Sampling Procedures in Estrogen Receptor Determinations

To determine the significance of proteolysis and delayed freezing of tumor samples on estrogen receptor levels, values from 19 of 31 biopsy specimens were compared with that in remaining tumor at the completion of mastectomy. There was a 15-100% decrease in receptor content. Time-decay studies on selected postmastectomy samples showed a further decrease in estrogen receptor content inversely proportional to the time it was exposed to room temperature. Factors that govern the valid measurement of receptor levels include tumor cell concentration, tumor necrosis, and time between devascularization of the specimen to freezing. A carefully procured histologically confirmed sample of fresh tumor is necessary for reliable estrogen receptor values

Combined use of N-acetylcysteine and Liberase improves the viability and metabolic function of human hepatocytes isolated from human liver

AbstractBackground aimsSuccessful hepatocyte isolation is critical for continued development of cellular transplantation. However, most tissue available for research is from diseased liver, and the results of hepatocyte isolation from such tissue are inferior compared with normal tissue. Liberase and N-acetylcysteine (NAC) have been shown separately to improve viability of isolated hepatocytes. This study aims to determine the effect of Liberase and NAC in combination on human hepatocyte isolation from normal and diseased liver tissues.MethodsHepatocytes were isolated from 30 liver specimens through the use of a standard collagenase digestion technique (original protocol) and another 30 with the addition of NAC and standard collagenase substituted by Liberase (new protocol). Viability and success, defined as maintenance of cell adhesion and morphology for 48 hours, were assessed. Metabolic function was assessed by means of albumin and urea synthesis.ResultsBaseline factors were similar for both groups. The delay to tissue processing was slightly shorter in the new protocol group (median, 2 versus 4 hours; P = 0.007). The success rate improved from 12 of 30 (40.0%) to 21 of 30 (70.0%) with the use of the new protocol (P = 0.037), and median viable cell yield increased from 7.3 × 104 to 28.3 × 104 cells/g tissue (P = 0.003). After adjusting for delay, success rate (P = 0.014) and viable cell yield/g tissue (P = 0.001) remained significantly improved. Albumin and urea synthesis were similar or superior in the new protocol group.ConclusionsNAC and Liberase improve the success of hepatocyte isolation, with a significantly higher yield of viable cells. The use of these agents may improve the availability of hepatocytes for transplantation and laboratory research

Carcass use by mesoscavengers drives seasonal shifts in Australian alpine scavenging dynamics

Context. Carrion is a high-energy and nutrient-rich resource that attracts a diverse group of vertebrate scavengers. However, despite the carrion pool being highly seasonal in its availability, there is little understanding of how scavengers utilise carcasses across all four seasons. Aim. To assess how season influences carcass-detection times by vertebrate scavengers and their rates of scavenging. Methods. We used remote cameras to monitor vertebrate scavenging at 15 eastern grey kangaroo (Macropus giganteus) carcasses in four consecutive seasons (summer, autumn, winter, and spring; total 58 carcasses) in the Australian Alps. Key results. In total, 745 599 remote-camera images were captured, within which 34 vertebrate species were identified, nine of which were recorded to actively scavenge. Time to first detection of carcasses by vertebrate scavengers was 5.3 and 9.6 times longer during summer (average 144 h) than during spring (average 34 h) and winter (average 24 h) respectively. Rates of vertebrate scavenging were highest in winter and spring, with brushtail possums (Trichosurus vulpecula) accounting for 78% of all scavenging events during winter, and ravens (Corvus spp.) accounting for 73% during spring. High rates of carcass use by these mesoscavengers may reflect a scarcity of other food sources, the demands of their breeding season, or a relative absence of scavenging by larger dominant species such as dingoes (Canis dingo) and wedge-tailed eagles (Aquila audax). Conclusions. These findings demonstrate the highly seasonal nature of vertebrate scavenging dynamics in an alpine ecosystem, and that mesoscavengers, not apex scavengers, can dominate the use of carcasses. Implications. Accounting for the effects of season is integral to understanding the way animals utilise carcasses in alpine and other strongly seasonal environments; and for developing further our knowledge of ecosystem processes linked to decomposition

Benefits of early treatment with natalizumab: A real-world study

BACKGROUND: The impact of early versus later high-efficacy disease-modifying therapy (DMT) in patients with multiple sclerosis (MS) is uncertain. This study reported the association of early versus later natalizumab treatment with real-world clinical outcomes in MS patients. METHODS: The study included 661 participants diagnosed with MS in 1994 or later from 7 US centers participating in the MS Partners Advancing Technology for Health Solutions (MS PATHS) network. Time to natalizumab treatment between diagnosis and first infusion (TTNT) was determined from the Tysabri Outreach: Unified Commitment to Health (TOUCH) registry. Clinical outcomes were defined using neuroperformance tests included in the Multiple Sclerosis Performance Test. Associations were tested using TTNT as a categorical and continuous variable. Linear mixed models addressed within-subject and within-site clustering. RESULTS: TTNT varied from 0.1 to 19.8 years (median [interquartile range] 4.2 [1.8, 9.0] years). A significant association between later natalizumab use and worse outcomes was demonstrated for walking speed (p \u3c 0.001), processing speed (p \u3c 0.001), manual dexterity (p \u3c 0.001), brain atrophy (p = 0.001), and T2 lesion volume (p = 0.02). Covariate-adjusted modelling of a sensitivity population diagnosed with MS in 2006 or later (n = 424) demonstrated significant associations between longer TTNT and worse walking speed (p \u3c 0.05), processing speed (p \u3c 0.001), and manual dexterity (p \u3c 0.001). CONCLUSION: Later initiation of natalizumab was associated with worse clinical and radiologic imaging outcomes. Thus, high-efficacy DMT may have greater benefit when started earlier in MS patients. These results provide a rationale for randomized controlled trials to further assess the impact of early highly-effective DMT use versus later escalation of therapy