SUMMARY
We conducted a phase I/II clinical trial of the safety and efficacy of intravesical administration of autologous IFN‐γ‐activated macrophages (MAK) in patients with superficial bladder cancer. ...Monocyte‐derived MAK cells were prepared in vitro
and patients received six instillations of 1·4 × 108 to
2·5 × 108 cells, once a week, for five consecutive weeks. Treatment was well tolerated, with seven grade 1 and five Grade 2 protocol‐related adverse effects. Nine out of 17 included patients had no recurrences during the year following the first instillation of MAK. The aim of the present study was to search for immune parameters related to local immunostimulation induced by MAK. Monitoring of the patients showed that urinary IL‐8, GM‐CSF and, to a lesser extent, IL‐18 were increased following MAK instillations, with inter‐individual differences. The urinary IL‐8 level was about 10‐fold higher than that observed for other cytokines, and its biological activity was reflected by a concomitant increase of urinary elastase, indicating neutrophil activation and degranulation. We also showed that nine out of 12 patients investigated presented an increase of urinary neopterin, a marker of IFN‐γ‐activated macrophages, 7 days after MAK instillation, while serum neopterin levels were almost stable. These results are in line with persistence of activated macrophages in the bladder wall after infusions. Moreover, there was evidence of macrophages in urine smears 2 months after the sixth MAK instillation, and the score of macrophages correlated with the quantity of neutrophils in the urine. Overall, this study provides evidence of a local immunostimulation induced by this novel and safe immunotherapeutic approach of MAK instillations in patients with superficial bladder cancer.
SUMMARY
The Fc receptor mediated antibody‐dependent cell‐mediated cytotoxicity (ADCC) and phagocytosis induced by bispecific antibody (BsAb) to the high‐affinity Fc receptor for IgG (FcγRI) and to ...human red blood group antigen RhD were studied in vitro, using human mononuclear leucocytes as effector cells. The results were compared with those obtained by using a human monoclonal IgGI anti‐RhD used alone and a reference human polyclonal anti‐RhD antibody. The effect of non‐specific human IgG on FcR‐mediated functions by mononuclear leucocytes was checked. The results demonstrate that BsAb presents a high resistance of Fc‐mediated function to blockade by non‐specific human IgG compared with that of both polyclonal and monoclonal anti‐RhD antibodies. These results further encourage possible clinical application of bispecfic antibody in passive immunotherapy.
We report on the final electroweak measurements performed with data taken at the Z resonance by the experiments operating at the electron–positron colliders SLC and LEP. The data consist of 17 ...million Z decays accumulated by the ALEPH, DELPHI, L3 and OPAL experiments at LEP, and 600 thousand Z decays by the SLD experiment using a polarised beam at SLC. The measurements include cross-sections, forward–backward asymmetries and polarised asymmetries. The mass and width of the Z boson,
m
Z
and
Γ
Z
, and its couplings to fermions, for example the
ρ
parameter and the effective electroweak mixing angle for leptons, are precisely measured:
m
Z
=
91.1875
±
0.0021
GeV
,
Γ
Z
=
2.4952
±
0.0023
GeV
,
ρ
ℓ
=
1.0050
±
0.0010
,
sin
2
θ
eff
lept
=
0.23153
±
0.00016
.
The number of light neutrino species is determined to be
2.9840
±
0.0082
, in agreement with the three observed generations of fundamental fermions.
The results are compared to the predictions of the Standard Model (SM). At the Z-pole, electroweak radiative corrections beyond the running of the QED and QCD coupling constants are observed with a significance of five standard deviations, and in agreement with the Standard Model. Of the many Z-pole measurements, the forward–backward asymmetry in b-quark production shows the largest difference with respect to its SM expectation, at the level of 2.8 standard deviations.
Through radiative corrections evaluated in the framework of the Standard Model, the Z-pole data are also used to predict the mass of the top quark,
m
t
=
173
-
10
+
13
GeV
, and the mass of the W boson,
m
W
=
80.363
±
0.032
GeV
. These indirect constraints are compared to the direct measurements, providing a stringent test of the SM. Using in addition the direct measurements of
m
t
and
m
W
, the mass of the as yet unobserved SM Higgs boson is predicted with a relative uncertainty of about 50% and found to be less than
285
GeV
at 95% confidence level.
Search for neutral MSSM Higgs bosons at LEP Casado, M.P.; Ouyang, Q.; Xu, R. ...
The European physical journal. C, Particles and fields,
09/2006, Letnik:
47, Številka:
3
Journal Article
Recenzirano
Odprti dostop
The four LEP collaborations, ALEPH, DELPHI, L3 and OPAL, have searched for the neutral Higgs bosons which are predicted by the Minimal Supersymmetric standard model (MSSM). The data of the four ...collaborations are statistically combined and examined for their consistency with the background hypothesis and with a possible Higgs boson signal. The combined LEP data show no significant excess of events which would indicate the production of Higgs bosons. The search results are used to set upper bounds on the cross-sections of various Higgs-like event topologies. The results are interpreted within the MSSM in a number of “benchmark” models, including CP-conserving and CP-violating scenarios. These interpretations lead in all cases to large exclusions in the MSSM parameter space. Absolute limits are set on the parameter cosβ and, in some scenarios, on the masses of neutral Higgs bosons.
Closed-circular HBV DNA was introduced into cells of the established human hepatoma culture HepG2. The culture medium of one of 40 single-cell clones contained HBV surface antigen (HBsAg), ...core-related antigens (HBc/eAg), and HBV DNA sequences. HBV DNA and DNA polymerase activity were detected in particles resembling both nucleocapsids and complete virions (Dane particles). Intracellular integrated and extrachromosomal HBV DNA sequences were detected. Relaxed-circular and single-stranded forms of viral DNA were identified as likely replicative intermediates of the HBV genome. In conclusion, in vitro production of Dane-like particles by transformed human hepatocytes has been achieved. This model should be valuable as a cell culture system for studying virus replication and virus-host cell interactions.
The nature of b-quark jet hadronisation has been investigated using data taken at the Z peak by the DELPHI detector at LEP. Two complementary methods are used to reconstruct the energy of weakly ...decaying b-hadrons,
. The average value of
is measured to be 0.699±0.011. The resulting
distribution is then analysed in the framework of two choices for the perturbative contribution (parton shower and Next to Leading Log QCD calculation) in order to extract measurements of the non-perturbative contribution to be used in studies of b-hadron production in other experimental environments than LEP. In the parton shower framework, data favour the Lund model ansatz and corresponding values of its parameters have been determined within PYTHIA 6.156 from DELPHI data:
with a correlation factor
ρ
=92.2%.
Combining the data on the b-quark fragmentation distributions with those obtained at the Z peak by ALEPH, OPAL and SLD, the average value of
is found to be 0.7092±0.0025 and the non-perturbative fragmentation component is extracted. Using the combined distribution, a better determination of the Lund parameters is also obtained:
with a correlation factor
ρ
=92.6%.
Neutrophils isolated from cancer patients treated with granulocyte colony-stimulating factor (G-CSF) express high levels of FcγRI. They exhibited an efficient killing of GD2+ neuroblastoma cells in ...the presence of an antidisialoganglioside (GD2) mouse monoclonal antibody (MoAb; 7A4, lgG3κ). However, this cytotoxicity was totally blocked by human mono-meric IgG. In contrast, a bispecific antibody (7A4 bis 22/MDX-260), prepared by chemically linking an F(ab') fragment of 7A4 with an F(ab') fragment of an anti-FcγRI MoAb, 22, which binds outside the Fc binding domain, triggered antibody-dependent cell cytotoxicity, even when neutrophils were preincubated with human monomeric IgG. F(ab' )2 22 MoAb abrogated the MDX-260 killing without affecting that of 7A4. The 3G8 MoAb, directed against the FcγRIII binding site, did not inhibit the cytotoxicity induced by either antibody. Thus, these results indicate that G-CSF-activated neutrophils exert their cytotoxic effect against neuroblastoma cells through FcγRI and not FcγRIII, and that the saturation of the high affinity FcγRI by monomeric IgG can be overcome by the use of bispecific antibodies binding epitopes outside the IgG FcγRI binding site. A combined administration of such bispecific antibodies and G-CSF may be, therefore, an efficient therapeutic approach to trigger tumor lysis by cytotoxic neutrophils in vivo.
Single photons detected by the DELPHI experiment at LEP2 in the years 1997–2000 are reanalysed to investigate the existence of a single extra dimension in a modified ADD scenario with slightly warped ...large extra dimensions. The data collected at centre-of-mass energies between 180 and 209 GeV for an integrated luminosity of ∼650 pb
−1
agree with the predictions of the Standard Model and allow a limit to be set on graviton emission in one large extra dimension. The limit obtained on the fundamental mass scale
M
D
is 1.69 TeV/
c
2
at 95% CL, with an expected limit of 1.71 TeV/
c
2
.
This report describes serologic evidence for a virus similar to that known as simian T-lymphotropic virus type III of African Green monkeys (STLV-III$_{\text{AGM}}$) infecting apparently healthy ...people in Senegal, West Africa, and the isolation of virus from these individuals. Serum samples from selected healthy West African people showed unusual serologic profiles when tested with antigens of HTLV-III/LAV, the etiologic agent of AIDS, and of STLV-III$_{\text{AGM}}$. The samples reacted strongly with all of the major viral antigens of STLV-III$_{\text{AGM}}$ but showed variable or no reactivity with the major viral antigens of HTLV-III/LAV by radioimmunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A new human T-lymphotropic virus (HTLV-IV) isolated from these people was grown in vitro and shown to have retroviral type particles, growth characteristics, and major viral proteins similar to those of the STLV-III and HTLV-III/LAV group of retroviruses. The gp120/160, gp32, p64, p55, p53, p24, and p15 proteins precipitated were the same size as and reactive with STLV-III$_{\text{AGM}}$ proteins. The serologic data suggest that this virus shares more common epitopes with STLV-III$_{\text{AGM}}$ than with the prototype HTLV-III/LAV that infects people in the United States and Europe. Further study of this virus and of the origin of the HTLV-III/LAV group of viruses may expand our understanding of the human AIDS virus.
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