bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk of tuberculin conversion among healthcare workers and the adoption of preventive measures
Authors: Baussano Iacopo , Bugiani Massimiliano , Carosso Aurelia , Mairano Dario , Pia Barocelli Anna , Tagna Marina , Cascio Vincenza , Piccioni Pavilio , Arossa Walter 
Published: August 2006

Background:In industrialised countries, occupational tuberculosis among healthcare workers (HCWs) is re-emerging as an important public health issue. To prevent and control tuberculosis transmission, several institutions have issued and implemented recommendations and practice guidelines.Objectives:To estimate the annual rate of tuberculosis infection (ARTI; per 100 person-years) among HCWs in Turin, the capital of the Piedmont region of Italy, to identify factors associated with variations in the ARTI and to evaluate the efficacy of the regional guidelines to prevent and control tuberculosis.Methods:The study was conducted between 1997 and 2004 on a cohort of HCWs. The tuberculosis infection was diagnosed through tuberculin skin testing (TST) conversion and defined as an induration increase of at least 10 mm from a previous negative TST. The ARTI and the hazard ratio for each at-risk subgroup, categorised according to working activities and settings, was estimated using exponential survival models. The efficacy of the regional guidelines was estimated by stratifying the analysis according to the moment of the implementation of the guidelines (before/after).Results:The 2182 study participants were drawn from the dynamic cohort. The overall adjusted ARTI was 1.6 (95% CI: 1.3 to 1.9)/100 person-years. Different workplaces (eg, administrative and infectious diseases inpatient services) and occupations (eg, clerical and medical workers) were associated with significantly different ARTIs, ranging between 0.62 and 2.62 and between 0.61 and 1.71, respectively, whereas the TST conversion risk differed by about 16–68% and 30–60%, respectively. The implementation of the guidelines coincided with overall ARTI reductions of 1.3/100 person-years, and concurrently the variations between ARTIs of different occupations and workplaces disappeared.Conclusions:The occupational risk categories for targeting the surveillance and prevention of tuberculosis transmission among HCWs were identified, and the introduction of preventive measures was observed to be effective in decreasing the overall risk of tuberculosis infection among HCWs.
CHEK2-Positive Breast Cancers in Young Polish Women
Authors: Cybulski Cezary , Górski Bohdan , Huzarski Tomasz , Byrski Tomasz , Gronwald Jacek , Dębniak Tadeusz , Wokołorczyk Dominika , Jakubowska Anna , Kowalska Elżbieta , Oszurek Oleg , Narod Steven A. , Lubiński Jan 
Published: August 2006

Abstract
Purpose: To investigate the contribution of CHEK2 mutations to early-onset breast cancer in Poland and to establish the characteristic features of these cancers.
Experimental Design: We studied 3,228 women diagnosed with breast cancer under the age of 51 years and 5,496 population controls. CHEK2 mutations were detected by RFLP-PCR or allele-specific oligonucleotide-PCR assays. Clinical and pathologic features of CHEK2-positive cases and CHEK2-negative cases were compared.
Results: A truncating CHEK2 mutation (1100delC or IVS2+1G&gt;A) was seen in 47 of 3,228 cases and in 34 of 5,496 controls (odds ratio, 2.4; P = 0.0001). The CHEK2 I157T missense mutation was present in 207 of 3,228 cases, compared with 264 of 5,496 controls (odds ratio, 1.4; P = 0.002). Breast cancers in women with a CHEK2 mutation were more commonly of lobular histology (21.5% versus 15.8%; P = 0.05), of size &gt;2 cm (54.8% versus 43.5%; P = 0.01), or of multicentric origin (28.7% versus 19.5%; P = 0.01) than were cancers from women without a CHEK2 mutation. Bilateral cancers were equally common in both subgroups.
Conclusion: Three founder alleles in CHEK2 contribute to early-onset breast cancer in Poland. Breast tumors which arise in carriers of CHEK2 mutations seem to be similar to those of breast cancers in the population at large.
Preoperative Serum Caveolin-1 as a Prognostic Marker for Recurrence in a Radical Prostatectomy Cohort
Authors: Tahir Salahaldin A. , Frolov Anna , Hayes Teresa G. , Mims Martha P. , Miles Brian J. , Lerner Seth P. , Wheeler Thomas M. , Ayala Gustavo , Thompson Timothy C. , Kadmon Dov 
Published: August 2006

Abstract
Purpose: Up-regulation of caveolin-1 (cav-1) is associated with virulent prostate cancer, and serum cav-1 levels are elevated in prostate cancer patients but not in benign prostatic hyperplasia. In this study, we evaluated the potential of high preoperative serum cav-1 levels to predict biochemical progression of prostate cancer. The value of the combined preoperative markers, prostate-specific antigen (PSA), biopsy Gleason score, and serum cav-1 for predicting biochemical recurrence was also investigated.
Experimental Design: Serum samples taken from 419 prostate cancer patients before radical prostatectomy were selected from our Specialized Programs of Research Excellence prostate cancer serum and tissue bank. Serum samples were obtained 0 to 180 days before surgery and all patients had complete data on age, sex, race, stage at enrollment, and follow-up for biochemical recurrence. Serum cav-1 levels were measured according to our previously reported ELISA protocol.
Results: Cav-1 levels were measured in the sera of 419 prostate cancer patients; the mean serum level was 4.52 ng/mL (median 1.01 ng/mL). Patients with high serum cav-1 levels had a 2.7-fold (P = 0.0493) greater risk of developing biochemical recurrence compared with those with low serum cav-1 levels. Importantly, patients with serum PSA ≥ 10 ng/mL and elevated levels of serum cav-1 had 2.44 times higher risk (P = 0.0256) of developing biochemical recurrence compared with patients with low levels of cav-1. In addition, high serum cav-1 levels combined with increasing biopsy Gleason score predicted much shorter recurrence-free survival in the group of patients with PSA ≥ 10 ng/mL (P = 0.0353). Cav-1 was also able to distinguish between high- and low- risk patients with biopsy Gleason score of seven, after adjusting, for patients PSA levels (P = 0.0429).
Conclusions: Overall, elevated preoperative levels of serum cav-1 predict decreased time to cancer recurrence. In the subset of patients with serum PSA of ≥10 ng/mL, the combination of serum cav-1 and biopsy Gleason score has the capacity to predict time to biochemical recurrence.
Antitumor Effect of Trastuzumab for Pancreatic Cancer with High HER-2 Expression and Enhancement of Effect by Combined Therapy with Gemcitabine
Authors: Kimura Kenjiro , Sawada Tetsuji , Komatsu Midori , Inoue Masafumi , Muguruma Kazuya , Nishihara Tamahiro , Yamashita Yoshito , Yamada Nobuya , Ohira Masaichi , Hirakawa Kosei 
Published: August 2006

Abstract
Purpose: The purpose of the present study was to evaluate whether trastuzumab has antitumor effect against pancreatic cancer and whether this effect is concordant with levels of HER-2, which is reportedly overexpressed in pancreatic cancer. We also investigated whether the effect is potentiated in combined therapy with gemcitabine.
Experimental Design: Using immunohistochemistry and FACScan, we analyzed HER-2 expression in 16 pancreatic cancer cell lines. The in vitro antiproliferative effect of trastuzumab, alone and in combination with gemcitabine, was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The in vitro antibody-dependent cell-mediated cytotoxicity of trastuzumab was investigated by 51Cr release assay. The in vivo antitumor effect of trastuzumab, alone and in combination with gemcitabine, was evaluated in nude mouse xenograft growth. The survival benefit was evaluated in a Capan-1 orthotopic implanted nude mouse model.
Results: HER-2 expression of 2+ or more was observed in 10 and of 3+ in 2 of the 16 cell lines. No in vitro growth-inhibitory effect of trastuzumab was found in any cell line, but trastuzumab induced antibody-dependent cell-mediated cytotoxicity in proportion to HER-2 expression level. Trastuzumab inhibited tumor growth in Capan-1 (HER-2: 3+) xenografts and prolonged survival in the orthotopic model. These effects were increased by combined therapy with gemcitabine. In contrast, trastuzumab exhibited no antitumor effect against PANC-1 (HER-2: 1+) or SW1990 (HER-2: 2+) xenografts.
Conclusions: The antitumor effect of trastuzumab in pancreatic cancer with high HER-2 expression was shown in vitro and in vivo. Clinical application of trastuzumab is expected in pancreatic cancer with 3+ HER-2 expression.
Phase I/II Study of Imatinib Mesylate for Recurrent Malignant Gliomas: North American Brain Tumor Consortium Study 99-08
Authors: Wen Patrick Y. , Yung W.K. Alfred , Lamborn Kathleen R. , Dahia Patricia L. , Wang Yanfeng , Peng Bin , Abrey Lauren E. , Raizer Jeffrey , Cloughesy Timothy F. , Fink Karen , Gilbert Mark , Chang Susan , Junck Larry , Schiff David , Lieberman Frank , Fine Howard A. , Mehta Minesh , Robins H. Ian , DeAngelis Lisa M. , Groves Morris D. , Puduvalli Vinay K. , Levin Victor , Conrad Charles , Maher Elizabeth A. , Aldape Kenneth , Hayes Michael , Letvak Laurie , Egorin Merrill J. , Capdeville Renaud , Kaplan Richard , Murgo Anthony J. , Stiles Charles , Prados Michael D. 
Published: August 2006

Abstract
Purpose: Phase I: To determine the maximum tolerated doses, toxicities, and pharmacokinetics of imatinib mesylate (Gleevec) in patients with malignant gliomas taking enzyme-inducing antiepileptic drugs (EIAED) or not taking EIAED. Phase II: To determine the therapeutic efficacy of imatinib.
Experimental Design: Phase I component used an interpatient dose escalation scheme. End points of the phase II component were 6-month progression-free survival and response.
Results: Fifty patients enrolled in the phase I component (27 EIAED and 23 non-EIAED). The maximum tolerated dose for non-EIAED patients was 800 mg/d. Dose-limiting toxicities were neutropenia, rash, and elevated alanine aminotransferase. EIAED patients received up to 1,200 mg/d imatinib without developing dose-limiting toxicity. Plasma exposure of imatinib was reduced by ∼68% in EIAED patients compared with non-EIAED patients. Fifty-five non-EIAED patients (34 glioblastoma multiforme and 21 anaplastic glioma) enrolled in the phase II component. Patients initially received 800 mg/d imatinib; 15 anaplastic glioma patients received 600 mg/d after hemorrhages were observed. There were 2 partial response and 6 stable disease among glioblastoma multiforme patients and 0 partial response and 5 stable disease among anaplastic glioma patients. Six-month progression-free survival was 3% for glioblastoma multiforme and 10% for anaplastic glioma patients. Five phase II patients developed intratumoral hemorrhages.
Conclusions: Single-agent imatinib has minimal activity in malignant gliomas. CYP3A4 inducers, such as EIAEDs, substantially decreased plasma exposure of imatinib and should be avoided in patients receiving imatinib for chronic myelogenous leukemia and gastrointestinal stromal tumors. The evaluation of the activity of combination regimens incorporating imatinib is under way in phase II trials.
Improving Antitumor Immune Responses by Circumventing Immunoregulatory Cells and Mechanisms
Authors: Lizée Gregory , Radvanyi Laszlo G. , Overwijk Willem W. , Hwu Patrick 
Published: August 2006

AbstractAlthough numerous immunotherapeutic strategies have been studied in patients with cancer, consistent induction of clinical responses remains a formidable challenge. Cancer vaccines are often successful at generating elevated numbers of tumor-specific T lymphocytes in peripheral blood, however, despite this, tumors usually continue to grow unabated. Recent evidence suggests that endogenous regulatory cells, known to play a major role in the induction of immune tolerance to self and prevention of autoimmunity, as well as suppressive myeloid cells invoked in the tumor-bearing state, may be largely responsible for preventing effective antitumor immune responses. This review will focus on the major regulatory cell subtypes, including CD4+CD25+ T-regulatory cells, type 1 regulatory T cells, natural killer T cells, and immature myeloid cells. Studies in humans and in animal models have shown a role for all of these cells in tumor progression, although the mechanisms by which they act to suppress immunity remain largely undefined. Elucidation of the dominant molecular mechanisms mediating immune suppression in vivo will allow more precise targeting of the relevant regulatory cell populations, as well as the development of novel strategies and clinical reagents that will directly block molecules that induce the suppression of antitumor immunity.
CHIR-258 Is Efficacious in A Newly Developed Fibroblast Growth Factor Receptor 3–Expressing Orthotopic Multiple Myeloma Model in Mice
Authors: Xin Xiaohua , Abrams Tinya J. , Hollenbach Paul W. , Rendahl Katherine G. , Tang Yan , Oei Yoko A. , Embry Millicent G. , Swinarski Debbie E. , Garrett Evelyn N. , Pryer Nancy K. , Trudel Suzanne , Jallal Bahija , Mendel Dirk B. , Heise Carla C. 
Published: August 2006

Abstract
Purpose: The ectopically expressed and deregulated fibroblast growth factor receptor 3 (FGFR3) results from a t(4;14) chromosomal translocation that occurs in ∼15% of multiple myeloma (MM) patients and confers a particularly poor prognosis. This study assesses the antimyeloma activity of CHIR-258, a small-molecule inhibitor of multiple receptor tyrosine kinases that is currently in phase I trials, in a newly developed FGFR3-driven preclinical MM animal model.
Experimental Design: We developed an orthotopic MM model in mice using a luciferase-expressing human KMS-11-luc line that expresses mutant FGFR3 (Y373C). The antimyeloma activity of CHIR-258 was evaluated at doses that inhibited FGFR3 signaling in vivo in this FGFR3-driven animal model.
Results: Noninvasive bioluminescence imaging detected MM lesions in nearly all mice injected with KMS-11-luc cells, which were mainly localized in the spine, skull, and pelvis, resulting in frequent development of paralysis. Daily oral administration of CHIR-258 at doses that inhibited FGFR3 signaling in KMS-11-luc tumors in vivo resulted in a significant inhibition of KMS-11-luc tumor growth, which translated into a significant improvement in animal survival.
Conclusions: Our data provide a relevant preclinical basis for clinical trials of CHIR-258 in FGFR3-positive MM patients.
SOCS up-regulation mobilizes autologous stem cells through CXCR4 blockade
Authors: Pello Oscar M. , del Carmen Moreno-Ortiz María , Rodríguez-Frade José Miguel , Martínez-Muñoz Laura , Lucas Daniel , Gómez Lucio , Lucas Pilar , Samper Enrique , Aracil Miguel , Martínez-A Carlos , Bernad Antonio , Mellado Mario 
Published: August 2006

AbstractThe chemokine CXCL12 influences self-renewal and differentiation of hematopoietic stem cell precursors in bone marrow by directing them toward specific stromalcell components. CXCL12 up-regulates members of the SOCS family through JAK/STAT activation, a mechanism that attenuates chemokine responses. SOCS expression may thus modulate retention of hematopoietic precursors (Sca-1+ c-Kit+Lin– cells) in bone marrow. We show that in bovine growth hormone transgenic mice and in growth hormone–treated mice, SOCS up-regulation correlated with a large number of Sca-1+ c-Kit+Lin– cells in blood. Retroviral transduction of SOCSs blocked in vitro migration of Sca-1+c-Kit+Lin– cells, as well as their capacity to reconstitute lethally irradiated mice. Furthermore, in lethally irradiated mice reconstituted with bone marrow infected by a tetracycline-regulated, SOCS-expressing lentiviral vector, doxycycline treatment promoted rapid, extensive precursor mobilization to the periphery. The results indicate that by blocking CXCR4-mediated functions, SOCSs modulate hematopoietic precursor cell retention in bone marrow, and suggest the therapeutic interest of SOCS manipulation in several pathologic situations.
Antigen recognition induces phosphatidylserine exposure on the cell surface of human CD8+ T cells
Authors: Fischer Karin , Voelkl Simon , Berger Jana , Andreesen Reinhard , Pomorski Thomas , Mackensen Andreas 
Published: August 2006

AbstractIn eukaryotic cells the phospholipid phosphatidylserine (PS) is restricted to the inner plasma-membrane leaflet. This lipid asymmetry, which is maintained by the concerted action of phospholipid transport proteins, is mainly lost during apoptosis. Here, we demonstrate that primary human CD8+ cytotoxic T lymphocytes (CTLs) expose PS on T-cell receptor (TCR)–mediated antigen (Ag) recognition. In contrast to PS externalization on apoptotic cells, activation-induced PS exposure is less pronounced and reversible. Fluorescence microscopic analysis revealed that PS is distributed nonhomogenously over the plasma membrane and concentrated in membrane lipid raft domains at the immunologic synapse. By studying the activity of PS transport proteins using a fluorescence-labeled PS analogue, we found that activation of CTLs inhibited the flippase-mediated inward-directed PS transport without affecting the outward transport. Shielding of exposed PS by annexin V protein during Ag recognition diminished cytokine secretion, activation, and cell-to-cell clustering of Ag-specific CTLs. In summary, our data demonstrate for the first time that externalized PS on Ag-stimulated CTLs is linked to T-cell activation and probably involved in cell-to-cell contact formation at the immunologic synapse.
Histone deacetylase inhibitors increase virus gene expression but decrease CD8+ cell antiviral function in HTLV-1 infection
Authors: Mosley Angelina Jane , Meekings Kiran N. , McCarthy Corinna , Shepherd Dawn , Cerundolo Vincenzo , Mazitschek Ralph , Tanaka Yuetsu , Taylor Graham P. , Bangham Charles R. 
Published: August 2006

AbstractThe dynamics of human T-lymphotropic virus type-1 (HTLV-1) provirus expression in vivo are unknown. There is much evidence to suggest that HTLV-1 gene expression is restricted: this restricted gene expression may contribute to HTLV-1 persistence by limiting the ability of the HTLV-1–specific CD8+ cell immune response to clear infected cells. In this study, we tested the hypothesis that derepression of HTLV-1 gene expression would allow an increase in CD8+ cell–mediated lysis of HTLV-1–infected cells. Using histone deacetylase enzyme inhibitors (HDIs) to hyperacetylate histones and increase HTLV-1 gene expression, we found that HDIs doubled Tax expression in naturally infected lymphocytes after overnight culture. However, the rate of CD8+ cell–mediated lysis of Tax-expressing cells ex vivo was halved. HDIs appeared to inhibit the CD8+ cell–mediated lytic process itself, indicating a role for the microtubule-associated HDAC6 enzyme. These observations indicate that HDIs may reduce the efficiency of cytotoxic T-cell (CTL) surveillance of HTLV-1 in vivo. The impact of HDIs on HTLV-1 proviral load in vivo cannot be accurately predicted because of the widespread effects of these drugs on cellular processes; we therefore recommend caution in the use of HDIs in nonmalignant cases of HTLV-1 infection.
H-NS controls metabolism and stress tolerance in Escherichia coli O157:H7 that influence mouse passage
Authors: Erol Irfan , Jeong Kwang-Cheol , Baumler David J , Vykhodets Boris , Ho Choi Sang , Kaspar Charles W 
Published: August 2006

Abstract

Background
H-NS is a DNA-binding protein with central roles in gene regulation and nucleoid structuring in Escherichia coli. There are over 60 genes that are influenced by H-NS many of which are involved in metabolism. To determine the significance of H-NS-regulated genes in metabolism and stress tolerance, an hns mutant of E. coli O157:H7 was generated (hns::nptI, FRIK47001P) and its growth, metabolism, and gastrointestinal passage compared to the parent strain (43895) and strain FRIK47001P harboring pSC0061 which contains a functional hns and 90-bp upstream of the open-reading frame.

Results
The hns mutant grew slower and was non-motile in comparison to the parent strain. Carbon and nitrogen metabolism was significantly altered in the hns mutant, which was incapable of utilizing 42 carbon, and 19 nitrogen sources that the parent strain metabolized. Among the non-metabolized substrates were several amino acids, organic acids, and key metabolic intermediates (i.e., pyruvate) that limit carbon acquisition and energy generation. Growth studies determined that the parent strain grew in LB containing 14 to 15% bile or bile salts, while the hns mutant grew in 6.5 and 9% of these compounds, respectively. Conversely, log-phase cells of the hns mutant were significantly (p < 0.05) more acid tolerant than the parent strain and hns mutant complemented with pSC0061. In mouse passage studies, the parent strain was recovered at a higher frequency (p < 0.01) than the hns mutant regardless of whether log- or stationary-phase phase cells were orally administered.

Conclusion
These results demonstrate that H-NS is a powerful regulator of carbon and nitrogen metabolism as well as tolerance to bile salts. It is likely that the metabolic impairments and/or the reduced bile tolerance of the E. coli O157:H7 hns mutant decreased its ability to survive passage through mice. Collectively, these results expand the influence of H-NS on carbon and nitrogen metabolism and highlight its role in the ability of O157:H7 strains to respond to changing nutrients and conditions encountered in the environment and its hosts.
Chemical resistance of the gram-negative bacteria to different sanitizers in a water purification system
Authors: Mazzola Priscila G , Martins Alzira MS , Penna Thereza CV 
Published: August 2006

Abstract

Background
Purified water for pharmaceutical purposes must be free of microbial contamination and pyrogens. Even with the additional sanitary and disinfecting treatments applied to the system (sequential operational stages), Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas alcaligenes, Pseudomonas picketti, Flavobacterium aureum, Acinetobacter lowffi and Pseudomonas diminuta were isolated and identified from a thirteen-stage purification system. To evaluate the efficacy of the chemical agents used in the disinfecting process along with those used to adjust chemical characteristics of the system, over the identified bacteria, the kinetic parameter of killing time (D-value) necessary to inactivate 90% of the initial bioburden (decimal reduction time) was experimentally determined.

Methods

Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas alcaligenes, Pseudomonas picketti, Flavobacterium aureum, Acinetobacter lowffi and Pseudomonas diminuta were called in house (wild) bacteria. Pseudomonas diminuta ATCC 11568, Pseudomonas alcaligenes INCQS , Pseudomonas aeruginosa ATCC 15442, Pseudomonas fluorescens ATCC 3178, Pseudomonas picketti ATCC 5031, Bacillus subtilis ATCC 937 and Escherichia coli ATCC 25922 were used as 'standard' bacteria to evaluate resistance at 25°C against either 0.5% citric acid, 0.5% hydrochloric acid, 70% ethanol, 0.5% sodium bisulfite, 0.4% sodium hydroxide, 0.5% sodium hypochlorite, or a mixture of 2.2% hydrogen peroxide (H2O2) and 0.45% peracetic acid.

Results
The efficacy of the sanitizers varied with concentration and contact time to reduce decimal logarithmic (log10) population (n cycles). To kill 90% of the initial population (or one log10 cycle), the necessary time (D-value) was for P. aeruginosa into: (i) 0.5% citric acid, D = 3.8 min; (ii) 0.5% hydrochloric acid, D = 6.9 min; (iii) 70% ethanol, D = 9.7 min; (iv) 0.5% sodium bisulfite, D = 5.3 min; (v) 0.4% sodium hydroxide, D = 14.2 min; (vi) 0.5% sodium hypochlorite, D = 7.9 min; (vii) mixture of hydrogen peroxide (2.2%) plus peracetic acid (0.45%), D = 5.5 min.

Conclusion
The contact time of 180 min of the system with the mixture of H2O2+ peracetic acid, a total theoretical reduction of 6 log10 cycles was attained in the water purified storage tank and distribution loop. The contact time between the water purification system (WPS) and the sanitary agents should be reviewed to reach sufficient bioburden reduction (over 6 log10).