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S Schwartz

Publications and source records attributed to S Schwartz.

At least 109 records · Page 6Linked to original sources
PubMed2000

Aquatic fate assessment of the polycyclic musk fragrance HHCB. Scenario and variability analysis in accordance with the EU risk assessment guidelines.

By means of the environmental fate and distribution models laid down in the Technical Guidance Documents (TGD) and implemented in the European Union System for the Evaluation of Substances (EUSES) environmental concentrations of the polycyclic musk fragrance HHCB (1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethyl-cyclopenta-[g]-2- benzopyrane; trade name: e.g. Galaxolide) were calculated for the aquatic environment under consideration of various scenarios. The results were then compared to monitoring data from the region of North Rhine-Westphalia (River Ruhr). An uncertainty analysis was carried out to determine sensitive parameters, to integrate environmental variability and to confirm the model's calculations. The standard scenario of EUSES overestimates the measured concentrations, which confirms the conservative nature of the calculations. The regional-specific scenarios lead to lower deviations from the measured values than the standard scenario. Deviations range from one to two orders of magnitude in the effluent of sewage treatment plants; they amount to one order of magnitude for surface water concentrations on a local scale and conform to monitoring data on a regional scale. The use of measured bioconcentration factors for fish instead of estimated ones reduces deviations remarkably. The investigation reveals that unrealistic worst-case calculations of HHCB can at best be ameliorated by the application of more realistic emission rates and measured bioconcentration factors. The use of regional-specific parameters also diminishes the deviations of the calculations from the measured concentrations.

Benzopyrans↗
PubMed2000

Proposals to overcome limitations in the EU chemical risk assessment scheme.

The notification of new chemicals in the European Union requires a risk assessment. A Technical Guidance Document (TGD) was prepared for assistance. The TGD proposes QSARs, regressions and models from various sources. Each method has its own range of applicability and its own restrictions. Regressions used in the assessment of indirect human exposure have a common regression range from log K(OW), 3.0-4.6. Most models are compartment models, which do not consider a spatial distribution of the chemical, and were originally developed for non-dissociating, lipophilic persistent chemicals with measurable vapor pressure. Taking this into account, the TGD is only applicable for a minority of chemical classes. Dissociating compounds, ions, polar and very non-polar compounds do not belong to them. The effect of mixtures cannot be considered, except for hydrocarbons. Using the example of plant uptake, it is shown that in certain cases uptake is underestimated by the model due to processes not considered. This may lead to a wrong security in risk assessment. To overcome these limitations, a set of alternative models with different application ranges should be developed. When no applicable method is available, it might be better not to use a model at all instead of an inadequate model, and look for other sources of information.

Europe↗
PubMed2000

Constitutive activation of FLT3 in acute myeloid leukaemia and its consequences for growth of 32D cells.

The receptor tyrosine kinase Flt3 is expressed on leukaemic blasts of most cases with acute myeloid leukaemia (AML). In order to evaluate the presence and significance of constitutive activation of Flt3 for leukaemogenesis, we (1) analysed the expression and activation status of the receptor in AML blasts; and (2) evaluated the functional consequences of constitutively active Flt3 in a myeloid progenitor cell line. Immunoprecipitation studies revealed Flt3 expression in a high proportion of AML cases (27/32) with ligand-dependent Flt3 autophosphorylation in 18, constitutive autophosphorylation in three and no autophosphorylation in six cases. Only one out of three samples with constitutively active Flt3 but 3/18 samples with ligand-dependent autophosphorylated Flt3 contained the recently described internal tandem repeat (ITR) mutations. To test the significance of Flt3 activation in myeloid cell function, we also characterized the biochemical and biological effects of the activating mutation D838V of Flt3 (FLt3D838V) on the factor-dependent myeloid progenitor cell line 32Dcl3: cells transfected with wild-type Flt3 (32D/Flt3) grew FLt3 ligand (FL) dependent, and the receptor was ligand dependently autophosphorylated. In contrast, the receptor was constitutively autophosphorylated in 32D/Flt3D838V cells, which grew independently of FL. We conclude that, in some AML samples, Flt3 is constitutively activated and that this does not correlate with ITR mutations in the juxtamembrane domain. Furthermore, constitutively active Flt3 confers factor independence to the myeloid progenitor cell line 32D. It remains to be determined whether activation of Flt3 is leukaemogenic in vivo and whether strategies aimed at inhibition of Flt3 activation could inhibit leukaemogenesis.

Acute Disease↗
PubMed2000

Tall cell papillary carcinoma of the thyroid: metastatic to the pancreas.

We present the case of a 53-year-old man with tall cell variant of papillary thyroid carcinoma that metastasized to the pancreas. The pancreas is a unique site of metastasis for differentiated thyroid cancer. The lesion in the neck and lung concentrated radioiodine, whereas the intrapancreatic lesions did not. Discordance between radioiodine studies and serum thyroglobulin in follow-up of patients with differentiated tall cell is reviewed and discussed.

Carcinoma, Papillary↗
PubMed2000

The diffusion of information technology among health maintenance organizations.

This article examines the information technology functions, staffing and cost, services provided, and advanced technologies among health maintenance organizations (HMOs) using a national sample of HMOs from mid-1995. HMOs have a well-developed capability to use data from administrative functions, such as claims processing. Nationally affiliated HMOs and HMOs in markets with greater HMO penetration support more IT functions. Relatively little work has been completed integrating clinical with administrative systems.

Data Collection↗
PubMed2000

Anxiety disorders and tic severity in juveniles with Tourette's disorder.

OBJECTIVE: It was hypothesized that comorbidity with anxiety disorders would predict tic severity in youths with Tourette's disorder (TD). METHOD: Subjects were 190 youths meeting DSM-III-R diagnostic criteria for TD who were consecutively referred to a pediatric psychopharmacology program between 1994 and 1997. Subjects were initially evaluated with a clinical interview and the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Epidemiologic version. Statistical analysis used t tests, chi 2 tests, and logistic regression analysis. RESULTS: One hundred thirty-four subjects were classified as mild/moderate and 56 as severe TD cases. No meaningful differences were found in socioeconomic status, gender distribution, or age at onset of TD between the 2 groups. The 2 groups could not be differentiated by the presence of comorbid mood or disruptive behavior disorders including attention-deficit hyperactivity disorder. Although obsessive-compulsive disorder (OCD) was overrepresented among the severe TD cases, the difference failed to reach statistical significance. Excluding social and simple phobias, all other anxiety disorders were more clearly overrepresented among subjects with severe TD; separation anxiety disorder most robustly predicted tic severity, irrespective of the presence of OCD or other anxiety disorders. CONCLUSION: Findings suggest that non-OCD anxiety disorders in general and separation anxiety disorder in particular may be significantly associated with tic severity in referred TD patients.

Anxiety Disorders↗
PubMed2000

PipMaker--a web server for aligning two genomic DNA sequences.

PipMaker (http://bio.cse.psu.edu) is a World-Wide Web site for comparing two long DNA sequences to identify conserved segments and for producing informative, high-resolution displays of the resulting alignments. One display is a percent identity plot (pip), which shows both the position in one sequence and the degree of similarity for each aligning segment between the two sequences in a compact and easily understandable form. Positions along the horizontal axis can be labeled with features such as exons of genes and repetitive elements, and colors can be used to clarify and enhance the display. The web site also provides a plot of the locations of those segments in both species (similar to a dot plot). PipMaker is appropriate for comparing genomic sequences from any two related species, although the types of information that can be inferred (e.g., protein-coding regions and cis-regulatory elements) depend on the level of conservation and the time and divergence rate since the separation of the species. Gene regulatory elements are often detectable as similar, noncoding sequences in species that diverged as much as 100-300 million years ago, such as humans and mice, Caenorhabditis elegans and C. briggsae, or Escherichia coli and Salmonella spp. PipMaker supports analysis of unfinished or "working draft" sequences by permitting one of the two sequences to be in unoriented and unordered contigs.

Animals↗
PubMed2000

Structure of chromosomal duplicons and their role in mediating human genomic disorders.

Chromosome-specific low-copy repeats, or duplicons, occur in multiple regions of the human genome. Homologous recombination between different duplicon copies leads to chromosomal rearrangements, such as deletions, duplications, inversions, and inverted duplications, depending on the orientation of the recombining duplicons. When such rearrangements cause dosage imbalance of a developmentally important gene(s), genetic diseases now termed genomic disorders result, at a frequency of 0.7-1/1000 births. Duplicons can have simple or very complex structures, with variation in copy number from 2 to >10 repeats, and each varying in size from a few kilobases in length to hundreds of kilobases. Analysis of the different duplicons involved in human genomic disorders identifies features that may predispose to recombination, including large size and high sequence identity between the recombining copies, putative recombination promoting features, and the presence of multiple genes/pseudogenes that may include genes expressed in germ cells. Most of the chromosome rearrangements involve duplicons near pericentromeric regions, which may relate to the propensity of such regions to accumulate duplicons. Detailed analyses of the structure, polymorphic variation, and mechanisms of recombination in genomic disorders, as well as the evolutionary origin of various duplicons will further our understanding of the structure, function, and fluidity of the human genome.

Animals↗
PubMed2000

The mosaic structure of human pericentromeric DNA: a strategy for characterizing complex regions of the human genome.

The pericentromeric regions of human chromosomes pose particular problems for both mapping and sequencing. These difficulties are due, in large part, to the presence of duplicated genomic segments that are distributed among multiple human chromosomes. To ensure contiguity of genomic sequence in these regions, we designed a sequence-based strategy to characterize different pericentromeric regions using a single (162 kb) 2p11 seed sequence as a point of reference. Molecular and cytogenetic techniques were first used to construct a paralogy map that delineated the interchromosomal distribution of duplicated segments throughout the human genome. Monochromosomal hybrid DNAs were PCR amplified by primer pairs designed to the 2p11 reference sequence. The PCR products were directly sequenced and used to develop a catalog of sequence tags for each duplicon for each chromosome. A total of 685 paralogous sequence variants were generated by sequencing 34.7 kb of paralogous pericentromeric sequence. Using PCR products as hybridization probes, we were able to identify 702 human BAC clones, of which a subset, 107 clones, were analyzed at the sequence level. We used diagnostic paralogous sequence variants to assign 65 of these BACs to at least 9 chromosomal pericentromeric regions: 1q12, 2p11, 9p11/q12, 10p11, 14q11, 15q11, 16p11, 17p11, and 22q11. Comparisons with existing sequence and physical maps for the human genome suggest that many of these BACs map to regions of the genome with sequence gaps. Our analysis indicates that large portions of pericentromeric DNA are virtually devoid of unique sequences. Instead, they consist of a mosaic of different genomic segments that have had different propensities for duplication. These biologic properties may be exploited for the rapid characterization of, not only pericentromeric DNA, but also other complex paralogous regions of the human genome.

Centromere↗
PubMed2000

Labeling effects of a controversial psychiatric diagnosis: a vignette experiment of late luteal phase dysphoric disorder.

During the 1990s debate arose about the inclusion of Late Luteal Phase Dysphoric Disorder in the fourth edition of the American Psychiatric Association's Diagnostic and Statistical Manual. Opponents argued that the inclusion of this category would increase stigma and be used as a legal defense for child abuse and other violent crimes. Proponents argued that it would decrease stigma and enhance treatment seeking. Using an experimental vignette design, we tested these propositions in a study of 307 men and women living in Putnam County, New York. In general, the results do not indicate a pervasive negative impact of this label. On the other hand, labeling the disorder a "psychiatric condition" did increase recommendations for psychiatric help.

Adolescent↗
PubMed2000

A prospective study of fever and bacteremia after flexible fiberoptic bronchoscopy in children.

STUDY OBJECTIVES: To assess the incidence of fever and bacteremia after fiberoptic bronchoscopy in immunocompetent children. DESIGN: Prospective study. PATIENTS: Immunocompetent children undergoing fiberoptic bronchoscopy between January 1997 and June 1998. MEASUREMENTS AND RESULTS: Ninety-one children were included in the study. Forty-four children (48%) developed fever within 24 h following bronchoscopy. Bacteremia was not detected in any of the cases at the time of the fever. Children who developed fever were younger than those who remained afebrile (mean age, 2.4 +/- 3.6 years vs 4.2 +/- 3.7 years; p = 0.025). In the fever group, 66% of the bronchoscopies were considered abnormal, compared to 45% in the nonfever group (p = 0.04). Of the fever group, 40.5% of BAL fluid cultures had significant bacterial growth, significantly higher compared to the nonfever group (13.2%; p = 0.006). Of the 80 patients in whom BAL was performed, fever occurred in 52.5% compared to only 18.2% in those who did not have BAL (p = 0.03). BAL fluid content of cell count, lipid-laden macrophages, and interleukin-8 were not significantly different in both groups. In a logistic regression analysis, the significant predictors for developing fever were positive bacterial culture (relative risk, 5.1; 95% confidence interval, 1.6 to 16.4; p = 0.007) and abnormal bronchoscopic findings (relative risk, 3.1, 95% confidence interval, 1.2 to 8.3; p = 0.02). When age < 2 years was included in the model, this factor became highly significant (relative risk, 5.01; 95% confidence interval, 1.83 to 13.75; p < 0.002). CONCLUSIONS: Fever following fiberoptic bronchoscopy is a common event in immunocompetent children and is not associated with bacteremia. Risks to develop this complication are age < 2 years, positive bacterial cultures in BAL fluid, and abnormal bronchoscopic findings.

Bacteremia↗
PubMed2000

Repaglinide/troglitazone combination therapy: improved glycemic control in type 2 diabetes.

OBJECTIVE: This multicenter open-label clinical trial compared the efficacy and safety of repaglinide/troglitazone combination therapy, repaglinide monotherapy, and troglitazone monotherapy in type 2 diabetes that had been inadequately controlled by sulfonylureas, acarbose, or metformin alone. RESEARCH DESIGN AND METHODS: Patients with type 2 diabetes (n = 256) who had inadequate glycemic control (HbA1c > or =7.0%) during previous monotherapy were randomly assigned to receive repaglinide (0.5-4.0 mg at meals), troglitazone (200-600 mg once daily), or a combination of repaglinide (1-4 mg at meals) and troglitazone (200-600 mg once daily). After a 4-6 week washout period, the trial assessed 22 weeks of treatment: 3 weeks (weeks 0-2) of forced titration, 11 weeks of fixed-dose treatment (weeks 3-13), and 8 weeks (weeks 14-21) of titration to maximum dose. Changes in HbA1c and fasting plasma glucose (FPG) values were measured. RESULTS: The combination therapy showed a significant reduction in mean HbA1c values (-1.7%) that was greater than with either type of monotherapy Repaglinide monotherapy resulted in a reduction of HbA1c values that was significantly greater than troglitazone (-0.8 vs. -0.4%) (P < 0.05). Combination therapy was more effective in reducing FPG values (-80 mg/dl) than either repaglinide (-43 mg/dl) or troglitazone (-46 mg/dl) monotherapies. Adverse events were similar in all groups. CONCLUSIONS: Combination therapy with repaglinide and troglitazone leads to better glycemic control than monotherapy with either agent alone. Repaglinide monotherapy was more effective in lowering HbA1c levels than troglitazone monotherapy Repaglinide/troglitazone combination therapy was effective and did not show unexpected adverse events.

Adult↗
PubMed2000

Therapy focused on lowering postprandial glucose, not fasting glucose, may be superior for lowering HbA1c. IOEZ Study Group.

OBJECTIVE: To compare the overall efficacy of combination therapies focused on fasting or postprandial blood glucose in patients with type 2 diabetes not adequately controlled with oral sulfonylurea agents alone. RESEARCH DESIGN AND METHODS: A total of 135 patients were randomly assigned for 3 months to 1 of 3 combination regimens with glyburide (G) that addressed postprandial blood glucose with insulin lispro (L+G), premeal blood glucose with metformin (M+G), or fasting blood glucose (FBG) with bedtime NPH insulin (NPH+G). RESULTS: At end point, HbA1c was significantly lower with all therapies (P = 0.001) and was significantly lower for L+G (7.68+/-0.88%) compared with either NPH+G (8.51+/-1.38%, P = 0.003) or M+G (8.31+/-1.31%, P = 0.025). FBG at end point was significantly lower for NPH+G (8.49+/-2.36 mmol/l) compared with either L+G (10.57+/-1.97 mmol/l, P = 0.001) or M+G (9.69+/-2.89 mmol/l, P = 0.029). The mean 2-h postprandial glucose after a test meal was significantly lower for L+G (10.87+/-2.88 mmol/l) versus NPH+G (12.21+/-3.12 mmol/, P = 0.052) or versus M+G (12.72+/-3.26 mmol/l, P = 0.009). The overall rate of hypoglycemia (episodes per 30 days) was low and not statistically significant between groups (P = 0.156). CONCLUSIONS: Adding a second antihyperglycemic agent, regardless of its timing of action, lowers HbA1c and glucose values. However, when insulin lispro was used to focus on postprandial blood glucose, there was a greater impact on overall metabolic control. These data support the importance of lowering postprandial blood glucose to optimize overall glycemic control and thus improve long-term outcomes.

Blood Glucose↗
PubMed2000

Hypercalcemia and T-cell lymphoma with acquired immunodeficiency syndrome: occurrence without human T-cell leukemia virus-I.

We describe the case of a patient with acquired immunodeficiency syndrome (AIDS) who had a CD4 cell count of 60/microL, bilateral hilar adenopathy, and hypercalcemia. Transbronchial biopsy showed T-cell anaplastic large cell lymphoma. Serology was negative for human T-cell leukemia virus-I (HTLV-I). This appears to be the first case of T-cell anaplastic large cell lymphoma occurring in an AIDS patient with hypercalcemia who was seronegative for HTLV-I.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Regulation of human papillomavirus late gene expression.

Human papillomaviruses (HPVs) comprise a large group of small DNA tumor viruses with tropism for squamous epithelial cells. The papillomavirus life cycle is strictly linked to the epithelial differentiation program and production of virus particles is dependent on terminal cell differentiation. The virus structural proteins L1 and L2 are therefore detected only in the upper layers with differentiated cells in the infected epithelium. This property is common to all known HPVs. However, the abundance of virus particles detected in vivo may vary between the various HPV types and one can divide the HPV types according to the amount of virus they produce. It is reasonable to speculate that the differentiation dependent production of L1 and L2 and the differences in L1 and L2 protein levels among various HPV types reflect an adaptation of the viruses to the environment of the host that results in escape from the immune surveillance for various periods of time and efficient transmission of virus in the human population. Our research group is interested in the regulation of expression of the HPV structural proteins L1 and L2. The results of our research are summarised in this article.

3' Untranslated Regions↗
PubMed1999

Long terminal repeat promoter/enhancer activity of different subtypes of HIV type 1.

Transcription of the HIV-1 provirus genome is regulated by a complex interplay between viral regulatory proteins and cellular transcription factors that interact with the viral long terminal repeat (LTR) region of HIV-1. However, several cellular transcription factors have been identified that can interact with the HIV-1 LTR; the significance of all of these factors is not clearly understood. In this study we have characterized the LTR region of different subtypes of HIV-1 with regard to nucleotide sequence and promoter activity. The LTR regions of HIV-1 from peripheral blood mononuclear cells of 29 infected individuals originating from 10 different geographical regions were sequenced and further analyzed for promoter/enhancer activity in transient transfection of HeLa cells, in the context of a reporter gene and in the context of the complete virus genome. We found several subtype-specific LTR sequences of the various HIV-1 strains, such as an insertion that created a potential third NF-kappaB site in the LTR of the subtype C strains. The USF-binding site in the NRE also contained subtype-specific sequences. Interestingly, the promoter/enhancer activities of the subtype C LTRs were higher than the activities of the other subtypes analyzed here (subtypes A, B, D, E, and G), suggesting that the potential third NF-kappaB site may confer higher LTR activity or that the subtype C NRE may be less potent. Thus, our data suggest that genetic diversity of the LTR may result in HIV-1 subtypes with different replicative properties.

Adult↗