Transfer of fat-soluble pesticides from contaminated feed to poultry tissues and eggs.

1. Implementation of Good Manufacturing Practice and HACCP (Hazard Analysis Critical Control Points) in the production of poultry feed requires efficient tools for profiling risks associated with pesticide use in the production of crops for feed. 2. This paper describes a simple model that may be of use in the first tiers of risk profiling of feeds. 3. The model adequately reproduced the pattern of residues in fat and eggs of laying hens dosed with a selection of lipophilic pesticides that may be used in the production of crops for poultry feeds: deltamethrin, diflubenzuron, fipronil, lindane, piperonyl butoxide and spinosad. 4. Simulations suggest results derived from studies on laying chickens can be extrapolated to other laying birds. 5. Poultry meat production systems focus on maximising growth of birds giving rise to significant potential for dilution of residues that transfer to fat from feed. 6. Simulations of residues in fat of chickens, ducks, geese and turkeys exposed to a lipophilic pesticide with an elimination half-life of one day at 10 mg/kg body weight/d from hatching to typical market ages suggest residues in fat that are highest in turkeys > chickens > geese > ducks. 7. The model is of use in interpreting published dosing studies and predicting likely residues in birds at times after last exposure/dosing.

Investigation of the ammonium chloride and ammonium acetate inhibition of oxygen evolution by Photosystem II.

Using EPR and EXAFS spectroscopies we show that high concentrations of ammonium cations at alkaline pH are required for (1) inhibition of oxygen evolution: (2) an alteration of the EPR properties of the oxygen evolving complex: (3) the ability to detect YZ; and (4) the slow reduction of the Mn complex leading to the appearance of EPR detectable Mn2+. The inhibition of S state cycling, slowing of YZ reduction, appearance of Mn2+ and the yield of a Hpp < 10 mT S3 type EPR signal are decreased by calcium addition. This indicates that these effects were probably associated with calcium depletion arising from the high concentration of ammonium cation. The ammonia-induced changes to the S2 multiline EPR signal are not affected by calcium addition. The appearance of Mn2+ is shown to be reversible on illumination, suggesting that the Mn reduced from the native state is located at or near the native site. Simulations of the interaction which give rise to the S3 EPR signal are also presented and discussed. These indicate that lineshape differences occur through small changes in the exchange component of the interaction between the manganese complex and organic radical, probably through minor structural changes between the variously treated samples.

Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer's disease.

Apolipoprotein E, type epsilon 4 allele (APOE epsilon 4), is associated with late-onset familial Alzheimer's disease (AD). There is high avidity and specific binding of amyloid beta-peptide with the protein ApoE. To test the hypothesis that late-onset familial AD may represent the clustering of sporadic AD in families large enough to be studied, we extended the analyses of APOE alleles to several series of sporadic AD patients. APOE epsilon 4 is significantly associated with a series of probable sporadic AD patients (0.36 +/- 0.042, AD, versus 0.16 +/- 0.027, controls [allele frequency estimate +/- standard error], p = 0.00031). Spouse controls did not differ from CEPH grandparent controls from the Centre d'Etude du Polymorphisme Humain (CEPH) or from literature controls. A large combined series of autopsy-documented sporadic AD patients also demonstrated highly significant association with the APOE epsilon 4 allele (0.40 +/- 0.026, p < or = 0.00001). These data support the involvement of ApoE epsilon 4 in the pathogenesis of late-onset familial and sporadic AD. ApoE isoforms may play an important role in the metabolism of beta-peptide, and APOE epsilon 4 may operate as a susceptibility gene (risk factor) for the clinical expression of AD.

Analysis of the c-FOS gene on chromosome 14 and the promoter of the amyloid precursor protein gene in familial Alzheimer's disease.

The c-FOS gene product, a putative transacting transcriptional regulator of the amyloid precursor protein (APP) gene, is a candidate locus for the familial Alzheimer's disease (FAD) mutation on chromosome 14 (FAD14). In light of this functional relationship, we investigated the nucleotide sequence and segregation of c-FOS and the nucleotide sequence of the 5' APP promoter. Single-stranded conformational polymorphisms (SSCPs) in the c-FOS gene revealed that c-FOS closely cosegregates with the FAD14 gene but does not show allelic association with FAD. A conservative third-position T-->C mutation was demonstrated in exon 2 (codon 84) of c-FOS, and a C-->G substitution was detected at -209 bp in the 5' promoter of APP. Neither were unique to FAD and are unlikely to be pathogenic or secondary modifiers of the FAD phenotype. We conclude that the c-FOS open reading frame is probably not the site of the FAD14 locus, but we cannot exclude the existence of modifier loci on chromosome 21.

Regional adoptive immunotherapy with interleukin-2 and lymphokine-activated killer (LAK) cells for liver metastases.

A phase lb trial of a novel regional approach to adoptive immunotherapy is reported. Patients with liver metastases received continuous high-dose infusion of interleukin-2 (IL-2) into the splenic artery or intravenous infusion with subsequent transfer of lymphokine-activated killer (LAK) cells into the portal vein or the hepatic artery. Trafficking studies revealed homogeneous distribution of the LAK cells within the liver. The usual side-effects of IL-2 and LAK cells occurred without limiting liver toxicity. One partial (7+ months) and two complete responses (36 and 26+ months) were observed in 9 patients with metastases from cutaneous melanoma. None of 6 patients with metastases from ocular melanoma responded.

Addition of dacarbazine or cisplatin to interferon-alpha/interleukin-2 in metastatic melanoma: toxicity and immunological effects.

The combination of chemotherapy and immunotherapy seems to improve response rate in metastatic melanoma. We investigated the effects on toxicity and immunological effects of a single dose of dacarbacin (DTIC; 850 mg/m2) or cisplatin (CDDP; 100 mg/m2) added to subsequent immunotherapy with interferon-alpha (IFN-alpha) and interleukin-2 (IL-2). Twelve patients, who did not respond to IFN-alpha/IL-2 alone were studied. Six received DTIC and IFN-alpha/IL-2, and six received CDDP and IFN-alpha/IL-2. DTIC did not add significant toxicity except for nausea. Significant thrombocytopenia was observed in two patients after CDDP. Although CDDP led to grade 3 nephrotoxicity in two patients, the IL-2-induced fluid retention was less severe than with IFN-alpha/IL-2 alone. Pharmacokinetics of IL-2 were not altered by DTIC, but higher IL-2 serum levels were found in patients with grade 3 nephrotoxicity after CDDP. The IL-2-related induction of secondary mediators (interferon-gamma, tumour necrosis factor-alpha, soluble CD25) was not impaired by chemotherapy and the induction of neopterin was significantly higher after addition of CDDP. One partial response was observed after addition of DTIC to IFN-alpha/IL-2, and one after addition of CDDP. The addition of a single dose of DTIC or CDDP to IFN-alpha/IL-2 is fairly well tolerated and does not abolish induction of secondary mediators. Randomized trials are necessary to test the clinical efficacy.

Acute hepatitis in adult Still's disease apparently resulting from oral iron substitution--a case report.

The authors report a case of a young woman with adult-onset Still's disease (AOSD) with massive hyperferritinaemia who developed acute florid hepatitis with intraparenchymatous histiocytic infiltration following oral iron substitution for presumed iron deficiency, which settled on withdrawal of the iron. This suggests that the iron exacerbated the macrophage hyperactivity which is presumed to be present in AOSD. Oral iron substitution in the acute phase of this disease may be inadvisable.

Uniforms vs. business clothes for occupational health nurses. A needs survey.

The occupational health nurses' role has grown to that of manager. They work to achieve corporate goals such as cost containment through promotion of wellness. They are well suited to the changing technology of the corporate community. The changing role of the occupational health nurse has been accompanied by a change in what they wear to work. Uniforms are no longer standard, and business clothes are increasing in popularity. A uniform committee at AT&T Bell Laboratories was formed to assess the need for change in clothing. A non-random survey was used to investigate what others in the field were wearing. Nurses from 89 companies in eight states completed a total of 274 questionnaires. As a result of the survey, nurses at AT&T Bell Laboratories were given the option of wearing a uniform, street clothes and laboratory coat, or just street clothes as job function indicated.

Physiologically based pharmacokinetic (PBPK) model for residues of lipophilic pesticides in poultry.

Physiologically based pharmacokinetic (PBPK) modelling has been used to examine the relative importance of physiological differences between laying hens and broiler chickens as well as between broiler chickens and ducks, geese, and turkeys in determining tissue residues. Following exposure in feed, there may be significant differences in tissue residues between laying hens and broiler chickens. The blood lipid content of laying versus broilers, the duration of exposure, and the fraction of the dose absorbed into the systemic circulation were important parameters together with tissue-to-blood partition coefficients. The potential for modelling to improve the extrapolation of residue transfer studies carried out using laying hens to broiler chickens and other poultry is demonstrated.

A new tool for the evaluation of crop residue trial data (day-zero-plus decline).

An approach is presented for the prediction of pesticide residue concentrations in food and feed commodities produced from foliar-treated crops. It uses limited residue trial data and relies on information on spray retention and decline rates of residues following application. The use of the simple approach is demonstrated for residues of a variety of pesticides and the results compared with data sets evaluated by the Joint FAO/WHO Meeting on Pesticide Residues (JMPR) using expert judgement and also with estimates of high residues obtained using statistical methods. It is proposed that the approach should constitute an additional tool for the risk assessment of pesticide residues; it contributes to the estimation of maximum residue limits (MRLs) and high and median residues, which are needed for risk assessment. The approach should be particularly useful in situations where only a few residue trials are available such as often occurs for minor crops.

Influence of physiological status on residues of lipophilic xenobiotics in livestock.

Data on the transfer of lipophilic xenobiotics from livestock feed and the environment to meat and milk are required for risk assessment purposes. Often, data are only available for lactating dairy cattle. Physiologically-based pharmacokinetic (PBPK) modeling has been used to explore differences between classes of food-producing animals. Blood and tissue levels of lipophilic xenobiotics under conditions approximating steady-state were simulated. Simulations of constant exposure were performed for lactating cows, non-lactating cattle, sheep, goats and swine. The tissue : blood partition coefficient, fat volume and fat blood flow were identified as critical determinants of predicted tissue concentrations. There may be significant breed differences in residues in milk and fat following exposure. Modeling was used to derive scaling factors that can be used to assist the extrapolation of transfer studies, carried out on lactating dairy cows, to other classes of cattle and different species.

Monitoring of pesticides and veterinary drugs in Australian cattle: verification of the residue control system.

The Australian National Residue Survey in partnership with the Australian Quarantine and Inspection Service and industry routinely monitors beef to ensure that regulatory requirements for residues are being met. In the 10-year period from 1997 to 2006 a total of 128,902 samples were subjected to residue testing covering veterinary drugs and veterinary and agricultural pesticides in a random monitoring program. Residues of agricultural and veterinary chemicals exceeded the Australian standard in 13 and 7 samples, respectively. Greater than 99% of samples did not contain detectable residues above the Australian standard while greater than 90% of samples did not contain any residues of compounds included in the survey. The results of the surveys provide verification that the Australian residue control system is appropriate and that the requirements of countries importing Australian meat products can be satisfied. The surveys have also demonstrated that industry based programs and state based regulatory controls over sites contaminated with organochlorine residues are effective in managing residues of these chemicals in cattle.

Investigation of the S3 electron paramagnetic resonance signal from the oxygen-evolving complex of photosystem 2: effect of inhibition of oxygen evolution by acetate.

An S3 electron paramagnetic resonance (EPR) signal is observed in a variety of photosystem 2 (PS2) samples in which the oxygen-evolving complex (OEC) has been inhibited. These signals have been proposed to be due to an interaction, S2X+, between the manganese cluster in an oxidation state equivalent to S2 and an organic radical, either oxidized histidine [Boussac et al. (1990) Nature 347, 303-306] or the tyrosine radical Yz+ [Hallahan et al. (1992) Biochemistry 31, 4562-4573]. We report that treatment of PS2 with acetate at pH 5.5 leads to a slowing of the reduction of Yz+ and allows the trapping of an S3-type state on freezing to 77 K following illumination at 277 K. The S3 EPR signal in acetate-treated PS2 has a broader and more complex line shape but otherwise has similar properties to other S3 signals. The addition to acetate-treated samples in the S1 state of the herbicide 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU), which allows only a single turnover of the reaction center, causes a large reduction in the yield of the S3 signal. Various anion and cation treatments change the S3 signal line shape and are used to show that acetate probably acts by binding and displacing chloride. We propose that a variety of treatments which affect calcium and chloride cofactor binding cause a modification of the S2 state of the manganese cluster, slow the reduction of Yz+, and allow an S3 EPR signal to be observed following illumination.(ABSTRACT TRUNCATED AT 250 WORDS)

A Strategy for Reducing and Analyzing Ordered Choice Data.

A major barrier to use of new measurement methodologies in behavioral research has been the difficulties encountered in collecting individual judgements. Balanced incomplete block design (BIBD) procedures offer enormous flexibility in the way judgmental data may be collected. The advantages and disadvantages of BIBDs are clarified and their use is demonstrated with an empirical example. A procedure for reducing data of this type to analyzable form is proposed and an analytical approach that is appropriate for the resulting data is illustrated.

A new system for ambulatory pulmonary artery pressure recording.

OBJECTIVE: To develop a complete system for the measurement, recording, and analysis of ambulatory pulmonary artery pressure. DESIGN: The new system consists of a pulmonary artery catheter, an ambulatory recorder, and a desktop computer. Pulmonary artery pressure is measured by a micromanometer tipped catheter with an in vivo calibration system to allow correction for zero drift. This catheter is plugged into a small battery powered recorder. The recorder has two input channels, one for pressure and one for an event marker. The pressure wave is sampled 32 times/s, processed by an in built computer, compressed, and stored in semi-conductor memory. On completion of a recording, data is transferred from the ambulatory recorder through a serial data link to an Acorn Archimedes desktop computer on which further data processing, statistical analysis, graphics, and printouts can be obtained. RESULTS: The system has been used in 18 patients, with technically successful recording in 14, less than 15 minutes of data loss in three, and 12 hours of data loss in one. CONCLUSIONS: A new system for ambulatory pulmonary artery monitoring has been developed and used clinically with success. It may provide new perspectives on the pathophysiology of disease as it applies to everyday life.

Characterization of the multiple EPR line shapes of iron-semiquinones in photosystem 2.

We have compared the temperature-dependence characteristics of the EPR signals of Qa and Qb iron-semiquinones from both purple bacterial and plant photosystems. The data obtained were analyzed and estimates of the splitting parameters of the non-heme Fe2+ spin sublevels obtained. The study confirms the similarities of the g = 1.8 Qa iron-semiquinone signal (D/k = 15.6 K, E/k = 3.3 K) formed in formate-treated plant photosystem 2 to the signal found in purple bacteria. However, the g = 1.9 Qa iron-semiquinone signal (D/k = 7.1 K, E/k = much less than 1 K), formed in photosystem 2 when bicarbonate remains bound, has a unique temperature behavior. A series of spectral features associated with the iron-semiquinone in bicarbonate-bound photosystem 2 appear as the temperature is lowered, and the analysis of these data requires that some of these features be assigned to the higher spin states. The results are discussed in terms of the requirement for bicarbonate to be a ligand of the non-heme iron.

Experimenting With Perceptual Change Strategies.

Nonmetric multidimensional scaling procedures are employed in this experimental evaluation of perceptual changes resulting from differences in the presentation of information about stimuli. Longitudinal MDS techniques are found to be useful in monitoring perceptual changes produced by various communication alternatives. Communication strategies aimed at changing the relationships among stimuli are more effective than those designed to change the perceptual space structure. Furthermore, providing comparative information about groups of stimuli has more apparent impact than providing information about a single stimulus.

[Comparison between line immunoassay (LIA) and enzyme-linked immunosorbent assay (ELISA) for the determination of antibodies to extractable nuclear antigenes (ENA) with reference to other laboratory results and clinical features]. / Der Nachweis von Autoantikörpern gegen extrahierbare nukleäre Antigene (ENA) mittels Line Immunoassay (LIA) im Vergleich mit dem Enzyme-linked Immunosorbent Assay (ELISA) in Relation zu anderen Laborparametern und zur Klinik.

INTRODUCTION: The line immunoassay (LIA) for the determination of antibodies to individual extractable antinuclear antigens (ENA) is a development of the enzyme-linked immunosorbent assay (ELISA) in which the antigens to be tested are adsorbed onto a nylon test strip. In addition, the antigen subspecificities B/B' and D in the case of Sm, the 70 kD, A and C components in the case of U1-snRNP and the Ro52 and Ro60 components in the case of SSA/Ro are present separately on the strips. The aim of the study was to determine whether the line immunoassay is suitable for routine laboratory use by means of a comparison with the ELISA. METHODS: Sera from 92 patients stored in our serum bank with known ENA profile as determined by ELISA and with at least one antibody to ENA were tested again with LIA. The clinical features and other available laboratory data taken from the patient records were used to classify the disease according to the relevant diagnostic criteria. In discrepant cases, antibodies to ENA were also determined by Western blot. These data were used to determine which of the two methods gave the more plausible results and to calculate the sensitivity and specificity for each autoantibody. RESULTS: There was good correlation between the two methods, especially for anti-CENP-B (centromere protein B) and anti-Jo1 (histidyl-tRNA transferase) antibodies. For anti-Sm, there was a trend toward higher specificity with the LIA in patients with systemic lupus erythematosus (SLE) if antibodies to Sm D were detected. The LIA was significantly more specific for the detection of antibodies to ribonucleoprotein (RNP) in mixed connective tissue disease and, if antibodies to the 70 kD component were present, also in SLE, although the sensitivity was significantly lower in this case. For anti-SSA/Ro, the specificity of the LIA was significantly higher than ELISA if anti-Ro60 was detected. In the case of anti-SS-B/La, anti-Scl70 (topoisomerase I), anti-CENP-B (centromere protein B) und anti-Jo-1 (histidyl-tRNA transferase), the sensitivity and specificity of the two methods were not significantly different. The LIA was significantly more specific but less sensitive for the detection of anti histone antibodies. CONCLUSION: The suitability of the LIA for routine laboratory determinations was confirmed.