrations of transferrin. Rotenone does not disturb transferrin's interaction with its extracellular receptor, indicating that its action must be intracellular. The following model is suggested: that separate pathways are entered by transferrin in the cell. The first pathway is preferentially utilized when transferrin is in short supply. It begins with an intracellular site which has a high affinity (and low capacity) for either iron or transferrin. The second pathway begins with an intracellular site which has a high capacity (but low affinity) for either iron or transferrin and is utilized when transferrin is in physiologic concentration (and the low-capacity, high-affinity site is saturated); the pathway it initiates is dominant when transferrin is abundant. We speculate that the high-affinity low-capacity pathway may serve to direct intracellular iron to sites which would be critically injured by iron excess.
Animals↗
Iron binding to apotransferrin.
The classic analysis of metal transfer between ligands suggests that the metal-binding ligand (M-L1) and the uncomplexed ligand (L2) form a mixed complex (L2-M-L1), and that transfer is effected with the dissociation of this complex to L2-M and L1. Spectroscopic data suggested that such mixed complexes formed when pyrophosphate-Fe and acetohydroxamate-Fe were added to apotransferrin: the initial species had a different absorbance maximum than the final transferrin-iron complex. We now show that similar spectroscopic changes are seen when free ferrous iron or iron liganded to ATP, citrate or nitrilotriacetate are added to apotransferrin. The evolving spectrum on the addition of iron to apotransferrin may thus reflect iron binding per se rather than the formation of a mixed ligand complex.
Adenosine Triphosphate↗
Decreased natural killer cell function in patients with classical Kaposi's sarcoma.
Natural killer (NK) cell activity of peripheral blood lymphocytes was evaluated in a group of 13 patients with classical Kaposi's sarcoma (KS). All patients had a normal T4/T8 ratio, and the disease was confined to the skin of the lower extremities. A group of 5 healthy subjects served as controls. NK cell function was significantly decreased in patients as compared to controls. Our result is similar to that found in another group of patients with AIDS-related KS with lymphadenopathy and an abnormal T4/T8 ratio. This suggests that decreased NK cell function is not a result of a progressive process and might be directly involved in the development of KS.
Aged↗
Growth hormone response to growth hormone-releasing hormone in schizophrenic patients.
Ten schizophrenic patients and five normal control subjects were challenged with growth hormone-releasing hormone in a pilot study investigating growth hormone secretion from the pituitary. The results suggest suprapituitary dysfunction in schizophrenia, but replication in a larger study is needed.
Adult↗
NMR studies of intracellular free calcium, free magnesium and sodium in the guinea pig reticulocyte and mature red cell.
During the maturation process reticulocytes lose their intracellular organelles and undergo changes in membrane lipid composition and ion transport properties. While several reports indicate differences in the levels of magnesium, sodium and calcium in reticulocytes and erythrocytes, controversy remains concerning the actual magnitude and direction of ionic alterations during reticulocyte maturation. One problem with all of these studies is that the techniques used are invasive and are limited to measuring only the total cell ion content. We have used 31P, 23Na and 19F nuclear magnetic resonance (NMR) spectroscopy to compare the intracellular free ion and phosphometabolite levels in guinea pig reticulocytes and mature red blood cells. In contrast to a sharply decreased concentration of ATP in erythrocytes in comparison to reticulocytes, the intracellular free magnesium, measured using 31P-NMR, was increased by about 65% upon maturation (150 mumol/l cell water in reticulocytes in comparison to 250 mumol/l cell water in erythrocytes). Sizeable but opposite changes in intracellular sodium (5.5 mumol/ml cells in reticulocytes vs. 8.5 mumol/ml cells in erythrocytes) and intracellular free calcium (99 nM vs. 31 nM in reticulocytes and mature red cells, respectively) were also observed, suggesting that alterations in the kinetics of membrane ion transport systems, accompanying changes in phospholipid and cholesterol content, occur during the process of red cell maturation. However, in contrast to dog red blood cells, there was no evidence for the presence of a Na+/Ca2+ exchanger in guinea pig reticulocytes or erythrocytes.
Animals↗
Low-Mr iron isolated from guinea pig reticulocytes as AMP-Fe and ATP-Fe complexes.
Guinea pig reticulocytes were pulse-labelled with 59Fe bound to transferrin. Haemolysates prepared from these reticulocytes were subjected to rapid (NH1)2SO1 precipitation and then chromatography on an anion-exchange resin. ATP-bound 59Fe was the dominant species in the reticulocyte cytosol; 2,3-bisphosphoglycerate and GTP iron complexes were not detected despite the fact that these were stable with (NH1)2SO1 precipitation and readily detected with anion-exchange chromatography. AMP-bound Fe was a minor component of the cytosol following rapid (NH1)2SO4 precipitation, and the major component when iron was released from transferrin by haemolysates. We speculate that ATP-Fe may be degraded in the cell to permit utilization of its iron for haem synthesis.
Adenosine Monophosphate↗
Distribution of tunichrome and vanadium in sea squirt blood cells sorted by flow cytometry.
Specialized blood cells of many tunicates accumulate high concentrations of vanadium and phenolic peptide pigments called tunichromes (TC). In order to determine whether V and TC reside in the same cells, Ascidia nigra and Ascidia ceratodes blood cell subpopulations were isolated by fluorescence-activated cell sorting (flow cytometry) and chemically analyzed. V was found in the spherical, green/grey signet ring cells, and to a lesser degree in the mulberry-shaped, yellow/green morula cells (MRs), whereas free TC was detected mainly in MRs.
Animals↗
Psychometric characteristics of the multidimensional health locus of control scales among psychiatric patients.
In a sample of 60 psychiatric patients recently discharged from inpatient or day hospital psychiatric facilities, we evaluated the psychometric characteristics of the Multidimensional Health Locus of Control (MHLC) scales. The scales demonstrated alpha reliabilities and intercorrelations similar to those reported by Wallston, Wallston, and DeVellis (1978). Factor analysis and a confirmatory LISREL analysis provided more qualified support for the hypothesized three-factor structure of the scales. The findings suggest, however, that the MHLC appears suitable for use among psychiatric patients, particularly in the combined forms (A and B) version.
Adolescent↗
Hemolysates reduce iron released from transferrin.
Transferrin donates iron to reticulocytes as follows: it binds to a receptor on the reticulocyte surface; the complex is endocytosed; both irons are released and the transferrin is recycled to the cell exterior. It has been proposed that the trigger for iron release after transferrin endocytosis is acidification of the endocytic vesicle. But this could account for removal of only one of transferrin's two irons, since only one of the irons is labile at acid pH. Moreover, iron continues to be removed from transferrin when acidification of the vesicle is blocked by a chloride-transport inhibitor. Thus a detailed explanation of iron removal from transferrin remains elusive. In earlier work we showed that iron can be removed from transferrin by whole hemolysates and also by the combined action of hemoglobin and ATP at pH 7. We now show that the iron released from transferrin by hemolysates, and by hemoglobin and ATP, is in the Fe(II) oxidation state. We also show that ADP and DPG can substitute for ATP and that NADH and NADPH can substitute for the hemoglobin, although with these substitutions Fe(II) is generated less efficiently. The reductive release of iron from transferrin is rapid enough to account for all the iron processed by a young reticulocyte. We speculate that transferrin iron may be reduced to Fe(II) before reaching the mitochondria.
Animals↗
Clozapine pharmacology and tardive dyskinesia.
Clozapine, an atypical neuroleptic, does not cause extrapyramidal symptoms of Parkinsonism and dystonia and appears to have a reduced or absent capacity to produce tardive dyskinesia. 37 subjects, most with chronic schizophrenia, were treated with clozapine and TD outcome was analyzed. A subset of these subjects underwent plasma and CSF studies. TD response was heterogenous, but a proportion of patients improved with clozapine treatment. Neurochemical data differed from published reports of classical neuroleptics with the most robust effect produced by clozapine seen in CSF norepinephrine levels. Other neurochemical data and implications for the mechanism of clozapine in TD are reviewed.
Adolescent↗
Hypogammaglobulinaemia in DiGeorge sequence.
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Agammaglobulinemia↗
A discrete model for streaming potentials in a single osteon.
A mathematical model for streaming potentials in an osteon is proposed, taking into account the microstresses in the vicinity of the Haversian Canal. With the help of the finite element method, a boundary problem for the fluid pressure amplitude in the osteon is investigated when the bone sample is subjected to harmonic loading. A numerical analysis of the intra-osteonal potential is performed. It is found that there exists an azimuthal asymmetry which increases with the enlargement of the Haversian Canal. The results of the numerical modeling of the intra-osteonal potential are in accordance with the available experimental data.
Action Potentials↗
Depression in hemodialysis patients.
Psychiatric evaluation of depression in medically ill patients using DSM-III-R or Research Diagnostic Criteria (RDC) is difficult because these diagnostic systems have not been validated for this population. Diagnosis of depression has been especially problematic in patients with end-stage renal disease (ESRD). This study found a 17.7% prevalence of RDC-defined minor depression and a 6.5% prevalence of major depression in 124 ESRD patients treated with hemodialysis. Vegetative symptoms of depression were less useful for discriminating between those with and without depression than were the psychological symptoms of suicidal ideation, depressed mood, and discouragement.
Depressive Disorder↗
Low molecular weight iron from guinea pig reticulocytes isolated by Sephadex G-25 chromatography.
As part of a continuing study of the low MW iron pool, guinea pig reticulocytes were incubated with 59Fe-labeled transferrin, and the reticulocyte hemolysate was chromatographed on Sephadex G-25. 59Fe, in amounts corresponding to that which was in a low MW peak eluting from an Ultrogel column and to that not precipitated by ammonium sulfate, adsorbed to the Sephadex column. The adsorbing 59Fe, on elution from the Sephadex with dilute formic acid, coeluted with phosphate and pentose. When EDTA was added to disrupt the putative iron complex, neither iron nor P adsorbed to the column, supporting the argument that they exist as a compound in the cytosol and adsorb and elute together for that reason. These observations provide additional evidence that P-containing compounds, probably originating as nucleotides, are important components of the low MW iron pool of cells.
Adsorption↗