bluuebunny/crossref_metadata_2025 huggingface dataset:
Coupling of Gab1 to C-Met, Grb2, and Shp2 Mediates Biological Responses
Authors: Schaeper Ute , Gehring Niels H. , Fuchs Klaus P. , Sachs Martin , Kempkes Bettina , Birchmeier Walter
Published: July 2002

Gab1 is a substrate of the receptor tyrosine kinase c-Met and involved in c-Met–specific branching morphogenesis. It associates directly with c-Met via the c-Met–binding domain, which is not related to known phosphotyrosine-binding domains. In addition, Gab1 is engaged in a constitutive complex with the adaptor protein Grb2. We have now mapped the c-Met and Grb2 interaction sites using reverse yeast two-hybrid technology. The c-Met–binding site is localized to a 13–amino acid region unique to Gab1. Insertion of this site into the Gab1-related protein p97/Gab2 was sufficient to confer c-Met–binding activity. Association with Grb2 was mapped to two sites: a classical SH3-binding site (PXXP) and a novel Grb2 SH3 consensus-binding motif (PX(V/I)(D/N)RXXKP). To detect phosphorylation-dependent interactions of Gab1 with downstream substrates, we developed a modified yeast two-hybrid assay and identified PI(3)K, Shc, Shp2, and CRKL as interaction partners of Gab1. In a trk-met-Gab1–specific branching morphogenesis assay, association of Gab1 with Shp2, but not PI(3)K, CRKL, or Shc was essential to induce a biological response in MDCK cells. Overexpression of a Gab1 mutant deficient in Shp2 interaction could also block HGF/SF-induced activation of the MAPK pathway, suggesting that Shp2 is critical for c-Met/Gab1-specific signaling.
Ubiquitination and proteasomal activity is required for transport of the EGF receptor to inner membranes of multivesicular bodies
Authors: Longva Karianne E. , Blystad Frøydis D. , Stang Espen , Larsen Astrid M. , Johannessen Lene E. , Madshus Inger H.
Published: July 2002

EGF, but not TGFα, efficiently induces degradation of the EGF receptor (EGFR). We show that EGFR was initially polyubiquitinated to the same extent upon incubation with EGF and TGFα, whereas the ubiquitination was more sustained by incubation with EGF than with TGFα. Consistently, the ubiquitin ligase c-Cbl was recruited to the plasma membrane upon activation of the EGFR with EGF and TGFα, but localized to endosomes only upon activation with EGF. EGF remains bound to the EGFR upon endocytosis, whereas TGFα dissociates from the EGFR. Therefore, the sustained polyubiquitination is explained by EGF securing the kinase activity of endocytosed EGFR. Overexpression of the dominant negative N-Cbl inhibited ubiquitination of the EGFR and degradation of EGF and EGFR. This demonstrates that EGF-induced ubiquitination of the EGFR as such is important for lysosomal sorting. Both lysosomal and proteasomal inhibitors blocked degradation of EGF and EGFR, and proteasomal inhibitors inhibited translocation of activated EGFR from the outer limiting membrane to inner membranes of multivesicular bodies (MVBs). Therefore, lysosomal sorting of kinase active EGFR is regulated by proteasomal activity. Immuno-EM showed the localization of intact EGFR on internal membranes of MVBs. This demonstrates that the EGFR as such is not the proteasomal target.
A novel polymer of tubulin forms the conoid of Toxoplasma gondii
Authors: Hu Ke , Roos David S. , Murray John M.
Published: July 2002

Toxoplasma gondii is an obligatory intracellular parasite, an important human pathogen, and a convenient laboratory model for many other human and veterinary pathogens in the phylum Apicomplexa, such as Plasmodium, Eimeria, and Cryptosporidia. 22 subpellicular microtubules form a scaffold that defines the cell shape of T. gondii. Its cytoskeleton also includes an intricate apical structure consisting of the conoid, two intraconoid microtubules, and two polar rings. The conoid is a 380-nm diameter motile organelle, consisting of fibers wound into a spiral like a compressed spring. FRAP analysis of transgenic T. gondii expressing YFP-α-tubulin reveals that the conoid fibers are assembled by rapid incorporation of tubulin subunits during early, but not late, stages of cell division. Electron microscopic analysis shows that in the mature conoid, tubulin is arranged into a novel polymer form that is quite different from typical microtubules.
p50–NF-κB Complexes Partially Compensate for the Absence of RelB: Severely Increased Pathology in p50−/−relB−/−Double-knockout Mice
Authors: Weih Falk , Durham Stephen K. , Barton Debra S. , Sha William C. , Baltimore David , Bravo Rodrigo
Published: July 2002

RelB-deficient mice (relB−/−) have a complex phenotype including multiorgan inflammation and hematopoietic abnormalities. To examine whether other NF-κB/Rel family members are required for the development of this phenotype or have a compensatory role, we have initiated a program to generate double-mutant mice that are deficient in more than one family member. Here we report the phenotypic changes in relB−/− mice that also lack the p50 subunit of NFκB (p50−/−). The inflammatory phenotype of p50−/−relB−/− double-mutant mice was markedly increased in both severity and extent of organ involvement, leading to premature death within three to four weeks after birth. Double-knockout mice also had strongly increased myeloid hyperplasia and thymic atrophy. Moreover, B cell development was impaired and, in contrast to relB−/− single knockouts, B cells were absent from inflammatory infiltrates. Both p50−/− and heterozygous relB−/+ animals are disease-free. In the absence of the p50, however, relB−/+ mice (p50−/−relB−/+) had a mild inflammatory phenotype and moderate myeloid hyperplasia. Neither elevated mRNA levels of other family members, nor increased κB-binding activities of NF-κB/Rel complexes could be detected in single- or double-mutant mice compared to control animals. These results indicate that the lack of RelB is, in part, compensated by other p50-containing complexes and that the “classical” p50-RelA–NF-κB activity is not required for the development of the inflammatory phenotype.
Regulation of Experimental Autoimmune Encephalomyelitis by Natural Killer (NK) Cells
Authors: Zhang Ben-ning , Yamamura Takashi , Kondo Takayuki , Fujiwara Michio , Tabira Takeshi
Published: July 2002

In this report, we establish a regulatory role of natural killer (NK) cells in experimental autoimmune encephalomyelitis (EAE), a prototype T helper cell type 1 (Th1)-mediated disease. Active sensitization of C57BL/6 (B6) mice with the myelin oligodendrocyte glycoprotein (MOG)35-55 peptide induces a mild form of monophasic EAE. When mice were deprived of NK cells by antibody treatment before immunization, they developed a more serious form of EAE associated with relapse. Aggravation of EAE by NK cell deletion was also seen in β2-microglobulin−/− (β2m−/−) mice, indicating that NK cells can play a regulatory role in a manner independent of CD8+ T cells or NK1.1+ T cells (NK–T cells). The disease enhancement was associated with augmentation of T cell proliferation and production of Th1 cytokines in response to MOG35-55. EAE passively induced by the MOG35-55-specific T cell line was also enhanced by NK cell deletion in B6, β2m−/−, and recombination activation gene 2 (RAG-2)−/− mice, indicating that the regulation by NK cells can be independent of T, B, or NK–T cells. We further showed that NK cells inhibit T cell proliferation triggered by antigen or cytokine stimulation. Taken together, we conclude that NK cells are an important regulator for EAE in both induction and effector phases.
Heat Shock Protein–Peptide Complexes, Reconstituted In Vitro, Elicit Peptide-specific Cytotoxic T Lymphocyte Response and Tumor Immunity
Authors: Blachere Nathalie E. , Li Zihai , Chandawarkar Rajiv Y. , Suto Ryuichiro , Jaikaria Navdeep S. , Basu Sreyashi , Udono Heiichiro , Srivastava Pramod K.
Published: July 2002

Heat shock protein (HSP) preparations derived from cancer cells and virus-infected cells have been shown previously to elicit cancer-specific or virus-specific immunity. The immunogenicity of HSP preparations has been attributed to peptides associated with the HSPs. The studies reported here demonstrate that immunogenic HSP–peptide complexes can also be reconstituted in vitro. The studies show that (a) complexes of hsp70 or gp96 HSP molecules with a variety of synthetic peptides can be generated in vitro; (b) the binding of HSPs with peptides is specific in that a number of other proteins tested do not bind synthetic peptides under the conditions in which gp96 molecules do; (c) HSP–peptide complexes reconstituted in vitro are immunologically active, as tested by their ability to elicit antitumor immunity and specific CD8+ cytolytic T lymphocyte response; and (d) synthetic peptides reconstituted in vitro with gp96 are capable of being taken up and re-presented by macrophage in the same manner as gp96– peptides complexes generated in vivo. These observations demonstrate that HSPs are CD8+ T cell response–eliciting adjuvants.
Gonococcal Invasion of Epithelial Cells Driven by P.IA, a Bacterial Ion Channel with GTP Binding Properties
Authors: van Putten Jos P.M. , Duensing Thomas D. , Carlson John
Published: July 2002

The neisserial porin P.I is a GTP binding protein that forms a voltage-gated channel that translocates into mammalian cell membranes and modulates host cell signaling events. Here, we report that P.I confers invasion of the bacterial pathogen Neisseria gonorrhoeae into Chang epithelial cells and that this event is controlled by GTP, as well as other phosphorus-containing compounds. Bacterial invasion was observed only for strains carrying the P.IA subtype of porin, which is typically associated with the development of disseminated neisserial disease, and did not require opacity outer membrane proteins, previously recognized as gonococcal invasins. Allelic replacement studies showed that bacterial invasiveness cotransferred with the P.IA (por1A) gene. Mutation of the P.I-associated protein Rmp did not alter the invasive properties. Cross-linking of labeled GTP to the porin revealed more efficient GTP binding to the P.IA than P.IB porin subtype. GTP binding was inhibited by an excess of unlabeled GTP, ATP, and GDP, as well as inorganic phosphate, but not by UTP or beta-glycerophosphate, fully in line with the respective invasion-inhibitory activities observed for these compounds. The P.IA-mediated cellular invasion may explain the more invasive behavior of P.IA strains in the natural infection and may broaden the basis for the development of a P.I-based gonococcal vaccine.
The Balance between Sphingosine and Sphingosine-1-Phosphate Is Decisive for Mast Cell Activation after Fc∈ Receptor I Triggering
Authors: Prieschl Eva E. , Csonga Robert , Novotny Veronica , Kikuchi Gary E. , Baumruker Thomas
Published: July 2002

Over the last few years, sphingolipids have been identified as potent second messenger molecules modulating cell growth and activation. A newly emerging facet to this class of lipids suggests a picture where the balance between two counterregulatory lipids (as shown in the particular example of ceramide and sphingosine-1-phosphate in T lymphocyte apoptosis) determines the cell fate by setting the stage for various protein signaling cascades. Here, we provide a further example of such a decisive balance composed of the two lipids sphingosine and sphingosine-1-phosphate that determines the allergic responsiveness of mast cells. High intracellular concentrations of sphingosine act as a potent inhibitor of the immunoglobulin (Ig)E plus antigen–mediated leukotriene synthesis and cytokine production by preventing activation of the mitogen-activated protein kinase pathway. In contrast, high intracellular levels of sphingosine-1-phosphate, also secreted by allergically stimulated mast cells, activate the mitogen-activated protein kinase pathway, resulting in hexosaminidase and leukotriene release, or in combination with ionomycin, give cytokine production. Equivalent high concentrations of sphingosine-1-phosphate are dominant over sphingosine as they counteract its inhibitory potential. Therefore, it might be inferred that sphingosine-kinase is pivotal to the activation of signaling cascades initiated at the Fc∈ receptor I by modulating the balance of the counterregulatory lipids.
A Single Amino Acid Determines the Immunostimulatory Activity of Interleukin 10
Authors: Ding Yaozhong , Qin Lihui , Kotenko Serguei V. , Pestka Sidney , Bromberg Jonathan S.
Published: July 2002

Cellular interleukin 10s (cIL-10s) of human and murine origin have extensive sequence and structural homology to the Epstein-Barr virus BCRF-I gene product, known as viral IL-10 (vIL-10). Although these cytokines share many immunosuppressive properties, vIL-10 lacks several of the immunostimulatory activities of cIL-10 on certain cell types. The molecular and cellular bases for this dichotomy are not currently defined. Here, we show that the single amino acid isoleucine at position 87 of cIL-10 is required for its immunostimulatory function. Substitution of isoleucine in cIL-10 with alanine, which corresponds to the vIL-10 residue, abrogates immunostimulatory activity for thymocytes, mast cells, and alloantigenic responses while preserving immunosuppressive activity for inhibition of interferon γ production and prolongation of cardiac allograft survival. Conversely, substitution of alanine with isoleucine in vIL-10 converts it to a cIL-10–like molecule with immunostimulatory activity. This single conservative residue alteration significantly affects ligand affinity for receptor; however, affinity changes do not necessarily alter specific activities for biologic responses in a predictable fashion. These results suggest complex regulation of IL-10 receptor–ligand interactions and subsequent biological responses. These results demonstrate that vIL-10 may represent a captured and selectively mutated cIL-10 gene that benefits viral pathogenesis by leading to ineffective host immune responses. The ability to manipulate the activity of IL-10 in either a stimulatory or suppressive direction may be of practical value for regulating immune responses for disease therapy, and of theoretical value for determining what aspects of IL-10 activity are important for normal T cell responses.
Discrete tomography: Determination of finite sets by X-rays
Authors: Gardner R. , Gritzmann Peter
Published: July 2002

We study the determination of finite subsets of the integer lattice

Z

n

{\Bbb Z}^n

,

n
≥
2

n\ge 2

, by X-rays. In this context, an X-ray of a set in a direction

u
u

gives the number of points in the set on each line parallel to

u
u

. For practical reasons, only X-rays in lattice directions, that is, directions parallel to a nonzero vector in the lattice, are permitted. By combining methods from algebraic number theory and convexity, we prove that there are four prescribed lattice directions such that convex subsets of

Z

n

{\Bbb Z}^n

(i.e., finite subsets

F
F

with

F
=

Z

n

∩
conv
⁡
F

F={\Bbb Z}^n\cap \operatorname {conv} F

) are determined, among all such sets, by their X-rays in these directions. We also show that three X-rays do not suffice for this purpose. This answers a question of Larry Shepp, and yields a stability result related to Hammer’s X-ray problem. We further show that any set of seven prescribed mutually nonparallel lattice directions in

Z

2

{\Bbb Z}^2

have the property that convex subsets of

Z

2

{\Bbb Z}^2

are determined, among all such sets, by their X-rays in these directions. We also consider the use of orthogonal projections in the interactive technique of successive determination, in which the information from previous projections can be used in deciding the direction for the next projection. We obtain results for finite subsets of the integer lattice and also for arbitrary finite subsets of Euclidean space which are the best possible with respect to the numbers of projections used.
Algebraic invariant curves for the Liénard equation
Authors: Żoła̧dek Henryk
Published: July 2002

Odani has shown that if

deg
⁡
g
≤
deg
⁡
f

\deg g\leq \deg f

then after deleting some trivial cases the polynomial system

x
˙

=
y
,

y
˙

=
−
f
(
x
)
y
−
g
(
x
)

\dot {x}=y,\,\,\dot {y}=-f(x)y-g(x)

does not have any algebraic invariant curve. Here we almost completely solve the problem of algebraic invariant curves and algebraic limit cycles of this system for all values of

deg
⁡
f

\deg f

and

deg
⁡
g

\deg g

. We give also a simple presentation of Yablonsky’s example of a quartic limit cycle in a quadratic system.
Splittings of Surfaces
Authors: Skora Richard
Published: July 2002

The main result characterizes small actions of surface groups on

R

\mathbf {R}

-trees.
Comparison of Maternal and Infant Outcomes between Vacuum Extraction and Forceps Deliveries
Authors: Wen Shi Wu , Liu Shiliang , Kramer Michael S. , Marcoux Sylvie , Ohlsson Arne , Sauvé Reg , Liston Robert
Published: July 2002

The authors conducted a population-based historical cohort study in the Canadian province of Quebec to assess the maternal and infant outcomes associated with vacuum extraction and forceps deliveries. The study database contains information on 305,391 mother-infant dyads (linked by a common institutional code and hospital chart number) for singleton live vaginal births with a nonbreech presentation at the gestational age of 37 or more completed weeks and a birth weight between 2,500 and 4,000 g during fiscal years 1991/1992 to 1995/1996. Of the births, 31,015 were delivered by vacuum extraction, and 18,727 were delivered by forceps. Compared with delivery by forceps, the adjusted risk ratios for third-/fourth-degree perineal laceration, intracranial hemorrhage, subdural or cerebral hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, cephalhematoma, and neonatal in-hospital death were 0.48 (95% confidence interval: 0.45, 0.50), 1.28 (95% confidence interval: 0.73, 2.25), 0.97 (95% confidence interval: 0.49, 1.93), 0.99 (95% confidence interval: 0.16, 5.97), 5.44 (confidence interval: 1.26, 23.43), 2.02 (95% confidence interval: 1.89, 2.16), and 0.93 (95% confidence interval: 0.32, 2.70), respectively. The authors conclude that vacuum extraction causes less maternal trauma but may increase the risk of cephalhematoma and certain types of intracranial hemorrhage (e.g., subarachnoid hemorrhage).
Living Arrangements, Social Integration, and Change in Functional Health Status
Authors: Michael Yvonne L. , Berkman Lisa F. , Colditz Graham A. , Kawachi Ichiro
Published: July 2002

Limited prospective data have examined the association between living arrangements and emotional well-being. The authors assessed whether older women living with a spouse were less likely to experience a decline in mental health, vitality, or physical function compared with women living alone or with nonspouse others. The association between living arrangement and 4-year change in functional health status was examined prospectively among 28,324 women aged 60–72 years in the Nurses' Health Study. After adjustment for age, baseline function, comorbid conditions, and health behaviors, women living alone had lower risk of decline in mental health (relative risk (RR) = 0.73, 95 percent confidence interval (CI): 0.65, 0.81) and vitality (RR = 0.72, 95 percent CI: 0.65, 0.80) compared with those living with a spouse. Contact with friends and relatives and level of social engagement were significantly protective against a decline in mental health among women living alone but not among women living with a spouse. These results suggest that women living independently are neither socially isolated nor at increased risk for decline in functional health status. In fact, these women actually fare better on measures of psychologic function than do women living with a spouse.
Mortality Reduction with Air Bag and Seat Belt Use in Head-on Passenger Car Collisions
Authors: Crandall Cameron S. , Olson Lenora M. , Sklar David P.
Published: July 2002

To assess the efficacy of occupant protection systems, the authors measured the mortality reduction associated with air bag deployment and seat belt use for drivers involved in head-on passenger car collisions in the United States. They used a matched case-control design of all head-on collisions involving two passenger cars reported to the Fatality Analysis Reporting System in 1992–1997, and driver mortality differences between the paired crash vehicles for air bag deployment and seat belt use were measured with matched-pair odds ratios. Conditional logistic regression was used to adjust for multiple effects. There were 9,859 head-on collisions involving 19,718 passenger cars and drivers. Air bag deployment reduced mortality 63% (crude odds ratio (OR) = 0.37, 95% confidence interval (CI): 0.32, 0.42), while lap-shoulder belt use reduced mortality 72% (OR = 0.28, 95% CI: 0.25, 0.31). In a conditional logistic model that adjusted for vehicle (rollover, weight, age) and driver (age, sex) factors, air bags (OR = 0.71, 95% CI: 0.58, 0.87) and any combination of seat belts (OR = 0.25, 95% CI: 0.22, 0.29) were both associated with reduced mortality. Combined air bag and seat belt use reduced mortality by more than 80% (OR = 0.18, 95% CI: 0.13, 0.25). Thus, this study confirms the independent effect of air bags and seat belts in reducing mortality.
Testosterone Concentrations in Women Aged 25–50 Years: Associations with Lifestyle, Body Composition, and Ovarian Status
Authors: Sowers MF. , Beebe J. L. , McConnell D. , Randolph John , Jannausch M.
Published: July 2002

While there is substantial evidence of the importance of endogenous and exogenous estrogen in reproductive health and chronic disease, there is little consideration of androgens in women's health. In the Michigan Bone Health Study (1992–1995), the authors examined the correlates of testosterone concentrations in pre- and perimenopausal women (i.e., age, menopausal status, body composition, and lifestyle behaviors) in a population-based longitudinal study including three annual examinations among 611 women aged 25–50 years identified through a census in a midwestern community. Current smokers had the highest testosterone concentrations with decreasing values in former and nonsmokers (p = 0.0001). Body composition measures (body mass index, body fat (%), weight (kg), lean body mass (kg), and fat mass (kg)) were significantly and positively associated with total testosterone concentrations in a dose-response manner. Hysterectomy with oophorectomy was associated with significantly lower testosterone concentrations. Alcohol consumption, physical activity, and dietary macronutrient intake were not associated with testosterone concentrations. This is one of the first studies to examine correlates of serum testosterone concentrations in anticipation of the growing interest in the role of androgens in women's health. The greater circulating levels of testosterone in obese women and smokers suggest that testosterone concentrations should be considered in the natural history of disease conditions where obesity and smoking are risk factors, including cardiovascular disease.
High Plasma Nonesterified Fatty Acids Are Predictive of Cancer Mortality but Not of Coronary Heart Disease Mortality: Results from the Paris Prospective Study
Authors: Aline Charles Marie , Fontbonne Annick , Thibult Nadine , Claude Jean-Roger , Warnet Jean-Michel , Rosselin Gabriel , Ducimetière Pierre , Eschwège Eveline
Published: July 2002

To assess the association of fasting plasma nonesterified fatty acid (NEFA) concentration with the risk of death from coronary heart disease and cancer, the authors computed 15-year mortality rates for the 4,589 working men aged 43–53 years who were included in the Paris Prospective Study between 1967 and 1972. A total of 251 and 126 men died from cancer and coronary heart disease, respectively. For coronary heart disease death, the age- and tobacco-adjusted relative risk for men in the highest 20% of the fasting plasma NEFA concentrations compared with those in the lowest 80% was 1.54 (95% confidence interval (CI): 1.01, 2.34). It became nonsignificant after further adjustment for blood pressure, iliac/thigh ratio, and plasma insulin and cholesterol concentrations. In contrast, a high fasting plasma NEFA concentration exhibited a strong independent relation with cancer mortality (relative risk = 1.66, 95% CI: 1.25, 2.21, after adjustment for age, cigarette consumption, heart rate, and body mass index). Despite pathophysiologic mechanisms linking NEFA metabolism with visceral fat and plasma glucose, insulin, and triglyceride concentrations, the plasma NEFA concentration does not appear to be a good marker for coronary heart disease risk. In contrast, an unexpected association with cancer mortality was found that may point to the need for further investigation.
Modeling Changes in CD4-positive T-Lymphocyte Counts after the Start of Highly Active Antiretroviral Therapy and the Relation with Risk of Opportunistic Infections The Aquitaine Cohort, 1996–1997
Authors: Binquet C. , Chêne G. , Jacqmin-Gadda H. , Journot V. , Savès M. , Lacoste D. , Dabis F.
Published: July 2002

After initiation of a treatment for human immunodeficiency virus type 1 infection containing a protease inhibitor, immune restoration associated with increases in CD4-positive (CD4+) T lymphocyte count may be delayed. In a sample of patients who had been prescribed protease inhibitors for the first time, the authors tested to see whether there was a minimal duration of CD4+ cell count increase before the increase had an impact on the occurrence of opportunistic infections. The evolution (difference between time t and baseline) of CD4+ cell count was modeled using a mixed effects linear model. Changes in CD4+ count estimated by this model were then included as time-dependent covariates in a proportional hazards model. Finally, the authors tested for the existence of a CD4+ change × time interaction. The authors used a sample of 553 French patients first prescribed protease inhibitors in 1996 and followed for a median of 16 months. During the first 120 days, there was no association between CD4+ change and the rate of opportunistic infections. After 120 days, each 50-cell/mm3 increase in CD4+ count was associated with a 60% (95% confidence interval: 45, 72) reduction in the incidence of opportunistic infections. These results, based on modeling of CD4+ cell response, at least indirectly reinforce the concept of a delayed but possible immune recovery with the use of protease inhibitors. The findings support the potential for interruption of certain types of prophylaxis against opportunistic infections under reasonable conditions of duration of antiretroviral therapy and sustained CD4+ cell response.
Is Shorter Always Better? Relative Importance of Questionnaire Length and Cognitive Ease on Response Rates and Data Quality for Two Dietary Questionnaires
Authors: Subar Amy F. , Ziegler Regina G. , Thompson Frances E. , Johnson Christine Cole , Weissfeld Joel L. , Reding Douglas , Kavounis Katherine H. , Hayes Richard B.
Published: July 2002

In this study, the authors sought to determine the effects of length and clarity on response rates and data quality for two food frequency questionnaires (FFQs): the newly developed 36-page Diet History Questionnaire (DHQ), designed to be cognitively easier for respondents, and a 16-page FFQ developed earlier for the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. The PLCO Trial is a 23-year randomized controlled clinical trial begun in 1992. The sample for this substudy, which was conducted from January to April of 1998, consisted of 900 control and 450 screened PLCO participants aged 55–74 years. Controls received either the DHQ or the PLCO FFQ by mail. Screenees, who had previously completed the PLCO FFQ at baseline, were administered the DHQ. Among controls, the response rate for both FFQs was 82%. Average amounts of time needed by controls to complete the DHQ and the PLCO FFQ were 68 minutes and 39 minutes, respectively. Percentages of missing or uninterpretable responses were similar between instruments for questions on frequency of intake but were approximately 3 and 9 percentage points lower (p ≤ 0.001) in the DHQ for questions on portion size and use of vitamin/mineral supplements, respectively. Among screenees, response rates for the DHQ and the PLCO FFQ were 84% and 89%, respectively, and analyses of questions on portion size and supplement use showed few differences. These data indicated that the shorter FFQ was not better from the perspective of response rate and data quality, and that clarity and ease of administration may compensate for questionnaire length.
Associations of Blood Lead, Dimercaptosuccinic Acid-chelatable Lead, and Tibia Lead with Neurobehavioral Test Scores in South Korean Lead Workers
Authors: Schwartz Brian S. , Lee Byung-Kook , Lee Gap-Soo , Stewart Walter F. , Lee Sung-Soo , Hwang Kyu-Yoon , Ahn Kyu-Dong , Kim Yong-Bae , Bolla Karen I. , Simon David , Parsons Patrick J. , Todd Andrew C.
Published: July 2002

The authors performed a cross-sectional study to evaluate associations between blood lead, tibia lead, and dimercaptosuccinic acid (DMSA)-chelatable lead and measures of neurobehavioral and peripheral nervous system function among 803 lead-exposed workers and 135 unexposed controls in South Korea. The workers and controls were enrolled in the study between October 1997 and August 1999. Central nervous system function was assessed with a modified version of the World Health Organization Neurobehavioral Core Test Battery. Peripheral nervous system function was assessed by measuring pinch and grip strength and peripheral vibration thresholds. After adjustment for covariates, the signs of the β coefficients for blood lead were negative for 16 of the 19 tests and blood lead was a significant predictor of worse performance on eight tests. On average, for the eight tests that were significantly associated with blood lead levels, an increase in blood lead of 5 µg/dl was equivalent to an increase of 1.05 years in age. In contrast, after adjustment for covariates, tibia lead level was not associated with neurobehavioral test scores. Associations with DMSA-chelatable lead were similar to those for blood lead. In these currently exposed workers, blood lead was a better predictor of neurobehavioral performance than was tibia or DMSA-chelatable lead, mainly in the domains of executive abilities, manual dexterity, and peripheral motor strength.
Metabolic Syndrome and Ischemic Heart Disease in Elderly Men and Women
Authors: Lindblad Ulf , Langer Robert D. , Wingard Deborah L. , Thomas Ronald G. , Barrett-Connor Elizabeth L.
Published: July 2002

Associations between metabolic syndrome components and prevalent ischemic heart disease (IHD) were investigated in a cross-sectional, community-based study of elderly men (n = 1,015) and women (n = 1,259) in Rancho Bernardo, California, in 1984–1987. In both sexes, there were significant positive associations between IHD defined by resting electrocardiogram criteria and age, systolic blood pressure, fasting and postchallenge hyperglycemia, total cholesterol/high density lipoprotein cholesterol (HDL cholesterol) ratio, and triglycerides and an inverse significant association with HDL cholesterol. High collinearity and interactions between serum insulin and metabolic syndrome variables were accounted for by uncorrelated principal components identified by factor analysis. In both men and women, three uncorrelated principal components were identified, representing a central metabolic factor (body mass index, fasting and 2-hour serum insulin, high serum triglycerides, and low HDL cholesterol), a glucose factor, and a blood pressure factor. In a multivariate model with age and sex, all three factors were significantly associated with IHD by electrocardiogram criteria; central metabolic factor (odds ratio (OR) = 1.6, p = 0.001), glucose factor (OR = 1.4, p < 0.001), blood pressure factor (OR = 1.2, p = 0.005), age (10 years) (OR = 1.8, p < 0.001), and female sex (OR = 0.5, p < 0.02). Similar results were obtained in analyses using clinically manifest IHD as the outcome. These results support the thesis that the metabolic syndrome exerts effects through different risk factors by different mechanisms.
Latex Sensitization in Health Care Workers and in the US General Population
Authors: Garabrant David H. , Roth H. Daniel , Parsad Romain , Ying Gui-Shuang , Weiss Jay
Published: July 2002

Sensitization to natural rubber latex is a prerequisite to type I immediate hypersensitivity reactions (urticaria, angioedema, anaphylaxis, and allergic rhinitis) that result from subsequent latex exposure. This study examines occupations in which latex glove use is common to determine whether it is associated with increased prevalence odds of latex sensitization (measured by latex-specific immunoglobulin E antibodies) by using data from 5,512 adults aged 17–60 years from the Third National Health and Nutrition Examination Survey (1988–1991). After other factors associated with latex sensitization were controlled for, there was a nonsignificant association between longest-held jobs in health care and latex sensitization (odds ratio (OR) = 1.49, 95 percent confidence interval (CI): 0.92, 2.40). For current occupations, latex sensitization was not associated with health care work in which gloves were used (OR = 1.17, 95 percent CI: 0.51, 2.65) or with other occupations in which latex glove use is common (OR = 1.01, 95 percent CI: 0.49, 2.07) compared with other occupations. Current health care workers who reported not using gloves were at increased risk of latex sensitization, both among those without a history of childhood atopy (OR = 2.30, 95 percent CI: 1.04, 5.13) and those with such a history (OR = 28.04, 95 percent CI: 3.64, 215.97). This odds ratio heterogeneity suggests that subjects with childhood atopy may be at high risk of latex sensitization.
Relation of Alleles of the Sodium-Potassium Adenosine Triphosphatase α2 Gene with Blood Pressure and Lead Exposure
Authors: Glenn Barbara S. , Stewart Walter F. , Schwartz Brian S. , Bressler Joseph
Published: July 2002

Lead is associated with elevated blood pressure, although the mechanism of action is unknown. Genetic differences in sodium-potassium adenosine triphosphatase (Na+-K+ATPase) could explain some of the variation in the strength of the blood pressure-blood lead relation that has been observed in previous studies. In 1996–1997, the authors studied the association of blood pressure, hypertension prevalence, and polymorphisms in the gene for the α2 subunit of Na+-K+ATPase (ATP1A2) among 220 former organolead manufacturing workers from New Jersey. Subjects were genotyped for a restriction fragment length polymorphism (RFLP) on the ATP1A2 gene. The association between blood lead and blood pressure was stronger among persons who were homozygous for the variant allele. Genotype was also associated with hypertension (adjusted odds ratio = 7.7; 95% confidence interval: 1.9, 31.4). Finally, the variant allele was 1.8 times more common among African Americans than among Caucasians. The RFLP may indicate susceptibility to the effect of lead on blood pressure. Moreover, the α2 gene (or a closely linked gene) may contribute to the pathophysiology of hypertension. However, because the number of subjects (especially African Americans) with the susceptible genotype in this study was small, these observations should be considered preliminary.
Life-Course Predictors of Ultrasonic Heel Measurement in a Cross-sectional Study of Immigrant Women from Southeast Asia
Authors: Lauderdale Diane S. , Salant Talya , Han Katherine L. , Tran Phuong L.
Published: July 2002

Few studies address chronic disease risk for Southeast Asians in the United States. In 1999, the authors conducted a cross-sectional study of bone mineral density (BMD) estimated from ultrasonic calcaneal measurements in women born in Southeast Asia who then lived in Chicago, Illinois. The study addressed three questions: Do Southeast-Asian women have relatively low BMD? What factors before and after immigration are associated with BMD? Are factors that reflect the childhood/adolescent environment equally associated with BMD for postmenopausal and premenopausal women? An interviewer-administered bilingual questionnaire collected immigration, reproductive, and lifestyle data from 213 women (aged 20–80 years) born in Vietnam, Cambodia, or Laos. The authors found that the estimated mean BMD of postmenopausal Southeast-Asian women was lower than the reference values for White women. Four summary indicators of childhood/adolescent environment were predictive of higher BMD: more years of education, earlier age at menarche, lower height, and coastal birth; these indicators were more strongly associated with BMD for premenopausal (multiple-partial R  2 = 0.21) than postmenopausal (R  2 = 0.06) women. Young-adult exposures (e.g., early first pregnancy and age at immigration) and proximal lifestyle factors (e.g., smoking, physical inactivity, vegetarian diet, and betel nut use) were also assessed as potential predictors of BMD.
Cross-sectional and Prospective Study of Exercise and Depressed Mood in the Elderly
Authors: Kritz-Silverstein Donna , Barrett-Connor Elizabeth , Corbeau Catherine
Published: July 2002

This study examined cross-sectional and prospective associations of exercise with depressed mood in a community-based sample of older men and women (aged 50–89 years in 1984–1987) in southern California. Regular strenuous exercise and exercise ≥3 times per week were reported; depressed mood was assessed by using the Beck Depression Inventory (BDI). After exclusion of persons with categorical depression and those rating themselves largely or extremely physically limited during the previous month, data on 932 men and 1,097 women were available for cross-sectional analysis. Exercise and depressed mood were reassessed for 404 men and 540 women in 1992–1995; these data were the focus of prospective analyses. In 1984–1987, exercise rates were high (>80%), and average BDI scores were low. Cross-sectional analyses indicated that before and after adjustment for covariates, exercise was significantly associated with less depressed mood. However, prospective analyses of the 944 persons who attended both clinic visits indicated no association between baseline exercise and either follow-up BDI score (p > 0.10) or change in BDI score between baseline and follow-up (p > 0.10). Results confirm that exercisers have less depressed mood. However, exercise does not protect against future depressed mood for those not clinically depressed at baseline.
Lung Cancer among Industrial Sand Workers Exposed to Crystalline Silica
Authors: Steenland Kyle , Sanderson Wayne
Published: July 2002

In 1997, the International Agency for Research on Cancer determined that crystalline silica was a human carcinogen but noted inconsistencies in the epidemiology. There are few exposure-response analyses. The authors examined lung cancer mortality among 4,626 industrial sand workers, estimating exposure via a job-exposure matrix based on 4,269 industrial hygiene samples collected in 1974–1995. The average length of employment was 9 years, and estimated average exposure was 0.05 mg/m3 (the National Institute of Occupational Safety and Health Recommended Exposure Limit). Results confirmed excess mortality from silicosis/pneumoconioses (standardized mortality ratio = 18.2, 95% confidence interval: 10.6, 29.1; 17 deaths). The lung cancer standardized mortality ratio was 1.60 (95% confidence interval: 1.31, 1.93; 109 deaths). Limited data suggested that smoking might account for 10–20% of the lung cancer excess. Exposure-response analyses by quartile of cumulative exposure (15-year lag) yielded standardized rate ratios of 1.00, 0.78, 1.51, and 1.57 (p for trend = 0.07). Nested case-control analyses after exclusion of short-term workers, who had high overall morality, yielded odds ratios by quartile of cumulative exposure (15-year lag) of 1.00, 1.35, 1.63, and 2.00 (p for trend = 0.08) and odds ratios by quartile of average exposure of 1.00, 0.92, 1.44, and 2.26 (p = 0.005). These data lend support to the labeling by the International Agency for Research on Cancer of silica as a human carcinogen. There are approximately 2 million US workers exposed to silica; 100,000 are exposed to more than 0.1 mg/m3.
Removing near-neighbour redundancy from large protein sequence collections.
Authors: Holm L , Sander C
Published: July 2002

MOTIVATION: To maximize the chances of biological discovery, homology searching must use an up-to-date collection of sequences. However, the available sequence databases are growing rapidly and are partially redundant in content. This leads to increasing strain on CPU resources and decreasing density of first-hand annotation. RESULTS: These problems are addressed by clustering closely similar sequences to yield a covering of sequence space by a representative subset of sequences. No pair of sequences in the representative set has >90% mutual sequence identity. The representative set is derived by an exhaustive search for close similarities in the sequence database in which the need for explicit sequence alignment is significantly reduced by applying deca- and pentapeptide composition filters. The algorithm was applied to the union of the Swissprot, Swissnew, Trembl, Tremblnew, Genbank, PIR, Wormpep and PDB databases. The all-against-all comparison required to generate a representative set at 90% sequence identity was accomplished in 2 days CPU time, and the removal of fragments and close similarities yielded a size reduction of 46%, from 260 000 unique sequences to 140 000 representative sequences. The practical implications are (i) faster homology searches using, for example, Fasta or Blast, and (ii) unified annotation for all sequences clustered around a representative. As tens of thousands of sequence searches are performed daily world-wide, appropriate use of the non-redundant database can lead to major savings in computer resources, without loss of efficacy. AVAILABILITY: A regularly updated non-redundant protein sequence database (nrdb90), a server for homology searches against nrdb90, and a Perl script (nrdb90.pl) implementing the algorithm are available for academic use from http://www.embl-ebi.ac. uk/holm/nrdb90. CONTACT: holm@embl-ebi.ac.uk
Uniform integration of genome mapping data using intersection
graphs
Authors: Harley Eric , Bonner Anthony , Goodman Nathan
Published: July 2002

Motivation: The methods for analyzing overlap data are distinct from those for analyzing probe data, making integration of the two forms awkward. Conversion of overlap data to probe-like data elements would facilitate comparison and uniform integration of overlap data and probe data using software developed for analysis of STS data.

Results: We show that overlap data can be effectively converted to probe-like data elements by extracting maximal sets of mutually overlapping clones. We call these sets virtual probes , since each set determines a site in the genome corresponding to the region which is common among the clones of the set. Finding the virtual probes is equivalent to finding the maximal cliques of a graph. We modify a known maximal-clique algorithm such that it finds all virtual probes in a large dataset within minutes. We illustrate the algorithm by converting fingerprint and Alu-PCR overlap data to virtual probes. The virtual probes are then analyzed using double-linkage intersection graphs and structure graphs to show that methods designed for STS data are also applicable to overlap data represented as virtual probes. Next we show that virtual probes can produce a uniform integration of different kinds of mapping data, in particular STS probe data and fingerprint and Alu-PCR overlap data. The integrated virtual probes produce longer double-linkage contigs than STS probes alone, and in conjunction with structure graphs they facilitate the identification and elimination of anomalies. Thus, the virtual-probe technique provides: (i) a new way to examine overlap data; (ii) a basis on which to compare overlap data and probe data using the same systems and standards; and (iii) a unique and useful way to uniformly integrate overlap data with probe data.

Availability: Freely available on request.

Contact: eharley@cs.toronto.edu
CAN P.S. 27 TURN A PROFIT? PROVISION OF PUBLIC EDUCATION BY FOR‐PROFIT SUPPLIERS
Authors: Lamdin Douglas J.
Published: July 2002

School districts in the United States have begun to use for‐profit contractors to provide management and instructional services. Studies of this phenomenon are limited because this alternative to public provision is relatively new. This article begins to fill the void by examining the conditions under which contractors can be financially viable and can improve quality. Also considered is the potential role of contractors in other policies to restructure public education.
Payoff Effects in Information Cascade Experiments
Authors: Anderson Lisa R.
Published: July 2002

Error rates are estimated using data from “information cascade” experiments. The econometric estimation assumes a logistic error structure and error rates are compared across three experimental treatments that differ only with respect to payoff structure. In a “no payoff” treatment subjects receive a fixed payment for participating in the experiment and earnings do not vary with decisions. In “payoff” and “double payoff” treatments earnings depend on each subject's decisions. The results indicate that rewarding correct decisions reduces the amount of decision error. However, increasing the payment for a correct decision does not reduce errors over the range of payoffs considered.