bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of xeroderma pigmentosum A protein predicts improved outcome in metastatic ovarian carcinoma
Authors: Stevens Ellen V. , Raffeld Mark , Espina Virginia , Kristensen Gunnar B. , Trope' Claes G. , Kohn Elise C. , Davidson Ben
Published: April 2005

BACKGROUND

The nucleotide excision repair (NER) proteins repair DNA adducts due to xenobiotics and cancer chemotherapy. The authors hypothesized that expression of the NER protein xeroderma pigmentosum A (XPA) would be reduced in a clinically significant fashion in metastatic ovarian carcinoma.

METHODS

Malignant effusion specimens were studied so that there was a uniform metastatic ovarian carcinoma population for study. XPA protein expression was analyzed by immunocytochemistry in 142 effusion specimens (109 peritoneal specimens, 33 pleural specimens) from 125 patients. Specimens were obtained at diagnosis (n = 76), and at disease recurrence (n = 66). Patients in the latter group received platinum‐based chemotherapy.

RESULTS

XPA was expressed in cancer cells in 136 of the 142 (96%) effusion specimens. Strongest expression occurred in leukocytes and reactive mesothelial cells. XPA expression did not correlate with treatment status, effusion site, International Federation of Gynecology and Obstetrics stage, histologic grade, or the extent of residual disease. More effusion tumor cells from patients with a complete response to chemotherapy expressed XPA compared with those with a partial or no response (P = 0.03, χ2 test). Patients with recurrent disease with XPA expressed in > 25% of tumor cells had better progression‐free survival (PFS) by univariate analysis (median = 0 vs. 11 months, P < 0.001; 95% confidence interval [CI], 1–5, 8–14) and overall survival (OS; median = 24 vs. 34 months, P = 0.04; 95% CI, 17–31, 24–44). XPA was the only predictor of PFS outcome by multivariate analysis (P = 0.03).

CONCLUSIONS

The results of the current study showed that XPA was widely expressed in metastatic ovarian carcinoma effusion specimens and in the cells of the effusion microenvironment. Paradoxically, XPA expression was associated with better response to chemotherapy and predicted better PFS and OS. Cancer 2005. Published 2005 by the American Cancer Society.
High incidence of disease recurrence in the brain and leptomeninges in patients with nonsmall cell lung carcinoma after response to gefitinib
Authors: Omuro Antonio M. P. , Kris Mark G. , Miller Vincent A. , Franceschi Enrico , Shah Neelam , Milton Daniel T. , Abrey Lauren E.
Published: April 2005

BACKGROUND

Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor that induces an early and dramatic response in 10% of patients with advanced nonsmall cell lung carcinoma (NSCLC). Long‐ term outcome and patterns of disease recurrence after response have not been described.

METHODS

The authors evaluated 139 patients with NSCLC treated with gefitinib at Memorial Sloan‐Kettering Cancer Center (New York, NY) between 1998 and 2002. They focused on patterns of disease recurrence, risk of brain metastases (BM) and leptomeningeal metastasis (LM), and long‐term outcome after initial response to gefitinib.

RESULTS

Of the 139 patients treated with gefitinib, 21 (15%) achieved a partial response. The median age of the responders was 64 years (range, 38–87 years), the median Karnofsky performance score was 80 (range, 60–90), and 4 of the patients were men. All responders had adenocarcinoma. The central nervous system (CNS) was the initial site of disease recurrence in 7 (33%) patients (BM in 5 and LM in 2). In 9 (43%) patients, the initial site of disease recurrence was the lung and in 1 it was the liver and bone. Four (57%) of the patients with disease recurrence in the CNS had lung disease under control. BM also developed in 2 patients who had initial disease recurrence in the lungs. The actuarial 5‐year incidence of CNS metastases was 60%. The median overall survival periods were 15 months and 23 months for patients with and without CNS metastases, respectively (P = 0.24).

CONCLUSIONS

The CNS was a frequent site of disease recurrence in patients with NSCLC after an initial response to gefitinib, regardless of disease control in the lungs. Patients should be carefully monitored for neurologic symptoms. Intrinsic resistance of metastatic clones, incomplete CNS penetrance of the drug, and longer survival are possible explanations for this high incidence. Cancer 2005. © 2005 American Cancer Society.
Prognostic model of event‐free survival for patients with androgen‐independent prostate carcinoma
Authors: Shulman Michael J. , Benaim Elie A.
Published: April 2005

BACKGROUND

The current study was conducted to develop a prognostic model of event‐free survival (EFS) in men with androgen‐independent prostate carcinoma (AIPC).

METHODS

Data from 160 patients diagnosed with AIPC between 1989–2002 were reviewed. No patient had received cytotoxic chemotherapy. A univariate Cox proportional hazards model identified significant predictors of EFS. Recursive partitioning analysis divided these significant variables into prognostic risk groups. The final prognostic model was tested with a Cox proportional hazards model.

RESULTS

The final prognostic risk model included the presence of metastatic disease at the time of androgen‐independent disease progression (P = 0.040), time to prostate‐specific antigen (PSA) recurrence (P = 0.043), and PSA doubling time (P < 0.01). Three highly independent risk groups were identified. The observed median EFSs were 6.1 months (95% confidence interval [95= CI], 3.4–8.8 months), 33.6 months (95= CI, 25.3–41.9 months), and 96.1 months (95= CI, 57.9–134.3 months) for the low‐risk, intermediate‐risk, and high‐risk groups, respectively. Each risk group was found to be independently predictive of EFS (P < 0.01). Patients who died of prostate carcinoma experienced significantly more clinical events than those who died of other causes (P < 0.01).

CONCLUSIONS

The prognostic model in the current study stratified patients into three highly significant and independent risk groups for EFS. A detailed PSA history and knowledge of metastatic disease are sufficient to risk‐stratify patients with AIPC. One very unique aspect of this model was that it was developed from a patient cohort that never received chemotherapy. Cancer 2005. © 2005 American Cancer Society.
Itraconazole added to a lipid formulation of amphotericin B does not improve outcome of primary treatment of invasive aspergillosis
Authors: Kontoyiannis Dimitrios P. , Boktour Maha , Hanna Hend , Torres Harrys A. , Hachem Ray , Raad Issam I.
Published: April 2005

BACKGROUND

Invasive aspergillosis (IA) is associated with poor outcome in patients with hematologic malignancy treated with amphotericin B (AMB)‐based therapy. Itraconazole (ITC), a triazole with activity against Aspergillus, has been used in combination with AMB or lipid formulations of AMB (LipoAMB) in the treatment of IA, although the efficacy of this strategy is uncertain.

METHODS

To determine whether the addition of ITC to LipoAMB improves outcome of IA, the authors retrospectively studied 179 consecutive patients with hematologic malignancies and definite or probable IA who received primary antifungal therapy with either LipoAMB (n = 146), or lipoAMB plus ITC (n = 33) between June 1993 and June 2003. In view of the erratic absorption of ITC tablets, only patients who received either intravenous or liquid ITC were analyzed. Patients who received < 1 week of treatment were excluded.

RESULTS

Evaluable patients in both groups (LipoAMB: n =101; ITC and LipoAMB: n = 11) had comparable distribution of risk factors of poor outcome such as neutropenia at onset of IA, persistent neutropenia, systemic steroids, previous antifungal prophylaxis, admission to the intensive care unit, disseminated IA, previous bone marrow transplant, and IA due to infection by a non‐fumigatus Aspergillus species. Response to primary antifungal therapy was equally poor in both groups (LipoAMB group: 10%; ITC and LipoAMB group: 0%; P = not significant).

CONCLUSIONS

In the authors' 10‐year study of patients with hematologic malignancy and IA, the response rate to LipoAMB given as primary therapy was very poor. In a comparable group of patients, the addition of ITC did not result in a therapeutic benefit. Cancer 2005. © 2005 American Cancer Society.
Expression and distribution of TTX‐sensitive sodium channel alpha subunits in the enteric nervous system
Authors: Bartoo Aaron C. , Sprunger Leslie K. , Schneider David A.
Published: April 2005

The expression and distribution of TTX‐sensitive voltage‐gated sodium channel (VGSC) alpha subunits in the enteric nervous system (ENS) has not been described. Using RT‐PCR, expression of Nav1.2, Nav1.3, Nav1.6, and Nav1.7 mRNA was detected in small and large intestinal preparations from guinea pigs. Expression of Nav1.1 mRNA as well as Nav1.1‐like immunoreactivity (‐li) were not observed in any intestinal region investigated. Nav1.2‐li was primarily observed within the soma of the majority of myenteric and submucosal neurons, although faint immunoreactivity was occasionally observed in ganglionic and internodal fibers. Nav1.3‐li was observed in dendrites, soma, and axons in a small group of myenteric neurons, as well as in numerous myenteric internodal fibers; immunoreactivity was rarely observed in the submucosal plexus. Nav1.6‐li was primarily observed in the initial axonal segment of colonic myenteric neurons. Nav1.7‐li was observed in dorsal root ganglia neurons but not in the myenteric plexus of the small and large intestine. In the ileum, 37% of Nav1.2‐li cell bodies colocalized with calbindin‐li while colocalization with calretinin‐li was rare. In contrast, 22% of Nav1.3‐li cell bodies colocalized with calretinin‐li but colocalization with calbindin‐li was not observed. In the colon, both Nav1.2‐li and Nav1.3‐li cell bodies frequently colocalized with either calretinin‐li or calbindin‐li. Nav1.2‐li cell bodies also colocalized with the majority of NeuN‐li cells in the small and large intestine. These data suggest that Nav1.1 may not be highly expressed in the ENS, but that Nav1.2, Nav1.3, and Nav1.6, and possibly Nav1.7, have broadly important and distinct functions in the ENS. J. Comp. Neurol. 486:117–131, 2005. © 2005 Wiley‐Liss, Inc.
β‐catenin–mediated cell‐adhesion is vital for embryonic forebrain development
Authors: Junghans Dirk , Hack Iris , Frotscher Michael , Taylor Verdon , Kemler Rolf
Published: April 2005

Forming a complex structure such as the mammalian brain requires a complex interplay between cells and different signalling cascades during embryonic development. β‐catenin plays pivotal roles in these processes by mediating cadherin‐based cell adhesion and Wnt signalling. We show for the first time that β‐catenin functions predominantly as a mediator of cell adhesion during early development of the mammalian telencephalon. Immunohistochemical analysis demonstrates that β‐catenin is localized, together with N‐cadherin, to adhesion junctions at the apical lining of the neuroepithelium. The ablation of β‐catenin specifically from the forebrain leads to a disruption of apical adherens junctions and a breakdown of neuroepithelial structures. We show that β‐catenin–deficient neuroepithelial cells delaminate and undergo apoptosis. Newborn β‐catenin mutants lack the entire forebrain and anterior facial structures. Our data also indicate a lack of TCF/LEF‐β‐catenin–dependent transcriptional activity in the telencephalon of Wnt reporter embryos. Together with the absence of nuclear β‐catenin, this finding suggests that canonical Wnt signalling is not active during early telencephalic development. In summary, we demonstrate that β‐catenin mediates cell–cell adhesion in the early telencephalon and is vital for maintaining the structural integrity of the neuroepithelium. Developmental Dynamics 233:528–539, 2005. © 2005 Wiley‐Liss, Inc.
Atoh1 null mice show directed afferent fiber growth to undifferentiated ear sensory epithelia followed by incomplete fiber retention
Authors: Fritzsch B. , Matei V.A. , Nichols D.H. , Bermingham N. , Jones K. , Beisel K.W. , Wang V.Y.
Published: April 2005

Inner ear hair cells have been suggested as attractors for growing afferent fibers, possibly through the release of the neurotrophin brain‐derived neurotrophic factor (BDNF). Atoh1 null mice never fully differentiate hair cells and supporting cells and, therefore, may show aberrations in the growth and/or retention of their innervation. We investigated the distribution of cells positive for Atoh1‐ or Bdnf‐mediated β‐galactosidase expression in Atoh1 null and Atoh1 heterozygotic mice and correlated the distribution of these cells with their innervation. Embryonic day (E) 18.5 Atoh1 null and heterozygotic littermates show Atoh1‐ and BDNF‐β‐galactosidase–positive cells in comparable distributions in the canal cristae and the cochlea apex. Atoh1‐β‐galactosidase–positive but only occasional Bdnf‐β‐galactosidase–positive cells are found in the utricle, saccule, and cochlea base of Atoh1 null mutant mice. Absence of Bdnf‐β‐galactosidase expression in the utricle and saccule of Atoh1 null mice is first noted at E12.5, a time when Atoh1‐β‐galactosidase expression is also first detected in these epithelia. These data suggest that expression of Bdnf is dependent on ATOH1 protein in some but does not require ATOH1 protein in other inner ear cells. Overall, the undifferentiated Atoh1‐ and Bdnf‐β‐galactosidase–positive cells show a distribution reminiscent of that in the six sensory epithelia in control mice, suggesting that ear patterning processes can form discrete patches of Atoh1 and Bdnf expression in the absence of ATOH1 protein. The almost normal growth of afferent and efferent fibers in younger embryos suggests that neither fully differentiated hair cells nor BDNF are necessary for the initial targeted growth of fibers. E18.5 Atoh1 null mice have many afferent fibers to the apex of the cochlea, the anterior and the posterior crista, all areas with numerous Bdnf‐β‐galactosidase–positive cells. Few fibers remain to the saccule, utricle, and the base of the cochlea, all areas with few or no Bdnf‐β‐galactosidase–positive cells. Thus, retention of fibers is possible with BDNF, even in the absence of differentiated hair cells. Developmental Dynamics 233:570–583, 2005. © 2005 Wiley‐Liss, Inc.
Muscle fiber differentiation in fish embryos as shown by in situ hybridization of a large repertoire of muscle‐specific transcripts
Authors: Chauvigné F. , Cauty C. , Rallière C. , Rescan P.Y.
Published: April 2005

Skeletal muscles are composed of different fiber types, largely defined by differential expression of protein isoforms involved in myofibrillogenesis or metabolism. To learn more about the gene activations that underlie the differentiation and the diversification of embryonic fish myotomal fibers, we investigated the developmental expression of 25 muscle genes in trout embryos by in situ hybridization of muscle‐specific transcripts. The earliest event of muscle differentiation, at approximately the 25‐somite stage, was the expression of a variety of muscle‐specific genes, including slow‐twitch and fast‐twitch muscle isoforms. The activation of these muscle genes started in the deep somitic domain, where the slow muscle precursors (the adaxial cells) were initially located, and progressively spread laterally throughout the width of the myotome. This mediolateral progression of gene expression was coordinated with the lateral migration of slow adaxial cells, which specifically expressed the slow myosin light chain 1 and the SLIM1/FHL1 genes. Subsequently, the fast and slow skeletal muscle isoforms precociously expressed in the course of the mediolateral wave of muscle gene activation became down‐regulated in the superficial slow fibers and the deep fast fibers, respectively. Finally, several muscle‐specific genes, including troponins, a slow myosin‐binding protein C, tropomodulins, and parvalbumin started their transcription only in late embryos. Taken together, these findings show in fish embryos that a common myogenic program is triggered in a mediolateral progression in all muscle cells. The acquisition of the slow phenotype involves the additional activation of several slow‐specific genes in migrating adaxial muscle cells. These events are followed by sequential gene activations and repressions in fast and slow muscle cells. Developmental Dynamics 233:659–666, 2005. © 2005 Wiley‐Liss, Inc.
Zac1 is expressed in progenitor/stem cells of the neuroectoderm and mesoderm during embryogenesis: Differential phenotype of the Zac1‐expressing cells during development
Authors: Valente Tony , Junyent Fèlix , Auladell Carme
Published: April 2005

Zac1, a new zinc‐finger protein that regulates both apoptosis and cell cycle arrest, is abundantly expressed in many neuroepithelia during early brain development. In the present work, we study the expression of Zac1 during early embryogenesis and we determine the cellular phenotype of the Zac1‐expressing cells throughout development. Our results show that Zac1 is expressed in the progenitor/stem cells of several tissues (nervous system, skeleton, and skeletal muscle), because they colocalize with several progenitor/stem markers (Nestin, glial fibrillary acidic protein, FORSE‐1, proliferating cell nuclear antigen, and bromodeoxyuridine). In postnatal development, Zac1 is expressed in all phases of the life cycle of the chondrocytes (from proliferation to apoptosis), in some limbic γ‐aminobutyric acid‐ergic neuronal subpopulations, and during developmental myofibers. Therefore, the intense expression of Zac1 in the progenitor/stem cells of different cellular lineages during the proliferative cycle, before differentiation into postmitotic cells, suggests that Zac1 plays an important role in the control of cell fate during neurogenesis, chondrogenesis, and myogenesis. Developmental Dynamics 233:667–679, 2005. © 2005 Wiley‐Liss, Inc.
dazed gene is necessary for late cell type development and retinal cell maintenance in the zebrafish retina
Authors: Perkins Brian D. , Nicholas Claire S. , Baye Lisa M. , Link Brian A. , Dowling John E.
Published: April 2005

Several molecules, such as growth factors and neurotrophic factors, are required both for the differentiation of specific retinal cell types and the long‐term cell survival of all retinal neurons. As diffusible factors, these molecules act non–cell‐autonomously. Here, we describe the loss of function phenotype for dazed (dzd), a gene that acts cell‐autonomously for retinal cell survival and affects the differentiation of rod photoreceptors and the Müller glia. By 3 days after fertilization, dazed mutant embryos have small eyes and slight heart edema. Acridine orange staining indicated a significant degree of retinal cell death occurring by 48 hr after fertilization, and histological analysis revealed that dying cells were found in the inner and outer nuclear layers and near the marginal zones. Although molecular and morphological differentiation of the inner retina and cone photoreceptors occurred, rod photoreceptors failed to differentiate beyond a small patch in the ventral retina and rod precursors failed to respond to exogenously added retinoic acid, which normally potentiated rod differentiation. Mosaic analysis indicated that the dazed gene acts cell‐autonomously for rod production and cell survival, as dazed clones failed to produce rods outside the ventral patch and dazed cells were not maintained in wild‐type hosts. Raising mutants under constant light resulted in severe retinal degeneration, whereas raising embryos under constant darkness did not provide any additional protection from cell death. Behavioral analysis showed that a subpopulation of adult fish that were heterozygous for the dazed mutation had elevated visual thresholds and were night blind, suggesting that dazed may also be required for long‐term dim‐light vision. Taken together, our studies suggest a role for the dazed gene in rod and Müller cell development and overall retinal cell survival and maintenance. Developmental Dynamics 233:680–694, 2005. © 2005 Wiley‐Liss, Inc.
Retroactive, a membrane‐anchored extracellular protein related to vertebrate snake neurotoxin‐like proteins, is required for cuticle organization in the larva of Drosophila melanogaster
Authors: Moussian Bernard , Söding Johannes , Schwarz Heinz , Nüsslein‐Volhard Christiane
Published: April 2005

Mutations in the rtv gene cause disarrangement of chitin fibers in the cuticle of the Drosophila larva, and occasionally the cuticle detaches from the epidermis. We have identified the rtv gene, and using the new HHpred homology detection method, we show that the Rtv protein defines a new family of disulfide‐rich proteins in insects that are related to vertebrate snake neurotoxin‐like proteins, including CD59 and transforming growth factor‐β type II receptors. Rtv is an extracellular membrane‐anchored protein exposing six aromatic residues that may mediate binding to chitin. We propose that this binding function of Rtv may assist the organization of chitin fibers at the epidermal cell surface during cuticle assembly. Developmental Dynamics 233:1056–1063, 2005. © 2005 Wiley‐Liss, Inc.
Function of the mammalian postorbital bar
Authors: Heesy Christopher P.
Published: April 2005

Complete postorbital bars, bony arches that encompass the lateral aspect of the eye and form part of a circular orbit, have evolved homoplastically multiple times during mammalian evolution. Numerous functional hypotheses have been advanced for postorbital bars, the most promising being that postorbital bars function to stiffen the lateral orbit in taxa that have significant angular deviation between the temporal fossa and the bony orbit. Without a stiff lateral orbit the anterior temporalis muscle and fascia potentially would pull on the postorbital ligament, deform the orbit, and cause disruption of oculomotor precision. Morphometric data were collected on 1,329 specimens of 324 taxa from 16 orders of extant eutherian and metatherian mammals in order to test whether the orientation of the orbit relative to the temporal fossa is correlated with the replacement of the postorbital ligament with bone. The allometric and ecological influences on orbit orientation across mammals are also explored. The morphometric results corroborate the hypothesis: Shifts in orbit orientation relative to the temporal fossa are correlated with the size of the postorbital processes, which replace the ligament. The allometric and ecological factors that influence orbit orientation vary across taxa. Postorbital bars stiffen the lateral orbital wall. Muscle pulleys, ligaments, and other connective tissue attach to the lateral orbital wall, including the postorbital bar. Without a stiff lateral orbit, deformation due to temporalis contraction would displace soft tissues contributing to normal oculomotor function. J. Morphol., 2005. © 2005 Wiley‐Liss, Inc.
Quantification of angiogenesis induced in rabbit cornea by breast carcinoma of women treated with tamoxifen
Authors: da Silva Benedito Borges , da Silva Raimundo Gerônimo , Borges Umbelina Soares , da Silveira Filho Marcos Antônio Guedes , Pimentel Igor Clausius Carvalho , Gebrim Luiz Henrique , Simões Manuel de Jesus , Baracat Edmund Chada
Published: April 2005

Background

The aim of this study was to evaluate the effect of tamoxifen on angiogenesis induced in rabbit cornea by breast carcinoma from post‐menopausal women.

Methods

Thirteen post‐menopausal women with operable, estrogen receptor‐positive breast carcinomas, treated with 20 mg of tamoxifen daily for 30 days prior to undergoing definitive surgery, participated in this study. Twenty‐six virgin female New Zealand white rabbits, 3–4 months old, weighing approximately 2.5 kg each, were divided into two groups of 13 animals and received corneal implants of tumor either pre‐ or post‐tamoxifen treatment. After 10 days, the animals were sacrificed, the region of the cornea between the tumor implant and the limbus was removed and quantification of angiogenesis was carried out by evaluating the entire hematoxylin‐eosin stained slide, using a 10× objective lens (100× magnification). Student t‐test was used in the statistical analysis of the data and statistical significance was established at P < 0.05.

Results

Mean microvessel count was 106.8 ± 5.9 pre‐tamoxifen treatment and 54 ± 5.6 post‐treatment. According to Student t‐test, there was a significant reduction in mean microvessel density following treatment with tamoxifen (P < 0.001).

Conclusions

Rabbit cornea proved to be an interesting experimental model for the quantification of angiogenesis. Tamoxifen, when administered for 30 days to post‐menopausal women with breast cancer, significantly inhibited angiogenesis induced by tumor fragments in rabbit cornea. J. Surg. Oncol. 2005;90:77–80. © 2005 Wiley‐Liss, Inc.
Activation of MMP‐2 and MMP‐9 in patients with oral squamous cell carcinoma
Authors: Patel Beena P. , Shah Pankaj M. , Rawal Upendra M. , Desai Amisha A. , Shah Shakuntala V. , Rawal Rakesh M. , Patel Prabhudas S.
Published: April 2005

Background and Objectives

Oral cancer accounts for one third of all malignancies in India where habit of tobacco consumption is the major etiologic factor, which causes field cancerization in oral mucosa. Multiple molecular events in oral mucosa due to field cancerization may be the cause of local and regional lymph node involvement in oral cancer resulting into low overall survival, high recurrence rate, and poor prognosis. Several matrix metalloproteinases (MMPs) have been shown to play an important role in the invasion and metastasis of oral squamous cell carcinoma (SCC). MMP‐2 and MMP‐9 are capable of degrading type‐IV collagen, which is a major component of basement membrane. Therefore, we studied MMP‐2 and MMP‐9 activation by gelatin zymography, which is cost effective alternate to ELISA method, in patients with oral SCCs to predict their role in metastatic potentials.

Materials and Methods

Thirty‐nine patients of oral SCCs were classified as non‐metastatic (n = 28), and metastatic (n = 11) according to regional lymph node involvement. Malignant and adjacent normal tissues of the patients were collected at the time of surgery. Gelatin zymography was carried out using 7.5% polyacrylamide gel under non‐denaturing and non‐reducing conditions. Zymograms were analyzed densitometrically. Latent and active forms of MMP‐2 and MMP‐9 were expressed as ng/50 μg of protein.

Results

Latent and active forms of MMP‐2 and MMP‐9 were significantly elevated in malignant tissues as compared to their adjacent normal tissues (P < 0.05). Total MMP‐2 and MMP‐9 activities were also significantly elevated in malignant tissues as compared to adjacent normal tissues (P = 0.005 and P = 0.028, respectively). Activation ratio of MMP‐2 and MMP‐9 were significantly elevated in malignant tissues as compared to adjacent normal tissues. Activation of MMP‐2 was prominent (11%) than MMP‐9 (5%) in malignant tissues. Activation ratio of MMP‐2 was significantly elevated in patients with lymph node metastasis than patients without lymph node metastasis (P = 0.005). Receiver's operating characteristic (ROC) curve analysis revealed that activation ratio of MMP‐2 discriminate better than and activation ratio of MMP‐9 between patients with and without lymph node metastasis. Activation ratio of MMP‐2 could predict risk of lymph node metastasis development in patients without lymph node involvement.

Conclusion

The study concluded that activation of MMP‐2 and MMP‐9 was significantly higher in malignant tissues as compared to adjacent normal tissues. Further, activation ratio of MMP‐2 was significantly elevated in patients with lymph node metastasis as compared to patients without lymph node metastasis, which could predict risk of lymph node metastasis development in node negative patients. J. Surg. Oncol. 2005;90:81–88. © 2005 Wiley‐Liss, Inc.
Extended survival in a patient with recurrent and metastatic adrenal cortical carcinoma by aggressive transarterial embolization—a case report
Authors: Li Shau‐Hsuan , Huang Cheng‐Hua , Ko Sheung‐Fat , Chou Fong‐Fu , Huang Shun‐Chen
Published: April 2005

The prognosis of inoperable recurrent or metastatic adrenal cortical carcinoma is poor due to lack of effective treatment modalities. We report a case of recurrent and metastatic adrenal cortical carcinoma in which prolonged survival of 58 months was achieved with aggressive three sequential transarterial embolization. It is probably the first reported case with the longest survival by transarterial embolization in the literature to date. A 60‐year‐old man received operation for left adrenal cortical carcinoma. Liver metastases, tumor bed recurrence, and spleen metastasis were noted during follow‐up. Three sequential transarterial embolization for metastatic liver tumors, tumor bed recurrence, and metastatic spleen tumor were performed and resulted in relief of symptoms and prolonged survival of 58 months after recurrence verified. Aggressive transarterial embolization seems to be a safe and effective procedure for symptoms relief, and may prolong survival in the management of inoperable adrenal cortical carcinoma. It can be considered in any patient with inoperable adrenal cortical carcinoma if not contraindicated. J. Surg. Oncol. 2005;90:101–105. © 2005 Wiley‐Liss, Inc.
Assault, psychiatric diagnoses, and sociodemographic variables in relation to help‐seeking behavior in a national sample of women
Authors: Lewis Sarah F. , Resnick Heidi S. , Ruggiero Kenneth J. , Smith Daniel W. , Kilpatrick Dean G. , Best Connie L. , Saunders Benjamin E.
Published: April 2005

Using a national probability household sample of 4,008 women, we estimated the prevalence and correlates of formal and informal help seeking. One‐year prevalences of formal help seeking (e.g., seeking help from professional) and informal help seeking (e.g., seeking help from a relative or friend) were 10.6 and 6.6%, respectively. In the final multivariable model, increased likelihood of informal help seeking was associated with younger age, history of sexual assault, and past‐year diagnoses of posttraumatic stress disorder (PTSD) and major depressive episode (MDE). Similarly, increased likelihood of formal help seeking was associated with younger age, Caucasian racial/ethnic status, history of sexual assault, history of physical assault, and past‐year diagnoses of PTSD and MDE. Implications for helping professionals and public education programs are discussed.
The role of loss of meaning in the pursuit of treatment for posttraumatic stress disorder
Authors: Fontana Alan , Rosenheck Robert
Published: April 2005

Clinical observation and theory suggest that people who have difficulty coping with their exposure to traumatic events often experience a loss of meaning to their lives. This article examines the contribution of loss of meaning to seeking help from clergy and/or mental health providers. Results support the hypotheses that veterans who have suffered a greater loss of meaning are more likely to seek help from clergy and from VA mental health professionals. We suggest that veterans who seek help from clergy are particularly desirous of achieving a restoration of meaning that is specific to their loss, and that this quest sustains a continued pursuit of mental health treatment, especially among those who seek help from the VA.
Treatment of residual insomnia after CBT for PTSD: Case studies
Authors: DeViva Jason C. , Zayfert Claudia , Pigeon Wilfred R. , Mellman Thomas A.
Published: April 2005

Insomnia is one of the most common symptoms of posttraumatic stress disorder (PTSD). Evidence suggests that insomnia may persist for many PTSD patients after other symptoms have responded to cognitive‐behavioral therapy (CBT). The present article reports the effects of administering a five‐session cognitive‐behavioral insomnia treatment to 5 patients who responded to CBT for PTSD yet continued to report insomnia. Insomnia treatment was associated with improvements on subjective sleep measures (Pittsburgh Sleep Quality Index, Insomnia Severity Index, and Beliefs and Attitudes about Sleep Scale) and self‐monitored sleep efficiency and related measures in 4 of 5 cases. Results highlight issues specific to treating insomnia in trauma populations and future directions for examining treatment of insomnia associated with PTSD.
Correlation between traumatic events and posttraumatic stress disorder among North Korean defectors in South Korea
Authors: Jeon WooTaek , Hong ChangHyung , Lee ChangHo , Kim Dong Kee , Han Mooyoung , Min SungKil
Published: April 2005

The number of North Korean defectors entering South Korea has been increasing rapidly since 1994. Two hundred North Korean defectors in South Korea were studied to identify their experiences of traumatic events in North Korea and during defection, and the correlation with Posttraumatic Stress Disorder (PTSD). Researchers conducted face‐to‐face interviews and assisted defectors in performing a self‐report assessment of this survey. The study questionnaire consisted of demographic characteristics, the Traumatic Experiences Scale for North Korean Defectors, and the PTSD part of the Structured Clinical Interview for DSM‐III‐R Korean version. Prevalence rate of PTSD in defectors was 29.5%, with a higher rate for women. In factor analysis, the 25 items of traumatic events experienced in North Korea were divided into three factors: Physical Trauma, Political‐Ideological Trauma, and Family‐Related Trauma. In addition, the 19 items of traumatic events during defection were grouped into four factors: Physical Trauma, Detection and Capture‐Related Trauma, Family‐Related Trauma, and Betrayal‐Related Trauma. In multifactorial logistic regression analysis, Family‐Related Trauma in North Korea had a significant odds ratio.
Deployment stressors, gender, and mental health outcomes among Gulf War I veterans
Authors: Vogt Dawne S. , Pless Anica P. , King Lynda A. , King Daniel W.
Published: April 2005

An Erratum has been published for this article in Journal of Traumatic Stress 18(3) 2005, 271–284 [].

Findings indicate that war‐zone exposure has negative implications for the postdeployment adjustment of veterans; however, most studies have relied on limited conceptualizations of war‐zone exposure and focused on male samples. In this study, an array of deployment stressors that were content valid for both female and male Gulf War I military personnel was examined to elucidate gender differences in war‐zone exposure and identify gender‐based differential associations between stressors and mental health outcomes. While women and men were exposed to both mission‐related and interpersonal stressors and both stressor categories were associated with mental health outcomes, women reported more interpersonal stressors and these stressors generally had a stronger impact on women's than on men's mental health. Exceptions are described, and implications are discussed.
Physiological arousal and dissociation in acute trauma victims during trauma narratives
Authors: Nixon Reginald D. V. , Bryant Richard A. , Moulds Michelle L. , Felmingham Kim L. , Mastrodomenico Julie A.
Published: April 2005

The aim of the present study was to examine whether the finding of suppressed physiological activity in dissociative rape‐trauma victims (Griffin, Resick, & Mechanic, 1997) was replicable in a nonsexual assault trauma group. A sample of 17 high‐dissociating (HD) participants and 18 low‐dissociating (LD) participants who had experienced a motor vehicle accident or physical assault described their trauma while skin conductance, heart rate activity, and self‐reported mood were recorded. HD individuals demonstrated a trend for elevated heart rate during the experiment compared with LD participants, but both groups displayed comparable skin‐conductance levels. Curve estimation analysis indicated that the two groups had a similar pattern of physiological responding during the trauma narratives. These findings challenge the notion that dissociative reactions are associated with reduced psychophysiological arousal after trauma.
Improving the amplitude‐modulated control experiment for multislice continuous arterial spin labeling
Authors: Werner Richard , Norris David G. , Alfke Karsten , Mehdorn H. Maximilian , Jansen Olav
Published: April 2005

The use of an amplitude‐modulated radiofrequency (RF) pulse for a control experiment is a proven method to control for off‐resonance effects in multislice continuous arterial spin labeling (CASL) experiments. This method is also known as double adiabatic inversion. The adiabaticity factor of a single half‐pulse, β1/2, and a new dimensionless parameter α, which is obtained from the labeling parameters and the flow velocity, are introduced. This makes it possible to distinguish three distinct cases: 1) With low α, a double inversion occurs. 2) With α ≥ ∼4, the efficiency with which the longitudinal magnetization is returned to the z‐axis depends on the phase of the amplitude modulation at the time the spins cross the center of the labeling plane. 3) In the intermediate region, the efficiency shows undesirable fluctuations. In a Bloch equation simulation, three optimized parameter sets are determined. Near ideal performance should always be achieved by combinations of parameters for which β1/2 ≥ ∼2 and α ∼ π/β1/2. The efficiency increases were realized in a volunteer study, showing the practical application of the suggested optimization. Magn Reson Med 53:1096–1102, 2005. © 2005 Wiley‐Liss, Inc.
Sodium ion apparent diffusion coefficient in living rat brain
Authors: Goodman James A. , Kroenke Christopher D. , Bretthorst G. Larry , Ackerman Joseph J. H. , Neil Jeffrey J.
Published: April 2005

The apparent diffusion coefficient (ADC) of Na+ was determined in live rat brain. The brain extracellular‐to‐intracellular Na+ content ratio is ∼8:2, which is the inverse of that for water in these spaces. Consequently, the ADC of Na+ is primarily affected by motion in the extracellular space, and Na+ can be viewed as a reporter molecule for motion in that space. Likewise, water ADC is dominated by intracellular motion. The brain Na+ ADC was 1.15 ± 0.09 μm2/ms, which is 61% of the aqueous Na+ free diffusion coefficient (Dfree) at 37°C (1.9 μm2/ms), while the ADC for brain water is 28% of the water Dfree at 37°C (3 μm2/ms). This suggests that the ADC of molecular species within the extracellular space is roughly twofold that within the intracellular space. In postmortem brain, both Na+ and water decrease to 17% of the respective Dfree values. These results are consistent with Na+ and water ADC values sharing the same biophysical determinants in postmortem brain. The observed difference between Na+ and water ADC/Dfree ratios in living brain tissue may be attributable to the extracellular environment hindering molecular displacements twofold less than the intracellular environment. Magn Reson Med 53:1040–1045, 2005. © 2005 Wiley‐Liss, Inc.
Oxygen‐enhanced proton imaging of the human lung using T2*
Authors: Pracht Eberhard D. , Arnold Johannes F. T. , Wang Tungte , Jakob Peter M.
Published: April 2005

Magnetic susceptibility gradients caused by tissue/air interfaces lead to very short T2* times in the human lung. These susceptibility gradients are dependent on the magnetic susceptibility of the respiratory gas and therefore should influence T2* relaxation. In this work, a technique for quantitative T2* mapping of the human lung during one breath hold is presented. Using this method, the lung T2* relaxation time was measured under normoxic (room air, 21% O2) and hyperoxic (100% O2) conditions to verify this assumption. The mean T2* difference between room air and 100% O2 is about 10% and contains ventilation information, since only ventilated regions contribute to signal change due to different susceptibility gradients. Magn Reson Med 53:1193–1196, 2005. © 2005 Wiley‐Liss, Inc.
Theoretical noise model for oxygenation‐sensitive magnetic resonance imaging
Authors: Wu Gaohong , Li Shi‐Jiang
Published: April 2005

Contrast‐to‐noise ratio (CNR) in blood oxygenation level‐dependent (BOLD) based functional MRI (fMRI) studies is a fundamental parameter to determine statistical significance and therefore to map functional activation in the brain. The CNR is defined here as BOLD contrast with respect to temporal fluctuation. In this study, a theoretical noise model based on oxygenation‐sensitive MRI signal formation is proposed. No matter what the noise sources may be in the signal acquired by a gradient‐echo echo‐planar imaging pulse sequence, there are only three noise elements: apparent spin density fluctuations,S0(t); transverse relaxation rate fluctuations,R(t); and thermal noise,n(t). The noise contributions fromS0(t),R(t), andn(t) to voxel time course fluctuations were evaluated as a function of echo time (TE) at 3 T. Both noise contributions caused byS0(t) andR(t) are significantly larger than that of thermal noise when TE = 30 ms. In addition, the fluctuations betweenS0(t) andR(t) are cross‐correlated and become a noise factor that is large enough and cannot be ignored. The experimentally measured TE dependences of noise, temporal signal‐to‐noise ratio, and BOLD CNR in finger‐tapping activation regions were consistent with the proposed model. Furthermore, the proposed theoretical models not only unified previously proposed BOLD CNR models, but also provided mechanisms for interpreting apparent controversies and limitations that exist in the literature. Magn Reson Med 53:1046–1054, 2005. © 2005 Wiley‐Liss, Inc.
In vivo prostate magnetic resonance spectroscopic imaging using two‐dimensional J‐resolved PRESS at 3 T
Authors: Kim Dong‐hyun , Margolis Daniel , Xing Lei , Daniel Bruce , Spielman Daniel
Published: April 2005

In vivo magnetic resonance spectroscopic imaging of the prostate using single‐voxel and multivoxel two‐dimensional (2D) J‐resolved sequences is investigated at a main magnetic field strength of 3 T. Citrate, an important metabolite often used to aid the detection of prostate cancer in magnetic resonance spectroscopic exams, can be reliably detected along with the other metabolites using this method. We show simulations and measurements of the citrate metabolite using 2D J‐resolved spectroscopy to characterize the spectral pattern. Furthermore, using spiral readout gradients, the single‐voxel 2D J‐resolved method is extended to provide the spatial distribution information as well all within a reasonable scan time (17 min). Phantom and in vivo data are presented to illustrate the multivoxel 2D J‐resolved spiral chemical shift imaging sequence. Magn Reson Med 53:1177–1182, 2005. © 2005 Wiley‐Liss, Inc.
Imaging of single human carcinoma cells in vitro using a clinical whole‐body magnetic resonance scanner at 3.0 T
Authors: Pinkernelle Jens , Teichgräber Ulf , Neumann Fabian , Lehmkuhl Lukas , Ricke Jens , Scholz Regina , Jordan Andreas , Bruhn Harald
Published: April 2005

The purpose of the present study was to examine whether single human carcinoma cells labeled with iron oxide nanoparticles could be detected by magnetic resonance (MR) imaging on a clinical 3‐T scanner using a surface coil only. WiDr human colon carcinoma cells were loaded with two kinds of iron oxide nanoparticles differing by coating and size: aminosilan‐coated (MagForce) and carboxy‐dextran‐coated particles (Resovist). The latter were preferred by the colon carcinoma cell line used here and taken up much faster (12 h) than the smaller carboxydextran‐coated Resovist (48 h). Labeled single carcinoma cells, distributed in an agarose gel in a monodisperse layer as controlled by light microscopy, became detectable as punctuate signal extinctions when using a small circularly polarized surface coil in conjunction with a T2*‐weighted GE sequence at 3 T. The threshold for the detectability of labeled colon carcinoma cells ranged at a load of 4–5 μg iron/106 cells. Obviating the need for special hardware additions, this study opens a new lane for single‐cell tracking on clinical 3‐T MR scanners amenable to patient studies. Magn Reson Med 53:1187–1192, 2005. © 2005 Wiley‐Liss, Inc.
Accurate myocardial T1 measurements: Toward quantification of myocardial blood flow with arterial spin labeling
Authors: Zhang Haosen , Shea Steve M. , Park Vivian , Li Debiao , Woodard Pamela K. , Gropler Robert J. , Zheng Jie
Published: April 2005

In this study, we investigated a method for accurately measuring myocardial T1 for the quantification of myocardial blood flow (MBF) with arterial spin labeling (ASL). A single‐shot gradient‐echo (GE)‐based ASL sequence with an adiabatic hyperbolic secant inversion recovery pulse was modified to acquire a pair of myocardial T1's within a breath‐hold. A multivariable regression algorithm that accounted for the magnetization saturation effects was developed to calculate T1. The MBF was then determined with a well‐developed model. The accuracy of our T1 calculation was first evaluated in a phantom, and then in six dogs for the MBF calculation, with (N = 4) and without (N = 2) coronary artery stenosis. In the phantom study, the accuracy of T1 measured with a slice‐selective inversion prepared pulse was within 2.5% of error. In healthy dogs, the MBF increased 2–5 times during vasodilation. In contrast, regional differences of MBF were well visualized in the stenotic dogs during vasodilation (perfusion reserve of 2.75 ± 0.83 in normal myocardium, and 1.46 ± 0.75 in the stenotic area). A correlation analysis revealed a close agreement in MBF between the ASL and microsphere (MS) in both healthy and stenotic dogs. In summary, the modified ASL technique and T1 regression algorithm proposed here provide an accurate measurement of myocardial T1 and demonstrate potential for reliably assessing MBF at steady state. Magn Reson Med 53:1135–1142, 2005. © 2005 Wiley‐Liss, Inc.
High‐resolution diffusion tensor imaging of human patellar cartilage: Feasibility and preliminary findings
Authors: Filidoro L. , Dietrich O. , Weber J. , Rauch E. , Oerther T. , Wick M. , Reiser M.F. , Glaser C.
Published: April 2005

MR diffusion tensor imaging (DTI) was used to analyze the microstructural properties of articular cartilage. Human patellar cartilage‐on‐bone samples were imaged at 9.4T using a diffusion‐weighted SE sequence (12 gradient directions, resolution = 39 × 78 × 1500 μm3). Voxel‐based maps of the mean diffusivity, fractional anisotropy (FA), and eigenvectors were calculated. The mean diffusivity decreased from the surface (1.45 × 10−3 mm2/s) to the tide mark (0.68 × 10−3 mm2/s). The FA was low (0.04–0.28) and had local maxima near the surface and in the portion of the cartilage corresponding to the radial layer. The eigenvector corresponding to the largest eigenvalue showed a distinct zonal pattern, being oriented tangentially and radially in the upper and lower portions of the cartilage, respectively. The findings correspond to current scanning electron microscopy (SEM) data on the zonal architecture of cartilage. The eigenvector maps appear to reflect the alignment of the collagenous fibers in cartilage. In view of current efforts to develop and evaluate structure‐modifying therapeutic approaches in osteoarthritis (OA), DTI may offer a tool to assess the structural properties of cartilage. Magn Reson Med 53:993–998, 2005. © 2005 Wiley‐Liss, Inc.
Active‐passive gradient shielding for MRI acoustic noise reduction
Authors: Edelstein William A. , Kidane Tesfaye K. , Taracila Victor , Baig Tanvir N. , Eagan Timothy P. , Cheng Yu‐Chung N. , Brown Robert W. , Mallick John A.
Published: April 2005

An important source of MRI acoustic noise—magnet cryostat warm‐bore vibrations caused by eddy‐current‐induced forces—can be mitigated by a passive metal shield mounted on the outside of a vibration‐isolated, vacuum‐enclosed shielded gradient set. Finite‐element (FE) calculations for a z‐gradient indicate that a 2‐mm‐thick Cu layer wrapped on the gradient assembly can decrease mechanical power deposition in the warm bore and reduce warm‐bore acoustic noise production by about 25 dB. Eliminating the conducting warm bore and other magnet parts as significant acoustic noise sources could lead to the development of truly quiet, fully functioning MRI systems with noise levels below 70 dB. Magn Reson Med 53:1013–1017, 2005. © 2005 Wiley‐Liss, Inc.