Stress-Related Changes in β-Endorphin Processing: The Limitations of Slaughterhouse Material

In the sheep, unlike many other species, a significant proportion (>25%) of immunoreactive β-endorphin in the anterior pituitary is post-translationally modified to opioid-inactive, α-N-acetylated forms. In a study to determine the precise molecular nature of α-N-acetylated β-endorphin immunoreactivity, we noted a striking difference in high-performance liquid chromatography profiles of anterior pituitary extracts between sheep killed on the farm, and age-, sex- and strain-matched slaughterhouse animals. These altered patterns of a-N-acetylated β-endorphin processing were reproduced in farm animals by chronic (≤ 4 days) treatment with the synthetic glucocorticoid dexamethasone; in contrast dexamethasone had no effect on a-N-acetylated β-endorphin processing in hypothalamo-pituitary disconnected sheep. These data suggest that (1) the change in processing is a stress response, mediated by prolonged glucocorticoid exposure, (2) this effect is central, rather than a direct effect on the pituitary, and (3) the relative abundance of various peptide sequences in slaughterhouse-derived material may not reflect their abundance under more physiological conditions.     

Modulation of human polymorphonuclear neutrophil functions by α1acid glycoprotein

₁-Acid glycoprotein (₁-AGP), a naturally occurring human plasma protein and acute-phase reactant, was extracted by a two-step procedure from sera collected from four healthy men. Its activity was testedin vitro on human polymorphonuclear (PMN) functions (migration, aggregation, O ₂ ^– generation). ₁,-AGP was not chemoattractant but inhibited the PMN response to the chemoattractant formylmethionyl-leucyl-phenylalanine without affecting spontaneous migration (Boyden and agarose methods of assessment). At concentrations between 0.15 and 0.45 mg/ml, ₁AGP exerted an aggregating effect with a maximal effective concentration of 0.3 mg/ml. ₁-AGP inhibited superoxide generation by PMNs stimulated either by opsonized zymosan or phorbol myristate acetate. This inhibition varied according to the intensity of the stimulation. At low stimulus concentrations, a dose-dependent inhibition of membrane-associated PMN responsiveness to soluble or particulate stimuli was observed. These findings suggest that ₁-AGP may be able to prevent PMN activation in the course of inflammatory processesin vivo.     

Estrogen receptor negative and progesterone receptor positive primary breast cancer: Pathological characteristics and clinical outcome

The expression of estrogen (ER) and progesterone (PgR) receptors was analyzed in a retrospective series of 3000 patients who had operable primary breast cancer. Patients were stratified according to ER and PgR status and the study was focused on the two groups (ER–PgR+ and ER–PgR–) of patients whose tumors contained low levels of ER (< 15 fmol/mg protein), regarding potential response to endocrine therapy. The comparison of clinical or histological characteristics between ER–PgR+ and ER–PgR– patients was analyzed as well as the disease-related death and survival. The mean follow-up was 86.3 months. Among the 529 ER–patients, 62 were PgR+ (12%), whereas 467 were PgR– (88%). The ER–PgR+ and ER–PgR– populations represented 2% and 15.6% of the overall population, respectively. In ER– tumors, the PgR status was significantly related to: age, menopausal status, tumor size, SBR grade, and histological type, but not to the type of surgical treatment or to lymph node involvement. ER–PgR+ tumors had smaller size (64% T1 vs 43%) (p=0.004) and were more frequently grade I (28% vs 12%) than ER–PgR– ones (p < 0.001). In addition, the patients with ER–PgR+ tumors were significantly younger (49.4 years vs 58.4 years; p < 0.0001), and were more frequently premenopausal (76% vs 36%; p < 0.001). The disease-free interval and the metastasis-free survival tended to be worse for ER–PgR– than for ER–PgR+ patients, but the difference was not statistically significant at 10 years. However, a small but significant difference in overall survival, in favor of the PgR+ group, was observed between the two groups during the first 5 years (p=0.03).We conclude that in combination with ER, PgR status defines a group of patients with clinical and biological specificity, which could be considered for specific endocrine therapy.     

Pressure control inverse ratio ventilation as a method to reduce peak inspiratory pressure and provide adequate ventilation and oxygenation

Nineteen patients with ARDS or pneumonia who were ventilated with PcIRV on the Siemens-Elema Servo 900 C were retrospectively reviewed. The PcIRV reduced peak airway pressure, PEEP, increased Paw, and improved ventilation and oxygenation in these patients. When these patients were compared with themselves on prior conventional IPPV, all had a decrease in PIP, an increase in Paw and most had a decrease in VE, with no change in PaCO2 and an increase in PaO2. The increase in Paw may have contributed to this improved arterial oxygenation. High levels of PIP and PEEP during IPPV have been identified as risk factors in the development of barotrauma and residual parenchymal pulmonary damage. We propose that PcIRV allows for adequate ventilation and oxygenation with decreases in PIP, extrinsically added PEEP and inspired O2 concentration. This mode of ventilation may decrease the morbidity associated with IPPV utilizing high PIP and PEEP.     

Isolation and characterization of fifteen microsatellite loci in Leopard grouper (Mycteroperca rosacea) via 454 pyrosequencing

Leopard grouper (Mycteroperca rosacea) are distributed from Bahía Magdalena, through the Gulf of California and as far south as Jalisco, Mexico. They are listed as Vulnerable on the IUCN Red List due to significant fishing-induced declines over the past decade. Microsatellite loci were isolated by constructing a shotgun genomic library and sequencing using 454 XL + titanium chemistry. We characterized 15 polymorphic loci in 120 samples from three geographic locations. Genotyping yielded 15–60 alleles per locus with observed levels of heterozygosity ranging from 0.575 to 0.975.