Hypercalcaemia and in vitro osteolysis associated with xenografts of squamous carcinomas of the tongue.

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Upregulation of glycolysis and oxidative phosphorylation in benzo[β]pyrene and arsenic-induced rat lung epithelial transformed cells

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Further observations on mechanisms of bone destruction by squamous carcinomas of the head and neck: the role of host stroma.

Mechanisms of bone invasion by squamous carcinomas of the head and neck have been investigated using fresh tumours and established tumour cell lines in an in vitro bone resorption assay with 45Ca-labelled mouse calvaria. Fresh tumours regularly resorb bone in vitro. Activity is consistently reduced by indomethacin. The tumours release E2 prostaglandins (PGE2) in amounts sufficient to account for approximately 50% of the bone resorption observed. Small amounts of non-prostaglandin (indomethacin-resistant) osteolytic factors are also produced. Control non-neoplastic tissues show a variable capacity to resorb bone in vitro; PGE2 levels in these tissues may be related to their content of inflammatory cells. Tumour cell lines also resorb bone in vitro but, for most lines, activity is not significantly blocked by indomethacin and PGE2 levels are generally insufficient to account for the osteolysis observed. Non-prostaglandin bone resorbing factors thus predominate. It is concluded that most squamous cancers of the head and neck are osteolytic in vitro and release a mixture of prostaglandin and non-prostaglandin factors which stimulate osteoclastic bone resorption. These factors are derived from both neoplastic and stromal elements, and are "tumour-associated" rather than "tumour-specific". In vitro bone resorption and prostaglandin release does not correlate with pathological features of the tumour or with post-operative survival

Device management of arrhythmias after Fontan conversion

ObjectivesWe assessed our pacemaker strategy, use of antitachycardia therapies, generator longevity, and need for programming changes in patients having Fontan conversion with arrhythmia surgery.MethodsBetween 1994 and 2008, of 121 consecutive patients having Fontan conversion and arrhythmia surgeries, 120 patients underwent pacemaker implantation at the time of Fontan conversion (mean age 22.9 ± 8.1 years). Prior pacemakers were in place in 32/120 (26.7%) patients. Between 1994 and 1998, single-chamber atrial antitachycardia pacemakers were implanted (n = 12); atrial rate-responsive pacemakers (n = 31) were implanted between 1998 and 2002. Dual-chamber rate-responsive pacemakers (n = 16) were used between 2002 and 2003, and subsequently dual-chamber antitachycardia pacemakers (n = 61) have become the pacemaker of choice. Leads have evolved from transatrial endocardial leads to epicardial unipolar and subsequently bipolar leads.ResultsAmong 87 patients with adequate follow-up, all are currently atrially paced at a minimum lower rate ≥70 beats per minute. Single-chamber atrial pacemakers were implanted in 43 (antitachycardia in 12), and dual-chamber pacemakers in 77 (antitachycardia in 61); multisite ventricular leads were placed in 7 patients. Far-field R-wave sensing in 78.6% of unipolar atrial leads led to use of epicardial bipolar leads. Late atrioventricular block (24%) led to routine implantation of dual-chamber pacemakers. Antitachycardia pacing was utilized in 7%. One patient required acute lead revision and 4 required late upgrade to dual-chamber pacemakers. There was no pacemaker-related infection. Twenty patients required generator change, and the mean device longevity was 7.53 years.ConclusionsCustomized pacemaker therapy can optimize management of patients following Fontan conversion. Device longevity is excellent. Based on our experience with 120 Fontan conversions, we recommend placement of a dual-chamber antitachycardia pacemaker with bipolar steroid-eluting epicardial leads in all patients at the time of the conversion

Heme Oxygenase-1 Expression Affects Murine Abdominal Aortic Aneurysm Progression.

Heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme degradation, is a cytoprotective enzyme upregulated in the vasculature by increased flow and inflammatory stimuli. Human genetic data suggest that a diminished HO-1 expression may predispose one to abdominal aortic aneurysm (AAA) development. In addition, heme is known to strongly induce HO-1 expression. Utilizing the porcine pancreatic elastase (PPE) model of AAA induction in HO-1 heterozygous (HO-1+/-, HO-1 Het) mice, we found that a deficiency in HO-1 leads to augmented AAA development. Peritoneal macrophages from HO-1+/- mice showed increased gene expression of pro-inflammatory cytokines, including MCP-1, TNF-alpha, IL-1-beta, and IL-6, but decreased expression of anti-inflammatory cytokines IL-10 and TGF-beta. Furthermore, treatment with heme returned AAA progression in HO-1 Het mice to a wild-type profile. Using a second murine AAA model (Ang II-ApoE-/-), we showed that low doses of the HMG-CoA reductase inhibitor rosuvastatin can induce HO-1 expression in aortic tissue and suppress AAA progression in the absence of lipid lowering. Our results support those studies that suggest that pleiotropic statin effects might be beneficial in AAA, possibly through the upregulation of HO-1. Specific targeted therapies designed to induce HO-1 could become an adjunctive therapeutic strategy for the prevention of AAA disease

Associations of passerine birds, rabbits, and ticks with \u3cem\u3eBorrelia miyamotoi and Borrelia andersonii\u3c/em\u3e in Michigan, U.S.A.

Background Wild birds contribute to maintenance and dissemination of vectors and microbes, including those that impact human, domestic animal, and wildlife health. Here we elucidate roles of wild passerine birds, eastern cottontail rabbits (Sylvilagus floridanus), and Ixodes dentatus ticks in enzootic cycles of two spirochetes, Borrelia miyamotoi and B. andersonii in a region of Michigan where the zoonotic pathogen B. burgdorferi co-circulates. Methods Over a four-year period, wild birds (n = 19,631) and rabbits (n = 20) were inspected for tick presence and ear tissue was obtained from rabbits. Samples were tested for Borrelia spirochetes using nested PCR of the 16S-23S rRNA intergenic spacer region (IGS) and bidirectional DNA sequencing. Natural xenodiagnosis was used to implicate wildlife reservoirs. Results Ixodes dentatus, a tick that specializes on birds and rabbits and rarely bites humans, was the most common tick found, comprising 86.5% of the 12,432 ticks collected in the study. The relapsing fever group spirochete B. miyamotoi was documented for the first time in ticks removed from wild birds (0.7% minimum infection prevalence; MIP, in I. dentatus), and included two IGS strains. The majority of B. miyamotoi-positive ticks were removed from Northern Cardinals (Cardinalis cardinalis). Borrelia andersonii infected ticks removed from birds (1.6% MIP), ticks removed from rabbits (5.3% MIP), and rabbit ear biopsies (5%) comprised twelve novel IGS strains. Six species of wild birds were implicated as reservoirs for B. andersonii. Frequency of I. dentatus larval and nymphal co-feeding on birds was ten times greater than expected by chance. The relatively well-studied ecology of I. scapularis and the Lyme disease pathogen provides a context for understanding how the phenology of bird ticks may impact B. miyamotoi and B. andersonii prevalence and host associations. Conclusions Given the current invasion of I. scapularis, a human biting species that serves as a bridge vector for Borrelia spirochetes, human exposure to B. miyamotoi and B. andersonii in this region may increase. The presence of these spirochetes underscores the ecological complexity within which Borrelia organisms are maintained and the need for diagnostic tests to differentiate among these organisms

Energetics and atomic mechanisms of dislocation nucleation in strained epitaxial layers

We study numerically the energetics and atomic mechanisms of misfit dislocation nucleation and stress relaxation in a two-dimensional atomistic model of strained epitaxial layers on a substrate with lattice misfit. Relaxation processes from coherent to incoherent states for different transition paths are studied using interatomic potentials of Lennard-Jones type and a systematic saddle point and transition path search method. The method is based on a combination of repulsive potential minimization and the Nudged Elastic Band method. For a final state with a single misfit dislocation, the minimum energy path and the corresponding activation barrier are obtained for different misfits and interatomic potentials. We find that the energy barrier decreases strongly with misfit. In contrast to continuous elastic theory, a strong tensile-compressive asymmetry is observed. This asymmetry can be understood as manifestation of asymmetry between repulsive and attractive branches of pair potential and it is found to depend sensitively on the form of the potential.Comment: 11 pages, 9 figures, to appear in Phys. Rev.

Threshold meson production and cosmic ray transport

An interesting accident of nature is that the peak of the cosmic ray spectrum, for both protons and heavier nuclei, occurs near the pion production threshold. The Boltzmann transport equation contains a term which is the cosmic ray flux multiplied by the cross section. Therefore when considering pion and kaon production from proton-proton reactions, small cross sections at low energy can be as important as larger cross sections at higher energy. This is also true for subthreshold kaon production in nuclear collisions, but not for subthreshold pion production.Comment: 9 pages, 1 figur

Prolonged response to first-line erlotinib for advanced lung adenocarcinoma

A 58-year-old, non-smoking female of Philippine origin presented with painful thoracic and neck nodal relapse of lung adenocarcinoma almost 5 years after left pneumonectomy for stage II non-small-cell lung cancer. She refused conventional chemotherapy or radiation because of toxicity concerns, but agreed to oral erlotinib 150 mg/day. Within weeks, her pain was well controlled, with softening of palpable neck nodes. Repeat scans after 7 months on erlotinib showed partial response of thoracic disease and nodal metastases. This response was maintained for 11 months on erlotinib, with symptomatic progression at the original sites of relapse by 15 months. Erlotinib was well tolerated, with grade 2–3 rash, and grade 1 dry cough and diarrhoea being the only significant toxicities. Importantly, the patient was able to maintain daily activities throughout erlotinib therapy