Prognosis of intravesical bacillus Calmette-Guerin therapy for superficial bladder cancer by immunological urinary measurements: statistically weighted syndrome analysis

PURPOSE: The goal of this research was to discover new biological indicators in urine which could be used for short-term prognosis of local Bacillus Calmette-Guerin (BCG) therapy outcome in patients with superficial bladder cancer. PATIENTS AND METHODS: We measured and statistically evaluated soluble immunological molecules in urine from bladder cancer patients (n = 34) receiving BCG intravesically. Urine was collected following each of 6 weekly treatments, processed and assayed. The data base included measurements of interleukin-1 (IL-2, IL-4, IL-6, IL-10, IL-12, soluble intercellular adhesion molecule-1 (sICAM-1), tumour necrosis factor-alpha (TNF alpha), soluble CD14 (sCD14), interferon-gamma (IFN gamma), GM-CSF, volume of urine and its pH. The clinical response was evaluated by urine histology and random quadrant biopsy 3 months after the start of therapy. Patients were divided into 2 groups, with good and poor therapeutic effect. The initial complete response rate was 62% (21/34). The data base was analyzed using traditional multivariate statistical methods and a pattern recognition method which deals with combinatorial-statistical analysis (statistically weighted syndromes (SWS) method) of the gradated features. The SWS method is capable of identifying robust patterns in small "fuzzy" sets with high dimensional objects and some missing values. RESULTS: Only one parameter gave significant differences at p < 0.05, GM-CSF at instillation 6. Repeated measurement analysis of variance, backward stepwise multiple logistic regression and linear discriminant analysis failed to show any significance. However, significant differences in the structure of correlation between features in the groups with and without therapeutic effect were observed and four highly informative variables (the masses of sICAM-1, TNF alpha, sCD14 and pH) relating to 5th-6th installations were selected by SWS. These features provided accurate individual prediction of therapeutic outcome for all our patients. Cross-validation analysis and computer simulation showed the statistically significant stability of the prediction. CONCLUSION: We have selected a set of urinary variables that could be considered as a perspective combination of indicators (syndromes) of outcome of pre-operation BCG therapy of patients with superficial bladder cancer. A larger patient database will provide testing and evaluation of the biological and clinical significance of selected features. The computational syndrome-disease approach should be applicable for the solution of decision-making problems for management of cancer.     

Solution structure of glutathione bound to human glutathione transferase P1-1: comparison of NMR measurements with the crystal structure

The conformation of the bound glutathione (GSH) in the active site of the human glutathione transferase P1-1 (EC 2.5.1.18) has been studied by transferred NOE measurements and compared with those obtained by X-ray diffraction data. Two-dimensional TRNOESY and TRROESY experiments have been performed under fast-exchange conditions. The family of GSH conformers, compatible with TRNOE distance constraints, shows a backbone structure very similar to the crystal model. Interesting differences have been found in the side chain regions. After restrained energy minimization of a representative NMR conformer in the active site, the sulfur atom is not found in hydrogen-bonding distance of the hydroxyl group of Tyr 7. This situation is similar to the one observed in an "atypical" crystal complex grown at low pH and low temperature. The NMR conformers display also a poorly defined structure of the glutamyl moiety, and the presence of an unexpected intermolecular NOE could indicate a different interaction of this substrate portion with the G-site. The NMR data seem to provide a snapshot of GSH in a precomplex where the GSH glutamyl end is bound in a different fashion. The existence of this precomplex is supported by pre-steady-state kinetic experiments [Caccuri, A. M., Lo Bello, M., Nuccetelli, M., Nicotra, M., Rossi, P., Antonini, G., Federici, G., and Ricci, G. (1998) Biochemistry 37, 3028-3034] and preliminary time-resolved fluorescence data.     

Relationship between cleaved L-selectin levels and the outcome of acute myeloid leukemia

High plasma levels of the shed form of L-selectin (sL-selectin) are frequently detectable in acute myeloid leukemia (AML). sL-selectin can inhibit blast cell adhesion to vascular endothelium and may thereby influence the phenotype of AML. In this study, we have investigated the relationship between sL-selectin levels and clinical presentation or disease outcome in 100 patients with AML. Fifty-eight patients were found to have sL-selectin levels >/=3.12 microgram/mL (>/=3 SD above the mean of healthy controls: "increased"). Patients with extramedullary disease such as lymphadenopathies, splenomegaly, hepatomegaly, and/or muco-cutaneous infiltration had significantly increased sL-selectin levels (P < .001). sL-selectin levels were significantly heterogeneous in the French-American-British subtypes (P = .0003). Patients with "normal" sL-selectin levels had higher probability of achieving complete remission (CR) than with "increased" levels: 81% versus 64%, respectively (P = .06). When adjusting for clinically relevant covariates predictive for CR (sex, age, Auer rods), "normal" sL-selectin levels were significantly associated with CR (odds ratio, 3.08; 95% confidence interval [CI], 1.10 to 8.58; P = .03). Moreover, patients with "increased" sL-selectin levels (>/=3.12 microgram/mL) had shorter event-free survival (EFS) (median 7.3 v 12 months, P = .008) and overall survival (median 1 v 2.05 years, P = .03) than patients with sL-selectin <3.12 microgram/mL. Multivariate statistical analysis (adjusted for age and presence of Auer rods) indicated that sL-selectin was an independent prognostic factor for EFS (hazard ratio [HR], 1.96; 95% CI, 1.21 to 3.17, P = .006) and overall survival (HR, 1.80; 95% CI, 1.09 to 2.98; P = .02). Thus, plasma sL-selectin may be a useful prognostic marker in the evaluation of AML at diagnosis.     

Effects of transdermal nitroglycerin on impedance to flow in the uterine, umbilical, and fetal middle cerebral arteries in pregnancies complicated by preeclampsia and intrauterine growth retardation

BACKGROUND: Uncertainty exists about the extent and consequences of a return to alcohol consumption after liver transplantation for alcoholic liver disease (ALD). AIMS: To determine the prevalence and consequences of alcohol consumption in patients transplanted for ALD. METHODS: A retrospective case controlled study of all patients transplanted for ALD at the Queen Elizabeth Hospital, Birmingham, between 1987 and 1996. RESULTS: Seventy patients with ALD were transplanted, of which 59 survived more than three months; 56 were interviewed. Twenty eight had consumed some alcohol after transplantation; for the nine "heavy drinkers" (HD), the median time to resumption of alcohol intake was six months and for the 19 "moderate drinkers" (MD) it was eight months. There was no significant difference in episodes of acute rejection or compliance with medication between those who were abstinent, MD, or HD. Histological evidence of liver injury was common in ALD patients who had returned to drink. Mild fatty change was found in 1/11 biopsy specimens from abstinent patients but moderate to severe fatty change and ballooned hepatocytes were seen in 3/5 MD and 2/5 HD specimens. Two HD patients had early fibrosis. One HD patient had died of alcohol related complications. CONCLUSIONS: Moderate to heavy alcohol consumption occurs in patients transplanted for ALD. Patient recall of abstinence advice is unreliable, and patients return to alcohol mainly within the first year after liver transplantation. Return to alcohol consumption after liver transplantation is associated with rapid development of histological liver injury including fibrosis.     

Fluid jet polishing of optical surfaces

We present a new finishing process that is capable of locally shaping and polishing optical surfaces of complex shapes. A fluid jet system is used to guide a premixed slurry at pressures less than 6 bars to the optical surface. We used a slurry comprising water and 10% #800 SiC abrasives (21.8 mum) to reduce the surface roughness of a BK7 sample from 350 to 25 nm rms and to vary the shape of a polished sample BK7, maintaining its surface roughness of 1.6 nm rms, thereby proving both the shaping and polishing possibilities of the presented method.     

Laser with rapid tuning of the spectrum shape

We have studied a laser system with quick electronic tuning of the spectrum shape and continuous distribution. The proposed method is based on separate control of phase and amplitude spatial distributions of resonator transmittance. Evolution of the spectral function of the diffractively coupled dispersive resonators and the model for the formation of the resonator with the spectral function given by its moments are studied theoretically. The synthesis of continuous spectra is investigated experimentally in the laser with a novel control element including a spatial acousto-optic modulator and a tunable lens telescope.     

Design and fabrication of a 24-channel acousto-optic spatial light modulator

Acousto-optic (AO) devices are important spatial light modulators. They can be used as light-beam deflectors, rf true-time-delay lines, etc. To increase their spur-free dynamic range, we present what to our knowledge is a novel multichannel AO device structure, in which different channels have different carrier frequencies, so a wideband signal can automatically be decomposed into a set of narrow-band signals. Design, fabrication, and testing of this 24-channel, 10-mus AO spatial light modulator are addressed.     

Phonon Scattering in Thin Silica Films Below 1 K

A method is described for studying thermal phonon scattering in thin films on dielectric substrates below a few Kelvin. It is used to study silica films on silicon substrates. Using Monte Carlo simulations with no free parameters, we find that thermally grown silica films 0.1 to 1.0 m thick scatter the phonons as strongly as bulk silica, and hence, have the same thermal conductivity as bulk silica, while a 0.1 m thick e-beam evaporated silica film has a thermal conductivity five times smaller than bulk silica, indicative of additional defects.     

Mobility and Localization of Carriers in a Quasi-One-Dimensional Electron System over Liquid Helium

The properties of a quasi-one-dimensional (Q1D) electron system on liquid helium are considered and the experiments on the carrier transport are presented. It has been shown that the electron mobility changes from high values close to that for bulk helium to very small values as a function of the Q1D channel width. Such a behaviour of is connected to a gradual transition from the regime of the quasi-free movement of the carriers in a Q1D system to the conditions of strong localization of the electrons. In the last case depends on temperature exponentially with the activation energy of a few degrees. It is predicted that in Q1D channels in regime of the localization two optical plasmon branches can exist. One of them (a high frequency branch) is connected with the oscillations of electrons in potential wells and another one has lower frequency and is due to the oscillations of dimples, which are created by localized electrons on the liquid helium surface, in the potential wells. Possible new experiments on study of magnetotransport, plasma oscillations and phase diagram of ordered-disordered states in a Q1D electron system of a finite length over liquid helium are proposed and discussed.     

Synthesis of luminescent yttrium silicate materials by the sol-gel method

The sol-gel method is shown to be useful for obtaining luminescent yttrium silicate-based materials with performance characteristics superior to commercial analogs. The effect of the phase composition of sol-gel luminophors on the spectral luminescence parameters is analyzed. A way to prepare materials with controlled granulometric composition is proposed.Translated from Steklo i Keramika, No. 11, pp. 23–26, November, 1996.