Increased Mortality in a Colony of Zebra Finches Exposed to Continuous Light

Over a 1-mo period, increased morbidity and mortality occurred in a flock of zebra finches (Taeniopygia guttata). Complete postmortem examination was performed on 6 of the affected birds, 4 of which subsequently were diagnosed with the avian gastric yeast previously known as megabacteriosis (Macrorhabdus ornithogaster). The remaining 2 birds were diagnosed with a cloacal abscess and with large bowel perforation and peritonitis. All the birds had been prophylactically treated with amphotericin B for megabacteria 2 mo previously. An environmental assessment revealed that the light cycle had been altered, and the birds were being exposed to constant light. With correction of the light cycle, the health of the birds improved dramatically. The remaining birds were treated again with amphotericin B, and baseline mortality returned to normal. The birds in this report show several similarities to previous reports of sleep deprivation syndrome in mammals.Over a 1-mo period (from late April to late May 2011), a marked increase in morbidity and mortality was noted in a flock of zebra finches (Taeniopygia guttata) at our facility (University of Washington). These birds were involved in a project studying the neural mechanisms of vocal learning. The finches were obtained from Magnolia Bird Farm (Anaheim, CA). In March 2011, a shipment of 50 male birds arrived and was moved into a new space with 2 rooms. One room housed breeding birds in cages containing breeding pairs and offspring; the other room, into which these new arrivals were placed, housed adult male birds in cages of 4 to 9 birds.Birds in the room containing the adult nonbreeders were affected exclusively. Clinical signs consisted of puffed and ruffled feathers, lethargy, increased respiratory effort, and feather loss. These signs were noted in birds that had not undergone experimental manipulation. Several of the birds that died or were euthanized after becoming sick and lethargic were necropsied. Findings on postmortem examination for the majority of cases included emaciated body condition, necrotizing enteritis and colitis and, in individual cases, included bowel perforation and peritonitis and severe pyogranulomatous abscessation. Megabacteriosis (avian gastric yeast; Macrorhabdus ornithogaster) was diagnosed histologically in 4 of the 6 birds evaluated. A light meter was placed in the housing room; results showed that the dark period of the light cycle was absent. The light cycle was corrected, and morbidity and mortality decreased dramatically.     

The role of the cerebellum in procedural learning—Are there implications for physiotherapists’ clinical practice?

Motor learning is the means by which we acquire skilled movements and consign them to permanent memory. Multiple brain areas are involved, and patients with neurological damage often experience difficulty when attempting to relearn previously learned skills. For these patients, the location of the lesion may be critical in influencing their motor skill relearning. The cerebellum has been described as an “on-line” comparator and corrector of movement, but recent research suggests that the cerebellum may also have a role in the later stages of motor learning, including the automation of movement patterns, although conflicting research in this area means that there is as yet no consensus. This knowledge may have implications for the way physiotherapists treat patients with cerebellar lesions. Some treatments in regular use by physiotherapists are discussed, and possible implications for practice are considered.     

The Rewards and Challenges of Becoming a Clinical Instructor

Frontline nurses working in the clinical area are a vital component to nursing education. Taking on the role of adjunct clinical instructor can be a rewarding way to increase one's own knowledge while performing the important task of educating the next generation of nurses.     

Proliferation kinetics of subpopulations of human marrow cells determined by quantifying in vivo incorporation of [2H2]-glucose into DNA of S-phase cells

This report investigated in vivo turnover kinetics of marrow hematopoietic progenitors and precursors using a recently developed stable isotope-mass spectrometric technique (SIMST). Human subjects were administered a 2-day infusion of 6,6-[2H2]-glucose, a nontoxic stable isotope-labeled form of glucose, which becomes incorporated into DNA of all S-phase cells. The percent [2H2]-glucose incorporated into DNA in the form of [2H2]-deoxyadenosine (%[2H2]-dA enrichment) was determined by gas chromatography-mass spectrometry. The rate constant of replacement of unlabeled by labeled DNA strands (labeling kinetics) was used to calculate population turnover kinetics of CD34+ cells, CD133+ cells, and CD133-CD34+ cells. The observed mean replacement half-life (t1/2) was 2.6 days for CD34+ cells, 2.5 days for CD133-CD34+ cells, and 6.2 days for CD133+ cells. Results from the estimated rate constant of replacement of labeled by unlabeled DNA (delabeling kinetics) also demonstrated slower turnover rates for CD133+ cells than for CD133-CD34+ cells. Although there was a relatively rapid initial decrease in the %[2H2]-dA enrichment, low levels of labeled DNA persisted in CD34+ cells for at least 4 weeks. The results indicate the presence of subpopulations of CD34+ cells with relatively rapid turnover rates and subpopulations with a slower t1/2 of 28 days. Results also demonstrate that in vivo [2H2]-glucose-SIMST is sensitive enough to detect differences in turnover kinetics between erythroid and megakaryocyte lineage cells. These studies are the first to demonstrate the use of in vivo [2H2]-glucose-SIMST to measure in vivo turnover kinetics of subpopulations of CD34+ cells and precursors in healthy human subjects.     

T-cell depletion and graft survival induced by anti-human CD3 immunotoxins in human CD3epsilon transgenic mice

BACKGROUND: Anti-CD3 immunotoxins are broad-spectrum immunosuppressive agents in a wide range of organ transplantation animal models with potential use in eliciting antigen-specific tolerance. However, the anti-CD3 immunotoxins used in animal studies do not cross-react with human T cells, limiting extrapolation to humans and hindering clinical development. METHODS: Three anti-human CD3-directed immunotoxins, DT389-scFv(UCHT1), scFv(UCHT1)-PE38, and UCHT1-CRM9, were compared in vitro and in transgenic mice, tg(epsilon)600+/-, that have T cells expressing both human and murine CD3epsilon antigens. RESULTS: These immunotoxins were extraordinarily potent in vitro against human or transgenic mouse T cells, with IC50 values in cellular assays ranging from pM to fM. Systemic administration of these immunotoxins dose-dependently depleted >99% of tg(epsilon)600+/- lymph node and spleen T cells in vivo. Depletion was specific for T cells. The loss of the concanavalin A-induced, but not the lipopolysaccharide-induced, splenic proliferative response from immunotoxin-treated animals further demonstrated specific loss of T-cell function. Immunotoxin treatment prolonged fully allogeneic skin graft survival in tg(epsilon)600+/- recipients to 25 days from 10 days in untreated animals. T-cells recovered to approximately 50% of normal levels after approximately 22 days in animals with or without skin grafts; T-cell recovery correlated with skin graft rejection. All three immunotoxins elicited >100 day median survival of fully allogeneic heterotopic heart grafts. By 100 days, T cells recovered to normal numbers in these animals, but the grafts showed chronic rejection. CONCLUSION: These immunotoxins profoundly deplete T cells in vivo and effectively prolong allogeneic graft survival.