Effect of a single dose (3 mg/kg) of diethylcarbamazine on Wuchereria bancrofti var pacifica microfilaraemia.
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Adolescent↗
Biomedical subjects
A Spiegel
Publications and source records attributed to A Spiegel.
[Epidemiology of primary liver cancer in French Polynesia].
Thirty-one cases of primary liver cancer recorded since 1980 to 1988 in French Polynesia are studied. Four risk factors are brought to the fore: male, more than 50 years old, birth in Austral archipelago and in this case AgHBs carriage. The relative risk for birth in Austral archipelago reach to 9.23. The relative risk for AgHBs carriers from this archipelago reach to 42.7. Costs of primary liver cancer and to immunization against hepatitis B virus are compared. Authors suggest to start an immunization program.
Adenoma, Bile Duct↗
A single diethylcarbamazine dose for treatment of Wuchereria bancrofti carriers in French Polynesia: efficacy and side effects.
In the fall of 1988, 14 Tahitian Wuchereria bancrofti carriers were treated by a single diethylcarbamazine (DEC) 3 mg/kg dose. Determination of blood microfilarial (mf) density was carried out on days 0, 7, 14, 30, 90 and 180 using the membrane filtration technique. Clinical signs and side effects were noted during the 3 days following treatment. Complete clearance of microfilaremia was observed in two carriers (negativation rate 14%). A decrease of mf density was noted in all of the 14 carriers, ranging from 35.2 to 99.2% (median 78.75%). The percentage decrease in mf density, determined for the whole group from the geometric mean of the 14 mf counts, was 86% by day 7 and reached 95% by day 180. Side effects were observed in 10 patients (71%) of whom 3 only were unable to perform usual activities for less than 24 hours. Though it induced an incomplete initial mf clearance, a single DEC 3 mg/kg dose was effective in reducing about 90% of the microfilaremia and in sustaining this reduction over a period of six months. Such long-term reduction (comparable to that observed in W. bancrofti carriers treated with a daily DEC 6 mg/kg dose during 12 days) is likely responsible for the consistent decrease of total mf counts observed in the Tahitian population which has been treated for years with single DEC doses given every six months.
Adolescent↗
[Reliability of the diagnosis of cerebrospinal meningitis during an epidemic. The epidemic in Chad in 1988].
The authors analysed the positive predictive value (PPV) of the clinical diagnosis during an epidemic of meningococcal meningitidis in Africa. This PPV was globally 73.3 +/- 11.2%. This PPV was fluctuating according to the standards of the diagnosis. Typical clinical meningitic syndrome without spinal picture: 85.7 +/- 10.3%, Non typical syndrome and macroscopical aspect of cerebrospinal fluid: 62.5 +/- 16.4%.
Chad↗
Immunolocalization of G protein alpha-subunits in the Drosophila CNS.
In order to uncover the role of G proteins in the integrative functioning and development of the nervous system, we have begun a multidisciplinary study of the G proteins present in the fruit fly, Drosophila melanogaster. In this report, we describe the distribution of 3 different G protein alpha-subunits in the adult Drosophila CNS as determined by immunocytochemical localization using affinity-purified antibodies generated to synthetic oligopeptide sequences unique to each alpha-subunit. Western blot analysis of membranes prepared from Drosophila heads indicates that antibodies specific for the Drosophila Go alpha and Gs alpha homologs recognize the appropriate protein species predicted by molecular cloning (Quan et al., 1989; Thambi et al., 1989). The Gi alpha homolog could not be detected in head membranes by Western blotting, consistent with the negligible levels of expression observed for Gi alpha on Northern blots of head mRNA (Provost et al., 1988). However, a Drosophila Gi alpha fusion protein could be detected by these antibodies following expression in E. coli. Immunolocalization studies revealed that the Go alpha and Gs alpha homologs are expressed at highest levels in neuropils and at intermediate levels in the cortex of all brain and thoracic ganglion areas. Only the lamina contained low levels of these alpha-subunits in the CNS. Additionally, Gs alpha appears to be associated with the cell membranes of neuronal cell bodies, while Go alpha has a more diffuse distribution, suggesting its presence in the cytoplasm as well as cell membranes. In contrast to the wide distribution of Go alpha and Gs alpha, Gi alpha has a surprisingly restricted distribution in the CNS. It is present at high levels only in photoreceptor cell terminations, glomerulae of the antennal lobes, and the ocellar retina. Little or no Gi alpha was detected in other brain regions or in the thoracic ganglion. Gi alpha, then, appears to be uniquely associated with some primary sensory afferents and their terminations, suggesting the presence of specific receptor and/or effector systems which mediate the transmission of primary sensory information in Drosophila.
Animals↗
[The detection of IgM antibodies to phenolglycolipid I for serodiagnosis of Hansen's disease and monitoring the contact population in Polynesia. Five year evaluation].
This study was conducted to assess the usefulness of IgM anti-PGLI antibody test, for the diagnosis of leprosy and of the subclinical infection among contact population. Even if the specificity (97.7%), sensitivity (98% for the multibacillary, but 36% for the paucibacillary) and efficiency (97.7%) of the test for the diagnosis of patients are good, its positive predictive value which is the proportion of true patients among the seropositive subjects detected in the population was very low (1.17% in Polynesia), because of the very low prevalence of leprosy. For the diagnosis of the subclinical infection, our experience based on the follow up of a population of 1,123 contacts, showed that such a control program would have low feasibility and low cost-effectiveness. After 5 years, the proportion of individuals developing the disease was not different among the seropositive than among the seronegative subjects. Finally, only 17.5% of the new cases of leprosy detected, were issued from the contact population followed. In conclusion and in a practical point of view, although this test may contribute to the diagnosis of patients, it is not likely useful neither for the diagnosis nor for the prognosis of leprosy in a population.
Antibodies, Bacterial↗
Immunological and molecular characterization of Go alpha-like proteins in the Drosophila central nervous system.
The alpha subunits of heterotrimeric G proteins are responsible for the coupling of receptors for a wide variety of stimuli to a number of intracellular effector systems. In the nervous system of vertebrates, high levels of a specific class of G protein (Go alpha) are expressed. The alpha subunit of Go serves as a substrate for modification by pertussis toxin (PTX). In this report, we demonstrate that the Drosophila heads contain high levels of a 40-kDa PTX substrate. Modification of this protein by PTX is modulated in a manner similar to that observed for vertebrate G proteins. The PTX substrate in Drosophila is also recognized specifically by antibodies raised against peptide sequences found specifically in vertebrate Go alpha. Vertebrate Go alpha probes were used to identify a Drosophila cDNA coding for a potential PTX substrate with high sequence identity (82%) to vertebrate Go alpha. An additional cDNA coding for a related Go alpha has also been isolated. The two cDNAs differ only in the 5'-untranslated and amino-terminal regions of the protein. This observation, in addition to Northern analysis, suggests that alternate splicing may generate a variety of Go alpha-like proteins in Drosophila. In situ hybridization of specific probes to tissue sections indicates that the mRNAs coding for Go alpha-like proteins in Drosophila are expressed primarily in neuronal cell bodies and, at lower levels, in the eyes.
Adenosine Diphosphate Ribose↗
[Electrophysiology of the peripheral nervous system in patients with stage II HIV infection].
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Acquired Immunodeficiency Syndrome↗
G proteins couple alpha-adrenergic and GABAb receptors to inhibition of peptide secretion from peripheral sensory neurons.
Regulation of neuronal calcium channels by GTP-binding proteins (G proteins) is likely to be an important mechanism by which inhibitory transmitters influence excitation-secretion coupling in presynaptic nerve endings. Here, we report that in peripheral sensory neurons from embryonic chick dorsal root ganglia (DRG), the G protein-mediated inhibition of voltage-dependent calcium channels may best explain how norepinephrine (NE) and GABA inhibit the electrically evoked, calcium-dependent release of substance P (SP). As is the case for the previously reported inhibitory actions of these transmitters on DRG cell calcium channels, we demonstrate that NE and GABA inhibit peptide secretion through activation of alpha-adrenergic and GABAb receptors that are functionally coupled to pertussis toxin (PTX)-sensitive G proteins. Pretreatment of DRG cell cultures with PTX blocked the ability of NE and GABA to inhibit the release of SP, an action correlated with PTX-catalyzed ADP-ribosylation of membrane proteins with apparent molecular weight (Mr) of 40-41 kDa. Western immunoblot analysis of chick DRG cell membrane proteins using antisera directed against synthetic peptides corresponding to amino acid sequences predicted from cDNAs for PTX-sensitive G protein alpha subunits revealed a minimum of 2 Gi-like proteins (Mr 40 and 41 kDa) and a third Go-like protein (Mr 40 kD). Significantly, these findings implicate Gi- and/or Go-like GTP-binding proteins as mediators of presynaptic inhibition in peripheral sensory neurons.
Adenosine Diphosphate Ribose↗
Modification of the rat adipocyte A1 adenosine receptor-adenylate cyclase system during chronic exposure to an A1 adenosine receptor agonist: alterations in the quantity of GS alpha and Gi alpha are not associated with changes in their mRNAs.
The A1-adenosine receptor (A1AR) adenylate cyclase system in rat adipocytes undergoes heterologous desensitization following chronic in vivo exposure to an A1AR agonist (+)-N6-(R-phenylisopropyl)adenosine [J. Biol. Chem. 262:841-847 (1987)]. This desensitization involves an absolute increase in adenylate cyclase activity and a refractoriness to receptor ligands that are inhibitory to adenylate cyclase. In this study, receptor changes were characterized using an A1AR antagonist radioligand, [3H]8-[4-[[[[(2-aminoethyl)amino]carbonyl]methyl] oxy]phenyl]-1,3-dipropyl xanthine. Saturation binding studies demonstrated a 47% decrease in total A1AR density without a change in KD. Agonist competition studies revealed a decreased percentage of receptors, from 55% to 35%, in the high affinity state following desensitization. An increase in GS alpha of 49% was found by Western blotting using specific GS alpha antibodies. Further, an antibody that recognizes Gi alpha 1 adn Gi alpha 2 was used to quantitate these subtypes of Gi alpha and both were decreased by 59% following desensitization. However, when an antibody that recognizes Gi alpha 3 was used, no change in Gi alpha 3 was found, demonstrating, in this case, differential regulation of Gi alpha subtypes. The mechanisms responsible for changes in GS alpha and Gi alpha were studied by measuring the levels of their mRNAs from normal and desensitized adipocytes. Using either labeled cDNAs (Gi alpha 2, Gi alpha 3) or oligonucleotides (GS alpha, Gi alpha 1), Northern analysis demonstrated that mRNAs for GS alpha and all three isoforms of Gi alpha are present in adipocytes but that there are no changes in the levels of any of these transcripts following desensitization. These data suggest that desensitization of the A1AR-adenylate cyclase system involves a down-regulation of A1ARs and an additional loss of A1AR agonist high affinity sites. Further, an increase in GS alpha, a decrease in Gi alpha 1 and Gi alpha 2, and no change in Gi alpha 3 were found. The regulation of GS alpha and the subtypes of Gi alpha in this system does not occur by altering the levels of their respective transcripts.
Adenylyl Cyclases↗
[Current quantitative approach to the splenic index in malaria: the median hypertrophied spleen].
The mean Hackett score is a commonly used index in malaria surveys. It is, however not suitable for comparing the distribution of hypertrophied spleens among small population samples, owing to the validity conditions of statistical tests. The authors suggest to use another index, the median Hackett score, which can be compared to the Tukey test. This test gives a graphical representation of hypertrophied spleen distribution, allowing for rapid and easy comparison. The lack of power of this test is compensated by its robustness (a consequence of its broad limits of validity), its graphical simplicity and its easy interpretation.
Child↗
Purification of heterotrimeric GTP-binding proteins from brain: identification of a novel form of Go.
Using high-resolution Mono-Q anion-exchange chromatography, we purified four distinct GTP-binding proteins from bovine brain. Each consists of alpha and associated beta/gamma subunits, and each is a substrate for pertussis toxin catalyzed ADP-ribosylation. We defined the relationship between the alpha subunits of the purified proteins and cloned cDNAs encoding putative alpha subunits (1) by performing immunoblots with peptide antisera with defined specificity and (2) by comparing the migration on two-dimensional gel electrophoresis of the purified proteins, and of the in vitro translated products of cDNAs encoding alpha subunits. Purified G proteins with alpha subunits of 39, 41, and 40 kDa (G39, G41, and G40 in order of abundance) correspond to the products of Go, Gi1, and Gi2 cDNAs. We purified a novel G protein with an alpha subunit slightly above 39 kDa (G39*). G39* is less abundant than G39, elutes earlier than G39 on Mono-Q chromatography, and has a more basic pI (6.0 vs 5.6) than G39. G39 and G39*, however, are indistinguishable on immunoblots with a large number of specific antisera. The data suggest that G39* may represent a novel form of Go, differing in posttranslational modification rather than primary sequence.
Animals↗
Signal transduction by guanine nucleotide-binding proteins.
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Animals↗
Antiserum raised against residues 159-168 of the guanine nucleotide-binding protein Gi3-alpha reacts with ependymal cells and some neurons in the rat brain containing cholecystokinin- or cholecystokinin- and tyrosine 3-hydroxylase-like immunoreactivities.
Antibodies raised against a synthetic deca-peptide corresponding to a specific sequence of Gi3-alpha protein (an inhibitory guanine nucleotide-binding protein) were used to analyze Gi3-alpha-like immunoreactivity in brain sections from colchicine-treated rats by indirect immunofluorescence histochemistry. Gi3-alpha-peptide-positive cell bodies were found in the ventral tegmental area and substantia nigra, and these cells were also cholecystokinin (CCK)- and tyrosine 3-hydroxylase-positive. Gi3-alpha-peptide staining was observed in perikarya in the hippocampus and in fibers in the nucleus accumbens, tuberculum olfactorium, bed nucleus of stria terminalis, and a spino-thalamic tract, where it coexisted with CCK-like immunoreactivity as well. No coexistence with CCK occurred in Gi3-alpha-peptide-positive ependymal cells outlining the aqueduct and ventricles. Preadsorption of Gi3-alpha antibodies with CCK-8 or CCK-33 did not alter Gi3-alpha-peptide staining. The occurrence of Gi3-alpha-peptide-like immunoreactivity in CCK-containing neurons may indicate the presence of Gi3-alpha protein and in CCK/dopamine neurons may indicate an association of this Gi protein with dopamine autoreceptors.
Animals↗
Immunochemical studies of the 36-kDa common beta subunit of guanine nucleotide-binding proteins: identification of a major epitope.
Twenty-four of 24 rabbits immunized with the beta subunit common to guanine nucleotide binding proteins developed antibodies reactive on immunoblots with the 15-kDa (amino-terminal) tryptic fragment of beta. Only 2 of 24 developed antibodies reactive with the 26-kDa (carboxy-terminal) tryptic fragment. The 15-kDa fragment-reactive antibodies were also detected in several nonimmune sera. Antibodies reactive with the 15-kDa fragment could be affinity-purified from all beta-immune sera by adsorption to a fusion protein encoded by a cDNA clone identified by expression vector screening. The 15-kDa fragment antibodies in nonimmune sera did not bind to the fusion protein. Limited amino acid sequence homology between the 36-kDa beta subunit and the protein encoded by the cDNA clone suggested that the amino-terminal decapeptide of beta contains a major epitope. A synthetic decapeptide, corresponding to the amino terminus of the 36-kDa beta subunit, effectively and specifically blocked binding of antibodies in beta-immune sera (but not in beta-reactive nonimmune sera) to nitrocellulose-bound 15-kDa fragment. The 15-kDa fragment-reactive antibodies could be affinity-purified from beta-immune sera on a matrix containing bound decapeptide; affinity-purified antibodies reacted equally well with the 36- and 35-kDa forms of the beta subunit. Native transducin beta/gamma complexes readily blocked binding of 15-kDa fragment-reactive antibodies in immune but not nonimmune sera from binding to the nitrocellulose-bound fragment. The results show that nonimmune sera may contain antibodies directed against an epitope of the 15-kDa fragment that is buried in the native beta/gamma complex. In contrast, the amino terminal decapeptide of the beta subunit is exposed on the surface of the native protein and contains a major antigenic site in both the 35- and 36-kDa forms.
Amino Acid Sequence↗
Identification of proteins in retinas and IPM from eyes with retinitis pigmentosa.
Opsin, the alpha-subunit of transducin, S-antigen, interphotoreceptor retinoid-binding protein (IRBP) and cathepsin D were assessed in autopsy eyes from patients with retinitis pigmentosa (RP) and normal autopsy eyes. Immunochemical methods were used to determine the presence of these proteins on Western blots of retinal homogenates from five RP donors and on blots of interphotoreceptor matrix (IPM) preparations from six other RP eyes. The amounts of immunoreactive opsin, S-antigen, alpha-transducin, and IRBP appeared below normal in retinas from RP eyes. All six IPM samples from patients with advanced RP had reduced amounts of S-antigen and no detectable IRBP or transducin. Cathepsin D (an RPE protein) was present in IPM or RP eyes in amounts comparable to that in IPMs from normal eyes. Small amounts of cathepsin D were also detected in retinas from both normal and RP eyes. These studies show that proteins specific to the photoreceptor-pigment epithelium complex in normal eyes can be detected in autopsy eyes from patients with RP and suggest that the observed reductions in photoreceptor-specific proteins occur as a consequence of photoreceptor loss.
Adult↗
GTP-binding proteins in brain and neutrophil are tethered to the plasma membrane via their amino termini.
Using specific antisera raised against synthetic peptides, we find that three distinct GTP-binding protein alpha subunits remain bound to the plasma membrane even after activation with nonhydrolyzable GTP analog. Trypsin cleaves each alpha subunit at a site near the amino-terminus, and quantitatively releases the large fragment (comprising all but an amino-terminal 2 kDa piece) from the membrane. Our results indicate that alpha subunits are essentially cytoplasmic proteins tethered to the inner surface of the membrane via an amino terminal stalk.
Animals↗
Differential distribution of signal-transducing G-proteins in retina.
We used specific antibodies in immunoblot studies of membrane fractions derived from bovine retina, and in immunohistochemical studies of sections of rat retina to determine the distribution of two guanine nucleotide binding proteins Go (a G-protein of unknown function discovered in the brain) and transducin, in retina. Both Go and transducin were readily detected in membranes derived from whole retina, and in crude rod outer segment membranes. Purification of rod outer segment membranes by sucrose density gradient centrifugation resulted in enrichment in transducin and depletion of Go immunoreactivity. Transducin-alpha immunoreactivity was localized to photoreceptor inner and outer segments and the outer nuclear layer. In contrast, Go-alpha immunoreactivity was localized in the inner and outer plexiform layers and ganglion cell layer. The results indicate that Go unlike transducin, is not associated with rod outer segment membranes and is therefore unlikely to function in phototransduction. Go is, however, relatively abundant in neural layers of retina where it may be involved in signal transduction.
Animals↗