bluuebunny/crossref_metadata_2025 huggingface dataset:
Isolation and Characterization of FecA- and FeoB-Mediated Iron Acquisition Systems of the SpirocheteLeptospira biflexaby Random Insertional Mutagenesis
Authors: Louvel Hélène , Saint Girons Isabelle , Picardeau Mathieu
Published: April 2005

The specific mechanisms by whichLeptospiraspp. acquire iron from their ecological niches are unknown. A major factor contributing to our ignorance of spirochetal biology is the lack of methods for genetic analysis of these organisms. In this study, we have developed a system for random transposon mutagenesis ofLeptospira biflexausing amarinertransposon,Himar1. To demonstrate the validity ofHimar1in vivo transposon mutagenesis inL. biflexa, a screen of mutants for clones impaired in amino acid biosynthesis was first performed, enabling the identification of tryptophan and glutamate auxotrophs. To investigate iron transporters, 2,000L. biflexatransposon mutants were screened onto media with and without hemin, thus allowing the identification of five hemin-requiring mutants, and the putative genes responsible for this phenotype were identified. Three mutants had distinct insertions in a gene encoding a protein which shares homology with the TonB-dependent receptor FecA, involved in ferric citrate transport. We also identified two mutants with aHimar1insertion into afeoB-like gene, the product of which is required for ferrous iron uptake in many bacterial organisms. Interestingly, the growth inhibition exhibited by thefecAandfeoBmutants was relieved by deferoxamine, suggesting the presence of a ferric hydroxamate transporter. These results confirm the importance of iron for the growth ofLeptospiraand its ability to use multiple iron sources.
Random Insertional Mutagenesis ofLeptospira interrogans, the Agent of Leptospirosis, Using amarinerTransposon
Authors: Bourhy Pascale , Louvel Hélène , Saint Girons Isabelle , Picardeau Mathieu
Published: April 2005

The recent availability of the complete genome sequences ofLeptospira interrogans, the agent of leptospirosis, has allowed the identification of several putative virulence factors. However, to our knowledge, attempts to carry out gene transfer in pathogenicLeptospiraspp. have failed so far. In this study, we show that theHimar1 marinertransposon permits random mutagenesis in the pathogenL. interrogans. We have identified genes that have been interrupted byHimar1insertion in 35L. interrogansmutants. This approach of transposon mutagenesis will be useful for understanding the spirochetal physiology and the pathogenic mechanisms ofLeptospira, which remain largely unknown.
Prospective noise induced changes to hearing among construction industry apprentices
Authors: Seixas N S , Goldman B , Sheppard L , Neitzel R , Norton S , Kujawa S G
Published: April 2005

Aims:To characterise the development of noise induced damage to hearing.

Methods:Hearing and noise exposure were prospectively monitored among a cohort of newly enrolled construction industry apprentices and a comparison group of graduate students, using standard pure tone audiometry and distortion product otoacoustic emissions (DPOAEs). A total of 328 subjects (632 ears) were monitored annually an average of 3.4 times. In parallel to these measures, noise exposure and hearing protection device (HPD) use were extensively monitored during construction work tasks. Recreational/non-occupational exposures also were queried and monitored in subgroups of subjects. Trade specific mean exposure Leqlevels, with and without accounting for the variable use of hearing protection in each trade, were calculated and used to group subjects by trade specific exposure level. Mixed effects models were used to estimate the change in hearing outcomes over time for each exposure group.

Results:Small but significant exposure related changes in DPOAEs over time were observed, especially at 4 kHz with stimulus levels (L1) between 50 and 75 dB, with less clear but similar patterns observed at 3 kHz. After controlling for covariates, the high exposure group had annual changes in 4 kHz emissions of about 0.5 dB per year. Pure tone audiometric thresholds displayed only slight trends towards increased threshold levels with increasing exposure groups. Some unexpected results were observed, including an apparent increase in DPOAEs among controls over time, and improvement in behavioural thresholds among controls at 6 kHz only.

Conclusions:Results indicate that construction apprentices in their first three years of work, with average noise exposures under 90 dBA, have measurable losses of hearing function. Despite numerous challenges in using DPOAEs for hearing surveillance in an industrial setting, they appear somewhat more sensitive to these early changes than is evident with standard pure tone audiometry.
Pulsatile Flow Improves Renal Function in High-Risk Cardiac Operations
Authors: Kocakulak Mustafa , Aşkin Göktan , Küçükaksu Süha , Tarcan Onurcan , Pişkin Erhan
Published: April 2005

The effects of pulsatile perfusion on microcirculation and renal function in high-risk patients were evaluated in this study. Pulsatile roller pumps with a pulsatile control module and membrane oxygenator were used in a clinical setting. 40 patients undergoing elective cardiac surgery with a high risk of either having chronically obstructive pulmonary disease or chronic renal failure were randomly included in the study to be perfused using pulsatile or continuous flows. Blood samples were collected at induction of anesthesia, at the time of aortic clamping and declamping and 1 and 24 h following cessation of the bypass. Urea and creatinine concentrations in blood were measured and systemic vascular resistance was calculated. Urine output, crystalloid and colloid infusions were recorded. We observed that pulsatile roller pump perfusion and the extracorporeal circuit used in the clinical study improved microcirculation and renal function in high-risk patients undergoing cardiopulmonary bypass.
Results and Complications after Ileal Pouch Anal Anastomosis: A Meta-Analysis of 43 Observational Studies Comprising 9,317 Patients
Authors: Hueting Willem E. , Buskens Erik , van der Tweel Ingeborg , Gooszen Hein G. , van Laarhoven Cees J.H.M.
Published: April 2005

Objective: To analyze the literature of ileal pouch anal anastomosis (IPAA) regarding complications and functional outcome, to provide audit data for individual surgeons and units to assess their own performance against and also to serve as reference standard for the assessment of novel alternatives. Background: IPAA is the standard restorative procedure for ulcerative colitis (UC) and familial adenomatous polyposis (FAP). This operation is, however, associated with distinct rates of failure, complications and fecal incontinence. Methods: A meta-analysis on pooled incidences of complications of IPAA was conducted. Medline search and cross-reference search identified studies on IPAA (n ≧ 50). Two authors independently performed the data extraction on study characteristics, diagnosis, type of operation, pouch-related complications, pouch failure and functional results. In case of disagreement consensus was reached by joint review of the study. Estimates of pouch-related complications, pouch failure and functional results are described as pooled percentages with 95% confidence interval. Results: The initial search based on 1,206 abstracts yielded 43 studies eligible for further analysis. Indications for IPAA were UC in 87.5%, FAP in 8.9% and other diagnoses in 3.6%. The median follow-up was 36.7 months. Pouch failure was 6.8%, increasing to 8.5% in case of follow-up of more than 60 months. Pelvic sepsis occurred in 9.5%. Severe, mild and urge fecal incontinence were reported in 3.7, 17, and 7.3%, respectively.No effect of experience, duration of follow-up and type of surgical technique on the incidence of pouch failure and pelvic sepsis was demonstrable. Conclusions: Current techniques for restorative surgery after proctocolectomy are associated with non-negligible complication rates and leave room for improvement and continuation of development of alternative procedures.
Overweight in Children and Adolescents
Authors: Daniels Stephen R. , Arnett Donna K. , Eckel Robert H. , Gidding Samuel S. , Hayman Laura L. , Kumanyika Shiriki , Robinson Thomas N. , Scott Barbara J. , St. Jeor Sachiko , Williams Christine L.
Published: April 2005

The prevalence of overweight among children and adolescents has dramatically increased. There may be vulnerable periods for weight gain during childhood and adolescence that also offer opportunities for prevention of overweight. Overweight in children and adolescents can result in a variety of adverse health outcomes, including type 2 diabetes, obstructive sleep apnea, hypertension, dyslipidemia, and the metabolic syndrome. The best approach to this problem is prevention of abnormal weight gain. Several strategies for prevention are presented. In addition, treatment approaches are presented, including behavioral, pharmacological, and surgical treatment. Childhood and adolescent overweight is one of the most important current public health concerns.
Enlarged Waist Combined With Elevated Triglycerides Is a Strong Predictor of Accelerated Atherogenesis and Related Cardiovascular Mortality in Postmenopausal Women
Authors: Tankó László B. , Bagger Yu Z. , Qin Gerong , Alexandersen Peter , Larsen Philip J. , Christiansen Claus
Published: April 2005

Background—

Upward trends of obesity urge more effective identification of those at cardiovascular risk. A simple dichotomous indicator, enlarged waist (≥88 cm) combined with elevated triglycerides (≥1.45 mmol/L) (EWET), was shown to offer advantages in identifying individuals with atherogenic “lipid overaccumulation” compared with other indicators, including the metabolic syndrome defined by the National Cholesterol Education Program (MS-NCEP). Whether EWET offers superior disease and event prediction in postmenopausal women, however, remains unknown.

Methods and Results—

A community-based sample of 557 women (48 to 76 years of age) were followed up for 8.5±0.3 years to assess the utility of EWET and MS-NCEP in estimating the risk of all-cause and cardiovascular mortality and the annual progression rate of aortic calcification. At baseline, 15.8% of women had EWET and 17.6% had MS-NCEP. All-cause mortality and cardiovascular mortality were increased in carriers of the dichotomous indicators (
P
<0.001). After adjustment for age, smoking, and LDL cholesterol, presence of EWET was associated with a 4.7-fold (95% CI, 2.2 to 9.8;
P
<0.001) increased risk and presence of MS-NCEP was associated with a 3.2-fold (95% CI, 1.5 to 6.5;
P
<0.001) increased risk for fatal cardiovascular events. Exclusion of women with prevalent diabetes did not change these trends; respective hazard ratios were 4.2 (95% CI, 1.9 to 9.3;
P
<0.001) and 2.5 (95% CI, 1.1 to 5.5;
P
<0.05). Among those who were discordant for EWET and MS-NCEP at baseline, those who had EWET alone (n=21) had a higher annual progression rate of aortic calcification compared with those who had MS-NCEP alone (n=31;
P
<0.05).

Conclusions—

The combined presence of EWET may be the best indicator of cardiovascular risk in postmenopausal women. Other components of the MS-NCEP add little medical value to screening in general practices.
Phosphorylation of GATA2 by Akt Increases Adipose Tissue Differentiation and Reduces Adipose Tissue–Related Inflammation
Authors: Menghini Rossella , Marchetti Valentina , Cardellini Marina , Hribal Marta L. , Mauriello Alessandro , Lauro Davide , Sbraccia Paolo , Lauro Renato , Federici Massimo
Published: April 2005

Background—

Obesity-related inflammation is emerging as a major cause of insulin resistance and cardiovascular diseases. GATA2 transcription factor is an inhibitor of adipogenesis and an activator of vascular cells. We hypothesized that GATA2 activity is controlled by insulin during adipogenesis, linking metabolic homeostasis and inflammation.

Methods and Results—

We show that insulin induces GATA2 phosphorylation on serine 401 in a PI-3K/Akt–dependent manner. Insulin-dependent phosphorylation of serine 401 impairs GATA2 translocation to the nucleus and its DNA binding activity. A GATA2 mutant not phosphorylable by Akt (GATA2
S401A
) acts similarly to wild-type GATA2. In contrast, a GATA2 mutant that mimics Akt phosphorylation (GATA2
S401D
) is restrained in the cytoplasm. Cultured preadipocytes bearing GATA2
S401A
do not convert to adipocytes and express high levels of inflammatory cytokines like monocyte chemotactic protein-1 (MCP-1). On the contrary, GATA2
S401D
preadipocytes differentiate to adipocytes. When GATA2
S401A
preadipocytes are injected in mice fed a high-fat diet, they do not differentiate adequately into adipocytes, maintaining the expression of inflammatory markers like MCP-1. In contrast, injection of GATA2
S401D
preadipocytes in mice fed a high-fat diet results in development of adipocytes and no expression of inflammatory markers.

Conclusions—

GATA2 could be a new target in the prevention and treatment of obesity-related inflammation and its complications.
Prospective Study of Body Mass Index and Risk of Stroke in Apparently Healthy Women
Authors: Kurth Tobias , Gaziano J. Michael , Rexrode Kathryn M. , Kase Carlos S. , Cook Nancy R. , Manson JoAnn E. , Buring Julie E.
Published: April 2005

Background—

Obesity is an escalating pandemic in the United States, and its association with coronary heart disease is well understood. Several studies have found positive associations between body mass index (BMI) and stroke in men, but the association with stroke and its subtypes is less clear in women.

Methods and Results—

This was a prospective cohort study among 39 053 women participating in the Women’s Health Study. BMI was measured as self-reported weight (in kilograms) divided by height (in meters) squared. Incident stroke was self-reported and confirmed by medical record review. We used the Cox proportional hazards model to evaluate the association between BMI and stroke. After a mean follow-up of 10 years, a total of 432 strokes (347 ischemic, 81 hemorrhagic, and 4 undefined) occurred. We found a statistically significant trend for increased risk of total and ischemic stroke across 7 BMI categories. With World Health Organization criteria, women who were obese (BMI ≥30 kg/m
2
) had hazard ratios of 1.50 (95% CI 1.16 to 1.94) for total stroke, 1.72 (95% CI 1.30 to 2.28) for ischemic stroke, and 0.82 (95% CI 0.43 to 1.58) for hemorrhagic stroke compared with women with BMI <25 kg/m
2
. Additional control for history of hypertension, diabetes, and elevated cholesterol substantially attenuated the hazard ratios for total and ischemic stroke. There was no effect modification for age, exercise, or smoking.

Conclusions—

In this large prospective cohort study among women, BMI was a strong risk factor for total and ischemic stroke but not for hemorrhagic stroke. The association was highly mediated by hypertension, diabetes, and elevated cholesterol.
Insulin-Mediated Upregulation of the Renin Angiotensin System in Human Subcutaneous Adipocytes Is Reduced by Rosiglitazone
Authors: Harte Alison , McTernan Philip , Chetty Rajkumar , Coppack Simon , Katz Jonathan , Smith Stephen , Kumar Sudhesh
Published: April 2005

Background—

Obesity-associated hypertension is likely to be due to multiple mechanisms. Identification of the renin-angiotensin system (RAS) within adipose tissue does, however, suggest a potential causal role for it in obesity-associated hypertension. Obese patients are often hyperinsulinemic, but mechanisms underlying insulin upregulation of the RAS in adipose tissue are unclear. Tumor necrosis factor-α (TNF-α), an inducer of angiotensinogen in hepatocytes, is elevated in hyperinsulinemic, obese individuals and may provide a link in mediating insulin upregulation of the RAS in adipose tissue. Furthermore, thiazolidinediones lower blood pressure in vivo, and downregulation of the RAS in adipose tissue may contribute to this effect. We therefore examined the effect of rosiglitazone (RSG) on the insulin-mediated upregulation of the RAS.

Methods and Results—

Sera were obtained from the arterial circulation and from venous blood by draining subcutaneous abdominal adipose tissue. Isolated human abdominal subcutaneous adipocytes (n=12) were treated with insulin (1 to 1000 nmol/L), insulin in combination with RSG (10 nmol/L), and RSG (10 nmol/L) alone to determine angiotensinogen expression and angiotensin II, bradykinin, and TNF-α secretion. Subcutaneous adipocytes were also treated with TNF-α (10 to 100 ng/mL) to examine the direct effect on angiotensinogen expression and angiotensin II secretion. The findings showed that the arteriovenous difference in angiotensin II levels was significant (>23%;
P
<0.001). Insulin increased TNF-α secretion in a concentration-dependent manner (
P
<0.01), whereas RSG (10 nmol/L) significantly reduced the insulin-mediated rise in TNF-α (
P
<0.001), as well as angiotensin and angiotensin II. TNF-α also increased angiotensinogen and angiotensin II in isolated adipocytes.

Conclusions—

The present in vivo data suggest that human subcutaneous adipose tissue is a significant source of angiotensin II. This study also demonstrates a potential TNF-α–mediated mechanism through which insulin may stimulate the RAS and may contribute to explain obesity-associated hypertension. RSG downregulates the RAS in subcutaneous adipose tissue, and this effect may contribute to the long-term effect of RSG on blood pressure.
Diet and Exercise Training Restore Blood Pressure and Vasodilatory Responses During Physiological Maneuvers in Obese Children
Authors: Ribeiro Maurício M. , Silva Alexandre G. , Santos Nelson S. , Guazzelle Isabel , Matos Luciana N.J. , Trombetta Ivani C. , Halpern Alfredo , Negrão Carlos E. , Villares Sandra M.F.
Published: April 2005

Background—

The effects of diet and diet plus exercise training on muscle vasodilatation during physiological maneuvers in obese children are unknown. We tested the hypothesis that (1) blood pressure (BP) and forearm vascular conductance (FVC) responses during handgrip exercise and mental stress would be altered in obese children and (2) diet plus exercise training would restore BP and FVC responses during exercise and mental stress in obese children.

Methods and Results—

Thirty-nine obese children (aged 10±0.2 years) were randomly divided into 2 groups: diet plus exercise training (n=21; body mass index [BMI]=28±0.5 kg/m
2
) and diet (n=18; BMI=30±0.4 kg/m
2
). Ten age-matched lean control children (BMI=17±0.5 kg/m
2
) were also studied. Forearm blood flow was measured by venous occlusion plethysmography. BP was monitored noninvasively. Handgrip exercise was performed at 30% maximal voluntary contraction for 3 minutes. Stroop color word test was performed for 4 minutes. Baseline BP was significantly higher and FVC was significantly lower in obese children. During exercise and mental stress, BP responses were significantly higher and FVC responses were significantly lower in obese children. Diet and diet plus exercise training significantly reduced body weight. Diet and diet plus exercise training significantly decreased BP levels during exercise and mental stress. Diet plus exercise training, in contrast to diet alone, significantly increased FVC responses during exercise (3.7±0.3 versus 5.6±0.4 U;
P
=0.01) and mental stress (3.5±0.5 versus 4.5±0.4 U;
P
=0.02). After diet plus exercise training, BP and FVC responses during exercise and mental stress were similar between obese children and the control group.

Conclusions—

Obesity exacerbates BP responses and impairs FVC responses during exercise and mental stress in children. Diet and exercise training restore BP and FVC responses in obese children.
Fast model-based migration velocity analysis and reflector shape estimation
Authors: Fei Weihong , McMechan George A.
Published: April 2005

Migration velocity analysis can be made more efficient by preselecting the traces that contribute to a series of common-reflection-point (CRP) gathers and migrating only those traces. The data traces that contribute to a CRP for one reflection point on one layer are defined in a two-step procedure. First, poststack parsimonious Kirchhoff depth migration of zero-offset (or stacked) traces defines approximate reflector positions and orientations. Then, ray tracing from the reflection points for nonzero reflection angles defines the source and receiver locations of the data traces in the CRP gather. These traces are then prestack depth migrated, and the interval velocity model adjustment is obtained by fitting the velocity that maximizes the stack amplitude over the predicted (nonhyperbolic) moveout. A small number (2–3) of iterations converge to a 2D model of layer shape and interval velocity. Further efficiency is obtained by implementing layer stripping. The computation time is greatly reduced by combining parsimonious migration with processing only the salient portions of the whole seismic data set. The algorithm can handle lateral velocity variation within each layer as well as constant velocity. The computation time of the proposed algorithm is of the same order as that of the standard rms velocity scan method, but it does not have the inherent assumptions of the velocity scan method and is faster than current iterative prestack depth migration velocity analysis methods for typical field data.
Study of Translational Control of Eukaryotic Gene Expression Using Yeast
Authors: HINNEBUSCH ALAN G. , ASANO KATSURA , OLSEN DEANNE S. , PHAN LON , NIELSEN KLAUS H. , VALÁŠEK LEOŠ
Published: April 2005

Abstract: Eukaryotic cells respond to starvation by decreasing the rate of general protein synthesis while inducing translation of specific mRNAs encoding transcription factors GCN4 (yeast) or ATF4 (humans). Both responses are elicited by phosphorylation of translation initiation factor 2 (eIF2) and the attendant inhibition of its nucleotide exchange factor eIF2B—decreasing the binding to 40S ribosomes of methionyl initiator tRNA in the ternary complex (TC) with eIF2 and GTP. The reduction in TC levels enables scanning ribosomes to bypass the start codons of upstream open reading frames in the GCN4 mRNA leader and initiate translation at the authentic GCN4 start codon. We exploited the fact that GCN4 translation is a sensitive reporter of defects in TC recruitment to identify the catalytic and regulatory subunits of eIF2B. More recently, we implicated the C‐terminal domain of eIF1A in 40S‐binding of TC in vivo. Interestingly, we found that TC resides in a multifactor complex (MFC) with eIF3, eIF1, and the GTPase‐activating protein for eIF2, known as eIF5. Our biochemical and genetic analyses indicate that physical interactions between MFC componens enhance TC binding to 40S subunits and are required for wild‐type translational control of GCN4. MFC integrity and eIF3 function also contribute to post‐assembly steps in the initiation pathway that impact GCN4 expression. Thus, apart from its critical role in the starvation response, GCN4 regulation is a valuable tool for dissecting the contributions of multiple translation factors in the eukaryotic initiation pathway.
Results of a Search for the Mechanisms of Steroid Receptor Regulation of Gene Expression
Authors: O'MALLEY BERT W.
Published: April 2005

Abstract: This publication provides a brief summary of a presentation given at the NICHD Anniversary Symposium that was designed to describe the research progress of the O'Malley laboratory over the past 30 years of its NICHD funding. It highlights a few of the lab's major discoveries during the course of the pursuit of its long‐standing goal to define the molecular pathway for steroid hormone action. The key discovery that set the scientific tone for the lab over the ensuing few decades began with the discovery that steroid hormones induced the nuclear production of specific mRNAs for ovalbumin and avidin in the chick oviduct. This completed the pathway from receptor to specific proteins and indicated that steroid receptors were transcription factors. More recently the lab discovered the first coactivators (e.g., SRC‐1) for steroid hormone receptors and has subsequently elucidated the many and diverse roles of nuclear coactivators in transcription reactions and in cell signaling.
Origins of Growth Factors: NGF and EGF
Authors: COHEN STANLEY
Published: April 2005

Abstract: This presentation describes the events that led to the sequential discoveries of nerve growth factor (NGF) and epidermal growth factor (EGF). Each was isolated during attempts to understand the biochemical basis for unexpected biological observations. The in vivo stimulation of the growth of specific nerve fibers following the transplantation of a mouse sarcoma into a chick embryo eventually resulted in the finding of NGF, not only in the transplanted tumor but also in snake venom and in the mouse salivary gland. Unexpectedly, treatment of newborn animals with extracts of the mouse salivary gland resulted not only in enhancement of nerve growth but also in precocious eyelid opening and tooth eruption. The latter observations led to the isolation of both EGF and its tyrosine kinase‐active receptor.
Epirubicin Increases Long-Term Survival in Adjuvant Chemotherapy of Patients With Poor-Prognosis, Node-Positive, Early Breast Cancer: 10-Year Follow-Up Results of the French Adjuvant Study Group 05 Randomized Trial
Authors: Bonneterre Jacques , Roché Henri , Kerbrat Pierre , Brémond Alain , Fumoleau Pierre , Namer Moïse , Goudier Marie-Josèphe , Schraub Simon , Fargeot Pierre , Chapelle-Marcillac Isabelle
Published: April 2005

Purpose

The French Adjuvant Study Group 05 (FASG-05) showed that fluorouracil 500 mg/m2, cyclophosphamide 500 mg/m2, and epirubicin 100 mg/m2 (FEC 100) was superior to the same regimen with epirubicin 50 mg/m2 (FEC 50) in terms of disease-free survival (DFS) and overall survival (OS) in adjuvant treatment of early breast cancer. We report 10-year data on efficacy, and long-term side effects for FASG-05.

Patients and Methods

We randomly assigned 565 patients to treatment with FEC 50 or FEC 100 after surgery. Postmenopausal patients also received tamoxifen for 3 years, and almost all patients (96%) also received radiotherapy.

Results

Median follow-up was 110 months. The 10-year DFS was 45.3% (95% CI, 41.9% to 48.7%) with FEC 50 and 50.7% (95% CI, 47.3% to 54.1%) with FEC 100 (Wilcoxon P = .036; log-rank P = .08). The 10-year OS was 50.0% (95% CI, 46.7% to 53.3%) with FEC 50 and 54.8% (95% CI, 51.3% to 58.3%) with FEC 100 (Wilcoxon P = .038; log-rank P = .05). Delayed cardiac toxicity (before relapse) occurred in four patients (1.5%) in the FEC 50 arm and three patients (1.1%) in the FEC 100 arm. Cardiac toxicity after relapse occurred in six (4.3%) and five (4.1%) patients treated with FEC 50 and FEC 100, respectively.

Conclusion

Treatment with adjuvant FEC 100 demonstrated superior DFS and OS versus FEC 50 at 10 years of follow-up. This survival advantage was not offset by long-term complications such as cardiac toxicity and second malignancy. Given the risk-benefit ratio, FEC 100 is a more optimal regimen for long-term survival in patients with poor prognosis.
Sentinel Node Biopsy After Neoadjuvant Chemotherapy in Breast Cancer: Results From National Surgical Adjuvant Breast and Bowel Project Protocol B-27
Authors: Mamounas Eleftherios P. , Brown Ann , Anderson Stewart , Smith Roy , Julian Thomas , Miller Barbara , Bear Harry D. , Caldwell Christopher B. , Walker Alonzo P. , Mikkelson Wendy M. , Stauffer Jay S. , Robidoux Andre , Theoret Heather , Sovan Atilla , Fisher Bernard , Wickerham D. Lawrence , Wolmark Norman
Published: April 2005

Purpose

Experience with sentinel node biopsy (SNB) after neoadjuvant chemotherapy is limited. We examined the feasibility and accuracy of this procedure within a randomized trial in patients treated with neoadjuvant chemotherapy.

Patients and Methods

During the conduct of National Surgical Adjuvant Breast and Bowel Project trial B-27, several participating surgeons attempted SNB before the required axillary dissection in 428 patients. All underwent lymphatic mapping and an attempt to identify and remove a sentinel node. Lymphatic mapping was performed with radioactive colloid (14.7%), with lymphazurin blue dye alone (29.9%), or with both (54.7%).

Results

Success rate for the identification and removal of a sentinel node was 84.8%. Success rate increased significantly with the use of radioisotope (87.6% to 88.9%) versus with the use of lymphazurin alone (78.1%, P = .03). There were no significant differences in success rate according to clinical tumor size, clinical nodal status, age, or calendar year of random assignment. Of 343 patients who had SNB and axillary dissection, the sentinel nodes were positive in 125 patients and were the only positive nodes in 70 patients (56.0%). Of the 218 patients with negative sentinel nodes, nonsentinel nodes were positive in 15 (false-negative rate, 10.7%; 15 of 140 patients). There were no significant differences in false-negative rate according to clinical patient and tumor characteristics, method of lymphatic mapping, or breast tumor response to chemotherapy.

Conclusion

These results are comparable to those obtained from multicenter studies evaluating SNB before systemic therapy and suggest that the sentinel node concept is applicable following neoadjuvant chemotherapy.
Prognostic Value of Histologic Subtypes in Renal Cell Carcinoma: A Multicenter Experience
Authors: Patard Jean-Jacques , Leray Emmanuelle , Rioux-Leclercq Nathalie , Cindolo Luca , Ficarra Vincenzo , Zisman Amnon , De La Taille Alexandre , Tostain Jacques , Artibani Walter , Abbou Claude C. , Lobel Bernard , Guillé François , Chopin Dominique K. , Mulders Peter F.A. , Wood Christopher G. , Swanson David A. , Figlin Robert A. , Belldegrun Arie S. , Pantuck Allan J.
Published: April 2005

Purpose

To analyze to what extent histologic subtype is of prognostic importance in renal cell carcinoma based on a large, international, multicenter experience.

Patients and Methods

Four thousand sixty-three patients from eight international centers were included in this retrospective study. Histologic subtype (1997 International Union Against Cancer [UICC] criteria of tumor response), age, sex, TNM stage, Fuhrman grade, tumor size, Eastern Cooperative Oncology Goup performance status (ECOG PS), and overall survival were determined in all cases. The prognostic values of clear cell, papillary, and chromophobe histologic features were assessed by uni- and multivariate analysis using the Kaplan-Meier method and Cox model, respectively.

Results

Clear cell, papillary, and chromophobe carcinomas accounted for 3,564 (87.7%), 396 (9.7%) and 103 (2.5%) cases, respectively. In univariate analysis, a trend toward a better survival was observed when clear cell, papillary, and chromophobe histologies were considered prognostic categories (log-rank P = .0007). However, in multivariate analysis, TNM stage, Fuhrman grade and ECOG PS, but not histology, were retained as independent prognostic variables (P < .001).

Conclusion

The stratification in three main renal cell carcinoma histologic subtypes as defined by the 1997 UICC–American Joint Committee on Cancer consensus should not be considered a major prognostic variable comparable to TNM stage, Fuhrman grade and ECOG PS.
Chemokine ReceptorCXCR4Expression in Colorectal Cancer Patients Increases the Risk for Recurrence and for Poor Survival
Authors: Kim Joseph , Takeuchi Hiroya , Lam Stella T. , Turner Roderick R. , Wang He-Jing , Kuo Christine , Foshag Leland , Bilchik Anton J. , Hoon Dave S.B.
Published: April 2005

Purpose

Liver metastasis is the predominant cause of colorectal cancer (CRC) related mortality. Chemokines, soluble factors that orchestrate hematopoetic cell movement, have been implicated in directing cancer metastasis, although their clinical relevance in CRC has not been defined. Our hypothesis was that the chemokine receptor CXCR4 expressed by CRC is a prognostic factor for poor disease outcome.

Methods

CRC cell lines (n = 6) and tumor specimens (n = 139) from patients with different American Joint Committee on Cancer (AJCC) stages of CRC were assessed. Microarray screening of select specimens and cell lines identified CXCR4 as a prominent chemokine receptor. CXCR4 expression in tumor and benign specimens was assessed by quantitative real-time reverse transcription polymerase chain reaction and correlated with disease recurrence and overall survival.

Results

High CXCR4 expression in tumor specimens (n = 57) from AJCC stage I/II patients was associated with increased risk for local recurrence and/or distant metastasis (risk ratio, 1.35; 95% CI, 1.09 to 1.68; P = .0065). High CXCR4 expression in primary tumor specimens (n = 35) from AJCC stage IV patients correlated with worse overall median survival (9 months v 23 months; RR, 2.53; 95% CI, 1.19 to 5.40; P = .016). CXCR4 expression was significantly higher in liver metastases (n = 39) compared with primary CRC tumors (n = 100; P < .0001).

Conclusion

CXCR4, a well-characterized chemokine receptor for T-cells, is differentially expressed in CRC. CXCR4 gene expression in primary CRC demonstrated significant associations with recurrence, survival, and liver metastasis. The CXCR4-CXCL12 signaling mechanism may be clinically relevant for patients with CRC and represents a potential novel target for disease-directed therapy.
Phase II Clinical Trial of Ixabepilone (BMS-247550), an Epothilone B Analog, in Metastatic and Locally Advanced Breast Cancer
Authors: Low Jennifer A. , Wedam Suparna B. , Lee James J. , Berman Arlene W. , Brufsky Adam , Yang Sherry X. , Poruchynsky Marianne S. , Steinberg Seth M. , Mannan Nitin , Fojo Tito , Swain Sandra M.
Published: April 2005

Purpose

Ixabepilone (BMS-247550) is an epothilone B analog that stabilizes microtubules and has antitumor activity in taxane-refractory patients in phase I studies. In a phase II trial, we evaluated the efficacy and safety of ixabepilone in women with metastatic and locally advanced breast cancer.

Patients and Methods

Breast cancer patients with measurable disease who had paclitaxel and/or docetaxel as prior neoadjuvant, adjuvant, or metastatic therapy were treated with ixabepilone at 6 mg/m2/d intravenously on days 1 through 5 every 3 weeks. Levels of glutamate (glu) -terminated and acetylated α-tubulin, markers of microtubule stabilization, were detected by Western blot and by immunohistochemistry in a subset of matched pre- and post-treatment tumor biopsies.

Results

Thirty-seven patients received 153 cycles of ixabepilone. The best responses were a complete response in one patient (3%), partial responses in seven patients (19%), and stable disease in 13 patients (35%). Grade 3 and 4 toxicities included neutropenia (35%), febrile neutropenia (14%), fatigue (14%), diarrhea (11%), nausea/vomiting (5%), myalgia/arthralgia (3%), and sensory neuropathy (3%). Two patients were removed from study because of prolonged grade 2 or 3 neurotoxicity, and three patients were removed from study for other grade 3 and 4 nonhematologic toxicities. Compared with baseline levels, levels of both glu-terminated and acetylated α-tubulin were increased in tumor biopsies performed after ixabepilone therapy.

Conclusion

An objective response was seen in 22% of the patients in a population who had been previously treated with a taxane. Sensory neuropathy was mild with grade 3 neurotoxicity rarely seen. Microtubule stabilization occurred in tumor biopsies after treatment with ixabepilone.
Risk Factors and Individual Probabilities of Melanoma for Whites
Authors: Cho Eunyoung , Rosner Bernard A. , Feskanich Diane , Colditz Graham A.
Published: April 2005

Purpose

Incidence and mortality of cutaneous melanoma is rising rapidly in the United States; therefore, identifying risk factors for melanoma and integrating them into a clinical and population risk estimation tool may help guide prevention efforts and identify participants for preventive interventions.

Methods

We examined risk factors for melanoma in three large prospective studies of women and men. We observed 152,949 women and 25,206 men free of cancer at baseline for up to 14 years.

Results

A total of 535 incident cases of invasive melanoma (444 women and 91 men) were included in the analysis. We combined the three studies to examine risk factors and to build a risk model to calculate melanoma risk score. Older age, male sex, family history of melanoma, higher number of nevi, history of severe sunburn, and light hair color were each associated with significantly elevated risk of melanoma and were included in the final risk prediction. Participants at the highest decile of risk had a more than three-fold increase in risk of melanoma compared with those in the lowest decile (observed relative risk, 3.61; expected relative risk, 4.20). The measure of discriminatory accuracy as summarized by an age-and sex-adjusted concordance statistic of 0.62 (95% CI, 0.58 to 0.65) indicated that the model had reasonable ability to differentiate those who will develop melanoma and those who will remain free from the disease.

Conclusion

We identified several risk factors for melanoma and developed statistical models with adequate performance and discriminatory accuracy.
Influence of Structure on the Unusual Spectral Behavior of 4-Dialkylamino-1,8-naphthalimide
Authors: Banthia Sandip , Samanta Anunay
Published: April 2005

Spectral behavior of 4-amino-1,8-naphthalimide derivatives differing in their amino functionality has been studied in different solvents with varying polarity. The results reveal that despite the +I effect of the methyl group, the charge-transfer absorption band maximum of N-ethyl-4-dimethylamino-1,8-naphthalimide (3) is blue-shifted with respect to that of the un-substituted and monoethyl-substituted derivatives, 1 and 2, respectively. AM1 calculations indicate a lower ground state dipole moment of 3 compared to 1 or 2. The single crystal structure of 3 suggests that low dipole moment and blue-shift of its CT maximum are due to twisting of the dimethylamino moiety relative to the 1,8-naphthalimide ring.
Preparation of mitotic chromosomes of leaf-cutting ants from the genera Atta and Acromyrmex
Authors: Santos-Colares M.C. , Viégas J. , Roth M.G. Martino , Loeck A.E.
Published: April 2005

Some modifications were made to the methodology of Imai et al. (Jpn. J. Genet. 63: 159-185, 1988) for cytogenetic analysis of the leaf-cutting ants Atta sexdens piriventris and Acromyrmex heyeri (Hymenoptera, Formicidae), shortening preparation time and improving chromosomal preparations. The brain ganglia of prepupae were dissected in a 0.0025% hypotonic solution of colchicine, placed on a glass slide on a cold plate (4 ± 1oC) for 20 min. The material was fixed directly on the cold slide (with cold fixative I), macerated with a histological needle and fixed again with fixative I, followed by fixatives II and III, all of them cold. The slide was flame-dried right after the use of fixative III, and it was allowed to air-dry at room temperature for 2 h. The resulting metaphases presented less contracted chromosomes, with separated and well defined sister chromatids at a high frequency, when the material was processed in the manner described and stained with 3% Giemsa in phosphate buffer (pH 6.8) for 15 min.
Induction of mutations for earliness in the soybean cultivar Paraná
Authors: Tulmann Neto A. , Alves M.C.
Published: April 2005

Mutation induction breeding through gamma ray seed treatment (22 krad) was used to obtain earliness in the soybean cultivar Paraná. Plants flowering earlier than Paraná were selected at the M3 generation. Eight mutant lines were isolated by further selections through several generations and tested in four yield trials carried out in 85/86 (Piracicaba) and 86/87 (Piracicaba, Sertãozinho and Assis) in São Paulo State. The following data were taken in these trials: number of days to flowering, yield, total plant height and height to pod insertion, flower color, pod pubescence and seed and plant growth type. Two of the mutants are of agronomic interest because they were, on average, seven to 10 days earlier in maturity than the control in all trials. Except for shorter plant height, the other agronomic characteristics remained unaltered.
Mapping of a novel viviparous unstable mutant of maize (vp 12)
Authors: Araujo Paula G. , Silva William J. da , Maluf Mirian P. , Prioli Laudenir M.
Published: April 2005

A new viviparous mutant of maize (Zea mays L.), associated with genetic instability and designated viviparous-12 (vp12), was identified in a synthetic Tuxpeño adapted to tropical regions. In the present work, the linkage group of this new locus was determined. Progenies of inbred line L477 segregating for the vp12 mutant were crossed with waxy-marked reciprocal translocation stocks. The phenotypic frequencies of the wx and vp12 mutants were analyzed in F2 progenies. The results demonstrated that the Viviparous-12 locus of maize is located on the long arm of chromosome 6.
Family names and the length of the Y chromosome in Brazilian blacks
Authors: Barbosa Ana A.L. , Cavalli Iglenir J. , Abé Kiyoko , Santos Maria G. , Azevêdo Eliane S.
Published: April 2005

The variability of the lengths of the heterochromatic and euchromatic segments of the human Y chromosome was studied by a quantitative method of densitometric measurement in 60 normal and unrelated black individuals (30 with and 30 without devotional surnames), living in Salvador, Bahia, northeastern Brazil. Thirty normal and unrelated Caucasian individuals of European origin, living in Curitiba, Paraná, south Brazil, were included as controls. The heterochromatic segment and total Y chromosome lengths were greater in caucasians than in blacks without devotional surnames, and these were greater than in blacks with devotional surnames. These findings are in agreement with previous reports of a higher percentage of black ancestry in blacks carrying devotional surnames than those carrying non-devotional ones.
Conflicting genomes, the demic theory & biodiversity
Authors: Hoenigsberg H.F.
Published: April 2005

Organismic-centered Darwinism, in order to use direct phenotypes to measure natural selection's effect, necessitates genome's harmony and uniform coherence plus large population sizes. However, modern gene-centered Darwinism has found new interpretations to data that speak of genomic incoherence and disharmony. As a result of these two conflicting positions a conceptual crisis in Biology has arisen. My position is that the presence of small, even pocket-size, demes is instrumental in generating divergence and phenotypic crisis. Moreover, the presence of parasitic genomes as in acanthocephalan worms, which even manipulate suicidal behavior in their hosts; segregation distorters that change meiosis and Mendelian ratios; selfish genes and selfish whole chromosomes, such as the case of B-chromosomes in grasshoppers; P-elements in Drosophila; driving Y-chromosomes that manipulate sex ratios making males more frequent, as in Hamilton's X-linked drive; male strategists and outlaw genes, are eloquent examples of the presence of real conflicting genomes and of a non-uniform phenotypic coherence and genome harmony. Thus, we are proposing that overall incoherence and disharmony generate disorder but also more biodiversity and creativeness. Finally, if genes can manipulate natural selection, they can multiply mutations or undesirable characteristics and even lethal or detrimental ones, hence the accumulation of genetic loads. Outlaw genes can change what is adaptively convenient even in the direction of the trait that is away from the optimum. The optimum can be "negotiated" among the variants, not only because pleiotropic effects demand it, but also, in some cases, because selfish, outlaw, P-elements or extended phenotypic manipulation require it. With organismic Darwinism the genome in the population and in the individual was thought to act harmoniously without conflicts, and genotypes were thought to march towards greater adaptability. Modern Darwinism has a gene-centered vision in which genes, as natural selection's objects can move in dissonance in the direction which benefits their multiplication. Thus, we have greater opportunities for genomes in permanent conflict.
Estimated frequency of B-chromosomes and population density of Astyanax scabripinnis paranae in a small stream
Authors: Porto-Foresti Fábio , Oliveira Claudio , Maistro Edson Luis , Foresti Fausto
Published: April 2005

A study was made of the frequency of B-chromosomes and the population density of Astyanax scabripinnis paranae (Pisces, Characidae, Tetragonopterinae) from three stretches of the Cascatinha stream (Botucatu, SP). In the first stretch the population was estimated to be about 212 individuals and among 35 karyotyped specimens, 23 carried one macro B-chromosome; in the second stretch the population was estimated to be about 650 individuals and among 20 specimens karyotyped, two possessed one macro B-chromosome; in the third stretch the population was estimated to be about 107 individuals and among 10 specimens karyotyped, one carried one macro B-chromosome. A significant difference was observed in the frequency of macro B-chromosomes in females (57%) and males (8.7%) (P = 0.0001). These data suggest that the B-chromosome frequency and the populational density are not directly related. The hypothesis of the existence of some adaptive effect conferred by the B-chromosomes to the specimens from the first stretch of the Cascatinha stream is presented and discussed
Use of canonical variates in genetic divergence studies
Authors: Ferreira Daniel Furtado , Rezende Gabriel Dehon Sampaio Peçanha
Published: April 2005

Exact correlation coefficients between a canonical variate and measured traits were derived to evaluate genetic divergence among varieties. This method allows the plant breeder to determine which traits contribute significantly to genetic divergence and, also, to identify the most important among them. An example is presented, related to a trial where 28 varieties of maize were evaluated for two traits
Predicting variety composite means without diallel crossing
Authors: Chaves Lázaro J , Miranda Filho José B. de
Published: April 2005

Prediction of variety composite means was shown to be feasible without diallel crossing the parental varieties. Thus, the predicted mean for a quantitative trait of a composite is given by: Yk = a1 sigmaVj + a2sigmaTj + a3 - a4, with coefficients a1 = (n - 2k)/k²(n - 2); a2 = 2n(k - 1)/k²(n - 2); a3 = n(k - 1)/k(n - 1)(n - 2); and a4 = n²(k - 1)/k(n - 1)(n - 2); summation is for j = 1 to k, where k is the size of the composite (number of parental varieties of a particular composite) and n is the total number of parent varieties. Vj is the mean of varieties and Tj is the mean of topcrosses (pool of varieties as tester), and and are the respective average values in the whole set. Yield data from a 7 x 7 variety diallel cross were used for the variety means and for the "simulated" topcross means to illustrate the proposed procedure. The proposed prediction procedure was as effective as the prediction based on Yk = - ( -)/k, where and refer to the mean of hybrids (F1) and parental varieties, respectively, in a variety diallel cross. It was also shown in the analysis of variance that the total sum of squares due to treatments (varieties and topcrosses) can be orthogonally partitioned following the reduced model Yjj’ = mu + ½(v j + v j’) + + h j+ h j’, thus making possible an F test for varieties, average heterosis and variety heterosis. Least square estimates of these effects are also given