Mechanisms underlying decreased protein and RNA synthesis in the rat spleen following whole-body X-irradiation.

Whole-body exposure of rats to 1000 R X-rays resulted in decreased rates in protein and RNA syntheses in the spleen from the fourth post-irradiation hour. These changes correspond well with impaired ability of nuclei to polymerise RNA, reduction in template efficiency of chromatin, decrease in the activity of RNA polymerase and inhibition in histone phosphorylation. Protection of the spleen by lead shielding during whole-body exposure to X-rays largely eliminated the observed alterations in protein and nucleic acid synthetic machineries. This suggests that the radiation-induced inhibition in protein and RNA syntheses is mainly due to the direct action of radiation on the spleen itself.     

Revisiting induction chemotherapy for head and neck cancer. References and reviews

Squamous cell carcinomas of the head and neck are highly responsive to induction chemotherapy. However, randomized trials have failed to demonstrate a survival advantage with the addition of induction chemotherapy to locoregional therapy consisting of surgery and/or radiation therapy. Currently, concomitant radiation and chemotherapy has emerged as a standard and has optimized locoregional control in head and neck cancer. In this setting, the addition of induction chemotherapy may further improve outcome by enhancing both locoregional and distant control. As interest in induction regimens is renewed, we elected to conduct a systematic review of trials of induction chemotherapy for locoregionally advanced head and neck cancer. The most studied combination-cisplatin plus fluorouracil (5-FU)--achieves objective response rates of about 80%. In a meta-analysis, induction with platinum/5-FU resulted in a small survival advantage over locoregional therapy alone. The introduction of a taxane into induction chemotherapy regimens has produced promising results. Induction chemotherapy should be the subject of further clinical research in head and neck cancer. Randomized clinical trials in which the control arm is concurrent chemoradiotherapy and the experimental arm is induction chemotherapy followed by concurrent chemoradiotherapy are planned. Platinum/taxane combinations are the preferred regimens for further study in the induction setting and a suitable platform with which to investigate the addition of novel targeted agents.     

Complexity analysis of dense array EEG signal reveals sex difference

This article deals with the complexity aspects of the recorded electroencephalogram (EEG) signal from male and female subjects. The analysis follows direct application of time series measures of global linear complexity and characterization of the embedded complexity in the signals using the nonlinear statistic of approximate entropy. The study reveals significant differences in complexity between the two sex groups during passive, no-task conditions, whereas no apparent variation exists during a mental task state. The detection of subtle changes as well as the ease in presenting a global picture of the complexity variation on the human cortical surface makes the nonlinear statistic a better marker of system complexity.     

Role of cAMP signaling in the mediation of dopamine-induced stimulation of GnRH secretion via D1 dopamine receptors in GT1-7 cells

Pharmacologically increasing cyclic adenosine monophosphate (cAMP) levels in GT1 gonadotropin-releasing hormone (GnRH) cell lines increased the secretion of GnRH. Dopamine (DA) increased the GnRH secretion in GT1 cells via a DA receptor positively coupled to adenylate cyclase. We then asked whether inhibition of the DA-induced increase in cAMP would block the stimulatory effect of DA on GnRH release. Expression of the cAMP-specific phosphodiesterase (PDE4D1) was used in a genetic approach to inhibit the DA-induced increase in cAMP levels. Cells were infected with an adenovirus vector (Ad) expressing PDE4D1 (PDE-Ad) or, for controls, with an empty Ad (Null-Ad). Infection with the PDE-Ad completely blocked the forskolin-induced stimulation of GnRH secretion and [Ca2+]i and decreased the majority of the release of cAMP into the culture medium. In contrast, although PDE-Ad infection blocked virtually all of the DA-induced increase in extracellular cAMP, the release of GnRH and the increase in [Ca2+]i were only delayed for approximately 15 min. GT1 cells express the D1 DA receptor which is positively coupled to adenylate cyclase but not the D5 DA receptor. These data suggest that the initial phase of the DA-induced secretion of GnRH is dependent on an increase in cAMP levels. However, it appears that an additional non-cAMP-regulated signaling pathway is involved in the stimulation of GnRH release via the D1 DA receptor.     

Summaries from The 58th Annual Meeting of the Japan Esophageal Society June 24–25, 2004, Tokyo

CONGRESS REPORT: SUMMARIES

Summaries from The 58th Annual Meeting of the Japan Esophageal Society June 24–25, 2004, Tokyo     

Can a practicing surgeon detect early lymphedema reliably?

BACKGROUND: Lymphedema may be identified by simpler circumference changes as compared with changes in limb volume. METHODS: Ninety breast cancer patients were prospectively enrolled in an academic trial, and seven upper extremity circumferences were measured quarterly for 3 years. A 10% volume increase or greater than 1 cm increase in arm circumference identified lymphedema with verification by a lymphedema specialist. Sensitivity and specificity of several different criteria for detecting lymphedema were compared using the academic trial as the standard. RESULTS: Thirty-nine cases of lymphedema were identified by the academic trial. Using a 10% increase in circumference at two sites as the criterion, half the lymphedema cases were detected (sensitivity 37%). When using a 10% increase in circumference at any site, 74.4% of cases were detected (sensitivity 49%). Detection by a 5% increase in circumference at any site was 91% sensitive. CONCLUSIONS: An increase of 5% in circumference measurements identified the most potential lymphedema cases compared with an academic trial.     

Distinct Biomarker Profiles in Ex Vivo T Cell Depletion Graft Manipulation Strategies: CD34+ Selection versus CD3+/19+ Depletion in Matched Sibling Allogeneic Peripheral Blood Stem Cell Transplantation

Various approaches have been developed for ex vivo T cell depletion in allogeneic stem cell transplantation to prevent graft-versus-host disease (GVHD). Direct comparisons of T cell depletion strategies have not been well studied, however. We evaluated cellular and plasma biomarkers in 2 different graft manipulation strategies, CD3⁺CD19⁺ cell depletion (CD3/19D) versus CD34⁺ selection (CD34S), and their associations with clinical outcomes. Identical conditions, including the myeloablative preparative regimen, HLA-identical sibling donor, GVHD prophylaxis, and graft source, were used in the 2 cohorts. Major clinical outcomes were similar in the 2 groups in terms of overall survival, nonrelapse mortality, and cumulative incidence of relapse; however, the cumulative incidence of acute GVHD trended to be higher in the CD3/19D cohort compared with the CD34S cohort. A distinct biomarker profile was noted in the CD3/19D cohort: higher levels of ST2, impaired Helios^? FoxP3⁺Treg reconstitution, and rapid reconstitution of naïve, Th2, and Th17 CD4 cells in the early post-transplantation period. In vitro graft replication studies confirmed that CD3/19D disproportionately depleted Tregs and other CD4 subset repertoires in the graft. This study confirms the utility of biomarker monitoring, which can be directly correlated with biological consequences and possible future therapeutic indications.     

Selective attention supports working memory maintenance by modulating perceptual processing of distractors

Selective attention has been shown to bias sensory processing in favor of relevant stimuli and against irrelevant or distracting stimuli in perceptual tasks. Increasing evidence suggests that selective attention plays an important role during working memory maintenance, possibly by biasing sensory processing in favor of to-be-remembered items. In the current study, we investigated whether selective attention may also support working memory by biasing processing against irrelevant and potentially distracting information. Event-related potentials (ERPs) were recorded while subjects (n = 22) performed a delayed-recognition task for faces and shoes. The delay period was filled with face or shoe distractors. Behavioral performance was impaired when distractors were congruent with the working memory domain (e.g., face distractor during working memory for faces) relative to when distractors were incongruent with the working memory domain (e.g., face distractor during shoe working memory). If attentional biasing against distractor processing is indeed functionally relevant in supporting working memory maintenance, perceptual processing of distractors is predicted to be attenuated when distractors are more behaviorally intrusive relative to when they are nonintrusive. As such, we predicted that perceptual processing of distracting faces, as measured by the face-sensitive N170 ERP component, would be reduced in the context of congruent (face) working memory relative to incongruent (shoe) working memory. The N170 elicited by distracting faces demonstrated reduced amplitude during congruent versus incongruent working memory. These results suggest that perceptual processing of distracting faces may be attenuated due to attentional biasing against sensory processing of distractors that are most behaviorally intrusive during working memory maintenance.