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Biomedical subjects

J Walz

Publications and source records attributed to J Walz.

At least 19 recordsLinked to original sources

Transition zone cancers undermine the predictive accuracy of Partin table stage predictions.

PURPOSE: The Partin tables represent the most widely used predictor of pathological stage in men with localized prostate cancer (PCa). The accuracy and performance of the tables have been tested across different populations. However, to our knowledge the potential limitations that may stem from differences between transition zone (TZ) and peripheral zone (PZ) prostate cancers has not been explored. We tested the predictive accuracy and performance of the Partin tables according to TZ vs PZ tumor predominance. MATERIALS AND METHODS: Preoperative serum prostate specific antigen, clinical stage and biopsy Gleason sum data on 1,990 patients treated with radical retropubic prostatectomy were used to define the 2001 Partin probabilities of organ confinement and seminal vesicle invasion (SVI). Data on 1,320 patients who underwent staging pelvic lymphadenectomy and radical retropubic prostatectomy were used to define the probabilities of lymph node invasion (LNI) and organ confined disease (OC). ROC area under the curve was used to assess the predictive accuracy of the 2001 Partin tables relative to observed extracapsular extension (ECE), SVI, LNI and OC. Performance characteristics for each prediction were explored graphically with local regression, nonparametric smoothing plots. Results were compared between 222 TZ cancers and 1,768 PZ cancers. RESULTS: The 1,990 radical retropubic prostatectomy specimens demonstrated ECE in 689 cases (34.6%) (TZ in 58 or 27.1% and PZ in 631 or 35.8%) and SVI in 224 (TZ in 13 or 6.1% and PZ in 211 or 11.9%). The 1,320 lymphadenectomy specimens demonstrated LNI in 56 cases (TZ in 2 or 0.9% and PZ in 54 or 4.6%). OC was found in 784 cases (59.4%) (TZ in 95 or 69.9% and PZ in 689 or 58.2%). Predictive accuracy was for ECE 76.4% (TZ 69.0% and PZ 77.2%), 78.0% for SVI (TZ 73.5% and PZ 78.3%), 78.6% for LNI (TZ 44.5% and PZ 79.9%) and 79.4% for OC (TZ 73.8% and PZ 80.0%). CONCLUSIONS: The biological tumor characteristics of TZ PCa differ from those of PZ PCa. These differences appear to undermine the accuracy of pathological stage predictions.

Humans↗

First laser-controlled antihydrogen production.

Lasers are used for the first time to control the production of antihydrogen (H ). Sequential, resonant charge exchange collisions are involved in a method that is very different than the only other method used so far-producing slow H during positron cooling of antiprotons in a nested Penning trap. Two attractive features are that the laser frequencies determine the H binding energy, and that the production of extremely cold H should be possible in principle-likely close to what is needed for confinement in a trap, as needed for precise laser spectroscopy.

Journal Article↗

First measurement of the velocity of slow antihydrogen atoms.

The speed of antihydrogen atoms is deduced from the fraction that passes through an oscillating electric field without ionizing. The weakly bound atoms used for this first demonstration travel about 20 times more rapidly than the average thermal speed of the antiprotons from which they form, if these are in thermal equilibrium with their 4.2 K container. The method should be applicable to much more deeply bound states, which may well be moving more slowly, and should aid the quest to lower the speed of the atoms as required if they are to be trapped for precise spectroscopy.

Journal Article↗

Driven production of cold antihydrogen and the first measured distribution of antihydrogen states.

Cold antihydrogen is produced when antiprotons are repeatedly driven into collisions with cold positrons within a nested Penning trap. Efficient antihydrogen production takes place during many cycles of positron cooling of antiprotons. A first measurement of a distribution of antihydrogen states is made using a preionizing electric field between separated production and detection regions. Surviving antihydrogen is stripped in an ionization well that captures and stores the freed antiproton for background-free detection.

Journal Article↗

Background-free observation of cold antihydrogen with field-ionization analysis of its states.

A background-free observation of cold antihydrogen atoms is made using field ionization followed by antiproton storage, a detection method that provides the first experimental information about antihydrogen atomic states. More antihydrogen atoms can be field ionized in an hour than all the antimatter atoms that have been previously reported, and the production rate per incident high energy antiproton is higher than ever observed. The high rate and the high Rydberg states suggest that the antihydrogen is formed via three-body recombination.

Journal Article↗

Continuous coherent Lyman- alpha excitation of atomic hydrogen.

The 1S-2P transition in atomic hydrogen has been observed for the first time with almost natural linewidth. We employ a unique source of continuous coherent Lyman- alpha radiation based on four-wave mixing in mercury. The output of the source has been improved 40-fold to yield 20 nW. This demonstration shows that laser cooling and detection with continuous Lyman- alpha radiation has excellent prospects for future experiments with antihydrogen.

Journal Article↗

The effect of fluvoxamine and behavior therapy on children and adolescents with obsessive-compulsive disorder.

OBJECTIVE: The efficacy of medications, consisting of serotonin partial and specific reuptake blockers, and behavior therapy, consisting of exposure and response prevention in addition to social skills training, cognitive therapy, and habit reversal, in the treatment of obsessive-compulsive disorder are well documented. The purpose of the study was to explore if adding behavior therapy to medication would enhance treatment efficacy. METHODS: Ten children/adolescents who had not previously responded to behavior therapy were randomly assigned to two groups: fluvoxamine alone or fluvoxamine with behavior therapy. All 10 patients received fluvoxamine for 10 weeks-five continued solely on fluvoxamine for one year and five engaged in behavior therapy for 20 sessions along with fluvoxamine and then continued solely on medication until the end of the year. RESULTS: Eight of 10 patients improved significantly on fluvoxamine at week 10 on the primary outcome variable, the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS). According to the other measurements-National Institute of Mental Health-Global Obses-sive-Compulsive Scale, Clinical Global Impression-Improvement (assessing level of im-provement from week to week), and Clinical Global Impression-Severity of Illness Scale (as-sessing how ill the patient is from week to week)-improvement was not as evident. According to the CY-BOCS, those who received a combination of fluvoxamine and exposure with response prevention showed significantly more improvement than those who only took medication. At two-year follow-up, all patients continued to improve, with those in the combined approach improving more than those in the medication-alone group. CONCLUSIONS: Future studies should determine the specific effect of each treatment group, combined and singularly. Reasons for discrepancy in improvement ratings as noted by the different instruments are discussed. The addition of behavior therapy to fluvoxamine seems to enhance treatment efficacy, according to the CY-BOCS.

Adolescent↗

Parental obsessive-compulsive disorder as a prognostic factor in a year long fluvoxamine treatment in childhood and adolescent obsessive-compulsive disorder.

Interest in the treatment of pediatric obsessive-compulsive disorder (OCD) has increased as our knowledge of adult OCD has expanded. Although adults are still the majority of patients, children and adolescents with OCD are being identified and treated more frequently. As this population is better identified, prognostic factors need to be addressed to improve treatment outcome. The purpose of this study was to determine the role of family psychiatric pathology in fluvoxamine treatment outcome. Eleven children and adolescents with OCD and one of their parents participated in the study. Four parents were diagnosed with OCD, six had an Axis I diagnosis other than OCD, and one had no mental disorder [Structured Clinical Interview for the DSM-Non-Patient edition (SCID-NP)]. Each patient received fluvoxamine for 58 weeks. Dependent measures included the Children Yale-Brown Obsessive Compulsive Scale (CY-BOCS), the NIMH-Global Obsessive Compulsive Scale (NIMH-GOCS) and the Clinical Global Impression (CGI). Based on CY-BOCS, CGI and NIMH-GOCS scores, patients with parents who have OCD showed a clinically and statistically significant reduction in symptoms from pre- to post-treatment. Patients whose parents did not have OCD also improved. However, the improvement was statistically but not clinically significant. The presence of OCD in one parent seems to modify a child's response to medication. The results suggest that family psychopathology, specifically presence of OCD, may contribute to treatment efficacy. Further research is suggested in this area.

Adolescent↗

Capsids of tricorn protease studied by electron cryomicroscopy.

Tricorn protease from the archaeon Thermoplasma acidophilum acts "downstream" of the proteasome; in conjunction with its aminopeptidase cofactors it converts peptides generated by the proteasome into free amino acids. The basic functional unit of Tricorn is a homohexamer of the 121-kDa subunit, 20 of which can assemble further to form an icosahedral capsid with a molecular mass of 14.6 MDa. We have used electron cryomicroscopy to determine the structure of the Tricorn capsids to a resolution of 1.3 nm.

Archaeal Proteins↗

Structure of VAT, a CDC48/p97 ATPase homologue from the archaeon Thermoplasma acidophilum as studied by electron tomography.

Valosine-containing protein-like ATPase from Thermoplasma acidophilum is a member of the superfamily of ATPases associated with a diversity of cellular activities and is closely related to CDC48 from yeast and p97 from higher eukaryotes and more distantly to N-ethylmaleimide-sensitive fusion protein. We have used electron tomography to obtain low-resolution (2-2.5 nm) three-dimensional maps of both the whole 500 kDa complex and the N-terminally truncated valosine-containing protein-like ATPase from T. acidophilum complex lacking the putative substrate binding domain.

Adenosine Triphosphatases↗

Proteasomes and other self-compartmentalizing proteases in prokaryotes.

The proteasome represents the major non-lysosomal proteolytic system in eukaryotes. It confines proteolytic activity to an inner compartment that is accessible to unfolded proteins only. The strategy of controlling intracellular breakdown of proteins by self-compartmentalization is also used by different types of prokaryotic energy-dependent proteases. Genomic sequencing data reveal that various combinations of these energy-dependent proteases occur in prokaryotic cells from different lineages.

Adenosine Triphosphatases↗

The preprotein translocation channel of the outer membrane of mitochondria.

The preprotein translocase of the outer membrane of mitochondria (TOM complex) facilitates the recognition, insertion, and translocation of nuclear-encoded mitochondrial preproteins. We have purified the TOM complex from Neurospora crassa and analyzed its composition and functional properties. The TOM complex contains a cation-selective high-conductance channel. Upon reconstitution into liposomes, it mediates integration of proteins into and translocation across the lipid bilayer. TOM complex particles have a diameter of about 138 A, as revealed by electron microscopy and image analysis; they contain two or three centers of stain-filled openings, which we interpret as pores with an apparent diameter of about 20 A. We conclude that the structure reported here represents the protein-conducting channel of the mitochondrial outer membrane.

1,2-Dipalmitoylphosphatidylcholine↗

26S proteasome structure revealed by three-dimensional electron microscopy.

In 26S proteasomes, "19S cap complexes" associate with either one or both ends of the barrel-shaped 20S core complex. These regulatory complexes which comprise about 20 different subunits, including 6 ATPases of the AAA family, are thought to recognize ubiquitinated substrate proteins, to dissociate and unfold them before threading them into the 20S core where they are degraded. Here, we examine the structure of 26S proteasomes from Drosophila embryos and Xenopus oocytes by electron microscopy. Image analysis reveals a rather flexible linkage between the 19S caps and the 20S core, with a peculiar wagging-type movement of the caps relative to the core. At this stage of the analysis, it is not clear whether this movement is relevant in terms of function. Three-dimensional reconstructions, taking this into account, provide first insights into the remarkably complex structure of the 19S caps and allows us to put forward a composite model of the entire 26S complex.

Animals↗

Electron cryomicroscopy of bacteriorhodopsin vesicles: mechanism of vesicle formation.

We obtained vesicles from purple membrane of Halobacterium halobium at different suspension compositions (pH, electrolytes, buffers), following the procedure of Kouyama et al. (1994) (J. Mol. Biol. 236:990-994). The vesicles contained bacteriorhodopsin (bR) and halolipid, and spontaneously formed during incubation of purple membrane suspension in the presence of detergent octylthioglucoside (OTG) if the protein:OTG ratio was 2:1 by weight. The size distribution of the vesicles was precisely determined by electron cryomicroscopy and was found to be almost independent on the incubation conditions (mean radius 17.9-19 nm). The size distribution in a given sample was close to the normal one, with a standard deviation of approximately +/- 1 nm. During dialysis for removal of the detergent, the vesicles diminished their radius by 2-2.5 nm. The results allow us to conclude that the driving force for the formation of bR vesicles is the preferential incorporation of OTG molecules in the cytoplasmic side of the membrane (with possible preferential delipidation of the extracellular side), which creates spontaneous curvature of the purple membrane. From the size distribution of the vesicles, we calculated the elasticity bending constant, K(B) approximately 9 x 10(-20) J, of the vesicle wall. The results provide some insight into the possible formation mechanisms of spherical assembles in living organisms. The conditions for vesicle formation and the mechanical properties of the vesicles could also be of interest with respect to the potential technological application of the bR vesicles as light energy converters.

Bacteriorhodopsins↗

Automated electron microscope tomography of frozen-hydrated chromatin: the irregular three-dimensional zigzag architecture persists in compact, isolated fibers.

The potential of electron microscope tomography as a tool for obtaining three-dimensional (3D) information about large macromolecular assemblies is greatly extended by automation of data collection. With the implementation of automated control of tilting, focusing, and digital image recording described here, tilt series of frozen-hydrated specimens can be collected with the requisite low dose. Long chromatin fibers were prepared in 90 mM monovalent ions to maintain a fully compact conformation, and after vitrification were completely contained within the ice layer. Tilt series of this material were recorded at 5 degrees tilt increments between +60 degrees and -60 degrees, with a cumulative dose of approximately 35 e-/A2 for the series. This extremely low dose data was successfully aligned, then reconstructed by weighted backprojection. The underlying architecture of the fibers is an irregular 3D zigzag of interconnected nucleosomes, with the linker DNA between successive nucleosomes in a largely extended conformation. The visualization of this structural motif within long, frozen-hydrated chromatin fibers at relatively high salt extends our previous studies on small fragments at low ionic strength and is in agreement with the observation of this architecture in chromatin fibers in situ in sectioned nuclei.

Animals↗