Effects of recombinant human growth hormone on HIV-1-specific T-cell responses,thymic output and proviral DNA in patients on HAART: 48-week follow-up

Background  

Efficacious immune-based therapy in treated chronic HIV-1 infection requires the induction of virus-specific CD4⁺ T cells and subsequent maturation and maintenance of specific memory CD8⁺ T cells. Concomitant daily administration of recombinant human growth hormone (rhGH) with highly active antiretroviral therapy (HAART) was used in chronically infected patients with lipodystrophy in an attempt to reconstitute these virus-specific T-cell responses.     

Previous infection with Staphylococcus aureus strains attenuated experimental encephalomyelitis

Background

Bacterial superantigens are potent T cell activators that can activate T cells with specificity for antigens of the central nervous system (CNS). In this study, we compared the effect of two S. aureus strains on experimental autoimmune encephalomyelitis (EAE) development. C57BL/6 female mice were infected with S. aureus ATCC 51650, which produces toxic shock syndrome toxin 1 (TSST-1+) or S. aureus ATCC 43300, which does not produce toxins (TOX-). Three days later, the animals were subjected to EAE induction by immunization with myelin oligodendrocyte glycoprotein (MOG). The weight variation, disease incidence and clinical score were recorded daily. Cytokines and Foxp3+ regulatory T cells in the brain were evaluated during the acute disease phase. Cytokines and Foxp3+ regulatory T cells in the spleen and histopathological analysis of the CNS were assessed during the chronic stage.

Results

Previous infection with both strains similarly decreased the clinical score; however, only the TSST-1+ strain clearly diminished inflammation in the CNS. The infections also modulated cytokine production in the spleen and CNS. Reduced production of IL-5 and IL-10 was detected in MOG-stimulated spleen cultures in the TOX- and TSST-1+ infected groups, respectively. In S. aureus stimulated cultures, there was an increased production of IFN-γ and IL-10 in both infected groups and an increased level of IL-5 in the TSST-1+ group. CNS infiltrating cell cultures from previously infected mice produced less IL-17 in response to MOG and more IFN-γ in response to S. aureus stimulation.

Conclusions

These results indicated that both strains attenuated clinical EAE manifestations, but only TSST-1 clearly decreased CNS inflammation.     

Use of ultraviolet-light irradiated multiple myeloma cells as immunogens to generate tumor-specific cytolytic T lymphocytes

Background

As the eradication of tumor cells in vivo is most efficiently performed by cytolytic T lymphocytes (CTL), various methods for priming tumor-reactive lymphocytes have been developed. In this study, a method of priming CTLs with ultraviolet (UV)-irradiated tumor cells, which results in termination of tumor cell proliferation, apoptosis, as well as upregulation of heat shock proteins (HSP) expression is described.

Methods

Peripheral blood mononuclear cells (PBMC) were primed weekly with UV-irradiated or mitomycin-treated RPMI 8226 multiple myeloma cells. Following three rounds of stimulation over 21 days, the lymphocytes from the mixed culture conditions were analyzed for anti-MM cell reactivity.

Results

By day 10 of cultures, PBMCs primed using UV-irradiated tumor cells demonstrated a higher percentage of activated CD8+/CD4- T lymphocytes than non-primed PBMCs or PBMCs primed using mitomycin-treated MM cells. Cytotoxicity assays revealed that primed PBMCs were markedly more effective (p < 0.01) than non-primed PBMCs in killing RPMI 8226 MM cells. Surface expression of glucose regulated protein 94 (Grp94/Gp96) and Grp78 were both found to be induced in UV-treated MM cells.

Conclusion

Since, HSP-associated peptides are known to mediate tumor rejection; these data suggest that immune-mediated eradication of MM cells could be elicited via a UV-induced HSP process. The finding that the addition of 17-allylamide-17-demethoxygeldanamycin (17AAG, an inhibitor of HSP 90-peptide interactions) resulted in decreased CTL-induced cytotoxicity supported this hypothesis. Our study, therefore, provides the framework for the development of anti-tumor CTL cellular vaccines for treating MM using UV-irradiated tumor cells as immunogens.     

Study of Light Hypernuclei by the (e,e′K +) Reaction

We have been performing Λ hypernuclear spectroscopic experiments by the (e,e′K ⁺) reaction since 2000 at Thomas Jefferson National Accelerator Facility (JLab). The (e,e′K ⁺) experiment can achieve a few 100 keV (FWHM) energy resolution compared to a few MeV (FWHM) by the (K ^?, π ^?) and (π ⁺, K ⁺) experiments. Therefore, more precise Λ hypernuclear structures can be investigated by the (e,e′K ⁺) experiment. ${^{7}_{\Lambda}{\rm He}}$ , ${^{9}_{\Lambda}{\rm Li}}$ , ${^{10}_{\Lambda}{\rm Be}}$ , ${^{12}_{\Lambda}{\rm B}}$ , ${^{28}_{\Lambda}{\rm Al}}$ , and ${^{52}_{\Lambda}{\rm V}}$ were measured in the experiment at JLab Hall-C. In addition, ${^{9}_{\Lambda}{\rm Li}}$ , ${^{12}_{\Lambda}{\rm B}}$ , and ${^{16}_{\Lambda}{\rm N}}$ were measured in the experiment at JLab Hall-A.     

Hot gluon matter in a constantA 0 background

We compute the effective action of finiteT SU(3) gauge theory in a constant diagonal background fieldA ₀(t,x)=B ₀ ³ T₃+B ₀ ⁸ T₈ in the general covariant background gauge up to terms of orderg ³.B ₀ ^3,8 shield the infrared singularities and the aim is to study whether the minimum of the effective action would determine their values dynamically. We find that the orderg ² term depends explicitly on the gauge fixing parameter ξ. Since the background field screens already at the tree diagram level the interactions of the six non-diagonal gluon fields they do not contribute to the plasmon-likeg ³ term. The two diagonal fieldsA ₀ ³ ,A ₀ ⁸ do, but the electric mass squared they develop will become negative if the background fields are larger than aboutT/g. Hence large background fields make the system unstable.     

Average temperature and multiplicities ofe + e − annihilation

Hadron temperatures ofe ⁺ e ^?→h \(\bar h\) from PEP experiments at 29 GeV are estimated using theP _⊥ distribution; rather small fluctuations are found for temperatures of π,K,..., Ξ with respect to the average \(\bar T = 196 \pm 7\) MeV. A semi-empirical formula including quark content ofh is proposed to account for multiplicities of π,K, ..., Δ in terms of a unique temperature \(\bar T\) . The formula is further extended to charmed particlesD, F, J/Ψ andΛ _c without free parameters. The property \(\bar T\) ~E _cm ^1/4 holds for other experiments of DESY andCESR.     

Coulomb excitation of radioactive 20, 21Na

The low-energy structures of the radioactive nuclei ^{20, 21}Na have been examined using Coulomb excitation at the TRIUMF-ISAC radioactive ion beam facility. Beams of ～ 5×10⁶ ions/s were accelerated to 1.7MeV/A and Coulomb excited in a 0.5mg/cm^2 ^natTi target. Two TIGRESS HPGe clover detectors perpendicular to the beam axis were used for $ \gamma$ -ray detection, while scattered nuclei were observed by the Si detector BAMBINO. For ²¹Na , Coulomb excitation from the 3/2⁺ ground state to the first excited 5/2⁺ state was observed, while for ²⁰Na , Coulomb excitation was observed from the 2⁺ ground state to the first excited 3⁺ and 4⁺ states. For both beams, B ( $ \lambda$ L) values were determined using the 2⁺ $ \rightarrow$ 0⁺ de-excitation in ⁴⁸Ti as a reference. The resulting B(E2) ↓ value for ²¹Na is 137±9 e^2fm^4, while the resulting B( $ \lambda$ L) ↓ values for ²⁰Na are 55±6 e^2fm^4 for the 3⁺ $ \rightarrow$ 2⁺ , 35.7±5.7 e^2 fm^4 for the 4⁺ $ \rightarrow$ 2⁺ , and 0.154±0.030 μ_N^2 for the 4⁺ $ \rightarrow$ 3⁺ transitions. This analysis significantly improves the measurement of the ²¹Na B(E2) value, and provides the first experimental determination of B( $ \lambda$ L) values for the proton dripline nucleus ²⁰Na .-1     

The process e + e − → bb̅W + W − at the next linear collider in the Minimal Supersymmetric Standard Model

The complete matrix element for e ⁺ e^? → bb?W⁺ W^? is computed at tree-level within the Minimal Supersymmetric Standard Model. Rates of interest to phenomenological analyses at the Next Linear Collider are given. In particular, we study:

• ? tt? production and decay tt? →(bW ⁺)(b?W ^?)
• ? ZH production followed by Z → bb? and H → W ⁺ W^?
• ? AH production followed by A→ bb? and H → W ⁺ W^?
• ? hW ⁺ W^? production followed by h→ bb?.

Top and Higgs finite width effects are included, as well as all those of the irreducible backgrounds.     

Mass spectrometer studies of the ion composition in the pink afterglow

The time dependences of the ion number densities in the pink afterglow of nitrogen, as represented by the ion wall currents, have been measured. The ions were extracted through an orifice from a flow system and analysed by a quadrupol mass spectrometer. It has been found thatN ₂ ⁺ ions are dominating in the early afterglow. With the beginning of the ionization processN ₃ ⁺ and at pressure >6 TorrN ₄ ⁺ become the majority ions. The ratio of the number densities(N ₃ ⁺ )/(N ₂ ⁺ ) reaches a maximum during the increase of the ionization processes before the maximum is reached. This behaviour suggestsN ₃ ⁺ ions to be the primary ions created by the ionization processes. The time dependences of the ion number densities (N ₂ ⁺ ), (N ₃ ⁺ ) and(N ₄ ⁺ ) are found to vary similar, showing that the ions are strongly coupled by conversion processes. The conversion processes are discussed. In the maximum of ionization at a total pressure of 4.4 Torr the ratios of the number densities of the afterglow ions (N ₂ ⁺ )∶(N ₃ ⁺ )∶(N ₄ ⁺) are 1∶1.9∶0.64.     

Electric properties of levels of 156Dy rotational bands

The nonadiabaticity of E0 transitions from 0 ₂ ⁺ states and 2 ₁ ⁺ bands in ¹⁵⁶Dy is examined within a phenomenological model that takes into account the mixing of K ^π = 0 ₁ ⁺ , 0 ₂ ⁺ , 0 ₃ ⁺ , 2 ₁ ⁺ states and 1⁺-bands. It is shown that the nonadiabaticity of E0 transitions is due primarily to the mixing of 0 ₂ ⁺ and 0 ₃ ⁺ bands.     

Energy dependence of e + e − → 6π and e + e − → N\bar N cross sections near N\bar N the threshold

Using recent BABAR, CMD-3 and SND data, the sum of e ⁺ e ^? → 3(π⁺π^?), 2(π⁺π^?π⁰), \(p\bar p\) , \(n\bar n\) cross sections is obtained. Unlike e ⁺ e ^? 3(π⁺π^?) and e ⁺ e ^? → 2(π⁺π^?π⁰) processes, no structures in total cross section are found near the \(N\bar N\) threshold within the limits of measurement errors.     

Weak contributions to angular asymmetries ine + e − annihilation

We study the energy and polarization dependence of angular asymmetries ine ^? e ⁺→ψ,Z ⁰→f \(\bar f\) (f=lepton or quark). Through the fragmentation of the quarks the corresponding asymmetries are obtained for the jet axis ine ^? e ⁺→ψ,Z ⁰→(Σq \(\bar q\) )→2 jets, and for inclusively produced hadronsh(h=π⁺,K ⁺ and π⁺ +K ⁺) ine ^? e ⁺→ψ,Z ⁰→(Σq \(\bar q\) )→(h+X)_2jet. In the Weinberg-Salam model these asymmetries come out big enough to show up already at upper PETRA and PEP energies.     

Gyromagnetic ratios of 4+ and 6+ states in156Gd and158Gd

The followingg-factors have been derived from time integral measurements of γ-γ angular correlations in the static magnetic hyperfine field of magnetized gadolinium metal probes:¹⁵⁶Gd:g(4 ₁ ⁺ )=+0.310(19)g(6 ₁ ⁺ )=+0.25(21)g(4 ₃ ⁺ , 1511 keV)=+0.809(27)¹⁵⁸Gd:g(4 ₁ ⁺ )=+0.409(15). The 5.35d ¹⁵⁶Tb sources were produced by the reaction¹⁵⁶Gd(d, 2n)¹⁵⁶Tb in our cyclotron. A carrier-free 150y ¹⁵⁸Tb source was obtained from ISOLDE/CERN. In comparison with the precisely knowng-factors of the 2 ₁ ⁺ states,g(2 ₁ ^su+ ,¹⁵⁶Gd) =+0.386(4) andg(2 ₁ ⁺ ,¹⁵⁸Gd)=0.381(4), we observe a large reduction for the¹⁵⁶Gd 4 ₁ ⁺ state whereasg increases slightly for¹⁵⁸Gd. The half-life of the 4 ₁ ⁺ state of¹⁵⁸Gd was remeasured as¹⁵⁸Gd:T _1/2(4 ₁ ⁺ )=148(2) ps. A measurement of the rotation in the 4 ₃ ⁺ state of¹⁵⁶Gd in external magnetic fields of various strengths up toB _ext=9.5 T did not confirm the anomalous dependence of the magnetic hyperfine field in gadolinium metal on the external field, which has been reported by Persson et al. [29].     

Adaptive behaviour of the spinal cord in the transition from quiet stance to walking

Background

Parkinson??s disease is characterized by a continuous loss of neurons within the substantia nigra (SN) leading to a depletion of dopamine. Within the adult SN as a non-neurogenic region, cells with mainly oligodendrocytic precursor characteristics, expressing the neuro-glial antigen-2 (NG2) are continuously generated. Proliferation of these cells is altered in animal models of Parkinson??s disease (PD). Exercise and environmental enrichment re-increase proliferation of NG2⁺ cells in PD models, however, a possible mechanistic role of dopamine for this increase is not completely understood. NG2⁺ cells can differentiate into oligodendrocytes but also into microglia and neurons as observed in vitro suggesting a possible hint for endogenous regenerative capacity of the SN. We investigated the role of dopamine in NG2-generation and differentiation in the adult SN stimulated by physical activity and environmental enrichment.

Results

We used the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-model for dopamine depletion and analysed newborn cells in the SN at different maturation stages and time points depending on voluntary physical activity, enriched environment and levodopa-treatment. We describe an activity- induced increase of new NG2-positive cells and also mature oligodendrocytes in the SN of healthy mice. Running and enriched environment refused to stimulate NG2-generation and oligodendrogenesis in MPTP-mice, an effect which could be reversed by pharmacological levodopa-induced rescue.

Conclusion

We suggest dopamine being a key regulator for activity-induced generation of NG2-cells and oliogodendrocytes in the SN as a potentially relevant mechanism in endogenous nigral cellular plasticity.     

Experimental study of the energy dependence of the reaction rate coefficients of the reaction CH 3 + with N2O and NH3

The kinetics of the reaction of CH ₃ ⁺ ions with N₂O and NH₃ has been investigated in He and Ar buffers using Selected Ion Flow Drift Tube technique (SIFDT). Both studied reactions proceed with nearly collisional rate at near thermal energies. The rate coefficient of the reaction of CH ₃ ⁺ with N₂O is decreasing more than one order of magnitude (from 1.2×10^?9cm³s^?1 up to 8×10^?11cm³s^?1) with reactant ion/reactant neutral average centre-of-mass kinetic energy (E _r) increasing from near thermal up to 2 eV. The dominant product of this reaction is the isomer HCO⁺ (≥94%) and the minor product is CH₃O⁺. The reaction of CH ₃ ⁺ with NH₃ has two binary channels with the dominant product ion CH₂NH ₂ ⁺ (>70%) and the minor product ion NH ₄ ⁺ (≈10%) and three body association channel with product CH₃NH ₃ ⁺ (≈20% at 0.32 Torr). The rate coefficient of this reaction is decreasing nearly by one order of magnitude with increasingE _r from near thermal up to 0.8eV, forE _r>0.8 eV the rate coefficient increases with increasingE _r. The experimental results are interpreted in terms of a simple model assuming the reactions to proceed via the formation of long-lived collision complexes.     

Improved generation of anti-tumor immunity by antigen dose limitation

Background  

The malignant cells of cutaneous T cell lymphoma (CTCL) display immunogenic peptides derived from the clonal T cell receptor (TCR) providing an attractive model for refinement of anti-tumor immunization methodology. To produce a clinically meaningful anti-tumor response, induction of cytotoxic anti-CTCL cells must be maximized while suppressive T regulatory cells (Treg) should be minimized. We have demonstrated that engulfment of apoptotic CTCL cells by dendritic cells (DC) can lead to either CD8 anti-CTCL responses or immunosuppressive Treg induction. Treg generation is favored when the number of apoptotic cells available for ingestion is high.     

Spectroscopy ofQ\bar Qg hybrid mesons

Hybrid mesons composed of a quark, an antiquark, and a gluon are studied in the case of heavy quarks. Their masses are calculated with the potential model which can interpret heavy quarkonium spectroscopy. The ground state of the hybrid mesons \(c\bar cg\) and \(b\bar bg\) is found to be almost spherically symmetric, whereas that of \(t\bar tg\) is two-centered as anH ₂ ⁺ molecule. The \(b\bar bg\left[ {t\bar tg} \right]\) ground state turns out to have a mass below the \(B\bar B\left[ {T\bar T} \right]\) threshold. The excited states contain 0^??, 1^?+ exotic states and 1^?? states which may be examined bye ⁺ e ^? colliders.     

Near resonance charge transfer from a laser excited donor state

A laser induced charge transfer from Na(3p) to hydrogen-ions at different kinetic energies has been studied. An enhancement factor of about 90% in the production rate of Lyman-α radiation has been demonstrated to occur only with H⁺ and Na(3p) atoms reaction; no enhancement was observed with either H ₂ ⁺ or H ₃ ⁺ ions. Absolute cross-section for the production of Lyman-α radiation during the collision of H⁺, H ₂ ⁺ and H ₃ ⁺ ions and Na(3p) and Na(3s) atoms have been measured in the energy range 1–600eV. The charge exchange reactions involving hydrogen-ions and Na(3p) atoms created by two different methods have also been compared.     

On the character of three 8+ states in 192Pb

Three low-lying 8⁺ states have been identified in ¹⁹²Pb . A newly observed cascade of $ \gamma$ -rays built directly on the 8⁺ ₁ state is compared to the previously identified, weakly rotational band above the 11^- $ \pi$ i _13/2 , h _9/2 isomer in the same nucleus, and to analogous structures in ¹⁹⁴Pb . The similarity of all four structures lends support to the suggestion that the 8⁺ ₁ configurations are of a similar oblate deformation to the 11^- isomers. The excitation energies of all three 8⁺ states in ¹⁹²Pb and ¹⁹⁰Pb are compared to systematics. The possibility that one of the 8⁺ states in ¹⁹²Pb is associated with a prolate shape is discounted.     

Untersuchung des Zerfalls von134Cs durch γ-γ-Winkelkorrelationsmessungen

γ-γ-angular correlation measurements with Ge(Li) detectors and NaJ(Tl) detectors provided theE2/M1 mixing ratios of the following gamma transitions: 3 ₁ ⁺ →2 ₂ ⁺ (475.3 keV), 2 ₂ ⁺ →2 ₁ ⁺ (563.3 keV), 4 ₂ ⁺ →4 ₁ ⁺ (569.4 keV), 3 ₁ ⁺ →2 ₁ ⁺ (1,039 keV). The angular correlation measurements were only consistent with spin 3 of the 1,643 keV level. The half life of the 1,401 keV level was determined by delayed coincidence techniques to beT _1/2 (1,401 keV)≦30 ps.