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Purine catabolism is regarded as a housekeeping function that remobilizes nitrogen for plant growth and development. However, emerging evidence suggests that certain purine metabolites might contribute to stress protection of plants. Here, we show that in Arabidopsis, the intermediary metabolite allantoin plays a role in abiotic stress tolerance via activation of abscisic acid ( ABA) metabolism. The aln loss-of-function of ALN, encoding allantoinase, results in increased allantoin accumulation, genome-wide up-regulation of stress-related genes and enhanced tolerance to drought-shock and osmotic stress in aln mutant seedlings. This phenotype is not caused by a general response to purine catabolism inhibition, but rather results from a specific effect of allantoin. Allantoin activates ABA production both through increased transcription of NCED3, encoding a key enzyme in ABA biosynthesis, and through post-translational activation via high-molecular-weight complex formation of BG1, a β-glucosidase hydrolysing glucose-conjugated ABA. Exogenous application of allantoin to wild-type plants also activates the two ABA-producing pathways that lead to ABA accumulation and stress-responsive gene expression, but this effect is abrogated in ABA-deficient and BG1-knockout mutants. We propose that purine catabolism functions not only in nitrogen metabolism, but also in stress tolerance by influencing ABA production, which is mediated by the possible regulatory action of allantoin. [ABSTRACT FROM AUTHOR]

Production of thromboxane (TX) A2 and PG I2/prostacyclin (PGI2) is increased in patients with atherosclerosis. However, their roles in atherogenesis have not been critically defined. To examine this issue, we cross-bred atherosclerosis-prone apoE-deficient mice with mice deficient in either the TXA receptor (TP) or the PGI receptor (IP). Although they showed levels of serum cholesterol and triglyceride similar to those of apoE-deficient mice, apoE-/-TP-/- mice exhibited a significant delay in atherogenesis, and apoE-/-IP-/- mice exhibited a significant acceleration in atherogenesis compared with mice deficient in apoE alone. The plaques in apoE-/-IP-/- mice showed partial endothelial disruption and exhibited enhanced expression of ICAM-1 and decreased expression of platelet endothelial cell adhesion molecule 1 (PECAM-1) in the overlying endothelial cells compared with those of apoE-/-TP-/- mice. Platelet activation with thrombin ex vivo revealed higher and lower sensitivity for surface P-selectin expression in platelets of apoE-/-IP-/- and apoE-/-TP-/- mice, respectively, than in those of apoE-/- mice. Intravital microscopy of the common carotid artery revealed a significantly greater number of leukocytes rolling on the vessel walls in apoE-/- mice than in either apoE-/-TP-/- or apoE-/- mice. We conclude that TXA2 promotes and PGI2 prevents the initiation and progression of atherogenesis through control of platelet activation and leukocyte-endothelial cell interaction. [ABSTRACT FROM AUTHOR]

We report a case of distant metastases developed 32 years after radical mastectomy for right breast cancer. A 70s-year-old women visited the local hospital because of productive cough. Chest computed tomography (CT) showed a 10 mm nodule in the right middle lobe, multiple lymph nodes swelling and small pleural nodules. Surgical biopsy of lung and pleural tumor provides the pathological diagnosis of solid-tubular carcinoma expressing estrogen receptor and progesterone receptor, suggesting metastatic lesions of breast cancer.

Voluntary apnea during dynamic exercise evokes marked bradycardia, peripheral vasoconstriction, and pressor responses. However, the mechanism(s) underlying the cardiovascular responses seen during apnea in exercising humans is unknown. We therefore tested the hypothesis that the muscle metaboreflex contributes to the apnea-induced pressor response during dynamic exercise. Thirteen healthy subjects participated in apnea and control trials. In both trials, subjects performed a two-legged dynamic knee extension exercise at a workload that elicited heart rates at ~100 beats/min. In the apnea trial, after reaching a steady state, subjects began voluntary apnea. Immediately after cessation of the apnea, arterial occlusion was initiated at both thighs and the subjects stopped exercising. The occlusion was sustained for 3 min in the postexercise period. In the control trial, the occlusion was started without subjects performing the apnea. The apnea induced marked bradycardia, pressor responses, and decreases in arterial O 2 saturation, cardiac output, and total vascular conductance. In addition, arterial blood pressure was significantly higher and total vascular conductance was significantly lower in the apnea trials than the control trials throughout the occlusion period. In separate sessions, we measured apnea-induced changes in exercising leg blood flow in the same subjects. Leg blood flow was significantly reduced by apnea and reached the resting level at the peak of the apnea response. We conclude that the muscle metaboreflex is activated by the decrease in O 2 delivery to the working muscle during apnea in exercising humans and contributes to the large pressor response. NEW & NOTEWORTHY We demonstrated that apnea during dynamic exercise activates the muscle metaboreflex in humans. This result indicates that a reduction in O 2 delivery to working muscle triggers the muscle metaboreflex during apnea. Activation of the muscle metaboreflex is one of the mechanisms underlying the marked apnea-induced pressor response.

Background: More than 20%of breast cancer patients who undergo myelosuppressive chemotherapy involving FEC(100) or TC experience febrile neutropenia(FN), and pegfilgrastim is commonly recommended as the primary prophylaxis. Delays and/or dose-reductions in chemotherapy should be avoided as much as possible to maximize the clinical benefits of these adjuvant chemotherapies., Purpose: This study assessed the relative dose intensity(RDI), efficacy, and safety of pegfilgrastim in patients with breast cancer. The incidence of FN was also evaluated., Methods: Twenty-six patients with breast cancer undergoing FEC(100)or TC were included in this retrospective study., Results: Of the 26 patients, 19 patients who underwent FEC(100)and 7 patients who underwent TC received 3.6 mg of pegfilgrastim 24 hours after administration of the myelosuppressive chemotherapy. Four and 14 patients who underwent FEC(100)achieved 85-99% and 100% RDI, respectively. All 7 patients who underwent TC achieved 100% RDI. Grade 3 and 4 adverse events, as assessed using the CTCAE, were observed in 11 patients who underwent FEC(100): 2 patients experienced leukocytopenia, 7 experienced neutropenia, 1 experienced thrombocytopenia, and 1 experienced FN. Four patients who underwent TC experienced Grade 3 and 4 adverse events: 1 patient each experienced bone pain, neutropenia, anemia, and FN., Conclusions: Pegfilgrastim can reduce the incidence of FN and maintain RDI in patients with breast cancer undergoing myelosuppressive chemotherapy.

A 68-year-old female with palmoplantar pustulosis was referred to our hospital in July, 2009 because of liver dysfunction, a positive test for HTLV-1, and circulating abnormal lymphocytes with irregularly shaped nuclei. A diagnosis of acute type adult T cell leukemia/lymphoma (ATLL) was made based on generalized lymph node swelling and high levels of serum LDH, in addition to the findings described above. The associated palmoplantar pustulosis responded to some extent to antibiotics, steroid ointment, and narrow band UBV light irradiation. For ATLL, she was serially treated with CHOP chemotherapy, an LSG 15 protocol, and CytaBOM protocol with consequent partial remission. These chemotherapies did not affect the palmoplantar pustulosis. For ATLL in partial remission, we performed allogeneic peripheral blood stem cell transplantation (allo-PBSCT) from a related donor (HTLV-1-negative) with a conditioning regimen consisting of fludarabine, melphalan, and total body irradiation with 3 Gy in February, 2010. After the engraftment of donor hematopoietic cells, ATLL cells disappeared and the patient currently (as of April, 2012) remains in complete remission (CR). The residual palmoplantar pustulosis was further improved soon after allo-PBSCT and disappeared on Day 84 after transplantation. This refractory skin disease has also been in CR to date.

We tested the hypotheses that the heart rate (HR) response to muscle metaboreflex activation induced by postexercise muscle ischemia (PEMI) varies considerably among subjects and that individual differences in the HR response are associated with differences in cardiac autonomic tone and/or arterial baroreflex function during PEMI. Fifty-one healthy subjects (36 men and 15 women) performed a 1-min isometric handgrip exercise at 50% maximal voluntary contraction, which was followed by a 3.5-min period of imposed PEMI. We estimated cardiac autonomic tone using spectral analysis of beat-to-beat variation in the R-R interval (RRI). In addition, the sensitivity of the arterial baroreflex control of HR (BRS) was evaluated using transfer function analysis of systolic arterial pressure (SAP) and RRI. Although the mean RRI during the PEMI and subsequent recovery period did not differ from the resting value, the variance among the individual differences in RRI between the rest and PEMI periods was significantly greater than between the rest and recovery periods. The changes in RRI elicited by PEMI correlated significantly with changes in the spectral power of the RRI variability in the high-frequency range and the BRS. By contrast, no significant correlation was observed between changes in RRI and changes in mean arterial pressure or the power of the RRI variability in the low-frequency range. This suggests that, in humans, the HR response to PEMI-induced activation of muscle metaboreflex varies considerably from individual to individual and that these differences reflect changes in cardiac parasympathetic tone and spontaneous BRS during PEMI.