bluuebunny/crossref_metadata_2025 huggingface dataset:
Heterogeneity of functional responses in differentiated myeloid cell lines reveals EPRO cells as a valid model of murine neutrophil functional activation
Authors: Gaines Peter , Chi Jeffrey , Berliner Nancy
Published: April 2005

Mature neutrophils display multiple functional responses upon activation that include chemotaxis, adhesion to and transmigration across endothelial cells, phagocytosis, and pathogen destruction via potent microbicidal enzymes and reactive oxygen species. We are using myeloid cell line models to investigate the signaling pathways that govern neutrophil functional activation. To facilitate these studies, we have performed a direct comparison of functional responses of human and murine myeloid cell line models upon neutrophil differentiation. Our results show that EPRO cells, promyelocytes that undergo complete neutrophil maturation, demonstrate a full spectrum of functional responses, including respiratory burst, chemotaxis toward two murine chemokines, and phagocytosis. We also extend previous studies of granulocyte-colony stimulating actor-induced 32Dcl3 cells, showing they domonstrate chemotaxis and phogocytosis but completely lack a respiratory burst as a result of the absent expression of a critical oxidase subunit, gp91phox. Induced human leukemic NB4 and HL-60 cells display a respiratory burst and phagocytosis but have defective chemotaxis to multiple chemoattractants. We also tested each cell line for the ability to up-regulate cell-surface membrane-activated complex-1 (Mac-1) expression upon activation, a response mediating neutrophil adhesion and a surrogate marker for degranulation. We show that EPRO cells, but not 32Dcl3 or NB4, significantly increase Mac-1 surface expression upon functional activation. Together, these data show that EPRO and MPRO cells demonstrate complete, functional activation upon neutrophil differentiation, suggesting these promyelocytic models accurately reflect the functional capacity of mature murine neutrophils.
Enhancement of antigen acquisition by dendritic cells and MHC class II-restricted epitope presentation to CD4+ T cells using VP22 DNA vaccine vectors that promote intercellular spreading following initial transfection
Authors: Mwangi Waithaka , Brown Wendy C , Splitter Gary A , Zhuang Yan , Kegerreis Kimberly , Palmer Guy H
Published: April 2005

Induction of immune responses against microbial antigens using DNA is an attractive strategy to mimic the immunity induced by live vaccines. Although DNA vaccines are efficacious in murine models, the requirement for multiple immunizations using high doses in outbred animals and humans has hindered deployment. This requirement is, in part, a result of poor vaccine spreading and suboptimal DC transfection efficiency. Incorporation of a signal that directs intercellular spreading of a DNA-encoded antigen is proposed to mimic live vaccine spreading and increase dendritic cell (DC) presentation. Bovine herpes virus 1 tegument protein, BVP22, is capable of trafficking to surrounding cells. To test the hypothesis that BVP22 enhances spreading and antigen presentation to CD4+ T cells, a DNA construct containing BVP22, fused in-frame to a sequence encoding a T cell epitope of Anaplasma marginale, was generated. A construct with reversed BVP22 sequence served as a negative control. Immunocytometric analysis of transfected primary keratinocytes, human embryonic kidney 293, COS-7, and Chinese hamster ovary cells showed that BVP22 enhanced intercellular spreading by ≥150-fold. Flow cytometric analysis of antigen-presenting cells (APCs) positively selected from cocultures of transfected cells and APCs showed that 5% of test APCs were antigen-positive, compared with 0.6% of control APCs. Antigen-specific CD4+ T cell proliferation demonstrated that BVP22 enhanced DC antigen presentation by ≥20-fold. This first report of the ability of BVP22 to increase DNA-encoded antigen acquisition by DCs and macrophages, with subsequent enhancement of major histocompatibility complex class II-restricted CD4+ T cell responses, supports incorporating a spreading motif in a DNA vaccine to target CD4+ T cell-dependent immunity in outbred animals.
Evaluation of Epothilone B Analog in Advanced Soft Tissue Sarcoma: A Phase II Study of the Phase II Consortium
Authors: Okuno Scott , Maples William J. , Mahoney Michelle R. , Fitch Tom , Stewart James , Fracasso Paula M. , Kraut Michael , Ettinger David S. , Dawkins Fitzroy , Erlichman Charles
Published: April 2005

Purpose

Epothilones are a new class of nontaxane tubulin polymerization agents that have activity in taxane-resistant tumors. Epothilone B (BMS-247550) is a semisynthetic analog of the natural product epothilone B. This study was performed to determine the activity of BMS-247550 in patients with soft tissue sarcomas (STSs) who had not received prior chemotherapy for metastatic disease.

Patients and Methods

Patients with measurable, advanced, or metastatic STS with no prior chemotherapy for metastatic disease were treated with BMS-2457550 50 mg/m2 intravenously during 1 hour every 21 days. All responses were confirmed 4 weeks later.

Results

Thirty-one patients (median age, 54 years; range, 19 to 78 years; 48% female) were entered onto the trial and were assessable for response. All but one patient had an Eastern Cooperative Oncology Group performance score of 0% or 1%, and 39% had received prior adjuvant chemotherapy. Mean follow-up was 22 months, with a confirmed response rate of 6% (95% CI, 0% to 17%). Median time to progression was 4.5 months (95% CI, 1.9 to 8.3 months), and 1 year progression-free survival was 17% (95% CI, 8% to 38%). Median survival was 16.4 months, with a 1-year survival of 61% (95% CI, 46% to 81%). Toxicity was mainly hematologic, with eight of 31 (26%) patients experiencing grade 3 to 4 leukopenia; 15 of 31 patients (48%) experienced grade 3 to 4 neutropenia. The grade 3 to 4 nonhematologic toxicities included neuropathies (26%), myalgia (13%), and fatigue (10%).

Conclusion

BMS-247550 has limited activity against STSs when given in this dose and schedule. The clinical toxicity is similar to that of taxanes.
Natural History of Rising Serum Prostate-Specific Antigen in Men With Castrate Nonmetastatic Prostate Cancer
Authors: Smith Matthew R. , Kabbinavar Fairooz , Saad Fred , Hussain Arif , Gittelman Marc C. , Bilhartz David L. , Wynne Chris , Murray Robin , Zinner Norman R. , Schulman Claude , Linnartz Ronald , Zheng Ming , Goessl Carsten , Hei Yong-Jiang , Small Eric J. , Cook Richard , Higano Celestia S.
Published: April 2005

Purpose

To describe the natural history of nonmetastatic prostate cancer and rising prostate-specific antigen (PSA) despite androgen deprivation therapy.

Patients and Methods:

The 201 patients in this report were the placebo control group from an aborted randomized controlled trial to evaluate the effects of zoledronic acid on time to first bone metastasis in men with prostate cancer, no bone metastases, and rising PSA despite androgen deprivation therapy. Relationships between baseline covariates and clinical outcomes were assessed by Cox proportional hazard analyses. Covariates in the model were baseline PSA, Gleason sum, history of bilateral orchiectomies, regional lymph node metastases at diagnosis, prior prostatectomy, time from androgen deprivation therapy to random assignment, time from diagnosis to random assignment, and PSA velocity.

Results

At 2 years, 33% of patients had developed bone metastases. Median bone metastasis–free survival was 30 months. Median time to first bone metastases and overall survival were not reached. Baseline PSA level greater than 10 ng/mL (relative risk, 3.18; 95% CI, 1.74 to 5.80; P < .001) and PSA velocity (4.34 for each 0.01 increase in PSA velocity; 95% CI, 2.30 to 8.21; P < .001) independently predicted shorter time to first bone metastasis. Baseline PSA and PSA velocity also independently predicted overall survival and metastasis-free survival. Other covariates did not consistently predict clinical outcomes.

Conclusion

Men with nonmetastatic prostate cancer and rising PSA despite androgen deprivation therapy have a relatively indolent natural history. Baseline PSA and PSA velocity independently predict time to first bone metastasis and survival.
Phase III Randomized Trial of Doxorubicin and Docetaxel Versus Doxorubicin and Cyclophosphamide As Primary Medical Therapy in Women With Breast Cancer: An Anglo-Celtic Cooperative Oncology Group Study
Authors: Evans T.R. Jeffry , Yellowlees Ann , Foster Elizabeth , Earl Helena , Cameron David A. , Hutcheon Andrew W. , Coleman Robert E. , Perren Timothy , Gallagher Christopher J. , Quigley Mary , Crown John , Jones Alison L. , Highley Martin , Leonard Robert C.F. , Mansi Janine L.
Published: April 2005

Purpose

To compare the clinical and pathologic response rates of doxorubicin and cyclophosphamide (AC) with doxorubicin and docetaxel (AD) as primary chemotherapy in women with primary or locally advanced breast cancer.

Patients and Methods

Eligible patients with histologically proven breast cancer with primary tumors ≥ 3 cm, inflammatory or locally advanced disease, and no evidence of metastases were randomly assigned to receive a maximum of six cycles of either doxorubicin (60 mg/m2) plus cyclophosphamide (600 mg/m2) administered intravenously (IV) every 3 weeks or doxorubicin (60 mg/m2) plus docetaxel (75 mg/m2) IV every 3 weeks, followed by surgery on completion of chemotherapy.

Results

A total of 363 patients were randomly assigned to AC (n = 180) or AD (n = 183). A complete clinical response was observed in 17% and 20% of patients treated with AC and AD, respectively (P = .42). Overall (complete and partial) clinical response rates for AC and AD were 61% and 70%, respectively (P = .06). There was no significant difference in either the pathologic complete response rates in the breast with AC (24%) and AD (21%; P = .61) or in the number of patients with positive axillary nodes at surgery with AC (61%) and AD (66%; P = .28). At a median follow-up of 32 months, there is no significant difference between the two groups for the number of relapses.

Conclusion

In contrast to the positive results reported for sequential docetaxel after AC as primary chemotherapy of breast cancer, our data do not suggest a benefit for simultaneous AD over AC.
Catalytic Subunit of Human Telomerase Reverse Transcriptase Is an Independent Predictor of Survival in Patients Undergoing Curative Resection of Hepatic Colorectal Metastases: A Multicenter Analysis
Authors: Dômont Julien , Pawlik Timothy M. , Boige Valérie , Rose Mathieu , Weber Jean-Christophe , Hoff Paulo M. , Brown Thomas D. , Zorzi Daria , Morat Luc , Pignon Jean-Pierre , Rashid Asif , Jaeck Daniel , Sabatier Laure , Elias Dominique , Tursz Thomas , Soria Jean-Charles , Vauthey Jean-Nicolas
Published: April 2005

Purpose

To determine the role of the catalytic subunit of human telomerase reverse transcriptase (hTERT) in predicting survival after resection of hepatic colorectal metastases (CRM).

Patients and Methods

Two hundred one patients who underwent curative resection of hepatic CRM between 1990 and 2000 were identified from a multicenter database. The CRM were analyzed for hTERT nucleolar expression by standard immunohistochemical techniques. hTERT expression and known clinicopathologic factors of survival were examined.

Results

With a median follow-up of 80 months, 152 patients (75.6%) had died; the 5-year overall survival was 30.7%. On univariate analysis, number of metastases greater than two (P = .0005), extrahepatic disease (P = .0054), disease-free interval less than 12 months (P = .006), carcinoembryonic antigen level greater than 200 ng/mL (P = .0071), and positive hTERT nucleolar staining (P < .0001) were associated with decreased survival. On multivariate analysis, three factors independently predicted survival: number of metastases (relative risk [RR] = 1.74; P = .0011); disease-free interval (RR = 1.70; P = .0035); and positive hTERT nucleolar staining (RR = 2.03; P < .0001). Patients with none or one of these factors had a 5-year survival rate of 48%, whereas those with two or three of these factors had a 5-year survival of 15% (P < .0001).

Conclusion

hTERT nucleolar expression is associated with worse survival after resection of hepatic CRM. hTERT expression in conjunction with number of hepatic metastases and disease-free interval may permit more accurate prediction of survival after resection of hepatic CRM.
Time From Treatment to Subsequent Diagnosis of Brain Metastases in Stage III Non–Small-Cell Lung Cancer: A Retrospective Review by the Southwest Oncology Group
Authors: Gaspar Laurie E. , Chansky Kari , Albain Kathy S. , Vallieres Eric , Rusch Valerie , Crowley John J. , Livingston Robert B. , Gandara David R.
Published: April 2005

Purpose

A retrospective review of the Southwest Oncology Group (SWOG) database was undertaken to review the incidence and timing of diagnosis of brain metastases in patients undergoing combined-modality therapy for stage III non–small-cell lung cancer (NSCLC).

Patients and Methods

Four hundred twenty-two eligible, assessable patients with stage IIIA/B NSCLC were treated on four SWOG protocols. Treatment varied with protocol but consisted of concurrent cisplatin-etoposide and radiation in all patients, with a surgery arm in two of the four protocols.

Results

Of the 422 total patients, 268 (64%) have experienced disease progression; 54 relapses (20%) were in brain only, 17 (6.5%) were in brain and other sites simultaneously, and 197 (63.5%) were in sites other than brain. Of the 268 patients with disease progression, progression in the brain only, in the brain and other sites, and not in the brain occurred in 20%, 6%, and 74% of patients, respectively. Time from treatment to diagnosis of disease progression in the brain in 71 patients was as follows: during treatment, 16 relapses (22.5%); 0 to 16 weeks after treatment, 17 relapses (24%); 16 weeks to 6 months after treatment, 10 relapses (14%); 6 to 12 months after treatment, 16 relapses (22.5%); and more than 12 months after treatment, 12 relapses (17%). Nonsquamous histology and young patient age were the only significant predictors for increased risk of early relapse with brain metastases.

Conclusion

Brain metastases often develop early in the course of treatment for stage IIIA/B NSCLC. The statistical designs of ongoing trials of prophylactic cranial irradiation in stage III NSCLC have taken this into account.
Depression, Correlates of Depression, and Receipt of Depression Care Among Low-Income Women With Breast or Gynecologic Cancer
Authors: Ell Kathleen , Sanchez Kathleen , Vourlekis Betsy , Lee Pey-Jiuan , Dwight-Johnson Megan , Lagomasino Isabel , Muderspach Laila , Russell Christy
Published: April 2005

Purpose

To assess the prevalence of depression among low-income, ethnic minority women with breast or gynecologic cancer, receipt of antidepressant medications or counseling services, and correlates of depression.

Patients and Methods

Study patients were 472 women receiving cancer care in an urban public medical center. Women had a primary diagnosis of breast (stage 0 to III) or gynecologic cancer (International Federation of Gynecology and Obstetrics stage 0 to IIIB). A diagnostic depression screen and baseline questionnaire were administered before or during active treatment or during active follow-up. Self-report data were collected on receipt of depression treatment, use of supportive counseling, pain and receipt of pain medication, functional status and well-being, and perceived barriers to cancer care.

Results

Twenty-four percent of women reported moderate to severe levels of depressive disorder (30% of breast cancer patients and 17% of gynecologic cancer patients). Only 12% of women meeting criteria for major depression reported currently receiving medications for depression, and only 5% of women reported seeing a counselor or participating in a cancer support group. Neither cancer stage nor treatment status was correlated with depression. Primary diagnosis of breast cancer, younger age, greater functional impairment, poorer social and family well-being, anxiety, comorbid arthritis, and fears about treatment side effects were correlated with depression.

Conclusion

Findings indicate that depressive disorder among ethnic minority, low-income women with breast or gynecologic cancer is prevalent and is correlated with pain, anxiety, and health-related quality of life. Because these women are unlikely to receive depression treatment or supportive counseling, there is a need for routine screening, evaluation, and treatment in this population.
Clinicopathologic Behavior of Gastric Adenocarcinoma in Hispanic Patients: Analysis of a Single Institution's Experience Over 15 Years
Authors: Yao James C. , Tseng Jennifer F. , Worah Samidha , Hess Kenneth R. , Mansfield Paul F. , Crane Christopher H. , Schnirer Isac I. , Reddy Satish , Chiang Silvia S. , Najam Azmeena , Yu Christina , Giacco Geoffrey G. , Xie Keping , Wu Tsung-Teh , Feig Barry W. , Pisters Peter W.T. , Ajani Jaffer A.
Published: April 2005

Purpose

To determine the clinicopathologic behavior of gastric adenocarcinoma in Hispanics by comparing Hispanic and non-Hispanic patients treated at a single cancer center.

Patients and Methods

Medical records of patients with invasive gastric cancer treated from 1985 to 1999 were reviewed. Diagnoses were pathologically confirmed. Differences in categorical variables were assessed using the χ2test. Logistic regression was used for multivariate analyses. Median survival was estimated using the Kaplan-Meier method. Cox proportional hazards modeling was used to assess the impact of covariates.

Results

Of 1,897 patients, 301 (15.9%) were Hispanic. Hispanics were significantly younger at diagnosis than non-Hispanic whites (53.1 ± 14.4 years v 59.4 ± 12.7 years, respectively; P < .005) or African Americans (57.6 ± 15.3 years, P < .005). Hispanics were less likely to have proximal gastric cancers compared with whites (38.9% v 59.5%, respectively; P < .005). Hispanics were more likely to have mucinous/signet-ring type histology (42.5%) than whites (27.4%) and African Americans (32.5%; P < .005). Hispanics were more likely to require total gastrectomy (51%) compared with whites (38%), African Americans (38%), and Asians (36%; P = .039). Among patients with metastases at diagnosis, Hispanics were less likely to have liver metastasis than whites (30% v 44%, respectively; P = .009) but more likely to have peritoneal metastasis than whites and African Americans (54% v 41% and 47%, respectively; P = .002). In Cox analyses, Asian race, earlier stage, papillary/tubular histology, distal location, and younger age were favorable predictors of survival.

Conclusion

Hispanic ethnicity does not impact survival in gastric adenocarcinoma. However, histology, metastasis pattern, tumor localization, and other clinical parameters differ sufficiently to warrant further investigation into the epidemiology, pathogenesis, and molecular biology of gastric cancer in this population.
Central Venous Lines in Children With Lesser Risk Acute Lymphoblastic Leukemia: Optimal Type and Timing of Placement
Authors: McLean Thomas W. , Fisher Christen J. , Snively Beverly M. , Chauvenet Allen R.
Published: April 2005

Purpose

In pediatric patients with acute lymphoblastic leukemia (ALL), the optimal time for central venous line (CVL) insertion and the optimal type of CVL (internal v external) is unclear. This study was undertaken to compare complication rates between early versus late line insertion, and between internal versus external lines in children with lesser risk ALL.

Patients and Methods

We performed a retrospective analysis of patients enrolled onto Pediatric Oncology Group (POG) protocol 9201. Data regarding demographics, CVL types and insertion dates, blood counts, and complications were reviewed through week 25 of therapy.

Results

Of 697 patients enrolled onto POG protocol 9201, 362 patients had sufficient data for analysis. When compared to late line placement (> day 15 of induction), early CVL placement (≤ day 15 of induction) was associated with an increased risk of having a positive blood culture (odds ratio, 2.2; 95% CI, 1.0 to 5.0; P = .05). When compared with internal CVLs (“ports”), external CVLs were associated with a positive blood culture (odds ratio, 3.1; 95% CI, 1.3 to 7.5; P = .01), thrombosis (odds ratio, 3.9; 95% CI, 1.5 to 10.3; P = .006), and CVL removal (odds ratio, 5.6; 95% CI, 2.7 to 11.6; P < .001).

Conclusion

In pediatric patients with lesser risk ALL, internal lines (ports) should be the preferred CVL type due to a lower risk of infectious and thrombotic complications. In addition, CVLs placed early in induction are associated with a higher risk of positive blood culture than those placed later in induction.
Staggered cell-intrinsic timing ofath5expression underlies the wave of ganglion cell neurogenesis in the zebrafish retina
Authors: Kay Jeremy N. , Link Brian A. , Baier Herwig
Published: April 2005

In the developing nervous system, progenitor cells must decide when to withdraw from the cell cycle and commence differentiation. There is considerable debate whether cell-extrinsic or cell-intrinsic factors are most important for triggering this switch. In the vertebrate retina, initiation of neurogenesis has recently been explained by a `sequential-induction' model– signals from newly differentiated neurons are thought to trigger neurogenesis in adjacent progenitors, creating a wave of neurogenesis that spreads across the retina in a stereotypical manner. We show here, however,that the wave of neurogenesis in the zebrafish retina can emerge through the independent action of progenitor cells – progenitors in different parts of the retina appear pre-specified to initiate neurogenesis at different times. We provide evidence that midline Sonic hedgehog signals, acting before the onset of neurogenesis, are part of the mechanism that sets the neurogenic timer in these cells. Our results highlight the importance of intrinsic factors for triggering neurogenesis, but they also suggest that early signals can modulate these intrinsic factors to influence the timing of neurogenesis many cell cycles later, thereby potentially coordinating axial patterning with control of neuron number and cell fate.
Multiple roles of the F-box protein Slimb inDrosophilaegg chamber development
Authors: Muzzopappa Mariana , Wappner Pablo
Published: April 2005

Substrate-specific degradation of proteins by the ubiquitin-proteasome pathway is a precise mechanism that controls the abundance of key cell regulators. SCF complexes are a family of E3 ubiquitin ligases that target specific proteins for destruction at the 26S-proteasome. These complexes are composed of three constant polypeptides – Skp1, Cullin1/3 and Roc1/Rbx1– and a fourth variable adapter, the F-box protein. Slimb (Slmb) is a Drosophila F-Box protein that fulfills several roles in development and cell physiology. We analyzed its participation in egg chamber development and found that slmb is required in both the follicle cells and the germline at different stages of oogenesis. We observed that in slmbsomatic clones, morphogenesis of the germarium and encapsulation of the cyst were altered, giving rise to egg chambers with extra germline cells and two oocytes. Furthermore, in slmb somatic clones, we observed ectopic Fasciclin 3 expression, suggesting a delay in follicle cell differentiation,which correlated with the occurrence of ectopic polar cells, lack of interfollicular stalks and mislocalization of the oocyte. Later in oogenesis,Slmb was required in somatic cells to specify the position, size and morphology of dorsal appendages. Mild overactivation of the Dpp pathway caused similar phenotypes that could be antagonized by simultaneous overexpression of Slmb, suggesting that Slmb might normally downregulate the Dpp pathway in follicle cells. Indeed, ectopic expression of a dad-LacZ enhancer trap revealed that the Dpp pathway was upregulated in slmb somatic clones and, consistent with this, ectopic accumulation of the co-Smad protein,Medea, was recorded. By analyzing slmb germline clones, we found that loss of Slmb provoked a reduction in E2f2 and Dp levels, which correlated with misregulation of mitotic cycles during cyst formation, abnormal nurse cell endoreplication and impairment of dumping of the nurse cell content into the oocyte.
Ssdp1 regulates head morphogenesis of mouse embryos by activating the Lim1-Ldb1 complex
Authors: Nishioka Noriyuki , Nagano Seiichi , Nakayama Rika , Kiyonari Hiroshi , Ijiri Takashi , Taniguchi Kenichiro , Shawlot William , Hayashizaki Yoshihide , Westphal Heiner , Behringer Richard R. , Matsuda Yoichi , Sakoda Saburo , Kondoh Hisato , Sasaki Hiroshi
Published: April 2005

The transcriptional activity of LIM-homeodomain (LIM-HD) proteins is regulated by their interactions with various factors that bind to the LIM domain. We show that reduced expression of single-stranded DNA-binding protein 1 (Ssdp1), which encodes a co-factor of LIM domain interacting protein 1 (Ldb1), in the mouse mutant headshrinker (hsk)disrupts anterior head development by partially mimicking Lim1mutants. Although the anterior visceral endoderm and the anterior definitive endoderm, which together comprise the head organizer, were able to form normally in Ssdp1hsk/hsk mutants, development of the prechordal plate was compromised. Head development is partially initiated in Ssdp1hsk/hsk mutants, but neuroectoderm tissue anterior to the midbrain-hindbrain boundary is lost, without a concomitant increase in apoptosis. Cell proliferation is globally reduced in Ssdp1hsk/hsk mutants, and approximately half also exhibit smaller body size, similar to the phenotype observed in Lim1 and Ldb1 mutants. We also show that Ssdp1 contains an activation domain and is able to enhance transcriptional activation through a Lim1-Ldb1 complex in transfected cells, and that Ssdp1 interacts genetically with Lim1 and Ldb1 in both head development and body growth. These results suggest that Ssdp1 regulates the development of late head organizer tissues and body growth by functioning as an essential activator component of a Lim1 complex through interaction with Ldb1.
Induction and migration of the anterior visceral endoderm is regulated by the extra-embryonic ectoderm
Authors: Rodriguez Tristan A. , Srinivas Shankar , Clements Melanie P. , Smith James C. , Beddington Rosa S. P.
Published: April 2005

The anterior visceral endoderm (AVE) is an extra-embryonic tissue required for specifying anterior pattern in the mouse embryo. The AVE is induced at the distal tip of the 5.5 dpc embryo and then migrates to the prospective anterior, where it imparts anterior identity upon the underlying epiblast (the tissue that gives rise to the embryo proper). Little is known about how the AVE is induced and what directs its migration. In this paper, we describe an essential role for another extra-embryonic tissue, the extra-embryonic ectoderm (ExE), in patterning the AVE and epiblast. Removal of the ExE in pre-gastrulation embryos leads to ectopic AVE formation, to a failure of AVE cell migration and to the assumption by the entire epiblast of an anterior identity. Ectopic transplantation of ExE cells inhibits AVE formation and leads to an expansion of the posterior epiblast marker T. These results demonstrate that the ExE restricts the induction of the AVE to the distal tip of the mouse embryo and is required to initiate the migration of these cells to the prospective anterior. Together, these data reveal a novel role for the ExE in the specification of the anteroposterior axis of the mouse embryo.
Efeitos da fratura de corpo da mandíbula no crescimento da maxila e da mandíbula: estudo experimental em ratos jovens
Authors: Rocha Elza Maria Villanova Fernandes da , Goulart Alan Cruvinel , Goldenberg Saul , Luz João Gualberto de Cerqueira
Published: April 2005

Objetivo: Observar os efeitos da fratura experimental de corpo de mandíbula no crescimento da maxila e mandíbula. Métodos: Utilizando ratos com um mês de idade. Estes foram distribuídos em dois grupos: experimental, onde foi efetuada a fratura de corpo de mandíbula à direita, e controle-operado, no qual foi realizado apenas o acesso cirúrgico. Aos três meses de idade foi realizada a eutanásia e após a maceração, a mandíbula foi desarticulada. O crânio foi submetido à incidência radiográfica axial e as hemi-mandibulas à incidência radiográfica lateral. Com base nestas, foram feitas mensurações cefalométricas por meio de um sistema de computador e os valores submetidos a análises estatísticas. Resultados: O comprimento da maxila, bem como a altura e o comprimento da mandíbula apresentaram diferença significante a menor para o lado direito, no grupo experimental. No grupo controle-operado houve diferença significante a menor para o comprimento da porção posterior da maxila e para a altura e comprimento da mandíbula para o lado direito. O grupo experimental quando comparado ao grupo controle-operado mostrou ser significativamente menor em todas as mensurações da maxila e mandíbula para ambos os lados, com exceção do comprimento da mandíbula. Conclusão: A fratura de corpo da mandíbula, bem como a abordagem cirúrgica, tiveram efeitos negativos no crescimento da maxila e da mandíbula.
Effects of Anemia and Left Ventricular Hypertrophy on Cardiovascular Disease in Patients with Chronic Kidney Disease
Authors: Weiner Daniel E. , Tighiouart Hocine , Vlagopoulos Panagiotis T. , Griffith John L. , Salem Deeb N. , Levey Andrew S. , Sarnak Mark J.
Published: April 2005

Left ventricular hypertrophy (LVH) and anemia are highly prevalent in moderate chronic kidney disease (CKD). Because anemia may potentiate the adverse effects of LVH on cardiovascular outcomes, the effect of both anemia and LVH on outcomes in CKD was examined. Data from four community-based longitudinal studies were pooled: Atherosclerosis Risk in Communities Study, Cardiovascular Health Study, Framingham Heart Study, and Framingham Offspring Study. Serum creatinine levels were calibrated indirectly across studies, and GFR was estimated using the Modification of Diet in Renal Disease equation. CKD was defined as GFR between 15 and 60 ml/min per 1.73 m2. LVH was based on electrocardiogram criteria. Anemia was defined as hematocrit <36% in women and 39% in men. The primary outcome was a composite of myocardial infarction, stroke, and death; a secondary cardiac outcome included only myocardial infarction and fatal coronary heart disease. Among 2423 patients with CKD, 96% had electrocardiogram and anemia data. Median follow-up was 102 mo. In adjusted analysis, LVH was associated with increased risk for composite and cardiac outcomes (hazard ratio [HR], 1.67 [95% confidence interval (CI), 1.34 to 2.07] and 1.62 [95% CI, 1.18 to 2.24], respectively), whereas anemia was associated with increased risk for the only composite outcome (HR, 1.51 [95% CI, 1.27 to 1.81]). The combination of anemia and LVH was associated with an increased risk for both study outcomes compared with individuals with neither risk factor (HR, 4.15 [95% CI, 2.62 to 6.56] and 3.92 [95% CI, 2.05 to 7.48];

P

= 0.02 and 0.01 for interaction term, respectively). The combination of anemia and LVH in CKD identifies a high-risk population.
Impact of Cadaveric Renal Transplantation on Survival in Patients Listed for Transplantation
Authors: Oniscu Gabriel C. , Brown Helen , Forsythe John L.R.
Published: April 2005

The aim of this study was to assess the magnitude of the survival benefit of renal transplantation compared with dialysis in patients selected for transplantation in Scotland. Longitudinal study of survival and mortality risk in all adult patients (1732) listed for a first transplant between January 1, 1989, and December 31, 1989, in Scotland. A time-dependant Cox regression analysis adjusted for comorbidity, sociodemographic and geographic factors, primary renal disease, time on dialysis, and year of listing compared the risk of death for patients receiving a first cadaveric transplant

versus

all patients on dialysis listed for transplantation. After adjustment for the covariates, the relative risk (RR) of death during the first 30 days after transplantation was 1.35 (95% confidence interval [CI], 0.63 to 2.86) compared with patients on dialysis (RR = 1). The long-term RR (at 18 mo) for the transplant recipients was 0.18 (95% CI, 0.08 to 0.42) when compared with patients on dialysis (RR = 1). This lower long-term risk of death was present in all patients undergoing transplantation, irrespective of their age group or primary renal disease. Similar results were seen when survival with a transplant was censored for graft failure. The projected life expectancy with a transplant was 17.19 yr compared with only 5.84 yr on dialysis. Despite an initial higher risk of death, long-term survival for patients who undergo transplantation is significantly better compared with patients who are listed but remain on dialysis. A successful transplant triples the life expectancy of a listed renal failure patient.
Sexual Assault Prevention With College-Aged Women: A Bibliotherapy Approach
Authors: Yeater Elizabeth A. , Naugle Amy E. , O’Donohue William , Bradley April R.
Published: April 2005

The present research evaluated the efficacy of a skills-based bibliotherapy approach to sexual assault prevention for college-aged women. One hundred and ten participants were followed prospectively for 16 weeks. A self-help book, written by the authors, was compared to a wait-list control on several self-report measures. Results revealed significant differences between groups, with bibliotherapy participants reporting decreased participation in risky dating behaviors and improvement in sexual communication strategies across a variety of dating situations. However, results suggested that the self-help book was no more effective than the wait-list control in reducing rates of sexual victimization. Limitations of the study and directions for future sexual assault prevention research with women are discussed.
Enantio‐ and Diastereoselective Michael Reaction of 1,3‐Dicarbonyl Compounds to Nitroolefins Catalyzed by a Bifunctional Thiourea.
Authors: Okino Tomotaka , Hoashi Yasutaka , Furukawa Tomihiro , Xu Xuenong , Takemoto Yoshiji
Published: April 2005

For Abstract see ChemInform Abstract in Full Text.
Mechanism of Monoreduction of Unsymmetrical Dinitrobenzenes Containing Heterocyclic Fragments by Metal Salts of Variable Valency.
Authors: Begunov R. S. , Demidova N. Yu. , Brodskii I. I. , Orlov V. Yu.
Published: April 2005

For Abstract see ChemInform Abstract in Full Text.
The Synthesis of Baclofen and GABOB via Rh(II) Catalyzed Intramolecular C—H Insertion of α‐Diazoacetamides.
Authors: Chen Zhenliang , Chen Zhiyong , Jiang Yaozhong , Hu Wenhao
Published: April 2005

For Abstract see ChemInform Abstract in Full Text.
Reaction of Octafluorocyclopentene with Various Carbon Nucleophiles.
Authors: Yamada Shigeyuki , Konno Tsutomu , Ishihara Takashi , Yamanaka Hiroki
Published: April 2005

For Abstract see ChemInform Abstract in Full Text.
Synthesis of Conjugated Enediynes via Palladium‐Catalyzed Cross‐Coupling Reactions of Potassium Alkynyltrifluoroborates.
Authors: Kabalka George W. , Dong Gang , Venkataiah Bollu
Published: April 2005

For Abstract see ChemInform Abstract in Full Text.
Heterocyclization of Functionalized Heterocumulenes with C,N‐ and C,O‐Binucleophiles. Part 5. Synthesis of Imidazo[1,5‐a]imidazole Derivatives by Cyclocondensation of 1‐Chloroalkyl Isocyanates with Imidazoles and Benzimidazole.
Authors: Vovk M. V. , Sukach V. A. , Pinchuk A. M. , Chernega A. N. , Pirozhenko V. V. , Howard J. A. K.
Published: April 2005

For Abstract see ChemInform Abstract in Full Text.
Mild, Selective, and High‐Yield Oxidation of Hantzsch 1,4‐Dihydropyridines with Lead(IV) Acetate.
Authors: Litvic Mladen , Cepanec Ivica , Filipan Mirela , Kos Karmen , Bartolincic Anamarija , Druskovic Vinka , Tibi Mohamed Majed , Vinkovic Vladimir
Published: April 2005

For Abstract see ChemInform Abstract in Full Text.
First Report on the Abnormal Dearylation/Alkylation Reaction in One‐Pot Hantzch Synthesis with 6‐Amino‐1,3‐dimethyl Uracil.
Authors: Agarwal Anu , Chauhan Prem M. S.
Published: April 2005

For Abstract see ChemInform Abstract in Full Text.
Synthesis of Novel 5‐Trifluoromethyl‐2,4,7‐trisubstituted Pyrido[2,3‐d]pyrimidines.
Authors: Ravikanth S. , Reddy G. Venkat , Maitraie D. , Rao V. V. V. N. S. Rama , Rao P. Shanthan , Narsaiah B.
Published: April 2005

For Abstract see ChemInform Abstract in Full Text.
Heterocyclization of Functionalized Heterocumulenes with C,N‐ and C,O‐Binucleophiles. Part 4. Reactions of 1‐Chloroalkylheterocumulenes and N‐(1‐Chloroalkylidene)carbamates with 2‐Benzimidazolylacetonitriles and Methyl 2‐Benzimidazolylacetates.
Authors: Vovk M. V. , Lebed' P. S. , Pirozhenko V. V. , Tsymbal I. F.
Published: April 2005

For Abstract see ChemInform Abstract in Full Text.
Synthesis of 3,4,5‐Tris(alkyloxy)benzyl Glycosides and Glycolipid Analogues.
Authors: Sato Reiko , Toma Kazunori , Nomura Kazufumi , Takagi Mutsumi , Yoshida Yoshiomi , Azefu Yasuo , Tamiaki Hitoshi
Published: April 2005

For Abstract see ChemInform Abstract in Full Text.
Some Aspects of the Willgerodt—Kindler Reaction and Connected Reactions
Authors: Purrello Giovanni
Published: April 2005

For Abstract see ChemInform Abstract in Full Text.
Marine Natural Products
Authors: Blunt John W. , Copp Brent R. , Munro Murray H. G. , Northcote Peter T. , Prinsep Michele R.
Published: April 2005

For Abstract see ChemInform Abstract in Full Text.
Homer expression in the Xenopus tadpole nervous system
Authors: Foa Lisa , Jensen Kendall , Rajan Indrani , Bronson Kim , Gasperini Robert , Worley Paul F. , Tu Jian C. , Cline Hollis T.
Published: April 2005

Homer proteins are integral components of the postsynaptic density and are thought to function in synaptogenesis and plasticity. In addition, overexpression of Homer in the developing Xenopus retinotectal system results in axonal pathfinding errors. Here we report that Xenopus contains the homer1 gene, expressed as the isoform, xhomer1b, which is highly homologous to the mammalian homer1b. The mammalian homer1 gene is expressed as three isoforms, the truncated or short form homer1a and the long forms homer1b and ‐1c. For Xenopus, we cloned three very similar variants of homer1b, identified as Xenopus xhomer1b.1, xhomer1b.2, and xhomer1b.3, which display up to 98% homology with each other and 90% similarity to mammalian homer1b. Furthermore, we demonstrate that Xenopus also contains a truncated form of the Homer1 protein, which could be induced by kainic acid injection and is likely homologous to the mammalian Homer1a. xHomer1b expression was unaffected by neuronal activity levels but was developmentally regulated. Within the brain, the spatial and temporal distributions of both Homer isoforms were similar in the neuropil and cell body regions. Homer1 was detected in motor axons. Differential distribution of the two isoforms was apparent: Homer1b immunoreactivity was prominent at junctions between soma and the ventricular surface; in the retina, the Mueller radial glia were immunoreactive for Homer1, but not Homer1b, suggesting the retinal glia contain only the Homer1a isoform. Homer1b expression in muscle was prominent throughout development and was aligned with the actin striations in skeletal muscle. The high level of conservation of the xhomer1 gene and the protein expression in the developing nervous system suggest that Homer1 expression may be important for normal neuronal circuit development. J. Comp. Neurol. 487:42–53, 2005. © 2005 Wiley‐Liss, Inc.
Distribution of galanin‐like immunoreactivity in the brain of the Siberian sturgeon (Acipenser baeri)
Authors: Adrio Fátima , Rodríguez Miguel Ángel , Rodríguez‐Moldes Isabel
Published: April 2005

Galanin is a 29‐amino acid peptide widely distributed in the central nervous system of vertebrates. The organization of galaninergic systems is well known in teleosts, the most advanced actinopterygians, but no data are available on primitive bony fish. To extend the evolutionary analysis of galaninergic systems we studied the distribution of galanin‐like immunoreactive (GAL‐ir) cells and fibers in the sturgeon brain, since chondrosteans are among the most primitive extant actinopterygians. Double‐immunolabeling experiments were performed to compare the distribution of galanin with that of neurophysin, tyrosine hydroxylase, and serotonin. Numerous GAL‐ir cells of cerebrospinal fluid‐contacting (CSF‐C) type were found in the ventral telencephalon, preoptic area, and in the tuberal and caudal hypothalamus. The distribution of GAL‐ir elements in the sturgeon brain shows many similarities to that observed in other vertebrates, but also important differences, such as the abundance of GAL‐ir CSF‐C cells, which appear to be a primitive characteristic. GAL‐ir neurons observed in the sturgeon telencephalic hemispheres perhaps represent the basic organization of common ancestors of bony fishes and tetrapods. In the preoptic‐hypophyseal system, GAL‐ir cells appeared to be related not only with neurophysin‐expressing neurons (in the tuberal hypothalamus) but also with serotoninergic and catecholamines‐synthesizing neurons (in preoptic and tuberal nuclei). Numerous GAL‐ir fibers were observed in the median eminence and neural lobe of the hypophysis, indicating that galanin may play a role in the modulation of hypophyseal secretion. GAL‐ir neurons were absent from the sturgeon brainstem, suggesting that their presence in other vertebrates could represent an evolutionary recent acquisition. J. Comp. Neurol. 487:54–74, 2005. © 2005 Wiley‐Liss, Inc.
Synthesis, Crystal Structure and Magnetic Properties of Heterodimetallic ReIVCuII Complexes
Authors: Tomkiewicz Alina , Mroziński Jerzy , Brüdgam Irene , Hartl Hans
Published: April 2005

The two rhenium(IV)‐copper(II) heterometallic complexes [CuLβ][ReCl4(ox)]·DMF (1) and [(CuLα)2Cl][ReCl4(ox)]Cl (2) (Lβ = N‐dl‐5,7,7,12,14,14‐hexamethyl‐1,4,8,11‐tetraazacyclotetradeca‐4,11‐diene and Lα = N‐dl‐5,7,7,12,12,14‐hexamethyl‐1,4,8,11‐tetraazacyclotetradeca‐4,14‐diene) were synthesized, and the crystal structures of both compounds were determined at 173(2) K. Complex 1 crystallizes in a monoclinic space group P21, with a = 9.365(2) Å, b = 15.150(2) Å, c = 10.776(1) Å, β = 110.01(1)°, Z = 2, whereas 2 crystallizes in an orthorhombic space group Pca21 with a = 16.660(5) Å, b = 16.017(5) Å, c = 17.066(5) Å, and Z = 4. The CuLβ macrocycle cation is approximately planar and coordinated from above and below by [ReCl4(ox)]2– units through the bis(bidentate) oxalato ligands. It features an oxalato‐bridged heterometallic ReIV–CuII zigzag chain, the shortest intrachain metal–metal distances are Re···Cu = 5.568(2) and 5.870(2) Å in the direction of the b axis. The crystal structure of 2 consists of dinuclear complex cations [(CuLα)2Cl]3+ with [ReCl4ox]2– and isolated Cl– as counter anions. Cu atoms in CuLα are only fivefold coordinated in a square pyramidal surrounding, and the cations (CuLα)2+ are connected in pairs by chloride. The intramolecular Cu···Cu separation is 4.885(3) Å, the shortest Re···Cu distance is 7.612(3) Å. The magnetic behavior of 1 and 2 has been investigated over the temperature range 1.7–300 K. Compound 1 behaves like a ferrimagnetic CuII‐ReIV dimetallic, one–dimensional chain with intrachain antiferromagnetic coupling. Compound 2 shows weak antiferromagnetic interactions within the CuII–CuII units. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Four New Lead(II) Thiolate Cluster Complexes – Unexpected Products of a Conventional Synthesis
Authors: Eichhöfer Andreas
Published: April 2005

The reaction of Pb(OOCCH3)2·3H2O with 2.1 equiv. of HS‐2,6‐(CH3)2C6H3 in ethanol/water is expected to give [Pb{S‐2,6‐(CH3)2C6H3}2]. However, we obtained an orange powder whose elemental analysis disagrees with that of the expected product and indicates small amounts of oxygen. Layering of concentrated solutions of this orange powder in dry THF with pentane under nitrogen results in the formation of a mixture of three identifiable crystalline compounds, namely [Pb10{S‐2,6‐(CH3)2C6H3}20], [Pb6S{S‐2,6‐(CH3)2C6H3}10(C4H8O)4] and [Pb8O2{S‐2,6‐(CH3)2C6H3}12]. In contrast, fractional crystallization from dilute solutions initially yielded only yellow crystals of [Pb14O6{S‐2,6‐(CH3)2C6H3}16]. Further concentration of the supernatant solution yielded, upon layering with pentane, [Pb6S{S‐2,6‐(CH3)2C6H3}10(C4H8O)4] and [Pb10{S‐2,6‐(CH3)2C6H3}20], which are almost completely separable by controlling the duration of the crystallization step and the amount of condensed pentane. Recrystallization of the crude orange powder under aerobic conditions produces pure [Pb14O6{S‐2,6‐(CH3)2C6H3}16] with a yield five times higher than that under nitrogen. This shows that it is sensitive to oxidation by oxygen in solution. The structures of all four complexes have been determined by single‐crystal X‐ray analysis. The net formed by the six oxygen and twelve lead atoms in the center of [Pb14O6{S‐2,6‐(CH3)2C6H3}16] resembles a small piece of a layer of the solid‐state structure of red PbO. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Novel Methanol‐Containing Oxomolybdate(V) Complexes: Synthesis and Structural Characterisation of Intermediates in the Formation of {Mo2O4}2+ Clusters from [MoOCl4(H2O)]– and [MoOBr4]– Precursors
Authors: Modec Barbara , Brenčič Jurij V.
Published: April 2005

A series of oxomolybdate(V) complexes with methanol was prepared by the reaction of (PyH)5[MoOCl4(H2O)]3Cl2 (1) or (PyH)[MoOBr4] (PyH+ = pyridinium cation, C5H5NH+) in methanol. (PyH)2[MoOCl4(MeOH)]Cl (2) is obtained upon substitution of coordinated water for methanol in 1. Small amounts of weak bases such as pyridine or trifluoroacetate promote further substitution chemistry at the labile sites, followed by dimerisation to the well‐known {Mo2O4}2+ core. A dinuclear anion with coordinated methanol can be isolated as its pyridinium salt, (PyH)2[Mo2O4Cl4(MeOH)2], in two crystalline modifications, either as a triclinic (3) or as an orthorhombic polymorph (4). After prolonged reaction times further assembly of dinuclear fragments takes place and tetranuclear [Mo4O8(OMe)2(MeOH)2Cl4]2– is formed. The products of the analogous reactions with (PyH)[MoOBr4] as the starting material depend largely upon the reaction temperature. Dinuclear (PyH)2[Mo2O4Br4(MeOH)2] (5), which crystallises in an orthorhombic unit cell and whose structure is isotypic to that of 4, is obtained only if the reaction takes place at low temperature (5 °C); under ambient conditions (PyH)2[Mo4O8(OMe)2(MeOH)2Br4] (6) is obtained instead. The tetranuclear anion of 6 consists of a commonly adopted assembly of two {Mo2O4}2+ units. The identity of the products was determined by infrared spectroscopy and X‐ray structure analyses. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)