Dietary arachidonic acid and docosahexaenoic acid regulate liver fatty acid desaturase (FADS) alternative transcript expression in suckling piglets.

Molecular regulation of fatty acid desaturase (Fads) gene expression by dietary arachidonic acid (ARA) and docosahexaenoic acid (DHA) during early post-natal period, when the demand for long chain polyunsaturated fatty acids (LC-PUFA) is very high, has not been well defined. The objective of the current study was to determine regulation of liver Fads1, Fads2 and Fads3 classical (CS) and alternative transcripts (AT) expression by dietary ARA and DHA, within the physiological range present in human breast milk, in suckling piglets. Piglets were fed one of six milk replacer formula diets (formula-reared groups, FR) with varying ARA and DHA content from days 3-28 of age. The ARA/DHA levels of the six formula diets were as follows (% total fatty acid, FA/FA): (A1) 0.1/1.0; (A2) 0.53/1.0; (A3-D3) 0.69/1.0; (A4) 1.1/1.0; (D2) 0.67/0.62; and (D1) 0.66/0.33. The control maternal-reared (MR) group remained with the dam. Fads1 expression was not significantly different between FR and MR groups. Fads2 expression was down-regulated significantly in diets with 1:1 ratio of ARA:DHA, compared to MR. Fads2 AT1 expression was highly correlated to Fads2 expression. Fads3 AT7 was the only Fads3 transcript sensitive to dietary LC-PUFA intake and was up-regulated in the formula diets with lowest ARA and DHA contents compared to MR. Thus, the present study provides evidence that the proportion of dietary ARA:DHA is a significant determinant of Fads2 expression and LC-PUFA metabolism during the early postnatal period. Further, the data suggest that Fads3 AT7 may have functional significance when dietary supply of ARA and DHA are low during early development.

It was not me: attribution of blame for criminal acts in psychiatric offenders.

The current article addresses the psychometric qualities of the German Version of Gudjonsson's Blame Attribution Inventory (GBAI), a self-report scale for measuring attribution of blame for crime. The GBAI was administered to a criminal sample of forensic and criminal inmates (n=107). Findings indicate that the German version of the Gudjonsson Blame Attribution Inventory possesses acceptable test-retest stability and good internal consistency. Factor analysis reproduced the three basic dimensions of the GBAI: external attribution, mental-element attribution, and guilt-feeling attribution. Forensic patients had higher mental-element attribution and guilt-feeling attribution scores than the prison inmates. Interestingly, sexual offenders who were prisoners, showed the lowest guilt-feeling attribution, while sexual offenders who were forensic patients had the highest guilt-feeling attribution scores. Since earlier research reported a tendency of faking good in sexual offenders, we suggest that the forensic sexual offenders may demonstrate a social desirable response tendency in an attempt to gain sympathy and/or earlier parole. All in all, our data show that the German version of the GBAI is a valuable tool for measuring attributional styles of offenders.

Immunogenicity of the rF1+rV vaccine for plague with identification of potential immune correlates.

The rF1+rV candidate sub-unit vaccine for plague, formulated by adsorption to alhydrogel, has been demonstrated to be immunogenic in the cynomolgus macaque in a clinically relevant dose-range (5-40 microg of each sub-unit) and regimen. Following two doses of vaccine, a specific IgG titre developed in a dose-related manner with predominance of the IgG1/IgG2 isotypes. Groups of macaques receiving only a single dose of vaccine at the 40 microg dose-level had a significantly reduced peak IgG response and faster decline to baseline. Serum collected at week 5 from 19 immunised animals competed with and displaced murine Mab7.3 from binding to the V antigen in vitro. By week 53 of the schedule, although absolute IgG titres had declined, 17/19 macaque sera tested contained competing antibody, indicating the durability of a functional immune response to rF1+rV in this species. Thirteen of these week 53 sera were passively transferred into groups of naive mice, and all conferred full or partial protection against subsequent challenge of the mice with plague. Generally, those sera which were most competitive with Mab 7.3 for binding to V antigen were fully protective by passive transfer, although one week-53 serum sample was fully protective by passive transfer but not active by competitive ELISA. The early development of protective immunity in macaques was also indicated from the protection conferred on naive mice by the passive transfer of immune macaque serum collected at 2-10 weeks of the immunisation schedule. Serum samples from representative macaques within this time period also inhibited the Yersinia-mediated cytotoxicity of J774 macrophages in a qualitative in vitro assay of type three secretion.

TNFalpha polymorphisms and risk of psoriatic arthritis.

BACKGROUND: Tumour necrosis factor alpha (TNFalpha) is a cytokine of critical importance in psoriatic arthritis. OBJECTIVES: (1) To examine the association between TNFalpha promoter gene polymorphisms and psoriatic arthritis in two well characterised Canadian populations with the disease; (2) to carry out a meta-analysis of all TNFalpha association studies in white psoriatic arthritis populations. METHODS: DNA samples were genotyped for five TNF variants by time of flight mass spectrometry using the Sequenom platform. All five single nucleotide polymorphisms were in the 5' flanking region of TNFalpha gene at the following positions: -1031 (T-->C), -863 (C-->A), -857 (C-->T), -308 (G-->A), and -238 (G-->A). Primary analyses were based on logistic regression. Summary estimates of disease/genotype relations from several studies were derived from random effects meta-analyses. RESULTS: 237 psoriatic arthritis subjects and 103 controls from Newfoundland and 203 psoriatic arthritis subjects and 101 controls from Toronto were studied. A combined analysis of data from both populations, showed a significant association between disease status and the -238(A) variant (p=0.01). The meta-analysis estimate for the -238(A) TNFalpha variant in eight psoriatic arthritis populations was also significant (odds ratio=2.29 (95% confidence interval, 1.48 to 3.55)). CONCLUSIONS: Analysis of TNFalpha variants in psoriatic arthritis populations shows that the -238 (A) variant is a significant risk factor for this disease.

Association of SEEK1 and psoriatic arthritis in two distinct Canadian populations.

OBJECTIVE: To examine the relationship between SNP +39604 in SEEK1 and psoriatic arthritis (PsA) in two distinct Canadian populations. METHODS: 103 patients with PsA and 105 ethnically matched controls from Newfoundland and 202 patients with PsA and 100 controls from Ontario were studied. Patients and controls were genotyped for SNP +39604 of SEEK1 by time of flight mass spectrometry, using the Sequenom platform. Genomic DNA was amplified by the Dynal RELI SSO HLA-Cw* typing kit for HLA-C typing. RESULTS: The frequency of the minor SEEK1(T) allele in subjects with PsA and controls was 48.5% and 32.4%, respectively (odds ratio (OR) = 2.0; p = 0.017), in the Newfoundland population and 46.5% and 38.0%, respectively (OR = 1.4; p = 0.16), in the Ontario population. Although SEEK1 is associated with PsA, particularly in the Newfoundland population, multivariate analysis showed that SEEK1 does not seem to be a further susceptibility factor if the HLA-Cw*0602 status is already known. No association was noted between SEEK1(T) allele and onset of psoriasis, PsA, or arthritis pattern. CONCLUSION: SEEK1 is associated with PsA in the Newfoundland founder population. This association is probably due to linkage disequilibrium between SEEK1 and HLA-Cw*0602 in this population.

Continuing evolution of H9N2 influenza viruses in Southeastern China.

H9N2 influenza viruses are panzootic in domestic poultry in Eurasia and since 1999 have caused transient infections in humans and pigs. To investigate the zoonotic potential of H9N2 viruses, we studied the evolution of the viruses in live-poultry markets in Hong Kong in 2003. H9N2 was the most prevalent influenza virus subtype in the live-poultry markets between 2001 and 2003. Antigenic and phylogenetic analysis of hemagglutinin (HA) showed that all of the 19 isolates found except one belonged to the lineage represented by A/Duck/Hong Kong/Y280/97 (H9N2). The exception was A/Guinea fowl/NT184/03 (H9N2), whose HA is most closely related to that of the human isolate A/Guangzhou/333/99 (H9N2), a virus belonging to the A/Chicken/Beijing/1/94-like (H9N2) lineage. At least six different genotypes were recognized. The majority of the viruses had nonstructural (and HA) genes derived from the A/Duck/Hong Kong/Y280/97-like virus lineage but had other genes of mixed avian virus origin, including genes similar to those of H5N1 viruses isolated in 2001. Viruses of all six genotypes of H9N2 found were able to replicate in chickens and mice without adaptation. The infected chickens showed no signs of disease, but representatives of two viral genotypes were lethal to mice. Three genotypes of virus replicated in the respiratory tracts of swine, which shed virus for at least 5 days. These results show an increasing genetic and biologic diversity of H9N2 viruses in Hong Kong and support their potential role as pandemic influenza agents.

The other side of malingering: supernormality.

Supernormality refers to the tendency to systematically deny the presence of common symptoms (e.g., intrusive thoughts). The current article describes the psychometric qualities of a 37-item self-report measure of supernormality (i.e., Supernormality Scale; SS). The SS was administered to nonclinical individuals (n=95), noncriminal psychiatric patients (n=28), nonpsychiatric delinquents (n=49), and a heterogeneous sample of forensic patients (n=59). Within the healthy control sample, some employees were instructed to feign supernormal behaviour, while others were asked to respond honestly to SS items. Findings indicate that the SS demonstrates adequate test-retest stability and internal consistency. In the forensic patient sample, elevated SS scores were significant related to denial of intrusive thoughts in a thought suppression paradigm. However, accuracy parameters for the SS (i.e., sensitivity and specificity) showed that there is room for improvement. Nevertheless, our findings indicate that the SS might be a useful research tool for measuring denial of common symptoms.

Pharmacology, distribution and development of muscarinic acetylcholine receptor subtypes in the optic tectum of Rana pipiens.

Visually evoked behaviors mediated by the frog optic tectum require cholinergic activity, but the receptor subtypes through which acetylcholine acts are not yet identified. Using quantitative autoradiography and scintillation spectrometry, we examined the binding of [3H]pirenzepine and [3H]AF-DX 384 in the laminated optic tectum of the frog. In mammalian systems, these substances bind excitatory (m1 and m3 subtypes) and inhibitory (m2 and m4 subtypes) muscarinic acetylcholine receptors, respectively. Pharmacological analyses, including the use of specific muscarinic toxins, confirmed the subtype selectivity of the radioligands in the frog brain. Binding sites for [3H]pirenzepine were distinct from those for [3H]AF-DX 384. In the adult tectum, [3H]pirenzepine demonstrated specific binding in tectal layers 5-9. [3H]Pirenzepine binding was also present in tadpoles as young as stage V, but all sampled stages of tadpole tectum had significantly less binding when compared to adults. Lesioning of the optic nerve had no effect on [3H]pirenzepine binding. Specific [3H]AF-DX 384 binding was found in all layers of the adult tectum. All sampled tadpole stages exhibited binding sites for [3H]AF-DX 384, but the densities of these sites were also significantly higher in adults than they were in developing stages. Short-term lesions of the optic nerve reduced [3H]AF-DX 384 binding in all tectal layers of the deafferented lobe when compared to the afferented one. Long-term lesions decreased [3H]AF-DX 384 sites in both lobes.These results indicate that multiple muscarinic acetylcholine receptor binding sites reside in the frog optic tectum at all stages of development, and their pharmacology resembles that of mammalian m1/m3, m2 and m4 subtypes. Our data indicate that few, if any, of these receptors are likely to be located on retinal ganglion cell terminals. Furthermore, the expression of inhibitory muscarinic subtypes seems to be regulated by different mechanisms than that for excitatory subtypes.

Distribution and development of nicotinic acetylcholine receptor subtypes in the optic tectum of Rana pipiens.

Acetylcholine allows the elicitation of visually evoked behaviors mediated by the frog optic tectum, but the mechanisms behind its effects are unknown. Although nicotinic acetylcholine receptors (nAChRs) exist in the tectum, their subtype has not been assessed. By using quantitative autoradiography, we examined the binding of [(3)H]cytisine and [(125)I]alpha-bungarotoxin in the laminated tectum. In mammalian systems, these radioligands bind with high affinity to alpha4 nAChR subunits and alpha7 nAChR subunits, respectively. [(3)H]Cytisine demonstrated high specific binding in adult frogs in retinorecipient layer 9, intermediate densities in layer 8, and low binding in layers 1-7 of the tectum. [(3)H]Cytisine binding was significantly higher in the tecta of adults than in those of tadpoles. Lesioning the optic nerve for 6 weeks decreased [(3)H]cytisine binding in layers 8/9 by 70+/-1%, whereas 6-month lesions decreased binding by 76+/-3%. Specific binding of [(125)I]alpha-bungarotoxin in adults was present only at intermediate levels in tectal layers 8 and 9, and undetectable in the deeper tectal layers. However, the nucleus isthmi, a midbrain structure reciprocally connected to the tectum, exhibited high levels of binding. There were no significant differences in tectal [(125)I]alpha-bungarotoxin binding between tadpoles and adults. Six-week lesions of the optic nerve decreased tectal [(125)I]alpha-bungarotoxin binding by 33+/-10%, but 6-month lesions had no effect. The pharmacokinetic characteristics of [(3)H]cytisine and [(125)I]alpha-bungarotoxin binding in the frog brain were similar to those demonstrated in several mammalian species. These results indicate that [(3)H]cytisine and [(125)I]alpha-bungarotoxin identify distinct nAChR subtypes in the tectum that likely contain non-alpha7 and alpha7 subunits, respectively. The majority of non-alpha7 receptors are likely associated with retinal ganglion cell terminals, whereas alpha7-containing receptors appear to have a different localization.

Activity-dependent regulation of substance P expression and topographic map maintenance by a cholinergic pathway.

We have assessed the role of activity in the adult frog visual system in modulating two aspects of neuronal plasticity: neurotransmitter expression and topographic map maintenance. Chronic treatment of one tectal lobe with the non-NMDA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione decreased the percentage of substance P-like immunoreactive (SP-IR) tectal cells in the untreated lobe while disrupting topographic map formation in the treated one. Treatment with the NMDA receptor antagonist d-(-)-2-amino-5-phosphonovaleric acid (d-AP-5) disrupted the topographic map but had no affect on SP-IR cells. These results indicate that maintenance of the topographic map is dependent on direct input from the glutamatergic retinal ganglion cells, whereas substance P (SP) expression is being regulated by a pathway that relays activity from one tectal lobe to the other. Such a pathway is provided by the cholinergic nucleus isthmi, which is reciprocally connected to the ipsilateral tectum and sends a projection to the contralateral one. Mecamylamine and atropine, antagonists of nicotinic and muscarinic receptors, respectively, were used together to block all cholinergic activity or alone to block receptor subclass activity. All three treatments decreased SP expression and disrupted the topographic map in the treated tectal lobe. We conclude that both SP expression and topographic map maintenance in the adult optic tectum are activity-dependent processes. Although our results are consistent with the maintenance of the topographic map through an NMDA receptor-based mechanism, they suggest that SP expression is regulated by a cholinergic interaction that depends on retinal ganglion cell input only for its activation.

Forearm and calf blood flow in response to cortical arousal in normal male and female subjects.

The aim of this study was to investigate cardiovascular changes, particularly in forearm and calf blood flows, in response to acute emotional stress in men and women. The study was approved by the Ethics Committee of the Queen's Medical Centre, Nottingham University. Fifty-six healthy non-smokers (29 men and 27 women) aged 19 to 22 years participated. Blood flow was measured by venous occlusion plethysmography using mercury-in-silastic strain gauges. Acute emotional stress (2 min) was elicited by a visual orientation task. During acute emotional stress, there were increases in heart rate (males = 40 +/- 3%, females = 49 +/- 5%) and mean arterial pressure (males = 24 +/- 2%, females = 22 +/- 2%), and hyperaemia and vasodilatation were observed in the forearm (males = 162 +/- 15%, females = 239 +/- 31%) and calf (males = 78 +/- 16%, females = 131 +/- 24%). Vasoconstriction also occurred in some subjects. Forearm vasodilatation was significantly greater than calf vasodilatation. Gender variation was apparent in the calf, where vasodilatation was significantly greater in females, and vasoconstriction was significantly greater in males. In some subgroups of men and women, mean values indicated that acute emotional stress elicited increases in forearm, but not in calf, blood flows and vascular conductances. This pattern is similar to that reported by Rusch et al. (see text), but the present findings indicate that vasodilatation in the forearm and calf in response to acute emotional stress is more common.

Community-acquired Legionnaires' disease following minimal exposure to a contaminated source.

A case of community-acquired Legionnaires' disease (LD) is described. The source of infection was traced to a push-on tap at the end of a long spur from the hot circulation system in a large old residential building which had been unoccupied for several weeks. Legionella pneumophila serogroup 1 subgroup Pontiac was isolated from the patient's sputum and from the contaminated water supply. Isolates were shown to be indistinguishable from one another when subtyped by pulsed field gel electrophoresis of chromosomal DNA.

On-line brain potential correlates of right parietal patients' attentional deficit.

EEG potentials evoked by cues and targets were recorded in Posner's visual cueing task from 10 patients with lesions of the right parietal cortex and from age-matched healthy subjects. The patients' N1 component evoked by left-side cues was reduced at the right-parietal recording site, suggesting a general impairment in processing left-side visual input. As usual, patients' keypress responses were delayed when left targets were preceded by right cues. There were two correlates of this delay in the patients' EEG potentials evoked by the critical combination of right cue/left target: their mean amplitude 160-280 ms after target onset ('Nd') was less negative than with other combinations of cue and target, and the following frontal P300 was enhanced. The Nd reduction seems to be an on-line measure of patients' momentary decrease of attention for the left hemifield, while the frontal P300 might reflect the patients' attempts at reorienting. In conclusion, different components were sensitive to different aspects of the patients' disorder, suggesting the utility of this approach for developing detailed hypotheses on the mechanisms of attentional deficits involved in visual extinction and neglect.

Reduction of P3b in patients with temporo-parietal lesions.

By recording event-related EEG potentials from patients with frontal, parietal, or temporo-parietal lesions, we wanted to determine the cortical area that is relevant to the P3b component, replicating the approach used by Knight and associates who found reduced P3bs in patients with temporo-parietal lesions. They used auditory and somatosensory stimuli. We wanted to replicate their findings in auditory and visual oddball tasks and analysed potentials evoked by targets and by standard stimuli. Temporo-parietal patients' P3bs were reduced with auditory targets and lacked a distinct Pz maximum with visual targets. Further, auditory N1 was reduced both with targets and standards, P3 to visual standards and P2 to auditory standards were reduced. Parietal patients' P3bs differed only slightly from the control group, being somewhat reduced over the lesioned hemisphere with visual stimuli. Their P3 to visual standards was, however, reduced to the same extent as was the temporo-parietal patients'. Frontal patients did not differ from the control group both in their P3b and in their P3 to standards but had a number of conspicuous features in modality-specific components. In sum, our results on P3b (as well as on N1) replicate Knight's findings, confirming his conclusion that integrity of the temporo-parietal junction is critical for P3b. Implications for hypotheses on P3 are discussed.