Dose limits for man do not adequately protect the ecosystem.
As has been noted by both of our participants, it is interesting to see that their views approached agreement during the course of the debate. This is not altogether unexpected since the topic is on that has many facets. It is fair to say that protecting man is an appropriate starting point for the protection of other more, or less, radiosensitive life forms sharing the planet with us. That there may be special situations requiring attention has been recognized by both of our participants. That the ICRP recognizes the need for further work on this topic is encouraging for ourselves as well as the 'bugs and bunnies'.


A three-dimensional net of Delta-tris(1,10-phenanthroline)ruthenium(II) in the dual-metal self-assembly of bis[tris(1,10-phenanthroline)ruthenium(II)] tetraisothiocyanatoiron(II) bis(perchlorate).
The title compound, [Ru(C(12)H(8)N(2))(3)](2)[Fe(NCS)(4)](ClO(4))(2), crystallizes in a tetragonal chiral space group (P4(1)2(1)2) and the assigned absolute configuration of the optically active molecules was unequivocally confirmed. The Delta-[Ru(II)(phen)(3)](2+) complex cations (phen is 1,10-phenanthroline) interact along the 4(1) screw axis parallel to the c axis, with an Ru...Ru distance of 10.4170 (6) A, and in the ab plane, with Ru...Ru distances of 10.0920 (6) and 10.0938 (6) A, defining a primitive cubic lattice. The Fe atom is situated on the twofold axis diagonal in the ab plane. The supramolecular architecture is supported by C-H...O interactions between the [Ru(II)(phen)(3)](2+) cation and the disordered perchlorate anion. This study adds to the relatively scarce knowledge about intermolecular interactions between [Ru(phen)(3)](2+) ions in the solid state, knowledge that eventually may also lead to a better understanding of the solution state interactions of this species; these are of immense interest because of the photochemical properties of these ions and their interactions with DNA.


Redox modulation of cellular stress response and lipoxin A4 expression by Coriolus versicolor in rat brain: Relevance to Alzheimer's disease pathogenesis.
Increasing evidence supports the notion that oxidative stress-driven neuroinflammation is an early pathological feature in neurodegenerative diseases. As a prominent intracellular redox system involved in neuroprotection, the vitagene system is emerging as a potential neurohormetic target for novel cytoprotective interventions. Vitagenes encode for cytoprotective heat shock proteins 70, heme oxygenase-1, thioredoxin and lipoxin A4. Emerging interest is now focusing on molecules capable of activating the vitagene system as novel therapeutic targets to minimize deleterious consequences associated with free radical-induced cell damage, such as in neurodegeneration. Mushroom-derived lipoxin A4 (LXA4) is an emerging endogenous eicosanoid able to promote resolution of inflammation, acting as an endogenous "braking signal" in the inflammatory process. Mushrooms have long been used in traditional medicine for thousands of years, being now increasingly recognized as rich source of polysaccharopeptides endowed with significant antitumor, antioxidant, antiviral, antibacterial and cytoprotective effects, thereby capable of stimulating host immune responses. Here we provide evidence of a neuroprotective action of the Coriolus mushroom when administered orally to rat. Expression of LXA4 was measured in different brain regions after oral administration of a Coriolus biomass preparation, given for 30 days. LXA4 up-regulation was associated with an increased content of redox sensitive proteins involved in cellular stress response, such as Hsp72, heme oxygenase-1 and thioredoxin. In the brain of rats receiving Coriolus, maximum induction of LXA4 was observed in cortex and hippocampus. Hsps induction was associated with no significant changes in IkBα, NFkB and COX-2 brain levels. Conceivably, activation of LXA4 signaling and modulation of stress-responsive vitagene proteins could serve as a potential therapeutic target for AD-related inflammation and neurodegenerative damage.


Ultrasonography in foreign body detection and localization.
The relative advantages and disadvantages of radiographic and ultrasonic studies in foreign body detection and localization are discussed. The value of ultrasonography in finding radiolucent orbital foreign bodies and its clear superiority in the localization of foreign bodies with respect to the walls of the eye is demonstrated by several examples. The information concerning the state of the lens, vitreous, and retina in such traumatized eyes which is obtained by ultrasonography represents a very important additional benefit of such study.


Treatment with chenodeoxycholic acid in cerebrotendinous xanthomatosis: clinical, neurophysiological, and quantitative brain structural outcomes.
Cerebrotendinous xanthomatosis (CTX) is a rare neurodegenerative disease related to sterols metabolism. It affects both central and peripheral nervous systems but treatment with chenodeoxycholic acid (CDCA) has been reported to stabilize clinical scores and improve nerve conduction parameters. Few quantitative brain structural studies have been conducted to assess the effect of CDCA in CTX. We collected retrospectively clinical, neurophysiological, and quantitative brain structural data in a cohort of 14 patients with CTX treated by CDCA over a mean period of 5 years. Plasma cholestanol levels normalized under treatment with CDCA within a few months. We observed a significant clinical improvement in patients up to 25 years old, whose treatment was initiated less than 15 years after the onset of neurological symptoms. Conversely, patients whose treatment was initiated more than 25 years after neurological disease onset continued their clinical deterioration. Eleven patients presented with a length-dependent peripheral neuropathy, whose electrophysiological parameters improved significantly under CDCA. Volumetric analyses in a subset of patients showed no overt volume loss under CDCA. Moreover, diffusion weighted imaging showed improved fiber integrity of the ponto-cerebellar and the internal capsule with CDCA. CDCA was well tolerated in all patients with CTX. CDCA may reverse the pathophysiological process in patients with CTX, especially if treatment is initiated early in the disease process. Besides tendon xanthoma, this study stresses the need to consider plasma cholestanol measurement in any patient with infantile chronic diarrhea and/or jaundice, juvenile cataract, learning disability and/or autism spectrum disorder, pyramidal signs, cerebellar syndrome or peripheral neuropathy.


Antiretroviral therapy in HIV-2-infected patients: changes in plasma viral load, CD4+ cell counts, and drug resistance profiles of patients treated in Abidjan, Côte d'Ivoire.
To describe changes in plasma viral load, CD4+ cell counts, and drug resistance profiles of HIV-2-infected patients receiving antiretroviral (ARV) therapy in Abidjan, Côte d'Ivoire. Consecutive blood samples were collected from 18 HIV-2-infected ARV-naive patients who had received ARV therapy in the UNAIDS drug access initiative (UNAIDS-DAI) in Abidjan between August 1998 and July 2000. Changes in HIV-2 plasma viral load, CD4+ cell counts, and genotypic and phenotypic drug resistance testing were determined. At baseline, 11 (61%) of the 18 patients initiated highly active antiretroviral therapy (HAART) and seven (39%) received dual therapy. No significant change in median viral load was observed at 2 months (P = 0.09), at 6 months (P = 0.06), and at 12 months of therapy (P = 0.26). No significant increase in CD4+ cell counts was observed at 12 months (P = 0.10). All four patients on indinavir-containing HAART had undetectable viral loads at 2-4 months of therapy. However, none of seven patients on nelfinavir-containing HAART had a substantial decrease in viral load. Viruses from 14 patients were analyzed, 12 of which (86%) had at least one primary resistance mutation that is known to confer resistance to HIV-1 virus. Three patients had the multi-drug-resistant mutation, Q151M, two of whom showed reduced susceptibility to zidovudine, didanosine, stavudine and zalcitabine. Our limited findings show that nelfinavir-containing regimens may have limited virologic benefit to HIV-2-infected patients.


Chemosensory proteins in the honey bee: Insights from the annotated genome, comparative analyses and expressional profiling.
Small chemosensory proteins (CSPs) belong to a conserved, but poorly understood protein family that has been implicated in transporting chemical stimuli within insect sensilla. However, their expression patterns suggest that these molecules are also critical for other functions including early development. Here we used both bioinformatics and experimental approaches to characterize the CSP gene family in a social insect, the Western honey bee Apis mellifera, and then compared its members to CSPs in other arthropods. The number of CSPs in the honey bee genome (six) is similar to that found in the sequenced dipteran species (four-seven), but is much lower than the number of CSPs in the moth or in the beetle (around 20 each). These differences seem to be the result of lineage specific expansions. Our analysis of CSPs in a number of arthropods reveals a conserved gene family found in both Mandibulates and Chelicerates. Expressional profiling in diverse tissues and throughout development reveals broader than expected patterns of expression with none of the CSPs restricted to the antennae and one found only in the queen ovaries and in embryos. We conclude that CSPs are multifunctional context-dependent proteins involved in diverse cellular processes ranging from embryonic development to chemosensory signal transduction. Some CSPs may function in cuticle synthesis, consistent with their evolutionary origins in the arthropods.


Comparative study of fat-suppressed Gd-enhanced MRI of hands in the early stage of rheumatoid arthritis (RA) and non-RA.
Abstract The object of this work was to evaluate the usefulness of fat-suppressed gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) for the diagnosis of early-stage rheumatoid arthritis. Forty wrists of patients who had suffered from stiff or swollen hands for 1-12 months were examined prospectively by MRI. Rheumatoid arthritis (RA) was proven in 21 patients, and the other 19 patients were not classified as having RA. Hypertrophy of the synovial membrane and tendon sheaths were evaluated by fat-suppressed Gd-enhanced MRI, and bone erosions were also evaluated by T1-enhanced MRI. These results were compared between two groups. Seventeen of 19 patients (89.5%) in the non-RA group showed little or no synovial hypertrophy, while 17 of 21 patients (81%) in the RA group showed moderate to severe hypertrophy of the synovial membrane. Little or no tenosynovitis was found in 14 of 19 patients (73.7%) in the non-RA group, while 14 of 21 patients (66.7%) in the RA group had moderate to severe tenosynovitis. No bone erosion was found in the non-RA group, while a few bone erosions were found in 10 of 21 patients (47.6%) of the RA group. Fat-suppressed, Gd-enhanced MRI was useful in differentiating early-stage RA from non-RA when all patients had some symptoms in their hands.


Meta-analysis of time-series studies of air pollution and mortality: effects of gases and particles and the influence of cause of death, age, and season.
A comprehensive, systematic synthesis was conducted of daily time-series studies of air pollution and mortality from around the world. Estimates of effect sizes were extracted from 109 studies, from single- and multipollutant models, and by cause of death, age, and season. Random effects pooled estimates of excess all-cause mortality (single-pollutant models) associated with a change in pollutant concentration equal to the mean value among a representative group of cities were 2.0% (95% CI 1.5-2.4%) per 31.3 microg/m3 particulate matter (PM) of median diameter < or = 10 microm (PM10); 1.7% (1.2-2.2%) per 1.1 ppm CO; 2.8% (2.1-3.5%) per 24.0 ppb NO2; 1.6% (1.1-2.0%) per 31.2 ppb O3; and 0.9% (0.7-1.2%) per 9.4 ppb SO2 (daily maximum concentration for O3, daily average for others). Effect sizes were generally reduced in multipollutant models, but remained significantly different from zero for PM10 and SO2. Larger effect sizes were observed for respiratory mortality for all pollutants except O3. Heterogeneity among studies was partially accounted for by differences in variability of pollutant concentrations, and results were robust to alternative approaches to selecting estimates from the pool of available candidates. This synthesis leaves little doubt that acute air pollution exposure is a significant contributor to mortality.


Preparation of fluconazole buccal tablet and influence of formulation expedients on its properties.
The aim of present study was to prepare buccal tablets of fluconazole for oral candidiasis. The dosage forms were designed to release the drug above the minimum inhibitory concentration for prolonged period of time so as to reduce the frequency of administration and to overcome the side effects of systemic treatment. The buccal tablets were prepared by using Carbopol 71G and Noveon AA-1 by direct compression method. Microcrystalline cellulose was used as the filler and its effect was also studied. The prepared dosage forms were evaluated for physicochemical properties, in vitro release studies and mucoadhesive properties using sheep buccal mucosa as a model tissue. Tablets containing 50% of polymers (Carbopol & Noveon) were found to be the best with moderate swelling along with favorable bioadhesion force, residence time and in vitro drug release. The in vitro drug release studies revealed that drug released for 8 h, which in turn may reduce dosing frequency and improved patient compliance in oral candidiasis patients.


Evaluation of the antioxidant activity of capsiate analogues in polar, nonpolar, and micellar media.
Synthesis of 10 capsiate analogues was conducted by lipase-mediated (Novozyme 435) esterification of vanillyl alcohol with different fatty acids. The antioxidant activity of the synthesized capsiates was evaluated using three in vitro assays: DPPH radical scavenging assay (polar medium), Rancimat assay (nonpolar medium), and autoxidation of linoleic acid (micellar medium). The objective of this study is to find the influence of structural characteristics of the alkyl chain of capsiate analogues on their antioxidant activity. In these assays, BHT and α-tocopherol were used as reference compounds. Both DPPH and Rancimat assays did not show any specific trend of antioxidant activity with the increase in lipophilicity and also with the type of fatty acids grafted to the phenolic moiety. In the Tween 20 micellar system for the inhibition of autoxidation of linoleic acid, vanillyl ester attached to a C18 alkyl chain (vanillyl stearate, oleate, and ricinoleate) exhibited maximum inhibition of autoxidation of linoleic acid.


Models of cognitive deficit and statistical hypotheses: multiple sclerosis, an example.
The purpose of the current study was to describe four models of cognitive deficit and to outline the statistical hypotheses underlying each model. The four models of cognitive deficit were (a) specific deficit; (b) subgroup deficit; (c) a syndrome dissociation model; and (d) a global function dissociation model. Neuropsychological data are analyzed to examine each of these four models in a sample of mild Multiple Sclerosis (MS) patients. The results suggest that for these subjects and tests, the specific deficit model best fits the data. The results are reviewed initially in the context of MS. There follows a consideration of statistical caveats and finally, general applications of the proposed procedures.


Synthesis of Polyfunctional Diorganomagnesium and Diorganozinc Reagents through In Situ Trapping Halogen-Lithium Exchange of Highly Functionalized (Hetero)aryl Halides in Continuous Flow.
We report a halogen-lithium exchange performed in the presence of various metal salts (ZnCl2 , MgCl2 ⋅LiCl) on a broad range of sensitive bromo- or iodo(hetero)arenes using BuLi or PhLi as the exchange reagent and a commercially available continuous-flow setup. The resulting diarylmagnesium or diarylzinc species were trapped with various electrophiles, resulting in the formation of polyfunctional (hetero)arenes in high yields. This method enables the functionalization of (hetero)arenes containing highly sensitive groups such as an isothiocyanate, nitro, azide, or ester. A straightforward scale-up was possible without further optimization.


[Resistance of Neisseria gonorrhoeae to 4 antibiotics: an analysis of the situation in Guangzhou in 2002].
To survey the antibiotic resistance and the prevalence of penicillinase-producing and highly tetracycline-resistant Neisseria gonorrhoeae (PPNG and TRNG) in Guangzhou in 2002. Minimum inhibitory concentrations (MIC) of the 4 antimicrobial agents, tetracycline, spectinomycin, ciprofloxacin and ceftriaxone, to 100 strains of Neisseria gonorrhoeae were determined by agar dilution method, and beta-lactamase was detected by iodine quantification method. There were 15 (15%) strains of PPNG and 28 (28%) strains of TRNG among the 100 strains of Neisseriae gonorrhoeae examined, with a resistant rate to ciprofloxacin as high as 98% and 32 (32%) strains identified to be highly resistant to the antibiotics (MIC >or=16 mg/L). No resistant strains to ceftriaxone and specitinomycin were identified, but ceftriaxone susceptibility of the strains was declining. The current antibiotic resistance of gonococci strains are still serious in Guangzhou, especially in the case of ciprofloxacin resistance. The strains are sensitive to spectinomycin and ceftriaxone, and continuous monitoring of the bacteria for their antibiotic resistance is necessary.


Smoking as the potential link between Kimmelstiel-Wilson lesion and non-diabetic nodular glomerulosclerosis in male patients - a single center retrospective study.
The histological pattern of nodular glomerulosclerosis (NGS) can be found both in diabetic nephropathy (Kimmelstiel-Wilson (KW) lesion) and non-diabetic nodular glomerulosclerosis (non-diab NGS). Chronic smoking is considered to be a potential cause of non-diab NGS, but the prevalence of smokers in KW is unknown. In a retrospective analysis, native renal biopsy specimens (n = 644, 2001 - 2011) were evaluated and male patients' characteristics, including smoking habits, were assessed within three groups: diabetic patients with KW (n = 15), diabetic patients with other classes of diabetic nephropathy (non-KW; n = 46), and patients with non-diab NGS (n = 7). The majority of patients in the KW and non-diab NGS groups (13/15 = 87%, 7/7 = 100%, respectively; p = 1.0 vs. KW) were smokers, unlike the non-KW group (16/46 = 35%; p = 0.001 vs. KW). Cigarette pack-years showed a similar pattern (KW: 15 (6 - 30), non-KW: 0 (0 - 21), non-diab NGS: 30 (16 - 33); p = 0.010 non-KW vs. KW, p = 0.008 non-KW vs. non-diab NGS). Other known factors responsible for the worsening of non-KW or the development of non-diab NGS did not differ in the groups (age, body mass index, duration of diabetes mellitus, HbA1c, prevalence of hypertension, duration of hypertension, serum cholesterol, triglyceride, estimated glomerular filtration rate, and renin-angiotensin-aldosteron system-blocker treatment). We propose that chronic cigarette smoking could play a pivotal role in the development of KW lesions.


Mu-class glutathione transferase from Xenopus laevis: molecular cloning, expression and site-directed mutagenesis.
A cDNA encoding a Mu-class glutathione transferase (XlGSTM1-1) has been isolated from a Xenopus laevis liver library, and its nucleotide sequence has been determined. XlGSTM1-1 is composed of 219 amino acid residues with a calculated molecular mass of 25359 Da. Unlike many mammalian Mu-class GSTs, XlGSTM1-1 has a narrow spectrum of substrate specificity and it is also less effective in conjugating 1-chloro-2,4-dinitrobenzene. A notable structural feature of XlGSTM1-1 is the presence of the Cys-139 residue in place of the Glu-139, as well as the absence of the Cys-114 residue, present in other Mu-class GSTs, which is replaced by Ala. Site-directed mutagenesis experiments indicate that Cys-139 is not involved in the catalytic mechanism of XlGSTM1-1 but may be in part responsible for its structural instability, and experiments in vivo confirmed the role of this residue in stability. Evidence indicating that Arg-107 is essential for the 1-chloro-2,4-dinitrobenzene conjugation capacity of XlGSTM1-1 is also presented.


Tourism Experiences and Self-Rated Health Among Older Adults in China.
To investigate factors associated with tourism experiences, and the association between tourism experiences and subsequent self-rated health. Multilevel logistic regression models and four waves of panel data from a large nationally representative survey of older adults in China were employed. Those who had a tourism experience tended to be younger, men, urban residents, have a higher socioeconomic status (SES), and frequently participate in leisure activities and exercise. However, controlling for SES, women were more likely than men to have a tourism experience. Notably, tourism was negatively associated with poor self-rated health and the association was robust to adjustments for a wide range of confounders. The net beneficial impact of tourism on self-rated health may operate through several mechanisms such as improvements in tourists' cognitive functioning, healthy lifestyles, self-esteen, family and social relations, and psychological and spirtual well-being. Tourism participation is an effective way to promote healthy aging.


Instrument-free visual detection of tetracycline on an autocatalytic DNA machine using a caged G-quadruplex as the signal reporter.
An instrument-free visual biosensor for the amplified detection of tetracycline has been successfully constructed using an autocatalytic DNA machine as the signal amplifier and a caged G-quadruplex as the signal reporter. The assay is ultrasensitive, enabling the visual detection of trace levels of tetracycline as low as 1 pM without instrumentation.


Abundance of wild rodents, ticks and environmental risk of Lyme borreliosis: a longitudinal study in an area of Mazury Lakes district of Poland.
The results of a longitudinal epidemiological survey in two contrasting habitats in an area of the Mazury Lakes district of Poland indicate that both host and vector (Ixodes ricinus) densities, may be the most important risk factors for the tick-transmitted spirochetes of Borrelia burgdirferi s.l. However, the results also highlight that even related host species, such as the wild rodents Apodemus flavicollis and Clethrionomys glareolus that share the same habitat, can show quite different dynamics of tick infestation. We provide evidence that the woodland populations of A. flavicollis and C. glareolus are more frequently infested with larvae than nymphs, and more frequently with both stages than M. arvalis in the neighbouring open fallow lands. The prevalence of infestation with larvae varied from 92 % for A. flavicollis, and 76 % for C. glareolus to 37 % for M. arvalis. Other factors, such as population age structure and sex, were also shown to impact on tick densities on hosts at particular times of the year and hence on the zoonotic risk. Moreover, particular species of rodents from different habitats, A. flavicollis (woodlands) and Microtus arvalis (fallow lands) carry infected immature I. ricinus ticks more frequently than C. glareolus voles (woodlands). Thus, the relative contribution of each species to the cumulative reservoir competence differs among species living in the woodland habitats and in relation to voles living in the fallow lands. It follows, therefore, that any factor which reduces the relative density of A. flavicollis in comparison to other hosts in the wild rodent community, will reduce also the risk of human exposure to Lyme borreliosis spirochetes.


Studies on porphyrin biosynthesis in erythrocytes after incubation with delta-aminolaevulinic acid in patients with acute leukemia.
Biosynthesis of porphyrins in erythrocytes after incubation with delta-aminolevulinic acid was studied by the method of IDELSON in a control group of 30 healthy males and females as well as in 13 patients (7 females and 6 males) followed up during the initial stage, in remission and relapse of acute leukemia. The total amount of synthesized porphyrins was increased at the onset and in relapse as compared with healthy controls on account of the increased biosynthesis of coproporphyrin. Reversely, the amount of synthesized porphobilinogen and protoporphyrin was decreased. During the initial stage and in relapse of acute leukemia the percentage of residual delta-amino-levulinic acid displayed no significant differences while the percentage of disappeared delta-aminolevulinic acid was increased. During the stage of remission an activation of biosynthesis of porphyrins and porphobilinogen was observed as compared with the controls. The changes established are possibly associated with the pathogenesis of the anaemic syndrome in patients with acute leukemia at the initial stage, in remission and relapse.


Sageretia thea (Osbeck.) modulated biosynthesis of NiO nanoparticles and their in vitro pharmacognostic, antioxidant and cytotoxic potential.
NiO nanoparticles are biosynthesized using Sageretia thea (Osbeck.) aqueous leave extracts and their biological activities are reported. Nanoparticles (∼18 nm) were characterized through XRD, ATR-FTIR, EDS, SAED, HR-SEM/TEM and Raman spectroscopy. Antibacterial activity was investigated against six pathogenic bacterial strains (gram positive and gram negative) and their corresponding minimum inhibitory concentrations (MICs) were calculated. UV-exposed nanoparticles were investigated to have reduced MICs relative to the NiO nanoparticles have not been exposed to UV. Moderate linear fungal growth inhibition was observed while Mucor racemosus (percentage inhibition 64% ± 2.30) was found to be most susceptible. Cytotoxicity was confirmed using brine shrimps lethality assay (IC50 42.60 μg/ml). MTT cytotoxicity was performed against Leishmania tropica-KWH23 promastigotes and amastigotes revealed significant percentage inhibition across the applied concentrations. IC50 values were calculated as 24.13 μg/ml and 26.74 μg/ml for the promastigote and amastigote cultures of Leishmania tropica. NiO nanoparticles were found. Moderate, antioxidant potential was concluded through assays like DPPH, TAP and TAC. Furthermore, protein kinase inhibition and alpha amylase inhibition is also reported.


Opposing Transcriptional Mechanisms Regulate Toxoplasma Development.
The Toxoplasma biology that underlies human chronic infection is developmental conversion of the acute tachyzoite stage into the latent bradyzoite stage. We investigated the roles of two alkaline-stress-induced ApiAP2 transcription factors, AP2IV-3 and AP2IX-9, in bradyzoite development. These factors were expressed in two overlapping waves during bradyzoite development, with AP2IX-9 increasing expression earlier than AP2IV-3, which peaked as AP2IX-9 expression was declining. Disruption of the AP2IX-9 gene enhanced, while deletion of AP2IV-3 gene decreased, tissue cyst formation, demonstrating that these factors have opposite functions in bradyzoite development. Conversely, conditional overexpression of FKBP-modified AP2IX-9 or AP2IV-3 with the small molecule Shield 1 had a reciprocal effect on tissue cyst formation, confirming the conclusions of the knockout experiments. The AP2IX-9 repressor and AP2IV-3 activator tissue cyst phenotypes were borne out in gene expression studies that determined that many of the same bradyzoite genes were regulated in an opposite manner by these transcription factors. A common gene target was the canonical bradyzoite marker BAG1, and mechanistic experiments determined that, like AP2IX-9, AP2IV-3 regulates a BAG1 promoter-luciferase reporter and specifically binds the BAG1 promoter in parasite chromatin. Altogether, these results suggest that the AP2IX-9 transcriptional repressor and the AP2IV-3 transcriptional activator likely compete to control bradyzoite gene expression, which may permit Toxoplasma to better adapt to different tissue environments and select a suitable host cell for long-term survival of the dormant tissue cyst. IMPORTANCEToxoplasma infections are lifelong because of the development of the bradyzoite tissue cyst, which is effectively invisible to the immune system. Despite the important clinical consequences of this developmental pathway, the molecular basis of the switch mechanisms that control tissue cyst formation is still poorly understood. Significant changes in gene expression are associated with tissue cyst development, and ApiAP2 transcription factors are an important mechanism regulating this developmental transcriptome. However, the molecular composition of these ApiAP2 complexes and the operating principles of ApiAP2 mechanisms are not well defined. Here we establish that competing ApiAP2 transcriptional mechanisms operate to regulate this clinically important developmental pathway.


Left ventricular afterload reduction by transcatheter aortic valve implantation in severe aortic stenosis and its prompt effects on comprehensive coronary haemodynamics.
In this study we aimed to test the hypothesis that left ventricular (LV) afterload reduction in severe aortic valve stenosis (AS) by transcatheter aortic valve implantation (TAVI) acutely improves coronary haemodynamics. This was a prospective, pathophysiologic study in 40 patients with severe AS undergoing TAVI. Endpoints were determined invasively immediately before and after TAVI without altering coronary stenotic lesions if present. Myocardial hyperaemia was induced by intravenous adenosine. The primary study endpoints were coronary flow reserve (thermodilution-derived CFR), and fractional flow reserve (FFR). The secondary study endpoint was coronary collateral flow index (CFI) as obtained during a one-minute coronary balloon occlusion. CFR was 1.9±0.9 before TAVI and 2.0±1.0 after TAVI (p=0.72). FFR was 0.90±0.08 before TAVI and 0.93±0.08 after TAVI (p=0.0021). The TAVI-induced increase in FFR was related to a significant decrease in hyperaemic mean aortic pressure from 71±16 mmHg before TAVI to 67±15 mmHg after TAVI (p=0.0099). Hyperaemic CFI increased from 0.127±0.083 before to 0.146±0.090 after TAVI (p=0.0508). CFR appears not to be acutely affected by LV afterload reduction among patients with severe AS in response to TAVI. However, it acutely improves FFR; this occurs via lowering of mean aortic pressure. Hyperaemic coronary collateral flow index tends to augment in response to TAVI.


A new strategy for the computer-assisted development of reversed-phase liquid chromatography separation methods of unknown sample mixtures.
A new strategy for the computer-assisted methods development in the reversed-phase liquid chromatographic separations of unknown sample mixtures has been developed using the latent spectral information in chromatogram raw data files of appropriately designed experiments, rather than resorting to elemental information functions (e.g., the number of peaks in chromatograms or similar criteria). The strategy developed allows unification of the approach for samples of both known and unknown composition and, thus, provide a general strategy for computer-aided tools in the chromatography laboratory. The operation principle of this strategy departs from extracting the spectra of components in the mixture chromatograms by resorting to multivariate curve resolution-alternating least squares (MCR-ALS). This technique allows the estimation of the true spectra for the individual components except when they have identical spectra or are fully overlapped. Thus, a convenient experimental design will try to perform separations of the sample mixture having at least partial resolution of components in some runs. This will allow estimating the spectra of components and, then, assign these components to the peaks in each run chromatogram. In this way, a retention model can be built for each component so computerized optimization process can be developed to provide the chromatographer with the best possible separation programs. Following this approach, strategies for sample mixtures of known and unknown composition are only different in the need of an initial spectrum discovery process for unknown mixtures and therefore a real general approach for the computer-assisted LC methods development is now available for the first time.


Investigations of signaling pathways in axon growth and guidance.
The retinotectal projection in chick is a well studied model system for axon guidance. The 'stripe assay' provides a unique tool for investigating underlying molecules and mechanisms of axon guidance by non-diffusible substrate bound molecules in vitro. By combining this assay with a modified 'Campenot chamber', we have now investigated the role of several second messenger systems in this type of axon guidance by confronting growing axons with various drugs that are known to influence intracellular signaling. We have shown that extracellular, and most probably intracellular Ca++ is not required for this type of axon guidance, which also rules out the need for Ca++-dependent adhesion molecules like cadherins. While at least calmodulin and protein kinase C seem to be involved in axon elongation, inhibiting their function did not alter the growth cones' choice. Inhibition of other kinases, G-proteins and signaling components also failed to influence this guidance. These results may indicate that parallel signaling pathways take part in the molecular mechanism of this type of axon guidance.


Functional and structural characterization of the two beta 1-adrenoceptor forms in turkey erythrocytes with molecular masses of 50 and 40 kilodaltons.
We have previously described a specific protease in turkey erythrocytes that converts the larger 50-kDa (P50) form of the beta 1-adrenoceptor to a smaller 40-kDa (P40) form [Jürss, R., Hekman, M., & Helmreich, E. J. M. (1985) Biochemistry 24, 3349-3354]. Further functional and structural characterization studies of the two forms are reported here. When purified P50 and P40 receptors were compared with respect to their relative capabilities to couple in lipid vesicles with pure stimulatory G-proteins (Gs-proteins) prepared from turkey erythrocytes or rabbit liver, a faster and larger activation of Gs-proteins was observed in response to l-isoproterenol and guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) with P40 than with P50 receptor. The kon values for P40 were 0.47 min-1 in the case of liver Gs and 0.22 min-1 in the case of erythrocyte Gs, whereas the corresponding values for P50 were 0.34 min-1 and 0.12 min-1, respectively. The binding properties of P50 and P40 forms of the receptor were not different, and desensitization of turkey erythrocytes on exposure to l-isoproterenol did not activate the protease. We furthermore ascertained that only the larger form with a molecular mass of 50 kDa carries the N-linked carbohydrates, which are removed on proteolytic conversion to the 40-kDa form and have either a triantennary or a tetraantennary nonfucosylated complex-type structure containing terminal sialyl residues.


[Headaches in children and adolescents. An etiopathogenic classification].
Headache is one of the most frequent reasons for presenting to Neuropaediatric units. Although in most cases the patient is not suffering from any serious disease, the parents and even the paediatrician do tend to fear that this is indeed the case. Evaluating a patient with headache requires a detailed interview, as well as a careful clinico-neurological examination. From these elements it is basically possible to sort headaches into four large groups: acute, acute-recurrent, chronic non-progressive and chronic progressive. Acute headaches are an emergency and it is therefore necessary to have an algorithm available which can be used regardless of the degree of complexity of the clinical environment in which the patient is being treated. Invasive studies such as a spinal tap and/or neuroradiological studies are often needed. The International Headache Society criteria have been adapted to the juvenile population for the diagnosis of patients suffering from acute-recurrent headaches (migraine). Chronic non-progressive headaches are a group in which prevalence increases with age and is the most frequently observed form of headache in adolescents. Emotional factors, situations involving family and/or social conflict, either alone or in combination, are usually predisposing or triggering factors in this type of headache. Chronic progressive headache is a consequence of some organic disorder. In the search for and treatment of headache we must not forget to calm the pain experienced by the patient.


Sentinel lymph node tumour burden using digital cell count estimation predicts outcomes in melanoma.
Cutaneous melanoma often metastasises in primis to sentinel lymph nodes (SLNs). Currently, there is no standardized method of characterizing the micrometastatic tumour burden in SLN biopsies for melanoma. Different criteria have been developed to evaluate SLN biopsies, yet none consider the number of cells identified. Here, we used software analysis to digitally quantify metastatic tumour burden within SLNs and correlated these data with clinicopathological and prognostic information. We identified 246 cases of SLN biopsies, including 63 positive (26%) and183 (74%) negative for metastatic melanoma. Digital cell counting was performed within the greatest metastatic focus and the entire metastatic tumour burden within the same SLN. Increasing cell count in the largest metastatic deposit correlated with the previously described Rotterdam [Spearman's r = 0.91; 95% confidence interval (CI) = 0.84, 0.94], Starz (Spearman's r = 0.78; 95% CI = 0.68, 0.87) and Dewar criteria (P < 0.01), validating our method of using cell count to define SLN tumour burden. Additionally, increasing cell count was associated with decreased metastasis-free survival (hazard ratio = 2.29; 95% CI = 1.22, 4.31). These data support the use of computerized cell count analysis for prognostication of outcomes in patients undergoing SLN biopsy.


Coronary calcium scanning adds incremental value to patients with positive stress tests.
The sensitivity of coronary calcification by electron beam tomography (EBT) for the detection of coronary atherosclerosis is well-established. Combining the anatomic information of EBT with the functional information of stress testing might reduce the high false-positive result rate seen with treadmill stress test (TMST) alone. No studies have reported the additive value of a negative EBT result (no coronary calcium) for excluding obstructive coronary artery disease (OCAD) in patients with a positive TMST result. This study evaluated the negative predictive value and potential clinical utility of EBT to identify patients with a falsely abnormal TMST. A coronary calcium score was determined by EBT for 153 symptomatic patients who underwent coronary angiography because of a positive TMST. The sensitivity, specificity, and predictive values of EBT were determined. A multiple logistic regression analysis compared conventional cardiac risk factors with coronary calcification by EBT for predicting OCAD. A receiver operating characteristic curve was generated plotting sensitivity versus false-positive rate. The false-positive rate of the TMST compared with angiography was 27% (41 of 153). The sensitivity of a nonzero coronary calcium score for OCAD was 98% (110 of 112), with a negative predictive value of 93%. According to multiple logistic regression, coronary calcification by EBT was a stronger predictor of OCAD than any conventional cardiac risk factor. EBT calcium added incremental value to the results of the TMST. Receiver operating characteristic curve analysis found an area under the curve of 0.91 (P <.001). The absence of coronary calcification by EBT reliably identified patients with a false-positive TMST result. The combination of EBT with TMST is a potentially useful diagnostic strategy to reduce the number of false-positive test results.


Coronary intervention in patients with diabetes, chronic renal disease, and the elderly: therapeutic implications.
Patients with diabetes mellitus, chronic renal disease, or advanced age who are undergoing percutaneous coronary intervention are at an increased risk of bleeding and thrombosis. This article reviews the clinical implications of these conditions and discusses the therapeutic options currently available for these patient groups.


A gene's-eye view of symbiont transmission.
Symbiotic associations between species are ubiquitous, but we only poorly understand why some symbioses evolve to be mutualistic and others to be parasitic. One prominent hypothesis holds that vertical transmission of symbionts from host parents to their offspring selects for symbionts that are benign or beneficial, while horizontal transmission of symbionts among unrelated hosts selects for symbionts that are less beneficial or outright harmful. A long-standing challenge to this hypothesis, however, is the existence of selfish genetic elements (SGEs). SGEs are passed exclusively from parent to offspring and are able to spread and persist in populations despite reducing the fitness of their hosts. Here I show that SGEs are in fact consistent with the transmission mode hypothesis if one measures transmission from the perspective of host genes instead of host organisms. Both meiotic drive genes and cytoplasmic sex ratio distorters require horizontal transmission, in the form of outbred sex, to spread as parasites. Transmission from parent to offpsring does not constrain SGEs to evolve toward mutualism. The gene-centered perspective I present here is applicable to symbioses at all levels of selection and brings closer together our understandings of cooperation within and between species.


Evaluation and treatment of velopharyngeal insufficiency: the University of Florida experience.
This retrospective study spans the years 1988 to 2000 and looks specifically at the treatment procedures and outcomes for the correction of velopharyngeal insufficiency (VPI). Ninety-eight patients underwent preoperative assessment by speech pathologists that included perceptual speech evaluation, videofluoroscopy, and, for some, nasendoscopy. Based on this evaluation protocol, a specific surgical procedure was chosen to serve the patients' needs. The four procedures of choice were the palatal pushback with a pharyngeal flap lining, sphincter pharyngoplasty, a superiorly based obturating pharyngeal flap, and Furlow palatoplasty. The criteria for selecting these procedures are reviewed. The results revealed VPI resolution and the establishment of normal nonnasal speech in more than 95% of the 75 patients for whom outcomes were determined. This study reiterates the importance of thorough preoperative evaluation and the individualization of the secondary corrective procedure.


Mood stabilizers target cellular plasticity and resilience cascades: implications for the development of novel therapeutics.
Bipolar disorder is a devastating disease with a lifetime incidence of about 1% in the general population. Suicide is the cause of death in 10 to 15% of patients and in addition to suicide, mood disorders are associated with many other harmful health effects. Mood stabilizers are medications used to treat bipolar disorder. In addition to their therapeutic effects for the treatment of acute manic episodes, mood stabilizers are useful as prophylaxis against future episodes and as adjunctive antidepressant medications. The most established and investigated mood-stabilizing drugs are lithium and valproate but other anticonvulsants (such as carbamazepine and lamotrigine) and antipsychotics are also considered as mood stabilizers. Despite the efficacy of these diverse medications, their mechanisms of action remain, to a great extent, unknown. Lithium's inhibition of some enzymes, such as inositol monophosphatase and glycogen synthase kinase-3, probably results in its mood-stabilizing effects. Valproate may share its anticonvulsant target with its mood-stabilizing target or may act through other mechanisms. It has been shown that lithium, valproate, and/or carbamazepine regulate numerous factors involved in cell survival pathways, including cyclic adenine monophospate response element-binding protein, brain-derived neurotrophic factor, bcl-2, and mitogen-activated protein kinases. These drugs have been suggested to have neurotrophic and neuroprotective properties that ameliorate impairments of cellular plasticity and resilience underlying the pathophysiology of mood disorders. This article also discusses approaches to develop novel treatments specifically for bipolar disorder.


Activity coefficients at infinite dilution measurements for organic solutes and water in the ionic liquid 1-ethyl-3-methylimidazolium trifluoroacetate.
The activity coefficients at infinite dilution, gamma13(infinity) for 29 solutes, alkanes, alkenes, alkynes, cycloalkanes, aromatic hydrocarbons, alcohols and water in the ionic liquid 1-ethyl-3-methylimidazolium trifluoroacetate ([EMIM][TFA]), were determined by gas-liquid chromatography at temperatures from 298.15-368.15 K. The partial molar excess enthalpies at infinite dilution DeltaH1(E,infinity) values were calculated from the experimental gamma13(infinity) values obtained over the temperature range. The selectivities for the hexane/benzene and cyclohexane/benzene separation were calculated from gamma13(infinity) and compared to the literature values for other ionic liquids, NMP and sulfolane.


[Not Available].
Heroism is described as a characteristic feature of the medical workers throughout the world, and particularly those from the socialist countries where a new, imbued by deep humanism society is being constructed. On the basis of numerous facts recorded, the author illustrates the unheard of heroism and self-renunciation of hundreds and hundreds of medical workers from many countries during the fulfilling of their human duty toward the casualty victims under most different circumstances--in peace, wars, revolutions and various social catastrophies. Facts are set forth proving the outstanding heroism of Russian and Soviet medical workers, of Bulgarian, Yugoslav, Polish, Czechoslovak and other physicians, who dedicated their work and lives to the welfare of peoples and for the victory of humanism and communism.


Normal vector magnetocardiogram. I. Correlation with the normal vector ECG.
The vector magnetocardiogram (VMCG) has been measured with the corrected unipositional VMCG lead system and analyzed statistically in 290 normal subjects. The morphologic study of the QRS waveforms showed that in the right-to-left (X) component, the triphasic qRs waveform appeared in 55% of the subjects. The superoinferior (Y) component was characterized by a prominent S wave in 96% of the subjects, and the anteroposterior (Z) component was also characterized by a prominent S wave in 95% . The VMGs were compared with the vector electrocardiograms (VECG) recorded in a subgroup of 200 subjects, in whom both the VMCG and VECG were available for computer analysis. The normal variability of the spatial vector magnitude measurements was significantly greater in the VMCG than in the VECG. Some similarities were observed in the waveforms of the time-averaged QRS complexes between the VMCG and VECG. Multiple linear regression analysis between the VMCG and VECG showed that maximally 27, 45, and 41% of the variation in the instantaneous QRS X, Y, and Z amplitudes of the VMCG, respectively, could be explained by the instantaneous X, Y, and Z amplitudes of the VECG.


Serum calcitonin negative medullary thyroid carcinoma.
Medullary thyroid carcinomas (MTC) constitute about 5 to 7% of thyroid neoplasms. They originate from parafollicular C cells which produce Calcitonin, a hormone which has an impact on calcium metabolism and represents the biochemical activity of MTC. In rare cases pre-operative serum calcitonin can be negative. We report on a 73-year-old female patient with a rare case of a serum calcitonin negative medullary thyroid carcinoma who suffered fulminant post-operative course and died of multiple metastasis. This case shows that in very rare cases MTCs do not secrete calcitonin making diagnosis and tumour follow-up difficult. To this date, only few reports describing this combination of circumstances were found in the English literature.


BCMA loss in the epoch of novel immunotherapy for multiple myeloma: from biology to clinical practice.
The treatment of multiple myeloma (MM) is evolving rapidly. In the past few years, chimeric antigen receptor modified T cells and bispecific antibodies are bringing new treatment options to patients with relapsed/refractory MM. Currently, B-cell maturation antigen (BCMA) has emerged as the most commonly used target of T-cell-based immunotherapies for relapsed/refractory MM. Clinical data have demonstrated promising efficacy and manageable safety profiles of both chimeric antigen receptor T-cell and bispecific antibody therapies in heavily pretreated relapsed/refractory MM. However, most patients suffer from relapses at later time points, and the mechanism of resistance remains largely unknown. Theoretically, loss of antigen is a potential tumor-intrinsic resistance mechanism against BCMA-targeted immunotherapies. Strategies to overcome this kind of drug resistance are, therefore, needed. In this review, we discuss the loss of BCMA in the new epoch of immunotherapy for MM.


Leishmania donovani Induced Cutaneous Leishmaniasis: An Insight into Atypical Clinical Variants in Sri Lanka.
Sri Lanka is a recent focus having Leishmania donovani induced cutaneous leishmaniasis (CL) as the main clinical entity. A separate clinical entity within profile of CL was described in this study. Laboratory confirmed cases of CL (n= 950, 2002-2014) were analysed. Most lesions showed known classical developmental stages of CL (CCL) observed in other CL endemic settings while few cases (13%, 122/950) showed atypical skin manifestations (ACL). Clinical, geographical, and treatment response patterns of ACL were different from those of CCL. ACL was mainly found among males (68.0%), in 21-40 year age group (51.6%), and reported delayed treatment seeking (23.5% vs 16.3% in CCL), more nonclassical onset (lesions other than acne form <1cm sized papules), (12.1 vs 2.7%, P<0.05.), more head and neck lesions (41.5%. vs 27.2%), more large lesions (>4cm), (18.6 vs 9.9%), and poor laboratory positivity rates (65.6% vs 88.2%) when compared to CCL. When compared to lesions reporting a typical onset, lesions reporting nonclassical onset were more likely to develop ACL later on (50.1% vs 10.7%). As compared to lesions on limbs, those on head and neck and trunk were more likely to be ACL (7.0%, 16.3%, and 22.8%, respectively, P<0.05). ACL features were not age or gender dependent. Highest proportion within ACL category (32.8%) and small proportion of CCL (10.1%) originated from less leishmaniasis prevalent areas (other regions) (P<0.05). North reported more ACL than South (15.9% vs 7.4%). A total of 95 CL cases with a significant travel history were further analyzed. Residents of other regions when acquired infection from North or South developed more ACL than residents in North or South (60.9% vs 15.9% and 42.9% vs 7.4% respectively). Patients in other regions when travelled to North developed more ACL than when they travelled to South (60.9%, 42.9%). ACL and CCL required an average of 18 doses over 16.7 months and 10 doses over 12 weeks, respectively, to achieve a complete clinical cure. Underlying host immunological factors, parasite strain variations and regional variations of both could be underlying etiologies. Established independent transmission within less leishmaniasis prevalent regions combined with an unusual clinical picture leading to poor clinical suspicion and low laboratory confirmation rate will pose potential difficulties in early case detection in these highly populated and commercialized areas. This in turn will further facilitate silent and high disease transmission.


Ultrasound and Risk Survey Evidence for Cystic Echinococcosis in La Rioja Province, Argentina.
Hydatidosis is a zoonosis of worldwide distribution with endemic areas in Argentina. The present epidemiological study was conducted to explore the presence of cystic echinococcosis in the rural community of Los Bordos (population 99), in the northern province of La Rioja, Argentina, during March 2018. The study included the search for cysts by abdominal ultrasound and a survey on family risk. Sixty-seven people agreed to undergo ultrasound examination, and five adults showed images compatible with hydatic cysts (7.5% prevalence). A family survey was applied to 29 households (78%), stratifying 24 families (83%) as high risk (95% confidence interval = 64.2-94.1) and 5 (17%) as low risk (95% confidence interval = 5.8-55.7) of transmission of the disease, respectively. The values were statistically different by the McNemar test. The goal of the present study, the first study of its kind in La Rioja, was to assess the family risk of echinococcosis among subjects with ultrasound images compatible with cystic echinococcosis.


Validation of the PHEEM instrument in a Danish hospital setting.
The Postgraduate Hospital Educational Environment Measure (PHEEM) has been translated into Danish and then validated with good internal consistency by 342 Danish junior and senior hospital doctors. Four of the 40 items are culturally dependent in the Danish hospital setting. Factor analysis demonstrated that seven items are interconnected. This information can be used to shorten the instrument by perhaps another three items.


An epidemiological study of brain tumours in the elderly.
An epidemiological study of brain tumours in elderly Japanese was undertaken on the basis of a report from the All Japan Brain Tumor Registry. Thus, the recent status of brain tumours in elderly Japanese could be clarified. Accordingly, the formerly compiled characteristics of brain tumours in the elderly should more or less be revised. However, we are all still facing the same unfavourable prognosis of brain tumours in the elderly as before.


Efficient in vivo xenogeneic retroviral vector-mediated gene transduction into human hepatocytes.
We developed a method for efficient retroviral vector-mediated gene transfer into human hepatocytes, using a human hepatocyte-bearing mouse model. Normal human hepatocytes were transplanted into the livers of immunodeficient and liver-damaged mice. Donor hepatocytes multiplied and replaced the host hepatocytes, which yielded human hepatocyte-bearing mice (human hepatocyte-chimeric mice). As control cells, rat hepatocytes were similarly transplanted. The replacement level reached 86% at 8 weeks and 100% at 5 weeks posttransplantation of human and rat hepatocytes, respectively. Human and rat hepatocytes in the host liver showed a high bromodeoxyuridine-labeling index during the first 2 weeks posttransplantation. Human- and rat-chimeric mice were injected 7 and 10 days posttransplantation, respectively, with retroviral vectors carrying the beta-galactosidase gene and were thereafter injected daily for 20 and 10 days, respectively. The level of beta-galactosidase-positive hepatocytes in the human- and rat-chimeric mice reached 7.1 +/- 1.8% at 8 weeks and 5.3 +/- 0.9% at 5 weeks after transplantation, respectively. The human hepatocyte-chimeric mouse will be useful for testing the ability of vectors to transduce human cells.


G gamma delta beta thalassaemia and g gamma HPFH (Hb Kenya type): comparison of 2 new cases.
Two new cases of G gamma delta beta thalassaemia and G gamma HPFH (Hb Kenya type) have been characterised in detail and compared with regard to haematological data, globin chains biosynthesis, and intracellular distribution of Hb F. The similarities and differences between these two conditions are discussed in relation to the possible underlying defects at the molecular level and to the control of the gamma delta beta gene complex in general.


Patterns of striatal dopamine depletion in early Parkinson disease: Prognostic relevance.
To investigate whether the patterns of striatal dopamine depletion on dopamine transporter (DAT) scans could provide information on the long-term prognosis in Parkinson disease (PD). We enrolled 205 drug-naive patients with early-stage PD, who underwent 18F-FP-CIT PET scans at initial assessment and received PD medications for 3 or more years. After quantifying the DAT availability in each striatal subregion, factor analysis was conducted to simplify the identification of striatal dopamine depletion patterns and to yield 4 striatal subregion factors. We assessed the effect of these factors on the development of levodopa-induced dyskinesia (LID), wearing-off, freezing of gait (FOG), and dementia during the follow-up period (6.84 ± 1.80 years). The 4 factors indicated which striatal subregions were relatively preserved: factor 1 (caudate), factor 2 (more-affected sensorimotor striatum), factor 3 (less-affected sensorimotor striatum), and factor 4 (anterior putamen). Cox regression analyses using the composite scores of these striatal subregion factors as covariates demonstrated that selective dopamine depletion in the sensorimotor striatum was associated with a higher risk for developing LID. Selective dopamine loss in the putamen, particularly in the anterior putamen, was associated with early development of wearing-off. Selective involvement of the anterior putamen was associated with a higher risk for dementia conversion. However, the patterns of striatal dopamine depletion did not affect the risk of FOG. These findings suggested that the patterns of striatal dopaminergic denervation, which were estimated by the equation derived from the factor analysis, have a prognostic implication in patients with early-stage PD.


Cancer risk among patients with multiple sclerosis: a population-based register study.
Cancer occurrence in patients with multiple sclerosis (MS) has been little studied, but associations with brain tumours, breast cancer, Hodgkin lymphoma and nasopharyngeal carcinoma have been suggested. We took advantage of population-based registers of MS and cancer to assess the risk of cancer following diagnosis of MS. Patients registered in the Danish Multiple Sclerosis Register were linked with the Danish Cancer Register to obtain information on cancer occurrence. The ratio of the observed to the number of expected cancers based on population-based incidence rates, i.e., the standardised incidence ratio (SIR), served as measure of the relative cancer risk. A database comprising all Danish women born after April 1, 1935, with information on all live-born children, was used in the analyses of breast cancer to adjust for reproductive factors. Overall 1,037 cancers were observed in 11,817 MS patients during 153,875 person-years of follow-up vs. an expected number of 1,098 (SIR = 0.94 [95% confidence interval CI: (0.89-1.00)]. The risk of brain tumours and Hodgkin lymphoma was not increased. A 16% overall reduced cancer risk in men with MS was explained by reduced numbers of cancers of the digestive, respiratory and genital organs. Though the overall cancer risk was not increased [SIR = 1.01(0.94-1.09), n = 676], female MS patients had an increased risk of breast cancer [SIR = 1.21 (1.05-1.39), n = 193]. Adjusting for parity and age at first child delivery did not change this risk estimate materially. In general MS patients are not at increased risk of cancer. Women with MS, however, seem to have a small excess risk of breast cancer, which cannot be attributed to reduced parity or delayed first child birth.


The regulation of MDM2 oncogene and its impact on human cancers.
Tumor suppressor p53 plays a central role in preventing tumor formation. The levels and activity of p53 is under tight regulation to ensure its proper function. Murine double minute 2 (MDM2), a p53 target gene, is an E3 ubiquitin ligase. MDM2 is a key negative regulator of p53 protein, and forms an auto-regulatory feedback loop with p53. MDM2 is an oncogene with both p53-dependent and p53-independent oncogenic activities, and often has increased expression levels in a variety of human cancers. MDM2 is highly regulated; the levels and function of MDM2 are regulated at the transcriptional, translational and post-translational levels. This review provides an overview of the regulation of MDM2. Dysregulation of MDM2 impacts significantly upon the p53 functions, and in turn the tumorigenesis. Considering the key role that MDM2 plays in human cancers, a better understanding of the regulation of MDM2 will help us to develop novel and more effective cancer therapeutic strategies to target MDM2 and activate p53 in cells.


Accessory function of human thymic dendritic cells in Con A-induced proliferation of autologous thymocyte subsets.
Human thymic dendritic cells (DC) have previously been shown to be intimately associated with thymocytes in situ and in culture. We report that thymic DC express LFA-3 and ICAM-1 adhesion molecules and may spontaneously associate with autologous thymocytes within mitogen-independent clusters. Moreover, the accessory activity of isolated human thymic DC was investigated in Con A-stimulation assays. By proliferation experiments, measured as [3H]TdR incorporation, we demonstrated that irradiated thymic DC strongly increase the mitogen-induced activation of autologous PBL as well as of unfractionated thymocytes. More interestingly, in coculture assays performed with purified thymocyte subsets, we have found that thymic DC greatly enhance the Con A proliferation of CD1- CD3bright thymocytes whereas the accessory activity toward the CD1+ CD3- thymocytes was very weak. Inhibition experiments demonstrated that the DC accessory activity is inhibited by anti-DR-related and anti-IL-2R mAb. However, blocking assays with anti-CD11b, anti-CD11c, anti-LFA-3, and anti-ICAM1 mAb showed that the accessory function obtained is similar to that with untreated cultures. We conclude that isolated human thymic DC may present potent DR- and IL-2-dependent accessory activity mainly directed toward the CD1- CD3bright thymocyte subpopulation, suggesting that thymic DC may be involved in the in vivo proliferation of mature thymocytes.


[Clinical observation of the treatment of 654-2 injection and "ganxian tui huang recipe" on liver cirrhosis with intractable jaundice].
To observe the effect of 654-2 injection and "GanXian Tui Huang Recipe" on hepatic fibrosis with intractable jaundice. 60 patients were treated for 3 months and randomly divided into control group and experiment group. The experiment group was treated with 654-2 injection and "Gan Xian Tui Huang Recipe" and the control group was treated with routine treatment. All the patients have high level of Nitrogen monoxide(NO), hyaluronic acid(HA > 400 ng/ml) and hepatic fibrosis with intractable jaundice. In experiment group, the serum total bilirubin(TB), globulin(GLB), HA and NO were significantly decreased to normal level; 40% of portal veins were narrowed, 50% of them were not changed; 30% of spleen were thinned, 40% of them were fixed. 1 year later, 20 patients were stable and 2 patients were recurrent in 22 patients of the experiment group; in 24 patients of the control group, 7 patients were stable, 10 patients had hypersplenia, 2 patients occurred hepatocarcinoma and 5 patients were recurrent. Effect of 654-2 injection and "Gan Xian Tui Huang Recipe" on hepatic fibrosis with intractable jaundice is significant.


ATP-activated cationic current in rabbit sino-atrial node cells.
The electrophysiological effect of extracellular ATP was investigated in voltage-clamped single cells from the rabbit sino-atrial node. External 0.5 mM ATP consistently activated a time-independent, weakly inwardly rectifying current (2.26 +/- 0.14 pA/pF at -100 mV, n = 23). This external ATP-activated current increased in a dose-dependent manner over the concentration range 0.01 to 1 mM ATP. However, non-hydrolysable ATP analogs (a, beta-methylene ATP and beta,r-methylene ATP) failed to activate this current. Moreover, adenosine, adenosine monophosphate and adenosine diphosphate were all ineffective in eliciting the ATP-activated current over the concentration range 0.5 to 1 mM, suggesting that it is regulated via the P2-purinoreceptor. The permeability sequence for the ATP-activated current among different cations (determined from reversal potential measurements) was 1.09: 1: 1: 0.24: 0.22 for K+, Na+, Cs+, Tris and N-methyl-D-glucamine. The current component was not affected by substitution of external Cl- by aspartate or by the application of a stilbene-derivative Cl- channel blocker. Thus, the ATP-activated current in rabbit sino-atrial node cells was non-selective for monovalent cations, and could be carried by large molecular ions, such as N-methyl-D-glucamine or Tris. We suggest that it might make some contribution to the chronotropic effects seen on release of transmitters from autonomic nerve endings in the heart.


Journey from pediatric intensive care to palliative care.
Approximately two-thirds of patients who die in the pediatric intensive care unit (PICU) do so following withdrawal of intensive care treatment. Most often when intensive care treatment is withdrawn, the child remains in the PICU for end-of-life care. This study aimed to examine the process of referral over a 6-year period of children from a PICU to children's hospices for end-of-life care. This study carried out a retrospective review of all children referred from a large tertiary-level United Kingdom PICU to children's hospices over a 6-year period. Information was collected both from the PICU and from the hospices involved. A total of 12 children were transferred over the 6-year period. Discussions about limitation of treatment occurred after an average of 9 days of ventilation, with time from initial referral to transfer taking an additional 4 days such that the mean stay on the PICU prior to transfer was 13 days. Two-thirds of families had prior contact with the palliative care team involved. One-third of the patients were transported to the hospice while still dependent on mechanical invasive ventilatory support. All children were extubated by a PICU consultant within 90 minutes of arrival at the hospice. Overall, eight children died soon after transfer, with four children surviving beyond 2 weeks after transfer. This study suggests that there is a feasible alternative location for withdrawal of intensive care and/or compassionate extubation. The study found that one-third of children transferred to hospice for end-of-life care survived the initial withdrawal of intensive therapy; hence, parallel planning should be discussed prior to transfer to hospice. Information gained from this study has contributed toward the creation of a national care pathway to support extubation within a children's palliative care framework.


The effect of decellularisation on the real time mechanical fatigue of porcine aortic heart valve roots.
Decellularised heart valve roots offer a promising option for heart valve replacement in young patients, having the potential to remodel and repair. Replacement heart valves have to undergo billions of opening and closing cycles throughout the patient's lifetime. Therefore, understanding the effect of cyclic loading on decellularised heart valve roots is important prior to human implantation. The aim of this preliminary study was to investigate the influence of low concentration sodium dodecyl sulphate (SDS) decellularisation treatment on the in vitro real time mechanical fatigue of porcine aortic heart valve roots under physiological real time cyclic loading conditions. This required a specific real time in vitro method to be developed, since previous methods relied on accelerated testing, which is non-physiological, and not appropriate for valve replacement materials that exhibit time dependent characteristics. The effects of the real time fatigue on hydrodynamic function and mechanical properties of the heart valve roots were assessed. The mechanical fatigue of decellularised porcine aortic heart valve roots (n = 6) was assessed and compared to cellular porcine aortic heart valve roots (n = 6) in a modified Real time Wear Tester (RWT) at a physiological frequency and under cyclic pressure conditions for a maximum of 1.2 million cycles. Periodically, the heart valve roots were removed from the RWT to assess the influence of cyclic loading on valve competency (static leaflet closure). At the end of testing further hydrodynamic performance parameters were ascertained, along with determination of leaflet material properties. A real time mechanical fatigue assessment method was developed and applied; with two cellular and two decellularised porcine aortic leaflets in different heart valve roots showing tears in the belly region. The decellularised aortic heart valve roots exhibited comparative functionality to the cellular heart valve roots under in vitro static and pulsatile hydrodynamic conditions. However, the material properties of the decellularised aortic leaflets were significantly altered following cyclic fatigue assessment and showed increases in elastin and collagen phase slopes and ultimate tensile strength compared to the cellular porcine aortic leaflets in the circumferential direction. This preliminary study demonstrated that low concentration SDS decellularised porcine aortic heart valve roots can withstand physiological cyclic deformations up to 1.2 million cycles in a RWT whilst maintaining their overall hydrodynamic function and leaflet mechanical properties. This is the first full report of preclinical mechanical fatigue assessment of decellularised porcine aortic heart valve roots under physiological real time conditions.


Recovery of simple motor skills after head injury.
The performance of 40 head-injured patients (HI) without peripheral upper body injuries and 88 normal controls were compared on finger tapping and grip strength 1 month and 1 year after injury. The HI group demonstrated deficits on both tasks 1 month after injury, but only finger tapping was impaired 1 year postinjury. While grip strength differentially improved in the HI group from 1 month to 1 year, finger tapping improved similarly in both groups. The pattern of results was similar when a subset of 25 HI patients without any evidence of focal lesions were examined. These results demonstrate (1) motor deficits are present 1 year after injury even in a sample of predominantly mild head-injury patients, (2) grip strength is more sensitive to recovery in the first year after head injury, and (3) finger tapping continues to be impaired 1 year after head injury possibly due to its speed requirements.


A preliminary study on hot and cool executive functions in bipolar disorder and on their association with emotion regulation strategies.
Individuals with bipolar disorder (BD) experience difficulties in cognitive and emotional regulation in different phases of illness. In the present study, we aimed at exploring differences on hot and cool executive functioning (EF) between BD patients in euthymia (BDe) and mania (BDm), and associations of hot and cool EF with emotion regulation strategies. Thirty-seven BD patients (among which 18 with a current manic episode and 19 in euthymia) and 15 healthy controls completed a battery of tests assessing hot and cool EF and emotion regulation strategies. Between group comparisons showed that in all the explored hot dimensions BDm subjects had significantly worse performances than BDe subjects, while in all the explored cool dimensions BDm subjects had significantly worse performances than HC subjects, with BDe patients having an intermediate profile. Results from bivariate correlations among BDe subjects (but not among BDm subjects) showed significant positive correlations (i) between elements of hot EF and elements of cool EF, and (ii) between cognitive reappraisal emotional regulation strategy and planning (i.e., a measure of cool EF), as well as a significant negative correlation between expressive suppression emotional regulation strategy and emotional intelligence. The results confirm previous findings on a role of impaired EF in BD, and suggest (i) that hot EF is more closely related to mood (i.e., state-dependant) than cool EF, and (ii) that BD patients can more effectively use emotion regulation strategies in association with EF during euthymia than during mania.


[Circadian rhythm in cytokines].
The well-known human circadian rhythm (CR) in body temperature may be due to CR in endogenous pyrogens such as interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF). We, therefore, investigated the daily variation in spontaneous and LPS-induced monokine release by peripheral blood cells (whole blood assay) in 10 healthy volunteers. Spontaneous release of monokines (IL-1, IL-6, TNF) showed a simultaneous significant peak at noon, whereas LPS-induced release of IL-1 and IL-6 was strictly correlated with the CR in body temperature with its significant maximum at 8.00 p.m. Since LPS-induced release of TNF showed a significant peak at 4.00 a.m., interleukins and TNF seem to be independently regulated. CR in IL-1 and IL-6 release are suggested to be responsible for the CR in body temperature.


Activation of aldehyde dehydrogenase-2 improves ischemic random skin flap survival in rats.
Random skin flaps have many applications in plastic and reconstructive surgeries. However, distal flap necrosis restricts wider clinical utility. Mitophagy, a vital form of autophagy for damaged mitochondria, is excessively activated in flap ischemia/reperfusion (I/R) injury, thus inducing cell death. Aldehyde dehydrogenase-2 (ALDH2), an allosteric tetrameric enzyme, plays an important role in regulating mitophagy. We explored whether ALDH2 activated by N-(1,3-benzodioxol-5-ylmethyl)-2,6-dichlorobenzamide (Alda-1) could reduce the risk of ischemic random skin flap necrosis, and the possible mechanism of action. Modified McFarlane flap models were established in 36 male Sprague-Dawley rats assigned randomly to three groups: a low-dose Alda-1 group (10 mg/kg/day), a high-dose Alda-1 group (20 mg/kg/day) and a control group. The percentage surviving skin flap area, neutrophil density and microvessel density (MVD) were evaluated on day 7. Oxidative stress was quantitated by measuring the superoxide dismutase (SOD) and malondialdehyde (MDA) levels. Blood perfusion and skin flap angiogenesis were assessed via laser Doppler flow imaging and lead oxide-gelatin angiography, respectively. The expression levels of inflammatory cytokines (IL-1β, IL-6, and TNF-α), vascular endothelial growth factor (VEGF), ALDH2, PTEN-induced kinase 1 (PINK1), and E3 ubiquitin ligase (Parkin) were immunohistochemically detected. Indicators of mitophagy such as Beclin-1, p62, and microtubule-associated protein light chain 3 (LC3) were evaluated by immunofluorescence. Alda-1 significantly enhanced the survival area of random skin flaps. The SOD activity increased and the MDA level decreased, suggesting that Alda-1 reduced oxidative stress. ALDH2 was upregulated, and mitophagy-related proteins (PINK1, Parkin, Beclin-1, p62, and LC3) were downregulated, indicating that ALDH2 inhibited mitophagy through the PINK1/Parkin signaling pathway. Treatment with Alda-1 reduced neutrophil infiltration and expressions of inflammatory cytokines. Alda-1 significantly upregulated VEGF expression, increased the MVD, promoted angiogenesis, and enhanced blood perfusion. ALDH2 activation can effectively enhance random skin flap viability via inhibiting PINK1/Parkin-dependent mitophagy. Moreover, enhancement of ALDH2 activity also exerts anti-inflammatory and angiogenic properties.


Effects of anti-swine zona serum on swine and murine in vitro fertilization.
No investigations have been reported concerning the action of anti-swine zona (anti-SZ) antibodies in a swine in vitro fertilization (IVF) system. We examined the effects of anti-SZ on homologous swine IVF and heterologous murine IVF. Swine IVF and sperm-zona binding were inhibited after treating swine ova with 2(2) and 2(1) dilutions of antiserum, producing fertility rates of 25.9% and 1.6% respectively, which are significantly lower than the control group fertility rate of about 70%. However, the murine ova could accept the capacitated homologous sperm, even after treatment with the antiserum-derived IgG, which had an antibody titer twice that of the starting antiserum. The antiserum-reacted swine ova exhibited a zona precipitate and a concentration-dependent resistance to pronase and required about 17 minutes to disappear after reacting with the starting antiserum, whereas the antiserum-reacted murine ova, which did not exhibit a zona precipitate, and the control ova disappeared within three minutes. These results indicate that antibody deposition on the zona greatly affects the degree of fertilization inhibition. The immunogens used were characterized zona constituent glycoproteins, and the antiserum raised against them was previously proven to be highly specific. Therefore, we believe that a basis has been established for analyzing the fertilization phenomena that take place at the zona using swine systems.


NTP-CERHR monograph on the potential human reproductive and developmental effects of styrene.
The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for styrene to cause adverse effects on reproduction and development in humans. Styrene was selected for evaluation because of (1) public concern about styrene exposure and (2) recently available exposure studies. Styrene (ethenylbenzene; CAS RN: 100-42-5) is a high production volume chemical (a million pounds or more produced each year) and is used in the production of polystyrene resins and as a co-polymer with acrylonitrile and 1,3-butadiene. Styrene is found in items such as foam cups, dental fillings, matrices for ion exchange filters, construction materials, and boats. It is also used in protective coatings, reinforced glass fiber, agricultural products, and as a food additive. The Food and Drug Administration regulates styrene for use as a synthetic flavoring substance and as a component of polymers in contact with dry food, and also regulates the amount of residual styrene monomer allowed in polystyrene intended for use in contact with food. The public can be exposed to styrene by ingesting food or drink that has been in contact with styrene polymers or through inhalation of polluted air and cigarette smoke. The results of this evaluation on styrene are published in a NTP-CERHR monograph that includes: (1) the NTP Brief, (2) the Expert Panel Report on the Reproductive and Developmental Toxicity of Styrene, and (3) public comments received on the expert panel report. The NTP reached its conclusion of negligible concern for adverse developmental and reproductive effects resulting from styrene exposures in humans based on information presented in the NTP-CERHR Expert Panel Report on the Reproductive and Developmental Toxicity of Styrene and the public comments on that report. This conclusion is based on estimated exposures in both the general population and in people whose occupation involves styrene exposure. The expert panel estimated styrene exposure in the general U.S. population to be less than 0.3 microg/kg body weight/day in nonsmokers and 3.51 and 2.86 microg/kg body weight/day in smokers ages 12-19 years and 20-70 years, respectively. Average occupational exposures are estimated to range from 1,400-52,000 microg/kg body weight/day. Studies in humans show no evidence that occupational exposures or exposure of the general population to styrene adversely affect reproduction or development. Further, data from experimental animal studies show no adverse reproductive or developmental effects at styrene doses far above human exposure levels. The NTP will transmit the NTP-CERHR monograph on styrene to federal and state agencies, interested parties, and the public and it will be available in electronic PDF format on the CERHR web site http://cerhr.niehs.nih.gov and in printed text or CD-ROM from the CERHR: M.D. Shelby, Ph.D., Director, CERHR, NIEHS, P.O. Box 12233, MD EC-32, Research Triangle Park, NC 27709, 919-541-3455 [phone], 919-316-4511 [fax], email@example.com [email].


[Spoligotypes of Mycobacterium tuberculosis in the Czech population (methods and pilot study)].
In the introduction the authors describe molecular genetic principles of spacer oligonucleotide typing of the M. tuberculosis complex and mention in detail the methodical procedure of implementation of this examination technique incl. computer analysis of results. In the pilot part of the study the authors describe examination of 71 strains of M. tuberculosis isolated from patients living in the capital of Prague and 37 strains from patients in the South Moravian region of the Czech Republic. In the group of Prague strains a total of 7 clusters was identified formed by 2-14 identical profiles of spoligotypes and 37 individually different profiles. In the South Moravian strains there were 6 clusters with 2-14 identical spoligotypes and 10 non-clustered profiles. In neither of the groups there were spoligotypes typical for the genetic family Beijing or Africa. The study is a preliminary molecular epidemiological analysis where DNA fingerprint RFLP profiles are compared with spoligotypes of strains of M. tuberculosis of patients from the capital of Prague and the South Moravian region of the Czech Republic.


The regulation of GH secretion by sex steroids.
Gonadal sex steroids modulate GH synthesis and secretion with effects on both the hypothalamus and anterior pituitary. In the post-pubertal animal, androgens and oestrogens modulate hypothalamic somatostatin (SS) and GHRH synthesis respectively. These effects may be direct as SS neurons express the androgen receptor and many GHRH neurons are oestrogen receptor positive. The neonatal steroid environment modulates the number of GHRH neurons in the adult hypothalamus, as well as their responsivity to post-pubertal steroids. Furthermore, both neonatal and post-pubertal steroids modulate hypothalamic synaptic organisation affecting the number of synaptic inputs and the morphology of glial cells. This in turn has important effects on the ability of the hypothalamus to drive the secretory pulsatility of anterior pituitary hormone release. At the level of the somatotroph, androgens and oestrogens have been reported to stimulate, inhibit or have no effect on GH synthesis. In primary cultures, we found no effect of either androgens or oestrogens on GH mRNA levels. However, the sex steroid environment significantly modified the response of somatotrophs to SS. Furthermore, males have more somatotrophs compared with female rats and this partially depends on the neonatal sex steroid environment. In conclusion, sex steroids have both organisational and activational effects on the GH axis. These effects range from modulating the number of hypothalamic neurons controlling GH secretion, their responsiveness to later steroids, and the synaptic connectivity and neuropeptide production, to modulation of somatotroph numbers in the anterior pituitary and their responsiveness to inputs controlling GH synthesis and secretion.


Taxonomic relationships among spotted fever group rickettsiae as revealed by antigenic analysis with monoclonal antibodies.
The spotted fever group (SFG) is made up of more than 20 different rickettsial species and strains. Study of the taxonomic relationships among the group has been attempted by phenotypic, genotypic, and phylogenetic analyses. In this study, we determined taxonomic relationships among the SFG rickettsiae by comparative analysis of immunogenic epitopes reactive against a panel of monoclonal antibodies. A total of 98 monoclonal antibodies, which were directed against epitopes on the major immunodominant proteins or on the lipopolysaccharide-like antigens of strains of Rickettsia africae, Rickettsia conorii, Rickettsia massiliae, Rickettsia akari, Rickettsia sibirica, and Rickettsia slovaca, were used in the study. The distribution and expression of the epitopes among 29 SFG rickettsiae and Rickettsia bellii were assessed by determination of reaction titers in a microimmunofluorescence assay. The results were scored as numerical taxonomic data, and cluster analysis was used to construct a dendrogram. The architecture of this dendrogram was consistent with previous taxonomic studies, and the implications of this and other findings are discussed.


In vivo demonstration of subcellular localization of anti-transferrin receptor monoclonal antibody-colloidal gold conjugate in brain capillary endothelium.
To study transcytosis at the blood-brain barrier (BBB) in vivo, we used the internal carotid artery perfusion technique in rats. Brain uptake of the OX26 anti-transferrin receptor antibody (IgG2a) coupled to 5-nm colloidal gold (OX26-Au) was morphologically examined after infusion or perfusion into the carotid artery for 10 min. The brain tissue was subsequently perfusion-fixed with 2% glutaraldehyde. By light microscopy, silver enhancement of vibratome sections revealed staining of the vascular tree. Electron microscopy showed binding of gold particles at the luminal plasma membrane of brain capillary endothelia, endocytosis in vesicles (50-100 nm), and particles beyond the abluminal plasma membrane. Studies were performed with an IgG2a isotype control, UPC10. Internal carotid artery infusion of [125I]-UPC10 showed no evidence of brain uptake or binding to endothelium. However, microvessel structures were identified after silver enhancement of vibratome sections of brain following internal carotid artery infusion of 5-nm colloidal gold conjugates of UPC10 (UPC10-Au). The morphologically observed binding of UPC10-Au to brain microvessels may be induced by gold conjugation. These studies describe the use of gold conjugates of antibodies to delineate the subcellular pathway involved in transcytosis through the BBB.


Histamine affects interleukin-4, interleukin-5, and interferon-gamma production by human T cell clones from the airways and blood.
High levels of histamine can be found in the airways of asthma patients. This study describes the effects of histamine on anti-CD3-induced production of IL-4, IL-5, and IFN-gamma by T cell clones from subjects with allergic asthma and healthy subjects. T cell clones were obtained from bronchoalveolar lavage (BAL) fluid and blood. The number of clones tested, and the percentage of clones in which histamine inhibited or enhanced cytokine production by more than 25%, were as follows: IL-4, 47, 8.5%, and 4.3%; IL-5, 43, 14%, and 30%; and IFN-gamma, 52, 40%, and 15%. Inhibition of IL-5 and IFN-gamma production was reversed by IL-2. The enhancement of IFN-gamma production was associated with an enhancement of both IL-2 production and proliferation. In 21% of the clones a combined effect consisting of inhibition of IFN-gamma production and enhancement of IL-5 production was found. This response was reversed by H2-receptor antagonists and was significantly associated with a histamine-induced increase in intracellular levels of cAMP. The role of cAMP in mediating the histamine effects was supported by the observations that the beta2-agonist salbutamol had effects similar to histamine and that high concentrations of PGE2 mimicked the inhibitory effects of histamine. Clones from BAL fluid and blood showed similar responses, as did clones from patients with asthma and from control subjects. The enhancement of IFN-gamma production by histamine, however, was found only in clones from healthy subjects. The results warrant further investigations on the role of cAMP in the regulation of cytokine production.


Concentrations of thyroxine-binding globulin in sera and peritoneal dialysates in patients on chronic peritoneal ambulatory dialysis.
Losses in thyroxine-binding globulin (TBG) in peritoneal dialysate and thyroid function were evaluated in patients undergoing continuous ambulatory peritoneal dialysis (CAPD), in comparison to patients on hemodialysis (HD) without TBG loss in the dialysate. The TBG concentration in the peritoneal dialysate was 0.26 +/- 0.09 microgram/ml (mean +/- SD, n = 24), with a daily loss of 2.47 +/- 0.94 mg. The serum TBG level in CAPD patients was 21.0 +/- 4.71 micrograms/ml (n = 24), which was not significantly different from that in HD patients (20.0 +/- 5.72 micrograms/ml, n = 24) or in healthy Japanese subjects. The serum TBG level correlated positively with the TBG loss and TBG level in the peritoneal dialysate (p less than 0.001). The serum T4 level in CAPD patients (4.93 +/- 1.38 microgram/dl, n = 24) was significantly greater than in HD patients (4.08 +/- 1.30 microgram/dl, n = 24, p less than 0.05).


Exacerbation of Wegener's granulomatosis during pregnancy: report of a case with tracheal stenosis and literature review.
Wegener's granulomatosis (WG) is a rare multisystem disease of unknown etiology. We describe a woman with WG who relapsed twice during 2 pregnancies with appearance of tracheal stenosis. During the first pregnancy which ended with a delivery of a healthy baby, the subglottic stenosis responded to laser radiation and glucocorticosteroid therapy. An uneventful therapeutic abortion was performed during the 2nd pregnancy. Our case brings to 15 the number of pregnancies which were recorded in 10 women with WG. Diagnosis of WG was done during pregnancy in 4 cases, and at the postpartum period in 3 cases. Eight pregnancies occurred in women with known WG, relapse occurred in 5 pregnancies. Two cases ended with maternal death. It seems therefore that pregnancy may have a significant contribution both to the relapse of WG and to its appearance.


[Hope as psychological resource for nurturant professionals (medicine case study)].
In the article, the issues concerning hope, which is one of the most important resources for specialists of many nurturant professions, are observed. The theoretical analysis of hope and its categorization from the perspective of subjective and resource-based view is given. The special scientific and practical interest to human subjective and personal resources is determined by their unique role not only in human life support, but also in overcoming hard situations and extreme obstacles, including crisis situations in professional activity, with the example of the profession of a doctor. The aim of the empirical research is studying the correlation between hope and such manifestations of subjective regulations medical practice as inner subjective control and failure avoidance motivation. 120 doctors (60 men and 60 women) working in St. Petersburg hospitals took part in the research. Several research methods were used, such as 'Resource map' application form, R. Snyder's hope scale adapted by K. Muzdybayev, 'Subjective control level' method by E. Bazhin, E. Golynkina and L. Etkind, 'Failure avoidance motivation' method by T. Ehlers. Doctors think that Hope and Optimism are among important components of their professional practice, together with willing features helping them to reach their goals (such as persistence, patience, eagerness, insistence and endurance) and such personal qualities as self-assuredness, motion control in different situations, ability to solve hard problems. According the data of correlation and regression analyses, the anticipation that hope is determined by high level of inner control locus and low failure avoidance motivation (responsibility for patients' lives) within medical practice. Most doctors have average or high level of hope, which lets determine this personal disposition quality as one of the important ones for this profession. Being the positive result of professional practice and not depending on the doctors' sex and specialization, hope is linked to achievement drive and most rates of inner locus control. Obtained results can be used for psychodiagnostics and development of such psychological results as faith, hope and optimism, helping to keep nurturant professionals' mental health.


[Influence of intravenous infusion of D-fructose on post-operative blood glucose level in burn patients].
To investigate the influence of intravenous infusion of 50 g/L fructose on post-operative blood glucose level in burn patients, and to evaluate its therapeutic value and safety. A prospective, randomized, double blinded clinical trial was conducted. Forty-one burn patients with burn area ranging between 10% -30% of total body surface (TBSA) and third degree burns ranging between 1% -10% TBSA were enrolled in the study and randomized into experiment group (E, n = 21, with intravenous infusion of 500 ml of 50 g/L fructose daily for 3 days after escharectomy) and control group ( C, n = 20, with intravenous infusion of glucose 1 day after escharectomy for 3 days). Intravenous infusion of other carbohydrate liquids or oral intake of sugar was withhold within 4 hours of fructose or glucose infusion. Physical signs and side effects were observed during the administration. The plasma glucose contents before operation and on 1, 2 and 3 post-operation day( POD) were measured. The serum content of lactic acid, uric acid, hepatic and renal function were determined before operation and on 4 POD. Physical signs before and after drug administration, and plasma glucose content before operation, as well as before and after fructose administration in 3 POD exhibited no obvious difference between the two groups ( P > 0. 05 ). The plasma glucose content was increased 3 days after operation in the control group, and it reached the peak on 3 POD [ (8. 4+/-3. 5) mmol/L] , which was markedly higher than that before glucose administration [ (6. 4+/-2.4) mmol/L, P <0. 01) ]. The plasma contents of lactic acid and uric acid showed no obvious difference ( P >0.05) between the two groups, and also no difference before and after operation ( P > 0. 05). No changes were observed in hepatic and renal functions. Intravenous infusion of 50 g/L D-fructose is safe because it exerts little influence on blood glucose level.


Memory of elapsed time and feeling of time discrepancy.
In dating past events, one sometimes recalls inaccurate dates and tends to estimate recent events too remotely and remote events too recently (telescoping). On the other hand, even when one knows the exact dates of events, subjective time could be elastic and often different from objective time. This Feeling of Time Discrepancy between objective and subjective elapsed times was examined with two autobiographical events. Results showed that (1) subjects reported a discrepancy even if the exact dates of events were known and (2) the discrepancy for entrance into university was higher than that for graduation from high school, even when they happened at almost same time. The results are discussed in terms of "location" and "distance" theories, Kemp's 1999 associative model of dating, and Conway's 2000 self-memory system. Autobiographical memory may be organized in terms of present self-concept with our past fitted to the present self-concept. However, if autobiographical memory changes greatly, we cannot share autobiographical memory with other people. We may be adapted to the present life by making only a sense of the subjective elapsed time of each event change with the accurate time information of the autobiographical facts held.


Accelerated corneal collagen cross-linking in pediatric patients: two-year follow-up results.
To evaluate the effectiveness and safety of accelerated corneal collagen cross-linking (ACXL) in patients below 14 years of age with progressive keratoconus. Thirty eyes of 18 patients with established progressive keratoconus underwent preoperative and postoperative visual acuity assessment, topography, and specular microscopy prior to ACXL and were followed up for 24 months. Mean age of the patients was 12.7 years with ten males and eight females. There was an improvement in the mean postoperative uncorrected distant visual acuity (from 0.76±0.26 to 0.61±0.25; P=0.005), mean corrected distant visual acuity (from 0.24±0.19 to 0.12±0.12; P<0.001), mean spherical refraction (from -3.04 DS±3.60 to -2.38 DS±3.37; P=0.28), mean cylinder (from -3.63 DC±1.82 to -2.80 DC±1.48; P=0.008), and spherical equivalent (from -4.70 D±3.86 to -3.75 D±3.49; P=0.15). Three eyes of two patients with vernal keratoconjunctivitis (VKC) showed progression. There were no intra- or postoperative complications. In pediatric patients ACXL is an effective and safe procedure for the management of keratoconus. Optimal management of VKC is important to arrest the progression of keratoconus.


Reductive Coupling between Aromatic Aldehydes and Ketones or Imines by Copper Catalysis.
The copper-catalyzed reductive coupling of two different carbonyl compounds has been achieved. The reaction of aromatic aldehydes and arylketones with a silylboronate in the presence of a catalytic amount of a CuCl-N-heterocyclic carbene (NHC) complex and a stoichiometric amount of alkoxide base yielded cross-coupled 1,2-diol derivatives. A reaction pathway is proposed that involves the catalytic formation of a nucleophilic α-silyloxybenzylcopper(I) species from the aromatic aldehyde and its subsequent coupling with the arylketone. This process was amenable to asymmetric catalysis. This copper catalyst system also enabled the reductive coupling between aromatic aldehydes and imines.