The efficacy and adverse event profile of dexamethasone, melphalan, actinomycin D, and cytosine arabinoside (DMAC) chemotherapy in relapsed canine lymphoma.

In this retrospective study, a chemotherapy protocol using dexamethasone, melphalan, actinomycin D, and cytosine arabinoside (DMAC) was evaluated for efficacy and adverse event profile as a first line rescue protocol in 86 client-owned dogs previously treated with a CHOP-based protocol. Forty-three dogs (43%) achieved remission (16% complete remission, 27% partial remission), and 57% were non-responders. The median overall progression-free survival (PFS) was 24 days. Adverse events included thrombocytopenia in 41% of dogs, neutropenia in 17% of dogs, and gastrointestinal toxicity in 13% of dogs. Overall, 16% (13/79) dogs experienced grade III to IV thrombocytopenia, 8% (6/74) dogs grade III to IV neutropenia and 1% (1/79) dogs grade III to IV gastrointestinal toxicity. The efficacy of the DMAC protocol is similar to that of other rescue protocols in dogs with relapsed lymphoma but is associated with shorter PFS. The main toxicity is thrombocytopenia, which may limit treatment.

Profil de l'efficacité et des événements indésirables de la chimiothérapie à la déxaméthasone, au melphalan, à l'actinomycine D et à la cytosine arabinoside (DMAC) pour les rechutes du lymphome canin. Dans cette étude rétrospective, un protocole de chimiothérapie utilisant la dexaméthasone, le melphalan, l'actinomycine D et le cytosine arabinoside (DMAC) a été évalué pour le profil d'efficacité et d'événements indésirables en tant que protocole de secours de première ligne chez 86 chiens, appartenant à des clients, antérieurement traités à l'aide d'un protocole CHOP. Quarante-trois chiens (43 %) sont parvenus à la rémission (16 % rémission complète, 27 % en rémission partielle) et 57 % n'ont pas répondu au traitement. La survie globale médiane sans progression était de 24 jours. Les événements indésirables incluaient la thrombocytopénie chez 41 % des chiens, la neutropénie chez 17 % des chiens et la toxicité gastro-intestinale chez 13 % des chiens. Dans l'ensemble, 16 % (13/79 chiens) ont eu une thrombocytopénie de grade III à IV, 8 % (6/74 chiens) une neutropénie de grades III à IV et 1 % (1/79 chiens) une toxicité gastro-intestinale de grade III à IV. L'efficacité du protocole DMAC est semblable à celle d'autres protocoles de secours chez les chiens atteints d'une rechute de lymphome, mais elle est associée à une survie globale médiane sans progression réduite. La principale toxicité est la thrombocytopénie, qui peut limiter le traitement.(Traduit par Isabelle Vallières).

Anergic CD4+ T cells form mature immunological synapses with enhanced accumulation of c-Cbl and Cbl-b.

CD4(+) T cell recognition of MHC:peptide complexes in the context of a costimulatory signal results in the large-scale redistribution of molecules at the T cell-APC interface to form the immunological synapse. The immunological synapse is the location of sustained TCR signaling and delivery of a subset of effector functions. T cells activated in the absence of costimulation are rendered anergic and are hyporesponsive when presented with Ag in the presence of optimal costimulation. Several previous studies have looked at aspects of immunological synapses formed by anergic T cells, but it remains unclear whether there are differences in the formation or composition of anergic immunological synapses. In this study, we energized primary murine CD4(+) T cells by incubation of costimulation-deficient, transfected fibroblast APCs. Using a combination of TCR, MHC:peptide, and ICAM-1 staining, we found that anergic T cells make mature immunological synapses with characteristic central and peripheral supramolecular activation cluster domains that were indistinguishable from control synapses. There were small increases in total phosphotyrosine at the anergic synapse along with significant decreases in phosphorylated ERK 1/2 accumulation. Most striking, there was specific accumulation of c-Cbl and Cbl-b to the anergic synapses. Cbl-b, previously shown to be essential in anergy induction, was found in both the central and the peripheral supramolecular activation clusters of the anergic synapse. This Cbl-b (and c-Cbl) accumulation at the anergic synapse may play an important role in anergy maintenance, induction, or both.

ECA3, a Golgi-localized P2A-type ATPase, plays a crucial role in manganese nutrition in Arabidopsis.

Calcium (Ca) and manganese (Mn) are essential nutrients required for normal plant growth and development, and transport processes play a key role in regulating their cellular levels. Arabidopsis (Arabidopsis thaliana) contains four P(2A)-type ATPase genes, AtECA1 to AtECA4, which are expressed in all major organs of Arabidopsis. To elucidate the physiological role of AtECA2 and AtECA3 in Arabidopsis, several independent T-DNA insertion mutant alleles were isolated. When grown on medium lacking Mn, eca3 mutants, but not eca2 mutants, displayed a striking difference from wild-type plants. After approximately 8 to 9 d on this medium, eca3 mutants became chlorotic, and root and shoot growth were strongly inhibited compared to wild-type plants. These severe deficiency symptoms were suppressed by low levels of Mn, indicating a crucial role for ECA3 in Mn nutrition in Arabidopsis. eca3 mutants were also more sensitive than wild-type plants and eca2 mutants on medium lacking Ca; however, the differences were not so striking because in this case all plants were severely affected. ECA3 partially restored the growth defect on high Mn of the yeast (Saccharomyces cerevisiae) pmr1 mutant, which is defective in a Golgi Ca/Mn pump (PMR1), and the yeast K616 mutant (Deltapmc1 Deltapmr1 Deltacnb1), defective in Golgi and vacuolar Ca/Mn pumps. ECA3 also rescued the growth defect of K616 on low Ca. Promoter:beta-glucuronidase studies show that ECA3 is expressed in a range of tissues and cells, including primary root tips, root vascular tissue, hydathodes, and guard cells. When transiently expressed in Nicotiana tabacum, an ECA3-yellow fluorescent protein fusion protein showed overlapping expression with the Golgi protein GONST1. We propose that ECA3 is important for Mn and Ca homeostasis, possibly functioning in the transport of these ions into the Golgi. ECA3 is the first P-type ATPase to be identified in plants that is required under Mn-deficient conditions.

An evaluation of a blind rotational technique for selective mainstem intubation.

OBJECTIVES: Although rare, massive hemoptysis and major bronchial disruptions are associated with high mortality. Selective ventilation of the uninvolved lung can increase the likelihood of survival. Specialized devices used for single lung ventilation are often not readily available and can be difficult to place in the emergency department. The authors evaluated a blind rotational technique for selective mainstem intubation using either a standard endotracheal tube (ET) or a directional-tip endotracheal tube (DTET). METHODS: This was a prospective, randomized trial on 25 human cadavers. The desired side of mainstem intubation was determined by randomization. Each cadaver was used for four ET, four DTET, and four control intubations. In the ET group, the trachea was intubated. The tube was then rotated 90 degrees in the direction of the desired placement and advanced until resistance was met. In the DTET group, the technique was identical, except the trigger was activated to flex the tip during advancement. In the control group, an ET was advanced in neutral alignment until resistance was met. A bronchoscopist blinded to the desired placement determined tube position. Comparison testing was performed using Pearson's chi-square test. RESULTS: When attempting to intubate the left mainstem, use of the ET with the rotational technique was successful 72.3% of the time (95% confidence interval [95% CI] = 57% to 84%). Intubation of the left mainstem using the DTET was successful 68.5% of the time (95% CI = 54% to 81%; p = 0.67). Attempts to selectively intubate the right mainstem using the rotational technique were highly successful in both groups: 94% for the ET (95% CI = 84% to 99%) versus 97.8% for the DTET (95% CI = 89% to 100%). Among controls, the right mainstem was intubated 93% of the time (95% CI = 86% to 97%). CONCLUSIONS: In a cadaveric model, the left mainstem bronchus can be selectively intubated with moderate reliability using this rotational technique. Use of a DTET confers no significant advantage. The ability to generalize these findings to living subjects is unknown.