Neuropeptides are potent modulators of human in vitro immunoglobulin E synthesis

We determined the effect of adrenocorticotropin hormone (ACTH) on the regulation of IgE synthesis. Depending on the concentration, ACTH enhanced or inhibited IgE synthesis in a culture system where IgE synthesis was induced with interleukin-4 (IL-4) and anti-CD40 monoclonal antibody in peripheral blood mononuclear cells. Similar effects on IgE synthesis were observed by adding ACTH-related peptides, e.g. corticotropin-releasing factor (CRF), the inducer of ACTH, or alpha-melanocyte stimulating hormone (alpha-MSH), a cleavage product of ACTH. However, ACTH had no effect on IgG or IgM synthesis in this culture system. ACTH did not act directly on either B or T cells as there was no influence on IgE synthesis in a system using purified B cells alone or co-cultured with T cells. The effect of ACTH on IgE synthesis was mediated by accessory cells. This was shown by priming purified CD14-positive monocytes with ACTH and reconstitution experiments. Therefore, these findings suggest that ACTH and the related peptides CRF and alpha-MSH can influence the microenvironment modulating an IL-4 and anti-CD40 monoclonal antibody driven class switching to IgE via accessory cells.     

Biobehavioral aspects of menopause: lessons from the Healthy Women Study

The Healthy Women Study is an ongoing natural history study of the menopause in a sample of relatively healthy women. We report data from this paper on the behavioral and biological changes that occur during the transition from pre- to postmenopausal status and argue for the importance of behavioral change interventions to prevent or attenuate some of the adverse changes due to the menopause.     

T-cell receptor V-gene usage in synovial fluid lymphocytes of patients with chronic arthritis

In this study we analyzed the usage frequencies of the TCR V-gene segments by alpha beta+ T cells present in synovial fluid of 17 patients with chronic arthritis, including rheumatoid arthritis. The results of this study, obtained from semiquantitative PCR analyses, showed that in all patients most of the TCR V alpha- and V beta-gene segments could be detected both in fresh PBMCs and in fresh SFMCs. The relative frequencies of use of these V-region genes were variable between the different patients. Although there was some skewing of increased usage frequencies of particular TCR V alpha and V beta genes among SFMC-derived TCRs when compared with PBMCs, we could not correlate such increased TCR V-gene usage with the inflammation in the joints as a disease-specific marker.     

Selenium lethality: role of glutathione and metallothionein

Male Sprague-Dawley rats (200-300 g) were pretreated (i.p.) with diethylmaleate (DEM; 3.1 mmol/kg) or propylene glycol (PG). After 1 h, three PG and three DEM groups received saline or sodium selenite (Se: 0.8 or 1.6 mg/kg) i.p. Eighty to one hundred percent mortality occurred within 3 h after Se in DEM-pretreated groups. Except for one PG and one DEM group, which were sacrificed after 1 h, the remaining groups received saline or Se (1.6 mg/kg) 25 h after pretreatment. No mortality occurred within 3 h after Se. Liver and kidney GSH decreased at 1 h, while liver MT increased at 28 h. The changes are related to Se-induced lethality.     

Assessment of surface structure of blood cells by phase-contrast and scanning electron microscopy in children

Study of red cell surface structure is a highly informative method for the assessment of the body status in health and disease. The authors have examined the surface red cell structure of infants in health and disease by phase-contrast and scanning electron microscopy and came to the conclusion on the high reliability of the data obtained by phase-contrast microscopy. They recommend this unsophisticated and informative method for clinical practice.     

Lactoferrin interaction with salmonellae potentiates antibiotic susceptibility in vitro

Interaction of lactoferrin (Lf) with the cell envelope (CE) and outer membrane (OM) of Salmonella typhimurium-type strain ATCC13311 was tested by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western-blot analyses. The peroxidase-labeled bovine Lf (BLf) and human Lf both recognized a heat-modifiable protein with an estimated molecular mass of 38 kD in the OM. Simultaneous immunoblotting with an antiporin monoclonal antibody specific for a conserved porin domain in members of enterobacteriaceae confirmed that the Lf-binding protein is a porin. Such Lf-binding porin proteins (37-39 kD range) were readily detected in nine other common Salmonella species: S. dublin, S. panama, S. rostock, S. abony, S. hartford, S, kentucky, S. pullorum, S. thompson, and S. virchow. The latter six species also demonstrated one to three weak Lf-reactive bands of low molecular weight in their CE. The antibiotic susceptibility of Salmonella in the presence of Lf was examined. A mixture containing sub-minimum inhibitory concentration (MIC) levels of Lf (MIC/4) and cefuroxime (MIC/2) inhibited the bacterial growth. Lf strongly potentiated the action of erythromycin (eightfold), whereas it increased the activity only by two-fold for ampicillin, ciprofloxacin, chloramphenicol, and rifampicin; similarly, these antibiotics also reduced the MIC of BLf by twofold in S. typhimurium. Such antimicrobial potentiation was not observed with BLf mixtures containing cefalexin, gentamycin, or polymyxin B against strain ATCC13311. BLf and cefuroxime also demonstrated potentiation of varying degrees (two to 16-fold) with nine other Salmonella species. These data established the binding of Lf to porins in salmonellae and a potentiation effect of Lf with certain antibiotics.     

Shopping in the healthcare information systems market--a search for well-camouflaged land mines

Proton MR spectra of the basal ganglia were obtained from 28 patients, 24 male and 14 female, median age 16.3 months (5 weeks to 31 years). They included 17 patients with normal MRI of the basal ganglia without metabolic disturbance (control group) and 11 patients with various metabolic diseases: one case each of high serum sodium and high serum osmolarity, cobalamin C deficiency, Leigh disease, Galloway-Mowat syndrome, Pelizaeus-Merzbacher disease, hemolytic-uremic syndrome and Wilson disease and two cases of Alagille syndrome and methylmalonic acidemia with abnormal MRI of the basal ganglia or blood or urine analysis (abnormal group). The MR spectrum was measured by using STEAM. The MR-visible water content of the region of interest was obtained. Levels of myoinositol, choline, creatine and N-acetylaspartate were measured using a semiquantitative approach, with absolute reference calibration. In the control group, there was a gradual drop of water content over the first year of life; N-acetylaspartate, creatine and myoinositol levels showed no significant change with age, in contrast to the occipital, parietal and cerebellar regions. Choline showed a gradual decrease for the first 2 years of life and then remained fairly constant. In the abnormal group the water content was not significantly different. N-Acetylaspartate was decreased in patients with high serum sodium and high serum osmolarity, cobalamin C deficiency, Leigh disease and one case of methylmalonic acidemia. Decreased creatine was also found in Leigh disease, and decreased choline in Galloway-Mowat syndrome and Wilson disease. Myoinositol was elevated in the patient with abnormally high serum sodium, and decreased in the hemolytic-uremic syndrome.     

Response of primary colon cancer cells in hybrid spheroids to 5-fluorouracil

The specific role of sulfhydryl groups in cell-mediated cytotoxicity (CMC) is still unknown. Here we demonstrate that natural killer cells and lymphokine-activated killer cells, when incubated with phenylarsine oxide (PAO), an organoarsenic compound showed a dose- and time-dependent inhibition of CMC and antibody-dependent cellular cytotoxicity (ADCC). PAO interacted directly with the effector cells (EC) without affecting the target cells (TC) or EC:TC conjugate formation. The loss of cytotoxicity was not due to lack of degranulation or to inhibition of serine esterases in PAO-treated cells. However, PAO inhibited the target-induced down regulation of phosphatidylinositol (PI) level in NK cells indicating that PAO blocked the cytolytic cascade at an early stage, upstream of PI. In addition, PAO also did not affect the disulfide link of the zeta-chain dimers, implicated in signal transduction in cytotoxic lymphocytes but did cause the rapid phosphorylation of the zeta chain. Finally, the effect of PAO on CMC was competitively blocked by dithiothreitol, a dithiol, but not by beta-mercaptoethanol, a mono-thiol. Taken together, these results indicate for the first time how sulfyhydryl groups may regulate CMC and ADCC.