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S Iyengar

Publications and source records attributed to S Iyengar.

At least 37 records · Page 2Linked to original sources
PubMed2000

New perspectives and evidence on political communication and campaign effects.

We review recent empirical evidence that shows political campaigns are more potent than widely believed, focusing on the conceptual and methodological advances that have produced these findings. Conceptually, a broader definition of effects--that includes learning and agenda-control, as well as vote choice--characterizes contemporary research. This research also features two kinds of interactive models that are more complex than the traditional hypodermic (message-based) approach. The resonance model considers the relationship between message content and receivers' predispositions, while the strategic model highlights the interactions between competing messages. Finally, we attribute the emergence of stronger evidence in favor of campaign effects to the use of new methodologies including experimentation and content analysis, as well as the more sophisticated use of sample surveys.

Communication Barriers↗
PubMed2000

Novel characteristics of a misprocessed mutant HERG channel linked to hereditary long QT syndrome.

Hereditary long QT syndrome (hLQTS) is a heterogeneous genetic disease characterized by prolonged QT interval in the electrocardiogram, recurrent syncope, and sudden cardiac death. Mutations in the cardiac potassium channel HERG (KCNH2) are the second most common form of hLQTS and reduce the delayed rectifier K(+) currents, thereby prolonging repolarization. We studied a novel COOH-terminal missense mutation, HERG R752W, which segregated with the disease in a family of 101 genotyped individuals. When the mutant cRNA was expressed in Xenopus oocytes it produced enhanced rather than reduced currents. Simulations using the Luo-Rudy model predicted minimal shortening rather than prolongation of the cardiac action potential. Consequently, a normal or shortened QT interval would be expected in contrast to the long QT observed clinically. This anomaly was resolved by our observation that the mutant protein was not delivered to the plasma membrane of mammalian cells but was retained intracellularly. We found that this trafficking defect was corrected at lower incubation temperatures and that functional channels were now delivered to the plasma membrane. However, trafficking could not be restored by chemical chaperones or E-4031, a specific blocker of HERG channels. Therefore, HERG R752W represents a new class of trafficking mutants in hLQTS. The occurrence of different classes of misprocessed channels suggests that a unified therapeutic approach for altering HERG trafficking will not be possible and that different treatment modalities will have to be matched to the different classes of trafficking mutants.

Action Potentials↗
PubMed2000

Use of serial analysis of gene expression to generate kidney expression libraries.

Chronic renal disease initiation and progression remain incompletely understood. Genome-wide expression monitoring should clarify mechanisms that cause progressive renal disease by determining how clusters of genes coordinately change their activity. Serial analysis of gene expression (SAGE) is a technique of expression profiling, which permits simultaneous, comparative, and quantitative analysis of gene-specific, 9- to 13-bp sequence tags. Using SAGE, we have constructed a tag expression library from ROP-+/+ mouse kidney. Tag sequences were sorted by abundance, and identity was determined by sequence homology searching. Analyses of 3,868 tags yielded 1,453 unique kidney transcripts. Forty-two percent of these transcripts matched mRNA sequence entries with known function, 35% of the transcripts corresponded to expressed sequence tag (EST) entries or cloned genes, whose function has not been established, and 23% represented unidentified genes. Previously characterized transcripts were clustered into functional groups, and those encoding metabolic enzymes, plasma membrane proteins (transporters/receptors), and ribosomal proteins were most abundant (39, 14, and 12% of known transcripts, respectively). The most common, kidney-specific transcripts were kidney androgen-regulated protein (4% of all transcripts), sodium-phosphate cotransporter (0.3%), renal cytochrome P-450 (0.3%), parathyroid hormone receptor (0.1%), and kidney-specific cadherin (0.1%). Comprehensively characterizing and contrasting gene expression patterns in normal and diseased kidneys will provide an alternative strategy to identify candidate pathways, which regulate nephropathy susceptibility and progression, and novel targets for therapeutic intervention.

Animals↗
PubMed1999

Development of topography within song control circuitry of zebra finches during the sensitive period for song learning.

Refinement of topographic maps during sensitive periods of development is a characteristic feature of diverse sensory and motor circuits in the nervous system. Within the neural system that controls vocal learning and behavior in zebra finches, axonal connections of the cortical nucleus lMAN demonstrate striking functional and morphological changes during vocal development in juvenile males. These circuits are uniquely important for song production during the sensitive period for vocal learning, and the overall size of these brain regions and their patterns of axonal connectivity undergo dramatic growth and regression during this time. Axonal connections to and from lMAN are topographically organized in adult males that have already learned song. We wondered whether the large-scale changes seen in lMAN circuitry during the time that vocal behavior is being learned and refined could be accompanied by the emergence of topographic mapping. However, results presented herein demonstrate that most of these song-control circuits show the same broad patterns of axonal connectivity between subregions of individual nuclei at the onset of song learning as seen in adult birds. Thus, coarse topographic organization is not dependent on the types of experience that are crucial for vocal learning. Furthermore, this maintenance of topographic organization throughout the period of song learning is clearly not achieved by maintenance of static axonal arbors. In fact, because the volumes of song-control nuclei are growing (or regressing), topography must be maintained by active remodeling of axonal arbors to adapt to the changes in overall size of postsynaptic targets. A salient exception to this pattern of conserved topography is the projection from lMAN to the motor cortical region RA: this pathway is diffusely organized at the onset of song learning but undergoes substantial refinement during early stages of song learning, suggesting that remodeling of axonal connections within this projection during the period of vocal learning may signify the production of increasingly refined vocal utterances.

Aging↗
PubMed1999

T cell-tropic HIV gp120 mediates CD4 and CD8 cell chemotaxis through CXCR4 independent of CD4: implications for HIV pathogenesis.

HIV entry is determined by one or more chemokine receptors. T cell-tropic viruses bind CXCR4, whereas macrophage-tropic viruses use CCR5 and other CCRs. Infection with CXCR4 and CCR5-tropic HIV requires initial binding to CD4, and chemotaxis induced by the CCR5-tropic envelope has been reported to be strictly dependent on CD4 binding. We demonstrate that, in contrast to CD4-dependent gp120 signaling via CCR5, envelope signaling through CXCR4 is CD4 independent, inducing chemotaxis of both CD4 and CD8 T cells. Signaling by virus or soluble envelope through CXCR4 may affect pathogenesis by attracting and activating target and effector cells.

CD4-Positive T-Lymphocytes↗
PubMed1999

Characterization of central and peripheral effects of septide with the use of five tachykinin NK1 receptor antagonists in the rat.

1. Effects of two tachykinin NK1 receptor selective agonists (septide and [Sar9, Met(O2)11]SP) were compared on the increases in mean arterial pressure (MAP), heart rate (HR) and motor behaviour following intracerebroventricular (i.c.v.) administration in unanaesthetized rat, and on the vascular permeability increases to intradermal (i.d.) injection in the anaesthetized rat. Moreover, five tachykinin NK1 receptor selective antagonists (LY303870, LY306740, LY303241, SR140333 and RP67580) were tested against the two agonists to compare their pharmacological profile. 2. [Sar9, Met(O2)11]SP and septide (10-100 pmol per rat, i.c.v.) were equipotent in increasing MAP and HR, yet they had dissimilar time-course. Both agonists increased dose-dependently face washing and sniffing while [Sar9, Met(O2)11]SP was the sole to produce grooming, septide was more potent than [Sar9, Met(O2)11]SP (6.5-650 pmol) in increasing vascular permeability. 3. For most centrally mediated responses, LY303870 and RP67580 were significantly more potent in inhibiting septide than [Sar9, Met(O2)11]SP. In some parameters, greater blockade was achieved when antagonists (particularly LY306740) were given 1 h instead of 10 min prior to i.c.v. septide. 4. All antagonists except LY303241 blocked dose-dependently the increases in vascular permeability to equipotent doses of [Sar9, Met(O2)11]SP and septide. LY303870 and LY306740 were more potent against septide. 5. The antagonism afforded by LY303870, LY306740 and LY303241 was stereoselective and only SR140333 was found to cause central and peripheral non specific effects. 6. The data confirm a distinct pharmacological profile for septide in vivo. RP67580 and LY306740 are currently the most valuable tachykinin NK1 receptor antagonists for in vivo studies in rat.

Acetamides↗
PubMed1999

Genetic susceptibility to end-stage renal disease.

New methods have been developed to uncover the genotypes that result in complex diseases. End-stage renal disease is a complex disease, without a simple correspondence between genotype and phenotype. Both population-based and family-based epidemiological studies and analysis of model organisms suggest that the pathogenesis of end-stage renal disease may have a genetic component. A number of studies have analyzed candidate nephropathy genes with little success, but recently several well-designed studies of multiplex families with diabetic nephropathy have identified candidate nephropathy susceptibility loci. To date, kidney disease-oriented research has focused on effector mechanisms responsible for the initiation and progression of chronic renal disease. However, because end-stage renal disease is a complex disease, interruption of a single effector pathway is unlikely to result in significant therapeutic benefit. Further understanding of the pathogenesis of kidney disease and the development of new kidney disease therapies will require continued application of genetic and genomic tools to kidney disease research.

Animals↗
PubMed1999

Characterization of neuropeptide Y-induced feeding in mice: do Y1-Y6 receptor subtypes mediate feeding?

The stimulation of food consumption after i.c.v. administration of various neuropeptide Y (NPY) receptor agonists was examined in CD-1 mice. These agonists, including endogenous peptides NPY, peptide YY (PYY), and pancreatic polypeptide, as well as several N-terminal truncated and synthetic peptides that are prototypic receptor agonists at Y1-Y6 NPY receptors ([Leu31Pro34]NPY, NPY2-36, NPY3-36, NPY13-36, PYY3-36, Pro34PYY, and D-Trp32NPY), showed varying abilities to elicit food consumption such that PYY > NPY2-36 = NPY = PYY3-36 > Pro34PYY > NPY3-36 >> [Leu31Pro34]NPY > NPY13-36 = D-Trp32NPY = pancreatic polypeptide. Published reports have suggested that NPY-induced feeding is mediated via the Y1 or the Y5 receptor subtypes. However, the relative ability of the various peptide analogs to elicit feeding differed from the relative ability of these peptides to bind to cloned Y1-Y6 receptors. The effects of prototypic Y1 receptor antagonists on NPY-induced feeding were also evaluated after i.c.v. administration. GR231118 (1229U91), a peptide Y1 antagonist, did not block NPY-induced feeding at the doses tested. BIBP3226, a nonpeptide Y1 receptor antagonist, as well as its opposite enantiomer, BIBP3435, which is inactive at Y1 receptors, blocked feeding elicited by NPY, [Leu31Pro34], or PYY at doses that did not cause overt behavioral dysfunction. The lack of effects with GR231118 and the nonstereoselective effects of BIBP3226 suggested that NPY-induced feeding in mice was not mediated via the Y1 receptor. Thus, by using currently available prototypic peptide NPY receptor agonists for Y1-Y6 receptors and peptide and nonpeptide Y1 receptor antagonists GR231118 and BIBP3226, the mediation of NPY-induced feeding cannot be unequivocally attributed to any one of the known NPY receptors. It is possible that NPY-induced feeding is mediated either by a combination of more than one NPY receptor subtype or by a unique NPY receptor subtype. Additional subtype-selective receptor antagonists, when available, will help to clarify this issue further.

Animals↗
PubMed1998

5HT1A receptor antagonists enhance the functional activity of fluoxetine in a mouse model of feeding.

Fluoxetine has been reported to suppress food intake in animal models of feeding. Fluoxetine increases extracellular serotonin in the brain. 5HT1A autoreceptors regulate synaptic levels of serotonin. A combination of a 5HT1A receptor antagonist and fluoxetine has been previously reported to enhance extracellular levels of serotonin over what is obtained with fluoxetine alone. Thus, a combination of fluoxetine and a 5HT1A antagonist could enhance the ability of fluoxetine to suppress appetite. Fluoxetine was tested in a model of feeding, in which CD-1 mice were trained to drink sweetened condensed milk. Fluoxetine was found to attenuate milk drinking, in a dose-dependent manner, at doses greater than 10 mg/kg, i.p. A 10 mg/kg dose of fluoxetine, which was ineffective by itself, was then combined either with 5-hydroxytryptophan (5HTP), a serotonin precursor, or with S(-) pindolol, a 5HT1A/beta adrenergic receptor antagonist or with LY206130, a more selective 5HT1A receptor antagonist. These treatment paradigms resulted in significant attenuation of the consumption of sweetened condensed milk. Since fluoxetine has been shown to be useful in the treatment of eating disorders and to promote weight loss in obese humans, although at doses greater than those required for the treatment of depression, a combination of fluoxetine with a 5HT1A receptor antagonist could be of clinical utility in the treatment of eating disorders and obesity.

Animals↗
PubMed1998

Kainate GluR5 receptor subtype mediates the nociceptive response to formalin in the rat.

In order to study the roles of the AMPA and kainate subtypes of non-NMDA glutamate receptors in the processing of persistent nociceptive information, compounds with varying activities at these receptors were examined for effects on the formalin-induced paw-licking behavior in rats. The selective AMPA antagonist, LY300164 and the mixed AMPA/kainate antagonist, NBQX, were compared for their effects on formalin-induced pain behavior. NBQX (3, 10, 20 mg/kg, i.p.), caused antinociception as well as ataxia whereas the selective AMPA antagonist, LY300164 (3,5,10 mg/kg, i.p.), did not cause antinociception at doses that did not produce ataxia. In view of the well documented distribution of kainate receptors on C fibres and of the kainate-preferring iGluR5 subtype on dorsal root ganglia (DRG), we tested a series of three decahydroisoquinolines with different profiles of activity between iGluR5 and AMPA receptors and all without activity on iGluR6, iGluR7 or KA2 subtypes. LY293558 (0.1, 1, 3, 5 mg/kg, i.p.), which had low micromolar affinity for both iGluR5 and 2 caused, like NBQX, both antinociceptive and ataxic effects. However, the selective iGluR5 antagonist LY382884 (5, 10, 30, 100 mg/kg, i.p.), exhibited antinociceptive actions without ataxia while the iGluR2 preferring antagonist LY302679 (5 mg/kg, i.p), caused ataxia but did not produce antinociceptive effects at that dose. These actions were stereoselective since the enantiomeric compounds, LY293559 and LY302680, were ineffective in these tests. The data strongly suggest an involvement of iGluR5 in the processing of nociceptive information.

Animals↗
PubMed1998

The nonpeptide NK-1 receptor antagonists LY303870 and LY306740 block the responses of spinal dorsal horn neurons to substance P and to peripheral noxious stimuli.

The effects of novel substance P (NK-1) receptor antagonists LY303870 and LY306740, as well as LY306155, the enantiomer of LY303870, were tested on the responses of nociceptive spinal dorsal horn neurons to iontophoretically applied substance P and to peripheral noxious stimuli. The peripheral stimuli included noxious thermal and pinch stimuli applied to the cutaneous receptive field in the hind paw and stimulation of the superficial peroneal nerve with a train of high-intensity electrical stimuli. Extracellular recordings were obtained using multi-barrel electrodes from L4-L7 segments of the spinal cord in cats anaesthetized with alpha-chloralose and spinalized at the L1 level. The antagonists were given i.v. (0.5-4.0 mg/kg). Responses to substance P were inhibited by LY303870 and by LY306740 in a dose-related manner, but were not affected by LY306155. Responses to peripheral noxious thermal stimulation were inhibited in a dose-related manner by LY303870 and LY306740, and only at higher doses (2 mg/kg or more) by LY306155. Responses to pinch stimuli were inhibited by LY303870 and LY306740. LY306155 lacked consistent effects on pinch responses. LY303870 selectively inhibited the late component of the response to electrical stimulation of the superficial peroneal nerve. When these three drugs were tested against the responses of dorsal horn neurons to the excitatory amino acid, N-methyl-D-aspartate, the responses were unaffected. These data suggest that LY303870 and LY306740 pass from the circulation into the spinal cord where they antagonize dorsal horn neuronal responses to substance P and nociceptive inputs.

Acetamides↗
PubMed1998

Actin-dependent receptor colocalization required for human immunodeficiency virus entry into host cells.

Human immunodeficiency virus (HIV) envelope binds CD4 and a chemokine receptor in sequence, releasing hydrophobic viral gp41 residues into the target membrane. HIV entry required actin-dependent concentration of coreceptors, which could be disrupted by cytochalasin D (CytoD) without an effect on cell viability or mitosis. Pretreatment of peripheral blood mononuclear cells, but not virus, inhibited entry and infection. Immunofluorescent confocal microscopy of activated cells revealed CD4 and CXCR4 in nonoverlapping patterns. Addition of gp120 caused polarized cocapping of both molecules with subsequent pseudopod formation, while CytoD pretreatment blocked these membrane changes completely.

Actins↗
PubMed1998

Analyses of cross species polymerase chain reaction products to infer the ancestral state of human polymorphisms.

In numerous population genetic and disease association studies decisions about the ancestry of polymorphic alleles are often made based on the relative frequency of the alleles in the extant populations with the most frequent allele being deemed as ancestral. However, the frequency of an allele in a population is generally not a perfect indicator of its ancestral status. A more accurate method to assess ancestral/derived status of polymorphic alleles involves identification of shared alleles between species. We used this strategy to examine genomic regions homologous to several human polymorphisms in four species of non-human primates. Cross species polymerase chain reaction (CS-PCR), with primers designed from human sequence, was used to investigate regions of interest. Nineteen polymorphisms at six loci (DRD2, HOXB@, PAH, D4S10, RBP3, and RET) were examined either by restriction fragment length analysis of PCR products (PCR-RFLP) or by direct sequencing. At seventeen of the eighteen PCR-RFLPs, non-human primates were monomorphic and identical to each other for either lack of restriction enzyme site or presence of the site. Thus, at these seventeen polymorphic sites the shared alleles are most likely to be the ancestral ones in humans. In several cases we have used sequence data to further demonstrate that the nucleotide at the site of the polymorphism is conserved between species confirming the hypothesis of a single ancestral allele. However, not all human alleles can be simply resolved into ancestral and derived; sequence data from one PCR-RFLP (in an intron of the PAH locus) and a single strand conformational polymorphism (SSCP) in the 3' untranslated region (UTR) of the DRD2 gene illustrate this point.

Alleles↗
PubMed1997

The rabbit ileum: a sensitive and selective preparation for the neuropeptide Y Y5 receptor.

The rabbit ileum shows high sensitivity to neuropeptide Y. Relaxations are obtained in this tissue with human pancreatic polypeptide > peptide YY > > [Leu31,Pro34]neuropeptide Y > rat pancreatic polypeptide > human neuropeptide Y in this order of potency that is indicative of a Y5 receptor. Effects of neuropeptide Y and congeners are not affected by neuropeptide Y Y1 receptor antagonist (BIBP 3226), but are reduced by the neuropeptide Y Y5 receptor antagonist JCF 104 (2-(naphtalen-1-yl)-3-phenylpropane-1,2-diamine). Rabbit ilea provide sensitive and selective neuropeptide Y Y5 receptor preparations.

Animals↗
PubMed1997

A clinical psychotherapy trial for adolescent depression comparing cognitive, family, and supportive therapy.

BACKGROUND: Previous studies in nonclinical samples have shown psychosocial treatments to be efficacious in the treatment of adolescent depression, but few psychotherapy treatment studies have been conducted in clinically referred, depressed adolescents. METHODS: One hundred seven adolescent patients with DSM-III-R major depressive disorder (MDD) were randomly assigned to 1 of 3 treatments: individual cognitive behavior therapy, systemic behavior family therapy (SBFT), or individual nondirective supportive therapy (NST). Treatments were 12 to 16 sessions provided in as many weeks. Intent-to-treat analyses were conducted using all follow-up data. RESULTS: Of the 107 patients enrolled in the study, 78 (72.9%) completed the study, 4 (3.7%) never initiated treatment, 10 (9.3%) had exclusionary criteria that were undetected at entry, 8 (7.5%) dropped out, and 7 (6.5%) were removed for clinical reasons. Cognitive behavior therapy showed a lower rate of MDD at the end of treatment compared with NST (17.1% vs 42.4%; P = .02), and resulted in a higher rate of remission (64.7%, defined as absence of MDD and at least 3 consecutive Beck Depression Inventory scores < 9) than SBFT (37.9%; P = .03) or NST (39.4%; p = .04). Cognitive behavior therapy resulted in more rapid relief in interviewer-rated (vs both treatments, P = .03) and self-reported depression (vs SBFT, P = .02). All 3 treatments showed significant and similar reductions in suicidality and functional impairment. Parents' views of the credibility of cognitive behavior therapy improved compared with parents' views of both SBFT (P = .01) and NST (P = .05). CONCLUSIONS: Cognitive behavior therapy is more efficacious than SBFT or NST for adolescent MDD in clinical settings, resulting in more rapid and complete treatment response.

Adolescent↗
PubMed1997

Mitochondrial versus nuclear admixture estimates demonstrate a past history of directional mating.

Six blood group antigens (ABO, RH, MNS, KK, KP, FY) and five plasma proteins (HP, GC, APOA4, FXIIIB, C1R) were typed in 790 individuals, and 12 mtDNA RFLP and deletion polymorphisms were typed in 657 individuals from the San Luis Valley, Colorado. The 790 nuclear typings were conducted on 399 Anglos and 391 Hispanics, while the 657 mitochondrial haplotypes were generated from 207 Anglos and 450 Hispanics. Chakraborty's ADMIX2 FORTRAN program was used to estimate the average Amerindian admixture using all nuclear loci simultaneously. Since there is no recombination in mtDNA, the sum of the frequencies of the Amerindian/Asian-specific mitochondrial haplotypes represents the level of Amerindian admixture. The nuclear estimates of Amerindian admixture were 33.15 +/- 2.41% for the Hispanics and 9.72 +/- 1.90% for the Anglos, while the strictly maternally inherited mtDNA estimates of Amerindian admixture were 85.11% for the Hispanics and 0.97% for the Anglos. This dramatic difference in estimated levels of admixture between the biparentally derived nuclear estimates and the uniparentally derived mtDNA estimates is indicative of past directional matings between Hispanic males and Amerindian females.

Blood Group Antigens↗
PubMed1997

Detection of major genes underlying several quantitative traits associated with a common disease using different ascertainment schemes.

Using the Problem 2A data sets of GAW10, we assessed the power of four ascertainment schemes to localize major genes underlying a disease trait; the schemes were based on disease or quantitative trait status of nuclear families. MAPMAKER/SIBS was used to perform sib-pair analysis for all four data sets using marker data from three chromosomes, 4, 5 and 8. Each scheme varied in power to identify major genes underlying the quantitative traits depending on the genetic architecture of the data set. Three different methods, Haseman-Elston quantitative trait locus (QTL) regression analysis, maximum likelihood variance estimation and a non-parametric method, were used to assess the strength of linkage in all four data sets. False positive mappings localizing to the same region of the genome, verifiable across all three methods did not occur. Two major genes, MG1 and MG2, were successfully assigned to chromosomes 5 and 8, respectively, by at least one of the ascertainment schemes. MG1 was localized under two schemes, selection of families with exactly two affected sibs and selection of families with two sibs who had extremely discordant values for Q1. Additional weak evidence of the location of MG1 was also obtained under the other two ascertainment schemes. MG2 could not be detected by analyzing data sets ascertained either by affected sib pairs or by sib pairs with extremely discordant values for Q1. In the data set ascertained by a third strategy, selection of families with sib pairs extremely discordant for Q2, MG2 could be mapped to chromosome 8. A random ascertainment scheme yielded a data set in which we could find weak evidence for MG1 and no evidence for MG2. Thus our ability to detect major genes underlying the QTL depended on several factors which included the ascertainment scheme, the population allele frequencies, linkage and epistasis.

Chromosome Mapping↗