bluuebunny/crossref_metadata_2025 huggingface dataset:
Lack of BK virus DNA sequences in most transitional‐cell carcinomas of the bladder
Authors: Rollison Dana E. , Sexton Wade J. , Rodriguez Alejandro R. , Kang Loveleen C. , Daniel Richard , Shah Keerti V.
Published: December 2006

BK virus (BKV), a common human polyomavirus infection latent in the kidneys, can reactivate with immunosuppression to cause renal disease. Some have suggested that BKV may contribute to the development of bladder cancer, and BKV sequences have been reported from bladder tumors. To further examine the role of BKV in human bladder cancer, a series of bladder tumors was investigated for BKV genomic sequences. Fresh‐frozen specimens from 76 transitional cell carcinoma tissues and 46 paired adjacent normal urothelial tissues archived at the H. Lee Moffitt Cancer Center were studied. All tissues were histopathologically reviewed. DNA extracted from the tissues was tested by quantitative real‐time polymerase chain reaction (QPCR) assays to detect BKV DNA sequences in the VP1 coding region. Amplification of ERV‐3 was conducted separately to quantify cell copy number. Conventional PCR targeting the BKV T‐antigen (T‐Ag) coding region and immunohistochemistry for BKV T‐Ag were also conducted on all tissues that tested positive for BKV by QPCR. Seventy‐three bladder tumors yielded ≥3,000 copies of ERV‐3, 4 (5.5%) of which tested positive for BKV with average copy numbers of 7.9, 15.8, 0.4 and 0.3 per 1,000 cells. Paired normal tissue was available for 2 of these BKV‐positive tumors, 1 of which was BKV‐positive (14.6 copies/1,000 cells). No other normal tissues were BKV‐positive by QPCR. The 6 BKV‐positive tissues by QPCR were also positive by conventional PCR, but all stained negative for BKV T‐Ag by immunohistochemistry. BKV is unlikely to be involved in the etiology of most bladder tumors. © 2006 Wiley‐Liss, Inc.
The impact of epidermal growth factor receptor gene status on gefitinib‐treated Japanese patients with non‐small‐cell lung cancer
Authors: Ichihara Shuji , Toyooka Shinichi , Fujiwara Yoshiro , Hotta Katsuyuki , Shigematsu Hisayuki , Tokumo Masaki , Soh Junichi , Asano Hiroaki , Ichimura Kouichi , Aoe Keisuke , Aoe Motoi , Kiura Katsuyuki , Shimizu Kenji , Date Hiroshi , Shimizu Nobuyoshi
Published: December 2006

We investigated the relationships between genetic factors and clinical outcome in Japanese non‐small‐cell lung cancer (NSCLC) patients treated with gefitinib. Ninety‐eight NSCLC patients who had been treated with gefitinib, were screened for mutations in epidermal growth factor receptor (EGFR) exons 18–21, KRAS exon2, and polymorphisms including the CA simple sequence repeat in intron1 (CA‐SSR1) and single nucleotide polymorphisms in the promoter region (−216G/T and −191C/A), using a PCR‐based assay and direct sequencing. The EGFR copy number status was also evaluated using a fluorescence in situ hybridization assay. EGFR and KRAS mutations were found in 38 (38.8%) and 8 (8.2%) of the 98 patients, respectively. A high EGFR copy number status was identified in 31 (41.3%) of the 75 assessable patients. Drug‐sensitive EGFR mutations limited to exon19 deletions and L858R were independent predictive factors of a stronger sensitivity to gefitinib (p = 0.0002), the overall survival (OS) (p = 0.0036), and prolonged progression‐free survival (PFS) (p < 0.0001). The EGFR copy number status was not related to a sensitivity to gefitinib and prolonged OS and PFS. Regarding polymorphisms, patients with a short CA‐SSR1 showed a prolonged OS as compared with those with a long length in patients with a drug‐sensitive EGFR mutation, although this difference was not significant (p = 0.13). Thus, drug‐sensitive EGFR mutations predict a favorable clinical outcome and a high EGFR copy number may not be related to clinical benefits in gefitinib‐treated Japanese patients with NSCLC. Our findings also suggest that the CA‐SSR1 length may influence the clinical outcome in patients with a drug‐sensitive EGFR mutation. © 2006 Wiley‐Liss, Inc.
Specific membrane recruitment of Uso1 protein, the essential endoplasmic reticulum‐to‐Golgi tethering factor in yeast vesicular transport
Authors: Noda Yoichi , Yamagishi Tomoe , Yoda Koji
Published: December 2006

Uso1 is a yeast essential protein that functions to tether vesicles in the ER‐to‐Golgi transport. Its recruitment to the ER‐derived vesicles has been demonstrated in in vitro membrane transport systems using semi‐intact cells. Here we report that the binding of Uso1 to specific membranes can be detected through simple sucrose density block centrifugation. The purified Uso1 protein binds to slowly sedimenting membranes generated from rapidly sedimenting P10 membranes. These membranes were produced dependent on ATP hydrolysis, contained COPII vesicle components, but had neither of the coat subunits or ER proteins, which indicates that they were representative of the uncoated ER‐derived COPII vesicles. The slowly sedimenting membranes of different origins were physically linked when they were mixed in the presence of Uso1. The C‐terminal acidic region was not required in membrane binding. The presence of membranes to which Uso1 could bind in the yeast cell lysate was detected using the current method. J. Cell. Biochem. 101: 686–694, 2007. © 2006 Wiley‐Liss, Inc.
Involvement of NO/cGMP signaling in the apoptotic and anti‐angiogenic effects of β‐lapachone on endothelial cells in vitro
Authors: Kung Hsiu‐Ni , Chien Chung‐Liang , Chau Gar‐Yang , Don Ming‐Jaw , Lu Kuo‐Shyan , Chau Yat‐Pang
Published: December 2006

Neovascularization is an essential process in tumor development, it is conceivable that anti‐angiogenic treatment may block tumor growth. In angiogenesis, nitric oxide (NO) is an important factor which mediates vascular endothelial cell growth and migration. β‐Lapachone (3,4‐dihydro‐2,2‐dimethyl‐2H‐naphtho‐[1,2‐b]pyran‐5,6‐dione), a natural product extracted from the lapacho tree (Tabebuia avellanedae), has been demonstrated to possess anti‐cancer and anti‐viral effects. Whether β‐lapachone can induce endothelial cell death or has an anti‐angiogenic effect is still an enigma. We investigated the in vitro effect of β‐lapachone on endothelial cells, including human vascular endothelial cell line, EAhy926, and human umbilical vascular endothelial cells (HUVEC). Our results revealed that (1) the intracellular cGMP levels and the mitochondria membrane potential (MMP) decreased, and calpain and caspases were activated, during β‐lapachone‐induced endothelial cell death; (2) co‐treatment with calpain inhibitors (ALLM or ALLN) or the intracellular calcium chelator, BAPTA, but not the general caspase inhibitor, zVAD‐fmk, provided significant protection against apoptosis by preventing the β‐lapachone‐induced MMP decrease and cytoplasmic calcium increase; (3) addition of NO downregulated the β‐lapachone‐induced cGMP depletion and protected the cells from apoptosis by blocking the MMP decrease and the calcium increase; and (4) exogenous NO protects endothelial cells against the cell death induced by β‐lapachone, but not the anti‐angiogenic effect. From all the data above, we demonstrated that NO can attenuate the apoptotic effect of β‐lapachone on human endothelial cells and suggest that β‐lapachone may have potential as an anti‐angiogenic drug. J. Cell. Physiol. 211: 522–532, 2007. © 2006 Wiley‐Liss, Inc.
Type I interferon response against viral and non‐viral gene transfer in human tumor and primary cell lines
Authors: Rautsi Outi , Lehmusvaara Saara , Salonen Tuula , Häkkinen Katja , Sillanpää Maarit , Hakkarainen Tanja , Heikkinen Sami , Vähäkangas Elisa , Ylä‐Herttuala Seppo , Hinkkanen Ari , Julkunen Ilkka , Wahlfors Jarmo , Pellinen Riikka
Published: December 2006

Background

Type I interferon (IFN‐α/β) response is one of the major host defence mechanisms against viruses. Some recent reports suggest that IFNs may interfere with the efficacy of both non‐viral and virus‐vector‐mediated therapeutic gene transfer.

Methods

The type I IFN response upon different gene transfer methods in human tumor and primary cell lines was studied by analysing IFN‐β mRNA expression, secretion of type I IFNs and accumulation of IFN‐α/β‐induced MxA protein (myxovirus resistance protein A).

Results

Infection with avirulent Semliki Forest virus A7[74] induced MxA protein accumulation and increased the IFN‐β mRNA level, whereas none of the studied virus vectors (adenovirus, CRAd, lentivirus or AAV) induced IFN response. However, plasmid DNA induced the accumulation of MxA protein when transfected with several commercial transfection reagents. RNA transfection appeared to be an efficient inducer of type I IFN response: replicating alphaviral RNA, eukaryotic total RNA, or mRNA all induced both MxA protein accumulation and IFN‐β expression. siRNA transfection failed to induce MxA response.

Conclusions

The non‐viral gene transfer methods have gained more interest in recent years due to their better safety profiles when compared to their viral counterparts. However, the efficiency of non‐viral gene transfer is well below those reached by viral vector systems. The type I interferon response induced by non‐viral methods may in part contribute to this inefficiency, while most currently used viral gene transfer vectors fail to induce or are able to suppress type I IFN response. Copyright © 2006 John Wiley & Sons, Ltd.
Quality of life in patients with hepatocellular carcinoma received surgical resection
Authors: Lee Lukas Jyuhn‐Hsiarn , Chen Chien‐Hung , Yao Grace , Chung Chih‐Wen , Sheu Jin‐Chuan , Lee Po‐Huang , Tsai Yih‐Jian , Wang Jung‐Der
Published: December 2006

Background

Hepatocellular carcinoma (HCC) is one the most common malignancies in the world. As the prognosis for HCC patients is poor, the quality of life (QOL) is becoming more important on the outcome assessments. The aim of this study was to evaluate QOL in HCC patients.

Methods

A total of 161 patients with HCC were enrolled at a university hospital. Most of these patients received surgical resections. They were assessed with Taiwan versions of WHOQOL‐BREF, EORTC QLQ‐C30, and utility measures. The WHOQOL‐BREF domain scores for the HCC patients were compared to healthy normative Taiwan population, using general linear models controlling for gender and age. Multiple logistic regressions were applied to explore association between a better QOL and clinical/sociodemographic variables.

Results

Compared with healthy people, the HCC patients had reduced QOL in physical domains, but better environmental QOL. After controlling gender, age, education, and employment, duration of HCC more than 1 year was associated with better QOL scores. WHOQOL‐BREF could be cross‐validated with EORTC QLQ‐C30.

Conclusions

Survival over 1 year was associated with better QOL in HCC patients. WHOQOL‐BREF could be a valid QOL instrument for the assessments of QOL in HCC patients. J. Surg. Oncol. 2007;95:34–39. © 2006 Wiley‐Liss, Inc.
Influence of epidermal growth factor receptor (EGFR) gene mutations on the expression of EGFR, phosphoryl‐Akt, and phosphoryl‐MAPK, and on the prognosis of patients with non‐small cell lung cancer
Authors: Sonobe Makoto , Nakagawa Masatsugu , Takenaka Kazumasa , Katakura Hiromichi , Adachi Masashi , Yanagihara Kazuhiro , Otake Yosuke , Wada Hiromi , Tanaka Fumihiro
Published: December 2006

Background and Objectives

In this paper we examined the influence of epidermal growth factor receptor (EGFR) gene mutations on EGFR expression, downstream mediators, and survival in patients with non‐small cell lung cancer (NSCLC).

Methods

We retrospectively analyzed the tumors of 53 patients with completely resected pathological stage I–IIIA NSCLC for the presence of EGFR gene mutations, the expression of EGFR mRNA and protein, phosphoryl‐Akt, and phosphoryl‐mitogen‐activated protein kinase (MAPK) using immunostaining, and patients' prognosis.

Results

EGFR mutations were associated with elevations in EGFR mRNA (P = 0.004) and protein (P = 0.029) expression, but not with the expression of phosphoryl‐Akt or phosphoryl‐MAPK. The 5‐year survival rate for all patients who exhibited an EGFR mutation was similar to those who were free of such mutations (71% vs. 56%, P = 0.252). However, the 5‐year survival rate of patients with either a stage I adenocarcinoma or large cell carcinoma who had an EGFR mutation was significantly greater than for those who did not have such a mutation (92% vs. 57%, P = 0.037).

Conclusions

EGFR gene mutations were significantly associated with higher EGFR expression, but not with p‐Akt or p‐MAPK status. In early stage NSCLC, the presence of an EGFR gene mutation bode well for the patient's prognosis. J. Surg. Oncol. 2007;95:63–69. © 2006 Wiley‐Liss, Inc.
Hedgehog signaling pathway is a possible therapeutic target for gastric cancer
Authors: Yanai Kosuke , Nagai Shuntaro , Wada Junji , Yamanaka Naoki , Nakamura Masafumi , Torata Nobuhiro , Noshiro Hirokazu , Tsuneyoshi Masazumi , Tanaka Masao , Katano Mitsuo
Published: December 2006

Background and Objectives

It has been shown that the hedgehog (Hh) signaling pathway is activated in gastric cancer. To investigate the viability of the Hh pathway as a therapeutic target, we analyzed activation of the Hh pathway in gastric cancer.

Methods

Surgically resected gastric carcinoma specimens and lymph nodes were analyzed immunohistochemically. We used the percentage of cancer cells with nuclear translocation of Gli1 as a marker of Hh pathway activation.

Results

Nuclear localization of Gli1 was higher in 28 undifferentiated‐type tumors than in 30 differentiated‐type tumors. Eighteen of the fifty‐eight cancer specimens consisted of a mixture of a histologically predominant part and a small area with different histology. In these 18 tumors, the percentage of cells showing nuclear staining of Gli1 was higher in the undifferentiated‐type part than in the differentiated‐type part. Nuclear staining of Gli1 in primary tumors was positively correlated with lymph node metastasis. The Gli1 nuclear staining percentage of metastatic lymph nodes correlated closely with that of each primary carcinoma. Cyclopamine, a Hh pathway inhibitor, suppressed the growth of gastric cancer cells in vitro.

Conclusions

The Hh pathway may be a useful therapeutic target for such as undifferentiated‐type gastric cancer with lymph node metastasis. J. Surg. Oncol. 2007;95:55–62. © 2006 Wiley‐Liss, Inc.
Balance between endoscopic and genetic information in the choice of ileorectal anastomosis for familial adenomatous polyposis
Authors: Valanzano Rosa , Ficari Ferdinando , Curia Maria Cristina , Aceto Gitana , Veschi Serena , Cama Alessandro , Battista Pasquale , Tonelli Francesco
Published: December 2006

Background and objectives

The number of rectal polyps and the site of mutations in the APC (Adenomatous polyposis coli) gene have been used to guide the surgical management in patients with familial adenomatous polyposis (FAP). The aim of this study is to assess the utility of the APC mutation screening compared to the degree of the rectal polyposis in surgical decision making.

Methods

The post‐surgical courses of 25 patients submitted to subtotal colectomy with ileorectal anastomosis (IRA) were reviewed. Preservation of the rectum was prospectively decided on the basis of well‐defined endoscopic criteria. The number of rectal polyps was assessed preoperatively and every 6–12 months. APC gene was screened for mutations by heteroduplex analysis, single strand conformation polymorphism, in vitro synthesized protein (IVSP), and DNA sequencing. Patients negative for APC mutations were tested for MYH mutations.

Results

On the basis of preoperative polyp rectal count we categorized patients as follows: Group I, 5 or fewer adenomas; Group II, 6–9 adenomas; Group III, 10 or more adenomas. After a follow‐up ranging from 12 to 225 months we have observed a significant difference of recurrent rectal adenomas between Groups I–II versus III. No difference was detected among patients of Group I and II. The mean number of adenomas/year/patient was 0.67, 1.62, and 9.29 for Group I, II, and III, respectively. Carpeting polyposis of the rectal stump developed in three patients with APC mutation at codon 1309 and two of them needed later proctectomy. Diffuse rectal polyposis was observed in one patient with mutation at exon 9 who had 10 small polyps at time of surgery. Mutation at the 5′‐end of APC (codons 144–232), mutation of MYH and unknown APC or MYH mutation were correlated with a low number of polyps both at presentation and follow‐up. No IRA patients developed rectal cancer.

Conclusions

In our experience fewer than 10 rectal polyps at presentation can predict a favorable outcome after IRA. Identification of specific germ‐line APC or MYH mutation can address the choice of surgical treatment. J. Surg. Oncol. 2007;95:28–33. © 2006 Wiley‐Liss, Inc.
Expression of C‐Myc mRNA in squamous cell carcinoma of the tongue
Authors: Vora Hemangini H. , Shah Neelam G. , Trivedi Trupti I. , Goswami Jignesh V. , Shukla Shilin N. , Shah Pankaj M.
Published: December 2006

Background

The aim of this study was to evaluate clinical significance of C‐myc mRNA in patients with tongue cancer.

Methods

C‐myc mRNA expression was studied by RT‐PCR in peripheral blood of 25 tongue cancer patients and 24 controls. C‐myc protein expression was studied by immunohistochemistry.

Results

In tongue cancer patients, pretherapeutic C‐myc mRNA expression was significantly higher as compared to controls. In tumor tissues, a trend of low expression of C‐myc mRNA was noted as compared to pretherapeutic blood. The mean pretherapeutic C‐myc mRNA level was lower in tobacco‐users, in older patients, in keratinizing tumors, in tumors showed lymphocytic infiltration as well as in non‐responders as compared to their respective counterparts. C‐myc mRNA expression was lower in tumors showed lymphatic permeation and in patients with a habit of tobacco use. Further, low C‐myc mRNA expression associated with poor prognosis. C‐myc protein expression was noted in 72% of the tumors and an inverse correlation was noted between C‐myc protein expression and disease stage. In early stage disease, an inverse correlation was noted while in advanced stage disease, a positive correlation was noted.

Conclusion

In tongue cancer, downregulation of C‐myc mRNA associated with advancement of the disease and worse prognosis. J. Surg. Oncol. 2007;95:70–78. © 2006 Wiley‐Liss, Inc.
Feasibility of concurrent adjuvant chemotherapy and radiotherapy after breast‐conserving surgery in early breast cancer
Authors: Han Sehwan , Kim Juree , Sohn Seungchang , Kwak Geum‐Hee , Kim Ji‐Young , Park Kyeongmee
Published: December 2006

Background

The optimal sequence of chemotherapy (CT) and radiotherapy (RT) remains uncertain after breast‐conserving surgery (BCS). The current study was performed to evaluate whether the concurrent RT with CT increases the toxicities.

Methods

Two hundred and thirty‐eight patients with stages I and II breast cancers were prospectively allocated to concurrent CT and RT (n = 133) and sequential CT and RT (n = 105) after BCS. In the sequential group, RT was started after the completion of three cycles of CT and additional three cycles of CT were delivered after RT.

Results

There was no significant difference in Grade 3 or 4 hematologic toxicities during CT between the two groups. Radiation related adverse effects were not different between the two groups. During the median follow‐up period of 42 months (range: 16–60 months), 18 patients (13.5%) of the concurrent group had systemic recurrence of breast cancer, whereas 20 patients (19.1%) of the sequential group had systemic recurrence. Disease‐free survival and local recurrence were not different between the two groups.

Conclusions

Concurrent CT and RT were not associated with increased toxicity and showed reasonable cosmetic results. The current study indicates that concurrent RT and CT after BCS is a feasible treatment modality with an advantage of shortening the treatment time. J. Surg. Oncol. 2007;95:45–50. © 2006 Wiley‐Liss, Inc.
Proposal for a new definition of true cardia carcinoma
Authors: Ichikura Takashi , Chochi Kentaro , Sugasawa Hidekazu , Mochizuki Hidetaka
Published: December 2006

Background and Objectives

It remains controversial whether cardia carcinoma should be categorized and treated as esophageal cancer or gastric cancer. The purpose of this study was to develop a reasonable definition of cardia carcinoma.

Methods

Patients with Siewert type II carcinomas were divided into two subgroups: 25 patients with a tumor center within 1 cm of the esophagogastric junction (EGJ) (type IIA) and 22 patients with tumor center 1–2 cm aboral of the EGJ (type IIB). Patients with subcardia carcinomas, 40 with invasion to the EGJ (type III) and 110 without (type IIIe−), were used as controls.

Results

The patients with type IIB carcinomas showed no different characteristics from those with type III or type IIIe− carcinomas, except for the stage of the disease. On the other hand, those with type IIA carcinomas were associated with a higher male/female ratio, higher incidences of elevated appearance, differentiated histology, and mediastinal node metastasis, and a significantly lower survival rate as compared with patients with subcardia carcinomas. Multivariate survival analysis revealed that type IIA is a significant prognostic determinant, but that type IIB is not.

Conclusion

Type IIA carcinomas should be treated as true cardia carcinoma; type IIB as subcardia carcinoma. Our results should be confirmed by a prospective study. J. Surg. Oncol. 2007;95:561–566. © 2006 Wiley‐Liss, Inc.
Differential apoptosis by gallotannin in human colon cancer cells with distinct p53 status
Authors: Al‐Ayyoubi Sahar , Gali‐Muhtasib Hala
Published: December 2006

Gallotannin (GT), a plant polyphenol, has shown anticarcinogenic activities in several animal models including colon cancer. In our previous study, we showed that GT inhibits 1,2‐dimethylhydrazine‐induced colonic aberrant crypt foci and tumors in Balb/c mice, thus supporting a role for GT as a chemopreventive agent in colon cancer. However, at the molecular level, GT's mechanism of chemoprevention is still unclear. In this study, we aim at identifying GT's potential molecular mechanisms of action in in vitro studies. We show that GT differentially inhibits the growth of two isogenic HCT‐116 (p53+/+, p53−/−) human colon cancer cells versus normal human intestinal epithelial cells (FHs 74Int). DNA flow cytometric analysis showed that GT induced S‐phase arrest in both HCT‐116 cell lines. Cell‐cycle arrest in p53 (+/+) cells was associated with an increase in p53 protein levels and p21 transcript and protein levels. The inhibition of cell‐cycle progression of HCT‐116 p53 (+/+) cells by GT correlated with a reduction in the protein levels of cyclin D1, pRb, and the Bax/Bcl‐2 ratio. Although GT did not induce apoptosis in p53 (+/+) cells, a significant induction of apoptosis was observed in p53 (−/−) cells as shown by TUNEL staining and flow cytometry analysis. Apoptosis induction in p53 (−/−) cells was associated with a significant increase in Bax/Bcl‐2 protein levels. Our results demonstrate that GT inhibits the growth of HCT‐116 colon cancer cells in a p53‐independent manner but exhibits differential sensitivity to apoptosis induction in HCT‐116 cells with distinct p53 status. © 2006 Wiley‐Liss, Inc.
Rural Internet access: over‐subscription strategies, regulation and equilibrium
Authors: Shin SeungJae , Weiss Martin B. , Tucci Jack
Published: December 2006

This paper presents an analysis of the Internet access market using a game theoretic model. In particular, we consider the Nash equilibrium of the service providers and examine their behavior on network investment and output level. We calibrate this model to fit the industry structure and data found in rural markets. In the first part of the paper, we examine the Internet industry structure and its characteristics. Based on the industry structure, we create a Cournot duopoly model, in which real world cost and revenue projections are used to find Internet access market equilibrium. In conclusion, we analyze social welfare of the equilibrium. These analyses allow us to explain the motivation for the rural ISPs' behavior, such as over‐subscription and under‐investment and to present an analytical framework for Internet industry policy makers. Copyright © 2007 John Wiley & Sons, Ltd.
Patterns of corporate governance and technical efficiency in Italian manufacturing
Authors: Destefanis Sergio , Sena Vania
Published: December 2006

The purpose of this paper is to analyse the relationship between the corporate governance system and technical efficiency in Italian manufacturing. We use a non‐parametric frontier technique (DEA) to derive technical efficiency measures for a sample of Italian firms taken from nine manufacturing industries. These measures are then related to the characteristics of the corporate governance system. Two of these characteristics turn out to have a positive impact on technical efficiency: the percentage of the company shares owned by the largest shareholder and the fact that a firm belongs to a pyramidal group. Interestingly, a trade‐off emerges between these influences, in the sense that one is stronger in industries where the other is weaker. Copyright © 2007 John Wiley & Sons, Ltd.
Preliminary evidence on the appointment of institutional solutions to franchisor moral hazard—the case of franchisee councils
Authors: Cochet Olivier , Ehrmann Thomas
Published: December 2006

Besides franchisee opportunistic behavior, franchisor moral hazard is a central concern in franchise chains. Economic literature thus far focused on the sharing of franchisee revenues as an incentive for curbing franchisor malfeasance. In this paper, we ask whether and how the obligations of chains may be enforced through institutional arrangements like franchisee councils. Consistent with expectations, the appointment of a council empirically turned out to be more likely as decision rights—a proxy for the scope of moral hazard—were increasingly allocated to companies' management. We found this relationship to be negatively moderated by the contractual share parameter. Copyright © 2007 John Wiley & Sons, Ltd.
Novel cyclooxygenase‐catalyzed bioactive prostaglandin F2α from physiology to new principles in inflammation
Authors: Basu Samar
Published: December 2006

Prostaglandin F2α (PGF2α), a foremost stable vasoactive cyclooxygenase (COX)‐catalyzed prostaglandin, regulates a number of key physiological functions such as luteolysis, ovarian function, luteal maintenance of pregnancy, and parturition as a constitutive part of ongoing reproductive processes of the body. It has recently been implicated in the regulation of intricate pathophysiological processes, such as acute and chronic inflammation, cardiovascular and rheumatic diseases. Since the discovery of a second isoform of COXs, it has been shown that PGF2α can be formed in vivo from arachidonic acid through both isoforms of COXs, namely cyclooxygenase‐1 (COX‐1) and cyclooxygenase‐2 (COX‐2). Being synthesized in various parts of the body, it metabolizes instantly to a number of rather inactive metabolites mainly in the lungs, liver, kidney, and efficiently excretes into the urine. 15‐Keto‐dihydro‐PGF2α, a major stable metabolite of PGF2α that reflects in vivo PGF2α biosynthesis, is found in larger quantities than its parent compound in the circulation and urine in basal physiological conditions, with short‐lived pulses during luteolysis, induced termination of pregnancy and parturition, and is increased in tissues and various body fluids during acute, sub‐chronic, and severe chronic inflammation. Further, the close relationship of PGF2α with a number of risk factors for atherosclerosis indicates its major role in inflammation pathology. This review addresses multiple aspects of PGF2α in addition to its emerging role in physiology to inflammation. © 2006 Wiley Periodicals, Inc. Med Res Rev, 27, No. 4, 435–468, 2007
Lipoxygenase inhibitors: A comparative QSAR study review and evaluation of new QSARs
Authors: Pontiki Eleni , Hadjipavlou‐Litina Dimitra
Published: December 2006

This paper contains a quantitative structure activity relationship (QSAR) study for lipoxygenase (LO) inhibitors. It reveals that in almost all cases, the clog P parameter plays an important part in the QSARs (linear or bilinear model). In some cases the steric factors such as the overall molar refractivity (CMR) or the substituents molar refractivity (MR) (linear or parabola) are important. Electronic effects are comparatively unimportant. The study shows that log P as calculated from the Clog P program is suitable for this form of QSAR study. © 2006 Wiley Periodicals, Inc. Med Res Rev, 28, No. 1, 39–117, 2008
Reduced oxygen concentration improves the developmental competence of mouse oocytes following in vitro maturation
Authors: Preis Kimberly A. , Seidel George E. , Gardner David K.
Published: December 2006

Reduced atmospheric oxygen concentration is beneficial to embryo development; however, optimal oxygen concentration for oocyte maturation remains undetermined. Likewise, there is no consensus of appropriate medium supplementation during maturation. The objective of this study was to determine whether oxygen tension (20% or 5% O2) and epidermal growth factor (EGF) affect oocyte metabolism and subsequent embryo development. Cumulus‐oocyte complexes (COCs) were collected from 28‐day‐old equine chorionic gonadotropin (eCG) primed or unprimed F1 (C57BL/6xCBA) mice. COCs were matured in defined medium in one of four groups: 20% O2, 20% O2 + EGF, 5% O2, 5% O2 + EGF. In vivo matured COCs were also collected for analysis. COCs from unprimed mice, matured in 5% O2 ± EGF or 20% O2 + EGF had higher metabolic rates than COCs matured in 20% O2 (P < 0.05). COCs from primed mice had higher metabolic rates when matured in the presence of EGF, regardless of oxygen tension (P < 0.01). Oxygen uptake and mitochondrial membrane potential were higher for in vivo matured oocytes and oocytes matured under 5% O2 compared to oocytes matured under 20% O2 (P < 0.05). Blastocyst formation was not different between maturation groups (primed or unprimed); however, embryo cell numbers were 20–45% significantly higher when COCs were matured at 5% O2 (P < 0.05). Results suggest that oocytes matured in physiological concentrations of oxygen have improved development and metabolic activity, more closely resembling in vivo maturation. These findings have implications for oocyte maturation in both clinical and research laboratories. Mol. Reprod. Dev. 74: 893–903, 2007. © 2006 Wiley‐Liss, Inc.
Serial triple quantum sodium MRI during non‐human primate focal brain ischemia
Authors: LaVerde G. , Nemoto E. , Jungreis C.A. , Tanase C. , Boada F.E.
Published: December 2006

Triple quantum (TQ) sodium MRI techniques with clinically acceptable 18‐min data acquisition times were demonstrated in vivo in a nonhuman primate model of focal brain ischemia. Focal brain ischemia was induced in four animals using embolization coils to occlude the posterior cerebral artery, and a balloon catheter to occlude the middle cerebral artery. A statistically significant increase (P < 0.001) in the TQ sodium MRI signal intensity in the ischemic hemisphere relative to the contralateral hemisphere was seen at all time points in all four animals. This increased TQ sodium MRI signal intensity was demonstrated as early as 0.6 hr after the onset of ischemia. The TQ sodium MRI hyperintensity corresponded to the anatomical location of the ischemic cortex, as indicated by the registration of the TQ imaging data with anatomical proton MRI data. The results demonstrate that early after the onset of ischemia, there was an increase in the TQ signal intensity in the ischemic hemisphere, and a negligible change in the single quantum (SQ) signal intensity. Magn Reson Med 57:201–205, 2007. © 2006 Wiley‐Liss, Inc.
Systematic investigation of balanced steady‐state free precession for functional MRI in the human visual cortex at 3 Tesla
Authors: Zhong Kai , Leupold Jochen , Hennig Juergen , Speck Oliver
Published: December 2006

Previous studies have applied balanced steady‐state free precession (bSSFP) to functional brain imaging. Methods that exploit the strong frequency dependence of the MR signal in the bSSFP transition band are strongly affected by field inhomogeneity and frequency drifts. Recent bSSFP studies using “on‐resonance” (in the bSSFP passband) acquisition claimed that higher sensitivity was achieved compared to traditional fMRI methods. However, the contrast mechanism that generates activation‐related signal changes in bSSFP imaging is not yet fully understood. We performed a systematic study of on‐resonance bSSFP signal behavior using a multiecho balanced SSFP sequence with different TRs at 3 Tesla. We conclude that intravoxel dephasing, or the off‐resonance averaged steady state, dominates the bSSFP signal decay and determines the bSSFP fMRI contrast. Experimental findings were confirmed by simulations based on existing theories for signal formation around blood vessels in inhomogeneous tissues. The activation‐induced signal change in on‐resonance bSSFP increases with TE, and the TE dependence of the contrast‐to‐noise ratio (CNR) in bSSFP is similar to that in gradient echo‐planar imaging (GE‐EPI). However, GE‐EPI has a significantly higher CNR efficiency. Magn Reson Med 57:67–73, 2007. © 2006 Wiley‐Liss, Inc.
3D radial projection technique with ultrashort echo times for sodium MRI: Clinical applications in human brain and skeletal muscle
Authors: Nielles‐Vallespin Sònia , Weber Marc‐André , Bock Michael , Bongers André , Speier Peter , Combs Stephanie E. , Wöhrle Johannes , Lehmann‐Horn Frank , Essig Marco , Schad Lothar R.
Published: December 2006

23Na MRI has the potential to noninvasively detect sodium (Na) content changes in vivo. The goal of this study was to implement 23Na MRI in a clinical setting for neurooncological and muscular imaging. Due to the biexponential T2 decay of the tissue Na signal with a short component, which ranges between 0.5–8 ms, the measurement of total Na content requires imaging techniques with echo times (TEs) below 0.5 ms. A 3D radial pulse sequence with a TE of 0.2 ms at a spatial resolution of 4 × 4 × 4 mm3 was developed that allows the acquisition and presentation of Na images on the scanner. This sequence was evaluated in patients with low‐ and high‐grade gliomas, and higher 23Na MR signals corresponding to an increased Na content were found in the tumor regions. The contrast‐to‐noise ratio (CNR) between tumor and white matter increased from 0.8 ± 0.2 to 1.3 ± 0.3 with tumor grade. In patients with an identified muscular 23Na channelopathy (Paramyotonia congenita (PC)), induced muscle weakness led to a signal increase of ∼18% in the 23Na MR images, which was attributed to intracellular Na+ accumulation in this region. Magn Reson Med 57:74–81, 2007. © 2006 Wiley‐Liss, Inc.
Fast 3D 1H spectroscopic imaging at 3 Tesla using spectroscopic missing‐pulse SSFP with 3D spatial preselection
Authors: Schuster Christian , Dreher Wolfgang , Geppert Christian , Leibfritz Dieter
Published: December 2006

Three‐dimensional (3D) 1H MR spectroscopic imaging (SI) allows metabolic changes in human tissue to be identified. In clinical practice, fast acquisition techniques are required to achieve an adequate spatial resolution within acceptable total measurement times. In this study a novel fast pulse sequence for 3D 1H SI based on the condition of steady‐state free precession (SSFP), termed “spectroscopic missing‐pulse SSFP” (spMP‐SSFP), is proposed. It combines 3D spatial preselection with the acquisition of full spin echoes (SEs), and thus makes subsequent phase correction of spectra redundant. The sequence was applied to a phantom and healthy human brains in vivo at 3 Tesla. Metabolic images are acquired with a spatial resolution of 1.8 cm3 within a total measurement time of about 6 min. With a lower signal‐to‐noise ratio (SNR) per unit measurement time compared to previous spectroscopic SSFP implementations, 3D spatial preselection can now be realized with spMP‐SSFP. Since the method does not require separate techniques for water and lipid suppression, and employs a simple data‐processing approach, spMP‐SSFP is a robust, fast SI method that requires only minimal user interaction. Magn Reson Med 57:82–89, 2007. © 2006 Wiley‐Liss, Inc.
Augmented generalized SENSE reconstruction to correct for rigid body motion
Authors: Bammer Roland , Aksoy Murat , Liu Chunlei
Published: December 2006

The correction of motion artifacts continues to be a significant problem in MRI. In the case of uncooperative patients, such as children, or patients who are unable to remain stationary, the accurate determination and correction of motion artifacts becomes a very important prerequisite for achieving good image quality. The application of conventional motion‐correction strategies often produces inconsistencies in k‐space data. As a result, significant residual artifacts can persist. In this work a formalism is introduced for parallel imaging in the presence of motion. The proposed method can improve overall image quality because it diminishes k‐space inconsistencies by exploiting the complementary image encoding capacity of individual receiver coils. Specifically, an augmented version of an iterative SENSE reconstruction is used as a means of synthesizing the missing data in k‐space. Motion is determined from low‐resolution navigator images that are coregistered by an automatic registration routine. Navigator data can be derived from self‐navigating k‐space trajectories or in combination with other navigation schemes that estimate patient motion. This correction method is demonstrated by interleaved spiral images collected from volunteers. Conventional spiral scans and scans corrected with proposed techniques are shown, and the results illustrate the capacity of this new correction approach. Magn Reson Med 57:90–102, 2007. © 2006 Wiley‐Liss, Inc.
Efficient in vivo 31P magnetization transfer approach for noninvasively determining multiple kinetic parameters and metabolic fluxes of ATP metabolism in the human brain
Authors: Du Fei , Zhu Xiao‐Hong , Qiao Hongyan , Zhang Xiaoliang , Chen Wei
Published: December 2006

ATP metabolism is controlled mainly by ATP synthase (ATPase) and creatine kinase (CK) reactions that regulate cerebral ATP production, transportation, and utilization. These coupled reactions constitute a chemical exchange metabolic network of PCr↔ATP↔Pi characterized by two forward and two reverse reaction fluxes, which can be studied noninvasively by in vivo 31P MRS combined with magnetization transfer (MT). However, it is still debated whether current MT approaches can precisely determine all of these fluxes. We developed and tested a modified in vivo 31P MT approach based on a multiple single‐site saturation (MSS) technique to study the entire PCr↔ATP↔Pi network in human occipital lobe at 7T. Our results reveal that 1) the MSS MT approach can explicitly determine all four reaction fluxes with a minimal number of 31P spectra; 2) the three‐spin exchange model accurately determines reverse reaction fluxes, resulting in equal forward and reverse fluxes for both CK and ATPase reactions; and 3) the ATP synthesis rate (8.8 ± 1.9 μmol/g/min, N = 11) measured in the human brain reflects cerebral oxidative phosphorylation. The MSS MT approach should provide an important modality for noninvasively studying the essential roles of ATP metabolism in brain bioenergetics, function, and diseases. Magn Reson Med 57:103–114, 2007. © 2006 Wiley‐Liss, Inc.
Quantitative BOLD: Mapping of human cerebral deoxygenated blood volume and oxygen extraction fraction: Default state
Authors: He Xiang , Yablonskiy Dmitriy A.
Published: December 2006

Since Ogawa et al. (Proc Natl Acad Sci USA 1990;87:9868–9872) made the fundamental discovery of blood oxygenation level‐dependent (BOLD) contrast in MRI, most efforts have been directed toward the study of dynamic BOLD (i.e., temporal changes in the MRI signal during changes in brain activity). However, very little progress has been made in elucidating the nature of BOLD contrast during the resting or baseline state of the brain, which is important for understanding normal human performance because it accounts for most of the enormous energy budget of the brain. It is also crucial for deciphering the consequences of baseline‐state impairment by cerebral vascular diseases. The objective of this study was to develop a BOLD MR‐based method that allows quantitative evaluation of tissue hemodynamic parameters, such as the blood volume, deoxyhemoglobin concentration, and oxygen extraction fraction (OEF). The proposed method, which we have termed quantitative BOLD (qBOLD), is based on an MR signal model that incorporates prior knowledge about brain tissue composition and considers signals from gray matter (GM), white matter (WM), cerebrospinal fluid (CSF), and blood. A 2D gradient‐echo sampling of spin‐echo (GESSE) pulse sequence is used for the acquisition of the MRI signal. The method is applied to estimate the hemodynamic parameters of the normal human brain in the baseline state. Magn Reson Med 57:115–126, 2007. © 2006 Wiley‐Liss, Inc.
Variance of estimated DTI‐derived parameters via first‐order perturbation methods
Authors: Chang Lin‐Ching , Koay Cheng Guan , Pierpaoli Carlo , Basser Peter J.
Published: December 2006

In typical applications of diffusion tensor imaging (DTI), DT‐derived quantities are used to make a diagnostic, therapeutic, or scientific determination. In such cases it is essential to characterize the variability of these tensor‐derived quantities. Parametric and empirical methods have been proposed to estimate the variance of the estimated DT, and quantities derived from it. However, the former method cannot be generalized since a parametric distribution cannot be found for all DT‐derived quantities. Although powerful empirical methods, such as the bootstrap, are available, they require oversampling of the diffusion‐weighted imaging (DWI) data. Statistical perturbation methods represent a hybrid between parametric and empirical approaches, and can overcome the primary limitations of both methods. In this study we used a first‐order perturbation method to obtain analytic expressions for the variance of DT‐derived quantities, such as the trace, fractional anisotropy (FA), eigenvalues, and eigenvectors, for a given experimental design. We performed Monte Carlo (MC) simulations of DTI experiments to test and validate these formulae, and to determine their range of applicability for different experimental design parameters, including the signal‐to‐noise ratio (SNR), diffusion gradient sampling scheme, and number of DWI acquisitions. This information should be useful for designing DTI studies and assessing the quality of inferences drawn from them. Magn Reson Med 57:141–149, 2007. Published 2006 Wiley‐Liss, Inc.
Automated estimation of tumor probability in prostate magnetic resonance spectroscopic imaging: Pattern recognition vs quantification
Authors: Kelm B. Michael , Menze Bjoern H. , Zechmann Christian M. , Baudendistel Klaus T. , Hamprecht Fred A.
Published: December 2006

Despite its diagnostic value and technological availability,1H NMR spectroscopic imaging (MRSI) has not found its way into clinical routine yet. Prerequisite for the clinical application is an automated and reliable method for the diagnostic evaluation of MRS images. In the present paper, different approaches to the estimation of tumor probability from MRSI in the prostate are assessed. Two approaches to feature extraction are compared: quantification (VARPRO, AMARES, QUEST) and subspace methods on spectral patterns (principal components, independent components, nonnegative matrix factorization, partial least squares). Linear as well as nonlinear classifiers (support vector machines, Gaussian processes, random forests) are applied and discussed. Quantification‐based approaches are much more sensitive to the choice and parameterization of the quantification algorithm than to the choice of the classifier. Furthermore, linear methods based on magnitude spectra easily achieve equal performance and also allow for biochemical interpretation in combination with subspace methods. Nonlinear methods operating directly on magnitude spectra achieve the best results but are less transparent than the linear methods. Magn Reson Med 57:150–159, 2007. © 2006 Wiley‐Liss, Inc.
Quantitative proton magnetic resonance spectroscopy of the human cervical spinal cord at 3 tesla
Authors: Marliani Anna Federica , Clementi Valeria , Albini‐Riccioli Luca , Agati Raffaele , Leonardi Marco
Published: December 2006

Cervical spinal cord spectroscopy has the potential to add metabolic information to spinal cord MRI and improve the clinical evaluation and research investigation of spinal cord diseases, such as multiple sclerosis (MS) and intraspinal tumors. However, in vivo proton MR spectroscopy (1H‐MRS) of the spinal cord is difficult to perform due to magnetic field inhomogeneities, physiological movements, and the size of the anatomical region of interest (ROI). For these reasons, few spinal cord 1H‐MRS studies have been undertaken and two preliminary studies on a 3T system were only recently presented as abstracts. In this work we demonstrate the feasibility of cervical spinal cord quantitative 1H‐MRS on a clinical 3T system, propose a study protocol, and report quantification results obtained from healthy volunteers. The main metabolite concentration ratios obtained in 10 healthy subjects, as provided by LCModel, were as follows: total N‐acetyl aspartate/creatine (tNAA/Cr) 1.4 ± 0.3, choline/creatine (Cho/Cr) 0.5 ± 0.1, and myoinositol/creatine (mI/Cr) 1.7 ± 0.2. A significant difference was found between spinal cord tNAA, Cr, Cho, and mI concentration ratios and brainstem concentrations previously acquired on the same system. Magn Reson Med 57:160–163, 2007. © 2006 Wiley‐Liss, Inc.
Serial in vivo MR tracking of magnetically labeled neural spheres transplanted in chronic EAE mice
Authors: Ben‐Hur Tamir , van Heeswijk Ruud B. , Einstein Ofira , Aharonowiz Michal , Xue Rong , Frost Emma E. , Mori Susumu , Reubinoff Benjamin E. , Bulte Jeff W.M.
Published: December 2006

Neural stem cell (NSC) transplantation has been shown to attenuate the severity of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Central to the future success of NSC transplantation in MS is the ability of transplanted cells to migrate from the site of transplantation to relevant foci of disease. Using magnetically labeled mouse neurospheres and human embryonic stem cell (hESC)‐derived neurospheres, we applied serial magnetic resonance imaging (MRI) to assess the biodynamics of transplanted cell migration in a chronic mouse EAE model. Magnetic labeling did not affect the in vitro and in vivo characteristics of cells as multipotential precursors. Cell migration occurred along white matter (WM) tracts (especially the corpus callosum (CC), fimbria, and internal capsule), predominantly early in the acute phase of disease, and in an asymmetric manner. The distance of cell migration correlated well with clinical severity of disease and the number of microglia in the WM tracts, supporting the notion that inflammatory signals promote transplanted cell migration. This study shows for the first time that hESC‐derived neural precursors also respond to tissue signals in an MS model, similarly to rodent cells. The results are directly relevant for designing and optimizing cell therapies for MS, and achieving a better understanding of in vivo cell dynamics and cell–tissue interactions. Magn Reson Med 57:164–171, 2007. © 2006 Wiley‐Liss, Inc.