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[The diagnosis and imaging of the a. hepatica after orthoptic liver transplantation--a comparison of frequency-modulated and amplitude-modulated color Doppler sonography].

PURPOSE: We examined whether amplitude-modulated color Doppler (power Doppler) sonography provides a better anatomic imaging of the vascular course of the hepatic artery after liver transplantation. PATIENTS AND METHODS: 82 patients were examined with Doppler sonography after liver transplantation. The distal section of the hepatic artery was imaged both with frequency-modulated color Doppler (color Doppler) and power Doppler and a Doppler spectrum derived from each mode for determination of the flow velocity. RESULTS: Native imaging of the hepatic artery was possible in 78/82 patients, in 2/82 patients only after administration of Levovist, and in 2/82 patients it could not be seen. In these two patients the diagnosis of hepatic artery occlusion was confirmed by angiography. The anatomic course was demonstrated more longitudinally by power Doppler than by color Doppler (p < 0.001; chi 2 test) which made the angle correction easier. A disadvantage of power Doppler was the lack of image contrast to the portal veins; thus evaluation of the vascular course in this section was better possible with color Doppler by means of a specifically generated aliasing in the flow of the hepatic artery (p < 0.001; chi 2 test). Determination of the flow velocity showed no significant differences between color and power Doppler supported duplex sonography. CONCLUSIONS: The combined use of color Doppler and power Doppler improves visualization of the hepatic artery after liver transplantation. The lack of visualization of the vessel after administration of Levovist is diagnostic for occlusion of the vessel.

Adult↗

Simultaneous in situ monitoring of surface and gas species and surface properties by modulation excitation polarization-modulation infrared reflection-absorption spectroscopy: CO oxidation over Pt film.

A method for in situ monitoring of surface and gas species utilizing separately the difference and sum reflectivity of two polarizations, normal and parallel to the surface, measured by polarization-modulation infrared reflection-absorption spectroscopy is presented. Surface and gas-phase spectra were separately but simultaneously obtained from the reflectivities. The technique is combined with modulation excitation spectroscopy to further enhance the sensitivity, and a small-volume cell was designed for this purpose. CO oxidation over a 40 nm Pt film on aluminum was investigated under moderate pressure (atmospheric pressure, 5% CO, and 5%-40% O2) at 373-433 K. The surface species involved in the oxidation process and the gas-phase species, both reactant (CO) and product (CO2), could be simultaneously monitored and analyzed quantitatively. In addition, the reflectivity change of the sample during the reaction was assigned to a near-surface bulk property change, that is, surface reconstruction to the oxide phase. Under an O2-rich atmosphere, two reactive phases, denoted as low- and high-activity phases, were identified. A large amount of atop CO was observed during the low-activity phase, while the adsorbed CO completely disappeared during the high-activity phase. The presence of an infrared-inactive CO2 precursor formed by the reaction between surface oxide and gaseous CO during the high-activity phase was inferred. The desorption of the CO2 precursor is facilitated under a CO-rich atmosphere, most likely, by surface reconstruction to metallic Pt and a competitive adsorption of CO on the surface.

Absorption↗

A hydrophobic domain of Ca2+-modulating cyclophilin ligand modulates calcium influx signaling in T lymphocytes.

Ca2+-modulating cyclophilin ligand (CAML) was originally described as a cyclophilin B-binding protein whose overexpression in T cells causes a rise in intracellular calcium, thus activating transcription factors responsible for the early immune response. As reported here, structure-function analysis of the CAML gene in Jurkat T cells indicates that two of CAML's putative membrane-spanning domains are necessary and sufficient for the modulation of intracellular calcium. We propose that the hydrophobic C-terminal tail of CAML forms its effector domain, thus implicating the N-terminal hydrophilic domain in a regulatory role. These findings define a novel protein motif that functions in intracellular calcium signaling.

Adaptor Proteins, Signal Transducing↗

High-performance photoelastic modulator for polarization modulation spectrometer.

A high-performance photoelastic modulator (PEM) has been built. It consists of a home-made PEM head and a home-built PEM driver that is based on the principle of the phase-locked loop (PLL) (PLL PEM driver). It was installed in our new type circular dichroism (CD) spectrometer for visible light region and its performance was evaluated. With the phase angle being set exactly to zero, the PEM is found to be about eight times more efficient than commercially available one. The efficiency of PEM depends not only on the efficiency of PEM driver but also on the quality of PEM head. The latter can be estimated from admittance-parameter measurements without installing it into a spectrometer. With substituting the PLL PEM driver for a conventional one, the PEM drive voltage can be reduced from one-half to one-third and the baseline shift for air blank that is a measure of the total performance of polarization modulation spectrometers becomes quite small.

Journal Article↗

A comparative dosimetric study on tangential photon beams, intensity-modulated radiation therapy (IMRT) and modulated electron radiotherapy (MERT) for breast cancer treatment.

Recently, energy- and intensity-modulated electron radiotherapy (MERT) has garnered a growing interest for the treatment of superficial targets. In this work. we carried out a comparative dosimetry study to evaluate MERT, photon beam intensity-modulated radiation therapy (IMRT) and conventional tangential photon beams for the treatment of breast cancer. A Monte Carlo based treatment planning system has been investigated, which consists of a set of software tools to perform accurate dose calculation, treatment optimization, leaf sequencing and plan analysis. We have compared breast treatment plans generated using this home-grown treatment optimization and dose calculation software forthese treatment techniques. The MERT plans were planned with up to two gantry angles and four nominal energies (6, 9, 12 and 16 MeV). The tangential photon treatment plans were planned with 6 MV wedged photon beams. The IMRT plans were planned using both multiple-gantry 6 MV photon beams or two 6 MV tangential beams. Our results show that tangential IMRT can reduce the dose to the lung, heart and contralateral breast compared to conventional tangential wedged beams (up to 50% reduction in high dose volume or 5 Gy in the maximum dose). MERT can reduce the maximum dose to the lung by up to 20 Gy and to the heart by up to 35 Gy compared to conventional tangential wedged beams. Multiple beam angle IMRT can significantly reduce the maximum dose to the lung and heart (up to 20 Gy) but it induces low and medium doses to a large volume of normal tissues including lung, heart and contralateral breast. It is concluded that MERT has superior capabilities to achieve dose conformity both laterally and in the depth direction, which will be well suited for treating superficial targets such as breast cancer.

Breast Neoplasms↗

Acute effects of levodopa on wrist movement in Parkinson's disease. Kinematics, volitional EMG modulation and reflex amplitude modulation.

Acute changes in motor performance due to levodopa were evaluated by a series of four motor tests unified by their focus on wrist flexion-extension movements. Subjects with idiopathic Parkinson's disease were evaluated with this battery of tests before (OFF) and after their usual morning dose of levodopa (ON). The test battery consisted of (i) repetitive self-paced movement in which velocity was to be maximized; (ii) visually guided tracking of a sinusoid and a square wave; and (iii) an assay of stretch reflex modulation during volitional sinusoidal tracking. The maximal wrist joint velocity of self-paced reciprocating flexion and extension movements increased after levodopa (ON), without significant changes in the movement period or amplitude. In the two tracking tasks, some subjects improved as evident by a lower root mean square (rms) error, but in similar numbers of subjects the rms error increased. Overall, the rms error, peak velocity or peak movement amplitude did not change after levodopa in either tracking task. Significant and consistent changes did occur after levodopa in an assay of reflex modulation during error-constrained tracking (Johnson et al., Brain 1991; 114: 443-60). The amplitude of volitional EMG increased after levodopa, with a concurrent reduction in reflex EMG. These changes are consistent with the noted increase in movement velocity. These results show that the effects of levodopa on movement velocity were not consistently translated into increased accuracy. The changes in the long latency reflex gain argue for a central control of this reflex, mediated by structures sensitive to levodopa. Finally, the results show that the quantitative evaluation of levodopa therapy cannot be unidimensional, but requires a battery of motor tests as undertaken in this study.

Aged↗

Progesterone receptor modulator CDB-2914 down-regulates vascular endothelial growth factor, adrenomedullin and their receptors and modulates progesterone receptor content in cultured human uterine leiomyoma cells.

BACKGROUND: This study was conducted to evaluate the effects of graded concentrations (10(-8), 10(-7) and 10(-6) M) of progesterone receptor (PR) modulator CDB-2914 on the protein contents of PR, of vascular endothelial growth factor (VEGF), adrenomedullin (ADM) and their receptors in cultured human uterine leiomyoma and matching myometrial cells. METHODS: PR-A, PR-B, VEGF-A, VEGF-B, VEGF receptor (VEGFR)-1, VEGFR-2, ADM and ADM receptor (ADMR) contents were assessed by Western blot analysis. RESULTS: Treatment with 100 ng/ml progesterone increased VEGF-A, VEGF-B and ADM contents in cultured leiomyoma cells and normal myometrial cells. The concomitant treatment with 10(-6) M CDB-2914 significantly decreased the progesterone-induced VEGF-A, VEGF-B and ADM contents in cultured leiomyoma cells but not in normal myometrial cells. CDB-2914 treatment alone decreased VEGFR-1, VEGFR-2 and ADMR contents in cultured leiomyoma cells but not in normal myometrial cells. CDB-2914 treatment increased PR-A and decreased PR-B contents in cultured leiomyoma cells in a dose-dependent manner compared with untreated cultures, whereas no significant changes in PR isoform contents were observed in normal myometrial cells. CONCLUSIONS: These results suggest that CDB-2914 down-regulates VEGF, ADM and their receptor contents and modulates PR isoform contents in cultured leiomyoma cells in a cell-type-specific manner.

Adrenomedullin↗

Light modulation of enzyme activity: activation of the light effect mediators by reduction and modulation of enzyme activity by thiol-disulfide exchange.

Light and dark modulation experiments with pea (Pisum sativum L.) chloroplast stromal fractions pretreated with dithiothreitol (to reduce protein disulfide bonds) or with 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) (to block sulfhydryl groups) suggest that light modulation involves thiol-disulfide exchange on the modulatable stromal enzyme protein. Light-dependent reduction of DTNB involves a photosynthetic electron transport chain component located on the reducing side of photosystem I prior to ferredoxin; DTNB may be acting as a light effect mediator substitute. The thylakoid-bound light effect mediator system, then, in its light-activated reduced form probably catalyzes thiol-disulfide exchange reactions on stromal enzymes.

Journal Article↗

The expression of CR1 and CR3 on non-modulated and modulated granulocytes of healthy blood donors as measured by flow cytofluorometry.

Complement receptors, CR1 and CR3, on neutrophils increase their cellular spontaneously at 37 degrees C or after mechanical stress during the cell preparation. We have established a cell preparation procedure and a cytofluorometric immunoassay method to evaluate the receptor expression in vivo in this study. The expression of CR1 and CR3 was studied after haemolysis in NH4Cl at different temperatures and incubation intervals. It was shown that cell preparation and receptor analysis must be performed at 15 degrees C or lower to avoid up-regulation of the receptor structures. Two minutes' incubation at 20 degrees C was sufficient to modulate the cells in this regard. Granulocytes from healthy blood donors were analysed and the mean fluorescence intensity (MFI), which reflects the number of receptors on the cell surface, showed a normal distribution for the CR1 (n = 158) and CR3 (n = 76) expression in the healthy population. The MFI of the two receptors showed a correlation (r = 0.71). Granulocytes from all donors could be modulated at 37 degrees C to a similar degree for both receptors (r = 0.76), despite the fact that they are supposed to be mobilized from different intracellular pools. A group of patients with localized inflammatory processes, such as sinusitis, differed from the healthy controls. In this group, the CR1 expression was not normally distributed, but 15 out of 26 patients (58%) had granulocytes with a CR1 expression exceeding the mean +/- SD of the normal population.

Adolescent↗

Purinoceptor modulation of noradrenaline release in rat tail artery: tonic modulation mediated by inhibitory P2Y- and facilitatory A2A-purinoceptors.

1. The effects of analogues of adenosine and ATP on noradrenaline release elicited by electrical stimulation (5 Hz, 2700 pulses) were studied in superfused preparations of rat tail artery. The effects of purinoceptor antagonists, of adenosine deaminase and of adenosine uptake blockade were also examined. Noradrenaline was measured by h.p.l.c. electrochemical detection. 2. The A1-adenosine receptor agonist, N6-cyclopentyladenosine (CPA; 0.1-100 nM) reduced, whereas the A2A-receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680; 3-30 nM) increased evoked noradrenaline overflow. These effects were antagonized by the A1-adenosine receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 20 nM) and the A2-adenosine receptor antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX; 100 nM), respectively. The P2Y-purinoceptor agonist, 2-methylthio-ATP (1-100 microM) reduced noradrenaline overflow, an effect prevented by the P2-purinoceptor antagonist, cibacron blue 3GA (100 microM) and suramin (100 microM). 3. Adenosine deaminase (2 u ml-1), DMPX (100 nM) and inhibition of adenosine uptake with S-(p-nitrobenzyl)-6-thioinosine (NBTI; 50 nM) decreased evoked noradrenaline overflow. DPCPX alone did not change noradrenaline overflow but prevented the inhibition caused by NBTI. The P2Y-purinoceptor antagonist, cibacron blue 3GA (100 microM) increased evoked noradrenaline overflow as did suramin, a non-selective P2-antagonist. 4. It is concluded that, in rat tail artery, inhibitory (A1 and P2Y) and facilitatory (A2A) purinoceptors are present and modulate noradrenaline release evoked by electrical stimulation. Endogenous purines tonically modulate noradrenaline release through activation of inhibitory P2Y and facilitatory A2A purinoceptors, whereas a tonic activation of inhibitory A1 purinoceptors seems to be prevented by adenosine uptake.

Adenosine↗

Lipase and its modulator from Pseudomonas sp. strain KFCC 10818: proline-to-glutamine substitution at position 112 induces formation of enzymatically active lipase in the absence of the modulator.

A lipase gene, lipK, and a lipase modulator gene, limK, of Pseudomonas sp. strain KFCC 10818 have been cloned, sequenced, and expressed in Escherichia coli. The limK gene is located immediately downstream of the lipK gene. Enzymatically active lipase was produced only in the presence of the limK gene. The effect of the lipase modulator LimK on the expression of active lipase was similar to those of the Pseudomonas subfamily I.1 and I.2 lipase-specific foldases (Lifs). The deduced amino acid sequence of LimK shares low homology (17 to 19%) with the known Pseudomonas Lifs, suggesting that Pseudomonas sp. strain KFCC 10818 is only distantly related to the subfamily I.1 and I.2 Pseudomonas species. Surprisingly, a lipase variant that does not require LimK for its correct folding was isolated in the study to investigate the functional interaction between LipK and LimK. When expressed in the absence of LimK, the P112Q variant of LipK formed an active enzyme and displayed 63% of the activity of wild-type LipK expressed in the presence of LimK. These results suggest that the Pro(112) residue of LipK is involved in a key step of lipase folding. We expect that the novel finding of this study may contribute to future research on efficient expression or refolding of industrially important lipases and on the mechanism of lipase folding.

Bacterial Proteins↗

Modulation of mRNA stability participates in stationary-phase-specific expression of ribosome modulation factor.

The expression of ribosome modulation factor (RMF) is induced during stationary phase in Escherichia coli. RMF participates in the dimerization of 70S ribosomes to form the 100S ribosome, which is the translationally inactive form of the ribosome. To elucidate the involvement of the control of mRNA stability in growth-phase-specific rmf expression, we investigated rmf mRNA stability in stationary-phase cells and cells inoculated into fresh medium. The rmf mRNA was found to have an extremely long half-life during stationary phase, whereas destabilization of this mRNA took place after the culture was inoculated into fresh medium. RMF and 100S ribosomes disappeared from cells 1 min after inoculation. In addition to control by ppGpp-dependent transcription, these results indicate that the modulation of rmf mRNA stability is also involved in the regulation of growth-phase-specific rmf expression. Unexpectedly, the postinoculation degradation of rmf mRNA was suppressed by the addition of rifampin, suggesting that de novo RNA synthesis is necessary for degradation. This degradation was also suppressed in both a poly(A) polymerase-deficient and an rne-131 mutant strain. We cloned and sequenced the 3'-proximal regions of rmf mRNAs and found that most of these 3' ends terminated at the rho-independent terminator with the addition of a one- to five-A oligo(A) tail in either stationary-phase or inoculated cells. No difference was observed in the length of the poly(A) tail between stationary-phase and inoculated cells. These results suggest that a certain postinoculation-specific regulatory factor participates in the destabilization of rmf mRNA and is dependent on polyadenylation.

Culture Media↗

Kaposi's sarcoma-associated herpesvirus mitochondrial K7 protein targets a cellular calcium-modulating cyclophilin ligand to modulate intracellular calcium concentration and inhibit apoptosis.

On viral infection, infected cells can become the target of host immune responses or can go through a programmed cell death process, called apoptosis, as a defense mechanism to limit the ability of the virus to replicate. To prevent this, viruses have evolved elaborate mechanisms to subvert the apoptotic process. Here, we report the identification of a novel antiapoptotic K7 protein of Kaposi's sarcoma-associated herpesvirus (KSHV) which expresses during lytic replication. The KSHV K7 gene encodes a small mitochondrial membrane protein, and its expression efficiently inhibits apoptosis induced by a variety of apoptogenic agents. The yeast two-hybrid screen has demonstrated that K7 targets cellular calcium-modulating cyclophilin ligand (CAML), a protein that regulates the intracellular Ca(2+) concentration. Similar to CAML, K7 expression significantly enhances the kinetics and amplitudes of the increase in intracellular Ca(2+) concentration on apoptotic stimulus. Mutational analysis showed that K7 interaction with CAML is required for its function in the inhibition of apoptosis. This indicates that K7 targets cellular CAML to increase the cytosolic Ca(2+) response, which consequently protects cells from mitochondrial damage and apoptosis. This is a novel viral antiapoptosis strategy where the KSHV mitochondrial K7 protein targets a cellular Ca(2+)-modulating protein to confer resistance to apoptosis, which allows completion of the viral lytic replication and, eventually, maintenance of persistent infection in infected host.

Adaptor Proteins, Signal Transducing↗

Opioid modulation of calcium current in cultured sensory neurons: mu-modulation of baroreceptor input.

We used the whole cell open-patch or perforated-patch technique to characterize mu-opioid modulation of Ca(2+) current (I(Ca)) in nodose sensory neurons and in a specific subpopulation of nodose cells, aortic baroreceptor neurons. The mu-opiate receptor agonist Tyr-D-Ala-Gly-MePhe-Gly-ol enkephalin (DAGO) inhibited I(Ca) in 95% of neonatal [postnatal day (P)1-P3] nodose neurons. To the contrary, only 64% of juvenile cells (P20-P35) and 61% of adult cells (P60-P110) responded to DAGO. DAGO-mediated inhibition of I(Ca) was naloxone sensitive, irreversible in the presence of guanosine 5'-O-(3-thiotriphosphate), absent with guanosine 5'-O-(2-thiodiphosphate), and eliminated with pertussis toxin; DAGO's inhibition of I(Ca) was G protein mediated. Incubation of neurons with omega-conotoxin GVIA eliminated the effect of DAGO in neonatal but not in juvenile cells. In the latter, DAGO reduced 37% of the current remaining in the presence of omega-conotoxin. In the subset of nodose neurons, aortic baroafferents, the effect of DAGO was concentration dependent, with an IC(50) of 1.82 x 10(-8) M. DAGO slowed activation of I(Ca), but activation curves constructed from tail currents were the same with and without DAGO (100 nM). In summary, mu-opiate modulation of I(Ca) in nodose neurons was demonstrated in three age groups, including specifically labeled baroafferents. The demonstration of a mechanism of action of mu-opioids on baroreceptor afferents provides a basis for the attenuation of the baroreflex that occurs at the level of the nucleus tractus solitarii.

Aging↗

Effect of family 22 carbohydrate-binding module on the thermostability of Xyn10B catalytic module from Clostridium stercorarium.

A family 22 carbohydrate-binding module (CBM22) from Clostridium stercorarium Xylanase10B raised the optimum temperature of the xylanase, but in the remaining activity of heating test, apparently the catalytic module alone showed higher remaining activity. Differential scanning calorimetry showed that CBM22 conferred resistance to thermal unfolding of the enzyme and prevented the enzyme from refolding after thermal unfolding.

Base Sequence↗

Nicotinic receptors modulate transmitter cross talk in the CNS: nicotinic modulation of transmitters.

Neuronal nicotinic acetylcholine receptors (nAChRs) in the CNS appear to exert a predominantly modulatory influence on brain mechanisms, despite being fast-acting ligand-gated ion channels. Many nAChRs have an extrasynaptic location on somatodendritic regions or presynaptic terminals. They influence local excitability by depolarization and can initiate short- and long-term changes by interfacing with Ca2+ signaling pathways (Dajas- Bailador and Wonnacott, 2004). The modulation of neurotransmitter release by presynaptic nAChRs is well-documented (Wonnacott, 1997): Both Na+ and Ca2+ fluxes associated with nAChR activation can influence transmitter release. It is also emerging that nAChRs, especially the alpha7 subtype, can exert an indirect effect on transmitter release, through modulation of amino acid transmitters. This complex scenario facilitates transmitter cross talk, which is the subject of this short review.

Animals↗

New developments on thromboxane and prostacyclin modulators part I: thromboxane modulators.

The pathogenesis of numerous cardiovascular, pulmonary, inflammatory, and thromboembolic diseases can be related to arachidonic acid (AA) metabolites. One of these bioactive metabolites of particular importance is thromboxane A(2) (TXA(2)). It is produced by the action of thromboxane synthase on the prostaglandin endoperoxide H(2)(PGH(2)), which results from the enzymatic degradation of AA by the cyclooxygenases. TXA(2) is a potent inducer of platelet aggregation, vasoconstriction and bronchoconstriction. It is involved in a series of major pathophysiological states such as asthma, myocardial ischemia, pulmonary hypertension, and thromboembolic disorders. Therefore, TXA(2) receptor antagonists, thromboxane synthase inhibitors and drugs combining both properties have been developed by several pharmaceutical companies since the early 1980s. Several compounds have been launched on the market and others are under clinical evaluation. Moreover, the recent literature reported the interest of thromboxane modulators, which combine another pharmacological activity such as, platelet activating factor antagonism, angiotensin II antagonism, or 5-lipoxygenase inhibition. In this review, we will propose a description of the recently described thromboxane modulators of major interest from both a pharmacological and a chemical point of view.

Arachidonic Acid↗

Serotonin differentially modulates responses to tones and frequency-modulated sweeps in the inferior colliculus.

Although almost all auditory brainstem nuclei receive serotonergic innervation, little is known about its effects on auditory neurons. We address this question by evaluating the effects of serotonin on sound-evoked activity of neurons in the inferior colliculus (IC) of Mexican free-tailed bats. Two types of auditory stimuli were used: tone bursts at the neuron's best frequency and frequency-modulated (FM) sweeps with a variety of spectral and temporal structures. There were two main findings. First, serotonin changed tone-evoked responses in 66% of the IC neurons sampled. Second, the influence of serotonin often depended on the type of signal presented. Although serotonin depressed tone-evoked responses in most neurons, its effects on responses to FM sweeps were evenly mixed between depression and facilitation. Thus in most cells serotonin had a different effect on tone-evoked responses than it did on FM-evoked responses. In some neurons serotonin depressed responses evoked by tone bursts but left the responses to FM sweeps unchanged, whereas in others serotonin had little or no effect on responses to tone bursts but substantially facilitated responses to FM sweeps. In addition, serotonin could differentially affect responses to various FM sweeps that differed in temporal or spectral structure. Previous studies have revealed that the efficacy of the serotonergic innervation is partially modulated by sensory stimuli and by behavioral states. Thus our results suggest that the population activity evoked by a particular sound is not simply a consequence of the hard wiring that connects the IC to lower and higher regions but rather is highly dynamic because of the functional reconfigurations induced by serotonin and almost certainly other neuromodulators as well.

Acoustic Stimulation↗