Predicting the response of a long-distance migrant to changing environmental conditions in winter.

Access to high-quality food is critical for long-distance migrants to provide energy for migration and arrival at breeding grounds in good condition. We studied effects of changing abundance and availability of a marine food, common eelgrass (Zostera marina L.), on an arctic-breeding, migratory goose, black brant (Brant bernicla nigricans Lawrence 1846), at a key non-breeding site, Bahía San Quintín, Mexico. Eelgrass, the primary food of brant, is consumed when exposed by the tide or within reach from the water's surface. Using an individual-based model, we predicted effects of observed changes (1991-2013) in parameters influencing food abundance and availability: eelgrass biomass (abundance), eelgrass shoot length (availability, as longer shoots more within reach), brant population size (availability, as competition greater with more birds), and sea level (availability, as less food within reach when sea level higher). The model predicted that the ability to gain enough energy to migrate was most strongly influenced by eelgrass biomass (threshold January biomass for migration = 60 g m-2 dry mass). Conversely, annual variation in population size (except for 1998), was relatively low, and variation in eelgrass shoot length and sea level were not strongly related to ability to migrate. We used observed data on brant body mass at Bahía San Quintín and annual survival to test for effects of eelgrass biomass in the real system. The lowest observed values of body mass and survival were in years when biomass was below 60 g m-2, although in some years of low biomass body mass and/or survival was higher. This suggests that the real birds may have some capacity to compensate to meet their energy demands when eelgrass biomass is low. We discuss consequences for brant population trends and conservation.

The diagnostic value of CT myelography, MR myelography, and both in neonatal brachial plexus palsy.

BACKGROUND AND PURPOSE: Although most infants with brachial plexus palsy recover function spontaneously, approximately 10-30% benefit from surgical treatment. Pre-operative screening for nerve root avulsions is helpful in planning reconstruction. Our aim was to compare the diagnostic value of CT myelography, MR myelography, and both against a surgical criterion standard for detection of complete nerve root avulsions in birth brachial plexus palsy. MATERIALS AND METHODS: Nineteen patients who underwent a preoperative CT and/or MR myelography and subsequent brachial plexus exploration were included. Imaging studies were analyzed for the presence of abnormalities potentially predictive of nerve root avulsion. Findings of nerve root avulsion on surgical exploration were used as the criterion standard to assess the predictive value of imaging findings. RESULTS: Ninety-five root levels were examined. When the presence of any pseudomeningocele was used as a predictor, the sensitivity was 0.73 for CT and 0.68 for MR imaging and the specificity was 0.96 for CT and 0.97 for MR imaging. When presence of pseudomeningocele with absent rootlets was used as the predictor, the sensitivity was 0.68 for CT and 0.68 for MR imaging and the specificity was 0.96 for CT and 0.97 for MR imaging. The use of both CT and MR imaging did not increase diagnostic accuracy. Rootlet findings in the absence of pseudomeningocele were not helpful in predicting complete nerve root avulsion. CONCLUSIONS: Findings of CT and MR myelography were highly correlated. Given the advantages of MR myelography, it is now the single technique for preoperative evaluation of nerve root avulsion at our institution.

Radioiodine retention on percutaneous endoscopic gastrostomy tubes.

An 80-year-old male with recurrent thyroid cancer and a percutaneous endoscopic gastrostomy (PEG) tube in situ was referred for radioiodine therapy and was administered 5510 MBq I-131 sodium iodide intravenously. Sequential whole-body images taken over the subsequent 7 days for dosimetric evaluation revealed an area of persistent high uptake in the abdomen. Delayed imaging with single photon emission CT/CT at 15 days post administration revealed this uptake to be at the junction of the PEG tube with the anatomically normal stomach wall. We hypothesise that the PEG tube became contaminated by radioiodine secreted in the gastric mucosa during therapy and this radioactivity subsequently decayed with an increased effective half-life relative to the stomach, leading to the apparent hot spot.

Impact of hyperglycemia on early embryo development and embryopathy: in vitro experiments using a mouse model.

BACKGROUND: The aim of this study is to model the processes of early embryopathy seen in human pregnancy complicated by maternal hyperglycemia secondary to maternal diabetes using a mouse embryo culture system. METHODS: Female mice were superovulated and mated in pairs. Two-cell embryos were harvested from the oviducts and cultured in vitro in KSOM medium (synthetic oviductal medium enriched with potassium) supplemented with 0.2, 5.56, 15.56 or 25.56 mM d-glucose. Cell proliferation, differentiation and apoptosis were assessed. Experiments were performed in constant, embryos exposed to a particular concentration of glucose (0.2, 5.56, 15.56 or 25.56 mM) from harvest to either Day 5 post fertilization (pf) or Day 8 pf, and fluctuating, embryos exposed to alternate high 25.56 mM and normal 5.56 mM concentrations of glucose between harvest and Day 5 pf, glycemic culture. RESULTS: Expected levels of blastocyst formation and hatching were seen at 0.2 and 5.56 mM concentrations of glucose but both were impaired at higher concentrations (chi(2), P < 0.005; P < 0.001). Total cell numbers (P < 0.002) and cell allocation to the inner cell mass (P < 0.01) were reduced, but with no evidence of enhanced apoptosis in the hyperglycemic cultures. Variation in hyperglycemic exposure of the embryos on Days 2, 3 and 4 showed no adverse effects of hyperglycemia up to 24 h, but 48 and 72 h exposures were equally embryopathic (P < 0.01). CONCLUSIONS: Hyperglycemic exposure for >24 h is toxic to early embryo development. These findings may explain the lower than expected implantation rates and higher than expected rates of congenital abnormality and early pregnancy loss seen in patients with diabetes, particularly those with poor diabetic control.

Positron emission tomography in oncology: a review.

Positron emission tomography is an evolving imaging tool that is becoming increasingly available for use in clinical practice. This overview will look at the current evidence for the use of positron emission tomography in imaging different tumour types and the different radiotracers that are either available or being evaluated in an investigational setting.

Detection of DNA damage and identification of UV-induced photoproducts using the CometAssay kit.

We introduce the first commercially available comet assay for the detection and quantification of DNA damage in individual eukaryotic cells. The major difficulty of the comet assay is the preparation of the slides needed to immobilize the samples throughout the lysis and electrophoretic procedures. The CometAssay kit uses a proprietary technology to precoat glass microscope slides to allow direct application of the agarose embedded sample without any additional slide treatment. In this report, we discuss the detection of DNA damage in individual cells exposed to ultraviolet irradiation using the new CometSlides and their cost compared to traditional slides.

Bax, but not Bcl-xL, decreases the lifetime of planar phospholipid bilayer membranes at subnanomolar concentrations.

Release of proteins through the outer mitochondrial membrane can be a critical step in apoptosis, and the localization of apoptosis-regulating Bcl-2 family members there suggests they control this process. We used planar phospholipid membranes to test the effect of full-length Bax and Bcl-xL synthesized in vitro and native Bax purified from bovine thymocytes. Instead of forming pores with reproducible conductance levels expected for ionic channels, Bax, but not Bcl-xL, created arbitrary and continuously variable changes in membrane permeability and decreased the stability of the membrane, regardless of whether the source of the protein was synthetic or native. This breakdown of the membrane permeability barrier and destabilization of the bilayer was quantified by using membrane lifetime measurements. Bax decreased membrane lifetime in a voltage- and concentration-dependent manner. Bcl-xL did not protect against Bax-induced membrane destabilization, supporting the idea that these two proteins function independently. Corresponding to a physical theory for lipidic pore formation, Bax potently diminished the linear tension of the membrane (i.e., the energy required to form the edge of a new pore). We suggest that Bax acts directly by destabilizing the lipid bilayer structure of the outer mitochondrial membrane, promoting the formation of a pore-the apoptotic pore-large enough to allow mitochondrial proteins such as cytochrome c to be released into the cytosol. Bax could then enter and permeabilize the inner mitochondrial membrane through the same hole.

Detection of fragmented DNA in apoptotic cells embedded in LR white: A combined histochemical (LM) and ultrastructural (EM) study.

We developed an improved method for the detection of double-strand DNA breaks in apoptotic cells at both the light (LM) and electron microscopic (EM) levels using a modification of the TdT (terminal deoxynucleotidyl transferase)-mediated dUTP nick end-labeling (TUNEL) technique. Cultured rat cerebellar granule cells were exposed to low potassium conditions to induce apoptosis. Twenty-four hr after treatment, one group of cells was fixed in situ with 4% paraformaldehyde and labeled for DNA fragmentation characteristic of apoptosis. Apoptotic cells were visualized with diaminobenzidine (DAB) and viewed by LM. The second group of cells was detached from the culture dish, pelleted, fixed with a 4% paraformaldehyde and 0. 2% glutaraldehyde mixture, and embedded in LR White. For LM, the modified TUNEL technique was performed on 1.5-microm LR White sections and apoptotic cells were visualized using an enzymatic reaction to generate a blue precipitate. For EM, thin sections (94 nm) were processed and DNA fragmentation was identified using modified TUNEL with streptavidin-conjugated gold in conjunction with in-depth ultrastructural detail. Alternate sections of cells embedded in LR White can therefore be used for LM and EM TUNEL-based detection of apoptosis. The present findings suggest that the modified TUNEL technique on LR White semithin and consecutive thin sections has useful application for studying the fundamental mechanism of cell death. (J Histochem Cytochem 47:561-568, 1999)

The 2-5A system in viral infection and apoptosis.

The 2-5A system is an established endogenous antiviral pathway. Interferon treatment of cells leads to an increase in basal, but latent, levels of 2-5A-dependent RNase (RNase L) and the family of 2'-5' oligoadenylate synthetases (OAS). Double-stranded RNA, thought to be derived from viral replication intermediates, activates OAS. Activated OAS converts ATP into unusual short 2'-5' linked oligoadenylates called 2-5A [ppp5'(A2'p5')2A]. The 2-5A binds to and activates RNase L which cleaves single stranded RNA with moderate specificity for sites 3' of UpUp and UpAp sequences, and thus leads to degradation of cellular rRNA. During apoptosis, generalized cellular RNA degradation, distinct from the differential expression of mRNA species that may regulate specific gene expression during apoptosis, has been observed. The mechanism of RNA breakdown during apoptosis has been commonly considered a non-specific event that reflects the generalized shut down of translation and homeostatic regulation during cell death. Due to the similar RNA degradation that occurs during both apoptosis and viral infection we investigated the potential role of RNase L in apoptosis. To investigate whether RNase L activity could lead to apoptosis, NIH3T3 cells were transfected with a lac-inducible vector containing the human RNase L gene. Treatment of these cells with isopropylthiogalactoside (IPTG) caused loss of cell viability that was confirmed as an apoptotic cell death by morphological and biochemical criteria. Similarly, specific allosteric activation of endogenous RNase L by introduction of 2-5A directly into L929 cells also induced apoptosis. In L929 cells poly(I).poly(C) treatment in combination with interferon caused an increase in apoptosis whereas neither interferon or double stranded RNA alone altered cell viability. Therefore, increased expression or activation of RNase L causes apoptosis. Inhibition of RNase L, specifically with a dominant negative mutant, suppressed poly(I)Ypoly(C)-induced apoptosis in interferon-primed fibroblasts. Poliovirus, a picornovirus with a single-stranded RNA genome, causes apoptosis of HeLa cells. Expression of the dominant negative inhibitor of RNase L in HeLa prevented virus-induced apoptosis and maintained cell viability. Thus, reduction or inhibition of RNase L activity prevents apoptosis. Both apoptosis and the 2-5A system can provide defense against viral infection in multicellular organisms by preventing production and therefore spread of progeny virus. RNase L appears to function in both mechanisms, therefore, initiation of apoptosis may be one mechanism for the antiviral activity of the 2-5A system.

The use of noninvasive positive pressure ventilation in the emergency department: results of a randomized clinical trial.

OBJECTIVE: To determine whether the use of noninvasive positive pressure ventilation (NPPV) in the emergency department (ED) will reduce the need for tracheal intubation and mechanical ventilation. DESIGN: Randomized, controlled, prospective clinical trial. SETTING: ED of Barnes-Jewish Hospital, a university-affiliated teaching hospital. PATIENTS: Twenty-seven patients meeting a predetermined definition of acute respiratory distress requiring hospital admission. INTERVENTIONS: Conventional medical therapy for the various etiologies of acute respiratory distress and the application of NPPV. MEASUREMENTS AND RESULTS: The primary outcome measure was the need for tracheal intubation and mechanical ventilation. Secondary outcomes also assessed included hospital mortality, hospital length of stay, acquired organ system derangements, and the utilization of respiratory care personnel. Sixteen patients (59.3%) were randomly assigned to receive conventional medical therapy plus NPPV, and 11 patients (40.7%) were randomly assigned to receive conventional medical therapy without NPPV. The two groups were similar at the time of randomization in the ED with regard to demographic characteristics, hospital admission diagnoses, and severity of illness. Tracheal intubation and mechanical ventilation was required in seven patients (43.8%) receiving conventional medical therapy plus NPPV and in five patients (45.5%) receiving conventional medical therapy alone (relative risk=0.96; 95% confidence interval=0.41 to 2.26; p=0.930). There was a trend towards a greater hospital mortality rate among patients in the NPPV group (25%) compared to patients in the conventional medical therapy group (0.0%) (p=0.123). Among patients who subsequently required mechanical ventilation, those in the NPPV group had a longer time interval from ED arrival to the start of mechanical ventilation compared to patients in the conventional medical therapy group (26.0+/-27.0 h vs 4.8+/-6.9 h; p=0.055). CONCLUSIONS: We conclude that the application of NPPV in the ED may delay tracheal intubation and the initiation of mechanical ventilation in some patients with acute respiratory distress. We also demonstrated that the application of NPPV was associated with an increased hospital mortality rate. Based on these preliminary observations, larger clinical investigations are required to determine if adverse patient outcomes can be attributed to the early application of NPPV in the ED. Additionally, improved patient selection criteria for the optimal administration of NPPV in the ED need to be developed.

A study of the interferon antiviral mechanism: apoptosis activation by the 2-5A system.

The 2-5A system contributes to the antiviral effect of interferons through the synthesis of 2-5A and its activation of the ribonuclease, RNase L. RNase L degrades viral and cellular RNA after activation by unique, 2'-5' phosphodiester-linked, oligoadenylates [2-5A, (pp)p5' A2'(P5'A2')]n, n >=2. Because both the 2-5A system and apoptosis can serve as viral defense mechanisms and RNA degradation occurs during both processes, we investigated the potential role of RNase L in apoptosis. Overexpression of human RNase L by an inducible promoter in NIH3T3 fibroblasts decreased cell viability and triggered apoptosis. Activation of endogenous RNase L, specifically with 2-5A or with dsRNA, induced apoptosis. Inhibition of RNase L with a dominant negative mutant suppressed poly (I).poly (C)-induced apoptosis in interferon-primed fibroblasts. Moreover, inhibition of RNase L suppressed apoptosis induced by poliovirus. Thus, increased RNase L levels induced apoptosis and inhibition of RNase L activity blocked viral-induced apoptosis. Apoptosis may be one of the antiviral mechanisms regulated by the 2-5A system.

Suicidality among HIV-positive psychiatric in-patients.

Rates of suicidality with HIV-infected, seriously mentally ill individuals were investigated. Fifty asymptomatic HIV-positive psychiatric in-patients were compared to a demographically-matched HIV-negative cohort. The groups were similar, except that seropositive subjects were less likely to be diagnosed with schizophrenia. Both groups had high rates of suicidality, with higher rates associated with non-schizophrenic diagnoses. HIV-positive subjects had higher rates of suicidality, with those diagnosed with schizophrenia showing the greatest difference from their HIV-negative counterparts. HIV-positive patients required less in-patient treatment. These data expand previous reports showing an association between HIV and increased suicidality, even among individuals with already elevated suicidal rates.

Risk of thromboembolism in chronic atrial flutter.

Anticoagulant therapy is not conventionally used in the treatment of patients with atrial flutter. This recommendation has been based on sparse clinical experience, and recent preliminary reports suggest a significant risk of thromboembolism for these patients. A retrospective study was undertaken to assess the frequency of thromboembolic events as well as potential risk factors for these events in a cohort of patients with atrial flutter referred for radiofrequency ablation treatment. Eighty-six consecutive patients with a primary diagnosis of atrial flutter were evaluated. A history of embolic events was noted in 12 of 86 patients (14%) with atrial flutter, with an annual risk of approximately 3%. There were no differences in the prevalence of coronary artery disease, cardiomyopathy, valvular disease, or atrial fibrillation between the 2 groups of patients having an embolic event and those of patients without embolic events. Left ventricular function and left atrial size were also similar between the 2 groups. The only significant risk factor was hypertension (p < 0.05). However, in a regression model with other clinical variables (i.e., age, gender, left atrial size, presence or absence of any cardiac disease, length of time in flutter, left ventricular function, type of flutter, flutter cycle length, type of secondary arrhythmias) no significant predictors were found. Patients with transient ischemic attacks or pulmonary emboli were then excluded from the analysis in order to compare the thromboembolic risk in the present study to that reported in major atrial fibrillation trials. The overall risk becomes 7% (6 of 86), which over a mean follow-up period of 4.5 years yields an annual risk of approximately 1.6%. Although this risk is only 1/3 of that for patients with atrial fibrillation, this risk is higher than previously recognized for patients with chronic atrial flutter. Anticoagulant therapy should be seriously considered for these patients.

Frequency of disabling symptoms in supraventricular tachycardia.

The purposes of this study were to describe: clinical symptoms in a sample of consecutive patients with supraventricular tachycardia (SVT); incidence of sudden death, syncope, and other disabling symptoms; whether these symptoms differ by tachycardia mechanism; and to identify predictor variables of syncope in patients with SVT. Data were collected from chart reviews of 167 consecutive patients with SVT admitted for radiofrequency ablation. Three patients (2%) had nonlethal cardiac arrest, and a total of 16% (26 of 183) received at least 1 external direct-current shock for arrhythmia management. Twenty percent of subjects (33 of 167) reported at least 1 episode of syncope which was preceded by palpitations. The most frequent symptoms were: palpitations (96%), dizziness (75%), and shortness of breath (47%). We found atrioventricular nodal reentrant tachycardia (AVNRT) in 64 patients, atrioventricular-reciprocating tachycardia (AVRT) in 59, atrial tachycardia in 22, and atrial flutter in 22. The symptom profiles of patients with AVNRT, AVRT, and atrial tachycardia were very similar, but differed significantly (p <0.05) from those reported in the atrial flutter group. Multivariate analysis showed that heart rate > or = 170 beats/min was the only independent risk factor for syncope. Chi-square analysis demonstrated that SVT patients with heart rate > or = 170 beats/min had significantly more dizziness and syncope. Thus, despite a low incidence of associated heart disease, and good left ventricular function, there was a high frequency of disabling, potentially life-threatening symptoms associated with episodes of SVT in this sample. SVT can have potentially lethal consequences, and is more disruptive than previously thought.

Structural elucidation of XR586, a peptaibol-like antibiotic from Acremonium persicinum.

A novel peptide, XR586, has been isolated from fermentations of Acremonium persicinum (Xenova culture collection number X21488). The structure of XR586 has been elucidated by means of NMR spectroscopy, electrospray and fast-atom bombardment MS, derivatization and enzymic digestion. It has been shown to be helical by CD measurements. XR586 shows many structural and conformational features in common with peptaibols, particularly the zervamicins. Peptaibol antibiotics are peptides, typically of 15-20 residues, containing a large proportion of alpha-aminoisobutyric acid (Aib) residues. These peptides adopt a helical conformation in solution and display anti-bacterial and toxic properties due to their ability to form pores in membranes. However, while XR586 contains several Aib residues, it lacks a terminal phenylalaninol and terminates in the sequence Phe-Gly. The lack of reduction of the penultimate residue at the C-terminus may indicate that this step is normally at the end of the biosynthetic pathway of peptaibols and occurs with cleavage of Gly. The 1H chemical shift assignments of XR586 are reported in Supplementary Publication SUP 50179 (3 pages), which has been deposited at the British Library Document Supply Centre, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1996) 313, 9 ("Deposition of data').

Novel beta-methoxyacrylates of the 9-methoxystrobilurin and oudesmansin classes produced by the basidiomycete Favolaschia pustulosa.

Submerged liquid cultures of the basidiomycete Favolaschia pustulosa (Xenova culture collection no. X27732) afforded the novel 9-methoxystrobilurin derivatives, 9-methoxystrobilurin L (1) and 9-methoxystrobilurin E (2), and the related oudemansin derivative, oudemansin L (3). Their structures were established by 2D NMR experiments. Compounds 1 and 3 possess a novel arrangement of two isoprenoid units fused to the aromatic nucleus. Both 1 and 2 have the EEE-configuration in the pentadienyl side chain as reported previously for 9-methoxystrobilurins. Compound 1 was cytotoxic to cells of the human B lymphoblastoid cell line (Jijoye), with an IC50 of 1.8 nM. This cytotoxicity was observed in a 5- day assay only and was not apparent after 2 days. Compound 1 showed some antibacterial activity against Bacillus subtilis (MIC = 0.9 microM) and antifungal activity against Candida albicans (MIC = 6 microM).