Gene expression differentiation in the reproductive tissues of Drosophila willistoni subspecies and their hybrids.

Early lineage diversification is central to understand what mutational events drive species divergence. Particularly, gene misregulation in interspecific hybrids can inform about what genes and pathways underlie hybrid dysfunction. In Drosophila hybrids, how regulatory evolution impacts different reproductive tissues remains understudied. Here, we generate a new genome assembly and annotation in Drosophila willistoni and analyse the patterns of transcriptome divergence between two allopatrically evolved D. willistoni subspecies, their male sterile and female fertile hybrid progeny across testis, male accessory gland, and ovary. Patterns of transcriptome divergence and modes of regulatory evolution were tissue-specific. Despite no indication for cell-type differences in hybrid testis, this tissue exhibited the largest magnitude of expression differentiation between subspecies and between parentals and hybrids. No evidence for anomalous dosage compensation in hybrid male tissues was detected nor was a differential role for the neo- and the ancestral arms of the D. willistoni X chromosome. Compared to the autosomes, the X chromosome appeared enriched for transgressively expressed genes in testis despite being the least differentiated in expression between subspecies. Evidence for fine genome clustering of transgressively expressed genes suggests a role of chromatin structure on hybrid gene misregulation. Lastly, transgressively expressed genes in the testis of the sterile male progeny were enriched for GO terms not typically associated with sperm function, instead hinting at anomalous development of the reproductive tissue. Our thorough tissue-level portrait of transcriptome differentiation between recently diverged D. willistoni subspecies and their hybrids provides a more nuanced view of early regulatory changes during speciation.

Factors controlling the reactivity of divalent metal ions towards pheophytin a.

In this study, we evaluate the factors which determine the reactivity of divalent metal ions in the spontaneous formation of metallochlorophylls, using experimental and computational approaches. Kinetic studies were carried out using pheophytin a in reactions with various divalent metal ions combined with non- or weakly-coordinative counter ions in a series of organic solvents. To obtain detailed insights into the solvent effect, the metalations with the whole set of cations were investigated in three solvents and with Zn2+ in seven solvents. The reactions were monitored using electronic absorption spectroscopy and the stopped-flow technique. DFT calculations were employed to shed light on the role of solvent in activating the metal ions towards porphyrinoids. This experimental and computational analysis gives detailed information regarding how the solvent and the counter ion assist/hinder the metalation reaction as activators/inhibitors. The metalation course is dictated to a large extent by the reaction medium, via either the activation or deactivation of the incoming metal ion. The solvent may affect the metalation in several ways, mainly via H-bonding with pyrrolenine nitrogens and the activation/deactivation of the incoming cation. It also seems to affect the activation enthalpy by causing slight conformational changes in the macrocyclic ligand. These new mechanistic insights contribute to a better understanding of the "metal-counterion-solvent" interplay in the metalation of porphyrinoids. In addition, they are highly relevant to the mechanisms of metalation reactions catalyzed by chelatases and explain the differences between the insertion of Mg2+ and other divalent cations.

Functional divergence of the miRNA transcriptome at the onset of Drosophila metamorphosis.

MicroRNAs (miRNAs) are endogenous RNA molecules that regulate gene expression posttranscriptionally. To date, the emergence of miRNAs and their patterns of sequence evolution have been analyzed in great detail. However, the extent to which miRNA expression levels have evolved over time, the role different evolutionary forces play in shaping these changes, and whether this variation in miRNA expression can reveal the interplay between miRNAs and mRNAs remain poorly understood. This is especially true for miRNA expressed during key developmental transitions. Here, we assayed miRNA expression levels immediately before (≥18BPF [18 h before puparium formation]) and after (PF) the increase in the hormone ecdysone responsible for triggering metamorphosis. We did so in four strains of Drosophila melanogaster and two closely related species. In contrast to their sequence conservation, approximately 25% of miRNAs analyzed showed significant within-species variation in male expression levels at ≥18BPF and/or PF. Additionally, approximately 33% showed modifications in their pattern of expression bias between developmental timepoints. A separate analysis of the ≥18BPF and PF stages revealed that changes in miRNA abundance accumulate linearly over evolutionary time at PF but not at ≥18BPF. Importantly, ≥18BPF-enriched miRNAs showed the greatest variation in expression levels both within and between species, so are the less likely to evolve under stabilizing selection. Functional attributes, such as expression ubiquity, appeared more tightly associated with lower levels of miRNA expression polymorphism at PF than at ≥18BPF. Furthermore, ≥18BPF- and PF-enriched miRNAs showed opposite patterns of covariation in expression with mRNAs, which denoted the type of regulatory relationship between miRNAs and mRNAs. Collectively, our results show contrasting patterns of functional divergence associated with miRNA expression levels during Drosophila ontogeny.

Functional evidence that a recently evolved Drosophila sperm-specific gene boosts sperm competition.

In many species, both morphological and molecular traits related to sex and reproduction evolve faster in males than in females. Ultimately, rapid male evolution relies on the acquisition of genetic variation associated with differential reproductive success. Many newly evolved genes are associated with novel functions that might enhance male fitness. However, functional evidence of the adaptive role of recently originated genes in males is still lacking. The Sperm dynein intermediate chain multigene family, which encodes a Sperm dynein intermediate chain presumably involved in sperm motility, originated from complex genetic rearrangements in the lineage that leads to Drosophila melanogaster within the last 5.4 million years since its split from Drosophila simulans. We deleted all the members of this multigene family resident on the X chromosome of D. melanogaster by chromosome engineering and found that, although the deletion does not result in a reduction of progeny number, it impairs the competence of the sperm in the presence of sperm from wild-type males. Therefore, the Sperm dynein intermediate chain multigene family contributes to the differential reproductive success among males and illustrates precisely how quickly a new gene function can be incorporated into the genetic network of a species.

KCH, the German preoperative score for isolated coronary artery bypass surgery: is it superior to the logistic EuroSCORE?

BACKGROUND: The accuracy of the logistic EuroSCORE in different patient populations has been questioned. Using the German registry database, the KoronarCHirurgie (KCH) score was introduced as a preoperative risk stratification tool specifically for patients who undergo isolated coronary artery bypass surgery in Germany. However, no direct statistical comparison of this score with the well-established logistic EuroSCORE has been previously performed. The aim of this study was to validate the preoperative German KCH score and to compare it to the logistic EuroSCORE for all coronary artery bypass surgery patients as well as for on-pump and off-pump subgroups. METHODS: We prospectively included all consecutive adult patients admitted to our department between January 1, 2007 and December 31, 2008, who underwent isolated coronary artery bypass surgery. The logistic EuroSCORE and the KCH-3.0 were calculated on admission to hospital. The outcome was defined as 30-day mortality. We performed calibration (Hosmer-Lemeshow test and Anderson-Grunkemeier Observed/Expected "O/E" mortality ratio) and discrimination (receiver operating characteristic "ROC" test) analyses of both scores. The accuracy of the scores was compared using DeLong's test. RESULTS: A total of 1461 patients (23.96 % females, mean age 66.94 ± 9.43 years) were included. The 30-day mortality rate was 2.87 %. The two models were comparable with regard to the prediction of an individual patient's risk of mortality in the whole study population and in the on-pump and off-pump subgroups (according to the ROC test and DeLong's test). Overall, there was no significant difference between observed and expected mortality according to the Hosmer-Lemeshow test ( P > 0.05). However, the KCH-3.0 was far less likely to overpredict mortality than the logistic EuroSCORE, as demonstrated by the observed mortality/expected mortality (O/E) ratios. The O/E ratio was 0.32 for the logistic EuroSCORE and 0.74 for the KCH-3.0. For the on-pump subgroup the O/E ratios were 0.37 and 0.80, respectively, and 0.24 and 0.63, respectively, for the off-pump subgroup. CONCLUSIONS: The KCH-3.0 is more reliable than the logistic EuroSCORE as a preoperative mortality prediction score for patients undergoing isolated coronary artery bypass surgery, providing predicted mortality rates that are closer to the actual mortality rates with a lower overprediction of mortality.

Coexistence of antiferromagnetic and spin cluster glass order in the magnetoelectric relaxor multiferroic PbFe 0.5 Nb 0.5 O3.

The coexistence of cluster glass with long-range antiferromagnetic order in the relaxor ferroelectric PbFe 0.5 Nb 0.5 O3 is elucidated. While the transition at T(N) = 153 K on the infinite antiferromagnetic cluster induces 3m symmetry with large EH2 magnetoelectric response, the disconnected subspace of isolated Fe3+ ions and finite clusters accommodates the cluster glass below T(g) = 10.6 K with field-induced m' symmetry and EH-type magnetoelectric response. Critical slowing-down, memory and rejuvenation after aging, occurrence of a de Almeida-Thouless phase line, and stretched exponential relaxation of remanence corroborate the glass nature.

Ephrin-A5 potentiates netrin-1 axon guidance by enhancing Neogenin availability.

Axonal growth cones are guided by molecular cues in the extracellular environment. The mechanisms of combinatorial integration of guidance signals at the growth cone cell membrane are still being unravelled. Limb-innervating axons of vertebrate spinal lateral motor column (LMC) neurons are attracted to netrin-1 via its receptor, Neogenin, and are repelled from ephrin-A5 through its receptor EphA4. The presence of both cues elicits synergistic guidance of LMC axons, but the mechanism of this effect remains unknown. Using fluorescence immunohistochemistry, we show that ephrin-A5 increases LMC growth cone Neogenin protein levels and netrin-1 binding. This effect is enhanced by overexpressing EphA4 and is inhibited by blocking ephrin-A5-EphA4 binding. These effects have a functional consequence on LMC growth cone responses since bath addition of ephrin-A5 increases the responsiveness of LMC axons to netrin-1. Surprisingly, the overexpression of EphA4 lacking its cytoplasmic tail, also enhances Neogenin levels at the growth cone and potentiates LMC axon preference for growth on netrin-1. Since netrins and ephrins participate in a wide variety of biological processes, the enhancement of netrin-1 signalling by ephrins may have broad implications.

Adropin, nesfatin-1 and angiotensin II receptor expression in the abdominal aorta in ovariectomized rats after nesfatin-1 treatment.

The aim of the research was to assess the effect of nesfatin-1 on the structure, flexibility parameters, and expression of adropin, nesfatin-1, and angiotensin II receptor type 1 (AT1R) in the abdominal aorta in ovariectomized rats. Fragments of aortas were collected after euthanasia of female sham-operated (CONT) and ovariectomized Wistar rats (EXP), which were administered intraperitoneal injection of physiological saline (CONT, n = 7; EXP-O, n = 7) or nesfatin-1 (EXP-N, n = 7) in an amount of 2 µg/kg b.w. once a day for 8 weeks. The samples of aortas were collected for measurement of elasticity as well as histomorphometric, immunohistochemical, FTIR, and Raman spectroscopy analysis. The ovariectomy caused a significant increase in the thickness of the total wall and its particular layers in the aorta, in comparison to the CONT and EXP-N groups. However, the ovariectomy led to a decrease in the amount of elastin, collagen (mature, immature collagen, collagen maturity ratio 1660 - 1690 cm-1), and amides, with a simultaneous increase in lipids, especially in the tunica intima-media of the abdominal aorta compared to the other groups. The use of nesfatin-1 significantly increased the amount of collagen, elastin and amides with a simultaneous decrease in the amount of lipids and the expression of AT1R, adropin and nesfatin-1 in the abdominal aorta of ovariectomized rats. In conclusion, our study showed that the ovariectomy surgery induced changes in the abdominal aorta wall characteristic for aging females. Application of nesfatin-1 may prevent the negative consequences in the vessel wall structure in females in conditions of estrogen deficiency and prevent atherosclerotic changes in the cardiovascular system.

Neuromusculin, a Drosophila gene expressed in peripheral neuronal precursors and muscles, encodes a cell adhesion molecule.

To unravel the molecular mechanisms of peripheral nervous system differentiation in Drosophila, we have screened for and identified genes that are expressed in sensory mother cells. Here, we describe a novel gene, neuromusculin (nrm), that is expressed in sensory mother cells and developing muscles. nrm encodes a member of the immunoglobulin superfamily. Immunoblots of Schneider 2 cells transfected with an nrm cDNA indicate that Nrm is present in a membrane-associated form and a secreted form. Cell aggregation assays suggest that Nrm is a homophilic cell adhesion molecule that is secreted or released after proteolysis, a mechanism that to our knowledge has not been described for immunoglobulin-like molecules. Genetic analyses indicate that nrm is an essential gene required for larval viability. We propose that Nrm may play a role as a cell adhesion molecule in clustering cells of the peripheral nervous system, neuronal fasciculation, and/or pathfinding.

Responses to iron limitation in Hordeum vulgare L. as affected by the atmospheric CO2 concentration.

Elevated atmospheric CO2 treatments stimulated biomass production in Fe-sufficient and Fe-deficient barley plants, both in hydroponics and in soil culture. Root/shoot biomass ratio was increased in severely Fe-deficient plants grown in hydroponics but not under moderate Fe limitation in soil culture. Significantly increased biomass production in high CO2 treatments, even under severe Fe deficiency in hydroponic culture, indicates an improved internal Fe utilization. Iron deficiency-induced secretion of PS in 0.5 to 2.5 cm sub-apical root zones was increased by 74% in response to elevated CO2 treatments of barley plants in hydroponics but no PS were detectable in root exudates collected from soil-grown plants. This may be attributed to suppression of PS release by internal Fe concentrations above the critical level for Fe deficiency, determined at final harvest for soil-grown barley plants, even without additional Fe supply. However, extremely low concentrations of easily plant-available Fe in the investigated soil and low Fe seed reserves suggest a contribution of PS-mediated Fe mobilization from sparingly soluble Fe sources to Fe acquisition of the soil-grown barley plants during the preceding culture period. Higher Fe contents in shoots (+52%) of plants grown in soil culture without Fe supply under elevated atmospheric CO2 concentrations may indicate an increased efficiency for Fe acquisition. No significant influence on diversity and function of rhizosphere-bacterial communities was detectable in the outer rhizosphere soil (0-3 mm distance from the root surface) by DGGE of 16S rRNA gene fragments and analysis of marker enzyme activities for C-, N-, and P-cycles.

[Descending necrotizing mediastinitis : Treatment concept with focus on thoracic surgery]. / Deszendierende nekrotisierende Mediastinitis : Therapiekonzept aus thoraxchirurgischer Sicht.

BACKGROUND: Descending necrotizing mediastinitis (DNM) originates from odontogenic or oropharyngeal infections which spread along preformed cervicothoracic spaces into the mediastinum and requires emergency multidisciplinary treatment. MATERIAL AND METHODS: A total of seven patients were diagnosed with DNM based on typical radiological features in a cervicothoracic computed tomography (CT) scan and subsequently underwent standardized transcervical and open transthoracic radical debridement. RESULTS: The initially detected polymicrobial spectrum of pathogens was dominated by streptococci followed by enterobacteriae. After calculated antibiotic treatment a shift in the spectrum of pathogens was noted and in particular a mycotic superinfection occurred in 43 % of the cases. Anterolateral thoracotomy was performed for radical removal of tissue necrosis and mediastinothoracic drainage extending to the posterior mediastinum was placed. In selected cases, cervico-mediastino-thoracic tubes were transmediastinally placed by the rendevouz technique either in the previsceral or retrovisceral mediastinal space. Despite predominantly advanced mediastinitis (Endo classification type II B) in this patient cohort, the mortality only reached 14 %. CONCLUSION: Rapid diagnosis, anatomical knowledge, understanding of the progression of infections as well as critical care, antimicrobial treatment and multidisciplinary radical surgical therapy are paramount for successful treatment of DNM. We favor anterolateral thoracotomy as the standard open transthoracic approach to the mediastinum. Placement of cervico-mediastino-thoracic irrigation drains can help to limit DNM.

Promoter hypermethylation of SHOX2 and SEPT9 is a potential biomarker for minimally invasive diagnosis in adenocarcinomas of the biliary tract.

BACKGROUND: Biliary tract carcinoma (BTC) is a fatal malignancy which aggressiveness contrasts sharply with its relatively mild and late clinical presentation. Novel molecular markers for early diagnosis and precise treatment are urgently needed. The purpose of this study was to evaluate the diagnostic and prognostic value of promoter hypermethylation of the SHOX2 and SEPT9 gene loci in BTC. METHODS: Relative DNA methylation of SHOX2 and SEPT9 was quantified in tumor specimens and matched normal adjacent tissue (NAT) from 71 BTC patients, as well as in plasma samples from an independent prospective cohort of 20 cholangiocarcinoma patients and 100 control patients. Receiver operating characteristic (ROC) curve analyses were performed to probe the diagnostic ability of both methylation markers. DNA methylation was correlated to clinicopathological data and to overall survival. RESULTS: SHOX2 methylation was significantly higher in tumor tissue than in NAT irrespective of tumor localization (p < 0.001) and correctly identified 71% of BTC specimens with 100% specificity (AUC = 0.918; 95% CI 0.865-0.971). SEPT9 hypermethylation was significantly more frequent in gallbladder carcinomas compared to cholangiocarcinomas (p = 0.01) and was associated with large primary tumors (p = 0.01) as well as age (p = 0.03). Cox proportional hazard analysis confirmed microscopic residual tumor at the surgical margin (R1-resection) as an independent prognostic factor, while SHOX2 and SEPT9 methylation showed no correlation with overall survival. Elevated DNA methylation levels were also found in plasma derived from cholangiocarcinoma patients. SHOX2 and SEPT9 methylation as a marker panel achieved a sensitivity of 45% and a specificity of 99% in differentiating between samples from patients with and without cholangiocarcinoma (AUC = 0.752; 95% CI 0.631-0.873). CONCLUSIONS: SHOX2 and SEPT9 are frequently methylated in biliary tract cancers. Promoter hypermethylation of SHOX2 and SEPT9 may therefore serve as a minimally invasive biomarker supporting diagnosis finding and therapy monitoring in clinical specimens.

P-element mutations affecting embryonic peripheral nervous system development in Drosophila melanogaster.

The Drosophila embryonic peripheral nervous system (PNS) is an excellent model system to study the molecular mechanisms governing neural development. To identify genes controlling PNS development, we screened 2000 lethal P-element insertion strains. The PNS of mutant embryos was examined using the neural specific marker MAb 22C10, and 92 mutant strains were retained for further analysis. Genetic and cytological analysis of these strains shows that 42 mutations affect previously isolated genes that are known to be required for PNS development: longitudinals lacking (19), mastermind (15), numb (4), big brain (2), and spitz (2). The remaining 50 mutations were classified into 29 complementation groups and the P-element insertions were cytologically mapped. The mutants were classified in five major classes on the basis of their phenotype: gain of neurons, loss of neurons, organizational defects, pathfinding defects and morphological defects. Herein we report the preliminary phenotypic characterization of each of these complementation groups as well as the embryonic lacZ expression pattern of each P-element strain. Our analysis indicates that in most of the P-element insertion strains, the lacZ reporter gene is not expressed in the developing PNS.

IMRT for breast. a planning study.

BACKGROUND AND PURPOSE: To evaluate the performance of ten different treatment-planning systems when intensity modulated (IMRT) plans are designed for breast treatments that include the irradiation of the internal mammary chain. PATIENTS AND METHODS: A dataset of five patients (CT images and volumes of interest) was distributed to design IMRT plans on the ten systems. To minimise biases, the same geometry and clinical planning aims were imposed on the individual plans. Results were analysed in terms of dose distributions and dose volume histograms. RESULTS AND CONCLUSIONS: For target coverage, the volume receiving more than 95% of the prescribed dose ranged from 77% (OTP) to 91% (Eclipse and Pinnacle), the volume receiving more than 107% ranged from 3.3% (Hyperion) to 23.2% (OTP). The mean dose to ipsilateral lung ranged from 13 Gy (Eclipse) to 18 Gy (OTP). The volume of the contralateral breast receiving more than 10 Gy ranged from 3% (Pinnacle) to 26% (Precise). The volume of heart receiving more than 20 Gy ranged from 7% (Eclipse) to 47% (Precise), the maximum significant dose to heart ranged from approximately 27 Gy (XiO) to approximately 49 Gy (Precise). The maximum significant dose to healthy tissue ranged from approximately 51 Gy (Eclipse) to approximately 62 Gy (OTP). It was also possible to show that the treatment geometry proposed here enables to minimise contralateral breast irradiation while keeping minimal ipsilateral lung (or heart) involvement and satisfactory target coverage.

The field-matching problem as it applies to the peacock three dimensional conformal system for intensity modulation.

PURPOSE: Intensity modulated beam systems have been developed as a means of creating a high-dose region that closely conforms to the prescribed target volume while also providing specific sparing of organs at risk within complex treatment geometries. The slice-by-slice treatment paradigm used by one such system for delivering intensity modulated fields introduces regions of dose nonuniformity where each pair of treatment slices abut. A study was designed to evaluate whether or not the magnitude of the nonuniformity that results from this segmental delivery paradigm is significant relative to the overall dose nonuniformity present in the intensity modulation technique itself. An assessment was also made as to the increase in nonuniformity that would result if errors were made in indexing during treatment delivery. METHODS AND MATERIALS: Treatment plans were generated to simulate correctly indexed and incorrectly indexed treatments of 4, 10, and 18 cm diameter targets. Indexing errors of from 0.1 to 2.0 mm were studied. Treatment plans were also generated for targets of the same diameter but of lengths that did not require indexing of the treatment couch. RESULTS: The nonuniformity that results from the intensity modulation delivery paradigm is 11-16% for targets where indexing is not required. Correct indexing of the couch adds an additional 1-2% in nonuniformity. However, a couch indexing error of as little as 1 mm can increase the total nonuniformity to as much as 25%. All increases in nonuniformity from indexing are essentially independent of target diameter. CONCLUSIONS: The dose nonuniformity introduced by the segmental strip delivery paradigm is small relative to the nonuniformity present in the intensity modulation paradigm itself. A positioning accuracy of better than 0.5 mm appears to be required when implementing segmental intensity modulated treatment plans.

New bradykinin analogs in contraction of rat uterus.

In this study, we evaluated 20 of our previously synthesized peptides on isolated rat uterus by Holton's procedure with minor modifications, and compared their activity with that assessed previously by their ability to inhibit vasodepressor response to exogenous bradykinin (BK) in conscious rats. We used [D-Arg(0), Hyp(3), Thi(5, 8), (D-Phe)(7)]BK, the B(2) antagonist of Vavrek and Stewart as a model when designing our analogs. We observed that, in the case of the rat uterus test, the activity of peptides modified by acylation of the N-terminus with various bulky groups depends substantially on the chemical character of the substituent. We also learned that, contrary to previous examples, acylation of the N-terminus of antagonists, which contain a sterically restricted fragment in the C-terminal part, may not improve their antagonistic potencies. Besides an improved characterization of a series BK analogs, our studies have provided new information on the structure-activity relationship, which in turn may be of value in the design of more potent and selective bradykinin antagonists. The results of our studies appear to support the hypothesis of others about the presence of different subtypes of B(2) receptors in rat uterus and blood vessels.

Theoretical considerations of monitor unit calculations for intensity modulated beam treatment planning.

A treatment planning system to compute intensity modulated radiotherapy (IMRT) treatments using inverse planning was investigated. The system was designed to optimize the intensity patterns required to treat a specified target volume with specified normal structure constraints. A beam model that uses the convolution of pencil beams was used to compute the dose distributions. A multileaf collimator leaf-setting sequence intended to produce the intensity pattern was computed along with the monitor units required to deliver each of a number of fixed-gantry modulated fields. Computer calculations are commonly verified using an independent manual procedure. It is difficult to calculate treatment delivery monitor units for this variant of IMRT using manual methods. Since manual calculations are not feasible, it is important both to understand and to verify the calculation of treatment monitor units by the planning system algorithm. A formal analysis was made of the dose calculation model and the monitor unit calculation embedded in the algorithm. Experimental verification of the dose delivered by plans computed with the methodology demonstrated an agreement of better than 4% between the dose model and measurements.

Stimulation of corticosterone secretion by the selective 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) in the rat.

The selective 5-HT1A receptor agonist 8-OH-DPAT increased serum corticosterone concentration in rats in a dose-dependent manner. The synthetic corticoid dexamethasone lowered the serum corticosterone level and abolished its rise induced by 8-OH-DPAT. The corticosterone response to 8-OH-DPAT was also antagonized by spiperone, (+/-)- and (-)-pindolol and (+/-)-propranolol, all of which have been shown to have a high affinity for 5-HT1A receptors, though in most cases no complete blockade was found. A partial antagonism of the response was also observed after flumazenil, a benzodiazepine antagonist. On the other hand, the 5-HT1B receptor antagonist 21009, the 5-HT2 receptor antagonists ketanserin and pirenperone, the 5-HT3 receptor antagonist ICS 205-930, the alpha 2-adrenoceptor antagonists yohimbine and idazoxan, the beta-adrenoceptor blocker with no affinity to 5-HT1 receptors, atenolol, the dopaminergic antagonist pimozide, the histamine receptor blocker chloropyramine and the opiate receptor antagonist naloxone did not affect the hormonal response to 8-OH-DPAT. The 8-OH-DPAT-induced corticosterone secretion was not affected either in rats pretreated with p-chlorophenylalanine (PCPA, an inhibitor of tryptophan hydroxylase) or p-chloroamphetamine (PCA, a drug-inducing lesion of serotonergic nerve terminals). It is concluded that 8-OH-DPAT-induced increase in serum corticosterone concentration results from its action at a site different than the adrenal cortex and is mediated by postsynaptic 5-HT1A receptors, whereas other subtypes (5-HT1B, 5-HT2, 5-HT3) of 5-HT receptors do not participate in this response.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunogenicity of methylcholanthrene-induced tumors tested by draining lymph node assay in syngeneic rats.

The immunogenic properties of MC-induced and not metastasizing tumors were tested in inbred Wistar and August strains by the aid of lymphocyte stimulation in syngeneic draining lymph nodes in the comparison with the opposite ones. The lymphocyte stimulation was estimated in vitro by the spontaneous incorporation of 3HTdR. It was found that the peak of the first response of draining lymph nodes was noted on the 7th day after injection of syngeneic tumor cells. This antitumor response was specific because: 1. the second immunological response of draining lymph nodes to the same tumor cells developed earlier and was higher than the first response and 2. the rats previously immunized with MC-induced tumor, and then challenged with syngeneic sarcoma or syngeneic fibroblasts exhibited the lack of the second response and only some cross-reactivity was observed by the use of the other MC-induced sarcoma. MC-induced tumors appeared earlier and more frequently in August than in Wistar strain, the level of syngeneic draining lymph node response to immunogenic tumors was higher in August than in Wistar rats despite of the lack of difference between the percentages of immunogenic tumors arising in these two rat strains.

Basic concepts of CORVUS dose model.

Basic concepts of the dose model utilized in the CORVUS treatment planning system are reviewed. Following the Peacock delivery tool (MIMiC) by NOMOS Corporation, CORVUS "delivers" radiation to a patient by means of narrow x-ray beams (pencil beams), which are subject to lateral electronic disequilibrium. Dose data for such beams are difficult to obtain experimentally. Therefore, the CORVUS dose model uses analytically calculated (rather than experimentally measured) narrow-beam dose data. The model is based on the idea that physical parameters necessary to calculate absorbed dose in narrow x-ray beams can be derived from measured broad-beam dose data. Calculation of central-axis and off-axis absorbed dose in narrow beams as well as a method of generating beam profiles are described.