First Measurement Using Elliptically Polarized Photons of the Double-Polarization Observable E for γp→pπ

We report the measurement of the helicity asymmetry E for the pπ^{0} and nπ^{+} final states using, for the first time, an elliptically polarized photon beam in combination with a longitudinally polarized target at the Crystal Ball experiment at MAMI. The results agree very well with data that were taken with a circularly polarized photon beam, showing that it is possible to simultaneously measure polarization observables that require linearly (e.g., G) and circularly polarized photons (e.g., E) and a longitudinally polarized target. The new data cover a photon energy range 270-1400 MeV for the pπ^{0} final state (230-842 MeV for the nπ^{+} final state) and the full range of pion polar angles, θ, providing the most precise measurement of the observable E. A moment analysis gives a clear observation of the pη cusp in the pπ^{0} final state.

Measurement of polarization observables T, P, and H in π0 and η photoproduction off quasi-free nucleons.

The target asymmetry T, recoil asymmetry P, and beam-target double polarization observable H were determined in exclusive π0 and η photoproduction off quasi-free protons and, for the first time, off quasi-free neutrons. The experiment was performed at the electron stretcher accelerator ELSA in Bonn, Germany, with the Crystal Barrel/TAPS detector setup, using a linearly polarized photon beam and a transversely polarized deuterated butanol target. Effects from the Fermi motion of the nucleons within deuterium were removed by a full kinematic reconstruction of the final state invariant mass. A comparison of the data obtained on the proton and on the neutron provides new insight into the isospin structure of the electromagnetic excitation of the nucleon. Earlier measurements of polarization observables in the γp→π0p and γp→ηp reactions are confirmed. The data obtained on the neutron are of particular relevance for clarifying the origin of the narrow structure in the ηn system at W=1.68GeV. A comparison with recent partial wave analyses favors the interpretation of this structure as arising from interference of the S11(1535) and S11(1650) resonances within the S11-partial wave.

Management of Oral Sub Mucous Fibrosis Using Three Different Flaps: Superficial Temporal, Nasolabial Flap, Buccal Fat Pad Flap Along with Active Physiotherapy- A Comparative Study.

To assess the efficacy of different flaps along with active physiotherapy for comprehensive management of OSMF. A total of 33 patients of oral submucous fibrosis were admitted and surgically treated. All patients were diagnosed with bilateral oral submucous fibrosis of buccal mucosa. All the patients had advanced oral sub mucous fibrosis with interincisal distance less than 20 mm. Eleven patients were treated with buccal pad of fat, eleven with nasolabial flap and eleven patients were treated with temporo-parietal fascia flap. Physiotherapy was started from the 5th postoperative day and the patients were followed regularly for one year to measure maximum interincisal distance. There was a significant corelation between post-operative mouth opening and regular physiotherapy, exercise and quitting of the habit irrespective of type of reconstruction flap used. On the basis of the result obtained from this study, significant improvement in mouth opening was seen in patients who performed aggressive physiotherapy irrespective of the flap used. Thus we conclude along with the surgical treatment, post-operative physiotherapy and cessation of habit are of equal importance for good prognosis in OSMF patients.

Measurement of Compton Scattering at MAMI for the Extraction of the Electric and Magnetic Polarizabilities of the Proton.

A precise measurement of the differential cross sections dσ/dΩ and the linearly polarized photon beam asymmetry Σ_{3} for Compton scattering on the proton below pion threshold has been performed with a tagged photon beam and almost 4π detector at the Mainz Microtron. The incident photons were produced by the recently upgraded Glasgow-Mainz photon tagging facility and impinged on a cryogenic liquid hydrogen target, with the scattered photons detected in the Crystal Ball/TAPS setup. Using the highest statistics Compton scattering data ever measured on the proton along with two effective field theories (both covariant baryon and heavy-baryon) and one fixed-t dispersion relation model, constraining the fits with the Baldin sum rule, we have obtained the proton electric and magnetic polarizabilities with unprecedented precision: α_{E1}=10.99±0.16±0.47±0.17±0.34, ß_{M1}=3.14±0.21±0.24±0.20±0.35; in units of 10^{-4} fm^{3} where the errors are statistical, systematic, spin polarizability dependent, and model dependent.

Single π 0 production off neutrons bound in deuteron with linearly polarized photons.

The quasifree γ → d → π 0 n ( p ) photon beam asymmetry, Σ , has been measured at photon energies, E γ , from 390 to 610 MeV, corresponding to center of mass energy from 1.271 to 1.424 GeV, for the first time. The data were collected in the A2 hall of the MAMI electron beam facility with the Crystal Ball and TAPS calorimeters covering pion center-of-mass angles from 49 ∘ to 148 ∘ . In this kinematic region, polarization observables are sensitive to contributions from the Δ ( 1232 ) and N(1440) resonances. The extracted values of Σ have been compared to predictions based on partial-wave analyses (PWAs) of the existing pion photoproduction database. Our comparison includes the SAID, MAID and Bonn-Gatchina analyses; while a revised SAID fit, including the new Σ measurements, has also been performed. In addition, isospin symmetry is examined as a way to predict π 0 n photoproduction observables, based on fits to published data in the channels π 0 p , π + n and π - p .

Measurement of the helicity asymmetry E for the reaction γ p → π 0 p : The CBELSA/TAPS Collaboration.

A measurement of the double-polarization observable E for the reaction γ p → π 0 p is reported. The data were taken with the CBELSA/TAPS experiment at the ELSA facility in Bonn using the Bonn frozen-spin butanol (C 4 H 9 OH) target, which provided longitudinally-polarized protons. Circularly-polarized photons were produced via bremsstrahlung of longitudinally-polarized electrons. The data cover the photon energy range from E γ = 600 to 2310 MeV and nearly the complete angular range. The results are compared to and have been included in recent partial wave analyses.

Observation of the pη

Data on the beam asymmetry Σ in the photoproduction of η mesons off protons are reported for tagged photon energies from 1130 to 1790 MeV (mass range from W=1748 MeV to W=2045 MeV). The data cover the full solid angle that allows for a precise moment analysis. For the first time, a strong cusp effect in a polarization observable has been observed that is an effect of a branch-point singularity at the pη^{'} threshold [E_{γ}=1447 MeV (W=1896 MeV)]. The latest BnGa partial wave analysis includes the new beam asymmetry data and yields a strong indication for the N(1895)1/2^{-} nucleon resonance, demonstrating the importance of including all singularities for a correct determination of partial waves and resonance parameters.

Helicity-Dependent Cross Sections for the Photoproduction of π

The double-polarization observable E and helicity-dependent cross sections σ_{1/2}, σ_{3/2} have been measured for the photoproduction of π^{0} pairs off quasifree protons and neutrons at the Mainz MAMI accelerator with the Crystal Ball/TAPS setup. A circularly polarized photon beam was produced by bremsstrahlung from longitudinally polarized electrons and impinged on a longitudinally polarized deuterated butanol target. The reaction products were detected with an almost 4π covering calorimeter. The results reveal for the first time the helicity- and isospin-dependent structure of the γN→Nπ^{0}π^{0} reaction. They are compared to predictions from reaction models in view of nucleon resonance contributions and also to a refit of one model that predicted results for the proton and for the neutron target. The comparison of the prediction and the refit demonstrates the large impact of the new data.

Signatures of the d

We report a measurement of the spin polarization of the recoiling neutron in deuterium photodisintegration, utilizing a new large acceptance polarimeter within the Crystal Ball at MAMI. The measured photon energy range of 300-700 MeV provides the first measurement of recoil neutron polarization at photon energies where the quark substructure of the deuteron plays a role, thereby providing important new constraints on photodisintegration mechanisms. A very high neutron polarization in a narrow structure centered around E_{γ}∼570 MeV is observed, which is inconsistent with current theoretical predictions employing nucleon resonance degrees of freedom. A Legendre polynomial decomposition suggests this behavior could be related to the excitation of the d^{*}(2380) hexaquark.

Study of η and η' Photoproduction at MAMI.

The reactions γp→ηp and γp→η^{'}p are measured from their thresholds up to the center-of-mass energy W=1.96 GeV with the tagged-photon facilities at the Mainz Microtron, MAMI. Differential cross sections are obtained with unprecedented statistical accuracy, providing fine energy binning and full production-angle coverage. A strong cusp is observed in the total cross section for η photoproduction at the energies in the vicinity of the η^{'} threshold, W=1896 MeV (E_{γ}=1447 MeV). Within the framework of a revised ηMAID isobar model, the cusp, in connection with a steep rise of the η^{'} total cross section from its threshold, can only be explained by a strong coupling of the poorly known N(1895)1/2^{-} state to both ηp and η^{'}p. Including the new high-accuracy results in the ηMAID fit to available η and η^{'} photoproduction data allows the determination of the N(1895)1/2^{-} properties.

Insight into the Narrow Structure in η Photoproduction on the Neutron from Helicity-Dependent Cross Sections.

The double polarization observable E and the helicity dependent cross sections σ_{1/2} and σ_{3/2} were measured for η photoproduction from quasifree protons and neutrons. The circularly polarized tagged photon beam of the A2 experiment at the Mainz MAMI accelerator was used in combination with a longitudinally polarized deuterated butanol target. The almost 4π detector setup of the Crystal Ball and TAPS is ideally suited to detect the recoil nucleons and the decay photons from η→2γ and η→3π^{0}. The results show that the narrow structure previously observed in η photoproduction from the neutron is only apparent in σ_{1/2} and hence, most likely related to a spin-1/2 amplitude. Nucleon resonances that contribute to this partial wave in η production are only N 1/2^{-} (S_{11}) and N 1/2^{+} (P_{11}). Furthermore, the extracted Legendre coefficients of the angular distributions for σ_{1/2} are in good agreement with recent reaction model predictions assuming a narrow resonance in the P_{11} wave as the origin of this structure.

The functional activity of inhibitory G protein (G(i)) is not increased in failing heart ventricle.

Beta-adrenergic receptor (ßAR) inotropic effects are attenuated and muscarinic receptor-mediated inhibition thereof is enhanced in heart failure. We investigated if increased G(i) activity contributes to attenuated ßAR-inotropic effects and potentiates muscarinic accentuated antagonism in failing rat ventricle. Contractility was measured in ventricular strips and adenylyl cyclase (AC) activity in ventricular membranes from rats with post-infarction heart failure (HF) or Sham-operated controls (Sham). The maximal ßAR-mediated inotropic effect of isoproterenol was reduced by ~70% and basal, ßAR- & forskolin-stimulated AC activity was significantly lower in HF vs. Sham. Carbachol-evoked antagonism of the ßAR-mediated inotropic response was complete only in HF despite a ~40% reduction in the ability of carbachol to inhibit ßAR-stimulated AC. However, neither the relative efficacy (contractility decreased by ~46%) nor the potency of carbachol to inhibit the ßAR inotropic response differed between Sham and HF ventricle. Pertussis toxin (PTX) inactivation of G(i) did not increase the maximal ßAR inotropic effect or the attenuated basal, ßAR- & forskolin-stimulated AC activity in HF, but increased the potency of isoproterenol only in Sham (~0.5 log unit). In HF ventricle pretreated with PTX, simultaneous inhibition of phosphodiesterases 3,4 (PDE3,4) alone produced a larger inotropic response than isoproterenol in ventricle untreated with PTX (84% and 48% above basal respectively). In the absence of PTX, PDE3,4 inhibition evoked negligible inotropic effects in HF. These data are not consistent with the hypothesis that increased G(i) activity contributes to the reduced ßAR-mediated inotropic response and AC activity in failing ventricle. The data, however, support the hypothesis that G(i), through chronic receptor independent inhibition of AC, together with PDE3,4 activity, is necessary to maintain a low basal level of contractility.

Cyclic AMP-dependent inotropic effects are differentially regulated by muscarinic G(i)-dependent constitutive inhibition of adenylyl cyclase in failing rat ventricle.

BACKGROUND AND PURPOSE: ß-Adrenoceptor (ß-AR)-mediated inotropic effects are attenuated and G(i) proteins are up-regulated in heart failure (HF). Muscarinic receptors constitutively inhibit cAMP formation in normal rat cardiomyocytes. We determined whether constitutive activity of muscarinic receptors to inhibit adenylyl cyclase (AC) increases in HF and if so, whether it modifies the reduced ß-AR- or emergent 5-HT4-mediated cAMP-dependent inotropic effects. EXPERIMENTAL APPROACH: Contractility and AC activity were measured and related to each other in rat ventricle with post-infarction HF and sham-operated (Sham) controls with or without blockade of muscarinic receptors by atropine and inactivation of G(i) protein by pertussis toxin (PTX). KEY RESULTS: Isoprenaline-mediated inotropic effects were attenuated and basal, isoprenaline- and forskolin-stimulated AC activity was reduced in HF compared with Sham. Atropine or PTX pretreatment increased forskolin-stimulated AC activity in HF hearts. ß-AR-stimulated AC and maximal inotropic response were unaffected by atropine in Sham and HF. In HF, the potency of serotonin (5-HT) to evoke an inotropic response was increased in the presence of atropine with no change in the maximal inotropic response. Interestingly, PTX pretreatment reduced the potency of 5-HT to evoke inotropic responses while increasing the maximal inotropic response. CONCLUSIONS AND IMPLICATIONS: Although muscarinic constitutive inhibition of AC is increased in HF, it does not contribute to the reduced ß-AR-mediated inotropic effects in rat ventricle in HF. The data support the hypothesis that there are differences in the functional compartmentation of 5-HT4 and ß-AR AC signalling in myocardium during HF.

5-HT4-elicited positive inotropic response is mediated by cAMP and regulated by PDE3 in failing rat and human cardiac ventricles.

BACKGROUND AND PURPOSE: The left ventricle in failing hearts becomes sensitive to 5-HT parallelled by appearance of functional G(s)-coupled 5-HT(4) receptors. Here, we have explored the regulatory functions of phosphodiesterases in the 5-HT(4) receptor-mediated functional effects in ventricular muscle from failing rat and human heart. EXPERIMENTAL APPROACH: Extensive myocardial infarctions were induced by coronary artery ligation in Wistar rats. Contractility was measured in left ventricular papillary muscles of rat, 6 weeks after surgery and in left ventricular trabeculae from explanted human hearts. cAMP was quantified by RIA. KEY RESULTS: In papillary muscles from postinfarction rat hearts, 5-HT(4) stimulation exerted positive inotropic and lusitropic effects and increased cAMP. The inotropic effect was increased by non-selective PDE inhibition (IBMX, 10 microM) and selective inhibition of PDE3 (cilostamide, 1 microM), but not of PDE2 (EHNA, 10 microM) or PDE4 (rolipram, 10 microM). Combined PDE3 and PDE4 inhibition enhanced inotropic responses beyond the effect of PDE3 inhibition alone, increased the sensitivity to 5-HT, and also revealed an inotropic response in control (sham-operated) rat ventricle. Lusitropic effects were increased only during combined PDE inhibition. In failing human ventricle, the 5-HT(4) receptor-mediated positive inotropic response was regulated by PDEs in a manner similar to that in postinfarction rat hearts. CONCLUSIONS AND IMPLICATIONS: 5-HT(4) receptor-mediated positive inotropic responses in failing rat ventricle were cAMP-dependent. PDE3 was the main PDE regulating this response and involvement of PDE4 was disclosed by concomitant inhibition of PDE3 in both postinfarction rat and failing human hearts. 5-HT, PDE3 and PDE4 may have pathophysiological functions in heart failure.

Valganciclovir prophylaxis in patients at high risk for the development of cytomegalovirus disease.

BACKGROUND: Despite advances in antiviral therapies, cytomegalovirus (CMV) remains the leading opportunistic infection in the transplant population. Valganciclovir (VGC), the L-valyl ester prodrug of ganciclovir (GCV), provides an excellent oral alternative to GCV for the prevention of CMV in transplant recipients. We investigated the use of VGC for CMV prevention in high-risk renal and pancreas transplant recipients. METHODS: Patients at high risk for development of CMV disease were defined as either those who had donor positive, recipient-negative serostatus (D+/R-), or those who received antilymphocyte antibody (ALA) therapy for either rejection treatment or induction. A retrospective review was conducted of all kidney and pancreas transplants performed between August 2001 and December 2003. A total of 341 transplants were performed, of which 109 received VGC, and 88 were included in this analysis. RESULTS: The overall incidence of CMV disease was 5.7% (5/88). All of the CMV episodes were in patients who were D+/R- (17.2% [5/29] versus 0% [0/59], P<0.001). Of these patients, all the episodes of CMV were in patients who received VGC prophylaxis for<100 days post transplant (29% [5/17] versus 0% [0/12], P=0.06). The overall incidence of leukopenia was 11% and thrombocytopenia was 7%, with the incidence between the D+/R- group and the ALA group being similar. CONCLUSION: VGC is an effective agent in preventing CMV disease in kidney and pancreas transplant recipients who are at high risk for developing the disease. The optimal length of prophylaxis in D+/R- patients is still undefined, while 3 months of prophylaxis appears to be sufficient in patients who received ALA therapy.

Does treatment of cadaveric organ donors with desmopressin increase the likelihood of pancreas graft thrombosis? Results of a preliminary study.

Desmopressin (DDAVP) is commonly used in cadaveric organ donors to treat diabetes insipidus. The thrombogenic potential of DDAVP is well known. Recent animal data have demonstrated that DDAVP impairs pancreas graft (PG) microcirculation and perfusion. The aim of this study was too evaluate the effect of DDAVP on the incidence of PG thrombosis in clinical pancreas transplantation. A retrospective review of simultaneous kidney-pancreas transplant (SKPT) entered in the Scientific Registry of Transplant Recipients (SRTR) between 10/5/87 and 9/27/02 was performed. Patients were included for analysis if there was definitive documentation as to whether DDAVP was (DDAVP-Y) or was not (DDAVP-N) administered to the donor. Both dose and duration of DDAVP treatment were not recorded by SRTR. A total of 2804 SKPTs were available for analysis. Mean follow-up was 1.75 years (range, 1 month to 8.4 years). A total of 1287 SKPT patients (46%) received a PG from a DDAVP-Y donor. Graft ischemia times, donor and recipient ages, recipient gender distribution, surgical techniques, and immunosuppressive regimens were similar in both groups. The overall incidence of PG thrombosis was 4.3%. The incidence of PG thrombosis in recipients of grafts from DDAVP-Y donors was 5.1% compared to 3.5% in recipients of grafts from DDAVP-N donors (P =.04). Fifty-eight percent of thrombosed PG came from DDAVP-Y donors compared to 42% from DDAVP-N donors (P =.04). We conclude that there appears to be a relationship between donor treatment with DDAVP and PG thrombosis. A prospective study is needed to verify these findings and to determine their clinical significance.

Long-term outcome of sirolimus rescue in kidney-pancreas transplantation.

The aim of this study was to evaluate long-term outcome of sirolimus (SRL) rescue in kidney-pancreas transplantation (KPTx). We reviewed 112 KPTx performed at our institution from 12/3/95 to 6/27/02. All patients received antibody (Ab) induction, tacrolimus (TAC), mycophenolate mofetil (MMF), and steroids. Thirty-five patients (31%) had SRL substituted for MMF for the following indications: (1) acute rejection (AR) of kidney or pancreas despite adequate TAC levels; (2) intolerance of full-dose MMF; (3) rising creatinine; and (4) TAC-induced hyperglycemia. Target SRL and TAC levels were 10 ng/mL and 5 ng/mL, respectively. Mean follow-up was 3 +/- 2 years overall and 1.2 +/- 0.5 years after SRL rescue. No patients died. One- and 3-year actuarial kidney and pancreas graft survival was 97%, 97%, and 95%, 90%, respectively. Of 10 patients switched to SRL for AR, 1 kidney failed from Ab-resistant AR, 1 kidney developed borderline AR, and the other 8 remain AR-free. Seven other patients developed AR despite therapeutic SRL levels; of these, 6 (86%) had mean TAC levels of <4.5 in the month preceding AR. Mean creatinine overall and for the rising creatinine group remained stable. All patients switched to SRL for TAC-induced hyperglycemia or MMF intolerance demonstrated biochemical or clinical improvement. Sirolimus-related infection or other serious adverse events (SAE) were uncommon. In conclusion, KPTx recipients can be safely switched to SRL with long-term stabilization of renal function, excellent graft and patient survival, and no increase in SAE. A minimum TAC level of 4.5 ng/mL may be necessary to prevent late AR.

P53 protein expression in transitional cell carcinoma of the bladder - experience of the University of Malaya Medical Centre.

OBJECTIVES: To study the incidence of p53 oncoprotein overexpression and its relationship to tumour grade, stage and clinical prognosis in a cohort of local Malaysian patients. METHODS: All cases of transitional cell carcinoma (TCC) of the bladder diagnosed and treated at the University of Malaya Medical Centre from January 1995 to December 2000 were retrieved from the hospital records. Sections from paraffin-embedded tissues were retrieved and stained for p53 oncoprotein using immunohistochemistry techniques. P53 oncoprotein results were analyzed in relation to tumour grade, stage and clinical prognosis. Fisher's exact test was used to evaluate the relationship between categorical variables and the Kaplan-Meier procedure was used to assess survival outcomes. The Cox regression model was used for multivariate analysis. RESULTS: A total of 64 cases were studied. The mean follow-up period was 23.7 months. The number of p53 positive cases was significantly higher in high-grade (G3) (p = 0.006) and muscle-invasive tumours ( summation operator T2, p = 0.035). The status of p53 expression had no significant association with recurrence-free (p = 0.594) or overall survival (p = 0.955). In multivariate analysis, a multiplicity of tumours at presentation (p = 0.004) and a history of cigarette smoking (p = 0.016) were independent predictors of recurrence. Tumour stage (p = 0.024) was the single independent predictor for poor overall survival. CONCLUSIONS: Overexpression of p53 is associated with TCC of higher grade and tumour stage. It had no significant impact on prognosis in this cohort of TCC cases.

Endothelial nitric oxide synthase gene-deficient mice demonstrate marked retardation in postnatal bone formation, reduced bone volume, and defects in osteoblast maturation and activity.

Nitric oxide (NO) has been implicated in the local regulation of bone metabolism. However, the contribution made by specific NO synthase (NOS) enzymes is unclear. Here we show that endothelial NOS gene knockout mice (eNOS-/-) have marked abnormalities in bone formation. Histomorphometric analysis of eNOS-/- femurs showed bone volume and bone formation rate was reduced by up to 45% (P: < 0.01) and 52% (P: < 0.01), respectively. These abnormalities were prevalent in young (6 to 9 weeks old) adults but by 12 to 18 weeks bone phenotype was restored toward wild-type. Dual energy X-ray absorptiometry analysis confirmed the age-related bone abnormalities revealing significant reductions in femoral (P: < 0.05) and spinal bone mineral densities (P: < 0.01) at 8 weeks that were normalized at 12 weeks. Reduction in bone formation and volume was not related to increased osteoclast numbers or activity but rather to dysfunctional osteoblasts. Osteoblast numbers and mineralizing activity were reduced in eNOS-/- mice. In vitro, osteoblasts from calvarial explants showed retarded proliferation and differentiation (alkaline phosphatase activity and mineral deposition) that could be restored by exogenous administration of a NO donor. These cells were also unresponsive to 17ss-estradiol and had an attenuated chemotactic response to transforming growth factor-beta. In conclusion, eNOS is involved in the postnatal regulation of bone mass and lack of eNOS gene results in reduced bone formation and volume and this is related to impaired osteoblast function.