bluuebunny/crossref_metadata_2025 huggingface dataset:
Adipocyte enhancer-binding protein 1 is a potential novel atherogenic factor involved in macrophage cholesterol homeostasis and inflammation
Authors: Majdalawieh Amin , Zhang Lei , Fuki Ilia V. , Rader Daniel J. , Ro Hyo-Sung
Published: February 2006

Peroxisome proliferator-activated receptor γ1 (PPARγ1) and liver X receptor α (LXRα) play pivotal roles in macrophage cholesterol homeostasis and inflammation, key biological processes in atherogenesis. Herein we identify adipocyte enhancer-binding protein 1 (AEBP1) as a transcriptional repressor that impedes macrophage cholesterol efflux, promoting foam cell formation, via PPARγ1 and LXRα down-regulation. Contrary to AEBP1 deficiency, AEBP1 overexpression in macrophages is accompanied by decreased expression of PPARγ1, LXRα, and their target genes ATP-binding cassette A1, ATP-binding cassette G1, apolipoprotein E, and CD36, with concomitant elevation in IL-6, TNF-α, monocyte chemoattractant protein 1, and inducible NO synthase levels. AEBP1, but not the C-terminally truncated DNA-binding domain mutant (AEBP1
ΔSty
), represses PPARγ1 and LXRα
in vitro
. Expectedly, AEBP1-overexpressing transgenic (AEBP1
TG
) macrophages accumulate considerable amounts of lipids compared with AEBP1 nontransgenic macrophages, making them precursors for foam cells. Indeed, AEBP1-overexpressing transgenic macrophages exhibit diminished cholesterol efflux compared with AEBP1 nontransgenic macrophages, whereas AEBP1-knockout (AEBP1
−/−
) macrophages exhibit enhanced cholesterol efflux compared with wild-type (AEBP1
+/+
) macrophages. Our
in vitro
and
ex vivo
experimental data strongly suggest that AEBP1 plays critical regulatory roles in macrophage cholesterol homeostasis, foam cell formation, and proinflammation. Thereby, we speculate that AEBP1 may be critically implicated in the development of atherosclerosis, and it may serve as a molecular target toward developing antiinflammatory, antiatherogenic therapeutic approaches.
Retinoic acid regulates sex-specific timing of meiotic initiation in mice
Authors: Koubova Jana , Menke Douglas B. , Zhou Qing , Capel Blanche , Griswold Michael D. , Page David C.
Published: February 2006

In mammals, meiosis is initiated at different time points in males and females, but the mechanism underlying this difference is unknown. Female germ cells begin meiosis during embryogenesis. In males, embryonic germ cells undergo G0/G1mitotic cell cycle arrest, and meiosis begins after birth. In mice, theStimulated by Retinoic Acid Gene 8(Stra8) has been found to be required for the transition into meiosis in both female and male germ cells.Stra8is expressed in embryonic ovaries just before meiotic initiation, whereas its expression in testes is first detected after birth. Here we examine the mechanism underlying the sex-specific timing ofStra8expression and meiotic initiation in mice. Our work shows that signaling by retinoic acid (RA), an active derivative of vitamin A, is required forStra8expression and thereby meiotic initiation in embryonic ovaries. We also discovered that RA is sufficient to induceStra8expression in embryonic testes and in vitamin A-deficient adult testesin vivo. Finally, our results show that cytochrome p450 (CYP)-mediated RA metabolism prevents prematureStra8expression in embryonic testes. Treatment with an inhibitor specific to RA-metabolizing enzymes indicates that a cytochrome p450 from the 26 family (CYP26) is responsible for delayingStra8expression in embryonic testes. Sex-specific regulation of RA signaling thus plays an essential role in meiotic initiation in embryonic ovaries and precludes its occurrence in embryonic testes. Because RA signaling regulatesStra8expression in both embryonic ovaries and adult testes, this portion of the meiotic initiation pathway may be identical in both sexes.
Peroxisome proliferator-activated receptor δ promotes very low-density lipoprotein-derived fatty acid catabolism in the macrophage
Authors: Lee Chih-Hao , Kang Kihwa , Mehl Isaac R. , Nofsinger Russell , Alaynick William A. , Chong Ling-Wa , Rosenfeld John M. , Evans Ronald M.
Published: February 2006

Significant attention has focused on the role of low-density lipoprotein (LDL) in the pathogenesis of atherosclerosis. However, recent advances have identified triglyceride-rich lipoproteins [e.g., very LDL (VLDL)] as independent risk predictors for this disease. We have previously demonstrated peroxisome proliferator-activated receptor (PPAR)δ, but not PPARγ, is the major nuclear VLDL sensor in the macrophage, which is a crucial component of the atherosclerotic lesion. Here, we show that, in addition to β-oxidation and energy dissipation, activation of PPARδ by VLDL particles induces key genes involved in carnitine biosynthesis and lipid mobilization mediated by a recently identified TG lipase, transport secretion protein 2 (also named desnutrin, iPLA2ζ, and adipose triglyceride lipase), resulting in increased fatty acid catabolism. Unexpectedly, deletion of PPARδ results in derepression of target gene expression, a phenotype similar to that of ligand activation, suggesting that unliganded PPARδ suppresses fatty acid utilization through active repression, which is reversed upon ligand binding. This unique transcriptional mechanism assures a tight control of the homeostasis of VLDL-derived fatty acid and provides a therapeutic target for other lipid-related disorders, including dyslipidemia and diabetes, in addition to coronary artery disease.
Controlling the shape, orientation, and linkage of carbon nanotube features with nano affinity templates
Authors: Wang Yuhuang , Maspoch Daniel , Zou Shengli , Schatz George C. , Smalley Richard E. , Mirkin Chad A.
Published: February 2006

Directed assembly of nanoscale building blocks such as single-walled carbon nanotubes (SWNTs) into desired architectures is a major hurdle for a broad range of basic research and technological applications (e.g., electronic devices and sensors). Here we demonstrate a parallel assembly process that allows one to simultaneously position, shape, and link SWNTs with sub-100-nm resolution. Our method is based on the observation that SWNTs are strongly attracted to COOH-terminated self-assembled monolayers (COOH-SAMs) and that SWNTs with lengths greater than the dimensions of a COOH-SAM feature will align along the boundary between the COOH-SAM feature and a passivating CH
3
-terminated SAM. By using nanopatterned affinity templates of 16-mercaptohexadecanonic acid, passivated with 1-octadecanethiol, we have formed SWNT dot, ring, arc, letter, and even more sophisticated structured thin films and continuous ropes. Experiment and theory (Monte Carlo simulations) suggest that the COOH-SAMs localize the solvent carrying the nanotubes on the SAM features, and that van der Waals interactions between the tubes and the COOH-rich feature drive the assembly process. A mathematical relationship describing the geometrically weighted interactions between SWNTs and the two different SAMs required to overcome solvent–SWNT interactions and effect assembly is provided.
Appearance of immature/transitional B cells in HIV-infected individuals with advanced disease: Correlation with increased IL-7
Authors: Malaspina Angela , Moir Susan , Ho Jason , Wang Wei , Howell Melissa L. , O’Shea Marie A. , Roby Gregg A. , Rehm Catherine A. , Mican JoAnn M. , Chun Tae-Wook , Fauci Anthony S.
Published: February 2006

Progression of HIV disease is associated with the appearance of numerous B cell defects. We describe herein a population of immature/transitional B cells that is overly represented in the peripheral blood of individuals with advancing HIV disease. These B cells, identified by the expression of CD10, were unresponsive by proliferation to B cell receptor triggering and possessed a phenotype and an Ig diversity profile that confirmed their immature/transitional stage of differentiation. Consistent with an immature status, their lack of proliferation to B cell receptor triggering was reversed with CD40 ligand, but not B cell activation factor. Finally, levels of CD10 expression on B cells were directly correlated with serum levels of IL-7, suggesting that increased levels of IL-7 modulate human B cell maturation either directly or indirectly by means of a homeostatic effect on lymphopenia. Taken together, these data offer insight into human B cell development as well as B cell dysfunction in advanced HIV disease that may be linked to IL-7-dependent homeostatic events.
Hutchinson–Gilford progeria mutant lamin A primarily targets human vascular cells as detected by an anti-Lamin A G608G antibody
Authors: McClintock Dayle , Gordon Leslie B. , Djabali Karima
Published: February 2006

Hutchinson–Gilford progeria syndrome (HGPS; Online Mendelian Inheritance in Man accession no.
176670
) is a rare disorder that is characterized by segmental premature aging and death between 7 and 20 years of age from severe premature atherosclerosis. Mutations in the
LMNA
gene are responsible for this syndrome. Approximately 80% of HGPS cases are caused by a G608 (GGC→GGT) mutation within exon 11 of
LMNA
, which elicits a deletion of 50 aa near the C terminus of prelamin A. In this article, we present evidence that the mutant lamin A (progerin) accumulates in the nucleus in a cellular age-dependent manner. In human HGPS fibroblast cultures, we observed, concomitantly to nuclear progerin accumulation, severe nuclear envelope deformations and invaginations preventable by farnesyltransferase inhibition. Nuclear alterations affect cell-cycle progression and cell migration and elicit premature senescence. Strikingly, skin biopsy sections from a subject with HGPS showed that the truncated lamin A accumulates primarily in the nuclei of vascular cells. This finding suggests that accumulation of progerin is directly involved in vascular disease in progeria.
Diabesity: A Polygenic Model of Dietary-Induced Obesity from Ad Libitum Overfeeding of Sprague–Dawley Rats and Its Modulation by Moderate and Marked Dietary Restriction
Authors: Keenan Kevin P. , Hoe Chao-Min , Mixson Lori , Mccoy Carol L. , Coleman John B. , Mattson Britta A. , Ballam Gordon A. , Gumprecht Laura A. , Soper Keith A.
Published: February 2006

This study compared the effects of ad libitum (AL) overfeeding and moderate or marked dietary restriction (DR) on the pathogenesis of a metabolic syndrome of diabesity comprised of age-related degenerative diseases and obesity in a outbred stock of Sprague–Dawley (SD) rats [Crl:CD (SD) IGS BR]. SD rats were fed Purina Certified Rodent Diet AL (group 1), DR at 72–79% of AL (group 2), DR at 68–72% of AL (group 3) or DR at 47–48% of AL (group 4) for 106 weeks. Interim necropsies were performed at 13, 26, and 53 weeks, after a 7-day 5-bromo-2-deoxyuridine (BrdU)-filled minipump implantation. Body weights, organ weights, carcass analysis, in-life data including estrous cyclicity, and histopathology were determined. At 6–7 weeks of age SD rats had 6% body fat. AL-feeding resulted in hypertriglyceridemia, hypercholesterolemia, and dietary-induced obesity (DIO) by study week 14, with 25% body fat that progressed to 36–42% body fat by 106 weeks. As early as 14 weeks, key biomarkers developed for spontaneous nephropathy, cardiomyopathy, and degenerative changes in multiple organ systems. Early endocrine disruption was indicated by changes in metabolic and endocrine profiles and the early development and progression of lesions in the pituitary, pancreatic islets, adrenals, thyroids, parathyroids, liver, kidneys, and other tissues. Reproductive senescence was seen by 9 months with declines in estrous cyclicity and pathological changes in the reproductive organs of both sexes fed AL or moderate DR, but not marked DR. The diabesity syndrome in AL-fed, DIO SD rats was readily modulated or prevented by moderate to marked DR. Moderate DR of balanced diets resulted in a better toxicology model by significantly improving survival, controlling adult body weight and obesity, reducing the onset, severity, and morbidity of age-related renal, endocrine, metabolic, and cardiac diseases. Moderate DR feeding reduces study-to-study variability, increases treatment exposure time, and increases the ability to distinguish true treatment effects from spontaneous aging. The structural and metabolic differences between the phenotypes of DIO and DR SD rats indicated changes of polygenic expression over time in this outbred stock. AL-overfeeding of SD rats produces a needed model of DIO and diabesity that needs further study of its patterns of polygenic expression and phenotype.
Androgen Dependent Mammary Gland Virilism in Rats Given the Selective Estrogen Receptor Modulator LY2066948 Hydrochloride
Authors: Rudmann Daniel G. , Cohen Ilene R. , Robbins Michelle R. , Coutant David E. , Henck Judith W.
Published: February 2006

A selective estrogen receptor modulator (SERM) is a nonsteroidal compound with tissue specific estrogen receptor (ER) agonist or antagonist activities. In animals, SERMs may produce morphologic changes in hormonally-sensitive tissues like the mammary gland. Mammary glands from female rats given the SERM LY2066948 hydrochloride (LY2066948) for 1 month at ≥ 175 mg/kg had intralobular ducts and alveoli lined by multiple layers of vacuolated, hypertrophied epithelial cells, resembling in part the morphology of the normal male rat mammary gland. We hypothesized that these SERM-mediated changes represented an androgen-dependent virilism of the female rat mammary gland. To test this hypothesis, the androgen receptor antagonist flutamide was co-administered with LY2066948 (175 mg/kg) to female rats for 1 month. Female rats given SERM alone had hyperandrogenemia and the duct and alveolar changes described here. Flutamide cotreatment did not affect serum androgen levels but completely blocked the SERM-mediated mammary gland change. In the mouse, a species that does not have the sex-specific differences in the mammary gland observed in the rat, SERM treatment resulted in hyperandrogenemia but did not alter mammary gland morphology. These studies demonstrate that LY2066948 produces species-specific, androgen-dependent mammary gland virilism in the female rat.
Drug-Induced Protoporphyria in Beagle Dogs
Authors: Greijdanus-van der Putten Sylvia W. M , van Esch Eric , Kamerman Jan , Ballering Leo A. P. , van den Dobbelsteen Diels J. , T de Rijk Eveline P. C.
Published: February 2006

As part of regulatory safety testing program, a 13-week oral toxicity study with a new antipsychotic drug candidate was performed in beagle dogs. During this study, dark red/brown feces were recorded in treated dogs and increases in liver parameters (alanine aminotransferase, alkaline phosphatase, bilirubin) were measured biochemically. At the end of the study, livers of high-dose (50 mg/kg) animals were (mottled) dark brown, sometimes with pale foci. Histopathological examination of these livers showed dark globular pigment deposits in the hepatocellular cytoplasm and within the bile canaliculi. Varying numbers of inflammatory cell infiltrates were additionally present in association with the deposits. These pigment deposits showed birefringency with characteristic “Maltese Cross”-like structures under polarized light. Electronmicroscopy revealed the typical, so-called “sunburst” pattern with radiating double-lined crystalline structures. These morphologic characteristics strongly indicated at the presence of porphyrins, which was definitely confirmed biochemically. Published reports of drug-induced hepatic porphyria in dogs are rare. The possible underlying mechanism in the dog and man is discussed.
Transcriptional repression induces a slowly progressive atypical neuronal death associated with changes of YAP isoforms and p73
Authors: Hoshino Masataka , Qi Mei-ling , Yoshimura Natsue , Miyashita Tomoyuki , Tagawa Kazuhiko , Wada Yo-ichi , Enokido Yasushi , Marubuchi Shigeki , Harjes Phoebe , Arai Nobutaka , Oyanagi Kiyomitsu , Blandino Giovanni , Sudol Marius , Rich Tina , Kanazawa Ichiro , Wanker Erich E. , Saitoe Minoru , Okazawa Hitoshi
Published: February 2006

Transcriptional disturbance is implicated in the pathology of polyglutamine diseases, including Huntington's disease (HD). However, it is unknown whether transcriptional repression leads to neuronal death or what forms that death might take. We found transcriptional repression-induced atypical death (TRIAD) of neurons to be distinct from apoptosis, necrosis, or autophagy. The progression of TRIAD was extremely slow in comparison with other types of cell death. Gene expression profiling revealed the reduction of full-length yes-associated protein (YAP), a p73 cofactor to promote apoptosis, as specific to TRIAD. Furthermore, novel neuron-specific YAP isoforms (YAPΔCs) were sustained during TRIAD to suppress neuronal death in a dominant-negative fashion. YAPΔCs and activated p73 were colocalized in the striatal neurons of HD patients and mutant huntingtin (htt) transgenic mice. YAPΔCs also markedly attenuated Htt-induced neuronal death in primary neuron and Drosophila melanogaster models. Collectively, transcriptional repression induces a novel prototype of neuronal death associated with the changes of YAP isoforms and p73, which might be relevant to the HD pathology.
NEDD1-dependent recruitment of the γ-tubulin ring complex to the centrosome is necessary for centriole duplication and spindle assembly
Authors: Haren Laurence , Remy Marie-Hélène , Bazin Ingrid , Callebaut Isabelle , Wright Michel , Merdes Andreas
Published: February 2006

The centrosome is the major microtubule organizing structure in somatic cells. Centrosomal microtubule nucleation depends on the protein γ-tubulin. In mammals, γ-tubulin associates with additional proteins into a large complex, the γ-tubulin ring complex (γTuRC). We characterize NEDD1, a centrosomal protein that associates with γTuRCs. We show that the majority of γTuRCs assemble even after NEDD1 depletion but require NEDD1 for centrosomal targeting. In contrast, NEDD1 can target to the centrosome in the absence of γ-tubulin. NEDD1-depleted cells show defects in centrosomal microtubule nucleation and form aberrant mitotic spindles with poorly separated poles. Similar spindle defects are obtained by overexpression of a fusion protein of GFP tagged to the carboxy-terminal half of NEDD1, which mediates binding to γTuRCs. Further, we show that depletion of NEDD1 inhibits centriole duplication, as does depletion of γ-tubulin. Our data suggest that centriole duplication requires NEDD1-dependent recruitment of γ-tubulin to the centrosome.
ATM regulates ATR chromatin loading in response to DNA double-strand breaks
Authors: Cuadrado Myriam , Martinez-Pastor Barbara , Murga Matilde , Toledo Luis I. , Gutierrez-Martinez Paula , Lopez Eva , Fernandez-Capetillo Oscar
Published: February 2006

DNA double-strand breaks (DSBs) are among the most deleterious lesions that can challenge genomic integrity. Concomitant to the repair of the breaks, a rapid signaling cascade must be coordinated at the lesion site that leads to the activation of cell cycle checkpoints and/or apoptosis. In this context, ataxia telangiectasia mutated (ATM) and ATM and Rad-3–related (ATR) protein kinases are the earliest signaling molecules that are known to initiate the transduction cascade at damage sites. The current model places ATM and ATR in separate molecular routes that orchestrate distinct pathways of the checkpoint responses. Whereas ATM signals DSBs arising from ionizing radiation (IR) through a Chk2-dependent pathway, ATR is activated in a variety of replication-linked DSBs and leads to activation of the checkpoints in a Chk1 kinase–dependent manner. However, activation of the G2/M checkpoint in response to IR escapes this accepted paradigm because it is dependent on both ATM and ATR but independent of Chk2. Our data provides an explanation for this observation and places ATM activity upstream of ATR recruitment to IR-damaged chromatin. These data provide experimental evidence of an active cross talk between ATM and ATR signaling pathways in response to DNA damage.
Killer cell lectin-like receptor G1 binds three members of the classical cadherin family to inhibit NK cell cytotoxicity
Authors: Ito Masayuki , Maruyama Takuma , Saito Naotoshi , Koganei Satoru , Yamamoto Kazuo , Matsumoto Naoki
Published: February 2006

Killer cell lectin-like receptor G1 (KLRG1) is an inhibitory receptor expressed on subsets of natural killer (NK) cells and T cells, for which no endogenous ligands are known. Here, we show that KLRG1 binds three of the classical cadherins (E-, N-, and R-), which are ubiquitously expressed in vertebrates and mediate cell–cell adhesion by homotypic or heterotypic interactions. By expression cloning using the mouse KLRG1 tetramer as a probe, we identified human E-cadherin as a xenogeneic ligand. We also identified a syngeneic interaction between mouse KLRG1 and mouse E-cadherin. Furthermore, we show that KLRG1 binds N- and R-cadherins. Finally, we demonstrate that E-cadherin binding of KLRG1 prevents the lysis of E-cadherin–expressing targets by KLRG1+ NK cells. These results suggest that KLRG1 ligation by E-, N-, or R-cadherins may regulate the cytotoxicity of killer cells to prevent damage to tissues expressing the cadherins.
H2-M3–restricted CD8+ T cells are not required for MHC class Ib–restricted immunity against Listeria monocytogenes
Authors: D'Orazio Sarah E.F. , Shaw Christine A. , Starnbach Michael N.
Published: February 2006

Studies using major histocompatibility complex (MHC)-Ia–deficient mice have shown that MHC-Ib–restricted CD8+ T cells can clear infections caused by intracellular pathogens such as Listeria monocytogenes. M3-restricted CD8+ T cells, which recognize short hydrophobic N-formylated peptides, appear to comprise a substantial portion of the MHC-Ib–restricted T cell response in the mouse model of L. monocytogenes infection. In this study, we isolated formyltransferase (fmt) mutant strains of L. monocytogenes that lacked the ability to add formyl groups to nascent polypeptides. These fmt mutant Listeria strains did not produce antigens that could be recognized by M3-restricted T cells. We showed that immunization of MHC-Ia–deficient mice with fmt mutant Listeria resulted in stimulation of a protective memory response that cleared subsequent challenge with wild-type L. monocytogenes, despite the fact that M3-restricted CD8+ T cells did not proliferate in these mice. These data suggest that M3-restricted T cells are not required for protection against L. monocytogenes and underscore the importance of searching for new antigen-presenting molecules among the large MHC-Ib family of proteins.
Cytolytic responses: cadherins put out the fire
Authors: Colonna Marco
Published: February 2006

Cytotoxic lymphocytes, such as natural killer (NK) cells and CD8+ T cells, provide an essential defense against intracellular pathogens and tumors. During target cell recognition, these cells receive both activating and inhibitory signals. The cell must evaluate these opposing signals and determine the appropriate response: activation or inhibition. Classically, inhibitory signals are mediated by receptors that recognize MHC class I molecules (1). But recent studies, including one in this issue, suggest that MHC class I-independent inhibitory signals can also result in inhibition of cytotoxic cells.
Clinical and Laboratory Features of Community-Associated Methicillin-ResistantStaphylococcus aureus:Is It Really New?
Authors: Johnson Leonard B. , Saeed Sajjad , Pawlak Joan , Manzor Odette , Saravolatz Louis D.
Published: February 2006

Objective.

To review the epidemiologic and molecular characteristics of community-associated methicillin-resistantStaphylococcus aureus(CA-MRSA) in Detroit, Michigan, to assess the risk factors for infection and the response to therapy.

Design.

Prospective clinical and laboratory study of 2003-2004 CA-MRSA isolates. Molecular features were compared with CA-MRSA isolates from 1980.

Setting.

A 600-bed urban academic medical center.

Patients.

Twenty-three patients with CA-MRSA infections from 2003-2004 were evaluated. In addition, laboratory analysis was performed on 13 CA-MRSA isolates from 1980.

Main Outcome Measures.

Laboratory analysis of isolates included antimicrobial susceptibility testing, pulsed-field genotyping, testing for Panton-Valentine leukocidin (PVL) genes, and staphylococcal cassette chromosomemectyping.

Results.

Patients were predominantly young African American males and presented with skin and soft-tissue infections. All isolates were resistant to erythromycin and highly susceptible to other agents. Patients were generally treated successfully with combination incision and drainage and systemic antibiotics. Among the 23 isolates, 20 (87%) were the same strain. This strain carried the staphylococcal cassette chromosomemectype IV and PVL genes and is genetically identical to USA 300. Thirteen isolates of patients from our community who presented with CA-MRSA infections in 1980 represented a single clone that is unique compared with the 2003-2004 isolates. This strain carried staphylococcal cassette chromosomemectype IVA but did not carry the PVL genes.

Conclusions.

In our community, CA-MRSA is largely due to a single clone with a type IVmecgene and PVL gene. The type IV staphylococcal cassette chromosomemectype can be demonstrated in CA-MRSA isolates from a remote period, suggesting that earlier outbreaks were not related to healthcare exposure.
The Role of Gowns in Preventing Nosocomial Transmission of Methicillin-ResistantStaphylococcus aureus(MRSA): Gown Use in MRSA Control
Authors: Grant J. , Ramman-Haddad L. , Dendukuri N. , Libman M. D.
Published: February 2006

During a 2-year period, a standard isolation protocol for control of methicillin-resistantStaphylococcus aureuswas compared with a similar protocol in which gowns were not used but the availability of alcohol-based hand disinfectant was increased. Intervention wards had 0.10 fewer new MRSA transmissions per ward per month, compared with control wards (P was not significant).
The Role of Institutional Epidemiologic Weight in Guiding Infection Surveillance and Control in Community and Hospital Populations
Authors: Hartley David M. , Furuno Jon P. , Wright Marc O. , Smith David L. , Perencevich Eli N.
Published: February 2006

Background.

Institutions such as hospitals, prisons, and long-term care facilities have been identified as focal points for the transmission of emerging infections. Cost-effective control of these infections in large populations requires the identification of optimal subpopulations for targeted infection control interventions. Our objective was to quantify and compare the relative impact that individual institutions or subpopulations have on wider population-level outbreaks of emerging pathogens.

Design.

We describe a simple mathematical model to compute the epidemiologic weight (EW) of an institution or subpopulation. The EW represents the rate at which newly infectious individuals exit the institution under consideration.

Setting.

A hypothetical academic tertiary-care hospital (700 beds, 5-day length of stay [LOS]) and prison (3098 inmates, 27-day LOS).

Patients.

Individuals entering a hospital in-patient prison ward and nonprisoners entering both medical and surgical intensive-care units and those admitted to the general medical and surgical wards.

Results.

The recent example of the community-acquired methicillin-resistantStaphylococcus aureusepidemic is used to illustrate the EW calculation. Hospitals and prisons, which often have vastly dissimilar populations sizes and LOSs and might have differing transmission rates, can have comparable EWs and thus contribute equally to an epidemic in the community.

Conclusions.

This method highlights the importance of measuring entrance and exit colonization prevalences for the optimal targeting of prevention measures. The EW not only identified superspreader institutions but also ranks them, enabling public health workers to optimize the allocation of resources to places where they are likely to be of most benefit.
The Influence of the Composition of the Nursing Staff on Primary Bloodstream Infection Rates in a Surgical Intensive Care Unit
Authors: Robert Jérôme , Fridkin Scott K. , Blumberg Henry M. , Anderson Betsy , White Nancy , Ray Susan M. , Chan Jinlene , Jarvis William R.
Published: February 2006

Objectives:

To determine the risk factors for acquisition of nosocomial primary bloodstream infections (BSIs), including the effect of nursing-staff levels, in surgical intensive care unit (SICU) patients.

Design:

A nested case-control study.

Setting:

A 20-bed SICU in a 1,000-bed inner-city public hospital.

Patients:

28 patients with BSI (case-patients) were compared to 99 randomly selected patients (controls) hospitalized ≥3 days in the same unit.

Results:

Case- and control-patients were similar in age, severity of illness, and type of central venous catheter (CVC) used. Case-patients were significantly more likely than controls to be hospitalized during a 5-month period that had lower regular-nurse-to-patient and higher pool-nurse-to-patient ratios than during an 8-month reference period; to be in the SICU for a longer period of time; to be mechanically ventilated longer; to receive more antimicrobials and total parenteral nutrition; to have more CVC days; or to die. Case-patients had significantly lower regular-nurse-to-patient and higher pool-nurse-to-patient ratios for the 3 days before BSI than controls. In multivariate analyses, admission during a period of higher pool-nurse-to-patient ratio (odds ratio [OR]=3.8), total parenteral nutrition (OR=1.3), and CVC days (OR=1.1) remained independent BSI risk factors.

Conclusions:

Our data suggest that, in addition to other factors, nurse staffing composition (ie, pool-nurse-to-patient ratio) may be related to primary BSI risk. Patterns in intensive care unit nurse staffing should be monitored to assess their impact on nosocomial infection rates. This may be particularly important in an era of cost containment and healthcare reform.
Evaluation of Two Retrospective Active Surveillance Methods for the Detection of Nosocomial Infection in Surgical Patients
Authors: Belío-Blasco Cristina , Torres-Fernández-Gil M. Antonia , Echeverría-Echarri J. Lorenzo , Gómez-López Luis I.
Published: February 2006

Objective:

To compare the sensitivity and specificity of two retrospective active surveillance methods based on review of the medical record and review of the discharge form in identifying nosocomial infection, taking the prospective surveillance method as the reference standard.

Design:

Blind comparison of three active nosocomial infection surveillance methods.

Setting:

Department of General Surgery of a tertiary-care hospital with a referral population of 266,000 people.

Methods:

All operated patients admitted to the Department of Surgery for more than 24 hours and discharged from January 1, 1994, to December 31, 1994, were included. Prospective surveillance consisted of daily review of the patient's record during hospitalization. Retrospective surveillance consisted of review of the medical record and the discharge form. Sensitivity and specificity of both retrospective methods were calculated.

Results:

Of the 1,514 patients included in the study, 1,476 (97.5%) were reviewed by means of the retrospective surveillance system. A total of 20, 8, and 4 hours per week was needed for the active prospective system, review of the medical record, and review of the hospital discharge form, respectively. The documented cumulative incidence of nosocomial infection was 21.8% for the prospective system, 19.6% for review of the medical record, and 12.6% for review of the discharge form. The overall sensitivity of review of the medical record was 88% and of the discharge form 56%, with a specificity of 99%. For review of the medical record, the highest sensitivity was 93%, for urinary tract infections; for review of the discharge form, the highest was 57%, for surgical-wound infection.

Conclusions:

The retrospective method of review of the medical record was the most efficient active surveillance strategy in detecting nosocomial infection in surgical patients
Tuberculosis Isolation Comparison of Written Procedures and Actual Practices in Three California Hospitals
Authors: Sutton Patrice M. , Nicas Mark , Harrison Robert J.
Published: February 2006

Objective:

To evaluate implementation of healthcare worker exposure control measures for tuberculosis (TB)-patient isolation, as specified by Centers for Disease Control and Prevention (CDC) guidelines and the hospital's TB-control policy.

Design:

Prospective multihospital study comparing CDC guidelines and hospital policy for TB-patient isolation to once-weekly observations of TB-patient isolation practices over 14 consecutive weeks at each hospital.

Setting:

Three urban hospitals (two county, one private community) in counties in California with a high incidence rate of TB.

Measurements:

Work practices for TB-patient isolation were observed and ventilation performance of isolation rooms was assessed while patient rooms were in use for TB isolation.

Results:

Of 170 TB-patient rooms observed, 119 (70%) involved a patient in a designated TB isolation room, the room was under negative pressure, the door was closed, and a “respiratory precautions” sign was on the door; 32 patient-room units (19%) were not under negative pressure or not designated as negative-pressure rooms. Of 151 patient-room units mechanically capable of negative pressure at a prior point in time, 16 (11%) were not under negative pressure at the time of use. Of 67 patient-room units equipped with continuous monitoring devices, 8 (12%) involved devices that did not accurately reflect the direction of airflow. Of the 62 healthcare workers observed using a respirator for TB, 40 (65%) did not don the respirator properly.

Conclusions:

Implementing CDC guidelines for TB-patient isolation was feasible but imperfect in the three hospitals. Day-to-day work practices deviated from hospital policy. Prospectively quantifying the implementation of a hospital TB isolation policy while the room is in use may lead to improved estimates of risk and may help to identify and thereby prevent avoidable healthcare worker exposures toMycobacterium tuberculosisaerosol. Auditing practices and verifying equipment performance is likely to identify unexpected problems in implementation of the TB control program.
Prevalence of Positive Tuberculin Skin Reactions in a Two-Step Testing Program at a Tertiary-Care Center in Eastern North Carolina
Authors: Swinker Marian
Published: February 2006

The results of performing two-step tuberculin skin testing of healthcare workers at a hospital in eastern North Carolina in 1997 and 1998 were reviewed. Of 1,248 new employees, approximately 500 required two-step testing, which identified only 5 new employees who might have been falsely labeled as converters during the subsequent year's surveillance testing.
Practical Guidelines for Vancomycin Usage, With Prospective Drug-Utilization Evaluation
Authors: Drori-Zeides Tayl , Raveh David , Schlesinger Yechiel , Yinnon Amos M.
Published: February 2006

To strengthen guidelines for vancomycin use, practical guidelines were developed. A prospective survey was conducted of all patients receiving vancomycin during two 1-month periods, 1 year apart, during which significant improvements were noted. Practical guidelines may contribute to appropriateness of vancomycin use, serve as educational tools, and facilitate improved surveillance.
Vancomycin Use in Pediatric Hematology-Oncology Patients
Authors: Hopkins Heidi A. , Sinkowitz-Cochran Ronda L. , Rudin Benjamin A. , Keyserling Harry L. , Jarvis William R.
Published: February 2006

A cross-sectional study was performed of pediatric hematology-oncology patients who received vancomycin; use was compared to the Centers for Disease Control and Prevention (CDC) recommendations for vancomycin use. Thirty-seven patients received 308 doses of vancomycin. All patients initially received vancomycin as empirical therapy; 100% of this use was not consistent with the CDC recommendations.
Nosocomial Pseudo-outbreak ofFusarium verticillioidesAssociated With Sterile Plastic Containers
Authors: Grigis Annalisa , Farina Claudio , Symoens Françoise , Nolard Nicole , Goglio Antonio
Published: February 2006

Twenty-six patients were implicated in a nosocomial pseudo-outbreak ofFusarium verticillioides. Examination of clinical records and handling procedures revealed a fungal contamination of supposedly sterile containers used for biological materials. An accurate system of monitoring permitted us to determine the origin of the infection and the means of its spread.
What's the Score?
Authors: Birnbaum David
Published: February 2006

If you have calculated a confidence interval for an infection rate and found the interval extending into meaningless negative numbers, chances are the error is due to use of approximation formulae. Many of us unknowingly were taught to use the Wald approximation, which does not always approximate the exact binomial distribution accurately. Poor approximation can occur in infection surveillance at both small and large sample sizes.
Control of Influenza in the Long-Term–Care Facility: A Review of Established Approaches and Newer Options
Authors: Arden Nancy H.
Published: February 2006

Influenza infections pose a serious threat to residents of nursing homes and other long-term–care facilities. Annual vaccination of residents and staff with the currently licensed inactivated influenza vaccine continues to be the mainstay of prevention. Live attenuated influenza vaccine, which is expected to be licensed in the United States in the near future, may offer added protection for elderly persons when administered in conjunction with inactivated vaccine. Antiviral agents also can be useful as an adjunct to vaccination, especially for control of institutional outbreaks. Two new antiviral agents that appear to be less toxic than amantadine and rimantadine have recently been approved.
Epidemiological Differences Between Sepsis Syndrome With Bacteremia and Culture-Negative Sepsis
Authors: Fariñas-Álvarez Concepción , Fariñas M. Carmen , Fernández-Mazarrasa Carlos , Llorca Javier , Delgado-Rodríguez Miguel
Published: February 2006

Objective:

To explore the association of putative disease markers and potential risk factors with the nosocomial sepsis syndrome.

Design:

Prospective case-control study matched for gender, age, and length of preinfection hospital stay.

Setting:

1,200-bed tertiary-care center in Spain.

Patients:

Cases were selected using the sepsis syndrome criteria of the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference and were divided into three groups: sepsis with bacteremia (109 cases), sepsis with positive culture other than blood (122 cases), and sepsis with negative culture (115 cases without documented infection but with sepsis syndrome, clinically suspected infection, and empirical antibiotic treatment). Controls were randomly selected from the daily list of inpatients. Data were collected prospectively. Crude and multiple-risk-factor-adjusted odds ratios and their 95% confidence intervals were computed using conditional logistic regression analysis.

Results:

Presence of coma in the 48 hours before sepsis, intensive care unit (ICU) stay, and decreased serum albumin levels at admission were common epidemiological markers identified for the three groups of cases. Having a central venous catheter was the main healthcare-related risk factor for bacteremia. ICU stay and nasogastric tube were the main risk factors for sepsis with positive culture other than blood. Coma within 48 hours before sepsis and the need of intensive care were the only two markers identified for culture-negative sepsis.

Conclusion:

Culture-negative sepsis does not behave like culture-positive sepsis, and this may imply that implementation of preventive measures to decrease the risk of bacteremia may not decrease the risk of sepsis syndrome.
Nosocomial Methicillin-ResistantStaphylococcus aureusBacteremia: Is It Any Worse Than Nosocomial Methicillin-SensitiveStaphylococcus aureusBacteremia?
Authors: Selvey Linda A. , Whitby Michael , Johnson Barbara
Published: February 2006

Objective:

To determine the comparative virulence of methicillin-resistantStaphylococcus aureus(MRSA) and methicillin-sensitiveS aureus(MSSA) by consideration of predisposing factors and outcomes in patients infected with these organisms in the healthcare setting.

Design:

Analysis of an historical cohort of 504 bacteremic patients (316 MSSA and 188 MRSA), examining factors associated with mortality.

Setting:

A 916-bed, university-affiliated, tertiary referral hospital.

Results:

Risk factors for the development of MRSA include male gender, admission due to trauma, immunosuppression, presence of a central vascular line or an indwelling urinary catheter, and a past history of MRSA infection. Overall mortality was 22%. Death due to bacteremia was significantly greater in the MRSA group (risk ratio, 1.68;P<.05), although these patients were not found to be more likely to die due to underlying disease during treatment of bacteremia. In those patients who recovered from bacteremia, no significant differences for the outcome of death could be determined between the MRSA and MSSA groups.

Conclusions:

There is a general consensus in the published literature that MRSA bacteremia is more likely to be associated with death, and we confirm this conclusion. However, in contrast to other studies, our MRSA cohort does not appear to be more at risk of death due to underlying disease during treatment for bacteremia. Similarly, the general consensus that MRSA patients have an increased overall mortality was not confirmed in our study. Differences in comorbidities of patients may provide some explanation of these conflicting results, while an alternate explanation is that MRSA strains are more virulent than MSSA in some centers. Perhaps the most plausible explanation is that treatment is provided earlier and in a more aggressive fashion in some centers, leading to an overall lower mortality rate in all staphylococcal bacteremias in these institutions.
Comparison of Blood-Culture Contamination Rates in a Pediatric Emergency Room: Newly Inserted Intravenous Catheters Versus Venipuncture
Authors: Ramsook Chris , Childers Kim , Cron Stanley G. , Nirken Milton
Published: February 2006

We compared contamination rates of blood cultures obtained either from newly inserted intravenous catheters or via venipuncture. Of 2,431 blood cultures, the overall contamination rate was 2.7% (intravenous catheter, 3.4%; venipuncture, 2.0%;P=.043). The site of lowest contamination was the antecubital fossa, making this the optimal choice for blood-culture sampling.
The Utility of Polysporin Ointment in the Eradication of Methicillin-Resistant Staphylococcus aureus Colonization: A Pilot Study
Authors: Fung Scott , O'Grady Sharon , Kennedy Catharine , Dedier Helen , Campbell Iivi , Conly John
Published: February 2006

We evaluated the efficacy of an ointment containing bacitracin, polymyxin B, and gramicidin for the eradication of colonization by methicillin-resistant Staphylococcus aureus in 11 medical patients, 10 (91%) of whom had previously failed a 1-week course of topical mupirocin. Mupirocin resistance was documented in 5 (45%) of 11 patients. Successful decolonization was achieved in 9 (82%) of 11 patients (based on 2 months of follow-up).
Analysis of Sharp-Edged Medical-Object Injuries at a Medical Center in Taiwan
Authors: Wang Fu-Der , Chen Yin-Yin , Liu Cheng-Yi
Published: February 2006

A total of 733 incidents by sharp-edged objects occurred among healthcare workers between 1995 and 1998. Injuries occurred most frequently among interns. The workplace location with the highest incidence of injury was the patient ward, and the object that most frequently inflicted injury was a needle. The most frequent work practice was recapping of syringes. One healthcare worker demonstrated seroconversion for hepatitis C.
The Burden of Infection in Long-Term Care
Authors: Strausbaugh Larry J. , Joseph Carol L.
Published: February 2006

Available data, although fragmentary, indicate that infections impose a large burden on long-term–care facilities (LTCFs) in the United States. Endemic infections occur with frequencies estimated to range between 1.64 and 3.83 million per year. These estimates rival or exceed the annual tally for nosocomial infections in acute-care settings. Infections associated with outbreaks caused by respiratory, gastrointestinal, and antimicrobial-resistant pathogens burden LTCFs even further. As judged by antimicrobial use, transfers to hospital, and mortality figures, infections in LTCFs are not trivial. Moreover, annual costs associated with these infections appear to exceed $1 billion. Recognition of the burden associated with infection in LTCFs helps to identify research priorities for this rapidly growing area of healthcare.
Streptococcus pneumoniaeSerotype 4 Outbreak in a Home for the Aged: Report and Review of Recent Outbreaks
Authors: Gleich Sheldon , Morad Yosef , Echague Ramon , Miller James R. , Kornblum John , Sampson Jacquelyn S. , Butler Jay C.
Published: February 2006

Objective:

To describe a pneumonia outbreak caused byStreptococcus pneumoniaeamong residents of a home for the aged and to review contemporary pneumococcal outbreaks.

Design:

Epidemiological investigation.

Methods:

Spneumoniaeisolates were serotyped and analyzed by pulsed-field gel electrophoresis. Paired sera were tested for antibodies to pneumococcal surface adhesin A protein (PsaA, a 37-kDa cell-wall protein). Pneumococcal outbreaks reported in the last decade in English were reviewed.

Results:

Pneumonia developed in 18 of 200 residents. In 11 (61%), a pneumococcal etiology was demonstrated.S pneumoniae,serotype 4, was isolated from the blood cultures of 3 patients; all isolates were indistinguishable by pulsed-field gel electrophoresis. Pneumococcal involvement was established in 2 by sputum culture and latex agglutination of parapneumonic fluid and in 6 others by a twofold rise in optical density of serum antibody reactive to PsaA. Pneumococcal immunization had not previously been received by any patient; mortality was 22%. No additional cases were noted following administration of pneumococcal vaccine and antibiotic prophylaxis with penicillin or erythromycin. Twenty-six outbreaks of invasive pneumococcal disease since 1990 were reviewed. Twelve occurred in the United States, and serotypes 23F, 14, and 4 accounted for 8 (67%) of 12 outbreaks. All confirmed serotypes in US outbreaks are included in the 23-valent vaccine. More than one half of pneumococcal outbreaks worldwide involved elderly persons in hospitals or long-term-care facilities.

Conclusions:

A pneumococcal pneumonia outbreak occurred among unvaccinated residents of a residential facility for the aged. Institutionalized elderly persons are at risk of outbreaks of pneumococcal disease and should be vaccinated.