bluuebunny/crossref_metadata_2025_split huggingface dataset:
GntR family of regulators in Mycobacterium smegmatis: a sequence and structure based characterization
Authors: Vindal Vaibhav , Suma Katta , Ranjan Akash 
Published: August 2007

Abstract

Background

Mycobacterium smegmatis is fast growing non-pathogenic mycobacteria. This organism has been widely used as a model organism to study the biology of other virulent and extremely slow growing species like Mycobacterium tuberculosis. Based on the homology of the N-terminal DNA binding domain, the recently sequenced genome of M. smegmatis has been shown to possess several putative GntR regulators. A striking characteristic feature of this family of regulators is that they possess a conserved N-terminal DNA binding domain and a diverse C-terminal domain involved in the effector binding and/or oligomerization. Since the physiological role of these regulators is critically dependent upon effector binding and operator sites, we have analysed and classified these regulators into their specific subfamilies and identified their potential binding sites.

Results
The sequence analysis of M. smegmatis putative GntRs has revealed that FadR, HutC, MocR and the YtrA-like regulators are encoded by 45, 8, 8 and 1 genes respectively. Further out of 45 FadR-like regulators, 19 were classified into the FadR group and 26 into the VanR group. All these proteins showed similar secondary structural elements specific to their respective subfamilies except MSMEG_3959, which showed additional secondary structural elements. Using the reciprocal BLAST searches, we further identified the orthologs of these regulators in Bacillus subtilis and other mycobacteria. Since the expression of many regulators is auto-regulatory, we have identified potential operator sites for a number of these GntR regulators by analyzing the upstream sequences.

Conclusion
This study helps in extending the annotation of M. smegmatis GntR proteins. It identifies the GntR regulators of M. smegmatis that could serve as a model for studying orthologous regulators from virulent as well as other saprophytic mycobacteria. This study also sheds some light on the nucleotide preferences in the target-motifs of GntRs thus providing important leads for initiating the experimental characterization of these proteins, construction of the gene regulatory network for these regulators and an understanding of the influence of these proteins on the physiology of the mycobacteria.
CHEK2 1100delC is prevalent in Swedish early onset familial breast cancer
Authors: Margolin Sara , Eiberg Hans , Lindblom Annika , Bisgaard Marie Luise 
Published: August 2007

Abstract

Background
A truncating variant, 1100delC, in check point-kinase CHEK2, has been identified as a risk factor for familial and sporadic breast cancer. The prevalence in healthy non-breast cancer cases is low and varies between populations.

Methods
We analyzed the prevalence of CHEK2 1100delC in 763 breast cancer patients with a defined family history and 760 controls from the Stockholm region. The breast cancer patients originated from; a population-based cohort (n = 452) and from a familial cancer clinic (n = 311), the detailed family history was known in both groups.

Results
The variant was found in 2.9% of the familial cases from the population-based cohort and in 1.9% from the familial cancer clinic. In total 2.2% of the patients with a family history of breast cancer carried the variant compared to 0.7% of the controls (p = 0.03). There was no increased prevalence in sporadic patients (0.3%). The variant was most frequent in young familial patients (5.1% of cases ≤45 years, p = 0.003). The mean age at diagnosis of variant carriers was 12 years lower than in non-carriers (p = 0.001).

Conclusion
In conclusion, CHEK2 1100delC exists in the Swedish population. The prevalence is increased in familial breast cancer and the variant seems to influence age at onset.
Healthcare in schizophrenia: effectiveness and progress of a redesigned care network
Authors: Tzeng Dong-Sheng , Lian Li-Chiu , Chang Chin-Un , Yang Chun-Yuh , Lee Gian-Tin , Pan Peter , Lung For-Wey 
Published: August 2007

Abstract

Background
The aim of this study was designed to investigate the care-effectiveness of different healthcare models for schizophrenic patients and the impact of it on caregivers.

Methods
Sample cases were randomly selected from southern Taiwan, 257 patients in redesigned care network, including a general hospital, a chronic ward, 10 outpatient clinics, and multialternative community programs, was compared to 247 patients in other traditional healthcare provider that were utilized as the control group. The quality of life (QOL) questionnaire and the Chinese health questionnaire (CHQ) were used.

Results
The controls had longer duration of illness (p = 0.001) and were older (p = 0.004). The average resource utilization in the study group (US$ 2737/year, per case) was higher than the control group (US$ 2041) (t = 7.91, p < 0.001). For the study group, the average length of stay was shorter, but the admission rate was higher. The QOL of the patients in the study group was better than that of the controls (p = 0.01). The family burden of the study group was lower (p = 0.035) and the score of general health questionnaire higher (p = 0.019).

Conclusion
We found that patients in the redesigned care network had a better QOL, lower family burden, decreased days of hospital stay, higher medical resource utilization and less frequent admission to a hospital, and the caregivers had better mental health. Although the costs were higher, the continued care network was more helpful in providing comprehensive mental illness services.
Patient, informal caregiver and care provider acceptance of a hospital in the home program in Ontario, Canada
Authors: Lemelin Jacques , Hogg William E , Dahrouge Simone , Armstrong Catherine Deri , Martin Carmel M , Zhang Wei , Dusseault Jo-Anne , Parsons-Nicota Joy , Saginur Raphael , Viner Gary 
Published: August 2007

Abstract

Background
Hospital in the home programs have been implemented in several countries and have been shown to be safe substitutions (alternatives) to in-patient hospitalization. These programs may offer a solution to the increasing demands made on tertiary care facilities and to surge capacity. We investigated the acceptance of this type of care provision with nurse practitioners as the designated principal home care providers in a family medicine program in a large Canadian urban setting.

Methods
Patients requiring hospitalization to the family medicine service ward, for any diagnosis, who met selection criteria, were invited to enter the hospital in the home program as an alternative to admission. Participants in the hospital in the home program, their caregivers, and the physicians responsible for their care were surveyed about their perceptions of the program. Nurse practitioners, who provided care, were surveyed and interviewed.

Results
Ten percent (104) of admissions to the ward were screened, and 37 patients participated in 44 home hospital admissions. Twenty nine patient, 17 caregiver and 38 provider surveys were completed. Most patients (88%–100%) and caregivers (92%–100%) reported high satisfaction levels with various aspects of health service delivery. However, a significant proportion in both groups stated that they would select to be treated in-hospital should the need arise again. This was usually due to fears about the safety of the program. Physicians (98%–100%) and nurse practitioners also rated the program highly. The program had virtually no negative impact on the physician workload. However nurse practitioners felt that the program did not utilize their full expertise.

Conclusion
Provision of hospital level care in the home is well received by patients, their caregivers and health care providers. As a new program, investment in patient education about program safety may be necessary to ensure its long term success. A small proportion of hospital admissions were screened for this program. Appropriate dissemination of program information to family physicians should help buy-in and participation. Nurse practitioners' skills may not be optimally utilized in this setting.
Genomic and proteomic profiling I: Leiomyomas in African Americans and Caucasians
Authors: Pan Qun , Luo Xiaoping , Chegini Nasser 
Published: August 2007

Abstract

Background
Clinical observations indicate that leiomyomas occur more frequently in African Americans compared to other ethnic groups with unknown etiology. To identify the molecular basis for the difference we compared leiomyomas form A. Americans with Caucasians using genomic and proteomic strategies.

Methods
Microarray, realtime PCR, 2D-PAGE, mass spectrometry, Western blotting and immunohistochemistry.

Results
Using Affymetrix U133A array and analysis based on P ranking (P < 0.01) 1470 genes were identified as differentially expressed in leiomyomas compared to myometrium regardless of ethnicity. Of these, 268 genes were either over-expressed (177 genes) or under-expressed (91 genes) based on P < 0.01 followed by 2-fold cutoff selection in leiomyomas of A. Americans as compared to Caucasians. Among them, the expression E2F1, RUNX3, EGR3, TBPIP, ECM2, ESM1, THBS1, GAS1, ADAM17, CST6, CST7, FBLN5, ICAM2, EDN1 and COL18 was validated using realtime PCR low-density arrays. 2D PAGE coupled with image analysis identified 332 protein spots of which the density/volume of 31 varied by greater than or equal to 1.5 fold in leiomyomas as compared to myometrium. The density/volume of 34 protein-spots varied by greater than or equal to 1.5 fold (26 increased and 8 decreased) in leiomyomas of A. Americans as compared to Caucasians. Tandem mass spectrometric analysis of 15 protein spots identified several proteins whose transcripts were also identified by microarray, including 14-3-3 beta and mimecan, whose expression was confirmed using western blotting and immunohistochemistry.

Conclusion
These findings imply that the level rather than the ethnic-specific expression of a number of genes and proteins may account for the difference between leiomyomas and possibly myometrium, in A. Americans and Caucasians. Further study using larger sample size is required to confirm these findings.
FCGR2A and FCGR3A Polymorphisms Associated With Clinical Outcome of Epidermal Growth Factor Receptor–Expressing Metastatic Colorectal Cancer Patients Treated With Single-Agent Cetuximab
Authors: Zhang Wu , Gordon Michael , Schultheis Anne M. , Yang Dong Yun , Nagashima Fumio , Azuma Mizutomo , Chang Heung-Moon , Borucka Eva , Lurje Georg , Sherrod Andy E. , Iqbal Syma , Groshen Susan , Lenz Heinz-Josef 
Published: August 2007

PurposeCetuximab, a chimeric immunoglobulin G 1 (IgG1) anti–epidermal growth factor receptor (EGFR) monoclonal antibody (mAb), has shown efficacy in 10% of patients with metastatic colorectal cancer (CRC). Recent studies demonstrate antibody-dependent cell-mediated cytotoxicity (ADCC) is one of the modes of action for rituximab and trastuzumab. Fragment c (Fc) portion of IgG1 mAb has shown to induce ADCC. Fragment c gamma receptors (FcγR) play an important role in initiating ADCC. Studies have shown that two IgG FcγR polymorphisms (FCGR2A-H131R and FCGR3A-V158F) independently predict response to rituximab in patients with follicular lymphoma. We tested the hypothesis of whether these two polymorphisms are associated with clinical outcome in metastatic CRC patients treated with single-agent cetuximab.Patients and MethodsThirty-nine metastatic CRC patients were enrolled onto the ImClone0144 trial. Using an allele-specific polymerase chain reaction (PCR) –based method, gene polymorphisms of FCGA2A-H131R and FCGA3A-V158F were assessed from genomic DNA extracted from peripheral blood samples.ResultsFCGR2A-H131R and FCGR3A-V158F polymorphisms were independently associated with progression-free survival (PFS; P = .037 and .055, respectively; log-rank test). Combined analysis of these two polymorphisms showed that patients with the favorable genotypes (FCGR2A, any histidine allele, and FCGR3A, any phenylalanine allele) showed a median PFS of 3.7 months (95% CI, 2.4 to 4.4 months), whereas patients with any two unfavorable genotypes (FCGR2A arginine/arginine or valine/valine) had a PFS of 1.1 months (95% CI, 1.0 to 1.4 months; P = .004; log-rank test).ConclusionOur preliminary data suggest that these two polymorphisms may be useful molecular markers to predict clinical outcome in metastatic CRC patients treated with cetuximab and that they may indicate a role of ADCC of cetuximab.
Noninvasive Evaluation of Late Anthracycline Cardiac Toxicity in Childhood Cancer Survivors
Authors: Hudson Melissa M. , Rai Shesh N. , Nunez Cesar , Merchant Thomas E. , Marina Neyssa M. , Zalamea Nia , Cox Cheryl , Phipps Sean , Pompeu Ronald , Rosenthal David 
Published: August 2007

Purpose Childhood cancer survivors treated with anthracyclines and cardiac radiation are at risk for late-onset cardiotoxicity. The purpose of this study was to delineate the relationship between clinical factors and abnormalities of noninvasive cardiac testing (NICT). Patients and Methods Participants were recruited from a long-term follow-up clinic. Study measures comprised physical examination, laboratory evaluation, echocardiogram, and ECG. Mean fractional shortening (FS) and afterload were compared for survivors who did (at risk [AR]) and did not (no risk [NR]) receive potentially cardiotoxic modalities, and with values expected for comparable age- and sex-matched controls. Results The 278 study participants (mean age, 18.1 years; median age, 16.8 years; range, 7.5 to 39.7 years) included 223 survivors AR for cardiotoxicity after treatment with anthracyclines (median dose ± standard deviation [SD], 202 ± 109 mg/m2) and/or cardiac radiation. Mean FS (± SD) was lower for AR (0.33 ± 0.06) compared with NR survivors (0.36 ± 0.05; P = .004) and normative controls (0.36 ± 0.04; P < .001). Mean afterload (± SD) was higher for AR (58 ± 21 g/cm2) compared with NR survivors (46 ± 15 g/cm2; P < .001) and normative controls (48 ± 13 g/cm2; P < .001). The distribution of FS and afterload among NR survivors did not differ from that of controls. After adjustment for age group at diagnosis and time since completion of therapy, anthracycline dose predicted decline in distribution of FS (P < .001) and increase in distribution of afterload (P < .001). Treatment with anthracycline doses ≥ 100 mg/m2 increased the risk of abnormal NICT; survivors who received ≥ 270 mg/m2 had a 4.5-fold excess risk of abnormal NICT (95% CI, 2.1 to 9.6) compared with controls. Conclusion Childhood cancer survivors treated with anthracycline doses ≥ 270 mg/m2 are at greatest risk for abnormalities of FS and afterload.
Phase I and Pharmacokinetic Study of Lapatinib in Combination With Capecitabine in Patients With Advanced Solid Malignancies
Authors: Chu Quincy S.C. , Schwartz Garry , de Bono Johann , Smith Deborah A. , Koch Kevin M. , Versola Melissa J. , Pandite Lini , Arya Nikita , Curtright Jan , Fleming Ronald A. , Ho Peter T.C. , Rowinsky Eric K. 
Published: August 2007

Purpose This phase I trial ( EGF10005 ) assessed the safety, optimally tolerated regimen (OTR), and pharmacokinetics of lapatinib and capecitabine in combination in patients with advanced solid malignancies. Patients and Methods Patients with previously treated, advanced solid malignancies were eligible. Cohorts of at least three patients each received once-daily oral lapatinib (continuous) and capecitabine (twice daily for 14 days every 21 days). Doses of lapatinib and capecitabine were escalated based on dose-limiting toxicities in the first treatment cycle until the OTR was reached. Additional patients were treated at the OTR dose level to further evaluate safety and for pharmacokinetic analyses. Results Forty-five patients were treated in the study. The OTR was determined to be lapatinib 1,250 mg/d plus capecitabine 2,000 mg/m2/d. The majority of drug-related adverse events were grade 1 to grade 2 in severity, with few grade 3 and no grade 4 toxicities. The most common drug-related toxicities (> 15% of patients) were diarrhea, nausea, rash, palmar-plantar erythrodysesthesia, mucositis, vomiting, and stomatitis. There were four confirmed responses (one complete response and three partial responses). The pharmacokinetics (area under the curve and maximum concentration) of lapatinib, capecitabine and its metabolites, fluorouracil, and α-fluoro-β-alanine, were not meaningfully altered by coadministration. Conclusion Lapatinib and capecitabine administered on a 3-week schedule were well tolerated, and no pharmacokinetic interaction was observed. Clinical activity was observed in patients with previously treated, advanced solid malignancies.
Trastuzumab and Metastatic Breast Cancer: Trastuzumab Use in Australia—Monitoring the Effect of an Expensive Medicine Access Program
Authors: Pearson Sallie-Anne , Ringland Clare L. , Ward Robyn L. 
Published: August 2007

PurposeData from clinical trials are used for drug registration; however, many cancer medicines are ultimately used off-label. This study examines the extent to which the clinical practice use of trastuzumab for the treatment of metastatic breast cancer differs from its use under trial conditions.MethodsThis study involved all women (N = 1,469) with metastatic breast cancer who received trastuzumab in Australia between December 2001 and March 2005. Given that Australia operates a universal health care system, administrative databases could be examined to determine the duration of therapy, rate of off-label use, compliance with cardiac monitoring, and the extent of drug wastage (volume and cost).ResultsA total of 433 enrollees (29.5%) received trastuzumab as monotherapy and 1,036 enrollees (70.5%) received the drug in combination with chemotherapy. A total of 321 women (22%) received off-label trastuzumab. The median duration of trastuzumab therapy was longer than that on trial: 5.6 v 3.1 months for enrollees receiving monotherapy and 12.5 v 6.9 months for concomitant chemotherapy. Only 47 (3%) of enrollees received cardiac monitoring before and during trastuzumab therapy. We estimated 24% of trastuzumab dispensed was discarded, at a cost of $21.1 million Australian. Alternative administration schedules and the addition of another vial size potentially reduce wastage to 6% of volume dispensed.ConclusionDebates about the use of expensive cancer medicines should consider postmarketing assessments as well as trial experience. The longer duration of trastuzumab use in clinical practice and the high rates of off-label use provide incentive for new clinical trials. Strategies to improve cardiac monitoring and to minimize drug wastage are issues that require immediate attention.
Association of Methylenetetrahydrofolate Reductase Gene Polymorphisms and Sex-Specific Survival in Patients With Metastatic Colon Cancer
Authors: Zhang Wu , Press Oliver A. , Haiman Christopher A. , Yang Dong Yun , Gordon Michael A. , Fazzone William , El-khoueiry Anthony , Iqbal Syma , Sherrod Andy E. , Lurje Georg , Lenz Heinz-Josef 
Published: August 2007

Purpose Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme regulating intracellular folate levels, which affects DNA synthesis and methylation. Two MTHFR gene polymorphisms, C677T and A1298C, are linked to altered enzyme activity. Several studies have shown these two polymorphisms to be associated with response to fluorouracil (FU) -based treatment in advanced colon cancer patients, but data are inconsistent and contradictory. Meanwhile, epidemiologic studies demonstrated that these MTHFR polymorphisms were associated with cancer risk in a sex-specific manner. We tested the hypothesis of whether these two polymorphisms are associated with sex-specific clinical outcome in metastatic colon cancer patients treated with FU-based chemotherapy. Patients and Methods This study included 318 patients (177 men and 141 women) with metastatic colon cancer treated between 1992 and 2003 at the University of Southern California/Norris Comprehensive Cancer Center or Los Angeles County/University of Southern California Medical Center. Peripheral blood samples were collected from each patient, and genomic DNA was extracted from WBCs. Two MTHFR gene polymorphisms (C677T and A1298C) were tested by fluorogenic 5′-nuclease assay. Results The A1298C polymorphism showed statistically significant differences in overall survival (OS) in female, but not male, patients with metastatic colon cancer (log-rank test, P = .038). Among females, OS was greater for patients with the A/A genotype (n = 67; median OS, 18.4 months) compared with patients with the A/C genotype (n = 50; median OS, 13.9 months) or C/C genotype (n = 10; median OS, 15.6 months). Conclusion Although preliminary, these data support the role of the A1298C polymorphism in MTHFR as prognostic marker in female patients with metastatic colon cancer. Further studies are needed to confirm these findings.
Directional asymmetry in responses of local interneurons in the crayfish deutocerebrum to hydrodynamic stimulation of the lateral antennular flagellum
Authors: Mellon DeForest , Humphrey Joseph A. C. 
Published: August 2007

SUMMARYWe have recorded spiking responses from single, bimodally sensitive local interneurons (Type I) in the crayfish deutocerebrum to hydrodynamic and odorant stimuli flowing in two directions past the lateral antennular flagellum. Changing the direction of seamless introductions (meaning, with minimal variations of fluid velocity magnitude) of odorant flow past the flagellum, from proximal→distal to distal→proximal, did not consistently affect the dose-dependent responses of Type I neurons. By contrast, changing the direction of an abruptly initiated flow of water (or odorant) past the flagellum resulted in consistently larger numbers of spikes in response to this hydrodynamic stimulation when the flow direction was proximal→distal. This response asymmetry is discussed in relation to its possible relevance regarding antennular flicking behavior. The putative involvement of flagellar hydrodynamic receptors, the beaked hairs, and the hydrodynamic flow asymmetries they are exposed to, are examined theoretically in the accompanying paper.
Thermal preference ofCaenorhabditis elegans: a null model and empirical tests
Authors: Anderson Jennifer L. , Albergotti Lori , Proulx Stephen , Peden Colin , Huey Raymond B. , Phillips Patrick C. 
Published: August 2007

SUMMARYThe preferred body temperature of ectotherms is typically inferred from the observed distribution of body temperatures in a laboratory thermal gradient. For very small organisms, however, that observed distribution might misrepresent true thermal preferences. Tiny ectotherms have limited thermal inertia, and so their body temperature and speed of movement will vary with their position along the gradient. In order to separate the direct effects of body temperature on movement from actual preference behaviour on a thermal gradient, we generate a null model (i.e. of non-thermoregulating individuals)of the spatial distribution of ectotherms on a thermal gradient and test the model using parameter values estimated from the movement of nematodes(Caenorhabditis elegans) at fixed temperatures and on a thermal gradient. We show that the standard lab strain N2, which is widely used in thermal gradient studies, avoids high temperature but otherwise does not exhibit a clear thermal preference, whereas the Hawaiian natural isolate CB4856 shows a clear preference for cool temperatures (∼17°C). These differences are not influenced substantially by changes in the starting position of worms in the gradient, the natal temperature of individuals or the presence and physiological state of bacterial food. These results demonstrate the value of an explicit null model of thermal effects and highlight problems in the standard model of C. elegans thermotaxis, showing the value of using natural isolates for tests of complex natural behaviours.