bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid and Simple Method for Detecting the Toxin B Gene of
Clostridium difficile
in Stool Specimens by Loop-Mediated Isothermal Amplification
Authors: Kato Haru , Yokoyama Toshiyuki , Kato Hideaki , Arakawa Yoshichika 
Published: December 2005

ABSTRACT

We applied the loop-mediated isothermal amplification (LAMP) assay to the detection of the toxin B gene (
tcdB
) of
Clostridium difficile
for identification of toxin B (TcdB)-positive
C. difficile
strains and detection of
tcdB
in stool specimens.
tcdB
was detected in all toxin A (TcdA)-positive, TcdB-positive (A
+
B
+
) and TcdA-negative, TcdB-positive (A
−
B
+
)
C. difficile
strains but not from TcdA-negative, TcdB-negative strains. Of the 74 stool specimens examined, A
+
B
+
or A
−
B
+
C. difficile
was recovered from 39 specimens, of which 38 specimens were LAMP positive and one was negative. Amplification was obtained in 10 specimens that were culture negative, indicating that LAMP is highly sensitive. The LAMP assay was applied to detection of
tcdB
in DNA extracted by a simple boiling method from 47 of those 74 specimens, which were cultured overnight in cooked-meat medium (CMM). Twenty-two of 24 culture-positive specimens were positive for LAMP on DNA from the culture in CMM. Four specimens were culture negative but positive by LAMP on DNA from CMM cultures. The LAMP assay is a reliable tool for identification of TcdB-positive
C. difficile
as well as for direct detection of
tcdB
in stool specimens with high sensitivity. Detection of
tcdB
by LAMP from overnight cultures in CMM could be an alternative method of diagnostic testing at clinical laboratories without special apparatus.
Association between Cellular Human Immunodeficiency Virus DNA Level and Immunological Parameters in Patients with Undetectable Plasma Viremia Level during Highly Active Antiretroviral Therapy
Authors: Sarmati Loredana , Parisi Saverio Giuseppe , Nicastri Emanuele , d'Ettorre Gabriella , Palmisano Lucia , Andreotti Mauro , Andreoni Carolina , Giuliano Marina , Gatti Francesca , Boldrin Caterina , Palù Giorgio , Vullo Vincenzo , Vella Stefano , Andreoni Massimo 
Published: December 2005

ABSTRACT

The association between human immunodeficiency virus (HIV) DNA load and immunologic parameters was investigated in 163 HIV-infected patients with undetectable plasma viremia during highly active antiretroviral therapy (HAART). Patients with HIV DNA below the 25th percentile (133 copies/10
6
peripheral blood mononuclear cells) had higher pre-HAART (
P
= 0.001) and current (
P
= 0.005) CD4 counts and a prolonged duration of treatment (
P
= 0.001). At adjusted analysis, prolonged duration of treatment was independently associated with lower (
P
= 0.006) and undetectable (
P
< 0.001) HIV DNA values.
Life-Threatening Invasive
Helcococcus kunzii
Infections in Intravenous-Drug Users and
ermA
-Mediated Erythromycin Resistance
Authors: Woo Patrick C. Y. , Tse Herman , Wong Samson S. Y. , Tse Cindy W. S. , Fung Ami M. Y. , Tam Dorothy M. W. , Lau Susanna K. P. , Yuen Kwok-yung 
Published: December 2005

ABSTRACT

We report the first two cases of life-threatening invasive
Helcococcus kunzii
infection, with primary bacteremia and empyema thoracis, respectively. Gram smears of both
H. kunzii
isolates showed a mixture of gram-positive and gram-negative cocci. The isolate from the first patient, resistant to erythromycin and clindamycin, possessed an
ermA
gene.
Correction of Defective Interdomain Interaction Within Ryanodine Receptor by Antioxidant Is a New Therapeutic Strategy Against Heart Failure
Authors: Yano Masafumi , Okuda Shinichi , Oda Tetsuro , Tokuhisa Takahiro , Tateishi Hiroki , Mochizuki Mamoru , Noma Toshiyuki , Doi Masahiro , Kobayashi Shigeki , Yamamoto Takeshi , Ikeda Yasuhiro , Ohkusa Tomoko , Ikemoto Noriaki , Matsuzaki Masunori 
Published: December 2005

Background—Defective interdomain interaction within the ryanodine receptor (RyR2) seems to play a key role in the pathogenesis of heart failure, as shown in recent studies. In the present study we investigated the effect of oxidative stress on the interdomain interaction, its outcome in the cardiac function in heart failure, and the possibility of preventing the problem with antioxidants.Methods and Results—Sarcoplasmic reticulum (SR) vesicles were isolated from dog left ventricular (LV) muscle (normal or rapid ventricular pacing for 4 weeks with or without the antioxidant edaravone). In the edaravone-treated paced dogs (EV+), but not in the untreated paced dogs (EV−), normal cardiac function was restored almost completely. In the SR vesicles isolated from the EV−, oxidative stress of the RyR2 (reduction in the number of free thiols) was severe, but it was negligible in EV+. The oxidative stress of the RyR2 destabilized interdomain interactions within the RyR2 (EV−), but its effect was reversed in EV+. Abnormal Ca2+leak through the RyR2 was found in EV− but not in EV+. The amount of the RyR2-bound FKBP12.6 was less in EV− than in normal dogs, whereas it was restored almost to a normal amount in EV+. The NO donor 3-morpholinosydnonimine (SIN-1) reproduced, in normal SR, several abnormal features seen in failing SR, such as defective interdomain interaction and abnormal Ca2+leak. Both cell shortening and Ca2+transients were impaired by SIN-1 in isolated normal myocytes, mimicking the pathophysiological conditions in failing myocytes. Incubation of failing myocytes with edaravone restored the normal properties.Conclusions—During the development of heart failure, edaravone ameliorated the defective interdomain interaction of the RyR2. This prevented Ca2+leak and LV remodeling, leading to an improvement of cardiac function and an attenuation of LV remodeling.
Between Tolerance and Intolerance in Medieval Spain: An Historiographic Enigma
Authors: Novikoff Alex 
Published: December 2005

AbstractThe nature of what has been termed "tolerance" and "intolerance" in the historiography of medieval Iberia has, while rarely defined, continued to provide much-employed organizing categories for the field. This paper reviews one focus of that historiography from the nineteenth into the twenty-first century: the relations among Muslims, Jews, and Christians, with respect to tolerance/intolerance and related categories (notably, convivencia). It analyzes, among other factors, the impact on this historiography of the intellectual, cultural, and political movements which have affected historians of medieval Iberia. It makes a case for the importance for specialists in the field to be keenly aware of these aspects of historiography at a time when medieval Spain is seen as offering a unique opportunity for testing theories of interfaith relations and social interaction
Precipitation Shifts over Western North America as a Result of Declining Arctic Sea Ice Cover: The Coupled System Response
Authors: Sewall Jacob O. 
Published: December 2005

Abstract
Changes in Arctic sea ice cover have the potential to impact midlatitude climate. A previous sensitivity study utilizing the National Center for Atmospheric Research’s (NCAR) atmospheric general circulation model [AGCM; Community Climate Model, version 3 (CCM3)] to explore climate sensitivity to declining Arctic sea ice cover suggested that, as Arctic sea ice cover is reduced, precipitation patterns over western North America will shift toward dryer conditions in southwestern North America and wetter conditions in northwestern North America. Here, three complementary lines of research validate and explore the robustness of this possible climate change impact: 1) repetition of the previous sensitivity study (specified constant Arctic sea ice cover and atmospheric CO2) with an updated version of the NCAR AGCM [third Community Atmosphere Model (CAM3)], 2) investigation of the climate response to dynamically reduced Arctic sea ice cover (driven by a quadrupling of atmospheric CO2) in the coupled NCAR Community Climate System Model (CCSMv3), and 3) analysis of similar results from six other coupled climate system models. Results from the CAM3 sensitivity study are similar to those from the original study with declining Arctic sea ice cover driving up to 25% less mean annual precipitation (MAP) over southwestern North America and up to an 8% increase in MAP over northwestern North America. The seven coupled models also reproduce this same general pattern. At the time of CO2 quadrupling, Arctic sea ice cover is reduced (up to 90% in boreal winter) and MAP over southwestern North America decreases by up to 30% while MAP in northwestern North America increases by up to 40%. These results represent a significant shift in the precipitation pattern over western North America and support the findings of the original sensitivity study in suggesting that, as future reductions in Arctic sea ice cover take place, there will be a substantial impact on water resources in western North America.
Clinical Experience With Intravenous and Oral Formulations of the Novel Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid in Patients With Advanced Hematologic Malignancies
Authors: O'Connor Owen A. , Heaney Mark L. , Schwartz Lawrence , Richardson Stacie , Willim Robert , MacGregor-Cortelli Barbara , Curly Tracey , Moskowitz Craig , Portlock Carol , Horwitz Steven , Zelenetz Andrew D. , Frankel Stanley , Richon Victoria , Marks Paul , Kelly William K. 
Published: December 2005

Purpose To document the toxicity and activity of the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) in patients with pretreated hematologic malignancies. Patients and Methods Two formulations of SAHA (intravenous [IV] and oral) have been assessed in two consecutive phase I trials. In both trials, dose escalation was performed in parallel and independently in patients with solid tumors and hematologic malignancies. Eligible patients were required to have adequate hepatic and renal function, an absolute neutrophil count ≥ 500/μL and a platelet count more than 25,000/mL. All patients provided informed consent for study inclusion. Results A total of 39 patients with hematologic malignancy were enrolled (14 on IV SAHA and 25 on oral SAHA), of whom 35 were treated. The spectrum of diseases included patients with diffuse large B-cell lymphoma (n = 12), Hodgkin's disease (HD; n = 12), multiple myeloma (n = 2), T-cell lymphoma (n = 3), mantle cell lymphoma (n = 2), small lymphocytic lymphoma (n = 2), and myeloid leukemia (n = 2). Major adverse events with the oral formulation included fatigue, diarrhea, anorexia, and dehydration, whereas myelosuppression and thrombocytopenia were more prominent with the IV formulation. Typically, the hematologic toxicities resolved shortly after SAHA was stopped. There was no neutropenic fever or neutropenic sepsis. Reduction in measurable tumor was observed in five patients. One patient with transformed small lymphocytic lymphoma met criteria for complete response, whereas another met the criteria for partial response (PR). One patient with refractory HD had a PR, whereas three patients had stable disease for up to 9 months. Conclusion These results suggest that SAHA has activity in hematologic malignancies including HD and select subtypes of non-Hodgkin's lymphoma.
Array-Based Comparative Genomic Hybridization Analysis Reveals Recurrent Chromosomal Alterations and Prognostic Parameters in Primary Cutaneous Large B-Cell Lymphoma
Authors: Dijkman Remco , Tensen Cornelis P. , Jordanova Ekaterina S. , Knijnenburg Jeroen , Hoefnagel Juliette J. , Mulder Aat A. , Rosenberg Carla , Raap Anton K. , Willemze Rein , Szuhai Károly , Vermeer Maarten H. 
Published: December 2005

Purpose To evaluate the clinical relevance of genomic aberrations in primary cutaneous large B-cell lymphoma (PCLBCL). Patients and Methods Skin biopsy samples of 31 patients with a PCLBCL classified as either primary cutaneous follicle center lymphoma (PCFCL; n = 19) or PCLBCL, leg type (n = 12), according to the WHO–European Organisation for Research and Treatment of Cancer (EORTC) classification, were investigated using array-based comparative genomic hybridization, fluorescence in situ hybridization (FISH), and examination of promoter hypermethylation. Results The most recurrent alterations in PCFCL were high-level DNA amplifications at 2p16.1 (63%) and deletion of chromosome 14q32.33 (68%). FISH analysis confirmed c-REL amplification in patients with gains at 2p16.1. In PCLBCL, leg type, most prominent aberrations were a high-level DNA amplification of 18q21.31-q21.33 (67%), including the BCL-2 and MALT1 genes as confirmed by FISH, and deletions of a small region within 9p21.3 containing the CDKN2A, CDKN2B, and NSG-x genes. Homozygous deletion of 9p21.3 was detected in five of 12 patients with PCLBCL, leg type, but in zero of 19 patients with PCFCL. Complete methylation of the promoter region of the CDKN2A gene was demonstrated in one PCLBCL, leg type, patient with hemizygous deletion, in one patient without deletion, but in zero of 19 patients with PCFCL. Seven of seven PCLBCL, leg type, patients with deletion of 9p21.3 and/or complete methylation of CDKN2A died as a result of their lymphoma. Conclusion Our results demonstrate prominent differences in chromosomal alterations between PCFCL and PCLBCL, leg type, that support their classification as separate entities within the WHO-EORTC scheme. Inactivation of CDKN2A by either deletion or methylation of its promoter could be an important prognostic parameter for the group of PCLBCL, leg type.
Evaluation of Two Phosphorylation Sites Improves the Prognostic Significance of Akt Activation in Non–Small-Cell Lung Cancer Tumors
Authors: Tsurutani Junji , Fukuoka Junya , Tsurutani Hiroko , Shih Joanna H. , Hewitt Stephen M. , Travis William D. , Jen Jin , Dennis Phillip A. 
Published: December 2005

Purpose Akt is a serine/threonine kinase that has been implicated in lung tumorigenesis and lung cancer therapeutic resistance. Full activation of Akt requires two phosphorylation events, but only one site of phosphorylation (S473) has been evaluated thus far in clinical non–small-cell lung cancer (NSCLC) specimens, which has resulted in conflicting results regarding the prognostic significance of Akt activation in NSCLC. In this study, we sought to determine whether evaluation of Akt phosphorylation at T308 would improve prognostic accuracy. Patients and Methods Phosphospecific antibodies against T308 and S473 were validated and used in an immunohistochemical analysis of tissue microarray slides containing NSCLC specimens (n = 300) and surrounding lung tissue specimens (n = 100). Results Phosphorylation of either S473 or T308 was positive in most NSCSLC specimens, but was detected rarely in surrounding normal tissues. When Akt activation was defined by using both sites of phosphorylation, Akt activation was specific for NSCLC tumors versus surrounding tissue (73.4% v 0%; P < .05), was higher in adenocarcinoma than in squamous cell carcinoma (78.1% v 68.5%; P = .040), and was associated with shorter overall survival for all stages of disease (log-rank P = .041). In multivariate analyses, increased phosphorylation of T308 alone was a poor prognostic factor for stage I patients or for tumors < 5 cm (log-rank P = .011 and P = .015, respectively). Conclusion These results suggest that monitoring phosphorylation of Akt at T308 improves the assessment of Akt activation, and show that Akt activation is a poor prognostic factor for all stages of NSCLC.
Impact of the Year 2000 Medicare Policy Change on Older Patient Enrollment to Cancer Clinical Trials
Authors: Unger Joseph M. , Coltman Charles A. , Crowley John J. , Hutchins Laura F. , Martino Silvana , Livingston Robert B. , Macdonald John S. , Blanke Charles D. , Gandara David R. , Crawford E. David , Albain Kathy S. 
Published: December 2005

Purpose A prior analysis by the Southwest Oncology Group (SWOG) showed that women and African American patients were adequately represented on cancer clinical treatment trials but that older patients were substantially underrepresented. Twenty-five percent of patients ≥ 65 years old were enrolled onto SWOG trials from 1993 to 1996, whereas 63% of all patients with cancer were ≥ 65 years old. Recognition of this under-representation led to a change in Medicare policy in 2000 to include coverage of routine patient care costs of clinical trials. We conducted an updated analysis of accrual trends. Methods The proportions of enrollment onto SWOG treatment trials by sex, race/ethnicity, and age (≥ 65 years) were computed for the years 1997 to 2000; corresponding rates in the United States were derived from US Census and National Cancer Institute Surveillance, Epidemiology, and End Results data. Additionally, method of payment data were analyzed over time (1993 to 2003) to assess whether patterns in method of payment changed with the new Year 2000 Medicare policy on clinical trials coverage. Results The results showed continued adequate representation by sex and race/ethnicity. Older patient accrual on SWOG trials increased significantly since 2000, with 31% of patients ≥ 65 years old enrolled from 1997 to 2000 and 38% enrolled from 2001 to 2003 (v 25% from 1993 to 1996). The percentage of patients using Medicare plus supplemental insurance also increased beginning in 2000, whereas the percentage of patients using Medicare alone remained the same. Conclusion Method of payment analyses provided evidence that the Year 2000 Medicare policy change had a positive impact, but only for those patients with supplemental private coverage of coinsurance costs. Improvements in the Medicare payment structure could further increase older patient participation in clinical trials.
A Pilot Study of an Investigational Testosterone Transdermal Patch System in Young Women with Spontaneous Premature Ovarian Failure
Authors: Kalantaridou Sophia N. , Calis Karim A. , Mazer Norman A. , Godoy Heidy , Nelson Lawrence M. 
Published: December 2005

Context: Evidence suggests that young women with spontaneous premature ovarian failure (sPOF) have significantly lower androgen levels than age-matched regularly menstruating women.
Objective: The objective of the study was to evaluate an investigational testosterone transdermal patch (TTP) designed to deliver the normal ovarian production rate of testosterone.
Design: This was an open-label study (2-month baseline period followed by 2-month treatment period).
Patients: Nine women with sPOF and a history of regular bleeding patterns on standard estrogen/progestogen cyclic treatment participated in the study. One subject with abnormal baseline levels was excluded.
Intervention: Four consecutive 28-d cycles of transdermal estradiol (E2; 0.1 mg/d) and sequential oral medroxyprogesterone acetate (MPA; 10 mg/d for the last 12 d of each cycle). During cycles 3 and 4, an investigational TTP (nominal delivery 150 μg/d) was applied twice weekly to the abdomen.
Main Outcome Measures: Steady-state pharmacokinetic profiles of free and total testosterone and scheduled vaginal bleeding patterns were studied.
Results: The mean (95% confidence interval) of the time-average free testosterone levels during TTP treatment was 7.5 (4.9–9.9) pg/ml; 26.0 (17.2–34.6) pmol/liter (with E2), and 6.9 (4.9–8.8) pg/ml; 23.9 (17.2–30.5) pmol/liter (with E2 and MPA). The confidence intervals of the means include the upper limit of normal for premenopausal women, i.e. 6.8 pg/ml (23.5 pmol/liter), although the mean values are slightly above this.
Conclusions: The addition of TTP to cyclic E2/MPA therapy in women with sPOF produced mean free testosterone levels that approximate the upper limit of normal. A 3-yr study to assess safety and effectiveness in this population is in progress.
Thyroid Hormone Concentrations, Disease, Physical Function, and Mortality in Elderly Men
Authors: van den Beld Annewieke W. , Visser Theo J. , Feelders Richard A. , Grobbee Diederick E. , Lamberts Steven W. J. 
Published: December 2005

Context: Physiological changes in thyroid hormone concentrations might be related to changes in the overall physical function in the elderly.
Objective: We determined to what extent thyroid hormone concentrations are related to physical function and mortality in elderly men.
Design: A longitudinal population study (the Zoetermeer study) was conducted. Mortality was registered in the subsequent 4 yr.
Participants: Four hundred three independently and ambulatory living men (aged 73–94 yr) participated.
Main Outcome Measures: The study examined the association between serum thyroid hormones and parameters of physical function as well as the association with mortality.
Methods: TSH, free T4 (FT4) total T4, T3, rT3, and T4-binding globulin were measured. Physical function was estimated by the number of problems in activities of daily living, a measure of physical performance score (PPS), leg extensor strength and grip strength, bone density, and body composition.
Results: Serum rT3 increased significantly with age and the presence of disease. Sixty-three men met the biochemical criteria for the low T3 syndrome (decreased serum T3 and increased serum rT3). This was associated with a lower PPS, independent of disease. Furthermore, higher serum FT4 (within the normal range of healthy adults) and rT3 (above the normal range of healthy adults) were related with a lower grip strength and PPS, independent of age and disease. Isolated low T3 was associated with a better PPS and a higher lean body mass. Low FT4 was related to a decreased risk of 4-yr mortality.
Conclusions: In a population of independently living elderly men, higher FT4 and rT3 concentrations are associated with a lower physical function. High serum rT3 may result from a decreased peripheral metabolism of thyroid hormones due to the aging process itself and/or disease and may reflect a catabolic state. Low serum FT4 is associated with a better 4-yr survival; this may reflect an adaptive mechanism to prevent excessive catabolism.