Influence of non-inherited maternal HLA-DR antigens on susceptibility to rheumatoid arthritis

OBJECTIVE: It has recently been observed that non-inherited maternal DR4 antigens (NIMAs) of DR4 negative rheumatoid arthritis (RA) patients were increased compared with non-inherited paternal DR4 antigens (NIPAs). The aim of this study was to determine the prevalence of non-inherited DR4 antigens and DRB1 alleles in parents of RA patients. METHODS: HLA-DR serology and DRB1 typing was performed in 97 RA patients and their parents. NIMA and NIPA frequencies were compared, stratified according to the presence of DR4 and/or the shared epitope (SE). RESULTS: In DR4 negative patients, NIMA DR4 was increased compared with NIPA DR4 (OR 3.10, 95% CI 0.76, 12.70). When combined with results from a previous study this increase was significant (OR 3.65, 95% CI 1.29, 10.31). The NIMA effect of SE positive DR4 subtypes in this study (OR 4.73, 95% CI 0.94, 23.8) was stronger than the NIMA effect of combined SE positive DRB1 alleles (OR 2.19 95% CI 0.36, 13.22). CONCLUSIONS: The association between non-inherited maternal HLA-DR4 alleles and the susceptibility to RA was observed in two independent populations.     

Isolation and stability of histidine-tagged proteins produced in plants via potyvirus gene vectors

A system for the expression and purification of histidine-tagged proteins from plants has been developed using a tobacco etch potyvirus (TEV)-derived gene vectors. The vectors offered a convenient polylinker and a choice of histidine tagging at the recombinant proteins' N or C termini. These vectors were utilized for expression of proteins encoded by beet yellows closterovirus (BYV). Approximately 4 micrograms/g of 20-kDa BYV protein was readily isolated from plants systemically infected by hybrid TEV. In contrast, only minute quantities of 22-kDa BYV capsid protein (CP) histidine-tagged at its N or C terminus could be purified. Rapid degradation of the recombinant CP has been implicated in its failure to accumulate in infected plants. Fusion with TEV HC-Pro stabilized the histidine-tagged BYV CP and facilitated purification of the fusion product from infected plants. This same fusion approach was successfully used with the 24-kDa minor BYV CP. The recombinant proteins were recognized by histidine-tag-specific monoclonal antibody in immunoblot analysis. These results demonstrate the utility of a designed series of TEV vectors for expression, detection, and purification of the recombinant proteins and suggest that intrinsic protein stability is a major factor in a recovery of recombinant proteins from plants.     

Two linear acetogenins from Goniothalamus gardneri

Two new acetogenins, gardnerilins A and B, have been isolated from the roots of Goniothalamus gardneri. Both are C35 acetogenins containing non-tetrahydrofuran rings. Their structures have been established on the basis of spectral evidence.     

Dietary cholestyramine reduces ochratoxin A-induced nephrotoxicity in the rat by decreasing plasma levels and enhancing fecal excretion of the toxin

Ochratoxin A (OTA) is a mycotoxin that may contaminate animal feed (oat, barley, and rye) and food (wheat, rice, coffee, beer, pig meat), leading to major health problems (e.g., nephropathy) in several animal species including humans. Several methods have been tested to reduce the toxicity of OTA in animals but with limited success. In rats, the effect of cholestyramine (CHA), a bile acid-binding resin, was investigated on OTA-induced nephrotoxicity and bioavailability. Animals were fed semisynthetic diets containing two levels of OTA: 1 or 3 ppm. At each level of OTA, the diets were enriched with 0.1, 1, and 5% of CHA. The results showed that CHA decreased the concentration of OTA in plasma. At 1 and 3 ppm of OTA in the diet, CHA is effective at a level of 0.1% and 5%, respectively. The excretion of OTA and its metabolites (ochratoxin alpha and hydroxylated ochratoxin A) in bile and urine was also decreased by addition of 5% CHA in the diet. This was associated with an increase of OTA excretion in feces. Enzymuria and renal morphology revealed that dietary CHA can decrease OTA-induced nephrotoxicity, probably by reducing renal exposure to the toxin. In conclusion, CHA can reduce OTA concentrations in plasma as well as reducing nephrotoxicity, which may be attributed to a decrease of bioavailability and/or enterohepatic circulation of the toxin.     

Fetal fast MR imaging: reproducibility, technical quality, and conspicuity of anatomy

PURPOSE: To evaluate the normal appearance of fetal anatomy, the conspicuity of fetal organs, the reproducibility of images, and the limitations to image quality with the use of half-Fourier, single-shot rapid acquisition with relaxation enhancement (RARE) magnetic resonance (MR) imaging. MATERIALS AND METHODS: Fifty-four fetuses of 49 pregnancies underwent MR imaging with the half-Fourier, single-shot RARE technique. Two reviewers attempted to identify 47 organs and anatomic regions in each fetus. Organ or region conspicuity, image quality, and the limitations of image quality were graded. RESULTS: Fetal anatomy was well depicted in fetuses over 20 weeks in gestational age. Fetal imaging was limited by gestational age of 20 weeks or less usually owing to the small size of the organ or region being evaluated and, less frequently, by motion. CONCLUSION: Half-Fourier, single-shot RARE MR imaging provided a detailed and reproducible evaluation of normal fetal anatomy, which can be used as a standard of reference in MR imaging of fetal anomalies.     

Evaluation of clothing systems to determine heat strain

This article describes the basic evaluation process and test methodology employed when temperature extremes for clothing systems must be considered as part of the U.S. Army's Health Hazard Assessment for material in the development and acquisition process. The goals of the evaluation are to select clothing systems that minimize the hazards of heat strain and to predict the heat strain for persons wearing such clothing. Clothing evaluations begin with biophysical assessments that determine the thermal characteristics (vapor permeability and insulation) for textiles via guarded hot plate tests and for clothing systems via thermal manikin tests. The results from biophysical tests can be used to select the textile and/or clothing with the best thermal characteristics. The data from manikin evaluations also can be used in prediction modeling. Human physiological testing is best done in a controlled laboratory environment, although for realism and user acceptability field trials may also be conducted. Proven test and measurement methods must be employed, and tests must control for confounding variables; subjects serve as their own controls, and test environment and procedures are consistent between trials. The process and test methodology described can be applied to the evaluation of civilian clothing systems as well as to the military systems for which they were developed.     

Zolpidem is differentiated from triazolam in humans using a three-response drug discrimination procedure

The discriminative stimulus effects of the imidazopyridine hypnotic zolpidem and the classic benzodiazepine hypnotic triazolam were examined in seven healthy volunteers using a three-response drug discrimination procedure and a within-subject design. During an initial sampling phase, the training drug conditions (placebo, 20 mg/70 kg zolpidem, and 0.5 mg/70 kg triazolam) were identified to subjects by letter codes before oral drug administration. During a subsequent training phase, subjects earned money for correct drug identifications made 3.75 h after drug administration. Five out of seven subjects acquired the three-response discrimination. Analyses of standardized and unstructured self-report questionnaires revealed that zolpidem and triazolam produced different profiles of effects; zolpidem was associated with a number of negative somatic symptoms including nausea, blurred vision, visual images/hallucinations, and heavy limbs, whereas triazolam was associated with greater sedative effects. These results demonstrate a distinct profile of discriminative stimulus and subjective effects for zolpidem, relative to triazolam, which is consistent with its somewhat distinct pharmacological profile, and provide evidence for the sensitivity of the three-response drug discrimination procedure for detecting between-drug differences.     

Long-term maintenance of weight loss: do people who lose weight through various weight loss methods use different behaviors to maintain their weight?

Obtaining high-quality radiographs of the proximal aspect of equine limbs is difficult because of the large muscles in these regions. The use of scintigraphy may provide further information. Abnormal bone scan findings of the ischial tuberosity or the third trochanter were found in 29 adult horses with obscure hind limb lameness between 1986 and 1996 at the Large Animal Clinic of the University of Bern. Each had abnormal radiopharmaceutical uptake but not all had radiographic changes. Radiopharmaceutical uptake ratios between the ischial tuberosity and the greater trochanter were calculated. The uptake ratio in a control group of 11 clinically sound horses was lower than in 11 lame horses with subjectively enhanced radiopharmaceutical uptake.     

An extended HLA-DQ-DR haplotype rather than DRB1 alone contributes to RA predisposition

A family with 1 case of retinitis pigmentosa (III-1) and 2 cases of Oguchi's disease (III-2, 3) was examined in terms of electrophysiology as well as molecular biology. The proband (III-3), a 42-year-old female, and 2 older brothers (III-1, 2, aged 52 and 45 years) and 2 unaffected members in the same family participated in this study. Corrected visual acuities of the individuals with Oguchi's disease (III-2, 3) were 1.2. On funduscopy, blood vessels stood out in relief against a metallic-appearing background and a Mizuo-Nakamura phenomenon was evident. Full-field electroretinograms (ERGs) recorded from the proband were indicative of rod dystrophy, but results of other electrophysiological examinations (multifocal ERG, pattern ERG and visual-evoked cortical potential recordings) were within normal limits. Patient III-1 had corrected visual acuities of RE 20 cm/m.m. and LE 30 cm/n.d., severe chorioretinal atrophy in both fundi, and full-field ERG revealed rod-cone dystrophy. Mutation of the arrestin gene (1147de1A) was detected in all 3 patients. Visual function in each patient coincides with that of retinitis pigmentosa or Oguchi's disease, respectively.