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PubMed1987

Review of the NIMH Israeli Kibbutz-City Study and the Jerusalem Infant Development Study.

The National Institute of Mental Health (NIMH) Israeli Kibbutz-City Study has followed the development of offspring of schizophrenic parents from middle childhood through early adulthood. During childhood, a subgroup of offspring of schizophrenic patients showed clear neurobehavioral deficits often accompanied by poor social competence. Early followup data suggest that this subgroup of high-risk children is at greatest risk for adult schizophrenia spectrum illness. The Jerusalem Infant Development Study has followed a similar population of children at risk for schizophrenia from before birth through middle childhood. A subgroup of dysfunctioning in the high-risk children showed sensorimotor dysfunctioning in the first year of life, which was followed by perceptual, motor, and attentional dysfunctioning in childhood--identical to that found in the NIMH cohort. Results from both studies support the hypothesis that schizophrenic illness involves constitutional factors whose expression can be observed as early as infancy. Results also illustrate the importance of using data-analytic approaches that (1) look for subgroups within high-risk groups rather than only group differences between high- and low-risk groups, and (2) examine profiles of behavior rather than only single variables.

Adolescent↗
PubMed1983

Hepatocyte changes following selenium accumulation in a freshwater teleost.

This report provides morphological and analytical data for a group of green sunfish collected from an area relatively free of metals and a second group of the same species collected from a lake into which selenium had been discharged. Neutron activation data of livers (and kidneys) collected from these fish show an average of about 11 ppm selenium (fresh weight) for both organs; other metals were not detected in the liver (or kidneys) of these fish. Ultrastructural examination of livers from fish of this group showed focal necrosis, areas of granular cytoplasm, fatty infiltration, increased numbers of Kupffer cells, and disorganized liver architecture--compared with those of controls. The presence of massive levels of selenium in the liver and concomitant hepatocyte changes suggests a causal relationship between these phenomena.

Animals↗
PubMedDate not supplied

Sex differences in opioid analgesia: "from mouse to man".

BACKGROUND: Numerous experimental studies, conducted primarily over the past 10 years, show that there are sex differences in opioid analgesia. This review summarizes the published literature on sex differences in analgesia produced by acute administration of drugs acting at mu-, kappa-, and delta-opioid receptors, in animals and humans. Additionally, methodological issues in research into opioid sex differences are discussed. CONCLUSIONS: Procedural variables that may influence the outcome of studies examining sex differences in opioid analgesia include modality and intensity of the noxious stimulus used in the pain test, opioid type (efficacy and selectivity), and experimental design and data analytic techniques. Subject variables that may be important to consider include subject genotype and gonadal steroid hormone state of the subject at the time of analgesia testing. Evidence is provided for multiple mechanisms underlying sex differences in opioid analgesia, including both pharmacokinetic and pharmacodynamic factors. Future research directions are suggested, such as examining sex differences in opioid tolerance development, sex differences in opioid analgesia using models of acute inflammatory pain and chronic pain, and sex differences in effects of opioids other than analgesia, which may limit their therapeutic use.

Analgesics, Opioid↗
PubMed2000

Metabolism and dosimetry of actinide elements in occupationally-exposed personnel of Russia and the United States: a summary progress report.

The United States Transuranium and Uranium Registries (USTUR) and the Dosimetry Registry of the Mayak Industrial Association (DRMIA) have been independently collecting tissues at autopsy of plutonium workers in their respective countries for nearly 30 y. The tissues are analyzed radiochemically and the analytical data are used to develop, modify, or refine biokinetic models that describe the depositions and translocations of plutonium and transplutonium elements in the human body. The purpose of this collaborative research project is to combine the unique information on humans, gathered by the two Registries, into a joint database and perform analyses of the data. A series of project tasks are directly concerned with dosimetry in Mayak workers and involve biokinetic modeling for actinide elements. Transportability coefficients derived from in-vitro solubility measurements of actinide-containing aerosols (as measured by the DRMIA) were related to specific workplaces within Mayak facilities. The transportability coefficients of inhaled aerosols significantly affected the translocation rates of plutonium from the respiratory tract to the systemic circulation. Parameters for a simplified lung model, used by Branch No. 1, Federal Research Center Institute of Biophysics (FIB-1) and the Mayak Production Association for dose assessment at long times after inhalation of plutonium-containing aerosols, were developed on the basis of joint USTUR and DRMIA data. This model has separate sets of deposition and transfer parameters for three aerosol transportability groups, allowing work histories of the workers to be considered in the dose-assessment process. FIB-1 biokinetic models were extended to include the distributions of actinide elements in systemic organs of workers, and a relationship between the health of individual workers and plutonium distribution in tissues was determined. Workers who suffered from liver diseases generally had a smaller fraction of systemic plutonium in the liver at death and a larger fraction in the skeleton than did relatively healthy workers. Also, the fraction of total systemic plutonium excreted per day was significantly greater for workers with liver diseases than for relatively healthy workers. These observations could have a considerable effect on organ dosimetry in health-impaired workers whose dose assessments were based solely on urinary excretion rates. A comparison of this model to other biokinetic models, such as those published by the International Commission for Radiological Protection, is currently underway as is the documentation of uncertainty estimates associated with the model.

Aerosols↗
PubMed2003

Thorium concentration in Pakistani diet.

To evaluate radiation doses due to ingestion of thorium activity by members of the public, baseline analytical data on thorium concentration in a typical Pakistani diet was generated. Food samples were collected from major districts/ cities of the country using the market basket method, and typical daily diets were prepared. Thorium concentration was determined by instrumental neutron activation analysis. It was found to vary from 1.6 ng g(-1) to 12 ng g(-1). The median value was 4.6 ng g(-1). This leads to median daily thorium intake of 2.7 microg d(-1). The geometric mean was 2.6 microg d(-1), which was 13% less than the ICRP value. Based on these measurements the average intake of 232Th activity was 10 mBq d(-1), and the average annual and committed effective doses for adults were estimated to be 8.8 x 10(-7) Sv y(-1) and 4.4 x 10(-5) Sv, respectively.

Diet↗
PubMed2001

Comparative study between gadobenate dimeglumine and gadobutrol in rats with brain ischemia: evaluation of somatosensory evoked potentials.

RATIONALE AND OBJECTIVES: The present study had two main objectives: to validate a rat model of brain ischemia in terms of somatosensory evoked potentials (SEPs) and to compare, using the validated model, the potential activity on the somatosensory function of the new, approved contrast agent gadobenate dimeglumine with that of gadobutrol, a specific contrast agent, for magnetic resonance imaging of the brain. METHODS: Rats were prepared for SEP recording at least 5 days before ischemia induction. Ischemia was induced by 30-minute right middle cerebral artery occlusion and 3-day reperfusion. The SEP responses, evoked contralaterally to the stimulated upper limb, were recorded from the primary somatosensory cortical area. Model validation, on day 3 after occlusion, was performed using iopromide, an iodinated contrast agent poorly neurotolerated in rats, intravenously injected at 7 g I/kg. The comparative study between gadobenate dimeglumine and gadobutrol was performed at an intravenously injected dose of 2 mmol/kg. Somatosensory evoked potential responses were measured as peak latencies (P2 and N2) and peak-to-peak amplitude (P2N2). The brain concentration of iopromide was measured by high-performance liquid chromatography, whereas that of the gadolinium contrast agent was measured by inductively coupled plasma-atomic emission spectrometry analysis; given the absence of metabolism for both contrast agents, the gadolinium content values can be interpreted as representing unmetabolized contrast agent. RESULTS: In the ischemic rats, the SEP responses of the lesioned hemisphere showed significant increases in P2, N2, and interpeak N2-P2 latencies and a significant reduction in peak-to-peak (P2N2) amplitude. In the validation experiments, iopromide dramatically increased the P2N2 amplitude of the SEP responses recorded from both hemispheres of ischemic rats without affecting the P2, N2, and interpeak N2-P2 latencies. The iopromide effect was coupled with high concentrations of the contrast agent in the brain. Iopromide had no effect on healthy rats. In the comparative study, gadobenate dimeglumine did not induce any alteration in SEP components of either the lesioned or unlesioned hemisphere of ischemic rats. In fact, no significant difference was found between responses obtained before and after gadobenate dimeglumine injection. Gadobutrol, administered at the same dose, on the whole showed the same behavior as gadobenate dimeglumine, although a slight but significant decrease in the P2 latency, a sign of excitatory activity, was observed 2 hours after injection. Analytic data indicated higher levels of contrast agent in the lesioned hemisphere versus the unlesioned hemisphere 2 hours after injection. CONCLUSIONS: Based on these results, three conclusions can be drawn: (1) the evaluation of SEPs in ischemic rats is a useful tool for assessing the potential neurological effects of a new contrast agent because ischemic and contrast agent effects can be clearly differentiated; (2) the experimental conditions used allow the contrast agents to penetrate into the brain, where their activity can be manifested and evaluated; and (3) the complete absence of neurological activity of gadobenate dimeglumine shows its safety profile and confirms its suitability for use in neurological diseases for which contrast-enhanced magnetic resonance imaging is indicated.

Animals↗
PubMed2000

Quality Enhancement Research Initiative for human immunodeficiency virus/acquired immunodeficiency syndrome: framework and plan. HIV-QUERI Executive Committee.

The Veterans Health Administration (VHA) sees approximately equal to 17,000 human immunodeficiency virus (HIV)-infected patients each year, which makes it the largest provider of HIV care in the United States. HIV causes chronic progressive disease that leads to early death. Newer combination antiretro viral treatments are effective but expensive and difficult to use. The HIV Quality Enhancement Research Initiative (HIV-QUERI) uses the QUERI process to identify high-risk and high-volume populations (step 1), which includes those already under VHA care for HIV, those who do not know of their infection, and those at risk for HIV. In identifying best practices (step 2), the HIV-QUERI will benefit greatly from existing guidelines for the care of established HIV infection, but gaps in knowledge regarding adherence to medication regimens and cost-effective screening are large. To identify existing practice patterns (step 3), the HIV-QUERI will develop a clean analytic data set based on Immunology Case Registry files and expand it through a survey of veterans. Interventions to improve care (step 4) will include national, regional, and site-specific feedback on performance relative to quality standards, as well as patient-level and provider-level interventions to improve adherence and support medical decision-making. To document that best practices improve outcomes and quality of life (steps 5 and 6), HIV-QUERI will track indicators on an ongoing basis by use of the Immunology Case Registry database and possible future waves of the survey. In addition, we will require that these issues be addressed in evaluations of HIV-QUERI interventions. In the present article, we present these steps within a framework and plan.

Benchmarking↗
PubMed2005

The use of single photon emission computed tomography in depressive disorders.

Single photon emission computed tomography (SPECT) and positron emission tomography (PET) have advanced our understanding of the biological underpinnings of depression. There is, however, considerable variability in the literature. Depression is a complex disorder with marked heterogeneity in diagnosis and treatment. There is also evidence of heterogeneity in pathophysiology. In addition, the literature is marked by inconsistencies in the use of imaging techniques and data-analytical procedures. In this review we have attempted to focus on the SPECT studies that have used more refined methodologies and more homogenous clinical sub-groups of patients. We have focused on the main diagnostic sub-types of depression and on specific issues such as treatment response, correlates of neuroimaging abnormalities in depression, and so-called 'emotional circuitry' - the connectivity of regions implicated in depression. The future of molecular imaging in depression will be determined by the pace of the development of useful ligands and the exciting opportunities emerging in the field of imaging genomics. Future studies must attend to several key confounds including clinical heterogeneity, medication and the problems surrounding recruitment of drug-naive patients. It remains the case that longitudinal studies are the design of choice if questions relating to state and trait are to be addressed. Molecular imaging will be used increasingly to quantify neuroreceptor and transporter binding, and the activity of neurtransmitters, allowing the neurochemistry of this complex condition to be explored.

Brain↗
PubMedDate not supplied

A meta-analytic examination of basal cardiovascular activity in posttraumatic stress disorder.

OBJECTIVE: The objective of this meta-analytic study was to determine whether individuals with posttraumatic stress disorder (PTSD) have higher levels of basal cardiovascular activity relative to comparable groups of individuals without PTSD. METHODS: Meta-analytic data methods were applied to 34 studies that gathered indicators of basal cardiovascular activity including: heart rate (HR), systolic blood pressure, and diastolic blood pressure on subjects diagnosed with PTSD and two types of comparison groups. In total, cardiovascular measures were analyzed for 2670 subjects across all studies. RESULTS: Results indicate that individuals with a current PTSD diagnosis have higher resting HR relative to both trauma-exposed individuals without a PTSD diagnosis and non-trauma-exposed individuals. The results also suggest that PTSD is associated with elevations in blood pressure; however, the effect sizes were smaller in magnitude than those obtained for heart rate. A subset analysis revealed that the effect sizes for comparisons on basal HR were greatest in studies with the most chronic PTSD samples. CONCLUSION: The meta-analysis supports previous qualitative reviews, finding a positive association between PTSD and basal cardiovascular activity. The discussion addresses possible mechanisms of action and the health-related implications of these findings.

Arousal↗
PubMed1999

Pharmacokinetics of 10B-p-boronophenylalanine in tumours, skin and blood of melanoma patients: a study of boron neutron capture therapy for malignant melanoma.

To optimize the neutron dose for boron neutron capture therapy (BNCT), the boron-10 (10B) concentration kinetics of 10B-p-boronophenylalanine (BPA) were analysed in 22 melanoma patients with primary or metastatic melanomas who received BPA and subsequently underwent BNCT or surgery. The blood concentration in nine patients receiving 179.7+/-14.9 mg/kg BPA increased with time during intravenous infusion, peaked at the end of administration and decreased thereafter. The peak values at the end of administration were 9.4 2.6 microg 10B/g blood, and half-lives for the initial and second components of the blood clearance were 2.8 and 9.2 h, respectively. Skin concentrations in the 10 patients varied from case to case; however, skin-to-blood ratios were relatively constant at 1.31+/-0.22 during the 6 h after the end of administration. Boron concentrations in the tumours resected from the seven patients who were operated on decreased in parallel to the blood values, the tumour-to-blood ratio being relatively constant at 3.40+/-0.83. The present analytical data of BPA pharmacokinetics support our previous approach for optimizing the timing of irradiation and setting the neutron flux large enough for tumour eradication but still tolerable for normal skin.

Adult↗
PubMedDate not supplied

Bone regeneration guided by resorbable collagen membranes in rabbits: a pilot study.

Artificial cross-shaped intrabony defects were created in the mandibles of 12 rabbits and the cavities covered with Type I highly cross-linked resorbable collagen membranes for 30 days. Similar cavities were prepared in three control animals and left uncovered for the same time period. Morphological and analytical data were obtained by means of light microscopy, scanning electron microscopy, and x-ray energy-dispersive spectrometry. After the experimental period, the membrane covered cavities were completely filled with regenerated bone. In the control specimens, the artificial cavities were occupied by fibrous connective tissue.

Animals↗
PubMed2006

Family cognitive behavioral therapy for child anxiety disorders.

OBJECTIVE: This study compared family-focused cognitive behavioral therapy (CBT; the Building Confidence Program) with traditional child-focused CBT with minimal family involvement for children with anxiety disorders. METHOD: Forty clinically anxious youth (6-13 years old) were randomly assigned to a family- or child-focused cognitive-behavioral therapy (CBT). Conditions were matched for therapist contact time. Both interventions included coping skills training and in vivo exposure, but the family CBT intervention also included parent communication training. Independent evaluator, parent, and child report measures with demonstrated validity and reliability were used to assess child anxiety symptom outcomes at pre- and posttreatment. The data analytic strategy involved an evaluable patient analysis. RESULTS: Compared with child-focused CBT, family CBT was associated with greater improvement on independent evaluators' ratings and parent reports of child anxiety--but not children's self-reports--at posttreatment. CONCLUSIONS: Both treatment groups showed improvement on all outcome measures, but family CBT may provide additional benefit over and above child-focused CBT. These findings provide preliminary support for the efficacy of the "Building Confidence" program and encourage further research in parental participation in treatment for childhood anxiety.

Adaptation, Psychological↗
PubMed2006

Anaerobic and aerobic metabolism of glycogen-accumulating organisms selected with propionate as the sole carbon source.

In the microbial competition observed in enhanced biological phosphorus removal (EBPR) systems, an undesirable group of micro-organisms known as glycogen-accumulating organisms (GAOs) compete for carbon in the anaerobic period with the desired polyphosphate-accumulating organisms (PAOs). Some studies have suggested that a propionate carbon source provides PAOs with a competitive advantage over GAOs in EBPR systems; however, the metabolism of GAOs with this carbon source has not been previously investigated. In this study, GAOs were enriched in a laboratory-scale bioreactor with propionate as the sole carbon source, in an effort to better understand their biochemical processes. Based on comprehensive solid-, liquid- and gas-phase chemical analytical data from the bioreactor, a metabolic model was proposed for the metabolism of propionate by GAOs. The model adequately described the anaerobic stoichiometry observed through chemical analysis, and can be a valuable tool for further investigation of the competition between PAOs and GAOs, and for the optimization of the EBPR process. A group of Alphaproteobacteria dominated the biomass (96 % of Bacteria) from this bioreactor, while post-fluorescence in situ hybridization (FISH) chemical staining confirmed that these Alphaproteobacteria produced poly-beta-hydroxyalkanoates (PHAs) anaerobically and utilized them aerobically, demonstrating that they were putative GAOs. Some of the Alphaproteobacteria were related to Defluvicoccus vanus (16 % of Bacteria), but the specific identity of many could not be determined by FISH. Further investigation into the identity of other GAOs is necessary.

Aerobiosis↗
PubMed2004

Structure of pre-S2 N- and O-linked glycans in surface proteins from different genotypes of hepatitis B virus.

The middle-sized (M) surface proteins of hepatitis B virus (HBV) and other orthohepadnaviruses contain a conserved N-glycan in their pre-S2 domain, which is essential for the secretion of viral particles. Recently, we also found O-glycans in the pre-S2 domain of M protein from woodchuck hepatitis virus (WHV) and HBV genotype D. Since the O-glycosylation motif is not conserved in all genotypes of HBV, the glycosylation patterns of HBV genotypes A and C were analysed. Pre-S2 (glyco)peptides were released from HBV-carrier-derived HBV subviral particles by tryptic digestion, purified by reversed-phase HPLC and identified by amino acid and amino-terminal sequence analysis as well as matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Pre-S2 N-glycans were characterized by anion-exchange chromatography, methylation analysis and on-target sequential exoglycosidase digestions in combination with MALDI-TOF-MS, demonstrating the presence of partially sialylated diantennary complex-type oligosaccharides in all genotypes examined. Pre-S2 O-glycans were characterized by on-target sequential exoglycosidase digestions in combination with MALDI-TOF-MS. The pre-S2 domain of M protein and, to a minor extent, of L (large) protein from HBV genotype C and D was partially O-glycosylated by Neu5Ac(alpha2-3)Gal(beta1-3)GalNAcalpha- or Gal(beta1-3)GalNAcalpha-units at Thr-37 within a conserved sequence context. Genotype A, containing no Thr at position 37 or 38, was not O-glycosylated. Analytical data further revealed that M protein is mostly amino-terminally acetylated in all examined genotypes and that the terminal methionine is partially oxidized. The findings may be relevant for the secretion and the immunogenicity of HBV.

Amino Acid Sequence↗
PubMed2005

Efficient integral-equation-based method for accurate analysis of scattering from periodically arranged nanostructures.

A plethora of applications are grounded on the physics of electromagnetic interaction with a periodic arrangement of nanostructures. These range from metamaterials and negative index materials to photonic band-gap structures to surface plasmon polariton optics to nanofrequency selective surfaces. There is therefore a need for rigorous physics based methods that are both accurate and fast to enable rapid design and analysis. Difficulties that need to be overcome to realize such a simulation tool are twofold: (i) at wavelengths in the range 200-1300 nm metals behave as dielectrics with negative real permittivity. Their frequency response must be explicitly accounted for in the simulation. (ii) The computational cost to compute response over a broad band of frequencies is high. This paper develops an integral-equation-based analysis technique that addresses these challenges. This integral equation relies on a periodic layered medium formulation. The Green's dyad for this formulation is derived, and separated into a superposition of two contributions: direct and reflected components. The means to accelerate the computation of the Green's dyad and the evaluation of inner products is prescribed. The proposed technique is validated extensively against available analytical data for hypothetical materials as well as silver. It is shown that this solver can accurately predict the enhanced transmission from perforated silver films for several configurations. While the application domain in this paper is the study of enhanced transmission in perforated silver films, the method presented herein is sufficiently general and can be applied to several other application domains with little or no change.

Journal Article↗
PubMed1984

Structure of the Primary Cell Walls of Suspension-Cultured Rosa glauca Cells: II. Multiple Forms of Xyloglucans.

Xyloglucans, characteristic hemicellulosic polysaccharides of plant primary walls, have been isolated from Rosa glauca suspension-cultured cells. The cell wall material was fractionated by two sequences of extraction based on solubilization of the hemicelluloses in alkaline and organic solvent systems, respectively. In both cases, only a part (about 50%) of the total xyloglucan could be extracted, the rest remaining tightly associated with cellulose and necessitating the use of acid to be solubilized. Purification of xyloglucans was effected by formation of a gel in appropriate mixtures of dimethyl sulfoxide and water. Further fractionation could be achieved on a cellulose column eluted with chaotropic solvents. This demonstrated the heterogeneity of xyloglucans in the primary cell walls. Analytical data show that all fractions are constituted with the same sugars: l-arabinose, l-fucose, d-galactose, d-xylose, and d-glucose, but their relative proportions differ, particularly the ratio of glucose to xylose which varies from 1.2 to 2 within the different xyloglucans. The structure of these hemicelluloses was established by methylation analysis and shown to consist of a (1 --> 4)-linked glucan backbone which carries substituents on the O-6 of glucose. Here again, the multiple forms of xyloglucans was suggested by the various patterns of substitutions found on the different fractions. The configuration of the linkages were established by (13)C nuclear magnetic resonance spectroscopy and shown to be beta for the glucan backbone, alpha for the xylosyl and fucosyl substituents, and beta for the galactosyl substituents. These configurations agree with the specific rotation of the xyloglucan.

Journal Article↗
PubMed1987

Purification and Partial Characterization of a Hydroxyproline-Rich Glycoprotein in a Graminaceous Monocot, Zea mays.

Graminaceous monocots generally contain low levels of hydroxyproline-rich Glycoproteins (HRGPs). As HRGPs are often at the cell surface, we used the intact cell elution technique (100 millimolar AlCl(3)) to isolate soluble surface proteins from Zea mays cell suspension cultures. Further fractionation of the trichloroacetic acid-soluble eluate on the cation exchangers phospho-cellulose and BioRex-70 gave several retarded, hence presumably basic fractions, which also contained hydroxyproline (Hyp). One of these fractions yielded a pure HRGP after a final purification step involving Superose-6 gel filtration. As this HRGP was unusually rich in threonine, (25 mole%) we designated it as a threonine-hydroxyproline-rich glycoprotein (THRGP); it contained about 27% carbohydrate occurring exclusively as arabinosylated Hyp, predominantly as the monosaccharide (15%), and trisaccharide (25%) with 48% Hyp nonglycosylated-a characteristically graminaceous monocot profile. Amino acid analysis confirmed the basic character, and gave a low alanine content. Reaction with Yariv artificial antigen was negative. These characteristics show that the THRGP is not an arabinogalactan protein. On the other hand, antibodies raised against tomato extensin P1 cross-reacted significantly with the THRGP; this cross-reactivity and the above analytical data provide the best evidence to date for the presence of extensin in a graminaceous monocot.

Journal Article↗