Expression of c-fos in regions of the basal limbic forebrain following intracerebroventricular corticotropin-releasing factor in unstressed or stressed male rats.

Corticotropin-releasing factor has an integrative role on the behavioral, endocrine and autonomic responses to stress. Immediate-early gene (c-fos) expression was used to determine patterns of neural activity in the limbic system following i.c.v. infusion of corticotropin-releasing factor. Either 250 or 1000 pmol corticotropin-releasing factor infused into the lateral ventricle of precannulated and handled male rats resulted in marked c-fos expression 60 or 120 min later in localized regions of the basal forebrain, including the ventrolateral septum, the dorsal and medial parvicellular divisions of the paraventricular nucleus, the central nucleus of the amygdala, and dorsal bed nucleus of the stria terminalis. Pre-infusion of alpha-helical corticotropin-releasing factor (2500 pmol), a competitive corticotropin-releasing factor antagonist of corticotropin-releasing factor, had no effect on immediate-early gene expression alone but reduced that elicited by exogenous i.c.v. corticotropin-releasing factor (250 pmol)--in some areas to control levels. Fifteen minutes of restraint stress, a situation in which corticotropin-releasing factor is released endogenously, also activated c-fos expression in a pattern that resembled corticotropin-releasing factor infusions but was not identical. There was enhanced expression in the dorsal and medial areas of the paraventricular nucleus, but not its magnocellular region, and increased expression in the ventrolateral septum; however, there was no detectable response on the central amygdala. Preinfusion of alpha-helical corticotropin-releasing factor (2500 pmol) had no significant effect on stress-induced c-fos expression in the ventrolateral septum or paraventricular nucleus. This suggests that corticotropin-releasing factor release may form only a part of the central neurochemical response to restraint stress. Rats given i.c.v. corticotropin-releasing factor (250 pmol) before restraint stress showed additive effects on c-fos in the ventrolateral septum but not in the paraventricular nucleus; the central nucleus of the amygdala reacted as if corticotropin-releasing factor alone had been infused. Corticosterone levels were raised by both stress and corticotropin-releasing factor, but pretreatment with alpha-helical corticotropin-releasing factor reduced them after either procedure, which correlates with c-fos expression in the paraventricular nucleus and ventrolateral septum. These results show that corticotropin-releasing factor induces a specific pattern of c-fos expression in localized regions of the amygdala, hypothalamus and septum, which may indicate a corresponding pattern of neural activation. Restraint, one form of stress, activates c-fos in a similar but not identical manner, suggesting that corticotropin-releasing factor may not be the only neuropeptide involved in the response to this stressor.(ABSTRACT TRUNCATED AT 400 WORDS)     

Extracorporeal treatment of thrombotic microangiopathy: a ten year experience.

We reviewed 24 episodes of thrombotic microangiopathy (TMA) representing 22 patients from July 1989 to July 1998. Nine cases presented with a community acquired (CA group) thrombotic thrombocytopenic purpura or hemolytic uremic syndrome (TTP/HUS), 3 cases were related to pregnancy (P group), 10 cases were compatible with TMA after bone marrow transplantation or chemotherapy (BMT/C group), and 2 cases had a background of scleraderma (SC group). Twenty episodes were treated exclusively with therapeutic plasma exchange (TPE) using fresh frozen plasma (FFP) replacement. In the BMT/C group, 4 patients underwent immunoadsorption with the Prosorba protein A column in addition to TPE. The CA, P, and SC groups had favorable outcomes with 78% (7 of 9), 100% (3 of 3), and 100% (2 of 2) survival, respectively. Despite intensive therapy, there was only 1 survivor in the BMT/C group (1 of 10). Successful outcome required up to 57 TPE treatments. We could not document any benefit to immunoadsorption with the Prosorba protein A column.     

Differences between jejunal myoelectric activity after a meal and during phase 2 of migrating motor complexes in healthy humans

Using an intraluminal probe with six pairs of annular electrodes, the myoelectric activity of the proximal jejunum was recorded during 48-hr sessions in 16 healthy volunteers receiving evening and noon meals (1000 kcal) and breakfast (400 kcal). In 10 subjects receiving no drug, the characteristics of the migrating motor complexes (period, duration of each phase, velocity of propagation of phase 3, duration of the postprandial disruption) varied markedly between subjects but were relatively constant from the first to the second day of recording. Single spike bursts propagated at a rate of 2–5 cm/sec, clusters of 3–10 spike bursts propagated at a rate of 0.5–1 cm/sec, and similar clusters recurring repetitively each 1.5–2 min were observed after the meals and very rarely in the fasted state during phase 2 of nocturnal migrating motor complexes. In six subjects, oral administration of codeine (50 mg) 1 hr before a meal induced migrating motor complexes in the postprandial state, with characteristics similar to that observed in the fasted state except a longer duration of phase 2. Single spike bursts and isolated and repetitive clusters of spike bursts were observed during phase 2 of the codeine-induced migrating motor complexes and after meals preceded by placebo, but very rarely during the phase 2 of nocturnal (fasted state) migrating motor complexes. It is concluded that the patterns of jejunal contractions consisting of propagated single spike bursts and isolated or repetitive spike bursts characterize the postprandial state in healthy humans and are dependent upon digesta flow.This work was presented in part at the Vth European Symposium on Gastrointestinal Motility, June 13–16, 1990, Augsburg, Germany, and has appeared in abstract form in theJournal of Gastrointestinal Motility 2: 161, 1990.     

A prognostic test for adenocarcinoma of the lung from gene expression profiling data.

Until recently, it has been impossible to determine which patients with resected stage I lung cancer are among the 30% who will die of metastatic cancer within 5 years of surgery. Bioinformatics tools applied to lung cancer expression profiling data have identified prognostic genes that have been used to develop predictor models, but thus far, these models have not been incorporated into routine clinical use because of their inherent complexity and requirement for relatively large numbers of genes. We have used ratios of gene expression to overcome these limitations. Here, we evaluate the ability of this technique to identify patients with stage I lung adenocarcinoma at risk for recurrence. We derived candidate ratio-based tests from analysis of 36 stage I lung adenocarcinoma samples using previously published expression profiling data. Eleven of these tests were identified for additional study and assessed for classification accuracy in an independent set of 60 stage I lung adenocarcinoma samples. We then evaluated the optimal ratio-based test in the independent samples using Kaplan-Meier survival analysis. Finally, we examined the ability of this test to predict outcome in a set of 97 stage I breast adenocarcinoma. We found that subsets of the independent lung cancer samples predicted to be associated with either good or poor outcome using the optimal ratio-based test differed significantly (P=0.0056) in terms of survival with a classification accuracy of 74% (P=0.0043, Fisher's exact test). When this test was applied to stage II and III lung cancers, most specimens were classified as poor outcome cancers. Interestingly, we found that the same test significantly (P=0.0417) predicted recurrence of stage I breast tumors, suggesting that at least some of the marker genes we identified may have generalized prognostic significance for adenocarcinoma. Our results provide additional evidence that expression ratios are highly accurate in predicting cancer recurrence and may be used in a simple test to predict response to surgical therapy in early-stage lung adenocarcinoma.     

Secular changes in body fat patterning in children and adolescents of Zaragoza (Spain), 1980-1995.

OBJECTIVE: To examine whether children and adolescents of Zaragoza (Spain) are becoming centrally obese to a greater extent than would be predicted by their relative body weights. DESIGN: Two cross-sectional surveys conducted in 1980 and 1995. SUBJECTS: The samples selected for the 1980 and 1995 surveys comprised 1553 and 701 male children, and 1311 and 659 female children, respectively, with ages ranging from 6.0 to 14.9 y. MEASUREMENTS: We measured four skinfold thicknesses (biceps, triceps, subscapular, suprailiac) and calculated some indices of fat patterning: triceps/subscapular skinfolds (T/SS), biceps+triceps/subscapular+suprailiac skinfolds (B+T/SS+SI), and (subscapular+suprailiac/biceps+triceps+subscapular+suprailiac skinfolds)x100 (trunk-to-total skinfolds %). RESULTS: In males, B+T/SS+SI, and trunk-to-total skinfolds % showed a significant trend to a central pattern of fat distribution from 1980 to 1995, at the ages of 6.5-11.5 y. In females, B+T/SS+SI and trunk-to-total skinfolds % showed a significant trend to a central pattern of fat distribution from 1980 to 1995, at the ages of 6.5 and 7.5 y. Similar results were obtained when we adjusted for BMI values. CONCLUSION: We have observed a trend to a central pattern of adipose tissue distribution, especially in males and at the youngest ages studied (6-11 y in males, and 6-7 y in females). These observations were independent of trends in BMI.     

Social stress does not interact with paradoxical sleep deprivation-induced memory impairment.

Extensive evidence has linked both paradoxical sleep (PS) and stress to memory processing. The purpose of the present study was to examine the effect of social instability stress on memory and to verify whether this stress interferes with the amnesic effect of PS deprivation using the modified multiple platform method. In addition to the PS-deprived group (put onto narrow platforms inside the deprivation tanks) two control groups were used: one of them remained in its home-cages and the other was placed inside the deprivation tanks, onto a grid that contained large platforms on it. All groups were subdivided in socially stable and unstable conditions. Immediately after 96 h of sleep deprivation, the animals were trained in three different memory tasks: inhibitory avoidance, classical fear conditioning to a discrete stimulus and contextual fear conditioning. Twenty-four hours after training, the animals were tested in order to assess task acquisition. The results showed that social instability did not impair the performance of animals nor interacted with PS deprivation in any of the tasks. Grid control animals presented a selective impairment in the inhibitory avoidance task and contextual, but not in the classical, fear conditioning task, compared to cage control rats. This finding could be due to the stress to which grid control animals were exposed (humidity and luminosity) during the manipulation period. PS-deprived animals exhibited poorer performance than the other groups in all tasks. As they also showed an increased threshold to shock-induced vocalisation, but not to flinch response, it is not possible to completely rule out a decreased response to noxious stimulation as a contributing factor for the present results with PS deprivation.     

ERRATUM

MT1-MMP correlates with MMP-2 activation potential seen after epithelial to mesenchymal transition in human breast carcinoma cells. Volume 15 Number 2. On p. 117, Figure 3, the incorrect figure was mistakenly placed during production. We apologise for the error and reproduce the correct figure here.Evaluation of flourometric and zymographic methods as activity assays for stromelysins and gelatinases. Volume 15 Number 1. On pp. 28, 29 and 30, the incomplete figures 1, 2, 3 and 4 were mistakenly placed during production. We apologise for the errors and reproduce the corrected figures here.     

Relationship between mast cell degranulation and jejunal myoelectric alterations in intestinal anaphylaxis in rats.

The effects of two degranulators of mast cells and intestinal anaphylaxis on jejunal myoelectric activity were compared in rats fasted for 15 hours. Attempts to antagonize the motility changes were performed using antagonists of histamine and serotonin and a cyclooxygenase and lipoxygenase inhibitor. Hooded Lister rats were chronically fitted with electrodes implanted in the jejunal wall. A group of rats was sensitized to egg albumin and challenged 14 days later by intraduodenal infusion of antigen. Sensitized animals had serum titers greater than or equal to 1:64. The other group was administered with mast cells degranulators. Both 48/80 (1 mg/kg), a degranulator of connective mast cells, and bromolasalocid (2 mg/kg), acting on connective and mucosal mast cells, induced a phase of total spiking inhibition followed by a progressive irregular spiking activity until the recovery of migrating myoelectric complex pattern (about 3 hours after injection). In contrast, antigen challenge disrupted the migrating myoelectric complex pattern, which was replaced by a peculiar pattern characterized by propagated spike burst, lasting 98 +/- 11.3 minutes. Chlorpheniramine (1 mg/kg) antagonized only the inhibitory phase induced by degranulators and was ineffective on the intestinal anaphylaxis-induced motor changes. Methysergide (1 mg/kg) and indomethacin (5 mg/kg) significantly reduced the degranulator effects as well as the anaphylaxis-induced alterations of intestinal motility. It is concluded that anaphylaxis-induced motor disturbances are relevant to mucosal mast cell degranulation involving 5-hydroxytryptamine and arachidonic acid derivative products, whereas histamine release appears to be a minor component.