Age-related decline in social interaction is associated with decreased c-Fos induction in select brain regions independent of oxytocin receptor expression profiles.

Social behavior decreases with aging, and we have previously found a substantial decline in social investigative behavior of old female rats. In this study we examined the neural activation pattern (c-Fos mRNA) of young (3 month) and old (18 month) female rats after brief 10 min exposure to a novel female rat in order to identify forebrain regions that show selective age-related alterations in their neural response to social investigation. We also measured relative oxytocin receptor expression (Oxtr mRNA) as a possible factor in age-related declines in c-Fos induction after social interaction. Young rats exposed to a social partner had a greater c-Fos mRNA response than those exposed to novel context alone in the lateral septum and septohypothalamic area, with blunted increases evident in old rats. In addition, c-Fos mRNA levels in the lateral septum were positively correlated with social investigative behavior. Interestingly, age-related differences in c-Fos gene induction were unrelated to the local amount of Oxtr expression within specific brain regions, although we found an age-related decline in Oxtr expression in the ventromedial hypothalamus. This functional neuroanatomical characterization may point to certain brain regions that are especially sensitive to age-related declines associated with social interaction behavior.

The behavioral and neurochemical effects of an inescapable stressor are time of day dependent.

Circadian rhythms are ∼24 h fluctuations in physiology and behavior that are synchronized with the light-dark cycle. The circadian system ensures homeostatic balance by regulating multiple systems that respond to environmental stimuli including stress systems. In rats, acute exposure to a series of uncontrollable tailshocks (inescapable stress, IS) produces an anxiety and depression-like phenotype. Anxiety- and fear-related behavioral changes produced by IS are driven by sensitization of serotonergic (5-hydroxytryptamine, 5-HT) neurons in the dorsal raphe nucleus (DRN). Because the circadian and serotonergic systems are closely linked, here we tested whether the DRN-dependent behavioral and neurochemical effects of IS are time of day dependent. Exposure to IS during the light (inactive) phase elicited the expected changes in mood related behaviors. In contrast, rats that underwent IS during the dark (active) phase were buffered against stress-induced changes in juvenile social exploration and shock-elicited freezing, both DRN-dependent outcomes. Interestingly, behavioral anhedonia, which is not a DRN-dependent behavior, was comparably reduced by stress at both times of day. Neurochemical changes complimented the behavioral results: IS-induced activation of DRN 5-HT neurons was greater during the light phase compared to the dark phase. Additionally, 5-HT1AR and 5-HTT, two genes that regulate 5-HT activity were up-regulated during the middle of the light cycle. These data suggest that DRN-dependent behavioral outcomes of IS are time of day dependent and may be mediated by circadian gating of the DRN response to stress.Lay summaryHere we show that the time of day at which a stressor occurs impacts the behavioral and neurochemical outcomes of the stressor. In particular, animals appear more vulnerable to a stressor that occurs during their rest phase. This work may have important implications for shift-workers and other populations that are more likely to encounter stressors during their rest phase.

Loss of imprinting of insulin-like growth factor-II (IGF2) gene in distinguishing specific biologic subtypes of Wilms tumor.

BACKGROUND: Loss of imprinting (LOI) of the insulin-like growth factor-II (IGF2) gene, an epigenetic alteration associated with expression of the normally silent maternal allele, was observed first in Wilms tumor. Although LOI has subsequently been detected in most adult tumors, the biologic role of LOI in cancer remains obscure. We analyzed the imprinting status of Wilms tumors with respect to pathologic subtype, stage, and patient's age at diagnosis and examined the expression of genes potentially affected by LOI. METHODS: Of 60 Wilms tumors examined, 25 were informative for an ApaI polymorphism in the IGF2 gene, allowing analysis of allele-specific gene expression, and could be classified by pathologic subtype. Gene expression was measured quantitatively by real-time polymerase chain reaction, and pathologic analysis was blinded for genetic status. All statistical tests were two-sided. RESULTS: We observed LOI of IGF2 in nine (90%) of 10 Wilms tumors classified as having a pathologic subtype associated with a later stage of renal development and in only one (6.7%) of 15 Wilms tumors with a pathologic subtype associated with an earlier stage of renal development (P< .001). LOI was associated with a 2.2-fold increase (95% confidence interval [CI] = 1.6-fold to 3.1-fold) in IGF2 expression (P< .001). Children whose Wilms tumors displayed LOI of IGF2 were statistically significantly older at diagnosis (median = 65 months; interquartile range [IQR] = 47-83 months) than children whose tumors displayed normal imprinting (median = 24 months; IQR = 13-35 months; P< .001). CONCLUSIONS: These data demonstrate a clear relationship between LOI and altered expression of IGF2 in Wilms tumors and provide a molecular basis for understanding the divergent pathogenesis of this cancer. Analysis of LOI could provide a valuable molecular tool for the classification of Wilms tumor.

Multidimensional imaging of the thorax: practical applications.

Over the past decade, faster CT scan times, thinner collimation, and the development of multirow detectors, coupled with the increasing capability of computers to process large amounts of data in short periods of time, have lead to an expansion in the ability to create diagnostically useful two-dimensional (2D) and three-dimensional (3D) images within the thorax. Applications within the thorax include, but are not limited to, evaluation of pulmonary and systemic vasculature, evaluation of the tracheobronchial tree, and delineation of diffuse lung disease. Pulmonary nodule volume and growth can be more accurately predicted, and represents an improvement in the evaluation of the solitary pulmonary nodule. Multiplanar images increase our understanding of thoracic anatomy and can help to guide bronchoscopic procedures. Because there are strengths and weaknesses to all the reconstruction algorithms, the utility of any given technique is dependent on the clinical question to be answered. For instance, although maximum intensity projection imaging (MIP) is helpful in the evaluation of micronodular lung disease, it is of little value in the diagnosis of aortic dissection. As the ability to generate faster and more precise multidimensional images grow, the demand for such imaging is likely to increase. In this review, the authors discuss the various reconstruction techniques available, followed by a discussion of the clinical applications.

Radiation exposure and image quality in chest CT examinations.

OBJECTIVE: The purpose of this study was to determine how changes in radiographic tube current affect patient dose and image quality in unenhanced chest CT examinations. SUBJECTS AND METHODS: Ten sets of CT images were obtained from patients undergoing CT-guided chest biopsies. For each patient, six images of the same region were obtained at settings between 40 and 280 mAs. CT data were used to reconstruct tomographic sections with a field of view limited to the normal contralateral lung. Images were printed using lung and mediastinal image display settings. Image quality was determined by asking radiologists to assess the perceived level of mottle in CT images. Five chest radiologists ranked the relative image quality of six images. Patient effective doses were computed for chest CT examinations performed at each milliampere-second setting. Radiologists indicated whether any perceived improvement of image quality at the higher radiation exposures was worth the additional radiation dose. RESULTS: The differences in quality of chest CT images generated at greater than or equal to 160 mAs were negligible. Reducing the radiographic technique factor below 160 mAs resulted in a perceptible reduction in image quality. Differences in CT image quality for radiographic techniques between 120 and 280 mAs were deemed to be insufficient to justify any additional patient exposure. However, the use of 40 mAs results in an inferior image quality that would justify increased patient exposure. CONCLUSION: Radiographic techniques for unenhanced chest CT examinations can be reduced from 280 to 120 mAs without compromising image quality.

Loss of imprinting of insulin-like growth factor-II in Wilms' tumor commonly involves altered methylation but not mutations of CTCF or its binding site.

Loss of imprinting (LOI) is the most common molecular abnormality in Wilms' tumor (WT), other embryonal cancers, and most other tumor types. LOI in WT involves activation of the normally silent maternal allele of the insulin-like growth factor-II (IGF2) gene, silencing of the normally active maternal allele of the H19 gene, and aberrant methylation of a differentially methylated region (DMR) upstream of the maternal copy of H19. Recently, the transcription factor CTCF, which binds to the H19 DMR, has been implicated in the maintenance of H19 and IGF2 imprinting. Here, we show that mutations in the CTCF gene or in the H19 DMR do not occur at significant frequency in WT, nor is there transcriptional silencing of CTCF. We also confirm that methylation of the H19 DMR in WT with LOI includes the CTCF core consensus site. However, some WTs with normal imprinting of IGF2 also show aberrant methylation of CTCF binding sites, indicating that methylation of these sites is necessary but not sufficient for LOI in WT.

Targeted disruption of the Kvlqt1 gene causes deafness and gastric hyperplasia in mice.

The KvLQT1 gene encodes a voltage-gated potassium channel. Mutations in KvLQT1 underlie the dominantly transmitted Ward-Romano long QT syndrome, which causes cardiac arrhythmia, and the recessively transmitted Jervell and Lange-Nielsen syndrome, which causes both cardiac arrhythmia and congenital deafness. KvLQT1 is also disrupted by balanced germline chromosomal rearrangements in patients with Beckwith-Wiedemann syndrome (BWS), which causes prenatal overgrowth and cancer. Because of the diverse human disorders and organ systems affected by this gene, we developed an animal model by inactivating the murine Kvlqt1. No electrocardiographic abnormalities were observed. However, homozygous mice exhibited complete deafness, as well as circular movement and repetitive falling, suggesting imbalance. Histochemical study revealed severe anatomic disruption of the cochlear and vestibular end organs, suggesting that Kvlqt1 is essential for normal development of the inner ear. Surprisingly, homozygous mice also displayed threefold enlargement by weight of the stomach resulting from mucous neck cell hyperplasia. Finally, there were no features of BWS, suggesting that Kvlqt1 is not responsible for BWS.

Electron flow between photosystem II and oxygen in chloroplasts of photosystem I-deficient algae is mediated by a quinol oxidase involved in chlororespiration.

In Chlamydomonas reinhardtii mutants deficient in photosystem I because of inactivation of the chloroplast genes psaA or psaB, oxygen evolution from photosystem II occurs at significant rates and is coupled to a stimulation of oxygen uptake. Both activities can be simultaneously monitored by continuous mass spectrometry in the presence of (18)O(2). The light-driven O(2) exchange was shown to involve the plastoquinone pool as an electron carrier, but not cytochrome b(6)f. Photosystem II-dependent O(2) production and O(2) uptake were observed in isolated chloroplast fractions. Photosystem II-dependent oxygen exchange was insensitive to a variety of inhibitors (azide, carbon monoxide, cyanide, antimycin A, and salicylhydroxamic acid) and radical scavengers. It was, however, sensitive to propyl gallate. From inhibitors effects and electronic requirements of the O(2) uptake process, we conclude that an oxidase catalyzing oxidation of plastoquinol and reduction of oxygen to water is present in thylakoid membranes. From the sensitivity of flash-induced O(2) exchange to propyl gallate, we conclude that this oxidase is involved in chlororespiration. Clues to the identity of the protein implied in this process are given by pharmacological and immunological similarities with a protein (IMMUTANS) identified in Arabidopsis chloroplasts.

Chest radiographic features of engraftment syndrome.

About the time of hematopoietic engraftment, patients undergoing autologous hematopoietic stem cell transplantation in the form of peripheral blood stem cell transplantation (PSCT) may develop an "engraftment syndrome" that includes fever, skin rash, and capillary leak. This condition is usually self-limited, as opposed to other early complications of bone marrow transplantation such as infection and drug reactions. This article describes the chest radiographic manifestations of engraftment syndrome. The medical records and chest radiographs of 50 consecutive breast cancer patients who underwent PSCT were retrospectively reviewed. Engraftment syndrome was diagnosed if the expected clinical findings occurred at the time of engraftment of neutrophils and no other cause was identified. The chest radiographs were correlated with the clinical course. Sixteen patients were found to have engraftment syndrome (32%). Of these, eight had abnormal radiographs. Radiographic findings consisted of pleural effusions and interstitial pulmonary edema. No patient progressed to adult respiratory distress syndrome. Interstitial pulmonary edema and pleural effusions were observed in association with engraftment syndrome from PSCT. Correlation of these findings with clinical history and neutrophil count is important so that engraftment syndrome can be distinguished from other causes of fever.

Lemierre syndrome: forgotten but not extinct--report of four cases.

Four cases of Lemierre syndrome are reported in which metastatic abscesses resulted from septic thrombosis of the internal jugular vein secondary to bacterial pharyngitis. While chest radiographic findings were nonspecific, results of computed tomography (CT) of the thorax in each case were highly suggestive of septic pulmonary emboli. Internal jugular venous thrombosis was demonstrated at ultrasonography and contrast material-enhanced CT.

Inhibition of chlororespiration by myxothiazol and antimycin A in Chlamydomonas reinhardtii.

Myxothiazol and antimycin A are shown to suppress the oxygen transient previously attributed to the flash-induced inhibition of chlororespiration in Chlamydomonas reinhardtii (Peltier et al. 1987, Biochim Biophys Acta 893: 83-90). However, these two compounds do not affect the photosynthetic electron transport chain as inferred by the insensitivity of the CO2-dependent photosynthetic O2 evolution and of the flash-induced electrochromic effect. Chlorophyll fluorescence induction measurements carried out in dark-adapted cells of a mutant of Chlamydomonas lacking photosystem 1, show that myxothiazol and antimycin A significantly increase the redox state of the photosystem 2 acceptors. We conclude from these results that chlororespiration is inhibited by myxothiazol and antimycin A and that the site of inhibition is located on the dark oxidation pathway of the plastoquinone pool. This inhibition is interpreted through the involvement of a myxothiazol and antimycin A sensitive cytochrome in the chlororespiratory chain.