Biased TCR repertoire in infiltrating lesional T cells in human Bancroftian filariasis

To investigate the hypothesis that T cells recognizing specific Ags localize to the site of disease activity in human bancroftian filariasis, we have compared the repertoire of TCR Vbeta gene segments in lesions vs blood in individual patients by RT-PCR ELISA. Vbeta14 and Vbeta24 were overrepresented (5% greater in tissue compared with PBMCs and/or tissue/PBMC ratios in the highest 5% of all tissue/PBMC ratios for all Vbetas for all subjects) in 50% and 40% of study subjects, respectively. Overrepresentation of these two Vbetas did not occur in any control subject. In comparing three patient groups, the proportion of individuals meeting at least one criterion for Vbeta14 overrepresentation was shown to increase in tandem with our current concepts of disease progression (asymptomatic filariasis = 25%; clinical filariasis with active infection = 60%; clinical filariasis without active infection = 71%). In 6 of the 10 individuals with Vbeta14 overrepresentation, Vbeta14 represented >20% of the entire lesional Vbeta repertoire. All but one of the 20 study subjects had at least one Vbeta gene segment that was overrepresented in tissue compared with PBMCs. Only a small number of Vbetas, usually three or less, were overrepresented in any single filariasis patient. However, in the same tissue, no differences between patient groups were found when IFN-gamma, TNF-alpha, IL-4, IL-5, and IL-12 mRNA expression were examined. Taken together, these findings suggest that, in principle, in essentially all patients, whether with subclinical or with clinical filariasis, distinct and limited T cell populations are concentrated in affected tissue.     

Linkage of proximal myotonic myopathy to chromosome 3q

We performed genetic linkage analysis in nine German proximal myotonic myopathy (PROMM) families using DNA-markers D3S1541 and D3S1589 from the region of the recently discovered gene locus of myotonic dystrophy type 2 (DM2) on chromosome 3q. Two-point analysis supplied an lod score of 5.9. We conclude that a gene causing PROMM is located on chromosome 3q. PROMM and DM2 may be allelic disorders or may be caused by closely linked genes.     

High-frequency retrotransposition of a marked I factor in Drosophila melanogaster correlates with a dynamic expression pattern of the ORF1 protein in the cytoplasm of oocytes

To study the expression of the I factor, a non-long-terminal-repeat retrotransposon responsible for I-R hybrid dysgenesis in Drosophila melanogaster, we have tagged the ORF1 protein (ORF1p) by inserting the HA epitope in its N-terminal region. In transgenic flies, this modification is compatible with a high rate of autonomous transposition and allows direct estimation of the transposition frequency. I factor transposes in the germline of females (SF) that are daughters from crosses between I strain males (which contain active copies of the I factor) and R strain females (which do not). We analyzed the expression pattern of ORF1p by indirect immunofluorescence. Its expression correlates with retrotransposition. During oogenesis ORF1p appears unexpectedly as a cytoplasmic product, which accumulates with a specific pattern into the oocyte. A comparison of the expression patterns under conditions that modify the transposing activity of the element clarifies some aspects of I-factor functioning in the transposition process.     

DISPLAY LIFE OF FRESH BEEF CONTAINING DIFFERENT LEVELS OF VITAMIN E AND INITIAL MICROBIAL CONTAMINATION

Strip loins from beef cattle fed diets supplemented or not supplemented with α-tocopheryl acetate (vitamin E; 500 IU·animal⁻¹·d^-1) were fabricated into steaks inoculated at three initial levels (1.7 to 1.9; 2.3 to 2.5; 6.4 to 7.1 log CFU/cm²) of bacterial contamination (from over aged retail steaks) and evaluated for psychrotrophic plate counts (PPC), overall appearance and color during 6 days of simulated retail display (0 to 4C). Initial contamination affected changes in PPC (P < 0.05) during display, while the highest level of initial contamination eliminated benefits of high vitamin E concentrations on product color within 4 days of retail display. However, increased vitamin E concentrations in steaks were associated with higher (P < 0.05) CIE a* values appearance scores when the level of initial contamination was less than 2.5 CFU/cm². Results indicated that vitamin E supplementation does not mask high levels of bacterial contamination.     

Regulation of the expression of peripheral benzodiazepine receptors and their endogenous ligands during rat sciatic nerve degeneration and regeneration: a role for PBR in neurosteroidogenesis

This study addresses (1) the relationship between headache presence/intensity at time of testing and neurocognitive performance, and (2) the probability that testing triggers or intensifies pain. Subjects were 125 patients with chronic posttraumatic headache (mean = 2.67 years post injury) who completed a 4-hour test battery emphasizing memory. Comparisons of 34 individual tests/subtests and the five Wechsler Memory Scale-Revised (WMS-R) indices of relative memory impairment for 73 patients with no headache or mild headache versus 52 patients with moderate to severe pain revealed no significant differences. Testing intensified existing headaches for 55% but triggered headache for only 1 of 20 (5%; P =.00003). Results support the validity of neuropsychological test performance regardless of pain level, although testing can be painful.     

Prevention of lens damage associated with cigarette smoke exposure in rats by alpha-tocopherol (vitamin E) treatment

PURPOSE: To evaluate the possible protective effect and mechanism of alpha-tocopherol (vitamin E) treatment on lens degeneration associated with in vivo exposure to cigarette smoke and to further clarify the role of iron in cigarette smoke-generated lens damage. METHODS: Twenty-eight male Wistar rats were randomly divided into four equal groups. Rats in groups 3 and 4 were exposed to cigarette smoke for 1 hour each day over 90 consecutive days, and rats in groups 1 and 2 were treated in similar fashion but only exposed to room air. Additionally, vitamin E was given to the rats in groups 2 and 4 via intramuscular route. At the end of the study, both eyes of all the animals were enucleated; one eye was prepared for histopathologic examination, and the fellow eye was used for the measurement of iron and calcium levels. RESULTS: Significantly higher iron and calcium levels were observed in the lenses of group 3 rats than in other groups. Similar comparisons performed between groups 1 and 2, groups 1 and 4, and groups 2 and 4 did not show any significant difference. Distinct histopathologic changes in the anterior lens epithelium, such as hyperplasia, hypertrophy, epithelial multilayering, and the presence of epithelial cells over posterior lens capsule, observed in group 3 rats were not present in other groups. CONCLUSIONS: Cataractogenesis after cigarette smoke exposure was associated with an accumulation of iron and calcium in the rat lens, and vitamin E supplementation protected such accumulations and cataractogenesis.     

Adrenomedullary secretion of epinephrine is increased in mild essential hypertension

To assess whether patients with mild essential hypertension have excessive activities of the sympathoneuronal and adrenomedullary systems, we examined total body and forearm spillovers and norepinephrine and epinephrine clearances in 47 subjects with mild essential hypertension (25 men, 22 women, aged 38.1 +/- 6.7 years) and 43 normotensive subjects (19 men, 24 women, aged 36.5 +/- 5.9 years). The isotope dilution method with infusions of tritiated norepinephrine and epinephrine was used at rest and during sympathetic stimulation by lower body negative pressure at -15 and -40 mm Hg. Hypertensive subjects had a higher arterial plasma epinephrine concentration (0.20 +/- 0.01 nmol.L-1: mean +/- SE) than normotensive subjects (0.15 +/- 0.01) (P < .01). The increased arterial plasma epinephrine levels appeared to be due to a higher total body epinephrine spillover rate in the hypertensive subjects (0.23 +/- 0.02 nmol.min-1.m-2) than the normotensive subjects (0.18 +/- 0.01) (P < .05) and not to a decreased plasma clearance of epinephrine. The arterial plasma norepinephrine level, total body and forearm norepinephrine spillover rates, and plasma norepinephrine clearance were not altered in the hypertensive subjects. The responses of the catecholamine kinetic variables to lower body negative pressure were not consistently different between normotensive and hypertensive individuals. These data indicate that individuals with mild essential hypertension (1) have elevated arterial plasma epinephrine concentrations that are due to an increased total body epinephrine spillover rate, indicating an increased adrenomedullary secretion of epinephrine; (2) have no increased generalized sympathoneuronal activity and no increased forearm norepinephrine spillover; and (3) have similar responses of both the sympathoneuronal and adrenomedullary systems to sympathetic stimulation by lower body negative pressure.     

Interrelationship between the Na+/glucose cotransporter and CFTR in Caco-2 cells: relevance to cystic fibrosis

Both the Na+-dependent glucose cotransporter (SGLT1) and the cystic fibrosis transmembrane conductance regulator (CFTR) modulate Na+ and fluid movement, although in opposite directions. Yet few studies have investigated a possible interrelationship between these two transporters. By using the Caco-2 human colon carcinoma cell line, we confirmed that the activities of these transporters increased with spontaneous differentiation to the enterocytic phenotype. We showed that SGLT1 was positively regulated by Cl- and that optimal activity of CFTR was dependent on the presence of glucose. We also demonstrated that inhibition of CFTR by glibenclamide or diphenylamine-2-carboxylate did not modify the activity of SGLT1 and inhibition of SGLT1 by phlorizin did not modify the activity of CFTR, although it resulted in inhibition of glycoconjugate synthesis. These results point to positive substrate-cross regulation of SGLT1 and CFTR and suggest that NaCl and glucose are important for not only Na+ absorption and fluid movement, but also for cAMP-dependent Cl- efflux, and glycoconjugate synthesis, functions that are known to be anomalous in cystic fibrosis.