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PubMed2003

Modulation of the activity of Bcl-2 in Waldenstrom's macroglobulinemia using antisense oligonucleotides.

Bcl-2 is an attractive target for anticancer therapy in a number of malignancies, as its expression is associated with inhibition of the apoptotic program and resistance to traditional therapeutic agents. Bcl-2 antisense therapy with G3139 (oblimersen sodium; Genasense, Genta Inc, Berkeley Heights, NJ) is in clinical trials for a number of malignancies, including an ongoing trial in myeloma. In vitro G3139 has been shown to downregulate Bcl-2 in myeloma cells, sensitizing them to chemotherapeutic agents. We have undertaken a project to evaluate antisense inhibition strategies in Waldenstrom's macroglobulinemia (WM), and whether the Bcl-2 pathway may provide a therapeutic target in this disease. We have shown that Bcl-2 is expressed in WM cells in vitro and that downregulation of Bcl-2 may be achieved by treatment with G3139. Treatment of WM cells with G3139 is associated with increased cell death and shows potential synergy with chemotherapeutic agents active in WM. Bcl-2 downregulation via G3139 antisense treatment may have potential anticancer efficacy in WM and further studies to address its effects on clinical specimens are warranted, in anticipation of using this agent in WM clinical trials.

Antineoplastic Agents↗
PubMed1999

[Experiences fo three year's routine operation of an anesthesia information management system (AIMS) at a university clinic in Giessin].

PURPOSE: In 1994, the Department of Anaesthesiology and Intensive Care Medicine of the Justus Liebig University at Giessen decided to install an Anaesthesia Information Management System (AIMS). Individual aspects and results from routine operation are presented, demonstrating the quality of the documentation and the value of information at the anaesthesiological workstation. The paper discusses which adaptations are necessary according to the experience gathered. METHODS: For the installation of the system Apple Macintosh Clients (Apple Computer, Inc., Cupertino, California) and a File Server were integrated into the partially existing hospital network. The hospital network had to be enlarged during the project according to the Anaesthesiological requirements. The software of the Hospital Information System (HIS) and an HTML browser were installed at individual workstation computers in addition to the Anaesthesia documentation software NarkoData (ProLogic GmbH, Erkrath). The remote control software Timbuktu (Farallon, Alameda, USA) has been added to facilitate remote administration. The file administration programme FileWave (Wave Research, Berkeley, USA) is used for file distribution. Since 1995, all anaesthesia procedures have been documented with the system, either by online or postoperative recording. Since 1997, the recorded information has been stored in a relational Oracle 7 data bank (Oracle Corporation). RESULTS: From 1995 to 1997, 60,405 anaesthesiological procedures have been recorded with the help of this AIMS at 111 decentralised workstations. In 1997, 87.8% of the 21,130 performed anaesthesia procedures have been recorded online with the system and 12.2% postoperatively. From 1995 to 1997, the number of recorded procedures increased by 6.4% from 19,854 to 21,130. Because of lacking interfaces at some patient monitoring stations, the automatic recording of patient data could only be implemented at 69 workstations (62%). With the corresponding access rights, important patient information from the HIS (diagnoses, laboratory results, etc.), records of previous Anaesthesia procedures, numerous statistics, and the whole information from the hospital's intranet (including e-mail) are available at the anaesthesiological workstation at any time. CONCLUSION: The implementation of the AIMS and an effective user support have been able to increase significantly the quality of documentation, the flow of information at the anaesthesia workplace and the number of recorded Anaesthesia procedures. All recorded data can be analysed immediately The expansion of the automatic data transfer from the patient monitoring, interfaces to other computer subsystems of the hospital and a practicable evaluation programme are necessary for further enhancing the efficiency of the AIMS.

Anesthesiology↗
PubMed1992

Body fat estimations by electrical impedance and infra-red interactance.

The purpose of this study was to examine body fat estimation using three methods of electrical impedance (the BIA-103 Body Composition Analyser--RJL Systems, Detroit; the BMR 2000 Body Composition Analyzer--Berkeley Medical Research, San Leandro; the BC300 Body Composition Analyzer--Spacelabs, Dallas) and an infra-red interactance method (Futrex 5000 Analyzer--Futrex Inc. Gaithersburg) as an alternative to hydrodensitometry. Five different groups were examined using at least one of the electrical systems and in all cases utilising hydrodensitometry as the criterion method. The results produced highly significant correlations between all methods, but caution is recommended due to the limited common variance in some cases. The individual electrical methods differed from hydrodensitometry by a maximum of 1.1% in obese women, by 21.6% in athletic adults, by 6.2% in the slightly obese group, by 8.1% in normal women and by 56.0% in normal children. Significant mean differences between one of the impedance methods and hydrodensitometry were only noted in two of the groups tested. This suggests, allowing for the limitations of hydrodensitometry itself, that the other three electrical methods appear to be reasonably valid alternatives to underwater weighing, especially for field work of an epidemiological nature.

Adipose Tissue↗
PubMed1987

On the late invention of the stereoscope.

It was not until 1838, when Wheatstone published his account of the stereoscope, that stereoscopic depth perception entered into the body of binocular phenomena. It is argued that the stereoscope was not invented earlier because the phenomenon of stereopsis based on disparity had not been adequately described. This was the case despite the fact that there had been earlier descriptions of tasks that could be performed better with two eyes than with one; the perceptual deficits attendant upon the loss of one eye had been remarked upon; analyses of the projections to each eye were commonplace, and binocular disparities were accurately illustrated; moreover, binocular microscopes and telescopes had been made over a century earlier. Theories of binocular vision were generally confined to accounting for singleness of vision with two eyes, and the concepts employed to account for this were visible direction, corresponding retinal points, and union in the brain. The application of these concepts inhibited any consideration of disparities, other than for yielding diplopia. When perception of the third dimension was addressed by Berkeley at the beginning of the eighteenth century, it was in the context of monocular vision and binocular convergence. Thereafter visual direction became the province for binocular vision and it was analysed in terms of geometrical optics, whereas visual distance was examined in the context of learned associations between vision and touch. This artificial division was challenged initially with respect to visual direction and later with respect to stereopsis. An additional factor delaying the invention of the stereoscope was that experiments on binocular vision generally involved abnormal convergence on extended objects. Wheatstone's accidental observation of stereopsis was under artificial conditions in which disparity alone defined the binocular depth perceived. Once invented the stereoscope was enthusiastically embraced by students of vision. It is suggested that the ease with which retinal disparity could be manipulated in stereopairs has led to an exaggeration of its importance in space perception. "The appearances, which are by this simple instrument rendered so obvious, may be easily inferred from the established laws of perspective; for the same object in relief is, when viewed by a different eye, seen from the two points of sight at a distance from each other equal to the line joining the two eyes. Yet they seem to have escaped the attention of every philosopher and artist who has treated of the subjects of vision and perspective." (Wheatstone 1838, page 371).

Depth Perception↗
PubMed2000

When texture takes precedence over motion in depth perception.

Both texture and motion can be strong cues to depth, and estimating slant from texture cues can be considered analogous to calculating slant from motion parallax (Malik and Rosenholtz 1994, report UCB/CSD 93/775, University of California, Berkeley, CA). A series of experiments was conducted to determine the relative weight of texture and motion cues in the perception of planar-surface slant when both texture and motion convey similar information. Stimuli were monocularly viewed images of planar surfaces slanted in depth, defined by texture and motion information that could be varied independently. Slant discrimination biases and thresholds were measured by a method of single-stimuli binary-choice procedure. When the motion and texture cues depicted surfaces of identical slants, it was found that the depth-from-motion information neither reduced slant discrimination thresholds, nor altered slant discrimination bias, compared to texture cues presented alone. When there was a difference in the slant depicted by motion and by texture, perceived slant was determined almost entirely by the texture cue. The regularity of the texture pattern did not affect this weighting. Results are discussed in terms of models of cue combination and previous results with different types of texture and motion information.

Analysis of Variance↗
PubMed2002

Is the acquisition of basic-colour terms in young children constrained?

We investigated whether the learning of colour terms in childhood is constrained by a developmental order of acquisition as predicted by Berlin and Kay [1969 Basic Color Terms (Berkeley, CA: University of California Press)]. Forty-three children, aged between 2 and 5 years and grouped according to language ability, were given two tasks testing colour conceptualisation. Colour comprehension was assessed in a spoken-word-to-colour-matching task in which a target colour was presented in conjunction with two distractor colours. Colour naming was measured in an explicit naming task in which colours were presented individually for oral naming. Results showed that children's knowledge of basic-colour terms varied across tasks and language age, providing little support for a systematic developmental order. In addition, we found only limited support for an advantage for the conceptualisation of primary (red, green, blue, yellow, black, white) compared to non-primary colour terms across tasks and language age. Instead, our data suggest that children acquire reliable knowledge of nine basic colours within a 3-month period (35.6 to 39.5 months) after which there is a considerable lag of up to 9 months before accurate knowledge of the final two colours (brown and grey) is acquired. We propose that children acquire colour term knowledge in two distinct time frames that reflect the establishment of, first, the exterior (yellow, blue, black, green, white, pink, orange, red, and purple) and, second, the interior structure (brown and grey) of conceptual colour space. These results fail to provide significant support for the order predicted by Berlin and Kay, and suggest, instead, that the development of colour term knowledge is largely unconstrained.

Aging↗
PubMed2005

Demonstration of cue recruitment: change in visual appearance by means of Pavlovian conditioning.

Until half a century ago, associative learning played a fundamental role in theories of perceptual appearance [Berkeley, G. (1709) An Essay Towards a New Theory of Vision (Dublin), 1st Ed.]. But starting in 1955 [Gibson, J. J. & Gibson, E. J. (1955) Psychol. Rev. 62, 32-41], most studies of perceptual learning have not been concerned with association or appearance but rather with improvements in discrimination ability. Here we describe a "cue recruitment" experiment, which is a straightforward adaptation of Pavlov's classical conditioning experiment, that we used to measure changes in visual appearance caused by exposure to novel pairings of signals in visual stimuli. Trainees viewed movies of a rotating wire-frame (Necker) cube. This stimulus is perceptually bistable. On training trials, depth cues (stereo and occlusion) were added to force the perceived direction of rotation. Critically, an additional signal was also added, contingent on rotation direction. Stimuli on test trials contained the new signal but not the depth cues. Over 45 min, two of the three new signals that we tested acquired the ability to bias perceived rotation direction on their own. Results were consistent across the eight trainees in each experiment, and the new cue's effectiveness was long lasting. Whereas most adaptation aftereffects on appearance are opposite in direction to the training stimuli, these effects were positive. An individual new signal can be recruited by the visual system as a cue for the construction of visual appearance. Cue recruitment experiments may prove useful for reexamining of the role of experience in perception.

Conditioning, Classical↗
PubMed2002

Identification in Drosophila melanogaster of the invertebrate G protein-coupled FMRFamide receptor.

We here describe the cloning and characterization of the functionally active Drosophila melanogaster (Drm) FMRFamide receptor, which we designated as DrmFMRFa-R. The full-length ORF of a D. melanogaster orphan receptor, CG 2114 (Berkeley Drosophila Genome Project), was cloned from genomic DNA. This receptor is distantly related to mammalian thyroid-stimulating hormone-releasing hormone receptors and to a set of Caenorhabditis elegans orphan receptors. An extract of 5,000 central nervous systems from the related but bigger flesh fly, Neobellieria bullata (Neb), was used to screen cells expressing the orphan receptor. Successive purification steps, followed by MS, revealed the sequence of two previously uncharacterized endogenous peptides, APPQPSDNFIRFamide (Neb-FIRFamide) and pQPSQDFMRFamide (Neb-FMRFamide). These are reminiscent of other insect FMRFamide peptides, having neurohormonal as well as neurotransmitter functions. Nanomolar concentrations of the Drm FMRFamides (DPKQDFMRFamide, TPAEDFMRFamide, SDNFMRFamide, SPKQDFMRFamide, and PDNFMRFamide) activated the cognate receptor in a dose-dependent manner. To our knowledge, the cloned DrmFMRFa-R is the first functionally active FMRFamide G protein-coupled receptor described in invertebrates to date.

Amino Acid Sequence↗
PubMed1995

Gene disruptions using P transposable elements: an integral component of the Drosophila genome project.

Biologists require genetic as well as molecular tools to decipher genomic information and ultimately to understand gene function. The Berkeley Drosophila Genome Project is addressing these needs with a massive gene disruption project that uses individual, genetically engineered P transposable elements to target open reading frames throughout the Drosophila genome. DNA flanking the insertions is sequenced, thereby placing an extensive series of genetic markers on the physical genomic map and associating insertions with specific open reading frames and genes. Insertions from the collection now lie within or near most Drosophila genes, greatly reducing the time required to identify new mutations and analyze gene functions. Information revealed from these studies about P element site specificity is being used to target the remaining open reading frames.

Animals↗
PubMed1997

Mathematical approaches to comparative linguistics.

The inference of the evolutionary history of a set of languages is a complex problem. Although some languages are known to be related through descent from common ancestral languages, for other languages determining whether such a relationship holds is itself a difficult problem. In this paper we report on new methods, developed by linguists Johanna Nichols (University of California, Berkeley), Donald Ringe and Ann Taylor (University of Pennsylvania, Philadelphia), and me, for answering some of the most difficult questions in this domain. These methods and the results of the analyses based on these methods were presented in November 1995 at the Symposium on the Frontiers of Science held by the National Academy of Sciences.

Journal Article↗
PubMed1998

A high throughput screen to identify secreted and transmembrane proteins involved in Drosophila embryogenesis.

Secreted and transmembrane proteins play an essential role in intercellular communication during the development of multicellular organisms. Because only a small number of these genes have been characterized, we developed a screen for genes encoding extracellular proteins that are differentially expressed during Drosophila embryogenesis. Our approach utilizes a new method for screening large numbers of cDNAs by whole-embryo in situ hybridization. The cDNA library for the screen was prepared from rough endoplasmic reticulum-bound mRNA and is therefore enriched in clones encoding membrane and secreted proteins. To increase the prevalence of rare cDNAs in the library, the library was normalized using a method based on cDNA hybridization to genomic DNA-coated beads. In total, 2,518 individual cDNAs from the normalized library were screened by in situ hybridization, and 917 of these cDNAs represent genes differentially expressed during embryonic development. Sequence analysis of 1,001 cDNAs indicated that 811 represent genes not previously described in Drosophila. Expression pattern photographs and partial DNA sequences have been assembled in a database publicly available at the Berkeley Drosophila Genome Project website (). The identification of a large number of genes encoding proteins involved in cell-cell contact and signaling will advance our knowledge of the mechanisms by which multicellular organisms and their specialized organs develop.

Animals↗
PubMed1999

Invariance of brain-wave representations of simple visual images and their names.

In two experiments, electric brain waves of 14 subjects were recorded under several different conditions to study the invariance of brain-wave representations of simple patches of colors and simple visual shapes and their names, the words blue, circle, etc. As in our earlier work, the analysis consisted of averaging over trials to create prototypes and test samples, to both of which Fourier transforms were applied, followed by filtering and an inverse transformation to the time domain. A least-squares criterion of fit between prototypes and test samples was used for classification. The most significant results were these. By averaging over different subjects, as well as trials, we created prototypes from brain waves evoked by simple visual images and test samples from brain waves evoked by auditory or visual words naming the visual images. We correctly recognized from 60% to 75% of the test-sample brain waves. The general conclusion is that simple shapes such as circles and single-color displays generate brain waves surprisingly similar to those generated by their verbal names. These results, taken together with extensive psychological studies of auditory and visual memory, strongly support the solution proposed for visual shapes, by Bishop Berkeley and David Hume in the 18th century, to the long-standing problem of how the mind represents simple abstract ideas.

Adult↗
PubMed2000

Functional expression of a multisubstrate deoxyribonucleoside kinase from Drosophila melanogaster and its C-terminal deletion mutants.

The occurrence of a deoxyribonucleoside kinase in Drosophila melanogaster (Dm-dNK) with remarkably broad substrate specificity has recently been indicated (Munch-Petersen, B., Piskur, J., and Søndergaard, L. (1998) J. Biol. Chem. 273, 3926-3931). To prove that the capacity to phosphorylate all four deoxyribonucleosides is in fact associated to one polypeptide chain, partially sequenced cDNA clones, originating from the Berkeley Drosophila genome sequencing project, were searched for homology with human deoxyribonucleoside kinases. The total sequence of one cDNA clone and the corresponding genomic DNA was determined and expressed in Escherichia coli as a glutathione S-transferase fusion protein. The purified and thrombin cleaved recombinant protein phosphorylated the four deoxyribonucleosides with high turnover and K(m) values similar to those of the native Dm-dNK, as well as the four ribonucleosides and many therapeutical nucleoside analogs. Dm-dNK has apparently the same origin as the mammalian kinases, thymidine kinase 2, deoxycytidine kinase, deoxyguanosine kinase, and the herpes viral thymidine kinases, but it has a unique C terminus that seems to be important for catalytic activity and specificity. The C-terminal 20 amino acids were dispensable for phosphorylation of deoxyribonucleosides but necessary for full activity with purine ribonucleosides. Removal of the C-terminal 20 amino acids increased the specific activity 2-fold, but 99% of the activity was lost after removal of the C-terminal 30 amino acids.

Amino Acids↗
PubMed2002

Regulation of cell signalling by vitamin E.

Vitamin E, the most important lipid-soluble antioxidant, was discovered at the University of California at Berkeley in 1922. Since its discovery, studies of the constituent tocopherols and tocotrienols have focused mainly on their antioxidant properties. In 1991 Angelo Azzi's group (Boscoboinik et al. 1991a,b) first described non-antioxidant cell signalling functions for alpha-tocopherol, demonstrating that vitamin E regulates protein kinase C activity in smooth muscle cells. At the transcriptional level, alpha-tocopherol modulates the expression of the hepatic alpha-tocopherol transfer protein, as well as the expression of liver collagen alphal gene, collagenase gene and alpha-tropomyosin gene. Recently, a tocopherol-dependent transcription factor (tocopherol-associated protein) has been discovered. In cultured cells it has been demonstrated that vitamin E inhibits inflammation, cell adhesion, platelet aggregation and smooth muscle cell proliferation. Recent advances in molecular biology and genomic techniques have led to the discovery of novel vitamin E-sensitive genes and signal transduction pathways.

Absorption↗
PubMed1988

Wartime losses and social bonding: influences across 40 years in men's lives.

By 1990 over half of all American men entering the retirement years will be veterans with a life history shaped by participation in the Armed Forces. This investigation traces the burden of war mortality and social bonding across the life span of 149 veterans of World War II and the Korean conflict. These veterans come from longitudinal samples at the Institute of Human Development, University of California, Berkeley. Data were also obtained from the record of a Marine unit that served on Iwo Jima. The study is organized around two lines of inquiry. The first examines the relationship between combat and social ties, with emphasis on exposure to combat deaths, the loss of comrades/friends, and postwar stress reactions. The second concerns the healing potential of social ties with service friends and spouses in later life. According to the analysis, heavy combat veterans are more likely than other veterans to have enduring ties from the service. But combat experience alone does not explain these ties; it is war trauma and especially the loss of significant others during war, both comrades and friends, that intensify and maintain postwar relationships. Painful memories of war and stress symptoms in later life are likely to weaken through exposure to a supportive community of service mates and spouses, an effect that suggests the healing potential of periodic reunions of the primary military unit and marital sharing.

Combat Disorders↗
PubMed2001

Twelve tips on choosing web teaching software.

Experimentation with the new technology of web-based teaching has meant that many medical schools are using more than one software system for delivery. In the medical faculty at the University of New South Wales at the end of 1999, three different software packages (WebTeach, Top Class and Learning Space) were used for mediating teaching and learning on the web. The type of applications for which web-based teaching is used also varied widely. They ranged from a distance-education coursework masters programme delivered via the web, to the provision of additional resource materials and case discussions to supplement undergraduate classes on campus. Once web-based teaching moves out of the experimental phase and into the mainstream there is usually pressure to standardize on one software system. This has the advantage of limiting costs for training and support but it may require some compromise on functionality. Faced with the need to limit the number of software packages in use at UNSW the published comparisons of web software (Landon, 2001; University of California at Berkeley; 2001; Marshall University, 2001; Murdoch University, 2001) were first investigated. These show in broad terms what each package will do but often lack sufficient detail to determine whether the package will meet specific requirements. To get a better idea of how different software packages operate under the pressure of day-to-day teaching, 15 academic course coordinators, instructional designers and educational developers from six Australian universities who are involved in designing and delivering web courses were interviewed. The authors also joined online user groups and asked questions of international users. The aim was to find out what strengths and weaknesses they had found in the packages they used and whether they would make the same choice again. The authors were particularly interested to find out what questions they would ask when considering a new package. The twelve tips that follow summarize their advice to those considering the choice of a web teaching package.

Journal Article↗
PubMed1987

Leksell stereotactic radiosurgery in the treatment of eye melanoma.

Current experiments indicate that a focussed single radiation treatment with a dose of 6000 to 9000 rads delivered to the 90% zone through a collimator of the Leksell stereotactic radiosurgical unit or 'gamma knife' to the rabbit eye melanoma model is capable of destroying the cancer totally and thus effecting a cure. The beneficial effect in these rabbit eye melanoma experiments appears to be similar to the results obtained by physicians using the Harvard and Berkeley cyclotrons in treating malignant neoplasms in the human eye. Therefore, it is proposed that a properly designed stereotactic radiosurgical unit can be used in patients with eye tumours similar to those selected for the cyclotron systems.

Animals↗
PubMedDate not supplied

Growth tracks in pre-pubertal children.

The present investigation characterizes common growth tracks in pre-pubertal children. Growth tracks denominate areas of probability within which subsequent measurements of the body height (or body height SDS) of a healthy individual will predominantly be found. Growth tracks are defined over several years and they are insensitive to the timing of measurements. The concept of growth tracks was developed to improve separating aberrant patterns from normal growth. Longitudinal data on height were obtained from six large national growth studies, performed at Berkeley, USA, Jena, Germany, Lublin, Poland, Paris, France, Prague, Czech Republic and Zurich, Switzerland with a total of 515 healthy boys and 532 healthy girls. Four hundred and two series of annual height measurements were available in pre-pubertal boys (aged 3-11 years), 416 series in pre-pubertal girls (aged 3-10). Body height was converted into height SDS. Thereafter, average personal height SDS was determined, and subtracted from height SDS, resulting in individual series of residual height SDS. These were sorted by cluster analysis and distributed into groups (clusters) according to similarity or dissimilarity (squared difference). We identified similar clusters, and named them 'growth tracks'. We found five pre-pubertal male growth tracks, each containing between 4 and 37% of the boys. Twenty boys could not be assigned to either one of the five tracks. Very similar results were obtained in girls, with five pre-pubertal growth tracks also, each containing between 3 and 50%. Twenty-three individuals grew irregularly and could not be assigned. Growth tracks are narrow, with an average width between 12.1 and 14.8% of the SD of body height. Most children exhibited almost horizontal height SDS patterns. Others showed linearly declining, rising, or intersection -shaped patterns. None of the patterns were predominantly found in particularly short or tall children. Preliminary data support the practical advantages of the concept of growth tracks.

Anthropometry↗