bluuebunny/crossref_metadata_2025 huggingface dataset:
The TRC8 E3 ligase ubiquitinates MHC class I molecules before dislocation from the ER
Authors: Stagg Helen R. , Thomas Mair , van den Boomen Dick , Wiertz Emmanuel J.H.J. , Drabkin Harry A. , Gemmill Robert M. , Lehner Paul J.
Published: September 2009

The US2 and US11 gene products of human cytomegalovirus promote viral evasion by hijacking the endoplasmic reticulum (ER)–associated degradation (ERAD) pathway. US2 and US11 initiate dislocation of newly translocated major histocompatibility complex class I (MHC I) from the ER to the cytosol for proteasome-mediated degradation, thereby decreasing cell surface MHC I. Despite being instrumental in elucidating the mammalian ERAD pathway, the responsible E3 ligase or ligases remain unknown. Using a functional small interfering RNA library screen, we now identify TRC8 (translocation in renal carcinoma, chromosome 8 gene), an ER-resident E3 ligase previously implicated as a hereditary kidney cancer gene, as required for US2-mediated MHC I ubiquitination. Depletion of TRC8 prevents MHC I ubiquitination and dislocation by US2 and restores cell surface MHC I. TRC8 forms an integral part of a novel multiprotein ER complex that contains MHC I, US2, and signal peptide peptidase. Our data show that the TRC8 E3 ligase is required for MHC I dislocation from the ER and identify a new complex associated with mammalian ERAD.
Clinical Pharmacology of Antibiotics: The Use of Intraperitoneal Antibiotics to Treat Dialysis-Associated Peritonitis
Authors: Washington Terrill G. , Eggleston Mark
Published: September 2009

Peritoneal dialysis has been successfully used in treating patients with end stage renal disease (ESRD) for approximately 40 years. Peritoneal infections are a frequent consequence of this procedure which has diminished its acceptance by physicians and patients alike. Since the development of an improved access catheter and automated dialysate delivery devices, peritoneal analysis has been gaining widespread acceptance as an alternative to hemodialysis in the treatment of patients with ESRD. Despite the improvement in the peritoneal dialysis systems, peritonitis continues to be a major complication for adult and pediatric patients undergoing continuous ambulatory peritoneal dialysis (CAPD).:‘-’ Although most patients have from less than one to four peritonitis episodes per year, some patients have no episodes of' peritonitis or have a significantly high occurrence (greater than four episodes) of peritonitis. Several reports have indicated that two thirds of the total number of ‘peritonitis episodes is due to gram-positive bacteria. Gram-negative bacteria accounts for approximately 15% and fungal infections account for less than 5%.
Sulbactam/Ampicillin
Authors: Salamone Francine R.
Published: September 2009

Sulbactam/ampicillin was recently marketed for use in several infections caused by beta-lactamase-producing organisms. Sulbactam is the second beta-lactamase inhibitor to become available in the United States. Interest in inhibition of beta-lactamases arose in the late 1960s when a combination consisting of an antibacterial agent and an enzyme inhibitor was found effective in the treatment of certain resistant gram-negative infections. It is now well accepted that the addition of a beta-lactamase inhibitor to a beta-lactam antibiotic may expand its usefulness in a variety of infections.

The penicillin derivatives, known as beta-lactam antibiotics, possess a four-membered ring (beta-lactam ring) fused to a second ring (Figure). It is the beta-lactam ring that is essential for the inhibition of bacterial cell wall synthesis and subsequent bactericidal activity of these agents. The development of resistance to beta-lactam antibiotics may occur by a number of mechanisms, although the most important is bacterial production of enzymes (beta-lactamases) that are capable of beta-lactam ring hydrolysis and inactivation.

Sulbactam resembles the penicillin derivatives in structure (Figure) and is able to preserve their activity by its ability to inhibit the action of beta-lactamases, particularly those of the Richmond classes II-V (gram-negative) and the group A beta-lactamases (gram-positive). Sulbactam is referred to as a “suicide inhibitor” because while forming an irreversible complex with the enzyme, it is destroyed in the process. By virtue of its ability to render the beta-lactamases inactive, sulbactam has been combined with ampicillin in an effort to restore its activity against a number of pathogens that have developed resistance by this mechanism.
Cluster Sampling in Hospital Surveillance
Authors: Burmeister Leon F.
Published: September 2009

Simple random sampling of individuals from a finite population is generally regarded as the most basic of all sample designs. However, it is not commonly used for several reasons. It is often difficult and time consuming to generate a complete listing, or sampling frame, of all individuals in the population. The use of a random number table is also time consuming with a realistically large population, although computer-generated simple random samples greatly reduce this inefficiency.
Expanding Roles of Hospital Epidemiology: Quality Assurance
Authors: Wenzel Richard P.
Published: September 2009

The role of hospital epidemiology is expanding. Today's hospital epidemiologists are being asked for advice by hospital administrators for matters outside of infection control. The latter relate to the optimal use of drugs, the level of health care provided by the employee health services and a number of issues related to the distribution and determinants of health care in the institution, all of which fall under the umbrella of quality assurance (QA). There is no doubt about the national preoccupation for monitoring health care and health care providers.
Disinfection of Water Distribution Systems for Legionella: A Review of Application Procedures and Methodologies
Authors: Muraca Paul W. , Yu Victor L. , Goetz Angella
Published: September 2009

Hospital-acquired legionella pneumonia is emerging as a major problem; potable water distribution systems have been shown to be the primary reservoirs for the legionella organisms. As a result, disinfection measures have been developed to eradicate the organism from the hospital water supply. Each disinfection modality differs in its design and application such that choosing an appropriate cost-effective control measure requires careful analysis and planning.

We assess in comparative fashion the disinfection modalities of thermal eradication (“heat-and-flush”), instantaneous steam-heating system, chlorination, ultraviolet light irradiation, ozonation and metal ionization. The theoretical bases, the actual procedure or system, the logistics of implementation, the costs and personnel requirements and the advantages and disadvantages are presented for each modality. Criteria for selection of a method, the use of combinations of methods, parameters for installation, pitfalls in implementation and a plan for subsequent environmental surveillance are discussed in detail.
Hospital Reimbursement Patterns Among Patients With Surgical Wound Infections Following Open Heart Surgery
Authors: Boyce John M. , Potter-Bynoe Gail , Dziobek Linda
Published: September 2009

Of the more than 200,000 patients who undergo open heart surgery annually in the United States, 2% to 10% will develop a post-operative infectionrelated to their surgery. The economic impact of such infections on hospitals under the prospective payment system is unclear. To study the effect of such infections on hospital costs and reimbursement patterns, we compared case patients with controls of similar age, sex, urgency of surgery and type of surgery. The postoperative stay for cases was significantly longer than for matched controls (26.8 days and 8.3 days, respectively; p = .0002). The mean hospital cost for case admissions ($25,957) was twice as high as for control admissions ($12,795) (p = .0002). Cases resulted in an average net loss to the hospital of $2,344 per patient, while controls yielded an average net gain of $3,196 per patient (p = .02). We conclude that hospitals have substantial financial incentives tominimize the incidence of postoperative wound infections associated with open heart surgery.
Infection Control Practices in Gastrointestinal Endoscopy in the United States: A National Survey
Authors: Gorse Geoffrey J. , Messner Roberta L.
Published: September 2009

Objectives:

To ascertain current infection control practices, endoscope cleaning procedures, perceived risks of infection, and implementation of universal precautions in gastrointestinal endoscopy units in the United States.

Design:

National mailed survey of gastroenterology nurses and associates conducted anonymously in March 1988.

Setting:

Completed surveys were received from all 50 states and Puerto Rico and from all practice settings. The most common practice setting was private/community hospitals (66%).

Participants:

Of the 4,952 survey forms mailed to all members and to interested non-members of the Society of Gastrointestinal Nurses and Associates, 2,158 (44%) were returned and 2,030 (41%) were completed and evaluable. Of the respondents, 1,487 (73%) were registered nurses.

Results:

Sixty-seven percent (n = 1,358) of the respondents routinely used an enzymatic cleaner as a step in the instrument decontamination process; 93% (n = 1,879) chemically disinfected instruments after each case; and 88% (n = 1,779) disinfected endoscopes with an aqueous glutaraldehyde product. Respondents reported that they and a significantly smaller proportion of physicians (p<.001) employed barrier precautions for all endoscopic cases involving possible contact with blood/body fluids of patients known (66% versus 57%, respectively) and not known (12% versus 8%, respectively) to have a bloodborne infection. Endoscopy-related infections, usually bacterial, were reported to have occurred at their institutions by 6% (n = 116) of respondents.

Conclusions:

We conclude that cleaning, disinfection, and sterilization procedures for gastrointestinal endoscopic instruments vary, that appropriate protective apparel is not always worn, and that some practices may lead to preventable endoscopy-related infection in patients.
Nosocomial Pneumonia in a Canadian Tertiary Center: A Prospective Surveillance Study
Authors: Louie M. , Dyck B. , Parker S. , Sekla L. , Nicolle L.E.
Published: September 2009

Objective:

To determine the contribution of etiologic agents, including Legionella pneumophila and respiratory viruses to nosocomial pneumonia at a tertiary care center.

Design:

Prospective surveillance of nosocomial pneumonia with standardized laboratory investigations.

Setting:

A 1,100-bed tertiary care center.

Patients:

All adult inpatients.

Results:

One hundred and thirty-five Nosocomial pneumonias (5.7/1,000 discharges) were identified. Four (3.0%) were L pneumophila sero-group 1 infections (0.17/1,000 discharges). LegionelIosis occurred in non-high-risk patients, and three cases would not have been identified without active surveillance. viral seroconversion was identified in seven (19%) of 36 cases with specimens available (0.59/1,000 discharges): five influenza B, one influenza A, and one respiratory syncytial virus. IgM serology was positive in one case each for Mycoplasma pneumoniae and Chlamydia species. No geographical clustering was observed for viral infections, and these would not have been identified without active surveillance. Mortality for all nosocomial pneumonia was 25%. Patient factors significantly associated with a poorer outcome included older age, underlying disease, low serum albumin, renal insufficiency, lower platelet count, endotracheal intubation, respiratory failure, bacteremia, and use of antacids.

Conclusions:

This prospective surveillance suggested that L pneumophila and viral agents were uncommon causes of nosocomial pneumonia at our institution during this surveillance period.
Effect of an Automated Sink on Handwashing Practices and Attitudes in High-Risk Units
Authors: Larson Elaine , McGeer Allison , Quraishi Z. Ahmed , Krenzischek Dina , Parsons B.J. , Holdford Jack , Hierholzer Walter J.
Published: September 2009

Objective:

To assess the effects of an automated sink on handwashing practices and attitudes of staff.

Design:

Quasi-experimental crossover design.

Setting:

Two high-risk patient care areas, one postanesthesia recovery room (Site 1), and one neonatal intensive care unit (Site 2) in two tertiary care hospitals.

Participants:

All patient care staff on study units; approximately 55 individuals.

Interventions:

An automated sink was installed to replace one handwashing sink for about five weeks; the sink was then crossed-over for an equivalent time period to the other location. Handwashing practices of all unit staff were observed in three two-hour observation periods/week. Questionnaires were distributed to staff two weeks after sink installation and at the study's end.

Results:

One thousand, six hundred ten handwashes were observed. Handwashing practices differed significantly by site. For both sites, hands were washed significantly better but significantly less often with the automated sink (all p<.001). Staff expressed negative attitudes, however, about certain features of the sink, and these negative attitudes increased over the study period.

Conclusions:

Automated devices must be flexible enough to allow adjustments based on staff acceptance. Application of new technology to improve hand hygiene requires a multifaceted approach to behavior change. (Infect Control Hosp Epidemiol. 1991;12:422-428.)
Prevention of Infectious Diseases in Ambulatory Care: Immunoprophylaxis and Chemoprophylaxis
Authors: Wald Tina G. , Tobacman Joanne K.
Published: September 2009

Objective:

To review the current recommendations for immunoprophylaxis and chemoprophylaxis of infection in adults, including those who are at increased risk from occupation, lifestyle, travel, or pre-existing medical conditions.

Design:

Review of the pertinent literature.

Setting:

Adult ambulatory care.

Conclusions:

Guidelines for the prevention of several diseases including measles, tuberculosis, and bacterial endocarditis recently have been changed. Current recommendations for immunization, immune globulin therapy, and chemotherapy for these and other common infections are reviewed.
Cryptococcal Ventricular-Peritoneal Shunt Infection: Clinical and Epidemiological Evaluation of Two Closely Associated Cases
Authors: Ingram Christopher W. , Haywood Hubert B. , Morris Vicki M. , Allen Robert L. , Perfect John R.
Published: September 2009

Objective:

To determine the cause of meningitis associated with Cryptococcus neoformans in two patients with recent ventricular-peritoneal (VP) shunt placement.

Design:

A retrospective review of materials, records, and concurrent cases of VP shunt procedures. Isolates of C neoformans from each patient were submitted for analysis by colony morphology, biochemical testing, and karyotyping by pulsed-field electrophoresis.

Setting:

Two 400-bed community hospitals.

Patients:

Two immunocompetent patients presented with symptoms of progressive hydrocephalus in August 1991. Each received a VP shunt on the same day by the same surgeon using materials from a common vendor and hospital.

Results:

Both patients presented within six to eight weeks with symptoms of fever, headache, rash, and cultures of cerebrospinal fluid (CSF) that yielded C neoformans. Each patient recovered after therapy with amphotericin B and flucytosine followed by several months of fluconazole, although one required replacement of the VP shunt for cure. Review of each patient's history and CSF characteristics at the time of shunt placement suggested re-activation of a pre-existing infection. Isolates of C neoformans from each patient were submitted for analysis by colony morphology, biochemical testing, and karyotyping by pulsed-field electrophoresis. Each isolate was found to be unique by chromosomal karyotyping.

Conclusions:

Our data and previous reports suggest that cryptococcal VP shunt infections appear to be a complication of shunts placed in previously infected persons rather than noso-transmission of cryptococcus during placement.
Signals and prepatterns: new insights into organ polarity in plants
Authors: Husbands Aman Y. , Chitwood Daniel H. , Plavskin Yevgeniy , Timmermans Marja C.P.
Published: September 2009

The flattening of leaves results from the interaction between upper (adaxial) and lower (abaxial) domains in the developing primordium. These domains are specified by conserved, overlapping genetic pathways involving several distinct transcription factor families and small regulatory RNAs. Polarity determinants employ a series of antagonistic interactions to produce mutually exclusive cell fates whose positioning is likely refined by signaling across the adaxial–abaxial boundary. Signaling candidates include a mobile small RNA—the first positional signal described in adaxial–abaxial polarity. Possible mechanisms to polarize the incipient primordium are discussed, including meristem-derived signaling and a model in which a polarized organogenic zone prepatterns the adaxial–abaxial axis.
Drosophila Minus is required for cell proliferation and influences Cyclin E turnover
Authors: Szuplewski Sébastien , Sandmann Thomas , Hietakangas Ville , Cohen Stephen M.
Published: September 2009

Turnover of cyclins plays a major role in oscillatory cyclin-dependent kinase (Cdk) activity and control of cell cycle progression. Here we present a novel cell cycle regulator, called minus, which influences Cyclin E turnover in Drosophila. minus mutants produce defects in cell proliferation, some of which are attributable to persistence of Cyclin E. Minus protein can interact physically with Cyclin E and the SCF Archipelago/Fbw7/Cdc4 ubiquitin–ligase complex. Minus does not affect dMyc, another known SCFAgo substrate in Drosophila. We propose that Minus contributes to cell cycle regulation in part by selectively controlling turnover of Cyclin E.
Regulating the regulator: an RNA decoy acts as an OFF switch for the regulation of an sRNA: Figure 1.
Authors: Mandin Pierre , Gottesman Susan
Published: September 2009

Many bacterial small regulatory RNAs (sRNAs) pair with mRNA targets, stimulating or inhibiting mRNA stability and/or translation. Regulation of these sRNAs is usually due to tight transcriptional regulation of synthesis.In this issue of Genes & Development and a related paper in Molecular Microbiology, Figueroa-Bossi and colleagues (pp. 2004–2015) and Overgaard and colleagues report a novel regulatory mechanism in which induction of a competing mRNA acts to titrate away the sRNA, allowing expression of an otherwise strongly inhibited target gene.
An ensemble model of competitive multi-factor binding of the genome
Authors: Wasson Todd , Hartemink Alexander J.
Published: September 2009

Hundreds of different factors adorn the eukaryotic genome, binding to it in large number. These DNA binding factors (DBFs) include nucleosomes, transcription factors (TFs), and other proteins and protein complexes, such as the origin recognition complex (ORC). DBFs compete with one another for binding along the genome, yet many current models of genome binding do not consider different types of DBFs together simultaneously. Additionally, binding is a stochastic process that results in a continuum of binding probabilities at any position along the genome, but many current models tend to consider positions as being either binding sites or not. Here, we present a model that allows a multitude of DBFs, each at different concentrations, to compete with one another for binding sites along the genome. The result is an “occupancy profile,” a probabilistic description of the DNA occupancy of each factor at each position. We implement our model efficiently as the software package COMPETE. We demonstrate genome-wide and at specific loci how modeling nucleosome binding alters TF binding, and vice versa, and illustrate how factor concentration influences binding occupancy. Binding cooperativity between nearby TFs arises implicitly via mutual competition with nucleosomes. Our method applies not only to TFs, but also recapitulates known occupancy profiles of a well-studied replication origin with and without ORC binding. Importantly, the sequence preferences our model takes as input are derived from in vitro experiments. This ensures that the calculated occupancy profiles are the result of the forces of competition represented explicitly in our model and the inherent sequence affinities of the constituent DBFs.
Bromodeoxyuridine Labeling of S-Phase Nuclei in the Starlet Sea Anemone Nematostella vectensis
Authors: Genikhovich Grigory , Technau Ulrich
Published: September 2009

INTRODUCTION

Bromodeoxyuridine (BrdU) is a thymidine analog that can be used to label cells in the S-phase of the cell cycle. BrdU penetrates the cell membrane and is rapidly integrated into the nucleotide pool, ready to be incorporated into DNA. A specific antibody against BrdU coupled to a fluorophore or an enzyme (alkaline phosphatase [AP] or horseradish peroxidase [HRP]) can detect BrdU incorporated into DNA. The method is simple and powerful, because the combination of pulse, continuous, and pulse-chase labeling allows deep insights into the cell-cycle dynamics and differentiation kinetics of a number of cycling and terminally differentiated cells. This protocol describes BrdU labeling of S-phase nuclei in the starlet sea anemone Nematostella vectensis.
Extraction of RNA from Small Amounts of Amphioxus Embryos for cDNA Synthesis by RT-PCR
Authors: Yu J.K. Sky , Holland Linda Z.
Published: September 2009

INTRODUCTION

This protocol describes a rapid method for obtaining total RNA from several hundred (or fewer) amphioxus embryos. This protocol uses a commercially available spin column kit and is especially useful for experiments involving very small amounts of starting material, such as embryos injected with transgenes or morpholino antisense oligonucleotides. After the target embryos are sorted and rinsed, they are lysed and homogenized in lysis buffer prepared with guanidine isothiocyanate and containing β-mercaptoethanol to release RNA and inactivate RNases. Ethanol is added to the sample to promote selective binding of RNA to the silica-based membrane in the spin column. After applying the sample to the spin column to bind RNA, DNA contamination is removed by DNase treatment on the spin column. Finally, DNase and digested DNA are washed away, and high-quality RNA is eluted in RNase-free water. The resulting RNA can be used directly to generate cDNA by reverse transcriptase polymerase chain reaction (RT-PCR) for more sensitive applications such as quantitative PCR (Q-PCR).
Predicting invasive phenotype with CDH1, CDH13, CD44, and TIMP3 gene expression in primary breast cancer
Authors: Celebiler (Cavusoglu) Aydan , Kilic Yalın , Saydam Serdar , Canda Tulay , Başkan Zuhal , Sevinc Ali Ibrahim , Sakizli Meral
Published: September 2009

We aimed to determine changes in the expression of the genes CDH1, CDH13, CD44, and TIMP3 to look for any relationship between them, HER2 and ESR1 expression at the RNA level, and the histopathological properties of tumors. We also analyzed the expression properties of double‐negative (estrogen receptor [ER] and human epidermal growth factor receptor [HER2] both negative) breast tumors. Expression status was studied in fresh tissue at the mRNA level with quantitative PCR using hydrolysis probes. Sixty‐two cancer patients and four normal controls were included in the study. When the tumor group was analyzed as a whole, the correlations of ESR1 with CDH1, CDH13, and TIMP3 were P < 0.05, P < 0.005, and P < 0.005, respectively. In ER‐positive tumors, CDH1 and CDH13 were correlated directly (P < 0.005) when HER2 was correlated with CDH1, CDH13, and TIMP3 indirectly (P < 0.005, P < 0.005, and P < 0.05, respectively). CDH1 and CD44 had a strong indirect correlation (P < 0.005) in ER‐negative tumors. There were significant differences in the expression levels of the CDH13, TIMP3, and CD44 genes (P < 0.005, P < 0.005, and P < 0.05, respectively) between the ER‐positive and ‐negative groups. All four genes were found to be correlated with invasive properties in both ER‐positive and ‐negative tumors. In double‐negative tumor samples, only CD44 had a significant and strong correlation with stage, lymph node involvement, and metastasis (P < 0.05, P < 0.005, and P < 0.05, respectively). As a conclusion, a decrease in CDH1, CDH13, and TIMP3 expression levels with an increase in CD44 can be used as an indicator for invasion in both ER‐positive and ‐negative breast tumors. In double‐negative tumor tissues, CD44 can be considered a marker for aggressive properties. (Cancer Sci 2009; 100: 2341–2345)
PC‐407, a celecoxib derivative, inhibited the growth of colorectal tumor in vitro and in vivo
Authors: Li Yuhua , Niu Yinbo , Wu Huanjie , Zhang Bangle , Sun Yang , Huang Haitao , Li Qian , Fan Lei , Liu Li , Mei Qibing
Published: September 2009

This study aimed to observe the growth‐inhibitory effect of PC‐407 (4‐[5‐naphthyl‐3‐(trifluoromethyl)‐1H‐pyrazol‐1‐yl] benzenesulfonamide), a celecoxib derivative synthesized in our lab, in human colorectal cancer cells and a colitis‐associated colorectal cancer (CACC) model, and investigate the relative molecular mechanisms. SW‐1116 (expressing a high level of cyclooxygenase‐2 [COX‐2]), HT‐29 (expressing a moderate level of COX‐2), and SW‐480 (no expression of COX‐2) cell lines were exposed to different concentrations of celecoxib (0–100 μmol/L) or PC‐407 (0–100 μmol/L). Then, COX‐2 levels were assessed by reverse transcription‐PCR and Western blotting. COX‐2 activity was evaluated by measuring prostaglandin E2 concentration using enzyme‐linked immunoassay. A mouse model of colitis‐associated carcinogenesis was employed to determine the effect of PC‐407 in vivo. PC‐407 inhibited cell growth in a concentration‐dependent manner, and the IC50 values of PC‐407 for growth inhibition of SW‐1116, HT‐29, and SW‐480 cells were 17.60 ± 3.02, 18.14 ± 2.81, and 8.13 ± 0.40 μmol/L, respectively. PC‐407 down‐regulated COX‐2 mRNA and protein levels and reduced prostaglandin E2 production significantly. In vivo, PC‐407 inhibited the genesis of CACC effectively. Our data indicate that PC‐407 can inhibit the growth of tumor both in vitro and in vivo and suggest that the effect probably involves inhibition of the COX‐2 pathway and other COX‐2‐independent pathways. (Cancer Sci 2009; 100: 2451–2458)
Arsenic trioxide and cisplatin synergism increase cytotoxicity in human ovarian cancer cells: Therapeutic potential for ovarian cancer
Authors: Zhang Ning , Wu Zhen‐Ming , McGowan Eileen , Shi Jun , Hong Zu‐Bei , Ding Chuan‐Wei , Xia Pu , Di Wen
Published: September 2009

Drug resistance is a major concern in the successful treatment of ovarian cancer. In the present study we report a combinational drug regime using arsenic trioxide (ATO) and cisplatin (CDDP) to increase therapeutic potentiality in ovarian cancer cells. ATO‐mediated growth inhibition and apoptosis in human suspension ovarian cancer COC1 cells were evaluated by MTT assay and annexin V assay using flow cytometry, respectively. cDNA arrays were performed to screen ATO‐mediated gene expression. Treatment of COC1 cells with ATO alone resulted in growth inhibition and apoptosis with a dose‐and time‐dependent fashion; further cDNA arrays showed that 34 genes (23 up‐regulated genes and 11 down‐regulated genes) may strongly associate with the antiproliferative and pro‐apoptotic effects induced by ATO. Furthermore, Chou–Talalay analysis was used to evaluate the combinational effect of ATO and CDDP as well as dose‐reduction index (DRI) in a panel of ovarian cancer cells including CDDP‐sensitive and ‐resistant cell lines. The combination index (CI) analysis indicated that the interaction effect of ATO/CDDP exhibited a wide range of synergism in all the adherent ovarian cancer cells (A2780, IGROV‐1, SKOV‐3, and R182) as well as 0.93 to 0.69 for IC50 to IC90 in suspension COC1 cells where CI < 1, =1, and >1, define synergism, additive effect, and antagonism, respectively. More intriguingly, the combination of ATO and CDDP yielded favorable DRIs ranging from 1.23‐fold to 13.51‐fold dose reduction. These results suggest that ATO and its combination with CDDP present therapeutic potential for ovarian cancer, and deserve further preclinical and clinical studies. (Cancer Sci 2009; 100: 2459–2464)
Distinctive cell properties of B cells carrying the BCL2 translocation and their potential roles in the development of lymphoma of germinal center type
Authors: Sakai Tomomi , Nishikori Momoko , Tashima Masaharu , Yamamoto Ryo , Kitawaki Toshio , Takaori‐Kondo Akifumi , Suzuki Takayo , Tsuzuki Shinobu , Uchiyama Takashi
Published: September 2009

The BCL2/IGH translocation is a hallmark of follicular lymphoma and germinal center B‐cell type diffuse large B‐cell lymphoma. Although a strong determinant of these histological subtypes, this translocation is insufficient by itself for lymphomagenesis, so that other genetic alterations are required. To clarify how the BCL2 translocation contributes to the development of specific lymphoma subtypes, we used chimeric mouse models and a bone marrow transplantation system to examine the biological features of BCL2‐overexpressing B cells. These cells showed a cell‐autonomous differentiation preference for follicular B cells. Their cell cycle progression was enhanced in wild‐type but not in Eμ‐BCL2 transgenic mice, indicating that the low proliferative activity of B cells in Eμ‐BCL2 transgenic mice is partly due to their specific microenvironment, which is caused by the abnormal B cells themselves. Moreover, in vitro experiments demonstrated that Eμ‐BCL2+ B cells have reduced responsiveness to terminal differentiation stimulation. According to these results, we hypothesize that B cells that have undergone BCL2/IGH translocation might possibly be forced to localize in follicles, and accumulate genetic abnormalities by being subjected to recurrent stimulation. Our findings lead us to propose that B cells carrying the BCL2/IGH translocation comprise a distinctive cell population that leads to the development of germinal center B‐cell type lymphoma. (Cancer Sci 2009; 100: 2361–2367)
Effects of moisture, nitrogen, grass competition and simulated browsing on the survival and growth of Acacia karroo seedlings
Authors: Mopipi Keletso , Trollope Winston S. W. , Scogings Peter F.
Published: September 2009

The effects of irrigation, nitrogen fertilization, grass competition and clipping were investigated for one growing season at the research farm of the University of Fort Hare in the Eastern Cape Province of South Africa. The aim of the experiment was to assess the short‐term performance of Acacia karroo seedlings under different environmental conditions and the implications of such factors on the long‐term recruitment of plant species in savanna rangelands. There were no significant treatment effects on the survival of A. karroo seedlings. Using stem length and basal diameter as growth parameters, it was observed that irrigation enhanced both variables, while nitrogen fertilization did not have any significant effects. Clipping, grass competition and their interaction greatly suppressed the growth of the seedlings. Clipping increased the mean stem length when they were irrigated and fertilized. Control and fertilized plants had the highest stem length in the absence of grass competition, while grass competition combined with clipping resulted in the lowest stem length in both irrigated and nonirrigated plants. It was concluded that in the presence of grass competition, controlled browsing could be a viable solution to the problem of bush encroachment in savanna rangelands.
Genetic structure of two populations of the Namibian giraffe, Giraffa camelopardalis angolensis
Authors: Brenneman Rick A. , Louis Jr Edward E. , Fennessy Julian
Published: September 2009

Two geographically distinct populations of giraffe (Giraffa camelopardalis) were sampled for this study, the northern Namib Desert and Etosha National Park. Population genetic parameters and relationships within subpopulations were estimated to better understand the genetic architecture of this isolated subspecies. Gene flow between the geographically separated populations can be attributed to recent translocation of giraffe between the two populations. Inbreeding estimates in the six subpopulations studied were low though we found evidence that genetic drift may be affecting the genetic diversity of the isolated populations in northern Namibia. Population dynamics of the sampling locations was inferred with relationship coefficient analyses. Recent molecular systematics of the Namibian giraffe populations indicates that they are distinct from the subspecies Giraffa camelopardalis giraffa and classified as G. c. angolensis. Based on genetic analyses, these giraffe populations of northern Namibia, the desert‐dwelling giraffe and those protected in Etosha National Park, are a distinct subspecies from that previously assumed; thus we add data on G. c. angolensis to our scientific knowledge of this giraffe of southern Africa.
Climate and landscape correlates of African lion (Panthera leo) demography
Authors: Celesia Gastone G. , Townsend Peterson A. , Kerbis Peterhans Julian C. , Gnoske Thomas P.
Published: September 2009

Although many studies have documented aspects of lion ecology, they have generally focused on single sites, leaving broader‐scaled factors unanalysed. We assessed range‐wide effects of eight biotic and 26 abiotic variables on lion distribution and ecology, based on data compiled from published sources on lion population ecology in 27 protected areas in Africa. Lion pride size and composition were independent of lion density; lion density and home range size were inversely related; and lion density was positively related to rainfall, soil nutrients and annual mean temperature, with some interactive effects between rainfall and soil nutrients. Lion demography was associated most strongly with rainfall, temperature and landscape features. Herbivore biomass and lion density were correlated in univariate regression analyses. However, because herbivore biomass was also related to rainfall and temperature, hierarchical partitioning (HP) allowed us to evaluate independent effects of each variable on lion demography revealing that herbivore biomass had negligible independent contributions. HP indicated that climatic parameters explained 62% of overall variance in demographic parameters, whereas landscape features explained only 32%; climatic parameters were fairly balanced between effects of temperature (34%) and rainfall (28%). Prey (herbivore) biomass is important for lion survival, but its effects appear secondary to environmental factors.
Ventricular tachycardia during hyperthermic intraperitoneal chemotherapy
Authors: Thix C. A. , Königsrainer I. , Kind R. , Wied P. , Schroeder T. H.
Published: September 2009

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) is used for selected gastrointestinal carcinomas. We report a case of ventricular tachycardia during HIPEC with cisplatin that persisted as long as the chemotherapy solution remained in the intra‐abdominal cavity. We hypothesise that high plasma levels of cisplatin with concomitant low magnesium levels caused the arrhythmia.
Oblique sub‐costal transversus abdominis plane (TAP) catheters: an alternative to epidural analgesia after upper abdominal surgery
Authors: Niraj G. , Kelkar A. , Fox A. J.
Published: September 2009

The authors present three cases where catheters placed in the oblique sub‐costal transversus abdominis plane provided prolonged analgesia after upper abdominal surgery. Patient 1 was admitted with severe sepsis following major hepatobiliary surgery. Bilateral catheters facilitated weaning from mechanical ventilation and provided adequate analgesia for 4 days. Patient 2 underwent emergency laparotomy for intestinal obstruction having refused consent for epidural analgesia. The transversus abdominis plane catheters provided a significant opioid sparing effect. A unilateral catheter offered rescue analgesia in patient 3 when the epidural catheter was displaced. We put forward a case for oblique sub‐costal transversus abdominis plane catheters as an alternative to epidural analgesia after upper abdominal surgery.
Tracheal intubation with restricted access: a randomised comparison of the Pentax‐Airway Scope and Macintosh laryngoscope in a manikin
Authors: Asai T.
Published: September 2009

Ten anaesthetists assessed the ease of tracheal intubation (time to see the glottis, to intubate the trachea and to ventilate), using the Pentax Airway Scope and Macintosh laryngoscope in a manikin, in three simulated circumstances of restricted laryngoscopy: (1) the patient lying supine on the ground; (2) the patient lying supine on the ground with the head close to a wall; (3) the patient confined to a car driver’s seat. For the Pentax Airway Scope, intubation was successful (within 2 min) in all three circumstances. For the Macintosh laryngoscope, intubation was successful in all cases in circumstance (1), eight in circumstance (2), and five in circumstance (3). In circumstances (2) and (3), the Pentax Airway Scope needed significantly shorter time to see the vocal cords (median [95% confidence interval] for difference: 4.5 [0.5–9.5] s in circumstance (2), and 12.5 [7.0–32.5] s in circumstance (3)), shorter time to intubate (median [95% confidence interval] for difference: 21.0 [5.5–38.5] s in circumstance (2), and 40.5 [17.5–64.0] s in circumstance (3)), and shorter time to ventilate the lungs (median [95% confidence interval] for difference: 18. 3 [4.5–36.0] s in circumstance (2), and 47.5 [16.0–84.5] s in circumstance (3)). These results indicate that, in situations where access to the patient’s head is restricted, the Pentax Airway Scope is more effective than the Macintosh laryngoscope.
The effect of flexion on the level of termination of the dural sac in paediatric patients
Authors: Koo B‐N. , Hong J‐Y. , Kim J. E. , Kil H. K.
Published: September 2009

Although the anatomy of the spinal cord and its associated structures have been well defined, the effects of body position relevant to neuraxial blockade have not been elucidated. This study was designed to determine the effect of body position on the end of the dural sac in children. After induction of anaesthesia, ultrasound examination was performed to evaluate the location of the dural sac end in the lateral position with a straight back and knee, and in the lateral position with the knees, legs, and neck flexed. The level of the end of the dural sac was determined in relation to the vertebrae. Our data demonstrate that the dural sac shifts significantly cephalad in the lateral flexed position used for neuraxial blockade (p < 0.001). These results suggest that the safety margin to avoid dural puncture during hiatal or S2‐3 approach for caudal block can be increased in younger children.
Rise in antiobesity drug prescribing for children and adolescents in the UK: a population‐based study
Authors: Viner Russell M. , Hsia Yingfen , Neubert Antje , Wong Ian C. K.
Published: September 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• The antiobesity drugs sibutramine and orlistat are not licensed for use in children and adolescents in the UK or USA.

• Clinical trials suggest antiobesity drugs are effective and well‐tolerated in obese adolescents.

WHAT THIS STUDY ADDS

• Prescribing of unlicensed antiobesity drugs in children and adolescents has increased significantly in the past 8 years.

• Most prescribed antiobesity drugs in children and adolescents are rapidly discontinued before patients can see clinical benefit, suggesting they are poorly tolerated or poorly efficacious.

AIMS The international childhood obesity epidemic has driven increased use of unlicensed antiobesity drugs, whose efficacy and safety are poorly studied in children and adolescents. We investigated the use of unlicensed antiobesity drugs (orlistat, sibutramine and rimonabant) in children and adolescents (0–18 years) in the UK.

METHODS Population‐based prescribing data from the UK General Practice Research Database between 1 January 1999 and 31 December 2006.

RESULTS A total of 452 subjects received 1334 prescriptions during the study period. The annual prevalence of antiobesity drug prescriptions rose significantly from 0.006 per 1000 [95% confidence interval (CI) 0.0007, 0.0113] in 1999 to 0.091 per 1000 (95% CI 0.07, 0.11) in 2006, a 15‐fold increase, with similar increases seen in both genders. The majority of prescriptions were made to those ≥14 years old, although 25 prescriptions were made for children <12 years old. Orlistat accounted for 78.4% of all prescriptions; only one patient was prescribed rimonabant. However, approximately 45% of the patients ceased orlistat and 25% ceased sibutramine after only 1 month. The estimated mean treatment durations for orlistat and sibutramine were 3 and 4 months, respectively.

CONCLUSIONS Prescribing of unlicensed antiobesity drugs in children and adolescents has dramatically increased in the past 8 years. The majority are rapidly discontinued before patients can see weight benefit, suggesting they are poorly tolerated or poorly efficacious when used in the general population. Further research into the effectiveness and safety of antiobesity drugs in clinical populations of children and adolescents is needed.
Relationship between blood alcohol concentration on admission and outcome in dimethoate organophosphorus self‐poisoning
Authors: Eddleston Michael , Gunnell David , Von Meyer Ludwig , Eyer Peter
Published: September 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Acute alcohol intoxication often complicates acute organophosphorus pesticide poisoning.

• No data are available on how alcohol intoxication affects outcome in acute organophosphorus pesticide poisoning.

• In particular, the relationships between plasma alcohol concentration and plasma organophosphorus concentration or outcome are unclear.

WHAT THIS STUDY ADDS

• Alcohol co‐ingestion is associated with higher concentrations of the organophosphorus insecticide dimethoate, probably due to larger ingestions.

• The higher concentrations of dimethoate found with alcohol co‐ingestion increase the risk of death in dimethoate poisoning. There was no detectable effect of the alcohol itself on outcome.

• Efforts to reduce deaths from insecticide self‐poisoning may benefit from concurrent efforts to reduce alcohol consumption.

AIMS Many patients acutely poisoned with organophosphorus insecticides have co‐ingested alcohol. Although clinical experience suggests that this makes management more difficult, the relationship between plasma concentration of alcohol and insecticide is unknown. We aimed to determine whether acute intoxication results in ingestion of larger quantities of insecticide in dimethoate self‐poisoning and a worse clinical outcome.

METHODS We set up a prospective study of acute dimethoate self‐poisoning in Sri Lankan district hospitals. An admission plasma sample was analysed to identify the ingested insecticide; in patients with detectable dimethoate, plasma alcohol was measured.

RESULTS Plasma from 37 of 72 (51.4%) dimethoate‐poisoned patients had detectable alcohol {median concentration 1.10 g l−1[110 mg dl−1][interquartile range (IQR) 0.78–1.65]} a median of 3 h post ingestion. The median plasma dimethoate concentration was higher in patients who had ingested alcohol [479 µmol l−1 (IQR 268–701) vs. 145 µmol l−1 (IQR 25–337); P < 0.001]. Plasma dimethoate concentration was positively correlated with plasma alcohol (Spearman's ρ= 0.34; P= 0.0032). The median alcohol concentration was higher in the 21 patients who died compared with survivors (0.94 vs. 0.0 g l−1, P= 0.018). Risk of death was greater amongst individuals who consumed alcohol [odds ratio (OR) 4.3, 95% confidence interval (CI) 1.2, 16.4]; this risk was abolished by controlling for dimethoate concentration (OR 0.3, 95% CI 0.0, 8.8), indicating that deaths were not due to the direct toxic effects of alcohol.

CONCLUSIONS Alcohol co‐ingestion is associated with higher plasma concentrations of dimethoate and increased risk of death. Larger studies are required to assess this finding's generalizability, since efforts to reduce deaths from self‐poisoning may benefit from concurrent efforts to reduce alcohol consumption.
Effect of efavirenz on high‐density lipoprotein antioxidant properties in HIV‐infected patients
Authors: Pereira S. A. , Batuca J. R. , Caixas U. , Branco T. , Delgado‐Alves J. , Germano I. , Lampreia F. , Monteiro E. C.
Published: September 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• In previous work, we showed a long‐term and concentration‐dependent beneficial effect of the non‐nucleoside reverse transcriptase inhibitor efavirenz (EFV) on high‐density lipoproteins (HDL) in human immunodeficiency virus (HIV)‐infected patients.

• Furthermore, it has been suggested that instead of the current practice of only measuring HDL‐chelesterol values, the evaluation of HDL function, namely its antioxidant properties, might be an improved tool for identifying subjects at increased risk for cardiovascular events.

• Paraoxonase‐1 (PON‐1) is an enzyme associated with HDL that is responsible for HDL antioxidant function.

WHAT THIS STUDY ADDS

• In the present work, we studied the effect of EFV on the activity of PON‐1 and showed, for the first time, that EFV‐based antiretroviral therapy is associated with a better antioxidant function, i.e. with a higher PON‐1 activity.

AIMS A long‐term and concentration‐dependent beneficial effect of efavirenz (EFV) on cholesterol associated with high‐density lipoprotein (HDL‐c) in human immunodeficiency virus (HIV)‐infected patients has been documented. Furthermore, it has been suggested that, instead of the current practice of only measuring HDL‐c values, the evaluation of HDL quality might be an improved tool for identifying subjects at increased risk of cardiovascular events. Paraoxonase‐1 (PON‐1) is an enzyme associated with HDL that is involved in the onset of cardiovascular disease and responsible for HDL antioxidant function. The aim of the present study was to investigate the effect of EFV on the circulating activity of PON‐1 in HIV‐infected patients.

METHODS The patients included were adults with a documented HIV‐1 infection, nontreated or treated with antiretroviral regimens including EFV 600 mg once daily as first therapeutic regimen for at least 3 months. The influence of treatment with EFV, HDL‐c and CD4 cell count on PON‐1 activity was analysed.

RESULTS HIV‐infected White patients treated with EFV had higher PON‐1 activity [77.35 U l−1 (65.66, 89.04)] (P < 0.05) and higher PON‐1 activity : HDL‐c ratio [1.88 (1.49, 2.28)] (P < 0.01) than untreated patients. PON‐1 activity was higher in Black patients (P < 0.001) and in patients with a CD4 cell count >500 cells ml−1 (P= 0.0120).

CONCLUSIONS EFV‐based antiretroviral regimens are associated with HDL particles with a better antioxidant function, i.e. with a higher PON‐1 activity. The PON‐1 activity of Black patients is higher than that found in Whites regardless of treatment. Ethnicity should be taken into consideration when studying drug effects on PON‐1 activity.