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In classical photogrammetric processing pipeline, the automatic tie point extraction plays a key role in the quality of achieved results. The image tie points are crucial to pose estimation and have a significant influence on the precision of calculated orientation parameters. Therefore, both relative and absolute orientations of the 3D model can be affected. By improving the precision of image tie point measurement, one can enhance the quality of image orientation. The quality of image tie points is under the influence of several factors such as the multiplicity, the measurement precision and the distribution in 2D images as well as in 3D scenes. In complex acquisition scenarios such as indoor applications and oblique aerial images, tie point extraction is limited while only image information can be exploited. Hence, we propose here a method which improves the precision of pose estimation in complex scenarios by adding a second iteration to the classical processing pipeline. The result of a first iteration is used as a priori information to guide the extraction of new tie points with better quality. Evaluated with multiple case studies, the proposed method shows its validity and its high potiential for precision improvement.

Dendritic cells (DCs) are essential in inducing adaptive immune responses against bacteria by expressing cytokines that skew T-cell responses toward protective Th17 cells. Although it is widely recognized that induction of these cytokines by DCs involves activation of multiple receptors, it is still incompletely characterized which combination of receptors specifically skews Th17-cell responses. Here we have identified a novel role for Fc gamma RIIa in promoting human Th17 cells. Activation of DCs by bacteria opsonized by serum IgG strongly promoted Th17 responses, which was Fc gamma RIIa-dependent and coincided with enhanced production of selected cytokines by DCs, including Th17-promoting IL-1 beta and IL-23. Notably, Fc gamma RIIa stimulation on DCs did not induce cytokine production when stimulated individually, but selectively amplified cytokine responses through synergy with TLR2, 4, or 5. Importantly, this synergy is mediated at 2 different levels. First, TLR-Fc gamma RIIa costimulation strongly increased transcription of pro-IL-1 beta and IL-23p19. Second, Fc gamma RIIa triggering induced activation of caspase-1, which cleaves pro-IL-1 beta into its bioactive form and thereby enhanced IL-1 beta secretion. Taken together, these data identified cross-talk between TLRs and Fc gamma RIIa as a novel mechanism by which DCs promote protective effector Th17-cell responses against bacteria. (Blood. 2012;120(1):112-121)

IL-17–producing CD4+ T helper (Th17) cells are important for immunity against extracellular pathogens and in autoimmune diseases. The factors that drive Th17 development in human remain a matter of debate. Here we show that, compared with classic CD28 costimulation, alternative costimulation via the CD5 or CD6 lymphocyte receptors forms a superior pathway for human Th17-priming. In the presence of the Th17-promoting cytokines IL-1β, IL-6, IL-23, and transforming growth factor-β (TGF-β), CD5 costimulation induces more Th17 cells that produce higher amounts of IL-17, which is preceded by prolonged activation of signal transducer and activator of transcription 3 (STAT3), a key regulator in Th17 differentiation, and enhanced levels of the IL-17–associated transcription factor retinoid-related orphan receptor-γt (ROR-γt). Strikingly, these Th17-promoting signals critically depend on CD5-induced elevation of IL-23 receptor (IL-23R) expression. The present data favor the novel concept that alternative costimulation via CD5, rather than classic costimulation via CD28, primes naive T cells for stable Th17 development through promoting the expression of IL-23R.

Cancer progression is facilitated by blood coagulation. Anticoagulants, such as Hirudin and low molecular weight heparins (LMWHs), reduce metastasis mainly by inhibition of thrombin formation and L- and P-selectin-mediated cell-cell adhesion. It is unknown whether the effects are dependent on cancer cell type. The effects of anticoagulants on tumor development of K1735 and B16 melanoma cells and CT26 colon cancer cells were investigated in mouse lung. Tumor load was determined noninvasively each week up to day 21 in all experiments using bioluminescence imaging. Effects of anticoagulants on tumor development of the three cell lines were correlated with the fibrin/fibrinogen content in the tumors, expression of tissue factor (TF), protease activated receptor (PAR)-1 and -4 and CD24, a ligand of L- and P-selectins. Hirudin inhibited tumor development of B16 cells in lungs completely but did not affect tumor growth of K1735 and CT26 cells. Low molecular weight heparin did not have an effect on K1735 melanoma tumor growth either. TF and PAR-4 expression was similar in the three cell lines. PAR-1 and CD24 were hardly expressed by K1735, whereas CT26 cells expressed low levels and B16 high levels of PAR-1 and CD24. Fibrin content of the tumors was not affected by LMWH. It is concluded that effects of anticoagulants are dependent on cancer cell type and are correlated with their CD24 and PAR-1 expression.

SummaryHow the development of antibacterial T helper 17 (Th17) cells is selectively promoted by antigen-presenting dendritic cells (DCs) is unclear. We showed that bacteria, but not viruses, primed human DCs to promote IL-17 production in memory Th cells through the nucleotide oligomerization domain 2 (NOD2)-ligand muramyldipeptide (MDP), a derivative of bacterial peptidoglycan. MDP enhanced obligate bacterial Toll-like receptor (TLR) agonist induction of IL-23 and IL-1, which promoted IL-17 expression in T cells. The role of NOD2 in this IL-23-IL-1-IL-17 axis could be confirmed in NOD2-deficient DCs, such as DCs from selected Crohn's disease patients. Thus, antibacterial Th17-mediated immunity in humans is orchestrated by DCs upon sensing bacterial NOD2-ligand MDP.

Il trattamento chirurgico del reflusso gastroesofageo ha visto le sue indicazioni evolvere grazie alla crescente efficacia del trattamento medico, che lascia alla chirurgia solo le forme recidivanti alla sospensione della terapia o i casi resistenti a quest’ultima. Una miglior conoscenza dell’anatomia funzionale del reflusso e delle diverse situazioni cliniche ha permesso di adattare l’atto chirurgico a tutte le situazioni. In questo articolo, dopo un ricordo dell’anatomia del giunto gastroesofageo e delle indagini preoperatorie, verranno descritte le principali tecniche eseguibili con accesso laparotomico in caso di reflusso gastroesofageo semplice o complicato. Nel reflusso gastroesofageo semplice l’analisi dei risultati pubblicati di queste diverse procedure permette di limitare la scelta alle fundoplicatio totali o parziali. Se le fundoplicatio complete garantiscono un’azione efficace e importante sul reflusso, le alterazioni funzionali postoperatorie sono piu frequenti che dopo fundoplicatio parziali. L’impiego dell’una o dell’altra dipende da scelte di scuola. Nelle forme piu complicate il ruolo della chirurgia e la tecnica realizzata dipendono dal tipo di complicazioni e devono essere discusse rispetto a ogni singola condizione clinica.

Las indicaciones del tratamiento quirurgico del reflujo gastroesofagico han evolucionado gracias a la eficacia creciente de los tratamientos medicos, que han limitado la cirugia a los casos que recidivan tras la interrupcion del tratamiento y a los que no responden a el. El mejor conocimiento de la anatomia funcional del reflujo y de las distintas situaciones clinicas ha permitido adaptar la intervencion quirurgica a cada situacion. En este articulo se recuerda la anatomia de la union gastroesofagica y de las exploraciones preoperatorias, para describir despues las tecnicas principales que se realizan por laparotomia en el reflujo gastroesofagico simple o complicado. En el reflujo simple, el analisis de los resultados publicados de los distintos tipos de intervenciones permite limitar la eleccion a las fundoplicaturas totales o parciales. Aunque las fundoplicaturas totales garantizan una gran eficacia en el tratamiento del reflujo, los trastornos funcionales postoperatorios son mas frecuentes que en las parciales. La utilizacion de uno u otro tipo de fundoplicatura depende de las preferencias de cada grupo. En las formas complicadas, la indicacion quirurgica y la tecnica que se realice dependen del tipo de complicacion y han de individualizarse para cada situacion clinica.

During germinal center (GC) reactions, B-lymphocytes with high-affinity B-cell receptors are selected. Regulation of apoptosis is a key process in selecting such wanted B-cells and in eliminating B-cells with unwanted specificities. In this paper, we show that apoptosis in human GC B-cells involves lysosomal destabilization, which is strictly controlled by caspase-8 activity, but not by caspase-9 activity. Ligation of CD40 provides resistance to lysosomal destabilization. Experimental lysosomal rupture by the lysosomotropic drug O-methyl-L-serine dodecylamide hydrochloride (MSDH) induces apoptosis in GC B-cells, including phosphatidyl serine exposure, mitochondrial inactivation, and DNA fragmentation. These apoptotic features occur in the absence of caspase-3 activity. Follicular dendritic cells (FDCs) protect binding B-lymphocytes from lysosomal destabilization, in both the absence and the presence of MSDH. Our study demonstrates that lysosomal leakage induces apoptosis of GC B-cells in a caspase-3-independent manner and that high-affinity binding to FDCs prevents lysosomal leakage and apoptosis in GC B-cells.

We present BeppoSAX spectra of the extremely luminous and massive object η Car observed in a very broad X-ray range (0.1-200 keV) during high state (December 1996) and egress from the last low state (March 1998). Both spectra are composed of at least two components, a soft one with kT s < 0.7 keV, and a hard with kT h = 4.7 keV. We found in March 1998 a large flux defect in the 1.5-4 keV range, while the flux remained constant below 1.5 keV and above 5 keV. We attribute this defect to a x3.5 increase of the absorbing matter in front of the hard component, while its temperature and unabsorbed luminosity were nearly the same in the two epochs. In December 1996 the PDS X-ray flux in the 13-20 keV range is larger than the extrapolated hard spectrum, indicating the presence of an even harder additional component, which possibly declined during the March 1998 low state. Conversely, we find that at that time, the flux of the 6.7 keV iron line was 40% stronger. Coordinated optical and NIR spectroscopic observations indicate that in March 1998 η Car was still in a state of low excitation of the emission line spectrum, with extended P Cygni absorptions. These results indicate that after the X-ray flux minimum, the hard component recovered its high state luminosity more rapidly than the high ionization spectral lines, but in the meantime it was partly occulted by a large amount of absorbing matter placed in front of the source. These results are discussed in the framework of the proposed binary model of η Car.

We report a case of 31-year-old woman presented with a chronic pelvic pain and a 3-cm left ovarian cyst on ultrasonography. At the time of laparoscopy, we observed two blue peritoneal lesions at the pelvic insertion of left round ligament. Histopathological examination of a biopsy showed a pigmentation due to a decorative tattoo of the left thigh.

GRB 991014 is one of the shortest gamma-ray bursts detected so far with the Wide Field Cameras aboard BeppoSAX, both in gamma-rays and X-rays. The duration is 9.6 sec in 2-28 keV and 3.2 sec in 40 to 700 keV (as measured between the times when 5 and 95% of the burst photons have been accumulated). We refine the InterPlanetary Network annulus of the burst, present the detection of the X-ray afterglow of GRB 991014 within this refined annulus, and discuss X-ray and gamma-ray observations of the prompt and afterglow emission. Except for the briefness of the prompt event, no other unusual aspects were found in the prompt and afterglow observations as compared to such measurements in previous gamma-ray bursts., accepted for publication in Astrophysical Journal

We report evidence of bursting activity from XTE 1709-267, following a series of deep observations of the Galactic Centre region performed with the WFCs on board BeppoSAX. The long exposure and the imaging capability of the instruments allowed for a better position determination for this source, tentatively classified as an X-ray nova by Marshall et al. (IAUC 6543) on the basis of the data collected by RXTE-PCA.

A continuous monitoring of the Galactic Centre region has been performed with the WFC s on board BeppoSAX on a time spread of about 7 months for a total of 500 ks exposure time. The long repeated observations allowed for the identification of 14 bursting sources, 2 of which uncataloged ( SAXJ1750-290, SAXJ1806-221 ) and 3 observed bursting for the first time ( GS1826-238, SLX1735-269, XTE1709-267 ). A summary of the monitoring of the Galactic Centre bursters is reported.

We report the discovery with BeppoSAX-WFC of two new X-ray sources that were only seen during bursts: SAX J1753.5-2349 and SAX J1806.5-2215. For both sources, no steady emission was detected above an upper limit of 5 mCrab (2 to 8 keV) for 3 10**5 s around the burst events. The single burst detected from SAX J1753.5-2349 shows spectral softening and a black body color temperature of 2.0 keV. Following the analogy with bursts in other sources the burst very likely originates in a thermonuclear flash on a neutron star. The first of two burst detected from SAX J1806.5-2215 does not show spectral softening and cannot be confirmed as a thermonuclear flash., 4 pages, 4 figures, to be published in Proceedings of the Symposium "The Active X-Ray Sky: Results from BeppoSAX and Rossi-XTE", Rome, Italy, 21-24 October, 1997, Nuclear Physics B Proceedings Supplements. Eds. L. Scarsi, H. Bradt, P. Giommi, and F. Fiore

We report three cases of isolated adrenal haematoma diagnosed at admission to the Emergency Department. Post-traumatic adrenal haematoma have been observed in 2% of patients with abdominal injury and can be life threatening in cases of bilateral haemorrhage with risk of acute adrenocortical insufficiency. Diagnosis remains difficult due to absence of clinical and biological specific parameters. Therefore, abdominal CT examination should be the gold standard in management of abdominal trauma patients.

M2 macrophages suppress inflammation in numerous disorders, including tumour formation, infection and obesity. However, the exact role of M2 macrophages in the context of several other diseases is still largely undefined. We here show that human M2 macrophages promote inflammation instead of suppressing inflammation on simultaneous exposure to complexed IgG (c-IgG) and TLR ligands, as occurs in the context of diseases such as rheumatoid arthritis (RA). c-IgG-TLR ligand co-stimulation of M2 macrophages selectively amplifies production of pro-inflammatory cytokines TNF-α, IL-1β and IL-6 and promotes Th17 responses, which all play a critical role in RA pathology. Induction of pro-inflammatory cytokines on c-IgG co-stimulation mainly depends on Fc gamma receptor IIa (FcγRIIa), which selectively amplifies cytokine gene transcription and induces caspase-1 activation. These data indicate that FcγR-TLR cross-talk may be targeted for treatment to attenuate inflammation in RA, by restoring the anti-inflammatory function of M2 macrophages., M2-polarized macrophages are generally considered anti-inflammatory, but whether polarization markers always reflect functional states remains debatable. Here the authors show that complexed IgG and TLR co-stimulation, observed in infections or rheumatoid arthritis, elicits an inflammatory response in M2 macrophages.

The two Wide Field Cameras (WFCs) cur- rently flying on the Italian/Dutch X-ray satellite BeppoSAX, image the X-ray sky in the energy range of 1:8 28 keV. The eld of view is 20, the angular resolu- tion is 5 arcmin and the energy resolution is 20% at 6 keV, while the source location accuracy will generally be bet- ter than one arcmin. All values are at Full Width Half Maximum. The design is based on the coded mask prin- ciple where mask and detector both have sizes of about 25:625: 6c m 2 . The detector is a Multi Wire Proportional Counter with a position resolution which is better than 0.5 mm for energies below 10 keV. The mask pattern is based on a so called triadic residue set with elements of 1m m 2 of which 33% are transparent for X-rays. The lim- iting sensitivity of the WFCs is a few mCrab in 10 5 s. The design and performance of the instrument is described here along with some calibration results and the principle of the image reconstruction. The WFCs represent the latest generation of coded mask X-ray cameras. Their unrivalled eld of view, com- bined with appropriate spatial and temporal resolution and modest energy resolution make the instruments very well suited to perform extensive studies of large areas of the sky and to study transient X-ray phenomena.

This paper deals with the accuracy of complex division in radix-two floating-point arithmetic. Assuming that a fused multiply-add (FMA) instruction is available and that no underflow/overflow occurs, we study how to ensure high relative accuracy in the component wise sense. Since this essentially reduces to evaluating accurately three expressions of the form ac+bd, an obvious approach would be to perform three calls to Kahan's compensated algorithm for 2 by 2 determinants. However, in the context of complex division, two of those expressions are such that ac and bd have the same sign, suggesting that cheaper schemes should be used here (since cancellation cannot occur). We first give a detailed accuracy analysis of such schemes for the sum of two nonnegative products, providing not only sharp bounds on both their absolute and relative errors, but also sufficient conditions for the output of one of them to coincide with the output of Kahan's algorithm. By combining Kahan's algorithm with this particular scheme, we then deduce two new division algorithms. Our first algorithm is a straight-line program whose component wise relative error is always at most 5u+13u2 with u the unit round off, we also provide examples of inputs for which the error of this algorithm approaches 5u, thus showing that our upper bound is essentially the best possible. When tests are allowed we show with a second algorithm that the bound above can be further reduced to 4.5u+9u2, and that this improved bound is reasonably sharp.

The mechanisms preventing detrimental T-cell responses against commensal skin bacteria remain elusive. Using monocyte-derived and skin-derived dendritic cells (DCs), we demonstrate that epidermal Langerhans cells (LCs), the DCs in the most superficial layer of the skin, have a poor capacity to internalize bacteria because of low expression of FcγRIIa. Furthermore, LCs show deficiency in processing and major histocompatibility complex II (MHC-II)-restricted presentation of bacterial antigens, as a result of a decreased expression of molecules involved in these functionalities. The reduced capacity to take up, process, and present bacterial antigens cannot be restored by LC activation by ectopically expressed Toll-like receptors or by cytokines. Consequently, bacteria-primed LCs poorly restimulate antibacterial memory CD4(+) T cells and inefficiently induce bacteria-specific effector CD4(+) T cells from naive T cells; however, they initiate the development of regulatory Foxp3(+)CD4(+) T cells, which are able to suppress the proliferation of autologous bystander T cells specific for the same bacteria. In contrast, dermal DCs that reside in the deeper dermal layer of the skin efficiently present bacterial antigens and provoke robust antibacterial naive and memory CD4(+) T-cell responses. In conclusion, LCs form a unique DC subset that is adapted at multiple levels for the maintenance of tolerance to bacterial skin flora.

Coronary arterioles demonstrate flow-dependent vasodilation that is mediated by endothelial release of nitric oxide. The signaling mechanisms for this response remain unknown. Because tyrosine kinases are an enzyme family linked to many signaling pathways, including some for mechanosensitive transduction, we hypothesized that tyrosine kinase activation is a critical step in flow-induced vasodilation. To test this hypothesis, coronary arterioles were isolated, cannulated with micropipettes, and perfused by two independent reservoir systems. Intraluminal pressure was set at 60 cmH2O, and flow was generated by changing the heights of the reservoirs in equal and opposite directions, thus establishing a pressure difference across the arteriole without altering intraluminal pressure. Vasodilatory responses to intraluminal flow and substance P (1 x 10(-12) to 1 x 10(-7) M) were evaluated before and after intraluminal application of the tyrosine kinase inhibitors genistein (5 microM) and piceatannol (10 microM). Exposure to these inhibitors did not alter spontaneous tone. Substance P caused dose-dependent vasodilation that was not affected by genistein or piceatannol. Increases in intraluminal flow (generated by pressure differences ranging from 4 to 60 cmH2O) elicited graded increases in diameter. Both genistein and piceatannol inhibited the vasodilatory responses to flow. Treatment with daidzein, an inactive analogue of genistein, had no effect on either the flow-induced responses or substance P-induced vasodilation. To further confirm that tyrosine kinase activation is involved in flow-induced vasodilation, vessels were exposed to flow in the absence or presence of genistein and subsequently stained with a fluorescein isothiocyanate-labeled phosphotyrosine antibody. Exposure to flow significantly increased fluorescence of endothelial cells. Genistein treatment reversed the flow-induced increase in tyrosine phosphorylation. These results indicate that endothelium-dependent, flow-induced vasodilation in isolated porcine coronary arterioles is accompanied by an increase in tyrosine kinase activity. We conclude that endothelium-dependent, nitroxidergic, flow-induced vasodilation is mediated, at least in part, by a signaling pathway involving a tyrosine kinase.

Objective: To assess the toxicological etiologies in agitated patients and to evaluate their initial clinical diagnosis in the light of toxicological results analysis. Design: Prospective clinical study. Setting: Emergency Department (ED) in a 2,650-bed University Hospital. Patients: Fifty-eight consecutively enrolled patients admitted to the ED in agitated states over a 6-month period. Measurements and results: All patients underwent laboratory tests including blood glucose, ethanol and serum drug screening. Toxicology tests were conducted by fluorescence polarization immunoassay and confirmed by high performance liquid chromatography/diode array detector and gas chromatography-mass spectrometry. The physician's initial diagnosis was evaluated in the light of toxicological analysis results. Serum toxicological analysis revealed that 50/58 patients were under the influence of alcohol and/or a drug. Benzodiazepines (22/58), selective serotonin reuptake inhibitors (5/58) and opiates (4/58) were the most frequently observed. The initial clinical diagnosis was alcohol intoxication in 39 patients, although 1 patient was not under the influence of alcohol and 16 also had benzodiazepine in their sera. Moreover, the diagnosis of serotonin syndrome was overlooked in two patients. Conclusion: Most agitated patients were under the influence of alcohol and/or a drug. Benzodiazepine alone or in association with alcohol was surprisingly frequent. A serotonin syndrome may explain the agitation state.

In mammals, the rate of somatic growth is rapid in early postnatal life but then slows with age, approaching zero as the animal approaches adult body size. To investigate the underlying changes in cell-cycle kinetics, [methyl-3H]thymidine and 5’-bromo-2’deoxyuridine were used to double-label proliferating cells in 1-, 2-, and 3-week-old mice for four weeks. Proliferation of renal tubular epithelial cells and hepatocytes decreased with age. The average cell-cycle time did not increase in liver and increased only 1.7 fold in kidney. The fraction of cells in S-phase that will divide again declined approximately 10 fold with age. Concurrently, average cell area increased approximately 2 fold. The findings suggest that somatic growth deceleration primarily results not from an increase in cell-cycle time but from a decrease in growth fraction (fraction of cells that continue to proliferate). During the deceleration phase, cells appear to reach a proliferative limit and undergo their final cell divisions, staggered over time. Concomitantly, cells enlarge to a greater volume, perhaps because they are relieved of the size constraint imposed by cell division. In conclusion, a decline in growth fraction with age causes somatic growth deceleration and thus sets a fundamental limit on adult body size.

Here we report the discovery in the X-ray band of the first afterglow of a gamma-ray burst. It was detected and quickly positioned by the Beppo-SAX satellite on 1997 February 28 (GRB970228). The X-ray afterglow source was detected with the X-ray telescopes aboard the same satellite about eight hours after the burst and faded away in a few days with a power law decay function. The energetic content of the X-ray afterglow results to be a significant fraction of gamma-ray burst energetics. The Beppo-SAX detection and fast imaging of GRB970228 started a multiwavelength campaign that lead to the identification of a fading optical source in a position consistent with the X-ray source.

We report three cases of isolated adrenal haematoma diagnosed at admission to the Emergency Department. Post-traumatic adrenal haematoma have been observed in 2% of patients with abdominal injury and can be life threatening in cases of bilateral haemorrhage with risk of acute adrenocortical insufficiency. Diagnosis remains difficult due to absence of clinical and biological specific parameters. Therefore, abdominal CT examination should be the gold standard in management of abdominal trauma patients.

An automatic computer-aided diagnosis algorithm to classify malignant and benign tumors in digitized mammograms was developed. Images selected from the publicly available data set “Digital Database for Screening Mammography” were used for evaluation of this algorithm. A new segmentation algorithm was used to segment the lesion. To represent spiculation we used features previously developed for mass detection. Features based on margin sharpness, location and contrast were also extracted. A k-nearest neighbor algorithm was used for feature selection. The average test results corresponded to Az value of 0.84 and 0.79 in a case and in an image based classification scheme respectively.

With interest we read the letter by Ayyoub and coworkers who compare the efficacy of Th17 differentiation from naive FOXP3+CD25+CD127− NTregs and conventional naive T cells.[1][1] We previously reported that compared with CD28, alternative costimulation via CD5 enhanced Th17 differentiation from

To identify neural tumor cell lines that could be used as models to study growth-related natriuretic peptide actions, we determined the effects of these peptides on the proliferation of human and rodent neuroblastoma cell lines. Subnanomolar concentrations of atrial natriuretic peptide (ANP) and type C natriuretic peptide (CNP) stimulated proliferation in all four cell lines. These actions were associated with cGMP elevation and were blocked by a protein kinase G inhibitor. These data imply the involvement of guanylyl cyclase (GC)-coupled natriuretic receptors. However, higher concentrations of ANP and CNP, and low concentrations of des-[Gln(18),Ser(19),Gly(20),Leu(21),Gly(22)]-ANP(4-23)-NH(2) (desANP(4-23)) (analog for NPR-C receptor) exerted antiproliferative actions in three of the cell lines. These effects were insensitive to a protein kinase G inhibitor and to HS-142-1, suggesting that growth-inhibitory actions involved a non-GC receptor. They did not appear to involve cAMP, protein kinase A, protein kinase C, or calcium mobilization but were abolished when constitutive mitogen-activated protein kinase activity was inhibited. Radioligand binding experiments revealed the presence of a uniform class of binding sites in NG108 cells and multiple binding sites in Neuro2a cells. Northern and reverse transcriptase-polymerase chain reaction analyses revealed differential gene expression for NPR-A/B/C in NG108 and Neuro2a cells. The results indicate that natriuretic peptides stimulate neuroblastoma cell proliferation through type NPR-A/B (GC) receptors. Higher concentrations of ANP and CNP exerted a mitogen-activated protein kinase-dependent antiproliferative action mediated by a non-GC receptor that interacts with desANP(4-23) with relatively high affinity.

An osteoid osteoma was discovered at the site of fusion of a mid-third femoral shaft fracture in an 18-year-old girl. This unusual localization was revealed by persistent pain after ablation of the material after fracture healing. Postoperatively, a discharge from the skin wound that persisted for a few days, raised the differential diagnosis between low-grade bone infection and an osteoid osteoma suggested by the patient's age and the clinical presentation. Computed tomography and leukocyte-labeled bone scintigraphy provided the diagnosis of osteoid osteoma that was confirmed at pathology examination after resection. Isotopic mapping of this very small intraosseous lesion that exhibited strong isotope uptake was particularly contributive.

There are few data in the literature concerning care provided to very elderly subjects referred to emergency care units. The emergency room setting would not be particularly adapted to management of this rising population. The purpose of our work was to assess the frequency of referral to emergency care units, the characteristics of the elderly population, and patient management.One hundred fifty consecutive patients aged over 90 years addressed to the emergency unit of the Charles Nicolle hospital in Rouen France were studied. These patients were cared for by the medical and surgical teams. We recorded, type of referral, hour and reason for admission, degree of handicap and residence, gravity at admission using the clinical classification for emergency care patients (CCMU), complementary tests performed in the emergency unit, duration of stay in the unit and subsequent referral. The characteristics of these "very" elderly patients aged over 90 years were compared with those of "elderly" patients aged 75-90 years.Over a period of 33 days, the unit cared for 4888 patients, including 150 very elderly patients aged over 90 years (mean age 92.6 years). Daily, 4.4 patients were referred by a primary care physician (76.), mainly between 8 a.m. and 8 p.m. (81.3%). Forty-two percent of the patients had a surgical problem. Two-thirds were unable to walk, one-third had cognitive disorders, and one-third had urinary incontinence. However, half of these very elderly patients lived in a private home. According to the CCMU classification, 14.6% of the patients had a life-threatening disorder. Complementary tests were ordered for most patients (85%). Mean duration of stay in the emergency unit was 3.6 +/- 2.6 days. One quarter of the patients returned to their former residence, with a higher percentage among the surgery patients (37%) than among the medical patients (14.6%). There was no significant difference between the "very elderly" and "elderly" patients in terms of type of referral, duration of stay in the unit and subsequent referral."Very elderly" patients are frequently addressed to emergency care units by their primary care physician. They have severe conditions with major handicaps that largely explain their hospitalization. Our results point out possible improvements for care in the emergency unit.

Wax reconstructions according to Born's methods were performed from serial 10-micron sections of the wrists of human embryos (B. Tardif) to study the triangular cartilage and central bone of the carpus. A subsequent morphological study of the adult scaphoid bone was conducted in the light of embryological data. The triangular cartilage was observed in 4 of 38 carpi of embryos with a craniocaudal length of 40 to 69 mm, flatten between the ulna and triquetrum, on the inferior surface of the mesenchymal bud of the triangular ligament. The central bone of the carpus is constant in the embryo, between the inferior surface of the radial chondrification centre, capitatum, trapezium and trapezoid. In one case, the two wrists of the same embryo presented two central nuclei, leading to the distinction of two different formations:--the constant C2 embryonic central bone, trapped between capitatum, trapezoid and trapezium, which participates in the constitution of the scaphoid by fusion with the radial chondrification centre;--the C1 central bone, a rare supernumerary bone in adults, close to the inferolateral angle of the lunatum, on the dorsal surface of the carpus. These embryological data support. Westoll's theory concerning the filiation of the thoracic limb since the fin of crossopterygians, with deviation of the mechanical axis related to the development of weightbearing on the ground. The scaphoid bone must to be assimilated to a cube, but to an irregular tetrahedron, composed of two inverted pyramids joined by their bases. The inferior pyramid, articulating with he trapezium, trapezoid and capitatum, is concerned by morphological variations of the bone, which can present variable configurations between the two extreme morphotypes: the massive type and the strangulated type. The inferior pyramid, constituting the scaphoid, is derived from the central cartilage and presents the same relations. Variations of the volume of this inferior part of the bone are related to the more or less marked regression of this chondrification centre of the embryonic carpus. These variations of the bone can be expressed in terms of a scaphoid index, by calculating the relationship between the greatest dimension and the width of the narrowed portion.

We report on the long term monitoring of the GINGA transient source GS 1826-238 performed with the BeppoSAX Wide Fiels Camera (WFC) instrument, during four different observing campaigns covering October 1996 - September 1999. WFC detection of type-I bursting activity from the source ruled out its proposed black hole candidacy and clearly suggested the compact object related to GS 1826-238 to be a weakly magnetized neutron star. The analysis of the arrival times of the observed 78 bursts lead to the discovery of a recurrence of ~5.75 hours with a spread of 38 minutes (FWHM) along more than 3 years monitoring data (Ubertini et al., 1999). We performed a more detailed analysis of the whole available data, and evidence of shortening of the recurrence time, together with a drastic narrowing in the spread (down to a few minutes) was observed on a one year time scale. Possible relation with the source X-ray persistent emission is discussed., 5 pages, 3 figures. Proc. of 5th Compton Symp., Portsmouth 1999

We investigated the spectral evolution in the 2--700 keV energy band of Gamma-Ray Bursts (GRBs) detected by the Gamma-Ray Burst Monitor (GRBM) and localized with the Wide Field Cameras (WFCs) aboard the BeppoSAX satellite before May 1998. Most of them have been followed-up with the Narrow Field Instruments aboard the same satellite. In the light of these results we discuss open issues on the GRB phenomenon. We find that the optically thin synchrotron shock model (SSM) provides an acceptable representation of most of the time-resolved GRB spectra extending down to 2 keV, except in the initial phases of several bursts and during the whole duration of the quite strong GRB970111, where a low-energy photon depletion with respect to the thin SSM spectrum is observed. We find that the X-ray afterglow starts at about 50% of the GRB duration, and that its fluence, as computed from the WFC light curve, is consistent with the decay law found from the afterglow NFI observations. We also investigate the hydrodynamical evolution of the GRB in our sample and their associated afterglow, when it was detected. We find that the photon index of the latest spectrum of the GRB prompt emission is correlated with the index of the afterglow fading law, when available, as expected on the basis of an external shock of a relativistic fireball., Comment: 35 pages, 1 LaTeX file, 20 postscript figures, 1 postscript table, accepted for pubblication in Astrophysical Journal Supplement Series. Corrected error bars in Fig.2/GRB980425/panel B and GRB980425 fluence in Tab. 3

Chronic anoperineal pain without any apparent etiology may be caused by compression of the pudendal nerve. This presentation illustrates the course of the pudendal nerve and the technique of computed tomography-guided infiltration of the nerve.

The transient X-ray source GS 1826-238 was monitored during five different observing periods between August 1996 and October 1998 with the BeppoSAX Wide Field Camera instrument in the framework of a deep observation of the Galactic Center region. A first detection of X-ray bursts from this source occurred, ruling out its previously suggested black hole candidacy and strongly suggesting the compact object to be a weakly magnetized neutron star. During the 2.5 years of monitoring, corresponding to ~2.0 Ms observing time, 70 bursts were detected from the source. We here report a quasi-periodicity of 5.76 h in the burst occurrence time which is present during all observations. This is the first example of quasi-periodic bursting over a period of years. It is in line with the history of a rather constant flux since the turn on in 1988 and points to a very stable accretion., 3 figures, accepted for publication in ApJ Letters

We present BeppoSAX GRBM and WFC light curves of GRB980425 and NFI follow-up data taken in 1998 April, May, and November. The first NFI observation has detected within the 8' radius error box of the GRB an X-ray source positionally consistent with the supernova SN 1998bw, exploded within a day of GRB980425, and a fainter X-ray source, not consistent with the position of the supernova. The former source is detected in the following NFI pointings and exhibits a decline of a factor of two in six months. If it is associated with SN 1998bw, this is the first detection of hard X-ray emission from a Type I supernova. The latter source exhibits only marginally significant variability. Based on these data, it is not possible to select either source as a firm candidate for the GRB counterpart., Comment: 2 pages, 1 PostScript figure, submitted to A&AS, Proc. of the Conference "Gamma-Ray Bursts in the Afterglow Era", held in Rome, 1998 November 3-6. Results concerning 'Source 2' have been updated

We report evidence of type-I X-ray bursting activity from the transient 1RXS J170930.2-263927 when it was in outburst early 1997. This identifies the source as a probable low-mass X-ray binary containing a neutron star. The error boxes of the detected bursts and of the persistent emission, as obtained with the Wide Field Cameras on board the BeppoSAX satellite, rule out an association with the proposed radio counterpart (Hjellming & Rupen 1997)., ApJ Letters, accepted Oct 13, 1998

The growth rate of rodent embryonic neuroblasts and human neuroblastoma cell lines is regulated in part by autocrine or paracrine actions of neuropeptides of the family that includes vasoactive intestinal peptide (VIP), peptide histidine isoleucine (PHI), and pituitary adenylate cyclase-activating peptide (PACAP). These peptides act via seven transmembrane G-protein-linked receptors coupled to cAMP elevation, phospholipase C activation, intracellular Ca2+ release, and/or of mitogen-activated protein (MAP) kinase activation. Here we investigated the action of these peptides on the mouse neuroblastoma cell line Neuro2a. PHI and VIP inhibited proliferation at concentrations as low as 10(-13) M and 10(-10) M, respectively. In contrast, PACAP action was biphasic, with stimulation occurring at subnanomolar doses and inhibition at higher doses. Peptide actions were studied further by measuring cAMP and ERK1/2 MAP kinase activity and by assessing 3H-thymidine incorporation in conjunction with a panel of signal transduction pathways inhibitors. The data obtained indicated that the PHI-inhibitory and PACAP-stimulatory activities were mediated by corresponding changes in activity of the MAP kinase pathway and independent of protein kinase A (PKA) or protein kinase C (PKC). In contrast, the inhibitory actions of VIP and PACAP were specifically blocked by antagonists of PKA. Northern blot analysis revealed gene expression for only the PACAP-preferring (PAC1) receptor. However, binding experiments using 125I-labeled PACAP27, PHI, and VIP, demonstrated the presence of PACAP-preferring sites, bivalent VIP/PACAP sites, and PHI-binding sites that did not interact with VIP. The studies demonstrate potent regulatory actions of PACAP, PHI, and VIP on neuroblastoma cell proliferation which appear to be mediated by multiple subsets of receptors which differentially couple to MAP kinase and PKA signaling pathways.

Neuroendocrine tumors, neuroblastoma in particular, commonly express the neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating peptide (PACAP) and their receptors. Retinoic acid (RA) has been shown to induce differentiation of neuroblastoma cell lines, possibly by augmenting or interfering with neuropeptide autocrine loops. We sought to determine which receptor gene subtypes are expressed in selected human neuroblastoma cell lines (SH-SY5Y, IMR-32, and LA-N-5), and the effect of RA on the VIP/PACAP ligand/receptor system. Expression of both PACAP1 and VIP1/PACAP2 receptor genes was detected by Northern analysis, which characteristically encode Type I (PACAP-preferring), and Type II (bivalent VIP/PACAP) receptors, respectively. Binding experiments carried out on IMR-32 cells, using 125I VIP and 125I PACAP-27 as tracers, corroborated that both receptor subtypes were expressed. In contrast to RA upregulation of VIP binding (confirmed here in IMR-32 cells), levels of both receptor mRNAs were reduced after RA treatment. VIP mRNA in each cell line was increased by RA, whereas PACAP mRNA, detected in IMR-32 cells only, was reduced. The studies indicate that several components of the VIP/PACAP autocrine system are regulated in neuroblastoma cell lines during RA differentiation.

There are many mechanisms that contribute to the regulation of coronary blood flow including vasodilatory metabolites, myogenic regulation, flow- or shear stress-mediated vasodilation, and neurohumoral influences. It is interesting to note that coronary arterioles of varying sizes appear to possess different sensitivities to these regulatory factors, but each appears to dominate the control of a particular segment of the microvasculature. For example, during metabolic hyperemia the smallest arterioles seem to be most sensitive to the effects of metabolites, but metabolic and myogenic mechanisms that dictate the tone of upstream microvessels likely act in concert to facilitate the overall adjustments in coronary vasomotor tone. Neurohumoral mechanisms, seem to modulate the robustness of these intrinisic adjustments, perhaps by restraining the extent of vasodilation. The purpose of this review is to discuss these many regulatory mechanisms and also present a framework by which the vasoactive reactions elicited by these different mechanisms are integrated into coordinated responses of the entire coronary vascular network.

A large number of studies now support the concept that exercise training alters functional control of the coronary circulation. Recent work has approached this area using ex vivo coronary arterial preparations (proximal coronary arteries, near-resistance arteries, resistance arterioles) isolated from exercise-trained animals and contracting independently of confounding in vivo influences. The combined results of these studies indicate that training-induced alterations in vascular control mechanisms do not occur uniformly throughout the coronary vascular tree. Proximal epicardial coronary arteries (approximately 2.0 mm diameter) isolated from exercise-trained pigs exhibited significantly reduced contractile responsiveness to the alpha-adrenergic receptor agonist, norepinephrine, but unaltered contractile responsiveness to K+, acetylcholine, and endothelin. Also, proximal arteries from exercise-trained animals demonstrated enhanced sensitivity to the vasodilator effects of adenosine. At the other end of the vascular spectrum, in resistance arterioles (150 microns diameter) the relaxation responses to adenosine were unaffected by exercise training, but bradykinin-induced vasodilation (endothelium-dependent) was significantly enhanced. In near-resistance arteries (150-240 microns diameter) responses to both bradykinin and adenosine were enhanced by exercise training. Thus, exercise training is associated with intrinsic vessel size-dependent alterations in coronary smooth muscle and endothelium-mediated regulatory mechanisms.

A technique for the closure of upper median sternotomy with absorbable polyglycolid acid sutures is described. In a consecutive series of 130 refixations, no major complications occurred. After a mean follow-up period of 66 +/- 61 months, the long-term results concerning sternotomy closure were determined in 86 patients: 84 (98%) sternotomies were completely consolidated, in 75 cases (87%) without any dislocation and in nine cases (11%) with a minor dislocation in the transverse osteotomy. In two patients (2%) who had received postoperative radio- and chemotherapy, an isolated pseudarthrosis of the transverse osteotomy was observed, whereas the median sternotomy was consolidated completely. As a result of our clinical experience, we consider the closure of partial upper sternotomy with absorbable polyglycoid acid sutures as a practical and safe technique.