Deep Learning Segmentation of the Nucleus Basalis of Meynert on 3T MRI.

BACKGROUND AND PURPOSE: The nucleus basalis of Meynert is a key subcortical structure that is important in arousal and cognition and has been explored as a deep brain stimulation target but is difficult to study due to its small size, variability among patients, and lack of contrast on 3T MR imaging. Thus, our goal was to establish and evaluate a deep learning network for automatic, accurate, and patient-specific segmentations with 3T MR imaging. MATERIALS AND METHODS: Patient-specific segmentations can be produced manually; however, the nucleus basalis of Meynert is difficult to accurately segment on 3T MR imaging, with 7T being preferred. Thus, paired 3T and 7T MR imaging data sets of 21 healthy subjects were obtained. A test data set of 6 subjects was completely withheld. The nucleus was expertly segmented on 7T, providing accurate labels for the paired 3T MR imaging. An external data set of 14 patients with temporal lobe epilepsy was used to test the model on brains with neurologic disorders. A 3D-Unet convolutional neural network was constructed, and a 5-fold cross-validation was performed. RESULTS: The novel segmentation model demonstrated significantly improved Dice coefficients over the standard probabilistic atlas for both healthy subjects (mean, 0.68 [SD, 0.10] versus 0.45 [SD, 0.11], P = .002, t test) and patients (0.64 [SD, 0.10] versus 0.37 [SD, 0.22], P < .001). Additionally, the model demonstrated significantly decreased centroid distance in patients (1.18 [SD, 0.43] mm, 3.09 [SD, 2.56] mm, P = .007). CONCLUSIONS: We developed the first model, to our knowledge, for automatic and accurate patient-specific segmentation of the nucleus basalis of Meynert. This model may enable further study into the nucleus, impacting new treatments such as deep brain stimulation.

[Feasibility of ultrasound radiomics-based models for classification of hepatic echinococcosis].

OBJECTIVE: To investigate the feasibility of establishment of ultrasound radiomics-based models for classification of hepatic echinococcosis, so as to provide insights into precision ultrasound diagnosis of hepatic echinococcosis. METHODS: The ultrasonographic images were retrospectively collected from 200 patients with hepatic echinococcosis in Shiqu County, Ganzi Tibetan Autonomous Prefecture, Sichuan Province in October 2014, and the regions of interest were plotted in ultrasonographic images of hepatic echinococcosis lesions. The ultrasound radiomics features of hepatic echinococcosis were extracted with 25 methods, and screened using pre-selection and the least absolute shrinkage and selection operator. Then, all ultrasonographic images were randomly assigned into the training and independent test sets according to the type of lesions at a ratio of 7:3. Machine learning models for classification of hepatic echinococcosis were created based on two classifiers, including kernel logistic regression (KLR) and medium Gaussian support vector machine (MGSVM). The receiver operating characteristic (ROC) curves were plotted, and the sensitivity, specificity and areas under the curves (AUC) of the created machine learning models for classification of hepatic echinococcosis were calculated. RESULTS: A total of 5 005 ultrasound radiomics features were extracted from 200 patients with hepatic echinococcosis using 25 methods, and 36 optimal radiomics features were screened through feature selection, based on which two machine learning models were created, including KLR and MGSVM. ROC curve analysis showed that MGS-VM presented a higher efficacy for hepatic echinococcosis classification than KLR in the training set, with a sensitivity of 0.82, a specificity of 0.78 and AUC of 0.88, while KLR presented a higher efficacy for hepatic echinococcosis classification than MGSVM in the independent test set, with a sensitivity of 0.82, a specificity of 0.72 and AUC of 0.86, respectively. CONCLUSIONS: Ultrasound radiomics-based machine learning models are feasible for hepatic echinococcosis classification.

Iron overload induces apoptosis of murine preosteoblast cells via ROS and inhibition of AKT pathway.

OBJECTIVE: This study investigates the inhibitory effect of iron overload on MC3T3-E1 cells and its molecular mechanism. METHODS: MC3T3-E1 cells were grown under different concentrations of FAC (ferric ammonium citrate), and the WST-8 assay was used to investigate the proliferation of cells following FAC with or without deferasirox. DCFH-DA fluorescence probe was applied to detect the cellular reactive oxygen species (ROS) level. The apoptotic cells were analyzed with Annexin V-FITC/PI and the Hoechst 33258 nuclear staining assay. The JC-1 staining assay was applied to observe the change in the mitochondrial transmembrane potential. The expression levels of caspase-3, PARP, Bcl-2 family proteins, and AKT kinase were detected with the Western blot assay. RESULTS: Iron overload had a cytotoxic effect on MC3T3-E1 cells in a dosage-dependent way and resulted in increasing level of intracellular ROS. Iron overload induced apoptosis in MC3T3-E1 cells via a caspase-dependent mechanism that is accompanied by mitochondria dysfunction and decreased expression of anti-apoptotic proteins. The expression levels of cleaved-caspase-3 and cleaved-PARP were upregulated, while the expression levels of caspase-9, caspase-7, caspase-3, and PARP were downregulated. Phosphorylation of AKT kinase decreased. CONCLUSION: Iron overload can generate ROS in cells, inhibit AKT kinase and its downstream proteins activity, and subsequently initiate apoptotic events.

Aspirin-triggered Lipoxin A4 attenuates mechanical allodynia in association with inhibiting spinal JAK2/STAT3 signaling in neuropathic pain in rats.

Aspirin-triggered Lipoxin A4 (ATL), as a Lipoxin A4 (LXA4) epimer, is endogenously produced by aspirin-acetylated cycloxygenase-2 (COX-2) and plays a vital role in endogenous anti-inflammation via the LXA4 receptor (ALX). Recent investigations have indicated that spinal neuroinflammation and the activation of the Janus Kinase 2 (JAK2)/Signal Transducers and Transcription Activators 3 (STAT3) signaling pathway are involved in neuropathic pain states. However, the effect of ATL on neuroinflammation and JAK2/STAT3 signaling in chronic constriction injury (CCI)-induced neuropathic pain in rats has not been well-studied. The present study demonstrated the anti-inflammatory and analgesic effect of ATL on neuropathic pain and assessed the role of spinal JAK2/STAT3 signaling on the effect of ATL. Intrathecal administration of ATL significantly attenuated mechanical allodynia via spinal ALX and inhibited the upregulation of pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α) on day 7 of CCI surgery. In addition, ATL markedly suppressed the upregulation of p-STAT3 induced by the neuropathic pain. Blockade of JAK2-STAT3 signaling with intrathecal administration of the JAK2 inhibitor AG490 or the STAT3 inhibitor S3I-201 clearly reduced mechanical allodynia and the upregulation of pro-inflammatory cytokines in CCI rats. Interestingly, inhibition of JAK2/STAT3 signaling via ATL or the specific signaling inhibitor (AG49, S3I-201) further promoted the increased expression of suppressor of cytokine signaling 3 (SOCS3) mRNA in the spinal cord induced by CCI surgery. Taken together, our results suggested that the analgesic effect of ATL was mediated by inhibiting spinal JAK2/STAT3 signaling and hence the spinal neuroinflammation in CCI rats.

Transcriptome sequencing of sea cucumber (Apostichopus japonicus) and the identification of gene-associated markers.

Sea cucumber (Apostichopus japonicus) is an ecologically and economically important species in East and South-East Asia. This project aimed to identify large numbers of gene-associated markers and differentially expressed genes (DEGs) after lipopolysaccharides (LPS) challenge in A. japonicus using high-throughput transcriptome sequencing. A total of 162 million high-quality reads of 174 million raw reads were obtained by deep sequencing using Illumina HiSeq™ 2000 platform. Assembly of these reads generated 94 704 unigenes, with read length ranging from 200 to 16 153 bp (average length of 810 bp). A total of 36 005 were identified as coding sequences (CDSs), 32 479 of which were successfully annotated. Based on the assembly transcriptome, we identified 142 511 high-quality single nucleotide polymorphisms (SNPs). Among them, 33 775, 63 120 and 45 616 were located in sequences without predicted CDS (non-CDSs), CDSs and untranslated regions (UTRs), respectively. These putative SNPs included 82 664 transitions and 59 847 transversions. Totally, 89 375 (59.1%) were distributed in 15 473 known genes. A total of 6417 microsatellites were detected in 5970 unigenes, 3216 of which were annotated and 2481 were successfully subjected for primer design. The numbers of simple sequence repeats (SSRs) identified in non-CDSs, CDSs and UTRs were 2367, 2316 and 1734. These potential SNPs and SSRs are expected to provide abundant resources for genetic, evolutionary and ecological studies in sea cucumber. Transcriptome comparison revealed 1330, 1347 and 1291 DEGs in the coelomocytes of A. japonicus at 4 h, 24 h and 72 h after LPS challenge, respectively. Approximately 58.4% (1802) of total DEGs have been successfully annotated.

Spinal interleukin-33 and its receptor ST2 contribute to bone cancer-induced pain in mice.

Cancer pain, particularly bone cancer pain, affects the quality of life of cancer patients, and current treatments are limited. Interleukin (IL)-33, a new member of the IL-1 super family, has been reported to be involved in the modulation of inflammatory pain. However, studies focused on its role in the modulation of cancer pain have been rare. The present study was designed to investigate whether spinal IL-33/ST2 signaling was involved in bone cancer-induced pain in mice. Bone cancer was induced via intra-femoral inoculation of 4T1 mammary carcinoma cells. The mice inoculated with carcinoma cells showed mechanical allodynia, heat hyperalgesia and a reduction in limb use, whereas phosphate-buffered saline or heat-killed cells-injected mice showed no significant difference compared to non-treated mice. The pain hypersensitive behaviors worsened over time and with bone destruction. Both the mRNA and the protein levels of IL-33 and relative cytokines (IL-1ß, IL-6, TNF-a) were significantly increased in the spinal cord after the inoculation of carcinoma cells. Intrathecal administration of ST2 antibody to block IL-33/ST2 signaling alleviated pain behaviors in a dose-dependent manner in bone cancer pain mice compared with vehicle-injected mice. Moreover, the ST2(-/-) mice showed a significant amelioration of limb use and heat hyperalgesia compared to wild-type mice. Meanwhile, concentrations of spinal IL-1ß, IL-6 and TNF-a in the cancer-bearing ST2(-/-) mice had no significant changes. These data further suggested that IL-33/ST2 signaling played a vital role in cancer pain. Our results provided evidence that IL-33 and its receptor ST2 may be a potential therapeutic target for the treatment of pain in bone cancer patients.

CO2 adsorption in mono-, di- and trivalent cation-exchanged metal-organic frameworks: a molecular simulation study.

A molecular simulation study is reported for CO(2) adsorption in rho zeolite-like metal-organic framework (rho-ZMOF) exchanged with a series of cations (Na(+), K(+), Rb(+), Cs(+), Mg(2+), Ca(2+), and Al(3+)). The isosteric heat and Henry's constant at infinite dilution increase monotonically with increasing charge-to-diameter ratio of cation (Cs(+) < Rb(+) < K(+) < Na(+) < Ca(2+) < Mg(2+) < Al(3+)). At low pressures, cations act as preferential adsorption sites for CO(2) and the capacity follows the charge-to-diameter ratio. However, the free volume of framework becomes predominant with increasing pressure and Mg-rho-ZMOF appears to possess the highest saturation capacity. The equilibrium locations of cations are observed to shift slightly upon CO(2) adsorption. Furthermore, the adsorption selectivity of CO(2)/H(2) mixture increases as Cs(+) < Rb(+) < K(+) < Na(+) < Ca(2+) < Mg(2+) ≈ Al(3+). At ambient conditions, the selectivity is in the range of 800-3000 and significantly higher than in other nanoporous materials. In the presence of 0.1% H(2)O, the selectivity decreases drastically because of the competitive adsorption between H(2)O and CO(2), and shows a similar value in all of the cation-exchanged rho-ZMOFs. This simulation study provides microscopic insight into the important role of cations in governing gas adsorption and separation, and suggests that the performance of ionic rho-ZMOF can be tailored by cations.

Molecular thermodynamic model for DNA melting in ionic and crowded solutions.

A molecular thermodynamic model is developed to predict DNA melting in ionic and crowded solutions. Each pair of nucleotides in the double-stranded DNA and each nucleotide in the single-stranded DNA are respectively represented by two types of charged Lennard-Jones spheres. The predicted melting curves and melting temperatures T(m) of the model capture the general feature of DNA melting and match fairly well with the available simulation and experimental results. It is found that the melting curve is steeper and T(m) is higher for DNA with a longer chain. With increasing the fraction of the complementary cytosine-guanine (CG) base pairs, T(m) increases almost linearly as a consequence of the stronger hydrogen bonding of the CG base pair than that of adenine-thymine (AT) base pair. At a greater ionic concentration, T(m) is higher due to the shielding effect of counterions on DNA strands. It is observed that T(m) increases in the presence of crowder because the crowder molecules occupy a substantial amount of system volume and suppress the entropy increase for DNA melting. At a given concentration, a larger crowder exhibits a greater suppression for DNA melting and hence a higher T(m). At the same packing fraction, however, a smaller crowder leads to a higher T(m).

Highly porous ionic rht metal-organic framework for H2 and CO2 storage and separation: a molecular simulation study.

The storage and separation of H2 and CO2 are investigated in a highly porous ionic rht metal-organic framework (rht-MOF) using molecular simulation. The rht-MOF possesses a cationic framework and charge-balancing extraframework NO3(-) ions. Three types of unique open cages exist in the framework: rhombicuboctahedral, tetrahedral, and cuboctahedral cages. The NO3(-) ions exhibit small mobility and are located at the windows connecting the tetrahedral and cuboctahedral cages. At low pressures, H2 adsorption occurs near the NO3(-) ions that act as preferential sites. With increasing pressure, H2 molecules occupy the tetrahedral and cuboctahedral cages and the intersection regions. The predicted isotherm of H2 at 77 K agrees well with the experimental data. The H2 capacity is estimated to be 2.4 wt % at 1 bar and 6.2 wt % at 50 bar, among the highest in reported MOFs. In a four-component mixture (15:75:5:5 CO2/H2/CO/CH4) representing a typical effluent gas of H2 production, the selectivity of CO2/H2 in rht-MOF decreases slightly with increasing pressure, then increases because of cooperative interactions, and finally decreases as a consequence of entropy effect. By comparing three ionic MOFs (rht-MOF, soc-MOF, and rho-ZMOF), we find that the selectivity increases with increasing charge density or decreasing free volume. In the presence of a trace amount of H2O, the interactions between CO2 and NO3(-) ions are significantly shielded by H2O; consequently, the selectivity of CO2/H2 decreases substantially.

Metal-organic framework MIL-101 for adsorption and effect of terminal water molecules: from quantum mechanics to molecular simulation.

MIL-101 is a chromium terephthalate-based mesoscopic metal-organic framework and one of the most porous materials reported to date. In this study, we investigate the adsorption of CO(2) and CH(4) in dehydrated and hydrated MIL-101 and the effect of terminal water molecules on adsorption. The atomistic structures of MIL-101 are constructed from experimental crystallographic data, energy minimization, and quantum mechanical optimization. The adsorption isotherm of CO(2) predicted from molecular simulation agrees well with experiment and is relatively insensitive to the method (Merz-Kollman or Mulliken) used to estimate the framework charges. Both the united-atom and five-site models of CH(4) predict the isotherm fairly well, though the former overestimates and the latter underestimates. Adsorption first occurs in the microporous supertetrahedra at low pressures and then in the mesoscopic cages with increasing pressure. In the dehydrated MIL-101, more adsorbate molecules are located near the exposed Cr(2) sites than the fluorine saturated Cr(1) sites. The terminal water molecules in the hydrated MIL-101 act as additional interaction sites and enhance adsorption at low pressures. This enhancement is more pronounced for CO(2) than for CH(4), because CO(2) is quadrapolar and interacts more strongly with the terminal water molecules. At high pressures, however, the reverse is observed, as the presence of terminal water molecules reduces free volume and adsorption. For the adsorption of CO(2)/CH(4) mixture, a higher selectivity is found in the hydrated MIL-101.

Proteomic analysis of differentially expressed proteins in rat liver allografts developed acute rejection.

BACKGROUND: Acute rejection (AR) after liver transplantation is a cell-mediated immune response that takes place within the allograft and results in graft dysfunction and failure, but the molecular mechanisms about hepatocyte dysfunction remain poorly understood. Here we characterized global protein expression changes in liver allograft during AR. METHODS: The effect of an alloantigen-dependent immunological response was evaluated by syngeneic and allogeneic rat orthotopic liver transplantation (OLT). Using a combination of two-dimensional gel electrophoresis and mass spectrometry, we identified 18 differentially expressed proteins in AR allograft compared with matched tolerance allograft. Serum chemistry and allograft histology were determined. RESULTS: Allogeneic OLT recipients exhibited elevated plasma levels of liver injury markers, progressive portal and venous inflammation and cellular infiltration in liver allograft compared with syngeneic OLT. 18 protein expressions altered by AR play important roles in metabolism, oxidative stress defense, signal transduction, biotransformation and transport. Decreased expression of protein disulfide isomerase in AR allograft was confirmed by Western blotting and immunohistochemistry. CONCLUSIONS: This study uncovered new mechanistic insights into graft dysfunction in AR of liver allograft. Several significantly altered protein expressions act coordinately in hepatocyte dysfunction by depressed energy, enhanced oxidative stress-induced molecular damage and restrained biotransformation. The present findings may open new avenues for the understanding and prevention of graft dysfunction and failure during AR.

Atomistic insight into adsorption, mobility, and vibration of water in ion-exchanged zeolite-like metal-organic frameworks.

The adsorption, mobility, and vibration of water in ion-exchanged rho-zeolite-like metal-organic frameworks (ZMOFs) are investigated using atomistic simulations. Because of the high affinity for the ionic framework and nonframework ions, water is strongly adsorbed in rho-ZMOFs with a three-step adsorption mechanism. At low pressures, water is preferentially adsorbed onto Na(+) ions, particularly at site II; with increasing pressure, adsorption occurs near the framework and finally in the large cage. Upon water adsorption, Na(+) ions are observed to redistribute from site I to site II and gradually hydrated with increasing pressure. In Li-, Na-, and Cs-exchanged rho-ZMOFs, the adsorption capacity and isosteric heat decrease with increasing ionic radius attributed to the reduced electrostatic interaction and free volume. The mobility of water in Na-rho-ZMOF increases at low pressures but decreases upon approaching saturation. With sufficient amount of water present, the mobility of Na(+) ions is promoted. The vibrational spectra of water in Na-rho-ZMOF exhibit distinct bands for librational motion, bending, and stretching. The librational motion has a frequency higher than bulk water due to confinement. With increasing loading and hence stronger coordinative attraction, the bending frequency shows a blue shift. Symmetric and asymmetric modes are observed in the stretching as a consequence of the strong water-ion interaction. This study provides a fundamental microscopic insight into the static and dynamic properties of water in charged ZMOFs and reveals the subtle interplay between water and nonframework ions.

[Modulatory effect of orphanin FQ on the IL-1beta transcripts in hippocampus].

Using in situ hybridization and immuno-fluorescent double labeling method, we investigated the function of orphanin FQ on interlenkin-lbeta (IL-lbeta) transcripts in hippocampus. Intracerebroventricularly (icv) administrated IL-lbeta antibody reduced IL-l and TNF-alpha secreted from peritoneal macrophage. The high level of IL-lbeta transcript in hippocampus elicited by traumatic stress was blocked by icv injection of orphanin FQ (0.55 nmol), which was reversed by orphanin FQ receptor antagonist ([phe(1)Psi(CH(2)-NH)Gly(2)] nociceptin-(1-l3)-NH(2)). Opioid receptor-like receptor transcripts were found in neuron, astrocyte and microglia. Based on the results, we conclude that orphanin FQ functions as a neuroimmune modulator, and provokes immune response via mediation of IL-lbeta derived from neuron, astrocyte and microglia in hippocampus.

Systemic infusion of naloxone reduces degeneration of rat substantia nigral dopaminergic neurons induced by intranigral injection of lipopolysaccharide.

A massive degeneration of dopamine-containing neurons in the substantia nigra (SN) in the midbrain is characteristic of Parkinson's disease. Inflammation in the brain has long been speculated to play a role in the pathogenesis of this neurological disorder. Recently, we reported that treatment of primary rat mesencephalic mixed neuron-glia cultures with lipopolysaccharide (LPS) led to the activation of microglia, resident immune cells of the brain, and subsequent death of dopaminergic neurons. The LPS-induced degeneration of dopaminergic neurons was significantly attenuated by the opiate receptor antagonist (-)-naloxone and its inactive isomer (+)-naloxone, with equal potency, through an inhibition of microglial activation and their production of neurotoxic factors. In this study, injection of LPS into the rat SN led to the activation of microglia and degeneration of dopaminergic neurons: microglial activation was observed as early as 6 h and loss of dopaminergic neurons was detected 3 days after the LPS injection. Furthermore, the LPS-induced loss of dopaminergic neurons in the SN was time- and LPS concentration-dependent. Systemic infusion of either (-)-naloxone or (+)-naloxone inhibited the LPS-induced activation of microglia and significantly reduced the LPS-induced loss of dopaminergic neurons in the SN. These in vivo results combined with our cell culture observations confirmed that naloxone protects dopaminergic neurons against inflammation-mediated degeneration through inhibition of microglial activation and suggest that naloxone would have therapeutic efficacy in the treatment of inflammation-related neurological disorders. In addition, the inflammation-mediated degeneration of dopaminergic neurons in the rat SN resulting from the targeted injection of LPS may serve as a useful model to gain further insights into the pathogenesis of Parkinson's disease.

An open-label preliminary trial of sertraline for treatment of major depression after acute myocardial infarction (the SADHAT Trial). Sertraline Anti-Depressant Heart Attack Trial.

BACKGROUND: Depression occurs frequently in patients with acute myocardial infarction and is associated with increased mortality rates. It is not known whether serotonin reuptake inhibitors would be safe and effective for patients with depression after myocardial infarction and whether such treatment would reduce mortality rates. METHODS AND RESULTS: We conducted a multicenter, open-label, pilot study of sertraline treatment in patients with major depressive disorder identified 5 to 30 days after admission for acute myocardial infarction. Outcome measures included cardiovascular and hemostatic function, adverse events, and mood ratings. Twenty-six patients were enrolled in the study. During treatment there were no significant changes in heart rate, blood pressure, cardiac conduction, or left ventricular ejection fraction, and there was a trend toward reduced ventricular ectopic activity. There were no changes in coagulation measures. Bleeding time increased in 12 patients, decreased in 4 patients, and was unchanged in 2 patients. Three (12%) patients withdrew from treatment prematurely because of adverse events. Significant improvements in mood ratings occurred over the course of treatment. CONCLUSIONS: Sertraline treatment was associated with clinical improvement and was well tolerated in >85% of the patients in this open-label treatment trial for patients with major depression after myocardial infarction. These results encourage further controlled trials to establish the effects of treatment for this high-risk population.

Glycyl-glutamine-enriched long-term total parenteral nutrition attenuates bacterial translocation following small bowel transplantation in the pig.

BACKGROUND: Improvements in immunosuppression, operative procedure, and posttransplant management have made clinical small bowel transplantation (SBT) feasible. Ischemia and reperfusion injury, total parenteral nutrition (TPN), and devoidment of enteral feeding lead to graft atrophy, gut barrier dysfunction, and bacterial translocation. Glutamine (Gln) is the principal fuel for the enterocyte. The influence of Gln dipeptide-supplemented TPN, especially long-term TPN, on intestinal graft permeability and bacterial translocation is not clear following SBT in the large animal model. Therefore, we studied the effect of glutamine dipeptide, glycyl-glutamine (Gly-Gln), on bacterial translocation following SBT in the pig, which has a physiology similar to humans. MATERIALS AND METHODS: The outbred pigs underwent segmental small bowel autotransplantation and were divided into two groups. In the STPN group (n = 5), the animal received standard TPN devoid of Gly-Gln for 28 days. In the GTPN group (n = 5), the animal received isonitrogenous (0.3 g/kg.day) and isocaloric (33 kcal/kg.day) TPN solution with 2% Gly-Gln for 28 days. RESULTS: At the end of the experiment, Gly-Gln-enriched TPN could maintain the plasma Gln level, graft mucosal Gln and protein concentrations, and skeletal muscle Gln and protein concentrations. Gly-Gln-enriched TPN significantly decreased the bacterial number of mesenteric lymph nodes in the liver and spleen and intestinal permeability to 99mTc-DTPA. There were no significant differences in body weight gain. CONCLUSIONS: The Gly-Gln-enriched long-term TPN may maintain the plasma Gln level, mucosal and muscle Gln, and protein concentrations and attenuate the intestinal permeability to 99mTc-DTPA and bacterial translocation following small bowel transplantation in the pig.

Naloxone and electroacunpunture (EA) improve the immune function of traumatized rats.

The present study was undertaken to examine the effects of intracerebroventricular (icv) injection of naloxone (an antagonist of opioid receptors) and electroacupuncture (EA) on the natural killer (NK) cell activity, lymphocyte proliferation and induction of interleukin-2 (IL-2) production of spleen lymphocytes of surgically traumatized rats. The NK cell activity, the spleen lymphocyte proliferation and the induction of IL-2 production were all significantly inhibited following traumatization. Compared to the traumatic group, the inhibition of the NK cell activity and the induction of IL-2 production were antagonised by icv injection of naloxone. EA stimulation of Zusanli (St 36) and Lanwei (Extra 33) points reduced the immunosuppression produced by trauma. The above results show that the central endogenous opioid peptidergic system may play an important role in immunosuppression. It is suggested that the endogenous opioid peptidergic system might act as an important modulatory system between CNS and the immune system.

Depression in patients with coronary artery disease.

Depression is more prevalent in patients with coronary artery disease (CAD) than in the general elderly population. Although CAD patients with depression have higher mortality rates, depression is often not recognized and treated in these patients. We administered structured psychiatric diagnostic interviews to 99 inpatients with CAD and diagnosed 23% with a major depressive episode (MDE) by DSM-IV criteria. Severity of medical illness and family history of psychopathology were indicators for increased risk for MDE. These findings may facilitate the recognition of CAD patients at greater risk for MDE.

Nucleotide sequence and expression of the genes for the alpha and beta subunits of phycocyanin in Cyanidium caldarium.

The nucleotide sequence of the plastid-encoded operon containing genes for the alpha (cpcA) and beta (cpcB) subunits of phycocyanin in the unicellular red alga Cyanidium caldarium is described. cpcB is located 5' to cpcA and the two genes are separated by a 102-bp spacer region. The transcription start site of cpcBA was mapped to 80 bp upstream of the ATG initiation codon of cpcB. Promoter-like elements similar to the -10 (TATAAT) and -35 (TTGACA) consensus promoters in bacteria were found 6 and 31 bp upstream of the transcription initiation site. Northern blotting revealed an abundant 1.3-kb cpcBA transcript in illuminated cells, but this transcript was undetectable in dark-grown cells. Expression levels of cpcBA in cells incubated with 10(-6) M heme in the dark were similar to those in cells illuminated for 24 h. Cells illuminated with 150 microM gabaculine (an inhibitor of delta-aminolevulinate synthesis) or 10 mM levulinic acid (an inhibitor of delta-aminolevulinate dehydrase) lacked detectable cpcBA transcripts. In cells illuminated with 200 microM N-methyl-mesoporphyrin IX (an inhibitor of ferrocheletase), inhibition of cpcBA expression and phycocyanin synthesis was similar. These results provide strong evidence that light induction of the cpcBA operon is dependent on synthesis of heme.