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R Schwartz

Publications and source records attributed to R Schwartz.

At least 19 recordsLinked to original sources
PubMed2006

HER2 expression as a potential marker for response to therapy targeted to the EGFR.

Since human epidermal growth factor receptor 2 (HER2) is known to participate with the epidermal growth factor receptor (EGFR) in mitogenic signalling, we hypothesised that HER2 overexpression might indicate responsiveness to EGFR targeted therapies. MCF7 breast cancer cells transfected with the HER2 gene were subcloned to establish a set of genetically related cell lines expressing graded levels of HER2 by immunoblot analysis. The subcloned cell lines and parental MCF7 cells were characterised by their growth characteristics, and cell by cell patterns of EGFR, HER2 and HER3 expression as well as levels of phosphorylated mitogen-activated protein kinase (MAPK) and AKT by laser scanning cytometry (LSC). Growth inhibition assays were used to characterise response to EGFR targeted therapy, and to determine the relationship between therapeutic response and levels of tyrosine kinase expression. The levels of growth inhibition of AG1478 and of the AG1478-trastuzumab combinations were correlated with levels of HER2 expression among the different cell lines. Among EGFR, HER2 and HER3, HER2 overexpression was the best single predictive marker, but combinations of two markers provided additional predictive information.

Antibodies, Monoclonal↗
PubMed2005

Contamination of the alluvial plain, feeding-stuffs and foodstuffs with polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans (PCDD/Fs), dioxin-like polychlorinated biphenyls (DL-PCBs) and mercury from the River Elbe in the light of the flood event in August 2002.

Meadow soils, feeding-stuffs and foodstuffs from the alluvial plain of the river Elbe were analyzed in respect of PCDD/Fs, DL-PCBs and mercury with a view to assessing the consequences of the extreme flood of August 2002. The PCDD/F concentrations in the soils range from 3 to 2100 ng WHO-TEQ/kg dm, and for the DL-PCBs the range was 0.32 to 28 ng WHO-TEQ/kg dm. On the basis of established threshold values >40% of the areas are only fit for restricted usage. Mercury concentrations range from 0.11 to 17 mg/kg dm, whereby the action value of 2 mg/kg dm is exceeded in about 50% of the soil samples. A cumulative memory effect from past floods rather than a recent contamination from August 2002 is documented. Soils taken from behind broken dykes showed significantly lower concentrations. Grass, hay and grass silage originating from pasture land in Lower Saxony were taken before and immediately after the flooding. PCDD/Fs range from 0.29 to 16 ng WHO-TEQ/kg, the maximum permitted value of 0.75 ng WHO-TEQ/kg was exceeded in about 50% of the samples. Muscle-tissue from cattle, sheep, lamb and a roe deer as well as untreated milk from individual cows returned values ranging from 0.76 to 5.9 pg WHO-PCDD/F-TEQ/g fat, and 10% of the samples returned values higher than the permitted maximum of 3 pg WHO-PCDD/F-TEQ/g fat. The action value of 2 pg WHO-PCDD/F-TEQ/g fat was exceeded in 33% of the samples. No direct connection between these results and the effects of the flood could be established. A major input path for PCDD/Fs is the tributary Mulde, which discharges contaminated sediments from its catchment area into the Elbe.

Animal Feed↗
PubMed2005

Results of radiotherapy of subfoveal neovascularization with 16 and 20 Gy.

PURPOSE: In a nonrandomized, prospective study the efficacy of radiotherapy with 16 and 20 Gray (Gy) for subfoveal neovascularization in age-related macular degeneration (ARMD) was analysed. MATERIAL AND METHODS: From 1996 to 1998, 63 eyes were irradiated with 16 Gy and 38 eyes with 20 Gy for exudative ARMD. A total of 12 eyes had classic ARMD, 89 eyes occult ARMD, median baseline visual acuity (VA) was 6/30 (range: 3/60-6/9.5), median age was 78 years. Risk factors (type of ARMD, baseline VA) were evenly distributed in both groups. Median follow-up was 1.3 years (range: 4 months-4.7 years). VA of +/-1 line or better and unchanged size and activity of the membrane in fluorescein angiography were defined as stable. Actuarial methods were used. RESULTS: Median loss of VA was -3 lines (range: -14 to +5), neovascularization remained unchanged or decreased in size and activity in 35 eyes. At 18 months, the probability of stabilized VA was 0.4 (95% confidence interval (CI): 0.3-0.5), at 24 months 0.3 (95% CI: 0.2-0.4). Radiation dose, type of ARMD or baseline VA had no significant impact on outcome of VA and membrane size and activity (P>0.05). Side effects were mild and transient increased tearing. CONCLUSION: In this study, the results after radiotherapy were comparable to the natural course of the disease. An impact of radiation dose (16 vs 20 Gy) on stabilizing visual acuity and subfoveal neovascularization could not be shown. The results of studies on dose escalation using very small fields and high radiation doses should be awaited.

Aged↗
PubMed2004

The Elbe flood in August 2002--occurrence of polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans (PCDD/F) and dioxin-like PCB in suspended particulate matter (SPM), sediment and fish.

As a result of extreme precipitation in August 2002 major flooding occurred in the catchment area of the rivers Elbe, Vltava (Moldau) and Mulde. Pollutants from industrial sites and from municipal sewage treatment works (STW) entered the Elbe and led to a serious pollution problem in the river. PCDD/F concentrations (in pg WHO-TEQ/g dw) in SPM ranged from 7-150, in sediments from 3-140; the "safe sediment value" of 20 was exceeded in 46% of the samples. 24 eels showed a wide concentration variation for these contaminants. The WHO-PCDD/F+PCB-TEQ values lay in the range from 11-56 pg/g ww, whereby the WHO-PCB-TEQ values were several times higher than the WHO-PCDD/F-TEQ values. The maximum permitted value of 4 pg WHO-PCDD/F/g ww (EU Directive No. 2375/2001) was reached or exceeded in 54% of the individuals. A statistical analysis using data from SPM and sediment samples showed that in the Czech river section the flooding activated a contamination source in the vicinity of the Spolana works. The influence of the tributary Mulde could be clearly demonstrated. Only a major clean-up of the contaminated sites in Bitterfeld can lead to a mid to long term improvement in respect of PCDD/F and dioxin-like PCB input into the Elbe.

Animals↗
PubMed2003

[Testing central retinal function with multifocal electroretinography before and after photodynamic therapy].

BACKGROUND: Photodynamic therapy (PDT) is applied for certain forms of choroidal neovascular membrane (CNV). The aim of this study was to investigate the effect of PDT on central retinal function as assessed by multifocal electroretinography (ERG). METHODS: 24 patients (25 eyes) with CNV (>50% classic 12 eyes) or occult (9 eyes) in age related macular degeneration (AMD) and CNV with pathological myopia (4 eyes) were treated by PDT using Verteporfin((R)). Before and a median of 6 weeks after therapy, central retinal function was examined using multifocal ERG (RetiScan, 61 hexagons, first-order response). RESULTS: In the area of treatment,we found a tendency of the amplitude of the first positive deflection (P1) to decrease and of the implicit time to increase, but both effects were not statistically significant. These alterations were more pronounced in eyes with occult CNV and in myopia-related CNV. Amplitude reduction and implicit time prolongation could also be found in the areas represented by the multifocal ERG but not treated. There was no significant correlation between change in visual acuity after PDT and amplitude of the multifocal ERG. CONCLUSION: The effects of PDT on retinal function seem to be moderate as assessed by multifocal ERG. An inherent problem of this investigation was the recruitment of nontreated patients as controls. Future goals are investigations of patients with repeated PDT and of long-term alterations in multifocal ERG after PDT.

Adult↗
PubMed2003

Platelet functional defects in women with unexplained menorrhagia.

Menorrhagia is a common clinical problem and is unexplained in more than 50% of women. Although studies suggest that von Willebrand's Disease (VWD) is found in a substantial number of women with unexplained menorrhagia, the prevalence of platelet defects in women with menorrhagia is unknown. To determine the prevalence of platelet and other hemostatic defects, we evaluated women ages 17-55 diagnosed with unexplained menorrhagia. Seventy-four women (52 white, 16 black, six other) were studied. Bleeding time was prolonged in 23 women (31.5%). Maximal percent platelet aggregation was decreased with one or more agonists in 35 (47.3%) women. The most commonly found platelet function defects were reduced aggregation responses to ristocetin in 22 women and to epinephrine in 16 women. Sixteen of 22 women with reduced ristocetin aggregation had von Willebrand ristocetin cofactor (VWF:RCo) and von Willebrand factor antigen (VWF:Ag) > 60%. Platelet ATP release was decreased with one or more agonists in 43 (58.1%) women. Of the black women studied, 11/16 (69%) had abnormal platelet aggregation studies compared with 20/52 white women (39%) (P = 0.06). Black women with menorrhagia had a higher prevalence of decreased platelet aggregation in response to ristocetin and epinephrine than did white women (P = 0.0075, P = 0.02). Ten women (13.5%) had VWF:RCo and/or VWF:Ag < 60%. Using race and blood group specific ranges, 5 (6.8%) women had decreased VWF:RCo, VWF:Ag and/or collagen binding (VWF:CB). Mild factor XI deficiency was found in two women and one woman with mild factor V deficiency and one hemophilia A carrier were identified. We conclude that the prevalence of platelet function defects and other inherited bleeding disorders is substantial in a multiracial US population of women with unexplained menorrhagia.

Adolescent↗
PubMed2001

p27-p16 fusion gene inhibits angioplasty-induced neointimal hyperplasia and coronary artery occlusion.

Inhibition of proliferative neointima formed by vascular smooth muscle cells is a potential target in preventing angioplasty-induced restenosis. We have created a potent antiproliferative by fusing the active regions of the p27 and p16 cell cycle inhibitors. Intravascular delivery of a replication-deficient adenoviral vector (AV) encoding this p27-p16 fusion protein, named W9, inhibited balloon injury-induced neointimal hyperplasia in rabbit carotid arteries. In a therapeutically more relevant model, AV-W9 was delivered to balloon-injured porcine coronary arteries in vivo using an infusion catheter. Of the three coronary arteries, two were injured with a 15-mm balloon catheter and either were left untreated or were treated with 10(12) viral particles of either AV-W9 or a control null virus. AV-W9 treatment significantly inhibited neointimal hyperplasia in this porcine arterial balloon injury model compared with untreated or control virus-treated vessels. The average intimal area of the AV-W9-treated group 10 days after balloon injury and treatment was 0.42+/-0.36 mm(2), whereas the AV-null group demonstrated an intimal area of 0.70+/-0.52 mm(2). At day 10 the average intimal thickness of the AV-W9-treated vessels was 9.1 microm (n=5, x 20 magnification) compared with 21.2 microm (n=5, x 20 magnification) in control virus-treated vessels. This trend was also observed at 28 days after balloon injury and gene transfer during which AV-W9-treated vessels demonstrated an average intimal thickness of 4.7 microm (n=8, x 20 magnification) compared with 13.3 microm (n=3, x 20 magnification) in control virus-treated vessels and 7.3 microm (n=5, x 20 magnification) in the sham-treated vessels. The AV-W9 treatment was safe and well tolerated. These data suggest that AV-W9 gene therapy may be useful in preventing angioplasty-induced intimal hyperplasia in the coronary artery.

Adenoviridae↗
PubMed2001

Seeing trees but not the forest: limited perception of large configurations in PD.

OBJECTIVE: To learn if Parkinson's disease (PD) is associated with a restricted attentional "floodlight." BACKGROUND: Different visual tasks may have different attentional requirements. Focused attention may be needed for some tasks; other tasks demand spatially distributed attention. Neglect after right cortical injury and dopamine depletion may limit the area over which attention can be spread. Although subjects with PD have dopamine depletion and can perform poorly on tests of visuospatial function, it is unclear if their attentional floodlight is restricted. METHODS: Eleven subjects with PD and 11 control subjects viewed different-sized letters on five printed stimulus sheets, 43 x 56 cm. On each sheet, four different large letters (14 cm2) were composed of four different medium-sized letters (2.5 cm2), which in turn were composed of four different small letters (0.4 cm2). Stimulus sheets were presented at 30- and 75-cm viewing distances. Subjects named "all the letters they could see." RESULTS: Subjects with PD named small- and medium-sized letters comparably to control subjects, but PD subjects named fewer large letters than control subjects (control = 65.68%, PD = 24.55%; group-by-letter-size interaction, p < 0.05). Subjects with PD who had undergone stereotactic pallidotomy named more letters than prepallidotomy PD subjects (p = 0.05). CONCLUSIONS: PD may affect the patient's ability to perceive large spatial configurations. As global configurations in subjects may be perceived preferentially over local patterns, it is possible that DA depletion induces an aberrant perceptual-attentional bias, such that patients have a narrowed attentional floodlight.

Aged↗
PubMed2001

Evolutionary internalized regularities.

Roger Shepard's proposals and supporting experiments concerning evolutionary internalized regularities have been very influential in the study of vision and in other areas of psychology and cognitive science. This paper examines issues concerning the need, nature, explanatory role, and justification for postulating such internalized constraints. In particular, I seek further clarification from Shepard on how best to understand his claim that principles of kinematic geometry underlie phenomena of motion perception. My primary focus is on the ecological validity of Shepard's kinematic constraint in the context of ordinary motion perception. First, I explore the analogy Shepard draws between internalized circadian rhythms and the supposed internalization of kinematic geometry. Next, questions are raised about how to interpret and justify applying results from his own and others' experimental studies of apparent motion to more everyday cases of motion perception in richer environments. Finally, some difficulties with Shepard's account of the evolutionary development of his kinematic constraint are considered.

Biological Evolution↗
PubMed2001

Reason for medical hospitalization among adult alcohol and drug abusers.

This study attempts to identify the associations between types of substance use and particular medical problems as causes of acute hospital admission on an inpatient substance abuse consultation service. Records of all consultations performed from 1994 to 1998 were analyzed. A total of 4,526 complete records were available. Cocaine (p < .01), heroin (p < .001), and injection drug (p < .001) users were more likely to be admitted to the hospital for infection. Both alcohol (p < .001) and marijuana (p < .001) users were more likely to be hospitalized for trauma related injuries. Individuals that used alcohol were also more likely to be admitted for the treatment of gastrointestinal disorders (p < .001). Clinicians who treat patients with these diagnoses should have a high index of suspicion of co-morbid substance use disorders. Effective treatment of substance use disorders can lead to a decrease in medical morbidity, improved outcomes for individual patients, and decreased costs for the health care system.

Adult↗
PubMed2001

Sentinel lymph node mapping in melanoma with technetium-99m dextran.

PURPOSE: The aim of this work is to evaluate the capability of Tc99m B Dextran as a lymphoscintigraphic agent in the detection of the sentinel node in skin lesions. MATERIALS AND METHODS: Forty-one patients with melanomas (39) and Merkel cell tumors (2) had perilesional intradermal injection of Tc99m-Dextran 2 hours before surgery. Serial gamma camera images and a handheld gamma probe were used to direct sentinel node biopsy. RESULTS: In 39/41 patients, lymph channels and 52 sentinel nodes (one to three sentinel nodes/patient) could be visualized. In one patient, with a dorsal melanoma, no lymph channels or lymph nodes could be demonstrated on the images and only minimal radioactivity was found in the regional nodes with the probe. Another patient with a facial lesion failed to demonstrate lymph channels or nodes. No adverse reactions were observed. CONCLUSION: Tc99m-Dextran provided good definition of lymph channels and sentinel node localization, without the risks related to the use of potentially hazardous labeled materials of biological origin.

Adolescent↗
PubMed2001

Whole proteome pI values correlate with subcellular localizations of proteins for organisms within the three domains of life.

Isoelectric point (pI) values have long been a standard measure for distinguishing between proteins. This article analyzes distributions of pI values estimated computationally for all predicted ORFs in a selection of fully sequenced genomes. Histograms of pI values confirm the bimodality that has been observed previously for bacterial and archaeal genomes () and reveal a trimodality in eukaryotic genomes. A similar analysis on subsets of a nonredundant protein sequence database generated from the full database by selecting on subcellular localization shows that sequences annotated as corresponding to cytosolic and integral membrane proteins have pI distributions that appear to correspond with the two observed modes of bacteria and archaea. Furthermore, nuclear proteins have a broader distribution that may account for the third mode observed in eukaryotes. On the basis of this association between pI and subcellular localization, we conclude that the bimodal character of whole proteome pI values in bacteria and archaea and the trimodal character in eukaryotes are likely to be general properties of proteomes and are associated with the need for different pI values depending on subcellular localization. Our analyses also suggest that the proportions of proteomes consisting of membrane-associated proteins may be currently underestimated.

Animals↗
PubMed2001

Network formalism for modeling functionally gradient piezoelectric plates and stacks and simulations of RAINBOW ceramic actuators.

A simple network representation is given for a stack of thin, homogeneous piezoelectric plates, executing a single thickness mode of motion. All plates may differ in thickness and material properties, including dielectric loss, ohmic conductivity, and viscous loss. Each plate is driven by a thickness-directed electric field, and all stack elements are connected electrically in series. Functionally gradient single plates and composites are readily modeled by the network, to a desired precision, using a sequence of circuit elements representing stepwise variations in material properties and layer thicknesses. Simulations of RAINBOW (Reduced And Internally Biased Oxide Wafer) ceramics are given.

Journal Article↗
PubMed2001

Frequencies of amino acid strings in globular protein sequences indicate suppression of blocks of consecutive hydrophobic residues.

Patterns of hydrophobic and hydrophilic residues play a major role in protein folding and function. Long, predominantly hydrophobic strings of 20-22 amino acids each are associated with transmembrane helices and have been used to identify such sequences. Much less attention has been paid to hydrophobic sequences within globular proteins. In prior work on computer simulations of the competition between on-pathway folding and off-pathway aggregate formation, we found that long sequences of consecutive hydrophobic residues promoted aggregation within the model, even controlling for overall hydrophobic content. We report here on an analysis of the frequencies of different lengths of contiguous blocks of hydrophobic residues in a database of amino acid sequences of proteins of known structure. Sequences of three or more consecutive hydrophobic residues are found to be significantly less common in actual globular proteins than would be predicted if residues were selected independently. The result may reflect selection against long blocks of hydrophobic residues within globular proteins relative to what would be expected if residue hydrophobicities were independent of those of nearby residues in the sequence.

Alkyl and Aryl Transferases↗
PubMed2001

Effects of ethanol intoxication on speech suprasegmentals.

The effects of ingesting ethanol have been shown to be somewhat variable in humans. To date, there appear to be but few universals. Yet, the question often arises: is it possible to determine if a person is intoxicated by observing them in some manner? A closely related question is: can speech be used for this purpose and, if so, can the degree of intoxication be determined? One of the many issues associated with these questions involves the relationships between a person's paralinguistic characteristics and the presence and level of inebriation. To this end, young, healthy speakers of both sexes were carefully selected and sorted into roughly equal groups of light, moderate, and heavy drinkers. They were asked to produce four types of utterances during a learning phase, when sober and at four strictly controlled levels of intoxication (three ascending and one descending). The primary motor speech measures employed were speaking fundamental frequency, speech intensity, speaking rate and nonfluencies. Several statistically significant changes were found for increasing intoxication; the primary ones included rises in F0, in task duration and for nonfluencies. Minor gender differences were found but they lacked statistical significance. So did the small differences among the drinking category subgroups and the subject groupings related to levels of perceived intoxication. Finally, although it may be concluded that certain changes in speech suprasegmentals will occur as a function of increasing intoxication, these patterns cannot be viewed as universal since a few subjects (about 20%) exhibited no (or negative) changes.

Adult↗
PubMed2001

Speaker identification utilizing noncontemporary speech.

The noncontemporariness of speech is important to both of the two general approaches to speaker identification. Ear-witness identification is one of them; in that instance, the time at which the identification is made is noncontemporary. A substantial amount of research has been carried out on this relationship and it now is well established that an auditor's memory for a voice decays sharply over time. It is the second approach to speaker identification which is of present interest. In this case, samples of a speaker's utterances are obtained at different points in time. For example, a threat call will be recorded and then sometime later (often very much later), a suspect' s exemplar recording will be obtained. In this instance, it is the speech samples that are noncontemporary and they are the materials that are subjected to some form of speaker identification. Prevailing opinion is that noncontemporary speech itself poses just as difficult a challenge to the identification process as does the listener's memory decay in earwitness identification. Accordingly, series of aural-perceptual speaker identification projects were carried out on noncontemporary speech: first, two with latencies of 4 and 8 weeks followed by 4 and 32 weeks plus two more with the pairs separated by 6 and 20 years. Mean correct noncontemporary identification initially dropped to 75-80% at week 4 and this general level was sustained for up to six years. It was only after 20 years had elapsed that a significant drop (to 33%) was noted. It can be concluded that a listener's competency in identifying noncontemporary speech samples will show only modest decay over rather substantial periods of time and, hence, this factor should have only a minimal negative effect on the speaker identification process.

Adult↗