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A number of imaging and neuropathological studies have reported structural abnormalities in white matter areas such as the corpus callosum in autism spectrum disorder (ASD). Differences in both global brain volume and the size of specific neural structures have been reported. In order to expand these previously reported findings and to describe more precisely the nature of such structural changes, we performed a voxel-based morphometric whole brain analysis, using a group-specific template, in male adolescents with ASD. Fifteen individuals with normal intelligence and ASD, and a group of 16 controls, matched for age, sex, and IQ, were investigated. High-resolution T1-weighted 3D data sets were acquired and analysed. Local white matter volume deficits were found in the corpus callosum, particularly in the anterior splenium and isthmus, and right hemisphere. White matter volume deficits were also found in the left middle temporal, right middle frontal, and left superior frontal gyri. No significant areas of increased white matter volume were found. Our findings support the hypothesis that reduced white matter volume in the corpus callosum and right hemisphere may play a role in the pathophysiology of ASD.

Gum arabic from Acacia senegal is commonly used as an additive in foodstuffs. Adulteration of gum arabic by other gums is a potential problem for reasons of safety and quality. This study aimed to develop and evaluate the use of enzyme-linked immunosorbent assays (ELISAs) for the detection of potential adulterants of gum arabic. Indirect competitive ELISAs (IC-ELISAs) were developed using the monoclonal antibodies SY CC7 (A. senegal), SY HH3 (Acacia seyal), and SY J1A1 (Combretum erythrophyllum). All IC-ELISAs had a working range of 0.005-10 mg/mL. The antibodies used were tested using the IC-ELISAs for cross-reactivity with other Acacia species and other gums. The antibodies were very specific for their respective antigens. Significant cross-reactivity was found for SY CC7 (between A. senegal and A. melliferae) and SY J1A1 (between C. erythrophyllum and A. seyal). The IC-ELISA was adapted further to test confectionery samples for the presence of gum arabic, which was successful, although recovery rates were reduced. Both IC- and plate trapped antigen ELISA (PTA-ELISA) formats were able to distinguish an adulterated sample of gum arabic when blended with either A. seyal or C. erythrophyllum. The PTA-ELISA was more sensitive for A. seyal than the IC-ELISA, but both were equally sensitive for C. erythrophyllum. The results suggest that the antibodies SY CC7, SY HH3, and SY J1A1 could be used in combination with each other for the detection of potential adulterants of A. senegal and the detection of gum arabic in foodstuffs.

Type 2 diabetes patients are subject to oxidative stress as a result of hyperglycemia. The aim of this study was to determine whether administration of the antioxidant folic acid, previously shown to reduce homocysteine levels, would reduce circulating levels of Hsp70 while improving the condition of type 2 diabetes patients with microalbuminuria. Plasma homocysteine fell from pretreatment values of 12.9 to 10.3 microM (P < 0.0001). The urine albumin-creatinine ratio fell from 12.4 to 10.4 mg/mM (P = 0.38). Pretreatment Hsp70 levels were higher in patients not taking insulin (5.32 ng/mL) compared with those on insulin (2.44 ng/mL) (P = 0.012). Folic acid supplementation resulted in a significant fall in Hsp70 (5.32 to 2.05 ng/mL) (P = 0.004). There was no change in Hsp70 in those receiving insulin. Folic acid supplementation in non-insulin-treated type 2 diabetes patients, therefore, resulted in a fall in Hsp70, reflecting an improvement in oxidative stress. The data shows that improvement in homocysteine status can lead to a reduction in Hsp70, indicating the possibility of its use as a marker for severity of disease.

Background: The Beta-Carotene and Retinol Efficacy Trial (CARET) tested the effect of daily beta-carotene (30 mg) and retinyl palmitate (25,000 IU) on the incidence of lung cancer, other cancers, and death in 18,314 participants who were at high risk for lung cancer because of a history of smoking or asbestos exposure. CARET was stopped ahead of schedule in January 1996 because participants who were randomly assigned to receive the active intervention were found to have a 28% increase in incidence of lung cancer, a 17% increase in incidence of death and a higher rate of cardiovascular disease mortality compared with participants in the placebo group., Methods: After the intervention ended, CARET participants returned the study vitamins to their study center and provided a final blood sample. They continue to be followed annually by telephone and mail self-report. Self-reported cancer endpoints were confirmed by review of pathology reports, and death endpoints were confirmed by review of death certificates. All statistical tests were two-sided., Results: With follow-up through December 31, 2001, the post-intervention relative risks of lung cancer and all-cause mortality for the active intervention group compared with the placebo group were 1.12 (95% confidence interval [CI] = 0.97 to 1.31) and 1.08 (95% CI = 0.99 to 1.17), respectively. Smoothed relative risk curves for lung cancer incidence and all-cause mortality indicated that relative risks remained above 1.0 throughout the post-intervention follow-up. By contrast, the relative risk of cardiovascular disease mortality decreased rapidly to 1.0 after the intervention was stopped. During the post-intervention phase, females had larger relative risks of lung cancer mortality (1.33 versus 1.14; P = .36), cardiovascular disease mortality (1.44 versus 0.93; P = .03), and all-cause mortality (1.37 versus 0.98; P = .001) than males., Conclusions: The previously reported adverse effects of beta-carotene and retinyl palmitate on lung cancer incidence and all-cause mortality in cigarette smokers and individuals with occupational exposure to asbestos persisted after drug administration was stopped although they are no longer statistically significant. Planned subgroup analyses suggest that the excess risks of lung cancer were restricted primarily to females, and cardiovascular disease mortality primarily to females and to former smokers.

There are an increasing number of studies reporting the presence of Hsps in human serum. We have investigated the release of Hsp70 into blood and culture medium from peripheral blood mononuclear cells (PBMCs), and whether this release is due to cell damage or active secretion from the cells. Intact Hsp70 was released from cells within whole blood and from purified PBMCs under normal culture conditions. Hsp70 release was rapid (0.1 ng/10(6) cells/h) over the first 2 h of culture and continued at a reduced rate up to 24 h (<0.025 ng/10(6) cells/h). Using viable cell counts and lactate dehydrogenase release we were able to confirm that the release of Hsp70 was not due to cellular damage. Hsp70 release was inhibited by monensin, methyl-beta-cyclodextrin, and methylamine, but not by brefeldin A. These data suggest that Hsp70 is released from cells via a non-classical pathway, possibly involving lysosomal lipid rafts.

Children with autistic spectrum disorder (ASD) may have poor audio-visual integration, possibly reflecting dysfunctional 'mirror neuron' systems which have been hypothesised to be at the core of the condition. In the present study, a computer program, utilizing speech synthesizer software and a 'virtual' head (Baldi), delivered speech stimuli for identification in auditory, visual or bimodal conditions. Children with ASD were poorer than controls at recognizing stimuli in the unimodal conditions, but once performance on this measure was controlled for, no group difference was found in the bimodal condition. A group of participants with ASD were also trained to develop their speech-reading ability. Training improved visual accuracy and this also improved the children's ability to utilize visual information in their processing of speech. Overall results were compared to predictions from mathematical models based on integration and non-integration, and were most consistent with the integration model. We conclude that, whilst they are less accurate in recognizing stimuli in the unimodal condition, children with ASD show normal integration of visual and auditory speech stimuli. Given that training in recognition of visual speech was effective, children with ASD may benefit from multi-modal approaches in imitative therapy and language training.

Aflatoxins are well recognized as a cause of liver cancer, but they have additional important toxic effects. In farm and laboratory animals, chronic exposure to aflatoxins compromises immunity and interferes with protein metabolism and multiple micronutrients that are critical to health. These effects have not been widely studied in humans, but the available information indicates that at least some of the effects observed in animals also occur in humans. The prevalence and level of human exposure to aflatoxins on a global scale have been reviewed, and the resulting conclusion was that approximately 4.5 billion persons living in developing countries are chronically exposed to largely uncontrolled amounts of the toxin. A limited amount of information shows that, at least in those locations where it has been studied, the existing aflatoxin exposure results in changes in nutrition and immunity. The aflatoxin exposure and the toxic affects of aflatoxins on immunity and nutrition combine to negatively affect health factors (including HIV infection) that account for >40% of the burden of disease in developing countries where a short lifespan is prevalent. Food systems and economics render developed-country approaches to the management of aflatoxins impractical in developing-country settings, but the strategy of using food additives to protect farm animals from the toxin may also provide effective and economical new approaches to protecting human populations.

Peer victimization is a common occurrence in school settings. This study investigated the relationship between peer victimization and school adjustment in a sample of 1,022 sixth-grade students. Measures used in this study include peer victimization, perceived peer non-support, school attachment, inattention problems, and academic achievement. Multivariate path analyses were conducted to test direct and mediation effects in the over-all model and to explore gender differences. The results provided support for the hypothesized model indicating that the relationship between peer victimization and school attachment is mediated by perceived peer non-support, and that school attachment is related to inattentive school behaviors and poor academic achievement. Paths indicated invariance across models for gender. Prevention and intervention implications of these findings are discussed.

Myeloid leukemia factor 1 (MLF1) is a novel oncoprotein involved in translocations associated with acute myeloid leukemia (AML), especially erythroleukemias. In this study, we demonstrate that ectopic expression of Mlf1 prevented J2E erythroleukemic cells from undergoing biological and morphological maturation in response to erythropoietin (Epo). We show that Mlf1 inhibited Epo-induced cell cycle exit and suppressed a rise in the cell cycle inhibitor p27(Kip1). Unlike differentiating J2E cells, Mlf1-expressing cells did not downregulate Cul1 and Skp2, components of the ubiquitin E3 ligase complex SCF(Skp2) involved in the proteasomal degradation of p27(Kip1). In contrast, Mlf1 did not interfere with increases in p27(Kip1) and terminal differentiation initiated by thyroid hormone withdrawal from erythroid cells, or cytokine-stimulated maturation of myeloid cells. These data demonstrate that Mlf1 interferes with an Epo-responsive pathway involving p27(Kip1) accumulation, which inhibits cell cycle arrest essential for erythroid terminal differentiation.

Aims: Gel electrophoresis revealed a band of molecular weight approximately 160 000 Da associated with the skeletal muscle sarcoplasmic reticulum (SR) vesicle preparations. This investigation sought to examine glycogen debranching enzyme associated with skeletal muscle SR., Methods: Sarcoplasmic reticulum samples were also taken from muscle whose glycogen content had been reduced either via stimulation of the sciatic nerve or alpha-amylase treatment of muscle homogenates., Results: The stimulation protocol reduced whole muscle glycogen by 86% (7.4 +/- 0.4 vs. 1.0 +/- 0.3 microg mg(-1) wet mass, P < or = 0.05). Glycogen associated with the SR was reduced by 82% in the stimulation protocol (533 +/- 82 vs. 96 +/- 7 microg mg(-1) protein) and by 94% in alpha-amylase treatment (493 +/- 11 vs. 29 +/- 2 microg mg(-1) protein), respectively. Gel electrophoresis and Western blots revealed that the content of glycogen debranching enzyme was reduced by approximately 53% as a result of muscle stimulation and by approximately 46% in alpha-amylase treatment (P < or = 0.05). In addition, glycogen debranching enzyme activity was reduced by 61% in stimulated samples compared with control (20.3 +/- 1.0 vs. 8.0 +/- 1.2 nmol mg(-1) min(-1), respectively), a value consistent with reductions observed from gel electrophoresis and Western blots., Conclusion: These results confirm that similar to glycogen phosphorylase, glycogen debranching enzyme is associated with the skeletal muscle SR and is dissociated under exercise conditions.

Imitative deficits have been associated with autistic spectrum disorder (ASD) for many years, most recently through more robust methodologies. A fresh, systematic review of the significance, characteristics, and underlying mechanism of the association is therefore warranted. From 121 candidates, we focused on 21 well-controlled studies involving 281 cases of ASD. Overall, children with ASD performed worse on imitative tasks (Combined Logit p value < .00005). The emerging picture is of delayed development in imitation, implicating a deficit in mapping neural codings for actions between sensory and motor modalities, rather than in motivation or executive function. We hypothesise that ASD is characterised by abnormal development of these mappings. such that they are biased towards object-oriented tasks at the expense of those required for action imitation per se.

Autistic spectrum disorder (ASD) has been associated with abnormal neuroanatomy in many imaging and neuropathological studies. Both global brain volume differences and differences in the size of specific neural structures have been reported. Here, we report a voxel-based morphometric whole brain analysis, using a group specific template, on 16 individuals of normal intelligence with autistic spectrum disorder (ASD), and a group of 16 age-, sex- and IQ-matched controls. Total grey matter volume was increased in the ASD group relative to the control group, with local volume increases in the right fusiform gyrus, the right temporo-occipital region and the left frontal pole extending to the medial frontal cortex. A local decrease in grey matter volume was found in the right thalamus. A decrease in global white matter volume in the ASD group did not reach significance. We found the increase in grey matter volume in ASD subjects was greatest in those areas recognised for their role in social cognition, particularly face recognition (right fusiform gyrus), mental state attribution: 'theory of mind' (anterior cingulate and superior temporal sulcus) and perception of eye gaze (superior temporal gyrus). The picture as a whole may reflect an abnormally functioning social cognitive neural network. We suggest that increased grey matter volume may play a pivotal role in the aetiology of the autistic syndrome.

The recent consensus that Amborellaceae, Nymphaeales, and Austrobaileyales form the three earliest-diverging lineages of angiosperms has led comparative biologists to reconsider the origin and early developmental evolution of the angiosperm seven-celled/eight-nucleate (Polygonum-type) female gametophyte. Illicium mexicanum (Illiciaceae; Austrobaileyales) develops a four-celled/four-nucleate female gametophyte. The ontogenetic sequence of the Illicium female gametophyte is consistent with that of all other Austrobaileyales and also with all Nymphaeales and is likely a plesiomorphy of angiosperms. A character analysis based on more than 250 embryological studies indicates that a transition from an ancestrally four-celled/four-nucleate Illicium-like female gametophyte to a seven-celled/eight-nucleate female gametophyte occurred in the common ancestor of the sister group to Austrobaileyales (a clade that includes monocots, eumagnoliids, and eudicots). Comparative analysis of reconstructed ancestral female gametophyte ontogenies identifies specific early stages of ontogeny that were modified during this transition. These modifications generated two important angiosperm novelties-a set of three persistent antipodal cells and a binucleate central cell, which upon fertilization yields a triploid endosperm. Early angiosperms are anatomically quite diverse in these two features, although triploid endosperm, composed of one paternal genome and two maternal genomes, is a conserved feature of the overwhelming majority of angiosperms.

Heat shock proteins (Hsps) are known to be induced in response to short-term stress. The present study aimed to evaluate the potential of Hsp70 as a biomarker of stress produced by increased temperature, osmotic pressure, and exposure to cadmium and sodium chloride in marine macroalgae and fresh water plant species. An indirect competitive enzyme-linked immunosorbent assay (IC-ELISA) was developed with a working range of 0.025-10 microg ml(-1) using a monoclonal antibody raised against purified Hsp70 of Phaseolus aureus (mung bean). Fucus serratus (toothed wrack), Chondrus crispus (Stackhouse or Carrageen moss), Ulva lactuca (sea lettuce) and Lemna minor (common duckweed) sample extracts were stressed for up to 24 h and then tested in the IC-ELISA. The presence of Hsp70 and cross-reactivity of the monoclonal antibody was confirmed by Western blot. The heat shock response was confirmed in each species using a 2-h 42 degrees C treatment. Following heat shock, Hsp70 concentrations increased to a peak at 2 h (F. serratus) or 4 h (L. minor), after which concentrations decreased. Osmotic and cadmium stresses also resulted in elevated Hsp70 concentrations in samples of F. serratus and L. minor when compared with unstressed controls. In both, osmotic and metal stress, the production of Hsp70 increased to a maximum and subsequently decreased as the stressor levels increased. Results suggest that Hsp70 IC-ELISA could potentially be applied to the detection of stress in these aquatic species, although it would probably be most effective when used in conjunction with other measurements to provide a stressor-specific biomarker profile or fingerprint., (Copyright 2004 Taylor & Francis Ltd)

Aims: Fatigue has been shown to cause intrinsic alterations in sarcoplasmic reticulum (SR) Ca2+ release., Methods: In this investigation, frog semitendinosus muscles were stimulated to fatigue, in vitro (80 Hz, 100 ms, 1 train s-1, 5 min). Immediately after stimulation, single fibres were removed and skinned using either chemically or mechanically skinning. Contralateral muscle were treated similarly but were not stimulated., Results: In fatigued, saponin skinned fibres, contracture responses to low [caffeine] (4-8 mm) were depressed compared with control. However, responses to high concentrations (10-15 mm) were not different between conditions. In the fatigued, mechanically skinned fibres, responses to chloride depolarization were depressed at all [chloride] (20-100 mm) compared with control., Conclusions: These results suggest that fatigue causes intrinsic alterations in both the SR Ca2+ release channel as well as communication between the transverse-tubule and the SR.

The aim of this work was to develop an assay capable of detecting adulteration of high premium milk with milk from cheaper sources. An indirect, competitive ELISA was developed for the rapid detection of cows' milk in the milk of goat, sheep, and buffalo. The assay uses a monoclonal antibody produced against bovine IgG. This antibody recognizes a species-specific epitope on the heavy chain of both bovine IgG1 and IgG2. A peroxidase-conjugated anti-mouse IgG antibody was used to detect bound monoclonal antibody and subsequent enzymatic conversion of substrate resulted in clear differences in absorbance when assaying different mixtures of milks adulterated with cows' milk. Once optimized, the ELISA was found to be highly specific. Detection limits of the assay are 1.0 microg/mL of bovine IgG, or 0.1% (vol/vol) adulteration with cows' milk. The assay was highly reproducible (CV < 10%) and performed equally well when used to detect bovine IgG in mixtures with the 3 types of milk tested. The ELISA performance makes it suitable for development as a kit, for use in the field as a high throughput screening ELISA.

Hemopoietic cells, apparently committed to one lineage, can be reprogrammed to display the phenotype of another lineage. The J2E erythroleukemic cell line has on rare occasions developed the features of monocytic cells. Subtractive hybridization was used in an attempt to identify genes that were up-regulated during this erythroid to myeloid transition. We report here on the isolation of hemopoietic lineage switch 5 (Hls5), a gene expressed by the monocytoid variant cells, but not the parental J2E cells. Hls5 is a novel member of the RBCC (Ring finger, B box, coiled-coil) family of genes, which includes Pml, Herf1, Tif-1alpha, and Rfp. Hls5 was expressed in a wide range of adult tissues; however, at different stages during embryogenesis, Hls5 was detected in the branchial arches, spinal cord, dorsal root ganglia, limb buds, and brain. The protein was present in cytoplasmic granules and punctate nuclear bodies. Isolation of the human cDNA and genomic DNA revealed that the gene was located on chromosome 8p21, a region implicated in numerous leukemias and solid tumors. Enforced expression of Hls5 in HeLa cells inhibited cell growth, clonogenicity, and tumorigenicity. It is conceivable that HLS5 is one of the tumor suppressor genes thought to reside at the 8p21 locus.

The purpose of this investigation was to determine whether there is a link between sarcoplasmic reticulum (SR) glycogen status and SR Ca2+ handling. In this investigation, skeletal muscle SR was purified from female Sprague-Dawley rats (200-250 g). Glycogen was extracted from the SR purified from one hindlimb, whereas the SR purified from the contralateral limb served as control. Before removal of the tissue, the animals were anesthetized with an intraperitoneal injection of ketamine (80 mg/kg) and xylazine (10 mg/kg). Both alpha-amylase treatment (AM) and removal of EDTA from the homogenization and storage buffers reduced the amount of glycogen associated with the SR (P < 0.05). AM treatment reduced the glycogen phosphorylase content of SR (P < 0.05). In contrast, creatine kinase (CK) and pyruvate kinase (PK) contents were increased after both glycogen extraction protocols (P < 0.05). Under exogenous ATP conditions, both AM and EDTA-free (EF) treatments resulted in an increase in Ca2+-stimulated ATPase activity when normalized to sarco(endo)plasmic reticulum calcium-ATPase (SERCA) content (P < 0.05). CK and PK-supported SR Ca2+ uptake was decreased (P < 0.05) in the AM group when normalized to SERCA and CK or SERCA and PK content, respectively. AM was more effective than the EF for extracting glycogen associated with purified SR. Glycogen extraction alters the yield of purified SR proteins and must be taken into account when investigating SR calcium handling. Removal of glycogen from purified SR causes a change in Ca2+-handling properties as measured by ATPase and uptake activities.

Unlabelled: Antipsychotic medications are often continued through pregnancy and may have important anesthetic interactions. For example, risperidone is an antipsychotic medication with therapeutic effects mediated by dopaminergic and serotonergic antagonism. However, it also possesses potent alpha-1 adrenergic antagonism. Here we report a case of a parturient with bipolar disease, controlled with lithium and risperidone, undergoing a spinal anesthetic for a cesarean delivery. The parturient developed exaggerated hypotension, refractory to conventional treatment with ephedrine and IV fluids, that eventually responded to large doses of phenylephrine. Risperidone alpha-antagonism should be a consideration for any patient receiving this medication during neuraxial anesthesia. Treatment of significant and refractory hypotension with an alpha-1 agonist such as phenylephrine may be warranted., Implications: Parturients receiving neuraxial blocks may be taking antipsychotic medications. Although the therapeutic effects of antipsychotic medications are mediated by dopaminergic and serotonergic antagonism, many possess alpha-adrenergic antagonist properties. We report a case of exaggerated hypotension during a spinal anesthetic for cesarean delivery that may have been a result of the alpha-adrenergic antagonism of risperidone.

Isoforms of the vitamin B(12) carrier protein transcobalamin (TC) might influence its cellular availability and contribute to the association between disrupted single-carbon metabolism and Alzheimer's disease (AD). We therefore investigated the relationships between the TC 776C>G (Pro259Arg) genetic polymorphism, total serum cobalamin and holo-TC levels, and disease onset in 70 patients with clinically diagnosed AD and 74 healthy elderly controls. TC 776C>G polymorphism was also determined for 94 histopathologically confirmed AD patients and 107 controls. Serum holo-TC levels were significantly higher in TC 776C homozygotes (p = 0.04). Kaplan-Meier survival functions differed between homozygous genotypes (Cox's F-Test F(42, 46) = 2.1; p = 0.008) and between 776C homozygotes and heterozygotes (Cox's F test F(46, 108) = 1.7; p = 0.02). Proportionately fewer TC 776C homozygotes appear to develop AD at any given age, but this will require confirmation in a longitudinal study., (Copyright 2004 S. Karger AG, Basel)

This study investigates the extent to which attitudes, family, and environmental correlates are associated with the escalation from nonviolent to violent offending among incarcerated youths. Escalation was defined as an adjudicated violent offense only after arrests and adjudications exclusively for nonviolent offenses. Data were collected from 50 respondents (25 escalators and 25 maintainers of nonviolent offending) incarcerated in a secure facility in the midwestern United States. Beliefs that power equates safety and a violent home environment were salient in understanding escalation in offending behavior, and prior criminal victimization was moderately significant. Implications for individual and family preventive interventions and delinquency theories are discussed.

Complement receptor 3 (CR3; CD18/CD11b) plays an important role in the recognition and clearance of Streptococcus pneumoniae (pneumococci) by neutrophils. The purpose of the present study was to characterize the modulation of CR3 surface expression on neutrophils exposed to pneumococci and to assess its functional significance. CR3 was detected with fluorescent phytoerythrin-labelled anti-CR3 (CD11b) antibodies, quantified with a fluorescence cell counter (FACS) and localized by confocal fluorescence microscopy. Uptake of fluorescent FITC-labelled pneumococci was quantified by FACS. Whole blood from healthy volunteers was exposed at 37 degrees C to killed whole type III Streptococcus pneumoniae (KSP; 10(8)/ml) or to a positive control ( Escherichia coli lipopolysaccharide) that enhanced CR3 surface expression on neutrophils to a comparable extent. Varying the concentration of KSP between 10(5) and 10(8) organisms/ml progressively augmented CR3 surface expression measured at 1 h, whereas the response declined at 10(9)/ml. The diminished response to 10(9) KSP/ml proved to be time-dependent, with surface CR3 up-regulated maximally within 5 min, and down-regulated thereafter. Labelling of CR3 during exposure demonstrated accelerated receptor sequestration, and confocal fluorescence microscopy demonstrated internalized CR3. Cooling to 16 degrees C, to inhibit the up-regulation of CR3 surface expression, also inhibited the uptake of FITC-labelled KSP and morphological changes. Accelerated down-regulation of surface CR3 expression by exposure to 10(9)/ml unlabelled KSP diminished the uptake of labelled KSP added subsequently. In contrast, lipopolysaccharide-induced up-regulation of CR3 expression increased the uptake of labelled KSP. Together, these experiments reveal dynamic modulation of CR3 expression on the surface of neutrophils exposed to pneumococci and a functional correlate of this modulation. Thus neutrophil expression of CR3 changes dynamically in response to exposure of neutrophils to progressively higher concentrations of pneumococci, conditions that mimic early neutrophil recruitment to densely infected lung tissue in acute pneumococcal pneumonia.

Poverty is associated with negative health outcomes, including depression. Little is known about the specific elements of poverty that contribute to depression, particularly among African American women at risk for type 2 diabetes. This study examined the relationships of economic and social resources to depression among African American women at high risk for the development of type 2 diabetes (N = 181) using the Conservation of Resources theory as a conceptual framework. Women were assessed at 3 time points in conjunction with a dietary change intervention. At baseline, 40% of women reported clinically significant depression, and 43.3% were below the poverty line. Depressed women reported fewer economic assets and greater economic distress than nondepressed peers. Multivariate logistic regression analyses indicated that nonwork status, lack of home ownership, low appraisal of one's economic situation, low self-esteem, and increased life events were significantly associated with depression at baseline. Longitudinal multivariate logistic regression models indicated that income, home ownership, future economic appraisal, life events, and self-esteem predicted depression trajectories at Time 3. These results speak to the multifaceted sources of stress in the lives of poor African American women. Interventions that address the economic and social factors associated with depression are needed.

Background: The influence of sex steroids upon brain development has been suggested to mediate sex differences in developmental psychopathology. The ratio of the length of index finger or second finger to the ring finger or fourth finger (the 2D:4D ratio) appears to be a marker of early sex hormone exposure, with low 2D:4D associated with high prenatal testosterone and high 2D:4D associated with high prenatal oestrogen. This relationship allows a non-invasive measure of the long-term influence of prenatal sex steroids. Behaviours such as hyperactivity and poor social cognition are common in preschoolers. An association between 2D:4D and these possible precursors of psychopathology would be most readily identified in this group., Aim: To identify relationships between 2D:4D ratio and behaviours in preschool children which constitute possible precursors of developmental psychopathology., Study Design: Population survey., Method: The 2D:4D ratio was measured in a group of preschool children and behavioural questionnaires were given to parents and teachers., Results: Sex differences in behaviours were small, whilst correlations with 2D:4D were strong. Low 2D:4D was related to hyperactivity and poor social cognitive function in girls, and high 2D:4D with emotional symptoms in boys., Conclusions: We suggest that during early brain development androgens increase the probability of hyperactivity and poor social cognition in girls. Early oestrogens increase the probability of emotional problems in boys.

We have developed a technology for improving avidity by making bivalent, trivalent, or tetravalent recombinant polypeptides. We designed tripartite proteins consisting of the Fab fragment of an antibody fused with a hinge derived from human immunoglobulin D that was further linked to polymerization domains derived from human coiled-coil proteins. We report here on the application of this method with a Fab domain directed against the major human rhinovirus receptor, intercellular adhesion molecule 1 (ICAM-1). Multivalent anti-ICAM-1 molecules were produced in bacteria and purified as soluble preassembled homogeneous proteins at high yield. These proteins successfully blocked rhinovirus infection in vitro, with the efficiency increasing from monomer to dimer, trimer, and tetramer. The diminished dissociation rate of these multivalent antibodies and their improved efficacy in preventing rhinovirus infection provide a foundation for producing prophylactic and therapeutic molecules against human rhinovirus, the causative agent of the majority of common colds.

The monoclonal antibody 1A6 binds to human intercellular adhesion molecule 1 (ICAM-1, CD54) and inhibits infection by 90% of human rhinovirus (HRV) serotypes. To make a therapeutic molecule for preventing and treating HRV infection, we humanized a single chain antibody (scFv), 1A6, by a structure-guided complementarity-determining region (CDR) grafting procedure. Our final humanized 1A6 scFv does not retain any mouse back mutations in the framework. Without changing the CDR sequences, the humanized 1A6 scFv demonstrates over 50-fold improvement in both affinity for ICAM-1 and protection efficacy against HRV infection in vitro.

The effects of a single bout of prolonged treadmill exercise [mean=81 (13) min] on sarcoplasmic reticulum (SR) Ca(2+) release, uptake and ATPase activity were determined in the costal region of rat diaphragm (D) and red gastrocnemius (RG). Glycogen depletion measurements made immediately following exercise suggested that treadmill running substantially recruited the fibers throughout both muscles. SR Ca(2+) ATPase activity, measured in isolated SR vesicles, decreased in the RG by 33% but remained unchanged in D in response to the exercise bout. This effect in RG was matched by a 37% decline in Ca(2+) uptake and a 28% depression in Ca(2+) release when measured in muscle homogenates. Conversely, Ca(2+) uptake increased between 157% and 263% in the D in the absence of any change in Ca(2+) release. These data show that the attenuation of SR function that has been consistently observed in limb muscle over the last several decades is absent in diaphragm despite the fact that its fibers appear to experience sufficient activity to deplete their glycogen. In fact, the large increase in Ca(2+) uptake in D shows that prolonged activity actually potentiates the ability of SR vesicles to sequester Ca(2+) in the absence of any increase in energy cost. Thus, it appears necessary to re-evaluate the role of exercise in regulating Ca(2+) sequestration by the SR as different muscles may respond in ways that are dictated by their function.

The monosporic seven-celled/eight-nucleate Polygonum-type female gametophyte has long served as a focal point for discussion of the origin and subsequent evolution of the angiosperm female gametophyte. In Polygonum-type female gametophytes, two haploid female nuclei are incorporated into the central cell, and fusion of a sperm cell with the binucleate central cell produces a triploid endosperm with a complement of two maternal and one paternal genomes, characteristic of most angiosperms. We document the development of a four-celled/four-nucleate female gametophyte in Nuphar polysepala (Engelm.) and infer its presence in many other ancient lineages of angiosperms. The central cell of the female gametophyte in these taxa contains only one haploid nucleus; thus endosperm is diploid and has a ratio of one maternal to one paternal genome. Based on comparisons among flowering plants, we conclude that the angiosperm female gametophyte is constructed of modular developmental subunits. Each module is characterized by a common developmental pattern: (1) positioning of a single nucleus within a cytoplasmic domain (pole) of the female gametophyte; (2) two free-nuclear mitoses to yield four nuclei within that domain; and (3) partitioning of three uninucleate cells adjacent to the pole such that the fourth nucleus is confined to the central region of the female gametophyte (central cell). Within the basal angiosperm lineages Nymphaeales and Illiciales, female gametophytes are characterized by a single developmental module that produces a four-celled/four-nucleate structure with a haploid uninucleate central cell. A second pattern, typical of Amborella and the overwhelming majority of eumagnoliids, monocots, and eudicots, involves the early establishment of two developmental modules that produce a seven-celled/eight-nucleate female gametophyte with two haploid nuclei in the central cell. Comparative analysis of ontogenetic sequences suggests that the seven-celled female gametophyte (two modules) evolved by duplication and ectopic expression of an ancestral Nuphar-like developmental module within the chalazal domain of the female gametophyte. These analyses indicate that the first angiosperm female gametophytes were composed of a single developmental module, which upon double fertilization yielded a diploid endosperm. Early in angiosperm history this basic module was duplicated, and resulted in a seven-celled/eight-nucleate female gametophyte, which yielded a triploid endosperm with the characteristic 2:1 maternal to paternal genome ratio.

The management of patients with suspected or known lung cancer is becoming increasingly complex. State-of-the-art care often requires input from many sources, including pulmonology, thoracic surgery, medical oncology, radiation oncology, pathology, and radiology. Valuable contributions to care also come from nursing, social work, psychology, psychiatry, pastoral care, and palliative care, among others. As a result, multidisciplinary input into care is vital. Patients with suspected lung cancer should be expeditiously evaluated and referred for management. Clear and understandable information on the diagnosis, treatment options, and possible outcomes should be provided. Treatment recommendations should be based on locally agreed-on adaptations of clinical practice guidelines. Provisions for ongoing care should be apparent to all concerned

Background: Previous researchers have suggested that a vegetarian diet or one rich in fish may protect against Alzheimer's disease (AD). However, assessing diet is difficult in AD patients. (15)N:(14)N isotopic ratios (delta(15)N) of body proteins can estimate long-term dietary habits in a way that does not depend on memory. delta(15)N is high in people who eat a lot of fish and low in vegetarians., Methods: To choose between the vegetarian and fish hypotheses of AD, we compared dietary questionnaire reports and delta(15)N of hair samples from AD patients and controls., Results: Patients' cognitive scores related directly to reported frequency of eating fish and to hair delta(15)N(AIR), but inversely to reported frequency of eating beans. Homocysteine levels related inversely to hair delta(15)N(AIR) in controls, but not in patients. Dietary questionnaire reports accounted for slightly more variance in delta(15)N(AIR) in patients than controls. Therefore, our questionnaire assessed dietary habits as reliably for individuals with AD as for cognitively unimpaired controls., Conclusions: A diet rich in fish may ameliorate AD, possibly by lowering homocysteine, but more vegetarian diets do not. In fact, eating beans correlated with worse cognition in AD patients. Further studies should test if restricting the intake of beans slows the progression of AD.

Background: The hippocampus is important for memory. Hippocampal atrophy and higher levels of homocysteine may both predict cognitive dysfunction in community-dwelling older people. We tested if higher homocysteine relates to hippocampal thinning in this group., Subjects: 156 community-dwelling volunteers without clinical memory problems., Method: We measured minimal hippocampal widths on magnetic resonance images and homocysteine in plasma., Results: Minimal hippocampal widths related inversely to homocysteine levels., Conclusions: Our results indicate that, even in healthy older people, homocysteine may damage the hippocampus. Reducing homocysteine levels in healthy older people may help to prevent Alzheimer's disease.

Deep observation boreholes in the vicinity of active production wells in Honolulu, Hawaii, exhibit the anomalous condition that fluid-column electrical conductivity logs and apparent profiles of pore-water electrical conductivity derived from induction conductivity logs are nearly identical if a formation factor of 12.5 is assumed. This condition is documented in three boreholes where fluid-column logs clearly indicate the presence of strong borehole flow induced by withdrawal from partially penetrating water-supply wells. This result appears to contradict the basic principles of conductivity-log interpretation. Flow conditions in one of these boreholes was investigated in detail by obtaining flow profiles under two water production conditions using the electromagnetic flowmeter. The flow-log interpretation demonstrates that the fluid-column log resembles the induction log because the amount of inflow to the borehole increases systematically upward through the transition zone between deeper salt water and shallower fresh water. This condition allows the properties of the fluid column to approximate the properties of water entering the borehole as soon as the upflow stream encounters that producing zone. Because this condition occurs in all three boreholes investigated, the similarity of induction and fluid-column logs is probably not a coincidence, and may relate to aquifer response under the influence of pumping from production wells.

A yeast two-hybrid screen was conducted to identify binding partners of Mlf1, an oncoprotein recently identified in a translocation with nucleophosmin that causes acute myeloid leukemia. Two proteins isolated in this screen were 14-3-3zeta and a novel adaptor, Madm. Mlf1 contains a classic RSXSXP sequence for 14-3-3 binding and is associated with 14-3-3zeta via this phosphorylated motif. Madm co-immunoprecipitated with Mlf1 and co-localized in the cytoplasm. In addition, Madm recruited a serine kinase, which phosphorylated both Madm and Mlf1 including the RSXSXP motif. In contrast to wild-type Mlf1, the oncogenic fusion protein nucleophosmin (NPM)-MLF1 did not bind 14-3-3zeta, had altered Madm binding, and localized exclusively in the nucleus. Ectopic expression of Madm in M1 myeloid cells suppressed cytokine-induced differentiation unlike Mlf1, which promotes maturation. Because the Mlf1 binding region of Madm and its own dimerization domain overlapped, the levels of Madm and Mlf1 may affect complex formation and regulate differentiation. In summary, this study has identified two partner proteins of Mlf1 that may influence its subcellular localization and biological function.

Recent investigations have suggested that changes in contractile protein expression contribute to reductions in skeletal muscle function during congestive heart failure (CHF). Myosin heavy chain (MHC), a major contractile protein, has been shown to undergo alterations in protein isoform expression during CHF. The purpose of this investigation was twofold: (1) to determine whether muscles of the same functional group undergo similar changes in MHC expression, and (2) determine whether the magnitude of alterations in MHC is related to the severity of CHF. Using the rat coronary ligation model, mild and severe forms of CHF were produced and muscles of the plantar flexor group were analyzed. Whole-muscle MHC isoform proportions were not altered in the soleus and white gastrocnemius muscle, however significant increases in the percentage of fast MHC isoforms (7-9% increases in MHC IIx and IIb expression) were found in the red gastrocnemius muscle. In addition, there were significant proportional increases (8%) in MHC type IIb at the expense of MHC type IIx in the plantaris muscle. Many of the changes in the proportions of MHC isoforms were significantly correlated with indices of CHF severity. This indicates that changes in skeletal muscle MHC isoform expression are related to the severity of CHF and suggests that some peripheral skeletal muscles are more susceptible to shifts in MHC expression due to CHF. These changes in MHC isoform expression may contribute to alterations in the physiological performance of skeletal muscle and exercise capacity during CHF.

Objective: This study evaluated the 3-month follow-up data of the Eat Well, Live Well Nutrition Program, a culturally specific, peer-led dietary change program designed to reduce the risk of type 2 diabetes in low-income African-American women. This peer-led program was delivered in the community and was tailored to the participants' stage of change for individual dietary patterns. We report the results of the 3-month intervention and the extent to which dietary changes and other key outcomes were maintained at a 3-month follow-up assessment., Research Design and Methods: Using an experimental control group design, 294 overweight African-American women (ages 25-55 years), recruited in collaboration with a neighborhood organization, completed pre- and posttest and 3-month follow-up interviews of dietary behaviors, knowledge, attitudes, fat intake, and weight., Results: Significant reductions were found in fat intake among women in the treatment condition when compared with women in the control group; these reductions were maintained at 3-month follow-up assessment. Likewise, significant changes in dietary patterns were reported after the study and were maintained, except for one dietary pattern (replacement)., Conclusions: This model of health promotion, which individually tailors dietary patterns through staging and use of peer educators, has the potential for decreasing fat intake and increasing and maintaining specific low-fat dietary patterns among overweight African-American women at risk for diabetes.

A 16-day-old white rhinoceros calf died suddenly while in excellent condition and showing no obvious previous clinical signs. It was the 9th calf of a mature female kept free-ranging with 11 other rhinoceros as well as various other game species on a 2000 hectare game breeding centre adjacent to the town of Lichtenburg and outlying cattle farmlands in the Northern Province. At post mortem examination, death was ascribed to heart failure. There was marked multifocal to coalescing subacute parasitic myocarditis with numerous protozoan bradyzoite cysts and free tachyzoites present amongst the predominantly round cell inflammatory infiltrate. The coccidian was positively identified as Neospora sp. using both polyclonal and murine monoclonal Neospora caninum antibody immunohistochemistry in the avidin-biotin technique. The parasites stained poorly with Toxoplasma gondii-specific immunoperoxidase staining. Ultrastructurally, a section of a bradyzoite-containing cyst, as well as tachyzoites, were largely but not totally consistent with those described for Neospora caninum. The dam showed no sign of illness. Neosporosis affecting white rhinoceros (Ceratotherium simum) has not previously been reported. A summarised overview of neosporosis from selected publications and a recent review is given.

Background: Topical over-the-counter remedies exist to aid in the control of seborrheic dermatitis and chronic dandruff on a superficial level. Low-dose systemic oral nickel and bromide therapy has shown promise in providing improvement and eventual clearing of the disease., Objective: The purpose of this study was to further evaluate the effect of an orally administered low-dose, homeopathic mineral therapy (Potassium bromide 1X, Sodium bromide 2X, Nickel sulfate 3X, Sodium chloride 6X) on seborrheic dermatitis and chronic dandruff., Methods: Forty-one patients with seborrheic dermatitis and/or chronic dandruff were assigned to one of two treatment groups: Active (containing the medication) or placebo (vehicle). Study medication was administered in a placebo-controlled, randomly-selected, double-blind study for 10 weeks. At the end of 10 weeks all patients crossed over to the active medication, under a different label for an additional 10 weeks in an open study format., Results: Twenty-nine patients completed the 10-week blinded portion of the study. After 10 weeks of treatment, the disease state of the active patients improved significantly over that of the placebo patients (p<0.04). The placebo patients' condition before and after crossover to active treatment was also evaluated, showing significant improvement (p<0.01) 10 weeks after crossing over to active medication., Conclusion: Oral therapy using a low-dose homeopathic preparation combining Potassium bromide 1X, Sodium bromide 2X, Nickel sulfate 3X, and Sodium chloride 6X, provides significant improvement in seborrheic dermatitis and dandruff after 10 weeks of dosing.

In flowering plants, the developmental and genetic basis for the establishment of an embryo-nourishing tissue differs from all other lineages of seed plants. Among extant nonflowering seed plants (conifers, cycads, Ginkgo, Gnetales), a maternally derived haploid tissue (female gametophyte) is responsible for the acquisition of nutrients from the maternal diploid plant, and the ultimate provisioning of the embryo. In flowering plants, a second fertilization event, contemporaneous with the fusion of sperm and egg to yield a zygote, initiates a genetically biparental and typically triploid embryo-nourishing tissue called endosperm. For over a century, triploid biparental endosperm has been viewed as the ancestral condition in extant flowering plants. Here we report diploid biparental endosperm in Nuphar polysepalum, a basal angiosperm. We show that diploid endosperms are common among early angiosperm lineages and may represent the ancestral condition among flowering plants. If diploid endosperm is plesiomorphic, the triploid endosperms of the vast majority of flowering plants must have evolved from a diploid condition through the developmental modification of the unique fertilization process that initiates endosperm.

It is thought that changes in sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) of skeletal muscle contribute to alterations in skeletal muscle function during congestive heart failure (CHF). It is well established that exercise training can improve muscle function. However, it is unclear whether similar adaptations will result from exercise training in a CHF patient. Therefore, the purpose of this study was to determine whether skeletal muscle during moderate CHF adapts to increased activity, utilizing the functional overload (FO) model. Significant increases in plantaris mass of the CHF-FO and sham-FO groups compared with the CHF and control (sham) groups were observed. Ca(2+) uptake rates were significantly elevated in the CHF group compared with all other groups. No differences were detected in Ca(2+) uptake rates between the CHF-FO, sham, and sham-FO groups. Increases in Ca(2+) uptake rates in moderate-CHF rats were not due to changes in SERCA isoform proportions; however, FO may have attenuated the CHF-induced increases through alterations in SERCA isoform expression. Therefore, changes in skeletal muscle Ca(2+) handling during moderate CHF may be due to alterations in regulatory mechanisms, which exercise may override, by possibly altering SERCA isoform expression.

We found earlier that deferoxamine (DFO), a drug used for treatment of iron overload, is active against a rat model of Pneumocystis carinii pneumonia (PCP). We had assumed a mode of action by deprivation of nutritional iron; however, data here show that DFO penetrates P. carinii, causing irreversible damage, thus indicating a different mode of action. Penetration was demonstrated by showing DFO uptake by high-pressure liquid chromatography analysis. By using calcein-AM as an indicator, exposure to DFO was shown to cause a reduction in P. carinii cytoplasmic free iron. Exposure to >or=100 microM DFO for >or=8 h in vitro caused growth to cease and cell numbers to decline over several days. This direct and irreversible damage to P. carinii led to the prediction that infrequent delivery of DFO to the lungs via an aerosol would be an effective treatment in the animal model of PCP. This prediction was confirmed by demonstrating that a once-a-week aerosol treatment of rats was 100% effective both as a prophylactic and as a curative treatment in a rat model of PCP.

Since the late 1980s a distinct form of focally-extensive mucoid to mucopurulent uterine body chronic placentitis,caused by nocardioform organisms, hasbeen recognised in horses in the USA state of Kentucky and possibly in other areas. This disease has led to increasing numbers of foal losses from late abortions, still-births, prematurity, or early neonatal deaths. The foals are usually not infected, but may be small or emaciated. Modes of infection and transmission are as yet unknown. Nocardia spp. and related nocardioform bacteria as causes of equine infertility, endometritis and foal death are briefly reviewed. A case of near full-term abortion involving a Friesian mare in the Pretoria district of Gauteng Province in South Africa during February 2000, with the same placental lesion as described in the Kentucky cases, is presented. Nocardioform organisms were visualised on impression smears and histological sections of affected foetal membranes, and were also cultured. The organism has been identified at the Livestock Disease Diagnostic Center of the University of Kentucky as an Amycolatopsis sp. of the less-commonly diagnosed group of nocardioforms causing placentitis in the USA. The organism was cultured from the uterus of the mare 18 days post-foaling, but after a 2-week course of oral trimethoprim and sulphamethoxazole, based on antibiogram sensitivity testing, a uterine flush yielded no growth. A semen sample from the sire of the aborted foal did not yield any Gram-positive filamentous branching bacteria. The mare subsequently conceived to a single insemination.

Patterns of reproductive isolation between two sympatric species of oaks, Quercus gambelii and Q. grisea, that exhibit strong ecological differentiation were examined. A full diallel cross using four trees of each species (i.e. all possible pollinations among eight trees) was performed. This design was repeated at two sites that represent different outcomes of sympatry: (1) a xeric mountain ridge where many hybrids are established (HZ); and (2) a mesic valley bottom where virtually no hybrids are established (MOCYN). By measuring fruit survival at several developmental stages, both the timing and strength of reproductive barriers within and between sites, species, cross types, and pollen dosage levels were examined. In three of four cases, heterospecific fruit set was significantly reduced compared to conspecific fruit set. This reduction occurred after the time of fertilization, but before the onset of embryo growth. Increasing the dose of pollen from an average of 9-194 grains/stigma did not affect this result. Thus, early postfertilization processes play a strong role in species fidelity in these oaks. Quercus gambelii experienced a five-fold decrease in conspecific fruit set at HZ relative to MOCYN. In contrast, heterospecific fruit set of Q. gambelii was the same at both sites. Poor Q. gambelii pollen performance is implicated as playing the major role in this result. One Q. gambelii individual at HZ was highly fecund, and had higher heterospecific than conspecific fruit set; slight introgression in this tree was detected uisng RAPD markers. The Environmental Emasculation Hypothesis that posits that environmental stress can increase the probability of hybrid formation by reducing the competitive ability of male gametes of one species is proposed.

Erythropoietin (Epo) and thyroid hormone (T(3)) are key molecules in the development of red blood cells. We have shown previously that the tyrosine kinase Lyn is involved in differentiation signals emanating from an activated erythropoietin receptor. Here we demonstrate that Lyn interacts with thyroid hormone receptor-interacting protein 1 (Trip-1), a transcriptional regulator associated with the T(3) receptor, providing a link between the Epo and T(3) signaling pathways. Trip-1 co-localized with Lyn and the T(3) receptor alpha in the cytoplasm/plasma membrane of erythroid cells but translocated to discrete nuclear foci shortly after Epo-induced differentiation. Our data reveal that T(3) stimulated the proliferation of immature erythroid cells, and inhibited maturation promoted by erythropoietin. Removal of T(3) reduced cell division and enhanced terminal differentiation. This was accompanied by large increases in the cell cycle inhibitor p27(Kip1) and by increasing expression of erythroid transcription factors GATA-1, EKLF, and NF-E2. Strikingly, a truncated Trip-1 inhibited both erythropoietin-induced maturation and T(3)-initiated cell division. This mutant Trip-1 acted in a dominant negative fashion by eliminating endogenous Lyn, elevating p27(Kip1), and blocking T(3) response elements. These data demonstrate that Trip-1 can simultaneously modulate responses involving both cytokine and nuclear receptors.

The purpose of the present study was to investigate the effects of fatiguing muscular activity on glycogen, glycogen phosphorylase (GP), and Ca(2+) uptake associated with the sarcoplasmic reticulum (SR). Tetanic contractions (100 ms, 75 Hz) of the gastrocnemius and plantaris muscles, elicited once per second for 15 min, significantly reduced force to 26.5 +/- 4.0% and whole muscle glycogen to 23% of rested levels. SR glycogen levels were 415.4 +/- 76.6 and 20.4 +/- 2.1 microg/mg SR protein in rested and fatigued samples, respectively. The optical density of GP from SDS-PAGE was reduced to 21% of control, whereas pyridoxal 5'-phosphate concentration, a quantitative indicator of GP content, was significantly reduced to 3% of control. GP activity after exercise, in the direction of glycogen breakdown, was reduced to 4% of control. Maximum SR Ca(2+) uptake rate was also significantly reduced to 81% of control. These data demonstrate that glycogen and GP associated with skeletal muscle SR are reduced after fatiguing activity.

Serum homocysteine is increased, and correlates inversely with cognitive scores, in Alzheimer's disease (AD), vascular dementia and "age-associated memory impairment". Elevated levels might signal accelerated cognitive decline, although this remains to be established. We therefore repeated Mini-Mental State Examinations, together with additional ADAS-Cog assessments, in 32 healthy elderly individuals to determine whether prior homocysteine levels predicted cognitive changes over a 5-year period. Homocysteine predicted follow-up cognitive scores and rate of decline in cognitive performance independently of age, sex, education, renal function, vitamin B status, smoking and hypertension (p < 0.001). Homocysteine predicted word recall (p = 0.01), orientation (p = 0.02) and constructional praxis scores (p < 0.0001). One subject, with the second highest initial homocysteine, had developed probable AD at follow-up. Fasting total serum homocysteine appears to be an independent predictor of cognitive decline in healthy elderly and exerts a maximal effect on spatial copying skills., (Copyright 2001 S. Karger AG, Basel)

The study examines the extent to which gender, personality attributes, household, community, and environmental factors are associated with violent behaviors in young adulthood. The authors present findings from a sample of 765 21-year-old individuals participating in a drug and delinquency prevention study. Personality attributes, opportunities, and social acceptability of antisocial behaviors were identified as accounting for gender differences and having more influence on violent behavior than environmental correlates. Implications for preventive intervention are discussed.

Various deficits in the cognitive functioning of people with autism have been documented in recent years but these provide only partial explanations for the condition. We focus instead on an imitative disturbance involving difficulties both in copying actions and in inhibiting more stereotyped mimicking, such as echolalia. A candidate for the neural basis of this disturbance may be found in a recently discovered class of neurons in frontal cortex, 'mirror neurons' (MNs). These neurons show activity in relation both to specific actions performed by self and matching actions performed by others, providing a potential bridge between minds. MN systems exist in primates without imitative and 'theory of mind' abilities and we suggest that in order for them to have become utilized to perform social cognitive functions, sophisticated cortical neuronal systems have evolved in which MNs function as key elements. Early developmental failures of MN systems are likely to result in a consequent cascade of developmental impairments characterised by the clinical syndrome of autism.