bluuebunny/crossref_metadata_2025 huggingface dataset:
Infection Stage-Dependent Modulation of Macrophage Activation inTrypanosoma congolense-Resistant and -Susceptible Mice
Authors: Noël Wim , Hassanzadeh Gholamreza , Raes Geert , Namangala Boniface , Daems Inge , Brys Lea , Brombacher Frank , Baetselier Patrick De , Beschin Alain
Published: October 2002

The contribution of cytokines and chemokines to resistance and susceptibility to African trypanosomiasis remains controversial. In the present study, the levels of type I and type II cytokines and of the MCP-1 chemokine were compared during the early and late stages ofTrypanosoma congolenseinfection in susceptible BALB/c and resistant C57BL/6 mice. Moreover, the status of macrophage activation was compared in these animals by analyzing the inducible nitric oxide synthase-arginase balance, tumor necrosis factor secretion, and expression of the FIZZ1 and YM genes. Data show that changing from a predominant type I cytokine environment in the early stage of infection to a predominant type II cytokine environment and an enhanced MCP-1 secretion in the late stage of infection correlates with resistance toT. congolense. Concomitantly, macrophage activation evolves from a classical to a predominant alternative phenotype. We further confirmed that the simultaneous occurrence of type I/type II cytokines in the early stage of infection in susceptible BALB/c mice, reflected by the presence of macrophages exhibiting a mixed classical/alternative activation phenotype, is associated with uncontrolled parasite growth and early death. Interleukin-4 (IL-4) and IL-13 signaling did not influence the susceptibility of BALB/c mice toT. congolenseinfection and interestingly were not the main trigger to alternative macrophage activation. InT. congolense-resistant C57BL/6 mice, our results corroborated the induction of FIZZ1 and YM gene expressions with the alternative pathway of macrophage activation. In susceptible BALB/c mice, however, YM but not FIZZ1 induction reflected the emergence of alternatively activated macrophages. Hence, the FIZZ1 and YM genes may be useful markers to discriminate between distinct populations of alternatively activated macrophages.
Interleukin-10 (IL-10) in Experimental Visceral Leishmaniasis and IL-10 Receptor Blockade as Immunotherapy
Authors: Murray Henry W. , Lu Christina M. , Mauze Smita , Freeman Sherry , Moreira Andre L. , Kaplan Gilla , Coffman Robert L.
Published: October 2002

Interleukin-10 (IL-10) is thought to promote intracellular infection, including human visceral leishmaniasis, by disabling Th1 cell-type responses and/or deactivating parasitized tissue macrophages. To develop a rationale for IL-10 inhibition as treatment in visceral infection, Th1 cytokine-driven responses were characterized inLeishmania donovani-infected BALB/c mice in which IL-10 was absent or overexpressed or its receptor (IL-10R) was blockaded. IL-10 knockout and normal mice treated prophylactically with anti-IL-10R demonstrated accelerated granuloma assembly and rapid parasite killing without untoward tissue inflammation; IL-12 and gamma interferon mRNA expression, inducible nitric oxide synthase reactivity, and responsiveness to antimony chemotherapy were also enhanced in knockout mice. In IL-10 transgenic mice, parasite replication was unrestrained, and except for antimony responsiveness, measured Th1 cell-dependent events were all initially impaired. Despite subsequent granuloma assembly, high-level infection persisted, and antimony-treated transgenic mice also relapsed. In normal mice with established infection, anti-IL-10R treatment was remarkably active, inducing near-cure by itself and synergism with antimony. IL-10's deactivating effects regulate outcome in experimental visceral leishmaniasis, and IL-10R blockade represents a potential immuno- and/or immunochemotherapeutic approach in this infection.
In Situ Detection of
Mycobacterium tuberculosis
Transcripts in Human Lung Granulomas Reveals Differential Gene Expression in Necrotic Lesions
Authors: Fenhalls Gael , Stevens Liesel , Moses Lorraine , Bezuidenhout Juanita , Betts Joanna C. , Helden Paul van , Lukey Pauline T. , Duncan Ken
Published: October 2002

We have used RNA-RNA in situ hybridization to detect the expression of several
Mycobacterium tuberculosis
genes in tuberculous granulomas in lung tissue sections from tuberculosis patients. The
M. tuberculosis
genes chosen fall into two classes. Four genes (
icl
,
narX
, and Rv2557 and Rv2558) have been implicated in the persistence of the bacterium in the host, and two genes (
iniB
and
kasA
) are upregulated in response to isoniazid exposure. Both necrotic and nonnecrotic granulomas were identified in all of the patients. Necrotic granulomas were divided into three zones: an outer lymphocyte cuff containing lymphocytes and macrophages, a transition zone consisting of necrotic material interspersed with macrophages, and a central acellular necrotic region. Transcripts of all of the genes studied were found in nonnecrotic granulomas and in the lymphocyte cuff of necrotic granulomas. Mycobacterial gene expression was associated with CD68-positive myeloid cells. Rv2557 and/or its homologue Rv2558,
kasA
, and
iniB
were expressed within the transition zone of necrotic granulomas, whereas
icl
and
narX
transcripts were absent from this area. There was no evidence of transcription of any of the genes examined in the central necrotic region, although mycobacterial DNA was present. The differential expression of genes within granulomas demonstrates that
M. tuberculosis
exists in a variety of metabolic states and may be indicative of the response to different microenvironments. These observations confirm that genes identified in models of persistence or in response to drug treatment in vitro are expressed in the human host.
Modulation of Cytosolic Ca
2+
Concentration in Airway Epithelial Cells by
Pseudomonas aeruginosa
Authors: Jacob Tobias , Lee Rebecca J. , Engel Joanne N. , Machen Terry E.
Published: October 2002

Modulation of cytosolic (intracellular) Ca
2+
concentration (Ca
i
) may be an important host response when airway epithelial cells are exposed to
Pseudomonas aeruginosa
. We measured Ca
i
in Calu-3 cells exposed from the apical or basolateral surface to cytotoxic and noncytotoxic strains of
P. aeruginosa
. Apical addition of either noncytotoxic strains or cytotoxic strains failed to affect Ca
i
over a 3-h time period, nor were changes observed after basolateral addition of noncytotoxic strains. In contrast, basolateral addition of cytotoxic strains caused a slow increase in Ca
i
from 100 nM to 200 to 400 nM. This increase began after 20 to 50 min and persisted for an additional 30 to 75 min, at which time the cells became nonviable.
P. aeruginosa
-induced increases in Ca
i
were blocked by the addition of the Ca channel blocker La
3+
to the basolateral but not to the apical chamber. Likewise, replacing the basolateral but not the apical medium with Ca-free solution prevented
P. aeruginosa
-mediated changes in Ca
i
. With isogenic mutants of PA103, we demonstrated that the type III secretion apparatus, the type III-secreted effector ExoU, and type IV pili were necessary for increased Ca
i
. We propose that translocation of ExoU through the basolateral surface of polarized airway epithelial cells via the type III secretion apparatus leads to release of Ca stored in the endoplasmic reticulum and activation of Ca channels in the basolateral membranes of epithelial cells.
Immunization with C5a Peptidase or Peptidase-Type III Polysaccharide Conjugate Vaccines Enhances Clearance of Group B Streptococci from Lungs of Infected Mice
Authors: Cheng Qi , Debol Steven , Lam Hong , Eby Ron , Edwards Lorri , Matsuka Yury , Olmsted Stephen B. , Cleary P. Patrick
Published: October 2002

Group B streptococci (GBS) are among the most common causes of life-threatening neonatal infections. Vaccine development since the late 1970s has focused on the capsular polysaccharides, but a safe, effective product is still not available. Our quest for a vaccine turned to the streptococcal C5a peptidase (SCPB). This surface protein is antigenically conserved across most if not all serotypes. A murine model was used to assess the impact of SCPB on clearance of GBS from the lungs of intranasally infected animals. Mutational inactivation of SCPB resulted in more-rapid clearance of streptococci from the lung. Immunization with recombinant SCPB alone or SCPB conjugated to type III capsular polysaccharide produced serotype-independent protection, which was evidenced by more-rapid clearance of the serotype VI strain from the lungs. Immunization of mice with tetanus toxoid-type III polysaccharide conjugate did not produce protection, confirming that protection induced by SCPB conjugates was independent of type III polysaccharide antigen. Histological evaluation of lungs from infected mice revealed that pathology in animals immunized with SCPB or SCPB conjugates was significantly less than that in animals immunized with a tetanus toxoid-polysaccharide conjugate. These experiments suggest that inclusion of C5a peptidase in a vaccine will both add another level to and broaden the spectrum of the protection of a polysaccharide vaccine.
Babesia bovisMerozoite Surface Antigen 2 Proteins Are Expressed on the Merozoite and Sporozoite Surface, and Specific Antibodies Inhibit Attachment and Invasion of Erythrocytes
Authors: Mosqueda Juan , McElwain Terry F. , Palmer Guy H.
Published: October 2002

TheBabesia bovismerozoite surface antigen 2 (MSA-2) locus encodes four proteins, MSA-2a1, -2a2, -2b, and -2c. With the use of specific antibodies, each MSA-2 protein was shown to be expressed on the surface of live extracellular merozoites and coexpression on single merozoites was confirmed. Individual antisera against MSA-2a, MSA-2b, and MSA-2c significantly inhibited merozoite invasion of bovine erythrocytes. As tick-derived sporozoites also directly invade erythrocytes, expression of each MSA-2 protein on the sporozoite surface was examined and verified. Finally, statistically significant inhibition of sporozoite binding to the erythrocytes was demonstrated by using antisera specific for MSA-2a, MSA-2b, and MSA-2c. These results indicate an important role for MSA-2 proteins in the initial binding and invasion of host erythrocytes and support the hypothesis that sporozoites and merozoites use common surface molecules in erythrocyte invasion.
The N-Terminal Domain of RTX Toxin ApxI of
Actinobacillus pleuropneumoniae
Elicits Protective Immunity in Mice
Authors: Seah J. N. , Frey J. , Kwang J.
Published: October 2002

We expressed three
Actinobacillus pleuropneumoniae
ApxI deletion derivatives to map the domain that could induce protective immunity. Antiserum to ApxI N-terminal covered by residues 40 to 380 was found to neutralize ApxI hemolytic activity but not ApxIII cytotoxicity. When used as a subunit vaccine in mice, this recombinant N-terminal fragment elicited protection against lethal infection with heterologous
A. pleuropneumoniae
serovars.
Role of Type 1 Fimbria- and P Fimbria-Specific Adherence in Colonization of the Neurogenic Human Bladder by
Escherichia coli
Authors: Hull Richard A. , Donovan William H. , Del Terzo Michael , Stewart Colleen , Rogers Margaret , Darouiche Rabih O.
Published: October 2002

Recent clinical studies suggest that the deliberate colonization of the human bladder with a prototypic asymptomatic bacteriuria-associated bacterium,
Escherichia coli
83972, may reduce the frequency of urinary tract infection in individuals with spinal cord injuries. However, the mechanism by which
E. coli
83972 colonizes the bladder is unknown. We examined the role in bladder colonization of the
E. coli
83972 genes
papG
and
fimH
, which respectively encode P and type 1 receptor-specific fimbrial adhesins.
E. coli
83972 and isogenic
papG
Δ and
papG
Δ
fimH
Δ mutants of
E. coli
83972 were compared for their capacities to colonize the neurogenic human bladder. Both strains were capable of stable colonization of the bladder. The results indicated that type 1 class-specific adherence and P class-specific adherence, while implicated as significant colonization factors in experiments that employed various animal model systems, were not required for colonization of the neurogenic bladder in human beings. The implications of these results with regard to the selection of potential vaccine antigens for the prevention of urinary tract infection are discussed.
PHENOMENOLOGICAL MODELING OF PHOTOEMISSION SPECTRA IN STRONGLY CORRELATED ELECTRON SYSTEMS
Authors: BYCZUK KRZYSZTOF , BULLA RALF , CLAESSEN RALPH , VOLLHARDT DIETER
Published: October 2002

A phenomenological approach is presented that allows one to model, and thereby interpret photoemission spectra of strongly correlated electron systems. A simple analytical formula for the self-energy is proposed. This self-energy describes both the coherent and incoherent parts of the spectrum (quasiparticle and Hubbard peaks, respectively). Free parameters in the expression are determined by fitting the density of states to experimental photoemission data. An explicit fitting is presented for the La 1-x Sr x TiO 3 system with 0.08 ≤ x ≤ 0.38. In general, our phenomenological approach provides information on the effective mass, the Hubbard interaction, and the spectral weight distribution in different parts of the spectrum. Limitations of this approach are also discussed.
KONDO IMPURITY MODEL FOR ANOMALOUS RESISTIVITY OF IMPURE Zr-Cu SUPERCONDUCTOR
Authors: MONDAL A. K. , ROY S. K.
Published: October 2002

Resistivity expressions are derived for disordered Zr 50- Cu 50 alloy considering the Kondo impurity model with extended BCS term to check the anomaly appearing above superconducting transition temperature as observed. The resistivity behaviors are discussed below and above the Kondo temperature and compared with the anomalies reported experimentally. Very good agreement between theoretical and experimental, natures of the resistivity curves are reported with a change in density of states (DOS) at the Fermi surface.
A NOVEL MODEL OF DIELECTRIC CONSTANT OF TWO-PHASE COMPOSITES WITH INTERFACIAL SHELLS
Authors: XUE QINGZHONG
Published: October 2002

Considering the interface effect between two phases in composite, we present a novel model of dielectric constant of two-phase composites with interfacial shells. Starting from Maxwell theory and average polarization theory, the formula of calculating the effective dielectric constant of two-phase random composites with interfacial shells is presented. The theoretical results on effective dielectric constant of alkyd resin paint/Barium titanate random composites with interfacial shells are in good agreement with the experimental data.
YAMABE TYPE EQUATIONS ON THREE DIMENSIONAL RIEMANNIAN MANIFOLDS
Authors: LI YANYAN , ZHU MEIJUN
Published: October 2002

A theorem of Escobar and Schoen asserts that on a positive three dimensional smooth compact Riemannian manifold which is not conformally equivalent to the standard three dimensional sphere, a necessary and sufficient condition for a C2 function K to be the scalar curvature function of some conformal metric is that K is positive somewhere. We show that for any positive C2 function K, all such metrics stay in a compact set with respect to C3 norms and the total Leray-Schauder degree of all solutions is equal to -1. Such existence and compactness results no longer hold in such generality in higher dimensions or on manifolds conformally equivalent to standard three dimensional spheres. The results are also established for more general Yamabe type equations on three dimensional manifolds.
A KNOTTED MINIMAL TREE
Authors: KUPERBERG KRYSTYNA
Published: October 2002

There is a finite set of points on the boundary of the three-dimensional unit ball whose minimal tree is knotted. This example answers a problem posed by Michael Freedman.
LOCAL MINIMIZERS FOR THE GINZBURG–LANDAU ENERGY NEAR CRITICAL MAGNETIC FIELD: PART II
Authors: SERFATY SYLVIA
Published: October 2002

As in Part I, we study local minimizers of the Ginzburg–Landau energy (depending on κ → +∞) for superconductors in a prescribed magnetic field hex.

For disc domains, we find and describe stable solutions of the associated equations and show how vortices appear as hex is raised from the first critical field Hc1.

We also study the asymptotic limit κ→∞ for hex=Hc1 and prove that the limiting magnetic field in the superconductor satisfies the London equation.
THE OSCILLATION PATTERN OF SOLUTIONS TO PARABOLIC EQUATIONS AS TIME GOES TO INFINITY
Authors: COMTE MYRIAM , HARAUX ALAIN
Published: October 2002

We consider the semilinear parabolic equation [Formula: see text] where Ω be a bounded, connected open subset of ℝN with a Lipschitz continuous boundary and f is a locally Lipschitz continuous function: ℝ→ℝ. If u is a bounded solution de (1.1) for which the ω-limit set satisfies [Formula: see text] the number of connected components of {x∈Ω; φ(x)≠=0}) is equal to a constant n∞ on ω(u) and there exists T>0 such that for all t≥T, the set {x∈Ω; u(t,x)≠0} has a finite number of connected components precisely equal to n∞.
Combined Use of Computed Tomography Coronary Calcium Scores and C-Reactive Protein Levels in Predicting Cardiovascular Events in Nondiabetic Individuals
Authors: Park Robert , Detrano Robert , Xiang Min , Fu Paul , Ibrahim Youhanna , LaBree Laurie , Azen Stanley
Published: October 2002

Background—

The South Bay Heart Watch is a prospective cohort study designed to appraise the value of coronary calcium and risk factors for predicting outcomes in asymptomatic adults. Two factors that may be related to subsequent cardiovascular events are coronary calcium (CAC, a manifestation of subclinical atherosclerosis) and high-sensitivity C-reactive protein (CRP, a measure of chronic inflammation).

Methods and Results—

Between December 1990 and December 1992, 1461 participants without coronary heart disease underwent baseline risk factor screening, computed tomography for CAC, and measurement of CRP. Participants were followed up for 6.4±1.3 years. Cox regression analyses were conducted for the 967 nondiabetics with CRP levels ≤10 mg/L to estimate the risk-factor–adjusted relative risks of CAC and CRP for the occurrence of (1) nonfatal myocardial infarction (MI) or coronary death and (2) any cardiovascular event (MI, coronary death, coronary revascularization, or stroke). CAC was a predictor of both end points (
P
<0.005), and CRP was a predictor of any cardiovascular event (
P
=0.03). Risk group analysis defined by tertiles for CAC (<3.7, 3.7 to 142.1, >142.1) and the 75th percentile for CRP (>4.05 mg/L) indicated that there was increasing risk with increasing calcium and CRP. Relative risks for the medium-calcium/low-CRP risk group to high-calcium/high-CRP risk group ranged from 1.8 to 6.1 for MI/coronary death (
P
=0.003) and 2.8 to 7.5 for any cardiovascular event (
P
<0.001).

Conclusions—

Participants without diabetes and those at intermediate risk may benefit from risk stratification based on high-sensitivity CRP levels and CAC, because both factors contribute independently toward the incidence of cardiovascular events.
Simvastatin Inhibits Inflammatory Properties of
Staphylococcus aureus
α-Toxin
Authors: Pruefer Diethard , Makowski Joachim , Schnell Martin , Buerke Ute , Dahm Manfred , Oelert Hellmut , Sibelius Ulf , Grandel Ulrich , Grimminger Friedrich , Seeger Werner , Meyer Jürgen , Darius Harald , Buerke Michael
Published: October 2002

Background—

Simvastatin, a 3-hydroxy-methylglutaryl coenzyme A reductase inhibitor, has been shown to lower serum cholesterol levels in clinical use. Moreover, statins exert beneficial effects in vascular diseases by inhibition of leukocyte rolling, adherence, and transmigration. The aim of this study was to determine if pretreatment with simvastatin attenuates
Staphylococcus aureus
α-toxin–induced increase in leukocyte-endothelial interactions during exotoxemia.

Methods and Results—

The effects of simvastatin on leukocyte-endothelial cell interactions were observed by intravital microscopy in the rat mesenteric microcirculation. Simvastatin (50 or 100 μg/kg) was administered 18 hours before the study. Activation of microcirculation was induced by bolus administration of 40 μg/kg
S aureus
α-toxin. Exotoxemia resulted in a significant and time-dependent increase in leukocyte rolling, adherence, and transmigration of leukocytes as well as P-selectin expression on the intestinal vascular endothelium. Pretreatment with simvastatin significantly inhibited exotoxin-induced leukocyte rolling from 71±10 to 14±4.7 cells/min (
P
<0.01) and adherence from 14±3.5 to 0.4±0.2 cells (
P
<0.01). In addition, simvastatin pretreatment significantly inhibited transmigration of leukocytes from 10.5±1.2 to 4.2±0.9 (
P
<0.05) cells. Immunohistochemical detection of endothelial cell adhesion molecule P-selectin showed a 50% decrease in endothelial cell surface expression after simvastatin treatment. Furthermore, simvastatin treatment resulted in enhanced expression of endothelial cell NO synthase III in the intestinal microcirculation.

Conclusions—

These results demonstrate that simvastatin interferes with exotoxin-induced leukocyte-endothelial cell interactions, which may be relevant in various infectious diseases. Statin treatment may offer a new therapeutic strategy for these clinical conditions.
ARBITER: Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol
Authors: Taylor Allen J. , Kent Steven M. , Flaherty Patrick J. , Coyle Louis C. , Markwood Thor T. , Vernalis Marina N.
Published: October 2002

Background—

Whether marked LDL reduction to levels well below 100 mg/dL would further reduce the burden of cardiovascular disease is controversial. We compared the effects of 2 statins with widely differing potencies for LDL reduction (pravastatin 40 mg/d and atorvastatin 80 mg/d) on carotid intima-media thickness (CIMT).

Methods and Results—

This was a single-center, randomized, clinical trial of 161 patients (mean age, 60 years; 71.4% male; 46% with known cardiovascular disease) that met National Cholesterol Education Program (NCEP) II criteria for lipid-lowering therapy. The effects of atorvastatin (80 mg/d; n=79) and pravastatin (40 mg/d; n=82) on CIMT were compared using blinded, serial assessments of the far wall of the distal common carotid artery. Baseline CIMT and other characteristics were similar between study groups. As anticipated, atorvastatin was substantially more potent for LDL reduction after 12 months: in the atorvastatin group, LDL cholesterol was 76±23 mg/dL after 12 months (−48.5%); LDL cholesterol was 110±30 mg/dL in the pravastatin group (−27.2%;
P
<0.001). Atorvastatin induced progressive CIMT regression over 12 months (change in CIMT, −0.034±0.021 mm), whereas CIMT was stable in the pravastatin group (change of 0.025± 0.017 mm;
P
=0.03).

Conclusions—

Marked LDL reduction (<100 mg/dL) with a high-potency statin provides superior efficacy for atherosclerosis regression at 1 year. This early effect on CIMT, a surrogate for clinical benefit, suggests that marked LDL reduction with synthetic statins may provide enhanced reduction in clinical coronary event rates.
Inflammatory Cytokine Concentrations Are Acutely Increased by Hyperglycemia in Humans
Authors: Esposito Katherine , Nappo Francesco , Marfella Raffaele , Giugliano Giovanni , Giugliano Francesco , Ciotola Myriam , Quagliaro Lisa , Ceriello Antonio , Giugliano Dario
Published: October 2002

Background—

Circulating levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) are elevated in diabetic patients. We assessed the role of glucose in the regulation of circulating levels of IL-6, TNF-α, and interleukin-18 (IL-18) in subjects with normal or impaired glucose tolerance (IGT), as well as the effect of the antioxidant glutathione.

Methods and Results—

Plasma glucose levels were acutely raised in 20 control and 15 IGT subjects and maintained at 15 mmol/L for 5 hours while endogenous insulin secretion was blocked with octreotide. In control subjects, plasma IL-6, TNF-α, and IL-18 levels rose (
P
<0.01) within 2 hours of the clamp and returned to basal values at 3 hours. In another study, the same subjects received 3 consecutive pulses of intravenous glucose (0.33 g/kg) separated by a 2-hour interval. Plasma cytokine levels obtained at 3, 4, and 5 hours were higher (
P
<0.05) than the corresponding values obtained during the clamp. The IGT subjects had fasting plasma IL-6 and TNF-α levels higher (
P
<0.05) than those of control subjects. The increase in plasma cytokine levels during the clamping lasted longer (4 hours versus 2 hours,
P
<0.01) in the IGT subjects than in the control subjects, and the cytokine peaks of IGT subjects after the first glucose pulse were higher (
P
<0.05) than those of control subjects. On another occasion, 10 control and 8 IGT subjects received the same glucose pulses as above during an infusion of glutathione; plasma cytokine levels did not show any significant change from baseline after the 3 glucose pulses.

Conclusions—

Hyperglycemia acutely increases circulating cytokine concentrations by an oxidative mechanism, and this effect is more pronounced in subjects with IGT. This suggests a causal role for hyperglycemia in the immune activation of diabetes.
Reliable Noninvasive Coronary Angiography With Fast Submillimeter Multislice Spiral Computed Tomography
Authors: Nieman Koen , Cademartiri Filippo , Lemos Pedro A. , Raaijmakers Rolf , Pattynama Peter M.T. , de Feyter Pim J.
Published: October 2002

Background—

Multislice spiral computed tomography (MSCT) is a promising technique for noninvasive coronary angiography, although clinical application has remained limited because of frequently incomplete interpretability, caused by motion artifacts and calcifications.

Methods and Results—

In 59 patients (53 male, aged 58±12 years) with suspected obstructive coronary artery disease, ECG-gated MSCT angiography was performed with a 16-slice MSCT scanner (0.42-s rotation time, 12×0.75-mm detector collimation). Thirty-four patients were given additional β-blockers (average heart rate: 56±6 min
−1
). After contrast injection, all data were acquired during an approximately 20-s breath hold. The left main (LM), left anterior descending (LAD), left circumflex (LCX), and right coronary artery (RCA), including ≥2.0-mm side branches, were independently evaluated by two blinded observers and screened for ≥50% stenoses. The consensus reading was compared with quantitative coronary angiography. MSCT was successful in 58 patients. Eighty-six of the 231 evaluated branches were significantly diseased. Without exclusion of branches, the sensitivity, specificity and positive and negative predictive value to identify ≥50% obstructed branches was 95% (82/86), 86% (125/145), 80% (82/102), and 97% (125/129), respectively. The overall accuracy for the LM, LAD, RCA, and LCX was 100%, 91%, 86%, and 81%, respectively. No obstructed LM, LAD, or RCA branches remained undetected. Classification of patients as having no, single, or multivessel disease was accurate in 78% (45/58) of patients and no patients with significant obstructions were incorrectly excluded.

Conclusions—

Improvements in MSCT technology, combined with heart rate control, allow reliable noninvasive detection of obstructive coronary artery disease.
QUEERING JEREMIAH
Authors: MacWilliam Stuart
Published: October 2002

Some criticism of queer theory has centred on its alleged ahistoricity in its treatment of historical texts and on its damage to the liberationist efforts of the identity-based feminist and lesbian and gay movements. This paper argues for queer theory's survival as both a valid academic methodological position, and an alternative liberationist approach to issues of gender and sexuality. Queer theory is then applied to the marriage metaphor in Jeremiah chs. 2–3. Recent feminist critiques of the prophetic use of the metaphor postulate a dichotomy between male and female readers' responses to the texts. In reply, this paper argues that there are serious breakdowns in gender divisions within what is a chaotic text; further, that the male reader implied in the text is forced to identify with not the faithful husband but the faithless wife; and finally that critics overlook the positive portrayal of the restored wife in the metaphor's 'third movement'. A queer reading does not wholly rehabilitate the text but suggests tentatively that the metaphor may be read as a subversion rather than a re-inscription of masculinist values.
Role of 4-1BB (CD137) in the functional activation of cord blood CD28−CD8+ T cells
Authors: Kim Young-June , Brutkiewicz Randy R. , Broxmeyer Hal E.
Published: October 2002

The CD28− subset of CD8+ T cells is associated with cytotoxic T lymphocyte (CTL) effector function. We investigated a potential role for 4-1BB, a costimulatory molecule structurally related to members of the tumor necrosis factor (TNF) receptor family, in the generation and functional activation of CD28− CTLs by using human cord blood (CB) cells composed exclusively of naive CD8+ T cells with few or no CD28− CTLs. The 4-1BB was induced preferentially on the CB CD28−CD8+ T cells when CD28 down-regulation was induced by interleukin 15 (IL-15) and IL-12 stimulation. Anti–4-1BB costimulation induced dramatic phenotypic changes in the CD28− CTLs, including restoration of CD28 expression as well as that of memory markers such as CD45RO and CC chemokine receptor 6 (CCR6). Anti–4-1BB costimulation also promoted long-term survival of CD28− CTLs, which were sensitive to activation-induced cell death upon anti-CD3 stimulation. The memory-type CD28+CTLs induced by anti–4-1BB costimulation acquired a greatly enhanced content of granzyme B, a cytolytic mediator, and enhanced cytotoxic activity as compared with CD28− CTLs. Strong cytotoxicity of memory-type CTLs to a 4-1BB ligand–expressing Epstein-Barr virus (EBV)–transformed B-cell line was almost completely abrogated by 4-1BB–Fc, a soluble form of 4-1BB, suggesting involvement of 4-1BB in cytolytic processes. Taken all together, our results suggest that 4-1BB plays a role in the differentiation of effector memory CTLs.
Crystalline-State Photoisomerization of α,β-Unsaturated Thioamide Analyzed by X-rays
Authors: Hosoya Takaaki , Ohhara Takashi , Uekusa Hidehiro , Ohashi Yuji
Published: October 2002

When a crystal of N,N-dibenzyl-1-cyclohexenecarbothioamide was exposed to UV light at 263 K, the cell dimensions were gradually changed with retention of the single crystal form. Since the crystal gradually decomposed after 330 h, the irradiation was stopped and the structure was analyzed by X-rays. The thioamide molecule was converted by 65.0% to the thiolactam molecule. The thioamide and thiolactam molecules were observed as a disordered structure in the crystal. The disordered structure clearly indicates that the hydrogen atom of one of the benzyl groups is extracted by one of the olefin carbon atoms of the cyclohexenyl group and that the benzyl carbon atom makes a bond with another olefin carbon to form a thiolactam ring. The mechanism of the ring formation and the chirality of the produced thiolactam are well explained from the reaction cavity.
Medialization of electrode array in cochlear implantation
Authors: Watts S. J. , Lindsey P. , Hawthorne M.
Published: October 2002

In the last few years, the main thrust of research into cochlear implantation has centred around the development of advanced multi-channel implants. A new area of development is now concentrating on maximizing the potential of each individual electrode in order to improve the quality of hearing. This study involved the medialization of the cochlear implant electrode array using a silastic positioner in five patients. Two parameters were measured, namely current units needed to produce a stapedial reflex, and impedance levels between the electrode and modiolus. On insertion of the cochlear implant, readings were taken before the insertion of the positioner, immediately afterwards and at two months.
Mediastinal tuberculosis in a 10-month-old child
Authors: Ahmed Aftab , Mirza Showkat , Rothera Michael P.
Published: October 2002

We report a rare case of mediastinal tuberculosis in a child who presented as a possible inhaled foreign body. A 10-month-old girl was admitted with a five-month history of cough, wheeze and problematic feeding, thought initially to be due to asthma. A clinical deterioration and subsequent X-rays suggested an inhaled foreign body. However, at direct laryngotracheobronchoscopy no foreign body was found and subsequent investigations revealed a subcarinal mediastinal mass. She underwent a thoracotomy and excision of the mass, the histological analysis of which revealed it to be of tuberculous origin. When a patient presents with symtoms of upper airway obstruction which are highly suggestive of a foreign body, other causes such as mediastinal tuberculosis must be borne in mind when no foreign body can be found. Although rare, cases of tuberculosis are apparently increasing and the otolaryngolgoist must be aware of its various manifestations and submit specimens for appropriate analysis. We also briefly review mediastinal lymphadenopathy due to tuberculosis.
Argon laser irradiation of the semicircular canal in two patients with benign paroxysmal positional vertigo
Authors: Nomura Yasuya
Published: October 2002

The results of long-term follow-up after surgical treatment of two patients with intractable benign paroxysmal positional vertigo are reported. Argon laser irradiation of the blue-lined posterior and lateral semicircular canals in one patient, and of only the posterior canal in the other was performed seven and six years ago, respectively. Argon laser irradiation was carried out 10 times in succession three mm along the canal to occlude it. The power applied each time was 1.5.W on the dial of the laser device for 0.5.sec. Relief of vertigo was noted on the second post-irradiation day. There has been no recurrence of vertigo in these patients.
Shape behavior of lipid vesicles as the basis of some cellular processes
Authors: Svetina Saša , Žekš Boštjan
Published: October 2002

The basic principles that govern the shape behavior of phospholipid vesicle shapes are discussed. The important membrane parameters of the system are defined by presenting the expressions for the relevant contributions to the system's mechanical energy. In the description of the rather unique shape behavior of lipid vesicles, the emphasis is on providing a qualitative understanding of the dependence of vesicle shape on the parameters of the system. The vesicle shape behavior is then related to biologically important phenomena. Some examples are given of how the results of the shape behavior of lipid vesicles can be applied to the analysis of cellular systems. Red blood cell shape and shape transformations, vesicle fission and fusion processes, and the phenomenon of cellular polarity are considered. It is reasoned that the current biological processes that involve changes of membrane conformation may have their origin in the general shape behavior of closed lamellar membranes. Anat Rec 268:215–225, 2002. © 2002 Wiley‐Liss, Inc.
Motility proteins and the origin of the nucleus
Authors: Dolan Michael F. , Melnitsky Hannah , Margulis Lynn , Kolnicki Robin
Published: October 2002

Hypotheses on the origin of eukaryotic cells must account for the origin of the microtubular cytoskeletal structures (including the mitotic spindle, undulipodium/cilium (so‐called flagellum) and other structures underlain by the 9(2)+2 microtubular axoneme) in addition to the membrane‐bounded nucleus. Whereas bacteria with membrane‐bounded nucleoids have been described, no precedent for mitotic, cytoskeletal, or axonemal microtubular structures are known in prokaryotes. Molecular phylogenetic analyses indicate that the cells of the earliest‐branching lineages of eukaryotes contain the karyomastigont cytoskeletal system. These protist cells divide via an extranuclear spindle and a persistent nuclear membrane. We suggest that this association between the centriole/kinetosome axoneme (undulipodium) and the nucleus existed from the earliest stage of eukaryotic cell evolution. We interpret the karyomastigont to be a legacy of the symbiosis between thermoacidophilic archaebacteria and motile eubacteria from which the first eukaryote evolved. Mutually inconsistent hypotheses for the origin of the nucleus are reviewed and sequenced proteins of cell motility are discussed because of their potential value in resolving this problem. A correlation of fossil evidence with modern cell and microbiological studies leads us to the karyomastigont theory of the origin of the nucleus. Anat Rec 268:290–301, 2002. © 2002 Wiley‐Liss, Inc.
Determinants of patient satisfaction in chronic illness
Authors: Bidaut‐Russell Michelle , Gabriel Sherine E. , Scott Christopher G. , Zinsmeister Alan R. , Luthra Harvinder S. , Yawn Barbara
Published: October 2002

Objective

To determine whether primary care provided by generalists versus subspecialists resulted in different levels of patient satisfaction among persons with chronic illness.

Methods

A survey containing the Primary Care Provider Questionnaire and the Health Status Questionnaire (HSQ) was mailed to 2 population‐based cohorts of patients with rheumatoid arthritis (RA) or diabetes mellitus (DM). All subjects were at least 35 years old and Rochester, Minnesota residents. Descriptive statistics, Spearman correlation coefficients, and multiple regression models were used to describe and compare the determinants of patient satisfaction.

Results

A total of 86 people (74% female) with RA and 208 people (56% male) with DM responded to the survey. Age range was 41–95 years and median disease duration was 8.7 years (RA) and 13.0 years (DM). Most patients described their health as fair or good. After adjusting for sex differences, RA patients were more likely than DM patients to report having a specialist as their primary care doctor. RA patients, whether reporting seeing a specialist or a generalist, had comparable HSQ physical health, mental health, social functioning, vitality, and bodily pain scores. DM patients seeing a specialist had more bodily pain and poorer physical functioning than those seeing a generalist. Across both chronic illnesses and physician specialties, median scores for patient satisfaction ranged from 17–18 for overall satisfaction (maximum 20); 30–33 for interpersonal skills (maximum 35); 23–26 for technical quality (maximum 30); and 20 for access to care (maximum 25). Multiple linear regression models revealed that 6.8–7.3% of the variation in satisfaction could be explained by HSQ scores, patient demographics, and physician specialty.

Conclusion

Both RA and DM patients were highly satisfied with their care, regardless of the specialty of the provider. Physician specialty, patient demographics, and HSQ scores explained only a small proportion in the variation in satisfaction. These findings point to the need for additional research to further elucidate the determinants of patient satisfaction.
Hydrophobicity and helicity of membrane‐interactive peptides containing peptoid residues
Authors: Tang Yan‐Chun , Deber Charles M.
Published: October 2002

Peptoid (N‐alkylglycyl) residues in peptides have been studied in a variety of applications, but their behavior in membrane environments has not been systematically investigated. We have synthesized a series of membrane‐interactive peptides of prototypic structure KKAAAXAAAAAXAAWAAXAAAKKKK‐amide, where X corresponds to the peptoid residues Nala (= sarcosine), Nval, Nile, Nleu, Nphe, and Ntrp. Investigation of their relative hydrophobic character by high‐performance liquid chromatography indicated an order of hydrophobicity Ntrp > Nphe > Nleu > Nile > Nval > Nala—largely parallel to the relative scale for these side‐chains in natural amino acids, although all values were significantly more “hydrophilic” than their amino acid correspondents. Conformations of peptoid‐containing peptides measured by circular dichroism spectroscopy were unordered in the presence of SDS micelles but helical for peptides with X = the corresponding amino acids, suggesting a general helix‐breaking tendency for the peptoid residues. However, peptides were able to form helical structures in the solvent n‐butanol, indicating that this conformation is possible if peptides became inserted into micellar phases. The latter notion was confirmed by increasing hydrophobic content of the peptides by embedding peptoid Nala residues in Leu‐rich rather than Ala‐rich sequences, which promoted peptide insertion and helical structure in micelles. The overall results suggest that judicious interspersing of amino acid and peptoid residues in peptide sequences can produce hydrophobic water‐soluble materials with membrane‐partitioning capacity. © 2002 Wiley Periodicals, Inc. Biopolymers 65: 254–262, 2002
Internal dynamics and ionization states of the macrophage migration inhibitory factor: Comparison between wild‐type and mutant forms
Authors: Soares T. A. , Lins R. D. , Straatsma T. P. , Briggs J. M.
Published: October 2002

The macrophage migration inhibitory factor (MIF) is a cytokine that shares a common structural architecture and catalytic strategy with three isomerases: 4‐oxalocrotonate tautomerase, 5‐carboxymethyl‐2‐hydroxymuconate isomerase, and D‐dopachrome tautomerase. A highly conserved N‐terminal proline acts as a base‐acid during the proton transfer reaction catalyzed by these enzymes. Such unusual catalytic strategy appears to be possible only due to the N‐terminal proline pKa shifted to 5.0–6.0 units. Mutations of this residue result in a significant decrease of the catalytic activity of MIF. Two hypotheses have been proposed to explain the catalytic inefficiency of MIF: the lower basicity of primary amines with regard to secondary ones and the increased flexibility resulting from the replacement of a proline by residues like glycine. To investigate that, we have performed molecular dynamics simulations of MIF wild‐type and its mutant P1G, as well as calculated the protonation properties of several mutant forms. It was found that the N‐terminal glycine does not show larger fluctuations compared to proline, but the former residue is more exposed to the solvent throughout the simulations. The apparent pKa of these residues displays very little change (as expected from the structural rigidity of MIF) and is not significantly affected by the surrounding ionizable residues. Instead, the hydrophobic character of the active site seems to be the main factor in determining the pKa of the N‐terminal residue and the catalytic efficiency of MIF. © 2002 Wiley Periodicals, Inc. Biopolymers 65: 313–323, 2002
Simple laboratory experiments to observe the manifestations of the sinc function
Authors: Traficante Daniel D. , McGregor Michael M.
Published: October 2002

In NMR spectroscopy, the sinc function manifests itself in a variety of ways, only two of which are discussed in this article. Specifically, the manifestation of this function is discussed in terms of the excitation pulse and in terms of the received signal in high‐resolution liquid‐state NMR. A mathematical theory has been published that predicts the relative intensities and phases of the RFs that excite the nuclei. However, another mathematical treatment is described here that is considerably easier to understand, but it applies only when the tip angle is small, e.g., less than approximately 10°. In addition, this theory is also used to predict the appearance of the sinc “wiggles” that appear when a Fourier transform is performed on a truncated free induction decay (FID) that has been zero‐filled. For the excitation pulse, the intensities of the frequencies delivered to the nuclei follow the classic (sin x)/x, or sinc function, when the tip angle is small. This is demonstrated by a simple experiment. The transmitter offset is stepped in a series of experiments, with each FID summed with all of the previously collected ones. When the series is completed, the FID is Fourier transformed. After correcting for instrumental effects, the resulting spectrum shows that the amplitudes of the excitation frequencies contained within the pulse follow the shape of a sinc function. To demonstrate the formation of sinc “wiggles,” the acquisition time for an FID is set so that it is very heavily truncated and then zero‐filled to eight times the original number of points. The Fourier transform shows that the “wiggles” cross the zero‐intensity line at intervals equal to half‐integer multiples of the reciprocal of the acquisition time, and not at integer multiples, as is often assumed. The difference is that the Fourier transform of a rectangular function of width τ is typically performed by integrating using the limits of −τ/2 to τ/2. In the real spectrum, this would produce zero‐crossing at an integer number of reciprocals of the width of the rectangle, i.e., 1/τ. In the laboratory, however, the limits of the collected signal are from 0 to τ. These limits produce crossings at intervals of 1/(2τ). © 2002 Wiley Periodicals, Inc. Concepts Magn Reson 14: 308–325, 2002
AMPA glutamate receptor subunits in the guinea pig hypothalamus: Distribution and colocalization with progesterone receptor
Authors: Warembourg Maryvonne , Leroy Daniele
Published: October 2002

Excitatory amino acids (EAAs), particularly glutamate, have been implicated in the control of luteinizing hormone (LH) secretion through facilitation of gonadotropin‐releasing hormone release. The effects of EAAs are mediated by means of ionotropic glutamate receptors, which are divided into N‐methyl‐D‐aspartate (NMDA) and non‐NMDA (kainate and AMPA) subtypes. Moreover, ovarian steroids are responsible for inducing the preovulatory surge of LH and are involved in the actions of EAAs on LH release. Progesterone is directly involved in the potentiating effect of ovarian steroids on the stimulating effect of AMPA neurotransmission on gonadotropin secretion. To broaden our understanding of the role of hypothalamic AMPA receptors in the steroid‐induced LH surge, we determined the cellular localization of AMPA receptors in the hypothalamus of guinea pigs by using antibodies that recognize the GluR1, GluR2, GluR2/3, or GluR4 subunits, and then we examined the neuroanatomic relationships between these receptors and the progesterone receptor (PR). Different patterns of immunostaining within the preoptic area and hypothalamus were evident with the antibodies to the four subunits with marked contrasts between moderate staining for GluR1, intensely stained structures for GluR2 and GluR2/3, and little specific staining for GluR4. Immunoreactive (IR) neurons were visualized in many regions, including the two regions known to contain a dense population of estradiol‐induced PR‐IR cells: the preoptic periventricular and ventrolateral hypothalamic nuclei. Approximately 60% of GluR1‐IR and 39% of GluR2‐IR cells in the preoptic region possessed PR, whereas 46% of GluR1‐IR and 54% of GluR2‐IR cells in the ventrolateral nucleus expressed PR. These neuroanatomic results suggest that the coordinated actions of progesterone and glutamatergic inputs on mammalian reproductive functions are integrated at the cellular level. J. Comp. Neurol. 453:305–321, 2002. © 2002 Wiley‐Liss, Inc.
The first synthesis of all possible isotopically labelled [D, 13C] methyl group combinations of 2,2‐dimethyl tetralone
Authors: Coumbarides Gregory S. , Eames Jason , Weerasooriya Neluka
Published: October 2002

A series of multi‐labelled [D, 13C] 2,2‐dimethyl tetralones were efficiently synthesized using a simple and diverse deprotonation–methylation strategy. All possible ten isotopic combinations were synthesized. The levels of [D, 13C] isotopic incorporation were quantitative and the synthetic yields were high. Copyright © 2002 John Wiley & Sons, Ltd.