bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolution of the mammary gland from the innate immune system?
Authors: Vorbach Claudia , Capecchi Mario R. , Penninger Josef M. 
Published: May 2006

AbstractThe mammary gland is a skin gland unique to the class Mammalia. Despite a growing molecular and histological understanding of the development and physiology of the mammary gland, its functional and morphological origins have remained speculative. Numerous theories on the origin of the mammary gland and lactation exist. The purpose of the mammary gland is to provide the newborn with copious amounts of milk, a unique body fluid that has a dual role of nutrition and immunological protection. Interestingly, antimicrobial enzymes, such as xanthine oxidoreductase or lysozyme, are directly involved in the evolution of the nutritional aspect of milk. We outline that xanthine oxidoreductase evolved a dual role in the mammary gland and hence provide new evidence supporting the hypothesis that the nutritional function of the milk evolved subsequent to its protective function. Therefore, we postulate that the mammary gland evolved from the innate immune system. In addition, we suggest that lactation partly evolved as an inflammatory response to tissue damage and infection, and discuss the observation that the two signaling pathways, NF‐kB and Jak/Stat, play central roles in inflammation as well as in lactation. BioEssays 28: 606–616, 2006. © 2006 Wiley Periodicals, Inc.
The ovotestis: an underdeveloped organ of evolution
Authors: Davison Angus 
Published: May 2006

AbstractIn animals that have separate sexes (gonochorists), many sperm are produced to fertilise a few eggs. As the male germline undergoes more mitoses, so the accumulated mutation frequency is elevated in sperm compared with ova, and evolution is ‘male‐driven’. In contrast, in many hermaphroditic animals, a single organ—the ovotestis—produces both ova and sperm. Since self‐renewing cells in the ovotestis may give rise to both cell types throughout life, ova in hermaphrodites could in theory have undergone as many cell divisions as sperm. Here, I consider some possible effects of the ovotestis on evolution. In particular, I hypothesise that the accumulated mutation frequency of nuclear genes in hermaphrodites (including species that change sex) may reach twice that compared with gonochorists. There may be an even greater increase in the mitochondrial mutation frequency. Further developmental studies and the accumulation of comparative data should allow hypothesis testing. If the prediction is correct, then it may provide the most‐straightforward explanation for the extraordinary diversity of mitochondrial DNA in some hermaphrodites, especially molluscs. BioEssays 28: 642–650, 2006. © 2006 Wiley Periodicals, Inc.
Repeated Confidence Intervals in Self‐Designing Clinical Trials and Switching between Noninferiority and Superiority
Authors: Hartung Joachim , Knapp Guido 
Published: May 2006

AbstractIn self‐designing clinical trials, repeated confidence intervals are derived for the parameter of interest where the results of the independent study stages are combined using the generalized inverse chi‐square‐method. The confidence intervals can be calculated at each interim analysis and always hold the predefined overall nominal confidence level. Moreover, the confidence intervals calculated during the course of the trial are nested in the sense that a calculated interval is completely contained in all the previously calculated intervals. During the course of the self‐designing trial the sample sizes as well as the number of study stages can be determined simultaneously in a completely adaptive way. The adaptive procedure allows an early stop for significance.The clinical trial may be originally designed either to show noninferiority or superiority. However, in each interim analysis, it is possible to change the planning from showing superiority to showing noninferiority or vice versa. Since the repeated confidence intervals are nested, there is no risk to loose the noninferiority once showed when, after an interim analysis, the trial is continued in an attempt to reach superiority.A simulation study investigates the behavior of the considered confidence intervals. The performance of the derived nested repeated confidence intervals is also demonstrated in examples showing both kinds of switching during an ongoing trial. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Gum mastic inhibits the expression and function of the androgen receptor in prostate cancer cells
Authors: He Mei‐Lan , Yuan Hui‐Qing , Jiang An‐Li , Gong Ai Yu , Chen Wei‐Wen , Zhang Peng‐Ju , Young Charles Y. F. , Zhang Jian‐Ye 
Published: May 2006

AbstractAccumulating evidence suggests that the androgen receptor (AR) may play an important role in the development and progression of prostate cancer. To find new, useful compounds that effectively may attenuate the function of AR in prostate cancer cells, the authors investigated the effect of gum mastic, a natural resin, on AR activity. An androgen‐responsive prostate cancer cell line LNCaP was used as a model for this study. Gene transfer, reverse transcriptase‐polymerase chain reaction analysis, electrophoretic mobility shift assay, and Western blot analysis were used to test the effect of gum mastic on the expression and function of the AR. To demonstrate the inhibitory effect of gum mastic on the function of the AR, the expression of androgen‐regulated genes, including prostate‐specific antigen (PSA), human kallikrein 2 (hK2), and NKX3.1 were measured. In addition, transient transfection assays with the PSA promoter and the AR promoter also were used to test the effects of mastic. The results showed that gum mastic inhibited the expression of the AR at the transcriptional level, resulting in the down‐regulation of both AR messenger RNA and protein levels. Therefore, the function of the AR was inhibited, as reflected by the reduced expression of NKX3.1 and PSA and by androgen‐stimulated growth. Because gum mastic exhibited a strong in vitro potency to attenuate the expression and function of the AR, further investigation will be required to determine whether this naturally occurring substance has in vivo potency to inhibit prostate cancer development. Cancer 2006. © 2006 American Cancer Society.
A nonsynonymous single‐nucleotide polymorphism in the PDZ‐Rho guanine nucleotide exchange factor (Ser1416Gly) modulates the risk of lung cancer in Mexican Americans
Authors: Gu Jian , Wu Xifeng , Dong Qiong , Romeo Martin J. , Lin Xin , Gutkind J. Silvio , Berman David M. 
Published: May 2006

AbstractBACKGROUNDBased on in vitro studies, Rho guanine nucleotide exchange factors (RhoGEFs) are key regulators of mitogenic and transforming pathways. At least 1 family member, PDZ‐RhoGEF, also integrates signaling between monomeric Rho G proteins and heterotrimeric G proteins through a so‐called regulator of G‐protein signaling (RGS) domain. Recently, the authors reported that 3 single‐nucleotide polymorphisms (SNPs) in 2 members of the RGS family were associated with significant reductions in the risk of cancer.METHODSFor the current report, the authors studied the risk of lung cancer associated with a nonsynonymous SNP (rs868188; Ser1416Gly) in PDZ‐RhoGEF in a large lung cancer case‐control study of 2260 Caucasians and 369 Mexican Americans.RESULTSCompared with individuals who had the wild‐type genotype (AA), Mexican Americans with the variant genotypes (AG and GG) had a significantly reduced risk for lung cancer (odds ratio [OR], 0.57; 95% confidence interval [95%CI], 0.34‐0.94). The protective effect appeared to be more evident in younger individuals (OR, 0.42; 95%CI, 0.20‐0.91), men (OR, 0.36; 95%CI, 0.18‐0.71), and ever smokers (OR, 0.50; 95%CI, 0.29‐0.88). A joint effect was observed between Ser1416Gly and polymorphisms in 2 cell‐cycle control genes: p53 (intron 3) and cyclin D1 (CCND1). Tallying the variant alleles of the 4 RGS gene SNPs, a gene‐dosage effect was apparent. Compared with individuals who had <3 variant alleles, patients with ≥3 variant alleles had a 51% reduction in lung cancer risk (OR, 0.49; 95%CI, 0.28‐0.88).CONCLUSIONSTo the authors' knowledge, this is the first epidemiological study to link PDZ‐RhoGEF polymorphisms with cancer risk. The results suggest that there are interactions between RGS2, RGS6, and PDZ‐RhoGEF and validate this family of proteins as key regulators of tumorigenesis. Cancer 2006. © 2006 American Cancer Society.
Cerebral metastases pathology after radiosurgery
Authors: Szeifert Gyorgy T. , Atteberry Dave S. , Kondziolka Douglas , Levivier Marc , Lunsford L. Dade 
Published: May 2006

AbstractBACKGROUNDTo the authors' knowledge, comprehensive human pathologic investigations that explore fundamental radiosurgical effects on metastatic brain tumors are sparse in the literature. The objective of this study was to analyze histopathologic findings in a set of clinically recurrent cerebral metastases after patients underwent stereotactic radiosurgery (SRS).METHODSIn a series of 7500 patients who underwent radiosurgery, 2020 patients (27%) harbored cerebral metastases. Eighteen of 2020 patients (0.9%) underwent subsequent craniotomy for tumor removal anywhere from 1 month to 59 months after they received high‐dose irradiation. Histologic and immunohistochemical investigations were performed on the surgically resected tissue specimens. These specimens were within the radiosurgical treatment volume of the metastatic tumor.RESULTSLight microscopy revealed 3 basic categories of histologic responses: acute‐type, subacute‐type, and chronic‐type tissue reactions. A moderate‐to‐intense inflammatory cell reaction was seen in the tissue responses of well controlled neoplasms (i.e., in patients who had neoplasms that required craniotomy for recurrent disease >5 months after SRS), whereas the inflammatory reaction was missing or sparse in poorly controlled neoplasms (patients who required craniotomy for recurrent disease <5 months after SRS). This reaction was seen within the irradiated tumor volume and not in the peritumoral area nor in areas remote from the radiosurgical treatment volume. Immunohistochemical characterization demonstrated the presence of prominent CD68‐positive macrophage and CD3‐positive T‐lymphocyte populations. A progressively severe vasculopathy also was observed with increasing time after radiosurgery.CONCLUSIONSAlthough causality has not been established, a brisk inflammatory response and more severe vasculopathy were observed in lesions in which recurrences were more delayed. Cancer 2006. © 2006 American Cancer Society.
Treatment options in lymph node‐positive prostate cancer
Authors: Swanson Gregory P. , Thompson Ian M. , Basler Joseph 
Published: May 2006

AbstractWith improved awareness and screening, the incidence of lymph node‐positive prostate cancer has declined dramatically over the last 50 years. Stage of cancer, prostate‐specific antigen, and grade are risk factors for positive lymph nodes; and those factors, along with the number of involved lymph nodes, are prognostic factors for outcome. Although the numbers have declined, the number of men with lymph node‐positive prostate cancer remains significant, and the current challenge is how best to treat these patients. Commonly used treatments include any combination of androgen ablation, surgery, and radiation. There have been a few studies with chemotherapy, and no treatment has been proven superior to the others. Consequently, there remain several reasonable alternatives to treatment, and long‐term survival is not unusual. Cancer 2006. © 2006 American Cancer Society.
Bone invasion in extremity soft‐tissue sarcoma
Authors: Ferguson Peter C. , Griffin Anthony M. , O'Sullivan Brian , Catton Charles N. , Davis Aileen M. , Murji Ally , Bell Robert S. , Wunder Jay S. 
Published: May 2006

AbstractBACKGROUNDThe purpose of the current study was to evaluate histologic bone invasion as a predictor of oncologic outcome in extremity soft‐tissue sarcoma (STS) patients presenting to a specialty sarcoma center between 1986 and 2001.METHODSAll patients who underwent surgery for extremity STS were identified from the prospective database at the study institution. Patient demographic features were compared using chi‐square analyses or independent‐sample Student t‐tests. The disease outcomes were compared for those with and without bone invasion using Kaplan–Meier survival analysis and Cox modeling.RESULTSIn a review of 874 patients with STS of the extremity, 48 patients (5.5%) had evidence of bone invasion. Patients with bone invasion presented with larger tumors that were more frequently deep in the extremity and more often had metastases at presentation. Patients with bone invasion had lower metastasis‐free survival but bone invasion was not found to be an independent prognostic factor (P = .274) on Cox modeling. Bone invasion was found to be prognostic of overall survival on multivariate analysis (P<.0001).CONCLUSIONSIn a small percentage of patients with STS, bone resection may be required to obtain an adequate surgical margin, thereby limiting the risk of local tumor recurrence. Histologic bone invasion portends a poorer prognosis in terms of overall survival. Cancer 2006. © 2006 American Cancer Society.
Prospective evaluation of the prognostic relevance of molecular staging for urothelial carcinoma
Authors: Copp Hillary L. , Chin Joseph L. , Conaway Mark , Theodorescu Dan 
Published: May 2006

AbstractBACKGROUNDNearly 50% of urothelial carcinoma patients with lymph node‐negative invasive cancers recur after radical surgery. In many cases, occult local or lymph node disease may be present but undetectable by current approaches. Reverse‐transcriptase polymerase chain reaction (RT‐PCR)‐detectable mRNA of Uroplakin II (UPII), a urothelial‐specific gene mRNA, was evaluated in perivesical and lymph node samples removed at radical surgery as a predictor of clinical recurrence.METHODSFrom November 1999 to August 2002, 46 patients with cTa‐T4N0M0 urothelial bladder cancer enrolled in a prospective clinical trial and underwent radical cystectomy and pelvic lymphadenectomy. RT‐PCR for UPII was performed on biopsies of the external surface of the bladder specimen and lymph nodes. Results were compared with conventional pathology. Patients were followed every 6 months for tumor recurrence.RESULTSPathologically node‐negative patients had a UPII RT‐PCR perivesical positivity of 27% and a lymph node positivity rate of 33%. All 22 UPII RT‐PCR node‐negative patients were pathologically node‐negative and all 13 with pathologically positive nodes had positive UPII RT‐PCR lymph node signals. In all, 46% of UPII RT‐PCR lymph node‐positive patients were pathologically node‐negative and 5% of pathologically node‐negative/UPII RT‐PCR node‐negative patients had disease recurrence, whereas 91% of pathologically node‐negative/UPII RT‐PCR node‐positive patients (P<.001) recurred. UPII RT‐PCR node positivity was a significant predictor of tumor recurrence in multivariate analysisCONCLUSIONSMolecular determination of lymph node metastases by UPII RT‐PCR node positivity apparently identifies patients with a poor prognosis and may be more predictive of disease recurrence than conventional pathologic analysis. Cancer 2006. © 2006 American Cancer Society.
Foxg1 is required for morphogenesis and histogenesis of the mammalian inner ear
Authors: Pauley Sarah , Lai Eseng , Fritzsch Bernd 
Published: May 2006

AbstractThe forkhead genes are involved in patterning, morphogenesis, cell fate determination, and proliferation. Several Fox genes (Foxi1, Foxg1) are expressed in the developing otocyst of both zebrafish and mammals. We show that Foxg1 is expressed in most cell types of the inner ear of the adult mouse and that Foxg1 mutants have both morphological and histological defects in the inner ear. These mice have a shortened cochlea with multiple rows of hair cells and supporting cells. Additionally, they demonstrate striking abnormalities in cochlear and vestibular innervation, including loss of all crista neurons and numerous fibers that overshoot the organ of Corti. Closer examination shows that some anterior crista fibers exist in late embryos. Tracing these fibers shows that they do not project to the brain but, instead, to the cochlea. Finally, these mice completely lack a horizontal crista, although a horizontal canal forms but comes off the anterior ampulla. Anterior and posterior cristae, ampullae, and canals are reduced to varying degrees, particularly in combination with Fgf10 heterozygosity. Compounding Fgf10 heterozygotic effects suggest an additive effect of Fgf10 on Foxg1, possibly mediated through bone morphogenetic protein regulation. We show that sensory epithelia formation and canal development are linked in the anterior and posterior canal systems. Much of the Foxg1 phenotype can be explained by the participation of the protein binding domain in the delta/notch/hes signaling pathway. Additional Foxg1 effects may be mediated by the forkhead DNA binding domain. Developmental Dynamics 235:2470–2482, 2006. © 2006 Wiley‐Liss, Inc.
αN‐catenin deficiency causes defects in axon migration and nuclear organization in restricted regions of the mouse brain
Authors: Uemura Masato , Takeichi Masatoshi 
Published: May 2006

AbstractαN‐catenin is a cadherin‐binding protein, widely expressed in the nervous system; and it plays a crucial role in cadherin‐mediated cell‐cell adhesion. Here we report the effects of αN‐catenin gene deficiency on brain morphogenesis. In addition to the previously reported phenotypes, we found that some of the axon tracts did not normally develop, in particular, axons of the anterior commissure failed to cross the midline, migrating, rather, to ectopic places. In restricted nuclei, a population of neurons was missing or their laminar arrangement was distorted. The ventricular structures were also deformed. These results indicate that αN‐catenin has diverse roles in the organization of the central nervous system, but only in limited portions of the brain. Developmental Dynamics 235:2559–2566, 2006. © 2006 Wiley‐Liss, Inc.
Geometrically Homogenous Series of Covalently Linked Zinc/Free‐Base Porphyrin Dimers of Varying Length; Design, Synthesis and Characterization
Authors: Ljungdahl Thomas , Pettersson Karin , Albinsson Bo , Mårtensson Jerker 
Published: May 2006

AbstractSinglet excitation energy transfer, SEET, can be mediated by a bridge, connecting an energy donor and acceptor, via a superexchange mechanism. The mediation efficiency depends on the energy difference between the first excited states of the donor and the bridge, ΔEDB, as well as the donor–acceptor distance, RDA. We have previously constructed a series of donor–bridge–acceptor, D–B–A, systems that allowed us to study how SEET depends on ΔEDB. To expand this study into a second dimension, the distance dependence, a new series of D–B–A systems were constructed. This series was based on the same zinc/free‐base porphyrin couple as the donor–acceptor pair in the previous series. Their relative orientation was also retained. In contrast to our first series, the bridges in the latter were of varying length. The bridges were oligo(phenyleneethynylene)phenylene (OPE) structures and the length was systematically changed by increasing the number of phenyleneethynylene units from 1 to 4. To obtain high quality samples, the D–B–A systems were assembled by a building block approach where the zinc and free‐base porphyrins were introduced separately using Heck alkynylations. The performance of the OPE structure as a mediator and scaffold is discussed in terms of singlet excited state energies and flexibility. For the first time, when combining the topical D–B–A systems with our previous subset, a homogeneous series of D–B–A systems has been synthesized that allows for studies of both the distance dependence and the energy difference dependence of SEET. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Altered immune response to CNS viral infection in mice with a conditional knock‐down of macrophage‐lineage cells
Authors: Carmen Jessica , Gowing Genevieve , Julien Jean‐Pierre , Kerr Douglas 
Published: May 2006

AbstractNeuroadapted Sindbis Virus (NSV) is a neuronotropic virus that causes hindlimb paralysis in susceptible mice and rats. The authors and others have demonstrated that though death of infected motor neurons occurs, bystander death of uninfected neurons also occurs and both contribute to the paralysis that ensues following infection. The authors have previously shown that the treatment of NSV‐infected mice with minocycline, an inhibitor that has many functions within the central nervous system (CNS), including inhibiting microglial activation, protects mice from paralysis and death. The authors, therefore, proposed that microglial activation may contribute to bystander death of motor neurons following NSV infection. Here, the authors tested the hypothesis using a conditional knock‐out of activated macrophage‐lineage cells, including endogenous CNS macrophage cells. Surprisingly, ablation of these cells resulted in more rapid death and similar weakness in the hind limbs of NSV‐infected animals compared with that of control animals. Several key chemokines including IL‐12 and monocyte chemoattractant protein‐1 (MCP‐1) did not become elevated in these animals, resulting in decreased infiltration of T lymphocytes into the CNS of the knock‐down animals. Either because of the decreased macrophage activation directly or because of the reduced immune cell influx, viral replication persisted longer within the nervous system in knock‐down mice than in wild type mice. The authors, therefore, conclude that although macrophage‐lineage cells in the CNS may contribute to neurodegeneration in certain situations, they also serve a protective role, such as control of viral replication. © 2006 Wiley‐Liss, Inc.
Reconstruction of the columella using the prefabricated reverse flow submental flap: A case report
Authors: Tan Onder , Kiroglu Ahmet Faruk , Atik Bekir , Yuca Koksal 
Published: May 2006

AbstractBackground.The reconstruction of columellar defects is still a challenging procedure because of limited local and regional flap options and the characteristics of the anatomy of this site. Although a number of methods are available to repair nasal columella defects, no treatment of choice ensuring an excellent texture‐ and color‐matched tissue in one stage has been determined to date.Method.In this case, we used a reverse‐flow submental island flap prefabricated with the costal cartilage for the reconstruction of a complex columellar defect.Result.The flap survived completely with reversible venous congestion. The cosmetic result and nasal respiratory function were acceptable during the follow‐up time of 6 months.Conclusion.We propose that the prefabricated reverse submental flap may be an alternative among the surgical options for columellar defects. This flap may also be considered in the reconstructive repertoire of other composite defects of the head and neck region. © 2006 Wiley Periodicals, Inc. Head Neck, 2006