Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “modulators”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 865 records · Page 48Linked to original sources
PubMed1995

Recognition of amplitude-modulation patterns in the presence of a distractor. I. Effects of correlation and frequency relation.

Listeners' ability to compare the amplitude modulation pattern of 200- and 500-Hz targets when distractors that were also amplitude modulated were presented simultaneously was evaluated. The amplitude modulations of the distractors were either uncorrelated, partially correlated, or fully correlated with the amplitude modulations of the comparisons. Relative to the case of no distractor, performance tended to decrease when a distractor was present, and the degree of interference increased as the modulation correlation between the comparisons and distractors decreased. Although the interference was greater when the comparisons and distractors were separated by 50 Hz, there was also significant interference when the separation was 300 Hz. Whether the comparison was higher or lower in frequency than the distractor had no overall effect. However, the effect of modulation correlation was greater when comparisons were higher than distractors rather than lower. Patterns of interference are compared to those found in studies of modulation detection and discrimination interference, and implications for the use of multiple-band signals that carry the amplitude envelopes from different spectral regions of a speech signal to convey speech are discussed.

Auditory Perception↗
PubMed1996

Across-channel processes in frequency modulation detection.

This study investigated how well listeners combine information about frequency changes imposed on different carrier frequencies. The pattern of frequency change over time was either identical or different across carriers; this is referred to as "coherence." Psychometric functions were measured for the detection of frequency modulation (FM) imposed on two sinusoidal carriers, with frequencies 1100 and 2000 Hz. The modulation of each carrier was equally detectable, as determined in preliminary experiments. A continuous pink noise background was used to mask the outputs of auditory filters tuned between the two carrier frequencies. In experiment 1, the carriers were gated synchronously with l-s steady state duration and 50-ms raised-cosine ramps. One cycle of 5-Hz sinusoidal FM was used, the carrier having unmodulated "fringes" on either side of this. The FM on the two carriers was symmetrically located about the temporal center of the stimulus. The relative timing of the onset of FM (lag) between the two carriers was systematically varied. When the FM overlapped partially or completely in time across carriers, detectability for coherent FM was often better than for incoherent FM, especially for lag = 0, and was also often better than predicted on the assumption that information about the FM on the two carriers was extracted independently and combined optimally. When the FM did not overlap in time across the carriers, the detectability of the combined FM was generally equal to or lower than the value predicted on this assumption. In experiment 2, the long steady-state fringes before and after the modulation were removed, and the modulation always started at the same time for the two carriers. The modulation rate was either 2.5, 5, or 10 Hz. Again, performance for coherent FM was generally better than for incoherent FM. The effect of FM coherence was greater at the lowest modulation rate but did not vary markedly with the number of modulation cycles. The detectability of coherent FM was well above the value predicted on the assumption that information from the two carrier frequencies was processed independently and combined optimally. These results indicate the auditory system has higher sensitivity to FM when the FM is coherent across carriers. Possible models to account for the results are discussed.

Auditory Perception↗
PubMed1996

Detection of auditory "events" based on amplitude and frequency modulation.

These experiments examined the ability of subjects to detect auditory "events" composed of a brief modulation in the temporal center of an otherwise steady sinusoid. In experiment 1, psychometric fluctuations were measured for detecting either amplitude modulation (AM) or frequency modulation (FM) composed of a single cycle of a raised-cosine function (either positive going or negative going); the modulation frequency was 10 Hz, so the event lasted for 100 ms. Then, psychometric functions were measured for stimuli with both AM and FM, using pairs of values of AM and FM that were equally detectable; pairs were always modulated in the same direction, so a positive amplitude excursion went together with a positive frequency excursion. Performance was compared with the "reference" detectability that would be predicted from the optimal combination of independent sources of information. When the AM and FM were synchronous, detectability was better than the reference detectability. When the FM was delayed by 100 ms relative to the AM, detectability was mostly equal to or less than the reference detectability. The better performance with synchronous AM and FM is consistent with an explanation based on an excitation-pattern model. Experiment 2 was similar to experiment 1, except that the event was a single cycle of sinusoidal modulation starting at 0 degree phase or 180 degrees phase. When the AM and FM were synchronous and in phase, detectability was better than the reference detectability. When the AM was delayed by 200 ms relative to the FM or had opposite starting phase, detectability was close to or below the reference detectability. However, for the case where the delay was 100 ms and the modulation had the same starting phase for AM and FM, detectability was better than the reference detectability. A control experiment using two successive cycles of either AM or FM showed a similar, but slightly smaller, effect. It appears that detectability can be enhanced when two successive events form a regular temporal pattern.

Auditory Perception↗
PubMed1997

Modeling auditory processing of amplitude modulation. II. Spectral and temporal integration.

A multi-channel model, describing the effects of spectral and temporal integration in amplitude-modulation detection for a stochastic noise carrier, is proposed and validated. The model is based on the modulation filterbank concept which was established in the accompanying paper [Dau et al., J. Acoust. Soc. Am. 102, 2892-2905 (1997)] for modulation perception in narrow-band conditions (single-channel model). To integrate information across frequency, the detection process of the model linearly combines the channel outputs. To integrate information across time, a kind of "multiple-look" strategy, is realized within the detection stage of the model. Both data from the literature and new data are used to validate the model. The model predictions agree with the results of Eddins [J. Acoust. Soc. Am. 93, 470-479 (1993)] that the "time constants" associated with the temporal modulation transfer functions (TMTF) derived for narrow-band stimuli do not vary with carrier frequency region and that they decrease monotonically with increasing stimulus bandwidth. The model is able to predict masking patterns in the modulation-frequency domain, as observed experimentally by Houtgast [J. Acoust. Soc. Am. 85, 1676-1680 (1989)]. The model also accounts for the finding by Sheft and Yost [J. Acoust. Soc. Am. 88, 796-805 (1990)] that the long "effective" integration time constants derived from the data are two orders of magnitude larger than the time constants derived from the cutoff frequency of the TMTF. Finally, the temporal-summation properties of the model allow the prediction of data in a specific temporal paradigm used earlier by Viemeister and Wakefield [J. Acoust. Soc. Am. 90, 858-865 (1991)]. The combination of the modulation filterbank concept and the optimal decision algorithm proposed here appears to present a powerful strategy for describing modulation-detection phenomena in narrow-band and broadband conditions.

Auditory Perception↗
PubMed1999

Center frequency modulation detection for harmonic complexes resembling vowel formants and its interference by off-frequency maskers.

Vowels are characterized by peaks in their spectral envelopes: the formants. To gain insight into the perception of speech as well as into the basic abilities of the ear, sensitivity to modulations in the positions of these formants is investigated. Frequency modulation detection thresholds (FMTs) were measured for the center frequency of formantlike harmonic complexes in the absence and in the presence of simultaneous off-frequency formants (maskers). Both the signals and the maskers were harmonic complexes which were band-pass filtered with a triangular spectral envelope, on a log-log scale, into either a LOW (near 500 Hz), a MID (near 1500 Hz), or a HIGH region (near 3000 Hz). They had a duration of 250 ms, and either an 80- or a 240-Hz fundamental. The modulation rate was 5 Hz for the signals and 10 Hz for the maskers. A pink noise background was presented continuously. In a first experiment no maskers were used. The measured FMTs were roughly two times larger than previously reported just-noticeable differences for formant frequency. In a second experiment, no significant differences were found between the FMTs in the absence of maskers and those in the presence of stationary (i.e., nonfrequency modulated) maskers. However, under many conditions the FMTs were increased by the presence of simultaneous modulated maskers. These results indicate that frequency modulation detection interference (FMDI) can exist for formantlike complex tones. The FMDI data could be divided into two groups. For stimuli characterized by a steep (200-dB/oct) slope, it was found that the size of the FMDI depended on which cues were used for detecting the signal and masker modulations. For stimuli with shallow (50-dB/oct) slopes, the FMDI was reduced when the signal and the masker had widely differing fundamentals, implying that the fundamental information is extracted before the interference occurs.

Auditory Threshold↗
PubMed1999

Intrinsic envelope fluctuations and modulation-detection thresholds for narrow-band noise carriers.

A model is presented which calculates the intrinsic envelope power of a bandpass noise carrier within the passband of a hypothetical modulation filter tuned to a specific modulation frequency. Model predictions are compared to experimentally obtained amplitude modulation (AM) detection thresholds. In experiment 1, thresholds for modulation rates of 5, 25, and 100 Hz imposed on a bandpass Gaussian noise carrier with a fixed upper cutoff frequency of 6 kHz and a bandwidth in the range from 1 to 6000 Hz were obtained. In experiment 2, three noises with different spectra of the intrinsic fluctuations served as the carrier: Gaussian noise, multiplied noise, and low-noise noise. In each case, the carrier was spectrally centered at 5 kHz and had a bandwidth of 50 Hz. The AM detection thresholds were obtained for modulation frequencies of 10, 20, 30, 50, 70, and 100 Hz. The intrinsic envelope power of the carrier at the output of the modulation filter tuned to the signal modulation frequency appears to provide a good estimate for AM detection threshold. The results are compared with predictions on the basis of the more complex auditory processing model by Dau et al.

Auditory Threshold↗
PubMed2005

Principles of N-methyl-D-aspartate receptor allosteric modulation.

N-methyl-D-aspartate (NMDA) receptors are glutamate-gated ion channels with complex participation in synaptic transmission, integration, and plasticity. They are highly permeable to Ca(2+), activate with characteristic kinetics, and generate currents with distinct amplitudes according to stimulation frequency. Multiple endogenous and pharmacological agents bind at distinct locations throughout the protein and modulate NMDA receptor responses with allosteric mechanisms. The NMDA receptor activation pathway consists of a series of consecutive, stepwise structural rearrangements rather than a binary, closed-open reaction. This high-resolution multistate gating reaction is used here to investigate the effects of ideal, state-specific modulators on physiologically relevant parameters of the macroscopic responses to single-pulse and high-frequency repetitive stimulation. The simulations suggest three significant aspects of NMDA receptor modulation: 1) modest, 1 kcal/mol bidirectional perturbations in receptor free energy cause up to a 50-fold change in the total charge transferred; 2) activators modulate primarily the response time course, whereas inhibitors are more effectively modulating current peak amplitude; and 3) state-specific modulators have opposite effects on charge transfer and current potentiation by high-frequency stimulation. The results imply that the magnitude of the NMDA receptor-mediated Ca(2+) influx and the receptor's ability to discriminate stimulation frequency can be controlled separately. Thus, a detailed mechanistic characterization of NMDA receptor allosteric effectors may identify function-specific modulators and provides a road map for the development of combinatorial strategies for local, transient tuning of specific receptor functions.

Allosteric Regulation↗
PubMed2006

Point mutations in the transmembrane region of GABAB2 facilitate activation by the positive modulator N,N'-dicyclopentyl-2-methylsulfanyl-5-nitro-pyrimidine-4,6-diamine (GS39783) in the absence of the GABAB1 subunit.

GABA(B) receptors are heterodimers of two subunits, GABA(B1) (GB1) and GABA(B2) (GB2). Agonists such as GABA and baclofen bind to the GB1 subunit only, whereas GB2 is essential for G protein activation. Positive allosteric modulators enhance the potency and efficacy of agonists at GABA(B) receptors and are of particular interest because they lack the sedative and muscle relaxant properties of agonists. In this study, we aimed to characterize the interaction of the positive modulator N,N'-dicyclopentyl-2-methylsulfanyl-5-nitro-pyrimidine-4,6-diamine (GS39783) with the GABA(B) receptor heterodimer. Using functional guanosine 5'-O-(3-[(35)S]thio)triphosphate binding assays, we observed positive modulation by GS39783 in different vertebrate species but not in Drosophila melanogaster. However, coexpression of D. melanogaster GB1 with rat GB2 yielded functional receptors positively modulated by GS39783. Together with data from rat/D. melanogaster GB2 subunit chimeras, this pointed to a critical role of the GB2 transmembrane region for positive modulation. We further characterized GS39783 function using point mutations. GS39783 positively modulated GABA responses but also showed considerable agonistic activity at heterodimers containing a mutant rat GB2 subunit with three amino acid substitutions in transmembrane domain VI. It was surprising that in contrast to wild-type rat GB2, this mutant subunit was also activated by GS39783 when expressed without GB1. The mutations of both G706T and A708P are necessary and sufficient for activation and identify a key region for the effect of GS39783 in the GB2 transmembrane region. Our data show that mutations of specific amino acids in GB2 can induce agonism in addition to positive modulation and facilitate GB2 activation in the absence of GB1.

Amino Acid Sequence↗
PubMed1999

Function of WW domains as phosphoserine- or phosphothreonine-binding modules.

Protein-interacting modules help determine the specificity of signal transduction events, and protein phosphorylation can modulate the assembly of such modules into specific signaling complexes. Although phosphotyrosine-binding modules have been well-characterized, phosphoserine- or phosphothreonine-binding modules have not been described. WW domains are small protein modules found in various proteins that participate in cell signaling or regulation. WW domains of the essential mitotic prolyl isomerase Pin1 and the ubiquitin ligase Nedd4 bound to phosphoproteins, including physiological substrates of enzymes, in a phosphorylation-dependent manner. The Pin1 WW domain functioned as a phosphoserine- or phosphothreonine-binding module, with properties similar to those of SRC homology 2 domains. Phosphoserine- or phosphothreonine-binding activity was required for Pin1 to interact with its substrates in vitro and to perform its essential function in vivo.

Amino Acid Sequence↗
PubMed2005

Cloning, sequencing, and expression of a Eubacterium cellulosolvens 5 gene encoding an endoglucanase (Cel5A) with novel carbohydrate-binding modules, and properties of Cel5A.

A novel Eubacterium cellulosolvens 5 gene encoding an endoglucanase (Cel5A) was cloned and expressed in Escherichia coli, and its enzymatic properties were characterized. The cel5A gene consists of a 3,444-bp open reading frame and encodes a 1,148-amino-acid protein with a molecular mass of 127,047 Da. Cel5A is a modular enzyme consisting of an N-terminal signal peptide, two glycosyl hydrolase family 5 catalytic modules, two novel carbohydrate-binding modules (CBMs), two linker sequences, and a C-terminal sequence with an unknown function. The amino acid sequences of the two catalytic modules and the two CBMs are 94% and 73% identical to each other, respectively. Two regions that consisted of one CBM and one catalytic module were tandemly connected via a linker sequence. The CBMs did not exhibit significant sequence similarity with any other CBMs. Analyses of the hydrolytic activity of the recombinant Cel5A (rCel5A) comprising the CBMs and the catalytic modules showed that the enzyme is an endoglucanase with activities with carboxymethyl cellulose, lichenan, acid-swollen cellulose, and oat spelt xylan. To investigate the functions of the CBMs and the catalytic modules, truncated derivatives of rCel5A were constructed and characterized. There were no differences in the hydrolytic activities with various polysaccharides or in the hydrolytic products obtained from cellooligosaccharides between the two catalytic modules. Both CBMs had the same substrate affinity with intact rCel5A. Removal of the CBMs from rCel5A reduced the catalytic activities with various polysaccharides remarkably. These observations show that CBMs play an important role in the catalytic function of the enzyme.

Amino Acid Sequence↗
PubMed1995

Phorbol ester-induced down modulation of tailless CD4 receptors requires prior binding of gp120 and suggests a role for accessory molecules.

The entry of human immunodeficiency virus type 1 into cells proceeds via a fusion mechanism that is initiated by binding of the viral glycoprotein gp120-gp41 to its cellular receptor CD4. Species- and tissue-specific restrictions to viral entry suggested the participation of additional membrane components in the postbinding fusion events. In a previous study (H. Golding, J. Manischewitz, L. Vujcic, R. Blumenthal, and D. Dimitrov, J. Virol. 68:1962-1968, 1994), it was found that phorbol myristate acetate (PMA) inhibits human immunodeficiency virus type 1 envelope-mediated cell fusion by inducing down modulation of an accessory component(s) in the CD4-expressing cells. The fusion inhibition was seen in a variety of cells, including T-cell transfectants expressing engineered CD4 receptors (CD4.401 and CD4.CD8) which are not susceptible to down modulation by PMA treatment. In the current study, it was found that preincubation of A2.01.CD4.401 cells with soluble monomeric gp120 for 1 h at 37 degrees C primed them for PMA-induced down modulation (up to 70%) of the tailless CD4 receptors. The gp120-priming effect was temperature dependent, and the down modulation may have occurred via clathrin-coated pits. Importantly, nonhuman cell lines expressing tailless CD4 molecules did not down modulate their CD4 receptors under the same conditions. The gp120-dependent PMA-induced down modulation of tailless CD4 receptors could be efficiently blocked by the human monoclonal antibodies 48D and 17B, which bind with increased avidity to gp120 that was previously bound to CD4 (M. Thali, J. P. Moore, C. Furman, M. Charles, D. D. Ho, J. Robinson, and J. Sodroski, J. Virol. 67:3978-3988, 1993). These findings suggest that gp120 binding to cellular CD4 receptors induces conformational changes leading to association of the gp120-CD4 complexes with accessory transmembrane molecules that are susceptible to PMA-induced down modulation and can target the virions to clathrin-coated pits.

Animals↗
PubMed2004

The spacing between cysteines two and three of the LDL-A module of Tva is important for subgroup A avian sarcoma and leukosis virus entry.

Rong et al. have demonstrated previously that with a few substitutions, the fourth repeat of human low-density lipoprotein (hLDL-A4) receptor can functionally replace the LDL-A module of Tva, the cellular receptor for subgroup A avian sarcoma and leukosis virus (ASLV-A), in viral entry (L. Rong, K. Gendron, and P. Bates, Proc. Natl. Acad. Sci. USA 95:8467-8472, 1998). Here we have shown that swapping the amino terminus of hLDL repeat 5 (hLDL-A5) with that of Tva, in addition to the corresponding substitutions made in human LDL-A4, was required to convert hLDL-A5 into an efficient ASLV-A receptor. These results substantiated our previous findings regarding the role of the specific residues in the viral interaction domain of Tva and demonstrated the critical role of the amino terminus of the Tva LDL-A module in ASLV-A infection. Furthermore, we have shown that the residues between cysteines 2 and 3 of the Tva LDL-A module in a Tva/LDL-A5 chimeric protein can be functionally replaced by the corresponding region of another LDL-A module, human LDL receptor-related protein repeat 22 (LDL-A22), to mediate efficient ASLV-A entry. Since the only conserved feature between the C2-C3 region of LDL-A22 and the Tva LDL-A module is that both contain nine amino acids of which none are conserved, we conclude that the spacing between C2 and C3 of the LDL-A module of Tva is an important determinant for ASLV-A entry. Thus, the present study provides strong evidence to support our hypothesis that one role of the N terminus of the LDL-A module of Tva is to allow proper folding and conformation of the protein for optimal interaction with the viral glycoprotein EnvA in ASLV-A entry.

Amino Acid Sequence↗
PubMed1994

Modulation of ion channels by protein phosphorylation and dephosphorylation.

Modulation of the properties of membrane ion channels is of fundamental importance for the regulation of neuronal electrical activity and of higher neural functions. Among the many potential molecular mechanisms for modulating the activity of membrane proteins such as ion channels, protein phosphorylation has been chosen by cells to play a particularly prominent part. This is not surprising given the central role of protein phosphorylation in a wide variety of cellular, metabolic, and signaling processes (26, 27, 48). As summarized here, regulation by phosphorylation is not restricted to one or another class of ion channel; rather, many, and perhaps all, ion channels are subject to modulation by phosphorylation. Similarly, a number of different protein kinase signaling pathways can participate in the regulation of ion channel properties, and it is not unusual to find that a particular channel is modulated by several different protein kinases, each influencing channel activity in a unique way. Finally, the biophysical mechanisms of modulation also exhibit a striking diversity that ranges from changes in desensitization rates to shifts in the voltage dependence and kinetics of channel activation and inactivation. The convergence of channel molecular biology with patch-clamp technology has been spectacularly productive, even allowing the identification of particular amino acid residues in ion channel proteins that participate in specific modulatory changes in channel biophysical properties. This task is far from complete, and no doubt there remain surprises in store for us, but nevertheless it is appropriate to ask where we go from here. One important direction will be to relate functional modulation, produced by phosphorylation, to changes in the three-dimensional structure of the ion channel protein. Unfortunately, structural studies of membrane proteins are extremely difficult, and to date there is no high resolution structure available for any ion channel protein. A complementary strategy that is more feasible with current technology is to investigate the ways in which channel modulation contributes to the regulation of cellular physiology. Novel computational approaches are being brought to bear on this complex issue, and their combination with channel molecular biology and biophysics should significantly advance our understanding of molecular mechanisms of neuronal plasticity.

Animals↗
PubMed1995

The radiographic signs of arthritis: a computer teaching module.

This article describes the steps involved in production of a computer teaching module on the radiographic diagnosis of arthritis. The module was part of a research project aimed at producing seven computer teaching modules. Several staff radiologists and residents were involved, as well as a consultant on medical education. A generic shell program was used as a frame for all seven modules. The author of each module then filled in the empty pages of the shell with the appropriate text and images, along with additional short program scripts. The module on the radiographic diagnosis of arthritis described and illustrated the basic radiographic signs of arthritis. Practice cases were also included, and interactive and hypermedia features were implemented. The modules were then evaluated by means of task list tests and interviews. The experience was judged to have been successful, although the amount of time spent by some authors was much more than expected.

Arthritis↗
PubMed2004

Comparison of Z-axis automatic tube current modulation technique with fixed tube current CT scanning of abdomen and pelvis.

PURPOSE: To compare image quality, diagnostic acceptability, and radiation exposure associated with 16-section multi-detector row computed tomographic (CT) examinations of abdomen and pelvis performed with z-axis modulation technique of automatic tube current modulation and with manual selection of fixed tube current. MATERIALS AND METHODS: Sixty-two consecutive subjects (mean age, 60 years; age range, 19-84 years; male-to-female ratio, 35:27) underwent follow-up CT of abdomen and pelvis with use of a 16-section multi-detector row scanner and z-axis modulation technique (10.5-12.0-HU noise index, 10-380 mA). Scanning parameters included 140 kVp, 0.5-1.0-second gantry rotation time, 0.938:1 beam pitch, and 5-mm reconstructed section thickness. For each subject, images obtained with z-axis modulation were compared with previous images obtained with fixed tube current (200-300 mA) and with other parameters identical. Images were compared for noise and diagnostic acceptability by two subspecialty radiologists using a five-point scale (1, unacceptable; 3, acceptable; 5, excellent) at five levels: upper liver at diaphragm, porta hepatis, right kidney hilum, iliac crest, and upper margin of acetabulum. Tube current and gantry rotation time used for acquisitions at these levels were recorded. Data were analyzed with parametric and nonparametric statistical tests. RESULTS: Although no significant differences were found (P =.34), images acquired with z-axis modulation at the levels of the upper liver (diaphragm) and acetabulum had a higher noise and lower diagnostic quality, compared with images acquired with fixed tube current. Compared with fixed tube current, z-axis modulation resulted in tube current-time product reduction in 54 (87%) of 62 examinations (mean reduction, 71.2 mAs) and increase in eight (13%) (mean increase, 17.0 mAs). CONCLUSION: Compared with manually selected fixed tube current, z-axis automatic tube current modulation resulted in reduced tube current-time product and similar image noise and diagnostic acceptability at CT of abdomen and pelvis.

Abdominal Neoplasms↗
PubMed2005

Detection of urinary tract stones at low-radiation-dose CT with z-axis automatic tube current modulation: phantom and clinical studies.

PURPOSE: To evaluate depiction of urinary tract calculi at computed tomography (CT) with a z-axis modulation technique at various noise indexes to reduce radiation dose and preserve image quality. MATERIALS AND METHODS: Sixteen radiopaque kidney stones (2.5-19.2 mm in diameter) were embedded in the collecting systems of two bovine kidneys immersed in a water bath. A kidney phantom was made by placing the kidneys in an elliptical Plexiglas phantom (32 x 20 x 20 cm) filled with physiologic saline. The phantom was scanned at 16-detector row CT with a fixed tube current (300 mA) and z-axis modulation at noise indexes of 14, 20, 25, 35, and 50; remaining imaging parameters were held constant. Two abdominal radiologists reviewed images from most to least noisy. Images were evaluated for presence of stones and size, site, and attenuation value of each stone. Readers also graded conspicuity and margins of each stone on a five-point scale. In addition, follow-up studies of 22 patients (mean age, 46 years; range, 26-57 years; male-female ratio, 14:8) with kidney and ureteral stones who underwent CT with z-axis modulation (noise index, 14 and 20) were evaluated in the same manner. Statistical analysis was performed with the Student t test, Wilcoxon signed rank test, and kappa test of interobserver agreement. Institutional review board approval was obtained, and informed consent was not needed. RESULTS: In the phantom study, all 16 stones were identified on images obtained with a fixed tube current and z-axis modulation at noise indexes of 14, 20, and 25 (with a reduction in radiation dose of up to 77% compared with that of fixed tube current scanning). Three stones (<5 mm) were not visualized with z-axis modulation at noise indexes of 35 and 50. No significant difference was shown for conspicuity of kidney stones in 22 patients who underwent CT with z-axis modulation (with a 43%-66% reduction in radiation dose) when compared with results of previous fixed tube current studies (P > .05). CONCLUSION: Kidney stones (< or =2.5 mm) can be adequately depicted with the z-axis modulation technique, with a 56%-77% reduction in radiation dose. In patients with urinary tract stones, the technique results in a 43%-66% reduction in radiation dose at noise indexes of 14 and 20 without compromising stone depiction.

Adult↗
PubMed2004

Functional proteomic analysis of a three-tier PKCepsilon-Akt-eNOS signaling module in cardiac protection.

Cardiac protective signaling networks have been shown to involve PKCepsilon. However, the molecular mechanisms by which PKCepsilon interacts with other members of these networks to form task-specific modules remain unknown. Among 93 different PKCepsilon-associated proteins that have been identified, Akt and endothelial nitric oxide (NO) synthase (eNOS) are of importance because of their independent abilities to promote cell survival and prevent cell death. The simultaneous association of PKCepsilon, Akt, and eNOS has not been examined, and, in particular, the formation of a module containing these three proteins and the role of such a module in the regulation of NO production and cardiac protection are unknown. The present study was undertaken to determine whether these molecules form a signaling module and, thereby, play a collective role in cardiac signaling. Using recombinant proteins in vitro and PKCepsilon transgenic mouse hearts, we demonstrate the following: 1) PKCepsilon, Akt, and eNOS interact and form signaling modules in vitro and in the mouse heart. Activation of either PKCepsilon or Akt enhances the formation of PKCepsilon-Akt-eNOS signaling modules. 2) PKCepsilon directly phosphorylates and enhances activation of Akt in vitro, and PKCepsilon activation increases phosphorylation and activation of Akt in PKCepsilon transgenic mouse hearts. 3) PKCepsilon directly phosphorylates eNOS in vitro, and this phosphorylation enhances eNOS activity. Activation of PKCepsilon in vivo increased phosphorylation of eNOS at Ser(1177), indicating eNOS activation. This study characterizes, for the first time, the physical, as well as functional, coupling of PKCepsilon, Akt, and eNOS in the heart and implicates these PKCepsilon-Akt-eNOS signaling modules as critical signaling elements during PKCepsilon-induced cardiac protection.

Animals↗
PubMed1989

Central respiratory modulation of medullary sympathoexcitatory neurons in rat.

The central respiratory generator exerts a modulatory influence on sympathetic nerve discharge. In cats the sympathoexcitatory neurons of the rostroventrolateral medulla (RVL) exhibit central respiratory modulation as well. Because RVL sympathoexcitatory neurons are largely responsible for the maintenance of sympathetic vasomotor tone, it is likely that the modulation of these neurons accounts for the central respiratory modulation of sympathetic discharge. In the present study experiments were performed to characterize the pattern of respiratory modulation of lumbar sympathetic nerve discharge (LSND) in the halothane-anesthetized rat. Phrenic-triggered averaging of LSND exhibited a small depression coincident with the onset of the phrenic burst followed by a large peak that was coincident with the cessation of the phrenic burst. Phrenic-triggered histograms of the activity of RVL sympathoexcitatory neurons exhibited three patterns of central respiratory modulation: inspiratory depression (I), inspiratory peak (II), and early inspiratory depression followed by a postinspiratory peak (III), a pattern that was very similar to that seen in LSND. Both nerve recording and single-unit recording experiments were performed in vagotomized rats with or without intact barosensory afferents. A comparison of the results suggested that, in the rat, the baroreflex does not modify or contribute to the central respiratory modulation of sympathetic output. Finally, a comparison was made between presumed nonadrenergic pacemaker-like neurons and putative C1 adrenergic neurons in the RVL. No differences were found in the patterns of central respiratory modulation.

Anesthesia, General↗