Visualization of lower extremity lymphedema in the same cohort using 99mTc-human serum albumin and 99mTc-phytate lymphoscintigraphy with SPECT-CT.

Lymphoscintigraphy with single-photon emission computed tomography (SPECT-CT) is useful in diagnosing lymphedema. However, there are multiple timings, techniques, and tracers utilized worldwide without any comparison. We examined and compared the image clarity with two different radiotracers, 99mTc human serum albumin (HSA) and 99mTc phytate (phytate), in the same patients. The study retrospectivity examined 46 limbs of 36 patients who underwent lymphoscintigraphy using HSA and phytate from January 2013 to September 2018. Tracer accumulation in the lymph nodes, linear pattern (LP), and dermal backflow (DBF) were qualitatively analyzed; contrast-to-noise ratios (CNR) of DBF and standardized uptake value ratio (SUVR) of LP were also quantitatively analyzed. Neither lymph node accumulation nor DBF identification showed significant difference. However, a significant difference was observed between the LP identification of the unaffected (p<0.001) and affected sides (p<0.001). On quantitative evaluation, CNR and SUVR of LP was significantly higher with HSA than with phytate (p<0.001). SUVR of LP was also significantly higher with HSA than with phytate in both unaffected (p=0.002) and affected (p=0.005) sides. Overall, images acquired with HSA were clearer than that with phytate, and the identification of LP was particularly better with HSA than with phytate. Thus, lymphoscintigraphy using HSA is preferred over phytate for both diagnosis and evaluation of disease severity and surgical site selection.

High molecular weight organic compounds (HMW-OCs) in severe winter haze: Direct observation and insights on the formation mechanism.

High molecular weight organic compounds (HMW-OCs), formed as secondary organic aerosols (SOA), have been reported in many laboratory studies. However, little evidence of HMW-OCs formation, in particular during winter season in the real atmosphere, has been reported. In January 2013, Beijing faced historically severe haze pollution, in which the hourly PM2.5 concentration reached as high as 974 µg m-3. Four typical haze events (HE1 to HE4) were identified, and HE2 (Jan. 9-16) was the most serious of these. Based on the hourly observed chemical composition of PM2.5 and the daily organic composition analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS), we found that abundant ion peaks in m/z 200-850 appeared on heavy haze days, whereas these were negligible on a clear day, indicating the existence of HMW-OCs in the wintertime haze. A negative nonlinear correlation between HMW-OCs and O3 suggested that gas oxidation was not likely to be the dominant mechanism for HMW-OCs formation. During the heavy haze events, the relative humidity and mass ratio of H2O/PM2.5 reached as high as 80% and 0.2, respectively. The high water content and its good positive correlation with HMW-OCs indicated that an aqueous-phase process may be a significant pathway in wintertime. The evidence that acidity was much higher during HE2 (0.37 µg m-3) than on other days, as well as its strong correlation with HMW-OCs, indicated that acid-catalyzed reactions likely resulted in HMW-OCs formation during the heavy winter haze in Beijing.

Large-scale psychological differences within China explained by rice versus wheat agriculture.

Cross-cultural psychologists have mostly contrasted East Asia with the West. However, this study shows that there are major psychological differences within China. We propose that a history of farming rice makes cultures more interdependent, whereas farming wheat makes cultures more independent, and these agricultural legacies continue to affect people in the modern world. We tested 1162 Han Chinese participants in six sites and found that rice-growing southern China is more interdependent and holistic-thinking than the wheat-growing north. To control for confounds like climate, we tested people from neighboring counties along the rice-wheat border and found differences that were just as large. We also find that modernization and pathogen prevalence theories do not fit the data.

High resolution, low hν photoelectron spectroscopy with the use of a microwave excited rare gas lamp and ionic crystal filters.

The need for not only bulk sensitive but also extremely high resolution photoelectron spectroscopy for studying detailed electronic structures of strongly correlated electron systems is growing rapidly. Moreover, easy access to such a capability in one's own laboratory is desirable. Demonstrated here is the performance of a microwave excited rare gas (Xe, Kr, and Ar) lamp combined with ionic crystal filters (sapphire, CaF(2), and LiF), which can supply three strong lines near the photon energy of hnyu hν=8.4, 10.0, and 11.6 eV, with the hν resolution of better than 600 µeV for photoelectron spectroscopy. Its performance is demonstrated on some materials by means of both angle-integrated and angle-resolved measurements.

Nicotine stimulates transcriptional activity of the human dopamine transporter gene.

Nicotine modulates dopaminergic activity in the central nervous system by acting on the reuptake system, including the dopamine transporter (DAT), although precisely remains unclear. Here we investigated the effect of nicotine on the transcriptional regulation of the human DAT (hDAT) gene by conducting luciferase reporter assays. Nicotine enhanced the transcription of hDAT gene constructs in transiently transfected SK-N-SH cells. Hexamethonium, a neuronal (ganglionic) nicotinic acetylcholine receptor antagonist, blocked the action of nicotine. Functional analyses placed the nicotine-responsive region -3.5 to -1.0 kb (from the transcription start site) upstream of the core promotor region. Deletion of intron 1, known as a silencer element of the hDAT gene, abolished nicotine's stimulatory effect. Nicotine failed to stimulate DAT promotor activity in non-neuronal CHO or COS-7 cells or in SK-N-AS cells, another neuronal cell line recently reported as a model for investigating DAT gene expression. These results suggest a nicotinic cholinergic mechanism to be involved in the nicotine-induced up-regulation of DAT gene expression.

5-Methoxy-N,N-diisopropyltryptamine (Foxy), a selective and high affinity inhibitor of serotonin transporter.

5-Methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT) is a synthetic orally active hallucinogenic tryptamine derivative, known also as Foxy or Foxy methoxy. However, few studies have examined its effects in vitro. In the present study, we investigated the actions of 5-MeO-DIPT against monoamine neurotransmitter transporters, including the transporters for dopamine (DAT), norepinephrine (NET), and serotonin (SERT), using COS-7 cells heterologously expressing these transporters and rat brain synaptosomes. 5-MeO-DIPT specifically inhibited the uptake of [3H]serotonin (5-HT) by the SERT-expressing COS-7 cells and rat striatal synaptosomes in a high affinity manner at concentrations similar to those for cocaine. The effect was reversible and competitive. 5-MeO-DIPT failed to stimulate reverse transport of [3H]5-HT through SERT, while it prevented the releasing action of methamphetamine. 5-MeO-DIPT induced cell toxicity at high concentrations in COS-7 cells, and it was not influenced by the expression of SERT. These results demonstrated that 5-MeO-DIPT acts as a competitive SERT inhibitor and has an inability to cause reverse transport, underlying its serotonergic actions.

Structure-activity relationship of trihexyphenidyl analogs with respect to the dopamine transporter in the on going search for a cocaine inhibitor.

A series of trihexyphenidyl (THP) analogs were used to search for a derivative that could serve as a cocaine inhibitor. A compound that blocks binding of the cocaine analog carboxyfluorotropane (CFT), allows dopamine uptake and exhibits low side effects could serve as a good candidate for that purpose. All analogs were tested for the extent to which they inhibit CFT binding, dopamine uptake and n-methyl scopolamine (NMS) binding. Several structure-function relationships emerged. Methylation/halogenation of THP's benzene ring enhanced the compound's ability to block CFT binding in comparison to its ability to block dopamine uptake (5a-e). Replacement of the cyclohexyl ring with a benzene ring tended to create compounds that had lower affinities to the dopamine transporter (7b compared to THP, 7d compared to 5h, 7c compared to 8c) and modification of THP's piperidine ring tended to enhance affinity to the dopamine transporter (5f-h, 8a, 8c). One analog (5f) that showed little muscarinic activity indicating that it would probably have few side effects was investigated for its effects as an in vivo cocaine inhibitor. However, it showed few antagonistic effects in vivo. Nevertheless, this work greatly elucidates the structure-function relationships required for potential cocaine inhibitors and so lays out promising directions for future research.

Transport of dopamine and levodopa and their interaction in COS-7 cells heterologously expressing monoamine neurotransmitter transporters and in monoaminergic cell lines PC12 and SK-N-SH.

The present study investigated the effects of levodopa, a precursor of dopamine (DA) therapeutically used for the treatment of Parkinson's disease, on DA transport in the two different systems, COS-7 cells heterologously expressing rat monoamine transporter cDNA and in monoaminergic cell lines PC12 and SK-N-SH. Levodopa enhanced uptake of [3H]DA and [3H]norepinephrine (NE) but not [3H]serotonin in the transfected COS-7 cells in a concentration-dependent manner. On the other hand, in PC12 and SK-N-SH cells where NET is functionally expressed, levodopa enhanced [3H]DA and [3H]NE uptake at low concentrations and inhibited the uptake at higher concentrations. The effects of levodopa on catecholamine transporters in the opposite direction suggest a different mechanism at the intra- and extracellular sites in a levodopa transport-dependent and independent manner.

Functional characterization of the splicing variants of human norepinephrine transporter.

Human norepinephrine transporter (NET) displays three splicing variants having different carboxy terminals, hNET, hNET C-t var1 and hNET C-t var2. Functional characterization of these isoforms was performed with transient expression system in COS-7 cells. Cells transfected with hNET C-t var2, but not hNET C-t var1, revealed a significant increase in [(3)H]norepinephrine (NE) uptake and [(3)H]nisoxetine binding as well as hNET, in association with their different cellular localization indicated by immunostaining using NET-specific antisera. Kinetic and pharmacological analyses of [(3)H]NE uptake revealed different characteristics between hNET and hNET C-t var2. These results suggest that hNET C-t var2 may participate in NE transport in a manner different from hNET at noradrenergic synapses or in other tissues including placenta where NET variants were found to exist.

Divergent consequences of success and failure in japan and north america: an investigation of self-improving motivations and malleable selves.

Self-enhancing and self-improving motivations were investigated across cultures. Replicating past research, North Americans who failed on a task persisted less on a follow-up task than those who succeeded. In contrast, Japanese who failed persisted more than those who succeeded. The Japanese pattern is evidence for a self-improving orientation: Failures highlight where corrective efforts are needed. Japanese who failed also enhanced the importance and the diagnosticity of the task compared with those who succeeded, whereas North Americans did the opposite. Study 2 revealed that self-improving motivations are specific to the tasks on which one receives feedback. Study 3 unpackaged the cultural differences by demonstrating that they are due, at least in part, to divergent lay theories regarding the utility of effort. Study 4 addressed the problem of comparing cultures on subjective Likert scales and replicated the findings with a different measure.

Effects of volatile and intravenous anesthetics on the uptake of GABA, glutamate and dopamine by their transporters heterologously expressed in COS cells and in rat brain synaptosomes.

Although the neurotransmitter uptake system is considered a possible target for the presynaptic action of anesthetic agents, observations are inconsistent concerning effects on the transporter and their clinical relevance. The present study examined the effects of volatile and intravenous anesthetics on the uptake of GABA, glutamate and dopamine in COS cells heterologously expressing the transporters for these neurotransmitters and in the rat brain synaptosomes. Halothane and isoflurane, but not thiamylal or thiopental, significantly inhibited uptake by COS cell systems of GABA, dopamine and glutamic acid in a concentration-dependent manner within clinically relevant ranges for anesthesia induced by these agents. Similarly, in synaptosomes halothane and isoflurane but not thiopental significantly suppressed the uptake of GABA and glutamic acid, respectively. These results do not support the hypothesis that volatile and intravenous anesthetics exert their action via specific inhibition of GABA uptake to enhance inhibitory GABAergic neuronal activity. Rather, they suggest that presynaptic uptake systems for various neurotransmitters including GABA may be the molecular targets for volatile anesthetic agents.

Differential effects of trihexyphenidyl on place preference conditioning and locomotor stimulant activity of cocaine and methamphetamine.

Cocaine produces rewarding and locomotor stimulant effects by increasing extracellular dopamine (DA) levels in the terminal areas of the mesolimbic DA system. Our recent in vitro studies have shown that a muscarinic receptor antagonist, trihexyphenidyl (THP) inhibits the binding of a cocaine analogue to the DA transporter at concentrations that are ineffective in inhibiting 3H-DA uptake, suggesting that THP may attenuate the actions of cocaine selectively. The present study examined whether THP could affect conditioned place preference (CPP) for and locomotor stimulant activity of cocaine and methamphetamine (MAP) in mice. Mice were injected with cocaine (10 mg/kg) or MAP (1 mg/kg) in one compartment of the CPP chamber 4 times every second day. On alternate days the animals received saline in the other compartment of the CPP chamber. Pretreatment with THP was made 10 min before cocaine or MAP injection. The CPP score and locomotor activity were assessed using a novel activity monitor, SCANET. Cocaine and MAP produced CPP for the drug-paired compartment. Pretreatment with THP (0.05-5 mg/kg) had no influence on cocaine-induced CPP at any dose tested. In contrast, MAP-induced CPP was completely antagonized by THP at 5 mg/kg, which produced no CPP by itself. Another muscarinic receptor antagonist, scopolamine (SCP, 3 mg/kg) neither caused CPP by itself nor affected the development of cocaine- or MAP-induced CPP. Both THP and SCP enhanced spontaneous, cocaine- or MAP-induced locomotor activity. Though the present conditioning treatments failed to develop locomotor sensitization to cocaine, THP, but not SCP, acted cooperatively with cocaine to develop locomotor sensitization. The development of locomotor sensitization to MAP was retarded by SCP but was not affected by THP. These results suggest that, contrary to our anticipation, THP has a unique characteristic of specifically counter-acting the rewarding properties of MAP via a non-cholinergic (muscarinic) mechanism.

Nerve growth factor down-regulates the expression of norepinephrine transporter in rat pheochromocytoma (PC12) cells.

Functional expression of norepinephrine transporter (NET) and its regulation were examined in rat pheochromocytoma cell line, PC12. Nerve growth factor (NGF) decreased [3H]-norepinephrine (NE) uptake in association with a decrease in NET mRNA levels. On the other hand, levels of tyrosine hydroxylase mRNA increased in PC12 cells treated with NGF for 4-24 h, while Oct-2 mRNA levels decreased at 4 h with NGF then recovered for 8-24 h in the presence of NGF. Both bFGF and EGF reduced [3H]NE uptake, although they failed to affect NET mRNA levels. To examine the NET transcriptional regulation, we identified the 5'-noncoding region of rat NET mRNA by the rapid amplification of cDNA end (RACE) method and cloned the 5'-flanking region of NET gene. The newly identified exon encodes the untranslated region of rat NET mRNA upstream of the known 5'-region including ATG start codon. Constructs having green fluorescent protein (GFP) as reporter were made with the cloned NET gene, and promoter activity was examined in CHO and SK-N-SH cells transiently transfected and in PC12 cells stably transfected with NET-GFP constructs. The results indicate that the 2.1 kb NET flanking region displays promoter activity and is responsible for the NGF-induced down-regulation of NET expression.

[Development and validation of a sympathy scale].

The authors developed a 22-item scale of interpersonal sympathy that is informed by relevant practices and meanings of contemporary Japanese cultural context. In three independent samples the scale was shown to be reasonably reliable (alpha > .80). Furthermore, the scale had a systematic relationship with related variables, hence exhibiting satisfactory construct validity. Specifically, sympathy was positively correlated with both a reported frequency of prosocial behaviors (Study 1) and emotional empathy (Study 2). Moreover, sympathy formed a higher-order factor with interdependent construal of self, which was orthogonal to another higher-order factor comprised of independent construal of self and self-esteem (Study 3). Finally, some directions for future research are discussed.

Collective construction of the self and social relationships: a rejoinder and some extensions.

This commentary elaborates on the basic thesis developed by Rothbaum, Pott, Azuma, Miyake, and Weisz and underscores the significance of the co-constructive process of the self and social relationship. Implications for future cultural psychological inquiry in this area are discussed.

Mutation in recR gene of Deinococcus radiodurans and possible involvement of its product in the repair of DNA interstrand cross-links.

We previously reported that some Deinococcus radiodurans mutants are sensitive to DNA interstrand cross-linking agents but resistant to UV and gamma-rays. We isolated DNA fragments from a D. radiodurans genomic library which complemented the mitomycin C sensitivity of one of these mutants. One 3.2kb-long fragment contains an open reading frame of approximately 700bp and the deduced amino acid sequence is very homologous to other prokaryotic RecR proteins. This open reading frame in the mitomycin C-sensitive mutant strain contains a frame shift mutation at its carboxyl terminal region. These data suggest that RecR protein plays an important role in the resistance to interstrand cross-links in this bacterium.

Mediation by platelet-activating factor of 12-hydroxyeicosatetraenoic acid-induced cytosolic free calcium concentration elevation in neutrophils.

12(R)-hydroxyeicosatetraenoic acid (HETE) shows biphasic increase in cytosolic free calcium concentration ([Ca2+]i) in rabbit and human neutrophils; the initial transient phase and the continuous falling phase. 12(S)-HETE was less potent in both species. BN50739, a platelet-activating factor (PAF) receptor antagonist, inhibited both phases of 12(R)-HETE-induced [Ca2+]i rise but did not affect leukotriene B4 (LTB4)-induced [Ca2+]i rise. N-tosyl-L-phenylalanine chloromethyl ketone (TPCK), a PAF synthesis inhibitor, and manoalide, a phospholipase A2 inhibitor, reduced 12(R)-HETE-induced [Ca2+]i rise. These blockers inhibited the continuous phase of [Ca2+]i rise induced by N-formyl-methionyl-leucyl-phenylalanine (FMLP) with little effect on the initial phase. It had no significant effect on LTB4-induced [Ca2+]i rise. SC-41930, a LTB4-receptor antagonist, did not block 12-HETE-induced [Ca2+]i rise. In 12(R)-HETE-, FMLP- and LTB4-stimulated cells, accumulations of cell-associated PAF and released PAF were detected but not in unstimulated cells. BN50739 did not affect the accumulation of cell-associated PAF and release of PAF in 12(R)-HETE-stimulated cells. These results suggest that 12(R)-HETE-induced and partially, FMLP-induced, but not LTB4-induced [Ca2+]i rise are mediated by PAF, which is produced and released by stimulation of the cells by 12(R)-HETE and FMLP, respectively.

Regulation of the development of allodynia by intrathecally administered P2 purinoceptor agonists and antagonists in mice.

Effects of agonists and antagonists of P2X-purinoceptors on the regulation of the development of allodynia were examined in mice; the drugs were administered intrathecally to the spinal cord. Suramin (5, 10 microg) and pyridoxalphosphate-6-azophenyl-2', 4'-disulfonic acid (PPADS), antagonists of P2X receptors, inhibited prostaglandin (PG) E(2)-induced allodynia. PPADS did not block glutamate-induced allodynia. alpha,beta-Methylene ATP (alpha, beta-meATP), an agonist of P2X receptor, elicited allodynia. alpha, beta-me ATP-induced allodynia was blocked by co-administration of alpha,beta-meATP with PPADS, MK 801 or N(omega)-nitro-L-arginine methyl ester (L-NAME). Suramin at higher doses (20, 40 microg) induced allodynia, which was inhibited by MK 801 or L-NAME. These results suggest that ATP P2X receptors in the spinal cord are involved in the regulation of tactile allodynia. Glutamate receptor and nitric oxide systems play an important role in the development of allodynia produced by alpha,beta-meATP and suramin.

Changes in seizure susceptibility to local anesthetics by repeated administration of cocaine and nomifensine but not GBR12935: possible involvement of noradrenergic system.

We examined cross-sensitization of cocaine and synthetic local anesthetics to their seizure susceptibility after repeated administration. Seizure susceptibility of procaine and lidocaine increased after the end of two days of treatment with a subconvulsive dose of cocaine. Acute treatment with nomifensine but not GBR12935, a specific inhibitor of the dopamine transporter, facilitated lidocaine-induced convulsion. Furthermore, daily treatment with nomifensine for two days enhanced lidocaine-induced convulsion. These results suggest the possible involvement of the brain noradrenergic system in the changes in seizure susceptibility after repeated administration of some local anesthetics.