Spironolactone interference in the immunoassay of androstenedione.
In an evaluation of androstenedione results from patient serum samples using the Siemens Immulite 2500 analyser and manual Coat-A-Count (CAC) methods, three outliers were evident with grossly elevated results in the CAC assay. The clinic notes of three patients with apparently high serum androstenedione concentrations by the CAC assay were checked for medications. The samples were all from patients with polycystic ovary syndrome taking 100-200 mg/d of a steroidal antiandrogen (spironolactone). Two other patients on 50 mg spironolactone per day had less markedly higher androstendione results with the CAC assay. In a further five patients who were selected since they were on spironolactone and had high androstenedione results by the CAC method, spironolactone was temporarily withdrawn and fresh blood samples obtained for analysis. Spironolactone treatment was associated with higher androstenedione concentrations measured by the CAC assay that reverted to normal on treatment withdrawal. Based on a single test with spironolactone at 1000 ng/mL, the manufacturer reported only 0.109% interference in the CAC assay. Spironolactone (and/or its metabolites) may interfere in the Siemens CAC assay for androstenedione but not in the Immulite 2500 assay. This experience highlights the need for information from clinicians on drug treatment when laboratory investigations are requested. Drug interferences in immunoassay are common and need evaluation beyond tests performed to certify laboratory reagents.


Effects of neuropeptide Y on the response of isolated blood vessels to norepinephrine and sympathetic field stimulation.
Although neuropeptide Y (NPY) is not a potent vasoconstrictor in many vascular beds, nanomolar concentrations of this peptide can potentiate the response of isolated blood vessels to sympathetic stimulation or exogenous vasoconstrictors. In the isolated perfused rabbit ear artery, NPY produces a concentration-related potentiation of the response to field stimulation. The potency of NPY in inducing potentiation of nerve-mediated vasoconstriction was not dependent on whether the NPY was administered intra- or extraluminally. In these perfused vessels the endothelium was intact. Similar potentiation of the response to field stimulation is also observed in superfused ring segments of rabbit ear artery, provided that the endothelium was not damaged mechanically. The response to field stimulation in the rabbit ear artery is mediated by the alpha-1 adrenoceptor; in contrast, stimulation induced contraction in the canine saphenous vein results from the activation of vascular alpha-2-adrenoceptors. Despite this difference, the effect of NPY in ring segments of canine saphenous vein was similar to that observed in the ear artery. NPY also produced an endothelium-dependent potentiation of the constrictor response to exogenous norepinephrine in superfused segments of both ear artery and saphenous vein. Although the NPY-induced potentiation of stimulation-induced vasoconstriction was not inhibited by indomethacin, suggesting that an arachidonic acid metabolite is not involved, the release of another endothelial-derived vasoconstrictor substance, as yet unidentified, by NPY may explain its ability to potentiate the responses to both nerve stimulation and a variety of exogenous vasoconstrictors.


[Five years of DiabCare--France: assessment and outlook].
The Declaration of Saint Vincent was the starting point for the European DiabCare system. Five years of French experience with this system now provide an opportunity for critical assessment. Within the perspective of quality assurance, DiabCare is an efficient developmental tool which should eventually allow the divergence between real and ideal quality to be reduced. On the basis of a European scientific reference system, each country uses its own funds to organise national campaigns with the assistance of pharmaceutical firms. Each year a transverse collection of a month's data concerning all hospitalised diabetic patients is done at the European level by means of a standardised form. Confidential and anonymous analysis of the data is then performed by the scientific committee of DiabCare-France and the CERIM of Lille. Each participating physician receives a report specifying the situation for his group and providing anonymous comparisons with national data. This rich database offers each centre the possibility for "personalised" appraisal and retrospective evaluation of modifications in medical practices. DiabCare is in fact of interest to a variety of persons and organisations. For the patient, the DiabCare sheet and the forthcoming Diabcard (smart card) are means of providing guidance for the annual checkup. The general practitioner or specialist has indications about his patients' condition and guidance for more rigorous management. Interestingly, DiabCare is the only evaluation programme approved by general practitioner unions. For the hospital department, DiabCare provides much more detailed information than PMSI, offering a department head useful arguments in support of specific budget allocations and allowing the care team to consider its activity and determine priorities. It is a useful and precise evaluation tool for hospitals in the perspective of future accreditation. For the national and international scientific community, it provides data which, though biased by voluntary participation and non-epidemiological, are useful for analysis and comparison of particular diabetological circumstances in the field. In this respect, it is noteworthy that the World Health Organisation (WHO), the International Diabetes Federation, and the CSD have supported this initiative. For WHO, care practices and payment systems differ considerably in European countries, so that the existence of a common tool for collecting and evaluating data allows relevant procedures to be identified more quickly and communicated and recommended to the different governments. Finally, in view of the human and economic burden caused by late complications of diabetes, society can benefit. Any improvement in the control of risk factors and the objective reduction of complications is important for survival of the health care system.


Coffee dietary fiber contents and structural characteristics as influenced by coffee type and technological and brewing procedures.
Coffee brews contain considerable amounts of soluble dietary fiber, mainly low substituted galactomannans and type II arabinogalactans. Factors possibly influencing the content and structures of dietary fiber in coffee brews, such as type of coffee, roasting and grinding degree, and brewing procedure, were studied. In addition, several commercial samples such as instant espresso, instant coffee, instant cappuccino, decaffeinated coffees, and coffee pads were analyzed. The dietary fiber contents of the coffee brews ranged from 0.14 to 0.65 g/100 mL (enzymatic-gravimetric methodology), proving an influence of the factors investigated. For example, the drip brew of an arabica coffee contained significantly more soluble dietary fiber than the drip brew of a comparable robusta coffee, and depending on the brewing procedure, the soluble dietary fiber content of beverages obtained from the same coffee sample ranged from 0.26 to 0.38 g/100 mL. Dietary fiber contents of coffee brews were enhanced only up to a certain degree of roast. Drip brews of decaffeinated arabica coffees (commercial samples) contained significantly less dietary fiber than any non-decaffeinated drip brew investigated in this study. The observed differences in the dietary fiber contents were accompanied by changes in the structural characteristics of fiber polysaccharides, such as galactomannan/arabinogalactan ratio, galactose substitution degree of mannans, or galactose/arabinose ratio of arabinogalactans as analyzed by methylation analysis.


Bone cement modeling for percutaneous vertebroplasty.
Vertebroplasty procedures provide a significant benefit for patients suffering from vertebral fractures. In order to address current issues of vertebroplasty procedures, an injection device able to control the bone cement viscosity has been developed. In addition, this device allows to protect the practitioner by removing him/her from the X-rays area. In this context, a study is first proposed to quantify the bone cement viscosity during its polymerization reaction on a rotational rheometer. These experimental measurements have led to the identification of a complete behavior law that takes into account the simultaneous effects of shear rate, time, and temperature. Based on this preliminary study, this article finally aims to prove the ability of estimating the viscosity of the flowing bone cement on the developed injection system. A final set of experiments validates that the injection device dedicated to vertebroplasty procedures can control the flowing bone cement viscosity by acting on the temperature. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1504-1515, 2019.


Critical importance of the triplet lifetime of photosensitizer in photodynamic therapy of tumor.
The relation between the lifetimes of the triplet states of various porphyrins and their photosensitizing effects on the photodynamic therapy (PDT) of tumor has been examined. Diethylene-triamine pentaacetic acid ester of 4-[1-(2-hydroxy-ethyloxy)ethyl]-2-vinyl deuteroporphyrin-IX gallium (III) complex (Ga-DP), zinc (II) complex (Zn-DP), and manganese (III) complex (Mn-DP) and Photofrin II (PII) are used as the photosensitizer. The triplet lifetimes have been measured for the samples adsorbed on filter paper (FP) and found to be 57 ms (Ga-DP), 26 ms (Zn-DP), less than or equal to 10 microseconds (Mn-DP) and 9 ms (PII). The phosphorescence of Ga-DP in tumor-bearing golden hamsters are measured both in tumor tissue and in liver. They show bi-exponential decay with the lifetimes of about 5 and 20 ms. From the values, the generation rate, kct[3O2], of singlet molecular oxygen in living animal tissue may be estimated to be an order of 10(2) s-1. The PDT effects have been quantitatively investigated for in vitro experiments; upon irradiation the growth inhibitions of mouse p388 leukemia cells are obtained as a function of concentration of Ga-DP, Zn-DP, Mn-DP and PII. The experimental results indicate that the PDT effects depend essentially on the triplet lifetimes of the photosensitizers.


Exploring corrective experiences in a successful case of short-term dynamic psychotherapy.
The concept of corrective emotional experience, originally formulated by psychoanalysts Alexander and French (1946), has been redefined by contemporary researchers to be theoretically nonspecific, that is, as "coming to understand or experience an event or relationship in a different or unexpected way" (Castonguay & Hill, 2011). Using postsession questionnaires, videotapes, and posttermination interviews, we explored whether (and how) a corrective experience occurred in a successful case of short-term dynamic psychotherapy (STDP; Davanloo, 1980). A 35-year-old woman suffering severe panic attacks was seen for 31 sessions by an experienced STDP therapist. The questionnaires and interviews focused on (a) perceived intrapsychic and interpersonal changes, and (b) how these changes came about. At termination, the client reported complete symptom relief, greater self-acceptance, improved relationships, and more emotional flexibility. Her corrective experience was evident in the qualitative themes, which showed that she came to understand and affectively experience her relationships with both parents differently. Moreover, the themes reflected both STDP-specific (e.g., confrontation of defenses) and nonspecific (e.g., rapport, acceptance) mechanisms of change. Conversation analysis (Sacks, 1995) of what the client described as "the 'gentle shove' of questions that make me see what I have been trying to ignore since childhood" showed, on a microlinguistic level, how she overcame resistance to strong emotional experience and expression.


Oestrogen production by blastocyst and early embryonic tissue of various species.
Oestrogen synthesis by the early embryo in vitro was studied with tissue from pigs, sheep, cows, roe deer, ferrets, cats, rabbits and a plains viscacha. Definitive evidence for aromatase activity and oestrogen synthesis in preimplantation trophoblast was obtained for the pig with the formation of oestrone, oestradiol-17 beta and oestradiol-17 alpha from 3H-labelled androstenedione and dehydroepiandrosterone. Aromatase activity was appreciably lower in all other species studied, and labelled oestrogens were recovered only from incubations of allantochorionic tissue of roe deer, recovered shortly after implantation, and from pooled samples of early embryonic tissue of cows. High aromatase activity in preimplantation trophoblast of pigs was associated with the maternal recognition of pregnancy and the occurrence of superficial implantation in this species.


Autografting followed by nonmyeloablative immunosuppressive chemotherapy and allogeneic peripheral-blood hematopoietic stem-cell transplantation as treatment of resistant Hodgkin's disease and non-Hodgkin's lymphoma.
To investigate the use of a nonmyeloablative fludarabine-based immunosuppressive regimen to allow engraftment of HLA-sibling donors' mobilized stem cells and induction of a graft-versus-lymphoma effect for patients with advanced resistant Hodgkin's disease and non-Hodgkin's lymphoma. Fifteen patients with Hodgkin's disease (n = 10) and non-Hodgkin's lymphoma (n = 5) were studied. All patients received cyclophosphamide and granulocyte colony-stimulating factor to mobilize autologous hematopoietic stem cells (HSCs). Subsequently, they received high-dose therapy with carmustine, etoposide, cytarabine, and melphalan and reinfusion of HSCs. At a median of 61 days after engraftment, patients were given fludarabine 30 mg/m(2) with cyclophosphamide 300 mg/m(2) daily for 3 days. Donor-mobilized HSC collections were prepared for fresh infusion and were not T-cell depleted. Methotrexate and cyclosporine were used to prevent graft rejection and as graft-versus-host disease (GVHD) prophylaxis. Combined treatment was well tolerated. After mini-allografting, hematologic recovery was prompt. Thirteen patients had 100% donor cell engraftment. Eleven patients achieved complete remission (CR) after the combined procedure. Nine patients, who were in partial remission after autografting, achieved CR after mini-allografting. Seven patients developed >/= grade 2 acute GVHD (aGVHD) and two developed extensive chronic GVHD (cGVHD). Three patients who received the highest number of donor lymphocyte infusions (DLIs) developed grade 3 GVHD (two patients) and extensive cGVHD (one patient). Ten patients are currently alive, and five are in continuous CR. Seven patients received DLI, with five CRs. Five patients died: one of progressive disease, two of progressive disease combined with aGVHD or cGVHD, one of extensive cGVHD, and one of infection. Fludarabine/cyclophosphamide was well tolerated and allowed consistent engraftment in lymphoma allografted patients. Response rates were high in this group of refractory and heavily pretreated patients. This dual procedure seems to be most promising in patients with end-stage malignant lymphomas.


Ultrasonic degradation of aqueous phenolsulfonphthalein (PSP) in the presence of nano-Fe/H2O2.
In this study, nano iron (nano-Fe) was successfully synthesized by sodium borohydride reduction of ferric chloride solution to enhance the ultrasonic degradation of phenolsulfonphthalein (PSP). The nano-Fe was characterized by scanning electron microscopy - energy dispersive spectroscopy (SEM-EDX), transmission electron microscopy (TEM), powder X-ray diffraction (XRD), attenuated total reflection - Fourier transform infrared spectroscopy (ATR-FTIR), and Brunauer, Emmett and Teller (BET) surface area determination. Experimental results demonstrated that a combined ultrasonic/nano-Fe/H2O2 system was more effective for PSP removal in combination than they were individually and there was a significant difference between the combined and single processes. The ultrasonic/nano-Fe/H2O2 degradation follows the Langmuir-Hinshelwood (L-H) kinetic model. The addition of nano-Fe and H2O2 to the ultrasonic reactor greatly accelerated the degradation of PSP (25 mg/L) from 12.5% up to 96.5%. These findings indicated that ultrasonic degradation in the presence of nano-Fe and H2O2 is a promising and efficient technique for the elimination of emerging micropollutants from aqueous solution.


Discrepancies between dimensions of interoception in autism: Implications for emotion and anxiety.
Emotions and affective feelings are influenced by one's internal state of bodily arousal via interoception. Autism Spectrum Conditions (ASC) are associated with difficulties in recognising others' emotions, and in regulating own emotions. We tested the hypothesis that, in people with ASC, such affective differences may arise from abnormalities in interoceptive processing. We demonstrated that individuals with ASC have reduced interoceptive accuracy (quantified using heartbeat detection tests) and exaggerated interoceptive sensibility (subjective sensitivity to internal sensations on self-report questionnaires), reflecting an impaired ability to objectively detect bodily signals alongside an over-inflated subjective perception of bodily sensations. The divergence of these two interoceptive axes can be computed as a trait prediction error. This error correlated with deficits in emotion sensitivity and occurrence of anxiety symptoms. Our results indicate an origin of emotion deficits and affective symptoms in ASC at the interface between body and mind, specifically in expectancy-driven interpretation of interoceptive information.


Morphofunctional alterations of the nonpregnant murine uterus in response to intense and exhaustive exercise are not related to oxidative stress.
Exercise is a common and noninvasive way to improve human health. In contrast, intense exercise causes damage in various tissues and is usually associated with metabolic changes in organs and tissues. Even though intense exercise is associated with dysfunctions in the female reproductive system, much less is known about the cellular mechanisms underlying its effects particularly on the nonpregnant uterus. We investigated whether the effects of an intense and exhaustive exercise (IEE) program on the isolated C57BL/6 uterine morphology and contractility might be related to increased levels of prooxidation markers. Female mice were submitted to 2 days of IEE. The daily exercise session consisted of a running session until exhaustion, with the treadmill speed set at 85% of each animal's maximum velocity. Training responses were evaluated through two parameters: time to exhaustion and maximum velocity. Absence of exercise-induced hypothalamic-pituitary-adrenal (HPA) axis activation was indirectly evaluated by maintenance of the adrenal gland weight. IEE reduced the thickness of the longitudinal muscular layer by 10%, impaired contractility in response to muscarinic stimulation (increased EC50 and decreased Emax), but showed a strong trend to decreasing the KCl-induced contraction; reduced lipid peroxidation; and did not alter the uterine protein oxidation of exercised animals compared with control. Altogether we provide evidence for the nonpregnant murine uterus being an important target to IEE, leading to morphofunctional alterations which could not be associated with tissue oxidative stress but might well be related with exercise-induced uterine dysfunctions.


Glucuronidation in the Caco-2 human intestinal cell line: induction of UDP-glucuronosyltransferase 1*6.
The ability of the differentiated human intestinal cell line, Caco-2, to glucuronidate various endobiotic and xenobiotic molecules was investigated. Glucuronidation of hydroxylated or carboxylic acid compounds such as 1-naphthol, thymol, androsterone, estriol, hyodeoxycholic acid, lithocholic acid, chloramphenicol, paracetamol and morphine could be determined in microsomal fractions of Caco-2 cells. The activity toward 1-naphthol was the highest glucuronidation activity measured in Caco-2 cells. This activity was specifically increased four-fold upon addition of beta-naphthoflavone into culture medium but not by rifampicine or clofibrate and was related to a biosynthesis of UDP-glucuronosyltransferase 1*6 (UGT1*6). alpha-Naphthoflavone did not affect the inducing property of beta-naphthoflavone. 7-Ethoxyresorufin-O-dealkylation activity, supported by cytochrome P4501A1, was induced more than 1000-times in Caco-2 cells by beta-naphthoflavone treatment, and this effect was partially abolished by alpha-naphthoflavone treatment. The results suggest that several isoforms, including UGT1*6, are expressed in Caco-2 cells.


Angiogenesis and signal transduction in endothelial cells.
Endothelial cells receive multiple information from their environment that eventually leads them to progress along all the stages of the process of formation of new vessels. Angiogenic signals promote endothelial cell proliferation, increased resistance to apoptosis, changes in proteolytic balance, cytoskeletal reorganization, migration and, finally, differentiation and formation of a new vascular lumen. We aim to review herein the main signaling cascades that become activated in angiogenic endothelial cells as well as the opportunities of modulating angiogenesis through pharmacological interference with these signaling mechanisms. We will deal mainly with the mitogen-activated protein kinases pathway, which is very important in the transduction of proliferation signals; the phosphatidylinositol-3-kinase/protein kinase B signaling system, particularly essential for the survival of the angiogenic endothelium; the small GTPases involved in cytoskeletal reorganization and migration; and the kinases associated to focal adhesions which contribute to integrate the pathways from the two main sources of angiogenic signals, i.e. growth factors and the extracellular matrix.


A technique for concomitant whole duodenopancreatectomy and hepatectomy for transplantation in the multiple organ donor.
A technique for removing both the liver and whole pancreas from multiple organ donors weighing 30 kilograms was described. All organs removed have had satisfactory primary function. It is hoped that popularization of this technique will permit the obtaining of more whole pancreases for transplantation.


[A method of reconstructing coronary stent and lumen image using zero cross point image for the purpose of improving sharpness].
Our purpose was to improve the sharpness of the coronary stent and lumen. We reconstructed volume rendering (VR) image and maximum intensity projection (MIP) images using the original image and a sharpened operator image with 8-neighbor Laplacian filter. The most suitable center number was 9, and the circumferential number was -1 on the sharpened operator image with 8-neighbor Laplacian filter. In the same way, the most suitable spatial filter was the FC43. VR and MIP images showed sharp stents. The VR image and MIP image fused the original image and sharpened the operator image with the 8-neighbor Laplacian filter, resulting in a clear lumen. The 8-neighbor sharpened operator image with 8-neighbor Laplacian filter was attached to the Aquilion64, and this method did not require extra hardware and software for reconstructing images of the stent and lumen.


Statistical interferometry based on a fully developed speckle field: an experimental demonstration with noise analysis.
A novel interferometric method named statistical interferometry is proposed and studied. In the method, in contrast to the conventional deterministic interferometry, the complete randomness of the two interfering light fields, i.e., the random interference of the fully developed speckle fields, plays an essential role and is used as a standard of phase in a statistical sense. Preliminary experiments were conducted to verify the validity of the method, followed by a computer simulation. As an experimental result, the accuracy of the measurements of an out-of-plane displacement was confirmed up to lambda/800 by comparison with the heterodyne interferometer. The method has the advantage of simplicity of the optical system required, while at the same time providing high accuracy.


A peptide histidine isoleucine/peptide histidine methionine-like peptide in the rabbit retina: colocalization with vasoactive intestinal peptide, synaptic relationships and activation of adenylate cyclase activity.
Antisera against peptide histidine isoleucine and peptide histidine methionine were found to label a subpopulation of amacrine and displaced amacrine cells in the rabbit retina with processes ramifying in sublaminas 1, 3 and 5 of the inner plexiform layer. Preadsorption controls demonstrated that this immunoreactivity was specific for a peptide histidine isoleucine- or peptide histidine methionine-like (peptide histidine isoleucine/peptide histidine methionine-like) peptide, and was not caused by cross-reactivity of the peptide histidine isoleucine or peptide histidine methionine antibodies with vasoactive intestinal peptide vasoactive intestinal peptide. In double-label studies, vasoactive intestinal peptide and peptide histidine isoleucine/peptide histidine methionine-like immunoreactivity were colocalized in the same population of retinal neurons. Electron microscopic analysis revealed that the peptide histidine isoleucine/peptide histidine methionine-labelled cells interacted with processes of bipolar cells, amacrine cells and ganglion cells. Peptide histidine methionine and peptide histidine isoleucine were slightly less potent than vasoactive intestinal peptide in stimulating adenylate cyclase activity in the rabbit retina, while the related peptides secretin, glucagon, and the C-terminal vasoactive intestinal peptide fragment, vasoactive intestinal peptide (10-28), showed little or no stimulatory activity. Stimulation of adenylate cyclase by high concentrations of vasoactive intestinal peptide and peptide histidine methionine were non-additive. These results suggest that a peptide histidine isoleucine/peptide histidine methionine-like peptide may function as a neuroactive peptide in the mammalian retina, and that this peptide appears to be cosynthesized and colocalized with vasoactive intestinal peptide and to mimic the activity of vasoactive intestinal peptide through interaction with vasoactive intestinal peptide receptor-adenylate cyclase complexes.


Serological abnormalities in families of patients with rheumatoid arthritis: eight to twelve years follow-up study.
Serum gammaglobulin level, the presence of rheumatoid factor and of anti-nuclear antibodies were re-examined after 8 to 12 years in families of 21 seropositive rheumatoid arthritis patients. In the time 8 members of the families developed rheumatoid arthritis and the number of persons with elevated serum gammaglobulins increased. Rheumatoid tests yielded variable results. No relationship could be demonstrated between development of disease symptoms and the earlier presence of rheumatoid factor.


Mouse peritoneal macrophages plated on mannan- and horseradish peroxidase-coated substrates lose the ability to phagocytose by their Fc receptors.
Ligand-conjugated substrates were used to study mouse macrophage receptor-ligand interactions. Both resident and thioglycollate-elicited macrophages plated on substrates conjugated with mannans and horseradish peroxidase (HRP), ligands for the Man/GlcNAc receptor, lost their ability to phagocytose zymosan. In addition, these macrophages also lost their ability to phagocytose IgG-coated erythrocytes (E(IgG] via their Fc receptors (FcR). The abrogation of Fc receptor-mediated phagocytosis occurred as early as 4 hr after macrophage plating on HRP-coated substrates and was dependent on the amount of HRP conjugated to the substrate. Macrophages plated on those substrates showed a 70% reduction in E(IgG) binding and the same decrease (approximately 35%) in binding of 125I-labeled Fab fragment of monoclonal anti-IgG2b FcR antibody as macrophages plated on dinitrophenyl-anti-dinitrophenyl IgG immune complexes. We interpret these results as showing that modulation of macrophage mannose/GlcNAc receptors induces modulation of FcR.


Neuropeptide FF selectively attenuates the effects of nociceptin on acutely dissociated neurons of the rat dorsal raphe nucleus.
Intracellular Ca2+ concentration ([Ca2+]i) was measured in neurons, acutely dissociated from the rat dorsal raphe nucleus (DRN), with the fluorescent calcium probe Fluo3. Nociceptin (300 nM) had no effect on resting [Ca2+]i but reduced the magnitude of the [Ca2+]i transient triggered by depolarization in 90% of neurons having polygonal or fusiform perikarya. In 94% of neurons with the same morphology 5-HT (30 microM) also reduced the magnitude of the [Ca2+]i transient. The selective 5-HT(1A) receptor antagonist 4-iodo-N-[2-[4-(methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-ben zamide hydrochloride (p-MPPI) (0.4 microM) strongly attenuated (by 72+/-7%, n=4) this effect. The responses to nociceptin and 5-HT were not affected by BaCl2 (100 microM). The neuropeptide FF analog [D-Tyr1, (N-Me)Phe3]NPFF (1DMe) altered neither the resting [Ca2+]i nor the [Ca2+]i transient triggered by depolarization but dose-dependently decreased the effect of nociceptin (EC50=1.8 nM, maximal reduction: 68+/-5%). 1DMe had no effect on the response to 5-HT. Another neuropeptide FF analog, exhibiting a different pharmacological activity in mice and rats, [D-Tyr1, D-Leu2, D-Phe3]NPFF (1 microM) also reduced the effect of nociceptin by 74+/-11% (n=4). Few neurons (5 out of 42), either with polygonal/fusiform or smaller ovoid cell bodies, responded to the mu-opioid receptor agonist [D-Ala2, (N-Me)Phe4, Gly-ol5]-enkephalin (DAGO) with a decrease in the depolarization-induced [Ca2+]i transient. 1DMe (100 nM) attenuated this response by 69+/-14%. These results suggest that, at the cellular level, neuropeptide FF selectively counteracts the effects of opioid receptor activation.


Grammatical agreement processing in reading: ERP findings and future directions.
In the domain of written sentence comprehension, the computation of agreement dependencies is generally considered as a form-driven processing routine whose domain is syntactic in nature. In the present review we discuss the main findings emerging in the Event-Related Potential (ERP) literature on sentence comprehension, focusing on the different dimensions of agreement patterns (features, values, constituents involved and language): Agreement mismatches usually evoke a biphasic electrophysiological pattern (Left Anterior Negativity - LAN, 300-450 msec and P600 after 500 msec). This ERP pattern is assumed to reflect rule-based computations sensitive to formal (inflectional) covariations of related words (trigger-target). Here we claim that agreement processing is sensitive to both the type of feature involved and the constituents that express the agreement dependency. More specifically, LAN could reflect violation of expectancy (elicited by the trigger) for the target functional morphology; later, trigger and target are structurally integrated at the sentence level (early P600). However, morphosyntactic information could trigger the activation of higher-level representations that are not strictly syntactic in nature. The recruitment of this additional non-syntactic information (mirrored by N400-like effects) indicates that rule-based computations of agreement dependencies are not blind to non-syntactic information but are often recruited to establish sentence-level relations.


Precision calculation of blackbody radiation shifts for optical frequency metrology.
We show that three group IIIB divalent ions, B(+), Al(+), and In(+), have anomalously small blackbody radiation (BBR) shifts of the ns(2) (1)S(0)-nsnp (3)P(0)(o) clock transitions. The fractional BBR shifts for these ions are at least 10 times smaller than those of any other present or proposed optical frequency standards at the same temperature, and are less than 0.3% of the Sr clock shift. We have developed a hybrid configuration-interaction + coupled-cluster method that provides accurate treatment of correlation corrections in such ions and yields a rigorous upper bound on the uncertainty of the final results. We reduce the BBR contribution to the fractional frequency uncertainty of the Al(+) clock to 4×10(-19) at T=300 K. We also reduce the uncertainties due to this effect at room temperature to 10(-18) level for B(+) and In(+) to facilitate further development of these systems for metrology and quantum sensing.


Development of a target-directed magnetic resonance contrast agent using monoclonal antibody-conjugated magnetic particles.
We developed a novel magnetic resonance (MR) imaging contrast agent, MAb-magnetite, that was prepared by covalently linking polyethylene glycol-coated magnetite to a monoclonal antibody specific for a human glioma cell-surface antigen. When MAb-magnetite was injected intravenously into tumor-bearing nude mice at a dose of 100 mumol Fe/kg body weight, a 50% decrease in the T2 signal intensity of the tumor was observed, immediately following administration and continued for 48 h. Microscopic observation of the tumor tissue demonstrated localization of MAb-magnetite in cancer cells. These results suggest that MAb-magnetite is a promising agent for MR imaging of neoplasms.


Signal transduction pathways associated with ATP-induced proliferation of colon adenocarcinoma cells.
In previous work, we have demonstrated that extracellular adenosine 5'-triphosphate (ATP) acts on intestinal Caco-2 cell P2Y receptors promoting a rapid increase in the phosphorylation of ERK1/2, p46 JNK and p38 MAP kinases (MAPKs). In this study, we investigated whether the extracellular ATP-P2Y receptor signalling pathways were required for the proliferation of Caco-2 cells. Confocal microscopy and immunobloting studies showed that ERK1/2 and JNK translocate into the nucleus of the cells stimulated by ATP, where they participate, together with p38 MAPK, in the phosphorylation of JunD, ATF-1 and ATF-2 transcription factors. In addition, ATP through the activation of MAPKs induces the expression of the immediate early genes products of the Jun family, c-Fos and MAP kinase phosphatase-1 (MKP-1). Moreover, ERK1/2 and p38 MAPK are involved in the phosphorylation of MKP-1 in Caco-2 cells. Of physiological significance, in agreement with the mitogenic role of the MAPK cascade, ATP increased Caco-2 cell proliferation, and this effect was blocked by UO126, SB203580 and SP600125, the specific inhibitors of ERK1/2, p38 MAPK and JNK1/2, respectively. Extracellular ATP induces proliferation of Caco-2 human colonic cancer cells by activating MAPK cascades and modulation of transcription factors. These findings and identification of the specific P2Y subtype receptors involved in the mitogenic effect of ATP on Caco-2 cells might be relevant for understanding tumor cell development, resistance to treatment regimens and the design of new therapeutic strategies.


Statin use in the metabolic syndrome.
The metabolic syndrome is a condition associated with obesity, insulin resistance, hypertension, dyslipidemia, hypercoagulability, and chronic inflammation, all of which increase the risk of cardiovascular disease (CVD). The Third National Cholesterol Education Program Adult Treatment Panel extensively discussed the metabolic syndrome because it is a major health issue in the United States due to the national epidemic of obesity. Statins cause significant CVD risk reduction in patients with the metabolic syndrome by alterations in lipid levels and possibly by decreasing inflammation. Because of the increased CVD risk associated with the metabolic syndrome and extensive clinical trial evidence documenting reduction of CVD risk with statin treatment, all patients with the metabolic syndrome should be evaluated as candidates for statin treatment as part of a multidisciplinary approach to reduce CVD risk.


Occurrence of organochlorine pesticides residue in Kuano river of eastern Uttar Pradesh.
Organochlorine pesticides residue (isomers of HCH alpha, beta, gamma and DDT) in Kuano river water at pre-monsoon and post-monsoon period were analyzed for the period June, 2004 to May, 2006 by TLC method. Results indicated that presence of isomers of HCH (alpha, beta, gamma) and DDT in both the study years even though the usage of both these pesticides is restricted. The higher concentration of pesticide was found in post monsoon. The total concentration of HCH ranges from 0.0002 to 0.020 microg l(-1) and 0.0002 to 0.009 microg l(-1) and total DDT concentration ranged from 0.0009 to 0.003 microg l(-1) and 0.00 to 0.0010 microg l(-1) during first and second year of study respectively. No temporal or spatial distribution pattern was found perhaps due to presence of multiple and aleatory sources. In most of the samples the pesticides residues detected were much higher than drinking water quality standards. It can be inferred that the environment maybe considerably degraded by these compounds, providing additional impact to the biota and bringing a potential risk to human health. More detailed Monitoring/studies have to be carried out on different months with a wider spectrum of pesticides to get a clear base line data for the entire location.


Signaling pathway factors expression in renal tissue of apoE-knockout mice.
Apolipoprotein E (apoE) is regarded as one of the major plasma lipoproteins, and it plays an important role in the transport and metabolism of lipids. apoE can be found in multiple tissues, such as liver, kidney, jejunum, urinary bladder, ileum, colon, brain, adrenal glands, lung, ovary, spleen, pancreas, and testis, etc. As a secreted protein, it plays an important role in the systemic lipoprotein metabolism and vascular wall homeostasis and in the pathogenesis of renal diseases. apoE-knockout (apoE(-/-)) mice is a classic model of atherosclerosis and renal diseases. However, no review summed up the signaling pathway factors expression in renal tissue of apoE-knockout mice. The literatures were searched extensively and this review was performed to review the signaling pathway factors expression in renal tissue of apoE-knockout mice.


Biosorption of lead(II) and cadmium(II) by protonated Sargassum glaucescens biomass in a continuous packed bed column.
Biosorption of lead(II) and cadmium(II) from aqueous solutions by protonated Sargassum glaucescens biomass was studied in a continuous packed bed column. The selective uptake of Pb2+ and Cd2+ was investigated in a binary system with initial concentration of 1 mM for each metal ion. The selective uptake capacities of Pb2+ and Cd2+ at complete exhaustion point were obtained 1.18 and 0.22 mmol/g, respectively; therefore, the biosorbent showed much higher relative affinity for Pb2+ than for Cd2+. The optimum range of empty bed contact time (EBCT) was identified as 5-10 min in the packed bed column. The efficiency of biosorbent regeneration by 0.1 M HCl was achieved about 60%, so that the maximum uptake capacity of Pb2+ by the regenerated biomass was determined to be 0.75 mmol/g while the same value for the original biomass was 1.24 mmol/g. The Thomas model was found in a suitable fitness with the experimental data (R2 > 0.90 and % < 50%) at all different operation stages. Monitoring of pH in the effluent of the column presented the simultaneous release of H+ with the uptake of heavy metals; hence, ion exchange was confirmed to be one of the main biosorption mechanisms.


Factors associated with delays in accessing HIV primary care in rural Arkansas.
While debate continues at what stage of human immunodeficiency virus (HIV) disease to begin combination antiretroviral therapy, a number of clinical and public health benefits are linked to early entry into primary care soon after first testing HIV positive. However, HIV-infected patients continue to test late and delay entry into care. We used routinely collected demographic and clinical information to examine which factors are associated with delays in seeking care in a predominantly rural, economically poor area of Arkansas. The study population is 75% African American and male and 70% lack health insurance; nearly one fourth were referred from prison. At diagnosis, two thirds of the population had CD4 counts below 500 cells per microliter. Days from initial HIV diagnosis to entry into care declined from a median of 178 in 1994 to 24 in 1998. In 1998, 75% of the population entered into primary care within 2 months of diagnosis. However, CD4 counts at HIV diagnosis also declined in this period, from a median of 427 in 1995 to 208 cells per microliter in 1998. More recent year of diagnosis was associated with a shorter delay in seeking care; males, and individuals lacking health insurance took significantly longer to enter into care than females and those with insurance, respectively. Our univariate finding of extensive delays in seeking care in the prison population did not hold in the multivariate analysis. We found significant delays in time to initial HIV diagnosis, and further considerable delays in males and those lacking health insurance in the time taken to enter into primary care.


Gelsolin amyloid angiopathy causes severe disruption of the arterial wall.
Hereditary gelsolin amyloidosis (HGA) is a dominantly inherited systemic disease reported worldwide. HGA is characterized by ophthalmological, neurological, and dermatological manifestations. AGel amyloid accumulates at basal lamina of epithelial and muscle cells, thus amyloid angiopathy is encountered in nearly every organ. HGA patients have cardiovascular, hemorrhagic, and potentially vascularly induced neurological problems. To clarify pathomechanisms of AGel angiopathy, we performed histological, immunohistochemical, and electron microscopic analyses on facial temporal artery branches from 8 HGA patients and 13 control subjects. We demonstrate major pathological changes in arteries: disruption of the tunica media, disorganization of vascular smooth muscle cells, and accumulation of AGel fibrils in arterial walls, where they associate with the lamina elastica interna, which becomes fragmented and diminished. We also provide evidence of abnormal accumulation and localization of collagen types I and III and an increase of collagen type I degradation product in the tunica media. Vascular smooth muscle cells appear to be morphologically and semi-quantitatively normal, only their basal lamina is often thickened. In conclusion, angiopathy in HGA results in severe disruption of arterial walls, characterized by prominent AGel deposition, collagen derangement and severe elastolysis, and it may be responsible for several, particularly hemorrhagic, disease manifestations in HGA.


Influence of vesicular storage and monoamine oxidase activity on [11C]phenylephrine kinetics: studies in isolated rat heart.
[11C]Phenylephrine (PHEN) is a radiolabeled analogue of norepinephrine that is transported into cardiac sympathetic nerve varicosities by the neuronal norepinephrine transporter and taken up into storage vesicles localized within the nerve varicosities by the vesicular monoamine transporter. PHEN is structurally related to two previously developed sympathetic nerve markers: [11C]-meta-hydroxyephedrine and [11C]epinephrine. To better characterize the neuronal handling of PHEN, particularly its sensitivity to neuronal monoamine oxidase (MAO) activity, kinetic studies in an isolated working rat heart system were performed. Radiotracer was administered to the isolated working heart as a 10-min constant infusion followed by a 110-min washout period. Two distinctly different approaches were used to assess the sensitivity of the kinetics of PHEN to MAO activity. In the first approach, oxidation of PHEN by MAO was inhibited at the enzymatic level with the MAO inhibitor pargyline. In the second approach, the two hydrogen atoms on the a-carbon of the side chain of PHEN were replaced with deuterium atoms ([11C](-)-alpha-alpha-dideutero-phenylephrine [D2-PHEN]) to inhibit MAO activity at the tracer level. The importance of vesicular uptake on the kinetics of PHEN and D2-PHEN was assessed by inhibiting vesicular monoamine transporter-mediated storage into vesicles with reserpine. Under control conditions, PHEN initially accumulated into the heart at a rate of 0.72+/-0.15 mL/min/g wet. Inhibition of MAO activity with either pargyline or di-deuterium substitution did not significantly alter this rate. However, MAO inhibition did significantly slow the clearance of radioactivity from the heart during the washout phase of the study. Blocking vesicular uptake with reserpine reduced the initial uptake rates of PHEN and D2-PHEN, as well as greatly accelerated the clearance of radioactivity from the heart during washout. These studies indicate that PHEN kinetics are sensitive to neuronal MAO activity. Under normal conditions, efficient vesicular storage of PHEN serves to protect the tracer from rapid metabolism by neuronal MAO. However, it is likely that leakage of PHEN from the storage vesicles and subsequent metabolism by MAO lead to an appreciable clearance of radioactivity from the heart.


5-fluorouracil-related gene expression levels in primary colorectal cancer and corresponding liver metastasis.
Gene expression levels of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP) and orotate phosphoribosyl transferase (OPRT) have been shown to be associated with response to 5-fluorouracil-based therapies. Analyzing these gene expression levels in liver metastases is important to obtain the best prediction of therapy. Our aim was to determine how TS, DPD, TP and OPRT gene expression levels in primary colorectal cancer (CRC) were related to those in liver metastases. Formalin-fixed, paraffin-embedded tumor specimens from 31 pairs of primary CRC and corresponding liver metastases were dissected by using laser-captured microdissection. RNA was extracted and cDNA was prepared by reverse-transcription. Quantitation of target gene and internal reference gene was performed using real-time PCR. No significant difference was seen between median mRNA expression levels of TS, DPD, TP and OPRT in primary cancer and those in corresponding liver metastases (median value: TS 1.48 vs. 1.43; p=0.92, DPD 0.19 vs.0.12; p=0.10, TP 1.20 vs. 0.98; p=0.39, OPRT 1.17 vs. 0.95; p=0.10). When matched tissue sets were compared on an individual basis, there was a significant correlation for TS mRNA expression between primary cancer and corresponding liver metastases (rs=0.52, p=0.0026). However, no correlation was seen between matched sets for DPD, TP or OPRT. Significant correlation was seen between DPD and TP expression levels in both primary CRC (rs=0.38, p=0.03) and liver metastases (rs=0.72, p<0.0001). A good prediction of TS mRNA levels in liver metastases can be obtained by measuring those of primary CRC, although no correlation was seen for DPD, TP and OPRT.


[Roles of CCAAT enhancer binding protein α in acute myeloblastic leukemia].
The CCAAT enhancer binding protein α (C/EBP α:p42 and p30),which encoded by CCAAT enhancer binding protein α (C/EBPα) gene,plays a pretty crucial role in the regulation of myeloid hematopoiesis.The disorder of CEBPA gene expression is an pivotal mechanism of acute myeloid leukemia (AML). The result of uncontrolled expression of C/EBP α gene is the over-expression of p30 and the incomplete loss of p42, both of which contribute to the occurrence of AML. Restoring the expression ratio of C/EBP α such as over-expression of p42 or blocking the carcinogenic pathway of p30 seems to be important for the treatment of AML caused by such causes. In order to better guide medical decision-making, this article reviews research progress on C/EBPα in the pathogenesis of AML.


Measurements and trend analysis of O2, CO2 and delta13C of CO2 from the high altitude research station Junfgraujoch, Switzerland--a comparison with the observations from the remote site Puy de Dôme, France.
Atmospheric O2 and CO2 flask measurements from the high altitude research station Jungfraujoch, Switzerland, and from the observatory at Puy de Dôme, France, are presented. Additionally, the Jungfraujoch delta13C record of CO2 is discussed. The observations on flask samples collected at the Jungfraujoch station show, since 2003, an enhancement of the oxygen trend which amounts to about 45 per meg/year with a corresponding CO2 increase of around 2.4 ppm/year. This enhancement is comparable with that observed at the Puy de Dôme station where oxygen, since mid 2002, has decreased with a rate of about 50 per meg/year whilst the CO2 increase was of around 1.7 ppm/year but exhibiting a higher variability. Several processes influence deltaO2/N2. However, these processes are marked with different oxidation ratios (O2:CO2) that can be used to distinguish them. The apparent slopes calculated from correlation plots between de-trended CO2 and deltaO2/N2 records as well as between corresponding trends are significantly larger than the observe ratios depending on processes within the ocean, it is to our understanding the only possibility to explain our observations. The stability of the deltaO2/N2 scale is critical in this regard, therefore, it is addressed here and we found no significant scale drift which would influence our trend calculations. In our view more important are criterions on the data selection before trend analysis.


Preoperative staging, prognostic factors, and outcome for extremity rhabdomyosarcoma: a preliminary report from the Intergroup Rhabdomyosarcoma Study IV (1991-1997).
During the fourth Intergroup Rhabdomyosarcoma (RMS) Study (IRS IV, 1991-97), a preoperative staging system was evaluated prospectively for the first time. The authors evaluated this staging system and the role of surgery in extremity RMS in contemporary multimodal therapy. A total of 139 patients (71 girls; median age, 6 years) were entered in IRS IV with extremity-site RMS. Stage was assigned by the IRSG Preoperative Staging System. Postsurgical group was determined by tumor status after initial surgical intervention. Multivariate analysis was performed using all pretreatment factors that were significant by univariate analysis, including clinical Group (i.e., I through IV), tumor invasiveness (T1,T2), nodal status (N0,N1), and tumor size (< or > or =5 cm). Failure-free survival rates (FFS) and survival rates were estimated using the Kaplan and Meier method. Preoperative staging and clinical group distribution were as follows: Stage 2, n = 34; Stage 3, n = 73; Stage 4, n = 32; Group I, n = 31; Group II, n = 21; Group III, n = 54; Group IV, n = 33. Three-year FFS was 55%, and the overall survival rate was 70%. Eighty-seven patients had either unresectable, gross residual disease (Group III) or metastases (Group IV). FFS was significantly worse for these patients with advanced disease, compared with that for patients with complete resection or with only microscopic residual tumor (i.e., Group I or II; Group I, 3-year FFS, 91%; Group II, 72%; Group III, 50%; Group IV, 23%; P<.001). Lymph nodes were evaluated surgically in 76 patients with positive results in 38. Clinically, 13 additional patients had nodal disease. Both stage and group were highly predictive of outcome and were highly correlated. By multivariate analysis, none of the other variables were predictors of FFS. This review confirms the utility of pretreatment staging for stratification of patients with extremity RMS with widely different risks of relapse, thereby paving the way for development of risk-based therapy. Group (operative staging) remains the most important predictor of FFS, emphasizing the importance of complete gross resection at initial surgical intervention, when feasible without loss of limb function. The high incidence of nodal disease in the patients who had lymph node biopsy confirms the need for surgical evaluation of lymph nodes to ensure accurate staging in children with extremity rhabdomyosarcoma.


Diet composition of Plagioscion squamosissimus (Heckel, 1840), a fish introduced into the Tietê River system.
Plagioscion squamosissimus is a species from the Amazon basin that was introduced into the Tietê River system. The present study aimed to analyse the feeding habits of this species in Bariri Reservoir and to verify the possible occurrence of ontogenetic changes in its diet composition. The samples were gathered in four periods of the year: February, June, September and November 2003. The fish were gathered with different fishing net meshes in three different reservoir portions. The alimentary items found in the stomachs were identified to the lowest possible taxonomic level and had abundance, occurrence frequency, volume and biomass determined. The Alimentary Index (IAi) was calculated for each alimentary item consumed by 'corvina' for each studied period. Comparisons among the diet of different size classes of P. squamosissimus were done using the similarity coefficient of Jaccard and the Cluster Analysis (UPGMA). The Friedman proof was performed to verify if there is a significant ontogenetic variation in the species diet and changes in the consumption of different alimentary categories by P. squamosissimus among the sampled periods. P. squamosissimus presented a piscivorous feeding habit, although other items were also consumed. The biggest values of IAi were obtained for the alimentary item fish in the months of June (0.47) and November (0.39). The item Ephemeroptera (Campsurinae) was the most representative in February (0.30) and June (0.45). Despite the fact that P. squamosissimus consumed an ample spectrum of alimentary items, the ontogenetic changes were evident through the exploration of aquatic insects by the younger classes and by a diet mainly composed of fish in adult individuals. The alimentary plasticity of P. squamosissimus evidenced in this study might have contributed to the success of this species in Bariri Reservoir.


Quality control in urodynamics: a review of urodynamic traces from one centre.
To investigate quality control in our unit and to enable other units to compare their results, as experience from central reviews of urodynamic traces for multicentre trials has suggested that poor quality control is common. All consecutive male urodynamic tests conducted over 1 year were reviewed. A list of criteria to assess the quality of the records was devised, based upon International Continence Society guidelines on "good urodynamic practice", and on other sources. Eligible traces were analysed for aspects of quality control, e.g. baseline pressures and coughs to test pressure transmission. The data were analysed to establish how often quality criteria were met, and identify areas for improvement. In 100 eligible traces, the baseline detrusor pressure was 0-10 cmH2O in 86, and - 5 to +10 cmH2O in 94%. Baseline intravesical and abdominal pressure were 30-50 cmH2O in 68% and 73% of cases, respectively. Coughs were present before filling in 94%, during filling in 95%, before voiding in 72% and after voiding in 87% of cases. The cough-test frequency was sufficient in 30% of traces. In 11 the intravesical pressure line fell out during voiding. Most of the traces assessed met the quality criteria defined, but significant defects were not uncommon. Some of the problems identified suggest areas of urodynamic technique which should be studied in more detail. We intend to modify our quality control practices, and hope to show an improvement on re-audit. We hope that other urodynamic departments will be encouraged to review their practice, and we aim to improve our results.


Plasma homocysteine and folate levels and dietary folate intake in adolescents and young adults who underwent kidney transplantation during childhood.
Hyperhomocysteinemia (hyper-Hcy) is an important and reversible cardiovascular disease risk factor. We examined the prevalence of hyper-Hcy, plasma folate levels, and dietary folate intake in adolescents and young adults who had undergone kidney transplantation during childhood to assess the necessity for managing dietary folate. This cross-sectional study was performed in 89 kidney transplant recipients (age at kidney transplantation: 12.6 ± 4.1 years; age during study: 21.2 ± 5.5 years). Hyper-Hcy and plasma folate deficiency were defined as plasma homocysteine (Hcy) >15 nmol/ml and plasma folate <3.0 ng/ml, respectively. Of the patients, 60 (67.4 %) had hyper-Hcy and 14 (15.7 %) had plasma folate deficiency. Plasma homocysteine levels correlated negatively with estimated glomerular filtration rate (eGFR; r = -0.565, p < 0.01) and plasma folate levels (r = -0.434, p < 0.01). For determinants of plasma homocysteine levels, a priori selected variables included kind of calcineurin inhibitor, age at kidney transplantation, pretransplant duration of dialysis, time since transplantation, age at examination, eGFR, and plasma folate. Stepwise multiple linear regression analysis revealed eGFR and plasma folate levels as significant independent variables influencing plasma homocysteine levels. Dietary folate intake in 11 of 16 patients (66.8 %) with eGFR ≥ 60 ml/min/1.73 m(2) was below the recommended dietary allowance for Japanese. The prevalence of hyper-Hcy and plasma folate deficiency, as well as the low dietary folate intake, suggest that dietary management of folate is necessary for adolescents and young adults who have undergone kidney transplantation during childhood.


A challenge for the 1990s: patient education.
The goal of health education is assisting patients to adapt to their illness, assuming responsibility for their therapeutic regimen, and working towards attaining their maximum level of wellness. There are three domains of learning behavior: cognitive (knowledge and information), affective (attitudes, values, and beliefs), and psychomotor (skills and performance). The use of these results in behavioral change. Effective nurse educators take advantage of every interaction to teach their patients. It is the nurse's responsibility to present information to the patient in such a way that it motivates, stimulates, and allows the patient to appreciate learning.


Role of onlay grafting with minimal internal fixation for occipitocervical fusion in oncologic patients.
The choice of fixation for occipitocervical arthrodesis remains controversial, especially in oncologic patients who need further radiographic evaluation or postoperative radiotherapy. We studied the long-term outcome of 20 patients who underwent occipitocervical fusions using onlay corticocancellous bone graft and wiring, with postoperative halo vest immobilization. Eight of these patients had postoperative radiotherapy for spinal tumors (group I), and 12 patients had occipitocervical fusions for other pathologies that did not require postoperative radiotherapy (group II). All patients had solid arthrodeses; however, there was a difference in the average time to fusion between patients who received pre- or postoperative radiotherapy and those who did not (p = 0.11). At an average follow-up of 54.5 months (range 24-92 months) 15 of 20 patients (75%) had excellent or good outcomes. A high fusion rate can be expected with reasonable intraoperative or postoperative complications.


Perinatal mortality in the infants of diabetic women.
The causes of 50 perinatal deaths which occurred over an 18-year period in the infants of women with either established (n = 205) or gestational (n = 2,442) diabetes were studied. The perinatal mortality rate in these groups was 5.4% and 1.6% respectively and the causes of deaths were similar in both groups. Intrauterine hypoxia was found to be the commonest cause of death, followed by congenital malformations and respiratory distress syndrome. The implications of these findings for measures to reduce such deaths are discussed.


Diagnosis in adolescents and adults with congenital heart disease. Prospective assessment of individual and combined roles of magnetic resonance imaging and transesophageal echocardiography.
The inability to obtain complete diagnoses with transthoracic echocardiography in many adults with congenital heart disease provided the incentive to evaluate prospectively the individual and combined roles of magnetic resonance imaging (MRI) and transesophageal echocardiography (TEE) as "second-line" techniques for unresolved diagnostic problems. Eighty-five patients were studied; 81 had MRI with a 0.5-T magnet to obtain spin-echo images, cine-MRI, and flow-velocity maps. Seventy-nine patients had TEE (37 biplane). A simple score (range, 0 to 1) was used for quantification of the results of MRI and TEE alone, for their comparison (in the 75 patients who had both), and for assessment of their combination. MRI, TEE, or their combination achieved a score of at least 0.75 in 18 of 25 diagnostic categories. A summary of the scores showed that for intracardiac anatomy. MRI scored 0.34, TEE scored 0.71 (P < .0001), and MRI plus TEE scored 0.84 (P < .003); for extracardiac anatomy, MRI scored 0.76, TEE scored 0.23 (P < .0001), and MRI plus TEE scored 0.84 (P = NS); and for hemodynamics and function, MRI scored 0.58, TEE scored 0.41 (P < .05), and MRI plus TEE scored 0.67 (P = NS). Total scores were MRI, 0.52; TEE, 0.50 (P = NS); and MRI plus TEE, 0.80 (P < .0001). MRI and TEE were inadequate for collateral and coronary arteries and pulmonary vascular resistance. Cine-MRI and flow-velocity maps comprised 43% of the MRI scores. Biplane TEE was better than single plane (scores of 0.59 versus 0.42, P < .0001). MRI and TEE are important and complementary "second-line" investigations for congenital heart disease. Analysis of their performance in a wide range of diagnostic categories provides guidelines for their judicious application. Where both are available, diagnostic catheterizations are either obviated or simplified.


Surgical versus medical treatment for epilepsy. I. Outcome related to survival, seizures, and neurologic deficit.
We conducted a retrospective parallel longitudinal cohort study comparing surgical and medical treatment for epilepsy. The surgical group contained 201 patients treated with resective surgery for epilepsy in Norway since the first operation in 1949 until January 1988. The 185 control group patients treated medically only were closely matched for year of treatment, age at treatment, sex, seizure type, and neurologic deficit before treatment. There was no significant difference in survival between the two groups. The total monthly seizure frequency in the first and second year after operation and last year of registration (median 9 years) was significantly lower in the surgical group than in the control group (Mann-Whitney U test, two-tailed p less than 0.0001). The patterns were similar, with significant differences for subgroups with similar pretreatment status, such as seizure frequency, age, etiology and EEG-focality. Twenty-three and four-tenths percent (n = 40) of the surgically treated, and 2.9% of the controls had contracted neurologic deficits within 2 years after treatment. The difference was significant (chi square = 32.89, p less than 0.0001). Psychosis or permanent psychotic symptoms were reported in 6.7% (n = 11) of the surgically treated patients, and we suspect a higher proportion of psychotic development in the surgical group than in the control group. We conclude that surgical treatment for partial epilepsy is more successful than medical treatment in producing seizure reduction, provided the indications for operation exist. Surgical treatment produces more neurologic deficits than medical treatment (and possibly more psychiatric morbidity), and this factor must be weighed against the reduction in seizure frequency. The two treatments are equal for longterm survival.


Molecular mechanisms involved in anti-inflammatory effects of proton pump inhibitors.
Interleukin (IL)-8 has been reported to participate in neutrophil infiltration in Helicobacter pylori (H. pylori)-induced gastritis in humans. In this study, we investigated the anti-inflammatory actions beyond the suppression of acid secretion by proton pump inhibitors (PPI), such as omeprazole and lansoprazole, on IL-8 production by gastric epithelial cells (MKN45) and human umbilical vein endothelial cells (HUVEC) and on the transendothelial migration of polymorphonuclear neutrophils (PMN). MKN45 and HUVEC were stimulated with H. pylori water extract (HPE) and IL-1beta, respectively, and nuclear factor kappa B (NFkappaB) activation and subsequent IL-8 production was assessed in the absence or presence of PPI. We also assessed the effect of PPI on IL-8-induced PMN transendothelial migration and on the alteration of cytoplasmic calcium concentration in formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated PMN. HPE and IL-1beta induced a significant increase in IL-8 production by MKN45 and HUVEC, respectively, along with NFkappaB activation, which was significantly inhibited by PPI. PPI also inhibited the IL-8-induced transendothelial migration of PMN and the fMLP-induced cytosolic calcium increase in PMN. PPI attenuate PMN-dependent gastric mucosal inflammation partly by interfering with NFkappaB activation in vascular endothelial cells and gastric epithelial cells, and partly by modulating the calcium concentration of PMN.


Oncocytic adrenocortical neoplasm arising from adrenal rest in the broad ligament of the uterus.
Oncocytic adrenocortical neoplasm is characterized by abundant eosinophilic cytoplasm containing mitochondria, occasional nuclear atypia and diffuse growth pattern. Oncocytic adrenocortical neoplasm arising in adrenal rest is, however, extremely rare. We report a case of oncocytic adrenocortical neoplasm arising in adrenal rest of the broad ligament with associated marked lipomatous metaplasia. A well circumscribed tumor was accidentally detected in the pelvic cavity of a 29 year old Japanese woman, adjacent to the broad ligament of the uterus. The tumor was composed of large eosinophilic cells associated with diffuse growth pattern and abundant mature adipose tissue admixed with foci of clear cells. Both steroidgenic factor 1 (SF-1) and alpha-inhibin were immunohistochemically positive in tumor cells. Abundant mitochondria detected by immunohistochemical and electron microscopic examination confirmed the diagnosis of oncocytic adrenocortical neoplasm. The absence of necrosis, capsular and vascular invasion as well as the low mitotic index indicated the benign potential of this tumor. The tumor cells were also positive for dehydroepiandrosteron-sulfotransferase (DHEA-ST), 17β-hydroxysteroid dehydrogenase type 5 (17β-HSD5), 3β-hydroxysteroid dehydrogenase (3β-HSD) and steroid 17α-hydroxylase (P450-c17), suggesting a possible production of testosterone of this tumor. This is the first reported case of oncocytic adrenocortical adenoma arising in adrenal rest of the broad ligament.


The role of polycomb repressive complexes in biliary tract cancer.
Polycomb group proteins are major epigenetic regulators that modify histone tails. They are organized in two multi-protein complexes called polycomb repressive complex (PRC) 1 and 2. Aberrant PRC activity is known to contribute to the development and aggressiveness of many cancers. Biliary tract cancer (BTC) is a rare malignancy associated with high chemoresistance and poor clinical outcome. Here we review the role of the PRC complexes and the effects of RNAi and drug-mediated inhibition of PRC1 and PRC2 in BTC. This review gives a short overview of the composition, biochemical functions and oncogenic role of PRC complexes. We then focus on and summarize the results of current studies that address the role of PRC in BTC. Finally, we discuss options and results of therapeutic targeting of PRC in BTC. Pharmacological inhibition of the two PRC complexes seems to be a promising strategy for treatment of BTC. To date, only few studies have addressed the therapeutic effect of PRC inhibition in BTC. Therefore, it will be important to test established PRC inhibitors, such as DZNep, as well as newly developed drugs, for example, PTC209, to gain more insight into the role of the PRC complexes in BTC and potentially to develop new therapeutic strategies.


Mammographic change in hysterectomized women on 0.625 mg/day of conjugated equine estrogen.
To compare the mammographic change before and after conjugated equine estrogen (CEE) 0.625 mg/day in hysterectomized women. A retrospective descriptive study. Menopause clinic, Maharaj Nakorn Chiang Mai Hospital. Dedicated mammograms and demographic data of 66 women who had been hysterectomized were reviewed. Post surgical menopausal women were recruited for the study. CEE 0.625 mg/day was given just after the operation. The baseline mammography was done before the initiation of HRT and they were compared with the follow-up mammography performed 12-18 months after therapy. The degree of increase in mammographic density was classified as follows: minimal changes (10-25% increased density), moderated change (26-50% increased density), and marked change (> 50% increased density). The mean age +/- SD was 47 +/- 4.3 years old. The mean duration +/- SD of hormone used was 13.5 +/- 2.4 months. The most common indication for operation was myoma uteri (43.9%). On the baseline mammogram, 5 cases had cystic change and one case had a small circumscribed solid mass suspected to be fibroadenoma. On the follow-up mammograms, there were 2 cases (3.0%) detected to have significantly increased breast density. One was moderately increased and the other was markedly increased, but cystic changes and one fibroadenoma were not changed. CEE has little effect on increased mammographic density.


Endometrial neoplasia: prognostic significance of ploidy status.
For several decades, clinical and histologic assessment of various phenotypic properties has provided a basis for treatment planning. However, it is recognized that, preoperatively, clinical assessment identifies only 20% of patients with advanced disease. Furthermore, the variability in intraoperative sampling, the subjectivity and limitations of histologic interpretation, and the variability in response to standardized treatment modalities represent concerns associated with the current treatment of endometrial carcinoma. Presumably, early dissemination, early recurrence, treatment refractoriness and, ultimately, compromised survival are reflections of the inherent biologic characteristics of the tumor. A reasonable assumption is that proscribed molecular events determine various behavioral characteristics of tumors that become manifested at the time of transformation rather than evolving as the tumor volume increases. Therefore, the identification of one or more of these quantifiable molecular variables that directly or indirectly assess tumor biology would assist clinicians in determining patient risk status and in selecting treatment options. As noted, DNA ploidy is an independent, broadly applicable, quantifiable predictor of progression-free survival in patients with endometrial cancer and, therefore, warrants designation as a major prognostic factor or therapeutic determinant. Aneuploidy implies the presence of an abnormal quantity of genomic material and imparts a progressively less favorable prognosis as the DNA index increases. These assayable aberrancies of cellular DNA content presumably reflect the more extreme alterations at the molecular level. Because neoplastic transformation is generally a multistep process, aberrations in several proto-oncogenes or tumor suppressor genes (or both) presumably must be realized before a clinical malignancy develops. A number of genes that encode for various regulatory proteins are overexpressed in endometrial cancer. Whether these aberrancies are fundamental to the pathogenesis of this disease process is unclear. Nevertheless, there appears to be an association between DNA ploidy and the overexpression of several regulatory genes, such as c-fms, K-ras, HER-2/neu, and p53. Although overexpression of these oncogenes and tumor suppressor genes harbor prognostic significance in endometrial cancer, the ploidy status of the tumor appears to represent the most cogent objective variable. As the etiopathogenesis of endometrial carcinoma becomes more discernible, one can envision a limited number of tissue-specific molecular-genetic indices characterizing the risk status of patients. Because the estimated number of deaths from endometrial cancer has doubled since 1987, reassessing of the therapeutic determinants for this disease process is important. The management objective for endometrial cancer by the turn of the century should be the identification of patients at high risk for advanced disease or post-treatment recurrences (or both) at the time of clinical declaration of symptoms and diagnosis. Such pretreatment identification would afford patients at high risk for advanced or recurrent disease access to physicians with special expertise and would facilitate the evaluation and application of new or modified therapeutic modalities. Equally important would be the identification of patients at low risk for untoward outcome, thereby avoiding the cost and morbidity of excessive therapeutic measures.


Disease Stage and Mode of Therapy Are Important Determinants of Treatment Outcomes for Medication-Related Osteonecrosis of the Jaw.
The treatment of patients with medication-related osteonecrosis of the jaw (MRONJ) is challenging. The purpose of the present study was to estimate the frequency and identify the factors associated with clinical improvement during treatment. We designed and implemented a retrospective cohort study and enrolled a sample of subjects diagnosed with MRONJ between 2004 and 2015. The primary predictor variables were a set of heterogeneous variables grouped into the following categories: demographic (age and gender) and clinical (location of necrosis, therapy duration, medication type, disease stage, and treatment type). The primary outcome variable was the treatment outcome, defined as stable or worse and improved or healed. The descriptive, bivariate, and multiple logistic statistics were computed, and statistical significance was defined as P < .05. The sample included 337 subjects with a mean age of 68.9 years. Of the 337 subjects, 256 were women (76%). A total of 143 patients (42.2%) experienced spontaneous necrosis. Twenty-four (7.1%) had had exposure to targeted antiangiogenic agents. Those with stage 1 or 2 disease were more likely to have better outcomes than those with stage 3 disease (stage 1, adjusted odds ratio [OR] 3.4, P = .005; stage 2, adjusted OR 2.2, P = .03). Treatment type was a significant variable. Subjects undergoing surgery were 28 times more likely to have a positive outcome than those receiving nonoperative therapy (adjusted OR 28.7, P < .0001). Subjects with MRONJ who presented with less severe disease or who underwent operative treatment were most likely to have improvement or complete healing of their MRONJ-related lesions.


Liquid chromatography-electrospray ionization tandem mass spectrometry and dynamic multiple reaction monitoring method for determining multiple pesticide residues in tomato.
A quick and sensitive liquid chromatography-electrospray ionization tandem mass spectrometry method, using dynamic multiple reaction monitoring and a 1.8-μm particle size analytical column, was developed to determine 57 pesticides in tomato in a 13-min run. QuEChERS (quick, easy, cheap, effective, rugged, and safe) method for samples preparations and validations was carried out in compliance with EU SANCO guidelines. The method was applied to 58 tomato samples. More than 84% of the compounds investigated showed limits of detection equal to or lower than 5 mg kg(-1). A mild (<20%), medium (20-50%), and strong (>50%) matrix effect was observed for 72%, 25%, and 3% of the pesticides studied, respectively. Eighty-one percent of the pesticides showed recoveries ranging between 70% and 120%. Twelve pesticides were detected in 35 samples, all below the maximum residue levels permitted in the Brazilian legislation; 15 samples exceeded the maximum residue levels established by the EU legislation for methamidophos; and 10 exceeded limits for acephate and four for bromuconazole.


Needle-based blocks for the 21st century ophthalmology.
This paper reviews history of the needle orbital blocks used in the earlier centuries and how they have evolved towards safer anaesthesia in the modern clinical practice. Material is derived from literature searches from major ophthalmic and anaesthetic journals on the use of orbital needle blocks over earlier centuries. Needle-based anaesthetic techniques were described shortly after the invention of reliable medical needles. Atkinson popularized the classical retrobulbar block in a series of papers published in the early 20th century. This technique,which utilises a relatively long needle inserted towards the apex of the muscle cone behind the globe, has been criticized by some as unsuitable for modern 21st century ophthalmic surgery because of the extremely rare potential for serious complications. Satisfactory anaesthesia and akinesia can be obtained with short sharp or dull needles with slightly higher volumes of local anaesthetic agent placed in the farthest inferotemporal quadrant. Aside from relative safety, modern needle blocks offer the advantage of lid akinesia without a need for a second injection for the seventh nerve that is often performed con-comitantly with retrobulbar block.


Cardiac troponin T lysine 210 deletion in a family with dilated cardiomyopathy.
The gene for cardiac troponin T (TNNT2) is 1 of 7 autosomal disease genes implicated in familial dilated cardiomyopathy (FDC). Identical deletions in exon 13 of TNNT2 have been reported in 2 families with FDC, but little is known about the frequency of this deletion among patients with FDC and idiopathic dilated cardiomyopathy (IDC) and the associated phenotype. Exon 13 of the cardiac troponin T gene was sequenced in 61 subjects with FDC and 53 subjects with IDC. A 3-base pair deletion (DeltaLys210), identified in 1 family with at least 7 clinically affected family members, is reported. Age of disease onset and disease severity varied widely among affected individuals; phenotypic findings included dilated cardiomyopathy, sudden cardiac death, conduction system disease including atrial fibrillation and atrioventricular block, and heart failure. Sudden-onset, rapidly progressive disease was observed in younger individuals. Cardiac troponin T exon 13 lysine deletions can cause FDC of varying severity and are an important but uncommon cause of FDC.


Pharyngo-oesophageal haemangioma with a positive cough impulse.
Benign tumours of both the pharynx and oesophagus are rarely seen, cavernous haemangiomas even less so. We present a case in which a large lesion was the cause of non-specific symptoms but which only appeared intermittently on nasendoscopic examination of the pharynx.


Adherence to gastroprotection during cyclooxygenase 2 inhibitor treatment and the risk of upper gastrointestinal tract events: a population-based study.
Guidelines recommend coprescription of gastroprotective agents (GPAs) in patients receiving cyclooxygenase 2 inhibitors (coxibs) who are at high risk of upper gastrointestinal (UGI) tract complications (i.e., patients with a previous complicated ulcer or with multiple risk factors). Suboptimal GPA adherence has been shown to diminish the gastroprotective effect during use of nonselective nonsteroidal antiinflammatory drugs, but little is known about the effect of GPA adherence during coxib treatment. We undertook this study to determine the association between GPA adherence and UGI tract events among patients receiving coxibs. Using primary care data from 3 databases, we conducted a case-control study in a cohort of patients age ≥50 years who were newly starting treatment with coxibs and concomitantly taking GPAs. Patients who had a UGI tract event (bleeding or symptomatic ulcer) were matched to event-free controls for age, sex, database, and calendar date. Coxib treatment intervals were defined as consecutive coxib prescriptions with intervening gaps not exceeding the duration of the previous coxib prescription. Adherence to GPAs was calculated as the proportion of days of coxib treatment covered by a GPA prescription. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated using conditional logistic regression analysis. The coxib plus GPA-treated cohort consisted of 14,416 coxib-treated patients who received GPAs for at least 1 day, yielding 16,442 coxib treatment intervals in which a GPA was coprescribed. Most patients were treated with coxibs for <30 days. Seventy-four patients had a UGI tract event during or shortly after a coxib treatment interval in which a GPA was coprescribed, with an incidence rate of 11.9 (95% CI 9.4-14.8) per 1,000 years of coxib treatment. The risk of UGI tract events was 1.97 (95% CI 0.84-4.60) for patients with <20% adherence to GPAs compared to patients with >80% adherence to GPAs. For every 10% decrease in GPA adherence, the risk of UGI tract events increased by 9% (OR 1.09 [95% CI 1.00-1.18]). Decreasing GPA adherence among coxib-treated patients is associated with an increased risk of UGI tract events.


SLE mortality in an oriental population.
We analysed the causes of 67 deaths, over a 4 y period, in our oriental population with systemic lupus erythematosus (SLE). The median disease duration was 48 +/- 60.5 months (range 1-250 months). The mean age at diagnosis and death were 30 and 35.1 y respectively. SLE alone accounted for death in 30 patients (44.8%), infection in 27 (40.3%), pulmonary embolism in 5 (7.5%), malignancy in 4 (5.9%) and rheumatic heart disease in 1 (1.5%). The major organ involvement in those with active disease at death were SLE related thrombocytopenia (n = 23/44, 52.3%), nephritis (n = 21/44), 47.7%), cerebral lupus (n = 16/44, 36.4%), and pulmonary haemorrhage (n = 12/44, 27.3%). As in other series, SLE and infection were the principal causes of death in our population. During this 4 y period, there was no late death due to atherosclerosis.


Facial affective relationship offers of patients with panic disorder.
Abstract The psychodynamic of patients with panic disorder is most often characterized by a domination of autonomy-dependency conflicts, including an ambivalent need for a positive relationship toward a significant object and an incapacity to express negative feelings because of fear of losing this relationship. Affective facial behavior can be considered as a tool for relationship regulation. The authors investigated facial affective indicators of this conflict in 20 women with panic disorder in their first psychotherapy session. A preponderance of facial smile and a lack of negative affective facial signals were expected. This was not confirmed for the total sample. A cluster analysis identified two subgroups of panic patients. One subgroup confirmed the assumption precisely. The other did as well but only insofar as the patients smiled more often than was seen in a mixed clinical control group that excluded panic disorders. In addition, the panic patients of this cluster showed much negative affect. The patients of the two panic clusters did not differ in panic and other symptoms but did so in their descriptions of their interpersonal behavior.


LightCycler gyrA mutation assay (GAMA) identifies heterogeneity in GyrA in Salmonella enterica serotypes Typhi and Paratyphi A with decreased susceptibility to ciprofloxacin.
Mutations in gyrA in strains of Salmonella enterica serotypes Typhi and Paratyphi A have been characterised by a LightCycler-based PCR-hybridisation gyrA mutation assay (GAMA) and by DNA sequencing. Four mutations (Ser-83 to Phe, Asp-87 to Asn, Ser-83 to Tyr and Asp-87 to Gly) have been identified in 13 strains of Typhi and three strains of Paratyphi A resistant to nalidixic acid (=nal(r)) and with decreased susceptibility to ciprofloxacin (=Cp(L)), with the mutation Ser-83 to Phe predominating. The results have demonstrated heterogeneity in gyrA in nal(r) Cp(L) strains of Typhi and Paratyphi A and may be useful for epidemiological investigations. No mutations in gyrA were identified in four Cp(L) strains of S. Typhi that were sensitive to nalidixic acid. The mechanism of decreased susceptibility to ciprofloxacin in these strains is under investigation.


Comparison of supercritical fluid extraction and solvent extraction of twenty-two organochlorine pesticides from eggs.
The recoveries of twenty-two organochlorine pesticides spiked in egg samples were extracted by supercritical fluid extraction (SFE) using carbon dioxide and solvent extraction using acetonitrile were compared. The extracts were cleaned up with C18 and Florisil SPE columns. At 0.1 ppm spike level, the recoveries were 52 - 100% by SFE and 53 - 93% by solvent extraction. The limits of detection calculated at 0.01 ppm spike level were 0.072 - 0.006 ppm for SFE and 0.06 - 0.006 ppm for solvent extraction. Both methods show improvement in sample preparation time and solvent consumption from the existing Soxhlet extraction method.


Switching and rectification of a single light-sensitive diarylethene molecule sandwiched between graphene nanoribbons.
The "open" and "closed" isomers of the diarylethene molecule that can be converted between each other upon photo-excitation are found to have drastically different current-voltage characteristics when sandwiched between two graphene nanoribbons (GNRs). More importantly, when one GNR is metallic and another one is semiconducting, strong rectification behavior of the "closed" diarylethene isomer with the rectification ratio >10(3) is observed. The surprisingly high rectification ratio originates from the band gap of GNR and the bias-dependent variation of the lowest unoccupied molecular orbital of the diarylethene molecule, the combination of which completely shuts off the current at positive biases. Results presented in this paper may form the basis for a new class of molecular electronic devices.


Cholecystitis and delayed emptying of the gallbladder.
A number of patients with symptoms of biliary colic have biliary tract disorders despite repeatedly normal oral cholecystograms. These patients will benefit from cholecystectomy. To better define such disorders, a test is needed that is noninvasive, relatively inexpensive and highly accurate. Delayed emptying of the gallbladder after a standard dosage oral cholecystogram using Telepaque is such a test. Twenty-eight patients with this finding underwent cholecystectomy. All gallbladder specimens exhibited both gross and pathologic changes. Twenty-six of the patients had relief of symptoms.


RMI 12330A, an inhibitor of adenylate cyclase and cyclic AMP-phosphodiesterase activities in the segmental ganglia of the leech Hirudo medicinalis.
The effect of RMI 12330A, an inhibitor of basal as well as serotonin-stimulated adenylate cyclase in the segmental ganglia of the leech Hirudo medicinalis, has been tested on cyclic AMP-phosphodiesterase activity in the same tissue. The drug dose-dependently inhibits high and low affinity enzyme, an effect first evident at an RMI 12330A concentration of 0.5 mM. For both enzyme activities the drug reduces Vmax without substantially influencing Km values. Both basal and serotonin-stimulated adenylate cyclase as well as cyclic AMP-phosphodiesterase activities are inhibited by RMI 12330A in a non-competitive manner.


Role of mechanical factors in the evaluation of pedicle screw type spinal fixation devices.
Prior to implantation, spinal implants are subjected to rigorous testing to ensure safety and efficacy. A full battery of tests for the devices may include many steps ranging from biocompatibility tests to in vivo animal studies. This paper describes some of the essential tests from a mechanical engineering perspective (e.g., motion, load sharing, bench type tests, and finite element model analyses). These protocols reflect the research experience of the past decade or so.


[Study on distribution of epidermal growth factor (EGF) in rat tissues].
Tissue distribution of epidermal growth-factor (EGF) in rat was investigated using a human EGF (hEGF) radioimmunoassay system. Antisera generated against hEGF reacted with hEGF and [21Leu] hEGF but not with mouse EGF, fibroblast growth factor (FGF), nerve growth factor (NGF), platelet derived growth factor (PDGF), and endothelial cell growth supplement (ECGS). Similar amounts of EGF immunoreactivity (EGF-IR) were found in the rat submandibular gland (32.8 +/- 4.59 ng/g tissue, n = 5) and duodenum (39.9 +/- 18.7 ng/g tissue, n = 9), whereas little EGF was detected in other tissues. No sex difference was observed in submandibular and duodenal EGF-IR, being different from the case of mouse in which ten times higher concentration of EGF-IR was found in male submandibular gland. Sephadex G-50 gel chromatography of submandibular and duodenal extracts revealed that each consisted of at least three different immunoreactive forms. The predominant EGF-IR was coeluted with 125I-EGF, significant amounts of EGF-IR was observed in the void volume fractions, and only small peaks of EGF-IR were present near Vt. These data clarified the presence of EGF-IR in rat submandibular and duodenal tissues and the molecular heterogeneity of EGF-IR and suggest some important role of EGF in the gastrointestinal function.


[2,6-Bis(5-methyl-2-pyridyl)phenyl-kappa(3)N,C(1),N']chloridoplatinum(II).
In the title compound, [Pt(C(18)H(15)N(2))Cl], the Pt(II) centre adopts a distorted square-planar coordination geometry due to the pincer-type monoanionic N-C-N tridentate ligand. The planar complexes stack via pi-pi interactions to form two-dimensional accumulated sheets. This packing pattern is in contrast to that in related pincer-type N-C-N complexes, which exhibit a one-dimensional columnar stacking.


Evaluation of Raman spectroscopy for the analysis of colored fibers: a collaborative study.
A collaborative study on Raman spectroscopy was carried out by members of the ENFSI (European Network of Forensic Science Institutes) European Fibres Group (EFG) on three dyed fibers: two red acrylics and one red wool. Raman instruments from six different manufacturers were tested as well as nine different laser wavelengths ranging from blue (lambda = 458 nm) to near infrared-NIR (lambda = 1064 nm). This represents the largest comparison study of Raman analytical parameters carried out on identical fiber samples. For the chosen fiber and dye samples, red lasers (lambda = 633 and 685 nm) gave the poorest spectral quality whereas blue (458 nm), green (514 nm) and near infrared lasers (785, 830 and 1064 nm) provided average results. Blue (488 nm) and green lasers (532 nm) globally gave the best quality spectra. Fluorescence problems were often encountered with some of the excitation wavelengths and therefore a flexible Raman instrument equipped with different lasers can be recommended to measure forensic fiber samples. The instrument should also be equipped with a Raman microscope in order to be able to focus on a single fiber. This study shows that Raman spectroscopy usually enables the identification of the main dye present in a colored fiber; however, minor dye components are much more difficult to detect. SERRS (Surface Enhanced Resonance Raman Scattering) techniques give an improvement of the dye's spectral intensity but no spectral improvement was observed for the two red acrylic and red wool fibers tested.


[Continuous ambulatory peritoneal dialysis (CAPD) in children and adolescents].
Continuous ambulatory peritoneal dialysis (CAPD) is a relatively new blood purification method applicable as an alternative to intermittent hemodialysis in the treatment of end-stage renal disease. In this report we discussed the results of more than five years of CAPD in 32 children and adolescents aged 0.1 to 18 years treated for up to 22 months as well as the advantages and disadvantages of this technique in comparison to hemodialysis. Technical survival after one year of treatment increased from 48% in patients treated before 1983 to 84% in patients treated thereafter. Simplicity of technical procedure and lack of pain are considered the major advantages. Thus home dialysis can be performed even under adverse conditions (e.g. in infants). Infections of the abdominal cavity and the catheter tunnel are severe complications of CAPD. In the course of the last two years the frequency of peritonitis dropped to one episode per treatment year. We want to stress that successful treatment can be achieved by adequately training patients and their parents to perform home dialysis on their own and by surveying patients regularly according to standardized treatment guidelines in a pediatric nephrology unit.


Differential expression of novel genes by bone marrow-derived macrophage populations.
In the present study, we have constructed a subtraction cDNA library to identify novel genes induced by IFN-gamma in GM-CSF-derived bone marrow macrophage (m phi). M theta were treated with 50 U/ml IFN-gamma for 40, 70 and 140 min to induce expression of early genes regulated by IFN-gamma, and the M phi were pooled. Poly(A)+RNA was prepared from both unactivated and IFN-gamma-stimulated m theta, and cDNA libraries were constructed in lambda ZAP. Genes expressed in common by both m theta populations were removed by subtraction using biotin-avidin precipitation of hybrid complexes. Further selection was performed by differential screening using cDNA prepared from mRNA of unactivated m phi as a probe, followed by colony hybridization to remove sister clones. Of 17 clones from which sequence information was obtained, two appeared to be identical with the murine genes, C10 (clone GM2B1) and Mac-2 (clone GM2C4) and an additional two clones had high similarity to human cDNAs encoding proteins of unknown function. cDNAs containing sequences which did not match published sequences were used to probe Northern blots prepared from both unstimulated and IFN-gamma-activated GM-CSF- and CSF-1-derived m phi. Five clones (GM1A2, GM1B4, GM1F2, GM2A12 and GM2B8) showed enhanced transcript levels following IFN-gamma treatment of GM-CSF-derived m phi, but demonstrated high constitutive transcript levels in CSF-l-derived m phi. In addition, C10 transcripts were constitutively expressed by GM-CSF-derived m phi, but not by CSF-1-derived m phi, even after activation by IFN-gamma. These data suggest that much of the functional heterogeneity of GM-CSF- and CSF-1-derived m phi resides in the differential expression of early genes specifically induced by IFN-gamma.


Capillary atmospheric pressure electron capture ionization (cAPECI): a highly efficient ionization method for nitroaromatic compounds.
We report on a novel method for atmospheric pressure ionization of compounds with elevated electron affinity (e.g., nitroaromatic compounds) or gas phase acidity (e.g., phenols), respectively. The method is based on the generation of thermal electrons by the photo-electric effect, followed by electron capture of oxygen when air is the gas matrix yielding O2(-) or of the analyte directly with nitrogen as matrix. Charge transfer or proton abstraction by O2(-) leads to the ionization of the analytes. The interaction of UV-light with metals is a clean method for the generation of thermal electrons at atmospheric pressure. Furthermore, only negative ions are generated and neutral radical formation is minimized, in contrast to discharge- or dopant assisted methods. Ionization takes place inside the transfer capillary of the mass spectrometer leading to comparably short transfer times of ions to the high vacuum region of the mass spectrometer. This strongly reduces ion transformation processes, resulting in mass spectra that more closely relate to the neutral analyte distribution. cAPECI is thus a soft and selective ionization method with detection limits in the pptV range. In comparison to standard ionization methods (e.g., PTR), cAPECI is superior with respect to both selectivity and achievable detection limits. cAPECI demonstrates to be a promising ionization method for applications in relevant fields as, for example, explosives detection and atmospheric chemistry.


The ant colony algorithm for feature selection in high-dimension gene expression data for disease classification.
The use of gene expression data to diagnose complex diseases represents an exciting area of medicine; however, such data sets are often noisy, requiring the selection of feature subsets to obtain maximum classification accuracy. Due to the high dimensions of many expression data sets, filter-based methods are commonly used, but often yield inconsistent results. Optimization algorithms can outperform filter methods, but often require preselection of features to achieve good results. To address the problems of many commonly used feature selection methods, the ant colony algorithm (ACA) is proposed for use on data sets with large numbers of features. The ACA is an optimization algorithm capable of incorporating prior information, allowing it to search the sample space more efficiently than other optimization methods. When applied to several high-dimensional data sets, the ACA was able to identify small subsets of highly predictive and biologically relevant genes without the need for extensive preselection of features. Using the selected genes to train a latent variable model yielded substantial increases in prediction accuracy when compared to several rank-based methods and results obtained in previous studies. The superiority of the ACA algorithm was validated through simulation.


Differences in C-terminal amino acid sequences between erythrocyte and liver cytochrome b5 isolated from pig and human. Evidence for two tissue-specific forms of cytochrome b5.
Two forms of cytochrome b5, a soluble erythrocyte form and a membrane-bound liver form, were purified from pig and human, and structural differences between them were analyzed. Porcine and human erythrocyte cytochrome b5 consisted of 97 amino acid residues and contained the same catalytic domain structure (residues 1-96) as that of the corresponding liver cytochrome b5, but had one amino acid replacement at the C-terminus (residue 97). These results suggest that erythrocyte cytochrome b5 is not derived from the liver protein by proteolysis but a translational product from another distinct mRNA of cytochrome b5.